Parasacral Perforator Flaps for Reconstruction of Sacral Pressure Sores.

PubMed

Lin, Chin-Ta; Chen, Shih-Yi; Chen, Shyi-Gen; Tzeng, Yuan-Sheng; Chang, Shun-Cheng

2015-07-01

Despite advances in reconstruction techniques, pressure sores continue to present a challenge to the plastic surgeon. The parasacral perforator flap is a reliable flap that preserves the entire contralateral side as a future donor site. On the ipsilateral side, the gluteal muscle itself is preserved and all flaps based on the inferior gluteal artery are still possible. We present our experience of using parasacral perforator flaps in reconstructing sacral defects. Between August 2004 and January 2013, 19 patients with sacral defects were included in this study. All the patients had undergone surgical reconstruction of sacral defects with a parasacral perforator flap. The patients' sex, age, cause of sacral defect, flap size, flap type, numbers of perforators used, rotation angle, postoperative complications, and hospital stay were recorded. There were 19 parasacral perforator flaps in this series. All flaps survived uneventfully except for 1 parasacral perforator flap, which failed because of methicillin-resistant Staphylococcus aureus infection. The overall flap survival rate was 95% (18/19). The mean follow-up period was 17.3 months (range, 2-24 months). The average length of hospital stay was 20.7 days (range, 9-48 days). No flap surgery-related mortality was found. Also, there was no recurrence of sacral pressure sores or infected pilonidal cysts during the follow-up period. Perforator-based flaps have become popular in modern reconstructive surgery because of low donor-site morbidity and good preservation of muscle. Parasacral perforator flaps are durable and reliable in reconstructing sacral defects. We recommend the parasacral perforator flap as a good choice for reconstructing sacral defects.

Sacral Variability in Tailless Species: Homo sapiens and Ochotona princeps.

PubMed

Tague, Robert G

2017-05-01

Homo sapiens is variable in number of sacral vertebrae, and this variability can lead to obstetrical complication. This study uses the comparative method to test the hypothesis that sacral variability in H. sapiens is associated with absence of a tail. Three species of lagomorphs are studied: Ochotona princeps (N = 271), which is tailless, and Lepus californicus (N = 212) and Sylvilagus audubonii (N = 206), which have tails. Results show that O. princeps has (1) higher diversity index for number of sacral vertebrae (0.49) compared to L. californicus (0.25) and S. audubonii (0.26) and (2) significantly higher percentage of individuals with the species-specific nonmodal number of sacral vertebrae (43.9%) compared to L. californicus (14.2%) and S. audubonii (15.5%). Comparison of H. sapiens (N = 1,030; individuals of age 20-39 years) with O. princeps shows similarities between the species in diversity index (also 0.49 in H. sapiens) and percentage of individuals with nonmodal number of sacral vertebrae (37.3% in H. sapiens). Homeotic transformation best explains the results. H. sapiens and O. princeps show propensity for caudal shift at the sacral-caudal border (i.e., homeotic transformation of the first caudal vertebra to a sacral vertebra). Caudal and cranial shift among presacral vertebrae increases or decreases this propensity, respectively. Increase in number of sacral vertebrae in H. sapiens by homeotic transformation reduces pelvic outlet capacity and can be obstetrically hazardous. Anat Rec, 300:798-809, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Comparative sacral morphology and the reconstructed tail lengths of five extinct primates: Proconsul heseloni, Epipliopithecus vindobonensis, Archaeolemur edwardsi, Megaladapis grandidieri, and Palaeopropithecus kelyus.

PubMed

Russo, Gabrielle A

2016-01-01

This study evaluated the relationship between the morphology of the sacrum-the sole bony link between the tail or coccyx and the rest of the body-and tail length (including presence/absence) and function using a comparative sample of extant mammals spanning six orders (Primates, Carnivora, Rodentia, Diprotodontia, Pilosa, Scandentia; N = 472). Phylogenetically-informed regression methods were used to assess how tail length varied with respect to 11 external and internal (i.e., trabecular) bony sacral variables with known or suspected biomechanical significance across all mammals, only primates, and only non-primates. Sacral variables were also evaluated for primates assigned to tail categories ('tailless,' 'nonprehensile short-tailed,' 'nonprehensile long-tailed,' and 'prehensile-tailed'). Compared to primates with reduced tail lengths, primates with longer tails generally exhibited sacra having larger caudal neural openings than cranial neural openings, and last sacral vertebrae with more mediolaterally-expanded caudal articular surfaces than cranial articular surfaces, more laterally-expanded transverse processes, more dorsally-projecting spinous processes, and larger caudal articular surface areas. Observations were corroborated by the comparative sample, which showed that shorter-tailed (e.g., Lynx rufus [bobcat]) and longer-tailed (e.g., Acinonyx jubatus [cheetah]) non-primate mammals morphologically converge with shorter-tailed (e.g., Macaca nemestrina) and longer-tailed (e.g., Macaca fascicularis) primates, respectively. 'Prehensile-tailed' primates exhibited last sacral vertebrae with more laterally-expanded transverse processes and greater caudal articular surface areas than 'nonprehensile long-tailed' primates. Internal sacral variables performed poorly compared to external sacral variables in analyses of extant primates, and were thus deemed less useful for making inferences concerning tail length and function in extinct primates. The tails lengths of

Bilateral chronic sacral neuromodulation for treatment of lower urinary tract dysfunction.

PubMed

Hohenfellner, M; Schultz-Lampel, D; Dahms, S; Matzel, K; Thüroff, J W

1998-09-01

Chronic sacral neuromodulation aims at functional restoration of selected forms of nonneurogenic and neurogenic bladder dysfunction. The original technique, as described by Tanagho and Schmidt, provides unilateral sacral nerve stimulation via an implanted stimulator powering an electrode inserted into a sacral foramen. Its drawback was that the implant failed unpredictably in some patients despite previous successful percutaneous test stimulation. Therefore, we modified the stimulation technique to improve the efficacy of chronic sacral neuromodulation. Guarded bipolar electrodes powered by an implantable neurostimulator were attached bilaterally directly to the S3 nerves through a sacral laminectomy in 9 women and 2 men (mean age 43.4 years). Of the patients 5 had urinary incontinence due to detrusor hyperactivity and 6 had urinary retention from detrusor hypocontractility. Mean followup with repeated urodynamics was 13 months (range 9 to 28). Four significant complications were encountered in 4 patients. In 10 patients the urological sequelae of the neurological disorder were alleviated significantly (50% or more), including 5 who experienced complete relief of symptoms. The efficacy of chronic sacral neuromodulation can be improved by bilateral attachment of electrodes directly to the sacral nerves.

Sacral Peak Pressure in Healthy Volunteers and Patients With Spinal Cord Injury: With and Without Liquid-Based Pad.

PubMed

Duetzmann, Stephan; Forsey, Lynn M; Senft, Christian; Seifert, Volker; Ratliff, John; Park, Jon

2015-01-01

The prevalence of sacral pressure ulcers in patients with spinal cord injuries is high. The sacral area is vulnerable to compressive pressure because of immobility and because the sacrum and posterior superior iliac prominence lie closely under the skin with no muscle layer in between. The aim of this study was to assess peak sacral pressure before and after use of PURAP, a liquid-based pad that covers only the sacral area and can be applied on any bed surface. Healthy volunteers (n = 12) and patients with spinal cord injuries (n = 10) took part; the patients had undergone spine surgery within 7 days before data collection. Participants were in bed, pretest pressure maps were generated, PURAP was placed for 15 minutes, and then posttest pressure maps were generated. Peak pressure was obtained every second and averaged over the entire period. Patients rated whether their comfort had improved when PURAP was in use. For healthy volunteers, mean pretest peak sacral pressure was 74.7 (SD = 16.2) mmHg; the posttest mean was 49.1 (SD = 7.5) mmHg (p < .001, Wilcoxon signed-rank test). For patients with spinal cord injuries, mean pretest peak sacral pressure was 105.7 (SD = 22.4) mmHg; the posttest mean was 81.4 (SD = 18.3) mmHg (p < .001, Wilcoxon signed-rank test). The pad reduced the peak sacral pressure in the patient group by 23% (range = 11%-42%) and in the volunteers by 32% (range = 19%-46%). Overall, 70% of the patients reported increased comfort with PURAP. Peak sacral pressure was reduced when PURAP was used. It covers only the sacral area but could help many patients with spinal cord injury because the prevalence of sacral pressure ulcers is high in this group. PURAP may be economically advantageous in countries and hospitals with limited financial resources needed for more expensive mattresses and cushions.

Sacral neuromodulation for women with Fowler's syndrome.

PubMed

Swinn, M J; Kitchen, N D; Goodwin, R J; Fowler, C J

2000-10-01

Neuromodulation of the sacral nerves has been found to be an effective therapy for a variety of lower urinary tract dysfunctions. The reported success rate for the period of trial stimulation (peripheral nerve evaluation test) prior to permanent implantation of a sacral nerve stimulator is variable, but generally reported to be in the region of 30-50%. We present here the results of the peripheral nerve evaluation test in 38 patients with urinary retention. 34 of the 38 had been found to have an abnormality of their striated urethral sphincter on electromyography using a concentric needle electrode, i.e., they had the disorder which was described by Fowler and coworkers in 1988. The overall success rate in this group was 68%. We believe that our relatively high success rate is due to sacral neuromodulation working via a mechanism which involves the urethral sphincter, an abnormality which had been demonstrated in 89% of these patients. Twelve of the patients subsequently underwent permanent implantation of a sacral nerve stimulator, and all of them have experienced a return of voiding. However, in 2 patients, there is a persisting need for self-catheterization. There is, however, a high reoperation rate.

Incidentally diagnosed giant invasive sacral schwannoma

PubMed Central

Togral, Guray; Arikan, Murat; Hasturk, Askin E.; Gungor, Safak

2014-01-01

Schwannomas are benign encapsulated tumors of Schwan cells that grow slowly along the peripheral myelin nerve fibers. Sacral spinal schwannomas are very rare, and the incidence of sacral schwannoma ranges from 1-5% of all spinal schwannomas, and only around 50 cases are reported in the literature. There are 3 defined types of sacral schwannomas. These are retroperitoneal or presacral, intra osseous, and spinal schwannomas. Patients commonly present with complaints of pain and paresthesia due to the spinal schwannoma extending to extra spinal tissues. Direct x-ray, CT, MRI, and scintigraphy are used for preoperative diagnosis and treatment planning. Local recurrence and transformation to malignancy is very rare. For this reason, the frequently preferred treatments are subtotal removal of the mass or simple enucleation. In our article, we discuss the clinical features and the surgical treatment we performed without the need for stabilization in an incidentally determined giant invasive schwannoma case. PMID:24983285

Developmental identity versus typology: Lucy has only four sacral segments.

PubMed

Machnicki, Allison L; Lovejoy, C Owen; Reno, Philip L

2016-08-01

Both interspecific and intraspecific variation in vertebral counts reflect the action of patterning control mechanisms such as Hox. The preserved A.L. 288-1 ("Lucy") sacrum contains five fused elements. However, the transverse processes of the most caudal element do not contact those of the segment immediately craniad to it, leaving incomplete sacral foramina on both sides. This conforms to the traditional definition of four-segmented sacra, which are very rare in humans and African apes. It was recently suggested that fossilization damage precludes interpretation of this specimen and that additional sacral-like features of its last segment (e.g., the extent of the sacral hiatus) suggest a general Australopithecus pattern of five sacral vertebrae. We provide updated descriptions of the original Lucy sacrum. We evaluate sacral/coccygeal variation in a large sample of extant hominoids and place it within the context of developmental variation in the mammalian vertebral column. We report that fossilization damage did not shorten the transverse processes of the fifth segment of Lucy's sacrum. In addition, we find that the extent of the sacral hiatus is too variable in apes and hominids to provide meaningful information on segment identity. Most importantly, a combination of sacral and coccygeal features is to be expected in vertebrae at regional boundaries. The sacral/caudal boundary appears to be displaced cranially in early hominids relative to extant African apes and humans, a condition consistent with the likely ancestral condition for Miocene hominoids. While not definitive in itself, a four-segmented sacrum accords well with the "long-back" model for the Pan/Homo last common ancestor. Am J Phys Anthropol 160:729-739, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

What questionnaires to use when measuring quality of life in sacral tumor patients: the updated sacral tumor survey.

PubMed

van Wulfften Palthe, Olivier D R; Janssen, Stein J; Wunder, Jay S; Ferguson, Peter C; Wei, Guo; Rose, Peter S; Yaszemski, Micheal J; Sim, Franklin H; Boland, Patrick J; Healey, John H; Hornicek, Francis J; Schwab, Joseph H

2017-05-01

Patient-reported outcomes are becoming increasingly important when investigating results of patient and disease management. In sacral tumor, the symptoms of patients can vary substantially; therefore, no single questionnaire can adequately account for the full spectrum of symptoms and disability. The purpose of this study is to analyze redundancy within the current sacral tumor survey and make a recommendation for an updated version based on the results and patient and expert opinions. A survey study from a tertiary care orthopedic oncology referral center was used. The patient sample included 70 patients with sacral tumors (78% chordoma). The following 10 questionnaires included in the current sacral tumor survey were evaluated: the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Item short form, PROMIS Pain Intensity short form, PROMIS Pain Interference short form, PROMIS Neuro-QOL v1.0 Lower Extremity Function short form, PROMIS v1.0 Anxiety short form, the PROMIS v1.0 Depression short form, the International Continence Society Male short form, the Modified Obstruction-Defecation Syndrome questionnaire, the PROMIS Sexual Function Profile v1.0, and the Stoma Quality of Life tool. We performed an exploratory factor analysis to calculate the possible underlying latent traits. Spearman rank correlation coefficients were used to measure to what extent the questionnaires converged. We hypothesized the existence of six domains based on current literature: mental health, physical health, pain, gastrointestinal symptoms, sexual function, and urinary incontinence. To assess content validity, we surveyed 32 patients, 9 orthopedic oncologists, 1 medical oncologist, 1 radiation oncologist, and 1 orthopedic oncology nurse practitioner with experience in treating sacral tumor patients on the relevance of the domains. Reliability as measured by Cronbach alpha ranged from 0.65 to 0.96. Coverage measured by floor and ceiling effects ranged from 0% to 52

What Questionnaires To Use When Measuring Quality Of Life In Sacral Tumor Patients? The Updated Sacral Tumor Survey

PubMed Central

van Wulfften Palthe, Olivier D.R.; Janssen, Stein J.; Wunder, Jay S.; Ferguson, Peter C.; Wei, Guo; Rose, Peter. S.; Yaszemski, Micheal J.; Sim, Franklin H.; Boland, Patrick J.; Healey, John H.; Hornicek, Francis J.; Schwab, Joseph H.

2017-01-01

Background context Patient reported outcomes are becoming increasingly important when investigating results of patient and disease management. In sacral tumor patients symptoms can vary substantially, therefore no single questionnaire can adequately account for the full spectrum of symptoms and disability. Purpose The purpose of this study is to analyze redundancy within the current sacral tumor survey and make a recommendation for an updated version based on the results and patient and expert opinions. Study design/setting A survey study from a tertiary care orthopaedic oncology referral center was used for this study. Patient sample The patient sample included 70 patients with sacral tumors (78% chordoma). Outcome measures The following ten questionnaires included in the current sacral tumor survey were evaluated: the Patient Reported Outcomes Measurement Information System (PROMIS) Global Item short form, PROMIS Pain Intensity short form, PROMIS Pain Interference short form, PROMIS Neuro-QOL v1.0 Lower Extremity Function short form, PROMIS v1.0 Anxiety short form, the PROMIS v1.0 Depression short form, the International Continence Society (ICS) Male short form, the Modified Obstruction-Defecation Syndrome (MODS) questionnaire, the PROMIS Sexual Function Profile v1.0, and The Stoma Quality Of Life tool. Methods We performed an exploratory factor analysis to calculate possible underlying latent traits. Spearman rank correlation coefficients were used to measure to what extent the questionnaires converged. We hypothesized the existence of six domains based on current literature: mental health, physical health, pain, gastrointestinal symptoms, sexual function, and urinary incontinence. To assess content validity, we surveyed 32 patients, nine orthopaedic oncologists, one medical oncologist, one radiation oncologist, and an orthopaedic oncology nurse practitioner with experience in treating sacral tumor patients on the relevance of the domains. Results Reliability as

Prophylactic Sacral Dressing for Pressure Ulcer Prevention in High-Risk Patients.

PubMed

Byrne, Jaime; Nichols, Patricia; Sroczynski, Marzena; Stelmaski, Laurie; Stetzer, Molly; Line, Cynthia; Carlin, Kristen

2016-05-01

Patients in intensive care units are likely to have limited mobility owing to hemodynamic instability and activity orders for bed rest. Bed rest is indicated because of the severity of the disease process, which often involves intubation, sedation, paralysis, surgical procedures, poor nutrition, low flow states, and poor circulation. These patients are predisposed to the development and/or the progression of pressure ulcers not only because of their underlying diseases, but also because of limited mobility and deconditioned states of health. To assess whether treating high-risk patients with a prophylactic sacral dressing decreases the incidence of unit-acquired sacral pressure ulcers. An evidence-based tool for identifying patients at high risk for pressure ulcers was used in 3 intensive care units at an urban tertiary care hospital and academic medical center. Those patients deemed at high risk had a prophylactic sacral dressing applied. Incidence rates were collected and compared for the 7 months preceding use of the dressings and for 7 months during the trial period when the dressing was used. After the sacral dressing began being used, the number of unit-acquired sacral pressure ulcers decreased by 3.4 to 7.6 per 1000 patient days depending on the unit. A prophylactic sacral dressing may help prevent unit-acquired sacral pressure ulcers. Implementation of an involved care team with heightened awareness and increased education along with a prophylactic sacral dressing in patients deemed high risk for skin breakdown are all essential for success. ©2016 American Association of Critical-Care Nurses.

Sacral orientation revisited.

PubMed

Peleg, Smadar; Dar, Gali; Steinberg, Nili; Peled, Nathan; Hershkovitz, Israel; Masharawi, Youssef

2007-07-01

A descriptive study of the sacral anatomic orientation (SAO) and its association with pelvic incidence (PI). To introduce the concept of SAO, establish a method for measuring it, and evaluate its association with pelvic orientation. Pelvic orientation (PO) is considered a key factor in spinal shape and balance. Sacral slope (SS), PI, and pelvic tilt (PT) are the most frequently used parameters for evaluating PO. Nevertheless, the association between the anatomic orientation of the sacrum and these parameters has never been established. The aim of the present study is to define the anatomic orientation of the sacrum, to establish a reliable method for measuring it, and to examine its association with PI. SAO was defined as the angle created between the intersection of a line running parallel to the superior endplate surface of the sacrum and a line running between the anterior superior iliac spine (ASIS) and the anterior-superior edge of the symphysis pubis. Methods for measuring SAO and PI on both skeletal populations and living individuals are described. The study was carried out on 424 skeletons (articulated pelves) using a three-dimensional digitizer and on 20 adult individuals using CT three-dimensional images (volume-rendering method). Reliability (intratester and intertester) was assessed using intraclass correlation test. A regression analysis was carried out to evaluate the association between the two measurements. The mean SAO and PI in the human skeletal population were found to be 48.46 degrees +/- 10.17 degrees and 54.08 degrees +/- 12.64 degrees , respectively and of the living individuals (CT) 52.76 degrees +/- 10.31 degrees and 57.14 degrees +/- 13.08 degrees , respectively. SAO and PI measurements were highly correlated (r = -0.824, and r = -0.828, P < 0.001 for skeletal material and living individuals, respectively). PI can be predicted via SAO, i.e., PI = [-0.971 x SAO] + 101.16 degrees . The newly suggested parameter (SAO) may be an important

The receptor tyrosine kinase RET regulates hindgut colonization by sacral neural crest cells.

PubMed

Delalande, Jean-Marie; Barlow, Amanda J; Thomas, Aaron J; Wallace, Adam S; Thapar, Nikhil; Erickson, Carol A; Burns, Alan J

2008-01-01

The enteric nervous system (ENS) is formed from vagal and sacral neural crest cells (NCC). Vagal NCC give rise to most of the ENS along the entire gut, whereas the contribution of sacral NCC is mainly limited to the hindgut. This, and data from heterotopic quail-chick grafting studies, suggests that vagal and sacral NCC have intrinsic differences in their ability to colonize the gut, and/or to respond to signalling cues within the gut environment. To better understand the molecular basis of these differences, we studied the expression of genes known to be essential for ENS formation, in sacral NCC within the chick hindgut. Our results demonstrate that, as in vagal NCC, Sox10, EdnrB, and Ret are expressed in sacral NCC within the gut. Since we did not detect a qualitative difference in expression of these ENS genes we performed DNA microarray analysis of vagal and sacral NCC. Of 11 key ENS genes examined from the total data set, Ret was the only gene identified as being highly differentially expressed, with a fourfold increase in expression in vagal versus sacral NCC. We also found that over-expression of RET in sacral NCC increased their ENS developmental potential such that larger numbers of cells entered the gut earlier in development, thus promoting the fate of sacral NCC towards that of vagal NCC.

Sacroplasty for Symptomatic Sacral Hemangioma: A Novel Treatment Approach

PubMed Central

Agarwal, V.; Sreedher, G.; Weiss, K.R.; Hughes, M.A.

2013-01-01

Summary Painful vertebral body hemangiomas have been successfully treated with vertebroplasty and kyphoplasty. Sacral hemangiomas are uncommon and as such painful sacral hemangiomas are rare entities. We report what we believe is only the second successful treatment of a painful sacral hemangioma with CT-guided sacroplasty. A 56-year-old woman with a history of right-sided total hip arthroplasty and lipoma excision presented to her orthopedic surgeon with persistent right-sided low back pain which radiated into her buttock and right groin and hindered her ability to walk and perform her activities of daily living. MRIs of the thoracic spine, lumbar spine and pelvis showed numerous lesions with imaging characteristics consistent with multiple hemangiomas including a 2.2×2.1 cm lesion involving the right sacrum adjacent to the right S1 neural foramen. Conservative measures including rest, physical therapy, oral analgesics and right-sided sacroiliac joint steroid injection did not provide significant relief. Given her lack of improvement and the fact that her pain localized to the right sacrum, the patient underwent CT-guided sacroplasty for treatment of a painful right sacral hemangioma. Under CT fluoroscopic guidance, a 10 gauge introducer needle was advanced through the soft tissues of the back to the margin of the lesion. Biopsy was then performed and after appropriate preparation, cement was then introduced through the needle using a separate cement filler cannula. Appropriate filling of the right sacral hemangioma was visualized using intermittent CT fluoroscopy. After injection of approximately 2.5 cc of cement, it was felt that there was near complete filling of the right sacral hemangioma. With satisfactory achievement of cement filling, the procedure was terminated. Pathology from biopsy taken at the time of the procedure was consistent with hemangioma. Image-guided sacroplasty with well-defined endpoints is an effective, minimally invasive and safe

Sacral neuromodulation for lower urinary tract dysfunction.

PubMed

Van Kerrebroeck, Philip E V; Marcelissen, Tom A T

2012-08-01

To review the technique, indications, results and working mechanisms of sacral neuromodulation (SNM) for lower urinary tract dysfunction. The available literature on SNM for lower urinary tract dysfunction was searched. Based on the information available in the literature and also based on personal experience, the urological indications, technique, mechanisms of action and results of SNM are presented and discussed. SNM for lower urinary tract dysfunction involves stimulation of the 3rd sacral nerve with an electrode implanted in the sacral foramen and connected to a pulse generator. The technique is accepted by the FDA since 1997. Currently, SNM for lower urinary tract dysfunction has been successfully used in about 26,000 patients with various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. The actual procedure of SNM consists of a minimal invasive technique and is effective in about 70% of the patients who have been implanted with a permanent system. Also, in pelvic pain, interesting results have been described. SNM modulates the micturition reflexes at different levels in the central nervous system. Sacral neuromodulation is a safe and effective therapy for various forms of lower urinary tract dysfunction, including urgency, frequency and urgency incontinence as well as non-obstructive urinary retention. It should be the first choice after failure of maximal conservative therapy.

Introduction of laparoscopic sacral colpopexy to a fellowship training program.

PubMed

Kantartzis, Kelly; Sutkin, Gary; Winger, Dan; Wang, Li; Shepherd, Jonathan

2013-11-01

Minimally invasive sacral colpopexy has increased over the past decade, with many senior physicians adopting this new skill set. However, skill acquisition at an academic institution in the presence of postgraduate learners is not well described. This manuscript outlines the introduction of laparoscopic sacral colpopexy to an academic urogynecology service that was not performing minimally invasive sacral colpopexies, and it also defines a surgical learning curve. The first 180 laparoscopic sacral colpopexies done by four attending urogynecologists from January 2009 to December 2011 were retrospectively analyzed. The primary outcome was operative time. Secondary outcomes included conversion to laparotomy, estimated blood loss, and intra- and postoperative complications. Linear regression was used to analyze trends in operative times. Fisher's exact test compared surgical complications and counts of categorical variables. Mean total operative time was 250 ± 52 min (range 146-452) with hysterectomy and 222 ± 45 (range 146-353) for sacral colpopexy alone. When compared with the first ten cases performed by each surgeon, operative times in subsequent groups decreased significantly, with a 6-16.3% reduction in overall times. There was no significant difference in the rate of overall complications regardless of the number of prior procedures performed (p = 0.262). Introduction of laparoscopic sacral colpopexy in a training program is safe and efficient. Reduction in operative time is similar to published learning curves in teaching and nonteaching settings. Introducing this technique does not add additional surgical risk as these skills are acquired.

Latissimus dorsi free flap for coverage of sacral radiodermatitis in the ambulatory patient

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stark, D.; Tofield, J.J.; Terranova, W.

1987-07-01

Ambulatory patients with large sacral ulcers can represent extremely challenging coverage problems. Technical options become fewer when sacral ulcers are coupled with radiation dermatitis. Latissimus dorsi free flap transfer, with direct anastomoses to sacral vessels, is described in 2 patients.

Effects of Low-frequency Current Sacral Dermatome Stimulation on Idiopathic Slow Transit Constipation.

PubMed

Kim, Jin-Seop; Yi, Seung-Ju

2014-06-01

[Purpose] This study aimed to determine whether low-frequency current therapy can be used to reduce the symptoms of idiopathic slow transit constipation (ISTC). [Subjects] Fifteen patients (ten male and five female) with idiopathic slow transit constipation were enrolled in the present study. [Results] Bowel movements per day, bowel movements per week, and constipation assessment scale scores significantly improved after low-frequency current simulation of S2-S3. [Conclusion] Our results show that stimulation with low-frequency current of the sacral dermatomes may offer therapeutic benefits for a subject of patients with ISTC.

Anterior sacral meningocele with presacral cysts: report of a case.

PubMed

Krivokapić, Zoran; Grubor, Nikica; Micev, Marjan; Colović, Radoje

2004-11-01

Anterior sacral meningocele is a rare anomaly most frequently presenting as a presacral mass. Since the first description in 1837, approximately 150 cases have been reported. The case presented is a 37-year-old female in whom an asymptomatic presacral mass was discovered during her first delivery. Because normal delivery was impossible, a cesarean section was performed. A year later, in a regional hospital a "cystic presacral tumor" was treated with biopsy and drainage. Four years later, she developed constipation caused by perineal compression for which she was admitted to our department in which two anterior presacral cysts were excised. The recovery was complicated with meningitis, which was successfully treated with antibiotics. Whenever a presacral mass is found, anterior sacral meningocele has to be a diagnostic consideration. The symptoms are usually related to the compression on rectum, bladder, and sacral nervous plexus. Rectal examination and radiography of the pelvis with the sacral bone showing the "scimitar sign" are the main diagnostic methods. Myelography, computed tomography, and magnetic resonance imaging are the best methods for identifying the precise anatomy of sacral meningocele and for proper planning of the operation. Transvaginal or transrectal aspiration and drainage are not advised, because they may result in a lethal outcome caused by sepsis.

The surgical management of sacral chordomas.

PubMed

Schwab, Joseph H; Healey, John H; Rose, Peter; Casas-Ganem, Jorge; Boland, Patrick J

2009-11-15

Retrospective case series. The purpose of this study was to evaluate factors that contribute to improved local control and survival. In addition, we sought to define the expected morbidity associated with treatment. Sacral chordomas are rare tumors presumed to arise from notochordal cells. Local recurrence presents a major problem in the management of these tumors and it has been correlated with survival. Resection of sacral tumors is associated with significant morbidity. Forty-two patients underwent resection for sacral chordoma between 1990 and 2005. Twelve patients had their initial surgery elsewhere. There were 12 female and 30 male patients. The proximal extent of the sacrectomy was at least S2 in 32 patients. Median survival was 84 months, and 5-year disease-free (DFS) and disease-specific survival (DSF) were 56% and 77%, respectively. Local recurrence (LR) and metastasis occurred in 17 (40%) and 13 (31%) patients, respectively. Local recurrence (P=0.0001), metastasis (P=0.0001), prior resection (P=0.046), and higher grade (P=0.05) were associated with a worse DSF. Prior resections (P=0.0001) and intralesional resections (P=0.01) were associated with a higher rate of LR. Intralesional resections were associated with a lower DSF (P=0.0001). Wide contaminated margins treated with cryosurgery and/or radiation were not associated with a higher LR rate. Rectus abdominus flaps were associated with decreased wound complications (P=0.01). Thirty-one (74%) patients reported that they self catheterize; and 16 (38%) patients required bowel training, while an additional twelve (29%) patients had a colostomy. Twenty-eight (67%) patients reported sexual dysfunction. Two (5%) patients died due to sepsis. Intralesional resection should be avoided as it is associated with a higher LR rate and worse survival. Rectus abdominus flaps ought to be considered as they lower the wound complication rate. Sacral resection is associated with significant morbidity.

Mechanisms underlying recurrent inhibition in the sacral parasympathetic outflow to the urinary bladder.

PubMed Central

de Groat, W C

1976-01-01

1. In cats with the sacral dorsal roots cut on one side electrical stimulation (15-40 c/s) of the central end of the transected ipsilateral pelvic nerve depressed spontaneous bladder contractions. The depression was abolished by transecting the ipsilateral sacral ventral roots. 2. Electrical stimulation of acutely or chronically transected ('deafferented') sacral ventral roots depressed spontaneous bladder contractions and the firing of sacral parasympathetic preganglionic neurones innervating the bladder. The depression of neuronal firing occurred ipsilateral and contralateral to the point of stimulation, but only occurred with stimulation of sacral roots containing preganglionic axons and only with stimulation of sacral roots containing preganglionic axons and only at intensities of stimulation (0-7-4V) above the threshold for activation of these axons. 3. The inhibitory responses were not abolished by strychnine administered by micro-electrophoresis to preganglionic neurones, but were blocked by the intravenous administration of strychnine. 4. The firing of preganglionic neurones elicited by micro-electrophoretic administration of an excitant amino acid (DL-homocysteic acid) was not depressed by stimulation of the ventral roots. 5. It is concluded that the inhibition of the sacral outflow to the bladder by stimulation of sacral ventral roots is related to antidromic activation of vesical preganglionic axons. Collaterals of these axons must excite inhibitory interneurones which in turn depress transmission at a site on the micturition reflex pathway prior to the preganglionic neurones. PMID:950603

Perforator-based island flap with a peripheral muscle patch for coverage of sacral sores.

PubMed

Chang, Jung Woo; Lee, Jang Hyun; Choi, Matthew Seung Suk

2016-06-01

Despite numerous therapeutic advances, the treatment of pressure sores remains a challenge. The increased use of perforator flaps enables surgeons to minimize donor-site morbidity by sparing the underlying muscle. In the presence of focal deep spaces, however, the inclusion of muscle would be beneficial. The goal of this study was to introduce a method for including a muscle patch at the periphery of a perforator-based island flap for coverage of sacral pressure sores. Between March 2010 and February 2015, 26 patients with stage IV sacral sores underwent perforator-based island flap reconstruction with a peripheral muscle patch. Patient characteristics, including sex, age, defect size, and postoperative complications, were recorded. All flaps survived without major complications. No flap necrosis was noted. The present study shows that a muscle patch incorporated into the periphery of a perforator-based flap can be transferred safely. This can be a good surgical option in cases where infection control or more volume is needed. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Effects of Low-frequency Current Sacral Dermatome Stimulation on Idiopathic Slow Transit Constipation

PubMed Central

Kim, Jin-Seop; Yi, Seung-Ju

2014-01-01

[Purpose] This study aimed to determine whether low-frequency current therapy can be used to reduce the symptoms of idiopathic slow transit constipation (ISTC). [Subjects] Fifteen patients (ten male and five female) with idiopathic slow transit constipation were enrolled in the present study. [Results] Bowel movements per day, bowel movements per week, and constipation assessment scale scores significantly improved after low-frequency current simulation of S2-S3. [Conclusion] Our results show that stimulation with low-frequency current of the sacral dermatomes may offer therapeutic benefits for a subject of patients with ISTC. PMID:25013277

Presacral abscess as a rare complication of sacral nerve stimulator implantation.

PubMed

Gumber, A; Ayyar, S; Varia, H; Pettit, S

2017-03-01

A 50-year-old man with intractable anal pain attributed to proctalgia fugax underwent insertion of a sacral nerve stimulator via the right S3 vertebral foramen for pain control with good symptomatic relief. Thirteen months later, he presented with signs of sepsis. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large presacral abscess. MRI demonstrated increased enhancement along the pathway of the stimulator electrode, indicating that the abscess was caused by infection introduced at the time of sacral nerve stimulator placement. The patient was treated with broad spectrum antibiotics, and the sacral nerve stimulator and electrode were removed. Attempts were made to drain the abscess transrectally using minimally invasive techniques but these were unsuccessful and CT guided transperineal drainage was then performed. Despite this, the presacral abscess progressed, developing enlarging gas locules and extending to the pelvic brim to involve the aortic bifurcation, causing hydronephrosis and radiological signs of impending sacral osteomyelitis. MRI showed communication between the rectum and abscess resulting from transrectal drainage. In view of the progressive presacral sepsis, a laparotomy was performed with drainage of the abscess, closure of the upper rectum and formation of a defunctioning end sigmoid colostomy. Following this, the presacral infection resolved. Presacral abscess formation secondary to an infected sacral nerve stimulator electrode has not been reported previously. Our experience suggests that in a similar situation, the optimal management is to perform laparotomy with drainage of the presacral abscess together with simultaneous removal of the sacral nerve stimulator and electrode.

Presacral abscess as a rare complication of sacral nerve stimulator implantation

PubMed Central

Gumber, A; Ayyar, S; Varia, H

2017-01-01

A 50-year-old man with intractable anal pain attributed to proctalgia fugax underwent insertion of a sacral nerve stimulator via the right S3 vertebral foramen for pain control with good symptomatic relief. Thirteen months later, he presented with signs of sepsis. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large presacral abscess. MRI demonstrated increased enhancement along the pathway of the stimulator electrode, indicating that the abscess was caused by infection introduced at the time of sacral nerve stimulator placement. The patient was treated with broad spectrum antibiotics, and the sacral nerve stimulator and electrode were removed. Attempts were made to drain the abscess transrectally using minimally invasive techniques but these were unsuccessful and CT guided transperineal drainage was then performed. Despite this, the presacral abscess progressed, developing enlarging gas locules and extending to the pelvic brim to involve the aortic bifurcation, causing hydronephrosis and radiological signs of impending sacral osteomyelitis. MRI showed communication between the rectum and abscess resulting from transrectal drainage. In view of the progressive presacral sepsis, a laparotomy was performed with drainage of the abscess, closure of the upper rectum and formation of a defunctioning end sigmoid colostomy. Following this, the presacral infection resolved. Presacral abscess formation secondary to an infected sacral nerve stimulator electrode has not been reported previously. Our experience suggests that in a similar situation, the optimal management is to perform laparotomy with drainage of the presacral abscess together with simultaneous removal of the sacral nerve stimulator and electrode. PMID:28071947

[Sacral pressure sores and their treatment].

PubMed

Bielecki, Marek; Skowroński, Rafał; Skowroński, Jan

2006-01-01

Sacral bed sores still present a serious problem in most surgery departments. They occur mainly in elderly patients of limited mobility. The treatment of such sores extends over long periods of time and therefore involves considerable costs. The material consisted of 11 sacral pressure ulcers treated surgically. The sores occurred in 4 severely disabled patients suffering from proximal third femur fractures, 4 patients with traumatic brain injury (treated in the Intensive Care Unit), and 3 patients suffering from bed sores after spinal cord injury. In 6 patients a fasciocutaneous flap was applied to the sores and in 5 cases a pedicled musculocutaneous gluteus maximus flap. The end results were assessed using Seiler's criteria. Complications of the "seroma" type were observed in 3 patients, and in 2 marginal necrosis. In all our patients complete healing was achieved within 2-4 weeks. On analysing our experience to date in surgical treatment of bed sores we are of the opinion that even extensive sacral sores can be covered with unilateral pedicled flaps provided that they are appropriately planned. Deep sores of the 4th degree sometimes with concomitant osteomyelitis require pedicled muscle flaps or in some cases musculocutaneous flaps to improve local circulation. The preparation of the patient for reconstruction surgery is just as important as the operation itself and therefore such preparation should never be neglected.

Pelvic trauma with displaced sacral fractures: functional outcome at one year.

PubMed

Tötterman, Anna; Glott, Thomas; Søberg, Helene Lundgaard; Madsen, Jan Erik; Røise, Olav

2007-06-01

A prospective single-cohort study of 31 patients surgically treated for pelvic injuries with displaced sacral fractures. To describe the medium term functional outcome in unstable sacral fractures. Displaced sacral fractures pose a special challenge in orthopedic surgery due to the high rate of associated injuries. Little information is available on the medium-term functional outcome of patients with injuries which include unstable sacral fractures. We examined 31 patients with displaced sacral fractures having 10 mm or more displacement, 1 year (mean, 1.4 years; range, 1.0-2.5 years) after injury. Data from a previous study were supplemented with functional outcome measures (work status, independence in ADL, and SF-36). An association between outcome and tested variables was sought. Fifteen months after injury, 65% of the patients had regained their independence in functions pertaining to daily activities; 33% had returned to work. All dimensions of perceived health were affected. Polytrauma and impairments relative to voiding and sexual function had a detrimental effect on outcome. Fracture characteristics were not predictive of poor outcome. Although the majority of patients achieved independent living, medium-term follow-up indicated significant residual disability. The complex nature of these fractures and the associated injuries should be considered in the rehabilitation of these patients.

Finding sacral: Developmental evolution of the axial skeleton of odontocetes (Cetacea).

PubMed

Buchholtz, Emily A; Gee, Jessica K

2017-07-01

Axial morphology was dramatically transformed during the transition from terrestrial to aquatic environments by archaeocete cetaceans, and again during the subsequent odontocete radiation. Here, we reconstruct the sequence of developmental events that underlie these phenotypic transitions. Archaeocete innovations include the loss of primaxial/abaxial interaction at the sacral/pelvic articulation and the modular dissociation of the fluke from the remainder of the tail. Odontocetes subsequently integrated lumbar, sacral, and anterior caudal vertebrae into a single torso module, and underwent multiple series-specific changes in vertebral count. The conservation of regional proportions despite regional fluctuations in count strongly argues that rates of somitogenesis can vary along the column and that segmentation was dissociated from regionalization during odontocete evolution. Conserved regional proportions also allow the prediction of the location and count of sacral homologs within the torso module. These predictions are tested with the analysis of comparative pudendal nerve root location and geometric morphometrics. We conclude that the proportion of the column represented by the sacral series has been conserved, and that its vertebrae have changed in count and relative centrum length in parallel with other torso vertebrae. Although the sacral series of odontocetes is de-differentiated, it is not de-regionalized. © 2017 Wiley Periodicals, Inc.

Cost of dressings for prevention of sacral pressure ulcers.

PubMed

Inoue, Kelly Cristina; Matsuda, Laura Misue

2016-01-01

to identify costs of dressings to prevent sacral pressure ulcers in an adult intensive care unit in Paraná, Brazil. secondary analysis study with 25 patients admitted between October 2013 and March 2014, using transparent polyurethane film (n=15) or hydrocolloid dressing (n=10) on the sacral region. The cost of each intervention was based on the unit amount used in each type of dressing, and its purchase price (transparent film = R$15.80, hydrocolloid dressing = R$68.00). the mean cost/patient was R$23.17 for use of transparent film and R$190.40 for use of hydrocolloid dressing. The main reason for changing the dressing was detachment. the transparent film was the most economically advantageous alternative to prevent sacral pressure ulcers in critical care patients. However, additional studies should be carried out including assessment of the effectiveness of both dressings.

[Four cases of urinary dysfunction associated with sacral herpes zoster].

PubMed

Matsuo, Tomohiro; Oba, Kojiro; Miyata, Yasuyoshi; Igawa, Tsukasa; Sakai, Hideki

2014-02-01

Herpes zoster is caused by the infection of Varicella-Zoster virus. The anatomical distribution of herpes zoster in the sacral area is only 6. 9%1). Moreover, the onset rate of herpes zoster with urinary dysfunction is 0.6%1). The lesion sites of herpes zoster which cause urinary dysfunction are almost lumber and sacral areas. We describe four cases of sacral herpes zoster with urinary dysfunction in this report. All patients were elderly people (66-84 years old), and all patients were administered anti-virus drugs and alpha 1-adrenergic receptor blockers. Because of urinary retention, three patients have performed clean intermittent self-catheterization (CIC) for several weeks. As the lesions of herpes zoster healed, each patient recovered from urinary dysfunction.

Transcutaneous sacral neurostimulation for irritative voiding dysfunction.

PubMed

Walsh, I K; Johnston, R S; Keane, P F

1999-01-01

Patients with irritative voiding dysfunction are often unresponsive to standard clinical treatment. We evaluated the response of such individuals to transcutaneous electrical stimulation of the third sacral nerve. 32 patients with refractory irritative voiding dysfunction (31 female and 1 male; mean age 47 years) were recruited to the study. Ambulatory transcutaneous electrical neurostimulation was applied bilaterally to the third sacral dermatomes for 1 week. Symptoms of frequency, nocturia, urgency, and bladder pain were scored by each patient throughout and up to 6 months following treatment. The mean daytime frequency was reduced from 11.3 to 7.96 (p = 0.01). Nocturia episodes were reduced from a mean of 2.6 to 1.8 (p = 0.01). Urgency and bladder pain mean symptom scores were reduced from 5.97 to 4.89 and from 1.48 to 0.64, respectively. After stopping therapy, symptoms returned to pretreatment levels within 2 weeks in 40% of the patients and within 6 months in 100%. Three patients who continued with neurostimulation remained satisfied with this treatment modality at 6 months. Transcutaneous third sacral nerve stimulation may be an effective and noninvasive ambulatory technique for the treatment of patients with refractory irritative voiding dysfunction. Following an initial response, patients may successfully apply this treatment themselves to ensure long-term relief.

Preliminary results of sacral transcutaneous electrical nerve stimulation for fecal incontinence.

PubMed

Leung, Edmund; Francombe, James

2013-03-01

Fecal incontinence is a common debilitating condition. The aim of this study is to investigate the feasibility of sacral transcutaneous electrical nerve stimulation as an alternative treatment modality for fecal incontinence. All consecutive patients who presented with fecal incontinence to the senior author's clinic were prospectively recruited between June 2009 and September 2010. The severity of their fecal incontinence was assessed by the Wexner and Vaizey scores and anal physiology. Any improvement following a period of sacral transcutaneous electrical nerve stimulation treatment was determined by repeating the scores. In addition, patient satisfaction with the procedure was assessed by using a patient impression score. Twenty female patients with a median age of 57.5 years (range, 30-86) were evaluated. The median follow-up was 10 months (range, 5-12 months). Two patients did not record a change in their Vaizey score. The overall mean Wexner score was 7.9 ± 4.2 before in comparison with 4.0 ± 3.1 after sacral transcutaneous electrical nerve stimulation treatment (p < 0.0001, CI = 2.2-5.7, SE = 0.832). The overall mean Vaizey score was 12.7 ± 5.7 before in comparison with 5.8 ± 5.6 after sacral transcutaneous electrical nerve stimulation treatment (p < 0.0001, CI = 4.5-9.4, SE = 1.162). The pretreatment patient impression score was set at a mean of 1 ± 0 in comparison with 2.8 ± 1.1 after sacral transcutaneous electrical nerve stimulation treatment (p < 0.0001, CI = 1.2-2.3, SE = 0.25). The preliminary results suggest sacral transcutaneous electrical nerve stimulation is a promising noninvasive alternative to existing modalities in the treatment of idiopathic fecal incontinence.

Intrapartum sacral stress fracture due to pregnancy-related osteoporosis: a case report.

PubMed

Oztürk, Gülcan; Külcü, Duygu Geler; Aydoğ, Ece

2013-01-01

Low back pain (LBP) and hip pain frequently occur during pregnancy and postpartum period. Although pelvic and mechanic lesions of the soft tissues are most responsible for the etiology, sacral fracture is also one of the rare causes. A 32-year-old primigravid patient presented with LBP and right hip pain which started 3 days after vaginal delivery. Although direct radiographic examination was normal, magnetic resonance imaging of the sacrum revealed sacral stress fracture. Lumbar spine and femoral bone mineral density showed osteoporosis as a risk factor. There were no other risk factors such as trauma, excessive weight gain, and strenuous physical activity. It is considered that the patient had sacral fatigue and insufficiency fracture in intrapartum period. The patient's symptoms subsided in 3 months after physical therapy and rest. In conclusion, sacral fractures during pregnancy and postpartum period, especially resulting from childbirth, are very rare. To date, there are two cases in the literature. In cases who even do not have risk factors related to vaginal delivery such as high birth weight infant and the use of forceps, exc., sacral fracture should be considered in the differential diagnosis of LBP and hip pain started soon after child birth. Pregnancy-related osteoporosis may lead to fracture during vaginal delivery.

Sacral neuromodulations for female lower urinary tract, pelvic floor, and bowel disorders.

PubMed

Wehbe, Salim A; Whitmore, Kristene; Ho, Mat H

2010-10-01

In recent years, sacral neuromodulation (SNM) has been investigated for the treatment of various types of lower urinary tract and bowel dysfunctions. This review discusses recently published data related to the therapeutic applications of SNM in female lower urinary tract, pelvic floor, and bowel disorders. SNM has been employed initially in the treatment of refractory idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. Since then, several studies, including randomized and controlled trials, have confirmed the therapeutic effects of SNM in these disorders. The applications of SNM are now extended to the treatment of other female pelvic problems, such as fecal incontinence, chronic constipation, interstitial cystitis/painful bladder syndrome, sexual dysfunction, and neurogenic disorders, with similar promising results. SNM is approved by the Food and Drug Administration for the treatment of idiopathic overactive bladder, urge urinary incontinence, and chronic nonobstructive urinary retention. SNM is not yet an approved method for the treatment of other pelvic disorders, but data supporting its benefit are emerging. The major advantage of SNM lies in its potential to treat the bladder, urethral sphincter, anal sphincters, and pelvic floor muscles simultaneously, which might result in better therapeutic effects.

The presence of a negative sacral slope in patients with ankylosing spondylitis with severe thoracolumbar kyphosis.

PubMed

Qian, Bang-Ping; Jiang, Jun; Qiu, Yong; Wang, Bin; Yu, Yang; Zhu, Ze-Zhang

2014-11-19

Pelvic retroversion is one of the mechanisms for regulating sagittal balance in patients with a kyphotic deformity. This retroversion is limited by hip extension, which prevents the pelvis from becoming excessively retroverted, achieving a sacral slope of <0°. However, a negative sacral slope can be found in some patients with ankylosing spondylitis with thoracolumbar kyphosis. The purpose of this study was to analyze this finding. We performed a retrospective review of 106 consecutive Chinese Han patients with ankylosing spondylitis with thoracolumbar kyphosis treated at our center from October 2005 to October 2012. Forty-one patients in whom the upper third of the femur was clearly visualized on lateral radiographs were analyzed. Seventeen had a sacral slope of <0° (group A) and twenty-four had a sacral slope of ≥0° (group B). Eight sagittal parameters were measured and compared between the two groups. Correlations among sacral slope, the femoral obliquity angle, and the other sagittal parameters were analyzed. Mean global kyphosis, lumbar lordosis, pelvic tilt, the sagittal vertical axis, and the femoral obliquity angle were significantly larger in group A than in group B, whereas mean pelvic incidence and sacral slope were significantly smaller in group A (p < 0.05 for all). Global kyphosis, lumbar lordosis, pelvic tilt, and the sagittal vertical axis were significantly negatively associated with sacral slope but positively associated with the femoral obliquity angle, whereas pelvic incidence was significantly positively associated with sacral slope but negatively associated with the femoral obliquity angle (p < 0.05 for all). The femoral obliquity angle was significantly negatively associated with sacral slope (p < 0.05). Negative sacral slope does exist in Chinese Han patients with ankylosing spondylitis with thoracolumbar kyphosis. This appears to be caused by severe kyphosis, an initially small sacral slope, and pronounced tilting of the femoral shaft

Interpedicular Approach in Percutaneous Sacroplasty for Treatment of Sacral Vertebral Body Pathologic Fractures

DOE Office of Scientific and Technical Information (OSTI.GOV)

F Latin-Small-Letter-Dotless-I rat, Ahmet Kemal, E-mail: ahmetfirat2@hotmail.com; Guemues, Burcak, E-mail: bgumus@yahoo.com; Kaya, Emin, E-mail: ekaya@inonu.edu.tr

2011-02-15

For this technique, bone needle is introduced into the S1 vertebral body through the interpedicular route by penetrating the central spinal canal at the level of S3-4 and passing through the vertebral body of S2-3 parallel to the anterior border of sacrum. With the interpedicular approach, two sacral vertebral bodies can be injected in one session and lower sacral body injection also is available. interpedicular technique is a safe, practical, and effective technique for the treatment of sacral vertebral body pathologic fractures.

Sacroplasty for symptomatic sacral hemangioma: a novel treatment approach. A case report.

PubMed

Agarwal, V; Sreedher, G; Weiss, K R; Hughes, M A

2013-06-01

Painful vertebral body hemangiomas have been successfully treated with vertebroplasty and kyphoplasty. Sacral hemangiomas are uncommon and as such painful sacral hemangiomas are rare entities. We report what we believe is only the second successful treatment of a painful sacral hemangioma with CT-guided sacroplasty. A 56-year-old woman with a history of right-sided total hip arthroplasty and lipoma excision presented to her orthopedic surgeon with persistent right-sided low back pain which radiated into her buttock and right groin and hindered her ability to walk and perform her activities of daily living. MRIs of the thoracic spine, lumbar spine and pelvis showed numerous lesions with imaging characteristics consistent with multiple hemangiomas including a 2.2×2.1 cm lesion involving the right sacrum adjacent to the right S1 neural foramen. Conservative measures including rest, physical therapy, oral analgesics and right-sided sacroiliac joint steroid injection did not provide significant relief. Given her lack of improvement and the fact that her pain localized to the right sacrum, the patient underwent CT-guided sacroplasty for treatment of a painful right sacral hemangioma. Under CT fluoroscopic guidance, a 10 gauge introducer needle was advanced through the soft tissues of the back to the margin of the lesion. Biopsy was then performed and after appropriate preparation, cement was then introduced through the needle using a separate cement filler cannula. Appropriate filling of the right sacral hemangioma was visualized using intermittent CT fluoroscopy. After injection of approximately 2.5 cc of cement, it was felt that there was near complete filling of the right sacral hemangioma. With satisfactory achievement of cement filling, the procedure was terminated. Pathology from biopsy taken at the time of the procedure was consistent with hemangioma. Image-guided sacroplasty with well-defined endpoints is an effective, minimally invasive and safe procedure

Sacral nerve stimulation can be an effective treatment for low anterior resection syndrome.

PubMed

Eftaiha, S M; Balachandran, B; Marecik, S J; Mellgren, A; Nordenstam, J; Melich, G; Prasad, L M; Park, J J

2017-10-01

Sacral nerve stimulation has become a preferred method for the treatment of faecal incontinence in patients who fail conservative (non-operative) therapy. In previous small studies, sacral nerve stimulation has demonstrated improvement of faecal incontinence and quality of life in a majority of patients with low anterior resection syndrome. We evaluated the efficacy of sacral nerve stimulation in the treatment of low anterior resection syndrome using a recently developed and validated low anterior resection syndrome instrument to quantify symptoms. A retrospective review of consecutive patients undergoing sacral nerve stimulation for the treatment of low anterior resection syndrome was performed. Procedures took place in the Division of Colon and Rectal Surgery at two academic tertiary medical centres. Pre- and post-treatment Cleveland Clinic Incontinence Scores and Low Anterior Resection Syndrome scores were assessed. Twelve patients (50% men) suffering from low anterior resection syndrome with a mean age of 67.8 (±10.8) years underwent sacral nerve test stimulation. Ten patients (83%) proceeded to permanent implantation. Median time from anterior resection to stimulator implant was 16 (range 5-108) months. At a median follow-up of 19.5 (range 4-42) months, there were significant improvements in Cleveland Clinic Incontinence Scores and Low Anterior Resection Syndrome scores (P < 0.001). Sacral nerve stimulation improved symptoms in patients suffering from low anterior resection syndrome and may therefore be a viable treatment option. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Sacral root neuromodulation in idiopathic nonobstructive chronic urinary retention.

PubMed

Shaker, H S; Hassouna, M

1998-05-01

Sacral root neuromodulation is becoming a superior alternative to the standard treatment of idiopathic nonobstructive urinary retention. We report results in 20 successive patients who underwent sacral foramen implantation to restore bladder function. After an initial, thorough baseline assessment 20 patients 19.43 to 55.66 years old with idiopathic nonobstructive urinary retention underwent percutaneous nerve evaluation. Response was assessed by a detailed voiding diary. Responders underwent implantation with an S3 foramen implant, and were followed 1, 3 and 6 months postoperatively, and every 6 months thereafter. Sacral root neuromodulation restored voiding capability in these patients. Bladders were emptied with minimal post-void residual urine, which decreased from 78.3 to 5.5 to 10.2% of the total voided volume from baseline to postoperative followup. These results were reflected in uroflowmetry and pressure-flow studies, which were almost normal after implantation. Furthermore, the urinary tract infection rate decreased significantly and associated pelvic pain improved substantially. The Beck depression inventory and SF-36 quality of life questionnaire indicated some improvement but reached significance in only 1 item. In addition, cystometrography showed no significant difference after 6 months of implantation compared with baseline values. Complications were minimal and within expectations. Sacral root neuromodulation is an appealing, successful modality for nonobstructive urinary retention. Only patients who have a good response to percutaneous nerve evaluation are candidates for implantation. The high efficacy in patients who undergo implantation, relative simplicity of the procedure and low complication rate make this a treatment breakthrough in this difficult group.

The Macroanatomy of the Sacral Plexus and Its Nerves in Eurasian Eagle Owls (Bubo bubo).

PubMed

Akbulut, Y; Demiraslan, Y; Aslan, K; Coban, A

2016-10-01

This study was carried out to reveal the formation of the sacral plexus in the Eurasian Eagle Owls (Bubo bubo) and the nerves originating from this plexus. Five EEOs, three of them were male and two were female, were provided from Wildlife Rescue and Rehabilitation Center of Kafkas University and used as materials. Following the euthanizing of the animals, abdominal cavity was opened. The nerves of plexus sacrales were dissected and photographed. It was detected that the sacral plexus was formed by the ventral ramus of five synsacral nerves. Moreover, it was determined that the roots of the sacral plexus formed three trunks: the truncus cranialis, the truncus medius and the truncus caudalis in fossa renalis. The availability of the n. ischiofemoralis and the availability of n. parafibularis were detected in the EEOs. Five branches were specified as having segregated from the sacral plexus: the n. cutaneus femoralis caudalis, the mutual root of n. fibularis with n. tibialis (n. ischiadicus), the rami musculares, the n. coxalis caudalis and the ramus muscularis. It was observed that the sacral plexus was linked to the lumbar plexus by the n. furcalis, to the pudendus plexus via the n. bigeminus. Consequently, the anatomic structure of the EEO's sacral plexus, the participating synsacral nerves to plexus and the innervation areas of these nerves were revealed. © 2015 Blackwell Verlag GmbH.

Dual-dermal-barrier fashion flaps for the treatment of sacral pressure sores.

PubMed

Hsiao, Yen-Chang; Chuang, Shiow-Shuh

2015-02-01

The sacral region is one of the most vulnerable sites for the development of pressure sores. Even when surgical reconstruction is performed, there is a high chance of recurrence. Therefore, the concept of dual-dermal-barrier fashion flaps for sacral pressure sore reconstruction was proposed. From September 2007 to June 2010, nine patients with grade IV sacral pressures were enrolled. Four patients received bilateral myocutaneous V-Y flaps, four patients received bilateral fasciocutaneous V-Y flaps, and one patient received bilateral rotation-advanced flaps for sacral pressure reconstruction. The flaps were designed based on the perforators of the superior gluteal artery in one patient's reconstructive procedure. All flaps' designs were based on dual-dermal-barrier fashion. The mean follow-up time was 16 months (range = 12-25). No recurrence was noted. Only one patient had a complication of mild dehiscence at the middle suture line, occurring 2 weeks after the reconstructive surgery. The dual-dermal fashion flaps are easily duplicated and versatile. The study has shown minimal morbidity and a reasonable outcome.

Sacral neuromodulation in the treatment of the unstable bladder.

PubMed

Bosch, J L

1998-07-01

Sacral neuromodulation as a treatment for urge incontinence in patients with an unstable bladder is the subject of ongoing clinical studies. Although approximately 75% of the patients treated with a permanent sacral foramen electrode implant have experienced significant improvements, it is now also clear that there is an initial failure rate of about 25%. Recent studies have pointed out the importance of improved patient selection on the basis of sex differences, urodynamic parameters and psychological factors. Also, newer forms of test stimulation and permanent electrode implantation are being explored in an effort to improve on the present results.

The predictive value of the sacral base pressure test in detecting specific types of sacroiliac dysfunction

PubMed Central

Mitchell, Travis D.; Urli, Kristina E.; Breitenbach, Jacques; Yelverton, Chris

2007-01-01

Abstract Objective This study aimed to evaluate the validity of the sacral base pressure test in diagnosing sacroiliac joint dysfunction. It also determined the predictive powers of the test in determining which type of sacroiliac joint dysfunction was present. Methods This was a double-blind experimental study with 62 participants. The results from the sacral base pressure test were compared against a cluster of previously validated tests of sacroiliac joint dysfunction to determine its validity and predictive powers. The external rotation of the feet, occurring during the sacral base pressure test, was measured using a digital inclinometer. Results There was no statistically significant difference in the results of the sacral base pressure test between the types of sacroiliac joint dysfunction. In terms of the results of validity, the sacral base pressure test was useful in identifying positive values of sacroiliac joint dysfunction. It was fairly helpful in correctly diagnosing patients with negative test results; however, it had only a “slight” agreement with the diagnosis for κ interpretation. Conclusions In this study, the sacral base pressure test was not a valid test for determining the presence of sacroiliac joint dysfunction or the type of dysfunction present. Further research comparing the agreement of the sacral base pressure test or other sacroiliac joint dysfunction tests with a criterion standard of diagnosis is necessary. PMID:19674694

[Sacral gigantocellular tumor treated with total sacrectomy and spinal-pelvic fixation].

PubMed

Savić, Milenko

2011-09-01

Total sacrectomy with spinal-pelvic fixation is considered to be a successful approach to the radical surgical treatment of extensive sacral tumors, however, technically very demanding, thus only rarely reported in the literature. We presented a patient with sacral gigantocellular tumor managed successfully using this method but with certain standard operative techniques improvements. A 30-year old patient with a pronounced painful syndrome and sphincter disorders was confirmed to have sacral gigantocellular tumor affecting a greater part of the sacrum. Tumor resection was performed in the first act out off retroperitoneal organs (colon and blood vessels), sacroiliac joints were open by the ventral side, the L5 discus removed, the S2-S5 roots cut off. In the second act, performed three weeks later, sacrectomy was completed by the reconstruction of pelvic ring and spinal-pelvic fixation. Then, the standard technique was modified to provide additional spinal fixation. The results of the operation (duration, blood loss, postoperative deficit) were quite comparable with, and in some aspects even better than the results published in the literature. Total sacrectomy with spinal-pelvic fixation can be a therapy of choice in patients with extensive sacral tumors requaring, however, the multidisciplinary approach and a considerable experience with instrumental spinal stabilization.

Restoration of bladder function in spastic neuropathic bladder using sacral deafferentation and different techniques of neurostimulation.

PubMed

Schumacher, S; Bross, S; Scheepe, J R; Alken, P; Jünemann, K P

1999-01-01

Conventional sacral anterior root stimulation (SARS) results in simultaneous activation of both the detrusor muscle and the external urethral sphincter. We evaluated the possibilities of different neurostimulation techniques to overcome stimulation induced detrusor-sphincter-dyssynergia and to achieve a physiological voiding. The literature was reviewed on different techniques of sacral anterior root stimulation of the bladder and the significance of posterior rhizotomy in patients with supraconal spinal cord injury suffering from the loss of voluntary bladder control, detrusor hyperreflexia and sphincter spasm. The achievement of selective detrusor activation would improve current sacral neurostimulation of the bladder, including the principle of "poststimulus voiding". This is possible with the application of selective neurostimulation in techniques of anodal block, high frequency block, depolarizing prepulses and cold block. Nowadays, sacral deafferentation is a standard therapy in combination with neurostimulation of the bladder because in conclusion advantages of complete rhizotomy predominate. The combination of sacral anterior root stimulation and sacral deafferentation is a successful procedure for restoration of bladder function in patients with supraconal spinal cord injury. Anodal block technique and cryotechnique are excellent methods for selective bladder activation to avoid detrusor-sphincter-dyssynergia and thus improve stimulation induced voiding.

Contribution of GABAA, Glycine, and Opioid Receptors to Sacral Neuromodulation of Bladder Overactivity in Cats.

PubMed

Jiang, Xuewen; Fuller, Thomas W; Bandari, Jathin; Bansal, Utsav; Zhang, Zhaocun; Shen, Bing; Wang, Jicheng; Roppolo, James R; de Groat, William C; Tai, Changfeng

2016-12-01

In α-chloralose-anesthetized cats, we examined the role of GABA A , glycine, and opioid receptors in sacral neuromodulation-induced inhibition of bladder overactivity elicited by intravesical infusion of 0.5% acetic acid (AA). AA irritation significantly (P < 0.01) reduced bladder capacity to 59.5 ± 4.8% of saline control. S1 or S2 dorsal root stimulation at threshold intensity for inducing reflex twitching of the anal sphincter or toe significantly (P < 0.01) increased bladder capacity to 105.3 ± 9.0% and 134.8 ± 8.9% of saline control, respectively. Picrotoxin, a GABA A receptor antagonist administered i.v., blocked S1 inhibition at 0.3 mg/kg and blocked S2 inhibition at 1.0 mg/kg. Picrotoxin (0.4 mg, i.t.) did not alter the inhibition induced during S1 or S2 stimulation, but unmasked a significant (P < 0.05) poststimulation inhibition that persisted after termination of stimulation. Naloxone, an opioid receptor antagonist (0.3 mg, i.t.), significantly (P < 0.05) reduced prestimulation bladder capacity and removed the poststimulation inhibition. Strychnine, a glycine receptor antagonist (0.03-0.3 mg/kg, i.v.), significantly (P < 0.05) increased prestimulation bladder capacity but did not reduce sacral S1 or S2 inhibition. After strychnine (0.3 mg/kg, i.v.), picrotoxin (0.3 mg/kg, i.v.) further (P < 0.05) increased prestimulation bladder capacity and completely blocked both S1 and S2 inhibition. These results indicate that supraspinal GABA A receptors play an important role in sacral neuromodulation of bladder overactivity, whereas glycine receptors only play a minor role to facilitate the GABA A inhibitory mechanism. The poststimulation inhibition unmasked by blocking spinal GABA A receptors was mediated by an opioid mechanism. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Safe Zone Quantification of the Third Sacral Segment in Normal and Dysmorphic Sacra.

PubMed

Hwang, John S; Reilly, Mark C; Shaath, Mohammad K; Changoor, Stuart; Eastman, Jonathan; Routt, Milton Lee Chip; Sirkin, Michael S; Adams, Mark R

2018-04-01

To quantify the osseous anatomy of the dysmorphic third sacral segment and assess its ability to accommodate internal fixation. Retrospective chart review of a trauma database. University Level 1 Trauma Center. Fifty-nine patients over the age of 18 with computed tomography scans of the pelvis separated into 2 groups: a group with normal pelvic anatomy and a group with sacral dysmorphism. The sacral osseous area was measured on computed tomography scans in the axial, coronal, and sagittal planes in normal and dysmorphic pelves. These measurements were used to determine the possibility of accommodating a transiliac transsacral screw in the third sacral segment. In the normal group, the S3 coronal transverse width averaged 7.71 mm and the S3 axial transverse width averaged 7.12 mm. The mean S3 cross-sectional area of the normal group was 55.8 mm. The dysmorphic group was found to have a mean S3 coronal transverse width of 9.49 mm, an average S3 axial transverse width of 9.14 mm, and an S3 cross-sectional area of 77.9 mm. The third sacral segment of dysmorphic sacra has a larger osseous pathway available to safely accommodate a transiliac transsacral screw when compared with normal sacra. The S3 segment of dysmorphic sacra can serve as an additional site for screw placement when treating unstable posterior pelvic ring fractures.

The superior gluteal artery perforator flap for reconstruction of sacral sores

PubMed Central

Chen, Weijian; Jiang, Bo; Zhao, Jiaju; Wang, Peiji

2016-01-01

This report describes our experiences using the superior gluteal artery perforator (SGAP) flaps for reconstruction of 2 sacral sore cases. A 47-year-old female patient and a 38-year-old man with sacral sores were treated in our unit. The size of the defects were approximately 5×6 cm2 and 8×9 cm2, the defects were repaired by SGAP flaps. The size of designed was SGAP flaps varied from 7×20 to 9×16 cm2. All flaps survived and healed primary, the texture, functions, and appearance of flaps were satisfactory, and also without region dysfunction of donor and recipient sites. The SGAP flap, which has reliable blood supply, preserves the gluteus maximus muscle and could be transferred simply and safely, is an ideal and reusable method to reconstruct sacral sores with low rate of postoperative recurrence and satisfactory appearance. PMID:27652367

Retention of urine and sacral paraesthesia in anogenital herpes simplex infection.

PubMed

Edis, R H

1981-01-01

Two definite and 2 probable cases of anogenital herpes simplex and sacral radiculitis are described. Symptoms were typical and consisted of paraesthesia and neuralgic pain in the perineum and legs, urinary retention and constipation occurring within several days to a week after an anogenital herpetic eruption. However, at presentation only 1 case had an obvious history of anogenital herpes simplex. Neurological signs were not striking and consisted of a reduced appreciation of light touch and pin prick over the sacral dermatomes and in 2 cases reduced anal sphincter tone. CSF examination in 3 patients showed a lymphocytosis. Bladder catheterisation was required for up to 2 weeks in 2 patients. The paraesthesia persisted for weeks to months. It should be more widely recognised that anogenital herpes simplex, with sacral radiculitis, is probably the commonest cause of acute retention of urine in young sexually active people.

Long-term efficacy and safety of sacral nerve stimulation for fecal incontinence.

PubMed

Mellgren, Anders; Wexner, Steven D; Coller, John A; Devroede, Ghislain; Lerew, Darin R; Madoff, Robert D; Hull, Tracy

2011-09-01

Sacral nerve stimulation is effective in the treatment of urinary incontinence and is currently under Food and Drug Administration review in the United States for fecal incontinence. Previous reports have focused primarily on short-term results of sacral nerve stimulation for fecal incontinence. The present study reports the long-term effectiveness and safety of sacral nerve stimulation for fecal incontinence in a large prospective multicenter study. Patients with fecal incontinent episodes more than twice per week were offered participation in this multicentered prospective trial. Patients showing ≥ 50% improvement during test stimulation were offered chronic implantation of the InterStim Therapy system (Medtronic; Minneapolis, MN). The aims of the current report were to provide 3-year follow-up data on patients from that study who underwent sacral nerve stimulation and were monitored under the rigors of an Food and Drug Administration-approved investigational protocol. One hundred thirty-three patients underwent test stimulation with a 90% success rate, of whom 120 (110 females) with a mean age of 60.5 years and a mean duration of fecal incontinence of 7 years received chronic implantation. Mean length of follow-up was 3.1 (range, 0.2-6.1) years, with 83 patients completing all or part of the 3-year follow-up assessment. At 3 years follow-up, 86% of patients (P < .0001) reported ≥ 50% reduction in the number of incontinent episodes per week compared with baseline and the number of incontinent episodes per week decreased from a mean of 9.4 at baseline to 1.7. Perfect continence was achieved in 40% of subjects. The therapy also improved the fecal incontinence severity index. Sacral nerve stimulation had a positive impact on the quality of life, as evidenced by significant improvements in all 4 scales of the Fecal Incontinence Quality of Life instrument at 12, 24, and 36 months of follow-up. The most common device- or therapy-related adverse events through the

A comparative, descriptive study of systemic factors and survival in elderly patients with sacral pressure ulcers.

PubMed

Jaul, Efraim; Menczel, Jacob

2015-03-01

Sacral pressure ulcers (PUs) are a serious complication in frail elderly patients. Thin tissue in the sacral area, low body mass index, and anatomical location contribute to the development of sacral PUs. A comparative, descriptive study was conducted to identify patient systemic factors associated with sacral PUs and to compare survival time in patients with and without PU. All consecutive patients with PUs (n = 77) and without sacral PUs (n = 53) admitted to the skilled nursing department of a geriatric hospital in Jerusalem, Israel between July 1, 2008 and December 31, 2011 were eligible to participate. Charts of previously admitted patients were abstracted and patients were prospectively followed until discharge, death, or the end of the study. Patient demographics, comorbidities, nutritional status, physical and cognitive function (measured using the Reisberg's Functional Assessment Staging Tool [FAST], Stages of Dementia of Alzheimer Scale, and the Glasgow Coma Scale), PU status, number of courses of antibiotic treatment during admission, length of hospitalization, and mortality were compared between patients admitted with and without a sacral PU using descriptive and univariate statistics. Logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals (CI) for sacral PU versus without PU by study covariate. The association between sacral PU and survival time was assessed using Kaplan-Meier models. Patients with a sacral PU were significantly older (average age 81.60 ±10.78 versus 77.06±11.19 years old, P = 0.02) and had a higher prevalence of dementia (70% versus 30%, P = 0.007), Parkinson's disease (92.3% versus 7.7%, P = 0.03), and anemia (67.7% versus 32.3%, P = 0.06) than patients admitted without a PU. Patients with a sacral PU also had a lower body mass index (23.1 versus 25.4, P = 0.04), and lower hemoglobin (10.54 versus 11.11, P = 0.03), albumin (26.2 versus 29.7, P = 0.002), and total protein levels (61.3 versus

Complications and troubleshooting of sacral neuromodulation therapy.

PubMed

Hijaz, Adonis; Vasavada, Sandip

2005-02-01

As evident from the authors' series, the complications of sacral neuromodulation have changed with the introduction of the tined lead and the placement of the generator over the back. In the earlier series, most complications were related to pain at the generator site, which was rare in the authors' series. The posterior location of the generator seems to be better tolerated than the anterior location, which could explain the rare need for revisions for pain at the generator site. Lead migration was observed in 8.4% of the original sacral neuromodulation study group series. This was seen rarely in the authors' series in either stage-one or stage-two revisions. As part of the routine work-up of patients who present with decreased function after a successful period response in stage two, the authors obtain a lateral radiograph of the sacrum; the authors have made the diagnosis of lead migration rarely (1/130; 0.6%). Spinelli and colleagues reported on the use of the tined lead in 15 patients, and observed no lead migration during either the screening period (average 38.8 days) or during follow-up of IPG implantation cases (average 11 months). The total infection rate in the whole series was 18/180 (10%), which was slightly higher than that reported by the sacral neuromodulation study group (6.1%). Revision rates for stage one and stage two were 12.2% and 20%, respectively. The revision rate in the original study group was 33.3%. Thus, with advancing technology, new problems may arise, but the implanting physician should be aware of the ways to evaluate and manage these complications and appropriately troubleshoot patients with suboptimal responses.

A novel three-dimensional printed guiding device for electrode implantation of sacral neuromodulation.

PubMed

Cui, Z; Wang, Z; Ye, G; Zhang, C; Wu, G; Lv, J

2018-01-01

The aim was to test the feasibility of a novel three-dimensional (3D) printed guiding device for electrode implantation of sacral neuromodulation (SNM). A 3D printed guiding device for electrode implantation was customized to patients' anatomy of the sacral region. Liquid photopolymer was selected as the printing material. The details of the device designation and prototype building are described. The guiding device was used in two patients who underwent SNM for intractable constipation. Details of the procedure and the outcomes are given. With the help of the device, the test needle for stimulation was placed in the target sacral foramen successfully at the first attempt of puncture in both patients. The time to implant a tined SNM electrode was less than 20 min and no complications were observed. At the end of the screening phase, symptoms of constipation were relieved by more than 50% in both patients and permanent stimulation was established. The customized 3D printed guiding device for implantation of SNM is a promising instrument that facilitates a precise and quick implantation of the electrode into the target sacral foramen. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

Sacral Stress Fracture Mimicking Lumbar Radiculopathy in a Mounted Police Officer: Case Report and Literature Review.

PubMed

Bednar, Drew A; Almansoori, Khaled

2015-10-01

Study Design Case report and review of the literature. Objective To present a unique case of L5 radiculopathy caused by a sacral stress fracture without neurologic compression. Methods We present our case and its clinical evolution and review the available literature on similar pathologies. Results Relief of the unusual mechanical loading causing sacral stress fracture led to rapid resolution of radiculopathy. Conclusion L5 radiculopathy can be caused by a sacral stress fracture and can be relieved by simple mechanical treatment of the fracture.

Congenital talipes equinovarus and congenital vertical talus secondary to sacral agenesis.

PubMed

Bray, Jonathan James Hyett; Crosswell, Sebastien; Brown, Rick

2017-05-05

Sacral agenesis is a rare congenital defect which is associated with foot deformities such as congenital talipes equinovarus (CTEV) and less commonly congenital vertical talus (CVT). We report a 3-year-old Caucasian girl who was born with right CTEV and left CVT secondary to sacral agenesis. Her right foot was managed with a Ponseti casting method at 2 weeks, followed by an Achilles tenotomy at 4 months. The left foot was initially managed with a nocturnal dorsi-flexion splint. Both feet remained resistant and received open foot surgery at 10 months producing plantigrade feet with neutral hindfeet. At 19 months, she failed to achieve developmental milestones and examinations revealed abnormal lower limb reflexes. A full body MRI was performed which identified the sacral agenesis. We advocate early MRI of the spine to screen for spinal defects when presented with resistant foot deformities, especially when bilateral. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Long-term results of sacral neuromodulation for women with urinary retention.

PubMed

Dasgupta, Ranan; Wiseman, Oliver J; Kitchen, Neil; Fowler, Clare J

2004-08-01

OBJECTIVE ; To review the long-term results of sacral nerve stimulation in the treatment of women with Fowler's syndrome, over a 6-year period at one tertiary referral centre. Between 1996 and 2002, 26 women with urinary retention were treated by implanting a sacral nerve stimulator. Their case records were reviewed for follow-up, complications and revision procedures, and the most recent uroflowmetry results. There were 20 patients (77%) still voiding spontaneously at the time of review (with two having deactivated their stimulator because of pregnancy). Fourteen patients (54%) required revision surgery, and the most common complications included loss of efficacy, implant-related discomfort and leg pain. The mean postvoid residual volume was 75 mL and mean maximum flow rate 20.8 mL/s. In young women with retention, for whom there is still no alternative to lifelong self-catheterization, sacral neuromodulation is effective for up to 5 years after implantation. However, there was a significant complication rate, in line with other reports, which may be improved by new technical developments.

[PELVIS/SACRAL syndrome with livedoid haemangioma and amniotic band].

PubMed

Bourrat, E; Lemarchand-Venencie, F; Jacquemont, M-L; El Ghoneimi, A; Wassef, M; Leger, J; Morel, P

2008-12-01

PELVIS or SACRAL syndrome denotes the association of local haemangioma and malformation in the pelvic region. In this paper, we report a case noteworthy on account of the initially livedoid appearance of the haemangioma as well as associated amniotic banding of an upper limb. A newborn male infant underwent left colostomy on the day of birth due to anal imperforation and anomalies of the external genital organs with sexual ambiguity. Examination of the skin and appendages revealed poorly delineated hypopigmentation in the sacrolumbar region and a fibrous groove around the right arm characteristic of amniotic band syndrome. Sacrolumbar and pelvic MRI scans revealed deviation towards the left of the last three sacral vertebrae with no medullary anomalies. Retrograde cystography showed a recto-uretral fistula. Progression of the infant's condition was marked by the appearance during the first month of a flat, violaceous, angiomatous, livedoid lesion in the middle of the buttocks and the perineum and a linear lesion on the rear aspect of the right lower limb. The skin biopsy of this lesion revealed a single capillary lobule at the dermal-hypodermal junction of non-specific appearance but with marked Glut1 expression by endothelial cells highly evocative of infantile haemangioma. Segmented haemangiomas are commonly associated with extracutaneous abnormalities. By analogy with PHACE syndrome, defined as association of segmented facial haemangioma with cerebral, ocular and cardio-aortic abnormalities, PELVIS/SACRAL syndrome denotes the association of segmented haemangioma of the loins (sacrolumbar region, buttocks or perineum=napkin haemangioma) with spinal dysraphia affecting the sacrolumbar spine, the terminal medullary cone, the genitourinary organs and the anal region to different degrees. Diagnosis of haemangioma associated with PELVIS/SACRAL syndrome may be delayed or complicated due to the macular, telangiectasic or livedoid appearance commonly seen. To our

Rectal ulcer in a patient with VZV sacral meningoradiculitis (Elsberg syndrome).

PubMed

Matsumoto, Hideyuki; Shimizu, Takahiro; Tokushige, Shin-ichi; Mizuno, Hideo; Igeta, Yukifusa; Hashida, Hideji

2012-01-01

This report describes the case of a 55-year-old woman with varicella-zoster virus (VZV) sacral meningoradiculitis (Elsberg syndrome) who presented with herpes zoster in the left S2 dermatome area, urinary retention, and constipation. Lumbar magnetic resonance imaging showed the left sacral nerve root swelling with enhancement. Thereafter, she suddenly showed massive hematochezia and hemorrhagic shock because of a rectal ulcer. To elucidate the relation between Elsberg syndrome and rectal ulcer, accumulation of similar cases is necessary. To avoid severe complications, attention must be devoted to the possibility of rectal bleeding in the early stage of Elsberg syndrome.

Pelvic X-ray misses out on detecting sacral fractures in the elderly - Importance of CT imaging in blunt pelvic trauma.

PubMed

Schicho, Andreas; Schmidt, Stefan A; Seeber, Kevin; Olivier, Alain; Richter, Peter H; Gebhard, Florian

2016-03-01

Patients aged 75 years and older with blunt pelvic trauma are frequently seen in the ER. The standard diagnostic tool in these patients is the plain a.p.-radiograph of the pelvis. Especially lesions of the posterior pelvic ring are often missed due to e.g. bowel gas projection and enteric overlay. With a retrospective study covering these patients over a 3 year period in our level I trauma centre, we were able to evaluate the rate of missed injuries in the a.p.-radiograph whenever a corresponding CT scan was performed. Age, gender, and accompanying fractures of the pelvic ring were recorded. The intrinsic test characteristics and the performance in the population were calculated according to standard formulas. Thus, 233 consecutive patients with blunt pelvic trauma with both conventional radiographic examination and computed tomography (CT) were included. Thereof, 56 (23%) showed a sacral fracture in the CT scan. Of 233 pelvic X-ray-images taken, 227 showed no sacral fracture. 51 (21.7%) of these were false negative, yielding a sensitivity of just 10.5%. Average age of patients with sacral fractures was 85.1±6.1 years, with 88% being female. Sacral fractures were often accompanied by lesions of the anterior pelvic ring with pubic bone fractures in 75% of sacrum fracture cases. Second most concomitant fractures are found at the acetabulum (23.3%). Plain radiographic imaging is especially likely to miss out fractures of the posterior pelvic ring, which nowadays can be of therapeutic consequence. Besides the physicians experience in the ED, profound knowledge of insensitivity of plain radiographs in finding posterior pelvic ring lesions is crucial for a reliable diagnostic routine. Since the high mortality caused by prolonged immobilisation due to pelvic ring injuries, all fractures should be identified. We therefore provide a diagnostic algorithm for blunt pelvic trauma in the elderly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Critical Anatomy Relative to the Sacral Suture: A Postoperative Imaging Study After Robotic Sacrocolpopexy.

PubMed

Crisp, Catrina C; Herfel, Charles V; Pauls, Rachel N; Westermann, Lauren B; Kleeman, Steven D

2016-01-01

This study aimed to characterize pertinent anatomy relative to the sacral suture placed at time of robotic sacrocolpopexy using postoperative computed tomography and magnetic resonance imaging. A vascular clip was placed at the base of the sacral suture at the time of robotic sacrocolpopexy. Six weeks postoperatively, subjects returned for a computed tomography scan and magnetic resonance imaging. Ten subjects completed the study. The middle sacral artery and vein coursed midline or to the left of midline in all the subjects. The left common iliac vein was an average of 26 mm from the sacral suture. To the right of the suture, the right common iliac artery was 18 mm away. Following the right common iliac artery to its bifurcation, the right internal iliac was on average 10 mm from the suture. The bifurcations of the inferior vena cava and the aorta were 33 mm and 54 mm further cephalad, respectively.The right ureter, on average, was 18 mm from the suture. The thickness of the anterior longitudinal ligament was 2 mm.The mean angle of descent of the sacrum was 70 degrees. Lastly, we found that 70% of the time, a vertebral body was directly below the suture; the disc was noted in 30%. We describe critical anatomy surrounding the sacral suture placed during robotic sacrocolpopexy. Proximity of both vascular and urologic structures within 10 to 18 mm, as well as anterior ligament thickness of only 2 mm highlights the importance of adequate exposure, careful dissection, and surgeon expertise.

Paraspinal Transposition Flap for Reconstruction of Sacral Soft Tissue Defects: A Series of 53 Cases from a Single Institute

PubMed Central

Chattopadhyay, Debarati; Agarwal, Akhilesh Kumar; Guha, Goutam; Bhattacharya, Nirjhar; Chumbale, Pawan K; Gupta, Souradip; Murmu, Marang Buru

2014-01-01

Study Design Case series. Purpose To describe paraspinal transposition flap for coverage of sacral soft tissue defects. Overview of Literature Soft tissue defects in the sacral region pose a major challenge to the reconstructive surgeon. Goals of sacral wound reconstruction are to provide a durable skin and soft tissue cover adequate for even large sacral defects; minimize recurrence; and minimize donor site morbidity. Various musculocutaneous and fasciocutanous flaps have been described in the literature. Methods The flap was applied in 53 patients with sacral soft tissue defects of diverse etiology. Defects ranged in size from small (6 cm×5 cm) to extensive (21 cm×10 cm). The median age of the patients was 58 years (range, 16-78 years). Results There was no flap necrosis. Primary closure of donor sites was possible in all the cases. The median follow up of the patients was 33 months (range, 4-84 months). The aesthetic outcomes were acceptable. There has been no recurrence of pressure sores. Conclusions The authors conclude that paraspinal transposition flap is suitable for reconstruction of large sacral soft tissue defects with minimum morbidity and excellent long term results. PMID:24967044

A large giant cell tumor of the sacrum. Advantage of an abdomino-sacral approach.

PubMed

Alla, Abubakr H; Mahadi, Seif I; Elhassan, Ahmed M; Ahmed, Mohamed E

2005-01-01

We report a case of giant cell tumor of the sacrum, presenting with sacral pain, swelling, and change of bowel habits. Rectal examination revealed a huge retrorectal mass fixed to the sacrum but not to the wall of the rectum. Abdominal ultrasonography, computed tomography CT scan, and magnetic resonance imaging MRI showed a huge pelvic mass invading the sacrum. Exploration via posterior sacral approach was not successful due to both, extensive bleeding and difficult accessibility. Re-exploration was carried out 2 days later with the patient in lithotomy position. Using abdomino-sacral approach the mass together with part of the sacrum and the whole coccyx were excised. Histopathology reported giant cell tumor of the sacrum with no evidence of mitosis. The patient was symptomless 12 months after surgery and on follow up.

Effect of surgical approach on physical activity and pain control after sacral colpopexy.

PubMed

Collins, Sarah A; Tulikangas, Paul K; O'Sullivan, David M

2012-05-01

We sought to compare recovery of activity and pain control after robotic (ROB) vs abdominal (ABD) sacral colpopexy. Women undergoing ROB and ABD sacral colpopexy wore accelerometers for 7 days preoperatively and the first 10 days postoperatively. They completed postoperative pain diaries and Short Form-36 questionnaires before and after surgery. At 5 days postoperatively, none of the 14 subjects in the ABD group and 4 of 28 (14.3%) in the ROB group achieved 50% total baseline activity counts (P = .283). At 10 days, 5 of 14 (35.7%) in the ABD group and 8 of 26 (30.8%) in the ROB group (P = .972) achieved 50%. Postoperative pain was similar in both groups. Short Form-36 vitality scores were lower (P = .017) after surgery in the ABD group, but not in the ROB group. Women undergoing ROB vs ABD sacral colpopexy do not recover physical activity faster, and pain control is not improved. Copyright © 2012 Mosby, Inc. All rights reserved.

Adhesive arachnoiditis after percutaneous fibrin glue treatment of a sacral meningeal cyst.

PubMed

Hayashi, Kazunori; Nagano, Junji; Hattori, Satoshi

2014-06-01

The authors present the case of a 64-year-old woman who was referred for severe sacral pain. She reported that her pain had been longstanding, and had greatly increased after percutaneous fibrin glue placement therapy for a sacral meningeal cyst 2 months earlier at a different hospital. An MRI scan obtained immediately after fibrin glue placement at that hospital suggested that fibrin glue had migrated superiorly into the subarachnoid space from the sacral cyst to the level of L-4. On admission to the authors' institution, physical examination demonstrated no abnormal findings except for perianal hypesthesia. An MRI study obtained at admission demonstrated a cystic lesion in the peridural space from the level of S-2 to S-4. Inhomogeneous intensity was identified in this region on T2-weighted images. Because the cauda equina and nerve roots appeared to be compressed by the lesion, total cyst excision was performed. The cyst cavity was filled with fluid that resembled CSF, plus gelatinous material. Histopathological examination revealed that the cyst wall was composed of hyaline connective tissue with some calcification. No nervous tissue or ganglion cells were found in the tissue. The gelatinous material was acellular, and appeared to be degenerated fibrin glue. Sacral pain persisted to some extent after surgery. The authors presumed that migrated fibrin glue caused the development of adhesive arachnoiditis. The risk of adhesive arachnoiditis should be considered when this therapy is planned. Communication between a cyst and the subarachnoid space should be confirmed to be sufficiently narrow to prevent the migration of injected fibrin glue.

Use of Sacral Nerve Stimulation for the Treatment of Overlapping Constipation and Fecal Incontinence

PubMed Central

Sreepati, Gouri; James-Stevenson, Toyia

2017-01-01

Patient: Female, 51 Final Diagnosis: Fecal incontinence Symptoms: Constipation • fecal incontinence Medication: — Clinical Procedure: Sacral nerve stimulator Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Fecal incontinence and constipation are common gastrointestinal complaints, but rarely occur concurrently. Management of these seemingly paradoxical processes is challenging, as treatment of one symptom may exacerbate the other. Case Report: A 51-year-old female with lifelong neurogenic bladder secondary to spina bifida occulta presented with progressive symptoms of daily urge fecal incontinence as well as hard bowel movements associated with straining and a sensation of incomplete evacuation requiring manual disimpaction. Pelvic floor testing showed poor ability to squeeze the anal sphincter, which indicated sphincter weakness as a major contributor to her fecal incontinence symptoms. Additionally, on defecography she was unable to widen her posterior anorectal angle or relax the anal sphincter during defecation consistent with dyssynergic defecation. A sacral nerve stimulator was placed for management of her fecal incontinence. Interestingly, her constipation also dramatically improved with sacral neuromodulation. Conclusions: This unique case highlights the emerging role of sacral nerve stimulation in the treatment of complex pelvic floor dysfunction with improvement in symptoms beyond fecal incontinence in a patient with dyssynergic-type constipation. PMID:28265107

Role of intraoperative radiotherapy in the treatment of sacral chordoma.

PubMed

Jullien-Petrelli, Ariel Christian; García-Sabrido, J L; Orue-Echebarria, M I; Lozano, P; Álvarez, A; Serrano, J; Calvo, F M; Calvo-Haro, J A; Lasso, J M; Asencio, J M

2018-04-01

Sacral chordoma is a rare entity with high local recurrence rates when complete resection is not achieved. To date, there are no series available in literature combining surgery and intraoperative radiotherapy (IORT). The objective of this study was to report the experience of our center in the management of sacral chordoma combining radical resection with both external radiotherapy and IORT. This is a retrospective case series. The patient sample included 15 patients with sacral chordoma resected in our center from 1998 to 2015. The outcome measures were overall survival (OS), disease-free survival (DFS), and rates of local and distant recurrences. We retrospectively reviewed the records of all the patients with sacral chordoma resected in our center from 1998 to December 2015. Overall survival, DFS, and rates of local and distant recurrences were calculated. Results between patients treated with or without IORT were compared. A total of 15 patients were identified: 8 men and 7 women. The median age was 59 years (range 28-77). Intraoperative radiotherapy was applied in nine patients and six were treated with surgical resection without IORT. In 13 patients, we performed the treatment of the primary tumor, and in two patients, we performed the treatment of recurrence disease. A posterior approach was used in four patients. Wide surgical margins (zero residue) were achieved in six patients, marginal margins (microscopic residue) were achieved in seven patients, and there were no patients with intralesional (R2) margins. At a median follow-up of 38 months (range 11-209 months), the 5-year OS in the IORT group was 100% versus 53% in the group of non-IORT (p=.05). The median DFS in the IORT group was 85 months, and that in the non-IORT group was 41 months. In the group without IORT, two patients died and nobody died during the follow-up in the group treated with IORT. High-sacrectomy treated patients had a median survival of 41 months, and low-sacrectomy treated

Acute urinary retention attributable to sacral herpes zoster.

PubMed

Acheson, J; Mudd, D

2004-11-01

Acute urinary retention in women is uncommon. A 63 year old woman presented with suprapubic pain, a palpable bladder, and multiple grouped vesicles on the right buttock. Catheterisation showed a residual of 2000 ml. A case is reported of acute urinary retention secondary to herpes zoster infection of the sacral nerves (S2-4).

Subarachnoid and basal cistern navigation through the sacral hiatus with guide wire assistance.

PubMed

Layer, Lauren; Riascos, Roy; Firouzbakht, Farhood; Amole, Adewumi; Von Ritschl, Rudiger; Dipatre, Pier; Cuellar, Hugo

2011-07-01

Intraspinal navigation with catheters and fiberscopes has shown feasible results for diagnosis and treatment of intraspinal and intracranial lesions. The most common approach, lumbar puncture, has allowed access to the spinal cord, however, coming with the difficulties of fiberscope damage and decreased torque for guidance. Our objective in this study is to allow an alternate access, the sacral hiatus, with guide wire assistance into the subarachnoid and intracranial structures, while easing the angle of entry and increasing torque. We advanced catheters with guide wire and fluoroscopy assistance into the sacral hiatus of three cadavers. After entry, the thecal sac was punctured and the catheter with guide wire was advanced rostrally until positioned in the basal cisterns of the brain. We confirmed catheter placement with contrast injection, autopsy, and dissection. In our study, the sacral hiatus was easily accessed, but resistance was found when attempting to puncture the thecal sac. The advancement of the catheter with guide wire assistance glided easily rostrally until some mild resistance was discovered at entry into the foramen magnum. With redirection, all catheters passed with ease into the basal cisterns. Positioning was confirmed with contrast injection with fluoroscopy evidence, autopsy, and dissection. There was no macroscopic or microscopic evidence of damage to the spinal roots, spinal cord, or cranial nerves. The sacral hiatus with guide wire assistance is an accessible conduit for uncomplicated entry into the subarachnoid and basal cistern space without damaging surrounding structures.

Critical dimensions of trans-sacral corridors assessed by 3D CT models: Relevance for implant positioning in fractures of the sacrum.

PubMed

Wagner, Daniel; Kamer, Lukas; Sawaguchi, Takeshi; Geoff Richards, R; Noser, Hansrudi; Uesugi, Masafumi; Ossendorf, Christian; Rommens, Pol M

2017-11-01

Trans-sacral implants can be used alternatively to sacro-iliac screws in the treatment of osteoporosis-associated fragility fractures of the pelvis and the sacrum. We investigated trans-sacral corridor dimensions, the number of individuals amenable to trans-sacral fixation, as well as the osseous boundaries and shape of the S1 corridor. 3D models were reconstructed from pelvic CT scans from 92 Europeans and 64 Japanese. A corridor of <12 mm was considered critical for trans-sacral implant positioning, and <8 mm as impossible. A statistical model of trans-sacral corridor S1 was computed. The limiting cranio-caudal diameter was 11.6 mm (±5.4) for S1 and 14 mm (±2.4) for S2. Trans-sacral implant positioning was critical in 52% of cases for S1, and in 21% for S2. The S1 corridor was impossible in 26%, with no impossible corridor in S2. Antero-superiorly, the S1 corridor was limited not only by the sacrum but in 40% by the iliac fossa. The statistical model demonstrated a consistent oval shape of the trans-section of corridor S1. Considering the variable in size and shape of trans-sacral corridors in S1, a thorough anatomical knowledge and preoperative planning are mandatory using trans-sacral implants. In critical cases, S2 is a veritable alternative. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2577-2584, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Prevalence of simple and complex sacral perineural Tarlov cysts in a French cohort of adults and children.

PubMed

Kuhn, Félix P; Hammoud, Sonia; Lefèvre-Colau, Marie-Martine; Poiraudeau, Serge; Feydy, Antoine

2017-02-01

To determine the prevalence of simple and complex sacral perineural Tarlov cysts (TCs) in a cohort of children and adults. Retrospective observational epidemiological study assessing 1100 consecutive sacral magnetic resonance (MR) studies, including 100 children and adolescents. All patients underwent 1.5T MR imaging with T1 and T2 weighted image acquisitions in sagittal and axial planes. All perineural cysts affecting the sacral nerve roots S1-S4 were quantitatively and qualitatively assessed. Two hundred and sixty-three sacral TCs were found in 132 adult patients (13.2%), with a female predominance (68%). None was found in children. The prevalence of TCs increased with age. The average number of cysts per patient was 2.0±1.2 with a maximum of 6 cysts in a single patient. Most of the cysts (87.5%) showed a homogenous central fluid collection and a parietal course of the nerve fibers. Complex patterns were present in 33 cysts (12.5%) within which 28 cysts showed endocystic crossing of nerve fibers and 5 cysts contained internal septations. Seventy cysts (26.6%) eroded the adjacent bone and 13 cysts (4.9%) extended to the pelvis. The prevalence of sacral TCs in our cohort corresponded to 13%, with a female predominance. Interestingly no TCs were found in children or adolescents (<18 years). In relation to the non-negligible percentage of complex cysts with internal septations, or endocystic crossing of nerve fibers, pre-interventional characterization of sacral TCs might help to choose an appropriate procedure in the treatment of rare symptomatic variants. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Sacral myeloradiculitis complicating genital herpes in a HIV-infected patient.

PubMed

Corral, I; Quereda, C; Navas, E; Pérez-Elias, M J; Jover, F; Moreno, S

2005-02-01

Myeloradiculitis is a rare neurological complication of herpes simplex type 2 (HSV-2) infection, frequently associated with a fatal outcome. Among patients with HIV infection, HSV-2 myeloradiculitis has occasionally been reported, always associated with advanced immunosuppression and AIDS. We report a patient with HIV infection but no history of previous opportunistic infections, who developed sacral myeloradiculitis immediately after an episode of genital herpes. Magnetic resonance imaging with gadolinium showed necrotizing myelitis in the conus medullaris and enhancement of sacral roots. CD4 lymphocyte count was 530/mm3. Other possible causes of myeloradiculitis in HIV-infected patients were appropriately excluded. Acyclovir therapy resulted in partial clinical improvement. This report shows that myeloradiculitis as a complication of genital herpes may occur in the early stages of HIV infection and may have a favourable outcome with antiviral treatment.

Can Navigation-assisted Surgery Help Achieve Negative Margins in Resection of Pelvic and Sacral Tumors?

PubMed

Abraham, John A; Kenneally, Barry; Amer, Kamil; Geller, David S

2018-03-01

at an average 27-month followup (range, 12-52 months). We queried a longitudinally maintained surgical database for any complications and noted which, if any, could have been directly related to the use of the navigation-assisted technique. In our series, 21 of 23 patients had a negative margin resection. In all patients the bone margin was negative, but two with sacral resections had positive soft tissue margins. Six of 23 patients experienced local recurrence within the study period. Three patients died during the study period. Seventeen patients demonstrated no evidence of disease at last recorded followup. We noted three intraoperative complications: one dural tear, one iliac vein laceration, and one bladder injury. Eight patients out of 23 had wound complications resulting in operative débridement. Two patients in the series developed transient postoperative femoral nerve palsy, which we believe were caused by stretch of the femoral nerve secondary to the placement of the reference array in the pubic ramus. Navigation-assisted resection of pelvic and sacral tumors resulted in a high likelihood of negative margin resection in this series, and we observed relatively few complications related specifically to the navigation. We have no comparison group without navigation, and future studies should indeed compare navigated with nonnavigated resection approaches in these anatomic locations. We did identify a potential navigation-related complication of femoral nerve palsy in this series and suggest careful placement and observation of the reference array during the operative procedure to lessen the likelihood of this previously unreported complication. We suggest it is worthwhile to consider the use of navigation-assisted surgery in resection of tumors of the pelvis and sacrum, but further study will be needed to determine its precise impact, if any, on local recurrence and other oncologic outcomes. Level IV, therapeutic study.

Giant anterior sacral meningocele presenting as bacterial meningitis in a previously healthy adult.

PubMed

Miletic, D; Poljak, I; Eskinja, N; Valkovic, P; Sestan, B; Troselj-Vukic, B

2008-02-01

Meningocele may be asymptomatic and incidentally discovered. Presenting as a retrorectal mass, sacral meningocele may produce urinary, rectal, and menstrual pain. Anterior sacral meningocele may be the cause of tethered cord syndrome. This article presents a case of a previously healthy 39-year-old man with large meningeal herniation that occupied the entire pelvis who developed symptoms of bacterial meningitis. A 39-year-old man was admitted with fever, chills, headache and photophobia. Escherichia coli was isolated from cerebrospinal fluid culture. Moderate improvement regarding meningeal symptoms was noted due to intravenous antibiotic therapy, but intense pain in the lower back associated with constipation, fecal and urinary incontinence, and saddle anesthesia developed. Abdominal ultrasound was negative. Plain radiographs and computed tomography demonstrated sacral bone defect and retrorectal expansive mass. MRI confirmed anterior sacral meningocele with cord tethering. After posterior laminectomy and dural opening, communication between meningocele and intrathecal compartment was obliterated. Computed tomography-guided percutaneous drainage through the ischiorectal fossa was performed to treat residual presacral cyst. Delayed diagnosis in our patient was related to misleading signs of bacterial meningitis without symptoms of intrapelvic expansion until the second week of illness. In our patient, surgical treatment was unavoidable due to resistive meningitis, acute back pain, and symptoms of space-occupying pelvic lesion. Neurosurgical approach was successful in treatment of meningitis and neurological disorders. Computed tomography-guided evacuation of the residual retrorectal cyst was less invasive than laparotomy, resulting in normalization of defecation and miction despite incomplete evacuation. Further follow-up studies may provide insight into the most effective treatment of such conditions.

Surface-functionalized nanoparticles for biosensing and imaging-guided therapeutics

NASA Astrophysics Data System (ADS)

Jiang, Shan; Win, Khin Yin; Liu, Shuhua; Teng, Choon Peng; Zheng, Yuangang; Han, Ming-Yong

2013-03-01

In this article, the very recent progress of various functional inorganic nanomaterials is reviewed including their unique properties, surface functionalization strategies, and applications in biosensing and imaging-guided therapeutics. The proper surface functionalization renders them with stability, biocompatibility and functionality in physiological environments, and further enables their targeted use in bioapplications after bioconjugation via selective and specific recognition. The surface-functionalized nanoprobes using the most actively studied nanoparticles (i.e., gold nanoparticles, quantum dots, upconversion nanoparticles, and magnetic nanoparticles) make them an excellent platform for a wide range of bioapplications. With more efforts in recent years, they have been widely developed as labeling probes to detect various biological species such as proteins, nucleic acids and ions, and extensively employed as imaging probes to guide therapeutics such as drug/gene delivery and photothermal/photodynamic therapy.

Prevalence of sacral dysmorphia in a prospective trauma population: Implications for a "safe" surgical corridor for sacro-iliac screw placement

PubMed Central

2011-01-01

Background Percutaneous sacro-iliac (SI) screw fixation represents a widely used technique in the management of unstable posterior pelvic ring injuries and sacral fractures. The misplacement of SI-screws under fluoroscopic guidance represents a critical complication for these patients. This study was designed to determine the prevalence of sacral dysmorphia and the radiographic anatomy of surgical S1 and S2 corridors in a representative trauma population. Methods Prospective observational cohort study on a consecutive series of 344 skeletally mature trauma patients of both genders enrolled between January 1, 2007, to September 30, 2007, at a single academic level 1 trauma center. Inclusion criteria included a pelvic CT scan as part of the initial diagnostic trauma work-up. The prevalence of sacral dysmorphia was determined by plain radiographic pelvic films and CT scan analysis. The anatomy of sacral corridors was analyzed on 3 mm reconstruction sections derived from multislice CT scan, in the axial, coronal, and sagittal plane. "Safe" potential surgical corridors at S1 and S2 were calculated based on these measurements. Results Radiographic evidence of sacral dysmorphia was detected in 49 patients (14.5%). The prevalence of sacral dysmorphia was not significantly different between male and female patients (12.2% vs. 19.2%; P = 0.069). In contrast, significant gender-related differences were detected with regard to radiographic analysis of surgical corridors for SI-screw placement, with female trauma patients (n = 99) having significantly narrower corridors at S1 and S2 in all evaluated planes (axial, coronal, sagittal), compared to male counterparts (n = 245; P < 0.01). In addition, the mean S2 body height was higher in dysmorphic compared to normal sacra, albeit without statistical significance (P = 0.06), implying S2 as a safe surgical corridor of choice in patients with sacral dysmorphia. Conclusions These findings emphasize a high prevalence of sacral

Prevalence of sacral dysmorphia in a prospective trauma population: Implications for a "safe" surgical corridor for sacro-iliac screw placement.

PubMed

Hasenboehler, Erik A; Stahel, Philip F; Williams, Allison; Smith, Wade R; Newman, Justin T; Symonds, David L; Morgan, Steven J

2011-05-10

Percutaneous sacro-iliac (SI) screw fixation represents a widely used technique in the management of unstable posterior pelvic ring injuries and sacral fractures. The misplacement of SI-screws under fluoroscopic guidance represents a critical complication for these patients. This study was designed to determine the prevalence of sacral dysmorphia and the radiographic anatomy of surgical S1 and S2 corridors in a representative trauma population. Prospective observational cohort study on a consecutive series of 344 skeletally mature trauma patients of both genders enrolled between January 1, 2007, to September 30, 2007, at a single academic level 1 trauma center. Inclusion criteria included a pelvic CT scan as part of the initial diagnostic trauma work-up. The prevalence of sacral dysmorphia was determined by plain radiographic pelvic films and CT scan analysis. The anatomy of sacral corridors was analyzed on 3 mm reconstruction sections derived from multislice CT scan, in the axial, coronal, and sagittal plane. "Safe" potential surgical corridors at S1 and S2 were calculated based on these measurements. Radiographic evidence of sacral dysmorphia was detected in 49 patients (14.5%). The prevalence of sacral dysmorphia was not significantly different between male and female patients (12.2% vs. 19.2%; P = 0.069). In contrast, significant gender-related differences were detected with regard to radiographic analysis of surgical corridors for SI-screw placement, with female trauma patients (n = 99) having significantly narrower corridors at S1 and S2 in all evaluated planes (axial, coronal, sagittal), compared to male counterparts (n = 245; P < 0.01). In addition, the mean S2 body height was higher in dysmorphic compared to normal sacra, albeit without statistical significance (P = 0.06), implying S2 as a safe surgical corridor of choice in patients with sacral dysmorphia. These findings emphasize a high prevalence of sacral dysmorphia in a representative trauma

Evaluation of the diagnostic accuracy of four-view radiography and conventional computed tomography analysing sacral and pelvic fractures in dogs.

PubMed

Stieger-Vanegas, S M; Senthirajah, S K J; Nemanic, S; Baltzer, W; Warnock, J; Bobe, G

2015-01-01

The purpose of our study was (1) to determine whether four-view radiography of the pelvis is as reliable and accurate as computed tomography (CT) in diagnosing sacral and pelvic fractures, in addition to coxofemoral and sacroiliac joint subluxation or luxation, and (2) to evaluate the effect of the amount of training in reading diagnostic imaging studies on the accuracy of diagnosing sacral and pelvic fractures in dogs. Sacral and pelvic fractures were created in 11 canine cadavers using a lateral impactor. In all cadavers, frog-legged ventro-dorsal, lateral, right and left ventro-45°-medial to dorsolateral oblique frog leg ("rollover 45-degree view") radiographs and a CT of the pelvis were obtained. Two radiologists, two surgeons and two veterinary students classified fractures using a confidence scale and noted the duration of evaluation for each imaging modality and case. The imaging results were compared to gross dissection. All evaluators required significantly more time to analyse CT images compared to radiographic images. Sacral and pelvic fractures, specifically those of the sacral body, ischiatic table, and the pubic bone, were more accurately diagnosed using CT compared to radiography. Fractures of the acetabulum and iliac body were diagnosed with similar accuracy (at least 86%) using either modality. Computed tomography is a better method for detecting canine sacral and some pelvic fractures compared to radiography. Computed tomography provided an accuracy of close to 100% in persons trained in evaluating CT images.

The sacral autonomic outflow is parasympathetic: Langley got it right.

PubMed

Horn, John P

2018-04-01

A recent developmental study of gene expression by Espinosa-Medina, Brunet and colleagues sparked controversy by asserting a revised nomenclature for divisions of the autonomic motor system. Should we re-classify the sacral autonomic outflow as sympathetic, as now suggested, or does it rightly belong to the parasympathetic system, as defined by Langley nearly 100 years ago? Arguments for rejecting Espinosa-Medina, Brunet et al.'s scheme subsequently appeared in e-letters and brief reviews. A more recent commentary in this journal by Brunet and colleagues responded to these criticisms by labeling Langley's scheme as a historical myth perpetuated by ignorance. In reaction to this heated exchange, I now examine both sides to the controversy, together with purported errors by the pioneers in the field. I then explain, once more, why the sacral outflow should remain known as parasympathetic, and outline suggestions for future experimentation to advance the understanding of cellular identity in the autonomic motor system.

Magnetic resonance imaging of the sacral plexus and piriformis muscles.

PubMed

Russell, J Matthew; Kransdorf, Mark J; Bancroft, Laura W; Peterson, Jeffrey J; Berquist, Thomas H; Bridges, Mellena D

2008-08-01

The objective was to evaluate the piriformis muscles and their relationship to the sacral nerve roots on T1-weighted MRI in patients with no history or clinical suspicion of piriformis syndrome. Axial oblique and sagittal T1-weighted images of the sacrum were obtained in 100 sequential patients (200 pairs of sacral roots) undergoing routine MRI examinations. The relationship of the sacral nerve roots to the piriformis muscles and piriformis muscle size were evaluated, as were clinical symptoms via a questionnaire. The S1 nerve roots were located above the piriformis muscle in 99.5% of cases (n=199). The S2 nerve roots were located above the piriformis muscle in 25% of cases (n=50), and traversed the muscle in 75% (n=150). The S3 nerve roots were located above the piriformis muscle in 0.5% of cases (n=1), below the muscle in 2.5% (n=5), and traversed the muscle in 97% (n=194). The S4 nerve roots were located below the muscle in 95% (n=190). The piriformis muscles ranged in size from 0.8-3.2 cm, with an average size of 1.9 cm. Nineteen percent of patients had greater than 3 mm of asymmetry in the size of the piriformis muscle, with a maximum asymmetry of 8 mm noted. The S1 nerve roots course above the piriformis muscle in more than 99% of patients. The S2 roots traverse the piriformis muscle in 75% of patients. The S3 nerve roots traverse the piriformis muscle in 97% of patients. Piriformis muscle size asymmetry is common, with muscle asymmetry of up to 8 mm identified.

Management of Sacral Tumors Requiring Spino-Pelvic Reconstruction with Different Histopathologic Diagnosis: Evaluation with Four Cases

PubMed Central

Togral, Guray; Hasturk, Askin Esen; Kekec, Fevzi; Parpucu, Murat; Gungor, Safak

2015-01-01

In this retrospective study, surgical results of four patients with sacral tumors having disparate pathologic diagnoses, who were treated with partial or total sacrectomy and lumbopelvic stabilization were abstracted. Two patients were treated with partial sacral resection and two patients were treated with total sacrectomy and spinopelvic fixation. Fixation methods included spinopelvic fixation with rods and screws in two cases, reconstruction plate in one case, and fresh frozen allografts in two cases. Fibular allografts used for reconstruction accelerated bony union and enhanced the stability in two cases. Addition of polymethyl methacrylate in the cavity in the case of a giant cell tumor had a positive stabilizing effect on fixation. As a result, we can conclude that mechanical instability after sacral resection can be stabilized securely with lumbopelvic fixation and polymethyl methacrylate application or addition of fresh frozen allografts between the rods can augment the stability of the reconstruction. PMID:26713133

Management of Sacral Tumors Requiring Spino-Pelvic Reconstruction with Different Histopathologic Diagnosis: Evaluation with Four Cases.

PubMed

Arıkan, Murat; Togral, Guray; Hasturk, Askin Esen; Kekec, Fevzi; Parpucu, Murat; Gungor, Safak

2015-12-01

In this retrospective study, surgical results of four patients with sacral tumors having disparate pathologic diagnoses, who were treated with partial or total sacrectomy and lumbopelvic stabilization were abstracted. Two patients were treated with partial sacral resection and two patients were treated with total sacrectomy and spinopelvic fixation. Fixation methods included spinopelvic fixation with rods and screws in two cases, reconstruction plate in one case, and fresh frozen allografts in two cases. Fibular allografts used for reconstruction accelerated bony union and enhanced the stability in two cases. Addition of polymethyl methacrylate in the cavity in the case of a giant cell tumor had a positive stabilizing effect on fixation. As a result, we can conclude that mechanical instability after sacral resection can be stabilized securely with lumbopelvic fixation and polymethyl methacrylate application or addition of fresh frozen allografts between the rods can augment the stability of the reconstruction.

Evaluation of the rostral projection of the sacral lamina as a component of degenerative lumbosacral stenosis in German shepherd dogs.

PubMed

Saunders, Harvey; Worth, Andrew J; Bridges, Janis P; Hartman, Angela

2018-05-20

To determine the association between a greater rostral projection of the sacral lamina and clinical signs of cauda equina syndrome (CES) in German shepherd dogs (GSD) with presumptive degenerative lumbosacral disease (DLSS). Retrospective cohort study. One hundred forty-three GSD (125 police dogs and 18 pet dogs) presenting for either CES or prebreeding evaluation. Fifty-five were classified as affected by CES and diagnosed with DLSS, and 88 were classified as unaffected on the basis of clinical and imaging findings. The position of the rostral edge of the sacral lamina was measured from radiographs and/or computed tomography (CT) scans. This position was compared between affected and unaffected dogs. In dogs that underwent both radiography and CT scanning, the agreement between sacral lamina localization using each imaging modality was determined. Owners/handlers were contacted to determine whether dogs subsequently developed clinical signs compatible with CES at a mean of 29 months (unaffected). The sacral lamina did not extend as far rostrally in affected dogs, compared to unaffected dogs (P = .04). Among the 88 dogs unaffected by CES at initial evaluation, 2 developed clinical signs consistent with CES at follow-up. Rostral projection of the sacral lamina, previously proposed as a potential risk factor in dogs with CES due to lumbosacral degeneration, was not associated with a diagnosis of DLSS in this study; the opposite was true. Rostral projection of the sacral lamina may not be a predisposing factor in the development of CES due to DLSS in GSD. © 2018 The American College of Veterinary Surgeons.

Sacral nerve root neuromodulation: an effective treatment for refractory urge incontinence.

PubMed

Shaker, H S; Hassouna, M

1998-05-01

Sacral foramina implants have been recognized recently as a method for treatment of refractory urinary urge incontinence. We study the outcome of the procedure with in-depth analysis of the results of 18 implanted cases. Patients with urinary urge incontinence were subjected to percutaneous nerve evaluation of the S3 roots as a temporary screening test to determine response to neuromodulation. Satisfactory responders were implanted with permanent sacral root neuroprosthesis. The study design included comprehensive voiding diaries for 4 consecutive days twice as a baseline, 1 with percutaneous nerve evaluation screening, 1 after the percutaneous nerve evaluation, 1 at the 1, 3 and 6 post-implantation visits, and every 6 months thereafter. Uroflowmetry and quality of life questionnaires were performed at the same intervals. Urodynamic study was done as a baseline and 6 months after implantation of the neuroprosthesis. All 18 patients (16 women and 2 men) with refractory urge incontinence received a sacral foramina neuroprosthesis after demonstrating a good response to the percutaneous nerve evaluation. Average patient age at presentation was 42.3+/-3.3 years (range 22 to 67) and duration of urinary symptoms was 6.6+/-1.3 years (range 1.2 to 18.8). Average followup was 18.8 months (range 3 to 83). Neuromodulation in these patients showed a marked reduction in leakage episodes from 6.49 to 1.98 times per 24 hours and in the leakage severity score. Eight patients became completely dry and 4 had average leakage episodes of 1 or less daily. Patients showed as well a decrease in urinary frequency with an increase in functional bladder capacity. Associated pelvic pain improved substantially. Cystometrograms demonstrated increased volume at first sensation by 50% and increased cystometric capacity by 15% with the disappearance of uninhibited contractions in 1 of the 4 patients who presented with it preoperatively. There was also noticeable improvement in the quality of life

The effect of multiple layers of linens on surface interface pressure: results of a laboratory study.

PubMed

Williamson, Rachel; Lachenbruch, Charlie; Vangilder, Catherine

2013-06-01

% to 64% depending on the linen combination. At 30°, the foam surface showed increases 6% to 29% (P <0.0001) compared with a FS baseline. If linens were wet, peak interface sacral pressures were equivalent to or less than pressures measured on the same pads when measured dry. The presence of linens on both surface types adversely affected the pressure redistribution capabilities of the surfaces; added layers increased pressure proportionally. The effect on interface pressure from the linen layers was more pronounced on the LAL than the foam surface. The study results illustrate that significant increases in peak interface pressure occur in a laboratory setting when linen layers are added to pressure redistribution surfaces. Results also indicated wetting incontinence pads on a support surface did not significantly increase interface pressure. Although additional preclinical and clinical studies are needed to guide practice, excessive linen usage for patients on therapeutic support surfaces should be discouraged.

Rare location of spondylitis tuberculosis;atlanto-axial, sacral and cervico-thoracic junction

NASA Astrophysics Data System (ADS)

Victorio; Nasution, M. D.; Ibrahim, S.; Dharmajaya, R.

2018-03-01

Three cases of rare location spondylitis tuberculosis are reported, each in atlantoaxial, cervico-thoracic junction,and sacral. The complaints were aweakness of motoric strength and local back pain. Patients’thoracal x-ray was normal, there was no complaint of acough, PCR forTB was early diagnostic and positive in all three cases, HIV negative, intraoperative tissue samplings were sent for histopathology examination and the results showed thespecific inflammatory process. Lesions were evaluated with computer tomography and/or MRI imaging.Preoperative TB regimens therapy were given for 2 weeks and continued for nine months. The surgical procedurewas done in all cases with excellent improvement of symptoms and motoric strength. In our institution,25 cases of total TB spondylitis were performed in 2 years, only 1 case eachwas found in atlanto-axial, cervico-thoracic and sacral.

Diffuse large cell lymphoma presenting as a sacral mass and lupus anticoagulant.

PubMed

Ediriwickrema, Lilangi S; Zaheer, Wajih

2011-12-01

A 67-year-old gentleman presented to Yale-New Haven Hospital (YNHH) for assessment of a supratherapeutic INR and sacral lesion. Hematologic workup revealed elevated ESR, PT, INR, PTT, and CRP, mixing studies that failed to correct, and a positive Russell Viper Venom Test (RVVT), which confirmed the presence of lupus anticoagulant (LA), a subtype of antiphospholipid syndrome (APA). Pathology of the patient's sacral lesion revealed diffuse large B-cell lymphoma. This case provides insight into the association between APA and lymphoid neoplasm. The patient's unique presentation is in marked contrast to other reports of APA and lymphoid malignancy, which are typically associated with elevated PTT, normal PT, minimal extranodal disease, and potential thrombotic complications. Further, treatment with Rituximab-CHOP chemotherapy led to excellent clinical response with tumor remission and normalization of PT and PTT.

The effect of low force chiropractic adjustments on body surface electromagnetic field.

PubMed

Zhang, John; Snyder, Brian J; Vernor, Lori

2004-03-01

The purpose of this study was to investigate the body surface electromagnetic field (EMF) changes using a sensitive magnetometer before and after a specific Toftness chiropractic adjustment in asymptomatic human subjects. Forty-four subjects were randomly assigned into control (20 subjects) and experimental groups (24 subjects) in a pre and post-test design. The Triaxial Fluxgate Magnetometer FGM-5DTAA (Walker Scientific, Worcester, Massachusetts) with five digit display and resolution of 1 nanotesla (nT) was used for EMF detection. The EMF in the research room and on the adjustment table was monitored and recorded. The subjects' body surface (cervical, thoracic, lumbar and sacral areas) EMF was determined in the prone position before and after the chiropractic adjustment. A low force Toftness chiropractic adjustment was applied to the cervical, thoracic, lumbar and sacral areas as determined by the practitioner. The EMF in the research room was recorded as 41611 nT at the Z axis (earth field), 13761 nT at the X axis and 7438 nT at the Y axis. The EMF on the adjusting table changed minimally during the 15 minute observation period. The EMF on the subjects' body surface decreased at 4 spinal locations after chiropractic adjustment. The EMF (mean +/- SD in nT) decreased significantly at the cervical region from 42449 +/- 907 to 41643 +/- 1165 (p < 0.01) and at the sacral regions from 43206 +/- 760 to 42713 +/- 552 (p < 0.01). The EMF at the lumbar and thoracic regions decreased but did not reach a statistically significant level. No significant changes of the body surface EMF were found in the control group. A low force Toftness chiropractic adjustment in the cervical and sacral areas resulted in a significant reduction of the cervical and sacral surface EMF. No significant body surface EMF changes were observed in the lumbar and thoracic regions. The mechanisms of the EMF reduction after chiropractic adjustment are not known.

The effect of low force chiropractic adjustments on body surface electromagnetic field

PubMed Central

Zhang, John; Snyder, Brian J; Vernor, Lori

2004-01-01

Objective The purpose of this study was to investigate the body surface electromagnetic field (EMF) changes using a sensitive magnetometer before and after a specific Toftness chiropractic adjustment in asymptomatic human subjects. Method Forty-four subjects were randomly assigned into control (20 subjects) and experimental groups (24 subjects) in a pre and post-test design. The Triaxial Fluxgate Magnetometer FGM-5DTAA (Walker Scientific, Worcester, Massachusetts) with five digit display and resolution of 1 nanotesla (nT) was used for EMF detection. The EMF in the research room and on the adjustment table was monitored and recorded. The subjects’ body surface (cervical, thoracic, lumbar and sacral areas) EMF was determined in the prone position before and after the chiropractic adjustment. A low force Toftness chiropractic adjustment was applied to the cervical, thoracic, lumbar and sacral areas as determined by the practitioner. Results The EMF in the research room was recorded as 41611 nT at the Z axis (earth field), 13761 nT at the X axis and 7438 nT at the Y axis. The EMF on the adjusting table changed minimally during the 15 minute observation period. The EMF on the subjects’ body surface decreased at 4 spinal locations after chiropractic adjustment. The EMF (mean ± SD in nT) decreased significantly at the cervical region from 42449 ± 907 to 41643 ± 1165 (p < 0.01) and at the sacral regions from 43206 ± 760 to 42713 ± 552 (p < 0.01). The EMF at the lumbar and thoracic regions decreased but did not reach a statistically significant level. No significant changes of the body surface EMF were found in the control group. Conclusion A low force Toftness chiropractic adjustment in the cervical and sacral areas resulted in a significant reduction of the cervical and sacral surface EMF. No significant body surface EMF changes were observed in the lumbar and thoracic regions. The mechanisms of the EMF reduction after chiropractic adjustment are not known. PMID

Feasibility of Using Ultrasonography to Establish Relationships Among Sacral Base Position, Sacral Sulcus Depth, Body Mass Index, and Sex.

PubMed

Lockwood, Michael D; Kondrashova, Tatyana; Johnson, Jane C

2015-11-01

Identifying relationships among anatomical structures is key in diagnosing somatic dysfunction. Ultrasonography can be used to visualize anatomical structures, identify sacroiliac landmarks, and validate anatomical findings and measurements in relation to somatic dysfunction. As part of the osteopathic manipulative medicine course at A.T. Still University-Kirksville College of Osteopathic Medicine, first-year students are trained to use ultrasonography to establish relationships among musculoskeletal structures. To determine the ability of first-year osteopathic medical students to establish sacral base position (SBP) and sacral sulcus depth (SSD) using ultrasonography and to identify the relationship of SBP and SSD to body mass index (BMI) and sex. Students used ultrasonography to obtain the distance between the skin and the sacral base (the SBP) and the distance between the skin and the tip of the posterior superior iliac spine bilaterally. Next, students calculated the SSD (the distance between the tip of the posterior superior iliac spine and the SBP). Data were analyzed with respect to side of the body, BMI, sex, and age. The BMI data were subdivided into normal (18-25 mg/kg) and overweight (25-30 mg/kg) groups. Ultrasound images of 211 students were included in the study. The SBP was not significantly different between the left and right sides (36.5 mm vs 36.5 mm; P=.95) but was significantly different between normal and overweight BMI categories (33.0 mm vs 40.0 mm; P<.001) and between men and women (34.1 mm vs 39.0 mm; P<.001). The SSD was not significantly different between left and right sides (18.9 mm vs 19.8 mm; P=.08), normal and overweight BMI categories (18.9 mm vs 19.7 mm, P=.21), or men and women (19.7 mm vs 19.0 mm; P=.24). No significant relationship was identified between age and SBP (P=.46) or SSD (P=.39); however, the age range was narrow (21-33 years). The study yielded repeatable and reproducible results when establishing SBP and SSD using

Neoadjuvant denosumab for the treatment of a sacral osteoblastoma.

PubMed

Reynolds, Jeremy J; Rothenfluh, Dominique A; Athanasou, Nick; Wilson, Shaun; Kieser, David C

2018-01-22

To present a case of aggressive sacral osteoblastoma (OB) treated with neoadjuvant denosumab therapy and en bloc resection. Case report of a 14-year-old male with an aggressive OB affecting the superior articular process of the left first sacral segment. The lesion was lytic and metabolically active and involved the left-sided posterior elements of S1-S3 with extension into the spinal canal, affecting the left S1, S2, S3, S4 and S5 nerve roots. He was treated for 1 month with neoadjuvant denosumab followed by en bloc resection. Denosumab therapy caused regression of the tumour and converted the diffuse infiltrative mass into a well-defined solid (osteoma-like) structure, aiding surgical resection and preserving the S1, S4 and S5 nerve roots. Histologically, the treated lesion showed abundant sclerotic woven bone and osteoblasts with absence of osteoclasts. A short course of denosumab caused tumour regression, ossification and conversion of an aggressive OB into a sclerotic, well-defined lesion thus aiding surgical resection and preservation of neural structures. Neoadjuvant therapy reduced osteoclast numbers but PET showed that the lesion remained FDG avid post-therapy.

[Primary genital herpes with sacral meningoradiculitis].

PubMed

Carron, P-N; Anguenot, J-L; Dubuisson, J-B

2004-02-01

Herpetic genital infection is a common sexually transmitted disease, caused in most cases by type 2 Herpes simplex virus (HSV2). This virus is characterized by its neurotropic properties and its ability to establish latency in sacral sensory ganglions. Some cases of genital primo-infection are complicated by viral replication dissemination to neigbhoring nerve structures like meninges and radicular terminations. In such cases muco-cutaneous manifestations are associated with peripheral neurological impairment in the form of meningo-radiculitis. Physicians should be familiar with these neurological symptoms knowing that they always regress completely. The present report illustrates these complications and reviews the potential neurological implications described in the literature.

F-18 FDG PET/CT findings of a case of sacral nerve root neurolymphomatosis that occurred during chemotherapy.

PubMed

Suga, Kazuyoshi; Yasuhiko, Kawakami; Matsunaga, Naofumi; Yujiri, Toshiaki; Nakazora, Tatsuki; Ariyoshi, Kouichi

2011-01-01

Neurolymphomatosis (NL) is a rare, unique subtype of lymphomatous infiltration of peripheral nerves. Clinical/radiologic diagnosis of NL is challenging. We report F-18 FDG PET/CT findings of a case of breast diffuse large B-cell lymphoma, in which NL developed regardless of regression of systemic lesions during induction chemotherapy. FDG PET/CT showed characteristic findings of well-demarcated, linear abnormal FDG uptake along a sacral vertebral foramen, leading to diagnosis of NL, with the finding of thickened nerve roots on magnetic resonance imaging. Altered chemotherapeutic regimen resulted in disappearance of these abnormal FDG uptake, with recovery of neurologic symptoms. Peripheral nerve NL may occur during chemotherapy, and FDG PET/CT can be a useful imaging modality in diagnosis and monitoring of therapeutic response of this disease.

Preparation, Surface Properties, and Therapeutic Applications of Gold Nanoparticles in Biomedicine.

PubMed

Panahi, Yunes; Mohammadhosseini, Majid; Nejati-Koshki, Kazem; Abadi, Azam Jafari Najaf; Moafi, Hadi Fallah; Akbarzadeh, Abolfazl; Farshbaf, Masoud

2017-02-01

Gold nanoparticles (AuNPs) due to their unique properties and manifold surface functionalities have been applied in bio-nanotechnology. The application of GNPs in recent medical and biological research is very extensive. Especially it involves applications such as detection and photothermalysis of microorganisms and cancer stem cells, biosensors; optical bio-imaging and observing of cells and these nanostructures also serve as practical platforms for therapeutic agents. In this review we studied all therapeutic applications of gold nanoparticles in biomedicine, synthesis methods, and surface properties. © Georg Thieme Verlag KG Stuttgart · New York.

SU-E-J-125: A Novel IMRT Planning Technique to Spare Sacral Bone Marrow in Pelvic Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGuire, S; Bhatia, S; Sun, W

Purpose: Develop an IMRT planning technique that can preferentially spare sacral bone marrow for pelvic cancer patients. Methods: Six pelvic cancer patients (two each with anal, cervical, and rectal cancer) were enrolled in an IRB approved protocol to obtain FLT PET images at simulation, during, and post chemoradiation therapy. Initially, conventional IMRT plans were created to maintain target coverage and reduce dose to OARs such as bladder, bowel, rectum, and femoral heads. Simulation FLT PET images were used to create IMRT plans to spare bone marrow identified as regions with SUV of 2 or greater (IMRT-BMS) within the pelvic bonesmore » from top of L3 to 5mm below the greater trochanter without compromising PTV coverage or OAR sparing when compared to the initial IMRT plan. IMRT-BMS plans used 8–10 beam angles that surrounded the subject. These plans were used for treatment. Retrospectively, the same simulation FLT PET images were used to create IMRT plans that spared bone marrow located in the sacral pelvic bone region (IMRT-FAN) also without compromising PTV coverage or OAR sparing. IMRT-FAN plans used 16 beam angles every 12° anteriorly from 90° – 270°. Optimization objectives for the sacral bone marrow avoidance region were weighted to reduce ≥V10. Results: IMRT-FAN reduced dose to the sacral bone marrow for all six subjects. The average V5, V10, V20, and V30 differences from the IMRT-BMS plan were −2.2 ± 1.7%, −11.4 ± 3.6%, −17.6 ± 5.1%, and −19.1 ± 8.1% respectively. Average PTV coverage change was 0.5% ± 0.8% from the conventional IMRT plan. Conclusion: An IMRT planning technique that uses beams from the anterior and lateral directions reduced the volume of sacral bone marrow that receives ≤10Gy while maintaining PTV coverage and OAR sparing. Additionally, the volume of sacral bone marrow that received 20 or 30 Gy was also reduced.« less

Application of posterior pelvic tilt taping for the treatment of chronic low back pain with sacroiliac joint dysfunction and increased sacral horizontal angle.

PubMed

Lee, Jung-hoon; Yoo, Won-gyu

2012-11-01

Kinesio Taping (KT) is a therapeutic method used by physical therapists and athletic trainers in combination with other treatment techniques for various musculoskeletal and neuromuscular problems. However, no research has evaluated the effect of KT in patients with low back pain (LBP). The purpose of this case was to describe the application of posterior pelvic tilt taping (PPTT) with Kinesio tape as a treatment for chronic LBP and to reduce the anterior pelvic tilt angle. Case report. The patien was a 20-year-old female amateur swimmer with a Cobb's angle (L1-S1) of 68°, a sacral horizontal angle of 45°, and pain in both medial buttock areas and sacroiliac joints. We performed PPTT with Kinesio tape for 2 weeks (six times per week for an average of 9 h each time). The patient’s radiographs showed that the Cobb's angle (L1-S1) had decreased from 68° to 47° and that the sacral horizontal angle had decreased from 45° to 31°. Reductions in hypomobility or motion asymmetry, as assessed by the motion palpation test, and in pain, as measured by the pain-provocation tests, were observed. On palpation for both medial buttock areas in the prone position, the patient felt no pain. The patient experienced no pain or stiffness in the low back area while performing forward flexion in the standing position with knees fully extended when washing dishes in the sink. The case study demonstrated that PPTT intervention favourably affected the pelvic inclination and sacral horizontal angle, leading to beneficial effects on sacroiliac joint dysfunction (SIJD) and medial buttock pain. Additional research on the clinical effects of this taping procedure requires greater numbers of athletes with SIJD or LBP who have inappropriate anterior pelvic tilt angles and hyperlordosis.

Diffuse Large Cell Lymphoma Presenting as a Sacral Mass and Lupus Anticoagulant

PubMed Central

Ediriwickrema, Lilangi S.; Zaheer, Wajih

2011-01-01

A 67-year-old gentleman presented to Yale-New Haven Hospital (YNHH) for assessment of a supratherapeutic INR and sacral lesion. Hematologic workup revealed elevated ESR, PT, INR, PTT, and CRP, mixing studies that failed to correct, and a positive Russell Viper Venom Test (RVVT), which confirmed the presence of lupus anticoagulant (LA), a subtype of antiphospholipid syndrome (APA). Pathology of the patient’s sacral lesion revealed diffuse large B-cell lymphoma. This case provides insight into the association between APA and lymphoid neoplasm. The patient’s unique presentation is in marked contrast to other reports of APA and lymphoid malignancy, which are typically associated with elevated PTT, normal PT, minimal extranodal disease, and potential thrombotic complications. Further, treatment with Rituximab-CHOP chemotherapy led to excellent clinical response with tumor remission and normalization of PT and PTT. PMID:22180680

Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment.

PubMed

Seri, M; Martucciello, G; Paleari, L; Bolino, A; Priolo, M; Salemi, G; Forabosco, P; Caroli, F; Cusano, R; Tocco, T; Lerone, M; Cama, A; Torre, M; Guys, J M; Romeo, G; Jasonni, V

1999-01-01

Anorectal malformations (ARMs) are common congenital anomalies that account for 1:4 digestive malformations. ARM patients show different degrees of sacral hypodevelopment while the hemisacrum is characteristic of the Currarino syndrome (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A gene responsible for CS has recently been mapped in 7q36. Among the genes localized in this critical region, sonic hedgehog (SHH) was thought to represent a candidate gene for CS as well as for ARM with different levels of sacral hypodevelopment according to its role in the differentiation of midline mesoderm. By linkage analysis we confirmed the critical region in one large family with recurrence of CS. In addition, the screening of SHH in 7 CS and in 15 sporadic ARM patients with sacral hypodevelopment allowed us to exclude its role in the pathogenesis of these disorders.

A 40-year-old woman with cauda equina syndrome caused by rectothecal fistula arising from an anterior sacral meningocele.

PubMed

Bergeron, Eric; Roux, Alain; Demers, Jacques; Vanier, Laurent E; Moore, Lynne

2010-11-01

We present a rare case of a rectothecal fistula arising from an anterior sacral meningocele in a patient with Currarino syndrome. The patient was a 40-year-old woman presenting with cauda equina syndrome and ascending meningitis. The meningocele was removed using an anterior abdominal approach. A sigmoid resection was performed with rectal on-table antegrade lavage followed by closure of the rectal fistula, closure of the rectal stump, and proximal colostomy. Closure of the sacral deficit was carried out by suturing a strip of well-vascularized omentum and fibrin glue. We discuss the characteristics, management, and evolution of this unusual case. Prompt surgical management using an anterior approach, resection of the sac, closure of the sacral deficit, and fecal diversion resulted in a satisfactory outcome.

Surgical management of U-shaped sacral fractures: a systematic review of current treatment strategies.

PubMed

König, M A; Jehan, S; Boszczyk, A A; Boszczyk, B M

2012-05-01

U-shaped sacral fractures usually result from axial loading of the spine with simultaneous sacral pivoting due to a horizontal fracture which leads to a highly unstable spino-pelvic dissociation. Due to the rarity of these fractures, there is lack of an agreed treatment strategy. A thorough literature search was carried out to identify current treatment concepts. The studies were analysed for mechanism of injury, diagnostic imaging, associated injuries, type of surgery, follow-up times, complications, neurological, clinical and radiological outcome. Sixty-three cases were found in 12 articles. No Class I, II or III evidence was found in the literature. The most common mechanism of injury was a fall or jump from height. Pre-operative neurological deficit was noted in 50 (94.3%) out of 53 cases (not available in 10 patients). The most used surgical options were spino-pelvic fixation with or without decompression and ilio-sacral screws. Post-operative complications occurred in 24 (38.1%) patients. Average follow-up time was 18.6 months (range 2-34 months). Full neurological recovery was noted in 20 cases, partial recovery in 14 and 9 patients had no neurological recovery (5 patients were lost in follow-up). Fracture healing was mentioned in 7 articles with only 1 case of fracture reduction loss. From the current available data, an evidence based treatment strategy regarding outcome, neurological recovery or fracture healing could not be identified. Limited access and minimal-invasive surgery focussing on sacral reduction and restoration seems to offer comparable results to large spino-pelvic constructs with fewer complications and should be considered as the method of choice. If the fracture is highly unstable and displaced, spino-pelvic fixation might offer better stability.

Sacral Bone Mass Distribution Assessed by Averaged Three-Dimensional CT Models: Implications for Pathogenesis and Treatment of Fragility Fractures of the Sacrum.

PubMed

Wagner, Daniel; Kamer, Lukas; Sawaguchi, Takeshi; Richards, R Geoff; Noser, Hansrudi; Rommens, Pol M

2016-04-06

Fragility fractures of the sacrum are increasing in prevalence due to osteoporosis and epidemiological changes and are challenging in their treatment. They exhibit specific fracture patterns with unilateral or bilateral fractures lateral to the sacral foramina, and sometimes an additional transverse fracture leads to spinopelvic dissociation. The goal of this study was to assess sacral bone mass distribution and corresponding changes with decreased general bone mass. Clinical computed tomography (CT) scans of intact pelves in ninety-one individuals (mean age and standard deviation, 61.5 ± 11.3 years) were used to generate three-dimensional (3D) models of the sacrum averaging bone mass in Hounsfield units (HU). Individuals with decreased general bone mass were identified by measuring bone mass in L5 (group 1 with <100 HU; in contrast to group 2 with ≥100 HU). In group 1, a large zone of negative Hounsfield units was located in the paraforaminal lateral region from S1 to S3. Along the trans-sacral corridors, a Hounsfield unit peak was observed laterally, corresponding to cortical bone of the auricular surface. The lowest Hounsfield unit values were found in the paraforaminal lateral region in the sacral ala. An intermediate level of bone mass was observed in the area of the vertebral bodies, which also demonstrated the largest difference between groups 1 and 2. Overall, the Hounsfield units were lower at S2 than S1. The models of averaged bone mass in the sacrum revealed a distinct 3D distribution pattern. The negative values in the paraforaminal lateral region may explain the specific fracture patterns in fragility fractures of the sacrum involving the lateral areas of the sacrum. Transverse fractures located between S1 and S2 leading to spinopelvic dissociation may occur because of decreased bone mass in S2. The largest difference between the studied groups was found in the vertebral bodies and might support the use of transsacral or cement-augmented implants

Establishing the Learning Curve of Robotic Sacral Colpopexy in a Start-up Robotics Program.

PubMed

Sharma, Shefali; Calixte, Rose; Finamore, Peter S

2016-01-01

To determine the learning curve of the following segments of a robotic sacral colpopexy: preoperative setup, operative time, postoperative transition, and room turnover. A retrospective cohort study to determine the number of cases needed to reach points of efficiency in the various segments of a robotic sacral colpopexy (Canadian Task Force II-2). A university-affiliated community hospital. Women who underwent robotic sacral colpopexy at our institution from 2009 to 2013 comprise the study population. Patient characteristics and operative reports were extracted from a patient database that has been maintained since the inception of the robotics program at Winthrop University Hospital and electronic medical records. Based on additional procedures performed, 4 groups of patients were created (A-D). Learning curves for each of the segment times of interest were created using penalized basis spline (B-spline) regression. Operative time was further analyzed using an inverse curve and sequential grouping. A total of 176 patients were eligible. Nonparametric tests detected no difference in procedure times between the 4 groups (A-D) of patients. The preoperative and postoperative points of efficiency were 108 and 118 cases, respectively. The operative points of proficiency and efficiency were 25 and 36 cases, respectively. Operative time was further analyzed using an inverse curve that revealed that after 11 cases the surgeon had reached 90% of the learning plateau. Sequential grouping revealed no significant improvement in operative time after 60 cases. Turnover time could not be assessed because of incomplete data. There is a difference in the operative time learning curve for robotic sacral colpopexy depending on the statistical analysis used. The learning curve of the operative segment showed an improvement in operative time between 25 and 36 cases when using B-spline regression. When the data for operative time was fit to an inverse curve, a learning rate of 11 cases

Perineal colostomy prolapse: a novel application of mesh sacral pexy.

PubMed

Landen, S; Ursaru, D; Delugeau, V; Landen, C

2018-01-01

Full thickness colonic prolapse following pseudocontinent perineal colostomy has not been previously reported. Possible contributing factors include a large skin aperture at the site of the perineal stoma, the absence of anal sphincters and mesorectal attachments and the presence of a perineal hernia. A novel application of sacral pexy combined with perineal hernia repair using two prosthetic meshes is described.

Comparison of gluteal perforator flaps and gluteal fasciocutaneous rotation flaps for reconstruction of sacral pressure sores.

PubMed

Chen, Yen-Chou; Huang, Eng-Yen; Lin, Pao-Yuan

2014-03-01

The gluteus maximus myocutaneous flap was considered the workhorse that reconstructed sacral pressure sores, but was gradually replaced by fasciocutaneous flap because of several disadvantages. With the advent of the perforator flap technique, gluteal perforator (GP) flap has gained popularity nowadays. The aim of this study was to compare the complications and outcomes between GP flaps and gluteal fasciocutaneous rotation (FR) flaps in the treatment of sacral pressure sores. Between April 2007 and June 2012, 63 patients underwent sacral pressure sore reconstructions, with a GP flap used in 31 cases and an FR flap used in 32 cases. Data collected on the patients included patient age, gender, co-morbidity for being bedridden and follow-up time. Surgical details collected included the defect size, operative time and estimated blood loss. Complications recorded included re-operation, dehiscence, flap necrosis, wound infection, sinus formation, donor-site morbidity and recurrence. The complications and clinical outcomes were compared between these two groups. We found that there was no significant difference in patient demographics, surgical complications and recurrence between these two groups. In gluteal FR flap group, all recurrent cases (five) were treated by reuse of previous flaps. Both methods are comparable, good and safe in treating sacral pressure sores. Gluteal FR flap can be performed without microsurgical dissection, and re-rotation is feasible in recurrent cases. The authors suggest using gluteal FR flaps in patients with a high risk of sore recurrence. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Extracorporeal Stimulation of Sacral Nerve Roots for Observation of Pelvic Autonomic Nerve Integrity: Description of a Novel Methodological Setup.

PubMed

Moszkowski, Tomasz; Kauff, Daniel W; Wegner, Celine; Ruff, Roman; Somerlik-Fuchs, Karin H; Kruger, Thilo B; Augustyniak, Piotr; Hoffmann, Klaus-Peter; Kneist, Werner

2018-03-01

Neurophysiologic monitoring can improve autonomic nerve sparing during critical phases of rectal cancer surgery. To develop a system for extracorporeal stimulation of sacral nerve roots. Dedicated software controlled a ten-electrode stimulation array by switching between different electrode configurations and current levels. A built-in impedance and current level measurement assessed the effectiveness of current injection. Intra-anal surface electromyography (sEMG) informed on targeting the sacral nerve roots. All tests were performed on five pig specimens. During switching between electrode configurations, the system delivered 100% of the set current (25 mA, 30 Hz, 200 μs cathodic pulses) in 93% of 250 stimulation trains across all specimens. The impedance measured between single stimulation array contacts and corresponding anodes across all electrode configurations and specimens equaled 3.7 ± 2.5 kΩ. The intra-anal sEMG recorded a signal amplitude increase as previously observed in the literature. When the stimulation amplitude was tested in the range from 1 to 21 mA using the interconnected contacts of the stimulation array and the intra-anal anode, the impedance remained below 250 Ω and the system delivered 100% of the set current in all cases. Intra-anal sEMG showed an amplitude increase for current levels exceeding 6 mA. The system delivered stable electric current, which was proved by built-in impedance and current level measurements. Intra-anal sEMG confirmed the ability to target the branches of the autonomous nervous system originating from the sacral nerve roots. Stimulation outside of the operative field during rectal cancer surgery is feasible and may improve the practicality of pelvic intraoperative neuromonitoring.

Microcirculatory responses of sacral tissue in healthy individuals and inpatients on different pressure-redistribution mattresses.

PubMed

Bergstrand, S; Källman, U; Ek, A-C; Engström, M; Lindgren, M

2015-08-01

The aim of this study was to explore the interaction between interface pressure, pressure-induced vasodilation, and reactive hyperaemia with different pressure-redistribution mattresses. A cross-sectional study was performed with a convenience sample of healthy young individuals, and healthy older individuals and inpatients, at a university hospital in Sweden. Blood flow was measured at depths of 1mm, 2mm, and 10mm using laser Doppler flowmetry and photoplethysmography. The blood flow, interface pressure and skin temperature were measured in the sacral tissue before, during, and after load while lying on one standard hospital mattress and three different pressure-redistribution mattresses. There were significant differences between the average sacral pressure, peak sacral pressure, and local probe pressure on the three pressure-redistribution mattresses, the lowest values found were with the visco-elastic foam/air mattress (23.5 ± 2.5mmHg, 49.3 ± 11.1mmHg, 29.2 ± 14.0mmHg, respectively). Blood flow, measured as pressure-induced vasodilation, was most affected in the visco-elastic foam/air group compared to the alternating pressure mattress group at tissue depths of 2mm (39.0% and 20.0%, respectively), and 10mm (56.9 % and 35.1%, respectively). Subjects in all three groups, including healthy 18-65 year olds, were identified with no pressure-induced vasodilation or reactive hyperaemia on any mattress (n=11), which is considered a high-risk blood flow response. Interface pressure magnitudes considered not harmful during pressure-exposure on different pressure-redistribution mattresses can affect the microcirculation in different tissue structures. Despite having the lowest pressure values compared with the other mattresses, the visco-elastic foam/air mattress had the highest proportion of subjects with decreased blood flow. Healthy young individuals were identified with the high-risk blood flow response, suggesting an innate vulnerability to pressure exposure

[Sacral neuromodulation in urology - development and current status].

PubMed

Schwalenberg, T; Stolzenburg, J-U; Kriegel, C; Gonsior, A

2012-01-01

Sacral neuromodulation (SNM) in urology is employed to treat refractory lower urinary tract dysfunction as well as chronic pelvic pain. Electrical stimulation of the sacral afferents (S2 - S4) causes activation and conditioning of higher autonomic and somatic neural structures and thereby influences the efferents controlling the urinary bladder, the rectum and their related sphincter systems. It is therefore possible to treat overactivity as well as hypocontractility and functional bladder neck obstruction. SNM treatment is conducted biphasically. Initially, test electrodes are placed to evaluate changes in micturition and pain parameters. If, in this first phase - called peripheral nerve evaluation (PNE test) - sufficient improvements are observed, the patient progresses to phase two which involves implantation of the permanent electrodes and impulse generator system. In recent years, the "two stage approach" with initial implantation of the permanent electrodes has been favoured as it increases treatment success rates. Long-term success rates of SNM vary significantly in the literature (50 - 80 %) due to heterogeneous patient populations as well as improved surgical approaches. With the introduction of "tined lead electrodes" (2002), tissue damage is reduced to a minimum. Technical innovation, financial feasibility (reimbursed in Germany since 2004) and wider application, especially in otherwise therapy-refractory patients or complex dysfunctions of the pelvis, have established SNM as a potent treatment option in urology. © Georg Thieme Verlag KG Stuttgart · New York.

Neurostimulation for bladder evacuation: is sacral root stimulation a substitute for microstimulation?

PubMed

Probst, M; Piechota, H J; Hohenfellner, M; Gleason, C A; Tanagho, E A

1997-04-01

To determine by anatomical and functional studies whether stimulation of sacral rootlets might permit selective stimulation of autonomic fibres, thus avoiding the detrusor/sphincter dyssynergia characteristic of current techniques of neurostimulation for bladder evacuation. In 10 male mongrel dogs, the S2 root was isolated and its constituent rootlets followed from their origin in the spinal cord to the point of exit from the dura. The entire root and the individual rootlets were then stimulated, including intra- and extra-dural stimulation and at proximal, mid and distal levels. Neuroanatomical and histological findings showed that rootlets of ventral S2 maintain their identity throughout their intradural course; some carry predominantly autonomic fibres, some predominantly somatic and some a mixture of the two. It appears surgically feasible to identify, isolate and sever the predominantly somatic rootlets intradurally, sparing the predominantly autonomic rootlets for inclusion in extradural electrode placement around the entire sacral root, thus eliminating sphincteric interference with detrusor contraction for voiding at low pressure.

A Prospective Randomized Clinical Trial of a Novel, Noninvasive Perfusion Enhancement System for the Prevention of Hospital-Acquired Sacral Pressure Injuries.

PubMed

Bharucha, Jitendra B; Seaman, Linda; Powers, Michele; Kelly, Erica; Seaman, Rodney; Forcier, Lea; McGinnis, Janice; Nodiff, Isabel; Pawlak, Brooke; Snyder, Samantha; Nodiff, Susan; Patel, Rohan; Squitieri, Rafael; Wang, Lansheng

2018-06-08

The purpose of this study was to determine the effectiveness of a novel, noninvasive perfusion enhancement system versus beds with integrated alternating pressure capabilities for the prevention of hospital-acquired sacral region (sacral, coccygeal, and ischium) pressure injuries in a high-risk, acute care patient population. A prospective randomized trial of high-risk inpatients without preexisting sacral region pressure injuries was conducted. The sample comprised 431 randomly enrolled adult patients in a 300-bed tertiary care community teaching hospital. Subjects were randomly allocated to one of 2 groups: control and experimental. Both groups received "standard-of-care" pressure injury prevention measures per hospital policy, and both were placed on alternating pressure beds during their hospital stays. In addition, patients in the experimental group used a noninvasive perfusion enhancement system placed on top of their alternating pressure beds and recovery chairs throughout their hospital stay. Fischer's exact probability test was used to compare group differences, and odds ratio (OR) were calculated for comparing pressure injury rates in the experimental and control groups. Three hundred ninety-nine patients completed the trial; 186 patients were allocated to the experimental group and 213 patients to the control group. Eleven patients in the control group versus 2 in the experimental group developed hospital-acquired sacral region pressure injuries (51.6% vs 1.07%; P = .024). Control patients were 5.04 times more likely to develop hospital-acquired sacral region pressure injuries (OR = 0.1996; 95% CI, 0.0437-0.9125). Patients using a noninvasive perfusion enhancement system developed significantly fewer hospital-acquired sacral pressure injuries than those using an alternating pressure bed without the perfusion enhancement system. These findings suggest that a perfusion enhancement system enhances the success of use of pressure redistributing beds for

Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

PubMed

Sheriff, M K; Shah, P J; Fowler, C; Mundy, A R; Craggs, M D

1996-07-01

To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

The Thoracic Lordosis Correction Improves Sacral Slope and Walking Ability in Neuromuscular Scoliosis.

PubMed

Kim, Do Yeon; Moon, Eun Su; Park, Jin Oh; Chong, Hyon Su; Lee, Hwan Mo; Moon, Seong Hwan; Kim, Sung Hoon; Kim, Hak Sun

2016-10-01

Retrospective study. To report on neuromuscular patients with preserved walking ability, but forward bending of the body due to thoracic lordosis, and to suggest thoracic lordosis correction as the surgical treatment. It is an established fact that lumbar lordosis or pelvic parameter is directly related to thoracic sagittal balance. However, the reverse relationship has not been fully defined yet. Loss of thoracic kyphosis results in positive sagittal balance, which causes walking difficulty. Neuromuscular patients with thoracic lordosis have not been reported yet, and there have been no reports on their surgical treatments. This study analyzed 8 patients treated with thoracic lordosis correction surgery. Every patient was diagnosed with muscular dystrophy. In thoracic lordosis correction surgery, anterior release was performed in the first stage and posterior segmental instrumentation was performed in the second stage. Radiographic parameters were compared and walking ability was evaluated with gait analysis. All patients were classified according to the modified Rancho Los Amigos Hospital system preoperatively and 2 years postoperatively to evaluate functional ability. The average follow-up period was 2.9 years. Before surgery, the mean thoracic sagittal alignment was -2.1-degree lordosis, the mean Cobb angle and sacral slope increased to 36.3 and 56.6 degrees, respectively. The anterior pelvic tilt in gait analysis was 29.3 degrees. At last follow-up after surgery, the mean thoracic sagittal alignment changed to 12.6-degree kyphosis, and the Cobb angle and sacral slope decreased to 18.9 and 39.5 degrees, respectively. Lumbar lordosis and the sacral slope showed significant positive correlation (P<0.001). The improvement in thoracic lordosis showed a significant correlation to the preoperative flexibility of the major curve (P=0.028). The anterior pelvic tilt in gait analysis improved to 15.4 degrees. The functional ability improved in 2 (50%) of 4 patients in

[Sacral nerve stimulation in the treatment of the lower urinary tract function disorders].

PubMed

Miotła, Paweł; Kulik-Rechberger, Beata; Skorupski, Paweł; Rechberger, Tomasz

2011-11-01

Functional disorders of the female lower urinary tract like urge incontinence, idiopathic urinary retention and symptoms of urgency-frequency occasionally do not respond properly to classical behavioral and pharmacological therapy Therefore, additional alternative therapies are needed to alleviate these bothersome symptoms. Sacral neuromodulation (SNS) utilize mild electrical pulses which activate or suppress neural reflexes responsible for voiding by stimulating the sacral nerves that innervate the bladder, external urethral sphincter and pelvic floor muscles. The exact mechanism of SNS action is not yet fully understood but it is assumed that it influences the neuroaxis at different levels of the central nervous system and restores the balance between inhibitory and activatory control over the voiding reflex. There is numerous evidence on the success of SNS not only in the treatment of refractory urge incontinence in adult and children but also in idiopathic urinary retention and symptoms of urgency-frequency

Mechanical comparison between lengthened and short sacroiliac screws in sacral fracture fixation: a finite element analysis.

PubMed

Zhao, Y; Zhang, S; Sun, T; Wang, D; Lian, W; Tan, J; Zou, D; Zhao, Y

2013-09-01

To compare the stability of lengthened sacroiliac screw and standard sacroiliac screw for the treatment of unilateral vertical sacral fractures; to provide reference for clinical applications. A finite element model of Tile type C pelvic ring injury (unilateral Denis type II fracture of the sacrum) was produced. The unilateral sacral fractures were fixed with lengthened sacroiliac screw and sacroiliac screw in six different types of models respectively. The translation and angle displacement of the superior surface of the sacrum (in standing position on both feet) were measured and compared. The stability of one lengthened sacroiliac screw fixation in S1 or S2 segment is superior to that of one sacroiliac screw fixation in the same sacral segment. The stability of one lengthened sacroiliac screw fixation in S1 and S2 segments respectively is superior to that of one sacroiliac screw fixation in S1 and S2 segments respectively. The stability of one lengthened sacroiliac screw fixation in S1 and S2 segments respectively is superior to that of one lengthened sacroiliac screw fixation in S1 or S2 segment. The stability of one sacroiliac screw fixation in S1 and S2 segments respectively is markedly superior to that of one sacroiliac screw fixation in S1 or S2 segment. The vertical and rotational stability of lengthened sacroiliac screw fixation and sacroiliac screw fixation in S2 is superior to that of S1. In a finite element model of type C pelvic ring disruption, S1 and S2 lengthened sacroiliac screws should be utilized for the fixation as regularly as possible and the most stable fixation is the combination of the lengthened sacroiliac screws of S1 and S2 segments. Even if lengthened sacroiliac screws cannot be systematically used due to specific conditions, one sacroiliac screw fixation in S1 and S2 segments respectively is recommended. No matter which kind of sacroiliac screw is used, if only one screw can be implanted, the fixation in S2 segment is more recommended

OnabotulinumtoxinA vs Sacral Neuromodulation on Refractory Urgency Urinary Incontinence in Women: A Randomized Clinical Trial.

PubMed

Amundsen, Cindy L; Richter, Holly E; Menefee, Shawn A; Komesu, Yuko M; Arya, Lily A; Gregory, W Thomas; Myers, Deborah L; Zyczynski, Halina M; Vasavada, Sandip; Nolen, Tracy L; Wallace, Dennis; Meikle, Susan F

2016-10-04

Women with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information. To assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence. Multicenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence. Cystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189). Primary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events. Of the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse

Effectiveness and Value of Prophylactic 5-Layer Foam Sacral Dressings to Prevent Hospital-Acquired Pressure Injuries in Acute Care Hospitals

PubMed Central

2017-01-01

PURPOSE: The purpose of this study was to examine the effectiveness and value of prophylactic 5-layer foam sacral dressings to prevent hospital-acquired pressure injury rates in acute care settings. DESIGN: Retrospective observational cohort. SAMPLE AND SETTING: We reviewed records of adult patients 18 years or older who were hospitalized at least 5 days across 38 acute care hospitals of the University Health System Consortium (UHC) and had a pressure injury as identified by Patient Safety Indicator #3 (PSI-03). All facilities are located in the United States. METHODS: We collected longitudinal data pertaining to prophylactic 5-layer foam sacral dressings purchased by hospital-quarter for 38 academic medical centers between 2010 and 2015. Longitudinal data on acute care, hospital-level patient outcomes (eg, admissions and PSI-03 and pressure injury rate) were queried through the UHC clinical database/resource manager from the Johns Hopkins Medicine portal. Data on volumes of dressings purchased per UHC hospital were merged with UHC data. Mixed-effects negative binomial regression was used to test the longitudinal association of prophylactic foam sacral dressings on pressure injury rates, adjusted for hospital case-mix and Medicare payments rules. RESULTS: Significant pressure injury rate reductions in US acute care hospitals between 2010 and 2015 were associated with the adoption of prophylactic 5-layer foam sacral dressings within a prevention protocol (−1.0 cases/quarter; P = .002) and changes to Medicare payment rules in 2014 (−1.13 cases/quarter; P = .035). CONCLUSIONS: Prophylactic 5-layer foam sacral dressings are an effective component of a pressure injury prevention protocol. Hospitals adopting these technologies should expect good value for use of these products. PMID:28816929

Risk factors for explantation due to infection after sacral neuromodulation: a multicenter retrospective case-control study.

PubMed

Myer, Emily N B; Petrikovets, Andrey; Slocum, Paul D; Lee, Toy Gee; Carter-Brooks, Charelle M; Noor, Nabila; Carlos, Daniela M; Wu, Emily; Van Eck, Kathryn; Fashokun, Tola B; Yurteri-Kaplan, Ladin; Chen, Chi Chiung Grace

2018-04-07

Sacral neuromodulation is an effective therapy for overactive bladder, urinary retention, and fecal incontinence. Infection after sacral neurostimulation is costly and burdensome. Determining optimal perioperative management strategies to reduce the risk of infection is important to reduce this burden. We sought to identify risk factors associated with sacral neurostimulator infection requiring explantation, to estimate the incidence of infection requiring explantation, and identify associated microbial pathogens. This is a multicenter retrospective case-control study of sacral neuromodulation procedures completed from Jan. 1, 2004, through Dec. 31, 2014. We identified all sacral neuromodulation implantable pulse generator implants as well as explants due to infection at 8 participating institutions. Cases were patients who required implantable pulse generator explantation for infection during the review period. Cases were included if age ≥18 years old, follow-up data were available ≥30 days after implantable pulse generator implant, and the implant was performed at the institution performing the explant. Two controls were matched to each case. These controls were the patients who had an implantable pulse generator implanted by the same surgeon immediately preceding and immediately following the identified case who met inclusion criteria. Controls were included if age ≥18 years old, no infection after implantable pulse generator implant, follow-up data were available ≥180 days after implant, and no explant for any reason <180 days from implant. Controls may have had an explant for reasons other than infection at >180 days after implant. Fisher exact test (for categorical variables) and Student t test (for continuous variables) were used to test the strength of the association between infection and patient and surgery characteristics. Significant variables were then considered in a multivariable logistic regression model to determine risk factors

Sacral neuromodulation for lower urinary tract dysfunction and impact on erectile function.

PubMed

Lombardi, Giuseppe; Mondaini, Nicola; Giubilei, Gianluca; Macchiarella, Angelo; Lecconi, Filippo; Del Popolo, Giulio

2008-09-01

The first sacral nerve stimulators were for urinary urgency incontinence, urgency-frequency, and nonobstructive urinary retention. Since then, observations have been made for benefits beyond voiding disorders. To evaluate if sacral neuromodulation (SNM) using the InterStim system (Medtronic Inc., Minneapolis, MN, USA) improves erectile function. From January 1999 to January 2007, 54 males, mean age 42.8, underwent a permanent SNM for lower urinary tract symptoms (LUTS). Pre-SNM only subjects with concomitant erectile impairment according to the five-item version of the International Index of Erectile Function (IIEF-5), with normal blood sexual hormonal status, and responding to an intracavernous injection test 10 microg were enrolled in our study. Three months after permanent implantation, the IIEF-5 was completed again. Those who benefited significantly in erectile function completed the IIEF-5 semiannually. A final checkup was performed in July 2007. A score of IIEF-5 equal to or higher than 25% compared to baseline indicated remarkable clinical enhancement. Presurgery, two patients were excluded. Overall, 22 subjects (42.3%) showed erectile impairment (14 were neurogenic). In the first visit post-SNM, five retentionists of neurogenic origin and two with overactive bladder syndrome of idiopathic origin achieved noticeable erectile improvement. Their median IIEF-5 score shifted from 14.6 to 22.2, and 15.5 to 22.5, respectively. During follow-up, two neurogenics lost the benefits concerning voiding and erection and recovered them after a new implant in the contralateral sacral S3 root. In the final visit, the seven responders reached an IIEF-5 score of at least 22. Our study showed a clinically important benefit of sexual function mainly for neurogenic retentionists. Future research should test SNM in a larger sample of subjects, exclusively with sexual dysfunctions, in order to better understand the mechanism of action of SNM on erectile function.

Characterization of herpes simplex virus type 2 latency-associated transcription in human sacral ganglia and in cell culture.

PubMed

Croen, K D; Ostrove, J M; Dragovic, L; Straus, S E

1991-01-01

The ability of herpes simplex virus type 2 (HSV-2) to establish latency in and reactivate from sacral dorsal root sensory ganglia is the basis for recurrent genital herpes. The expression of HSV-2 genes in latently infected human sacral ganglia was investigated by in situ hybridization. Hybridizations with a probe from the long repeat region of HSV-2 revealed strong nuclear signals overlying neurons in sacral ganglia from five of nine individuals. The RNA detected overlaps with the transcript for infected cell protein O but in the opposite, or "anti-sense," orientation. These observations mimic those made previously with HSV-1 in human trigeminal ganglia and confirm the recent findings during latency in HSV-2-infected mice and guinea pigs. Northern hybridization of RNA from infected Vero cells showed that an HSV-2 latency-associated transcript was similar in size to the larger (1.85 kb) latency transcript of HSV-1. Thus, HSV-1 and HSV-2 latency in human sensory ganglia are similar, if not identical, in terms of their cellular localization and pattern of transcription.

Comparison of fasciocutaneous V-Y and rotational flaps for defect coverage of sacral pressure sores: a critical single-centre appraisal.

PubMed

Djedovic, Gabriel; Metzler, Julia; Morandi, Evi M; Wachter, Tanja; Kühn, Shafreena; Pierer, Gerhard; Rieger, Ulrich M

2017-12-01

Pressure sore rates remain high in both nursing homes as well as in hospitals. Numerous surgical options are available for defect coverage in the sacral region. However, objective data is scarce as to whether a specific flap design is superior to another. Here, we aim to compare two fasciocutaneous flap designs for sacral defect coverage: the gluteal rotation flap and the gluteal V-Y flap. All primary sacral pressure sores of grades III-IV that were being covered with gluteal fasciocutaneous rotational or V-Y flaps between January 2008 and December 2014 at our institution were analysed. A total of 41 patients received a total of 52 flaps. Of these, 18 patients received 20 gluteal rotational flaps, and 23 patients received 32 V-Y flaps. Both groups were comparable with regards to demographics, comorbidities and complications. Significantly more V-Y flaps were needed to cover smaller defects. Mean length of hospital stay was significantly prolonged when surgical revision had to be carried out. Both flap designs have proven safe and reliable for defect coverage after sacral pressure sores. Gluteal rotational flaps appear to be more useful for larger defects. Both flap designs facilitate their reuse in case of pressure sore recurrence. Complication rates appear to be comparable in both designs and to the current literature. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Sacral herpes-zoster infection presenting as sciatic pain.

PubMed

Ablin, J; Symon, Z; Mevorach, D

1996-06-01

Acute herpes-zoster infection is a painful dermatomal lesion that can be manifested by a wide array of neurologic symptoms. We present a 55-year-old female with non-Hodgkin's lymphoma, who developed a left sciatic pain involving the S roots. Two weeks later, the patient developed fever and vesicular rash over the left gluteal area. Herpes-zoster infection was diagnosed and confirmed by the presence of immunoglobulin M (IgM) antibodies against varicella-zoster. The pain and rash resolved, after treatment with acyclovir. In the appropriate clinical setting, sacral herpes-zoster infection ought to be considered in the differential diagnosis of new-onset sciatic pain.

Urodynamic results, clinical efficacy, and complication rates of sacral intradural deafferentation and sacral anterior root stimulation in patients with neurogenic lower urinary tract dysfunction resulting from complete spinal cord injury.

PubMed

Krasmik, D; Krebs, Jörg; van Ophoven, Arndt; Pannek, Jürgen

2014-11-01

To investigate the outcome and complications of sacral deafferentation (SDAF) and sacral anterior root stimulation (SARS) in patients with neurogenic lower urinary tract dysfunction (NLUTD) resulting from complete spinal cord injury (SCI). Retrospective chart analysis of 137 patients who underwent SDAF/SARS at a single institution. Patients were categorized as being at risk of renal damage when the maximum detrusor pressure was >40 cmH2 O or detrusor compliance was <20 ml/cmH2 O. After a mean follow-up time of 14.8 ± 5.3 years, SDAF/SARS treatment significantly (P < 0.001) reduced the number of patients suffering from elevated detrusor pressure from 65 to 2, and from low detrusor compliance from 62 to 13, respectively. Mean bladder capacity significantly (P < 0.001) improved from 272.4 ± 143.0 to 475.0 ± 82.7 ml. The mean number of symptomatic UTI also decreased significantly (P < 0.001) from 6.2 ± 4.5 to 2.5 ± 2.6 per year. The number of patients suffering from incontinence had significantly (P < 0.001) decreased from 70 to 44. At the last follow-up visit, 107 (78.1%) patients were still using the stimulator. A total of 84 complications requiring surgical revision were observed. Defects of the stimulator cables or the receiver plate were the most common events (n = 38). The retrospective design pertains to the limitations of the study. Sacral deafferentation and SARS are an effective treatment option for refractory NLUTD in patients with complete SCI, despite a substantial long-term complication rate. © 2014 Wiley Periodicals, Inc.

A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts.

PubMed

Goldstein, Irwin; Komisaruk, Barry R; Rubin, Rachel S; Goldstein, Sue W; Elliott, Stacy; Kissee, Jennifer; Kim, Choll W

2017-09-01

Since 14 years of age, the patient had experienced extreme penile pain within seconds of initial sexual arousal through masturbation. Penile pain was so severe that he rarely proceeded to orgasm or ejaculation. After 7 years of undergoing multiple unsuccessful treatments, he was concerned for his long-term mental health and for his future ability to have relationships. To describe a novel collaboration among specialists in sexual medicine, neurophysiology, and spine surgery that led to successful management. Collaborating health care providers conferred with the referring physician, patient, and parents and included a review of all medical records. Elimination of postpubertal intense penile pain during sexual arousal. The patient presented to our sexual medicine facility at 21 years of age. The sexual medicine physician identifying the sexual health complaint noted a pelvic magnetic resonance imaging report of an incidental sacral Tarlov cyst. A subsequent sacral magnetic resonance image showed four sacral Tarlov cysts, with the largest measuring 18 mm. Neuro-genital testing result were abnormal. The neurophysiologist hypothesized the patient's pain at erection was produced by Tarlov cyst-induced neuropathic irritation of sensory fibers that course within the pelvic nerve. The spine surgeon directed a diagnostic injection of bupivacaine to the sacral nerve roots and subsequently morphine to the conus medullaris of the spinal cord. The bupivacaine produced general penile numbness; the morphine selectively decreased penile pain symptoms during sexual arousal without blocking penile skin sensation. The collaboration among specialties led to the conclusion that the Tarlov cysts were pathophysiologically mediating the penile pain symptoms during arousal. Long-term follow-up after surgical repair showed complete symptom elimination at 18 months after treatment. This case provides evidence that (i) Tarlov cysts can cause sacral spinal nerve root radiculitis through

Procedural techniques in sacral nerve modulation.

PubMed

Williams, Elizabeth R; Siegel, Steven W

2010-12-01

Sacral neuromodulation involves a staged process, including a screening trial and delayed formal implantation for those with substantial improvement. The advent of the tined lead has revolutionized the technology, allowing for a minimally invasive outpatient procedure to be performed under intravenous sedation. With the addition of fluoroscopy to the bilateral percutaneous nerve evaluation, there has been marked improvement in the placement of these temporary leads. Thus, the screening evaluation is now a better reflection of possible permanent improvement. Both methods of screening have advantages and disadvantages. Selection of a particular procedure should be tailored to individual patient characteristics. Subsequent implantation of the internal pulse generator (IPG) or explantation of an unsuccessful staged lead is straightforward outpatient procedure, providing minimal additional risk for the patient. Future refinement to the procedure may involve the introduction of a rechargeable battery, eliminating the need for IPG replacement at the end of the battery life.

Trans-sacral resection of a solitary fibrous tumor in the pelvis: report of a case.

PubMed

Katsuno, Hidetoshi; Maeda, Koutarou; Hanai, Tsunekazu; Sato, Harunobu; Masumori, Koji; Koide, Yoshikazu; Matsuoka, Hiroshi; Noro, Tomohito; Takakuwa, Yasunari; Hanaoka, Ryouta

2011-11-01

Solitary fibrous tumors (SFTs) develop most commonly in the pleura, although they have occasionally been reported to arise in the pelvic cavity. We report a case of an SFT presenting as a painless nodule in the pelvis of a 56-year-old woman. Histologically, the tumor was composed of spindle-shaped cells arranged without pattern, with short and narrow fascicles and interspersed bundles of thick collagen, and numerous blood vessels with a focally hemangiopericytoma-like appearance. Immunohistochemically, the tumor cells strongly expressed vimentin, CD34, and bcl-2. The tumor was excised via a trans-sacral approach, without preoperative transcatheter embolization, and the patient remains well more than 2 years after her operation. To our knowledge, this is the first case of an SFT in the pelvis, which was excised completely via a trans-sacral approach.

Sacral Nerve Stimulation for Pediatric Lower Urinary Tract Dysfunction: Development of a Standardized Pathway with Objective Urodynamic Outcomes.

PubMed

Schober, Megan S; Sulkowski, Jason P; Lu, Peter L; Minneci, Peter C; Deans, Katherine J; Teich, Steven; Alpert, Seth A

2015-12-01

We propose that sacral nerve stimulation is a valid adjunctive therapy for refractory pediatric lower urinary tract dysfunction, and that prospective collection of preoperative and postoperative validated questionnaires and urodynamic data in a standardized fashion is beneficial in characterizing patient response. Patients were candidates for sacral nerve stimulation if they had refractory voiding dysfunction and standard treatments had failed. Preoperative evaluation included urodynamic studies, spinal magnetic resonance imaging, and validated bladder and bowel related questionnaires. Children were stratified into 2 groups, ie overactive bladder with or without incontinence (group 1) and detrusor underactivity/urinary retention requiring clean intermittent catheterization (group 2). A staged procedure was used with initial test lead placement, followed by permanent device insertion 2 weeks later if patients demonstrated symptom improvement with test lead. Postoperatively children were followed with questionnaires and at least 1 urodynamic study. A total of 26 children underwent sacral nerve stimulation. Mean patient age was 10.8 years and median followup was 1.2 years. There were 23 patients in group 1 and 4 in group 2 (1 patient was included in both groups). In group 1 voiding dysfunction scores improved significantly, and urodynamic studies revealed a significant decrease in mean number of uninhibited contractions and maximum detrusor pressure during the filling phase. In group 2 there was significant improvement in mean post-void residual. Sacral nerve stimulation is a treatment option that may produce significant improvement in objective and subjective measures of bladder function in children with refractory lower urinary tract dysfunction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Laparoscopic Sacral Colpopexy: The "6-Points" Technique.

PubMed

Schaub, Marie; Lecointre, Lise; Faller, Emilie; Boisramé, Thomas; Baldauf, Jean-Jacques; Wattiez, Arnaud; Akladios, Cherif Youssef

To illustrate laparoscopic sacral colpopexy for pelvic organ prolapse, a new method using a simplified mesh fixation technique, with only 6 fixing points. Step-by-step explanation of the surgery using video (educative video). The video was approved by the local institutional review board. University Hospital of Strasbourg, France (Canadian Task Force Classification III). Women with multicompartment prolapse. We first dissected the promontorium and vertically incise the posterior parietal peritoneum on the right pelvic sidewall up the pouch of Douglas. We then dissect the rectovaginal septum up to the anal cap, laterally exposing the puborectalis muscle on each side. Middle rectal vessels can be coagulated and cut without increasing the risk of digestive disorders (especially constipation), but it is preferable to conserve them if the space is sufficient for suture. Then, we dissect the vesicovaginal space and realized the subtotal hysterectomy. Finally, we realized the fastening of the anterior and posterior meshes. The particularity is that we performed only 6 points for fixing the meshes: 1 on the puborectalis muscle on each side without tension (to reduce the risk of mesh contracture, dyspareunia, and chronic pelvic pain), 1 for the fixing of the anterior mesh on the anterior vaginal wall at the level of the bladder neck, and 1 on each side of the cervix for the reconstitution of the pericervical ring gathering together the anterior mesh, the pubocervical fascia, and the insertion of the uterosacral ligament at the level of the cervix and the posterior mesh. The sixth stitch fastened 1 of 2 meshes to the anterior paravertebral ligament at the level of the sacral promontory. We finished with the peritonization. The duration of surgery lasts approximately 120 minutes in well-experienced hands. Based on our experience the 6-point technique was relatively simple (few laparoscopic stiches) with few operative difficulties and was also associated with a low rate of

Proximal sacral deformity: a common element in lytic isthmic spondylolisthesis at L5 and in degenerative spondylolisthesis at L4-L5 segment. Two apparently very different etiopathogenic entities.

PubMed

Gallego-Goyanes, A; Barahona-Lorenzo, D; Díez-Ulloa, M A

A radiographic study was carried out to investigate the relationship between proximal sacral sagittal anatomy (either kyphosis or lordosis) and either isthmic or degenerative spondylolisthesis. In addition, we studied whether there is a relationship between proximal sacral kyphosis and the degree of such listhesis in the case of L5 isthmic spondylolisthesis. Lateral standing x-rays were used from 173 patients, ninety of whom had degenerative spondylolisthesis L4-L5, and eighty-three an isthmic spondylolisthesis of L5 (67 low-grade and 16 high-grade) and compared with a control group of 100 patients adjusted by age and gender, without any type of spondylolisthesis. Listhesis was graded using Meyerding's classification and the proximal sacral kyphosis angle (CSP) was measured between S1 and S2 posterior walls, according to Harrison's method. In our series, there was a proximal sacral kyphosis in both types of spondylolisthesis, greater in the lytic type. By contrast, the control group had a proximal sacral lordosis. The differences were statistically significant. Therefore, we concluded that there was a proximal sacral kyphosis in patients with both degenerative and isthmic lytic spondylolisthesis, but with our results, we were not able to ascertain whether it is a cause or a consequence of this listhesis. Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Sacral stress fracture after lumbar and lumbosacral fusion. How to manage it? A proposition based on three cases and literature review.

PubMed

Scemama, C; D'astorg, H; Guigui, P

2016-04-01

Sacral fracture after lumbosacral instrumentation could be a source of prolonged pain and a late autonomy recovery in old patients. Diagnosis remains difficult and usually delayed. No clear consensus for efficient treatment of this complication has been defined. Aim of this study was to determine how to manage them. Three patients who sustained sacral fracture after instrumented lumbosacral fusion performed for degenerative disease of the spine are discussed. History, physical examinations' findings and radiographic features are presented. Pertinent literature was analyzed. All patients complained of unspecific low back and buttock pain a few weeks after index surgery. Diagnosis was done on CT-scan. We always choose revision surgery with good functional results. Sacral stress fracture has to be reminded behind unspecific buttock or low back pain. CT-scan seems to be the best radiological test to do the diagnosis. Surgical treatment is recommended when lumbar lordosis and pelvic incidence mismatched. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Comparison of gluteal fasciocutaneous rotational flaps and myocutaneous flaps for the treatment of sacral sores

PubMed Central

Ip, F. K.

2005-01-01

To compare the outcomes of gluteal fasciocutaneous rotational flaps and myocutaneous flaps in the treatment of sacral sores, together with a review of surgical complications in two matched cohorts. Thirty-eight patients (18 gluteal fasciocutaneous rotational flaps and 20 myocutaneous flaps) were reviewed retrospectively at a mean follow-up of 58 weeks. The rate of healing of the sore, the sore healing time, and the incidence of surgical complications, together with rate of recurrence, were obtained by chart review. Treatment groups were matched by patient characteristics, operative time and blood loss. The rate of healing of the sore, sore healing time and complication rate were comparable in the two groups but the rate of recurrence was lower to a statistically significant extent in myocutaneous flap patients. The authors suggest that both methods are comparable, good and safe in treating sacral sores; myocutaneous flaps are more durable. PMID:16333656

Does cortical bone thickness in the last sacral vertebra differ among tail types in primates?

PubMed

Nishimura, Abigail C; Russo, Gabrielle A

2017-04-01

The external morphology of the sacrum is demonstrably informative regarding tail type (i.e., tail presence/absence, length, and prehensility) in living and extinct primates. However, little research has focused on the relationship between tail type and internal sacral morphology, a potentially important source of functional information when fossil sacra are incomplete. Here, we determine if cortical bone cross-sectional thickness of the last sacral vertebral body differs among tail types in extant primates and can be used to reconstruct tail types in extinct primates. Cortical bone cross-sectional thickness in the last sacral vertebral body was measured from high-resolution CT scans belonging to 20 extant primate species (N = 72) assigned to tail type categories ("tailless," "nonprehensile short-tailed," "nonprehensile long-tailed," and "prehensile-tailed"). The extant dataset was then used to reconstruct the tail types for four extinct primate species. Tailless primates had significantly thinner cortical bone than tail-bearing primates. Nonprehensile short-tailed primates had significantly thinner cortical bone than nonprehensile long-tailed primates. Cortical bone cross-sectional thickness did not distinguish between prehensile-tailed and nonprehensile long-tailed taxa. Results are strongly influenced by phylogeny. Corroborating previous studies, Epipliopithecus vindobonensis was reconstructed as tailless, Archaeolemur edwardsi as long-tailed, Megaladapis grandidieri as nonprehensile short-tailed, and Palaeopropithecus kelyus as nonprehensile short-tailed or tailless. Results indicate that, in the context of phylogenetic clade, measures of cortical bone cross-sectional thickness can be used to allocate extinct primate species to tail type categories. © 2017 Wiley Periodicals, Inc.

Sacral neuromodulation for the treatment of neurogenic lower urinary tract dysfunction caused by multiple sclerosis: a single-centre prospective series.

PubMed

Engeler, Daniel S; Meyer, Daniel; Abt, Dominik; Müller, Stefanie; Schmid, Hans-Peter

2015-10-23

Sacral neuromodulation is well established in the treatment of refractory, non-neurogenic lower urinary tract dysfunction, but its efficacy and safety in patients with lower urinary tract dysfunction of neurological origin is unclear. Only few case series have been reported for multiple sclerosis. We prospectively evaluated the efficacy and safety of sacral neuromodulation in patients with multiple sclerosis. Seventeen patients (13 women, 4 men) treated with sacral neuromodulation for refractory neurogenic lower urinary tract dysfunction caused by multiple sclerosis were prospectively enrolled (2007-2011). Patients had to have stable disease and confirmed neurogenic lower urinary tract dysfunction. Voiding variables, adverse events, and subjective satisfaction were assessed. Sixteen (94 %) patients had a positive test phase with a >70 % improvement. After implantation of the pulse generator (InterStim II), the improvement in voiding variables persisted. At 3 years, the median voided volume had improved significantly from 125 (range 0 to 350) to 265 ml (range 200 to 350) (p < 0.001), the post void residual from 170 (range 0 to 730) to 25 ml (range 0 to 300) (p = 0.01), micturition frequency from 12 (range 6 to 20) to 7 (range 4 to 12) (p = 0.003), and number of incontinence episodes from 3 (range 0 to 10) to 0 (range 0 to 1) (p = 0.006). The median subjective degree of satisfaction was 80 %. Only two patients developed lack of benefit. No major complications occurred. Chronic sacral neuromodulation promises to be an effective and safe treatment of refractory neurogenic lower urinary tract dysfunction in selected patients with multiple sclerosis.

Effect of Carbon Ion Radiotherapy for Sacral Chordoma: Results of Phase I-II and Phase II Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imai, Reiko, E-mail: r_imai@nirs.go.j; Kamada, Tadashi; Tsuji, Hiroshi

2010-08-01

Purpose: To summarize the results of treatment for sacral chordoma in Phase I-II and Phase II carbon ion radiotherapy trials for bone and soft-tissue sarcomas. Patients and Methods: We performed a retrospective analysis of 38 patients with medically unresectable sacral chordomas treated with the Heavy Ion Medical Accelerator in Chiba, Japan between 1996 and 2003. Of the 38 patients, 30 had not received previous treatment and 8 had locally recurrent tumor after previous resection. The applied carbon ion dose was 52.8-73.6 Gray equivalents (median, 70.4) in a total of 16 fixed fractions within 4 weeks. Results: The median patient agemore » was 66 years. The cranial tumor extension was S2 or greater in 31 patients. The median clinical target volume was 523 cm{sup 3}. The median follow-up period was 80 months. The 5-year overall survival rate was 86%, and the 5-year local control rate was 89%. After treatment, 27 of 30 patients with primary tumor remained ambulatory with or without supportive devices. Two patients experienced severe skin or soft-tissue complications requiring skin grafts. Conclusion: Carbon ion radiotherapy appears effective and safe in the treatment of patients with sacral chordoma and offers a promising alternative to surgery.« less

Effects of acute urinary bladder overdistension on bladder response during sacral neurostimulation.

PubMed

Bross, S; Schumacher, S; Scheepe, J R; Zendler, S; Braun, P M; Alken, P; Jünemann, K

1999-10-01

Urinary retention and micturition disorders after overdistension are clinically well-known complications of subvesical obstruction. We attempted to evaluate whether bladder overdistension influences bladder response and whether overdistension supports detrusor decompensation. Following lumbal laminectomy in 9 male foxhounds, the sacral anterior roots S2 and S3 were placed into a modified Brindley electrode for reproducible and controlled detrusor activation. The bladder was filled in stages of 50 ml from 0 to 700 ml, corresponding to an overdistension. At each volume, the bladder response during sacral anterior root stimulation was registered. After overdistension, the bladder was refilled stepwise from 0 to 300 ml and stimulated. In all dogs, the bladder response was influenced by the intravesical volume. The maximum pressure (mean 69.1 cm H(2)O) was observed at mean volume of 100 ml. During overdistension, a significant reduction in bladder response of more than 80% was seen. After overdistension, a significant reduction in intravesical pressure of 19.0% was observed. In 2 cases, reduction in bladder response was more than 50% after a single overdistension. We conclude that motoric bladder function is influenced during and after overdistension. A single bladder overdistension can support acute and long-lasting detrusor decompensation. In order to protect motoric bladder function, bladder overdistension must be prevented.

Sacral medial telangiectatic vascular nevus: a study of 43 children.

PubMed

Patrizi, A; Neri, I; Orlandi, C; Marini, R

1996-01-01

Medial telangiectatic vascular nevi are capillary vascular malformations frequently observed at birth occurring mostly on the face or on the nape as a single lesion or as multiple macules affecting more than one site simultaneously. In 1990, Metzker and Shamir reported a medial telangiectatic vascular nevus (MTVN) in the sacral region along the midline and called this particular variety of MTVN 'butterfly-shaped mark'. Our study was performed to investigate the morphology and localization of an MTVN in the sacral region (sMTVN) in a group of Caucasian children. We observed 43 children with sMTVN, ranging in age from 1 month to 12 years (mean 8 years), for a period of 6 years. sMTVN was found as a red-violet macular lesion of rhomboid or triangular shape in 16 patients and as a group of little red-violet macules in 10 patients. In 16 patients moreover the whole back was involved with many small red-violet spots on and around the spinal column, and in 1 patient with classic sMTVN satellite macules were also present over both buttocks. Four patients suffered from epilepsy with mental deficiency. In 6 patients, the family history showed sMTVN in one or more members of the family. No case presented an association with spina bifida. In our study, sMTVN shows a morphological polymorphism while Metzker and Shamir reported the same clinical aspect in all 25 of their patients. In accordance with these authors, we noted that sMTVN persist into childhood and adult life in the same way as occipital MTVN.

Effectiveness and Value of Prophylactic 5-Layer Foam Sacral Dressings to Prevent Hospital-Acquired Pressure Injuries in Acute Care Hospitals: An Observational Cohort Study.

PubMed

Padula, William V

The purpose of this study was to examine the effectiveness and value of prophylactic 5-layer foam sacral dressings to prevent hospital-acquired pressure injury rates in acute care settings. Retrospective observational cohort. We reviewed records of adult patients 18 years or older who were hospitalized at least 5 days across 38 acute care hospitals of the University Health System Consortium (UHC) and had a pressure injury as identified by Patient Safety Indicator #3 (PSI-03). All facilities are located in the United States. We collected longitudinal data pertaining to prophylactic 5-layer foam sacral dressings purchased by hospital-quarter for 38 academic medical centers between 2010 and 2015. Longitudinal data on acute care, hospital-level patient outcomes (eg, admissions and PSI-03 and pressure injury rate) were queried through the UHC clinical database/resource manager from the Johns Hopkins Medicine portal. Data on volumes of dressings purchased per UHC hospital were merged with UHC data. Mixed-effects negative binomial regression was used to test the longitudinal association of prophylactic foam sacral dressings on pressure injury rates, adjusted for hospital case-mix and Medicare payments rules. Significant pressure injury rate reductions in US acute care hospitals between 2010 and 2015 were associated with the adoption of prophylactic 5-layer foam sacral dressings within a prevention protocol (-1.0 cases/quarter; P = .002) and changes to Medicare payment rules in 2014 (-1.13 cases/quarter; P = .035). Prophylactic 5-layer foam sacral dressings are an effective component of a pressure injury prevention protocol. Hospitals adopting these technologies should expect good value for use of these products.

Relative Importance of Hip and Sacral Pain Among Long-Term Gynecological Cancer Survivors Treated With Pelvic Radiotherapy and Their Relationships to Mean Absorbed Doses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waldenstroem, Ann-Charlotte, E-mail: ann-charlotte.waldenstrom@oncology.gu.se; Department of Oncology, Sahlgrenska University Hospital, Gothenburg; Olsson, Caroline

Purpose: To investigate the relative importance of patient-reported hip and sacral pain after pelvic radiotherapy (RT) for gynecological cancer and its relationship to the absorbed doses in these organs. Methods and Materials: We used data from a population-based study that included 650 long-term gynecological cancer survivors treated with pelvic RT in the Gothenburg and Stockholm areas in Sweden with a median follow-up of 6 years (range, 2-15) and 344 population controls. Symptoms were assessed through a study-specific postal questionnaire. We also analyzed the hip and sacral dose-volume histogram data for 358 of the survivors. Results: Of the survivors, one inmore » three reported having or having had hip pain after completing RT. Daily pain when walking was four times as common among the survivors compared to controls. Symptoms increased in frequency with a mean absorbed dose >37.5 Gy. Also, two in five survivors reported pain in the sacrum. Sacral pain also affected their walking ability and tended to increase with a mean absorbed dose >42.5 Gy. Conclusions: Long-term survivors of gynecological cancer treated with pelvic RT experience hip and sacral pain when walking. The mean absorbed dose was significantly related to hip pain and was borderline significantly related to sacral pain. Keeping the total mean absorbed hip dose below 37.5 Gy during treatment might lower the occurrence of long-lasting pain. In relation to the controls, the survivors had a lower occurrence of pain and pain-related symptoms from the hips and sacrum compared with what has previously been reported for the pubic bone.« less

Exhausted implanted pulse generator in sacral nerve stimulation for faecal incontinence: What next in daily practice for patients?

PubMed

Duchalais, Emilie; Meurette, Guillaume; Perrot, Bastien; Wyart, Vincent; Kubis, Caroline; Lehur, Paul-Antoine

2016-02-01

The efficacy of sacral nerve stimulation in faecal incontinence relies on an implanted pulse generator known to have a limited lifespan. The long-term use of sacral nerve stimulation raises concerns about the true lifespan of generators. The aim of the study was to assess the lifespan of sacral nerve stimulation implanted pulse generators in daily practice, and the outcome of exhausted generator replacement, in faecal incontinent patients. Faecal incontinent patients with pulse generators (Medtronic Interstim™ or InterstimII™) implanted in a single centre from 2001 to 2014 were prospectively followed up. Generator lifespan was measured according to the Kaplan-Meier method. Patients with a generator explanted/turned off before exhaustion were excluded. Morbidity of exhausted generator replacement and the outcome (Cleveland Clinic Florida Faecal Incontinence (CCF-FI) and Faecal Incontinence Quality of Life (FIQL) scores) were recorded. Of 135 patients with an implanted pulse generator, 112 (InterstimII 66) were included. Mean follow-up was 4.9 ± 2.8 years. The generator reached exhaustion in 29 (26%) cases. Overall median lifespan of an implanted pulse generator was approximately 9 years (95% CI 8-9.2). Interstim and InterstimII 25th percentile lifespan was 7.2 (CI 6.4-8.3) and 5 (CI 4-not reached) years, respectively. After exhaustion, generators were replaced, left in place or explanted in 23, 2 and 4 patients, respectively. Generator replacement was virtually uneventful. CCF-FI/FIQL scores remained unchanged after generator replacement (CCF-FI 8 ± 2 vs 7 ± 3; FIQL 3 ± 0.6 vs 3 ± 0.5; p = ns). In this study, the implanted pulse generator observed median lifespan was 9 years. After exhaustion, generators were safely and efficiently replaced. The study also gives insight into long-term needs and costs of sacral nerve stimulation (SNS) therapy.

A case of Capnocytophaga canimorsus sacral abscess in an immunocompetent patient.

PubMed

Joswig, H; Gers, B; Dollenmaier, G; Heilbronner, R; Strahm, C

2015-04-01

We report a unique case of sacral Capnocytophaga canimorsus abscess successfully treated with surgery and antibiotics. Close contact to a dog was assumed to be the most likely source of infection. Established risk factors for invasive C. canimorsus infection such as splenectomy, alcoholism or overt immunosuppression could not be identified. The role of cigarette smoking, portal of entry and the possible relevance of altered skin microbiota as well as the diagnostic value of polymerase chain reaction are discussed in the light of the scarce literature of spinal C. canimorsus infections.

Formation of the sacrum requires down-regulation of sonic hedgehog signaling in the sacral intervertebral discs.

PubMed

Bonavita, Raffaella; Vincent, Kathleen; Pinelli, Robert; Dahia, Chitra Lekha

2018-05-21

In humans, the sacrum forms an important component of the pelvic arch, and it transfers the weight of the body to the lower limbs. The sacrum is formed by collapse of the intervertebral discs (IVDs) between the five sacral vertebrae during childhood, and their fusion to form a single bone. We show that collapse of the sacral discs in the mouse is associated with the down-regulation of sonic hedgehog (SHH) signaling in the nucleus pulposus (NP) of the disc, and many aspects of this phenotype can be reversed by experimental postnatal activation of HH signaling. We have previously shown that SHH signaling is essential for the normal postnatal growth and differentiation of intervertebral discs elsewhere in the spine, and that loss of SHH signaling leads to pathological disc degeneration, a very common disorder of aging. Thus, loss of SHH is pathological in one region of the spine but part of normal development in another. © 2018. Published by The Company of Biologists Ltd.

Effective treatment of dyssynergic defecation using sacral neuromodulation in a patient with cerebral palsy.

PubMed

Chan, Daniel K; Barker, Matthew A

2015-01-01

Dyssynergic defecation is a complex bowel problem that leads to chronic constipation and abdominal pain. Management is often challenging owing to the incoordination of multiple pelvic floor muscles involved in normal defecation. We report a case of dyssynergic defecatory dysfunction in a patient with cerebral palsy treated with sacral neuromodulation. At presentation, Sitz marker study and magnetic resonance defecography showed evidence of chronic functional constipation. Anorectal manometry, rectal anal inhibitory reflex, and rectal sensation study showed intact reflex and decreased first sensation of lower canal at 50 mL. After stage 2 of InterStim implant placement, bowel habits improved to once- to twice-daily soft solid bowel movements from no regular solid bowel movements. Fecal incontinence improved from daily liquid and small solid loss to no stool leakage. In patients with systemic medical problems contributing to defecatory dysfunction and bowel incontinence, such as cerebral palsy, sacral neuromodulation was found to provide significant relief of bowel symptoms in addition to associated abdominal pain. As a result of intervention, the patient reported significant improvement in quality of life and less limitations due to dyssynergic defecation.

Psoas compartment and sacral plexus block via electrostimulation for pelvic limb amputation in dogs.

PubMed

Congdon, Jonathon M; Boscan, Pedro; Goh, Clara S S; Rezende, Marlis

2017-07-01

To assess the efficacy of psoas compartment and sacral plexus block for pelvic limb amputation in dogs. Prospective clinical study. A total of 16 dogs aged 8±3 years and weighing 35±14 kg (mean±standard deviation). Dogs were administered morphine (0.5 mg kg -1 ) and atropine (0.02 mg kg -1 ); anesthesia was induced with propofol and maintained with isoflurane. Regional blocks were performed before surgery in eight dogs with bupivacaine (2.2 mg kg -1 ) and eight dogs were administered an equivalent volume of saline. The lumbar plexus within the psoas compartment was identified using electrolocation lateral to the lumbar vertebrae at the fourth-fifth, fifth-sixth and sixth-seventh vertebral interspaces. The sacral plexus, ventrolateral to the sacrum, was identified using electrolocation. Anesthesia was monitored using heart rate (HR), invasive blood pressure, electrocardiography, expired gases, respiratory frequency and esophageal temperature by an investigator unaware of the group allocation. Pelvic limb amputation by coxofemoral disarticulation was performed. Dogs that responded to surgical stimulation (>10% increase in HR or arterial pressure) were administered fentanyl (2 μg kg -1 ) intravenously for rescue analgesia. Postoperative pain was assessed at extubation; 30, 60 and 120 minutes; and the morning after surgery using a visual analog scale (VAS). The number of intraoperative fentanyl doses was fewer in the bupivacaine group (2.7±1.1 versus 6.0±2.2; p<0.01). Differences in physiologic variables were not clinically significant. VAS scores were lower in bupivacaine dogs at extubation (0.8±1.9 versus 3.8±2.5) and at 30 minutes (1.0±1.4 versus 4.3±2.1; p<0.05). Psoas compartment (lumbar plexus) and sacral plexus block provided analgesia during pelvic limb amputation in dogs. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Diagnosis and treatment of posterior sacroiliac complex pain: a systematic review with comprehensive analysis of the published data.

PubMed

King, Wade; Ahmed, Shihab U; Baisden, Jamie; Patel, Nileshkumar; Kennedy, David J; Duszynski, Belinda; MacVicar, John

2015-02-01

To assess the evidence on the validity of sacral lateral branch blocks and the effectiveness of sacral lateral branch thermal radiofrequency neurotomy in managing sacroiliac complex pain. Systematic review with comprehensive analysis of all published data. Six reviewers searched the literature on sacral lateral branch interventions. Each assessed the methodologies of studies found and the quality of the evidence presented. The outcomes assessed were diagnostic validity and effectiveness of treatment for sacroiliac complex pain. The evidence found was appraised in accordance with the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system of evaluating scientific evidence. The searches yielded two primary publications on sacral lateral branch blocks and 15 studies of the effectiveness of sacral lateral branch thermal radiofrequency neurotomy. One study showed multisite, multidepth sacral lateral branch blocks can anesthetize the posterior sacroiliac ligaments. Therapeutic studies show sacral lateral branch thermal radiofrequency neurotomy can relieve sacroiliac complex pain to some extent. The evidence of the validity of these blocks and the effectiveness of this treatment were rated as moderate in accordance with the GRADE system. The literature on sacral lateral branch interventions is sparse. One study demonstrates the face validity of multisite, multidepth sacral lateral branch blocks for diagnosis of posterior sacroiliac complex pain. Some evidence of moderate quality exists on therapeutic procedures, but it is insufficient to determine the indications and effectiveness of sacral lateral branch thermal radiofrequency neurotomy, and more research is required. Wiley Periodicals, Inc.

A urodynamic study of surface neuromodulation versus sham in detrusor instability and sensory urgency.

PubMed

Bower, W F; Moore, K H; Adams, R D; Shepherd, R

1998-12-01

We studied the effect of surface neuromodulation on cystometric pressure and volume parameters in women with detrusor instability or sensory urgency. Electrical current was delivered to the suprapubic region and third sacral foramina via a transcutaneous electrical nerve stimulator with sham neuromodulation control. A consecutive series of women with proved detrusor instability or sensory urgency were randomized to 3 surface neuromodulation groups. Volume and pressure parameters were the main outcomes of transcutaneous electrical nerve stimulation applied during second cystometric fill. Sham transcutaneous electrical nerve stimulation did not alter the outcome measures. However, neuromodulation delivered across the suprapubic and sacral skin effected a reduction in mean maximum height of detrusor contraction. A current which inhibits motor activity was not superior to that which inhibits sensory perception in reducing detrusor pressure. Response in sensory urgency was poor. Results from our sham controlled study suggest that short-term surface neuromodulation via transcutaneous electrical nerve stimulation may have a role in the treatment of detrusor instability. Future studies must examine the clinical effect of long-term surface neuromodulation.

The effect of early operative stabilization on late displacement of zone I and II sacral fractures.

PubMed

Emohare, Osa; Slinkard, Nathaniel; Lafferty, Paul; Vang, Sandy; Morgan, Robert

2013-02-01

This study was designed to evaluate the effect on displacement of early operative stabilization on unstable fractures when compared to stable fractures of the sacrum. Patient consisted of those sustaining traumatic pelvic fractures that also included sacral fractures of Denis type I and type II classification, who were over 18 at the time of the study. Patients were managed emergently, as judged appropriate at the time and then subsequently divided into two cohorts, comprising those who were either treated operatively or non-operatively. The operative group comprised those treated with either internal fixation or external fixation. Twenty-eight patients had zone II fractures, and 20 had zone I fractures. Zone II fractures showed average displacements of 6.5mm and 6.9mm in the rostral-caudal and anteroposterior directions, respectively, at final follow up. Zone I fractures had average displacements of 6.6mm and 6.1mm in both directions. There were no significant differences between zone I and II sacral fractures (rostral-caudal P=0.74, anteroposterior P=0.24). Average changes in fracture displacement in patients with zone I fractures were 0.6-1.0mm in both directions. Average changes in zone II fractures were 1.8-1.5mm in both directions. There were no significant differences between the average changes in zone I and II fractures in any direction (rostral-caudal P=0.64, anteroposterior P=0.68) or in average displacements at final follow up in any of zone or the entire cohort. Statistically significant differences were noted in average changes in displacement in zone II fractures in the anteroposterior plane (P=0.03) and the overall cohort in the anteroposterior plane (P=0.02). Operative fixation for unstable sacral fractures ensures displacement at follow up is comparable with stable fractures treated non operatively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Sacral nerve stimulation for neuromodulation of the lower urinary tract.

PubMed

Hubsher, Chad P; Jansen, Robert; Riggs, Dale R; Jackson, Barbara J; Zaslau, Stanley

2012-10-01

Sacral neuromodulation (SNM) has become a standard treatment option for patients suffering from urinary urge incontinence, urgency-frequency, and/or nonobstructive urinary retention refractory to conservative and pharmacologic treatment. Since its initial development, the manufacturer of InterStim therapy (Medtronic, Inc., Minneapolis, MN, USA), has introduced technical modifications, while surgeons and researchers have adapted and published various innovations and alterations of the implantation technique. In this article, we feature our SNM technique including patient selection, comprehensive dialogue/evaluation, procedure details, and appropriate follow up. Although there is often great variability in patients with lower urinary tract dysfunction, we maintain that great success can be achieved with a systematic and methodical approach to SNM.

Multielectrode array recordings of bladder and perineal primary afferent activity from the sacral dorsal root ganglia

NASA Astrophysics Data System (ADS)

Bruns, Tim M.; Gaunt, Robert A.; Weber, Douglas J.

2011-10-01

The development of bladder and bowel neuroprostheses may benefit from the use of sensory feedback. We evaluated the use of high-density penetrating microelectrode arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized cats. Neural signals were recorded while the bladder volume was modulated and mechanical stimuli were applied to the perineal region. In two experiments, 48 units were observed that tracked bladder pressure with their firing rates (79% from S2). At least 50 additional units in each of the three experiments (274 total; 60% from S2) had a significant change in their firing rates during one or more perineal stimulation trials. This study shows the feasibility of obtaining bladder-state information and other feedback signals from the pelvic region with a sacral DRG electrode interface located in a single level. This natural source of feedback would be valuable for providing closed-loop control of bladder or other pelvic neuroprostheses.

Medtronic, Inc.; premarket approval of the Interstim Sacral Nerve Stimulation (SNS) System--FDA. Notice.

PubMed

1998-01-29

The Food and Drug Administration (FDA) is announcing its approval of the application by Medtronic, Inc., Minneapolis, MN, for premarket approval, under the Federal Food, Drug, and Cosmetic Act (the act), of the Interstim Sacral Nerve Stimulation (SNS) System. After reviewing the recommendation of the Gastroenterology and Urology Devices Panel, FDA's Center for Devices and Radiological Health (CDRH) notified the applicant, by letter of September 29, 1997, of the approval of the application.

Evaluation of the Diagnostic Accuracy of Conventional 2-Dimensional and 3-Dimensional Computed Tomography for Assessing Canine Sacral and Pelvic Fractures by Radiologists, Orthopedic Surgeons, and Veterinary Medical Students.

PubMed

Stieger-Vanegas, Susanne M; Senthirajah, Sri Kumar Jamie; Nemanic, Sarah; Baltzer, Wendy; Warnock, Jennifer; Hollars, Katelyn; Lee, Scott S; Bobe, Gerd

2015-08-01

To determine, using 3 groups of evaluators of varying experience reading orthopedic CT studies, if 3-dimensional computed tomography (3D-CT) provides a more accurate and time efficient method for diagnosis of canine sacral and pelvic fractures, and displacements of the sacroiliac and coxofemoral joints compared with 2-dimensional computed tomography (2D-CT). Retrospective clinical and prospective study. Dogs (n = 23): 12 dogs with traumatic pelvic fractures, 11 canine cadavers with pelvic trauma induced by a lateral impactor. All dogs had a 2D-CT exam of the pelvis and subsequent 3D-CT reconstructions from the 2D-CT images. Both 2D-CT and 3D-CT studies were anonymized and randomly presented to 2 veterinary radiologists, 2 veterinary orthopedic surgeons, and 2 veterinary medical students. Evaluators classified fractures using a confidence scale and recorded the duration of evaluation for each modality and case. 3D-CT was a more time-efficient technique for evaluation of traumatic sacral and pelvic injuries compared with 2D-CT in all evaluator groups irrespective of experience level reading orthopedic CT studies. However, for radiologists and surgeons, 2D-CT was the more accurate technique for evaluating sacral and pelvic fractures. 3D-CT improves sacral and pelvic fracture diagnosis when added to 2D-CT; however, 3D-CT has a reduced accuracy for evaluation of sacral and pelvic fractures if used without concurrent evaluation of 2D-CT images. © Copyright 2014 by The American College of Veterinary Surgeons.

A multi-level rapid prototyping drill guide template reduces the perforation risk of pedicle screw placement in the lumbar and sacral spine.

PubMed

Merc, Matjaz; Drstvensek, Igor; Vogrin, Matjaz; Brajlih, Tomaz; Recnik, Gregor

2013-07-01

The method of free-hand pedicle screw placement is generally safe although it carries potential risks. For this reason, several highly accurate computer-assisted systems were developed and are currently on the market. However, these devices have certain disadvantages. We have developed a method of pedicle screw placement in the lumbar and sacral region using a multi-level drill guide template, created with the rapid prototyping technology and have validated it in a clinical study. The aim of the study was to manufacture and evaluate the accuracy of a multi-level drill guide template for lumbar and first sacral pedicle screw placement and to compare it with the free-hand technique under fluoroscopy supervision. In 2011 and 2012, a randomized clinical trial was performed on 20 patients. 54 screws were implanted in the trial group using templates and 54 in the control group using the fluoroscopy-supervised free-hand technique. Furthermore, applicability for the first sacral level was tested. Preoperative CT-scans were taken and templates were designed using the selective laser sintering method. Postoperative evaluation and statistical analysis of pedicle violation, displacement, screw length and deviation were performed for both groups. The incidence of cortex perforation was significantly reduced in the template group; likewise, the deviation and displacement level of screws in the sagittal plane. In both groups there was no significantly important difference in deviation and displacement level in the transversal plane as not in pedicle screw length. The results for the first sacral level resembled the main investigated group. The method significantly lowers the incidence of cortex perforation and is therefore potentially applicable in clinical practice, especially in some selected cases. The applied method, however, carries a potential for errors during manufacturing and practical usage and therefore still requires further improvements.

Robot-assisted radiofrequency ablation of a sacral S1-S2 aggressive hemangioma.

PubMed

Kaoudi, A; Capel, C; Chenin, L; Peltier, J; Lefranc, M

2018-05-16

Aggressive vertebral hemangiomas are rare tumors of the spine. The treatment management strategy usually consists of vertebroplasty, radiation therapy or in rare cases of surgical strategy. We present a case of a bulging sacral S1-S2 hemangioma in the spinal canal that could not be managed in the usual manner. Here, we demonstrate the usefulness of radiofrequency ablation technique as an alternative treatment as well as robotic assistance for optimal placement of the ablation probe within the lesion. Copyright © 2018. Published by Elsevier Inc.

Spastic long-lasting reflexes in the awake rat after sacral spinal cord injury.

PubMed

Bennett, D J; Sanelli, L; Cooke, C L; Harvey, P J; Gorassini, M A

2004-05-01

Following chronic sacral spinal cord transection in rats the affected tail muscles exhibit marked spasticity, with characteristic long-lasting tail spasms evoked by mild stimulation. The purpose of the present paper was to characterize the long-lasting reflex seen in tail muscles in response to electrical stimulation of the tail nerves in the awake spastic rat, including its development with time and relation to spasticity. Before and after sacral spinal transection, surface electrodes were placed on the tail for electrical stimulation of the caudal nerve trunk (mixed nerve) and for recording EMG from segmental tail muscles. In normal and acute spinal rats caudal nerve trunk stimulation evoked little or no EMG reflex. By 2 wk after injury, the same stimulation evoked long-lasting reflexes that were 1) very low threshold, 2) evoked from rest without prior EMG activity, 3) of polysynaptic latency with >6 ms central delay, 4) about 2 s long, and 5) enhanced by repeated stimulation (windup). These reflexes produced powerful whole tail contractions (spasms) and developed gradually over the weeks after the injury (< or =52 wk tested), in close parallel to the development of spasticity. Pure low-threshold cutaneous stimulation, from electrical stimulation of the tip of the tail, also evoked long-lasting spastic reflexes, not seen in acute spinal or normal rats. In acute spinal rats a strong C-fiber stimulation of the tip of the tail (20 x T) could evoke a weak EMG response lasting about 1 s. Interestingly, when this C-fiber stimulation was used as a conditioning stimulation to depolarize the motoneuron pool in acute spinal rats, a subsequent low-threshold stimulation of the caudal nerve trunk evoked a 300-500 ms long reflex, similar to the onset of the long-lasting reflex in chronic spinal rats. A similar conditioned reflex was not seen in normal rats. Thus there is an unusually long low-threshold polysynaptic input to the motoneurons (pEPSP) that is normally inhibited by

Hydronephrosis Presenting 6 Months After Sacral Colpopexy: Case Report and Literature Review.

PubMed

Weber LeBrun, Emily; Santamaria, Estefania; Moy, Louis

The aim of this study was to describe a case of uterovaginal prolapse managed with robotic-assisted sacral colpopexy complicated by severe right-sided hydronephrosis despite normal intraoperative cystoscopy. A 68-year-old woman presented with a worsening vaginal bulge over the past 2 years. Tricompartment stage 2 uterovaginal prolapse, with dominant cystocele and skin erosion at the posterior fourchette from prolapse friction, was identified on physical examination, and the patient underwent pelvic reconstructive surgery, including sacral colpopexy. The patient was discharged on postoperative day 4 after being treated for a urinary tract infection. At her 6-week postoperative visit, the patient demonstrated normal vaginal support. She presented 6 months postoperatively with right-sided hydronephrosis with an almost imperceptible stricture where the right iliac vessels cross the pelvic brim, demonstrating a delayed manifestation of ureteral injury. She underwent open ureteroscopy, ureteroneocystostomy with vesicopsoas hitch, and ureteral stent placement. Ureteroscopy demonstrated a very mild narrowed caliber of the ureter just above the sacroiliac joint without overt obstruction. Follow-up intravenous pyelogram demonstrated no evidence of damage or obstruction. At nearly 1-year follow-up, the patient remained asymptomatic and had normal renal function. This case demonstrates the challenges of an uncommon, but highly morbid, complication of pelvic reconstructive surgery. Even when adequate visualization of the ureters and delicate ureteral dissection is achieved throughout surgery, occult injuries can still occur. Surgeons should maintain a high index of suspicion of ureteral injury when evaluating patients for late presentations of postoperative complications.

A new technique for long time catheterization of sacral epidural canal in rabbits.

PubMed

Erkin, Yüksel; Aydın, Zeynep; Taşdöğen, Aydın; Karcı, Ayşe

2013-01-01

In this study we aimed to develop a simple and practical technique for chronic sacral epidural catheterization of rabbits. We included ten rabbits weighing 2-2.5 kg in the study. After anesthesia and analgesia, we placed an epidural catheter by a 2 cm longitudinal skin incision in the tail above the sacral hiatus region. We confirmed localization by giving 1% lidocaine (leveling sensory loss and motor function loss of the lower extremity). The catheter was carried forward through a subcutaneous tunnel and fixed at the neck. Chronic caudal epidural catheter placement was succesful in all rabbits. The catheters stayed in place effectively for ten days. We encountered no catheter complications during this period. The localization of the catheter was reconfirmed by 1% lidocaine on the last day. After animals killing, we performed a laminectomy and verified localization of the catheter in the epidural space. Various methods for catheterization of the epidural space in animal models exist in the literature. Epidural catheterization of rabbits can be accomplished by atlanto-occipital, lumbar or caudal routes by amputation of the tail. Intrathecal and epidural catheterization techniques defined in the literature necessitate surgical skill and knowledge of surgical procedures like laminectomy and tail amputation. Our technique does not require substantial surgical skill, anatomical integrity is preserved and malposition of the catheter is not encountered. In conclusion, we suggest that our simple and easily applicable new epidural catheterization technique can be used as a model in experimental animal studies.

Surgical anesthesia with a combination of T12 paravertebral block and lumbar plexus, sacral plexus block for hip replacement in ankylosing spondylitis: CARE-compliant 4 case reports.

PubMed

Ke, Xijian; Li, Ji; Liu, Yong; Wu, Xi; Mei, Wei

2017-06-26

Anesthesia management for patients with severe ankylosing spondylitis scheduled for total hip arthroplasty is challenging due to a potential difficult airway and difficult neuraxial block. We report 4 cases with ankylosing spondylitis successfully managed with a combination of lumbar plexus, sacral plexus and T12 paravertebral block. Four patients were scheduled for total hip arthroplasty. All of them were diagnosed as severe ankylosing spondylitis with rigidity and immobilization of cervical and lumbar spine and hip joints. A combination of T12 paravertebral block, lumbar plexus and sacral plexus block was successfully used for the surgery without any additional intravenous anesthetic or local anesthetics infiltration to the incision, and none of the patients complained of discomfort during the operations. The combination of T12 paravertebral block, lumbar plexus and sacral plexus block, which may block all nerves innervating the articular capsule, surrounding muscles and the skin involved in total hip arthroplasty, might be a promising alternative for total hip arthroplasty in ankylosing spondylitis.

[An adult case of intradural lumbo-sacral lipoma].

PubMed

Hatayama, T; Sakoda, K; Tokuda, Y; Uozumi, T

1992-10-01

A rare case of lumbo-sacral lipoma in an adult case is reported. A 55-year-old male was admitted to the Department of Neurosurgery, Mazda Hospital, after a history of one year of urinary incontinence. Neurologically, no motor or sensory disturbance of the lower extremities was found in this patient. MRI showed a mass with high signal intensity on T2-weighted image, located between L3 to S2 vertebral segments. Metrizamide-CT scan demonstrated the outline of this hypodense mass at the same location as shown on MRI image. A L3 through L5 laminectomy was performed and the tumor was subtotally removed. Microscopic examination revealed that the tumor mass was made up of mature lipoma cells. Postoperative course of the patient was uneventful. The urinary incontinence was improved slightly. No motor or sensory deficit was found. We thought that MRI was useful for the correct diagnosis of lumbosacral lipoma. And it is best managed by operative removal of the tumor as early as possible after it is diagnosed.

Delayed Union of a Sacral Fracture: Percutaneous Navigated Autologous Cancellous Bone Grafting and Screw Fixation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huegli, R. W.; Messmer, P.; Jacob, A. L.

2003-09-15

Delayed or non-union of a sacral fracture is a serious clinical condition that may include chronic pain, sitting discomfort, gait disturbances, neurological problems, and inability to work. It is also a difficult reconstruction problem. Late correction of the deformity is technically more demanding than the primary treatment of acute pelvic injuries. Open reduction, internal fixation (ORIF), excision of scar tissue, and bone grafting often in a multi-step approach are considered to be the treatment of choice in delayed unions of the pelvic ring. This procedure implies the risk of neurological and vascular injuries, infection, repeated failure of union, incomplete correctionmore » of the deformity, and incomplete pain relief as the most important complications. We report a new approach for minimally invasive treatment of a delayed union of the sacrum without vertical displacement. A patient who suffered a Malgaigne fracture (Tile C1.3) was initially treated with closed reduction and percutaneous screw fixation (CRPF) of the posterior pelvic ring under CT navigation and plating of the anterior pelvic ring. Three months after surgery he presented with increasing hip pain caused by a delayed union of the sacral fracture. The lesion was successfully treated percutaneously in a single step procedure using CT navigation for drilling of the delayed union, autologous bone grafting, and screw fixation.« less

Evidence that the notochord may be pivotal in the development of sacral and anorectal malformations.

PubMed

Qi, Bao Quan; Beasley, Spencer W; Frizelle, Francis A

2003-09-01

The notochord is known to organize normal development of central axial structures, such as the spinal cord, vertebral column, and anorectum, but its role in abnormal development of these organs has not been well documented. The current study has used Ethylenethiourea to induce anorectal malformations in fetal rats, allowing investigation of abnormalities of the notochord and their relationship to the axial structural abnormalities that occur. Timed-mated pregnant rats were fed Ethylenethiourea by gavage on gestational day 10. Their embryos were harvested on gestational days 13 to 16 and sectioned in either the transverse or sagittal plane. Sections were stained with H and E and examined serially. Anorectal malformations were identified in 29 of 34 embryos and neural tube defects in 24, ranging from an accessory neural tube to lumbo-sacral rachischisis. There was no tail or only a rudimentary tail in the majority of embryos. Abnormalities of the notochord in the lumbo-sacral area included ventro-dorsal branching, ventral deviation, and ectopic notochordal tissue. Most abnormal notochord branches and ectopic notochordal tissue were abnormally close to or in contact with the wall of the cloaca or neural tube. Given the known role of the notochord in controlling normal development, this study would suggest that abnormal notochord development may be pivotal in producing neural tube defects and anorectal malformations, possibly by altering sonic hedgehog signalling.

Combined V-Y Fasciocutaneous Advancement and Gluteus Maximus Muscle Rotational Flaps for Treating Sacral Sores

PubMed Central

Choi, Eun Jeong; Moon, Suk Ho; Lee, Yoon Jae

2016-01-01

The sacral area is the most common site of pressure sore in bed-ridden patients. Though many treatment methods have been proposed, a musculocutaneous flap using the gluteus muscles or a fasciocutaneous flap is the most popular surgical option. Here, we propose a new method that combines the benefits of these 2 methods: combined V-Y fasciocutaneous advancement and gluteus maximus muscle rotational flaps. A retrospective review was performed for 13 patients who underwent this new procedure from March 2011 to December 2013. Patients' age, sex, accompanying diseases, follow-up duration, surgical details, complications, and recurrence were documented. Computed tomography was performed postoperatively at 2 to 4 weeks and again at 4 to 6 months to identify the thickness and volume of the rotational muscle portion. After surgery, all patients healed within 1 month; 3 patients experienced minor complications. The average follow-up period was 13.6 months, during which time 1 patient had a recurrence (recurrence rate, 7.7%). Average thickness of the rotated muscle was 9.43 mm at 2 to 4 weeks postoperatively and 9.22 mm at 4 to 6 months postoperatively (p = 0.087). Muscle thickness had not decreased, and muscle volume was relatively maintained. This modified method is relatively simple and easy for reconstructing sacral sores, provides sufficient padding, and has little muscle donor-site morbidity. PMID:27366755

Clinical Outcome of Sacral Chordoma With Carbon Ion Radiotherapy Compared With Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishida, Yoshihiro, E-mail: ynishida@med.nagoya-u.ac.j; Kamada, Tadashi; Imai, Reiko

Purpose: To evaluate the efficacy, post-treatment function, toxicity, and complications of carbon ion radiotherapy (RT) for sacral chordoma compared with surgery. Methods and Materials: The records of 17 primary sacral chordoma patients treated since 1990 with surgery (n = 10) or carbon ion RT (n = 7) were retrospectively analyzed for disease-specific survival, local recurrence-free survival, complications, and functional outcome. The applied carbon ion dose ranged from 54.0 Gray equivalent (GyE) to 73.6 GyE (median 70.4). Results: The mean age at treatment was 55 years for the surgery group and 65 years for the carbon ion RT group. The medianmore » duration of follow-up was 76 months for the surgery group and 49 months for the carbon ion RT group. The local recurrence-free survival rate at 5 years was 62.5% for the surgery and 100% for the carbon ion RT group, and the disease-specific survival rate at 5 years was 85.7% and 53.3%, respectively. Urinary-anorectal function worsened in 6 patients (60%) in the surgery group, but it was unchanged in all the patients who had undergone carbon ion RT. Postoperative wound complications requiring reoperation occurred in 3 patients (30%) after surgery and in 1 patient (14%) after carbon ion RT. The functional outcome evaluated using the Musculoskeletal Tumor Society scoring system revealed 55% in the surgery group and 75% in the carbon ion RT group. Of the six factors in this scoring system, the carbon ion RT group had significantly greater scores in emotional acceptance than did the surgery group. Conclusion: Carbon ion RT results in a high local control rate and preservation of urinary-anorectal function compared with surgery.« less

Onset of Action of Sacral Neuromodulation in Lower Urinary Tract Dysfunction-What is the Optimal Duration of Test Stimulation?

PubMed

Jairam, Ranjana; Drossaerts, Jamie; Marcelissen, Tom; van Koeveringe, Gommert; van Kerrebroeck, Philip

2018-06-01

Since the development of sacral neuromodulation, a large number of patients with lower urinary tract symptoms have been treated with this procedure. A test stimulation is performed prior to implantation. At centers worldwide the duration of this test stimulation varies considerably since it is not certain when the onset of the therapy effect can be expected. The objective of this prospective study was to evaluate the average onset time of sacral neuromodulation in patients with lower urinary tract symptoms. All patients who were eligible for treatment with sacral neuromodulation were asked to participate in this study. A voiding diary was filled out prior to and during test stimulation using an implanted tined lead. Success was defined as a 50% or greater improvement compared to baseline in any of the main complaint parameters. The Mann-Whitney U test was used to compare the mean time to success between patients with overactive bladder syndrome and patients with nonobstructive urinary retention. Of the 45 patients 24 with nonobstructive urinary retention and 21 with overactive bladder syndrome agreed to participate and were included in study. Test stimulation was successful in 29 patients (64%). Mean time to success in all patients was 3.3 days (range 1 to 9). There was no significant difference in mean time to success between cases of overactive bladder syndrome and nonobstructive urinary retention (3.25 and 3.5 days, respectively, p = 0.76). The results imply that a test stimulation of more than 2 weeks is not necessary if a cutoff of 50% or greater improvement is adopted. However, further improvement can be expected with prolonged test stimulation. This might be important since it might have implications for long-term results. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Sacral hemangiopericytoma involving the retrorectal space: report of a case.

PubMed

Zentar, Aziz; Sall, Ibrahima; Ali, Abdelmounaim Ait; Bouchentouf, Sidi Mohammed; Quamous, Mohammed; Chahdi, Hafsa; Hajjouji, Abderahmane; Fahssi, Mohammed; El Kaoui, Hakim; Al Bouzidi, Abderahmane; Marjani, Mohammed; Sair, Khalid; Bousselmame, Nabil

2009-01-01

A primary hemangiopericytoma (HP) of the bone is rare, because the vast majority of these tumors arise in soft tissue. This report presents a case of a hemangiopericytoma in the sacrum (S1-S2) with extension to the retrorectal space. Only a few cases of osseous hemangiopericytomas in the sacrum and involving the retrorectal space have so far been reported. The difficult diagnosis of HP and the surgical strategy was chosen according to the location of the lesion in the sacrum and retrorectal space. A local excision was indicated. A sacral resection should be considered for tumors below S4. This report demonstrated the safety of this strategy. Adjuvant radiotherapy is useful in HP. The value of chemotherapy is still doubtful, although patients with high-grade tumors or metastatic spread seem to gain substantial benefit. Due to the often unpredictable behavior of this neoplasm, extended follow-up is strongly recommended.

Chronic idiopathic anal pain. Results of a diagnostic-therapeutic protocol in a colorectal referral unit.

PubMed

Armañanzas, Laura; Arroyo, Antonio; Ruiz-Tovar, Jaime; López, Alberto; Santos, Jair; Moya, Pedro; Gómez, María Amparo; Candela, Fernando; Calpena, Rafael

2015-01-01

Chronic idiopathic anal pain (CIAP) remains a diagnosis of exclusion. Its study and management still lack a standardized protocol. The aim of this study is to evaluate the results obtained with the diagnostic-therapeutic protocol established in our service. We performed a retrospective study of patients diagnosed with CIAP at the Colorectal Unit of the General University Hospital of Elche, between 2005 and 2011. We evaluated 57 patients with a diagnosis of chronic anal pain for functional anorectal disease (FAD). After the application of our diagnostic protocol, final diagnosis of chronic anal pain (CAP) was achieved in 43 cases (75%), including 22 cases of descending perineum syndrome, 12 of proctalgia fugax, 2 of pudendal neuritis and 7 of coccydynia. In 14 patients exclusion diagnosis of CIAP was established. Among the therapies used on patients with CIAP, biofeedback combined with conservative measures improved symptoms in 43% of the cases. Sacral nerve stimulation was assessed in patients who did not respond to other treatments. Through proper anamnesis, physical examination and complementary tests, a specific diagnosis of the cause of CAP by FAD can be achieved, reducing exclusion diagnosis of CIAP to 25% of cases. Conservative measures combined with biofeedback achieved an improvement in pain in more than 40% of the cases of CIAP in our study. Sacral nerve stimulation can be considered as a treatment option in refractory cases. Copyright © 2013 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Morphometric study of the true S1 and S2 of the normal and dysmorphic sacralized sacra.

PubMed

Firat, Ayşegül; Alemdaroğlu, Kadir Bahadır; Özmeriç, Ahmet; Yücens, Mehmet; Göksülük, Dinçer

2017-06-12

This study aimed to generate data for the S1 and S2 alar pedicle and body and the alar orientations for both dysmorphic and normal sacra. The study comprised two groups: Group N consisted of 53 normal sacra and Group D included 10 dysmorphic sacra. Various features such as alar pedicle circumference; anterior, middle, and posterior axis of the sacral ala; sacral body height and width; and sagittal thickness were measured. In group N, the median anterior axis of the alae was observed to be 30° on the right and 25° on the left, the median midline axis was found to be 20° on the right and 15° on the left, and the median posterior alar axis was -15° on the right and -20° on the left. The true S1 and S2 alar pedicle circumferences were observed to be significantly smaller in group D, which demonstrated a shorter S1 alar pedicle mean circumference, significantly narrower S1 body mean width, and considerably tapered sagittal thickness. Our analysis indicated that dysmorphic sacra have a lower sagittal thickness and width of bodies and smaller alar pedicles, which explains the difficulties in their percutaneous fixation.

Clinical outcome of trans-sacral interbody fusion after partial reduction for high-grade l5-s1 spondylolisthesis.

PubMed

Smith, J A; Deviren, V; Berven, S; Kleinstueck, F; Bradford, D S

2001-10-15

A clinical retrospective study was conducted. To evaluate the clinical and radiographic outcome of reduction followed by trans-sacral interbody fusion for high-grade spondylolisthesis. In situ posterior interbody fusion with fibula allograft has improved the fusion rates for patients with high-grade spondylolisthesis. The use of this technique in conjunction with partial reduction has not been reported. Nine consecutive patients underwent treatment of high-grade (Grade 3 or 4) spondylolisthesis with partial reduction followed by posterior interbody fusion using cortical allograft. The average age at the time of surgery was 27 years (range, 8-51 years), and the average follow-up period was 43 months (range, 24-72 months). Before surgery, eight patients had low back pain, seven patients had radiating leg pain, and five patients had hamstring tightness. The average grade of spondylolisthesis by Meyerding grading was 3.9 (range, 3-5). Charts and radiographs were evaluated, and outcomes were collected by use of the modified SRS outcomes instrument. Radiographic indexes demonstrated significant improvement with partial reduction and fusion. The slip angle, as measured from the inferior endplate of L5, improved from 41.2 degrees (range, 24-82 degrees ) before surgery to 21 degrees (range, 5-40 degrees ) after surgery. All the patients were extremely or somewhat satisfied with surgery. The two patients who underwent this operation without initial instrumentation experienced fractures of their interbody grafts. Both of these patients underwent repair of the pseudarthrosis with placement of trans-sacral pedicle screw instrumentation and subsequent fusion. Partial reduction followed by posterior interbody fusion is an effective technique for the management of high-grade spondylolisthesis in pediatric and adult patient populations, as assessed by radiographic and clinical criteria. Pedicle screw instrumentation with the sacral screws capturing L5 is recommended when this

Sacral chordomas: Impact of high-dose proton/photon-beam radiation therapy combined with or without surgery for primary versus recurrent tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Lily; De Laney, Thomas F.; Liebsch, Norbert J.

2006-08-01

Purpose: To assess the efficacy of definitive treatment of sacral chordoma by high-dose proton/photon-beam radiation therapy alone or combined with surgery. Methods and Materials: The records of 16 primary and 11 recurrent sacral chordoma patients treated from November 1982 to November 2002 by proton/photon radiation therapy alone (6 patients) or combined with surgery (21 patients) have been analyzed for local control, survival, and treatment-related morbidity. The outcome analysis is based on follow-up information as of 2005. Results: Outcome results show a large difference in local failure rate between patients treated for primary and recurrent chordomas. Local control results by surgerymore » and radiation were 12/14 vs. 1/7 for primary and recurrent lesions. For margin-positive patients, local control results were 10 of 11 and 0 of 5 in the primary and recurrent groups, respectively; the mean follow-up on these locally controlled patients was 8.8 years (4 at 10.3, 12.8, 17, and 21 years). Radiation alone was used in 6 patients, 4 of whom received {>=}73.0 Gy (E); local control was observed in 3 of these 4 patients for 2.9, 4.9, and 7.6 years. Conclusion: These data indicate a high local control rate for surgical and radiation treatment of primary (12 of 14) as distinct from recurrent (1 of 7) sacral chordomas. Three of 4 chordomas treated by {>=}73.0 Gy (E) of radiation alone had local control; 1 is at 91 months. This indicates that high-dose proton/photon therapy offers an effective treatment option.« less

Enlargement of sacral subcutaneous meningocele associated with retained medullary cord.

PubMed

Shirozu, Noritoshi; Morioka, Takato; Inoha, Satoshi; Imamoto, Naoyuki; Sasaguri, Takakazu

2018-04-27

A retained medullary cord (RMC) is a rare closed spinal dysraphism with a robust elongated neural structure continuous from the conus and extending to the dural cul-de-sac. Four cases of RMC extending down to the base of an associated subcutaneous meningocele at the sacral level have been reported. We report an additional case of RMC, in whom serial MRI examination revealed an enlargement of the meningocele associated with RMC over a 3-month period between 8 and 11 months of age, when he began to stand. At the age of 12 months, untethering of the cord was performed. Histologically, the presence of ependyma-lined central canals in the dense neuroglial cores was noted in all cord-like structures in the intradural and intrameningocele sacs and at the attachment to the meningocele. It is conceivable that the hydrodynamic pressure with standing position and the check valve phenomenon were involved in meningocele enlargement. We should be mindful of these potential morphological changes.

Potential of Surface Enhanced Raman Spectroscopy (SERS) in Therapeutic Drug Monitoring (TDM). A Critical Review

PubMed Central

Jaworska, Aleksandra; Fornasaro, Stefano; Sergo, Valter; Bonifacio, Alois

2016-01-01

Surface-Enhanced Raman Spectroscopy (SERS) is a label-free technique that enables quick monitoring of substances at low concentrations in biological matrices. These advantages make it an attractive tool for the development of point-of-care tests suitable for Therapeutic Drug Monitoring (TDM) of drugs with a narrow therapeutic window, such as chemotherapeutic drugs, immunosuppressants, and various anticonvulsants. In this article, the current applications of SERS in the field of TDM for cancer therapy are discussed in detail and illustrated according to the different strategies and substrates. In particular, future perspectives are provided and special concerns regarding the standardization of self-assembly methods and nanofabrication procedures, quality assurance, and technology readiness are critically evaluated. PMID:27657146

Pubectomy and stereotactic radiotherapy for the treatment of a non-resectable sacral osteosarcoma causing pelvic canal obstruction in a dog

PubMed Central

Randall, Victoria D.; Boston, Sarah E.; Gardner, Heather L.; Griffin, Lynn; Oblak, Michelle L.; Kubicek, Lyndsay

2016-01-01

A pubectomy was carried out to relieve obstruction of the pelvic canal in a 6-year-old dog diagnosed with sacral osteosarcoma. Two days after surgery, the dog was ambulatory with normal urination and defecation. Pubectomy is a viable option to relieve clinical signs in patients with pelvic canal obstruction due to a non-resectable tumor. PMID:27587885

Comparison of Lumbar Lordosis in Lateral Radiographs in Standing Position with supine MR Imaging in consideration of the Sacral Slope.

PubMed

Benditz, Achim; Boluki, Daniel; Weber, Markus; Zeman, Florian; Grifka, Joachim; Völlner, Florian

2017-03-01

Purpose  To investigate the influence of sacral slope on the correlation between measurements of lumbar lordosis obtained by standing radiographs and magnetic resonance images in supine position (MRI). Little information is available on the correlation between measurements of lumbar lordosis obtained by radiographic and MR images. Most relevant studies have shown correlations for the thoracic spine, but detailed analyses on the lumbar spine are lacking. Methods  MR images and standing lateral radiographs of 63 patients without actual low back pain or radiographic pathologies of the lumbar spine were analyzed. Standing radiographic measurements included the sagittal parameters pelvic incidence (PI) pelvic tilt (PT), and sacral slope (SS); MR images were used to additionally measure lumbar L1-S1 lordosis and single level lordosis. Differences between radiographic and MRI measurements were analyzed and divided into 4 subgroups of different sacral slope according to Roussouly's classification. Results  Global lumbar lordosis (L1-S1) was 44.99° (± 10 754) on radiographs and 47.91° (± 9.170) on MRI, yielding a clinically relevant correlation (r = 0.61, p < 0.01). Measurements of single level lordosis only showed minor differences. At all levels except for L5 / S1, lordosis measured by means of standing radiographs was higher than that measured by MRI. The difference in global lumbar L1-S1 lordosis was -2.9°. Analysis of the Roussouly groups showed the largest difference for L1-S1 (-8.3°) in group 2. In group 4, when measured on MRI, L5 / S1 lordosis (25.71°) was lower than L4 / L5 lordosis (27.63°) compared to the other groups. Conclusions  Although measurements of global lumbar lordosis significantly differed between the two scanning technologies, the mean difference was just 2.9°. MRI in supine position may be used for estimating global lumbar lordosis, but single level lordosis should be determined by means of standing

Surface modification of medical implant materials with hydrophilic polymers for enhanced biocompatibility and delivery of therapeutic agents

NASA Astrophysics Data System (ADS)

Urbaniak, Daniel J.

2004-11-01

In the research reported here, the surface modification of medical grade poly(dimethyl siloxane), polyetherurethane, and stainless steel through gamma-radiation grafting of hydrophilic polymers was investigated. Emphasis was placed on developing improved and simplified surface modification methods that produce more stable and more bioacceptible hydrophilic graft surfaces. As a result of this research, new surface modification techniques were developed that yield significantly improved surface stability unachievable using previous surface modification techniques. The surface modification of poly(dimethyl siloxane) with hydrophilic polymers was carried out using gamma radiation initiated graft polymerization. The addition of alkali metal hydroxides afforded a unique way to enhance the grafting of N-vinyl-2 pyrrolidone, dimethylacryamide, 2-methacryloyloxyethyl phosphoryl choline, N,N-dimethyl-N-(methacryloyloxyethyl)-N-(3-sulfopropyl)-ammonium-betaine, N,N-dimethyl-N-(methacrylamidopropyl)-N-(3-sulfopropyl)-ammonium-betaine, and copolymers thereof to silicones. Ethanolamine was found to further enhance the grafting of some hydrophilic polymers to silicone. The resulting hydrophilic surface grafts were resistant to hydrophobic surface rearrangement. This process overcomes previous problems inherent in silicone surface modification. The technique was also found to moderately enhance the grafting of hydrophilic monomers to polyetherurethane and to 316-L stainless steel. The surface modification of 316-L stainless steel was further enhanced by treating the substrates with a chromium III methacrylate bonding agent prior to irradiation. The coatings were evaluated for their potential use as depots for delivering therapeutic agents. The release of ofloxacin from surface-modified poly(dimethyl siloxane) and dexamethasone from surface-modified 316-L stainless steel was evaluated by in-vitro experiments. Therapeutic levels of drugs were released from surface-modified specimens

[Effectiveness of Sacral Intervertebral Epidural Block for Umbilical Hernia Repair in Children].

PubMed

Nagamine, Norimitsu; Furuya, Atsushi; Suzuki, Sho; Kondo, Satoko; Kiuchi, Riko; Suzuki, Satomi; Nonaka, Akihiko

2015-02-01

Effectiveness of sacral intervertebral epidural block (S 2-3 block) for umbilical hernia repair has not been clarified. We investigate 24 children, undergoing umbilical hernia repair; mean age of 3 years (age range: 20-65 months). Under general anesthesia, epidural block was performed at S 2-3 interspace with 1 ml x kg(-1) ropivacaine (0.2%) at injecting rate of 1 ml x sec(-1) followed by 0.25 ml x kg(-1) normal saline. In all cases, neither systolic blood pressure nor heart rate increased > 15% from those just before the block. Postoperative analgesics were given in 6 patients (25%) rectally. Mean time between the block and the administration of analgesic was 10.5 hours. S 2-3 block can be effective for postoperative pain in umbilical hernia repair.

Sacral neuromodulation and Botulinum toxin A for refractory idiopathic overactive bladder: a cost-utility analysis in the perspective of Italian Healthcare System.

PubMed

Bertapelle, Maria Paola; Vottero, Mario; Popolo, Giulio Del; Mencarini, Marco; Ostardo, Edoardo; Spinelli, Michele; Giannantoni, Antonella; D'Ausilio, Anna

2015-08-01

To assess the relative cost-effectiveness of two therapeutic strategies: one starting with sacral neuromodulation (SNM) versus one starting with Botulinum toxin A (BTX-A) for the management of refractory incontinent idiopathic overactive bladder (OAB) patients, from the perspective of the Italian National Health Service (INHS). Direct medical costs (2011) and benefits (quality-adjusted life years-QALYs) were assessed over a ten-year time frame adapting to the Italian practice a published Markov model. Clinical inputs were based on the published literature and on the expert opinion. Resource consumption rates were provided by clinical experts; unit costs were collected from a single hospital accounting and from standard tariff lists and public prices. Interventional procedures and management of adverse events were costed through a micro-costing approach. The primary outcome was incremental costs per QALYs gained (i.e. differential costs divided by differential benefits). Deterministic (DSA) and probabilistic (PSA) sensitivity analyses were conducted to assess the robustness of the model. Starting with SNM appears to be cost effective (i.e. under 40.000/QALY) from year three (21,259/QALY) onwards and becomes dominant (i.e. more effective and less costly) at year ten: cumulative costs were 32,975 for early SNM and 33,309 for early BTX-A, while cumulative QALYs were 7.52 and 6.93, respectively. At year ten, DSA suggests the results robustness and 99.8 % of the PSA iterations fell within the cost-effectiveness threshold. A therapeutic strategy starting with SNM may be considered cost effective in the midterm and cost saving in the long-term treatment of idiopathic OAB from the INHS perspective.

MAdCAM-1 expressing sacral lymph node in the lymphotoxin beta-deficient mouse provides a site for immune generation following vaginal herpes simplex virus-2 infection.

PubMed

Soderberg, Kelly A; Linehan, Melissa M; Ruddle, Nancy H; Iwasaki, Akiko

2004-08-01

The members of the lymphotoxin (LT) family of molecules play a critical role in lymphoid organogenesis. Whereas LT alpha-deficient mice lack all lymph nodes and Peyer's patches, mice deficient in LT beta retain mesenteric lymph nodes and cervical lymph nodes, suggesting that an LT beta-independent pathway exists for the generation of mucosal lymph nodes. In this study, we describe the presence of a lymph node in LT beta-deficient mice responsible for draining the genital mucosa. In the majority of LT beta-deficient mice, a lymph node was found near the iliac artery, slightly misplaced from the site of the sacral lymph node in wild-type mice. The sacral lymph node of the LT beta-deficient mice, as well as that of the wild-type mice, expressed the mucosal addressin cell adhesion molecule-1 similar to the mesenteric lymph node. Following intravaginal infection with HSV type 2, activated dendritic cells capable of stimulating a Th1 response were found in this sacral lymph node. Furthermore, normal HSV-2-specific IgG responses were generated in the LT beta-deficient mice following intravaginal HSV-2 infection even in the absence of the spleen. Therefore, an LT beta-independent pathway exists for the development of a lymph node associated with the genital mucosa, and such a lymph node serves to generate potent immune responses against viral challenge.

RGD Peptide Cell-Surface Display Enhances the Targeting and Therapeutic Efficacy of Attenuated Salmonella-mediated Cancer Therapy.

PubMed

Park, Seung-Hwan; Zheng, Jin Hai; Nguyen, Vu Hong; Jiang, Sheng-Nan; Kim, Dong-Yeon; Szardenings, Michael; Min, Jung Hyun; Hong, Yeongjin; Choy, Hyon E; Min, Jung-Joon

2016-01-01

Bacteria-based anticancer therapies aim to overcome the limitations of current cancer therapy by actively targeting and efficiently removing cancer. To achieve this goal, new approaches that target and maintain bacterial drugs at sufficient concentrations during the therapeutic window are essential. Here, we examined the tumor tropism of attenuated Salmonella typhimurium displaying the RGD peptide sequence (ACDCRGDCFCG) on the external loop of outer membrane protein A (OmpA). RGD-displaying Salmonella strongly bound to cancer cells overexpressing αvβ3, but weakly bound to αvβ3-negative cancer cells, suggesting the feasibility of displaying a preferential homing peptide on the bacterial surface. In vivo studies revealed that RGD-displaying Salmonellae showed strong targeting efficiency, resulting in the regression in αvβ3-overexpressing cancer xenografts, and prolonged survival of mouse models of human breast cancer (MDA-MB-231) and human melanoma (MDA-MB-435). Thus, surface engineering of Salmonellae to display RGD peptides increases both their targeting efficiency and therapeutic effect.

Sacral nerve stimulation enhances epithelial barrier of the rectum: results from a porcine model.

PubMed

Meurette, G; Blanchard, C; Duchalais-Dassonneville, E; Coquenlorge, S; Aubert, P; Wong, M; Lehur, P-A; Neunlist, M

2012-03-01

The mechanism of action of sacral nerve stimulation (SNS) remains largely elusive. The aims of this study were to develop a clinically relevant animal model for percutaneous SNS and to describe its effect on the epithelial barrier of the rectum. Under general anesthesia and after percutaneous electrode placement for S3 nerve root stimulation, six pigs underwent unilateral stimulation and six bilateral stimulation. Animals were stimulated for 3 h using an external pulse generator (1-2.5 V; 14 Hz; 210 μs). Six animals underwent electrode implantation without stimulation and served as controls. Full-thickness rectal biopsies were performed prior to and after stimulation. Paracellular permeability was evaluated by measuring sulfonic acid flux across the rectal mucosa in Ussing chambers. Histological assessment of mucosal thickness, epithelial desquamation, and mucus expression were performed. Percutaneous stimulation resulted in successful anal contractions whose amplitude and uniformity was enhanced following bilateral compared with unilateral stimulation. In controls, paracellular permeability significantly increased during the stimulation period whereas it remained unchanged following unilateral stimulation. In contrast, permeability was significantly reduced by bilateral stimulation. This effect was associated with a concomitant reduction in mucosal thickness and a trend toward increased amount of mucus on surface epithelium compared with controls. The development of a porcine model of percutaneous SNS revealed the ability of neuromodulation to reinforce rectal epithelial barrier. Furthermore, our results suggest that SNS could be used for treatment of gastrointestinal pathologies with reduced rectal mucosal barrier functions. © 2012 Blackwell Publishing Ltd.

The Unresolved Case of Sacral Chordoma: From Misdiagnosis to Challenging Surgery and Medical Therapy Resistance

PubMed Central

Garofalo, Fabio; Christoforidis, Dimitrios; di Summa, Pietro G.; Gay, Béatrice; Cherix, Stéphane; Raffoul, Wassim; Matter, Maurice

2014-01-01

Purpose A sacral chordoma is a rare, slow-growing, primary bone tumor, arising from embryonic notochordal remnants. Radical surgery is the only hope for cure. The aim of our present study is to analyse our experience with the challenging treatment of this rare tumor, to review current treatment modalities and to assess the outcome based on R status. Methods Eight patients were treated in our institution between 2001 and 2011. All patients were discussed by a multidisciplinary tumor board, and an en bloc surgical resection by posterior perineal access only or by combined anterior/posterior accesses was planned based on tumor extension. Results Seven patients underwent radical surgery, and one was treated by using local cryotherapy alone due to low performance status. Three misdiagnosed patients had primary surgery at another hospital with R1 margins. Reresection margins in our institution were R1 in two and R0 in one, and all three recurred. Four patients were primarily operated on at our institution and had en bloc surgery with R0 resection margins. One had local recurrence after 18 months. The overall morbidity rate was 86% (6/7 patients) and was mostly related to the perineal wound. Overall, 3 out of 7 resected patients were disease-free at a median follow-up of 2.9 years (range, 1.6-8.0 years). Conclusion Our experience confirms the importance of early correct diagnosis and of an R0 resection for a sacral chordoma invading pelvic structures. It is a rare disease that requires a challenging multidisciplinary treatment, which should ideally be performed in a tertiary referral center. PMID:24999463

Urinary retention, erectile dysfunction and meningitis due to sacral herpes zoster: a case report and review of the literature.

PubMed

Erol, B; Avci, A; Eken, C; Ozgok, Y

2009-01-01

Zona zoster infection is often associated with painful erythematous vesicular eruptions of the skin or mucous membranes. Varicella zoster virus which stays latent in the sensorial root ganglia causes zona zoster infection. The most recognized feature of zona zoster is the dermatomal distribution of vesicular rashes. In the present case report, we state an unusual presentation of sacral zona zoster with urinary retention, erectile dysfunction and meningitis. Copyright 2009 S. Karger AG, Basel.

Utility of the omentum in sacral reconstruction following total sacrectomy due to recurrent and irradiated giant cell tumour of the spine

PubMed Central

Unal, Cigdem; Eren, Guler Gamze; Isil, Eda; Alponat, Ahmet; Sarlak, Ahmet

2012-01-01

Reconstruction of the lumbosacral region after surgical excision of irradiated and recurrent spinal giant cell tumours remains a challenging problem. In this case report, we describe the use of the pedicled omentum flap in reconstruction of an irradiated and infected wide sacral defect of a 19-year-old male patient. The patient had radiotherapy and subsequent wide surgical resection after recurrence of the tumour. A myocutaneous flap from the gluteal area had failed previously. Local flap options could not be used because of the recent radiotherapy to the gluteal area. Since the patient had a laparotomy for tumour resection and a colostomy, abdominal muscles were not considered reliable for reconstructive procedures. A pedicled omentum flap was chosen as a reconstructive option because of its rich blood supply, large surface area, and angiogenic capacity. This report aims to describe the use of the pedicled omentum flap for reconstruction of the lumbosacral area following surgical resection of a spinal tumour, when gluteal and abdominal flap options for reconstruction are jeopardised. PMID:22754172

Utility of the omentum in sacral reconstruction following total sacrectomy due to recurrent and irradiated giant cell tumour of the spine.

PubMed

Unal, Cigdem; Eren, Guler Gamze; Isil, Eda; Alponat, Ahmet; Sarlak, Ahmet

2012-01-01

Reconstruction of the lumbosacral region after surgical excision of irradiated and recurrent spinal giant cell tumours remains a challenging problem. In this case report, we describe the use of the pedicled omentum flap in reconstruction of an irradiated and infected wide sacral defect of a 19-year-old male patient. The patient had radiotherapy and subsequent wide surgical resection after recurrence of the tumour. A myocutaneous flap from the gluteal area had failed previously. Local flap options could not be used because of the recent radiotherapy to the gluteal area. Since the patient had a laparotomy for tumour resection and a colostomy, abdominal muscles were not considered reliable for reconstructive procedures. A pedicled omentum flap was chosen as a reconstructive option because of its rich blood supply, large surface area, and angiogenic capacity. This report aims to describe the use of the pedicled omentum flap for reconstruction of the lumbosacral area following surgical resection of a spinal tumour, when gluteal and abdominal flap options for reconstruction are jeopardised.

Residual neurological function after sacral root resection during en-bloc sacrectomy: a systematic review.

PubMed

Zoccali, Carmine; Skoch, Jesse; Patel, Apar S; Walter, Christina M; Maykowski, Philip; Baaj, Ali A

2016-12-01

Sacrectomy is a highly demanding surgery representing the main treatment for primary tumors arising in the sacrum and pelvis. Unfortunately, it is correlated with loss of important function depending on the resection level and nerve roots sacrificed. The current literature regarding residual function after sacral resection comes from several small case series. The goal of this review is to appraise residual motor function and gait, sensitivity, bladder, bowel, and sexual function after sacrectomies, with consideration to the specific roots sacrificed. An exhaustive literature search was conducted. All manuscripts published before May 2015 regarding residual function after sacrectomy were considered; if a clear correlation between root level and functioning was not present, the paper was excluded. The review identified 15 retrospective case series, totaling 244 patients; 42 patients underwent sacrectomies sparing L4/L4, L4/L5 and L5/L5; 45 sparing both L5 and one or both S1 roots; 8 sparing both S1 and one S2; 48 sparing both S2; 11 sparing both S2 and one S3, 54 sparing both S3, 9 sparing both S3 and one or both S4, and 27 underwent unilateral variable resection. Patients who underwent a sacrectomy maintained functionally normal ambulation in 56.2 % of cases when both S2 roots were spared, 94.1 % when both S3 were spared, and in 100 % of more distal resections. Normal bladder and bowel function were not present when both S2 were cut. When one S2 root was spared, normal bladder function was present in 25 % of cases; when both S2 were spared, 39.9 %; when one S3 was spared, 72.7 %; and when both S3 were spared, 83.3 %. Abnormal bowel function was present in 12.5 % of cases when both S1 and one S2 were spared; in 50.0 % of cases when both S2 were spared; and in 70 % of cases when one S3 was spared; if both S3 were spared, bowel function was normal in 94 % of cases. When even one S4 root was spared, normal bladder and bowel function were present in 100 % of

Fetal median sacral artery anatomy study by micro-CT imaging.

PubMed

Meignan, P; Binet, A; Cook, A R; Lardy, H; Captier, G

2018-04-30

The median sacral artery (MSA) is the termination of the dorsal aorta, which undergoes a complex regression and remodeling process during embryo and fetal development. The MSA contributes to the pelvic vascularization and may be injured during pelvic surgery. The embryological steps of MSA development, anastomosis formation and anatomical variations are linked, but not fully understood. The pelvic vascularization and more precisely the MSA of a human fetus at 22 weeks of gestation (GW) were studied using micro-CT imaging. Image treatment included arterial segmentations and 3D visualization. At 22 GW, the MSA was a well-developed straight artery in front of the sacrum and was longer than the abdominal aorta. Anastomoses between the MSA and the internal pudendal arteries and the superior rectal artery were detected. No evidence was found for the existence of a coccygeal glomus with arteriovenous anastomosis. Micro-CT imaging and 3D visualization helped us understand the MSA central role in pelvic vascularization through the ilio-aortic anastomotic system. It is essential to know this anastomotic network to treat pathological conditions, such as sacrococcygeal teratomas and parasitic ischiopagus twins (for instance, fetus in fetu and twin-reversed arterial perfusion sequence).

Effectiveness of surface enhanced Raman spectroscopy of tear fluid with soft substrate for point-of-care therapeutic drug monitoring

NASA Astrophysics Data System (ADS)

Yamada, K.; Endo, T.; Imai, H.; Kido, M.; Jeong, H.; Ohno, Y.

2016-03-01

We have developed the point-of-care therapeutic drug monitoring kit based on Raman Spectroscopy of tear fluid. In this study, we were examined a soft substrate for an optimal lattice based on nanoimprint lithography using cyclo-olefin polymer to improve the sensitivity for measuring drug concentration in tear fluid. This is photonics crystal which is one of the nano-photonics based device was fabricated. Target is Sodium Phenobarbital which is an anticonvulsant agent. We show the effectiveness of Surface Enhanced Raman Spectroscopy of tear fluid with soft substrate for point-of-care therapeutic drug monitoring.

Design of a surface plasmon resonance immunoassay for therapeutic drug monitoring of amikacin.

PubMed

Losoya-Leal, Adrian; Estevez, M-Carmen; Martínez-Chapa, Sergio O; Lechuga, Laura M

2015-08-15

The therapeutic drug monitoring (TDM) of pharmaceutical drugs with narrow therapeutic ranges is of great importance in the clinical setting. It provides useful information towards the enhancement of drug therapies, aiding in dosage control and toxicity risk management. Amikacin is an aminoglycoside antibiotic commonly used in neonatal therapies that is indicated for TDM due to the toxicity risks inherent in its use. Current techniques for TDM such as high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are costly, time consuming, and cannot be performed at the site of action. Over the last decades, surface plasmon resonance (SPR) biosensors have become increasingly popular in clinical diagnostics due to their ability to detect biomolecular interactions in real-time. We present an SPR-based competitive immunoassay for the detection of the antibiotic amikacin, suitable for TDM in both adults and neonates. We have obtained high specificity and sensitivity levels with an IC50 value of 1.4ng/mL and a limit of detection of 0.13ng/mL, which comfortably comply with the drug's therapeutic range. Simple dilution of serum can therefore be sufficient to analyze low-volume real samples from neonates, increasing the potential of the methodology for TDM. Compared to current TDM conventional methods, this SPR-based immunoassay can provide advantages such as simplicity, potential portability, and label-free measurements with the possibility of high throughput. This work is the foundation towards the development of an integrated, simple use, highly sensitive, fast, and point-of-care sensing platform for the opportune TDM of antibiotics and other drugs in a clinical setting. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of low force chiropractic adjustments for 4 weeks on body surface electromagnetic field.

PubMed

Zhang, John; Snyder, Brian J

2005-01-01

To study the effects of 4 weeks of low-force chiropractic adjustments on body surface electromagnetic fields (EMFs). Thirty-five chiropractic students randomly assigned into control (17 subjects) and experimental groups (28 subjects). A triaxial fluxgate magnetometer was used for EMF detection. The subjects' body surface EMF was determined in the prone position before and after the chiropractic adjustment. A Toftness low-force chiropractic adjustment was applied to the cervical, thoracic, lumbar, and sacral areas as determined by the practitioner. Heart rate variability analysis was recorded once a week to determine autonomic nervous system activity in both the control and experimental groups. The EMF on the subjects' body surface decreased after chiropractic adjustment at the cervical, thoracic, lumbar, and sacral regions in all 6 visits during the 4-week treatment period. The EMF showed a downtrend over the 4-week period after the low-force adjustment. The same changes were not observed in the control group. The chiropractic adjustment group had a slight decrease in heart rate over the 4-week treatment period, and no significant change was observed in the control group. Heart rate variability analysis did not show consistent changes before and after the low-force adjustments during the treatment period. Low-force chiropractic adjustment in the cervical and thoracic areas resulted in a consistent reduction of the body surface EMF after 4 weeks of active treatment. No statistically significant differences were found in the heart rate and heart rate variability in the 4-week study.

How Does the Level of Sacral Resection for Primary Malignant Bone Tumors Affect Physical and Mental Health, Pain, Mobility, Incontinence, and Sexual Function?

PubMed

Phukan, Rishabh; Herzog, Tyler; Boland, Patrick J; Healey, John; Rose, Peter; Sim, Franklin H; Yazsemski, Michael; Hess, Kathryn; Osler, Polina; DeLaney, Thomas F; Chen, Yen-Lin; Hornicek, Francis; Schwab, Joseph

2016-03-01

), S1 (N = 8), S2 (N = 10), S3 (N = 5), and S4 (N = 4). One-way analysis of variance tests on means or ranks were used to conduct statistical analysis between levels. Patients with more caudal resections had higher physical health (95% confidence interval [CI] total sacrectomy 36-42 versus S4 50-64, p < 0.001), less intense pain (95% CI total sacrectomy 47-60 versus S4 28-37, p < 0.001), less interference resulting from pain (95% CI total sacrectomy 58-69 versus S4 36-51, p = 0.004), higher mobility (95% CI total sacrectomy 24-46 versus S4 59-59, p = 0.002), and were more functionally able to achieve orgasm (95% CI S1 1-1 versus S4 2.2-5.3, p = 0.043). No difference was found for PROMIS Global Item Mental Health Subscore, Sex Interest, Sex Satisfaction, modified obstruction and defecation score, and International Continence Society Voiding and Incontinence although this could be the result of an inadequate sample size. Our analysis on patient-reported quality of life based on the level of bony resection in patients who underwent resection for primary sacral tumor indicates that patients with higher resections have more pain and loss of physical function in comparison to patients with lower resections. Additionally, use of the PROMIS outcomes allows for comparisons to normative data. Level III, therapeutic study.

Effect of spinal anterior root stimulation and sacral deafferentation on bladder and sexual dysfunction in spinal cord injury.

PubMed

Zaer, Hamed; Rasmussen, Mikkel Mylius; Zepke, Franko; Bodin, Charlotte; Domurath, Burkhard; Kutzenberger, Johannes

2018-05-10

Spinal cord injury (SCI) is a highly devastating injury with a variety of complications; among them are neurogenic bladder, bowel, and sexual dysfunction. We aimed to evaluate the effect of sacral anterior root stimulation with sacral deafferentation (SARS-SDAF) on neurogenic bladder and sexual dysfunction in a large well-defined spinal cord injury cohort. In the manner of cross-sectional study, subjects undergone SARS-SDAF between September 1986 and July 2011 answered a questionnaire concerning conditions before and after surgery in the department of Neuro-Urology, Bad Wildungen, Germany. In total 287 of 587 subjects were analyzed. Median age was 49 years (range 19-80), median time from SCI to surgery was 10 years (range 0-49), and from surgery to follow-up 13 years (range 1-25). Of the analyzed subjects, 100% of both gender used SARS for bladder emptying. On the visual analogue scale (VAS) ranging from 0 to 10 (best), satisfaction with SARS-SDAF was 10 concerning bladder emptying, however 5 and 8 regarding sexual performance, for female and male users, respectively. Baseline and follow-up comparison showed a decline in self-intermittent catheterization (p < 0.0001), partial catheterization by attendant (p = 0.0125), complete catheterization and suprapubic catheterization (p < 0.0001), transurethral catheterization (p < 0.0011), and fewer cases of involuntary urine leakage (p < 0.0001). The SARS-SDAF is a beneficial multi-potential treatment method with simultaneous positive effect on multi-organ dysfunction among SCI subjects.

Albumin based versatile multifunctional nanocarriers for cancer therapy: Fabrication, surface modification, multimodal therapeutics and imaging approaches.

PubMed

Kudarha, Ritu R; Sawant, Krutika K

2017-12-01

Albumin is a versatile protein used as a carrier system for cancer therapeutics. As a carrier it can provide tumor specificity, reduce drug related toxicity, maintain therapeutic concentration of the active moiety like drug, gene, peptide, protein etc. for long period of time and also reduce drug related toxicities. Apart from cancer therapy, it is also utilized in the imaging and multimodal therapy of cancer. This review highlights the important properties, structure and types of albumin based nanocarriers with regards to their use for cancer targeting. It also provides brief discussion on methods of preparation of these nanocarriers and their surface modification. Applications of albumin nanocarriers for cancer therapy, gene delivery, imaging, phototherapy and multimodal therapy have also been discussed. This review also provides brief discussion about albumin based marketed nano formulations and those under clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical Structure and Surface Modification of Dendritic Nanomaterials Tailored for Therapeutic and Diagnostic Applications.

PubMed

Myung, Ja Hye; Hsu, Hao-Jui; Bugno, Jason; Tam, Kevin A; Hong, Seungpyo

2017-01-01

Dendritic nanomaterials have attracted a great deal of scientific interest due to their high capacity for multifunctionalization and potential in various biomedical applications, such as drug/gene delivery and diagnostic systems. Depending on the molecular structure and starting monomers, several different types of dendrimers have been developed, including poly(amidoamine) (PAMAM), poly(propylenimine) (PPI), and poly(L-lysine) (PLL) dendrimers, in addition to modified dendritic nanomaterials, such as Janus dendrimers and dendritic block copolymers. The chemical structure and surface modification of dendritic nanomaterials have been found to play a critical role in governing their biological behaviors. In this review, we present a comprehensive overview focusing on the synthesis and chemical structures of dendrimers and modified dendritic nanomaterials that are currently being investigated for drug delivery, gene delivery, and diagnostic applications. In addition, the impact of chemical surface modification and functionalization to the dendritic nanomaterials on their therapeutic and diagnostic applications are highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transcutaneous spinal direct current stimulation of the lumbar and sacral spinal cord: a modelling study

NASA Astrophysics Data System (ADS)

Fernandes, Sofia R.; Salvador, Ricardo; Wenger, Cornelia; de Carvalho, Mamede; Miranda, Pedro C.

2018-06-01

Objective. Our aim was to perform a computational study of the electric field (E-field) generated by transcutaneous spinal direct current stimulation (tsDCS) applied over the thoracic, lumbar and sacral spinal cord, in order to assess possible neuromodulatory effects on spinal cord circuitry related with lower limb functions. Approach. A realistic volume conductor model of the human body consisting of 14 tissues was obtained from available databases. Rubber pad electrodes with a metallic connector and a conductive gel layer were modelled. The finite element (FE) method was used to calculate the E-field when a current of 2.5 mA was passed between two electrodes. The main characteristics of the E-field distributions in the spinal grey matter (spinal-GM) and spinal white matter (spinal-WM) were compared for seven montages, with the anode placed either over T10, T8 or L2 spinous processes (s.p.), and the cathode placed over right deltoid (rD), umbilicus (U) and right iliac crest (rIC) areas or T8 s.p. Anisotropic conductivity of spinal-WM and of a group of dorsal muscles near the vertebral column was considered. Main results. The average E-field magnitude was predicted to be above 0.15 V m-1 in spinal cord regions located between the electrodes. L2-T8 and T8-rIC montages resulted in the highest E-field magnitudes in lumbar and sacral spinal segments (>0.30 V m-1). E-field longitudinal component is 3 to 6 times higher than the ventral-dorsal and right-left components in both the spinal-GM and WM. Anatomical features such as CSF narrowing due to vertebrae bony edges or disks intrusions in the spinal canal correlate with local maxima positions. Significance. Computational modelling studies can provide detailed information regarding the electric field in the spinal cord during tsDCS. They are important to guide the design of clinical tsDCS protocols that optimize stimulation of application-specific spinal targets.

Biomimetic Particles as Therapeutics

PubMed Central

Green, Jordan J.

2015-01-01

In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

Transient paraplegia due to accidental intrathecal bupivacaine infiltration following pre-emptive analgesia in a patient with missed sacral dural ectasia.

PubMed

Kanna, P Rishimugesh; Sekar, Chelliah; Shetty, Ajoy Prasad; Rajasekaran, Shanmughanathan

2010-11-15

A case report with review of the literature. To highlight the need for careful magnetic resonance imaging evaluation for the presence of incidental lumbosacral dural anomalies before attempting caudal epidural interventions. Pre-emptive analgesia through the caudal epidural route provides good postoperative pain relief in spine surgeries. Several precautions have been advised in the literature. Presence of sacral-dural ectasia should be considered a relative contraindication for this procedure. A 50-year old woman underwent posterior instrumented spinal fusion for L4-L5 spondylolisthesis under general anesthesia. She received single shot caudal epidural analgesia at the start of the procedure. After complete emergence from anesthesia, she had complete motor and sensory loss below the T12 spinal level, which reversed to normal neurology in 6 hours. Retrospective evaluation of the patient's magnetic resonance imaging showed an ectatic, low lying lumbosacral dural sac which had been overlooked in the initial evaluation. The drugs given by the caudal route have been accidentally administered into the thecal sac causing a brief period of neurologic deficit. This unexpected complication has been reported only in the pediatric literature before. It is important to look for the presence of lumbosacral dural anomalies before planning caudal epidural injections in adults also. Sacral dural ectasia and other lumbosacral anomalies must be recognized as contraindications for caudal epidural pre-emptive analgesia for spine surgery. Other modes of postoperative pain relief should be tried in these patients.

Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation

PubMed Central

Almeida, Freya M Freyre; Blanco, Aracelys; Trujillo, Heidy; Hernández, Dunia; García, Daymir; Alba, José S; Abad, Matilde López; Merino, Nelson; Lobaina, Yadira

2016-01-01

ABSTRACT The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys. Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study. How to cite this article Freyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel

The inhibitory effect of sacral dorsal root ganglion stimulation on nociceptive and nonnociceptive bladder reflexes in cats.

PubMed

Wang, Zhaoxia; Liao, Limin; Deng, Han; Li, Xing; Chen, Guoqing

2018-05-01

To investigate the inhibitory effects of electrical stimulation of sacral dorsal root ganglion (DRG) on bladder activity under non-nociceptive and nociceptive bladder conditions in cats. 12 cats were divided into non-nociceptive and nociceptive groups. Saline was used to distend the bladder and induce non-nociceptive bladder activity, while acetic acid (AA, 0.25%) was used to induce nociceptive bladder overactivity, S1 or S2 DRG stimulation was applied via a pair of hook electrodes placed in the right S1 and S2 DRG. In both non-nociceptive and nociceptive groups, stimulation at 3 and 5 Hz significantly increased bladder capacity (BC) and no significantly different between the two frequencies. In non-nociceptive group, S1 DRG stimulation at 3 Hz was as effective (increasing BC to 139.7 ± 5.6 and 166.9 ± 12.21% of control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 129.2 ± 5.6 and 160.5 ± 13.3% of control). In nociceptive group, AA reduced the BC to 62.6 ± 11.7% of saline control. S1 DRG stimulation at 3 Hz was also as effective (increasing BC to 54.9 ± 5.5 and 61.9 ± 6.0% of saline control at 1T and 3/2T, respectively) as S2 DRG stimulation (increases BC to 58.3 ± 3.7 and 65.6 ± 3.7% of control). This study showed the effective inhibition on bladder activity under both non-nociceptive and nociceptive conditions, suggesting the possibility of sacral DRG stimulation to treat bladder overactivity.

Antibody Therapeutics in Oncology.

PubMed

Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

2016-03-01

One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment.

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus.

PubMed

Hur, Jian

2015-06-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention.

Objective evaluation by reflectance spectrophotometry can be of clinical value for the verification of blanching/non blanching erythema in the sacral area.

PubMed

Sterner, Eila; Fossum, Bjöörn; Berg, Elisabeth; Lindholm, Christina; Stark, André

2014-08-01

Early detection of non blanching erythema (pressure ulcer category I) is necessary to prevent any further skin damage. An objective method to discriminate between blanching/non blanching erythema is presently not available. The purpose of this investigation was to explore if a non invasive objective method could differentiate between blanching/non blanching erythema in the sacral area of patients undergoing hip fracture surgery. Seventy-eight patients were included. The sacral area of all patients was assessed using (i) conventional finger-press test and (ii) digital reading of the erythema index assessed with reflectance spectrophotometry. The patients were examined at admission and during 5 days postsurgery. Reflectance spectrophotometry measurements proved able to discriminate between blanching/non blanching erythema. The reliability, quantified by the intra-class correlation coefficient, was excellent between repeated measurements over the measurement period, varying between 0·82 and 0·96, and a significant change was recorded in the areas from day 1 to day 5 (P < 0·0001). The value from the reference point did not show any significant changes over the same period (P = 0·32). An objective method proven to identify early pressure damage to tissue can be a valuable tool in clinical practice. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Theranostic Multibranched Gold Nanoantennas for Cancer Diagnostics via Surface Enhanced Raman Spectroscopy and Photothermal Therapeutics

NASA Astrophysics Data System (ADS)

Weinstein-Webb, Joseph A.

Cancer is the second leading cause of death globally according to the World Health Organization. Especially dangerous and lethal are the breast cancers that have genetic mutations for surface receptors utilized in drug therapy. This resistance calls for new and innovative treatments that be optimized for cancers based on an individual patient basis/cancer phenotype. Nanoparticle based diagnostics and therapeutics have recently emerged as a novel platform for management and mitigation of cancer at all stages. Gold nanostructures, specifically, have multiple characteristics that make them ideal for cancer theranostics including: (i) high biocompatibility, (ii) ease of bioconjugation, (iii) ability to tune their plasmon resonance to absorb tissue penetrating near infrared light, (iv) their use as contrast agents, and (v) ability to convert light to heat when excited at the plasmon resonance for photothermal ablation of cancer cells. Further, due to their adaptability as a platform, the nanoparticles affect the battle against cancer in multiple different strategies. These theranostic gold nanoprobes can be incorporated into point of care diagnostic (POCD) systems for biomarker detection, used as theranostic probes to delivery multiplex SERS receptor imaging and photothermal therapy or be involved in future immunotherapy treatments. In this work we demonstrate the use of near-infrared light absorbing multibranched gold nanoantennas (MGNs) to simultaneously deliver diagnostic and therapeutic (theranostic) capabilities in cancer models. More aggressive cancer cell lines require approaches that are versatile and multifunctional, and the possibilities for the usage in diagnostics or therapeutics for these theranostic MGNs are abundant.

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus

PubMed Central

2015-01-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention. PMID:26157595

Characteristics Associated With Treatment Response in Women Undergoing OnabotulinumtoxinA and Sacral Neuromodulation for Refractory Urgency Urinary Incontinence

PubMed Central

Richter, HE; Amundsen, CL; Erickson, SW; Jelovsek, JE; Komesu, Y; Chermansky, C; Harvie, H; Albo, M; Myers, D; Gregory, WT; Wallace, D

2017-01-01

Purpose To identify clinical and demographic characteristics associated with onabotulinumtoxinA and sacral neuromodulation treatment response in women with refractory urgency urinary incontinence. Material and Methods Data were analyzed from the Refractory Overactive Bladder: Sacral Neuromodulation vs Botulinum Toxin Assessment trial. Baseline participant characteristics and clinical variables associated with two definitions of treatment response: 1) reduction in mean daily urgency incontinence episodes over 6 months 2) ≥50% decrease in urgency incontinence episodes across 6 months were identified. Linear and logistic regression models were fit to estimate mean reductions in incontinence episodes and adjusted odds ratios for incidence of ≥50% decrease with 95% confidence intervals, respectively. Results For both treatments, a greater reduction in mean daily urgency incontinence episodes was associated with higher Health Utility Index scores (P=0.002) and higher baseline incontinence episodes (P<0.001). Increased age was associated with less reduction in incontinence episodes (P<0.001). Increasing body mass index (aOR 0.82 per 5 points, 95% CI 0.70, 0.96) was associated with reduced achievement of ≥50% decrease in incontinence episodes after both treatments. Greater age (aOR 0.44 per 10 years, 95% CI 0.30, 0.65) and higher functional comorbidity index (aOR 0.84 per point, 95% CI 0.71, 0.99) were associated with reduced achievement of ≥50% decrease in urgency incontinence episodes in the onabotulinuntoxinA group only (P=0.016; P=0.031, respectively). Conclusion Increasing age, body mass index, and functional comorbidity are negatively associated with treatment response while greater incontinence frequency and health utility is associated with a greater response to third line treatments for refractory urgency incontinence. PMID:28501541

Techniques of lumbar-sacral spine fusion in spondylosis: systematic literature review and meta-analysis of randomized clinical trials.

PubMed

Umeta, Ricardo S G; Avanzi, Osmar

2011-07-01

Spine fusions can be performed through different techniques and are used to treat a number of vertebral pathologies. However, there seems to be no consensus regarding which technique of fusion is best suited to treat each distinct spinal disease or group of diseases. To study the effectiveness and complications of the different techniques used for spinal fusion in patients with lumbar spondylosis. Systematic literature review and meta-analysis. Randomized clinical studies comparing the most commonly performed surgical techniques for spine fusion in lumbar-sacral spondylosis, as well as those reporting patient outcome were selected. Identify which technique, if any, presents the best clinical, functional, and radiographic outcome. Systematic literature review and meta-analysis based on scientific articles published and indexed to the following databases: PubMed (1966-2009), Cochrane Collaboration-CENTRAL, EMBASE (1980-2009), and LILACS (1982-2009). The general search strategy focused on the surgical treatment of patients with lumbar-sacral spondylosis. Eight studies met the inclusion criteria and were selected with a total of 1,136 patients. Meta-analysis showed that patients who underwent interbody fusion presented a significantly smaller blood loss (p=.001) and a greater rate of bone fusion (p=.02). Patients submitted to fusion using the posterolateral approach had a significantly shorter operative time (p=.007) and less perioperative complications (p=.03). No statistically significant difference was found for the other studied variables (pain, functional impairment, and return to work). The most commonly used techniques for lumbar spine fusion in patients with spondylosis were interbody fusion and posterolateral approach. Both techniques were comparable in final outcome, but the former presented better rates of fusion and the latter the less complications. Copyright © 2011 Elsevier Inc. All rights reserved.

Excited-State Proton Transfer on the Surface of a Therapeutic Protein, Protamine.

PubMed

Awasthi, Ankur A; Singh, Prabhat K

2017-11-16

Proton transfer reactions on biosurfaces play an important role in a myriad of biological processes. Herein, the excited-state proton transfer reaction of 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) has been investigated in the presence of an important therapeutic protein, Protamine (PrS), using ground-state absorption, steady-state, and detailed time-resolved emission measurements. HPTS forms a 1:1 complex with Protamine with a high association constant of 2.6 × 10 4 M -1 . The binding of HPTS with Protamine leads to a significant modulation in the ground-state prototropic equilibrium causing a downward shift of 1.1 unit in the acidity constant (pK a ). In contrast to a large number of reports of slow proton transfer of HPTS on biosurfaces, interestingly, HPTS registers a faster proton transfer event in the presence of Protamine as compared to that of even the bulk aqueous buffer medium. Furthermore, the dimensionality of the proton diffusion process is also significantly reduced on the surface of Protamine that is in contrast to the behavior of HPTS in the bulk aqueous buffer medium, where the proton diffusion process is three-dimensional. The effect of ionic strength on the binding of HPTS toward PrS suggests a predominant role of electrostatic interaction between anionic HPTS and cationic Protamine, which is further supported by molecular docking simulations which predict that the most preferable binding site for HPTS on the surface of Protamine is surrounded by multiple cationic arginine residues.

Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading.

PubMed

Sutaria, Dhruvitkumar S; Badawi, Mohamed; Phelps, Mitch A; Schmittgen, Thomas D

2017-05-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

Neuromodulation by implant for treating lower urinary tract symptoms and dysfunction.

PubMed

Bemelmans, B L; Mundy, A R; Craggs, M D

1999-08-01

Patients with irritative micturition complaints, pelvic pain, involuntary urine loss or urinary retention are sometimes difficult to treat. The advent of direct sacral nerve stimulation offers a therapeutic alternative if conservative measures fail and surgery is considered. This paper reviews therapeutic neuromodulation by implant for treating lower urinary tract symptoms and dysfunction. The international literature is reviewed on topics such as the physiological basis of neuromodulation, techniques of acute testing and chronic implantation, and clinical results. Future developments and ways for possible improvement are discussed. The mode of action of neuromodulation is probably through restoring the correct balance between excitatory and inhibitory impulses from and to the pelvic organs at a sacral and supra-sacral level. Depending on the predefined success criteria, average success rates of definitive implants vary from 50 to 70%. From the data it seems that patients with urge incontinence and urinary retention are the best candidates for neuromodulation. In the literature the lack of standardisation of selection criteria, stimulation parameters and definitions of success is striking. Neuromodulation by implant is a useful therapeutic alternative. It should at least be considered in patients with therapy-resistant urge incontinence and urinary retention before proceeding to surgery. Issues such as underlying physiology, methodological standardisation, technical improvements, and patient selection must be addressed in future research.

Minimally invasive trans-sacral approach to L5-S1 interbody fusion: Preliminary results from 1 center and review of the literature.

PubMed

Bradley, W Daniel; Hisey, Michael S; Verma-Kurvari, Sunita; Ohnmeiss, Donna D

2012-01-01

Lumbar interbody fusion has long been used for the treatment of painful degenerative spinal conditions. The anterior approach is not feasible in some patients, and the posterior approach is associated with a risk of neural complications and possibly muscle injury. A trans-sacral technique was developed that allows access to the L5-S1 disc space. The purposes of this study were to investigate the clinical outcome of trans-sacral interbody fusion in a consecutive series of patients from 1 center and to perform a comprehensive review of the literature on this procedure. A literature search using PubMed was performed to identify articles published on trans-sacral axial lumbar interbody fusion (AxiaLIF). Articles reviewed included biomechanical testing, feasibility of the technique, and clinical results. The data from our center were collected retrospectively from charts for the consecutive series, beginning with the first case, of all patients undergoing fusion using the AxiaLIF technique. In most cases, posterior instrumentation was also used. A total of 41 patients with at least 6 months' follow-up were included (mean follow-up, 22.2 months). The primary clinical outcome measures were visual analog scales separately assessing back and leg pain and the Oswestry Disability Index. Radiographic assessment of fusion was also performed. In the group of 28 patients undergoing single-level AxiaLIF combined with posterior fusion, the visual analog scale scores assessing back and leg pain and mean Oswestry Disability Index scores improved significantly (P < .01). In the remaining 13 patients, back pain improved significantly with a trend for improvement in leg pain. Reoperation occurred in 19.5% of patients; in half of these, reoperation was not related to the anterior procedure. A review of the literature found that the AxiaLIF technique was similar to other fusion techniques with respect to biomechanical properties and produced acceptable clinical outcomes, although results

Pregnancy in women with Fowler's syndrome treated with sacral neuromodulation.

PubMed

Khunda, Azar; Karmarkar, Roopali; Abtahi, Bahareh; Gonzales, Gwen; Elneil, Sohier

2013-07-01

Our aim was to determine the impact of pregnancy on sacral neuromodulation (SNM) and vice versa in patients with Fowler's syndrome (FS), which is typified by chronic urinary retention (CUR). We performed a retrospective study of pregnancy in patients with FS who underwent a two-stage SNM implantation. Data were obtained using a standard questionnaire and clinical interview. There were a total of ten patients with 13 pregnancies. The SNM was switched off in ten of the 13 pregnancies, with CUR recurring in nine of the ten pregnancies and recurrent urinary tract infections (UTI) occurring in four of these pregnancies (more than three UTI in the pregnancy). Those in whom the device was left on continued to void normally. One woman had a first trimester miscarriage, eight pregnancies went to term, and four deliveries were premature. Caesarean section was performed in eight pregnancies for obstetric reasons. Four pregnancies resulted in a vaginal delivery. There were no congenital anomalies reported. Following delivery, four of nine women experienced dysfunction of their SNM device when it was switched back on. Turing off the SNM during pregnancy results in recurrence of CUR, with an increased risk of recurrent UTI associated with preterm delivery. This did not impact foetal well-being. The option of keeping the SNM on during pregnancy should therefore be considered, and as caesarean section affects the SNM device, we advise that caesarean section should only be performed for obstetric reasons.

Aggregation and Particle Formation of Therapeutic Proteins in Contact With a Novel Fluoropolymer Surface Versus Siliconized Surfaces: Effects of Agitation in Vials and in Prefilled Syringes.

PubMed

Teska, Brandon M; Brake, Jeffrey M; Tronto, Gregory S; Carpenter, John F

2016-07-01

We examined the effects of an accelerated agitation protocol on 2 protein therapeutics, intravenous immunoglobulin (IVIG) and Avastin (bevacizumab), in contact with a novel fluoropolymer surface and more typical siliconized surfaces. The fluoropolymer surface provides "solid-phase" lubrication for the syringe plunger-obviating the need for silicone oil lubrication in prefilled syringes. We tested the 2 surfaces in a vial system and in prefilled glass syringes. We also examined the effects of 2 buffers, phosphate-buffered saline (PBS) and 0.2-M glycine, with and without the addition of polysorbate 20, on agitation-induced aggregation of IVIG. Aggregation was monitored by measuring subvisible particle formation and soluble protein loss. In both vials and syringes, protein particle formation was much lower during agitation with the fluoropolymer surface than with the siliconized surface. Also, particle formation was greater in PBS than in glycine buffer, an effect attributed to lower colloidal stability of IVIG in PBS. Polysorbate 20 in the formulation greatly inhibited protein particle formation. Overall, the fluoropolymer plunger surface in an unsiliconized glass barrel was demonstrated to be a viable solution for eliminating silicone oil droplets from prefilled syringe formulations and providing a consistent system for rationale formulation development and simplified particle analysis. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Descriptive Cadaveric Study Comparing the Accuracy of Ultrasound Versus Fluoroscopic Guidance for First Sacral Transforaminal Injections: A Comparison Study.

PubMed

Thompson, Bradley F; Pingree, Matthew J; Qu, Wenchun; Murthy, Naveen S; Lachman, Nirusha; Hurdle, Mark Friedrich

2018-04-01

Ultrasound is rarely used for guiding lumbosacral epidural steroid injections due to its technical limitations. For example, sonographic imaging lacks the ability to confirm epidural spread and identify vascular uptake. The perceived risk that these limitations pose to human subjects has precluded any large scale clinical trials to date. To compare the accuracy of ultrasound versus fluoroscopic guidance for first sacral transforaminal epidural injections. Cadaveric comparative study using dichotomous outcomes. A fluoroscopy suite and anatomic laboratory at an academic medical center. Four unembalmed adult human cadavers with no history of spinal surgery. Eight sites were injected twice by one interventionalist, using fluoroscopic and ultrasound guidance. In the fluoroscopy arm, contrast spread was assessed using computed tomography. In the ultrasound arm, latex spread was assessed using gross anatomic dissection. Any visible evidence of epidural spread constituted a positive result. Comparison of the success of obtaining epidural contrast flow was the primary outcome measure. Secondary outcome measures included average duration, rate of intravascular uptake, and quantity of intravascular uptake. All injections performed in both the ultrasound arm and the fluoroscopy arm had positive epidural spread. The average duration was 3.03 minutes with fluoroscopy and 4.76 minutes with ultrasound. The rate of intravascular uptake was 37.5% with fluoroscopy and 50% with ultrasound. Within the ultrasound arm, greater intravascular spread and duration variability were recorded. Although ultrasonography can provide reliable image guidance for cannulating the first sacral foramen in cadavers, it would have limited clinical utility due to its inability to visualize relevant neurovascular structures deep to the osseus roof and exclude intravascular uptake. IV. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Equivalent square formula for determining the surface dose of rectangular field from 6 MV therapeutic photon beam.

PubMed

Apipunyasopon, Lukkana; Srisatit, Somyot; Phaisangittisakul, Nakorn

2013-09-06

The purpose of the study was to investigate the use of the equivalent square formula for determining the surface dose from a rectangular photon beam. A 6 MV therapeutic photon beam delivered from a Varian Clinac 23EX medical linear accelerator was modeled using the EGS4nrc Monte Carlo simulation package. It was then used to calculate the dose in the build-up region from both square and rectangular fields. The field patterns were defined by various settings of the X- and Y-collimator jaw ranging from 5 to 20 cm. Dose measurements were performed using a thermoluminescence dosimeter and a Markus parallel-plate ionization chamber on the four square fields (5 × 5, 10 × 10, 15 × 15, and 20 × 20 cm2). The surface dose was acquired by extrapolating the build-up doses to the surface. An equivalent square for a rectangular field was determined using the area-to-perimeter formula, and the surface dose of the equivalent square was estimated using the square-field data. The surface dose of square field increased linearly from approximately 10% to 28% as the side of the square field increased from 5 to 20 cm. The influence of collimator exchange on the surface dose was found to be not significant. The difference in the percentage surface dose of the rectangular field compared to that of the relevant equivalent square was insignificant and can be clinically neglected. The use of the area-to-perimeter formula for an equivalent square field can provide a clinically acceptable surface dose estimation for a rectangular field from a 6 MV therapy photon beam.

ACHIEVING THE PROMISE OF THERAPEUTIC EXTRACELLULAR VESICLES: THE DEVIL IS IN DETAILS OF THERAPEUTIC LOADING

PubMed Central

Sutaria, Dhruvitkumar S.; Badawi, Mohamed; Phelps, Mitch A.; Schmittgen, Thomas D.

2017-01-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics. PMID:28315083

Sacral Nerve Stimulation For Urinary Urge Incontinence, Urgency-Frequency, Urinary Retention, and Fecal Incontinence

PubMed Central

2005-01-01

Executive Summary Objective The aim of this review was to assess the effectiveness, safety, and cost of sacral nerve stimulation (SNS) to treat urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence. Background: Condition and Target Population Urinary urge incontinence, urgency-frequency, urinary retention, and fecal incontinence are prevalent, yet rarely discussed, conditions. They are rarely discussed because patients may be uncomfortable disclosing their symptoms to a health professional or may be unaware that there are treatment options for these conditions. Briefly, urge incontinence is an involuntary loss of urine upon a sudden urge. Urgency-frequency is an uncontrollable urge to void, which results in frequent, small-volume voids. People with urgency-frequency may or may not also experience chronic pelvic pain. Urinary retention refers to the inability to void despite having the urge to void. It can be caused by a hypocontractile detrusor (weak or no bladder muscle contraction) or obstruction due to urethral overactivity. Fecal incontinence is a loss of voluntary bowel control. The prevalence of urge incontinence, urgency-frequency, and urinary retention in the general population is 3.3% to 8.2%, and the prevalence of fecal incontinence is 1.4% to 1.9%. About three-quarters of these people will be successfully treated by behaviour and/or drug therapy. For those who do not respond to these therapies, the options for treatment are management with diapers or pads, or surgery. The surgical procedures are generally quite invasive, permanent, and are associated with complications. Pads and/or diapers are used throughout the course of treatment as different therapies are tried. Patients who respond successfully to treatment may still require pads or diapers, but to a lesser extent. The Technology Being Reviewed: Sacral Nerve Stimulation Sacral nerve stimulation is a procedure where a small device attached to an electrode is

Protection of Nonself Surfaces from Complement Attack by Factor H-Binding Peptides: Implications for Therapeutic Medicine

PubMed Central

Wu, You-Qiang; Qu, Hongchang; Sfyroera, Georgia; Tzekou, Apostolia; Kay, Brian K.; Nilsson, Bo; Ekdahl, Kristina Nilsson; Ricklin, Daniel; Lambris, John D.

2011-01-01

Exposure of nonself surfaces such as those of biomaterials or transplanted cells and organs to host blood frequently triggers innate immune responses, thereby affecting both their functionality and tolerability. Activation of the alternative pathway of complement plays a decisive role in this unfavorable reaction. Whereas previous studies demonstrated that immobilization of physiological regulators of complement activation (RCA) can attenuate this foreign body-induced activation, simple and efficient approaches for coating artificial surfaces with intact RCA are still missing. The conjugation of small molecular entities that capture RCA with high affinity is an intriguing alternative, as this creates a surface with autoregulatory activity upon exposure to blood. We therefore screened two variable cysteine-constrained phage-displayed peptide libraries for factor H-binding peptides. We discovered three peptide classes that differed with respect to their main target binding areas. Peptides binding to the broad middle region of factor H (domains 5–18) were of particular interest, as they do not interfere with either regulatory or binding activities. One peptide in this group (5C6) was further characterized and showed high factor H-capturing activity while retaining its functional integrity. Most importantly, when 5C6 was coated to a model polystyrene surface and exposed to human lepirudin-anticoagulated plasma, the bound peptide captured factor H and substantially inhibited complement activation by the alternative pathway. Our study therefore provides a promising and novel approach to produce therapeutic materials with enhanced biocompatibility. PMID:21339361

Increased yield pressure in the anal canal during sacral nerve stimulation: a pilot study with the functional lumen imaging probe.

PubMed

Haas, S; Liao, D; Gregersen, H; Lundby, L; Laurberg, S; Krogh, K

2017-02-01

Sacral nerve stimulation (SNS) is a well-established treatment for fecal incontinence but its mode of action remains obscure. Anal sphincter function is usually evaluated with manometry but resistance to distension may be a more appropriate parameter than luminal pressure. The functional lumen imaging probe allows detailed description of distension properties of the anal canal. Our objective in this study was to characterize the impact of SNS on distension properties of the anal canal in patients with idiopathic fecal incontinence. We studied 10 women (median age 64 [44-79] years) with idiopathic fecal incontinence at baseline and during SNS. The luminal geometry of the anal canal was examined with the FLIP at rest and during squeeze and the distensibility of the anal canal was investigated during filling of the bag. All patients were successfully treated with SNS and the mean Wexner Incontinence Score was reduced from 14.9 ± 4 to 7.1 ± 4.8 (P<.001). The pressure required to open the narrowest point of the anal canal during distension (yield pressure) increased from 14.5 ± 12.2 mmHg at baseline to 20.5 ± 13.3 mmHg during SNS (P<.01). The pressure-strain elastic modulus increased non-significantly from 2.2 ± 0.5 to 2.9 ± 1.6 kPa, indicating increased stiffness of the anal canal. The yield pressure and the resistance to distension increased in response to SNS for idiopathic fecal incontinence. This will inevitably increase the resistance to flow through the anal canal, which may contribute to the benefits of sacral nerve stimulation. © 2016 John Wiley & Sons Ltd.

Accuracy of clinical neurological examination in diagnosing lumbo-sacral radiculopathy: a systematic literature review.

PubMed

Tawa, Nassib; Rhoda, Anthea; Diener, Ina

2017-02-23

Lumbar radiculopathy remains a clinical challenge among primary care clinicians in both assessment and diagnosis. This often leads to misdiagnosis and inappropriate treatment of patients resulting in poor health outcomes, exacerbating this already debilitating condition. This review evaluated 12 primary diagnostic accuracy studies that specifically assessed the performance of various individual and grouped clinical neurological tests in detecting nerve root impingement, as established in the current literature. Eight electronic data bases were searched for relevant articles from inception until July 2016. All primary diagnostic studies which investigated the accuracy of clinical neurological test (s) in diagnosing lumbar radiculopathy among patients with low back and referred leg symptoms were screened for inclusion. Qualifying studies were retrieved and independently assessed for methodological quality using the 'Quality Assessment of Diagnostic tests Accuracy Studies' criteria. A total of 12 studies which investigated standard components of clinical neurological examination of (sensory, motor, tendon reflex and neuro-dynamics) of the lumbo-sacral spine were included. The mean inter-observer agreement on quality assessment by two independent reviewers was fair (k = 0.3 - 0.7). The diagnostic performance of sensory testing using MR imaging as a reference standard demonstrated a sensitivity (confidence interval 95%) 0.61 (0.47-0.73) and a specificity of 0.63 (0.38-0.84). Motor tests sensitivity was poor to moderate, ranging from 0.13 (0.04-0.31) to 0.61 (0.36-0.83). Generally, the diagnostic performance of reflex testing was notably good with specificity ranging from (confidence interval 95%) 0.60 (0.51-0.69) to 0.93 (0.87-0.97) and sensitivity ranging from 0.14 (0.09-0.21) to 0.67 (0.21-0.94). Femoral nerve stretch test had a high sensitivity of (confidence interval 95%) 1.00 (0.40-1.00) and specificity of 0.83 (0.52-0.98) while SLR test recorded a mean

Kinetic analysis of a monoclonal therapeutic antibody and its single-chain homolog by surface plasmon resonance.

PubMed

Patel, Rekha; Andrien, Bruce A

2010-01-01

Monoclonal antibodies (mAbs) and antibody fragments have become an emerging class of therapeutics since 1986. Their versatility enables them to be engineered for optimal efficiency and decreased immunogenicity, and the path to market has been set by recent regulatory approvals. One of the initial criteria for success of any protein or antibody therapeutic is to understand its binding characteristics to the target antigen. Surface plasmon resonance (SPR) has been widely used and is an important tool for ligand-antigen binding characterization. In this work, the binding kinetics of a recombinant mAb and its single-chain antibody homolog, single-chain variable fragment (scFv), was analyzed by SPR. These two proteins target the same antigen. The binding kinetics of the mAb (bivalent antibody) and scFv (monovalent scFv) for this antigen was analyzed along with an assessment of the thermodynamics of the binding interactions. Alternative binding configurations were investigated to evaluate potential experimental bias because theoretically experimental binding configuration should have no impact on binding kinetics. Self-association binding kinetics in the proteins' respective formulation solutions and antigen epitope mapping were also evaluated. Functional characterization of monoclonal and single-chain antibodies has become just as important as structural characterization in the biotechnology field.

Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets.

PubMed

Haq, Iram J; Gray, Michael A; Garnett, James P; Ward, Christopher; Brodlie, Malcolm

2016-03-01

Cystic fibrosis (CF) is a life-limiting disease characterised by recurrent respiratory infections, inflammation and lung damage. The volume and composition of the airway surface liquid (ASL) are important in maintaining ciliary function, mucociliary clearance and antimicrobial properties of the airway. In CF, these homeostatic mechanisms are impaired, leading to a dehydrated and acidic ASL. ASL volume depletion in CF is secondary to defective anion transport by the abnormal cystic fibrosis transmembrane conductance regulator protein (CFTR). Abnormal CFTR mediated bicarbonate transport creates an unfavourable, acidic environment, which impairs antimicrobial function and alters mucus properties and clearance. These disease mechanisms create a disordered airway milieu, consisting of thick mucopurulent secretions and chronic bacterial infection. In addition to CFTR, there are additional ion channels and transporters in the apical airway epithelium that play a role in maintaining ASL homeostasis. These include the epithelial sodium channel (ENaC), the solute carrier 26A (SLC26A) family of anion exchangers, and calcium-activated chloride channels. In this review we discuss how the ASL is abnormal in CF and how targeting these alternative channels and transporters could provide an attractive therapeutic strategy to correct the underlying ASL abnormalities evident in CF. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties

NASA Astrophysics Data System (ADS)

in, Su-Ll; Gwak, Young S.; Kim, Hye Rim; Razzaq, Abdul; Lee, Kyeong-Seok; Kim, Hee Young; Chang, Suchan; Lee, Bong Hyo; Grimes, Craig A.; Yang, Chae Ha

2016-10-01

Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. Our work offers a unique pathway for achieving a comfortable and improved acupuncture therapeutic effect.

Hierarchical Micro/Nano-Porous Acupuncture Needles Offering Enhanced Therapeutic Properties

PubMed Central

In, Su-ll; Gwak, Young S.; Kim, Hye Rim; Razzaq, Abdul; Lee, Kyeong-Seok; Kim, Hee Young; Chang, SuChan; Lee, Bong Hyo; Grimes, Craig A.; Yang, Chae Ha

2016-01-01

Acupuncture as a therapeutic intervention has been widely used for treatment of many pathophysiological disorders. For achieving improved therapeutic effects, relatively thick acupuncture needles have been frequently used in clinical practice with, in turn, enhanced stimulation intensity. However due to the discomforting nature of the larger-diameter acupuncture needles there is considerable interest in developing advanced acupuncture therapeutical techniques that provide more comfort with improved efficacy. So motivated, we have developed a new class of acupuncture needles, porous acupuncture needles (PANs) with hierarchical micro/nano-scale conical pores upon the surface, fabricated via a simple and well known electrochemical process, with surface area approximately 20 times greater than conventional acupuncture needles. The performance of these high-surface-area PANs is evaluated by monitoring the electrophysiological and behavioral responses from the in vivo stimulation of Shenmen (HT7) points in Wistar rats, showing PANs to be more effective in controlling electrophysiological and behavioral responses than conventional acupuncture needles. Comparative analysis of cocaine induced locomotor activity using PANs and thick acupuncture needles shows enhanced performance of PANs with significantly less pain sensation. Our work offers a unique pathway for achieving a comfortable and improved acupuncture therapeutic effect. PMID:27713547

Long term safety of sacral nerve modulation in medicare beneficiaries.

PubMed

Chughtai, Bilal; Sedrakyan, Art; Isaacs, Abby; Lee, Richard; Te, Alexis; Kaplan, Steven

2015-09-01

Sacral nerve stimulation (SNS) is FDA approved as second-line therapy for both urinary and bowel control. However, there is limited evidence regarding long term safety. We determined adverse events associated with SNS among Medicare beneficiaries. We used the 5% national random sample of Medicare claims for 2001-2011 to identify patients. Patients who underwent SNS implantation were identified with Current Procedure Terminology (CPT-4) codes. We determined safety of SNS using analysis of complication occurrences on day of surgery and during 5 years following initial procedure. SAS v9.3 statistical package was used. One thousand four hundred seventy-four patients underwent treatment with SNS in the 5% national sample of Medicare patients within the time period. Representative of real-world patients undergoing SNS surgery, comorbidities included hypertension (69.3%), diabetes (29.4%), chronic pulmonary disease (25.5%), hypothyroidism (25.2%), and depression (22.7%). Few complications occurred on day of surgery. At 90 days, 3.2% of patients had bowel complications, 2.0% urological, 9.4% infectious, and 1.5% stroke. Overall, bowel, neurological health event occurrences were consistent with prior year rates, while infectious events decreased. Of 206 patients who were followed for at least 5 years, 17.3% had devices removed and 11.3% replaced, with 26.1% having at least one of those, leaving 73.9% with original devices. Urological, infectious, and bowel complication occurrences were low after SNS among Medicare beneficiaries with multiple comorbidities. There were infrequent serious complications like hemorrhage and stroke postoperatively. Although SNS appears safe in this high-risk population, a comprehensive registry will ensure continuous safety. © 2014 Wiley Periodicals, Inc.

Intraoperative indocyanine green fluorescent angiography-assisted modified superior gluteal artery perforator flap for reconstruction of sacral pressure sores.

PubMed

Chang, Chun-Kai; Wu, Chien-Ju; Chen, Chun-Yu; Wang, Chi-Yu; Chu, Tzi-Shiang; Hsu, Kuo-Feng; Chiu, Han-Ting; Liu, Hung-Hui; Chou, Chang-Yi; Wang, Chih-Hsin; Lin, Chin-Ta; Dai, Niann-Tzyy; Tzeng, Yuan-Sheng

2017-12-01

Pressure sores are often observed in patients who are bedridden. They can be a severe problem not only for patients and their caregivers but also for plastic surgeons. Here, we describe a new method of superior gluteal artery perforator flap harvesting and anchoring with the assistance of intraoperative indocyanine green fluorescent angiography. In this report, we describe the procedure and outcomes for 19 patients with grades III and IV sacral pressure sores who underwent the operation between September 2015 and November 2016. All flaps survived, and two experienced wound-edge partial dehiscence. With the assistance of this imaging device, we were able to acquire a reliable superior gluteal artery perforator flap and perform modified operations with it that are safe, easy to learn and associated with fewer complications than are traditional. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Mechanisms of Plasma Therapeutics

NASA Astrophysics Data System (ADS)

Graves, David

2015-09-01

In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

Vaginal sacrospinous colpopexy and laparoscopic sacral colpopexy for vaginal vault prolapse.

PubMed

Marcickiewicz, J; Kjöllesdal, M; Engh, M Ellström; Eklind, S; Axén, C; Brännström, M; Stjerndahl, J-H

2007-01-01

Vaginal sacrospinous colpopexy (VSC) and laparoscopic sacral colpopexy (LSC) both correct vault prolapse. The present study compares the perioperative course and long-term results of VSC and LSC. This retrospective study of post-hysterectomy vault prolapse involved 111 patients operated with either VSC (n=51) or LSC (n=60). The median time for the postoperative follow-up visit was 33.6 (range: 13-60) months for the LSC group and 38.4 (range: 7-108) months for the VSC group. Prolapse grade as well as the patient's satisfaction was recorded at the follow-up visit. Operation time was significantly shorter in the VSC group (median: 62 min) compared to the LSC group (median: 129 min). The rate of perioperative complications was low in both groups. There were 3 laparotomies in the LSC group, due to perioperative complications. The inpatients days were similar, with 3.7 days (1-18) and 4.0 days (2-21) in the VSC and the LSC group, respectively. Surgery for the recurrence of vault prolapse at any time before the follow-up visit did not occur in the VSC group, but occurred in 7 patients in the LSC group. At the follow-up visit, there was no recurrence of vault prolapse in either group. The subjective success rate was 82% in the VSC and 78% in the LSC group. This study indicates that VSC and LSC are two equally effective surgical procedures to correct vaginal vault prolapse, but the LSC technique requires a longer operating time.

Identification of viral microRNAs expressed in human sacral ganglia latently infected with herpes simplex virus 2.

PubMed

Umbach, Jennifer L; Wang, Kening; Tang, Shuang; Krause, Philip R; Mont, Erik K; Cohen, Jeffrey I; Cullen, Bryan R

2010-01-01

Deep sequencing of small RNAs isolated from human sacral ganglia latently infected with herpes simplex virus 2 (HSV-2) was used to identify HSV-2 microRNAs (miRNAs) expressed during latent infection. This effort resulted in the identification of five distinct HSV-2 miRNA species, two of which, miR-H3/miR-I and miR-H4/miR-II, have been previously reported. Three novel HSV-2 miRNAs were also identified, and two of these, miR-H7 and miR-H9, are derived from the latency-associated transcript (LAT) and are located antisense to the viral transcript encoding transactivator ICP0. A third novel HSV-2 miRNA, miR-H10, is encoded within the unique long (U(L)) region of the genome, 3' to the U(L)15 open reading frame, and is presumably excised from a novel, latent HSV-2 transcript distinct from LAT.

Sacral neuromodulation and pregnancy: Results of a national survey carried out for the neuro-urology committee of the French Association of Urology (AFU).

PubMed

Roulette, Pauline; Castel-Lacanal, Evelyne; Sanson, Sylvain; Caremel, Romain; Phé, Véronique; Bart, Stéphane; Duchêne, Franck; De Sèze, Marianne; Even, Alexia; Manunta, Andréa; Scheiber-Nogueira, Maria C; Mouracade, Pascal; Loche, Catherine-Marie; Chartier-Kastler, Emmanuel; Ruffion, Alain; Karsenty, Gilles; Gamé, Xavier

2018-02-01

To assess the impact of sacral neuromodulation (SNM) on pregnancy and vice-versa, by identifying women who had received SNM for lower-urinary tract symptoms (LUTS) and had become pregnant. A cross-sectional descriptive study was carried out based on responses to an on-line questionnaire sent to practitioners listed on the InterStim enCaptureTM National Registry. Questions were related to pre-pregnancy health and SNM efficacy, deactivation of the device, its impact on LUTS, childbirth, the infant, its reactivation and postpartum effectiveness. Twenty-seven pregnancies were recorded among 21 women. Six women had had a pregnancy prior to implantation, two of whom had had a c-section. A total of 18.5% of women had the device disabled prior to conception. The others had their device disabled during the first trimester and did not reactivate it before delivery. Complications were reported in 25.9% of pregnancies: six women had urinary infections, including three of the four treated for chronic retention of urine (CRU), and 1 woman had pain at the stimulation site. There were 24 live births (including one premature birth and four c-sections), one spontaneous miscarriage and two voluntary interruptions of pregnancy. No neonatal disorders have been reported. Effectiveness of sacral neuromodulation decreased in 20% in postpartum. In 27 pregnancies established during SNM for LUTS, 18.5% of patients deactivated their case before pregnancy and the others switched it off during the first trimester. Three-quarters of women with CRU had urinary infection. No adverse effects on fetuses were found. SNM effectiveness deteriorated in 20% cases after childbirth. © 2017 Wiley Periodicals, Inc.

[Cystomanometric study of bladder sensation during sacral neuromodulation test].

PubMed

Leclers, François; Mourey, Eric; Galas, Jean Marie; Cormier, Luc; Mangin, Philippe

2005-04-01

Prospective clinical and urodynamic study evaluating modification of bladder sensation during sacral neuromodulation (SNM). 24 consecutive patients with non-neurological hyperactive bladder underwent an SNM test. Questioned about their symptoms before and during the test by the urinary handicap assessment scale, patients were divided into two groups: A (improved) and B (not improved). Group A consisted of patients obtaining 50% improvement of their symptoms with SNM followed by return of symptoms at the end of the test, while the other patients constituted group B. We then compared the cystomanometric results according to their clinical response. The mean age was 53 years: 10 patients with a good response constituted group A (n=10, i.e. 42%) and 14 patients with a poor response constituted group B (n=14, i.e. 58%). Clinically, in patients with a good response, SNM decreased urge incontinence by 100%, day-time frequency by 89% and protections by 55%. Urodynamic assessment in group A during the test demonstrated a significant increase of +23% of bladder capacity (p<0.01), +57% of the volume of onset of the first unstable contraction (p<0.004), +83% of bladder volume to the first urge to urinate BI (p<0.001) and +46% to urgency B3 (p<0.04). During SNM, cystometry revealed that 1 or 2 bladder filling volumes were increased at B1 and/or B3 in 100% of improved subjects. In contrast, 1 or 2 volumes decreased at B1 and/or B3 in 58% of non-improved subjects. No significant difference of intensity of unstable contractions was observed between the 2 groups during SNM (p=0.31). A significant correlation was observed between the two methods of clinical and urodynamic assessment. Our results suggest the use of the cystomanometric increase of bladder volume at B1 and B3 as selection criterion for candidates for SNM with non-neurological hyperactive bladder.

Sexual response in patients treated with sacral neuromodulation for lower urinary tract symptoms or fecal incontinence.

PubMed

van Voskuilen, A C; Oerlemans, D J; Gielen, N; Lansen-Koch, S M P; Weil, E H J; van Lankveld, J J D M; van den Hombergh, U; Baeten, C G M I; van Kerrenbroeck, P E V

2012-01-01

To determine whether sacral neuromodulation (SNM) for urinary symptoms or fecal incontinence gives improvement of female sexual function and whether improvement is due to physiological or psychological factors. Between 2002 and 2008, 8 patients had an array of questionnaires before and after SNM implantation. The questionnaires were: the Questionnaire for Screening for Sexual Dysfunctions, the Golombok Rust Inventory of Sexual Satisfaction, the Symptom Checklist-90, the Maudsley Marital Questionnaire and the McGill-Mah Orgasm Questionnaire. Three of these 8 patients underwent vaginal plethysmography before and after implantation. No statistically significant changes were found, although there seems to be a trend toward improvement in orgasm scores. In plethysmography all 3 patients showed increased vaginal pulse amplitude with the stimulator turned on with both erotic and non-erotic stimuli. This study does not show a clear effect of SNM on sexual function, although there seems to be an improvement in orgasm scores. The lack of response on psychological questionnaires and the increase in vaginal pulse amplitude after SNM implantation indicate that there might be a physiological response. Copyright © 2012 S. Karger AG, Basel.

The influence of thermoplastic thoraco lumbo sacral orthoses on standing balance in subjects with idiopathic scoliosis.

PubMed

Khanal, Minoo; Arazpour, Mokhtar; Bahramizadeh, Mahmood; Samadian, Mohammad; Hutchins, Stephen W; Kashani, Reza Vahab; Mardani, Mohammad A; Tari, Hossein Vahid; Aboutorabi, Atefeh; Curran, Sarah; Sadeghi, Heidar

2016-08-01

Idiopathic scoliosis patients have postural equilibrium problems. The objective of this study was to assess postural control in subjects with idiopathic scoliosis following a 4-month intervention in an unbraced position. Quasi-experimental. Eight healthy girls and eight girls with idiopathic scoliosis took part. A Kistler force platform was used with a frequency of 100 Hz for recording data. The center of pressure was recorded in different positions out of brace for scoliosis and healthy subjects. Test conditions were single limb and double limb stance, with eyes open and closed, and foam and rigid surfaces. The data reflected a weak balance of idiopathic scoliosis subjects compared to healthy subjects. After 1 and 4 months of wearing the brace, center of pressure and center of gravity sway increased in the majority of the tests, although there were no significant differences in any of the test conditions (p > 0.05). While the center of pressure sway in medio-lateral direction decreased after 4 months of wearing a brace, in other variables center of pressure and center of gravity sway increased. Idiopathic scoliosis patients have weak balance in comparison to healthy subjects. In addition, following a period of 4 months of wearing a brace, balance parameters in the scoliosis subjects did not improve. The results show that we need more follow-up of orthoses wearing in idiopathic scoliosis subjects and suggest more studies at least 1-year follow-up to identify the efficiency of brace wear on balance. Scoliosis can alter postural stability and balance performance during quiet standing. Spinal deformity can alter a subject's ability to compensate for postural changes and cause gait deviations. This study investigated balance differences between the healthy and idiopathic scoliosis patients and the results of thoraco lumbo sacral orthosis brace wear. It might provide some new insight into the conservative treatment of idiopathic scoliosis patients for

Chronic monitoring of lower urinary tract activity via a sacral dorsal root ganglia interface

NASA Astrophysics Data System (ADS)

Khurram, Abeer; Ross, Shani E.; Sperry, Zachariah J.; Ouyang, Aileen; Stephan, Christopher; Jiman, Ahmad A.; Bruns, Tim M.

2017-06-01

Objective. Our goal is to develop an interface that integrates chronic monitoring of lower urinary tract (LUT) activity with stimulation of peripheral pathways. Approach. Penetrating microelectrodes were implanted in sacral dorsal root ganglia (DRG) of adult male felines. Peripheral electrodes were placed on or in the pudendal nerve, bladder neck and near the external urethral sphincter. Supra-pubic bladder catheters were implanted for saline infusion and pressure monitoring. Electrode and catheter leads were enclosed in an external housing on the back. Neural signals from microelectrodes and bladder pressure of sedated or awake-behaving felines were recorded under various test conditions in weekly sessions. Electrodes were also stimulated to drive activity. Main results. LUT single- and multi-unit activity was recorded for 4-11 weeks in four felines. As many as 18 unique bladder pressure single-units were identified in each experiment. Some channels consistently recorded bladder afferent activity for up to 41 d, and we tracked individual single-units for up to 23 d continuously. Distension-evoked and stimulation-driven (DRG and pudendal) bladder emptying was observed, during which LUT sensory activity was recorded. Significance. This chronic implant animal model allows for behavioral studies of LUT neurophysiology and will allow for continued development of a closed-loop neuroprosthesis for bladder control.

Improved sexual and urinary function in women with sacral nerve stimulation.

PubMed

Gill, Bradley C; Swartz, Mia A; Firoozi, Farzeen; Rackley, Raymond R; Moore, Courtenay K; Goldman, Howard B; Vasavada, Sandip P

2011-01-01

  Urinary and sexual function improve following sacral nerve stimulation (SNS) for refractory overactive bladder. No significant associations between these changes have been found. Whether improvements in sexual function are independent of or secondary to improvements in urinary function remains unclear. The aim of this study was to analyze changes in urinary and sexual function in a homogeneous sample of patients undergoing SNS for urge urinary incontinence and subsequently identify associations between the two.   A prospective database was created. Enrollees underwent a full history and physical examination at the first office visit. Multiple-day voiding diaries with validated and investigator-designed questionnaires were administered at baseline and follow-up as standard implantation procedures and to assess changes in urinary and sexual function, respectively. Analyses were completed using data from patients who were sexually active at baseline and follow-up.   Statistically significant improvements in urinary and sexual function occurred according to multiple metrics. Patient global impression scales categorized all patients' urinary conditions as improved, with most being less severe. Validated urinary symptom and quality of life scores improved significantly. After treatment, most patients were incontinent less often with sexual activity and felt less restricted from sexual activity by fear of incontinence. Validated quantification of sexual function demonstrated significant improvements in overall sexual function, arousal, and satisfaction. No significant associations between changes in urinary and sexual function were noted; however, trends appeared to exist between the two.   Improved sexual function was not significantly associated with improved urinary function after SNS despite apparent trends between the two. Larger samples are required to definitively demonstrate this conclusion. © 2011 International Neuromodulation Society.

The different roles of opioid receptors in the inhibitory effects induced by sacral dorsal root ganglion stimulation on nociceptive and nonnociceptive conditions in cats.

PubMed

Wang, Zhaoxia; Liao, Limin; Deng, Han; Li, Xing; Chen, Guoqing; Liao, Xiwen

2018-06-04

To examine the roles of opioid receptors in the inhibition of nociceptive and nonnociceptive bladder reflexes by sacral dorsal root ganglion (DRG) stimulation in cats. Hook electrodes were placed in the right S1 and S2 DRG of cats. The bladders were infused with physiologic saline or 0.25% acetic acid (AA). Naloxone (0.1, 0.3, and 1 mg/kg), an opioid receptor antagonist, was administered intravenously. S1 or S2 DRG stimulation was applied before and after administering the drug. Multiple cystometrograms were performed to determine the effects of DRG stimulation and opioid receptors on the micturition reflex under nociceptive and non-nociceptive conditions. AA significantly (P < 0.01) reduced bladder capacity (BC). DRG stimulation at threshold (T) and 1.5 T significantly increased BC of the saline control under nociceptive and non-nociceptive conditions. When saline was infused, naloxone (0.1-1 mg/kg) significantly (P < 0.01) reduced BC; however, naloxone did not change BC during AA irritation. During saline infusion, naloxone (0.3 and 1 mg/kg) partly blocked S1 DRG stimulation-induced inhibition but had only a slight effect on S2 DRG stimulation. During AA infusion, naloxone (0.3 and 1 mg/kg) only partially blocked S1 DRG stimulation at T intensity but not during 1.5 T stimulation. However, no doses of naloxone significantly affected S2 DRG stimulation. Opioid receptors play a role in sacral DRG stimulation on non-nociceptive condition but are not involved in the inhibitory effect of stimulation in nociceptive conditions. © 2018 Wiley Periodicals, Inc.

Neuromodulation: urodynamic effects of sacral (S3) spinal nerve stimulation in patients with detrusor instability or detrusor hyperflexia.

PubMed

Bosch, J L; Groen, J

1998-05-01

The aim of this study was to determine the urodynamic effects of sacral (S3) nerve stimulation in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment. A total of 24 patients with idiopathic detrusor instability and five with neurogenic hyperreflexia were studied urodynamically before and 6 months after a permanent S3 foramen electrode implant. The urodynamic studies at follow-up were done with the stimulus on. Clinically, the average voiding frequency, the number of leakage episodes and pad use per 24 h decreased significantly. Improvement in several urodynamic parameters was noted. In the idiopathic as well as in the neurogenic group, the correlation between symptomatic and urodynamic improvement was incomplete. Neuromodulation leads to improvement of several urodynamic parameters in patients with urge incontinence due to detrusor overactivity which has been refractory to conservative treatment and appears to be a valuable treatment option in these patients.

Identification of Viral MicroRNAs Expressed in Human Sacral Ganglia Latently Infected with Herpes Simplex Virus 2▿

PubMed Central

Umbach, Jennifer L.; Wang, Kening; Tang, Shuang; Krause, Philip R.; Mont, Erik K.; Cohen, Jeffrey I.; Cullen, Bryan R.

2010-01-01

Deep sequencing of small RNAs isolated from human sacral ganglia latently infected with herpes simplex virus 2 (HSV-2) was used to identify HSV-2 microRNAs (miRNAs) expressed during latent infection. This effort resulted in the identification of five distinct HSV-2 miRNA species, two of which, miR-H3/miR-I and miR-H4/miR-II, have been previously reported. Three novel HSV-2 miRNAs were also identified, and two of these, miR-H7 and miR-H9, are derived from the latency-associated transcript (LAT) and are located antisense to the viral transcript encoding transactivator ICP0. A third novel HSV-2 miRNA, miR-H10, is encoded within the unique long (UL) region of the genome, 3′ to the UL15 open reading frame, and is presumably excised from a novel, latent HSV-2 transcript distinct from LAT. PMID:19889786

Long-term follow-up of sacral neuromodulation for lower urinary tract dysfunction.

PubMed

Peeters, Karlien; Sahai, Arun; De Ridder, Dirk; Van Der Aa, Frank

2014-05-01

To report our long-term experience of sacral neuromodulation (SNM) for various lower urinary tract dysfunctions but with a focus on efficacy, safety, re-interventions and degree of success. This is a single tertiary referral centre study that included 217 patients (86% female) who received an implantable pulse generator (IPG) (Interstim™, Medtronic, Minneapolis, USA) between 1996 and 2010. Success was considered if the initial ≥50% improvement in any of primary voiding diary variables persisted compared with baseline, but was further stratified. The mean duration of follow-up was 46.88 months. Success and cure rates were ≈70% and 20% for urgency incontinence, 68% and 33% for urgency frequency syndrome and 73% and 58% for idiopathic retention. In those patients with an unsuccessful therapy outcome, the mean time to failure was 24.6 months after implantation. There were 88 (41%) patients who had at least one device or treatment related surgical re-intervention. The re-intervention rate was 1.7 per patient with most of them (47%) occurring ≤2 years of follow-up. SNM appears effective in the long-term with a success rate after definitive IPG implant of ≈70% and complete cure rates ranging between 20% and 58% depending on indication. Patients with idiopathic retention appear to do best. The re-intervention rate is high with most occurring ≤2 years of implantation. It is likely that with the newer techniques used, efficacy and re-intervention rates will improve. © 2013 The Authors. BJU International © 2013 BJU International.

Percutaneous cannulated screw fixation of sacral fractures and sacroiliac joint disruptions with CT-controlled guidewires performed by interventionalists: single center experience in treating posterior pelvic instability.

PubMed

Fischer, Sebastian; Vogl, Thomas J; Marzi, Ingo; Zangos, Stephan; Wichmann, Julian L; Scholtz, Jan-Erik; Mack, Martin G; Schmidt, Sven; Eichler, Katrin

2015-02-01

The purpose of our study was to evaluate minimally invasive sacroiliac screw fixation for treatment of posterior pelvic instability with the help of CT controlled guidewires, assess its accuracy, safety and effectiveness, and discuss potential pitfalls. 100 guidewires and hollow titan screws were inserted in 38 patients (49.6±19.5 years) suffering from 35 sacral fractures and/or 16 sacroiliac joint disruptions due to 33 (poly-)traumatic, 2 osteoporotic and 1 post-infectious conditions. The guidewire and screw positions were analyzed in multiplanar reconstructions. The mean minimal distance between guidewire and adjacent neural foramina was 4.5±2.01mm, with a distinctly higher precision in S1 than S2. Eight guidewires showed cortical contacts, resulting in a total of 2% mismatched screws with subsequent wall violation. The fracture gaps were reduced from 3.6±0.53mm to 1.2±0.54mm. During follow-up 3 cases of minor iatrogenic sacral impaction (<5mm) due to the bolting and 2 cases of screw loosening were observed. Interventional time was 84.0min with a mean of 2.63 screws per patient whilst acquiring a mean of 93.7 interventional CT-images (DLP 336.7mGycm). The treatment of posterior pelvic instability with a guidewire-based screw insertion technique under CT-imaging results in a very high accuracy and efficacy with a low complication rate. Careful attention should be drawn to radiation levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Carbon Ion Radiation Therapy for Unresectable Sacral Chordoma: An Analysis of 188 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Imai, Reiko, E-mail: r_imai@nirs.go.jp; Kamada, Tadashi; Araki, Nobuhito

2016-05-01

Purpose: To evaluate the results of carbon ion radiation therapy administered to 188 patients with unresectable primary sacral chordomas. Patients and Methods: One hundred eighty-eight patients were treated with carbon ion radiation therapy at a single institute between 1996 and 2013 and retrospectively analyzed. The median age was 66 years. The highest proximal invasion reached past S2 level in 137 patients. The median clinical target volume was 345 cm{sup 3}. One hundred six patients received 67.2 gray equivalents (GyE)/16 fractions (fr), 74 patients received 70.4 GyE/16 fr, 7 patients received 73.6 GyE/16 fr, and 1 patient received 64.0 GyE/16 fr. Results: The median follow-upmore » period was 62 months (range, 6.8-147.5 months). Seventy percent of patients were followed for 5 years or until death. The 5-year local control, overall survival, and disease-free survival rates were 77.2%, 81.1%, and 50.3%, respectively. Forty-one patients had a local recurrence. Sex, tumor volume, level of proximal invasion, and irradiated dose were unrelated to local control. There was grade 3 toxicity of the peripheral nerves in 6 patients and grade 4 toxicity of the skin in 2 patients. Ambulation remained in 97% of patients. Conclusions: Carbon ion radiation therapy was safe and effective for unresectable chordoma and provided good local control and survival while preserving ambulation.« less

Baseline factors predictive of patient satisfaction with sacral neuromodulation for idiopathic fecal incontinence.

PubMed

Duelund-Jakobsen, Jakob; van Wunnik, Bart; Buntzen, Steen; Lundby, Lilli; Laurberg, Søren; Baeten, Cor

2014-07-01

Sacral neuromodulation (SNM) is an established treatment for fecal incontinence (FI). A recent study from our group found that the relationship between patient satisfaction and clinical outcome is complex and does not match the traditional used success criteria. Therefore, the ability to predict patient satisfaction must be given priority. The aim of the present study is to identify baseline factors predictive of patient satisfaction, with SNM, for idiopathic FI. We analyzed data from patients treated with SNM for idiopathic FI in Aarhus, Denmark, and Maastricht, The Netherlands. A questionnaire considering self-reported satisfaction was mailed to these patients and compared to baseline characteristics. Logistic regression was used to determine the predictive value of baseline demographic and diagnostic variables. In total, 131 patients were included in the analysis. Patient satisfaction with the current treatment result was reported in 75 patients. Fifty-six patients were dissatisfied with SNM treatment, after median 46 months (range 11-122) with permanent implantation. Pudendal nerve terminal motor latency (PNTML) was the solely identified predictor for long-term patient satisfaction. A subgroup univariate-logistic regression analysis showed that PNTML ≤ 2.3 ms at the side of lead implantation was a statistically significant predictor for patient satisfaction (odds ratio (OR) 2.3, 95% confidence interval (CI) 1.01-5.24, p = 0.048). Baseline PNTML measurement may be predictive of long-term satisfaction with SNM therapy for idiopathic FI. Further studies are needed to confirm this result.

Acute herpes zoster neuralgia: retrospective analysis of clinical aspects and therapeutic responsiveness.

PubMed

Haas, N; Holle, E; Hermes, B; Henz, B M

2001-01-01

Although the efficacy of modern antiviral agents for the treatment of herpes zoster is unquestioned, their ability to affect the associated pain remains controversial. We have therefore evaluated the inpatient hospital records of 550 patients with herpes zoster with regard to pain-related clinical aspects and therapeutic responsiveness. Intensity of pain was quantified by calculating a daily pain equivalence index (PEI) on the basis of different classes of pain medication and the number of tablets used in each category. The mean age of patients was 66.7 years, cranial segments were predominantly involved (55%), 64% of patients suffered from associated diseases and 77% experienced herpes-related pain. The PEI was 0.90 in the entire patient population, with significantly higher values in women and in patients with 3 or more associated diseases. It was lower in sacral and cranial nerve involvement, and it decreased rapidly in patients prior to discharge from hospital. Although there were significant differences in hospital stay between patients who received aciclovir and those who did not (mean 20.3 vs. 23.8 days), and for high- versus low-dose oral or intravenous administration, no significant differences were noted between the two groups for initial PEI values and during the course of observation, irrespective of the route of administration or the dose of aciclovir and the individual patient's PEI value. The groups were otherwise closely similar with regard to basic demographic and clinical data. 23.3% predominantly aged female patients with more associated diseases than the total patient population had a persistently elevated PEI and stayed in hospital beyond 21 days (mean 35.1 days), representing patients who went on to postherpetic neuralgia. These data further delineate clinical aspects of acute herpes zoster neuralgia, underline the unsolved therapeutic problems associated with this condition despite otherwise effective antiviral treatment, and characterise a

Sacral extradural arachnoid cyst in association with split cord malformation.

PubMed

Habibi, Zohreh; Hanaei, Sara; Nejat, Farideh

2016-09-01

Split cord malformation (SCM) is a congenital disease that can be associated with other spinal anomalies. Few cases of concurrent intradural arachnoid cyst and SCM have been sporadically reported; however, sacral extradural arachnoid cyst (SEAC) with SCM is very rare. The report describes our experience with simultaneous surgery in patients with concurrent SEAC and SCM in an effort to document the treatment of the rare spinal concomitant anomalies. The present study is designed as a case series. This is a continuous series of patients with coexisting SCM and SEAC who were presented to our institution. The lower extremities weakness and deformity, radiological imaging, urodynamic tests, and surgical aspects of the patient population are documented. Cases with concomitant anomalies were consecutively enrolled among 73 patients who were operated on for SCM between 2008 and 2014. Clinical data and surgical findings were prospectively filed and retrospectively evaluated. There were seven patients (2 boys and 5 girls), with age ranging from 18 to 119 months (mean: 56.71±39.49). Type I SCM was detected in six cases, and type II SCM was detected in one case. Tethering of the cord was detected in all seven patients, and six patients (85.7%) had syrinx formation rostral to the level of SCM. All patients had at least one kind of urological dysfunctions manifesting as neurogenic bladder. On surgery, fistulous orifice of the meningeal cyst was found and ligated in six cases, and the other one was repaired via sealing the cyst walls as near as possible to the thecal sac. In patients with symptomatic SCM, the signs of concurrent SEAC may be masqueraded by the former condition. It would be impossible to attribute a given sign, particularly urological signs, to either SCM or SEAC. Whatever the sign and nature, both conditions are better to be managed surgically in one session under a single anesthesia to prevent duplicate complications of further anesthesia and interventions in

Use of computed tomography to define a sacral safe corridor for placement of 2.7 mm cortical screws in feline sacroiliac luxation.

PubMed

Philp, Helen; Durand, Alexane; De Vicente, Felipe

2018-06-01

Objectives This study aimed to define a safe corridor for 2.7 mm cortical sacroiliac screw insertion in the dorsal plane (craniocaudal direction) using radiography and CT, and in the transverse plane (dorsoventral direction) using CT in feline cadavers. A further aim was to compare the values obtained by CT with those previously reported by radiography in the transverse plane. Methods Thirteen pelvises were retrieved from feline cadavers and dissected to expose one of the articular surfaces of the sacrum. A 2.7 mm screw was placed in the sacrum to a depth of approximately 1 cm in each exposed articular surface. Dorsoventral radiography and CT scanning of each specimen were performed. Multiplanar reconstructions were performed to allow CT evaluation in both the dorsal and transverse planes. Calculations were made to find the maximum, minimum and optimum angles for screw placement in craniocaudal (radiography and CT) and dorsoventral (CT) directions when using a 2.7 mm cortical screw. Results Radiographic measurement showed a mean optimum craniocaudal angle of 106° (range 97-112°). The mean minimum angle was 95° (range 87-107°), whereas the mean maximum angle was 117° (108-124°). Measurement of the dorsal CT scan images showed a mean optimum craniocaudal angle of 101° (range 94-110°). The mean minimum angle was 90° (range 83-99°), whereas the mean maximum angle was 113° (104-125°). The transverse CT scan images showed a mean dorsoventral minimum angle of 103° (range 95-113°), mean maximum angle of 115° (104-125°) and mean optimum dorsoventral angle of 111° (102-119°). Conclusions and relevance An optimum craniocaudal angle of 101° is recommended for 2.7 mm cortical screw placement in the feline sacral body, with a safety margin between 99° and 104°. No single angle can be recommended in the dorsoventral direction and therefore preoperative measuring on individual cats using CT images is recommended to establish the ideal individual angle in the

Muscle-splitting approach to superior and inferior gluteal vessels: versatile source of recipient vessels for free-tissue transfer to sacral, gluteal, and ischial regions.

PubMed

Park, S

2000-07-01

The superior gluteal vessel has been reported as a recipient in free-tissue transfer for the coverage of complex soft-tissue defects in the lumbosacral region, where a suitable recipient vessel is difficult to find. The characteristics of proximity, vessel caliber, and constancy make the superior gluteal vessel preferable to previously reported recipient vessels. However, there are technical difficulties in microsurgery (e.g., short pedicle length and deep location) and muscle injury (transection of the muscle) associated with use of the superior gluteal vessel. The purpose of this article is to present a modification of an approach to the gluteal vessel to alleviate technical difficulties and minimize muscle injury. From August of 1997 to January of 1999, six patients received microvascular transfer of the latissimus dorsi muscle or myocutaneous flap to the sacral (4) and ischial (2) regions. The causes of defects were tumor (1), trauma (1), and pressure sores (4). A muscle-splitting approach was used on the superior gluteal vessel and was later applied to the inferior gluteal vessel. The gluteus maximus muscle was split as needed in the direction of its fibers, and the perforators were dissected down to the superior or inferior gluteal artery and vein deep into the muscle. The follow-up period ranged from 6 to 22 months, and all of the flaps survived with complete recovery of the lesion. The major drawbacks of using the superior and inferior gluteal vessels can be overcome with the muscle-splitting approach, which provides increased accessibility and additional length to the vascular pedicle while causing minimal injury to the muscle itself. It also proves to be an easy, safe, and reliable method of dissection. When free-tissue transfer to sacral, gluteal, and ischial regions is indicated, the muscle-splitting approach to the superior and inferior gluteal vessels is a recommended option in the selection of a recipient vessel.

An economic appraisal of the Australian Medical Sheepskin for the prevention of sacral pressure ulcers from a nursing home perspective

PubMed Central

2010-01-01

Background Many devices are in use to prevent pressure ulcers, but from most little is known about their effects and costs. One such preventive device is the Australian Medical Sheepskin that has been proven effective in three randomized trials. In this study the costs and savings from the use of the Australian Medical Sheepskin were investigated from the perspective of a nursing home. Methods An economic model was developed in which monetary costs and monetary savings in respect of the sheepskin were balanced against each other. The model was applied to a fictional (Dutch) nursing home with 100 beds for rehabilitation patients and a time horizon of one year. Input variables for the model consisted of investment costs for using the sheepskin (purchase and laundry), and savings through the prevented cases of pressure ulcers. The input values for the investment costs and for the effectiveness were empirically based on a trial with newly admitted rehabilitation patients from eight nursing homes. The input values for the costs of pressure ulcer treatment were estimated by means of four different approaches. Results Investment costs for using the Australian Medical Sheepskin were larger than the monetary savings obtained by preventing pressure ulcers. Use of the Australian Medical Sheepskin involves an additional cost of approximately €2 per patient per day. Preventing one case of a sacral pressure ulcer by means of the Australian Medical Sheepskin involves an investment of €2,974 when the sheepskin is given to all patients. When the sheepskin is selectively used for more critical patients only, the investment to prevent one case of sacral pressure ulcers decreases to €2,479 (pressure ulcer risk patients) or €1,847 (ADL-severely impaired patients). The factors with the strongest influence on the balance are the frequency of changing the sheepskin and the costs of washing related to this. The economic model was hampered by considerable uncertainty in the

Updated Outcome and Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High-Dose Photon/Proton Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabolizadeh, Peyman, E-mail: peyman.kabolizadeh@beaumont.org; Chen, Yen-Lin; Liebsch, Norbert

Purpose: Treatment of spine and sacral chordoma generally involves surgical resection, usually in conjunction with radiation therapy. In certain circumstances where resection may result in significant neurologic or organ dysfunction, patients can be treated definitively with radiation therapy alone. Herein, we report the outcome and the assessment of tumor response to definitive radiation therapy. Methods and Materials: A retrospective analysis was performed on 40 patients with unresected chordoma treated with photon/proton radiation therapy. Nineteen patients had complete sets of imaging scans. The soft tissue and bone compartments of the tumor were defined separately. Tumor response was evaluated by the modifiedmore » Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric analysis. Results: With a median follow-up time of 50.3 months, the rates of 5-year local control, overall survival, disease-specific survival, and distant failure were 85.4%, 81.9%, 89.4%, and 20.2%, respectively. Eighty-four computed tomographic and magnetic resonance imaging scans were reviewed. Among the 19 patients, only 4 local failures occurred, and the median tumor dose was 77.4 GyRBE. Analysis at a median follow-up time of 18 months showed significant volumetric reduction of the total target volume (TTV) and the soft tissue target volume (STTV) within the first 24 months after treatment initiation, followed by further gradual reduction throughout the rest of the follow-up period. The median maximum percentage volumetric regressions of TTV and STTV were 43.2% and 70.4%, respectively. There was only a small reduction in bone target volume over time. In comparison with the modified RECIST, volumetric analysis was more reliable, more reproducible, and could help in measuring minimal changes in the tumor volume. Conclusion: These results continue to support the use of high-dose definitive radiation therapy for selected patients with unresected spine and sacral chordomas

A new concept of efficient therapeutic drug monitoring using the high-resolution continuum source absorption spectrometry and the surface enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Xing, Yanlong; Fuss, Harald; Lademann, Jürgen; Huang, Mao Dong; Becker-Ross, Helmut; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora; Esser, Norbert

2018-04-01

In this study, a new therapeutic drug monitoring approach has been tested based on the combination of CaF molecular absorption using high-resolution continuum source absorption spectrometry (HR-CSAS) and surface enhanced Raman spectroscopy (SERS). HR-CSAS with mini graphite tube was successfully tested for clinical therapeutic drug monitoring of the fluorine-containing drug capecitabine in sweat samples of cancer patients: It showed advantageous features of high selectivity (no interference from Cl), high sensitivity (characteristic mass of 0.1 ng at CaF 583.069 nm), low sample consumption (down to 30 nL) and fast measurement (no sample pretreatment and less than 1 min of responding time) in tracing the fluorine signal out of capecitabine. However, this technique has the disadvantage of the total loss of the drug's structure information after burning the sample at very high temperature. Therefore, a new concept of combining HR-CSAS with a non-destructive spectroscopic method (SERS) was proposed for the sensitive sensing and specific identification of capecitabine. We tested and succeed in obtaining the molecular characteristics of the metabolite of capecitabine (named 5-fluorouracil) by the non-destructive SERS technique. With the results shown in this work, it is demonstrated that the combined spectroscopic technique of HR-CSAS and SERS will be very useful in efficient therapeutic drug monitoring in the future.

Recent Advances on Inorganic Nanoparticle-Based Cancer Therapeutic Agents

PubMed Central

Wang, Fenglin; Li, Chengyao; Cheng, Jing; Yuan, Zhiqin

2016-01-01

Inorganic nanoparticles have been widely investigated as therapeutic agents for cancer treatments in biomedical fields due to their unique physical/chemical properties, versatile synthetic strategies, easy surface functionalization and excellent biocompatibility. This review focuses on the discussion of several types of inorganic nanoparticle-based cancer therapeutic agents, including gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and mesoporous silica nanoparticles. Several cancer therapy techniques are briefly introduced at the beginning. Emphasis is placed on how these inorganic nanoparticles can provide enhanced therapeutic efficacy in cancer treatment through site-specific accumulation, targeted drug delivery and stimulated drug release, with elaborations on several examples to highlight the respective strategies adopted. Finally, a brief summary and future challenges are included. PMID:27898016

Recent Advances on Inorganic Nanoparticle-Based Cancer Therapeutic Agents.

PubMed

Wang, Fenglin; Li, Chengyao; Cheng, Jing; Yuan, Zhiqin

2016-11-25

Inorganic nanoparticles have been widely investigated as therapeutic agents for cancer treatments in biomedical fields due to their unique physical/chemical properties, versatile synthetic strategies, easy surface functionalization and excellent biocompatibility. This review focuses on the discussion of several types of inorganic nanoparticle-based cancer therapeutic agents, including gold nanoparticles, magnetic nanoparticles, upconversion nanoparticles and mesoporous silica nanoparticles. Several cancer therapy techniques are briefly introduced at the beginning. Emphasis is placed on how these inorganic nanoparticles can provide enhanced therapeutic efficacy in cancer treatment through site-specific accumulation, targeted drug delivery and stimulated drug release, with elaborations on several examples to highlight the respective strategies adopted. Finally, a brief summary and future challenges are included.

The immediate effects of therapeutic keyboard music playing for finger training in adults undergoing hand rehabilitation.

PubMed

Zhang, Xiaoying; Liu, Songhuai; Yang, Degang; Du, Liangjie; Wang, Ziyuan

2016-08-01

[Purpose] The purpose of this study was to examine the immediate effects of therapeutic keyboard music playing on the finger function of subjects' hands through measurements of the joint position error test, surface electromyography, probe reaction time, and writing time. [Subjects and Methods] Ten subjects were divided randomly into experimental and control groups. The experimental group used therapeutic keyboard music playing and the control group used grip training. All subjects were assessed and evaluated by the joint position error test, surface electromyography, probe reaction time, and writing time. [Results] After accomplishing therapeutic keyboard music playing and grip training, surface electromyography of the two groups showed no significant change, but joint position error test, probe reaction time, and writing time obviously improved. [Conclusion] These results suggest that therapeutic keyboard music playing is an effective and novel treatment for improving joint position error test scores, probe reaction time, and writing time, and it should be promoted widely in clinics.

Effectiveness of using a new polyurethane foam multi-layer dressing in the sacral area to prevent the onset of pressure ulcer in the elderly with hip fractures: A pragmatic randomised controlled trial.

PubMed

Forni, Cristiana; D'Alessandro, Fabio; Gallerani, Pina; Genco, Rossana; Bolzon, Andrea; Bombino, Caterina; Mini, Sandra; Rocchegiani, Laura; Notarnicola, Teresa; Vitulli, Arianna; Amodeo, Alfredo; Celli, Guglielmo; Taddia, Patrizia

2018-06-01

Hip fractures in the elderly are a serious problem for the health service due to the high rate of complications. One of these complications is pressure ulcers that, according to the literature, occur in 8.8% to 55% of patients and mainly arise in the sacral area. The present randomised controlled trial tests whether applying a new innovative multi-layer polyurethane foam dressing (ALLEVYN LIFE™), reduces the onset of pressure ulcers in the sacral area. From March to December 2016, 359 fragility hip fracture patients were randomly divided into 2 groups: 182 in the control group and 177 in the experimental group. Pressure ulcers occurred overall in 36 patients (10%): 8 patients (4.5%) in the experimental group compared to 28 (15.4%) in the control group: P = 0.001, relative risk 0.29 (95% CI 0.14-0.61) with NNT of 9 (95% CI 6-21). In the experimental group the onset of pressure ulcers occurred on average on the 6th day compared to the 4th day in the control group (HR 4.4). Using polyurethane foam is effective at reducing the rate of pressure ulcers in the sacrum in elderly patients with hip fracture. The adhesiveness of this device also enables costs to be kept down. © 2018 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Quantification of equine sacral and iliac motion during gait: a comparison between motion capture with skin-mounted and bone-fixated sensors.

PubMed

Goff, L; Van Weeren, P R; Jeffcott, L; Condie, P; McGowan, C

2010-11-01

Information regarding movement at the ilium and sacrum in nonlame horses during normal gait may assist in understanding the biomechanics of the equine sacroiliac joint. To determine the amount and direction of motion at the ilium and sacrum using 3D orientation sensors during walk and trot in sound Thoroughbreds. To compare results from sensors fixed to the skin with results from sensors fixed to bone-implanted pins. Three 3D wireless orientation sensors were mounted to the skin over the tuber sacrale (TS) and sacrum of 6 horses and motion at the ilium and sacrum was recorded for lateral bending (LB) flexion-extension (F-E) and axial rotation (AR) during walk and trot. This process was repeated with the orientation sensors mounted to the same pelvic landmarks via Steinmann pins. Mean walk values were greater than trot values using pin-mounted sensors for all planes of movement (P < 0.05). Walk had 1.64 ± 0.22° (mean ± s.e.) more LB than trot (pin-mounted) yet 0.68 ± 0.22° less than trot when skin-mounted; 3.45 ± 0.15° more F-E (pin- and skin-mounted), and 4.99 ± 0.4° more AR (pin-mounted), but trot had 3.4 ± 0.40° more AR than walk with skin mounting. Using pinned sensors for trot resulted in less LB (2.47 ± 0.22°), F-E (1.12 ± 0.15°) and AR (10.62 ± 0.40°); and for walk less F-E (1.12 ± 0.15°) and AR (2.15 ± 0.40°) compared to skin-mounted. Poor correlation existed between mean values for skin- and pin-mounted data for walk and trot, for all planes of motion. Movements were smaller at trot with bone-fixated sensors compared to walk, suggesting increased muscular control of movement at the trot. The apparent increase in skin motion at the trot and no clear correlation between skin- and bone-mounted sensors indicates inaccuracies when measuring sacral and iliac movement with skin mounting. © 2010 EVJ Ltd.

Can the possibility of transverse iliosacral screw fixation for first sacral segment be predicted preoperatively? Results of a computational cadaveric study.

PubMed

Jeong, Jin-Hoon; Jin, Jin Woo; Kang, Byoung Youl; Jung, Gu-Hee

2017-10-01

The purpose of this study was to predict the possibility of transverse iliosacral (TIS) screw fixation into the first sacral segment (S 1 ) and introduce practical anatomical variables using conventional computed tomography (CT) scans. A total of 82 cadaveric sacra (42 males and 40 females) were used for continuous 1.0-mm slice CT scans, which were imported into Mimics ® software to produce a three-dimensional pelvis model. The anterior height (BH) and superior width (BW) of the elevated sacral segment was measured, followed by verification of the safe zone (SZ S1 and SZ S2 ) in a true lateral view. Their vertical (VD S1 and VD S2 ) and horizontal (HD S1 and HD S2 ) distances were measured. VD S1 less than 7mm was classified as impossible sacrum, since the transverse fixation of 7.0 mm-sized IS screw could not be done safely. Fourteen models (16.7%; six females, eight males) were assigned as the impossible sacrum. There was no statistical significance regarding gender (p=0.626) and height (p=0.419). The average values were as follows: BW, 31.4mm (SD 2.9); BH, 16.7mm (SD 6.8); VD S1 , 13.4mm (SD 6.1); HD S1 , 22.5mm (SD 4.5); SZ S1 , 239.5mm 2 (SD 137.1); VD S2 , 15.5mm (SD 3.0); HD S2 , 18.3mm (SD 2.9); and SZ S2 , 221.1mm 2 (SD 68.5). Logistic regression analysis identified BH (p=0.001) and HD S1 (p=0.02) as the only statistically significant variables to predict the possibility. Receiver operating characteristic curve analysis established a cut-off value for BH and HD S1 of impossible sacrum of 20.6mm and 18.6mm, respectively. BH and HD S1 could be used to predict the possibility of TIS screw fixation. If the BH exceeds 20.6mm or HD S1 is less than 18.6mm, TIS screw fixation for S 1 should not be undertaken because of narrowed SZ. Copyright © 2017 Elsevier Ltd. All rights reserved.

A review of the surface and internal anatomy of the caudal canal in children.

PubMed

Lees, David; Frawley, Geoff; Taghavi, Kiarash; Mirjalili, Seyed Ali

2014-08-01

The anatomy of the sacral hiatus and caudal canal is prone to significant variation, yet studies assessing this in the pediatric population remain limited. Awareness of the possible anatomical variations is critical to the safety and success of caudal epidural blocks, particularly when image guidance is not employed. This systematic review analyzes the available evidence on the clinical anatomy of the caudal canal in pediatric patients, emphasizing surface anatomy and internal anatomical variations. A literature search using three electronic databases and standard pediatric and anatomy reference texts was conducted yielding 24 primary and seven secondary English-language sources. Appreciating that our current landmark-guided approaches to the caudal canal are not well studied in the pediatric population is important for both clinicians and researchers. © 2014 John Wiley & Sons Ltd.

The cost-benefit of using soft silicone multilayered foam dressings to prevent sacral and heel pressure ulcers in trauma and critically ill patients: a within-trial analysis of the Border Trial.

PubMed

Santamaria, Nick; Liu, Wei; Gerdtz, Marie; Sage, Sarah; McCann, Jane; Freeman, Amy; Vassiliou, Theresa; DeVincentis, Stephanie; Ng, Ai W; Manias, Elizabeth; Knott, Jonathan; Liew, Danny

2015-06-01

Little is known about the cost-benefit of soft silicone foam dressings in pressure ulcer (PU) prevention among critically ill patients in the emergency department (ED) and intensive care unit (ICU). A randomised controlled trial to assess the efficacy of soft silicone foam dressings in preventing sacral and heel PUs was undertaken among 440 critically ill patients in an acute care hospital. Participants were randomly allocated either to an intervention group with prophylactic dressings applied to the sacrum and heels in the ED and changed every 3 days in the ICU or to a control group with standard PU prevention care provided during their ED and ICU stay. The results showed a significant reduction of PU incidence rates in the intervention group (P = 0·001). The intervention cost was estimated to be AU$36·61 per person based on an intention-to-treat analysis, but this was offset by lower downstream costs associated with PU treatment (AU$1103·52). Therefore, the average net cost of the intervention was lower than that of the control (AU$70·82 versus AU$144·56). We conclude that the use of soft silicone multilayered foam dressings to prevent sacral and heel PUs among critically ill patients results in cost savings in the acute care hospital. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Recent progress in the therapeutic applications of nanotechnology.

PubMed

Solomon, Melani; D'Souza, Gerard G M

2011-04-01

The field of pharmaceutical and medical nanotechnology has grown rapidly in recent decades and offers much promise for therapeutic advances. This review is intended to serve as a quick summary of the major areas in the therapeutic application of nanotechnology. Nanotechnology for therapeutic application falls into two broad categories of particulate systems and nanoengineered devices. Recent studies appear to focus on the development of multifunctional particles for drug delivery and imaging and the development of nanotechnology-based biosensors for diagnostic applications. Cancer treatment and diagnosis appears to be the principal focus of many of these applications, but nanotechnology is also finding application in tissue engineering and surface engineering of medical implants. Particulate drug delivery systems in general appear to be poised for increased use in the clinic, whereas nanoengineered implants and diagnostic sensors might well be the next major wave in the medical use of nanotechnology.

The Therapeutic School.

ERIC Educational Resources Information Center

Rice, John Steadman

2002-01-01

Contributes to the recent research on specific institutional carriers of the therapeutic culture, such as the state, the corporation, and the self- help movement, defining therapeutic discourse and discussing the therapeutic ethic, the therapeutic school, schools of education and their critics, and disappointing results of therapeutic schooling.…

CyberKnife frameless single-fraction stereotactic radiosurgery for tumors of the sacrum.

PubMed

Gerszten, Peter C; Ozhasoglu, Cihat; Burton, Steven A; Welch, William C; Vogel, William J; Atkins, Barbara A; Kalnicki, Shalom

2003-08-15

lesions are relatively short treatment time in an outpatient setting and minimal or no side effects. This new technique offers a new and important therapeutic modality for the primary treatment of a variety of sacral tumors or for lesions not amenable to open surgical techniques.

Feasibility of ultrasound-guided epidural access at the lumbo-sacral space in dogs.

PubMed

Liotta, Annalisa; Busoni, Valeria; Carrozzo, Maria Valentina; Sandersen, Charlotte; Gabriel, Annick; Bolen, Géraldine

2015-01-01

Epidural injections are commonly performed blindly in veterinary medicine. The aims of this study were to describe the lumbosacral ultrasonographic anatomy and to assess the feasibility of an ultrasound-guided epidural injection technique in dogs. A cross sectional anatomic atlas of the lumbosacral region and ex vivo ultrasound images were obtained in two cadavers to describe the ultrasound anatomy and to identify the landmarks. Sixteen normal weight canine cadavers were used to establish two variations of the technique for direct ultrasound-guided injection, using spinal needles or epidural catheters. The technique was finally performed in two normal weight cadavers, in two overweight cadavers and in five live dogs with radiographic abnormalities resulting of the lumbosacral spine. Contrast medium was injected and CT was used to assess the success of the injection. The anatomic landmarks to carry out the procedure were the seventh lumbar vertebra, the iliac wings, and the first sacral vertebra. The target for directing the needle was the trapezoid-shaped echogenic zone between the contiguous articular facets of the lumbosacral vertebral canal visualized in a parasagittal plane. The spinal needle or epidural catheter was inserted in a 45° craniodorsal-caudoventral direction through the subcutaneous tissue and the interarcuate ligament until reaching the epidural space. CT examination confirmed the presence of contrast medium in the epidural space in 25/25 dogs, although a variable contamination of the subarachnoid space was also noted. Findings indicated that this ultrasound-guided epidural injection technique is feasible for normal weight and overweight dogs, with and without radiographic abnormalities of the spine. © 2014 American College of Veterinary Radiology.

Intranasal delivery: physicochemical and therapeutic aspects.

PubMed

Costantino, Henry R; Illum, Lisbeth; Brandt, Gordon; Johnson, Paul H; Quay, Steven C

2007-06-07

Interest in intranasal (IN) administration as a non-invasive route for drug delivery continues to grow rapidly. The nasal mucosa offers numerous benefits as a target issue for drug delivery, such as a large surface area for delivery, rapid drug onset, potential for central nervous system delivery, and no first-pass metabolism. A wide variety of therapeutic compounds can be delivered IN, including relatively large molecules such as peptides and proteins, particularly in the presence of permeation enhancers. The current review provides an in-depth discussion of therapeutic aspects of IN delivery including consideration of the intended indication, regimen, and patient population, as well as physicochemical properties of the drug itself. Case examples are provided to illustrate the utility of IN dosing. It is anticipated that the present review will prove useful for formulation scientists considering IN delivery as a delivery route.

Next Generation Antibody Therapeutics Using Bispecific Antibody Technology.

PubMed

Igawa, Tomoyuki

2017-01-01

Nearly fifty monoclonal antibodies have been approved to date, and the market for monoclonal antibodies is expected to continue to grow. Since global competition in the field of antibody therapeutics is intense, we need to establish novel antibody engineering technologies to provide true benefit for patients, with differentiated product values. Bispecific antibodies are among the next generation of antibody therapeutics that can bind to two different target antigens by the two arms of immunoglobulin G (IgG) molecule, and are thus believed to be applicable to various therapeutic needs. Until recently, large scale manufacturing of human IgG bispecific antibody was impossible. We have established a technology, named asymmetric re-engineering technology (ART)-Ig, to enable large scale manufacturing of bispecific antibodies. Three examples of next generation antibody therapeutics using ART-Ig technology are described. Recent updates on bispecific antibodies against factor IXa and factor X for the treatment of hemophilia A, bispecific antibodies against a tumor specific antigen and T cell surface marker CD3 for cancer immunotherapy, and bispecific antibodies against two different epitopes of soluble antigen with pH-dependent binding property for the elimination of soluble antigen from plasma are also described.

Evaluation of the axonics modulation technologies sacral neuromodulation system for the treatment of urinary and fecal dysfunction.

PubMed

Cohn, Joshua A; Kowalik, Casey G; Kaufman, Melissa R; Reynolds, W Stuart; Milam, Douglas F; Dmochowski, Roger R

2017-01-01

Sacral neuromodulation (SNM) remains one of the few effective treatments for refractory bladder and bowel dysfunction. However, SNM is associated with frequent need for surgical intervention, in many cases because of a failed battery. A rechargeable SNM system, with a manufacturer-reported battery life of 15 years or more, has entered post-market clinical testing in Europe but has not yet been approved for clinical testing in the United States. Areas covered: We review existing neuromodulation technologies for the treatment of lower urinary tract and bowel dysfunction and explore the limitations of available technology. In addition, we discuss implantation technique and device specifications and programming of the rechargeable SNM system in detail. Lastly, we present existing evidence for the use of SNM in bladder and bowel dysfunction and evaluate the anticipated trajectory of neuromodulation technologies over the next five years. Expert commentary: A rechargeable system for SNM is a welcome technological advance. However surgical revision not related to battery changes is not uncommon. Therefore, while a rechargeable system would be expected to reduce costs, it will not eliminate the ongoing maintenance associated with neuromodulation. No matter the apparent benefits, all new technologies require extensive post-market monitoring to ensure safety and efficacy.

Paper-basd surface enhanced Raman spectroscopy of pnenobarbital sodium for point-of-care therapeutic drug monitoring

NASA Astrophysics Data System (ADS)

Yokoyama, Moe; Yamada, Kenji; Nishimura, Takahiro; Kido, Michiko; Jeong, Hieyong; Ohno, Yuko

2015-03-01

Therapeutic drug monitoring (TDM) contributes to safe and effective pharmacotherapy in clinical fields. A simple, rapid, low-cost, and minimally-invasive drug measurement method attracts much interest for point-of-care TDM. Tear fluids can be collected minimally-invasively compared to blood sampling and there is a correlation between a drug concentration in tears and that in bloods. Surface enhanced Raman spectroscopy (SERS) with paper-based substrate is useful for point-of-care TDM owing to inexpensiveness and high-sensitivity. Paper is also a safe tear collection tool. Then we are studying on a paper-based SERS of tear specimen for point-of-care TDM. In this paper, to improve sensitivity in measuring drug concentration in tear fluids, we fabricated a SERS substrate by coating gold nano-rods on a paper substrate and evaluated whether the fabricated substrate can enhance Raman scattering. Sodium phenobarbital (PB), an anti-convulsant agent, was used as a target. In experiment, the fabricated substrate indicated the lower detection limit of PB in a solution than a plain paper substrate. This result showed the potential of the paper based SERS substrate to measure drug concentration in tears simply and inexpensively.

[Functional dyspepsia, constipation and faecal incontinence].

PubMed

Wiesel, Paul; Frei, Alain

2007-01-24

Regarding functional dyspepsia, constipation, fecal incontinence, the main therapeutic acquisitions of the period are the following: for functional dyspepsia, remember that alarm signs are not absolute signs of seriousness; for constipation, encourage and repeat advises such as physical exercise; for fecal incontinence the transcutaneous neuro-modulation and the TENS (Transcutaneous Electrical Nerve Stimulation) are potential alternatives to sacral neuro-modulation.

Restricted access magnetic materials prepared by dual surface modification for selective extraction of therapeutic drugs from biological fluids

NASA Astrophysics Data System (ADS)

Wang, Yu; Wang, Yuxia; Chen, Lei; Wan, Qian-Hong

2012-02-01

Magnetic porous particles with dual functionality have been prepared by a two-step procedure and evaluated as novel restricted access materials for extraction of therapeutic agents from biological fluids. The magnetic silica particles served as scaffolds were first modified with diol groups, which were then converted to octadecyl esters through reaction with stearoyl chloride. In the second step, the octadecyl esters on the exterior surface were hydrolyzed by the action of lipase to yield magnetic particles with hydrophobic reversed-phase ligands on the inner surface and biocompatible diol groups on the outer surface. The restricted access behavior of the resulting materials was confirmed by differential binding of small molecules such as methotrexate (MTX), leucovorin (LV) and folic acid (FA) relative to bovine serum albumin. While MTX, LV and FA were all bound to the magnetic particles with high affinity, the adsorption of the protein was markedly reduced due to size exclusion effect. The utility of the magnetic particles for sample preparation was tested in solid-phase extraction of MTX, LV and FA from spiked human serum and the effects of the SPE conditions on the recovery of the analytes were systematically studied. Moreover, the magnetic particle-based sample preparation procedure coupled with reversed-phase liquid chromatography analysis was validated in terms of specificity, linearity and reproducibility. The method was shown to be free from interference of endogenous compounds and linear over the concentration range of 0.5-10 μg/mL for the three drugs studied. The limits of detection for the three drugs in serum were in the range of 0.160-0.302 μg/mL. Reproducibility expressed as the RSD of the recovery for ten replicated extractions at three different concentrations was found to be less than 8.93%. With a unique combination of surface functionality with magnetic cores, the restricted access magnetic particles may be adapted in automated and high

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

PubMed

Kuche, Kaushik; Maheshwari, Rahul; Tambe, Vishakha; Mak, Kit-Kay; Jogi, Hardi; Raval, Nidhi; Pichika, Mallikarjuna Rao; Kumar Tekade, Rakesh

2018-05-17

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Protein-Based Therapeutic Killing for Cancer Therapies.

PubMed

Serna, Naroa; Sánchez-García, Laura; Unzueta, Ugutz; Díaz, Raquel; Vázquez, Esther; Mangues, Ramón; Villaverde, Antonio

2018-03-01

The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nasal-nanotechnology: revolution for efficient therapeutics delivery.

PubMed

Kumar, Amrish; Pandey, Aditya Nath; Jain, Sunil Kumar

2016-01-01

In recent years, nanotechnology-based delivery systems have gained interest to overcome the problems of restricted absorption of therapeutic agents from the nasal cavity, depending upon the physicochemical properties of the drug and physiological properties of the human nose. The well-tolerated and non-invasive nasal drug delivery when combined with the nanotechnology-based novel formulations and carriers, opens the way for the effective systemic and brain targeting delivery of various therapeutic agents. To accomplish competent drug delivery, it is imperative to recognize the interactions among the nanomaterials and the nasal biological environment, targeting cell-surface receptors, drug release, multiple drug administration, stability of therapeutic agents and molecular mechanisms of cell signaling involved in patho-biology of the disease under consideration. Quite a few systems have been successfully formulated using nanomaterials for intranasal (IN) delivery. Carbon nanotubes (CNTs), chitosan, polylactic-co-glycolic acid (PLGA) and PLGA-based nanosystems have also been studied in vitro and in vivo for the delivery of several therapeutic agents which shown promising concentrations in the brain after nasal administration. The use of nanomaterials including peptide-based nanotubes and nanogels (NGs) for vaccine delivery via nasal route is a new approach to control the disease progression. In this review, the recent developments in nanotechnology utilized for nasal drug delivery have been discussed.

Sacral neurostimulation for urinary retention: 10-year experience from one UK centre.

PubMed

Datta, Soumendra N; Chaliha, Charlotte; Singh, Anubha; Gonzales, Gwen; Mishra, Vibhash C; Kavia, Rajesh B C; Kitchen, Neil; Fowler, Clare J; Elneil, Sohier

2008-01-01

To report our 10-year experience of sacral neurostimulation (SNS) for women in urinary retention, comparing the original one-stage with the newer two-stage technique, as SNS therapy is a well-established treatment for urinary retention secondary to urethral sphincter overactivity (Fowler's syndrome). Between 1996 and 2006, 60 patients with urinary retention had a SNS device inserted; their case records were reviewed and data on efficacy, follow-up, need for continued clean intermittent self-catheterization (CISC), complications and operative revision rate were assessed. Overall, 43 of 60 (72%) women were voiding spontaneously, with a mean postvoid residual volume of 100 mL; 30 (50%) no longer needed to use CISC. During a total of 2878 months of SNS experience, adverse event episodes included lead migration in 20, 'box-site' pain in 19, leg pain/numbness in 18 and loss of response/failure in 18 patients; 53% of the women required a surgical revision related to their implanted stimulator. The efficacy of the two-stage was similar to that of the one-stage procedure (73% vs 70%). Women with a normal urethral sphincter electromyogram had worse outcomes than women with an abnormal test (43% vs 76%). Although the efficacy was no different in those taking analgesia/antidepressant medication, this group of women had a higher surgical revision rate. Failure and complications for the one-stage procedure were not restricted to the early follow-up period. The mean battery life of the implant was 7.31 years. SNS has sustained long-term efficacy but the procedure has a significant complication rate. At present, the two-stage technique has comparable efficacy to the one-stage technique but a longer-term follow-up is required. The National Institute of Clinical Excellence recommended the use of SNS in women with urinary incontinence who fail to respond adequately to anticholinergic therapy, but patients choosing this treatment should be made aware of the high complication rate

Lumbar lordosis and sacral slope in lumbar spinal stenosis: standard values and measurement accuracy.

PubMed

Bredow, J; Oppermann, J; Scheyerer, M J; Gundlfinger, K; Neiss, W F; Budde, S; Floerkemeier, T; Eysel, P; Beyer, F

2015-05-01

Radiological study. To asses standard values, intra- and interobserver reliability and reproducibility of sacral slope (SS) and lumbar lordosis (LL) and the correlation of these parameters in patients with lumbar spinal stenosis (LSS). Anteroposterior and lateral X-rays of the lumbar spine of 102 patients with LSS were included in this retrospective, radiologic study. Measurements of SS and LL were carried out by five examiners. Intraobserver correlation and correlation between LL and SS were calculated with Pearson's r linear correlation coefficient and intraclass correlation coefficients (ICC) were calculated for inter- and intraobserver reliability. In addition, patients were examined in subgroups with respect to previous surgery and the current therapy. Lumbar lordosis averaged 45.6° (range 2.5°-74.9°; SD 14.2°), intraobserver correlation was between Pearson r = 0.93 and 0.98. The measurement of SS averaged 35.3° (range 13.8°-66.9°; SD 9.6°), intraobserver correlation was between Pearson r = 0.89 and 0.96. Intraobserver reliability ranged from 0.966 to 0.992 ICC in LL measurements and 0.944-0.983 ICC in SS measurements. There was an interobserver reliability ICC of 0.944 in LL and 0.990 in SS. Correlation between LL and SS averaged r = 0.79. No statistically significant differences were observed between the analyzed subgroups. Manual measurement of LL and SS in patients with LSS on lateral radiographs is easily performed with excellent intra- and interobserver reliability. Correlation between LL and SS is very high. Differences between patients with and without previous decompression were not statistically significant.

Recognition-mediated activation of therapeutic gold nanoparticles inside living cells

NASA Astrophysics Data System (ADS)

Kim, Chaekyu; Agasti, Sarit S.; Zhu, Zhengjiang; Isaacs, Lyle; Rotello, Vincent M.

2010-11-01

Supramolecular chemistry provides a versatile tool for the organization of molecular systems into functional structures and the actuation of these assemblies for applications through the reversible association between complementary components. Use of this methodology in living systems, however, represents a significant challenge owing to the chemical complexity of cellular environments and lack of selectivity of conventional supramolecular interactions. Herein, we present a host-guest system featuring diaminohexane-terminated gold nanoparticles (AuNP-NH2) and complementary cucurbit[7]uril (CB[7]). In this system, threading of CB[7] on the particle surface reduces the cytotoxicity of AuNP-NH2 through sequestration of the particle in endosomes. Intracellular triggering of the therapeutic effect of AuNP-NH2 was then achieved through the administration of 1-adamantylamine (ADA), removing CB[7] from the nanoparticle surface, causing the endosomal release and concomitant in situ cytotoxicity of AuNP-NH2. This supramolecular strategy for intracellular activation provides a new tool for potential therapeutic applications.

The impact of office chair features on lumbar lordosis, intervertebral joint and sacral tilt angles: a radiographic assessment.

PubMed

De Carvalho, Diana; Grondin, Diane; Callaghan, Jack

2017-10-01

The purpose of this study was to determine which office chair feature is better at improving spine posture in sitting. Participants (n = 28) were radiographed in standing, maximum flexion and seated in four chair conditions: control, lumbar support, seat pan tilt and backrest with scapular relief. Measures of lumbar lordosis, intervertebral joint angles and sacral tilt were compared between conditions and sex. Sitting consisted of approximately 70% of maximum range of spine flexion. No differences in lumbar flexion were found between the chair features or control. Significantly more anterior pelvic rotation was found with the lumbar support (p = 0.0028) and seat pan tilt (p < 0.0001). Males had significantly more anterior pelvic rotation and extended intervertebral joint angles through L1-L3 in all conditions (p < 0.0001). No one feature was statistically superior with respect to minimising spine flexion, however, seat pan tilt resulted in significantly improved pelvic posture. Practitioner Summary: Seat pan tilt, and to some extent lumbar supports, appear to improve seated postures. However, sitting, regardless of chair features used, still involves near end range flexion of the spine. This will increase stresses to the spine and could be a potential injury generator during prolonged seated exposures.

Mass transfer of therapeutics through natural human plaque biofilms: a model for therapeutic delivery to pathological bacterial biofilms.

PubMed

Robinson, Colin

2011-09-01

Bacterial biofilms in the mouth are prime mediators of the destruction of the dental and oral tissues. This brief review summarises recent work using a device for generating intact plaque in the mouth on natural enamel surfaces such that quantitative studies of mass transfer through natural plaque biofilms could be carried out in relation to plaque architecture. This data is discussed against the background of existing information. The device revealed complex plaque architecture with high a surface area to mass ratio decreasing from the exterior of the biofilm towards the tissue surface. Fluoride, a potent inhibitor of caries was concentrated in the outer regions of the biofilm. This implies some restriction of diffusion and possibly binding to the high surface area of the outer biofilm. Whilst all components examined conformed to this distribution pattern, some relatively uncharged materials penetrated the bacterial biomass whilst other, more highly charged materials tended to be restricted to the channels or biomass surface. Plaque architecture was robust but could be altered using detergent indicating that biomass architecture and chemistry could be manipulated as a possible means of facilitating mass transport of therapeutics. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Therapeutic hypothermia for severe traumatic brain injury].

PubMed

Bouzat, P; Francony, G; Oddo, M; Payen, J-F

2013-11-01

Therapeutic hypothermia (TH) is considered a standard of care in the post-resuscitation phase of cardiac arrest. In experimental models of traumatic brain injury (TBI), TH was found to have neuroprotective properties. However, TH failed to demonstrate beneficial effects on neurological outcome in patients with TBI. The absence of benefits of TH uniformly applied in TBI patients should not question the use of TH as a second-tier therapy to treat elevated intracranial pressure. The management of all the practical aspects of TH is a key factor to avoid side effects and to optimize the potential benefit of TH in the treatment of intracranial hypertension. Induction of TH can be achieved with external surface cooling or with intra-vascular devices. The therapeutic target should be set at a 35°C using brain temperature as reference, and should be maintained at least during 48 hours and ideally over the entire period of elevated intracranial pressure. The control of the rewarming phase is crucial to avoid temperature overshooting and should not exceed 1°C/day. Besides its use in the management of intracranial hypertension, therapeutic cooling is also essential to treat hyperthermia in brain-injured patients. In this review, we will discuss the benefit-risk balance and practical aspects of therapeutic temperature management in TBI patients. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Engineering DNA scaffolds for delivery of anticancer therapeutics.

PubMed

Sun, Wujin; Gu, Zhen

2015-07-01

Engineering DNA nanostructures with programmability in size, shape and surface chemistry holds tremendous promise in biomedical applications. As an emerging platform for drug delivery, DNA nanostructures have been extensively studied for delivering anticancer therapeutics, including small-molecule drug, nucleic acids and proteins. In this mini-review, current advances in utilizing DNA scaffolds as drug carriers for cancer treatment were summarized and future challenges were also discussed.

Drug-Free Macromolecular Therapeutics – A New Paradigm in Polymeric Nanomedicines

PubMed Central

Chu, Te-Wei; Kopeček, Jindřich

2015-01-01

This review highlights a unique research area in polymer-based nanomedicine designs. Drug-free macromolecular therapeutics induce apoptosis of malignant cells by the crosslinking of surface non-internalizing receptors. The receptor crosslinking is mediated by the biorecognition of high-fidelity natural binding motifs (such as antiparallel coiled-coil peptides or complementary oligonucleotides) that are grafted to the side chains of polymers or attached to targeting moieties against cell receptors. This approach features the absence of low-molecular-weight cytotoxic compounds. Here, we summarize the rationales, different designs, and advantages of drug-free macromolecular therapeutics. Recent developments of novel therapeutic systems for B-cell lymphomas are discussed, as well as relevant approaches for other diseases. We conclude by pointing out various potential future directions in this exciting new field. PMID:26191406

Cubosomes and other potential ocular drug delivery vehicles for macromolecular therapeutics.

PubMed

Hartnett, Terence E; O'Connor, Andrea J; Ladewig, Katharina

2015-01-01

Many macromolecular therapeutics designed to treat posterior segment eye diseases (PSEDs) are administered through frequent ocular injection, which can further deteriorate eye health. Due to the high frequency of injection and the high cost of the therapeutics, there is a need to develop new ways in which to deliver these therapeutics: ways which are both safer and more cost effective. Using the most common PSED, age-related macular degeneration, as an example of a debilitating ocular disease, this review examines the key barriers limiting the delivery of macromolecular therapeutics to the posterior segment of the eye and defines the key requirements placed on particulate drug delivery vehicles (DDVs) to be suitable for this application. Recent developments in macromolecular drug delivery to treat this disease as well as the remaining shortcomings in its treatment are surveyed. Lastly, an emerging class of DDVs potentially suited to this application, called cubosomes, is introduced. Based on their excellent colloidal stability and high internal surface area, cubosomes hold great potential for the sustained release of therapeutics. Novel production methods and a better understanding of the mechanisms through which drug release from these particles can be controlled are two major recent developments toward successful application.

DISTINCT ANTIBODY SPECIES: STRUCTURAL DIFFERENCES CREATING THERAPEUTIC OPPORTUNITIES

PubMed Central

Muyldermans, Serge; Smider, Vaughn V.

2016-01-01

Antibodies have been a remarkably successful class of molecules for binding a large number of antigens in therapeutic, diagnostic, and research applications. Typical antibodies derived from mouse or human sources use the surface formed by complementarity determining regions (CDRs) on the variable regions of the heavy chain/light chain heterodimer, which typically forms a relatively flat binding surface. Alternative species, particularly camelids and bovines, provide a unique paradigm for antigen recognition through novel domains which form the antigen binding paratope. For camelids, heavy chain antibodies bind antigen with only a single heavy chain variable region, in the absence of light chains. In bovines, ultralong CDR-H3 regions form an independently folding minidomain, which protrudes from the surface of the antibody and is diverse in both its sequence and disulfide patterns. The atypical paratopes of camelids and bovines potentially provide the ability to interact with different epitopes, particularly recessed or concave surfaces, compared to traditional antibodies. PMID:26922135

Changes in Pelvic Incidence, Pelvic Tilt, and Sacral Slope in Situations of Pelvic Rotation.

PubMed

Jin, Hai-Ming; Xu, Dao-Liang; Xuan, Jun; Chen, Jiao-Xiang; Chen, Kai; Goswami, Amit; Chen, Yu; Kong, Qiu-Yan; Wang, Xiang-Yang

2017-08-01

Digitally reconstructed radiograph-based study. Using a computer-based method to determine what degree of pelvic rotation is acceptable for measuring the pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). The effectiveness of a geometrical formula used to calculate the angle of pelvic rotation proposed in a previous article was assessed. It is unclear whether PI, PT, and SS are valid with pelvic rotation while acquiring a radiograph. Ten 3-dimensionally reconstructed models were established with software and placed in a neutral orientation to orient all of the bones in a standing position. Next, 140 digitally reconstructed radiographs were obtained by rotating the models around the longitudinal axis of each pelvis in the software from 0 to 30 degrees at 2.5-degree intervals. PI, PT, and SS were measured. The rotation angle was considered to be acceptable when the change in the measured angle (compared with the "correct" position) was <6 degrees. The rotation angle (α) on the images was calculated by a geometrical formula. Consistency between the measured value and the set angle was assessed. The acceptable maximum angle of rotation for reliable measurements of PI was 17.5 degrees, and the changes in PT and SS were within an acceptable range (<6 degrees) when the pelvic rotation increased from 0 to 30 degrees. The effectiveness of the geometrical formula was shown by the consistency between the set and the calculated rotation angles of the pelvis (intraclass correlation coefficient=0.99). Our study provides insight into the influence of pelvic rotation on the PI, PT, and SS. PI changes with pelvic rotation. The acceptable maximum angle for reliable values of PI, PT, and SS was 17.5 degrees, and the rotation angle of the pelvis on a lateral spinopelvic radiograph can be calculated reliably.

Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

ERIC Educational Resources Information Center

Alsharif, Naser Z.; And Others

1997-01-01

Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

Sacral Insufficiency Fractures After Preoperative Chemoradiation for Rectal Cancer: Incidence, Risk Factors, and Clinical Course

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herman, Michael P.; Kopetz, Scott; Bhosale, Priya R.

2009-07-01

Purpose: Sacral insufficiency (SI) fractures can occur as a late side effect of pelvic radiation therapy. Our goal was to determine the incidence, risk factors, and clinical course of SI fractures in patients treated with preoperative chemoradiation for rectal cancer. Materials and Methods: Between 1989 and 2004, 562 patients with non-metastatic rectal adenocarcinoma were treated with preoperative chemoradiation followed by mesorectal excision. The median radiotherapy dose was 45 Gy. The hospital records and radiology reports of these patients were reviewed to identify those with pelvic fractures. Radiology images of patients with pelvic fractures were then reviewed to identify those withmore » SI fractures. Results: Among the 562 patients, 15 had SI fractures. The 3-year actuarial rate of SI fractures was 3.1%. The median time to SI fractures was 17 months (range, 2-34 months). The risk of SI fractures was significantly higher in women compared to men (5.8% vs. 1.6%, p = 0.014), and in whites compared with non-whites (4% vs. 0%, p = 0.037). On multivariate analysis, gender independently predicted for the risk of SI fractures (hazard ratio, 3.25; p = 0.031). Documentation about the presence or absence of pain was available for 13 patients; of these 7 (54%) had symptoms requiring pain medications. The median duration of pain was 22 months. No patient required hospitalization or invasive intervention for pain control. Conclusions: SI fractures were uncommon in patients treated with preoperative chemoradiation for rectal cancer. The risk of SI fractures was significantly higher in women. Most cases of SI fractures can be managed conservatively with pain medications.« less

Cancer stem cell-targeted therapeutics and delivery strategies.

PubMed

Ahmad, Gulzar; Amiji, Mansoor M

2017-08-01

Cancer initiating or stem cells (CSCs) are a small population of cells in the tumor mass, which have been reported to be present in different types of cancers. CSCs usually reside within the tumor and are responsible for reoccurrence of cancer. The imprecise, inaccessible nature and increased efflux of conventional therapeutic drugs make these cells resistant to drugs. We discuss the specific markers for identification of these cells, role of CSCs in chemotherapy resistance and use of different therapeutic means to target them, including elucidation of specific cell markers, exploitation of different signaling pathways and use of nanotechnology. Area covered: This review covers cancer stem cell signaling which are used by these cells to maintain their quiescence, stemness and resistant phenotype, distinct cell surface markers, contribution of these cells in drug resistance, inevitability to cure cancer and use of nanotechnology to overcome this hurdle. Expert opinion: Cancer stem cells are the main culprit of our failure to cure cancer. In order to cure cancer along with other cells types in cancer, cancer stem cells need to be targeted in the tumor bed. Nanotechnology solutions can facilitate clinical translation of the therapeutics along with other emerging technologies to cure cancer.

Economic evaluation of sacral neuromodulation in overactive bladder: A Canadian perspective.

PubMed

Hassouna, Magdy M; Sadri, Hamid

2015-01-01

Refractory overactive bladder (OAB) with urge incontinence is an underdiagnosed condition with substantial burden on the healthcare system and diminished patient's quality-of-life. Many patients will fail conservative treatment with optimized medical-therapy (OMT) and may benefit from minimally invasive procedures, including sacral-neuromodulation (SNM) or botulinum-toxin (BonT-A). The goal of this study was to estimate the cost-efectiveness of SNM vs. OMT and BonT-A as important parameters from coverage and access to a therapy. A Markov model with Monte-Carlo simulation was used to assess the incremental cost effectiveness ratio (ICER) of SNM vs. BonT-A and OMT both in deterministic and probabilistic analysis from a provincial payer perspective over a 10-year time horizon with 9-month Markov-cycles. Clinical data, healthcare resource utilization, and utility scores were acquired from recent publications and an expert panel of 7 surgeons. Cost data (2014-Dollars) were derived from provincial health insurance policy, drug benefit formulary, and hospital data. All cost and outcomes were discounted at a 3% rate. The annual (year 1-10) incremental quality-adjusted life years for SNM vs. BonT-A was 0.05 to 0.51 and SNM vs. OMT was 0.19 to 1.76. The annual incremental cost of SNM vs. BonT-A was $7237 in year 1 and -$9402 in year 10 and was between $8878 and -$11 447 vs. OMT. In the base-case deterministic analysis, the ICER for SNM vs. BonT-A and OMT were within the acceptable range ($44 837 and $15 130, respectively) at the second year of therapy, and SNM was dominant in consequent years. In the base-case analysis the probability of ICER being below the acceptability curve (willingness-to-pay $50 000) was >99% for SNM vs. BonT-A at year 3 and >95% for OMT at year 2. SNM is a cost-effective treatment option to manage patients with refractory OAB when compared to either BonT-A or OMT. From a Canadian payers' perspective, SNM may be considered a first-line treatment option

Covalent binding of nanoliposomes to the surface of magnetotactic bacteria for the synthesis of self-propelled therapeutic agents.

PubMed

Taherkhani, Samira; Mohammadi, Mahmood; Daoud, Jamal; Martel, Sylvain; Tabrizian, Maryam

2014-05-27

The targeted and effective delivery of therapeutic agents remains an unmet goal in the field of controlled release systems. Magnetococcus marinus MC-1 magnetotactic bacteria (MTB) are investigated as potential therapeutic carriers. By combining directional magnetotaxis-microaerophilic control of these self-propelled agents, a larger amount of therapeutics can be delivered surpassing the diffusion limits of large drug molecules toward hard-to-treat hypoxic regions in solid tumors. The potential benefits of these carriers emphasize the need to develop an adequate method to attach therapeutic cargos, such as drug-loaded nanoliposomes, without substantially affecting the cell's ability to act as delivery agents. In this study, we report on a strategy for the attachment of liposomes to MTB (MTB-LP) through carbodiimide chemistry. The attachment efficacy, motility, and magnetic response of the MTB-LP were investigated. Results confirm that a substantial number of nanoliposomes (∼70) are efficiently linked with MTB without compromising functionality and motility. Cytotoxicity assays using three different cell types (J774, NIH/3T3, and Colo205) reveal that liposomal attachments to MTB formulation improve the biocompatibility of MTB, whereas attachment does not interfere with liposomal uptake.

Arrayed antibody library technology for therapeutic biologic discovery.

PubMed

Bentley, Cornelia A; Bazirgan, Omar A; Graziano, James J; Holmes, Evan M; Smider, Vaughn V

2013-03-15

Traditional immunization and display antibody discovery methods rely on competitive selection amongst a pool of antibodies to identify a lead. While this approach has led to many successful therapeutic antibodies, targets have been limited to proteins which are easily purified. In addition, selection driven discovery has produced a narrow range of antibody functionalities focused on high affinity antagonism. We review the current progress in developing arrayed protein libraries for screening-based, rather than selection-based, discovery. These single molecule per microtiter well libraries have been screened in multiplex formats against both purified antigens and directly against targets expressed on the cell surface. This facilitates the discovery of antibodies against therapeutically interesting targets (GPCRs, ion channels, and other multispanning membrane proteins) and epitopes that have been considered poorly accessible to conventional discovery methods. Copyright © 2013. Published by Elsevier Inc.

Progress in cystic fibrosis and the CF Therapeutics Development Network

PubMed Central

Rowe, Steven M; Borowitz, Drucy S; Burns, Jane L; Clancy, John P; Donaldson, Scott H; Retsch-Bogart, George; Sagel, Scott D; Ramsey, Bonnie W

2013-01-01

Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised. PMID:22960984

Progress in cystic fibrosis and the CF Therapeutics Development Network.

PubMed

Rowe, Steven M; Borowitz, Drucy S; Burns, Jane L; Clancy, John P; Donaldson, Scott H; Retsch-Bogart, George; Sagel, Scott D; Ramsey, Bonnie W

2012-10-01

Cystic fibrosis (CF), the most common life-shortening genetic disorder in Caucasians, affects approximately 70 000 individuals worldwide. In 1998, the Cystic Fibrosis Foundation (CFF) launched the CF Therapeutics Development Network (CF-TDN) as a central element of its Therapeutics Development Programme. Designed to accelerate the clinical evaluation of new therapies needed to fulfil the CFF mission to control and cure CF, the CF-TDN has conducted 75 clinical trials since its inception, and has contributed to studies as varied as initial safety and proof of concept trials to pivotal programmes required for regulatory approval. This review highlights recent and significant research efforts of the CF-TDN, including a summary of contributions to studies involving CF transmembrane conductance regulator (CFTR) modulators, airway surface liquid hydrators and mucus modifiers, anti-infectives, anti-inflammatories, and nutritional therapies. Efforts to advance CF biomarkers, necessary to accelerate the therapeutic goals of the network, are also summarised.

Augmented liver targeting of exosomes by surface modification with cationized pullulan.

PubMed

Tamura, Ryo; Uemoto, Shinji; Tabata, Yasuhiko

2017-07-15

Exosomes are membrane nanoparticles containing biological substances that are employed as therapeutics in experimental inflammatory models. Surface modification of exosomes for better tissue targetability and enhancement of their therapeutic ability was recently attempted mainly using gene transfection techniques. Here, we show for the first time that the surface modification of exosomes with cationized pullulan, which has the ability to target hepatocyte asialoglycoprotein receptors, can target injured liver and enhance the therapeutic effect of exosomes. Surface modification can be achieved by a simple mixing of original exosomes and cationized pullulan and through an electrostatic interaction of both substances. The exosomes modified with cationized pullulan were internalized into HepG2 cells in vitro to a significantly greater extent than unmodified ones and this internalization was induced through the asialoglycoprotein receptor that was specifically expressed on HepG2 cells and hepatocytes. When injected intravenously into mice with concanavalin A-induced liver injury, the modified exosomes accumulated in the liver tissue, resulting in an enhanced anti-inflammatory effect in vivo. It is concluded that the surface modification with cationized pullulan promoted accumulation of the exosomes in the liver and the subsequent biological function, resulting in a greater therapeutic effect on liver injury. Exosomes have shown potentials as therapeutics for various inflammatory disease models. This study is the first to show the specific accumulation of exosomes in the liver and enhanced anti-inflammatory effect via the surface modification of exosomes using pullulan, which is specifically recognized by the asialoglycoprotein receptor (AGPR) on HepG2 cells and hepatocytes. The pullulan was expressed on the surface of PKH-labeled exosomes, and it led increased accumulation of PKH into HepG2 cells, whereas the accumulation was canceled by AGPR inhibitor. In the mouse

Sacral Neuromodulation for Refractory Bladder Pain Syndrome/Interstitial Cystitis: a Global Systematic Review and Meta-analysis.

PubMed

Wang, Junpeng; Chen, Yang; Chen, Jiawei; Zhang, Guihao; Wu, Peng

2017-09-08

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a common debilitating disease and there has not been consistently effective treatment. We aimed to evaluate all available literature regarding the efficacy and safety of sacral neuromodulation (SNM) for refractory BPS/IC. A comprehensive search of Pubmed, Web of Science and Cochrane Library through May 2016 was conducted. A total of 17 studies enrolling 583 patients were identified. Pooled analyses demonstrated that SNM was associated with great reduction in pelvic pain (weighted mean difference [WMD] -3.99; 95% confidence interval [CI] -5.22 to -2.76; p < 0.00001), Interstitial Cystitis Problem and Symptom Index scores (WMD -6.34; 95% CI -9.57 to -3.10; p = 0.0001; and WMD -7.17; 95% CI -9.90 to -4.45; p < 0.00001, respectively), daytime frequency (WMD -7.45; 95% CI -9.68 to -5.22; p < 0.00001), nocturia (WMD -3.01; 95% CI -3.56 to -2.45; p < 0.00001), voids per 24 hours (WMD -9.32; 95% CI -10.90 to -7.74; p < 0.00001) and urgency (WMD -1.08; 95% CI -1.79 to -0.37; p = 0.003) as well as significant improvement in average voided volume (WMD 95.16 ml; 95% CI 63.64 to 126.69; p < 0.0001). The pooled treatment success rate was 84% (95% CI 76% to 91%). SNM-related adverse events were minimal. Current evidence indicates that SNM might be effective and safe for treating refractory BPS/IC.

A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries.

PubMed

Liu, Liang Qin; Moody, Julie; Traynor, Michael; Dyson, Sue; Gall, Angela

2014-11-01

Electrical stimulation (ES) can confer benefit to pressure ulcer (PU) prevention and treatment in spinal cord injuries (SCIs). However, clinical guidelines regarding the use of ES for PU management in SCI remain limited. To critically appraise and synthesize the research evidence on ES for PU prevention and treatment in SCI. Review was limited to peer-reviewed studies published in English from 1970 to July 2013. Studies included randomized controlled trials (RCTs), non-RCTs, prospective cohort studies, case series, case control, and case report studies. Target population included adults with SCI. Interventions of any type of ES were accepted. Any outcome measuring effectiveness of PU prevention and treatment was included. Methodological quality was evaluated using established instruments. Twenty-seven studies were included, 9 of 27 studies were RCTs. Six RCTs were therapeutic trials. ES enhanced PU healing in all 11 therapeutic studies. Two types of ES modalities were identified in therapeutic studies (surface electrodes, anal probe), four types of modalities in preventive studies (surface electrodes, ES shorts, sacral anterior nerve root implant, neuromuscular ES implant). The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations, and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters, and conduct more rigorous trials.

A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries

PubMed Central

Liu, Liang Qin; Moody, Julie; Traynor, Michael; Dyson, Sue; Gall, Angela

2014-01-01

Context Electrical stimulation (ES) can confer benefit to pressure ulcer (PU) prevention and treatment in spinal cord injuries (SCIs). However, clinical guidelines regarding the use of ES for PU management in SCI remain limited. Objectives To critically appraise and synthesize the research evidence on ES for PU prevention and treatment in SCI. Method Review was limited to peer-reviewed studies published in English from 1970 to July 2013. Studies included randomized controlled trials (RCTs), non-RCTs, prospective cohort studies, case series, case control, and case report studies. Target population included adults with SCI. Interventions of any type of ES were accepted. Any outcome measuring effectiveness of PU prevention and treatment was included. Methodological quality was evaluated using established instruments. Results Twenty-seven studies were included, 9 of 27 studies were RCTs. Six RCTs were therapeutic trials. ES enhanced PU healing in all 11 therapeutic studies. Two types of ES modalities were identified in therapeutic studies (surface electrodes, anal probe), four types of modalities in preventive studies (surface electrodes, ES shorts, sacral anterior nerve root implant, neuromuscular ES implant). Conclusion The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations, and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters, and conduct more rigorous trials. PMID:24969965

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma.

PubMed

Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C

2016-02-01

Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44(high)EpCAM(low/-) CD24(+) cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs.

Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma

PubMed Central

Biddle, Adrian; Gammon, Luke; Liang, Xiao; Costea, Daniela Elena; Mackenzie, Ian C.

2016-01-01

Cancer stem cells (CSCs) drive tumour spread and therapeutic resistance, and can undergo epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) to switch between epithelial and post-EMT sub-populations. Examining oral squamous cell carcinoma (OSCC), we now show that increased phenotypic plasticity, the ability to undergo EMT/MET, underlies increased CSC therapeutic resistance within both the epithelial and post-EMT sub-populations. The post-EMT CSCs that possess plasticity exhibit particularly enhanced therapeutic resistance and are defined by a CD44highEpCAMlow/− CD24+ cell surface marker profile. Treatment with TGFβ and retinoic acid (RA) enabled enrichment of this sub-population for therapeutic testing, through which the endoplasmic reticulum (ER) stressor and autophagy inhibitor Thapsigargin was shown to selectively target these cells. Demonstration of the link between phenotypic plasticity and therapeutic resistance, and development of an in vitro method for enrichment of a highly resistant CSC sub-population, provides an opportunity for the development of improved chemotherapeutic agents that can eliminate CSCs. PMID:26981578

On the advancement of therapeutic penality: therapeutic authority, personality science and the therapeutic community.

PubMed

McBride, Ruari-Santiago

2017-09-01

In this article I examine the advancement of therapeutic penality in the UK, a penal philosophy that reimagines prison policy, practices and environments utilising psychological knowledge. Adopting a historical approach, I show how modern therapeutic penality is linked to the emergence of personality science in the nineteenth century and the development of the democratic therapeutic community (DTC) model in the twentieth century. I outline how at the turn of the twenty-first century a catalytic event generated a moral panic that led the British government to mobilise psychological knowledge and technologies in an attempt to manage dangerous people with severe personality disorder. Tracing subsequent developments, I argue psychological ways of talking, thinking and acting have obtained unparalleled salience in domains of penality and, in turn, radically transformed the conditions of imprisonment. © 2017 Foundation for the Sociology of Health & Illness.

How Did the Pelvis and Vertebral Column Become a Functional Unit during the Transition from Occasional to Permanent Bipedalism?

PubMed

Tardieu, Christine; Hasegawa, Kazuhiro; Haeusler, Martin

2017-05-01

The functional linkage between pelvis and spine remained long hidden to science. Here, we recount the history of research that led in 1992 to the discovery of the "angle of sacral incidence" by the team of G. Duval-Beaupère. This angle, formed between a ray from the hip joint center to the superior sacral surface and the perpendicular to the sacral surface, was later called pelvic incidence. Specific to each individual, pelvic incidence is tightly correlated with the degree of lumbar lordosis. It is each individual's "signature" for an efficient sagittal balance since it represents the sum of two positional parameters, sacral slope and pelvic tilt. The simultaneous experimental determination of the trunk line of gravity permitted Duval-Beaupère's team to elucidate the conditions of an efficient sagittal balance of the trunk on the lower limbs. We present an in vivo EOS study of eight spino-pelvic parameters describing the sagittal balance in 131 adults. We observe a chain of correlations between the six angular parameters and discuss the functional significance of these results. We show that pelvic incidence increases and lumbar lordosis develops when the infant learns to walk, leading to a correlation between these parameters. This process of association between pelvis and spine might have acquired a solid genetic basis during hominid evolution by natural selection acting on both pelvis and spine. We suggest that this process of functional integration was only possible in the context of bipedal locomotion becoming permanent and stereotyped, expressed by a relatively invariant, periodic walking cycle. Anat Rec, 300:912-931, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics

NASA Astrophysics Data System (ADS)

Chen, Kuan-Ju

Over the past decades, significant efforts have been devoted to explore the use of various nanoparticle-based systems in the field of nanomedicine, including molecular imaging and therapy. Supramolecular synthetic approaches have attracted lots of attention due to their flexibility, convenience, and modularity for producing nanoparticles. In this dissertation, the developmental story of our size-controllable supramolecular nanoparticles (SNPs) will be discussed, as well as their use in specific biomedical applications. To achieve the self-assembly of SNPs, the well-characterized molecular recognition system (i.e., cyclodextrin/adamantane recognition) was employed. The resulting SNPs, which were assembled from three molecular building blocks, possess incredible stability in various physiological conditions, reversible size-controllability and dynamic disassembly that were exploited for various in vitro and in vivo applications. An advantage of using the supramolecular approach is that it enables the convenient incorporation of functional ligands onto SNP surface that confers functionality ( e.g., targeting, cell penetration) to SNPs. We utilized SNPs for molecular imaging such as magnetic resonance imaging (MRI) and positron emission tomography (PET) by introducing reporter systems (i.e., radio-isotopes, MR contrast agents, and fluorophores) into SNPs. On the other hand, the incorporation of various payloads, including drugs, genes and proteins, into SNPs showed improved delivery performance and enhanced therapeutic efficacy for these therapeutic agents. Leveraging the powers of (i) a combinatorial synthetic approach based on supramolecular assembly and (ii) a digital microreactor, a rapid developmental pathway was developed that is capable of screening SNP candidates for the ideal structural and functional properties that deliver optimal performance. Moreover, SNP-based theranostic delivery systems that combine reporter systems and therapeutic payloads into a

Acoustic pressure wound therapy to facilitate granulation tissue in sacral pressure ulcers in patients with compromised mobility: a case series.

PubMed

Schmuckler, Jo

2008-08-01

Electrical stimulation and other modalities are recommended for treatment of pressure ulcers in spinal cord injury patients but their use may be limited by clinical contraindications such as necrosis and infection. Acoustic pressure wound therapy can be used to address infection and has no known contraindications related to wound status. A retrospective nonconsecutive study was conducted involving five inpatients with sacral pressure ulcers and compromised mobility (spinal cord injury, ventilator/mobility dependency, or persistent vegetative state) treated with acoustic pressure wound therapy three times per week, 4 to 6 minutes per session, for 5 weeks to 5.5 months. Acoustic pressure wound therapy was administered until necrotic tissue was removed, granulation was complete, drainage resolved to moderate levels, and wound size was compatible with indications for high-voltage electrical stimulation. Within 1 to 4 weeks of starting acoustic pressure wound therapy, four out of five wounds with substantial yellow slough or eschar demonstrated 100% granulation tissue and wound area and volume decreased 71% to 97% and 75% to 99%, respectively. Subsequent treatments included electrical stimulation alone (three patients) or in conjunction with negative pressure wound therapy (one patient), and silver foam (one patient). Acoustic pressure wound therapy was found to be an effective option in preparing wounds for subsequent therapy.

Therapeutic drug levels

MedlinePlus

... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

The surface science of nanocrystals

NASA Astrophysics Data System (ADS)

Boles, Michael A.; Ling, Daishun; Hyeon, Taeghwan; Talapin, Dmitri V.

2016-02-01

All nanomaterials share a common feature of large surface-to-volume ratio, making their surfaces the dominant player in many physical and chemical processes. Surface ligands -- molecules that bind to the surface -- are an essential component of nanomaterial synthesis, processing and application. Understanding the structure and properties of nanoscale interfaces requires an intricate mix of concepts and techniques borrowed from surface science and coordination chemistry. Our Review elaborates these connections and discusses the bonding, electronic structure and chemical transformations at nanomaterial surfaces. We specifically focus on the role of surface ligands in tuning and rationally designing properties of functional nanomaterials. Given their importance for biomedical (imaging, diagnostics and therapeutics) and optoelectronic (light-emitting devices, transistors, solar cells) applications, we end with an assessment of application-targeted surface engineering.

Percutaneous tibial nerve stimulation vs sacral nerve stimulation for faecal incontinence: a comparative case-matched study.

PubMed

Al Asari, S; Meurette, G; Mantoo, S; Kubis, C; Wyart, V; Lehur, P-A

2014-11-01

The study assessed the initial experience with posterior tibial nerve stimulation (PTNS) for faecal incontinence and compared it with sacral nerve stimulation (SNS) performed in a single centre during the same timespan. A retrospective review of a prospectively collected database was conducted at the colorectal unit, University Hospital, Nantes, France, from May 2009 to December 2010. Seventy-eight patients diagnosed with chronic severe faecal incontinence underwent neurostimulation including PTNS in 21 and SNS in 57. The main outcome measures were faecal incontinence (Wexner score) and quality of life (Fecal Incontinence Quality of Life, FIQL) scores in a short-term follow-up. No significant differences were observed in patients' characteristics. Of 57 patients having SNS, 18 (32%) failed peripheral nerve evaluation and 39 (68%) received a permanent implant. Two (5%) developed a wound infection. No adverse effects were recorded in the PTNS group. There was no significant difference in the mean Wexner and FIQL scores between patients having PTNS and SNS at 6 (P = 0.39 and 0.09) and 12 months (P = 0.79 and 0.37). A 50% or more improvement in Wexner score was seen at 6 and 12 months in 47% and 30% of PTNS patients and in 50% and 58% of SNS patients with no significant difference between the groups. Posterior tibial nerve stimulation is a valid method of treating faecal incontinence in the short term when conservative treatment has failed. It is easier, simpler, cheaper and less invasive than SNS with a similar short-term outcome. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

How collaboration in therapy becomes therapeutic: the therapeutic collaboration coding system.

PubMed

Ribeiro, Eugénia; Ribeiro, António P; Gonçalves, Miguel M; Horvath, Adam O; Stiles, William B

2013-09-01

The quality and strength of the therapeutic collaboration, the core of the alliance, is reliably associated with positive therapy outcomes. The urgent challenge for clinicians and researchers is constructing a conceptual framework to integrate the dialectical work that fosters collaboration, with a model of how clients make progress in therapy. We propose a conceptual account of how collaboration in therapy becomes therapeutic. In addition, we report on the construction of a coding system - the therapeutic collaboration coding system (TCCS) - designed to analyse and track on a moment-by-moment basis the interaction between therapist and client. Preliminary evidence is presented regarding the coding system's psychometric properties. The TCCS evaluates each speaking turn and assesses whether and how therapists are working within the client's therapeutic zone of proximal development, defined as the space between the client's actual therapeutic developmental level and their potential developmental level that can be reached in collaboration with the therapist. We applied the TCCS to five cases: a good and a poor outcome case of narrative therapy, a good and a poor outcome case of cognitive-behavioural therapy, and a dropout case of narrative therapy. The TCCS offers markers that may help researchers better understand the therapeutic collaboration on a moment-to-moment basis and may help therapists better regulate the relationship. © 2012 The British Psychological Society.

Nanostructured Surfaces for Drug Delivery and Anti-Fibrosis

NASA Astrophysics Data System (ADS)

Kam, Kimberly Renee

Effective and cost-efficient healthcare is at the forefront of public discussion; on both personal and policy levels, technologies that improve therapeutic efficacy without the use of painful hypodermic needle injections or the use of harsh chemicals would prove beneficial to patients. Nanostructured surfaces as structure-mediated permeability enhancers introduce a potentially revolutionary approach to the field of drug delivery. Parental administration routes have been the mainstay technologies for delivering biologics because these therapeutics are too large to permeate epithelial barriers. However, there is a significant patient dislike for hypodermic needles resulting in reduced patient compliance and poor therapeutic results. We present an alternative strategy to harness the body's naturally occurring biological processes and transport mechanisms to enhance the drug transport of biologics across the epithelium. Our strategy offers a paradigm shift from traditional biochemical drug delivery vehicles by using nanotopography to loosen the epithelial barrier. Herein, we demonstrate that nanotopographical cues can be used to enable biologics > 66 kDa to be transported across epithelial monolayers by increasing paracellular transport. When placed in contact with epithelial cells, nanostructured films significantly increase the transport of albumin, IgG, and a model therapeutic, etanercept. Our work highlights the potential to use drug delivery systems which incorporate nanotopographical cues to increase the transport of biologics across epithelial tissue. Furthermore, we describe current advancements in nano- and microfabrication for applications in anti-fibrosis and wound healing. Influencing cellular responses to biomaterials is crucial in the field of tissue engineering and regenerative medicine. Since cells are surrounded by extracellular matrix features that are on the nanoscale, identifying nanostructures for imparting desirable cellular function could greatly

[Therapeutic nursing: a systematic review].

PubMed

Lautenschläger, S; Müller, C; Immenschuh, U; Muser, J; Behrens, J

2014-08-01

For some years therapeutic service catalogues have been established in medical rehabilitation which have broadened our previous understanding of nursing actions. Currently, therapeutic nursing plays a prominent role in neurological early rehabilitation because the operations and procedures coding system (OPS) 8-552 within the DRG-System (Diagnosis Related Groups) states that therapeutic nursing must be carried out by specially trained nursing personnel. This requirement leads to inconsistencies in nursing practice and the medical service of the health insurance (MDK) since a definition of therapeutic nursing is lacking. A previous review of therapeutic nursing in 2003 focused primarily on the development of the therapeutic nursing role, but not on therapeutic nursing itself. The following article contains the first systematic review of the current state of research regarding a definition of therapeutic nursing. For this purpose, a systematic study was conducted to examine if there are, nationally or internationally, any definitions of therapeutic nursing and to identify what the therapeutic aspects of nursing are. The research included following database; Medline, Cinahl and Embase. Additionally, a research by hand of several German journals as well as textbooks and specialized literature was carried out. 5 studies were selected which define the term "therapeutic nursing". Among these are one review, one primary study, one theoretical discussion and one dissertation. Further twenty four studies were identified which do not define the term, but are closely related to the subject, and use or characterize the term in various contexts. The publications examined provided indications of duties, interventions and roles nurses should perform, but not how to carry these out, nor what is therapeutic about the nursing. At the same time, the low number of studies reveals that therapeutic nursing has barely been examined and demonstrates the lack of theoretically grounding

Gold Nanoparticles-enabled Efficient Dual Delivery of Anticancer Therapeutics to HeLa Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farooq, Muhammad U.; Novosad, Valentyn; Rozhkova, Elena A.

Colloidal gold nanoparticles (AuNPs) are of interest as non-toxic carriers for drug delivery owing to their advanced properties, such as extensive surface-to-volume ratio and possibilities for tailoring their charge, hydrophilicity and functionality through surface chemistries. To date, various biocompatible polymers have been used for surface decoration of AuNPs to enhance their stability, payloads capacity and cellular uptake. This study describes a facile one-step method to synthesize stable AuNPs loaded with combination of two anticancer therapeutics, -bleomycin and doxorubicin. Anticancer activities, cytotoxicity, uptake and intracellular localization of the AuNPs were demonstrated in HeLa cells. We show that the therapeutic efficacy ofmore » the nanohybrid drug was strongly enhanced by the active targeting by the nanoscale delivery system to HeLa cells with a significant decrease of the half-maximal effective drug concentration, through blockage of HeLa cancer cell cycle. These results provide rationale for further progress of AuNPs-assisted combination chemotherapy using two drugs at optimized effective concentrations which act via different mechanisms thus decreasing possibilities of development of the cancer drug resistance, reduction of systemic drug toxicity and improvement of outcomes of chemotherapy.« less

Gold Nanoparticles-enabled Efficient Dual Delivery of Anticancer Therapeutics to HeLa Cells

DOE PAGES

Farooq, Muhammad U.; Novosad, Valentyn; Rozhkova, Elena A.; ...

2018-02-13

Colloidal gold nanoparticles (AuNPs) are of interest as non-toxic carriers for drug delivery owing to their advanced properties, such as extensive surface-to-volume ratio and possibilities for tailoring their charge, hydrophilicity and functionality through surface chemistries. To date, various biocompatible polymers have been used for surface decoration of AuNPs to enhance their stability, payloads capacity and cellular uptake. This study describes a facile one-step method to synthesize stable AuNPs loaded with combination of two anticancer therapeutics, -bleomycin and doxorubicin. Anticancer activities, cytotoxicity, uptake and intracellular localization of the AuNPs were demonstrated in HeLa cells. We show that the therapeutic efficacy ofmore » the nanohybrid drug was strongly enhanced by the active targeting by the nanoscale delivery system to HeLa cells with a significant decrease of the half-maximal effective drug concentration, through blockage of HeLa cancer cell cycle. These results provide rationale for further progress of AuNPs-assisted combination chemotherapy using two drugs at optimized effective concentrations which act via different mechanisms thus decreasing possibilities of development of the cancer drug resistance, reduction of systemic drug toxicity and improvement of outcomes of chemotherapy.« less

A cost-utility analysis of sacral anterior root stimulation (SARS) compared with medical treatment in patients with complete spinal cord injury with a neurogenic bladder.

PubMed

Morlière, Camille; Verpillot, Elise; Donon, Laurence; Salmi, Louis-Rachid; Joseph, Pierre-Alain; Vignes, Jean-Rodolphe; Bénard, Antoine

2015-12-01

Sacral anterior root stimulation (SARS) and posterior sacral rhizotomy restores the ability to urinate on demand with low residual volumes, which is a key for preventing urinary complications that account for 10% of the causes of death in patients with spinal cord injury with a neurogenic bladder. Nevertheless, comparative cost-effectiveness results on a long time horizon are lacking to adequately inform decisions of reimbursement. This study aimed to estimate the long-term cost-utility of SARS using the Finetech-Brindley device compared with medical treatment (anticholinergics+catheterization). The following study design is used for the paper: Markov model elaborated with a 10-year time horizon; with four irreversible states: (1) initial treatment, (2) year 1 of surgery for urinary complication, (3) year >1 of surgery for urinary complication, and (4) death; and reversible states: urinary calculi; Finetech-Brindley device failures. The sample consisted of theoretical cohorts of patients with a complete spinal cord lesion since ≥1 year, and a neurogenic bladder. Effectiveness was expressed as quality adjusted life years (QALYs). Costs were valued in EUR 2013 in the perspective of the French health system. A systematic review and meta-analyses were performed to estimate transition probabilities and QALYs. Costs were estimated from the literature, and through simulations using the 2013 French prospective payment system classification. Probabilistic analyses were conducted to handle parameter uncertainty. In the base case analysis (2.5% discount rate), the cost-utility ratio was 12,710 EUR per QALY gained. At a threshold of 30,000 EUR per QALY the probability of SARS being cost-effective compared with medical treatment was 60%. If the French Healthcare System reimbursed SARS for 80 patients per year during 10 years (anticipated target population), the expected incremental net health benefit would be 174 QALYs, and the expected value of perfect information (EVPI

Therapeutic friendliness and the development of therapeutic leverage by mental health nurses in community rehabilitation settings.

PubMed

Gardner, Andrew

2010-01-01

In a world dominated by technology and driven by fiscal policy emphasis, the therapeutic relationship as a healing modality is still a central theme to mental health nurses (MHN) in their everyday work. This research, as part of a PhD program, used a constructivist grounded theory approach to explore the process of therapeutic relationships and professional boundaries. The current paper outlines how therapeutic friendliness provides a connection for the therapeutic relationship to develop but in doing so requires a balancing of the therapeutic relationship and constant maintenance of the professional boundary. The authors also discuss how community mental health nurses (CMHN) invest in the therapeutic relationship in order to develop a therapeutic alliance and how the alliance between the CMHN and the client facilitates the use of therapeutic leverage applied by the CMHN as part of the therapeutic process.

Nanoparticles for Imaging, Sensing, and Therapeutic Intervention

PubMed Central

2014-01-01

Nanoparticles have the potential to contribute to new modalities in molecular imaging and sensing as well as in therapeutic interventions. In this Nano Focus article, we identify some of the current challenges and knowledge gaps that need to be confronted to accelerate the developments of various applications. Using specific examples, we journey from the characterization of these complex hybrid nanomaterials; continue with surface design and (bio)physicochemical properties, their fate in biological media and cells, and their potential for cancer treatment; and finally reflect on the role of animal models to predict their behavior in humans. PMID:24641589

Development of a Humanized Monoclonal Antibody with Therapeutic Potential against West Nile Virus

PubMed Central

Oliphant, Theodore; Engle, Michael; Nybakken, Grant E.; Doane, Chris; Johnson, Syd; Huang, Ling; Gorlatov, Sergey; Mehlhop, Erin; Marri, Anantha; Chung, Kyung Min; Ebel, Gregory D.; Kramer, Laura D.; Fremont, Daved H.; Diamond, Michael S.

2006-01-01

Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated mAbs against domain III of the WNV E protein. MAbs that strongly neutralized WNV localized to a surface patch on the lateral face of domain III. Convalescent antibodies from human patients who had recovered from WNV infection also detected this epitope. One mAb, E16, neutralized 10 different strains in vitro, and demonstrated therapeutic efficacy in mice, even when administered as a single dose 5 d after infection. A humanized version of E16 was generated that retained antigen specificity, avidity, and neutralizing activity. In post-exposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and thus, may be a viable treatment option against WNV infection in humans. PMID:15852016

Issues in formulary management: therapeutic interchange. The value, cost, and quality of therapeutic interchange.

PubMed

Mahoney, C D

1992-10-01

Therapeutic interchange is a process of substituting a prescribed medication with one that offers therapeutic and cost benefits. The practice not only provides short-term savings but also is associated with decreases in lengths of stay in hospitals and total hospital drug expenses. There may be medicolegal implications when FDA-approved indications differ for interchanged drugs. The potential for liability is decreased when a standard of care is met, but since standards can change, guidelines should be reviewed regularly. High-tech, high-cost drugs are sometimes appropriate for therapeutic interchange. Pharmacy and therapeutics committees should assure best value by considering indirect expenses, quality, and therapeutic outcome, as well as product cost. Therapeutic interchange programs enable pharmacy managers to neutralize or at least slow the rate of drug cost increases, ensuring appropriate utilization of resources and more favorable patient outcomes.

Graphene-based platforms for cancer therapeutics.

PubMed

Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

2016-01-01

Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management.

Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application.

PubMed

Yamashita, Takuma; Takahashi, Yuki; Takakura, Yoshinobu

2018-01-01

Exosomes are cell-derived vesicles with a diameter 30-120 nm. Exosomes contain endogenous proteins and nucleic acids; delivery of these molecules to exosome-recipient cells causes biological effects. Exosomes derived from some types of cells such as mesenchymal stem cells and dendritic cells have therapeutic potential and may be biocompatible and efficient agents against various disorders such as organ injury. However, there are many challenges for the development of exosome-based therapeutics. In particular, producing exosomal formulations is the major barrier for therapeutic application because of their heterogeneity and low productivity. Development and optimization of producing methods, including methods for isolation and storage of exosome formulations, are required for realizing exosome-based therapeutics. In addition, improvement of therapeutic potential and delivery efficiency of exosomes are important for their therapeutic application. In this review, we summarize current knowledge about therapeutic application of exosomes and discuss some challenges in their successful use.

Chaperoning G Protein-Coupled Receptors: From Cell Biology to Therapeutics

PubMed Central

Conn, P. Michael

2014-01-01

G protein-coupled receptors (GPCRs) are membrane proteins that traverse the plasma membrane seven times (hence, are also called 7TM receptors). The polytopic structure of GPCRs makes the folding of GPCRs difficult and complex. Indeed, many wild-type GPCRs are not folded optimally, and defects in folding are the most common cause of genetic diseases due to GPCR mutations. Both general and receptor-specific molecular chaperones aid the folding of GPCRs. Chemical chaperones have been shown to be able to correct the misfolding in mutant GPCRs, proving to be important tools for studying the structure-function relationship of GPCRs. However, their potential therapeutic value is very limited. Pharmacological chaperones (pharmacoperones) are potentially important novel therapeutics for treating genetic diseases caused by mutations in GPCR genes that resulted in misfolded mutant proteins. Pharmacoperones also increase cell surface expression of wild-type GPCRs; therefore, they could be used to treat diseases that do not harbor mutations in GPCRs. Recent studies have shown that indeed pharmacoperones work in both experimental animals and patients. High-throughput assays have been developed to identify new pharmacoperones that could be used as therapeutics for a number of endocrine and other genetic diseases. PMID:24661201

Human Leukocyte Antigen-Presented Macrophage Migration Inhibitory Factor is a Surface Biomarker and Potential Therapeutic Target for Ovarian Cancer

PubMed Central

Patterson, Andrea M; Kaabinejadian, Saghar; McMurtrey, Curtis P; Bardet, Wilfried; Jackson, Ken W; Zuna, Rosemary E; Husain, Sanam; Adams, Gregory P; MacDonald, Glen; Dillon, Rachelle L.; Ames, Harold; Buchli, Rico; Hawkins, Oriana E; Weidanz, Jon A; Hildebrand, William H

2015-01-01

T cells recognize cancer cells via human leukocyte antigen (HLA)/peptide complexes and, when disease overtakes these immune mechanisms, immunotherapy can exogenously target these same HLA/peptide surface markers. We previously identified an HLA-A2-presented peptide derived from macrophage migration inhibitory factor (MIF) and generated antibody RL21A against this HLA-A2/MIF complex. The objective of the current study was to assess the potential for targeting the HLA-A2/MIF complex in ovarian cancer. First, MIF peptide FLSELTQQL was eluted from the HLA-A2 of the human cancerous ovarian cell lines SKOV3, A2780, OV90, and FHIOSE118hi and detected by mass spectrometry. By flow cytometry, RL21A was shown to specifically stain these four cell lines in the context of HLA-A2. Next, partially matched HLA-A*02:01+ ovarian cancer (n=27) and normal fallopian tube (n=24) tissues were stained with RL21A by immunohistochemistry to assess differential HLA-A2/MIF complex expression. Ovarian tumor tissues revealed significantly increased RL21A staining compared to normal fallopian tube epithelium (p<0.0001), with minimal staining of normal stroma and blood vessels (p<0.0001 and p<0.001 compared to tumor cells) suggesting a therapeutic window. We then demonstrated the anti-cancer activity of toxin-bound RL21A via the dose-dependent killing of ovarian cancer cells. In summary, MIF-derived peptide FLSELTQQL is HLA-A2-presented and recognized by RL21A on ovarian cancer cell lines and patient tumor tissues, and targeting of this HLA-A2/MIF complex with toxin-bound RL21A can induce ovarian cancer cell death. These results suggest that the HLA-A2/MIF complex should be further explored as a cell-surface target for ovarian cancer immunotherapy. PMID:26719579

Multifunctional mesoporous silica nanoparticles for combined therapeutic, diagnostic and targeted action in cancer treatment.

PubMed

Rosenholm, Jessica M; Sahlgren, Cecilia; Lindén, Mika

2011-07-01

The main objective in the development of nanomedicine is to obtain delivery platforms for targeted delivery of drugs or imaging agents for improved therapeutic efficacy, reduced side effects and increased diagnostic sensitivity. A (nano)material class that has been recognized for its controllable properties on many levels is ordered mesoporous inorganic materials, typically in the form of amorphous silica (SiO2). Characteristics for this class of materials include mesoscopic order, tunable pore dimensions in the (macro)molecular size range, a high pore volume and surface area, the possibility for selective surface functionality as well as morphology control. The robust but biodegradable ceramic matrix moreover provides shelter for incorporated agents (drugs, proteins, imaging agents, photosensitizers) leaving the outer particle surface free for further modification. The unique features make these materials particularly amenable to modular design, whereby functional moieties and features may be interchanged or combined to produce multifunctional nanodelivery systems combining targeting, diagnostic, and therapeutic actions. This review covers the latest developments related to the use of mesoporous silica nanoparticles (MSNs) as nanocarriers in biomedical applications, with special focus on cancer therapy and diagnostics.

MACROMOLECULAR THERAPEUTICS

PubMed Central

Yang, Jiyuan; Kopeček, Jindřich

2014-01-01

This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

Therapeutics incorporating blood constituents.

PubMed

Charoenphol, Phapanin; Oswalt, Katie; Bishop, Corey J

2018-04-05

Blood deficiency and dysfunctionality can result in adverse events, which can primarily be treated by transfusion of blood or the re-introduction of properly functioning sub-components. Blood constituents can be engineered on the sub-cellular (i.e., DNA recombinant technology) and cellular level (i.e., cellular hitchhiking for drug delivery) for supplementing and enhancing therapeutic efficacy, in addition to rectifying dysfunctioning mechanisms (i.e., clotting). Herein, we report the progress of blood-based therapeutics, with an emphasis on recent applications of blood transfusion, blood cell-based therapies and biomimetic carriers. Clinically translated technologies and commercial products of blood-based therapeutics are subsequently highlighted and perspectives on challenges and future prospects are discussed. Blood-based therapeutics is a burgeoning field and has advanced considerably in recent years. Blood and its constituents, with and without modification (i.e., combinatorial), have been utilized in a broad spectrum of pre-clinical and clinically-translated treatments. This review article summarizes the most up-to-date progress of blood-based therapeutics in the following contexts: synthetic blood substitutes, acellular/non-recombinant therapies, cell-based therapies, and therapeutic sub-components. The article subsequently discusses clinically-translated technologies and future prospects thereof. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Macromolecular therapeutics.

PubMed

Yang, Jiyuan; Kopeček, Jindřich

2014-09-28

This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

[Therapeutic cloning in debate].

PubMed

de Wert, G

2001-11-03

Human embryos can be conceived by cell nuclear transfer in order to isolate human embryonic stem cells (hES cells) for research into autologous cell therapy (therapeutic cloning). However, this technique broaches the major ethical problem concerning the instrumental use of human preimplantation embryos. From the viewpoint of subsidiarity, it is argued that various potential alternatives for therapeutic cloning should first be investigated further. The question as to whether therapeutic cloning should be allowed only becomes apparent when research with surplus embryos obtained in the course of in-vitro fertilization suggests that usable transplants can be obtained in vitro from hES cells, and when the potential alternatives for therapeutic cloning are either less promising or need more time for development than is currently expected.

[Alternative treatments for interstitial cystitis].

PubMed

Gamé, X; Bart, S; Castel-Lacanal, E; De Sèze, M; Karsenty, G; Labat, J-J; Rigaud, J; Scheiber-Nogueira, M C; Ruffion, A

2009-06-01

Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.

Psychodynamic Perspective on Therapeutic Boundaries

PubMed Central

Bridges, Nancy A.

1999-01-01

Discussion of boundaries in therapeutic work most often focuses on boundary maintenance, risk management factors, and boundary violations. The psychodynamic meaning and clinical management of boundaries in therapeutic relationships remains a neglected area of discourse. Clinical vignettes will illustrate a psychodynamic, developmental-relational perspective using boundary dilemmas to deepen and advance the therapeutic process. This article contributes to the dialogue about the process of making meaning and constructing therapeutically useful and creative boundaries that further the psychotherapeutic process. PMID:10523432

[Nuclear transfer and therapeutic cloning].

PubMed

Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

2005-03-01

Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

Graphene-based platforms for cancer therapeutics

PubMed Central

Patel, Sunny C; Lee, Stephen; Lalwani, Gaurav; Suhrland, Cassandra; Chowdhury, Sayan Mullick; Sitharaman, Balaji

2016-01-01

Graphene is a multifunctional carbon nanomaterial and could be utilized to develop platform technologies for cancer therapies. Its surface can be covalently and noncovalently functionalized with anticancer drugs and functional groups that target cancer cells and tissue to improve treatment efficacies. Furthermore, its physicochemical properties can be harnessed to facilitate stimulus responsive therapeutics and drug delivery. This review article summarizes the recent literature specifically focused on development of graphene technologies to treat cancer. We will focus on advances at the interface of graphene based drug/gene delivery, photothermal/photodynamic therapy and combinations of these techniques. We also discuss the current understanding in cytocompatibility and biocompatibility issues related to graphene formulations and their implications pertinent to clinical cancer management. PMID:26769305

Particle Transport in Therapeutic Magnetic Fields

NASA Astrophysics Data System (ADS)

Puri, Ishwar K.; Ganguly, Ranjan

2014-01-01

Iron oxide magnetic nanoparticles, in ferrofluids or as magnetic microspheres, offer magnetic maneuverability, biochemical surface functionalization, and magnetic relaxation under the influence of an alternating field. The use of these properties for clinical applications requires an understanding of particles, forces, and scalar transport at various length scales. This review explains the behavior of magnetic nano- and microparticles during magnetic drug targeting and magnetic fluid hyperthermia, and the microfluidic transport of these particles in bioMEMS (biomedical microelectromechanical systems) devices for ex vivo therapeutic and diagnostic applications. Magnetic particle transport, the momentum interaction of these particles with a host fluid in a flow, and thermal transport in a particle-infused tissue are characterized through the governing electrodynamic, hydrodynamic, and scalar transport equations.

Therapeutic Inertia and Treatment Intensification.

PubMed

Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

2018-01-29

This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

Combination therapeutics in complex diseases.

PubMed

He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

2016-12-01

The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Development of Multifunctional Nanoparticles for Targeted Drug Delivery and Non-invasive Imaging of Therapeutic Effect

PubMed Central

Sajja, Hari Krishna; East, Michael P.; Mao, Hui; Wang, Andrew Y.; Nie, Shuming; Yang, Lily

2011-01-01

Nanotechnology is a multidisciplinary scientific field undergoing explosive development. Nanometer-sized particles offer novel structural, optical and electronic properties that are not attainable with individual molecules or bulk solids. Advances in nanomedicine can be made by engineering biodegradable nanoparticles such as magnetic iron oxide nanoparticles, polymers, dendrimers and liposomes that are capable of targeted delivery of both imaging agents and anticancer drugs. This leads toward the concept and possibility of personalized medicine for the potential of early detection of cancer lesions, determination of molecular signatures of the tumor by non-invasive imaging and, most importantly, molecular targeted cancer therapy. Increasing evidence suggests that the nanoparticles, whose surface contains a targeting molecule that binds to receptors highly expressed in tumor cells, can serve as cancer image contrast agents to increase sensitivity and specificity in tumor detection. In comparison with other small molecule contrast agents, the advantage of using nanoparticles is their large surface area and the possibility of surface modifications for further conjugation or encapsulation of large amounts of therapeutic agents. Targeted nanoparticles ferry large doses of therapeutic agents into malignant cells while sparing the normal healthy cells. Such multifunctional nanodevices hold the promise of significant improvement of current clinical management of cancer patients. This review explores the development of nanoparticles for enabling and improving the targeted delivery of therapeutic agents, the potential of nanomedicine, and the development of novel and more effective diagnostic and screening techniques to extend the limits of molecular diagnostics providing point-of-care diagnosis and more personalized medicine. PMID:19275541

Surface-modified polymers for cardiac tissue engineering.

PubMed

Moorthi, Ambigapathi; Tyan, Yu-Chang; Chung, Tze-Wen

2017-09-26

Cardiovascular disease (CVD), leading to myocardial infarction and heart failure, is one of the major causes of death worldwide. The physiological system cannot significantly regenerate the capabilities of a damaged heart. The current treatment involves pharmacological and surgical interventions; however, less invasive and more cost-effective approaches are sought. Such new approaches are developed to induce tissue regeneration following injury. Hence, regenerative medicine plays a key role in treating CVD. Recently, the extrinsic stimulation of cardiac regeneration has involved the use of potential polymers to stimulate stem cells toward the differentiation of cardiomyocytes as a new therapeutic intervention in cardiac tissue engineering (CTE). The therapeutic potentiality of natural or synthetic polymers and cell surface interactive factors/polymer surface modifications for cardiac repair has been demonstrated in vitro and in vivo. This review will discuss the recent advances in CTE using polymers and cell surface interactive factors that interact strongly with stem cells to trigger the molecular aspects of the differentiation or formulation of cardiomyocytes for the functional repair of heart injuries or cardiac defects.

Immunogenicity of therapeutic proteins. Part 2: impact of container closures.

PubMed

Sharma, Basant

2007-01-01

Immunogenicity as a potential consequence of therapeutic protein administration is increasingly being scrutinized in the biopharmaceuticals industry, particularly with the imminent introduction of biosimilar products. Immunogenicity is an important safety aspect requiring rigorous investigation to fully appreciate its impact. Factors involved in product handling, such as storage temperature, light exposure, and shaking, have been implicated in immunogenicity, while container closure systems are no less important. Intended to provide a stable environment for the dosage form, container closures may also interact with a product, affecting performance and potentially enhancing immunogenicity. Glass surfaces, air-liquid interfaces, and lubricants can mediate protein denaturation, while phthalates in plastics and latex rubber are sources of extractables and leachates that may contaminate a product, causing allergic reactions and increasing immunogenicity. The manufacture of therapeutic proteins therefore requires rigorous safety evaluations not just in the context of the product, but also product containment.

Frequency of an accessory popliteal efferent lymphatic pathway in dogs.

PubMed

Mayer, Monique N; Sweet, Katherine A; Patsikas, Michael N; Sukut, Sally L; Waldner, Cheryl L

2018-05-01

Staging and therapeutic planning for dogs with malignant disease in the popliteal lymph node are based on the expected patterns of lymphatic drainage from the lymph node. The medial iliac lymph nodes are known to receive efferent lymph from the popliteal lymph node; however, an accessory popliteal efferent pathway with direct connection to the sacral lymph nodes has also been less frequently reported. The primary objective of this prospective, anatomic study was to describe the frequency of various patterns of lymphatic drainage of the popliteal lymph node. With informed client consent, 50 adult dogs with no known disease of the lymphatic system underwent computed tomographic lymphography after ultrasound-guided, percutaneous injection of 350 mg/ml iohexol into a popliteal lymph node. In all 50 dogs, the popliteal lymph node drained directly to the ipsilateral medial iliac lymph node through multiple lymphatic vessels that coursed along the medial thigh. In 26% (13/50) of dogs, efferent vessels also drained from the popliteal lymph node directly to the internal iliac and/or sacral lymph nodes, coursing laterally through the gluteal region and passing over the dorsal aspect of the pelvis. Lymphatic connections between the right and left medial iliac and right and left internal iliac lymph nodes were found. Based on our findings, the internal iliac and sacral lymph nodes should be considered when staging or planning therapy for dogs with malignant disease in the popliteal lymph node. © 2018 American College of Veterinary Radiology.

CranioSacral Therapy and Visceral Manipulation: A New Treatment Intervention for Concussion Recovery

PubMed Central

Roland, Melinda; Fryer-Dietz, Sally; Dettmann-Ahern, Dee

2017-01-01

Abstract Background: Military service members and veterans face health issues related to traumatic brain injury (TBI), especially during combat, use of heavy equipment, and exposures to environmental hazards and explosives. There were 400,000 TBIs reported in deployed U.S. troops in 2012. Athletes are also subject to TBI. Studies have indicated that some manual therapies could be helpful for treating patients who have post-concussive syndrome. Objective: This case series report describes the effects of CranioSacral Therapy (CST), Visceral Manipulation (VM), and Neural Manipulation (NM) modalities for treating patients who have post-concussion syndrome. The goal of this study was to evaluate these effects on immobility, pain intensity, quality of life, sleep disorders, and cognition in these patients. Materials and Methods: This single-blinded case series was conducted at the Upledger Institute, in West Palm Beach, FL. The patients were 11 male retired professional football players from the National Football League and the Canadian Football League who had been medically diagnosed with post-concussion syndrome. Each participant received a morning and afternoon 2-hour session of these three specific manual therapies, which were capable of accessing and addressing the structural, vascular, and neurologic tissues of the cranium and brain—as well addressing far-reaching ramifications throughout the body following trauma. The main outcome measures were scores on the: Impact Neurocognitive Test; Dynavisiontm Test; Short Form–36 Quality of Life Survey, Headache Impact Test, Dizziness Handicap Inventory; a numeric pain rating scale; orthopedic range of motion tests (ROM); and vestibular testing. Hours of sleep were also checked. These outcome measures were registered at baseline, after treatment, and after a 3-month follow up. Results: Statistically significant differences were seen with a decrease in overall pain rating scale scores (P = 0.0448), and cervicogenic

Measuring Therapeutic Alliance with Children in Residential Treatment and Therapeutic Day Care

ERIC Educational Resources Information Center

Roest, Jesse; van der Helm, Peer; Strijbosch, Eefje; van Brandenburg, Mariëtte; Stams, Geert Jan

2016-01-01

Purpose: This study examined the construct validity and reliability of a therapeutic alliance measure (Children's Alliance Questionnaire [CAQ]) for children with psychosocial and/or behavioral problems, receiving therapeutic residential care or day care in the Netherlands. Methods: Confirmatory factor analysis of a one-factor model ''therapeutic…

Feasibility of therapeutic pneumoperitoneum in a large animal model using a microvaporisator.

PubMed

Reymond, M A; Hu, B; Garcia, A; Reck, T; Köckerling, F; Hess, J; Morel, P

2000-01-01

Multimodal therapy is used increasingly in advanced gastrointestinal tumors. Potential benefits of using an intraoperative adjuvant therapy during laparoscopy for cancer have been documented in animal studies. The aim of this study was to develop a device that could deliver such an intraoperative drug therapy. We developed a micropump suitable for minimally invasive surgery procedures that allowed microdroplets of therapeutic substance to be distributed into the pneumoperitoneum (CO2), creating a "therapeutic pneumoperitoneum." A closed-loop control system regulates drug delivery according to the gas flow. In vitro, the micropump is able to aerosolize various aqueous and ethanol solutions, including cytostatic and bacteriostatic drugs and adhesion-modulating agents. The size of the microdroplets has been optimized to prevent visual artifacts. The micropump was tested in an animal model (pig). The system was inserted into a 5-mm trocar. After insufflation of a 12-mm CO2 pneumoperitoneum, laparoscopic sigmoid colon resections could be performed with no special difficulties. No fog developed, and no system-related complication was observed. At autopsy, the active principle was distributed to all exposed peritoneal surfaces. As opposed to conventional peritoneal washing, therapeutic pneumoperitoneum reaches the entire peritoneal surface, allowing an optimal drug distribution. Drug diffusion into the tissues is enhanced by the intraperitoneal pressure. Precise determination of the instantaneous and total drug quantity is possible. Therefore, this drug delivery system has several advantages over conventional irrigation. Its potential domains of application are locoregional cancer therapy, prevention of port-site recurrences, immunomodulation, analgesia, peritonitis, and prevention of postoperative adhesions.

Therapeutic HPV vaccines.

PubMed

Hancock, Gemma; Hellner, Karin; Dorrell, Lucy

2018-02-01

High-risk human papillomavirus (HPV) infection is known to be a necessary factor for cervical and anogenital malignancies. Cervical cancers account for over a quarter of a million deaths annually. Despite the availability of prophylactic vaccines, HPV infections remain extremely common worldwide. Furthermore, these vaccines are ineffective at clearing pre-existing infections and associated preinvasive lesions. As cervical dysplasia can regress spontaneously, a therapeutic HPV vaccine that boosts host immunity could have a significant impact on the morbidity and mortality associated with HPV. Therapeutic vaccines differ from prophylactic vaccines in that they are aimed at generating cell-mediated immunity rather than neutralising antibodies. This review will cover various therapeutic vaccine strategies in development for the treatment of HPV-associated lesions and cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Clinical Therapeutic Effect of Oblique Needling with Tuina in Relieving Sacroiliac Joint Injury].

PubMed

Kuang, Jia-yi; Li, Yu-xuan; He, Yu-feng; Gan, Lin; Wang, Ai-ming; Tang, Shao-hua; Lu, Fei-yu; Yang, Li-juan; Cat, Xue-ling; Quan, Jian-lin

2016-04-01

To observe the therapeutic effect of oblique needling in combination with Tuina at the sacroiliac joint for patients experiencing sacroiliac joint injury. One hundred and twenty patients with sacroiliac joint injury were randomized into routine Tuina group and oblique needling combined with Tuina (Acu+ Tuina) group (n = 60 in each group). For patients of the Tuina group, routine Tuina as rotating, pressing-rubbing, digital pressing, articular moving, etc. was manipulated at Shangliao (BL 31), Ciliao (BL 32), Zhongliao (BL 31), Xialiao (BL 30), Huantiao (GB 30), Zhibian (BL 54), Weizhong (BL 40) and sacroiliac joint area. For patients of the Acu+Tuina group, the anatomical points between the bilateral iliac crests and the sacral joints were punctured obliquely with disposable acupuncture needles. The treatment was conducted for 30 min every time, once daily for 3 weeks except weekends. The Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI, concerning intensity of pain, lifting, ability to care for oneself, ability to walk, ability to sit, sexual function, ability to stand, social life, sleep quality, and ability to travel) were employed to evaluate the patients' reactions and functional activity changes before and after the treatment. Following the treatment, of the two 60 patients in the Tuina and Acu + Tuina groups, 12 and 26 cases were cured, 20 and 20 experienced marked improvement, 16 and 11 were effective, 12 and 3 invalid, with the effective rates being 80% and 95%, respectively. The effective rate of the Acu+ Tuina group was significantly superior to that of the Tuina group (P<0.05). The VAS scores and OD were considerably decreased in both groups after the treatment and were significantly lower in the Acu+Tuina group than in the Tuina group (P<0.01). Oblique needling the anatomical points in the sacroiliac joint region combined with Tuina manipulation is evidently better than simple Tuina in reducing pain and in improving functional activity

[Adipose-derived stromal cells (ASC) - basics and therapeutic approaches in otorhinolaryngology].

PubMed

Frölich, K; Hagen, R; Kleinsasser, N

2014-06-01

Adipose-derived Stromal Cells (ASC) - Basics and Therapeutic Approaches in Otorhinolaryngology Mesenchymal stem cells from adipose tissue can be easily harvested with less discomfort, low donor-site morbidity and high amount compared to bone marrow-derived stem cells. Due to their multilineage differentiation potential in various cell types, immunmodulatory properties and their capability to enhance wound healing, ASC are a promising cell source for tissue engineering approaches and regenerative medicine. They are characterized by the expression of specific surface marker proteins and their differentiation potential into the mesenchymal lineages. Whereas only preclinical studies are published for otorhinolaryngology-related therapeutic options using ASC, various diseases, for instance graft-versus-host disease, have already been treated with ASC in single cases or clinical trials. Safety and genomic stability of ASC as well as the risk of spontaneous malignant transformation are still disputed. This review summarizes the current literature on characterization and anatomic localization of ASC. In addition, beside the presentation of preclinical studies concerning therapeutic approaches in otorhinolaryngology as well as of current clinical applications, the issue of safety of ASC in human stem cell therapy is discussed. © Georg Thieme Verlag KG Stuttgart · New York.

Characterization of the surface properties of MgO using paper spray mass spectrometry.

PubMed

Zheng, Yajun; Zhang, Xiaoling; Bai, Zongquan; Zhang, Zhiping

2016-08-01

Significant advances have been made in the preparation of different morphologies of magnesium oxide (MgO), but the relationship between MgO morphology and its interactions with therapeutic drugs is rarely studied. Herein, we investigated the interactions between different morphologies of MgO and therapeutic drugs using paper spray mass spectrometry. Different morphologies of MgO including trapezoidal, needle-like, flower-like and nest-like structures were prepared through a facile precipitation method. The as-obtained MgO particles were then coated onto the surface of filter paper via vacuum filtration strategy. The coated papers with different morphologies of MgO were used as the substrates for paper spray mass spectrometry to explore the interactions between different MgO and therapeutic drugs. Through investigating the interactions between different morphologies of MgO coated papers and therapeutic drugs, it demonstrated that, in contrast to the trapezoidal, needle-like and nest-like MgO coated papers, different drugs in dried blood spots (DBS) were more favourably eluted off from the paper coated with flower-like MgO due to its weaker surface basicity. Also, the signal intensities of different drugs during paper spray were highly dependent on their elution behaviours. Paper spray mass spectrometry (MS) provides an avenue to elaborate the surface properties of MgO with different structures. The surface basicity of MgO played a crucial role in determining the elution behaviours of therapeutic drugs in DBS, and a more favourable elution behaviour tended to result in a higher MS signal. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

NASA Astrophysics Data System (ADS)

Balivada, Sivasai

Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

Transferrin receptors and the targeted delivery of therapeutic agents against cancer

PubMed Central

Daniels, Tracy R.; Bernabeu, Ezequiel; Rodríguez, José A.; Patel, Shabnum; Kozman, Maggie; Chiappetta, Diego A.; Holler, Eggehard; Ljubimova, Julia Y.; Helguera, Gustavo; Penichet, Manuel L.

2012-01-01

Background Traditional cancer therapy can be successful in destroying tumors, but can also cause dangerous side effects. Therefore, many targeted therapies are in development. The transferrin receptor (TfR) functions in cellular iron uptake through its interaction with transferrin. This receptor is an attractive molecule for the targeted therapy of cancer since it is upregulated on the surface of many cancer types and is efficiently internalized. This receptor can be targeted in two ways: 1) for the delivery of therapeutic molecules into malignant cells or 2) to block the natural function of the receptor leading directly to cancer cell death. Scope of review In the present article we discuss the strategies used to target the TfR for the delivery of therapeutic agents into cancer cells. We provide a summary of the vast types of anti-cancer drugs that have been delivered into cancer cells employing a variety of receptor binding molecules including Tf, anti-TfR antibodies, or TfR-binding peptides alone or in combination with carrier molecules including nanoparticles and viruses. Major conclusions Targeting the TfR has been shown to be effective in delivering many different therapeutic agents and causing cytotoxic effects in cancer cells in vitro and in vivo. General significance The extensive use of TfR for targeted therapy attests to the versatility of targeting this receptor for therapeutic purposes against malignant cells. More advances in this area are expected to further improve the therapeutic potential of targeting the TfR for cancer therapy leading to an increase in the number of clinical trials of molecules targeting this receptor. PMID:21851850

Latest technologic and surgical developments in using InterStim Therapy for sacral neuromodulation: impact on treatment success and safety.

PubMed

Spinelli, Michele; Sievert, Karl-Dietrich

2008-12-01

This article accompanies a "surgery in motion" DVD on sacral neuromodulation (SNM) with InterStim Therapy, which visualizes the implantation of the InterStim II system. The article describes the technical and surgical developments of SNM and their impact on treatment success, safety, and patient's quality of life (QoL). Relevant literature on SNM with regard to technical changes and related clinical outcomes has been reviewed. Since its introduction in the early 1990s, SNM has proven useful in the treatment of several types of chronic urinary (and bowel) dysfunction. Recent technical improvements in devices and, in particular, the introduction of the tined lead 5 yr ago made SNM progress from an elaborate, open-surgery, general anesthesia, one-stage implant procedure to a minimally invasive, local anesthesia, percutaneous technique in two stages. The permanent tined lead implant enables a longer patient testing period (minimum of 14 d recommended) and less lead migration. This has considerably reduced technical failures and improved the success rate of the test phase; the response rate was almost doubled to approximately 80%. These improvements also affected tolerability, resulting in increased QoL for the patient. The use of the recently introduced smaller implantable neurostimulator InterStim II seems to further improve patient comfort and makes the implant procedure for the physician easier and shorter. However, this must be further addressed in clinical studies. SNM with InterStim Therapy using the tined lead offers an efficient treatment modality for patients in whom conservative treatment has failed.

SaFaRI: sacral nerve stimulation versus the FENIX magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation.

PubMed

Williams, Annabelle E; Croft, Julie; Napp, Vicky; Corrigan, Neil; Brown, Julia M; Hulme, Claire; Brown, Steven R; Lodge, Jen; Protheroe, David; Jayne, David G

2016-02-01

Faecal incontinence is a physically, psychologically and socially disabling condition. NICE guidance (2007) recommends surgical intervention, including sacral nerve stimulation (SNS), after failed conservative therapies. The FENIX magnetic sphincter augmentation (MSA) device is a novel continence device consisting of a flexible band of interlinked titanium beads with magnetic cores that is placed around the anal canal to augment anal sphincter tone through passive attraction of the beads. Preliminary studies suggest the FENIX MSA is safe, but efficacy data is limited. Rigorous evaluation is required prior to widespread adoption. The SaFaRI trial is a National Institute of Health Research (NIHR) Health Technology Assessment (HTA)-funded UK multi-site, parallel group, randomised controlled, unblinded trial that will investigate the use of the FENIX MSA, as compared to SNS, for adult faecal incontinence resistant to conservative management. Twenty sites across the UK, experienced in the treatment of faecal incontinence, will recruit 350 patients randomised equally to receive either SNS or FENIX MSA. Participants will be followed-up at 2 weeks post-surgery and at 6, 12 and 18 months post-randomisation. The primary endpoint is success, as defined by device in use and ≥50 % improvement in the Cleveland Clinic Incontinence Score (CCIS) at 18 months post-randomisation. Secondary endpoints include complications, quality of life and cost effectiveness. SaFaRI will rigorously evaluate a new technology for faecal incontinence, the FENIX™ MSA, allowing its safe and controlled introduction into current clinical practice. These results will inform the future surgical management of adult faecal incontinence.

Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

PubMed

Kelly, Cynthia W

2008-04-01

To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

Capacity of mesoporous bioactive glass nanoparticles to deliver therapeutic molecules

NASA Astrophysics Data System (ADS)

El-Fiqi, Ahmed; Kim, Tae-Hyun; Kim, Meeju; Eltohamy, Mohamed; Won, Jong-Eun; Lee, Eun-Jung; Kim, Hae-Won

2012-11-01

Inorganic bioactive nanomaterials are attractive for hard tissue regeneration, including nanocomponents for bone replacement composites and nanovehicles for delivering therapeutics. Bioactive glass nanoparticles (BGn) have recently gained potential usefulness as bone and tooth regeneratives. Here we demonstrate the capacity of the BGn with mesopores to load and deliver therapeutic molecules (drugs and particularly genes). Spherical BGn with sizes of 80-90 nm were produced to obtain 3-5 nm sized mesopores through a sono-reacted sol-gel process. A simulated body fluid test of the mesoporous BGn confirmed their excellent apatite forming ability and the cellular toxicity study demonstrated their good cell viability up to 100 μg ml-1. Small molecules like chemical drug (Na-ampicillin) and gene (small interfering RNA; siRNA) were introduced as model drugs considering the mesopore size of the nanoparticles. Moreover, amine-functionalization allowed switchable surface charge property of the BGn (from -20-30 mV to +20-30 mV). Loading of ampicillin or siRNA saturated within a few hours (~2 h) and reflected the mesopore structure. While the ampicillin released relatively rapidly (~12 h), the siRNA continued to release up to 3 days with almost zero-order kinetics. The siRNA-nanoparticles were easily taken up by the cells, with a transfection efficiency as high as ~80%. The silencing effect of siRNA delivered from the BGn, as examined by using bcl-2 model gene, showed dramatic down-regulation (~15% of control), suggesting the potential use of BGn as a new class of nanovehicles for genes. This, in conjunction with other attractive properties, including size- and mesopore-related high surface area and pore volume, tunable surface chemistry, apatite-forming ability, good cell viability and the possible ion-related stimulatory effects, will potentiate the usefulness of the BGn in hard tissue regeneration.Inorganic bioactive nanomaterials are attractive for hard tissue regeneration

Therapeutic Engagement as a Predictor of Retention in Adolescent Therapeutic Community Treatment

ERIC Educational Resources Information Center

Abdel-Salam, Sami; Gunter, Whitney D.

2014-01-01

The adolescent drug problem places a huge toll on society and a heavy burden on the criminal justice system. Research regarding the benefits of therapeutic community (TC) treatment for adolescents has shown it to be effective. Despite the ability of therapeutic communities to lower drug relapse and reduce criminality, a great deal remains unknown…

Identification of Novel Tumor-Associated Cell Surface Sialoglycoproteins in Human Glioblastoma Tumors Using Quantitative Proteomics

PubMed Central

Autelitano, François; Loyaux, Denis; Roudières, Sébastien; Déon, Catherine; Guette, Frédérique; Fabre, Philippe; Ping, Qinggong; Wang, Su; Auvergne, Romane; Badarinarayana, Vasudeo; Smith, Michael; Guillemot, Jean-Claude; Goldman, Steven A.; Natesan, Sridaran; Ferrara, Pascual; August, Paul

2014-01-01

Glioblastoma multiform (GBM) remains clinical indication with significant “unmet medical need”. Innovative new therapy to eliminate residual tumor cells and prevent tumor recurrences is critically needed for this deadly disease. A major challenge of GBM research has been the identification of novel molecular therapeutic targets and accurate diagnostic/prognostic biomarkers. Many of the current clinical therapeutic targets of immunotoxins and ligand-directed toxins for high-grade glioma (HGG) cells are surface sialylated glycoproteins. Therefore, methods that systematically and quantitatively analyze cell surface sialoglycoproteins in human clinical tumor samples would be useful for the identification of potential diagnostic markers and therapeutic targets for malignant gliomas. In this study, we used the bioorthogonal chemical reporter strategy (BOCR) in combination with label-free quantitative mass spectrometry (LFQ-MS) to characterize and accurately quantify the individual cell surface sialoproteome in human GBM tissues, in fetal, adult human astrocytes, and in human neural progenitor cells (NPCs). We identified and quantified a total of 843 proteins, including 801 glycoproteins. Among the 843 proteins, 606 (72%) are known cell surface or secreted glycoproteins, including 156 CD-antigens, all major classes of cell surface receptor proteins, transporters, and adhesion proteins. Our findings identified several known as well as new cell surface antigens whose expression is predominantly restricted to human GBM tumors as confirmed by microarray transcription profiling, quantitative RT-PCR and immunohistochemical staining. This report presents the comprehensive identification of new biomarkers and therapeutic targets for the treatment of malignant gliomas using quantitative sialoglycoproteomics with clinically relevant, patient derived primary glioma cells. PMID:25360666

Identification of novel tumor-associated cell surface sialoglycoproteins in human glioblastoma tumors using quantitative proteomics.

PubMed

Autelitano, François; Loyaux, Denis; Roudières, Sébastien; Déon, Catherine; Guette, Frédérique; Fabre, Philippe; Ping, Qinggong; Wang, Su; Auvergne, Romane; Badarinarayana, Vasudeo; Smith, Michael; Guillemot, Jean-Claude; Goldman, Steven A; Natesan, Sridaran; Ferrara, Pascual; August, Paul

2014-01-01

Glioblastoma multiform (GBM) remains clinical indication with significant "unmet medical need". Innovative new therapy to eliminate residual tumor cells and prevent tumor recurrences is critically needed for this deadly disease. A major challenge of GBM research has been the identification of novel molecular therapeutic targets and accurate diagnostic/prognostic biomarkers. Many of the current clinical therapeutic targets of immunotoxins and ligand-directed toxins for high-grade glioma (HGG) cells are surface sialylated glycoproteins. Therefore, methods that systematically and quantitatively analyze cell surface sialoglycoproteins in human clinical tumor samples would be useful for the identification of potential diagnostic markers and therapeutic targets for malignant gliomas. In this study, we used the bioorthogonal chemical reporter strategy (BOCR) in combination with label-free quantitative mass spectrometry (LFQ-MS) to characterize and accurately quantify the individual cell surface sialoproteome in human GBM tissues, in fetal, adult human astrocytes, and in human neural progenitor cells (NPCs). We identified and quantified a total of 843 proteins, including 801 glycoproteins. Among the 843 proteins, 606 (72%) are known cell surface or secreted glycoproteins, including 156 CD-antigens, all major classes of cell surface receptor proteins, transporters, and adhesion proteins. Our findings identified several known as well as new cell surface antigens whose expression is predominantly restricted to human GBM tumors as confirmed by microarray transcription profiling, quantitative RT-PCR and immunohistochemical staining. This report presents the comprehensive identification of new biomarkers and therapeutic targets for the treatment of malignant gliomas using quantitative sialoglycoproteomics with clinically relevant, patient derived primary glioma cells.

Engineering novel targeted nanoparticle formulations to increase the therapeutic efficacy of conventional chemotherapeutics against multiple myeloma

NASA Astrophysics Data System (ADS)

Ashley, Jonathan D.

Multiple myeloma (MM) is a hematological malignancy which results from the uncontrolled clonal expansion of plasma cells within the body. Despite recent medical advances, this disease remains largely incurable, with a median survival of ˜7 years, owing to the development of drug resistance. This dissertation will explore new advances in nanotechnology that will combine the cytotoxic effects of small molecule chemotherapeutics with the tumor targeting capabilities of nanoparticles to create novel nanoparticle formulations that exhibit enhanced therapeutic indices in the treatment of MM. First, doxorubicin was surfaced conjugated onto micellar nanoparticles via an acid labile hydrazone bond to increase the drug accumulation at the tumor. The cell surface receptor Very Late Antigen-4 (VLA-4; alpha4beta1) is expressed on cancers of hematopoietic origin and plays a vital role in the cell adhesion mediated drug resistance (CAM-DR) in MM. Therefore, VLA-4 antagonist peptides were conjugated onto the nanoparticles via a multifaceted procedure to actively target MM cells and simultaneously inhibit CAM-DR. The micellar doxorubicin nanoparticles were able to overcome CAM-DR and demonstrated improved therapeutic index relative to free doxorubicin. In addition to doxorubicin, other classes of therapeutic agents, such as proteasome inhibitors, can be incorporated in nanoparticles for improved therapeutic outcomes. Utilizing boronic acid chemistry, bortezomib prodrugs were synthesized using a reversible boronic ester bond and then incorporated into liposomes. The different boronic ester bonds that could be potentially used in the synthesis of bortezomib prodrugs were screened based on stability using isobutylboronic acid. The liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity in MM cells in vitro, and dramatically reduced the non-specific toxicities associated with free bortezomib while maintaining significant tumor growth

Transdermal delivery of therapeutic agent

NASA Technical Reports Server (NTRS)

Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

2008-01-01

A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

[Health security--GMOs in therapeutics].

PubMed

Trouvin, J-H

2003-03-01

The recent progress in human therapeutics has been made possible thanks to molecular biology and its use in producing proteins having the same sequence and structure as that of human proteins. The use of GMOs allows production of proteins with high added value in therapeutics, which are of satisfactory quality. GMOs may also be directly administered to patients as gene therapy vectors. However, the use of GMOs in therapeutics must take into consideration some risks, particularly those of microbiological contamination, of neo-antigenicity as well as environmental risks with regard to the way of use of the GMO. Nevertheless, those risks are taken in due consideration in the development of these new medicinal products; solutions have been found to allow their use in therapeutics with a very positive benefit/risk ratio. Medicinal products from biotechnology have enabled considerable therapeutic progress without compromising health security.

Therapeutic cloning in the mouse

PubMed Central

Mombaerts, Peter

2003-01-01

Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

Assembled nanomedicines as efficient and safe therapeutics for articular inflammation.

PubMed

Che, Ling; Zhou, Jianzhi; Li, Shuhui; He, Hongmei; Zhu, Yuxuan; Zhou, Xing; Jia, Yi; Liu, Yao; Zhang, Jianxiang; Li, Xiaohui

2012-12-15

Highly efficient nanomedicines were successfully fabricated by the indomethacin (IND) directed self-assembly of β-cyclodextrin (β-CD)-conjugated polyethyleneimine (PEI-CD), taking advantage of the multiple interactions between drug and polymer. These nanoscaled assemblies exhibited spherical shape and positively charged surface. Compared with the commercial tablet, the relative oral bioavailability of IND-nanomedicines was significantly enhanced. Evaluation based on either carrageenan-induced paw edema or complete Freund's adjuvant (CFA)-induced arthritis suggested the newly developed nanomedicines were more effective than raw IND or IND tablet in terms of prophylactic effect and therapeutic activity. Even the low dose of nanomedicines offered the comparable results to those of control groups at the high dosage in most cases. Moreover, the nanoformulation exhibited ameliorated gastrointestinal stimulation. All these positive results indicated that this type of nanomedicines might serve as a highly efficient and effective delivery nanoplatform for the oral delivery of water-insoluble therapeutics. Copyright © 2012 Elsevier B.V. All rights reserved.

Targeting of adhesion molecules as a therapeutic strategy in multiple myeloma.

PubMed

Neri, Paola; Bahlis, Nizar J

2012-09-01

Multiple myeloma (MM) is a clonal disorder of plasma cells that remains, for the most part, incurable despite the advent of several novel therapeutic agents. Tumor cells in this disease are cradled within the bone marrow (BM) microenvironment by an array of adhesive interactions between the BM cellular residents, the surrounding extracellular matrix (ECM) components such as fibronectin (FN), laminin, vascular cell adhesion molecule-1 (VCAM-1), proteoglycans, collagens and hyaluronan, and a variety of adhesion molecules on the surface of MM cells including integrins, hyaluronan receptors (CD44 and RHAMM) and heparan sulfate proteoglycans. Several signaling responses are activated by these interactions, affecting the survival, proliferation and migration of MM cells. An important consequence of these direct adhesive interactions between the BM/ECM and MM cells is the development of drug resistance. This phenomenon is termed "cell adhesion-mediated drug resistance" (CAM-DR) and it is thought to be one of the major mechanisms by which MM cells escape the cytotoxic effects of therapeutic agents. This review will focus on the adhesion molecules involved in the cross-talk between MM cells and components of the BM microenvironment. The complex signaling networks downstream of these adhesive molecules mediated by direct ligand binding or inside-out soluble factors signaling will also be reviewed. Finally, novel therapeutic strategies targeting these molecules will be discussed. Identification of the mediators of MM-BM interaction is essential to understand MM biology and to elucidate novel therapeutic targets for this disease.

Residential therapeutic communities in the mainstream: diversity and issues.

PubMed

De Leon, G

1995-01-01

Not all residential drug abuse treatment programs are therapeutic communities (TCs), not all TCs are in residential settings, and not all programs that call themselves TCs employ the same social and psychological models of treatment. The term "therapeutic community" is widely used to represent a distinct approach in almost any setting, including community residences, hospital wards, prisons, and homeless shelters. One effect of this labeling has been to cloud understanding of the TC as a drug abuse treatment approach, how well it works, where it works best, and for which clients it is most appropriate. This article attempts to further a general understanding of residential TCs. Distinctions are drawn between residential drug abuse treatment and residential TCs. The diversity of programs within the TC modality is described in terms of modifications of the model and applications to special populations; and the essential elements of the TC program model are briefly outlined. Finally, movement into the mainstream has surfaced issues for the TC in terms of policy and practice, several of which are highlighted.

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

PubMed Central

Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Katano, Takahito; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

2015-01-01

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID:26269667

Nanoparticles for targeted delivery of therapeutics and small interfering RNAs in hepatocellular carcinoma

PubMed Central

Varshosaz, Jaleh; Farzan, Maryam

2015-01-01

, ganglioside GM1 cell surface ligand, epidermal growth factor receptor receptors, monoclonal antibodies, retinoic acid receptors, integrin receptors targeted by Arg-Gly-Asp peptide, folate, and transferrin receptors are the most widely studied cell surface receptors which are used for the site specific delivery of drugs and siRNA-based therapeutics in HCC and discussed in detail in this article. PMID:26576089

Bio-active engineered 50 nm silica nanoparticles with bone anabolic activity: therapeutic index, effective concentration, and cytotoxicity profile in vitro

PubMed Central

Ha, Shin-Woo; Sikorski, James A.; Weitzmann, M. Neale; Beck, George R.

2014-01-01

Silica-based nanomaterials are generally considered to be excellent candidates for therapeutic applications particularly related to skeletal metabolism however the current data surrounding the safety of silica based nanomaterials is conflicting. This may be due to differences in size, shape, incorporation of composite materials, surface properties, as well as the presence of contaminants following synthesis. In this study we performed extensive in vitro safety profiling of ~50 nm spherical silica nanoparticles with OH-terminated or Polyethylene Glycol decorated surface, with and without a magnetic core, and synthesized by the Stöber method. Nineteen different cell lines representing all major organ types were used to investigate an in vitro lethal concentration (LC) and results revealed little toxicity in any cell type analyzed. To calculate an in vitro therapeutic index we quantified the effective concentration at 50% response (EC50) for nanoparticle-stimulated mineral deposition activity using primary bone marrow stromal cells (BMSCs). The EC50 for BMSCs was not substantially altered by surface or magnetic core. The calculated Inhibitory concentration 50% (IC50) for pre-osteoclasts was similar to the osteoblastic cells. These results demonstrate the pharmacological potential of certain silica-based nanomaterial formulations for use in treating bone diseases based on a favorable in vitro therapeutic index. PMID:24333519

The Therapeutic Relationship: Enhancing Referrals.

PubMed

Coyle, Mary Kathleen

2018-05-19

This article focuses on the ways rehabilitation nurses use the therapeutic relationship to lessen barriers some veterans experience when a referral to mental health treatment is recommended. Veterans presenting with posttraumatic stress symptoms are discussed, and possible interventions within the therapeutic relationship are proposed. Veterans' perception of mental health stigma, building a collaborative therapeutic relationship, recommending a referral and assessments of stress responses, posttraumatic stress symptoms, suicide risk, and intervention strategies are proposed. When changes in functioning and suicidality occur in veterans with posttraumatic stress disorder symptoms, it is important to screen and engage veterans at risk. When veterans in the rehabilitation process present with a need for mental health referral, barriers to treatment may include the stigma of mental health treatment. Rehabilitation nurses using the therapeutic relationship act as change agents to assist veterans in overcoming these barriers to treatment. The therapeutic relationship provides nurses with a foundation to provide opportunities for veterans to be supported and to seek treatment.

Bacteriophage Procurement for Therapeutic Purposes

PubMed Central

Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

2016-01-01

Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

Inhalation delivery of protein therapeutics.

PubMed

Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

2013-04-01

Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

Chicanoizing the Therapeutic Community

ERIC Educational Resources Information Center

Aron, William S.; And Others

1974-01-01

Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

MULTI-STAGE DELIVERY NANO-PARTICLE SYSTEMS FOR THERAPEUTIC APPLICATIONS

PubMed Central

Serda, Rita E.; Godin, Biana; Blanco, Elvin; Chiappini, Ciro; Ferrari, Mauro

2010-01-01

Background The daunting task for drug molecules to reach pathological lesions has fueled rapid advances in Nanomedicine. The progressive evolution of nanovectors has led to the development of multi-stage delivery systems aimed at overcoming the numerous obstacles encountered by nanovectors on their journey to the target site. Scope of Review This review summarizes major findings with respect to silicon-based drug delivery vectors for cancer therapeutics and imaging. Based on rational design, well established silicon technologies have been adapted for the fabrication of nanovectors with specific shapes, sizes, and porosities. These vectors are part of a multi-stage delivery system that contains multiple nano-components, each designed to achieve a specific task with the common goal of site-directed delivery of therapeutics. Major Conclusions Quasi-hemispherical and discoidal silicon microparticles are superior to spherical particles with respect to margination in the blood, with particles of different shapes and sizes having unique distributions in vivo. Cellular adhesion and internalization of silicon microparticles is influenced by microparticle shape and surface charge, with the latter dictating binding of serum opsonins. Based on in vitro cell studies, the internalization of porous silicon microparticles by endothelial cells and macrophages is compatible with cellular morphology, intracellular trafficking, mitosis, cell cycle progression, cytokine release, and cell viability. In vivo studies support superior therapeutic efficacy of liposomal encapsulated siRNA when delivered in multi-stage systems compared to free nanoparticles. PMID:20493927

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

PubMed Central

Gross, Christina; Berry-Kravis, Elizabeth M; Bassell, Gary J

2012-01-01

Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS. PMID:21796106

Integrins in bone metastasis formation and potential therapeutic implications.

PubMed

Clëzardin, P

2009-11-01

Integrins constitute a family of cell surface receptors that are heterodimers composed of noncovalently associated alpha and beta subunits. Integrins bind to extracellular matrix proteins and immunogobulin superfamily molecules. They exert a stringent control on cell migration, survival and proliferation. However, their expression and functions are often deregulated in cancer, and many lines of evidence implicate them as key regulators during progression from primary tumor growth to metastasis. Here, we review the role of integrins in bone metastasis formation and present evidence that the use of integrin-targeted therapeutic agents may be an efficient strategy to block tumor metastasis.

EXETRA Perspectives: Concepts in Therapeutic Recreation.

ERIC Educational Resources Information Center

Neal, Larry L.; Edginton, Christopher R.

Fifteen papers address issues in therapeutic recreation for disabled persons from the perspectives of practitioners, educators, and students. The following papers are presented. "Therapeutic Recreation Service: The Past and Challenging Present" (H. Sessoms); "Therapeutic Recreatiion in an Era of Limits: A Crisis...A Challenge... An Opportunity"…

21 CFR 890.5975 - Therapeutic vibrator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Therapeutic vibrator. 890.5975 Section 890.5975 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5975 Therapeutic...

21 CFR 890.5975 - Therapeutic vibrator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Therapeutic vibrator. 890.5975 Section 890.5975 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5975 Therapeutic...

21 CFR 890.5660 - Therapeutic massager.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Therapeutic massager. 890.5660 Section 890.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5660 Therapeutic...

21 CFR 890.5660 - Therapeutic massager.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Therapeutic massager. 890.5660 Section 890.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5660 Therapeutic...

21 CFR 890.5660 - Therapeutic massager.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Therapeutic massager. 890.5660 Section 890.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5660 Therapeutic...

21 CFR 890.5660 - Therapeutic massager.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Therapeutic massager. 890.5660 Section 890.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5660 Therapeutic...

21 CFR 890.5660 - Therapeutic massager.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Therapeutic massager. 890.5660 Section 890.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES PHYSICAL MEDICINE DEVICES Physical Medicine Therapeutic Devices § 890.5660 Therapeutic...

21 CFR 880.5160 - Therapeutic medical binder.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Therapeutic medical binder. 880.5160 Section 880...) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use Therapeutic Devices § 880.5160 Therapeutic medical binder. (a) Identification. A therapeutic medical binder is a...

21 CFR 880.5160 - Therapeutic medical binder.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Therapeutic medical binder. 880.5160 Section 880...) MEDICAL DEVICES GENERAL HOSPITAL AND PERSONAL USE DEVICES General Hospital and Personal Use Therapeutic Devices § 880.5160 Therapeutic medical binder. (a) Identification. A therapeutic medical binder is a...

Sacroplasty procedural extravasation with high viscosity bone cement: comparing the intraoperative long-axis versus short-axis techniques in osteoporotic cadavers.

PubMed

Miller, Jeffrey W; Diani, Art; Docsa, Steve; Ashton, Kristi; Sciamanna, Michele

2017-09-01

Percutaneous sacroplasty involves image-guided injection of bone cement for sacral insufficiency fractures to alleviate pain and facilitate mobility. Correct sacral placement of the cement and the risk of cement extravasation present procedural challenges. This study compares the occurrence, number, location, and surface area of high viscosity radiopaque bone cement extravasation via biplane fluoroscopy with Dyna CT between the fluoroscopically-guided intraoperative long-axis and short-axis sacroplasty techniques in osteoporotic cadavers. Ten osteoporotic cadavers underwent bilateral percutaneous instillation of VertaPlex HV High Viscosity Radiopaque Bone Cement. Long- and short-axis sacroplasty techniques were randomly assigned to zone 1 of the left or right sacral ala of each cadaver. Cement extravasation data were summarized by technique (long-axis vs short-axis) and time period (15-min and 3-hour post-procedure syngo DynaCT scan) in the form of point and CI estimates for the true proportions of cement extravasation. No procedural sacral extravasation differences were observed between the long-axis and short-axis sacroplasty techniques. There were no occurrences of intra-procedural or post-procedural cement extravasation at 15 min or 3 hours in association with either the long-axis sacroplasty technique or the short-axis sacroplasty technique. The long- and short-axis sacroplasty techniques, using high viscosity cement with careful post-procedural positioning, result in no occurrence of cement extravasation in porous osteoporotic cadaver bone. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Developing microRNA therapeutics.

PubMed

van Rooij, Eva; Purcell, Angela L; Levin, Arthur A

2012-02-03

Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target.

Three-dimensional navigation is more accurate than two-dimensional navigation or conventional fluoroscopy for percutaneous sacroiliac screw fixation in the dysmorphic sacrum: a randomized multicenter study.

PubMed

Matityahu, Amir; Kahler, David; Krettek, Christian; Stöckle, Ulrich; Grutzner, Paul Alfred; Messmer, Peter; Ljungqvist, Jan; Gebhard, Florian

2014-12-01

To evaluate the accuracy of computer-assisted sacral screw fixation compared with conventional techniques in the dysmorphic versus normal sacrum. Review of a previous study database. Database of a multinational study with 9 participating trauma centers. The reviewed group included 130 patients, 72 from the navigated group and 58 from the conventional group. Of these, 109 were in the nondysmorphic group and 21 in the dysmorphic group. Placement of sacroiliac (SI) screws was performed using standard fluoroscopy for the conventional group and BrainLAB navigation software with either 2-dimensional or 3-dimensional (3D) navigation for the navigated group. Accuracy of SI screw placement by 2-dimensional and 3D navigation versus conventional fluoroscopy in dysmorphic and nondysmorphic patients, as evaluated by 6 observers using postoperative computerized tomography imaging at least 1 year after initial surgery. Intraobserver agreement was also evaluated. There were 11.9% (13/109) of patients with misplaced screws in the nondysmorphic group and 28.6% (6/21) of patients with misplaced screws in the dysmorphic group, none of which were in the 3D navigation group. Raw agreement between the 6 observers regarding misplaced screws was 32%. However, the percent overall agreement was 69.0% (kappa = 0.38, P < 0.05). The use of 3D navigation to improve intraoperative imaging for accurate insertion of SI screws is magnified in the dysmorphic proximal sacral segment. We recommend the use of 3D navigation, where available, for insertion of SI screws in patients with normal and dysmorphic proximal sacral segments. Therapeutic level I.

Therapeutic application of RNAi: is mRNA targeting finally ready for prime time?

PubMed Central

Grimm, Dirk; Kay, Mark A.

2007-01-01

With unprecedented speed, RNA interference (RNAi) has advanced from its basic discovery in lower organisms to becoming a powerful genetic tool and perhaps our single most promising biotherapeutic for a wide array of diseases. Numerous studies document RNAi efficacy in laboratory animals, and the first clinical trials are underway and thus far suggest that RNAi is safe to use in humans. Yet substantial hurdles have also surfaced and must be surmounted before therapeutic RNAi applications can become a standard therapy. Here we review the most critical roadblocks and concerns for clinical RNAi transition, delivery, and safety. We highlight emerging solutions and concurrently discuss novel therapeutic RNAi-based concepts. The current rapid advances create realistic optimism that the establishment of RNAi as a new and potent clinical modality in humans is near. PMID:18060021

[Predictors of the therapeutic discharge in patients with dual pathology admitted to a therapeutic community with a psychiatric unit].

PubMed

Madoz-Gúrpide, Agustín; García Vicent, Vicente; Luque Fuentes, Encarnación; Ochoa Mangado, Enriqueta

2013-01-01

This study aims to analyze the variables on which depends therapeutic discharge, in patients with a severe dual diagnosis admitted to a professional therapeutic community where their pathology is treated. 325 patients admitted between June 2000 and June 2009 to the therapeutic community. This is a retrospective, cross-sectional study with no control group, based on the detailed analysis of the information collected in a model of semi-structured clinical interview designed in the therapeutic community. The 29.5% of the individuals included in the sample were therapeutically discharged. Of all the variables introduced in this analysis the most significant ones were gender, age at the beginning of treatment, education level, opiate dependence, polidrug abuse, and the presence of psychotic disorders and borderline personality disorder. In our study, gender determines the type of discharge, being therapeutic discharge more frequent among women. A higher educational also increases a better prognosis with a higher rate of therapeutic discharge among individuals with higher education level. A later age at the beginning of the treatment reduces the likelihood of therapeutic discharge. Likewise, polidrug abuse, diagnosis of psychotic disorders and borderline personality disorder are associated to a lower rate of therapeutic discharge. Recognizing these characteristics will allow the early identification of those patients more at risk of dropping treatment hastily, while trying to prevent it by increasing the therapeutic intensity.

Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases

PubMed Central

Takeuchi, Hideyuki; Suzumura, Akio

2014-01-01

Microglia are macrophage-like resident immune cells that contribute to the maintenance of homeostasis in the central nervous system (CNS). Abnormal activation of microglia can cause damage in the CNS, and accumulation of activated microglia is a characteristic pathological observation in neurologic conditions such as trauma, stroke, inflammation, epilepsy, and neurodegenerative diseases. Activated microglia secrete high levels of glutamate, which damages CNS cells and has been implicated as a major cause of neurodegeneration in these conditions. Glutamate-receptor blockers and microglia inhibitors (e.g., minocycline) have been examined as therapeutic candidates for several neurodegenerative diseases; however, these compounds exerted little therapeutic benefit because they either perturbed physiological glutamate signals or suppressed the actions of protective microglia. The ideal therapeutic approach would hamper the deleterious roles of activated microglia without diminishing their protective effects. We recently found that abnormally activated microglia secrete glutamate via gap-junction hemichannels on the cell surface. Moreover, administration of gap-junction inhibitors significantly suppressed excessive microglial glutamate release and improved disease symptoms in animal models of neurologic conditions such as stroke, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Recent evidence also suggests that neuronal and glial communication via gap junctions amplifies neuroinflammation and neurodegeneration. Elucidation of the precise pathologic roles of gap junctions and hemichannels may lead to a novel therapeutic strategies that can slow and halt the progression of neurodegenerative diseases. PMID:25228858

Therapeutic touch for anxiety disorders.

PubMed

Robinson, J; Biley, F C; Dolk, H

2007-07-18

Anxiety disorders are a common occurrence in today's society. There is interest from the community in the use of complementary therapies for anxiety disorders. This review examined the currently available evidence supporting the use of therapeutic touch in treating anxiety disorders. To examine the efficacy and adverse effects of therapeutic touch for anxiety disorders. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) (search date 13/01/06), the Controlled Trials website and Dissertation Abstracts International. Searches of reference lists of retrieved papers were also carried out and experts in the field were contacted. Inclusion criteria included all published and unpublished randomised and quasi-randomised controlled trials comparing therapeutic touch with sham (mimic) TT, pharmacological therapy, psychological treatment, other treatment or no treatment /waiting list. The participants included adults with an anxiety disorder defined by the Diagnostic and Statistical Manual (DSM-IV),the International Classification of Diseases (ICD-10), validated diagnostic instruments, or other validated clinician or self-report instruments. Two review authors independently applied inclusion criteria. Further information was sought from trialists where papers contained insufficient information to make a decision about eligibility. No randomised or quasi-randomised controlled trials of therapeutic touch for anxiety disorders were identified. Given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders.

Bio-active engineered 50 nm silica nanoparticles with bone anabolic activity: therapeutic index, effective concentration, and cytotoxicity profile in vitro.

PubMed

Ha, Shin-Woo; Sikorski, James A; Weitzmann, M Neale; Beck, George R

2014-04-01

Silica-based nanomaterials are generally considered to be excellent candidates for therapeutic applications particularly related to skeletal metabolism however the current data surrounding the safety of silica based nanomaterials is conflicting. This may be due to differences in size, shape, incorporation of composite materials, surface properties, as well as the presence of contaminants following synthesis. In this study we performed extensive in vitro safety profiling of ∼ 50 nm spherical silica nanoparticles with OH-terminated or Polyethylene Glycol decorated surface, with and without a magnetic core, and synthesized by the Stöber method. Nineteen different cell lines representing all major organ types were used to investigate an in vitro lethal concentration (LC) and results revealed little toxicity in any cell type analyzed. To calculate an in vitro therapeutic index we quantified the effective concentration at 50% response (EC50) for nanoparticle-stimulated mineral deposition activity using primary bone marrow stromal cells (BMSCs). The EC50 for BMSCs was not substantially altered by surface or magnetic core. The calculated Inhibitory concentration 50% (IC50) for pre-osteoclasts was similar to the osteoblastic cells. These results demonstrate the pharmacological potential of certain silica-based nanomaterial formulations for use in treating bone diseases based on a favorable in vitro therapeutic index. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Bioimpedance means of skin condition monitoring during therapeutic and cosmetic procedures].

PubMed

Alekseenko, V A; Kus'min, A A; Filist, S A

2008-01-01

Engineering and technological problems of bioimpedance skin surface mapping are considered. A typical design of a device based on a PIC 16F microcontroller is suggested. It includes a keyboard, LCD indicator, probing current generator with programmed frequency tuning, and units for probing current monitoring and bioimpedance measurement. The electrode matrix of the device is constructed using nanotechnology. A microcontroller-controlled multiplexor provides scanning of interelectrode impedance, which makes it possible to obtain the impedance image of the skin surface under the electrode matrix. The microcontroller controls the probing signal generator frequency and allows layer-by-layer images of skin under the electrode matrix to be obtained. This makes it possible to use reconstruction tomography methods for analysis and monitoring of the skin condition during therapeutic and cosmetic procedures.

New Postcranial Material of the Early Caseid Casea broilii Williston, 1910 (Synapsida: Caseidae) with a Review of the Evolution of the Sacrum in Paleozoic Non-Mammalian Synapsids

PubMed Central

LeBlanc, Aaron R. H.; Reisz, Robert R.

2014-01-01

Here we use the description of a new specimen of the small caseid synapsid Casea broilii that preserves the sacral, pelvic and hind limb regions in great detail and in three dimensions, as a unique opportunity to reevaluate the early stages in the evolution of the sacrum in the lineage that led to mammals. We place this new material in the context of sacral evolution in early caseid synapsids and conclude that the transition from two to three sacral vertebrae occurred in small-bodied species, suggesting that it was not an adaptation to heavy weight bearing. Furthermore, we compare descriptions of sacral anatomy among known early synapsids, including caseids, ophiacodontids, edaphosaurids, varanopids, and sphenacodontians and review sacral evolution in early synapsids. Based on the descriptions of new species of caseids, edaphosaurids, and varanopids over the past several decades, it is clear that a sacrum consisting of three vertebrae evolved independently at least four times in synapsids during the Late Carboniferous and Early Permian. Furthermore, similarities in the morphologies of the sacral vertebrae and ribs of these early synapsids lead us to conclude that an anterior caudal vertebra had been incorporated into the sacral series convergently in these groups. Given the repeated acquisition of a three-vertebra sacrum in early synapsids and no apparent link to body size, we argue that this sacral anatomy was related to more efficient terrestrial locomotion than to increased weight bearing. PMID:25545624

Combination therapy of potential gene to enhance oral cancer therapeutic effect

NASA Astrophysics Data System (ADS)

Yeh, Chia-Hsien; Hsu, Yih-Chih

2015-03-01

The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

[Proteins support stem cells - use of protein therapeutics in hematopoietic stem cell transplantation].

PubMed

Meyer, Sara Christina; Stern, Martin

2011-11-01

Hematopoietic stem cell transplantation (HSCT) has evolved from a largely experimental therapeutic approach three decades ago to a well-established therapy today for many malignant and non-malignant disorders of the hematopoietic and the immune system. Although it is per se a therapy by transmission of cells, protein therapeutics such as growth factors and antibodies are relevant in all phases of a HSCT and substantially contribute to the success of this often only curative treatment. This review discusses HSCT with a particular focus on the protein therapeutics involved. Granulocyte colony stimulating factor (G-CSF) for mobilization of stem cells to the peripheral blood, the polyclonal anti-T-cell globulin (ATG) and the monoclonal antibodies alemtuzumab and etanercept for prophylaxis and therapy of graft versus host disease (GvHD) are highlighted. Also rituximab, palivizumab and polyclonal intravenous immunoglobulins for treating infections in post-transplant patients are discussed. Since our understanding of cell surface receptors, cytokine and signaling pathways is increasing, there will emerge new targets for directed therapy by proteins in the future. They may have the potential to further improve the success and to widen theapplication of HSCT.

Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

PubMed

Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

2016-01-01

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

Oligonucleotide therapeutics in neurodegenerative diseases.

PubMed

Scoles, Daniel R; Pulst, Stefan M

2018-03-21

Therapeutics that directly target RNAs are promising for a broad spectrum of disorders, including the neurodegenerative diseases. This is exemplified by the FDA approval of Nusinersen, an antisense oligonucleotide (ASO) therapeutic for spinal muscular atrophy (SMA). RNA targeting therapeutics are currently under development for amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias. We have used an ASO approach toward developing a treatment for spinocerebellar ataxia type 2 (SCA2), for targeting the causative gene ATXN2. We demonstrated that reduction of ATXN2 expression in SCA2 mice treated by intracerebroventicular injection (ICV) of ATXN2 ASO delayed motor phenotype onset, improved the expression of several genes demonstrated abnormally reduced by transcriptomic profiling of SCA2 mice, and restored abnormal Purkinje cell firing frequency in acute cerebellar sections. Here we discuss RNA abnormalities in disease and the prospects of targeting neurodegenerative diseases at the level of RNA control using ASOs and other RNA-targeted therapeutics.

Advances in Therapeutic Cancer Vaccines.

PubMed

Wong, Karrie K; Li, WeiWei Aileen; Mooney, David J; Dranoff, Glenn

2016-01-01

Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines. © 2016 Elsevier Inc. All rights reserved.

Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model

NASA Astrophysics Data System (ADS)

Al-Ghobashy, Medhat A.; Elmeshad, Aliaa N.; Abdelsalam, Rania M.; Nooh, Mohammed M.; Al-Shorbagy, Muhammad; Laible, Götz

2017-04-01

Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ɛ-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. In conclusion: i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

Development and Pre-Clinical Evaluation of Recombinant Human Myelin Basic Protein Nano Therapeutic Vaccine in Experimental Autoimmune Encephalomyelitis Mice Animal Model.

PubMed

Al-Ghobashy, Medhat A; ElMeshad, Aliaa N; Abdelsalam, Rania M; Nooh, Mohammed M; Al-Shorbagy, Muhammad; Laible, Götz

2017-04-20

Recombinant human myelin basic protein (rhMBP) was previously produced in the milk of transgenic cows. Differences in molecular recognition of either hMBP or rhMBP by surface-immobilized anti-hMBP antibodies were demonstrated. This indicated differences in immunological response between rhMBP and hMBP. Here, the activity of free and controlled release rhMBP poly(ε-caprolactone) nanoparticles (NPs), as a therapeutic vaccine against multiple sclerosis (MS) was demonstrated in experimental autoimmune encephalomyelitis (EAE) animal model. Following optimization of nanoformulation, discrete spherical, rough-surfaced rhMBP NPs with high entrapment efficiency and controlled release pattern were obtained. Results indicated that rhMBP was loaded into and electrostatically adsorbed onto the surface of NPs. Subcutaneous administration of free or rhMBP NPs before EAE-induction reduced the average behavioral score in EAE mice and showed only mild histological alterations and preservation of myelin sheath, with rhMBP NPs showing increased protection. Moreover, analysis of inflammatory cytokines (IFN-γ and IL-10) in mice brains revealed that pretreatment with free or rhMBP NPs significantly protected against induced inflammation. i) rhMBP ameliorated EAE symptoms in EAE animal model, ii) nanoformulation significantly enhanced efficacy of rhMBP as a therapeutic vaccine and iii) clinical investigations are required to demonstrate the activity of rhMBP NPs as a therapeutic vaccine for MS.

21 CFR 884.5900 - Therapeutic vaginal douche apparatus.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Therapeutic vaginal douche apparatus. 884.5900... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Therapeutic Devices § 884.5900 Therapeutic vaginal douche apparatus. (a) Identification. A therapeutic vaginal douche...

21 CFR 884.5900 - Therapeutic vaginal douche apparatus.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Therapeutic vaginal douche apparatus. 884.5900... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Therapeutic Devices § 884.5900 Therapeutic vaginal douche apparatus. (a) Identification. A therapeutic vaginal douche...

21 CFR 884.5900 - Therapeutic vaginal douche apparatus.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Therapeutic vaginal douche apparatus. 884.5900... (CONTINUED) MEDICAL DEVICES OBSTETRICAL AND GYNECOLOGICAL DEVICES Obstetrical and Gynecological Therapeutic Devices § 884.5900 Therapeutic vaginal douche apparatus. (a) Identification. A therapeutic vaginal douche...

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in the Treatment of Eye Diseases.

PubMed

Harrell, C Randall; Simovic Markovic, Bojana; Fellabaum, Crissy; Arsenijevic, Aleksandar; Djonov, Valentin; Arsenijevic, Nebojsa; Volarevic, Vladislav

2018-05-18

Mesenchymal stem cells (MSCs) were, due to their immunomodulatory and pro-angiogenic characteristics, extensively explored as new therapeutic agents in cell-based therapy of uveitis, glaucoma, retinal and ocular surface diseases.Since it was recently revealed that exosomes play an important role in biological functions of MSCs, herewith we summarized current knowledge about the morphology, structure, phenotype and functional characteristics of MSC-derived exosomes emphasizing their therapeutic potential in the treatment of eye diseases.MSC-derived exosomes were as efficient as transplanted MSCs in limiting the extent of eye injury and inflammation. Immediately after intravitreal injection, MSC-derived exosomes, due to nano-dimension, diffused rapidly throughout the retina and significantly attenuated retinal damage and inflammation. MSC-derived exosomes successfully delivered trophic and immunomodulatory factors to the inner retina and efficiently promoted survival and neuritogenesis of injured retinal ganglion cells. MSC-derived exosomes efficiently suppressed migration of inflammatory cells, attenuated detrimental Th1 and Th17 cell-driven immune response and ameliorated experimental autoimmune uveitis. MSC-derived exosomes were able to fuse with the lysosomes within corneal cells, enabling delivering of MSC-derived active β-glucuronidase and consequent catabolism of accumulated glycosaminoglycans, indicating their therapeutic potential in the treatment of Mucopolysaccharidosis VII (Sly Syndrome). Importantly, beneficent effects were noticed only in animals that received MSC-derived exosomes and were not seen after therapy with fibroblasts-derived exosomes confirming specific therapeutic potential of MSCs and their products in the treatment of eye diseases.In conclusion, MSC-derived exosomes represent potentially new therapeutic agents in the therapy of degenerative and inflammatory ocular diseases.

Cost profiles and budget impact of rechargeable versus non-rechargeable sacral neuromodulation devices in the treatment of overactive bladder syndrome.

PubMed

Noblett, Karen L; Dmochowski, Roger R; Vasavada, Sandip P; Garner, Abigail M; Liu, Shan; Pietzsch, Jan B

2017-03-01

Sacral neuromodulation (SNM) is a guideline-recommended third-line treatment option for managing overactive bladder. Current SNM devices are not rechargeable, and require neurostimulator replacement every 3-6 years. Our study objective was to assess potential cost effects to payers of adopting a rechargeable SNM neurostimulator device. We constructed a cost-consequence model to estimate the costs of long-term SNM-treatment with a rechargeable versus non-rechargeable device. Costs were considered from the payer perspective at 2015 reimbursement levels. Adverse events, therapy discontinuation, and programming rates were based on the latest published data. Neurostimulator longevity was assumed to be 4.4 and 10.0 years for non-rechargeable and rechargeable devices, respectively. A 15-year horizon was modeled, with costs discounted at 3% per year. Total budget impact to the United States healthcare system was estimated based on the computed per-patient cost findings. Over the 15-year horizon, per-patient cost of treatment with a non-rechargeable device was $64,111 versus $36,990 with a rechargeable device, resulting in estimated payer cost savings of $27,121. These cost savings were found to be robust across a wide range of scenarios. Longer analysis horizon, younger patient age, and longer rechargeable neurostimulator lifetime were associated with increased cost savings. Over a 15-year horizon, adoption of a rechargeable device strategy was projected to save the United States healthcare system up to $12 billion. At current reimbursement rates, our analysis suggests that rechargeable neurostimulator SNM technology for managing overactive bladder syndrome may deliver significant cost savings to payers over the course of treatment. Neurourol. Urodynam. 36:727-733, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Intracavitary Therapeutics for Pleural Malignancies.

PubMed

Murthy, Vivek; Mangalick, Keshav; Sterman, Daniel H

2018-03-01

Pleural malignancies remain a serious therapeutic challenge, and are frequently refractory to standard treatment; however, they have the advantage of occurring in an enclosed cavity readily accessible for examination, biopsy, and serial sampling. Novel therapeutics can be administered via intracavitary delivery to maximize efficacy by targeting the site of involvement and potentially mitigating the adverse effects of systemic therapies. The easy accessibility of the pleural space lends itself well to repeated sampling and analysis to determine efficacy and toxicity of a given treatment paradigm. These factors support the rationale for delivery of novel therapeutics directly into the pleural space. Copyright © 2017 Elsevier Inc. All rights reserved.

Oncolytic Viruses: Therapeutics With an Identity Crisis.

PubMed

Breitbach, Caroline J; Lichty, Brian D; Bell, John C

2016-07-01

Oncolytic viruses (OV) are replicating viral therapeutics for the treatment of cancer and have been in laboratory development for about twenty years. Recently, the FDA approved Imlygic, a herpes virus based therapeutic for the treatment of melanoma and thus OVs have entered a new era where they are a weapon in the armament of the oncologist. OVs are unique therapeutics with multiple mechanisms of therapeutic activity. The exact path for their development and eventual uptake by pharmaceutical companies is somewhat clouded by an uncertain identity. Are they vaccines, tumour lysing therapeutics, inducers of innate immunity, gene therapy vectors, anti-vascular agents or all of the above? Should they be developed as stand-alone loco-regional therapeutics, systemically delivered tumour hunters or immune modulators best tested as combination therapeutics? We summarize data here supporting the idea, depending upon the virus, that OVs can be any or all of these things. Pursuing a "one-size fits all" approach is counter-productive to their clinical development and instead as a field we should build on the strengths of individual virus platforms. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Language Patterns and Therapeutic Change.

ERIC Educational Resources Information Center

Phoenix, Valdemar G.; Lindeman, Mary L.

Noting that the mental health practitioner needs highly developed linguistic and communicative skills in order to precipitate therapeutic changes, this paper discusses the nature of the contexts of therapeutic interaction. It examines verb tense as a linguistic context marker and shows how various schools of therapy can use it. In addition, it…

Teaching clinical pharmacology and therapeutics with an emphasis on the therapeutic reasoning of undergraduate medical students

PubMed Central

Richir, Milan C.; Tichelaar, Jelle; Geijteman, Eric C. T.

2008-01-01

Background The rational prescribing of drugs is an essential skill of medical doctors. Clinical pharmacologists play an important role in the development of these skills by teaching clinical pharmacology and therapeutics (CP&T) to undergraduate medical students. Although the approaches to teaching CP&T have undergone many changes over the last decennia, it is essential that the actual teaching of CP&T continues to be a major part of the undergraduate medical curriculum. Objectives The learning objectives of CP&T teaching in terms of developing the therapeutic competencies of undergraduate medical students are described, with an emphasis on therapeutic decision-making. On the basis of current theories of cognitive psychology and medical education, context-learning is presented as an effective approach by which to achieve therapeutic competencies. An example of a CP&T curriculum is presented. PMID:18228012

Clinical Pharmacology & Therapeutics: Past, Present, and Future.

PubMed

Waldman, S A; Terzic, A

2017-03-01

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation, and utilization continuum to catalyze, evolve, and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation, and application ushering therapeutic innovation into modern healthcare. © 2017 American Society for Clinical Pharmacology and Therapeutics.

[Study toward practical use of oligonucleotide therapeutics].

PubMed

Inoue, Takao; Yoshida, Tokuyuki

2014-01-01

Over the past decade, oligonucleotide-based therapeutics such as antisense oligonucleotides and small interfering RNAs (siRNAs) have been developed extensively. For example, mipomersen (Kynamro; ISIS Pharmaceuticals), which is a second-generation antisense oligonucleotide administered by subcutaneous injection, has recently been approved by the FDA for the treatment of homozygous familial hypercholesterolemia. On the other hands, methods for the evaluation of quality, efficacy and safety of oligonucleotide therapeutics have not been fully discussed. Furthermore, the regulatory guidance specific for oligonucleotide therapeutics has not been established yet. Under these circumstances, we started to collaborate with Osaka University and PMDA to discuss regulatory science focused on oligonucleotide therapeutics. Through the collaboration, we would like to propose the possible design of quality evaluation and preclinical safety-evaluation of oligonucleotide therapeutics.

Polymer therapeutics: concepts and applications.

PubMed

Haag, Rainer; Kratz, Felix

2006-02-13

Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.

[Therapeutic drug monitoring of levetiracetam].

PubMed

Dailly, Eric; Bouquié, Régis; Bentué-Ferrer, Danièle

2010-01-01

Levetiracetam is an anticonvulsant drug used to treat partial seizures, myoclonic seizures of juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures. A review of the literature with an evidence-based medicine method highlighted parameters (age, renal failure, pregnancy, combination with other anticonvulsant drugs) which affect levetiracetam pharmacokinetics but no significant relationship between plasma concentration of levetiracetam and efficacy or toxicity. Concentrations usually observed in therapeutics is from 6 to 18 mg/L. However, the determination of an individual therapeutic concentration, associated with an effective and well tolerated therapy, could be recommended particularly before pregnancy. Consequently, therapeutic drug monitoring of levetiracetam which is not currently recommended could be possibly useful in specific clinical situations.

Therapeutic effects of different drugs on obstructive sleep apnea/hypopnea syndrome in children.

PubMed

Zhang, Jing; Chen, Jie; Yin, Yong; Zhang, Lei; Zhang, Hao

2017-12-01

This study aimed to compare the therapeutic effects of different drugs on obstructive sleep apnea/hypopnea syndrome (OSAHS) in children by using a network meta-analysis approach. PubMed, Embase and Cochrane Library were searched from the inception of each database to November 2015. Randomized controlled trials (RCTs) concerning the comparisons in the therapeutic effects of eight placebo-controlled drugs on OSAHS in children were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the weighted mean difference (WMD) and surface under the cumulative ranking curves (SUCRA) of therapeutic effects of eight drugs on OSAHS in children. A total of seven RCTs were finally incorporated into our network meta-analysis. Pairwise meta-analysis results revealed that therapeutic effect of placebo was significantly poorer than that of intranasal mometasone furoate, montelukast, budesonide and fluticasone concerning apnea hypopnea index (AHI) value [WMD=1.40, 95% confidence interval (CI)=1.17-1.63; WMD=2.80, 95% CI=1.01-4.59; WMD=3.50, 95% CI=3.34-3.66; WMD=7.20, 95% CI=5.26-9.14, respectively], and fluticasone is better than placebo concerning sleep efficiency (WMD=3.50, 95% CI=2.42-4.58); regarding visual analogue scale, the therapeutic effect of placebo was poorer compared with sucralfate and clindamycin (WMD=1.94, 95% CI=1.13-2.75; WMD=1.06, 95% CI=0.22-1.90), and sucralfate is better than clindamycin (WMD=-0.88, 95% CI=-1.65 to -0.11). However, network meta-analysis results showed no obvious difference in the therapeutic effects of different drugs on OSAHS regarding AHI and sleep efficiency. Furthermore, the best SUCRA value was very high for fluticasone concerning AHI (86.6%) and budesonide concerning sleep efficiency (94.0%) for OSAHS treatment. Fluticasone and budesonide have relatively good effects in the treatment of OSAHS in children, thus providing an important guiding significance for the treatment of OSAHS in children.

Therapeutic cloning in individual parkinsonian mice

PubMed Central

Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

2009-01-01

Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

Therapeutic drug monitoring of psychotropic medications

PubMed Central

Mitchell, Philip B

2000-01-01

Therapeutic drug monitoring (TDM) of a number of psychotropic medications has proven to be of value, enabling minimization of the limitations of considerable genetic variability in their metabolism and the high rates of poor compliance with many psychiatric disorders. Therapeutic ranges have been established for lithium, some of the tricyclic antidepressants, and clozapine. TDM has also been shown to be useful in avoiding toxicity (as many psychotropics have narrow therapeutic indices), particularly that due to interactions with other compounds. PMID:10759685

Emerging therapeutics in sleep.

PubMed

Saper, Clifford B; Scammell, Thomas E

2013-09-01

The development of new therapeutics for sleep disorders is increasingly dependent upon understanding the basic brain circuitry that underlies sleep-wake regulation, and how it may be pharmacologically manipulated. In this review, we consider the pathophysiological basis of major sleep disorders that often are seen by neurologists, including excessive daytime sleepiness, insomnia, narcolepsy, rapid eye movement sleep behavior disorder, and restless legs syndrome, as well as circadian disorders, and we review the current and potential future therapeutic approaches. Copyright © 2013 American Neurological Association.

Superparamagnetic nanoparticles for cancer diagnostics and therapeutics

NASA Astrophysics Data System (ADS)

Kohler, Nathan

2005-11-01

This dissertation describes the development of a magnetic nanoparticle conjugate that can potentially serve as both a contrast enhancement agent in magnetic resonance imaging (MRI) and as a drug carrier in controlled drug release, targeted for cancer diagnostics and therapeutics. In this work, we developed a unique method to synthesize well-dispersed 10-nm superparamagnetic iron oxide nanoparticles (SPION) without using chemical surfactants. This approach is especially advantageous for subsequent surface modification of nanoparticles with functional coatings. To target the SPION for cancer cells in vivo to facilitate MRI contrast enhancement of tumors, we immobilized folic acid on the particle surface. Folic acid is a low molecular weight growth factor over-expressed on many forms of cancer. The covalent immobilization of folic acid to the nanoparticle surface was characterized with FTIR and the intracellular uptake of the folic acid nanoparticles was visualized with scanning confocal microscopy. To use SPION for controlled drug release, we immobilized methotrexate (MTX), a chemotherapeutic drug, to the nanoparticle surface. MTX-modified nanoparticles have several combined advantages including real-time monitoring of drug delivery using MRI, higher intracellular concentrations of methotrexate that increase cellular cytotoxicity, and reduced non-specific uptake by healthy cells within the body. We successfully conducted drug release experiments demonstrating that MTX was released under low pH conditions that mimic the intracellular conditions in the lysozome. To assess cellular cytotoxicity, we tested MTX-nanoparticle conjugates in human breast cancer cells (MCF-7), human cervical cancer cells (HeLa), and glioma cells (9L), and showed that the drug efficacy of MTX-nanoparticle conjugates was similar to that of free MTX. To improve nanoparticle circulation time and intracellular uptake, we developed a novel bifunctional poly(ethylene glycol) (PEG) SAM capable of

R.D. Laing's theological hinterland: the contrast between mysticism and communion.

PubMed

Miller, Gavin

2012-06-01

Contrasting elements in R.D. Laing's psychiatry can be traced to two kinds of Christian theology: mystical theology and corporate theology. On one hand, Laing's mystical theology combined with psychoanalytic theory, to provide a New Age psychotherapeutic account of the recovery of authentic selfhood via metanoia. On the other, his incarnational, corporate theology promoted social inclusion of the mentally ill, particularly via therapeutic communities. For Laing, as for other post-war British Christians, a turn inwards, to mysticism and the sacralization of the self, and a turn outwards, to social and political activism, were ways of negotiating with the decline of traditional Christianity.

Programmable Bio-surfaces for Biomedical Applications.

PubMed

Shiba, Kiyotaka

2017-01-01

A peptide can be used as a functional building block to construct artificial systems when it has sufficient transplantability and functional independence in terms of its assigned function. Recent advances in in vitro evolution systems have been increasing the list of peptides that specifically bind to certain targets, such as proteins and cells. By properly displaying these peptides on solid surfaces, we can endow the inorganic materials with various biological functions, which will contribute to the development of diagnosis and therapeutic medical devices. Here, the methods for the peptide-based surface functionalization are reviewed by focusing on sources of peptides as well as methods of immobilization.

Borrelia burgdorferi glycosaminoglycan-binding proteins: a potential target for new therapeutics against Lyme disease.

PubMed

Lin, Yi-Pin; Li, Lingyun; Zhang, Fuming; Linhardt, Robert J

2017-12-01

The spirochete bacterium Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, the most common vector-borne disease in Europe and the United States. The spirochetes can be transmitted to humans via ticks, and then spread to different tissues, leading to arthritis, carditis and neuroborreliosis. Although antibiotics have commonly been used to treat infected individuals, some treated patients do not respond to antibiotics and experience persistent, long-term arthritis. Thus, there is a need to investigate alternative therapeutics against Lyme disease. The spirochete bacterium colonization is partly attributed to the binding of the bacterial outer-surface proteins to the glycosaminoglycan (GAG) chains of host proteoglycans. Blocking the binding of these proteins to GAGs is a potential strategy to prevent infection. In this review, we have summarized the recent reports of B. burgdorferi sensu lato GAG-binding proteins and discussed the potential use of synthetic and semi-synthetic compounds, including GAG analogues, to block pathogen interaction with GAGs. Such information should motivate the discovery and development of novel GAG analogues as new therapeutics for Lyme disease. New therapeutic approaches should eventually reduce the burden of Lyme disease and improve human health.

Borrelia burgdorferi glycosaminoglycan-binding proteins: a potential target for new therapeutics against Lyme disease

PubMed Central

Lin, Yi-Pin; Li, Lingyun; Zhang, Fuming; Linhardt, Robert J.

2017-01-01

The spirochete bacterium Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, the most common vector-borne disease in Europe and the United States. The spirochetes can be transmitted to humans via ticks, and then spread to different tissues, leading to arthritis, carditis and neuroborreliosis. Although antibiotics have commonly been used to treat infected individuals, some treated patients do not respond to antibiotics and experience persistent, long-term arthritis. Thus, there is a need to investigate alternative therapeutics against Lyme disease. The spirochete bacterium colonization is partly attributed to the binding of the bacterial outer-surface proteins to the glycosaminoglycan (GAG) chains of host proteoglycans. Blocking the binding of these proteins to GAGs is a potential strategy to prevent infection. In this review, we have summarized the recent reports of B. burgdorferi sensu lato GAG-binding proteins and discussed the potential use of synthetic and semi-synthetic compounds, including GAG analogues, to block pathogen interaction with GAGs. Such information should motivate the discovery and development of novel GAG analogues as new therapeutics for Lyme disease. New therapeutic approaches should eventually reduce the burden of Lyme disease and improve human health. PMID:29116038

Therapeutic touch and dementia care: an ongoing journey.

PubMed

Doherty, Donna; Wright, Stephen; Aveyard, Barry; Sykes, Meg

2006-12-01

Touch is considered a core aspect of care provision and therapeutic relationships. Therapeutic touch allows nurses to facilitate healing and forge therapeutic relationships through touch or non-touch and maintain channels of communication often lost in dementia as the disease progresses. This article reports the findings of a research project to examine the effectiveness of therapeutic touch in dementia care.

The Relationship Between Osteoarthritis of the Lumbar Facet Joints and Lumbosacropelvic Morphology.

PubMed

Sahin, Mehmet Sukru; Ergün, Adviye; Aslan, Akın

2015-10-01

Cross-sectional study. To investigate the relation between lumbosacropelvic morphology and the presence and degree of facet joint degeneration. Osteoarthritis of the facet joints is one of the most common degenerative changes in the spine. It is considered to be formed secondary to repetitive stress or trauma and spinal deformity with secondary overload. The cause(s) of facet joints osteoarthritis, however, have not been clearly identified. Abdominal computed tomography (CT) images of 723 patients which were taken between the years 2010 and 2014 were evaluated retrospectively. Patients with prior lumbar spinal surgery, serious congenital anomalies on CT, incomplete or complete lumbosacral transition, severe scoliosis, were excluded from the study. To eliminate the age- and sex-related differences in spinopelvic morphology, a study group was formed of the remaining subjects by including patients from a specific age group (30-35 yr) and same sex (females). For each patient the presence and grade of facet joint degeneration was investigated. In addition, pelvic incidence (PI), sacral slope and the angles of L1-L5 lumbar lordosis, sacral table, L5 vertebra posterior, and sacral kyphosis were measured for each patient. Sacral slope, sacral kyphosis, and L1-L5 lumbar lordosis angle were significantly higher in patients with osteoarthritic compared with normal subjects (P = 0.015, P = 0.018, P = 0.016). L5 vertebra posterior and sacral table angle were found to be significantly lower in patients with osteoarthritic than in normal subjects (P = 0.019, P = 0.007). The degree of facet joint degeneration was noticed to increase parallel to the decrease in the sacral table angle and L5 vertebra posterior angle, and to the increase in the L1-L5 lumbar lordosis, PI, and sacral slope. A close relation exists between the presence and degree of degeneration in the facet joint and lumbosacral pelvic morphology. Prevalence and degree of the degeneration in facet joint increases as

DELIVERY OF THERAPEUTIC PROTEINS

PubMed Central

Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

2009-01-01

The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

Engaging therapeutic citizenship and clientship: Untangling the reasons for therapeutic pacifism among people living with HIV in urban Zambia.

PubMed

Patterson, Amy S

2016-10-01

This article explores the reasons for therapeutic pacifism among people living with HIV (PLHIVs) in urban Zambia. It contributes to a growing ethnography on global health, biosociality, and patient-provider dynamics. Therapeutic citizenship is a biopolitical citizenship that includes claims and ethical projects that emerge from techniques to control and manage bodies. In some contexts, therapeutic citizenship has included activism and claims-making against local, national, and international power brokers. This article investigates therapeutic citizenship in the specific context of impoverished urban Zambian compounds, sites of food insecurity, unemployment, and political exclusion, as well as targets for donor, NGO, and faith-based organisation projects and PLHIV support group proliferation. The article utilises data from participant observations at two Lusaka AIDS clinics, interviews, and focused discussions with support groups of PLHIVs. It argues that PLHIVs continuously negotiate subjectivities related to kinship, clientship, religious belief, and political citizenship in processes that complicate therapeutic citizenship. Rather than fostering participation in PLHIV support groups or challenging 'politics as usual' through activist claims-making to institutions of biopower, these processes lead to therapeutic pacifism.

[The therapeutic function of cosmetic surgery].

PubMed

Saboye, J

2012-08-01

The therapeutic purpose or not of cosmetic surgery is the criterion chosen by the tax authorities to secure acts for aesthetic purposes to VAT. Purpose and necessity of medical therapy are often confused. Yet there are two distinct concepts. In the case of cosmetic surgery, its therapeutic purpose is recognized by physicians and judges. This is the psychological improvement after surgery, well be secondary to surgery, although be desired by the WHO, which demonstrates the therapeutic purpose of cosmetic surgery. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Biopharmaceutical production: Applications of surface plasmon resonance biosensors.

PubMed

Thillaivinayagalingam, Pranavan; Gommeaux, Julien; McLoughlin, Michael; Collins, David; Newcombe, Anthony R

2010-01-15

Surface plasmon resonance (SPR) permits the quantitative analysis of therapeutic antibody concentrations and impurities including bacteria, Protein A, Protein G and small molecule ligands leached from chromatography media. The use of surface plasmon resonance has gained popularity within the biopharmaceutical industry due to the automated, label free, real time interaction that may be exploited when using this method. The application areas to assess protein interactions and develop analytical methods for biopharmaceutical downstream process development, quality control, and in-process monitoring are reviewed. 2009 Elsevier B.V. All rights reserved.

Proteases as therapeutics

PubMed Central

Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

2015-01-01

Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

"Difficult" Colorectal Polyps - Therapeutic Approach.

PubMed

Alecu, M; Simion, L; Ionescu, S; Brătucu, E; Straja, N D

2015-01-01

Endoscopic polypectomy is the gold standard in the treatment of colorectal polyps. The importance of polypectomy rests primarily on the fact that polyp-type lesions present a high risk of malignant degeneration, colorectal polyps being able, if left unattended therapeutically, to generate a colorectal cancer (CRC) - a lesion with a far more negative prognosis. Although preferable, endoscopic polypectomy of colorectal polyps is not always possible, multiple factors generating difficulties in performing this therapeutic measure. We performed a retrospective study in the First Surgical Clinic of the "Prof. Dr. Alexandu Trestioreanu" Bucharest Oncology Institute, spanning a period of 3 years (2008-2011), in which time 224 patients were diagnosed by colonoscopy with colorectal polyps, of whom 222 patients benefited from endoscopic polypectomy. The aim of the study was to identify "difficult" polyps and to identify the criteria for endoscopic surgery versus classic surgery as a therapeutic indication. Presence of "difficult" polyps was observed in 37.56% of the patients diagnosed with colorectal polyps. In over 88% of cases endoscopic polypectomy was possible, and for the remaining patients classic surgery was the therapeutic solution opted for. Presence of "difficult" polyps generates inconveniences in performing endoscopic polypectomy, increasing the risk of postoperative complication occurrence, as well as the duration of the operation. If the criteria for characterizing polyps as "difficult" are relatively well-established, the choice between endoscopic and classic surgery as a therapeutic measure is left at the free will of the operating surgeon, with the exception of situations in which classic surgery is resorted to for oncological reasons. Celsius.

Individualised cancer therapeutics: dream or reality? Therapeutics construction.

PubMed

Shen, Yuqiao; Senzer, Neil; Nemunaitis, John

2005-11-01

The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi.

Cell-surface marker discovery for lung cancer

PubMed Central

Cohen, Allison S.; Khalil, Farah K.; Welsh, Eric A.; Schabath, Matthew B.; Enkemann, Steven A.; Davis, Andrea; Zhou, Jun-Min; Boulware, David C.; Kim, Jongphil; Haura, Eric B.; Morse, David L.

2017-01-01

Lung cancer is the leading cause of cancer deaths in the United States. Novel lung cancer targeted therapeutic and molecular imaging agents are needed to improve outcomes and enable personalized care. Since these agents typically cannot cross the plasma membrane while carrying cytotoxic payload or imaging contrast, discovery of cell-surface targets is a necessary initial step. Herein, we report the discovery and characterization of lung cancer cell-surface markers for use in development of targeted agents. To identify putative cell-surface markers, existing microarray gene expression data from patient specimens were analyzed to select markers with differential expression in lung cancer compared to normal lung. Greater than 200 putative cell-surface markers were identified as being overexpressed in lung cancers. Ten cell-surface markers (CA9, CA12, CXorf61, DSG3, FAT2, GPR87, KISS1R, LYPD3, SLC7A11 and TMPRSS4) were selected based on differential mRNA expression in lung tumors vs. non-neoplastic lung samples and other normal tissues, and other considerations involving known biology and targeting moieties. Protein expression was confirmed by immunohistochemistry (IHC) staining and scoring of patient tumor and normal tissue samples. As further validation, marker expression was determined in lung cancer cell lines using microarray data and Kaplan–Meier survival analyses were performed for each of the markers using patient clinical data. High expression for six of the markers (CA9, CA12, CXorf61, GPR87, LYPD3, and SLC7A11) was significantly associated with worse survival. These markers should be useful for the development of novel targeted imaging probes or therapeutics for use in personalized care of lung cancer patients. PMID:29371917

The validity of compliance monitors to assess wearing time of thoracic-lumbar-sacral orthoses in children with spinal cord injury.

PubMed

Hunter, Louis N; Sison-Williamson, Mitell; Mendoza, Melissa M; McDonald, Craig M; Molitor, Fred; Mulcahey, M J; Betz, Randal R; Vogel, Lawrence C; Bagley, Anita

2008-06-15

Prospective multicenter observation. To determine the validity of 3 commercially available at recording thoracic-lumbar-sacral orthosis (TLSO) wearing time of children with spinal cord injury (SCI) and to assess each monitor's function during daily activities. A major limitation to studies assessing the effectiveness of spinal prophylactic bracing is the patient's compliance with the prescribed wearing time. Although some studies have begun to use objective compliance monitors, there is little documentation of the validity of the monitors during activities of daily life and no comparisons of available monitors. Fifteen children with SCI who wore a TLSO for paralytic scoliosis were observed for 4 days during their rehabilitation stay. Three compliance monitors (2 temperature and 1 pressure sensitive) were mounted onto each TLSO. Time of brace wear from the monitors was compared with the wear time per day recorded in diaries. Observed versus monitored duration of brace wear found the HOBO (temperature sensitive) to be the most valid compliance monitor. The HOBO had the lowest average of difference and variance of difference scores. The correlation between the recorded daily entries and monitored brace wear time was also highest for the HOBO in analysis of dependent and independent scores. Bland-Altman plots showed that the pressure sensitive monitor underestimated wear time whereas the temperature monitors overestimated wear time. Compliance to prescribed wearing schedule has been a barrier to studying TLSO efficacy. All 3 monitors were found to measure TLSO compliance, but the 2 temperature monitors were more in agreement with the daily diaries. Based on its functional advantages compared with the HOBO, the StowAway TidbiT will be used to further investigate the long-term compliance of TLSO bracing in children with SCI.

Therapeutic touch and post-Hurricane Hugo stress.

PubMed

Olson, M; Sneed, N; Bonadonna, R; Ratliff, J; Dias, J

1992-06-01

This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study.

Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

PubMed

Ling, Hui

The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer.

Technical Note: Enhancing the surface dose using a weak longitudinal magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carlone, Marco, E-mail: marco.carlone@rmp.uhn.on.ca; Keller, Harald; Rezaee, Mohammad

2016-06-15

Purpose: The surface dose in radiotherapy is subject to the physical properties of the radiation beam and collimator. The purpose of this work is to investigate the manipulation of surface dose using magnetic fields produced with a resistive magnet. Better understanding of the feasibility and mechanisms of altered surface dose could have important clinical applications where the surface dose must be increased for therapeutic goals, or reduced to enhance the therapeutic benefit. Methods: A resistive magnet capable of generating a peak magnetic field up to 0.24 T was integrated with a cobalt treatment unit. The magnetic fringe field of themore » magnet was small due to the self-shielding built within the magnet. The magnetic field at the beam collimation jaws of the cobalt irradiator was less than 10 G. The surface dose and depth dose were measured for varying magnetic field strengths. Results: The resistive magnet was able to alter the dose in the buildup region of the {sup 60}Co depth dose significantly, and the magnitude of dose enhancement was directly related to the strength of the longitudinal magnetic field. Peak magnetic fields as low as 0.08 T were able to affect the surface dose. At a peak field of 0.24 T, the authors measured a surface dose enhancement of 2.8-fold. Conclusions: Surface dose enhancement using resistive magnets is feasible. Further experimental study is needed to understand the origin of the scattered electrons that contribute to the increase in surface dose.« less

Generation of Well-Defined Micro/Nanoparticles via Advanced Manufacturing Techniques for Therapeutic Delivery

PubMed Central

Zhang, Peipei; Xia, Junfei; Luo, Sida

2018-01-01

Micro/nanoparticles have great potentials in biomedical applications, especially for drug delivery. Existing studies identified that major micro/nanoparticle features including size, shape, surface property and component materials play vital roles in their in vitro and in vivo applications. However, a demanding challenge is that most conventional particle synthesis techniques such as emulsion can only generate micro/nanoparticles with a very limited number of shapes (i.e., spherical or rod shapes) and have very loose control in terms of particle sizes. We reviewed the advanced manufacturing techniques for producing micro/nanoparticles with precisely defined characteristics, emphasizing the use of these well-controlled micro/nanoparticles for drug delivery applications. Additionally, to illustrate the vital roles of particle features in therapeutic delivery, we also discussed how the above-mentioned micro/nanoparticle features impact in vitro and in vivo applications. Through this review, we highlighted the unique opportunities in generating controllable particles via advanced manufacturing techniques and the great potential of using these micro/nanoparticles for therapeutic delivery. PMID:29670013

Therapeutic touch is not therapeutic for procedural pain in very preterm neonates: a randomized trial.

PubMed

Johnston, Celeste; Campbell-Yeo, Marsha; Rich, Bonnie; Whitley, Julie; Filion, Francoise; Cogan, Jennifer; Walker, Claire-Dominique

2013-09-01

Preterm neonates below 30 weeks' gestational age undergo numerous painful procedures. Many management approaches are not appropriate for this population. Therapeutic Touch, an alternative approach based on the theory of energy medicine, has been shown to promote physiological stability in preterm neonates and reduce pain in some adult studies. The objective was to determine whether Therapeutic Touch is efficacious in decreasing pain in preterm neonates. Infants < 30 weeks' gestational age participated in a randomized control trial in 2 level III neonatal intensive care units. All evaluations, analyses, and heel lance procedure were conducted with only the therapist knowing the group assignment. Immediately before and after the heel lance procedure, the therapist performed nontactile Therapeutic Touch (n = 27) with infant behind curtains, leaving the curtained area for the heel lance, performed by another. In the sham condition (n = 28), the therapist stood by the incubator with hands by her side. The Premature Infant Pain Profile was used for pain response and time for heart rate to return to baseline for recovery. Heart rate variability and stress response were secondary outcomes. There were no group differences in any of the outcomes. Mean Premature Infant Pain Profile scores across 2 minutes of heel lance procedure in 30-second blocks ranged from 7.92 to 8.98 in the Therapeutic Touch group and 7.64 to 8.46 in the sham group. Therapeutic Touch given immediately before and after heel lance has no comforting effect in preterm neonates. Other effective strategies involving actual touch should be considered.

[Electrocoagulation on a fragment of anterior abdominal rectal muscle for the control of presacral bleeding during rectal resection].

PubMed

Casal Núñez, José Enrique; Martínez, María Teresa García; Poblador, Alejandro Ruano

2012-03-01

Presacral venous haemorrhage during rectal movement is low, but is often massive, and even fatal. Our objective is the "in vitro" determination of the results of electrocoagulation applied to a fragment of muscle on the sacral bone surface during rectal resection due to a malignant neoplasm of the rectum. Single-pole coagulation was applied "in vitro" with the selector at maximum power on a 2×2 cms muscle fragment, applied to the anterior side of the IV sacral vertebra until reaching boiling point. The method was used on 6 patients with bleeding of the presacral venous plexus. In the "in vitro" study, boiling point was reached in 90 seconds from applying the single-pole current on the muscle fragment. Electrocoagulation was applied to a 2×2 cm rectal muscle fragment in 6 patients with presacral venous haemorrhage, using pressure on the surface of the presacral bone, with the stopping of the bleeding being achieved in all cases. The use of indirect electrocoagulation on a fragment of the rectus abdominis muscle is a straightforward and highly effective technique for controlling presacral venous haemorrhage. Copyright © 2011 AEC. Published by Elsevier Espana. All rights reserved.

MicroRNA therapeutics in cardiovascular medicine

PubMed Central

Thum, Thomas

2012-01-01

Cardiovascular diseases are the most common causes of human morbidity and mortality despite significant therapeutic improvements by surgical, interventional and pharmacological approaches in the last decade. MicroRNAs (miRNAs) are important and powerful mediators in a wide range of diseases and thus emerged as interesting new drug targets. An array of animal and even human miRNA-based therapeutic studies has been performed, which validate miRNAs as being successfully targetable to treat a wide range of diseases. Here, the current knowledge about miRNAs therapeutics in cardiovascular diseases on their way to clinical use are reviewed and discussed. PMID:22162462

The ability of multi-site, multi-depth sacral lateral branch blocks to anesthetize the sacroiliac joint complex.

PubMed

Dreyfuss, Paul; Henning, Troy; Malladi, Niriksha; Goldstein, Barry; Bogduk, Nikolai

2009-01-01

To determine the physiologic effectiveness of multi-site, multi-depth sacral lateral branch injections. Double-blind, randomized, placebo-controlled study. Outpatient pain management center. Twenty asymptomatic volunteers. The dorsal innervation to the sacroiliac joint (SIJ) is from the L5 dorsal ramus and the S1-3 lateral branches. Multi-site, multi-depth lateral branch blocks were developed to compensate for the complex regional anatomy that limited the effectiveness of single-site, single-depth lateral branch injections. Bilateral multi-site, multi-depth lateral branch green dye injections and subsequent dissection on two cadavers revealed a 91% accuracy with this technique. Session 1: 20 asymptomatic subjects had a 25-g spinal needle probe their interosseous (IO) and dorsal sacroiliac (DSI) ligaments. The inferior dorsal SIJ was entered and capsular distension with contrast medium was performed. Discomfort had to occur with each provocation maneuver and a contained arthrogram was necessary to continue in the study. Session 2: 1 week later; computer randomized, double-blind multi-site, multi-depth lateral branch blocks injections were performed. Ten subjects received active (bupivicaine 0.75%) and 10 subjects received sham (normal saline) multi-site, multi-depth lateral branch injections. Thirty minutes later, provocation testing was repeated with identical methodology used in session 1. Presence or absence of pain for ligamentous probing and SIJ capsular distension. Seventy percent of the active group had an insensate IO and DSI ligaments, and inferior dorsal SIJ vs 0-10% of the sham group. Twenty percent of the active vs 10% of the sham group did not feel repeat capsular distension. Six of seven subjects (86%) retained the ability to feel repeat capsular distension despite an insensate dorsal SIJ complex. Multi-site, multi-depth lateral branch blocks are physiologically effective at a rate of 70%. Multi-site, multi-depth lateral branch blocks do not

The effects of therapeutic touch on pain.

PubMed

Monroe, Carolyn Magdalen

2009-06-01

To better understand how Therapeutic Touch can be used in today's health care arena, this integrative literature review will examine current research that will help answer the question, Does Therapeutic Touch reduce pain? An extensive search was conducted of the online databases MEDLINE, CINAHL, Cochrane Library, EMBASE, PsychLIT, and PubMed to retrieve research articles published from 1997 to 2007. Seven studies that were conducted between 1997 and 2004 were found and only five of the seven were included as pertinent evidence to answer the question. All of the research that was reviewed to answer whether Therapeutic Touch could significantly reduce pain revealed a majority of statistically significant positive results for implementing this intervention. Because there are no identified risks to Therapeutic Touch as a pain relief measure, it is safe to recommend despite the limitations of current research. Therapeutic Touch should be considered among the many possible nursing interventions for the treatment of pain.

Fractures of the Sacrum After Chemoradiation for Rectal Carcinoma: Incidence, Risk Factors, and Radiographic Evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Han Jo; Boland, Patrick J.; Meredith, Dennis S.

Purpose: Sacral insufficiency fractures after adjuvant radiation for rectal carcinoma can present similarly to recurrent disease. As a complication associated with pelvic radiation, it is important to be aware of the incidence and risk factors associated with sacral fractures in the clinical assessment of these patients. Methods and Materials: Between 1998 and 2007, a total of 582 patients with locally advanced rectal carcinoma received adjuvant chemoradiation and surgical excision. Of these, 492 patients had imaging studies available for review. Hospital records and imaging studies from all 492 patients were retrospectively evaluated to identify risk factors associated with developing a sacralmore » insufficiency fracture. Results: With a median follow-up time of 3.5 years, the incidence of sacral fractures was 7.1% (35/492). The 4-year sacral fracture free rate was 0.91. Univariate analysis showed that increasing age ({>=}60 vs. <60 years), female sex, and history of osteoporosis were significantly associated with shorter time to sacral fracture (P=.01, P=.004, P=.001, respectively). There was no significant difference in the time to sacral fracture for patients based on stage, radiotherapy dose, or chemotherapy regimen. Multivariate analysis showed increasing age ({>=}60 vs. <60 years, hazard ratio [HR] = 2.50, 95% confidence interval [CI] = 1.22-5.13, P=.01), female sex (HR = 2.64, CI = 1.29-5.38, P=.008), and history of osteoporosis (HR = 3.23, CI = 1.23-8.50, P=.02) were independent risk factors associated with sacral fracture. Conclusions: Sacral insufficiency fractures after pelvic radiation for rectal carcinoma occur more commonly than previously described. Independent risk factors associated with fracture were osteoporosis, female sex, and age greater than 60 years.« less

Chordomas of the Skull Base, Mobile Spine, and Sacrum: An Epidemiologic Investigation of Presentation, Treatment, and Survival.

PubMed

Zuckerman, Scott L; Bilsky, Mark H; Laufer, Ilya

2018-05-01

Chordomas are rare primary bone tumors that arise from the axial skeleton. Our objective was to analyze trends in radiation and surgery over time and determine location-based survival predictors for chordomas of the skull base, mobile spine, and sacrum. A retrospective cohort study of the SEER (Surveillance Epidemiology and End Results) database from 1973 to 2013 was conducted. All patients had histologically confirmed chordomas. The principal outcome measure was overall survival (OS). The cohort included 1616 patients: skull base (664), mobile spine (444), and sacrum (508). Skull base tumors presented earliest in life (47.4 years) and sacral tumors presented latest (62.7 years). Rates of radiation remained stable for skull base and mobile spine tumors but declined for sacral tumors (P = 0.006). Rates of surgical resection remained stable for skull base and sacral tumors but declined for mobile spine tumors (P = 0.046). Skull base chordomas had the longest median survival (162 months) compared with mobile spine (94 months) and sacral tumors (87 months). Being married was independently associated with improved OS for skull base tumors (hazard ratio, 0.73; 95% confidence interval, 0.53-0.99; P = 0.044). Surgical resection was independently associated with improved OS for sacral chordomas (hazard ratio, 0.48; 95% confidence interval, 0.34-0.69; P < 0.001). Surgical resection for mobile spine chordomas and radiation for sacral chordomas decreased over time. Patients with skull base tumors survived longer than did patients with mobile spine and sacral chordomas, and surgical resection was associated with improved survival in sacral chordomas only. Understanding the behavior of these tumors can help cranial and spinal surgeons improve treatment in this patient population. Copyright © 2018 Elsevier Inc. All rights reserved.

Therapeutic writing and chronic pain: experiences of therapeutic writing in a cognitive behavioural programme for people with chronic pain.

PubMed

Furnes, Bodil; Dysvik, Elin

2012-12-01

To examine the experiences of therapeutic writing from the perspectives of patients attending a chronic pain management programme. Pain is a multifaceted experience. Increased awareness, understanding and gaining new insights are essential aspects of dealing with chronic pain. It is crucial to find powerful ways to cope with chronic pain. Several studies point to writing as a tool for managing such demanding life experiences. Therapeutic writing in a cognitive behavioural approach may be used to facilitate the rehabilitation process. A qualitative study with a descriptive and explorative design including a phenomenological perspective was used. A consecutive sample of 34 outpatients with chronic pain was recruited to an eight-week group-based pain management programme. A therapeutic writing tool was developed and included as part of the homework tasks. Guidelines were used to initiate and guide the therapeutic writing activity. Written reports were collected after completion. Three thematic findings emerged from the analysis: 'increased understanding of chronic pain as a multifaceted experience', 'new insights into managing the chronic pain situation' and 'different performances lead to different experiences with therapeutic writing'. Increased awareness, understanding and new insights are essential to dealing with chronic pain. People with chronic pain need tools and skills for optimal adaptation. Our findings suggest therapeutic writing may strengthen cognitive behavioural therapy by facilitating cognitive restructuring processes. Therapeutic writing may be used as a tool to express individual experiences and to improve adaptation to chronic pain. © 2012 Blackwell Publishing Ltd.

Targeting tissue factor as a novel therapeutic oncotarget for eradication of cancer stem cells isolated from tumor cell lines, tumor xenografts and patients of breast, lung and ovarian cancer.

PubMed

Hu, Zhiwei; Xu, Jie; Cheng, Jijun; McMichael, Elizabeth; Yu, Lianbo; Carson, William E

2017-01-03

Targeting cancer stem cell (CSC) represents a promising therapeutic approach as it can potentially fight cancer at its root. The challenge is to identify a surface therapeutic oncotarget on CSC. Tissue factor (TF) is known as a common yet specific surface target for cancer cells and tumor neovasculature in several solid cancers. However, it is unknown if TF is expressed by CSCs. Here we demonstrate that TF is constitutively expressed on CD133 positive (CD133+) or CD24-CD44+ CSCs isolated from human cancer cell lines, tumor xenografts from mice and breast tumor tissues from patients. TF-targeted agents, i.e., a factor VII (fVII)-conjugated photosensitizer (fVII-PS for targeted photodynamic therapy) and fVII-IgG1Fc (Immunoconjugate or ICON for immunotherapy), can eradicate CSC via the induction of apoptosis and necrosis and via antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, respectively. In conclusion, these results demonstrate that TF is a novel surface therapeutic oncotarget for CSC, in addition to cancer cell TF and tumor angiogenic vascular endothelial TF. Moreover, this research highlights that TF-targeting therapeutics can effectively eradicate CSCs, without drug resistance, isolated from breast, lung and ovarian cancer with potential to translate into other most commonly diagnosed solid cancer, in which TF is also highly expressed.

The renaissance of complement therapeutics

PubMed Central

Ricklin, Daniel; Mastellos, Dimitrios C.; Reis, Edimara S.; Lambris, John D.

2018-01-01

The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond. PMID:29199277

Therapeutic Antibodies by Phage Display.

PubMed

Shim, Hyunbo

2016-01-01

Antibody phage display is a major technological platform for the generation of fully human antibodies for therapeutic purposes. The in vitro binder selection by phage display allows researchers to have more extensive control over binding parameters and facilitates the isolation of clinical candidate antibodies with desired binding and/or functional profiles. Since the invention of antibody phage display in late 1980s, significant technological advancements in the design, construction, and selection of the antibody libraries have been made, and several fully human antibodies generated by phage display are currently approved or in various clinical development stages. In this review, the background and details of antibody phage display technology, and representative antibody libraries with natural or synthetic sequence diversity and different construction strategies are described. The generation, optimization, functional and biophysical properties, and preclinical and clinical developments of some of the phage display-derived therapeutic antibodies approved for use in patients or in late-stage clinical trials are also discussed. With evolving novel disease targets and therapeutic strategies, antibody phage display is expected to continue to play a central role in the development of the next generation of therapeutic antibodies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cystic fibrosis gene modifier SLC26A9 modulates airway response to CFTR-directed therapeutics.

PubMed

Strug, Lisa J; Gonska, Tanja; He, Gengming; Keenan, Katherine; Ip, Wan; Boëlle, Pierre-Yves; Lin, Fan; Panjwani, Naim; Gong, Jiafen; Li, Weili; Soave, David; Xiao, Bowei; Tullis, Elizabeth; Rabin, Harvey; Parkins, Michael D; Price, April; Zuberbuhler, Peter C; Corvol, Harriet; Ratjen, Felix; Sun, Lei; Bear, Christine E; Rommens, Johanna M

2016-10-15

Cystic fibrosis is realizing the promise of personalized medicine. Recent advances in drug development that target the causal CFTR directly result in lung function improvement, but variability in response is demanding better prediction of outcomes to improve management decisions. The genetic modifier SLC26A9 contributes to disease severity in the CF pancreas and intestine at birth and here we assess its relationship with disease severity and therapeutic response in the airways. SLC26A9 association with lung disease was assessed in individuals from the Canadian and French CF Gene Modifier consortia with CFTR-gating mutations and in those homozygous for the common Phe508del mutation. Variability in response to a CFTR-directed therapy attributed to SLC26A9 genotype was assessed in Canadian patients with gating mutations. A primary airway model system determined if SLC26A9 shows modification of Phe508del CFTR function upon treatment with a CFTR corrector. In those with gating mutations that retain cell surface-localized CFTR we show that SLC26A9 modifies lung function while this is not the case in individuals homozygous for Phe508del where cell surface expression is lacking. Treatment response to ivacaftor, which aims to improve CFTR-channel opening probability in patients with gating mutations, shows substantial variability in response, 28% of which can be explained by rs7512462 in SLC26A9 (P = 0.0006). When homozygous Phe508del primary bronchial cells are treated to restore surface CFTR, SLC26A9 likewise modifies treatment response (P = 0.02). Our findings indicate that SLC26A9 airway modification requires CFTR at the cell surface, and that a common variant in SLC26A9 may predict response to CFTR-directed therapeutics.

The therapeutic relationship: historical development and contemporary significance.

PubMed

O'Brien, A J

2001-04-01

The therapeutic relationship is a concept held by many to be fundamental to the identity of mental health nurses. While the therapeutic relationship was given formal expression in nursing theory in the middle of the last century, its origins can be traced to attendants' interpersonal practices in the asylum era. The dominance of medical understandings of mental distress, and the working-class status of asylum attendants, prevented the development of an account of mental health nursing based on attendants' relationships with asylum inmates. It was left to Peplau and other nursing theorists to describe mental health nursing as a therapeutic relationship in the 1940s and later. Some distinctive features of colonial life in New Zealand suggest that the ideal of the attendant as the embodiment of bourgeoisie values seems particularly unlikely to have been realized in the New Zealand context. However, New Zealand literature from the 20th century shows that the therapeutic relationship, as part of a general development of a therapeutic discourse, came to assume a central place in conceptualizations of mental health nursing. While the therapeutic relationship is not by itself a sufficient basis for professional continuity, it continues to play a fundamental role in mental health nurses' professional identity. The way in which the therapeutic relationship is articulated in the future will determine the meaning of the therapeutic relationship for future generations of mental health nurses.

Woodland in Practical Skills Therapeutic Education

ERIC Educational Resources Information Center

Mata, Paula; Gibons, Kenneth; Mata, Fernando

2016-01-01

Modern urban life provides less opportunities to contact with nature, which is a potential cause of developmental deviances in children. We investigated the potential therapeutic effect of woodlands, within the context of Practical Skills Therapeutic Education at the Ruskin Mill College, UK. Data on physical and emotional perceptions were…

Intracellular delivery of polymeric nanocarriers: a matter of size, shape, charge, elasticity and surface composition.

PubMed

Agarwal, Rachit; Roy, Krishnendu

2013-06-01

Recent progress in drug discovery has enabled the targeting of specific intracellular molecules to achieve therapeutic effects. These next-generation therapeutics are often biologics that cannot enter cells by mere diffusion. Therefore, it is imperative that drug carriers are efficiently internalized by cells and reach specific target organelles before releasing their cargo. Nanoscale polymeric carriers are particularly suitable for such intracellular delivery. Although size and surface charge have been the most studied parameters for nanocarriers, it is now well appreciated that other properties, for example, particle shape, elasticity and surface composition, also play a critical role in their transport across physiological barriers. It is proposed that a multivariate design space that considers the interdependence of particle geometry with its mechanical and surface properties must be optimized to formulate drug nanocarriers for effective accumulation at target sites and efficient intracellular delivery.

Nanoscale analysis of caspofungin-induced cell surface remodelling in Candida albicans

NASA Astrophysics Data System (ADS)

El-Kirat-Chatel, Sofiane; Beaussart, Audrey; Alsteens, David; Jackson, Desmond N.; Lipke, Peter N.; Dufrêne, Yves F.

2013-01-01

The advent of fungal pathogens that are resistant to the classic repertoire of antifungal drugs has increased the need for new therapeutic agents. A prominent example of such a novel compound is caspofungin, known to alter cell wall biogenesis by inhibiting β-1,3-d-glucan synthesis. Although much progress has been made in understanding the mechanism of action of caspofungin, little is known about its influence on the biophysical properties of the fungal cells. Here, we use atomic force microscopy (AFM) to demonstrate that caspofungin induces major remodelling of the cell surface properties of Candida albicans. Caspofungin causes major morphological and structural alterations of the cells, which correlate with a decrease of the cell wall mechanical strength. Moreover, we find that the drug induces the massive exposure of the cell adhesion protein Als1 on the cell surface and leads to increased cell surface hydrophobicity, two features that trigger cell aggregation. This behaviour is not observed in yeast species lacking Als1, demonstrating the key role that the protein plays in determining the aggregation phenotype of C. albicans. The results show that AFM opens up new avenues for understanding the molecular bases of microbe-drug interactions and for developing new therapeutic agents.The advent of fungal pathogens that are resistant to the classic repertoire of antifungal drugs has increased the need for new therapeutic agents. A prominent example of such a novel compound is caspofungin, known to alter cell wall biogenesis by inhibiting β-1,3-d-glucan synthesis. Although much progress has been made in understanding the mechanism of action of caspofungin, little is known about its influence on the biophysical properties of the fungal cells. Here, we use atomic force microscopy (AFM) to demonstrate that caspofungin induces major remodelling of the cell surface properties of Candida albicans. Caspofungin causes major morphological and structural alterations of the

Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC

PubMed Central

Basher, Fahmin; Jeng, Emily K.; Wong, Hing; Wu, Jennifer

2016-01-01

Shedding of the human NKG2D ligand MIC (MHC class I-chain-related molecule) from tumor cell surfaces correlates with progression of many epithelial cancers. Shedding-derived soluble MIC (sMIC) enables tumor immune escape through multiple immune suppressive mechanisms, such as disturbing natural killer (NK) cell homeostatic maintenance, impairing NKG2D expression on NK cells and effector T cells, and facilitating the expansion of arginase I+ myeloid suppressor cells. Our recent study has demonstrated that sMIC is an effective cancer therapeutic target. Whether targeting tumor-derived sMIC would enhance current active immunotherapy is not known. Here, we determined the in vivo therapeutic effect of an antibody co-targeting sMIC with the immunostimulatory IL-15 superagonist complex, ALT-803, using genetically engineered transplantable syngeneic sMIC+ tumor models. We demonstrate that combined therapy of a nonblocking antibody neutralizing sMIC and ALT-803 improved the survival of animals bearing sMIC+ tumors in comparison to monotherapy. We further demonstrate that the enhanced therapeutic effect with combined therapy is through concurrent augmentation of NK and CD8 T cell anti-tumor responses. In particular, expression of activation-induced surface molecules and increased functional potential by cytokine secretion are improved greatly by the administration of combined therapy. Depletion of NK cells abolished the cooperative therapeutic effect. Our findings suggest that administration of the sMIC-neutralizing antibody can enhance the anti-tumor effects of ALT-803. With ALT-803 currently in clinical trials to treat progressive solid tumors, the majority of which are sMIC+, our findings provide a rationale for co-targeting sMIC to enhance the therapeutic efficacy of ALT-803 or other IL-15 agonists. PMID:26625316

Cooperative therapeutic anti-tumor effect of IL-15 agonist ALT-803 and co-targeting soluble NKG2D ligand sMIC.

PubMed

Basher, Fahmin; Jeng, Emily K; Wong, Hing; Wu, Jennifer

2016-01-05

Shedding of the human NKG2D ligand MIC (MHC class I-chain-related molecule) from tumor cell surfaces correlates with progression of many epithelial cancers. Shedding-derived soluble MIC (sMIC) enables tumor immune escape through multiple immune suppressive mechanisms, such as disturbing natural killer (NK) cell homeostatic maintenance, impairing NKG2D expression on NK cells and effector T cells, and facilitating the expansion of arginase I+ myeloid suppressor cells. Our recent study has demonstrated that sMIC is an effective cancer therapeutic target. Whether targeting tumor-derived sMIC would enhance current active immunotherapy is not known. Here, we determined the in vivo therapeutic effect of an antibody co-targeting sMIC with the immunostimulatory IL-15 superagonist complex, ALT-803, using genetically engineered transplantable syngeneic sMIC+ tumor models. We demonstrate that combined therapy of a nonblocking antibody neutralizing sMIC and ALT-803 improved the survival of animals bearing sMIC+ tumors in comparison to monotherapy. We further demonstrate that the enhanced therapeutic effect with combined therapy is through concurrent augmentation of NK and CD8 T cell anti-tumor responses. In particular, expression of activation-induced surface molecules and increased functional potential by cytokine secretion are improved greatly by the administration of combined therapy. Depletion of NK cells abolished the cooperative therapeutic effect. Our findings suggest that administration of the sMIC-neutralizing antibody can enhance the anti-tumor effects of ALT-803. With ALT-803 currently in clinical trials to treat progressive solid tumors, the majority of which are sMIC+, our findings provide a rationale for co-targeting sMIC to enhance the therapeutic efficacy of ALT-803 or other IL-15 agonists.

Current Therapeutic Approach to Hypertrophic Scars

PubMed Central

Mokos, Zrinka Bukvić; Jović, Anamaria; Grgurević, Lovorka; Dumić-Čule, Ivo; Kostović, Krešimir; Čeović, Romana; Marinović, Branka

2017-01-01

Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome. PMID:28676850

Student Wellbeing and the Therapeutic Turn in Education

ERIC Educational Resources Information Center

Wright, Katie

2014-01-01

This article considers current concerns with promoting student mental health and wellbeing against the backdrop of critiques of the "therapeutic turn" in education. It begins by situating accounts of "therapeutic education" within broader theorisation of therapeutic culture. In doing so, the importance of this work is…

Therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemia/reperfusion injury in rats.

PubMed

Guo, Chao; Zhu, Yanrong; Weng, Yan; Wang, Shiquan; Guan, Yue; Wei, Guo; Yin, Ying; Xi, Miaomaio; Wen, Aidong

2014-01-01

Breviscapine injection is a Chinese herbal medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used for treating cardiovascular and cerebrovascular diseases. However, the therapeutic time window and the action mechanism of breviscapine are still unclear. The present study was designed to investigate the therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemic/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2h followed by 24h of reperfusion. Experiment part 1 was used to investigate the therapeutic time window of breviscapine. Rats were injected intravenously with 50mg/kg breviscapine at different time-points of reperfusion. After 24h of reperfusion, neurologic score, infarct volume, brain water content and serum level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2 was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2-nonenal (4-HNE), 8-hydroxyl-2'- deoxyguanosine (8-OHdG) and the antioxidant capacity of ischemia cortex were measured by ELISA and ferric-reducing antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot analysis were used to analyze the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Part 1: breviscapine injection significantly ameliorated neurologic deficit, reduced infarct volume and water content, and suppressed the levels of NSE in a time-dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover, breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24h of reperfusion. The therapeutic time window of breviscapine injection for cerebral ischemia/reperfusion injury seemed to be within 5h after reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway

[Self-selection processes in the choice of the therapeutic training approach: differences in therapeutic attitudes, personality traits and attributional complexity].

PubMed

Taubner, Svenja; Munder, Thomas; Möller, Heidi; Hanke, Wiebke; Klasen, Jennifer

2014-06-01

Treatment approaches differ to a great extent in terms of basic psychological assumptions and practical procedures. This creates questions about the fitting of therapist and therapeutic approach. This paper examines the influence of therapeutic attitudes, mentalization interest and personality traits on the decision for an approach. 184 participants of training programs in one of the 3 licensed treatment approaches in Germany were examined with questionnaires at the beginning of their training. Participants significantly differed in terms of therapeutic attitudes and the metallization interest but not in personality traits except openness. Satisfaction with training was not related to the individual fit of participants to the therapeutic attitudes typical for their approach. Therapeutic attitudes, the extent of mentalization interest, and openness may play a role in self-selection processes in the choice of the approach. © Georg Thieme Verlag KG Stuttgart · New York.

Short-duration therapeutic massage reduces postural upper trapezius muscle activity.

PubMed

Domingo, Antoinette R; Diek, Melissa; Goble, Kathleen M; Maluf, Katrina S; Goble, Daniel J; Baweja, Harsimran S

2017-01-18

Massage therapy has historically been used as a therapeutic treatment to help reduce pain and promote relaxation. The aim of this study was to investigate the effect of therapeutic massage on the upper trapezius muscles, which are commonly associated with increased muscle tension. This was a randomized crossover study. Seventeen healthy individuals (nine women; 24.5±4.0 years) participated in the study. All individuals participated in two sessions that were held 24 h apart. In one of the sessions, the participants received a moderate pressure massage applied to the shoulders and neck. In the other session, participants sat quietly. The order of the sessions was counterbalanced across participants. Muscle activity, as measured by surface electromyography, of the upper trapezius muscles was recorded. The amount of muscle activity change following massage was compared with the change in muscle activity following quiet sitting. Muscle activity of the upper trapezius reduced significantly (19.3%; P=0.004) following massage compared with muscle activity following quiet sitting (1.0%). Our findings suggest that short-duration moderate pressure massage leads to a reduction in upper trapezius muscle activity. This result has potential implications for clinical populations such as those with chronic neck pain.

Clinical Pharmacology & Therapeutics: Past, Present and Future

PubMed Central

Waldman, SA; Terzic, A

2016-01-01

Clinical Pharmacology & Therapeutics (CPT), the definitive and timely source for advances in human therapeutics, transcends the drug discovery, development, regulation and utilization continuum to catalyze, evolve and disseminate discipline-transformative knowledge. Prioritized themes and multidisciplinary content drive the science and practice of clinical pharmacology, offering a trusted point of reference. An authoritative herald across global communities, CPT is a timeless information vehicle at the vanguard of discovery, translation and application ushering therapeutic innovation into modern health care. PMID:28194770

Development of Optically Active Nanostructures for Potential Applications in Sensing, Therapeutics and Imaging

NASA Astrophysics Data System (ADS)

Joshi, Padmanabh

Materials at nanoscale are finding manifold applications in the various fields like sensing, plasmonics, therapeutics, to mention a few. Large amount of development has taken place regarding synthesis and exploring the novel applications of the various types of nanomaterials like organic, inorganic and hybrid of both. Yet, it is believed that the full potential of different nanomaterials is yet to be fully established stimulating researchers to explore more in the field of nanotechnology. Building on the same premise, in the following studies we have developed the nanomaterials in the class of optically active nanoparticles. First part of the study we have successfully designed, synthesized, and characterized Ag-Fe3O4 nanocomposite substrate for potential applications in quantitative Surface Enhanced Raman Scattering (SERS) measurements. Quantitative SERS-based detection of dopamine was performed successfully. In subsequent study, facile, single-step synthesis of polyethyleneimine (PEI) coated lanthanide based NaYF4 (Yb, Er) nanoparticles was developed and their application as potential photodynamic therapy agent was studied using excitations by light in near infra-red and visible region. In the following and last study, synthesis and characterization of the conjugated polymer nanoparticles was attempted successfully. Functionalization of the conjugated nanoparticles, which is a bottleneck for their potential applications, was successfully performed by encapsulating them in the silica nanoparticles, surface of which was then functionalized by amine group. Three types of optically active nanoparticles were developed for potential applications in sensing, therapeutics and imaging.

Therapeutic cloning and reproductive liberty.

PubMed

Sparrow, Robert

2009-04-01

Concern for "reproductive liberty" suggests that decisions about embryos should normally be made by the persons who would be the genetic parents of the child that would be brought into existence if the embryo were brought to term. Therapeutic cloning would involve creating and destroying an embryo, which, if brought to term, would be the offspring of the genetic parents of the person undergoing therapy. I argue that central arguments in debates about parenthood and genetics therefore suggest that therapeutic cloning would be prima facie unethical unless it occurred with the consent of the parents of the person being cloned. Alternatively, if therapeutic cloning is thought to be legitimate, this undermines the case for some uses of reproductive cloning by implying that the genetic relation it establishes between clones and DNA donors does not carry the same moral weight as it does in cases of normal reproduction.

Quercetin and the ocular surface: What we know and where we are going

PubMed Central

McKay, Tina B

2017-01-01

Flavonoids are a class of plant and fungus secondary metabolites that serve functional roles in protecting against UV-induced oxidative stress, mediating auxin signaling, and promoting microbial defense. Flavonoids are extremely abundant in nature where their potent antioxidant capacity and very low toxicity makes them highly attractive as potential therapeutic agents. In terms of clinical applications, neither the Food and Drug Administration (FDA) nor the European Food Safety Authority (EFSA) has approved any health claims or drugs related to the use of flavonoids for therapeutic purposes. Quercetin is a common flavonol that has been shown to have potent antioxidant, anti-inflammatory, and anti-fibrotic activities both in vitro and in vivo in various tissues. Recently, the application of quercetin as a therapeutic has been gaining attention in the ocular surface scientific community in the study of dry eye, keratoconus, inflammation, and neovascularization of the cornea. This review will discuss the latest findings and the use of quercetin for the treatment of dystrophies of the ocular surface. Impact statement The eye represents a small portion of the human body, accounting for one decimal fraction of the anterior body surface. The cornea is an avascular, transparent tissue that acts as a primary barrier against mechanical and infectious damaging agents, protecting the internal structures of the eye. Corneal survival and function are affected by a number of factors including but not limited to injury, trauma, infection, genetics, and environment. Corneal injury, or trauma, often leads to loss of corneal transparency and even blindness. The concept of “curing” corneal opacity has been discussed in published form for over 200 years. Currently, full corneal transplant is the only treatment option. There is a strong interest in developing natural therapeutic products that come with minimum side effects. A novel antioxidant flavonoid, quercetin, has been

Quercetin and the ocular surface: What we know and where we are going.

PubMed

McKay, Tina B; Karamichos, Dimitrios

2017-03-01

Flavonoids are a class of plant and fungus secondary metabolites that serve functional roles in protecting against UV-induced oxidative stress, mediating auxin signaling, and promoting microbial defense. Flavonoids are extremely abundant in nature where their potent antioxidant capacity and very low toxicity makes them highly attractive as potential therapeutic agents. In terms of clinical applications, neither the Food and Drug Administration (FDA) nor the European Food Safety Authority (EFSA) has approved any health claims or drugs related to the use of flavonoids for therapeutic purposes. Quercetin is a common flavonol that has been shown to have potent antioxidant, anti-inflammatory, and anti-fibrotic activities both in vitro and in vivo in various tissues. Recently, the application of quercetin as a therapeutic has been gaining attention in the ocular surface scientific community in the study of dry eye, keratoconus, inflammation, and neovascularization of the cornea. This review will discuss the latest findings and the use of quercetin for the treatment of dystrophies of the ocular surface. Impact statement The eye represents a small portion of the human body, accounting for one decimal fraction of the anterior body surface. The cornea is an avascular, transparent tissue that acts as a primary barrier against mechanical and infectious damaging agents, protecting the internal structures of the eye. Corneal survival and function are affected by a number of factors including but not limited to injury, trauma, infection, genetics, and environment. Corneal injury, or trauma, often leads to loss of corneal transparency and even blindness. The concept of "curing" corneal opacity has been discussed in published form for over 200 years. Currently, full corneal transplant is the only treatment option. There is a strong interest in developing natural therapeutic products that come with minimum side effects. A novel antioxidant flavonoid, quercetin, has been gaining

Therapeutic hypothermia: applications in pediatric cardiac arrest.

PubMed

Kochanek, Patrick M; Fink, Ericka L; Bell, Michael J; Bayir, Hülya; Clark, Robert S B

2009-03-01

There is a rich history for the use of therapeutic hypothermia after cardiac arrest in neonatology and pediatrics. Laboratory reports date back to 1824 in experimental perinatal asphyxia. Similarly, clinical reports in pediatric cold water drowning victims represented key initiating work in the field. The application of therapeutic hypothermia in pediatric drowning victims represented some of the seminal clinical use of this modality in modern neurointensive care. Uncontrolled application (too deep and too long) and unique facets of asphyxial cardiac arrest in children (a very difficult insult to affect any benefit) likely combined to result in abandonment of therapeutic hypothermia in the mid to late 1980s. Important studies in perinatal medicine have built upon the landmark clinical trials in adults, and are once again bringing therapeutic hypothermia into standard care for pediatrics. Although more work is needed, particularly in the use of mild therapeutic hypothermia in children, there is a strong possibility that this important therapy will ultimately have broad applications after cardiac arrest and central nervous system (CNS) insults in the pediatric arena.

Targeting therapeutics to the glomerulus with nanoparticles.

PubMed

Zuckerman, Jonathan E; Davis, Mark E

2013-11-01

Nanoparticles are an enabling technology for the creation of tissue-/cell-specific therapeutics that have been investigated extensively as targeted therapeutics for cancer. The kidney, specifically the glomerulus, is another accessible site for nanoparticle delivery that has been relatively overlooked as a target organ. Given the medical need for the development of more potent, kidney-targeted therapies, the use of nanoparticle-based therapeutics may be one such solution to this problem. Here, we review the literature on nanoparticle targeting of the glomerulus. Specifically, we provide a broad overview of nanoparticle-based therapeutics and how the unique structural characteristics of the glomerulus allow for selective, nanoparticle targeting of this area of the kidney. We then summarize literature examples of nanoparticle delivery to the glomerulus and elaborate on the appropriate nanoparticle design criteria for glomerular targeting. Finally, we discuss the behavior of nanoparticles in animal models of diseased glomeruli and review examples of nanoparticle therapeutic approaches that have shown promise in animal models of glomerulonephritic disease. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

PubMed

Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

2007-01-01

The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.

21 CFR 884.5900 - Therapeutic vaginal douche apparatus.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Therapeutic vaginal douche apparatus. 884.5900... Devices § 884.5900 Therapeutic vaginal douche apparatus. (a) Identification. A therapeutic vaginal douche apparatus is a device that is a bag or bottle with tubing and a nozzle. The apparatus does not include...

21 CFR 884.5900 - Therapeutic vaginal douche apparatus.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Therapeutic vaginal douche apparatus. 884.5900... Devices § 884.5900 Therapeutic vaginal douche apparatus. (a) Identification. A therapeutic vaginal douche apparatus is a device that is a bag or bottle with tubing and a nozzle. The apparatus does not include...

Multifunctional mesoporous bioactive glasses for effective delivery of therapeutic ions and drug/growth factors.

PubMed

Wu, Chengtie; Chang, Jiang

2014-11-10

Regeneration of large-size bone defects represents a significant challenge clinically, which requires the use of scaffolds with multifunction, such as anti-bacterial activity, and stimulation of osteogenesis and angiogenesis. It is known that functional ions or drug/growth factors play an important role to stimulate tissue regeneration. Mesoporous bioactive glasses (MBG) possess excellent bioactivity and drug-delivery ability as well as effective ionic release in the body fluids microenvironment due to its specific mesoporous structure and large surface area. For these reasons, functional ions (e.g. lithium (Li), strontium (Sr), Copper (Cu) and Boron (B)) and drug/growth factors (e.g. dexamethasone, vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)) have been incorporated into MBG, which shows high loading efficiency and effective release. The release of therapeutic ions and drug/growth factors from MBG offers it multifunctional properties, such as improved osteogenesis, angiogenesis, anti-bacterial/cancer activity. However, there is no a systematic review about delivery of therapeutic ions and drugs/growth factors from MBG for the functional effect on the tissue regeneration despite that significant progress has been achieved in the past five years. Therefore, in this review, we mainly focused on the new advances for the functional effect of delivering therapeutic ions and drugs/growth factors on the ostegeogenesis, angiogenesis and antibacterial activity. It is expected that the review will offer new concept to develop multifunctional biomaterials for bone regeneration by the synergistic effect of therapeutic ions and drug/growth factors. Copyright © 2014 Elsevier B.V. All rights reserved.

A pragmatic definition of therapeutic synergy suitable for clinically relevant in vitro multicompound analyses.

PubMed

Kashif, Muhammad; Andersson, Claes; Åberg, Magnus; Nygren, Peter; Sjöblom, Tobias; Hammerling, Ulf; Larsson, Rolf; Gustafsson, Mats G

2014-07-01

For decades, the standard procedure when screening for candidate anticancer drug combinations has been to search for synergy, defined as any positive deviation from trivial cases like when the drugs are regarded as diluted versions of each other (Loewe additivity), independent actions (Bliss independence), or no interaction terms in a response surface model (no interaction). Here, we show that this kind of conventional synergy analysis may be completely misleading when the goal is to detect if there is a promising in vitro therapeutic window. Motivated by this result, and the fact that a drug combination offering a promising therapeutic window seldom is interesting if one of its constituent drugs can provide the same window alone, the largely overlooked concept of therapeutic synergy (TS) is reintroduced. In vitro TS is said to occur when the largest therapeutic window obtained by the best drug combination cannot be achieved by any single drug within the concentration range studied. Using this definition of TS, we introduce a procedure that enables its use in modern massively parallel experiments supported by a statistical omnibus test for TS designed to avoid the multiple testing problem. Finally, we suggest how one may perform TS analysis, via computational predictions of the reference cell responses, when only the target cell responses are available. In conclusion, the conventional error-prone search for promising drug combinations may be improved by replacing conventional (toxicology-rooted) synergy analysis with an analysis focused on (clinically motivated) TS. ©2014 American Association for Cancer Research.

Synthesis of Multifunctional Nanoparticles for Cancer Diagnostics and Therapeutics

NASA Astrophysics Data System (ADS)

Fang, Chen

2011-12-01

Magnetic nanoparticles (MNPs) have attracted enormous research attention due to their unique magnetic properties that enable the detection by the non-invasive medical imaging modality---magnetic resonance imaging (MRI). By incorporating advanced features, such as specific targeting, multimodality, therapeutic delivery, the detectability and applicability of MNPs have been dramatically expanded. Smart and rational design on structure, composition and surface chemistry is essential to achieving desired properties in MNP systems, such as high sensitivity and colloidal stability, target specificity and/or multimodality. The goal of this research is to develop MNP-based platforms for the detection, diagnosis and treatment of cancer. MNPs with high contrast enhancement were coated with poly(ethylene glycol) (PEG)-based polymers to render aqueous stability and confer therapeutic-loading capability. Tumor-specific MNPs were developed by functionalization of nanoparticles with chlorotoxin (CTX) or arginine-glycine-aspartic acid (RGD) that targets, respectively, MMP-2 receptor or alphavbeta3 integrin overexpressed on a variety of cancer cells. The effects of ligands' molecular targets on the temporal and spatial distribution of MNPs within tumors were also investigated both in vitro and in vivo. All MNPs exhibited excellent long-term stability in cell culture media. CTX-labeled MNP exhibited sustained accumulation, penetration and distribution in the tumor mass. These findings revealed the influence of the targeting ligands on the intratumoral distribution of the ligand-enabled nanoprobes. To demonstrate the ability of nanoparticles as drug carrier, anthracyline chemotherapeutic drugs doxorubicin and mitoxantrone were attached to iron oxide nanoparticles. The theragnostic nanoparticles showed sufficient contrast enhancement and comparable anti-neoplastic efficacy in vitro. With flexible surface chemistry, our nanoparticle platform can be used in a modular fashion to

Therapeutic touch and postoperative pain: a Rogerian research study.

PubMed

Meehan, T C

1993-01-01

This article details Meehan's research study concerning the conceptualization of therapeutic touch within Rogers' science of unitary human beings and an investigation of the effects of therapeutic touch on pain experience in postoperative patients. Using a single trial, single-blind, three-group design, 108 postoperative patients were randomly assigned to receive one of the following: therapeutic touch, a placebo control intervention which mimicked therapeutic touch, or the standard intervention of a narcotic analgesic. Using a visual analogue scale, pain was measured before and one hour following intervention. The hypothesis, that therapeutic touch would significantly decrease postoperative pain compared to the placebo control intervention, was not supported. Secondary analyses suggest that therapeutic touch may decrease patients' need for analgesic medication. Implications for further research and practice are suggested.

SATPdb: a database of structurally annotated therapeutic peptides

PubMed Central

Singh, Sandeep; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Bhalla, Sherry; Usmani, Salman Sadullah; Gautam, Ankur; Tuknait, Abhishek; Agrawal, Piyush; Mathur, Deepika; Raghava, Gajendra P.S.

2016-01-01

SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics. PMID:26527728

Therapeutic Modalities in Diabetic Nephropathy: Future Approaches*

PubMed Central

Reeves, William Brian; Rawal, Bishal B.; Abdel-Rahman, Emaad M.; Awad, Alaa S.

2012-01-01

Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Several therapeutic interventions for the treatment of diabetic nephropathy have been developed and implemented over the past few decades with some degree of success. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are therefore urgently needed. Recently, several novel therapeutic strategies have been explored in treating DN patients including Islet cell transplant, Aldose reductase inhibitors, Sulodexide (GAC), Protein Kinase C (PKC) inhibitors, Connective tissue growth factor (CTGF) inhibitors, Transforming growth factor-beta (TGF-β) inhibitors and bardoxolone. The benefits and risks of these agents are still under investigation. This review aims to summarize the utility of these novel therapeutic approaches. PMID:23293752

Therapeutic Vaccines for Chronic Infections

NASA Astrophysics Data System (ADS)

Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

2004-07-01

Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

Contamination levels of human pharmaceutical compounds in French surface and drinking water.

PubMed

Mompelat, S; Thomas, O; Le Bot, B

2011-10-01

The occurrence of 20 human pharmaceutical compounds and metabolites from 10 representative therapeutic classes was analysed from resource and drinking water in two catchment basins located in north-west France. 98 samples were analysed from 63 stations (surface water and drinking water produced from surface water). Of the 20 human pharmaceutical compounds selected, 16 were quantified in both the surface water and drinking water, with 22% of the values above the limit of quantification for surface water and 14% for drinking water). Psychostimulants, non-steroidal anti-inflammatory drugs, iodinated contrast media and anxiolytic drugs were the main therapeutic classes of human pharmaceutical compounds detected in the surface water and drinking water. The results for surface water were close to results from previous studies in spite of differences in prescription rates of human pharmaceutical compounds in different countries. The removal rate of human pharmaceutical compounds at 11 water treatment units was also determined. Only caffeine proved to be resistant to drinking water treatment processes (with a minimum rate of 5%). Other human pharmaceutical compounds seemed to be removed more efficiently (average elimination rate of over 50%) by adsorption onto activated carbon and oxidation/disinfection with ozone or chlorine (not taking account of the disinfection by-products). These results add to the increasing evidence of the occurrence of human pharmaceutical compounds in drinking water that may represent a threat to human beings exposed to a cocktail of human pharmaceutical compounds and related metabolites and by-products in drinking water.

Hypothermia after cardiac arrest: expanding the therapeutic scope.

PubMed

Bernard, Stephen

2009-07-01

Therapeutic hypothermia for 12 to 24 hrs following resuscitation from out-of-hospital cardiac arrest is now recommended by the American Heart Association for the treatment of neurological injury when the initial cardiac rhythm is ventricular fibrillation. However, the role of therapeutic hypothermia is uncertain when the initial cardiac rhythm is asystole or pulseless electrical activity, or when the cardiac arrest is primarily due to a noncardiac cause, such as asphyxia or drug overdose. Given that survival rate in these latter conditions is very low, it is unlikely that clinical trials will be undertaken to test the efficacy of therapeutic hypothermia in this setting because of the very large sample size that would be required to detect a significant difference in outcomes. Therefore, in patients with anoxic brain injury after nonventricular fibrillation cardiac arrest, clinicians will need to balance the possible benefit of therapeutic hypothermia with the possible side effects of this therapy. Given that the side effects of therapeutic hypothermia are generally easily managed in the critical care setting, and there is benefit for anoxic brain injury demonstrated in laboratory studies, consideration may be given to treat comatose post-cardiac arrest patients with therapeutic hypothermia in this setting. Because the induction of therapeutic hypothermia has become more feasible with the development of simple intravenous cooling techniques and specialized equipment for improved temperature control in the critical care unit, it is expected that therapeutic hypothermia will become more widely used in the management of anoxic neurological injury whatever the presenting cardiac rhythm.

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Quantitative evaluation of the lumbosacral sagittal alignment in degenerative lumbar spinal stenosis

PubMed Central

Makirov, Serik K.; Jahaf, Mohammed T.; Nikulina, Anastasia A.

2015-01-01

Goal of the study This study intends to develop a method of quantitative sagittal balance parameters assessment, based on a geometrical model of lumbar spine and sacrum. Methods One hundred eight patients were divided into 2 groups. In the experimental group have been included 59 patients with lumbar spinal stenosis on L1-5 level. Forty-nine healthy volunteers without history of any lumbar spine pathlogy were included in the control group. All patients have been examined with supine MRI. Lumbar lordosis has been adopted as circular arc and described either anatomical (lumbar lordosis angle), or geometrical (chord length, circle segment height, the central angle, circle radius) parameters. Moreover, 2 sacral parameters have been assessed for all patients: sacral slope and sacral deviation angle. Both parameters characterize sacrum disposition in horizontal and vertical axis respectively. Results Significant correlation was observed between anatomical and geometrical lumbo-sacral parameters. Significant differences between stenosis group and control group were observed in the value of the “central angle” and “sacral deviation” parameters. We propose additional parameters: lumbar coefficient, as ratio of the lordosis angle to the segmental angle (Kl); sacral coefficient, as ratio of the sacral tilt (ST) to the sacral deviation (SD) angle (Ks); and assessment modulus of the mathematical difference between sacral and lumbar coefficients has been used for determining lumbosacral balance (LSB). Statistically significant differences between main and control group have been obtained for all described coefficients (p = 0.006, p = 0.0001, p = 0.0001, accordingly). Median of LSB value of was 0.18 and 0.34 for stenosis and control groups, accordingly. Conclusion Based on these results we believe that that spinal stenosis is associated with an acquired deformity that is measureable by the described parameters. It's possible that spinal stenosis occurs in patients with an

Development of Antibody Therapeutics against Flaviviruses

PubMed Central

Sun, Haiyan; Chen, Qiang; Lai, Huafang

2017-01-01

Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates. PMID:29295568

Reflection of a therapeutic touch experience: case study 2.

PubMed

Green, C A

1998-02-01

The purpose of this case study was to explore the experience of both giving and receiving Therapeutic Touch. A subjective account of the Therapeutic Touch experience is given in an attempt to throw light on its unique creative and therapeutic qualities. In most instances it was shown that the experience of both giving and receiving Therapeutic Touch was a parallel experience. This case study explores the effects of Therapeutic Touch on a client experiencing pain and associated anxiety. Whilst a response to treatment was observed, the need for further case studies and research studies in this area was identified.

Creation of hydrophilic nitric oxide releasing polymers via plasma surface modification.

PubMed

Pegalajar-Jurado, A; Joslin, J M; Hawker, M J; Reynolds, M M; Fisher, E R

2014-08-13

Herein, we describe the surface modification of an S-nitrosated polymer derivative via H2O plasma treatment, resulting in polymer coatings that maintained their nitric oxide (NO) releasing capabilities, but exhibited dramatic changes in surface wettability. The poly(lactic-co-glycolic acid)-based hydrophobic polymer was nitrosated to achieve a material capable of releasing the therapeutic agent NO. The NO-loaded films were subjected to low-temperature H2O plasma treatments, where the treatment power (20-50 W) and time (1-5 min) were varied. The plasma treated polymer films were superhydrophilic (water droplet spread completely in <100 ms), yet retained 90% of their initial S-nitrosothiol content. Under thermal conditions, NO release profiles were identical to controls. Under buffer soak conditions, the NO release profile was slightly lowered for the plasma-treated materials; however, they still result in physiologically relevant NO fluxes. XPS, SEM-EDS, and ATR-IR characterization suggests the plasma treatment resulted in polymer rearrangement and implantation of hydroxyl and carbonyl functional groups. Plasma treated samples maintained both hydrophilic surface properties and NO release profiles after storage at -18 °C for at least 10 days, demonstrating the surface modification and NO release capabilities are stable over time. The ability to tune polymer surface properties while maintaining bulk properties and NO release properties, and the stability of those properties under refrigerated conditions, represents a unique approach toward creating enhanced therapeutic biopolymers.

Targeting Host Cell Surface Nucleolin for RSV Therapy: Challenges and Opportunities.

PubMed

Mastrangelo, Peter; Norris, Michael J; Duan, Wenming; Barrett, Edward G; Moraes, Theo J; Hegele, Richard G

2017-09-19

Nucleolin (NCL) has been reported as a cellular receptor for the human respiratory syncytial virus (RSV). We studied the effects of re-purposing AS1411, an anti-cancer compound that binds cell surface NCL, as a possible novel strategy for RSV therapy in vitro and in vivo. AS1411 was administered to RSV-infected cultures of non-polarized (HEp-2) and polarized (MDCK) epithelial cells and to virus-infected mice and cotton rats. Results of in vitro experiments showed that AS1411, used in micromolar concentrations, was associated with decreases in the number of virus-positive cells. Intranasal administration of AS1411 (50 mg/kg) to RSV-infected mice and cotton rats was associated with partial reductions in lung viral titers, decreased virus-associated airway inflammation, and decreased IL-4/IFN-γ ratios when compared to untreated, infected animals. In conclusion, our findings indicate that therapeutic use of AS1411 has modest effects on RSV replication and host response. While the results underscore the challenges of targeting cell surface NCL as a potential novel strategy for RSV therapy, they also highlight the potential of cell surface NCL as a therapeutic target.

[The delivery of therapeutic plasma: Therapeutic plasma of today and tomorrow].

PubMed

Garraud, O

2016-11-01

Since plasma for direct therapeutic use comprises no cellular fraction, it has long stood for a standardized and rather simple component; meanwhile, rules for its issuing to patients have long been strict. During the very last years, there has been a paradigm shift as novel indications have raised and possible needs for distinct types of plasma depending on the missing clotting factors in the patient. During the same period of time, plasma inactivated by solvent-detergent, which was a labile component in France, has been re-qualified by European authorities as a plasma derived-drug. The French recommendations for use of plasma - though quite recently revised (2012) - are disputed by some experts and would merit a revisit. This state-of-the art manuscript aims at presenting the novel situation of therapeutic plasma and suggesting possible evolution. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Differential changes in the spinal segmental locomotor output in Hereditary Spastic Paraplegia.

PubMed

Martino, G; Ivanenko, Y; Serrao, M; Ranavolo, A; Draicchio, F; Rinaldi, M; Casali, C; Lacquaniti, F

2018-03-01

A comprehensive treatment of Hereditary Spastic Paraplegia (HSP) should consider the specific pathophysiological changes in the spinal cord. Here we reported a detailed characterization of the spinal motoneuronal output in HSP during locomotion. We recorded kinematics and electromyographic (EMG) activity of 12 leg muscles in 29 patients with pure forms of HSP and compared them with 30 controls while walking at matched speeds. We assessed the spinal locomotor output by evaluating EMG patterns and by mapping them onto the rostrocaudal location of the spinal motoneuron pools. The activity profiles of muscles innervated from the sacral segments were significantly wider in patients. Similarly, spinal maps revealed a tendency for spreading the main loci of activation, involving initially the sacral segments and, at more severe stages, the lumbar segments. The degeneration of the corticospinal tract in HSP is associated with a widening of spinal locomotor output spreading from caudal to rostral segments. The findings highlight pathophysiologically relevant differential changes in the spinal locomotor output in HSP related to the specific innervation of muscles in the spinal cord, and might be helpful for developing future therapeutic strategies and identifying physiological markers of the disease. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

PubMed Central

Blatt, Katharina; Cerny-Reiterer, Sabine; Schwaab, Juliana; Sotlar, Karl; Eisenwort, Gregor; Stefanzl, Gabriele; Hoermann, Gregor; Mayerhofer, Matthias; Schneeweiss, Mathias; Knapp, Sylvia; Rülicke, Thomas; Hadzijusufovic, Emir; Bauer, Karin; Smiljkovic, Dubravka; Willmann, Michael; Reiter, Andreas; Horny, Hans-Peter

2015-01-01

The Ki-1 antigen (CD30) is an established therapeutic target in patients with Hodgkin lymphoma and anaplastic large-cell lymphoma. We have recently shown that CD30 is expressed abundantly in the cytoplasm of neoplastic mast cells (MCs) in patients with advanced systemic mastocytosis (SM). In the current study, we asked whether CD30 is expressed on the surface of neoplastic MCs in advanced SM, and whether this surface structure may serve as therapeutic target in SM. As assessed by flow cytometry, CD30 was found to be expressed on the surface of neoplastic MCs in 3 of 25 patients (12%) with indolent SM, 4 of 7 patients (57%) with aggressive SM, and 4 of 7 patients (57%) with MC leukemia. The immature RAS-transformed human MC line MCPV-1.1 also expressed cell surface CD30, whereas the KIT-transformed MC line HMC-1.2 expressed no detectable CD30. The CD30-targeting antibody-conjugate brentuximab-vedotin inhibited proliferation in neoplastic MCs, with lower IC50 values obtained in CD30+ MCPV-1.1 cells (10 µg/mL) compared with CD30− HMC-1.2 cells (>50 µg/mL). In addition, brentuximab-vedotin suppressed the engraftment of MCPV-1.1 cells in NSG mice. Moreover, brentuximab-vedotin produced apoptosis in all CD30+ MC lines tested as well as in primary neoplastic MCs in patients with CD30+ SM, but did not induce apoptosis in neoplastic MCs in patients with CD30− SM. Furthermore, brentuximab-vedotin was found to downregulate anti-IgE–induced histamine release in CD30+ MCs. Finally, brentuximab-vedotin and the KIT D816V-targeting drug PKC412 produced synergistic growth-inhibitory effects in MCPV-1.1 cells. Together, CD30 is a promising new drug target for patients with CD30+ advanced SM. PMID:26486787

Modes of therapeutic action.

PubMed

Jones, E E

1997-12-01

The dialectic in psychoanalysis between theories about the mutative effects of interpretation and psychological knowledge and those concerning the effects of interpersonal interaction constitutes an important tension for approaches to psychoanalytic technique. This essay briefly summarises the thinking around these alternative conceptualisations of therapeutic action, and introduces a new empirically derived model, that of 'repetitive interaction structure', which attempts to bridge therapeutic action by insight and by relationship. Interaction structure is a way of formulating those aspects of the analytic process that have come to be termed intersubjectivity, transference-countertransference enactments and role responsiveness. The concept operationalises important aspects of interpersonal interaction, and can help specify the two-person patterns that emerge in an analysis. Patient and analyst interact in repetitive ways; these patterns of interaction, which are slow to change, probably reflect the psychological structure of both patient and analyst, whether psychic structure is conceptualised in terms of object-representations or compromise formations and impulse-defence configurations. Therapeutic action is located in the experience, recognition and understanding by patient and analyst of these repetitive interactions. Interaction structures stress the importance of the intrapsychic as a basis for what becomes manifest in the interactive field. Clinical illustrations from a psychoanalysis are provided, and research on repetitive interaction structures is described.

Fibrin matrices: The versatile therapeutic delivery systems.

PubMed

Ahmad, Ejaj; Fatima, Munazza Tamkeen; Hoque, Mehboob; Owais, Mohammad; Saleemuddin, Mohammed

2015-11-01

Fibrin sealants, that have been employed for over a century by surgeons to stop post surgery bleeding, are finding novel applications in the controlled delivery of antibiotics and several other therapeutics. Fibrinogen can be easily purified from blood plasma and converted by thrombolysis to fibrin that undergoes spontaneous aggregation to form insoluble clot. During the gelling, fibrin can be formulated into films, clots, threads, microbeads, nanoconstructs and nanoparticles. Whole plasma clots in the form of beads and microparticles can also be prepared by activating endogenous thrombin, for possible drug delivery. Fibrin formulations offer remarkable scope for controlling the porosity as well as in vivo degradability and hence the release of the associated therapeutics. Binding/covalent-linking of therapeutics to the fibrin matrix, crosslinking of the matrix with bifunctional reagents and coentrapment of protease inhibitors have been successful in regulating both in vitro and in vivo release of the therapeutics. The release rates can also be remarkably lowered by preentrapment of therapeutics in insoluble particles like liposomes or by anchoring them to the matrix via molecules that bind them as well as fibrin. Copyright © 2015 Elsevier B.V. All rights reserved.