Long-term safety and outcome of fludarabine, cyclophosphamide and mitoxantrone (FCM) regimen in previously untreated patients with advanced follicular lymphoma: 12 years follow-up of a phase 2 trial.

PubMed

Magnano, Laura; Montoto, Silvia; González-Barca, Eva; Briones, Javier; Sancho, Juan Manuel; Muntañola, Ana; Salar, Antonio; Besalduch, Joan; Escoda, Lourdes; Moreno, Carol; Domingo-Domenech, Eva; Estany, Cristina; Oriol, Albert; Altés, Albert; Pedro, Carmen; Gardella, Santiago; Asensio, Antoni; Vivancos, Pilar; Fernández de Sevilla, Alberto; Ribera, Josep María; Colomer, Dolors; Campo, Elias; López-Guillermo, Armando

2017-04-01

Fludarabine combinations are very affective in follicular lymphoma (FL) with high rates of complete response and prolonged survival. However, late toxicities could be a concern. The aim of the present study was to analyze the long-term impact on survival, relapse and late toxicities of a trial of treatment with fludarabine, mitoxantrone and cyclophosphamide (FCM regimen) for untreated patients with advanced stage FL. One hundred and twenty patients enrolled in a phase 2 trial of treatment with FCM regimen between 2000 and 2003 were evaluated. After a median follow-up of 12 years, 52 patients eventually relapsed/progressed with 10 year progression-free survival (PFS) of 46 %. Ten patients showed histological transformation to aggressive lymphoma with a risk of transformation of 2 and 9 % at 5 and 10 years, respectively. Three patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) and seven solid neoplasms with an overall risk of 3 and 8 % at 5 and 10 years, respectively. Twenty-six patients eventually died during the follow-up. Overall survival at 10 years was 83 %. In conclusion, FCM regimen allows excellent long-lasting response in previously untreated patients with FL. The incidence of late events including histological transformation and secondary neoplasia is low but not negligible.

Docetaxel as adjuvant and neoadjuvant treatment for patients with breast cancer.

PubMed

Heys, Steven D; Sarkar, Tarun; Hutcheon, Andrew W

2004-10-01

Developments in the role of adjuvant and neoadjuvant chemotherapy for the treatment of patients with breast cancer have focused on the taxes, in particular, docetaxel. This paper discusses the rationale for the introduction of docetaxel into the management of patients following surgery and also its role in those patients with locally-advanced disease, focussing on key clinical trials. The addition of docetaxel to standard adjuvant chemotherapeutic regimens does seem to result in an increased survival in some patients with early-stage disease. In the neoadjuvant setting, the addition of docetaxel to standard regimens does increase pathological response rates, which is a surrogate marker of eventual outcome.

Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification.

PubMed

Ferreira, Carlos R; Ziegler, Shira G; Gupta, Ashutosh; Groden, Catherine; Hsu, Kevin S; Gahl, William A

2016-05-01

Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate-repleted for his rickets for more than 7 years without worsening of vascular calcification. © 2016 Wiley Periodicals, Inc.

Otogenic Meningitis: A Comparison of Diagnostic Performance of Surgery and Radiology.

PubMed

Bruschini, Luca; Fortunato, Simona; Tascini, Carlo; Ciabotti, Annalisa; Leonildi, Alessandro; Bini, Belinda; Giuliano, Simone; Abbruzzese, Arturo; Berrettini, Stefano; Menichetti, Francesco

2017-01-01

Development of intracranial complications from middle ear infections might be difficult to diagnose. We compared radiological and surgical findings of 26 patients affected by otogenic meningitis. Results of our analysis showed that surgery is more reliable than imaging in revealing bone defects. Therefore, suggest that surgery be performed for diagnosis and eventual management of all cases of suspected otogenic meningitis.

Surgery in the nursing home patient.

PubMed

Zenilman, M E

1994-02-01

Will a Geriatric Surgical Consult Service eventually develop into yet another surgical subspecialty? Precedent has been set in surgical fields such as pediatric and plastic surgery, and surely the expanding patient population will demand that some surgeons take care of the geriatric surgical patient full time. Those surgeons doing so will therefore become recognized experts and will be frequently consulted. The surgical problems faced by this unique patient population observed in our small series are most often straightforward. More complicated issues related to wound and intravenous line care, breast disease, and alimentary tract disease should be easily handled by an aggressive, conscientious, well-trained general surgeon.

Ketoconazole hepatotoxicity in a patient treated for environmental illness and systemic candidiasis

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

Brusko, C.S.; Marten, J.T.

1991-12-01

Environmental illness, a hypothesized disease caused by exposure to substances such as combustion products, pesticides, food additives, and Candida albicans, is discussed. The case of a patient with environmental illness and systemic candidiasis for six weeks with ketoconazole, liver enzyme concentrations increased. One month after discontinuation of ketoconazole, the liver enzyme concentrations decreased; however, over the next five months, liver enzymes and bilirubin increased. The patient developed encephalopathy and eventually was transferred to a medical center for possible liver transplant. A review of the literature pertaining to ketoconazole hepatotoxicity is also presented.16 references.

[Obstructive cholangiopathy: are endoscopic retrograde cholangiopancreatography and papillotomy always really necessary?].

PubMed

Pierie, J P; van Vroonhoven, T J

1999-07-17

In two women aged 76 and 29 years, who presented with cholangitis and small ductus choledochus calculi and with painless icterus respectively, endoscopic retrograde cholangiopancreatography (ERCP) was carried out with papillotomy. Both developed a duodenal perforation which, however, could not be localized. The first patient eventually died, the second recovered after prolonged hospitalization. A third patient, a 53-year-old man, developed abdominal pain and fever four days after laparoscopic cholecystectomy. ERCP was planned, but in the meantime the patient showed signs of recovery. The ERCP was carried out nevertheless. It failed and the patient suffered a prolonged recovery with necrotizing pancreatitis and multiple operations necessitating a temporary colostoma. In all three patients the endoscopic procedure was performed routinely without strict individualized indication. ERCP and papillotomy may be relatively safe procedures, but it should always be considered whether they will really serve the patient.

Eventual Suicide in Interrupted and Uninterrupted Attempters: A Challenge to the Cry-for-Help Hypothesis.

ERIC Educational Resources Information Center

Steer, Robert A.; And Others

1988-01-01

Followed patients (N=499) hospitalized for suicide attempts (attempters) between 1970 and 1975 until 1982. Found under six percent eventually committed suicide. Found the interrupted attempters were approximately three times more likely to commit suicide than were the uninterrupted attempters. (Author/ABL)

Postoperative conversion disorder.

PubMed

Afolabi, Kola; Ali, Sameer; Gahtan, Vivian; Gorji, Reza; Li, Fenghua; Nussmeier, Nancy A

2016-05-01

Conversion disorder is a psychiatric disorder in which psychological stress causes neurologic deficits. A 28-year-old female surgical patient had uneventful general anesthesia and emergence but developed conversion disorder 1 hour postoperatively. She reported difficulty speaking, right-hand numbness and weakness, and right-leg paralysis. Neurologic examination and imaging revealed no neuronal damage, herniation, hemorrhage, or stroke. The patient mentioned failing examinations the day before surgery and discontinuing her prescribed antidepressant medication, leading us to diagnose conversion disorder, with eventual confirmation by neuroimaging and follow-up examinations. Copyright © 2016 Elsevier Inc. All rights reserved.

Behcet's disease with recurrent thoracic aortic aneurysm combined with femoral artery aneurysm: a case report and literature review.

PubMed

Zhang, Shi-Huai; Zhang, Fu-Xian

2017-09-06

Aneurysm or pseudoaneurysm is the main vascular complication of Behcet's disease. Most hospitals adopt endovascular treatment. We report a case of Behcet's disease with recurrent thoracic aortic aneurysm combined with femoral artery aneurysm. The patient underwent two rounds of endovascular surgery, but developed new aneurysms immediately after surgery. Eventually, the patient died due to rupture of recurrent aneurysm. For vasculo-Behcet's disease, we suggest performing the operation during the stable period. At the same time, glucocorticoids could be used with immunosuppressants preoperatively and postoperatively.

Discontinuation of penicillamine in the absence of alternative orphan drugs (trientine-zinc): a case of decompensated liver cirrhosis in Wilson's disease.

PubMed

Ping, C C; Hassan, Y; Aziz, N A; Ghazali, R; Awaisu, A

2007-02-01

To report a case of early-decompensated liver cirrhosis secondary to discontinuation of penicillamine therapy in a patient with Wilson's disease. A 33-year-old Chinese female patient was diagnosed with Wilson's disease, for which penicillamine 250 mg p.o. once daily was prescribed. However, the patient developed intolerance and penicillamine was discontinued without alternative treatment. Five months later, she developed decompensated liver cirrhosis with hepatic encephalopathy. Eventually, the patient died because of the complications of sepsis and decompensated liver failure. Chelating agent is the mainstay of treatment in Wilson's disease, which is an inherited disorder of hepatic copper metabolism. Therapy must be instituted and continued for life once diagnosis is confirmed. Interruption of therapy can be fatal or cause irreversible relapse. Penicillamine given orally is the chelating agent of first choice. However, its unfavourable side-effects profile leads to discontinuation of therapy in 20-30% of patients. In most case reports, cessation of penicillamine without replacement treatment causes rapid progression to fulminant hepatitis, which is fatal unless liver transplantation is performed. In this, we highlight a case of discontinuation of penicillamine in a patient with Wilson's disease without substitution with alternative regimen. This was caused by unavailability of the alternative agents such as trientine in our country. Consequently, the patient progressed to decompensated liver cirrhosis with encephalopathy and eventually passed-away within 5 months. One recent study supports a combination of trientine and zinc in treating patient with decompensated liver cirrhosis. This combination is capable of reversing liver failure and prevents the need of liver transplantation. Both trientine and zinc are not registered in Malaysia. Therefore, liver transplantation was probably the only treatment option for this patient. Hence, non-availability of orphan drugs in clinical practice is certainly a subject of serious concern. Systems for better management of patients with rare diseases need to be instituted by all the institutions concerned.

Magnetic resonance imaging for pain after surgical treatment for athletic pubalgia and the "sports hernia".

PubMed

Zoga, Adam C; Meyers, William C

2011-09-01

Magnetic resonance (MR) imaging technique and findings in the setting of athletic pubalgia, including injury at the rectus abdominis/adductor aponeurosis, are becoming widely recognized. A subset of these patients is treated with various pelvic floor repairs, mesh reinforcements, and tendon releases. Most of these patients do well after intervention, but some have persistent or refractory groin pain, and others eventually develop new injuries in the pubic region or elsewhere about the pelvic girdle. This review describes the expected and some unexpected MRI findings in patients with recurrent or persistent groin pain after a "sports hernia" repair. © Thieme Medical Publishers.

Is the disease course predictable in inflammatory bowel diseases?

PubMed Central

Lakatos, Peter Laszlo; Kiss, Lajos S

2010-01-01

During the course of the disease, most patients with Crohn’s disease (CD) may eventually develop a stricturing or a perforating complication, and a significant number of patients with both CD and ulcerative colitis will undergo surgery. In recent years, research has focused on the determination of factors important in the prediction of disease course in inflammatory bowel diseases to improve stratification of patients, identify individual patient profiles, including clinical, laboratory and molecular markers, which hopefully will allow physicians to choose the most appropriate management in terms of therapy and intensity of follow-up. This review summarizes the available evidence on clinical, endoscopic variables and biomarkers in the prediction of short and long-term outcome in patients with inflammatory bowel diseases. PMID:20518079

Surgical excision for recurrent herpes simplex virus 2 (HSV-2) anogenital infection in a patient with human immunodeficiency virus (HIV).

PubMed

Arinze, Folasade; Shaver, Aaron; Raffanti, Stephen

2017-10-01

Recurrent anogenital herpes simplex virus infections are common in patients with human immunodeficiency virus (HIV), of whom approximately 5% develop resistance to acyclovir. We present a case of a 49-year-old man with HIV who had an 8-year history of recurrent left inguinal herpes simplex virus type 2 ulcerations. He initially responded to oral acyclovir, but developed resistance to acyclovir and eventually foscarnet. The lesion progressed to a large hypertrophic mass that required surgical excision, which led to resolution without recurrences. Our case highlights the importance of surgical excision as a treatment option in refractory herpes simplex virus anogenital infections.

Aortic intimal sarcoma masquerading as bilateral renal artery stenosis.

PubMed

Sethi, Supreet; Pothineni, Naga Krishna; Syal, Gaurav; Ali, Syed Mujtaba; Krause, Michelle W

2013-01-01

Aortic intimal sarcoma is a rare tumor with poor prognosis. The most common manifestations are thromboembolic phenomena and vascular obstruction. We present a case of aortic intimal sarcoma causing bilateral renal artery stenosis which manifested as resistant hypertension and acute kidney inury. Multiple attempts to stent the renal arteries were unsuccessful. Eventually the patient developed acute limb ischemia and oliguric kidney failure as complications of the primary tumor.

Sunitinib dose escalation overcomes transient resistance in clear cell renal cell carcinoma and is associated with epigenetic modifications.

PubMed

Adelaiye, Remi; Ciamporcero, Eric; Miles, Kiersten Marie; Sotomayor, Paula; Bard, Jonathan; Tsompana, Maria; Conroy, Dylan; Shen, Li; Ramakrishnan, Swathi; Ku, Sheng-Yu; Orillion, Ashley; Prey, Joshua; Fetterly, Gerald; Buck, Michael; Chintala, Sreenivasulu; Bjarnason, Georg A; Pili, Roberto

2015-02-01

Sunitinib is considered a first-line therapeutic option for patients with advanced clear cell renal cell carcinoma (ccRCC). Despite sunitinib's clinical efficacy, patients eventually develop drug resistance and disease progression. Herein, we tested the hypothesis whether initial sunitinib resistance may be transient and could be overcome by dose increase. In selected patients initially treated with 50 mg sunitinib and presenting with minimal toxicities, sunitinib dose was escalated to 62.5 mg and/or 75 mg at the time of tumor progression. Mice bearing two different patient-derived ccRCC xenografts (PDX) were treated 5 days per week with a dose-escalation schema (40-60-80 mg/kg sunitinib). Tumor tissues were collected before dose increments for immunohistochemistry analyses and drug levels. Selected intrapatient sunitinib dose escalation was safe and several patients had added progression-free survival. In parallel, our preclinical results showed that PDXs, although initially responsive to sunitinib at 40 mg/kg, eventually developed resistance. When the dose was incrementally increased, again we observed tumor response to sunitinib. A resistant phenotype was associated with transient increase of tumor vasculature despite intratumor sunitinib accumulation at higher dose. In addition, we observed associated changes in the expression of the methyltransferase EZH2 and histone marks at the time of resistance. Furthermore, specific EZH2 inhibition resulted in increased in vitro antitumor effect of sunitinib. Overall, our results suggest that initial sunitinib-induced resistance may be overcome, in part, by increasing the dose, and highlight the potential role of epigenetic changes associated with sunitinib resistance that can represent new targets for therapeutic intervention. ©2014 American Association for Cancer Research.

Hyperacute cerebral fat embolism in a patient with femoral shaft fracture.

PubMed

Chen, Po-Chuan; Hsu, Chin-Wang; Liao, Wen-I; Chen, Yu-Long; Ho, Cheng-Hsuan; Tsai, Shih-Hung

2013-09-01

Fat embolism syndrome is a potentially fatal complication and occurs most commonly after long bone fracture. In patients who sustained severe trauma, both cerebral fat embolism(CFE) and diffuse axonal injury (DAI) could be the cause of altered consciousness in the absence of marked intracranial lesions in cranial computed tomography. However, distinguishing CFE and DAI can be difficult clinically. Generally, DAI develops immediately after the insult, whereas CFE occurs 48 to 72 hours after the trauma and even after internal fixation for the fractures. Fat embolism syndrome develops within an average of 48.5 hours after long bone fracture [1] but has never been reported to occur in less than 2 hours. Here, we present a patient who developed hyperacute CFE and eventually had poor neurological outcome, in contrast to previous reports stating that CFE usually has a long latent period and favorable outcomes.

Real-time landmark-based unrestrained animal tracking system for motion-corrected PET/SPECT imaging

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

J.S. Goddard; S.S. Gleason; M.J. Paulus

2003-08-01

Oak Ridge National Laboratory (ORNL) and Jefferson Lab and are collaborating to develop a new high-resolution single photon emission tomography (SPECT) instrument to image unrestrained laboratory animals. This technology development will allow functional imaging studies to be performed on the animals without the use of anesthetic agents. This technology development could have eventual clinical applications for performing functional imaging studies on patients that cannot remain still (Parkinson's patients, Alzheimer's patients, small children, etc.) during a PET or SPECT scan. A key component of this new device is the position tracking apparatus. The tracking apparatus is an integral part of themore » gantry and designed to measure the spatial position of the animal at a rate of 10-15 frames per second with sub-millimeter accuracy. Initial work focuses on brain studies where anesthetic agents or physical restraint can significantly impact physiologic processes.« less

A case of ALK-rearranged non-small cell lung cancer that responded to ceritinib after development of resistance to alectinib.

PubMed

Makuuchi, Yosuke; Hayashi, Hidetoshi; Haratani, Koji; Tanizaki, Junko; Tanaka, Kaoru; Takeda, Masayuki; Sakai, Kazuko; Shimizu, Shigeki; Ito, Akihiko; Nishio, Kazuto; Nakagawa, Kazuhiko

2018-05-01

The second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and ceritinib are standard treatment options for patients with non-small cell lung cancer (NSCLC) positive for ALK fusion genes. However, almost all patients eventually develop resistance to these drugs. We here report a case of ALK -rearranged NSCLC that developed resistance to alectinib but remained sensitive to ceritinib. The L1196M mutation within the ALK fusion gene was detected after failure of consecutive treatment with crizotinib and alectinib, but no other mechanism underlying acquired resistance to ALK-TKIs was found to be operative. Given the increasing application of ALK-TKIs to the treatment of patients with ALK -rearranged NSCLC, further clinical evaluation is warranted to provide a better understanding of the mechanisms of acquired resistance to these agents and to inform treatment strategies for such tumors harboring secondary mutations.

Recurrent implantation failure in IVF: features of cycles that eventually ended in conception.

PubMed

Bord, Ilia; Tamir, Belle; Harlev, Avraham; Har-Vardi, Iris; Lunenfeld, Eitan; Friger, Michael; Levitas, Eliahu

2016-04-01

To evaluate the characteristics of patients and IVF cycles with recurrent implantation failure who eventually succeeded to conceive compared to those who failed to do so. In a retrospective study, we explored our database for patients younger than 35 years old who underwent at least three unsuccessful fresh IVF cycles. The following parameters were analyzed: cause of infertility, FSH level, stimulation cycle characteristics, fertilization rate, the type of luteal support, and cycle outcome. Uterine cavity assessment was also included. The relationship between endometrial scratching and the outcome of the following IVF cycle was assessed for the subsequent pregnancy rate. The study included 184 patients who underwent 854 IVF cycles. There were no statistically significant differences between patients who eventually conceived and those who did not in terms of ovarian reserve and response to gonadotropin treatment. IVF cycles that eventually ended with conception were characterized by shorter stimulation (10.87 ± 2.17 versus 11.34 ± 2.33 days, p < 0.05), higher estrogen level on the day of hCG administration (1661 ± 667 versus 1472 ± 633 pg/ml, p = 0.009), more fertilized oocytes via ICSI (5.04 ± 4.29 versus 3.85 ± 3.45, p = 0.002), and more embryos available for transfer (5.98 ± 3.89 versus 5.12 ± 3.31, p = 0.002). Combined estrogen and progesterone luteal support combined with endometrial scratching prior to the subsequent IVF cycle has been positively related to increased pregnancy rates. Young patients with RIF having a normal ovarian reserve and satisfactory ovarian response to superovulation should be encouraged to pursue IVF, even though the probability to conceive is relatively low compared to the general IVF population.

A patient with Graves' disease who survived despite developing thyroid storm and lactic acidosis.

PubMed

Yoshino, Tetsuhiro; Kawano, Daisuke; Azuhata, Takeo; Kuwana, Tsukasa; Kogawa, Rikimaru; Sakurai, Atsushi; Tanjoh, Katsuhisa; Yanagawa, Tatsuo

2010-11-01

A 56-year-old woman with Graves' disease presented with the complaints of diarrhea and palpitations. Physical examination and laboratory data revealed hypothermia and signs of mild hyperthyroidism, heart failure, hepatic dysfunction with jaundice, hypoglycemia, and lactic acidosis. The patient was diagnosed as having developed the complication of thyroid storm in the absence of marked elevation of the thyroid hormone levels, because of the potential hepatic and cardiac dysfunctions caused by heavy alcohol drinking. A year later, after successful treatment, the patient remains well without any clinical evidence of heart failure or hepatic dysfunction. Thyroid storm associated with lactic acidosis and hypothermia is a serious condition and has rarely been reported. Prompt treatment is essential even if the serum thyroid hormone levels are not markedly elevated. We present a report about this patient, as her life could eventually be saved.

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution.

PubMed

Dilia, Giuggioli; Michele, Colaci; Emanuele, Cocchiara; Amelia, Spinella; Federica, Lumetti; Clodoveo, Ferri

2018-01-01

Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0-156) months. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset.

Should we ever give steroids to ARDS patients?

PubMed Central

Hough, Catherine L.

2014-01-01

The development and severity of ARDS are closely related to dysregulated inflammation, and the duration of ARDS and eventual outcomes are related to persistent inflammation and abnormal fibroproliferation. Corticosteroids are potent modulators of inflammation and inhibitors of fibrosis that have been used since the description of the acute respiratory distress syndrome in attempts to improve outcomes. Randomized controlled trials of steroids for ARDS have answered some, but not all, questions regarding efficacy for prevention and treatment. First, there is no evidence that corticosteroids prevent the development of ARDS among patients at risk. Second, high dose and short course treatment with steroids does not improve the outcomes of patients with ARDS. And third, while there is compelling data that low dose and prolonged treatment with steroids improves pulmonary physiology in patients with ARDS, additional studies are needed to recommend treatment with steroids for ARDS. PMID:25453425

Underlying pathology and associated factors of hemiplegic shoulder pain.

PubMed

Kalichman, Leonid; Ratmansky, Motti

2011-09-01

The prevalence of hemiplegic shoulder pain is approximately 22%-23% in the general population of stroke survivors and approximately 54%-55% among stroke patients in rehabilitation settings. Hemiplegic shoulder pain causes a reduced quality-of-life, poor functional recovery, depression, disturbed sleep, and prolonged hospitalization. Herein, we attempted to understand, based on a literature review and experts' opinion, the pathologic processes underlying hemiplegic shoulder pain and the major associated factors contributing to its development. The systematization of underlying pathologies was proposed, which might eventually enable a more constructive clinical approach in evaluating and treating patients with hemiplegic shoulder pain.

Combination Therapy Improves Survival in Prostate Cancer Model | Center for Cancer Research

Cancer.gov

Surgery and radiotherapy are the recommended treatments for localized prostate cancer. Recurrent prostate cancer, however, is often treated with androgen-deprivation therapy. Most patients who undergo this type of therapy eventually develop castration-resistant prostate cancer (CRPC). Though initially androgen-related therapies for CRPC had been thought to be ineffective, further studies have demonstrated that the disease remains dependent on the signaling of androgens, such as testosterone, for its continued progression. This development suggests that alternative strategies for manipulating androgen signaling may prove useful for treating CRPC.

Sonographic Characteristics and Interval Changes of Subacute Thyroiditis.

PubMed

Lee, Yoo Jin; Kim, Dong Wook

2016-08-01

This study aimed to assess the sonographic characteristics and interval changes of subacute thyroiditis using follow-up sonography. From January 2008 to December 2014, 85 patients with clinically suspected subacute thyroiditis underwent sonographic examinations by a single radiologist. Subacute thyroiditis was confirmed on the basis of the clinical, sonographic, and cytohistopathologic findings. On the initial and follow-up sonograms, the individual sonographic findings and interval changes were retrospectively investigated by the same radiologist. According to the sonographic configuration, subacute thyroiditis lesions were categorized as nodular or non-nodular. The interval changes in the lesions were classified as follows: "disappeared," "decreased," "increased," "eventually smaller," "eventually larger," or "no interval change." Subacute thyroiditis was confirmed in 64 of the 85 patients. In these 64 patients, nodular (n = 39) and non-nodular (n = 35) lesions were found; 10 patients had both nodular and non-nodular lesions. Of the 64 patients, 41 underwent sonographic follow-up. In both nodular and non-nodular lesions, the common interval changes included disappeared, decreased, and eventually smaller patterns. Although the increased pattern was found only in 4 nodular lesions, there was no significant difference in the interval changes between nodular and non-nodular lesions. On follow-up sonography, a new lesion was detected in 6 patients. The prevalence rate of nodular subacute thyroiditis lesions on sonography was high, and the interval changes in the lesions were variable.

Retaining customers in a managed care market. Hospitals must understand the connection between patient satisfaction, loyalty, retention, and revenue.

PubMed

Gemme, E M

1997-01-01

Traditionally, health care patients have been treated by health care professionals as people with needs rather than as customers with options. Although managed care has restricted patient choice, choice has not been eliminated. The premise of this article is that patients are primary health care consumers. Adopting such a premise and developing an active customer retention program can help health care organizations change their culture for the better, which may lead to higher customer retention levels and increased revenues. Customer retention programs based on service excellence that empower employees to provide excellent care can eventually lead to a larger market share for health care organizations trying to survive this era of intense competition.

Large datasets, logistics, sharing and workflow in screening.

PubMed

Cook, Tessa S

2018-03-29

Cancer screening initiatives exist around the world for different malignancies, most frequently breast, colorectal, and cervical cancer. A number of cancer registries exist to collect relevant data, but while these data may include imaging findings, they rarely, if ever, include actual images. Additionally, the data submitted to the registry are usually correlated with eventual cancer diagnoses and patient outcomes, rather than used with the individual's future screenings. Developing screening programs that allow for images to be submitted to a central location in addition to patient meta data and used for comparison to future screening exams would be very valuable in increasing access to care and ensuring that individuals are effectively screened at appropriate intervals. It would also change the way imaging results and additional patient data are correlated to eventual outcomes. However, it introduces logistical challenges surrounding secure storage and transmission of data to subsequent screening sites. In addition, in the absence of standardized protocols for screening, comparing current and prior imaging, especially from different equipment, can be challenging. Implementing a large-scale screening program with an image-enriched screening registry-effectively, an image-enriched electronic screening record-also requires that incentives exist for screening sites, physicians, and patients to participate; to maximize coverage, participation may have to be supported by government agencies. Workflows will also have to be adjusted to support registry participation for all screening patients in an effort to create a large, robust data set that can be used for future screening efforts as well as research initiatives.center.

Repair Mechanism of UV-damaged DNA in Xeroderma Pigmentosum | Center for Cancer Research

Cancer.gov

Xeroderma pigmentosum (XP) is a rare, inherited disorder characterized by extreme skin sensitivity to ultraviolet (UV) rays from sunlight. XP is caused by mutations in genes involved in nucleotide excision repair (NER) of damaged DNA. Normal cells are usually able to fix this damage before it leads to problems; however, the DNA damage is not repaired normally in patients with XP. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die. XP patients have more than a 10,000-fold increased risk of developing skin cancer. Kenneth Kraemer, M.D., in CCR’s Dermatology Branch, has been studying XP patients at the Clinical Center for more than 40 years.

Prediction of disease course in inflammatory bowel diseases.

PubMed

Lakatos, Peter Laszlo

2010-06-07

Clinical presentation at diagnosis and disease course of both Crohn's disease (CD) and ulcerative colitis are heterogeneous and variable over time. Since most patients have a relapsing course and most CD patients develop complications (e.g. stricture and/or perforation), much emphasis has been placed in the recent years on the determination of important predictive factors. The identification of these factors may eventually lead to a more personalized, tailored therapy. In this TOPIC HIGHLIGHT series, we provide an update on the available literature regarding important clinical, endoscopic, fecal, serological/routine laboratory and genetic factors. Our aim is to assist clinicians in the everyday practical decision-making when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases.

Patient-Focused Drug Development: A New Direction for Collaboration.

PubMed

Perfetto, Eleanor M; Burke, Laurie; Oehrlein, Elisabeth M; Epstein, Robert S

2015-01-01

Patient-Focused Drug Development (PFDD) is a new initiative from the Food and Drug Administration (FDA) intended to bring patient perspectives into an earlier stage of product development. The goal is that patients will be able to provide context for benefit-risk assessments and input to review divisions, and also aid in the development of new assessment tools, study endpoints, and risk communications. This paper provides a summary on what is known to date about FDA's PFDD initiative and describes implications for patients, researchers, payers, and the biopharmaceutical industry. It also provides a roadmap for stakeholders to consider in defining their role in and in shaping PFDD's direction, and for expanding PFDD principles to conditions beyond the current 20 under FDA consideration. A search was conducted of the peer-reviewed and gray literature using PubMed and Google. This included laws, FDA guidance documents, the peer-reviewed literature, and FDA presentations for content relevant to the search term "patient-focused drug development." Currently, FDA activities within PFDD are limited to gaining patient insights through 20 disease-specific meetings. However, many stakeholders see the initiative much more generally as representing a broad shift toward patient centeredness in biopharmaceutical product development. Depending upon the trajectory taken and whether or not all PFDD aims are eventually addressed, the initiative has the potential to change product development in fundamental ways. Further research should explore how patient input on disease manifestation and treatment options is best ascertained from patients and documented before initiating and during drug development.

Central nervous system aspergillosis in an immunocompetent patient: cure in a hospice setting with very high-dose itraconazole.

PubMed

Palanisamy, Akilesh; Chao, Stephanie D; Fouts, Michelle; Kerr, Derek

2005-01-01

Aspergillosis of the central nervous system (CNS) is a rare condition with exceedingly high mortality. This study describes the case of an immunocompetent 42-year-old man with a history of intravenous drug use and hepatitis C who developed multiple Aspergillus lesions in the cerebellum. Despite neurosurgery and antifungal therapy with amphotericin B, he had a protracted hospital course with multiple complications, eventually developing cognitive and motor impairment due to progressive cerebellar lesions. After transfer to hospice and palliative care service, oral itraconazole was escalated to 1600 mg/day with the hope of palliating headache, nausea, and cognitive impairment. Remarkably, the patient stabilized and improved over time. After 14 months, this unprecedented high-dose regimen was discontinued, and the patient was discharged home with only mild cerebellar motor impairment.

Offspring of depressed and anxious patients: Help-seeking after first onset of a mood and/or anxiety disorder.

PubMed

Havinga, Petra J; Hartman, Catharina A; Visser, Ellen; Nauta, Maaike H; Penninx, Brenda W J H; Boschloo, Lynn; Schoevers, Robert A

2018-02-01

Offspring of patients with depressive and/or anxiety disorders are at high risk of developing a similar disorder themselves. Early recognition and treatment may have substantial effects on prognosis. The main aim of this study was to examine the time to initial help-seeking and its determinants in offspring after the first onset of a mood and/or anxiety disorder. Data are presented of 215 offspring with a mood and/or anxiety disorder participating in a cohort study with 10 year follow-up. We determined age of disorder onset and age of initial help-seeking. Offspring characteristics (gender, IQ, age of onset, disorder type, suicidal ideation) and family characteristics (socioeconomic status, family functioning) were investigated as potential predictors of the time to initial help-seeking. The estimated overall proportion of offspring of depressed/anxious patients who eventually seek help after onset of a mood and/or anxiety disorder was 91.9%. The time to initial help-seeking was more than two years in 39.6% of the offspring. Being female, having a mood disorder or comorbid mood and anxiety disorder (relative to anxiety) and a disorder onset in adolescence or adulthood (relative to childhood) predicted a shorter time to initial help-seeking. Baseline information relied on retrospective reports. Age of onsets and age of initial help-seeking may therefore be subject to recall bias. Although most offspring eventually seek help after onset of a mood/anxiety disorder, delays in help-seeking were common, especially in specific subgroups of patients. This information may help to develop targeted strategies to reduce help-seeking delays. Copyright © 2017 Elsevier B.V. All rights reserved.

Cytomegalovirus Retinitis in Three Pediatric Cases with Acute Lymphoblastic Leukemia: Case Series and Review of the Literature.

PubMed

Demir, Sevliya Öcal; Çeliker, Hande; Karaaslan, Ayşe; Kadayifci, Eda Kepenekli; Akkoç, Gülşen; Atıcı, Serkan; Yakut, Nurhayat; Şenay, Emel; Kazokoğlu, Haluk; Koç, Ahmet; Bakır, Mustafa; Soysal, Ahmet

2016-11-22

Cytomegalovirus (CMV) retinitis is typically diagnosed in patient with AIDS and those who underwent allogeneic hematopoietic cell transplant. However, it may develop in patients with acute lymphoblastic leukemia (ALL) who have not undergone hematopoietic cell transplantation. To increase awareness of CMV retinitis in this group, we describe 3 patients ages 3, 9, and 12, with ALL who developed CMV retinitis. The diagnosis of CMV retinitis was made on the basis of ophthalmological findings suggesting typical retinal lesions. In 2 cases, CMV DNAemia was present, while in 1 patient CMV DNA was detected only in vitreous fluid using the PCR technique. All cases were treated with intravenous ganciclovir for 2 or 3 weeks as induction therapy, followed by oral valganciclovir prophylaxis. Initially, active retinitis lesions resolved in all cases; however, in 1 patient CMV retinitis relapsed 3 times during follow-up. In this case, by using foscarnet therapy, satisfactory responses were achieved and the progression of CMV retinitis lesions stopped and eventually regressed.

The natural history and management of patients with congenital deficits associated with lumbosacral lipomas.

PubMed

Tu, Albert; Hengel, Ross; Cochrane, D Douglas

2016-04-01

Many patients with lumbosacral lipoma are asymptomatic; however, a significant proportion will have neurological deficits present at birth. Implication of these deficits with respect to natural history and management are not well understood. A retrospective review of all infants with lumbosacral lipoma seen at BCCH between 1997 and 2013 was carried out. The study population was stratified on the presence of a congenital, non-progressive deficit and subdivided on treatment approach. The subsequent developments of deficits resulting in untethering procedures were recorded. Of the 44 infants in this study, 24 patients had no neurologic deficit while 20 patients had a fixed, non-progressive deficit evident at birth. Ten of 24 patients without a neurological deficit at birth underwent a prophylactic untethering with 3 eventually requiring repeat untethering after, on average, 62.7 months. Eleven of 14 asymptomatic, monitored patients required untethering for clinical deterioration. Two required a second untethering procedure after 48.7 months. Ten of 20 infants with congenital deficits present at birth underwent prophylactic untethering, and 4 required further surgery after 124 months. Ten patients underwent observation with 8 eventually requiring surgery. Two required repeat untethered after 154 months. The complication rates and operative burden for patients are similar whether prophylactic or delayed surgery is performed. The presence of congenital neurologic deficit does not affect the likelihood of deterioration in patients managed expectantly; prophylactic detethering of these patients did not prevent delayed neurologic deterioration. Comparing the need for repeat surgery in prophylactically untethered patients with initial untethering of patients operated upon at the time of deterioration, prophylactic untethering may confer a benefit with respect to subsequent symptomatic tethering if complication rates are low. However, in a setting with multidisciplinary follow-up, a period of observation for patients and intervention when patients become symptomatic is an acceptable approach for patients with or without congenital deficits.

Utility of pleural fluid analysis in predicting tube thoracostomy/decortication in parapneumonic effusions.

PubMed

Poe, R H; Marin, M G; Israel, R H; Kallay, M C

1991-10-01

Recommended criteria for surgical drainage of parapneumonic effusions include evidence of frank purulence, a glucose level less than 40 mg/dl, a pH of less than 7.00, or an LDH greater than 1,000 IU/L. To test the utility of these criteria, we reviewed the three-year experience of three Rochester, NY, hospitals. We identified 133 patients undergoing thoracentesis for putative parapneumonic effusions. Of 91 patients with neutrophilic exudates, 43 met one or more criteria for tube thoracostomy: 48 did not. Twenty-one of the 43, including 9 with frank empyema, underwent immediate drainage. Of the 22 who did not, 11 eventually required tube thoracostomy and/or decortication. Of the 48 not meeting any of the criteria, 7 also came to surgery. Using whether the patients eventually underwent surgery as a measure of outcome, we calculated for those patients not undergoing immediate drainage the sensitivity, specificity, positive predictive values, and negative predictive values for each of the criteria. The four criteria have relatively high specificity ranging from 82 to 96 percent, but have low sensitivity varying from only 18 percent for a positive Gram stain to 53 percent for a fluid LDH greater than 1,000 IU/L. We conclude that these criteria have limited usefulness in predicting the need for eventual chest tube drainage/decortication. Patients not meeting the criteria require close follow-up as well.

Traumatic Tricuspid Regurgitation Following Cardiac Massage

PubMed Central

Na, Sungwon; Nam, Sang Beom; Lee, Yong Kyung; Oh, Young Jun

2007-01-01

We report a 66-yr-old male patient who developed tricuspid regurgitation secondary to internal cardiac massage. After uneventful off-pump coronary artery bypass surgery, the subject experienced cardiac arrest in the intensive care unit. External cardiac massage was initiated and internal cardiac massage was performed eventually. A transesophageal echocardiography revealed avulsion of the anterior papillary muscle and chordae to the anterior leaflet after successful cardiopulmonary resuscitation. Emergency repair of the papillary muscle was performed under cardiopulmonary bypass. PMID:17728519

US FDA perspective on regulatory issues affecting circulatory assist devices.

PubMed

Sapirstein, Wolf; Chen, Eric; Swain, Julie; Zuckerman, Bram

2006-11-01

There has been a rapid development in mechanical circulatory support systems in the decade since the US FDA first approved a mechanical device to provide the circulatory support lacking from a failing heart. Devices are presently approved for marketing by the FDA to replace a failing ventricle, the Ventricular Assist Device or the entire heart, Total Artificial Heart. Contemporaneous with, and permitted by, improvement in technology and design, devices have evolved from units located extracorporeally to paracorporeal systems and totally implanted devices. Clinical studies have demonstrated a parallel improvement in the homeostatic adequacy of the circulatory support provided. Thus, while the circulatory support was initially tolerated for short periods to permit recovery of cardiac function, this technology eventually provided effective circulatory support for increasing periods that permitted the FDA to approve devices for bridging patients in end-stage cardiac failure awaiting transplant and eventually a device for destination therapy where patients in end-stage heart failure are not cardiac transplant candidates. The approved devices have relied on displacement pumps that mimic the pulsatility of the physiological system. Accelerated development of more compact devices that rely on alternative pump mechanisms have challenged both the FDA and device manufacturers to assure that the regulatory requirements for safety and effectiveness are met for use of mechanical circulatory support systems in expanded target populations. An FDA regulatory perspective is reviewed of what can be a potentially critical healthcare issue.

Anaplastic Large Cell Lymphoma Associated With Breast Implants

PubMed Central

Ravi-Kumar, Shalini; Sanaei, Omid; Vasef, Mohammad; Rabinowitz, Ian; Fekrazad, Mohammad Houman

2012-01-01

A forty two years old woman with a history of bilateral breast augmentation for cosmetic reasons was presented for poor healing of the surgical site. Tissue and periprosthetic fluid were removed from the wound site revealing an atypical lymphoid infiltrate. Subsequently the patient developed axillary lymph adenopathy. Excisional biopsy was performed. Flow cytometry was non-diagnostic. She continued to heal poorly and eventually had removal of implant during a simple mastectomy. A nodular area in the breast specimen showed ALK negative anaplastic large cell lymphoma (ALCL). The patient was treated in the private section, with only a pathology consultation being done at our institution (Figures 1-3). PMID:25734041

Pemphigus foliaceus with pustular presentation in a patient with psoriasis*

PubMed Central

de Sousa, Vando Barbosa; Santana, Cândida Naira Lima e Lima; Pereira, Daniele do Nascimento; Gripp, Alexandre Carlos

2017-01-01

Pemphigus foliaceus is a chronic autoimmune disease of the skin, clinically characterized by scaly and crusty cutaneous erosions involving the seborrheic areas. The patient can eventually become erythrodermic. There are reports of atypical cases of pemphigus foliaceus with pustules and neutrophils, and clinical differentiation from generalized pustular psoriasis of von Zumbusch is difficult. We report the case of a 55-year-old man with a history of psoriasis vulgaris that has developed pemphigus foliaceus with pustules, triggered by withdrawal of systemic corticosteroids. This is the first report associating this atypical form of pemphigus with psoriasis, suggesting that an overlap with generalized pustular psoriasis can occur. PMID:29267466

West Nile virus encephalomyelitis with polio-like paralysis & nigral degeneration.

PubMed

Schafernak, Kristian T; Bigio, Eileen H

2006-11-01

Patients infected with West Nile virus (WNV) may develop acute neurologic disease, which can be severe or even fatal, including WNV meningitis, encephalitis, and an irreversible acute flaccid paralysis or poliomyelitis-like syndrome. Movement disorders have also been described. We report combined neuronal loss, gliosis, and neurofibrillary tangle formation in the substantia nigra of a 41-year-old man with a history of WNV encephalomyelitis and poliomyelitis-like paralysis. Clinically our patient did not display parkinsonism, however, it is interesting to speculate whether, in the absence of the residual subacute poliomyelitis-like syndrome, the neuropathologic findings could have eventually evolved clinically into WNV-associated postencephalitic parkinsonism.

Steroid Induced Bilateral Avascular Necrosis of Head of Femur in an Adult Male Patient - A Case Report.

PubMed

Jadeja, Dharamvirsinh; Solanki, Vipul; Chavada, Bhavesh; Tripathi, Chandrabhanu

2016-01-01

A 28 year old male patient, known case of pemphigus vulgaris was on dexamethasone pulse therapy. Total 7 pulses were given after that he developed avascular necrosis of head of femur on both sides, which was confirmed by digital X- ray and MRI. Avascular necrosis is a disabling and progressive condition in young patients gradually leads to femoral head collapse and eventual total hip arthroplasty. As per WHO-UMC causality assessment criteria, the association between reaction and drug was possible, Naranjo's score was 7. According to Modified Schumock and Thornton's criteria, this reaction was not preventable. The Modified Hartwig and Siegel's scale showed that the reaction was severe (level 6). Here we present a case where the use of steroid for pemphigus vulgaris resulting in the development of bilateral avascular necrosis of head of femur.

Local and Regional Spread of Primary Conjunctival Squamous Cell Carcinoma.

PubMed

Desai, Shilpa J; Pruzan, Noelle L; Geske, Michael J; Jeng, Bennie H; Bloomer, Michele M; Vagefi, M Reza

2016-04-06

Two cases of biopsy-proven conjunctival squamous cell carcinoma (SCC) that developed local and regional spread are described. The cases involved a 65-year-old woman and a 79-year-old man who were initially treated at outside institutions for SCC of the conjunctiva. The patients did not have a history of immune compromise. The female patient presented with direct extension into the lacrimal gland but deferred recommended exenteration. Despite eventual exenteration, she developed metastasis to a neck node 6 months later, which was treated with radiotherapy. The male patient presented with local recurrence and a parotid node metastasis treated with exenteration, parotidectomy, selective neck dissection, and postoperative radiotherapy. Review of the outside pathology of both cases revealed positive tumor margins at the time of original resection. Local control of conjunctival SCC is of critical importance to reduce the risk of orbital extension and regional spread.

Deep Sternal Wound Infection after Open-Heart Surgery: A 13-Year Single Institution Analysis.

PubMed

Juhl, Alexander Andersen; Hody, Sofie; Videbaek, Tina Senholt; Damsgaard, Tine Engberg; Nielsen, Per Hostrup

2017-04-20

The present study aimed to compare the clinical outcome for patients with or without muscle flap reconstruction after deep sternal wound infection due to open-heart surgery. The study was a retrospective cohort study, including patients who developed deep sternal wound infection after open-heart surgery in the Western Denmark Region from 1999 to 2011. Journals of included patients were reviewed for clinical data regarding the treatment of their sternal defect. Patients were divided into two groups depending on whether they received a muscle-flap-based sternal reconstruction or traditional rewiring of the sternum. A total of 130 patients developed deep sternal wound infection in the study period. In all, 12 patients died before being discharged, leaving a total of 118 patients for analysis. Of these, 50 (42%) patients received muscle flap reconstruction. Muscle flap recipients had significantly longer total hospital stays (p <0.001). However, after receiving muscle flap reconstruction, patients were discharged after a median of 14 days, with 74% not needing additional surgery. It is difficult to predict which patients eventually require muscle flap reconstruction after deep sternal wound infection. Although patients receiving muscle flap reconstructions have longer hospital stays, they are quickly discharged after the reconstruction.

CCC meets ICU: redefining the role of critical care of cancer patients.

PubMed

von Bergwelt-Baildon, Michael; Hallek, Michael J; Shimabukuro-Vornhagen, Alexander A; Kochanek, Matthias

2010-11-08

Currently the majority of cancer patients are considered ineligible for intensive care treatment and oncologists are struggling to get their patients admitted to intensive care units. Critical care and oncology are frequently two separate worlds that communicate rarely and thus do not share novel developments in their fields. However, cancer medicine is rapidly improving and cancer is eventually becoming a chronic disease. Oncology is therefore characterized by a growing number of older and medically unfit patients that receive numerous novel drug classes with unexpected side effects. All of these changes will generate more medically challenging patients in acute distress that need to be considered for intensive care. An intense exchange between intensivists, oncologists, psychologists and palliative care specialists is warranted to communicate the developments in each field in order to improve triage and patient treatment. Here, we argue that "critical care of cancer patients" needs to be recognized as a medical subspecialty and that there is an urgent need to develop it systematically. As prognosis of cancer improves, novel therapeutic concepts are being introduced and more and more older cancer patients receive full treatment the number of acutely ill patients is growing significantly. This development a major challenge to current concepts of intensive care and it needs to be redefined who of these patients should be treated, for how long and how intensively.

Anesthesiology training using 3D imaging and virtual reality

NASA Astrophysics Data System (ADS)

Blezek, Daniel J.; Robb, Richard A.; Camp, Jon J.; Nauss, Lee A.

1996-04-01

Current training for regional nerve block procedures by anesthesiology residents requires expert supervision and the use of cadavers; both of which are relatively expensive commodities in today's cost-conscious medical environment. We are developing methods to augment and eventually replace these training procedures with real-time and realistic computer visualizations and manipulations of the anatomical structures involved in anesthesiology procedures, such as nerve plexus injections (e.g., celiac blocks). The initial work is focused on visualizations: both static images and rotational renderings. From the initial results, a coherent paradigm for virtual patient and scene representation will be developed.

Developing Practice Guidelines for Psychoanalysis

PubMed Central

GRAY, SHEILA HAFTER

1996-01-01

Consensus-based practice guidelines codify clinical intelligence and the rich oral tradition in medicine. Because they reflect actual practice, they are readily accepted by clinicians as a basis for external review. This article illustrates the development of guidelines for a psychoanalytic approach to the large pool of patients who present with a depression. It suggests an integrated biopsychosocial approach to these individuals that is useful in current practice, and it offers propositions that may be tested in future research undertakings. Eventually, practice guidelines such as these may form the basis of economical systems of health care that avoid arbitrary, clinically untenable limitations on services. PMID:22700290

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

Multiple sclerosis - New treatment modalities

PubMed Central

Totaro, Rocco; Di Carmine, Caterina; Marini, Carmine; Carolei, Antonio

2015-01-01

Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability. The place in therapy of newer treatment implies careful balancing of risk-benefit profile as well as accurate patient selection. Hence the widening of therapeutic arsenal provides greater opportunity for personalized therapy but also entails a complex trade-off between efficacy, tolerability, safety and eventually patient preference. PMID:26831413

Prediction of disease course in inflammatory bowel diseases

PubMed Central

Lakatos, Peter Laszlo

2010-01-01

Clinical presentation at diagnosis and disease course of both Crohn’s disease (CD) and ulcerative colitis are heterogeneous and variable over time. Since most patients have a relapsing course and most CD patients develop complications (e.g. stricture and/or perforation), much emphasis has been placed in the recent years on the determination of important predictive factors. The identification of these factors may eventually lead to a more personalized, tailored therapy. In this TOPIC HIGHLIGHT series, we provide an update on the available literature regarding important clinical, endoscopic, fecal, serological/routine laboratory and genetic factors. Our aim is to assist clinicians in the everyday practical decision-making when choosing the treatment strategy for their patients suffering from inflammatory bowel diseases. PMID:20518078

Nasal septal abscess caused by anaerobic bacteria of oral flora.

PubMed

Hyo, Yukiyoshi; Fukushima, Hisaki; Harada, Tamotsu; Hara, Hirotaka

2018-06-07

Although nasal septal abscess (NSA) was formerly common, it has become rare since the development of antibiotics. NSA, if left untreated, can lead to intracranial complications such as meningitis and eventually result in saddle-nose deformity. NSA often occurs after injury, and indigenous skin bacteria such as Staphylococcus aureus are frequently detected. We treated a patient who had injured the upper alveolus in a fall on the stairs and developed NSA two weeks later. Anaerobic bacteria, including Veillonella parvula and Peptostreptococcus sp., were detected. Symptoms were relieved by needle and incisional drainage. Our patient represents a very rare case of NSA in terms of the cause of onset and the detected bacteria. Early drainage can result in good outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Lymphoedema of the upper limb: a rare complication of thyroid surgery?

PubMed Central

Stephen, Christopher; Munnoch, David Alexander

2016-01-01

A 40-year-old woman underwent an elective thyroidectomy for a non-toxic, multinodular goitre. In the early postoperative period, the patient developed a significant unilateral swelling of the right upper limb, which was subsequently confirmed to be lymphoedema. This was eventually treated successfully using liposuction and compression garment therapies. We report the case due to its rarity and present a possible explanation for such an unexpected complication based on known anatomical variations of lymphatic drainage of the upper limb. PMID:27090542

Allergic reaction to stainless steel sternotomy wires requiring removal: A case report and literature review.

PubMed

Lopez, J; Sachithanandan, A; Leow, M

2016-06-01

Hypersensitivity to stainless steel sternal sutures are an uncommon occurrence. We present a case of such a patient who developed chronic tissue overgranulation over a sternotomy wound eight weeks post-operatively. Primary suspicion was infection, a more common complication however radiological and laboratory investigation showed otherwise. Conservative management provided limited ephemeral success. After ensuring adequate sternal bone healing, the sutures and granulation tissue were eventually surgically removed without complication and the reoperated wound healed well.

Fetal-onset Congenital Dyserythropoietic Anemia Type 1 due to a Novel Mutation With Severe Iron Overload and Severe Cholestatic Liver Disease.

PubMed

Chin, Hui-Lin; Lee, Le Ye; Koh, Pei Lin

2018-04-17

We report a rare case of severe congenital dyserythropoietic anemia type 1 with fetal onset. Our patient presented with fetal hydrops from 19 weeks of gestation, requiring multiple intrauterine transfusions. At birth, she had severe hemolytic anemia with severe jaundice, and was subsequently transfusion dependent. She eventually developed severe iron overload and fulminant liver failure before her demise at 5 months of age. Genetic testing revealed a novel mutation in CDAN1.

Toys and games in play therapy.

PubMed

Meschiany, A; Krontal, S

1998-01-01

The present article discusses the difference between play therapy with toys and play therapy with games from a psychodynamic point of view. Toys are regarded as offering the child an opportunity to develop a variety of transference reactions, while games, because of their inherent competitive characteristic, restrain the scope of possible transference reactions. The authors claim that therapists should consider these eventualities when choosing which games or toys are to be available in the therapy room. This choice might determine, in advance, the initial characteristics of the patient's transference.

Modification of the actions of some neuroactive drugs by growth hormone

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

Tang, L.C.; Cotzias, G.C.

The flat serum growth hormone (GH) patterns of untreated parkinsonian patients develop diurnal rises during treatment with levodopa. This chronic exposure to excesses of GH might lead to the eventual emergence of the ''on-off'' phenomenon, which would indicate a need for animal experiments. Pretreatment of mice with GH increased (1) cerebral dopa and dopamine concentrations in levodopa-treated mice, (2) cerebral accumulation of injected tritiated apomorphine and tritiated thymidine, and (3) behavioral responses to levodopa, L-m-tyrosine, apomorphine hydrochloride, and oxotremorine. (auth)

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution

PubMed Central

Emanuele, Cocchiara; Amelia, Spinella; Clodoveo, Ferri

2018-01-01

Background Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. Methods We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Results Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0–156) months. Conclusions LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset. PMID:29666638

Alectinib: a selective, next-generation ALK inhibitor for treatment of ALK-rearranged non-small-cell lung cancer.

PubMed

Santarpia, Mariacarmela; Altavilla, Giuseppe; Rosell, Rafael

2015-06-01

Crizotinib was the first clinically available anaplastic lymphoma kinase (ALK) inhibitor, showing remarkable activity against ALK-rearranged non-small-cell lung cancer (NSCLC). Despite initial responses, acquired resistance to crizotinib inevitably develops, with the brain being a common site of relapse. Alectinib is a highly selective, next-generation ALK inhibitor with potent inhibitory activity also against ALK mutations conferring resistance to crizotinib, including the gatekeeper L1196M substitution. In a Phase I/II study from Japan, alectinib was found to be highly active and safe in crizotinib-naïve, ALK-rearranged NSCLC patients. Alectinib also demonstrated promising antitumor activity in crizotinib-resistant patients, including those with CNS metastases. Based on these data, the drug received Breakthrough Therapy Designation by the US FDA and has been recently approved in Japan for the treatment of ALK-positive, advanced NSCLC patients. However, patients may eventually develop resistance to alectinib, highlighting the need for novel therapeutic strategies to further improve the management of ALK-rearranged NSCLC.

Development of Graft-Site Candidiasis in 3 Solid Organ Transplant Recipients from the Same Donor.

PubMed

El-Bandar, Nasrin; Kroy, Daniela C; Fuller, Tom Florian; Kramer, Jürgen; Liefeldt, Lutz; Budde, Klemens; Blobel, Conrad; Miller, Kurt; Friedersdorff, Frank

2017-07-11

BACKGROUND Graft-site candidiasis rarely develops in solid organ transplant recipients; however, severe life-threatening complications can occur. We report the course of 3 solid organ transplant recipients developing graft-site candidiasis. CASE REPORT All grafts, consisting of 2 kidneys and 1 liver, were procured from a single donor. Patient data were collected from our database. Candida albicans was isolated from a swab taken during multiple-organ recovery. Complications associated with candidiasis occurred in all 3 recipients with preservation of the liver transplant. Both renal transplant recipients had vascular complications, eventually resulting in graft nephrectomy and subsequent return to dialysis. The patients recovered completely without residual effects of their prior fungal infection. CONCLUSIONS Fungal infections in solid organ transplant recipients are rare. Since the sequelae of these infections are serious and usually pertain to more than 1 recipient at a time, antifungal prophylaxis may be warranted in select donors.

Multiple myeloma.

PubMed Central

MacLennan, I. C.; Drayson, M.; Dunn, J.

1994-01-01

Multiple myeloma occurs in over 2000 new patients in England and Wales each year. It presents most frequently as bone pain and patients tend to become dehydrated and may develop renal failure. No available treatment is curative, but about two thirds of patients achieve a stable response with low dose combination chemotherapy. Combination chemotherapy including doxorubicin and carmustine with the alkylating agents cyclophosphamide and melphalan achieve a higher stable response rate than conventional treatment with melphalan and prednisone without additional haematological toxicity. These responses are associated with loss of bone pain and patients remain symptom free for months without further treatment. Relapse occurs on average in a little under two years and, though second responses are frequently obtained, the disease eventually becomes refractory. This paper looks at who should be treated and the benefits that may be expected from the treatments available. PMID:8068084

An evaluation of bone scans as screening procedures for occult metastases in primary breast cancer.

PubMed Central

Baker, R R; Holmes, E R; Alderson, P O; Khouri, N F; Wagner, H N

1977-01-01

Preoperative bone scans were obtained in 104 patients with operable breast cancer. Areas of increased radioactivity detected by the bone scan were correlated with appropriate radiographs. One of 64 patients (1.5%) with clinical Stage I and Stage II breast cancer had a metastatic lesion detected by the preoperative bone scan. In contrast, 10 of 41 patients (24%) with Stage III breast cancer had occult metastatic lesions detected by the preoperative bone scan. The majority of patients with abnormal bone scans and no radiographic evidence of a benign lesion to explain the cause of the increased radioactivity proved to have metastatic breast cancer on follow-examination. Even though 20% of patients with operable breast cancer will eventually develop bone metastases, our results indicate that preoperative bone scans are not an effective means of predicting which patients with Stage I and Stage II disease will develop metastatic breast cancer. Because of the considerably increased frequency of detection of occult metastases in patients with Stage III breast cancer, bone scans should be obtained routinely in the preoperative assessment of these patients. Images Figs. 1a and b. Figs. 2a and b. Figs. 3a-d. PMID:889378

Enteral autonomy, cirrhosis, and long term transplant-free survival in pediatric intestinal failure patients.

PubMed

Fullerton, Brenna S; Sparks, Eric A; Hall, Amber M; Duggan, Christopher; Jaksic, Tom; Modi, Biren P

2016-01-01

Patient selection for transplant evaluation in pediatric intestinal failure is predicated on the ability to assess long-term transplant-free survival. In light of trends toward improved survival of intestinal failure patients in recent decades, we sought to determine if the presence of biopsy-proven hepatic cirrhosis or the eventual achievement of enteral autonomy were associated with transplant-free survival. After IRB approval, records of all pediatric intestinal failure patients (parenteral nutrition (PN) >90 days) treated at a single intestinal failure center from February 2002 to September 2014 were reviewed. Chi-squared, Mann-Whitney, and log-rank testing were performed as appropriate. Of 313 patients, 174 eventually weaned off PN. Liver biopsies were available in 126 patients (most common indication was intestinal failure associated liver disease, IFALD), and 23 met histologic criteria for cirrhosis. Transplant-free survival for the whole cohort of 313 patients was 94.7% at 1 year and 89.2% at 5 years. Among patients with liver biopsies, transplant-free survival in cirrhotics vs. noncirrhotics was 95.5% vs. 94.1% at one year and 95.5% vs. 86.7% at 5 years (P=0.29). Transplant-free survival in patients who achieved enteral autonomy compared with patients who remained PN dependent was 98.2% vs. 90.3% at one year and 98.2% vs. 76.9% at 5 years (P<0.001). There was no association between cirrhosis and eventual enteral autonomy (P=0.88). Achieving enteral autonomy was associated with improved transplant-free survival in pediatric intestinal failure patients. There was no association between histopathological diagnosis of cirrhosis and transplant-free survival in the cohort. These data suggest that automatic transplant referral may not be required for histopathological diagnosis of cirrhosis alone, and that ongoing efforts aimed at achievement of enteral autonomy remain paramount in pediatric intestinal failure. Copyright © 2016 Elsevier Inc. All rights reserved.

Malaria in South America: a drug discovery perspective.

PubMed

Cruz, Luiza R; Spangenberg, Thomas; Lacerda, Marcus V G; Wells, Timothy N C

2013-05-24

The challenge of controlling and eventually eradicating malaria means that new tools are urgently needed. South America's role in this fight spans both ends of the research and development spectrum: both as a continent capable of discovering and developing new medicines, and also as a continent with significant numbers of malaria patients. This article reviews the contribution of groups in the South American continent to the research and development of new medicines over the last decade. Therefore, the current situation of research targeting malaria control and eradication is discussed, including endemicity, geographical distribution, treatment, drug-resistance and diagnosis. This sets the scene for a review of efforts within South America to discover and optimize compounds with anti-malarial activity.

Predictive factors for outcomes of patients undergoing endoscopic therapy for bile leak after hepatobiliary surgery.

PubMed

Yabe, Shuntaro; Kato, Hironari; Mizukawa, Sho; Akimoto, Yutaka; Uchida, Daisuke; Seki, Hiroyuki; Tomoda, Takeshi; Matsumoto, Kazuyuki; Yamamoto, Naoki; Horiguchi, Shigeru; Tsutsumi, Koichiro; Okada, Hiroyuki

2017-05-01

Endoscopic procedures are used as first-line treatment for bile leak after hepatobiliary surgery. Advances have been made in endoscopic techniques and devices, but few reports have described the effectiveness of endoscopic procedures and the management principles based on severity of bile leak. We evaluated the effectiveness of an endoscopic procedure for the treatment of bile leak after hepatobiliary surgery. Fifty-eight patients underwent an endoscopic procedure for suspected bile leak after hepatobiliary surgery; the presence of bile leak on endoscopic retrograde cholangiopancreatography (ERCP) was evaluated retrospectively. Two groups were created based on bile leak severity at ERCP. We defined success as follows: technical, successful placement of the plastic stent at the intended bile duct; clinical, improvement in symptoms of bile leak; and eventual, disappearance of bile leak at ERCP. We evaluated several factors that influenced the success of the endoscopic procedure and the differences between bile leak severity. Success rates were as follows: technical, 90%; clinical, 79%; and eventual, 71%. Median interval between first endoscopic procedure and achievement of eventual success was 135 days (IQR, 86-257 days). Bile leak severity was the only independent factor associated with eventual success (P = 0.01). Endoscopic therapy is safe and effective for postoperative bile leak. Bile leak severity is the most important factor influencing successful endoscopic therapy. © 2016 Japan Gastroenterological Endoscopy Society.

Normalization of Elevated Tumor Marker CA27-29 after Bilateral Lung Transplantation in a patient with Breast Cancer and Idiopathic Pulmonary Fibrosis.

PubMed

Copur, Mehmet Sitki; Wurdeman, Julie Marie; Nelson, Debra; Ramaekers, Ryan; Gauchan, Dron; Crockett, David

2017-12-11

Solid tumors involving glandular organs express mucin glycoprotein which is eventually shed into the circulation. As aresult these proteins can easily be measured in the serum and be used as potential tumor markers. The most commonly used tumor markers for breast cancer are CA 27-29 and CA 15-3, which both measure the glycoprotein product of the mucin-1 (MUC1) gene. CA 27-29 has been approved by the US Food and Drug Administration for monitoring disease activity in breast cancer patients. Most oncology clinical practice guidelines do not recommend the use of tumor markers for routine surveillance of early stage disease but recognize their utility in the metastatic setting. Herein, we present a patient with stage III-A breast cancer and pre-existing hypersensitivity pneumonitis who is found to have an elevated serum tumor marker CA 27-29. After successful curative intent treatment of her early stage breast cancer, she developed gradual and progressive worsening of her lung disease with eventual development of severe pulmonary fibrosis requiring bilateral lung transplantation. As part of the pre-transplant evaluation, she was found to have an elevation of serum tumor marker CA 27-29. While the diagnostic evaluation, including imaging studies was negative for the presence of recurrent disease, the serial serum tumor marker CA 27-29 levels remained persistently elevated. The decision was made for her to undergo bilateral lung transplantation. Shortly after surgery her CA27-29 tumor marker level returned to normal range, and it has continued to remain in the normal range with no evidence of breast cancer recurrence.

Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

PubMed Central

Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

2013-01-01

Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

DNA-based immunotherapy for HPV-associated head and neck cancer.

PubMed

Aggarwal, Charu

2016-10-01

Squamous cell carcinoma of the head and neck (SCCHN) accounts for 3% of all cancers. Most patients present with locally advanced disease, where multimodality therapies are used with curative intent. Despite favorable early local treatment results, about one third of the patients will eventually develop metastatic disease. Immunotherapy offers a novel therapeutic strategy beyond cytotoxic chemotherapy, with initial approvals in melanoma and non-small-cell lung cancer. HPV-associated SCCHN is a distinct subset, with unique epidemiology and treatment outcomes. Both subsets of SCCHN (HPV-related or not) are particularly favorable for immunotherapy, as immune evasion and dysregulation have been shown to play a key role in the initiation and progression of disease. This review focuses on the latest developments in immunotherapy in SCCHN, with a particular focus on DNA-based approaches including vaccine and adoptive cellular therapies.

Cushing's disease in a young woman with anorexia nervosa: pathophysiological implications.

PubMed

Katz, J L; Weiner, H; Kream, J; Zumoff, B

1986-12-01

This report describes a 17-year old student who was found to have Cushing's syndrome two years after she had developed anorexia nervosa (AN). The Cushing's syndrome was treated with bilateral resection of enlarged, hyperplastic, non-tumorous adrenal glands. The diagnosis was further confirmed four years later when, two to three years after new symptoms had appeared, an ACTH secreting pituitary adenoma (that is, Cushing's disease) was found on surgery. The possible mechanism for the development of Cushing's disease in a patient with prior anorexia nervosa, a sequence of events reported once previously, is discussed. It is suggested that increased hypothalamic-pituitary corticotroph stimulation in association with the anorexia nervosa, a now well-established endocrine phenomenon, activated an occult, inactive pituitary basophil adenoma in this patient, eventually resulting in autonomous pituitary overproduction of ACTH by the tumor.

The pharmacogenomics of drug resistance to protein kinase inhibitors

PubMed Central

Gillis, Nancy K.; McLeod, Howard L.

2016-01-01

Dysregulation of growth factor cell signaling is a major driver of most human cancers. This has led to development of numerous drugs targeting protein kinases, with demonstrated efficacy in the treatment of a wide spectrum of cancers. Despite their high initial response rates and survival benefits, the majority of patients eventually develop resistance to these targeted therapies. This review article discusses examples of established mechanisms of drug resistance to anticancer therapies, including drug target mutations or gene amplifications, emergence of alternate signaling pathways, and pharmacokinetic variation. This reveals a role for pharmacogenomic analysis to identify and monitor for resistance, with possible therapeutic strategies to combat chemoresistance. PMID:27620953

Total Artificial Heart Implantation as a Bridge to Heart Transplantation in an Active Duty Service Member With Amyloid Cardiomyopathy.

PubMed

Scully, Michael S; Wessman, Dylan E; McKee, James M; Francisco, Gregory M; Nayak, Keshav R; Kobashigawa, Jon A

2017-03-01

Cardiac involvement by light-chain (AL) amyloid occurs in up to 50% of patients with primary AL amyloidosis. The prognosis of amyloid heart disease is poor with 1-year survival rates of 35 to 40%. Historically, heart transplantation was considered controversial for patients with AL amyloid cardiomyopathy (CM) given the systemic nature of the disease and poor survival. We present a case report of an active duty service member diagnosed with advanced cardiac amyloid who underwent total artificial heart transplant as a bridge to heart transplant and eventual autologous stem cell transplant. A 47-year-old active duty male initially evaluated for atypical chest pain was found to have severe concentric left ventricular hypertrophy on echocardiogram but normal voltage on electrocardiogram. Cardiac magnetic resonance imaging, laboratory studies, and bone marrow biopsy established the diagnosis of cardiac amyloidosis. At the time of diagnosis, the patient's prognosis was very poor with a median survival of 5 months on the basis of the Mayo Clinic revised prognostic staging system for amyloidosis. The patient developed rapidly progressive left ventricular dysfunction and heart failure leading to cardiac arrest. The patient received a total artificial heart as a bridge to orthotopic heart and kidney transplantation and eventual stem cell transplant. He continues to be in remission and has a fair functional capacity without restriction in activities of daily living or moderate exercise. Amyloid CM is a rare and devastating disease. The natural course of the disease has made heart transplant in these patients controversial. Modern advancements in chemotherapies and advanced heart failure treatments have improved outcomes for select patients with AL amyloid CM undergoing heart transplantation. There is ongoing research seeking improvement in treatment options and outcomes for patients with this deadly disease. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Aphasia with elation, hypermusia, musicophilia and compulsive whistling.

PubMed Central

Jacome, D E

1984-01-01

A musically naive patient with dominant fronto-temporal and anterior parietal infarct developed transcortical mixed aphasia. From early convalescence, he exhibited elated mood with hyperprosody and repetitive, spontaneous whistling and whistling in response to questions. He often spontaneously sang without error in pitch, melody, rhythm and lyrics, and spent long periods of time listening to music. His behaviour progressively improved in parallel with very good recovery of verbal skills. Musicality and singing are rarely tested at the bedside. Preservation of these abilities in aphasics might portend eventual recovery. PMID:6707680

The application of cure models in the presence of competing risks: a tool for improved risk communication in population-based cancer patient survival.

PubMed

Eloranta, Sandra; Lambert, Paul C; Andersson, Therese M-L; Björkholm, Magnus; Dickman, Paul W

2014-09-01

Quantifying cancer patient survival from the perspective of cure is clinically relevant. However, most cure models estimate cure assuming no competing causes of death. We use a relative survival framework to demonstrate how flexible parametric cure models can be used in combination with competing-risks theory to incorporate noncancer deaths. Under a model that incorporates statistical cure, we present the probabilities that cancer patients (1) have died from their cancer, (2) have died from other causes, (3) will eventually die from their cancer, or (4) will eventually die from other causes, all as a function of time since diagnosis. We further demonstrate how conditional probabilities can be used to update the prognosis among survivors (eg, at 1 or 5 years after diagnosis) by summarizing the proportion of patients who will not die from their cancer. The proposed method is applied to Swedish population-based data for persons diagnosed with melanoma, colon cancer, or acute myeloid leukemia between 1973 and 2007.

A case of atypical Bartonella henselae infection in a patient with methimazole-induced agranulocytosis

PubMed Central

Kaysin, Alexander; Viera, Anthony J

2015-01-01

Antithyroid medications such as methimazole and propylthiouracil are commonly used to treat hyperthyroid disorders. Thionamide-induced agranulocytosis is a rare but life-threatening potential side effect of these medicines. In addition to routine monitoring of blood counts, healthcare workers caring for patients on such medication need to be mindful of atypical presentations of acute agranulocytosis throughout the treatment course. The manifestations of underlying infectious aetiologies can be mistaken for more common illness and result in delayed diagnosis. We present a case of a 41-year-old woman receiving methimazole for Grave's disease, who presented to outpatient care with high fever, pharyngitis, lymphadenopathy and jaundice. After failing to respond to empiric antibiotics, a diagnosis of neutropenia was made and the patient was admitted for inpatient care with eventual recovery following a course of granulocyte colony-stimulating factor. A diagnosis of atypical Bartonella henselae was eventually made and treated appropriately. The patient was later discharged and underwent radioactive iodine ablation. PMID:26315358

Challenges of univentricular physiology in heterotaxy.

PubMed

Jacobs, Marshall L; Mavroudis, Constantine

2011-04-01

Patients with heterotaxy syndrome exhibit an extensive constellation of congenital cardiac malformations, making these patients a challenging group to manage surgically. Many of these patients' hearts do not lend themselves to separation of the pulmonary and systemic circulations except by some modification of the Fontan procedure. Palliative procedures early in life are directed at creating a satisfactory balance of pulmonary and systemic blood flow and at the same time ensuring unobstructed pulmonary venous return. Early conversion from parallel pulmonary and systemic circulations to superior cavopulmonary connections is important, to reduce volume work of the systemic ventricle. Heterotaxy patients are generally considered a high-risk population with respect to eventual Fontan procedure. It is important to appreciate the unique and variable anatomy of the sinus node and conduction system and the potential for occult pulmonary venous obstruction, atrioventricular valve regurgitation, and recurrent cyanosis, which may be related to the development of pulmonary arteriovenous malformations.

Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments.

PubMed

Sandoval, Julio; Gomez-Arroyo, Jose; Gaspar, Jorge; Pulido-Zamudio, Tomas

2015-10-01

Despite significant advances in pharmacological treatments, pulmonary arterial hypertension remains an incurable disease with an unreasonably high morbidity and mortality. Although specific pharmacotherapies have shifted the survival curves of patients and improved exercise endurance as well as quality of life, it is also true that these pharmacological interventions are not always accessible (particularly in developing countries) and, perhaps most importantly, not all patients respond similarly to these drugs. Furthermore, many patients will continue to deteriorate and will eventually require an additional, non-pharmacological, intervention. In this review we analyze the role of atrial septostomy and Potts anastomosis in the management of patients with pulmonary arterial hypertension, we summarize the current worldwide clinical experience (case reports and case series), and discuss why these interventional/surgical strategies might have a therapeutic role beyond that of a "bridge" to transplantation. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Treatment of Leptomeningeal Carcinomatosis in a Patient with Metastatic Pancreatic Cancer: A Case Report and Review of the Literature

PubMed Central

Johnson, William Rainey; Theeler, Brett J.; Van Echo, David; Young, Patrick; Kwok, Mary

2018-01-01

Pancreatic cancer is the fourth leading cause of cancer-related death with a median survival of 3–11 months when metastatic. We present a patient with metastatic pancreatic cancer and an exceptional response to initial systemic chemotherapy with FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin). Despite evidence of disease control on body imaging, he developed symptomatic leptomeningeal disease and brain metastases 29 months into treatment. He received aggressive treatment with capecitabine and irinotecan, intrathecal topotecan, and eventually bevacizumab. He did well for 36 weeks on this regimen until developing sepsis. This patient significantly outlived his expected survival and, moreover, did so with very good quality of life. This case demonstrates the natural history of pancreatic cancer progressing to involve the central nervous system when systemic disease is otherwise responsive to chemotherapy. It is the first case to demonstrate the potential effectiveness of intrathecal topotecan in combination with systemic chemotherapy for the treatment of leptomeningeal metastases of pancreatic cancer. PMID:29867436

Pregnancy and pulmonary hypertension: a practical approach to management

PubMed Central

Condliffe, Robin; Wilson, Vicki J; Gandhi, Suarabh V; Elliot, Charlie A

2013-01-01

Pulmonary hypertension remains a major cause of cardiac maternal death in the developed world. Over the last two decades, effective therapies for pulmonary hypertension have been developed, improving symptoms and survival. Consequently, increasing numbers of women with pulmonary hypertension and childbearing potential exist, with a number considering pregnancy. Patients with pulmonary hypertension may also present for the first time during pregnancy or shortly following delivery. The last decade has seen increasing reports of women with pulmonary hypertension surviving pregnancy using a variety of approaches but there is still a significant maternal mortality at between 12% and 33%. Current recommendations counsel that patients with known pulmonary hypertension should be strongly advised to avoid pregnancy with the provision of clear contraceptive advice and termination of pregnancy should be considered in its eventuality. In patients who are fully informed and who have been counselled regarding the risks of continuing with pregnancy, there is growing evidence that a multi-professional approach with expert care in pulmonary hypertension centres may improve outlook, although the mortality remains high. PMID:27656247

A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.

PubMed

Park, Seonmi; Gianotti-Sommer, Andreia; Molina-Estevez, Francisco Javier; Vanuytsel, Kim; Skvir, Nick; Leung, Amy; Rozelle, Sarah S; Shaikho, Elmutaz Mohammed; Weir, Isabelle; Jiang, Zhihua; Luo, Hong-Yuan; Chui, David H K; Figueiredo, Maria Stella; Alsultan, Abdulraham; Al-Ali, Amein; Sebastiani, Paola; Steinberg, Martin H; Mostoslavsky, Gustavo; Murphy, George J

2017-04-11

Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Development of an algorithm to plan and simulate a new interventional procedure.

PubMed

Fujita, Buntaro; Kütting, Maximilian; Scholtz, Smita; Utzenrath, Marc; Hakim-Meibodi, Kavous; Paluszkiewicz, Lech; Schmitz, Christoph; Börgermann, Jochen; Gummert, Jan; Steinseifer, Ulrich; Ensminger, Stephan

2015-07-01

The number of implanted biological valves for treatment of valvular heart disease is growing and a percentage of these patients will eventually undergo a transcatheter valve-in-valve (ViV) procedure. Some of these patients will represent challenging cases. The aim of this study was to develop a feasible algorithm to plan and in vitro simulate a new interventional procedure to improve patient outcome. In addition to standard diagnostic routine, our algorithm includes 3D printing of the annulus, hydrodynamic measurements and high-speed analysis of leaflet kinematics after simulation of the procedure in different prosthesis positions as well as X-ray imaging of the most suitable valve position to create a 'blueprint' for the patient procedure. This algorithm was developed for a patient with a degenerated Perceval aortic sutureless prosthesis requiring a ViV procedure. Different ViV procedures were assessed in the algorithm and based on these results the best option for the patient was chosen. The actual procedure went exactly as planned with help of this algorithm. Here we have developed a new technically feasible algorithm simulating important aspects of a novel interventional procedure prior to the actual procedure. This algorithm can be applied to virtually all patients requiring a novel interventional procedure to help identify risks and find optimal parameters for prosthesis selection and placement in order to maximize safety for the patient. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Systemic Epstein-Barr virus infection associated with membranous nephropathy in children.

PubMed

Araya, C E; González-Peralta, R P; Skoda-Smith, S; Dharnidharka, V R

2006-03-01

Epstein-Barr virus (EBV) infection can cause diverse renal manifestations ranging from microscopic hematuria to acute renal failure. Membranous nephropathy (MN) is an uncommon and usually secondary cause of nephrotic syndrome in children, and has been reported after chronic infections and antigenemia. We report two pediatric cases of secondary MN associated with acute and chronic systemic EBV infection. Patient 1 had a liver transplant for cirrhosis due to biliary atresia and developed chronic EB viremia. Membranous nephropathy occurred 3 years later and with aggressive therapy has partially subsided, in temporal association with a drop in blood EBV PCR levels. The other patient had a primary immunodeficiency and developed a lymphoproliferative disorder attributed to EBV. Nephrotic syndrome developed at initial presentation and was associated with MN on biopsy. The patient cleared the virus from blood, which was associated with eventual resolution of the MN. We postulate that EB viremia in patients lacking a fully competent immune system, but without a renal allograft, may create a susceptible environment for chronic systemic EB antigenemia that can then lead to immune-complex MN in the kidney. The association of EBV with renal histological changes consistent with MN has been suggested but not directly described before.

Estimating the future number of cases in the Ebola epidemic--Liberia and Sierra Leone, 2014-2015.

PubMed

Meltzer, Martin I; Atkins, Charisma Y; Santibanez, Scott; Knust, Barbara; Petersen, Brett W; Ervin, Elizabeth D; Nichol, Stuart T; Damon, Inger K; Washington, Michael L

2014-09-26

The first cases of the current West African epidemic of Ebola virus disease (hereafter referred to as Ebola) were reported on March 22, 2014, with a report of 49 cases in Guinea. By August 31, 2014, a total of 3,685 probable, confirmed, and suspected cases in West Africa had been reported. To aid in planning for additional disease-control efforts, CDC constructed a modeling tool called EbolaResponse to provide estimates of the potential number of future cases. If trends continue without scale-up of effective interventions, by September 30, 2014, Sierra Leone and Liberia will have a total of approximately 8,000 Ebola cases. A potential underreporting correction factor of 2.5 also was calculated. Using this correction factor, the model estimates that approximately 21,000 total cases will have occurred in Liberia and Sierra Leone by September 30, 2014. Reported cases in Liberia are doubling every 15-20 days, and those in Sierra Leone are doubling every 30-40 days. The EbolaResponse modeling tool also was used to estimate how control and prevention interventions can slow and eventually stop the epidemic. In a hypothetical scenario, the epidemic begins to decrease and eventually end if approximately 70% of persons with Ebola are in medical care facilities or Ebola treatment units (ETUs) or, when these settings are at capacity, in a non-ETU setting such that there is a reduced risk for disease transmission (including safe burial when needed). In another hypothetical scenario, every 30-day delay in increasing the percentage of patients in ETUs to 70% was associated with an approximate tripling in the number of daily cases that occur at the peak of the epidemic (however, the epidemic still eventually ends). Officials have developed a plan to rapidly increase ETU capacities and also are developing innovative methods that can be quickly scaled up to isolate patients in non-ETU settings in a way that can help disrupt Ebola transmission in communities. The U.S. government and international organizations recently announced commitments to support these measures. As these measures are rapidly implemented and sustained, the higher projections presented in this report become very unlikely.

Osimertinib, a third-generation tyrosine kinase inhibitor targeting non-small cell lung cancer with EGFR T790M mutations.

PubMed

McCoach, C E; Jimeno, A

2016-10-01

Oncogenic driver mutations in the epidermal growth factor receptor (EGFR) gene have provided a focus for effective targeted therapy. Unfortunately, all patients eventually develop resistance to frontline therapy with EGFR tyrosine kinase inhibitors (TKIs). The majority of patients develop a large subclonal population of tumor cells with a T790M mutation that renders these cells resistant to first-generation TKIs. Osimertinib is a third-generation EGFR TKI that was designed to overcome resistance from T790M mutations. This agent has demonstrated strong preclinical activity, and in the clinic it has demonstrated a high objective response rate and progression-free survival in patients with EGFR double mutations (L858R/T790M and exon 19 deletion/T790M). It is now approved by the FDA for patients who have a documented T790M mutation and who have progressed on a prior TKI. Osimertinib is also approved in the E.U. and Japan. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

Iron overload cardiomyopathy: from diagnosis to management.

PubMed

Díez-López, Carles; Comín-Colet, Josep; González-Costello, José

2018-05-01

Iron overload cardiomyopathy (IOC) is an important predictor of prognosis in a significant number of patients with hereditary hemochromatosis and hematologic diseases. Its prevalence is increasing because of improved treatment strategies, which significantly improve life expectancy. We will review diagnosis, treatment, and recent findings in the field. The development of preclinical translational disease models during the last years have helped our understanding of specific disease pathophysiological pathways that might eventually change the outcomes of these patients. IOC is an overlooked disease because of the progressive silent disease pattern and the lack of physicians' expertise. It mainly affects patients with hemochromatosis and hematologic diseases and its prevalence is expected to increase with the improvement in life expectancy of hematologic disorders. Early diagnosis of IOC in patients at risk by means of biochemical parameters and cardiac imaging can lead to early treatment and improved prognosis. The mainstay of treatment of IOC is conventional heart failure treatment, combined with phlebotomies or iron chelation in the context of anemia. The development of preclinical models has provided a comprehensive look into specific pathophysiological pathways with potential treatment strategies that must be sustained by future randomized trials.

[Congenital heart disease in adulthood].

PubMed

Baumgartner, Helmut; Däbritz, Sabine

2008-03-15

While a few decades ago only a minority of patients, particularly of those with complex congenital heart disease, could reach adulthood, progress of pediatric cardiology and cardiac surgery allows now the survival of the majority. Thus, adult cardiology is faced with a new challenging patient population. Since only a few congenital heart defects can be cured, regular follow-up during adult life is of major importance. Residual as well as consequently developed lesions must be recognized. Optimal timing of surgery or catheter intervention is necessary to provide the best long-term outcome. Despite optimal treatment part of the patients will develop long-term complications such as arrhythmias, pulmonary hypertension and, eventually, heart failure. Acute complications such as arrhythmias, aortic dissection or rupture, endocarditis, cerebral events due to embolism, bleeding or abscesses, and pulmonary embolism or bleeding must be recognized early and treated appropriately. Management of noncardiac surgery, pregnancy and delivery can be challenging. Another task is counseling regarding exercise and sports, choice of profession, driving and insurance issues. Finally, psychosocial issues must be taken into account for appropriate care of this special patient group.

Diagnostic Value of Isolated Mentalis Versus Mentalis Plus Upper Limb Electromyography in Idiopathic REM Sleep Behavior Disorder Patients Eventually Developing a Neurodegenerative Syndrome.

PubMed

Fernández-Arcos, Ana; Iranzo, Alex; Serradell, Mónica; Gaig, Carles; Guaita, Marc; Salamero, Manel; Santamaria, Joan

2017-04-01

To compare two electromyographic (EMG) montages, isolated mentalis muscle versus mentalis in combination with upper limb muscles in the baseline diagnostic video-polysomnography (V-PSG) of patients with idiopathic REM sleep behaviors disorder (IRBD) who eventually were diagnosed with a clinically defined neurodegenerative syndrome. Forty-nine patients were included. At baseline, diagnosis of RBD was based on a typical history of dream enactment behaviors plus V-PSG showing REM sleep with qualitative increased EMG activity and/or abnormal behaviors. Quantification of EMG activity (tonic, phasic and "any") in the mentalis and upper limb muscles (biceps brachii-BB, n = 36 or flexor digitorum superficialis-FDS, n = 13) was performed manually and compared with published cut-offs. Nine (18.4%) patients had either tonic or phasic EMG below the cut-offs for the isolated mentalis and four of them (11.1 %) also had values below the cut-off for the mentalis combined with BB. All 13 patients recorded with the FDS were above the mentalis combined with FDS cut-off. For the diagnosis of IRBD, sensitivity of isolated mentalis was 81.6% and of the combination of mentalis plus upper limb muscles was 91.8% (p = .03). Audiovisual analysis showed abnormal REM sleep behaviors in all nine patients with values below the cut-offs. Quantification of EMG activity in the upper limbs combined with the mentalis increases the ability to diagnose IRBD when compared with the isolated measurement of the mentalis. Detection of typical abnormal behaviors during REM sleep with audiovisual analysis is essential for the diagnosis of IRBD in patients with EMG values below the published cut-offs. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Cancer disclosure: experiences of Iranian cancer patients.

PubMed

Valizadeh, Leila; Zamanzadeh, Vahid; Rahmani, Azad; Howard, Fuchsia; Nikanfar, Ali-Reza; Ferguson, Caleb

2012-06-01

This study explored Iranian patients' experiences of cancer disclosure, paying particular attention to the ways of disclosure. Twenty cancer patients were invited to participate in this qualitative inquiry by research staff in the clinical setting. In-depth, semistructured interview data were analyzed through content analysis. The rigor of the study was established by principles of credibility, transferability, dependability, and confirmability. Four themes emerged: the atmosphere of non-disclosure, eventual disclosure, distress in knowing, and the desire for information. Non-disclosure was the norm for participants, and all individuals involved made efforts to maintain an atmosphere of non-disclosure. While a select few were informed of their diagnosis by a physician or another patient, the majority eventually became aware of their diagnosis indirectly by different ways. All participants experienced distress after disclosure. The participants wanted basic information about their prognosis and treatments from their treating physicians, but did not receive this information, and encountered difficulty accessing information elsewhere. These challenges highlight the need for changes in current medical practice in Iran, as well as patient and healthcare provider education. © 2012 Blackwell Publishing Asia Pty Ltd.

A Prospective, Quantitative Evaluation of Fatty Infiltration Before and After Rotator Cuff Repair.

PubMed

Lansdown, Drew A; Lee, Sonia; Sam, Craig; Krug, Roland; Feeley, Brian T; Ma, C Benjamin

2017-07-01

Current evaluation of muscle fatty infiltration has been limited by subjective classifications. Quantitative fat evaluation through magnetic resonance imaging (MRI) may allow for an improved longitudinal evaluation of the effect of surgical repair on the progression of fatty infiltration. We hypothesized that (1) patients with isolated full-thickness supraspinatus tendon tears would have less progression in fatty infiltration compared with patients with full-thickness tears of multiple tendons and (2) patients with eventual failed repair would have higher baseline levels of fatty infiltration. Cohort study; Level of evidence, 2. Thirty-five patients with full-thickness rotator cuff tears were followed longitudinally. All patients received a shoulder MRI, including the iterative decomposition of echoes of asymmetric length (IDEAL) sequence for fat measurement, prior to surgical treatment and at 6 months after surgical repair. Fat fractions were recorded for all 4 rotator cuff muscles from measurements on 4 sagittal slices centered at the scapular-Y. Demographics and tear characteristics were recorded. Baseline and follow-up fat fractions were compared for patients with isolated supraspinatus tears versus multitendon tears and for patients with intact repairs versus failed repairs. Statistical significance was set at P < .05. The mean fat fractions were significantly higher at follow-up than at baseline for the supraspinatus (9.8% ± 7.0% vs 8.3% ± 5.7%; P = .025) and infraspinatus (7.4% ± 6.1% vs 5.7% ± 4.4%; P = .027) muscles. Patients with multitendon tears showed no significant change for any rotator cuff muscle after repair. Patients with isolated supraspinatus tears showed a significant progression in the supraspinatus fat fraction from baseline to follow-up (from 6.8% ± 4.9% to 8.6% ± 6.8%; P = .0083). Baseline supraspinatus fat fractions were significantly higher in patients with eventual failed repairs compared with those with intact repairs (11.7% ± 6.8% vs 7.1% ± 4.8%; P = .037). Contrary to our initial hypothesis, patients with isolated supraspinatus tears showed a significant progression of fatty infiltration. Patients with eventual repair failure had higher baseline fat fractions in the supraspinatus.

Life-threatening urethral hemorrhage after placement of a Foley catheter in a patient with uroseptic disseminated intravascular coagulation due to chronic urinary retention induced by untreated benign prostatic hyperplasia.

PubMed

Ikegami, Yukihiro; Yoshida, Keisuke; Imaizumi, Tsuyoshi; Isosu, Tsuyoshi; Kurosawa, Shin; Murakawa, Masahiro

2016-10-01

A 77-year-old man with severe septic disseminated intravascular coagulation following urinary infection was transported to our hospital. He had developed urinary retention induced by untreated prostatic hyperplasia. Immediate drainage with a Foley catheter was successfully carried out, but the hematuria progressed to life-threatening hemorrhage. Complete hemostasis was impossible by surgical treatment because the tissue around the prostatic urethra was very fragile and hemorrhagic. Organized treatments (continuous hemodiafiltration combined with polymyxin-B immobilized fiber column hemoperfusion and systemic treatment with antibiotics and coagulation factors) were commenced soon after the operation. The patient eventually recovered from the septic disseminated intravascular coagulation. This case report illustrates the risk of placement of Foley catheters in patients with severe septic disseminated intravascular coagulation.

Imitating the Great Imitator The Intersection of Sarcoidosis and Hodgkin's Lymphoma A Report of Two Cases.

PubMed

Outlaw, Darryl; Mehta, Amitkumar; Dalvi, Sam R

2018-06-01

Sarcoidosis and Hodgkin's lymphoma represent two distinct diseases with different pathogenic mechanisms, therapeutic interventions, and prognoses. Nevertheless, both diseases can have overlapping presentations, thus blurring the line between successful identification and treatment. A propensity to develop one of these diseases following diagnosis of the other has long been appreciated. Here we review two cases of presumed sarcoidosis that were ultimately diagnosed as Hodgkin's lymphoma. Both patients initially presented with non-specific symptoms and underwent a thorough workup, including histological evaluation demonstrating non-caseating granulomas without evidence of malignancy. Both patients started sarcoid-directed therapies with relapse of symptoms. Repeat imaging and tissue biopsy eventually led to the diagnosis of stage IVB Hodgkin's lymphoma. After the initiation of Hodgkin's-directed therapies, both patients showed marked clinical responses, and entered complete remission.

Adrenal insufficiency secondary to tuberculosis: the value of telemedicine in the remote diagnosis of Addison's disease in Ebeye, Republic of the Marshall Islands.

PubMed

Bush, Lisabeth A; Ruess, Lynne; Jack, Tom; Person, Donald A

2009-01-01

A young Marshallese woman presented with the insidious development of fever, cough, fatigue, profound weakness, massive weight loss, cachexia, alopecia, amenorrhea, and periumbilical hyperpigmentation. Limited laboratory studies revealed anemia, leukocytosis, and hyponatremia. Imaging studies, as well as digital photographs, transmitted over the Internet, using the secure Pacific Island Health Care Project (PIHCP), store-and-forward telemedicine system, suggested the diagnosis of disseminated tuberculosis, and antimycobacterial antibiotics were begun. Sputum cultures eventually grew Mycobacterium tuberculosis. Based on the constellation of clinical signs and symptoms, the transmitted images, and limited laboratory data, adrenal tuberculosis (Addison's disease) with adrenal insufficiency was diagnosed and corticosteroids were initiated. The patient responded dramatically This case underscores the utility of telemedicine in the diagnosis and treatment of patients with unusual conditions, rarely seen today in the United States, from remote sites in the Developing World.

Identification of inactivity behavior in smart home.

PubMed

Poujaud, J; Noury, N; Lundy, J-E

2008-01-01

To help elderly people live independently at home, the TIMC-IMAG laboratory developed Health Smart Homes called 'HIS'. These smart Homes are composed of several sensors to monitor the activities of daily living of the patients. Volunteers have accepted to be monitored during 2 years in their own flats. During one year, we carried out our survey on one elderly patient. Thanks to this experimentation, we will access to relevant information like physiological, environmental and activity. This paper focuses on daily living activity. We will introduce an original data splitting method based on the relationship between the frame of time and the location in the flat. Moreover we will present two different methods to determine a threshold of critical inactivity and eventually we will discuss their possible utilities.

Acne at the Regional Dermatology Training Centre (RDTC), Tanzania. Clinical, social, and demografic characteristics of patients with focus on severity factors.

PubMed

Amani, U A; Mshana, J; Kiprono, S; Mavura, D; Masenga, E J; Cazzaniga, S; Todd, G; Beltraminelli, H

2018-05-05

Acne is a common dermatosis and is associated with a significant disease burden. Despite this, studies from Sub-Saharan Africa are rare. However, the prevalence of acne vulgaris in developing countries is increasing, eventually due to the adoption of a western life style especially in urban areas. We conducted an analytical, cross-sectional, hospital-based study between September 2012 and February 2013 (6 months) at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania. The clinical, social, and demographic characteristics of patients with acne were assessed. The study was approved by the KCMU-CO Ethical Board. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A Wearable Body Controlling Device for Application of Functional Electrical Stimulation

PubMed Central

Jeffery, Nicholas D.

2018-01-01

In this research, we describe a new balancing device used to stabilize the rear quarters of a patient dog with spinal cord injuries. Our approach uses inertial measurement sensing and direct leg actuation to lay a foundation for eventual muscle control by means of direct functional electrical stimulation (FES). During this phase of development, we designed and built a mechanical test-bed to develop the control and stimulation algorithms before we use the device on our animal subjects. We designed the bionic test-bed to mimic the typical walking gait of a dog and use it to develop and test the functionality of the balancing device for stabilization of patient dogs with hindquarter paralysis. We present analysis for various muscle stimulation and balancing strategies, and our device can be used by veterinarians to tailor the stimulation strength and temporal distribution for any individual patient dog. We develop stabilizing muscle stimulation strategies using the robotic test-bed to enhance walking stability. We present experimental results using the bionic test-bed to demonstrate that the balancing device can provide an effective sensing strategy and deliver the required motion control commands for stabilizing an actual dog with a spinal cord injury. PMID:29670039

A Wearable Body Controlling Device for Application of Functional Electrical Stimulation.

PubMed

Taghavi, Nazita; Luecke, Greg R; Jeffery, Nicholas D

2018-04-18

In this research, we describe a new balancing device used to stabilize the rear quarters of a patient dog with spinal cord injuries. Our approach uses inertial measurement sensing and direct leg actuation to lay a foundation for eventual muscle control by means of direct functional electrical stimulation (FES). During this phase of development, we designed and built a mechanical test-bed to develop the control and stimulation algorithms before we use the device on our animal subjects. We designed the bionic test-bed to mimic the typical walking gait of a dog and use it to develop and test the functionality of the balancing device for stabilization of patient dogs with hindquarter paralysis. We present analysis for various muscle stimulation and balancing strategies, and our device can be used by veterinarians to tailor the stimulation strength and temporal distribution for any individual patient dog. We develop stabilizing muscle stimulation strategies using the robotic test-bed to enhance walking stability. We present experimental results using the bionic test-bed to demonstrate that the balancing device can provide an effective sensing strategy and deliver the required motion control commands for stabilizing an actual dog with a spinal cord injury.

[Systemic paracoccidioidomycosis with central nervous system involvement].

PubMed

Duarte, A L; Baruffa, G; Terra, H B; Renck, D V; de Moura, D; Petrucci, C

1999-01-01

A clinical case of a patient bearing systemic paracoccidioidomycosis with regional ganglionic and oral exposure and later pulmonary involvement is presented. The patient was treated with specific drugs (amphotericin B, itraconazole, sulfamethoxazole-trimethoprim) and followed throughout a 6-year period and eventually died showing an extensive involvement of the central nervous system.

Comparison of Outcomes of antibiotic Drugs and Appendectomy (CODA) trial: a protocol for the pragmatic randomised study of appendicitis treatment

PubMed Central

Davidson, Giana H; Flum, David R; Talan, David A; Kessler, Larry G; Lavallee, Danielle C; Bizzell, Bonnie J; Farjah, Farhood; Stewart, Skye D; Krishnadasan, Anusha; Carney, Erin E; Wolff, Erika M; Comstock, Bryan A; Monsell, Sarah E; Heagerty, Patrick J; Ehlers, Annie P; DeUgarte, Daniel A; Kaji, Amy H; Evans, Heather L; Yu, Julianna T; Mandell, Katherine A; Doten, Ian C; Clive, Kevin S; McGrane, Karen M; Tudor, Brandon C; Foster, Careen S; Saltzman, Darin J; Thirlby, Richard C; Lange, Erin O; Sabbatini, Amber K; Moran, Gregory J

2017-01-01

Introduction Several European studies suggest that some patients with appendicitis can be treated safely with antibiotics. A portion of patients eventually undergo appendectomy within a year, with 10%–15% failing to respond in the initial period and a similar additional proportion with suspected recurrent episodes requiring appendectomy. Nearly all patients with appendicitis in the USA are still treated with surgery. A rigorous comparative effectiveness trial in the USA that is sufficiently large and pragmatic to incorporate usual variations in care and measures the patient experience is needed to determine whether antibiotics are as good as appendectomy. Objectives The Comparing Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial for acute appendicitis aims to determine whether the antibiotic treatment strategy is non-inferior to appendectomy. Methods/Analysis CODA is a randomised, pragmatic non-inferiority trial that aims to recruit 1552 English-speaking and Spanish-speaking adults with imaging-confirmed appendicitis. Participants are randomised to appendectomy or 10 days of antibiotics (including an option for complete outpatient therapy). A total of 500 patients who decline randomisation but consent to follow-up will be included in a parallel observational cohort. The primary analytic outcome is quality of life (measured by the EuroQol five dimension index) at 4 weeks. Clinical adverse events, rate of eventual appendectomy, decisional regret, return to work/school, work productivity and healthcare utilisation will be compared. Planned exploratory analyses will identify subpopulations that may have a differential risk of eventual appendectomy in the antibiotic treatment arm. Ethics and dissemination This trial was approved by the University of Washington’s Human Subjects Division. Results from this trial will be presented in international conferences and published in peer-reviewed journals. Trial registration number NCT02800785. PMID:29146633

A high-risk patient with long-QT syndrome with no response to cardioselective beta-blockers.

PubMed

Toyota, Naoki; Miyazaki, Aya; Sakaguchi, Heima; Shimizu, Wataru; Ohuchi, Hideo

2015-09-01

We present a case of a high-risk 19-year-old female with long-QT syndrome (LQTS) with compound mutations. She had a history of aborted cardiac arrest and syncope and had received treatment with propranolol for 15 years. However, because she developed adult-onset asthma we tried to switch propranolol, a nonselective beta-blocker, to beta-1-cardioselective agents, bisoprolol and metoprolol. These resulted in both a markedly prolonged corrected QT interval and the development of LQTS-associated arrhythmias. Eventually, propranolol was reinitiated at a higher dose with the addition of verapamil, and she has had no further cardiac or asthmatic events for 5 years.

Treatment Options in Gastrointestinal Cutaneous Fistulas

PubMed Central

Ashkenazi, Itamar; Turégano-Fuentes, Fernando; Olsha, Oded; Alfici, Ricardo

2017-01-01

Enterocutaneous fistulas occur most commonly following surgery. A minority of them is caused by a myriad of other etiologies including infection, malignancy, and radiation. While some fistulas may close spontaneously, most patients will eventually need surgery to resolve this pathology. Successful treatment entails adoption of various methods of treatment aimed at control of sepsis, protection of surrounding skin and soft tissue, control of fistula output, and maintenance of nutrition, with eventual spontaneous or surgical closure of the fistula. The aim of this article is to review the various treatment options in their appropriate context. PMID:28825016

Quantitative Imaging in Cancer Clinical Trials

PubMed Central

Yankeelov, Thomas E.; Mankoff, David A.; Schwartz, Lawrence H.; Lieberman, Frank S.; Buatti, John M.; Mountz, James M.; Erickson, Bradley J.; Fennessy, Fiona M.M.; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L.; Linden, Hannah M.; Kinahan, Paul; Zhao, Binsheng; Hylton, Nola M.; Gillies, Robert J.; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L.

2015-01-01

As anti-cancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. While traditional, anatomic CT and MRI exams are useful in many settings, there is increasing evidence that these methods cannot answer the fundamental biological and physiological questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients, and to provide a more efficient path for the development of improved targeted therapies. PMID:26773162

An unusual tachycardia.

PubMed

Hanon, Sam; Shapiro, Michael; Schweitzer, Paul

2004-07-01

The following article presents an unusual case of atrial tachycardia, initially misdiagnosed due to a lack of clear P waves. The diagnosis was eventually confirmed using the atrial electrogram from the patient's pacemaker.

ASC-J9(®) suppresses castration resistant prostate cancer progression via degrading the enzalutamide-induced androgen receptor mutant AR-F876L.

PubMed

Wang, Ronghao; Lin, Wanying; Lin, Changyi; Li, Lei; Sun, Yin; Chang, Chawnshang

2016-08-28

Androgen deprivation therapy (ADT) with the newly developed powerful anti-androgen enzalutamide (Enz, also known as MDV3100) has promising therapeutic effects to suppress castration resistant prostate cancer (CRPC) and extending patients' lives an extra 4.8 months. However, most Enz therapy eventually fails with the development of Enz resistance. The detailed mechanisms how CRPC develops Enz resistance remain unclear and may involve multiple mechanisms. Among them, the induction of the androgen receptor (AR) mutant AR-F876L in some CRPC patients may represent one driving force that confers Enz resistance. Here, we demonstrate that the AR degradation enhancer, ASC-J9(®), not only degrades wild-type AR, but also has the ability to target AR-F876L. The consequence of suppressing AR-F876L may then abrogate AR-F876L mediated CRPC cell proliferation and metastasis. Thus, developing ASC-J9(®) as a new therapeutic approach may represent a novel therapy to better suppress CRPC that has already developed Enz resistance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development of effective skin cancer treatment and prevention in xeroderma pigmentosum.

PubMed

Lambert, W Clark; Lambert, Muriel W

2015-01-01

Xeroderma pigmentosum (XP) is a rare, recessively transmitted genetic disease characterized by increasingly marked dyspigmentation and xerosis (dryness) of sun-exposed tissues, especially skin. Skin cancers characteristically develop in sun-exposed sites at very much earlier ages than in the general population; these are often multiple and hundreds or even thousands may develop. Eight complementation groups have been identified. Seven groups, XP-A…G, are associated with defective genes encoding proteins involved in the nucleotide excision DNA repair (NER) pathway that recognizes and excises mutagenic changes induced in DNA by sunlight; the eighth group, XP-V, is associated with defective translesion synthesis (TLS) bypassing such alterations. The dyspigmentation, xerosis and eventually carcinogenesis in XP patients appear to be due to their cells' failure to respond properly to these mutagenic DNA alterations, leading to mutations in skin cells. A subset of cases, especially those in some complementation groups, may develop neurological degeneration, which may be severe. However, in most XP patients, in the past the multiple skin cancers have led to death at an early age due to either metastases or sepsis. Using either topical 5-fluorouracil or imiquimod, we have developed a protocol that effectively prevents most skin cancer development in XP patients. © 2014 The American Society of Photobiology.

Transient Hypothyroidism after Radioiodine for Graves’ Disease: Challenges in Interpreting Thyroid Function Tests

PubMed Central

Sheehan, Michael T.; Doi, Suhail A.R.

2016-01-01

Graves’ disease is the most common cause of hyperthyroidism and is often managed with radioactive iodine (RAI) therapy. With current dosing schemes, the vast majority of patients develop permanent post-RAI hypothyroidism and are placed on life-long levothyroxine therapy. This hypothyroidism typically occurs within the first 3 to 6 months after RAI therapy is administered. Indeed, patients are typically told to expect life-long thyroid hormone replacement therapy to be required within this timeframe and many providers expect this post-RAI hypothyroidism to be complete and permanent. There is, however, a small subset of patients in whom a transient post-RAI hypothyroidism develops which, initially, presents exactly as the typical permanent hypothyroidism. In some cases the transient hypothyroidism leads to a period of euthyroidism of variable duration eventually progressing to permanent hypothyroidism. In others, persistent hyperthyroidism requires a second dose of RAI. Failure to appreciate and recognize the possibility of transient post-RAI hypothyroidism can delay optimal and appropriate treatment of the patient. We herein describe five cases of transient post-RAI hypothyroidism which highlight this unusual sequence of events. Increased awareness of this possible outcome after RAI for Graves’ disease will help in the timely management of patients. PMID:26864507

Patient-specific embryonic stem cells derived from human SCNT blastocysts.

PubMed

Hwang, Woo Suk; Roh, Sung Il; Lee, Byeong Chun; Kang, Sung Keun; Kwon, Dae Kee; Kim, Sue; Kim, Sun Jong; Park, Sun Woo; Kwon, Hee Sun; Lee, Chang Kyu; Lee, Jung Bok; Kim, Jin Mee; Ahn, Curie; Paek, Sun Ha; Chang, Sang Sik; Koo, Jung Jin; Yoon, Hyun Soo; Hwang, Jung Hye; Hwang, Youn Young; Park, Ye Soo; Oh, Sun Kyung; Kim, Hee Sun; Park, Jong Hyuk; Moon, Shin Yong; Schatten, Gerald

2005-06-17

Patient-specific, immune-matched human embryonic stem cells (hESCs) are anticipated to be of great biomedical importance for studies of disease and development and to advance clinical deliberations regarding stem cell transplantation. Eleven hESC lines were established by somatic cell nuclear transfer (SCNT) of skin cells from patients with disease or injury into donated oocytes. These lines, nuclear transfer (NT)-hESCs, grown on human feeders from the same NT donor or from genetically unrelated individuals, were established at high rates, regardless of NT donor sex or age. NT-hESCs were pluripotent, chromosomally normal, and matched the NT patient's DNA. The major histocompatibility complex identity of each NT-hESC when compared to the patient's own showed immunological compatibility, which is important for eventual transplantation. With the generation of these NT-hESCs, evaluations of genetic and epigenetic stability can be made. Additional work remains to be done regarding the development of reliable directed differentiation and the elimination of remaining animal components. Before clinical use of these cells can occur, preclinical evidence is required to prove that transplantation of differentiated NT-hESCs can be safe, effective, and tolerated.

Health activism and the logic of connective action. A case study of rare disease patient organisations

PubMed Central

Vicari, Stefania; Cappai, Franco

2016-01-01

ABSTRACT This exploratory work investigates the role of digital media in expanding health discourse practices in a way to transform traditional structures of agency in public health. By focusing on a sample of rare disease patient organisations as representative of contemporary health activism, this study investigates the role of digital communication in the development of (1) bottom-up sharing and co-production of health knowledge, (2) health public engagement dynamics and (3) health information pathways. Findings show that digital media affordances for patient organisations go beyond the provision of social support for patient communities; they ease one-way, two-way and crowdsourced processes of health knowledge sharing, exchange and co-production, provide personalised routes to health public engagement and bolster the emergence of varied pathways to health information where experiential knowledge and medical authority are equally valued. These forms of organisationally enabled connective action can help the surfacing of personal narratives that strengthen patient communities, the bottom-up production of health knowledge relevant to a wider public and the development of an informational and eventually cultural context that eases patients’ political action. PMID:27499676

Patient-specific assessment of left ventricular thrombogenesis risk after acute myocardial infarction: a pilot clinical study

NASA Astrophysics Data System (ADS)

Rossini, L.; Khan, A.; Del Alamo, J. C.; Martinez-Legazpi, P.; Pérez Del Villar, C.; Benito, Y.; Yotti, R.; Barrio, A.; Delgado-Montero, A.; Gonzalez-Mansilla, A.; Fernandez-Avilés, F.; Bermejo, J.

2016-11-01

Left ventricular thrombosis (LVT) is a major complication of acute myocardial infarction (AMI). In these patients, the benefits of chronic anticoagulation therapy need to be balanced with its pro-hemorrhagic effects. Blood stasis in the cardiac chambers, a risk factor for LVT, is not addressed in current clinical practice. We recently developed a method to quantitatively assess the blood residence time (RT) inside the left ventricle (LV) based on 2D color-Doppler velocimetry (echo-CDV). Using time-resolved blood velocity fields acquired non-invasively, we integrate a modified advection equation to map intraventricular stasis regions. Here, we present how this tool can be used to estimate the risk of LVT in patients with AMI. 73 patients with a first anterior-AMI were studied by echo-CDV and RT analysis within 72h from admission and at a 5-month follow-up. Patients who eventually develop LVT showed early abnormalities of intraventricular RT: the apical region with RT>2s was significantly larger, had a higher RT and a longer wall contact length. Thus, quantitative analysis of intraventricular flow based on echocardiography may provide subclinical markers of LV thrombosis risk to guide clinical decision making.

Telangiectatic osteosarcoma.

PubMed

Colomina, Jordi; Peiro, Ana; Trullols, Laura; Garcia, Isidre

2013-04-01

To review records of 8 patients with telangiectatic osteosarcoma (TOS) and determine whether pathologic fractures correlate with recurrence and survival. Records of 4 men and 4 women aged 17 to 44 (mean, 28) years treated for TOS were reviewed. RESULTS; Of the 8 patients, 4 developed a pathologic fracture and 4 did not. In each group, 2 patients underwent limb salvage surgery and 2 underwent amputation. All patients received neoadjuvant and adjuvant chemotherapy with a combination of at least 2 of the following drugs: doxorubicin, methotrexate, cisplatin, and vincristin. After a mean follow-up of 5.6 (range, 2-16) years, all 4 patients with a pathologic fracture and 2 of the 4 patients without a pathologic fracture were still alive and disease-free. For the remaining patients, one died after 31 months from progression of a lung metastasis, and the other was alive with the disease and had had 2 recurrences, a lung metastasis, and an infection with Klebsiella oxytoca that eventually led to an amputation. The presence of a pathologic fracture in patients with TOS was not associated with worse outcome in terms of recurrence and survival.

Informed Strangers: Witnessing and Responding to Unethical Care as Student Nurses.

PubMed

Engel, Joyce; Salfi, Jenn; Micsinszki, Samantha; Bodnar, Andrea

2017-01-01

Nursing students occupy a unique perspective in clinical settings because they are informed, through education, about how patient care ought to happen. Given the brevity of placements and their "visiting status" in clinical sites, students are less invested in the ethos of specific sites. Subsequently, their perspectives of quality care are informed by what should happen, which might differ from that of nurses and patients. The purpose of this study was to identify predominant themes in patient care, as experienced by students, and the influence that these observations have on the development of their ethical reasoning. Using a qualitative descriptive approach in which 27 nursing student papers and three follow-up in-depth interviews were analyzed, three main themes emerged: Good employee, poor nurse; damaged care; and negotiating the gap. The analysis of the ethical situations in these papers suggests that students sometimes observe care that lacks concern for the dignity, autonomy, and safety of patients. For these student nurses, this tension led to uncertainty about patient care and their eventual profession.

The U.S. and Japanese amorphous silicon technology programs A comparison

NASA Technical Reports Server (NTRS)

Shimada, K.

1984-01-01

The U.S. Department of Energy/Solar Energy Research Institute Amorphous Silicon (a-Si) Solar Cell Program performs R&D on thin-film hydrogenated amorphous silicon for eventual development of stable amorphous silicon cells with 12 percent efficiency by 1988. The Amorphous Silicon Solar Cell Program in Japan is sponsored by the Sunshine Project to develop an alternate energy technology. While the objectives of both programs are to eventually develop a-Si photovoltaic modules and arrays that would produce electricity to compete with utility electricity cost, the U.S. program approach is research oriented and the Japanese is development oriented.

Postprostatectomy Erectile Dysfunction: A Review

PubMed Central

Salonia, Andrea; Briganti, Alberto; Montorsi, Francesco

2016-01-01

In the current era of the early diagnosis of prostate cancer (PCa) and the development of minimally invasive surgical techniques, erectile dysfunction (ED) represents an important issue, with up to 68% of patients who undergo radical prostatectomy (RP) complaining of postoperative erectile function (EF) impairment. In this context, it is crucial to comprehensively consider all factors possibly associated with the prevention of post-RP ED throughout the entire clinical management of PCa patients. A careful assessment of both oncological and functional baseline characteristics should be carried out for each patient preoperatively. Baseline EF, together with age and the overall burden of comorbidities, has been strongly associated with the chance of post-RP EF recovery. With this goal in mind, internationally validated psychometric instruments are preferable for ensuring proper baseline EF evaluations, and questionnaires should be administered at the proper time before surgery. Careful preoperative counselling is also required, both to respect the patient's wishes and to avoid false expectations regarding eventual recovery of baseline EF. The advent of robotic surgery has led to improvements in the knowledge of prostate surgical anatomy, as reflected by the formal redefinition of nerve-sparing techniques. Overall, comparative studies have shown significantly better EF outcomes for robotic RP than for open techniques, although data from prospective trials have not always been consistent. Preclinical data and several prospective randomized trials have demonstrated the value of treating patients with oral phosphodiesterase 5 inhibitors (PDE5is) after surgery, with the concomitant potential benefit of early re-oxygenation of the erectile tissue, which appears to be crucial for avoiding the eventual penile structural changes that are associated with postoperative neuropraxia and ultimately result in severe ED. For patients who do not properly respond to PDE5is, proper counselling regarding intracavernous treatment should be considered, along with the further possibility of surgical treatment for ED involving the implantation of a penile prosthesis. PMID:27574591

Emerging Good Practices for Transforming Value Assessment: Patients' Voices, Patients' Values.

PubMed

Perfetto, Eleanor M; Harris, Jason; Mullins, C Daniel; dosReis, Susan

2018-04-01

Patient engagement is a transformative strategy for improving value assessment. US value framework developers have increased engagement activities, but more needs to be learned about how to best achieve meaningful patient engagement in value assessment. The objective was to glean good practices in patient engagement emerging from patient community experiences, to be used in value assessment. The National Health Council Value Workgroup conducted a survey and held a focus group with its member advocacy organizations to gather experiences with value framework developers and views on emerging good practices. Ten of 13 organizations completed the survey; reporting 13 interactions with four framework developers. Most rated experiences as "good" to "very good." Emerging good practices included (1) engage early; (2) engage a range of patients; (3) leverage patient-provided information, data resources, and outreach mechanisms; (4) be transparent; and (5) appreciate and accommodate resource constraints. Twelve of 13 organizations participated in the focus group, and this produced 30 emerging good practices in four areas: (1) timing; (2) methodology and data; (3) partnering; and (4) characterizing engagement. Patient engagement was limited in early development of value frameworks but has increased in the past few years. Patient groups report positive experiences that can serve as emerging good practices. These groups also reported experienced challenges in their interactions and recommended good practices to mitigate those challenges. The growing pool of patient engagement experiences can be translated into good practices to advance a patient-centered, value-driven health care ecosystem. Lessons learned from these early experiences can help establish recommend emerging good practices that can eventually result in best practices and standards in the field. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Clinical Features of Early and Late Postoperative Hypothyroidism After Lobectomy.

PubMed

Park, Suyeon; Jeon, Min Ji; Song, Eyun; Oh, Hye-Seon; Kim, Mijin; Kwon, Hyemi; Kim, Tae Yong; Hong, Suck Joon; Shong, Young Kee; Kim, Won Bae; Sung, Tae-Yon; Kim, Won Gu

2017-04-01

Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur. We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC). This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up. Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001). Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery. Copyright © 2017 by the Endocrine Society

Missed Radiation Therapy and Cancer Recurrence

Cancer.gov

Patients who miss radiation therapy sessions during cancer treatment have an increased risk of their disease returning, even if they eventually complete their course of radiation treatment, according to a new study.

Massive macroglossia, amyloidosis and myeloma.

PubMed Central

Jacobs, P.; Sellars, S.; King, H. S.

1988-01-01

A 74 year old man with light-chain myeloma developed amyloidosis with macroglossia after 10 years of therapy with alkylating agents. Over a 2-year period his tongue enlarged to persistently protrude from his mouth, inhibit his speech, interfere with normal swallowing and eventually threaten his airway. As a life-saving procedure the tumorous anterior two-thirds of the tongue was resected, with excellent primary healing. Within two weeks the patient's speech became comprehensible and his ability to eat returned to normal. Although rare in amyloidosis, massive macroglossia may occur and surgical correction is easily achieved. Images Figure 1 PMID:3150784

Aberrant regeneration of the third cranial nerve.

PubMed

Shrestha, U D; Adhikari, S

2012-01-01

Aberrant regeneration of the third cranial nerve is most commonly due to its damage by trauma. A ten-month old child presented with the history of a fall from a four-storey building. She developed traumatic third nerve palsy and eventually the clinical features of aberrant regeneration of the third cranial nerve. The adduction of the eye improved over time. She was advised for patching for the strabismic amblyopia as well. Traumatic third nerve palsy may result in aberrant regeneration of the third cranial nerve. In younger patients, motility of the eye in different gazes may improve over time. © NEPjOPH.

Master's level education in biomedical optics: four-year experience at the University of Latvia

NASA Astrophysics Data System (ADS)

Spigulis, Janis

2000-06-01

Pilot program for Master's studies on Biomedical Optics has been developed and launched at University of Latvia in 1995. The Curriculum contains several basic subjects like Fundamentals of Biomedical Optics, Medical Lightguides, Anatomy and Physiology, Lasers and Non-coherent Light Sources, Optical Instrumentation for Healthcare, Optical Methods for Patient Treatment, Basic Physics, etc. Special English Terminology and Laboratory-Clinical Praxis are also involved, and the Master Theses is the final step for the degree award. Following one four-year teaching experience, some observations, conclusions and eventual future activities are discussed.

Development of drug resistance mutations in patients on highly active antiretroviral therapy: does competitive advantage drive evolution.

PubMed

Kolber, Michael A

2007-01-01

Most physicians that treat individuals with HIV-1 disease are able to successfully suppress viral replication with the pharmacologic armamentarium available today. For the majority of patients this results in immune reconstitution and improved quality of life. However, a large fraction of these patients have transient elevations in their viral burden and even persistence of low-level viremia. In fact, many individuals whose viral load is suppressed to < 50 c/ml have evidence of low-level viral replication. The impact of low-level viremia and persistent viral replication is an area of significant study and interest owing to the potential for the development of drug resistance mutations. Here the fundamental question is whether and perhaps what factors provide a venue for the development of resistant virus. The concern is clearly the eventual progression of disease with the exhaustion of treatment options. The purpose of this review is to evaluate the current literature regarding the effect of low-level viremia on the development of drug resistance mutations. Herein, we discuss the impact of different levels of viral suppression on the development of mutations. In addition, we look at the role that resistance and fitness play in determining the survival of a breakthrough mutation within the background of drug.

Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

PubMed

Haywood, Matthew James; Vijendren, Ananth; Acharya, Vikas; Mulla, Rohinton; Panesar, Miss Jaan

2017-03-06

We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans , with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery. 2017 BMJ Publishing Group Ltd.

Novel putative pharmacological therapies to protect the right ventricle in pulmonary hypertension: a review of current literature

PubMed Central

Schulz, Rainer; Sliwa, Karen; Schermuly, Ralph Theo; Lecour, Sandrine

2017-01-01

Pulmonary hypertension (PH) is defined by elevated mean pulmonary artery pressure following the pathological remodelling of small pulmonary arteries. An increase in right ventricular (RV) afterload results in RV hypertrophy and RV failure. The pathophysiology of PH, and RV remodelling in particular, is not well understood, thus explaining, at least in part, why current PH therapies have a limited effect. Existing therapies mostly target the pulmonary circulation. Because the remodelled RV fails to support normal cardiac function, patients eventually succumb from RV failure. Developing novel therapies that directly target the function of the RV may therefore benefit patients with PH. In the past decade, several promising studies have investigated novel cardioprotective strategies in experimental models of PH. This review aims to comprehensively discuss and highlight these novel experimental approaches to confer, in the long‐term, greater health benefit in patients with PH. PMID:28099680

Productivity loss of caregivers of schizophrenia patients: a cross-sectional survey in Japan.

PubMed

Sruamsiri, Rosarin; Mori, Yasuhiro; Mahlich, Jörg

2018-04-27

When a family member is diagnosed with schizophrenia, it causes stress to the caregiver that can eventually result in missed work days and lower work performance. This study aims at revealing productivity costs for caregivers of schizophrenia patients in Japan. A cross-sectional survey of caregivers was conducted and resulted in 171 respondents. The assessment of work productivity included calculating the costs of absenteeism, presenteeism and total productivity costs. This was accomplished using the "Work Productivity and Activity Impairment Questionnaire" (WPAI). A relative majority of caregivers in the sample provided care for their spouse (47%), 18% cared for their brother or sister and 16% provided care for their child. Per capita productivity costs totaled JPY 2.42 million, with JPY 2.36 million (97%) of that amount being due to presenteeism. The burden on caregivers is substantial enough to warrant structured support programs aimed at maintaining careers' physical and mental health, helping them provide more effective care to schizophrenia patients and eventually increase productivity at work.

Electroencephalographic Response to Sodium Nitrite May Predict Delayed Cerebral Ischemia After Severe Subarachnoid Hemorrhage.

PubMed

Garry, Payashi S; Rowland, Matthew J; Ezra, Martyn; Herigstad, Mari; Hayen, Anja; Sleigh, Jamie W; Westbrook, Jon; Warnaby, Catherine E; Pattinson, Kyle T S

2016-11-01

Aneurysmal subarachnoid hemorrhage often leads to death and poor clinical outcome. Injury occurring during the first 72 hours is termed "early brain injury," with disruption of the nitric oxide pathway playing an important pathophysiologic role in its development. Quantitative electroencephalographic variables, such as α/δ frequency ratio, are surrogate markers of cerebral ischemia. This study assessed the quantitative electroencephalographic response to a cerebral nitric oxide donor (intravenous sodium nitrite) to explore whether this correlates with the eventual development of delayed cerebral ischemia. Unblinded pilot study testing response to drug intervention. Neuroscience ICU, John Radcliffe Hospital, Oxford, United Kingdom. Fourteen World Federation of Neurosurgeons grades 3, 4, and 5 patients (mean age, 52.8 yr [range, 41-69 yr]; 11 women). IV sodium nitrite (10 μg/kg/min) for 1 hour. Continuous electroencephalographic recording for 2 hours. The alpha/delta frequency ratio was measured before and during IV sodium nitrite infusion. Seven of 14 patients developed delayed cerebral ischemia. There was a +30% to +118% (range) increase in the alpha/delta frequency ratio in patients who did not develop delayed cerebral ischemia (p < 0.0001) but an overall decrease in the alpha/delta frequency ratio in those patients who did develop delayed cerebral ischemia (range, +11% to -31%) (p = 0.006, multivariate analysis accounting for major confounds). Administration of sodium nitrite after severe subarachnoid hemorrhage differentially influences quantitative electroencephalographic variables depending on the patient's susceptibility to development of delayed cerebral ischemia. With further validation in a larger sample size, this response may be developed as a tool for risk stratification after aneurysmal subarachnoid hemorrhage.

Creating Simulated Microgravity Patient Models

NASA Technical Reports Server (NTRS)

Hurst, Victor; Doerr, Harold K.; Bacal, Kira

2004-01-01

The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

The invisible hands made visible: recognizing the value of informal care in healthcare decision-making.

PubMed

van Exel, Job; Bobinac, Ana; Koopmanschap, Marc; Brouwer, Werner

2008-12-01

The healthcare sector depends heavily on the informal care provided by families and friends of those who are ill. Informal caregivers may experience significant burden as well as health and well-being effects. Resource allocation decisions, in particular from a societal perspective, should account explicitly for these effects in the social environment of patients. This is not only important to make a complete welfare economic assessment of treatments, but also to ensure the lasting involvement of informal caregivers in the care-giving process. Measurement and valuation techniques for the costs and effects of informal care have been developed and their use is becoming more common. Decision-makers in healthcare - and eventually families and patients - would be helped by more uniformity in methods.

A case of traumatic pancreaticoduodenal injury: a simple and an organ-preserving approach as damage control surgery.

PubMed

Choi, Sae Byeol; You, Jiyoung; Choi, Sang Yong

2012-01-10

Traumatic pancreaticoduodenal injury still remains challenging with high morbidity and mortality. Optimal management by performing simple and fast damage control surgery ensures better outcomes. A 36-year-old man was admitted with a combined pancreaticoduodenal injury after being assaulted. More than 80% of duodenal circumference (first portion) was disrupted and the neck of the pancreas was transected. Primary repair of the duodenum and pancreaticogastrostomy were performed. The stump of the proximal pancreatic duct was also sutured. The patient developed an intra-abdominal abscess with pancreatic fistula that eventually recovered by conservative treatment. Pancreaticogastrostomy can be a treatment option for pancreatic transection. Rapid and simple damage control surgery with functional preservation of the organ will be beneficial for trauma patients.

A long-term longitudinal follow-up of depressed patients treated with ECT with special focus on development of dementia.

PubMed

Berggren, Åke; Gustafson, Lars; Höglund, Peter; Johanson, Aki

2016-08-01

In this study, the long term effects of ECT on patients with depression were investigated through repeated rCBF and EEG measures as well as clinical characteristics over several years. The aim of the investigation was to establish an association with the eventual development of dementia. A cohort of forty-nine patients (21 men and 28 women) with a mean age of 61 years underwent ECT. A subsequent evaluation from medical records and three rating-scales for diagnosis of Alzheimer´s disease (AD), fronto-temporal dementia (FTD), and for vascular dementia (VaD), revealed that 17 patients (8 men and 9 women), had developed dementia. These cases were compared to the 32 patients (13 men and 19 women), who had not developed dementia. Initially, the dementia group, compared to those without dementia, showed a lower hemispheric CBF (left side; p=.029, right side; p=.033), and a lower mean occipital EEG frequency (p=.048). After the first ECT-series, an increase in general disorientation (p=.015), personal disorientation (p=.009), and subsequently, spatial disorientation (p=.021), were seen in the dementia group. There were no differences in the clinical response or remissions after treatment in the groups. The small sample-size, which did not allow for the comparison of characteristics between different dementias. Depressed older patients who later developed dementia showed lower hemispheric mean level of CBF and EEG mean frequency before ECT and higher personal and spatial disorientation following ECT. Copyright © 2016 Elsevier B.V. All rights reserved.

Remyelination Therapy in Multiple Sclerosis.

PubMed

Harlow, Danielle E; Honce, Justin M; Miravalle, Augusto A

2015-01-01

Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high-throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in preclinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients.

Host response biomarkers in the diagnosis of sepsis: a general overview.

PubMed

Parlato, Marianna; Cavaillon, Jean-Marc

2015-01-01

Critically ill patients who display a systemic inflammatory response syndrome (SIRS) are prone to develop nosocomial infections. The challenge remains to distinguish as early as possible among SIRS patients those who are developing sepsis. Following a sterile insult, damage-associated molecular patterns (DAMPs) released by damaged tissues and necrotic cells initiate an inflammatory response close to that observed during sepsis. During sepsis, pathogen-associated molecular patterns (PAMPs) trigger the release of host mediators involved in innate immunity and inflammation through identical receptors as DAMPs. In both clinical settings, a compensatory anti-inflammatory response syndrome (CARS) is concomitantly initiated. The exacerbated production of pro- or anti-inflammatory mediators allows their detection in biological fluids and particularly within the bloodstream. Some of these mediators can be used as biomarkers to decipher among the patients those who developed sepsis, and eventually they can be used as prognosis markers. In addition to plasma biomarkers, the analysis of some surface markers on circulating leukocytes or the study of mRNA and miRNA can be helpful. While there is no magic marker, a combination of few biomarkers might offer a high accuracy for diagnosis.

Patient satisfaction is a best practice.

PubMed

2009-10-01

There are several best practices ED physicians and nurses can adopt to minimize the likelihood of a lawsuit, but perhaps none is more important than ensuring high patient satisfaction scores. Research shows a definite correlation between increasing patient satisfaction and decreasing the medical malpractice frequency. Bad outcomes are more likely to lead to lawsuits if the patient doesn't like their doctor or nurse. Being attuned to patients and their perspective is one of the best ways to prevent complaints, which eventually can lead to lawsuits.

Case Report: A Rosette-forming Glioneuronal Tumor in the Tectal Plate in a Patient with Neurofibromatosis Type I.

PubMed

Sieg, Emily P; Payne, Russell; Langan, Sara; Specht, Charles S

2016-11-01

We report the case of a 41-year-old female with neurofibromatosis Type 1 (NF1) who developed a rosette-forming glioneuronal tumor (RGNT) in the tectal plate. This tumor was diagnosed in 2002 when the patient presented with obstructive hydrocephalus, which was subsequently treated with a ventriculoperitoneal shunt and then an endoscopic third ventriculostomy. Initially thought to be a pilocytic astrocytoma, it was followed with serial magnetic resonance imaging (MRI) until tumor progression and development of a large fourth ventricular cystic component prompted resection via suboccipital craniotomy. Histological examination demonstrated an RGNT, a WHO Grade 1 tumor, with neurocytic rosettes, perivascular pseudorosettes, and elements resembling a pilocytic astrocytoma. Initially, the patient did well after her craniotomy, but postoperative complications set in that eventually led to her death. In this case report, we describe a relatively rare tumor that, despite its benign nature, leads to frequent complications and deficits due to its surgically challenging location. Along with previously reported examples, this cases raises the possibility of a causal relationship between NF1 and RGNT.

Beyond anorexia -cachexia. Nutrition and modulation of cancer patients' metabolism: supplementary, complementary or alternative anti-neoplastic therapy?

PubMed

Laviano, Alessandro; Seelaender, Marilia; Sanchez-Lara, Karla; Gioulbasanis, Ioannis; Molfino, Alessio; Rossi Fanelli, Filippo

2011-09-01

Anorexia and muscle wasting are frequently observed in cancer patients and influence their clinical outcome. The better understanding of the mechanisms underlying behavioral changes and altered metabolism yielded to the development of specialized nutritional support, which enhances utilization of provided calories and proteins by counteracting some of the metabolic derangements occurring during tumor growth. Inflammation appears to be a key factor determining the cancer-associated biochemical abnormalities eventually leading to anorexia and cachexia. Interestingly, inflammation is also involved in carcinogenesis, cancer progression and metastasis by impairing immune surveillance, among other mechanisms. Therefore, nutritional interventions aiming at modulating inflammation to restore nutritional status may also result in improved response to pharmacological anti-cancer therapies. Recent clinical data show that supplementation with nutrients targeting inflammation and immune system increases response rate and survival in cancer patients. This suggests that nutrition therapy should be considered as an important adjuvant strategy in the multidimensional approach to cancer patients. Copyright © 2011 Elsevier B.V. All rights reserved.

Diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients.

PubMed

Siri-Angkul, Natthaphat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

2018-05-18

Thalassemia is among the most common genetic diseases. Patients with severe forms of the disease are transfusion-dependent, leading to iron overload. A condition which can eventually develop in the iron-loaded heart is iron overload cardiomyopathy, a debilitating disease that accounts for the majority of deaths in thalassemia patients. Areas covered: This review article provides a comprehensive summary of the diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients, with discussion covering current weak points and potential improvements of the relevant diagnostic and therapeutic strategies. Expert commentary: Current limitations of various diagnostic techniques for iron overload cardiomyopathy include suboptimal accuracy, untimely detection, or inadequate accessibility, and novel modalities are required to overcome these shortcomings. Treatment should address key pathophysiologic mechanisms of iron overload cardiomyopathy, which include cardiac iron mishandling and iron-induced oxidative injury. Apart from the promotion of iron removal by chelators, prevention of cardiac iron deposition and attenuation of oxidative damage should also be rigorously investigated on a cell-to-bedside basis.

Mesenteric-portal axis thrombosis and deep venous thrombosis in a patient with inferior vena cava agenesis.

PubMed

Lluis Pons, Laia; Chahri Vizcarro, Nadia; Llaverias Borrell, Silvia; Miquel Abbad, Carlos

2017-06-01

Splenoportal axis thrombosis not associated with cirrhosis or neoplasms has a prevalence lower than 5 per 10,000 people. An etiologic factor responsible for portal thrombosis is finally identified in most cases, usually systemic thrombogenic factors or predisposing local factors. However, despite a detailed study of all etiologic factors, up to 30% of cases are eventually considered as idiopathic in origin. We report the case of a 41-year-old patient who presented with abdominal pain and lower extremity edema. The patient was diagnosed with portal and mesenteric-portal confluence thrombosis, bilateral deep venous thrombosis and right lumbar vein thrombosis based on an abdominal CT scan. This was associated with a likely congenital inferior vena cava agenesis. This malformation is present in approximately 5% of patients with deep vein thrombosis even though it represents a rare cause of portal thrombosis. The fact that several thromboses developed simultaneously makes this a unique and isolated case in the current literature as no similar cases have been reported thus far.

Physical Activity Monitoring in Patients with Chronic Obstructive Pulmonary Disease

PubMed Central

Liao, Shu-Yi; Benzo, Roberto; Ries, Andrew L.; Soler, Xavier

2014-01-01

Reduced physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is associated with increased morbidity and mortality (e.g. exacerbations) and eventually leads to disability, depression, and social and physical isolation. Measuring PA in this population is important to accurately characterize COPD and to help clinicians during a baseline evaluation and patient follow-up. Also, it may help increase adherence to PA programs. There are reliable objective and subjective methods available to measure PA. Recently, several new monitors have been developed that have improved accuracy of such measurements. Because these devices provide real-time feedback, they may help to improve participant self-motivation strategies and reinforce daily lifestyle modifications, one of the main goals in COPD management. This review focuses on describing available instruments to measure PA, specifically in patients with COPD. The reliability, validity, advantages, limitations, and clinical applications of questionnaires, pedometers, and accelerometers are discussed. Finally, based on current published literature, we propose recommendations about which methods may be most useful in different research or clinical settings. PMID:28848818

The long-term outcome of restorative operation in Crohn's disease: influence of location, prognostic factors and surgical guidelines.

PubMed Central

Trnka, Y M; Glotzer, D J; Kasdon, E J; Goldman, H; Steer, M L; Goldman, L D

1982-01-01

The course of all 113 patients with Crohn's disease whose initial procedure involved an anastomosis operated upon from 1942 to 1972 was followed through 1980. The calculated cumulative 30-year total mortality was 23.4%, 16.7% disease-related. The cumulative recurrence rate was 29% at five years, 52% at ten years, 64% at 15 years and 84% at 25 years, with no important differences between disease locations and types of operation. Sex, age, duration, granulomas, enteral or perirectal fistulas and length of the resection, the disease, and the proximal resection margin had no significant influence on the rates of development of recurrent disease or on functional outcome. By far the most common site of recurrence was the neo-terminal ileum, but in ileocolitis compared with ileitis, recurrence was 5.2 times more likely (p = 0.0001) to involve the adjacent or remote colon as well. Moreover, only 1/63 ileitis patients eventually required ileostomy, whereas 15/47 patients with ileocolitis or colitis ultimately required this procedure (p less than 0.001). The current status of the patients was excellent or good in 64% and unwell or dead related in 24%. Urolithiasis developed in 19%. PMID:7114939

Alexithymia and personality traits of patients with inflammatory bowel disease

PubMed Central

La Barbera, D.; Bonanno, B.; Rumeo, M. V.; Alabastro, V.; Frenda, M.; Massihnia, E.; Morgante, M. C.; Sideli, L.; Craxì, A.; Cappello, M.; Tumminello, M.; Miccichè, S.; Nastri, L.

2017-01-01

Psychological factors, specific lifestyles and environmental stressors may influence etiopathogenesis and evolution of chronic diseases. We investigate the association between Chronic Inflammatory Bowel Diseases (IBD) and psychological dimensions such as personality traits, defence mechanisms, and Alexithymia, i.e. deficits of emotional awareness with inability to give a name to emotional states. We analyzed a survey of 100 patients with IBD and a control group of 66 healthy individuals. The survey involved filling out clinical and anamnestic forms and administering five psychological tests. These were then analyzed by using a network representation of the system by considering it as a bipartite network in which elements of one set are the 166 individuals, while the elements of the other set are the outcome of the survey. We then run an unsupervised community detection algorithm providing a partition of the 166 participants into clusters. That allowed us to determine a statistically significant association between psychological factors and IBD. We find clusters of patients characterized by high neuroticism, alexithymia, impulsivity and severe physical conditions and being of female gender. We therefore hypothesize that in a population of alexithymic patients, females are inclined to develop psychosomatic diseases like IBD while males might eventually develop behavioral disorders. PMID:28150800

My Story: Real Stories of People Living with Thalassemia

MedlinePlus

... My Story Recommend on Facebook Tweet Share Compartir Real Stories from People living with Thalassemia On this ... blood diseases. Eventually, I would really like to travel the world and treat patients in places where ...

Depression and Suicide Risk

MedlinePlus

... due to another medical disorder Relationship Between Depression & Suicide: 1. Depression is the psychiatric diagnosis most commonly associated with ... of patients with treated depression eventually die by suicide. xiv 4. Depression is present in at least 50 percent of ...

Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain.

PubMed

Kortlever, Joost T P; Janssen, Stein J; Molleman, Jeroen; Hageman, Michiel G J S; Ring, David

2016-06-01

Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms? We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain. There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms. Nonspecific diagnoses are not harmful. Prospective randomized research is merited to determine if nonspecific, descriptive diagnoses are better for patients than specific diagnoses that imply pathophysiology in the absence of discrete verifiable pathophysiology.

Munchausen's syndrome: a medico-legal dilemma.

PubMed

Mydlo, J H; Macchia, R J; Kanter, J L

1997-07-01

In his or her life-long career, the physician will eventually encounter a patient with factitious disorder, or Munchausen's syndrome. We discuss two patients complaining of renal colic that were identified as having Munchausen's syndrome. We review the literature to identify certain aspects of the disease and to discuss the medical and legal implications for the treating physician and hospital.

Personalized Medicine and Opioid Analgesic Prescribing for Chronic Pain: Opportunities and Challenges

PubMed Central

Bruehl, Stephen; Apkarian, A. Vania; Ballantyne, Jane C.; Berger, Ann; Borsook, David; Chen, Wen G.; Farrar, John T.; Haythornthwaite, Jennifer A.; Horn, Susan D.; Iadarola, Michael J.; Inturrisi, Charles E.; Lao, Lixing; Mackey, Sean; Mao, Jianren; Sawczuk, Andrea; Uhl, George R.; Witter, James; Woolf, Clifford J.; Zubieta, Jon-Kar; Lin, Yu

2013-01-01

Use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy. This paper discusses the concept of data-based personalized prescribing of opioid analgesics as a means to achieve this goal. Strengths, weaknesses, and potential synergism of traditional randomized placebo-controlled trial (RCT) and practice-based evidence (PBE) methodologies as means to acquire the clinical data necessary to develop validated personalized analgesic prescribing algorithms are overviewed. Several predictive factors that might be incorporated into such algorithms are briefly discussed, including genetic factors, differences in brain structure and function, differences in neurotransmitter pathways, and patient phenotypic variables such as negative affect, sex, and pain sensitivity. Currently available research is insufficient to inform development of quantitative analgesic prescribing algorithms. However, responder subtype analyses made practical by the large numbers of chronic pain patients in proposed collaborative PBE pain registries, in conjunction with follow-up validation RCTs, may eventually permit development of clinically useful analgesic prescribing algorithms. Perspective Current research is insufficient to base opioid analgesic prescribing on patient characteristics. Collaborative PBE studies in large, diverse pain patient samples in conjunction with follow-up RCTs may permit development of quantitative analgesic prescribing algorithms which could optimize opioid analgesic effectiveness, and mitigate risks of opioid-related abuse and mortality. PMID:23374939

Attributing a monetary value to patients' time: A contingent valuation approach.

PubMed

van den Berg, Bernard; Gafni, Amiram; Portrait, France

2017-04-01

It is hard to ignore the importance of patient time investment in the production of health since the influential paper by Grossman (1972). Patients' time includes time to admission, travel time, waiting time, and treatment time and can be substantial. Patients' time is, however, often ignored in economic analyses. This may lead to biased results and inappropriate policy recommendations, which may eventually influence patients' health, wellbeing and welfare. How to value patient time is not straightforward. Although there is some emerging literature on the monetary valuation of patient time, an important challenge remains to develop an approach that can be used to monetarily value time of patients not participating in the labour market. We aim to contribute to the health economics literature by describing and empirically illustrating how to monetarily value the time of patients not participating in the labour market comprehensively, using the contingent valuation method. It is worth noting that our method can also be applied to people participating in the labour market. This paper describes the development of the contingent valuation survey. We apply our survey approach to a sample of 238 Dutch patients not participating in the labour market: n = 107 Radiotherapy department (data collected between November 2011 and January 2013); n = 44 Rehabilitation department (March 2012-May 2012); n = 87 Orthopaedics department (January to June 2013). Results show that those patients value waiting time the highest (€30.10 per hour) and value travel and treatment time equally with respectively €13.20 and €13.32 per hour. This paper encourages future empirical research refining and applying the developed survey methodology to create more data on how other subgroups of individuals value their patients' time. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitivity of imatinib-resistant T315I BCR-ABL CML to a synergistic combination of ponatinib and forskolin treatment.

PubMed

Oaxaca, Derrick M; Yang-Reid, Sun Ah; Ross, Jeremy A; Rodriguez, Georgialina; Staniswalis, Joan G; Kirken, Robert A

2016-09-01

Tyrosine kinase inhibitors (TKIs) have dramatically improved the life expectancy of patients suffering from chronic myeloid leukemia (CML); however, patients will eventually develop resistance to TKI therapy or adverse side effects due to secondary off-target mechanisms associated with TKIs. CML patients exhibiting TKI resistance are at greater risk of developing an aggressive and drug-insensitive disease. Drug-resistant CML typically arises in response to spontaneous mutations within the drug binding sites of the targeted oncoproteins. To better understand the mechanism of drug resistance in TKI-resistant CML patients, the BCR-ABL transformed cell line KCL22 was grown with increasing concentrations of imatinib for a period of 6 weeks. Subsequently, a drug-resistant derivative of the parental KCL22 cell line harboring the T315I gatekeeper mutation was isolated and investigated for TKI drug sensitivity via multi-agent drug screens. A synergistic combination of ponatinib- and forskolin-reduced cell viability was identified in this clinically relevant imatinib-resistant CML cell line, which also proved efficacious in other CML cell lines. In summary, this study provides new insight into the biological underpinnings of BCR-ABL-driven CML and potential rationale for investigating novel treatment strategies for patients with T315I CML.

Intrinsic resistance to EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer with activating EGFR mutations

PubMed Central

Wang, Jun; Wang, Baocheng; Chu, Huili; Yao, Yunfeng

2016-01-01

Identifying activating EGFR mutations is a useful predictive strategy that helps select a population of advanced non-small-cell lung cancer (NSCLC) patients for treatment with EGFR tyrosine kinase inhibitors (TKIs). Patients with sensitizing EGFR mutations (predominantly an in-frame deletion in exon 19 and an L858R substitution) are highly responsive to first-generation EGFR TKIs, such as gefitinib and erlotinib, and show improved progression-free survival without serious side effects. However, all patients with activating EGFR mutations who are initially responsive to EGFR TKIs eventually develop acquired resistance after a median progression-free survival of 10–16 months, followed by disease progression. Moreover, ~20%–30% of NSCLC patients have no objective tumor regression on initial EGFR TKI treatment, although they harbor an activating EGFR mutation. These patients represent an NSCLC subgroup that is defined as having intrinsic or primary resistance to EGFR TKIs. Different mechanisms of acquired EGFR TKI resistance have been identified, and several novel compounds have been developed to reverse acquired resistance, but little is known about EGFR TKI intrinsic resistance. In this review, we summarize the latest findings involving mechanisms of intrinsic resistance to EGFR TKIs in advanced NSCLC with activating EGFR mutations and present possible therapeutic strategies to overcome this resistance. PMID:27382309

Transient Hypothyroidism after Radioiodine for Graves' Disease: Challenges in Interpreting Thyroid Function Tests.

PubMed

Sheehan, Michael T; Doi, Suhail A R

2016-03-01

Graves' disease is the most common cause of hyperthyroidism and is often managed with radioactive iodine (RAI) therapy. With current dosing schemes, the vast majority of patients develop permanent post-RAI hypothyroidism and are placed on life-long levothyroxine therapy. This hypothyroidism typically occurs within the first 3 to 6 months after RAI therapy is administered. Indeed, patients are typically told to expect life-long thyroid hormone replacement therapy to be required within this timeframe and many providers expect this post-RAI hypothyroidism to be complete and permanent. There is, however, a small subset of patients in whom a transient post-RAI hypothyroidism develops which, initially, presents exactly as the typical permanent hypothyroidism. In some cases the transient hypothyroidism leads to a period of euthyroidism of variable duration eventually progressing to permanent hypothyroidism. In others, persistent hyperthyroidism requires a second dose of RAI. Failure to appreciate and recognize the possibility of transient post-RAI hypothyroidism can delay optimal and appropriate treatment of the patient. We herein describe five cases of transient post-RAI hypothyroidism which highlight this unusual sequence of events. Increased awareness of this possible outcome after RAI for Graves' disease will help in the timely management of patients. © 2016 Marshfield Clinic.

Delayed Single Stage Perineal Posterior Urethroplasty.

PubMed

Ali, Shahzad; Shahnawaz; Shahzad, Iqbal; Baloch, Muhammad Umar

2015-06-01

To determine the delayed single stage perineal posterior urethroplasty for treatment of posterior urethral stricture/distraction defect. Descriptive case series. Department of Urology, Jinnah Postgraduate Medical Centre, Karachi, from January 2009 to December 2011. Patients were selected for delayed single stage perineal posterior urethroplasty for treatment of posterior urethral stricture / distraction defect. All were initially suprapubically catheterized followed by definitive surgery after at least 3 months. Thirty male patients were analyzed with a mean follow-up of 10 months, 2 patients were excluded as they developed failure in first 3 months postoperatively. Mean patient's age was 26.25 ± 7.9 years. On follow-up, 7 patients (23.3%) experienced recurrent stricture during first 10 months. Five (16.6%) patients were treated successfully with single direct visual internal urethrotomy. Two patients (6.6%) had more than one direct visual internal urethrotomy and considered failed. Re-do perineal urethroplasty was eventually performed. The overall success rate was 93.3% with permissive criteria allowing single direct visual internal urethrotomy and 76.6% with strict criteria allowing no more procedures postoperatively. Posterior anastomotic urethroplasty offers excellent long-term results to patients with posterior urethral trauma and distraction defect even after multiple prior procedures.

Intrinsic brain connectivity predicts impulse control disorders in patients with Parkinson's disease.

PubMed

Tessitore, Alessandro; De Micco, Rosa; Giordano, Alfonso; di Nardo, Federica; Caiazzo, Giuseppina; Siciliano, Mattia; De Stefano, Manuela; Russo, Antonio; Esposito, Fabrizio; Tedeschi, Gioacchino

2017-12-01

Impulse control disorders can be triggered by dopamine replacement therapies in patients with PD. Using resting-state functional MRI, we investigated the intrinsic brain network connectivity at baseline in a cohort of drug-naive PD patients who successively developed impulse control disorders over a 36-month follow-up period compared with patients who did not. Baseline 3-Tesla MRI images of 30 drug-naive PD patients and 20 matched healthy controls were analyzed. The impulse control disorders' presence and severity at follow-up were assessed by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting-state networks. We also compared internetwork connectivity between patients. Finally, a multivariate Cox regression model was used to investigate baseline predictors of impulse control disorder development. At baseline, decreased connectivity in the default-mode and right central executive networks and increased connectivity in the salience network were detected in PD patients with impulse control disorders at follow-up compared with those without. Increased default-mode/central executive internetwork connectivity was significantly associated with impulse control disorders development (P < 0.05). Our findings demonstrated that abnormal brain connectivity in the three large-scale networks characterizes drug-naive PD patients who will eventually develop impulse control disorders while on dopaminergic treatment. We hypothesize that these divergent cognitive and limbic network connectivity changes could represent a potential biomarker and an additional risk factor for the emergence of impulse control disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

First-line therapy for advanced non-small cell lung cancer with activating EGFR mutation: is combined EGFR-TKIs and chemotherapy a better choice?

PubMed

Wang, Shuyun; Gao, Aiqin; Liu, Jie; Sun, Yuping

2018-03-01

As the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the median progression-free survival (PFS) up to 18.9 months. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, which limits the first-line PFS. To overcome the resistance and improve overall survival, researchers have tried to identify the resistance mechanisms and develop new treatment strategies, among which a combination of EGFR-TKIs and cytotoxic chemotherapy is one of the hotspots. The data from preclinical and clinical studies on combined EGFR-TKIs and chemotherapy have shown very interesting results. Here, we reviewed the available preclinical and clinical studies on first-line EGFR-TKIs-chemotherapy combination in patients with advanced NSCLC harboring activating EGFR mutation, aiming to provide evidences for more potential choices and shed light on clinical treatment.

Systemic lupus erythematosus presenting with Kikuchi-Fujimoto's disease as a long-term sequela of drug-induced hypersensitivity syndrome. A possible role of Epstein-Barr virus reactivation.

PubMed

Aota, N; Hirahara, K; Kano, Y; Fukuoka, T; Yamada, A; Shiohara, T

2009-01-01

Drug-induced hypersensitivity syndrome (DIHS) is a severe form of drug eruptions associated with viral reactivations. Autoimmune diseases have been reported to develop several months or years after the resolution of DIHS. We describe a 36-year-old man with cervical lymphadenopathy and an erythematous eruption affecting the face and neck, which evolved into clinically evident systemic lupus erythematosus. He had had an episode of DIHS 4 years previously, in which human herpesvirus-6 and Epstein-Barr virus (EBV) were reactivated. Expression of EBV-encoded RNA was detected in the lymph node. On the basis of findings in this patient, we suggest that EBV is pathogenically important in the sequence of events leading to the onset of systemic lupus erythematosus and that patients with a history of DIHS may be at a risk of eventually developing autoimmune diseases. 2008 S. Karger AG, Basel

Peer Review Documents Related to the Evaluation of ...

EPA Pesticide Factsheets

BMDS is one of the Agency's premier tools for estimating risk assessments, therefore the validity and reliability of its statistical models are of paramount importance. This page provides links to peer review and expert summaries of the BMDS application and its models as they were developed and eventually released documenting the rigorous review process taken to provide the best science tools available for statistical modeling. This page provides links to peer reviews and expert summaries of the BMDS applications and its models as they were developed and eventually released.

Most recent developments in strategies to reduce the progression of structural changes in osteoarthritis: today and tomorrow

PubMed Central

Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Raynauld, Jean-Pierre

2006-01-01

Osteoarthritis (OA), the most common of all arthritic conditions, is a social and financial burden to all nations. The most recent research has significantly advanced our understanding of the cause of OA and risk factors associated with it. These findings have provided useful information that has helped in the daily management of patients with OA. Some preventative measures and a number of therapeutic agents and drugs are available, which may help to reduce the progression of OA in certain patients. Moreover, the most recent progress in research has significantly enhanced our knowledge of the factors involved in the development of the disease and of the mechanisms responsible for its progression. This has allowed identification of several new therapeutic targets in a number of pathophysiological pathways. Consequently, the field is opening up to a new era in which drugs and agents that can specifically block important mechanisms responsible for the structural changes that occur in OA can be brought into development and eventually into clinical trials. PMID:16569256

Oxygenator in short-term LVAD circuit: a rescue in post-LVAD pulmonary complications.

PubMed

Mohite, Prashant N; Patil, Nikhil P; Popov, Aron-Frederik; Bahrami, Toufan; Simon, Andre R

2016-10-01

Pulmonary complications after left ventricular assist device (LVAD) implantation, though infrequent, can be potentially catastrophic. A 62-year-old female with cardiogenic shock, supported on short-term LVAD, developed pulmonary oedema. An oxygenator was introduced into the LVAD circuit, which improved the gas exchange and, eventually, after weaning off the oxygenator, the patient received long-term LVAD. The introduction of an oxygenator into the short-term LAVD circuit is a lifesaving manoeuvre in such a situation. It offers freedom of introducing and removing the oxygenator into the LVAD circuit without opening the chest and competing for LVAD flow. © The Author(s) 2016.

Entrepreneurial Aspirations

NASA Technical Reports Server (NTRS)

1998-01-01

Recom Technologies, Inc., was established in 1980 by Jack Lee, a former NASA contractor. After forming the new company, Recom was awarded NASA contracts, which eventually grew to 50 percent of the company's business. Two companies have spun-off from Recom, both of which have their basis in NASA technology. The first is Attention Control Systems, Inc. with utilizes intelligent planning software that Recom developed for NASA Ames Computational Sciences Division in a hand-held planner used as an aid in cognitive rehabilitation of brain injury patients. The second is MiraNet, Inc. who uses CLIPS as the foundation for WEXpert, the first rules based help system on the Web.

A method and technical equipment for an acute human trial to evaluate retinal implant technology

NASA Astrophysics Data System (ADS)

Hornig, Ralf; Laube, Thomas; Walter, Peter; Velikay-Parel, Michaela; Bornfeld, Norbert; Feucht, Matthias; Akguel, Harun; Rössler, Gernot; Alteheld, Nils; Lütke Notarp, Dietmar; Wyatt, John; Richard, Gisbert

2005-03-01

This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 µm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

Circulating Angiogenic Factors and the Risk of Preeclampsia in Systemic Lupus Erythematosus Pregnancies.

PubMed

Leaños-Miranda, Alfredo; Campos-Galicia, Inova; Berumen-Lechuga, María Guadalupe; Molina-Pérez, Carlos José; García-Paleta, Yolanda; Isordia-Salas, Irma; Ramírez-Valenzuela, Karla Leticia

2015-07-01

To investigate whether angiogenic factors are associated with risk of developing preeclampsia in pregnant women with systemic lupus erythematosus (SLE). We performed a nested case-control study within a cohort of SLE women with singleton pregnancies. The study included 42 patients with SLE who eventually developed preeclampsia and 75 normal SLE pregnancies. Serum samples were collected at 4-week intervals (from weeks 12 to 36). Serum samples were analyzed for soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng). Women destined to develop preeclampsia had lower PlGF levels and higher sFlt-1 and sEng levels, and a higher sFlt-1/PlGF ratio than normal pregnancies. These changes became significant at 12 weeks in patients destined to develop either early onset (< 34 weeks, p ≤ 0.003) or late-onset preeclampsia (≥ 34 weeks, p ≤ 0.02). The risk to develop preeclampsia was higher among patients with PlGF concentration values in the lowest quartile or with sFlt-1 and sEng levels, and sFlt-1/PlGF ratio, in the highest quartile of the normal SLE pregnancies distribution. The OR were higher and appeared earlier in patients destined to develop early onset preeclampsia (OR ≥ 16.2, from Week 12 onward) than in patients who presented preeclampsia later (OR ≥ 8.9, from Week 24 onward). Changes in circulating concentrations of sFlt-1, PlGF, sEng, and the sFlt-1/PlGF ratio precede the onset of preeclampsia in SLE pregnancies. The risk profile of circulating angiogenic factors for developing preeclampsia distinctly evolves depending on whether this condition is manifested earlier or later.

Multiple polyps and colorectal cancer.

PubMed

Alecu, M; Simion, L; Straja, Nd; Brătucu, E

2014-01-01

Malignant degeneration as a possible course of evolution of colorectal polyps renders their diagnosis and therapeutic management a prophylactic act in the prevention of colorectal cancer (CRC). The study was conducted over a period of 3 years (2008-2011), during which 1,368 colonoscopies were performed in our service. The aim of the study was to identify patients presenting multiple colorectal polyps and to determine their risk factors for developing CRC, as well as to establish the appropriate therapeutic conduct. Presence of multiple polyps was recorded in over 40% of the patients identified with colorectal polyps of any kind. Dysplastic modifications observed during the histopathology exam presented a high incidence in the case of patients with multiple polyps, ranging from low-grade dysplasia to incipient CRC. Dysplastic modifications and carcinomatous foci were identified mostly among patients with multiple polyps.Only benign lesions or in situ carcinomas benefited from endoscopic treatment, poorly differentiated carcinomas or those invading the submucosa being treated by conventional surgery. Patients diagnosed with colorectal polyps require a rigorous post-therapy follow-up protocol, able to identify any eventual polyposis recurrence. Celsius.

A case of severe chlorite poisoning successfully treated with early administration of methylene blue, renal replacement therapy, and red blood cell transfusion: case report.

PubMed

Gebhardtova, Andrea; Vavrinec, Peter; Vavrincova-Yaghi, Diana; Seelen, Mark; Dobisova, Anna; Flassikova, Zora; Cikova, Andrea; Henning, Robert H; Yaghi, Aktham

2014-08-01

The case of a 55-year-old man who attempted suicide by ingesting <100 mL of 28% sodium chlorite solution is presented. On arrival in the intensive care unit, the patient appeared cyanotic with lowered consciousness and displayed anuria and chocolate brown serum.Initial laboratory tests revealed 40% of methemoglobin. The formation of methemoglobin was effectively treated with methylene blue (10% after 29 hours).To remove the toxin, and because of the anuric acute renal failure, the patient received renal replacement therapy. Despite these therapeutic measures, the patient developed hemolytic anemia and disseminated intravascular coagulation, which were treated with red blood cell transfusion and intermittent hemodialysis. These interventions led to the improvement of his condition and the patient eventually fully recovered. Patient gave written informed consent.This is the third known case of chlorite poisoning that has been reported. Based upon this case, we suggest the management of sodium chlorite poisoning to comprise the early administration of methylene blue, in addition to renal replacement therapy and transfusion of red blood cells.

A Case of Severe Chlorite Poisoning Successfully Treated With Early Administration of Methylene Blue, Renal Replacement Therapy, and Red Blood Cell Transfusion

PubMed Central

Gebhardtova, Andrea; Vavrinec, Peter; Vavrincova-Yaghi, Diana; Seelen, Mark; Dobisova, Anna; Flassikova, Zora; Cikova, Andrea; Henning, Robert H.; Yaghi, Aktham

2014-01-01

Abstract The case of a 55-year-old man who attempted suicide by ingesting <100 mL of 28% sodium chlorite solution is presented. On arrival in the intensive care unit, the patient appeared cyanotic with lowered consciousness and displayed anuria and chocolate brown serum. Initial laboratory tests revealed 40% of methemoglobin. The formation of methemoglobin was effectively treated with methylene blue (10% after 29 hours). To remove the toxin, and because of the anuric acute renal failure, the patient received renal replacement therapy. Despite these therapeutic measures, the patient developed hemolytic anemia and disseminated intravascular coagulation, which were treated with red blood cell transfusion and intermittent hemodialysis. These interventions led to the improvement of his condition and the patient eventually fully recovered. Patient gave written informed consent. This is the third known case of chlorite poisoning that has been reported. Based upon this case, we suggest the management of sodium chlorite poisoning to comprise the early administration of methylene blue, in addition to renal replacement therapy and transfusion of red blood cells. PMID:25144325

Informed Strangers: Witnessing and Responding to Unethical Care as Student Nurses

PubMed Central

Engel, Joyce; Salfi, Jenn; Micsinszki, Samantha; Bodnar, Andrea

2017-01-01

Nursing students occupy a unique perspective in clinical settings because they are informed, through education, about how patient care ought to happen. Given the brevity of placements and their “visiting status” in clinical sites, students are less invested in the ethos of specific sites. Subsequently, their perspectives of quality care are informed by what should happen, which might differ from that of nurses and patients. The purpose of this study was to identify predominant themes in patient care, as experienced by students, and the influence that these observations have on the development of their ethical reasoning. Using a qualitative descriptive approach in which 27 nursing student papers and three follow-up in-depth interviews were analyzed, three main themes emerged: Good employee, poor nurse; damaged care; and negotiating the gap. The analysis of the ethical situations in these papers suggests that students sometimes observe care that lacks concern for the dignity, autonomy, and safety of patients. For these student nurses, this tension led to uncertainty about patient care and their eventual profession. PMID:28932765

Outcome of Endodontically Treated Teeth Diagnosed With Cracked Tooth

DTIC Science & Technology

2015-06-01

However, variable symptoms complicate the diagnosis (9). In a study of 32 patients presenting with diffuse longstanding orofacial pain eventually...883-92. 22)Byrnjulsen A, Fristad I, Grevstad T, Hals-Kvinnsland I. Incompletely fractured teeth associated with diffuse longstanding orofacial pain ...cracked tooth is highly associated with discomfort. Patients often describe a momentary, sudden, sharp, lancinating pain that results in continuous tooth

Effects of Aging and Environmental Conditions on Ammunition/Explosives Storage Magazines - Paper 2

DTIC Science & Technology

2010-07-01

characterized as destructive. The destructive category is apparently limited to reactions with impure dolomitic aggregates and are a result of either...extreme pressures that eventually overcome the tensile strength of the structure. These pressures will cause spalling, map cracking, discoloration, or...fill with this gel and expand to create extreme tensile pressures . These pressures cause micro-scale cracking and eventually develop into

Systemic amyloidosis: unusual presentation mistaken for a recurrent scabies infection.

PubMed

Haley, Erin M; Nabatian, Adam S; Kopp, Sandra A; Falasca, Gerald F; Haupt, Helen M; Halpern, Analisa V

2014-06-01

We report the case of a 63-year-old woman with a history of undifferentiated connective-tissue disease, polyarthritis, and bilateral carpal tunnel syndrome who presented with generalized pruritus and erythematous and excoriated papules on the trunk and extremities. Empiric scabies treatment was unsuccessful. Patch testing and T-cell receptor gene rearrangement studies were unremarkable. The patient was found to have mild interstitial lung disease and hypogammaglobulinemia. Eventually a diagnosis of primary systemic amyloidosis was made after she developed frank lingual hypertrophy despite normal initial serum protein electrophoresis and negative abdominal fat pad aspiration. Diagnosis was confirmed with lingual biopsy. This case demonstrates an unusual presentation of primary systemic amyloidosis consisting of arthritis and intense debilitating pruritus without primary skin lesions for a full year prior to diagnosis of multiple myeloma. The patient responded to treatment with chemotherapy and corticosteroids.

Fibrosarcoma of the mandible following supravoltage irradiation. Report of a case.

PubMed

Moloy, P J; Kowal, K A; Siegel, W M

1989-10-01

Supravoltage irradiation is commonly thought not to be carcinogenic. Several recent studies question this concept, as does our case report. A 50-year-old woman with stage 1 squamous carcinoma of the left side of the tongue was treated in 1973 with 73 Gy of supravoltage irradiation. Twelve years later a painful, ulcerated lesion that eventually was shown to be fibrosarcoma developed in the contralateral mandible. The fibrosarcoma in this case fulfills all criteria for diagnosing radiation-induced neoplasia and demonstrates that supravoltage irradiation, like other forms of irradiation, can cause malignancy. The occasional occurrence of sarcoma should be recalled during follow-up of patients treated with supravoltage radiation. Similarly, the possibility of radiation-induced tumors should be considered in planning treatment for younger patients with tumors that can be treated equally well by surgery or irradiation.

[Interleukins network in rheumatoid arthritis pathophysiology: beyond proinflammatory cytokines].

PubMed

Sánchez-Ramón, Silvia; López-Longo, Francisco Javier; Carreño, Luis

2011-03-01

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and progressive destruction of the joint cartilage and underlying bone, together with diverse extra-articular manifestations. Cytokines act as soluble effector mediators of the inflammatory process. Therapeutic neutralization with monoclonal antibodies against the pro-inflammatory cytokines TNF-alpha and interleukin 1 (IL-1) has shown a clear efficacy on inflammation and clinical manifestations of RA, although a percentage of patients do not respond. This review covers new relevant cytokines in the RA physiopathology and potential biomarkers of inflammation. The current challenge is to develop biomarkers that enable an earlier diagnosis, as well as prognostic markers and new therapeutic candidates. Combined administration of several of these cytokines could eventually address a personalized treatment approach for each patient. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer.

PubMed

Aydin, Ahmet Murat; Woldu, Solomon L; Hutchinson, Ryan C; Boegemann, Martin; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Krabbe, Laura-Maria

2017-01-01

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile. We review the mechanism of action and clinical evidence of atezolizumab for metastatic urothelial bladder cancer, and discuss this drug within the context of ongoing developments in this dynamic field of immunooncology.

Spotlight on atezolizumab and its potential in the treatment of advanced urothelial bladder cancer

PubMed Central

Aydin, Ahmet Murat; Woldu, Solomon L; Hutchinson, Ryan C; Boegemann, Martin; Bagrodia, Aditya; Lotan, Yair; Margulis, Vitaly; Krabbe, Laura-Maria

2017-01-01

Metastatic urothelial carcinoma of the bladder is an aggressive malignancy with poor prognosis, reflecting a lack of effective systemic therapies. The current standard of care includes multiagent platinum-based chemotherapy; however a majority of patients do not respond to treatment and most eventually succumb to disease. Recently, renewed interest in immunotherapy in the form of immune-checkpoint inhibition has gained widespread attention for a number of malignancies. Atezolizumab, an anti-PDL1 antibody, has been shown to be effective in a subset of patients previously treated with or unfit for platinum-based chemotherapy, and has shown durable responses with a good tolerability profile. We review the mechanism of action and clinical evidence of atezolizumab for metastatic urothelial bladder cancer, and discuss this drug within the context of ongoing developments in this dynamic field of immunooncology. PMID:28331342

A projection pursuit algorithm to classify individuals using fMRI data: Application to schizophrenia.

PubMed

Demirci, Oguz; Clark, Vincent P; Calhoun, Vince D

2008-02-15

Schizophrenia is diagnosed based largely upon behavioral symptoms. Currently, no quantitative, biologically based diagnostic technique has yet been developed to identify patients with schizophrenia. Classification of individuals into patient with schizophrenia and healthy control groups based on quantitative biologically based data is of great interest to support and refine psychiatric diagnoses. We applied a novel projection pursuit technique on various components obtained with independent component analysis (ICA) of 70 subjects' fMRI activation maps obtained during an auditory oddball task. The validity of the technique was tested with a leave-one-out method and the detection performance varied between 80% and 90%. The findings suggest that the proposed data reduction algorithm is effective in classifying individuals into schizophrenia and healthy control groups and may eventually prove useful as a diagnostic tool.

Continuous dopaminergic stimulation in a patient treated with daytime Levodopa-carbidopa intestinal gel and overnight Rotigotine: a case report.

PubMed

Imbriani, Paola; Schirinzi, Tommaso; D'Elia, Alessio; Pisani, Antonio

2017-08-23

Patients with Parkinson's disease (PD) receiving long-term L-Dopa therapy eventually develop motor complications with unpredictable "on-off" response fluctuations and involuntary movements, leading to progressive disability. Hence, the search for alternative therapeutic choices based on continuous dopaminergic stimulation (CDS) becomes crucial for the treatment of advanced PD. Here, we describe the case of a 70-year-old man with a 9-year history of PD, treated with daytime levodopa-carbidopa intestinal gel (LCIG) and overnight Rotigotine transdermal patch. LCIG monotherapy significantly reduced motor fluctuations and prevented the appearance of unpredictable off periods; concurrently, overnight Rotigotine improved his sleep quality and morning akinesia. Both LCIG and Rotigotine induce CDS, which conceptually mimics physiologic striatal dopamine receptor function. Hence, they both represent a good therapeutic option for the treatment of advanced PD.

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

Ruckdeschel, J.C.; Baxter, D.H.; McKneally, M.F.

Intrapleural immunotherapy, radiotherapy and chemotherapy were employed in that sequence in 22 patients with Stage III non-oat cell bronchogenic carcinoma confined to the thorax. Seven patients received intrapleural BCG in a pilot study and 15 were randomized between intrapleural BCG and intrapleural saline. Isoniazid was begun on day 14 and irradiation (3000 rad in 10 fractions) to the primary lesion, mediastinum and ipsilateral supraclavicular nodes was started on day 21. One to two weeks following irradiation, CAMP chemotherapy was initiated (Cyclophosphamide 300 mg/M/sup 2/ iv, d. 1,8; Adriamycin 20 mg/M/sup 2/ iv, d. 1,8; Methotrexate 15 mg/M/sup 2/ iv, d.more » 1,8 and Procarbazine 100 mg/M/sup 2/ p.o., d. 1 to 10). Chemotherapy was given for a total of six months. Two patients expired prior to radiotherapy (1 tumor progression, 1 myocardial infarction) and 2 patients were lost to follow-up. Nausea, vomiting, alopecia and fatigue were universal side effects of the chemotherapy. Esophagitis occurred in 9 patients, 7 prior to and 2 after initiation of Adriamycin. In only one case did Adriamycin exacerbate a previous radiation esophagitis. No patient developed clinical radiation pneumonitis, although all had eventual radiation fibrosis. Congestive heart failure occurred in 1 patient with known valvular heart disease and responded to diuretics. Three patients developed localized herpes zoster infections. One patient developed radiation myelitis one year after initiating therapy and six months after completing all chemotherapy. The major side effect was leukopenia with relative platelet sparing. Although significant morbidity was encountered in this primarily older patient population (mean age 64.8 years) recall reactions involving irradiated intrathoracic structures were not a significant clinical problem.« less

Korean Guidelines for the Appropriate Use of Cardiac CT

PubMed Central

Kim, Young Jin; Kim, Sung Mok; Kim, Jeong A; Yang, Dong Hyun; Hong, Yoo Jin

2015-01-01

The development of cardiac CT has provided a non-invasive alternative to echocardiography, exercise electrocardiogram, and invasive angiography and cardiac CT continues to develop at an exponential speed even now. The appropriate use of cardiac CT may lead to improvements in the medical performances of physicians and can reduce medical costs which eventually contribute to better public health. However, until now, there has been no guideline regarding the appropriate use of cardiac CT in Korea. We intend to provide guidelines for the appropriate use of cardiac CT in heart diseases based on scientific data. The purpose of this guideline is to assist clinicians and other health professionals in the use of cardiac CT for diagnosis and treatment of heart diseases, especially in patients at high risk or suspected of heart disease. PMID:25741189

Regenerative immunology: the immunological reaction to biomaterials.

PubMed

Cravedi, Paolo; Farouk, Samira; Angeletti, Andrea; Edgar, Lauren; Tamburrini, Riccardo; Duisit, Jerome; Perin, Laura; Orlando, Giuseppe

2017-12-01

Regenerative medicine promises to meet two of the most urgent needs of modern organ transplantation, namely immunosuppression-free transplantation and an inexhaustible source of organs. Ideally, bioengineered organs would be manufactured from a patient's own biomaterials-both cells and the supporting scaffolding materials in which cells would be embedded and allowed to mature to eventually regenerate the organ in question. While some groups are focusing on the feasibility of this approach, few are focusing on the immunogenicity of the scaffolds that are being developed for organ bioengineering purposes. This review will succinctly discuss progress in the understanding of immunological characteristics and behavior of different scaffolds currently under development, with emphasis on the extracellular matrix scaffolds obtained decellularized animal or human organs which seem to provide the ideal template for bioengineering purposes. © 2017 Steunstichting ESOT.

Achalasia following gastro-oesophageal reflux.

PubMed Central

Smart, H L; Mayberry, J F; Atkinson, M

1986-01-01

Five patients initially presenting with symptomatic gastro-oesophageal reflux, proven by radiology or pH monitoring, subsequently developed achalasia, confirmed by radiology and manometry, after an interval of 2-10 years. During this period dysphagia, present as a mild and intermittent symptom accompanying the initial reflux in 3 of the 5, became severe and resulted in oesophageal stasis of food in all. Three of the 5 had a demonstrable hiatal hernia. In none was reflux a troublesome symptom after Rider-Moeller dilatation or cardiomyotomy undertaken for the achalasia. Gastro-oesophageal reflux does not protect against the subsequent development of achalasia. It is suggested that the autonomic damage eventually leading to achalasia may in its initial phases cause gastro-oesophageal reflux. Images Figure 1. A Figure 1. B Figure 2. PMID:3950898

The use of biodegradable plates and screws to stabilize facial fractures.

PubMed

Bell, R Bryan; Kindsfater, Craig S

2006-01-01

The purpose of this preliminary retrospective study was to review the demographics and outcome of patients with a variety of facial fractures that were stabilized with PL bone plates and screws. The records of 295 consecutive patients with facial fractures treated by open reduction and internal fixation, performed by the author from 2001 through 2004, were retrospectively reviewed. Patients were selected to receive biodegradable fixation on the basis of mechanism of injury, the degree of bony displacement demonstrated on clinical and radiographic examination, patient age, and fracture pattern or location. Outcome measures such as infection, non-union, and mal-union were identified and subjectively assessed. Descriptive statistics were recorded and analyzed. Two hundred eighty-one patients met the criteria for inclusion in the study with follow-up of 3 weeks to 3 years. Fifty-nine (21%) patients were identified as having received biodegradable plates and screws. All patients eventually went on to satisfactory healing with favorable restoration of form and function. Complications occurred in 16 patients overall (6%). Of these, 2 patients were treated with resorbable plates and screws; 1 patient with a zygomatico-maxillary complex fracture developed a sterile abscess that presented 1 year postoperatively and responded to local measures. Another patient with a Le Fort I fracture developed an anterior open bite necessitating Le Fort I osteotomy for correction. Favorable healing can be observed through the use of biodegradable PL plates and screws to stabilize selected midface fractures in patients of all ages, as well as mandible fractures in early childhood.

A Parent-Report Instrument for Identifying One-Year-Olds at Risk for an Eventual Diagnosis of Autism: The First Year Inventory

ERIC Educational Resources Information Center

Reznick, J. Steven; Baranek, Grace T.; Reavis, Shaye; Watson, Linda R.; Crais, Elizabeth R.

2007-01-01

A parent-report instrument, the First Year Inventory (FYI), was developed to assess behaviors in 12-month-old infants that suggest risk for an eventual diagnosis of autism. The target behaviors were identified from retrospective and prospective studies. FYIs were mailed to 5,941 families and 25% (N = 1,496) were returned, with higher return rates…

Case reports - When bronchial obstruction in the young adult is not asthma and inhalers do not help.

PubMed

Sigvard, Anne; Bødtger, Uffe

2016-08-01

Localised bronchial obstruction is a rare differential diagnosis to asthma. We describe two younger patients treated unsuccessfully for asthma and eventually diagnosed with localised bronchoconstriction. Bronchoscopy revealed bronchoconstriction: Tracheobronchomalacia in case 1 and fixed obstruction in case 2. A systematic approach to the asthma patient with absent response to therapy facilitates rational use of therapeutic and diagnostic resources.

[Some ethical considerations, especially identity, during xenotransplantation].

PubMed

Cüer, P

2000-05-01

Provided that a pandemic due to retroviruses or prions eventually transmitted by animals is under control, in accordance with the fundamental ethical rule to serve the best interest of the patient, any organ xenotransplantation raises an important ethical dilemma: how to deliver proper and adapted information to the patient on the preservation of his identity. Xenotransplantation of any part of the brain seems to us unethical.

Reconstruction of thoracic burn sequelae by scar release and flap resurfacing.

PubMed

Angrigiani, Claudio; Artero, Guillermo; Castro, Gaston; Khouri, Roger K

2015-12-01

In the USA, 450,000 thermal burns receive medical treatment annually. Burn scars are commonly excised and covered with skin grafts. Long-term, these treatments commonly leave patients with discomfort, reduced total lung capacity and forced vital capacity, and restriction of thoracic expansion and shoulder joint mobility. In this article, we present our experience with using scar release and immediate flap reconstruction to treat thoracic restriction due to burn sequelae. From 1998 to 2014, we enrolled 16 patients with anterior thoracic burn sequelae that had previously been treated conservatively or with skin grafts that eventually recidivated. Preoperatively, we measured thoracic circumference in expiration and inspiration, %FVC, %FEV1, and shoulder mobility. All patients underwent anterior thoracic scar release and immediate flap resurfacing. At 2 weeks to 3 months postoperatively (mean, 2.6 months), mean thoracic circumference upon inspiration increased from 83.6 cm±5.7 to 86.5 cm±5.8 (p<0.0000000001). Mean %FVC improved from 76.0%±2.64% to 88.2%±4.69% (p<0.0000001). Mean %FEV1 improved from 79.2%±3.85 to 87.8%±2.98 (p<0.000001). All 14 patients who had restricted shoulder mobility preoperatively no longer had restricted shoulder mobility postoperatively. The mean patient-reported satisfaction was 4.6/5 (range, 3-5). At a mean follow up of 2.5 years, none of the contractures recidivated. Complications included 2 cases of tissue necrosis of the distal end of the flap. In one case, the flap was restored; in the other case, the patient eventually had to receive a new flap. Additional complications included two local infections that were successfully treated with oral and local antibiotics and two hematomas that were drained and eventually healed without tissue loss. Scar releases and flaps provide a safe and effective method for the correction of restricted thoracic expansion, respiratory restriction, decreased range of shoulder motion, and discomfort from thoracic burn sequelae. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

Analysis of volumetric response of pituitary adenomas receiving adjuvant CyberKnife stereotactic radiosurgery with the application of an exponential fitting model.

PubMed

Yu, Yi-Lin; Yang, Yun-Ju; Lin, Chin; Hsieh, Chih-Chuan; Li, Chiao-Zhu; Feng, Shao-Wei; Tang, Chi-Tun; Chung, Tzu-Tsao; Ma, Hsin-I; Chen, Yuan-Hao; Ju, Da-Tong; Hueng, Dueng-Yuan

2017-01-01

Tumor control rates of pituitary adenomas (PAs) receiving adjuvant CyberKnife stereotactic radiosurgery (CK SRS) are high. However, there is currently no uniform way to estimate the time course of the disease. The aim of this study was to analyze the volumetric responses of PAs after CK SRS and investigate the application of an exponential decay model in calculating an accurate time course and estimation of the eventual outcome.A retrospective review of 34 patients with PAs who received adjuvant CK SRS between 2006 and 2013 was performed. Tumor volume was calculated using the planimetric method. The percent change in tumor volume and tumor volume rate of change were compared at median 4-, 10-, 20-, and 36-month intervals. Tumor responses were classified as: progression for >15% volume increase, regression for ≤15% decrease, and stabilization for ±15% of the baseline volume at the time of last follow-up. For each patient, the volumetric change versus time was fitted with an exponential model.The overall tumor control rate was 94.1% in the 36-month (range 18-87 months) follow-up period (mean volume change of -43.3%). Volume regression (mean decrease of -50.5%) was demonstrated in 27 (79%) patients, tumor stabilization (mean change of -3.7%) in 5 (15%) patients, and tumor progression (mean increase of 28.1%) in 2 (6%) patients (P = 0.001). Tumors that eventually regressed or stabilized had a temporary volume increase of 1.07% and 41.5% at 4 months after CK SRS, respectively (P = 0.017). The tumor volume estimated using the exponential fitting equation demonstrated high positive correlation with the actual volume calculated by magnetic resonance imaging (MRI) as tested by Pearson correlation coefficient (0.9).Transient progression of PAs post-CK SRS was seen in 62.5% of the patients receiving CK SRS, and it was not predictive of eventual volume regression or progression. A three-point exponential model is of potential predictive value according to relative distribution. An exponential decay model can be used to calculate the time course of tumors that are ultimately controlled.

Peer Review of EPA's Draft BMDS Document: Exponential ...

EPA Pesticide Factsheets

BMDS is one of the Agency's premier tools for estimating risk assessments, therefore the validity and reliability of its statistical models are of paramount importance. This page provides links to peer review of the BMDS applications and its models as they were developed and eventually released documenting the rigorous review process taken to provide the best science tools available for statistical modeling. This page provides links to peer review of the BMDS applications and its models as they were developed and eventually released documenting the rigorous review process taken to provide the best science tools available for statistical modeling.

Case management for the subacute patient in a skilled nursing facility.

PubMed

Carr, D D

2000-01-01

The goal of case management has always been to manage care, cost, and outcomes. The Balanced Budget Act of 1997 and the subsequent implementation of managed care and the prospective payment system have introduced many challenges to the postacute care delivery system. The implementation of sound clinical, fiscal, and operational strategies is critical to the continued delivery of quality services and the maximization of revenue. The implementation of case management principles provides an opportunity to balance care with cost. This article focuses on the development and implementation of a case management program at a skilled nursing facility that specifically addresses the needs of a subacute population. The program's purpose is to promote efficiency, efficacy, and effectiveness of services for short-term subacute patients who will eventually return to the community. The long-term goal of the program is to classify all patients into case management categories and assign them to RN case managers or social workers, based on acuity and need.

Successful management of severe neuroinvasive eastern equine encephalitis.

PubMed

Wendell, Linda C; Potter, N Stevenson; Roth, Julie L; Salloway, Stephen P; Thompson, Bradford B

2013-08-01

Eastern Equine Encephalitis (EEE) virus is an arbovirus that mostly causes asymptomatic infection in humans; however, some people can develop a neuroinvasive infection associated with a high mortality. We present a case of a patient with severe neuroinvasive EEE. A 21-year-old man initially presented with headache, fever, and vomiting and was found to have a neutrophilic pleocytosis in his cerebrospinal fluid. He eventually was diagnosed with EEE, treated with high-dose methylprednisolone and intravenous immunoglobulin. His course in the NeuroIntensive Care Unit was complicated by cerebral edema and intracranial hypertension, requiring osmotherapy, pentobarbital and placement of an external ventricular device, and subclinical seizures, necessitating multiple anti-epileptic drugs A multifaceted approach including aggressive management of cerebral edema and ICP as well as treatment with immunomodulating agents and cessation of seizures may prevent brain herniation, secondary neurologic injury and death in patients with EEE. Effective management and treatment in our patient contributed to a dramatic recovery and ultimate good outcome.

Osteoarthritis: detection, pathophysiology, and current/future treatment strategies.

PubMed

Sovani, Sujata; Grogan, Shawn P

2013-01-01

Osteoarthritis (OA) is a disease of the joint, and age is the major risk factor for its development. Clinical manifestation of OA includes joint pain, stiffness, and loss of mobility. Currently, no pharmacological treatments are available to treat this specific joint disease; only symptom-modifying drugs are available. Improvement in imaging technology, identification of biomarkers, and increased understanding of the molecular basis of OA will aid in detecting the early stages of disease. Yet the development of interventional strategies remains elusive and will be critical for effective prevention of OA-associated joint destruction. The potential of cell-based therapies may be applicable in improving joint function in mild to more advanced cases of OA. Ongoing studies to understand the basis of this disease will eventually lead to prevention and treatment strategies and will also be a key in reducing the social and economic burden of this disease. Nurses are advised to provide an integrative approach of disease assessment and management in OA patients' care with a focus on education and implementation. Knowledge and understanding of OA and how this affects the individual patient form the basis for such an integrative approach to all-round patient care and disease management.

Leptospirosis in New Orleans.

PubMed

Toliver, Herman L; Krane, N Kevin

2014-02-01

Leptospirosis is an unusual but reemerging zoonotic infectious disease in the United States where the diagnosis may not be suspected when patients initially present. The case report of a patient from New Orleans who presented with jaundice, hypotension and acute kidney injury is presented. In this patient, a broad differential diagnosis was considered on presentation and serologic testing for leptospirosis eventually confirmed the diagnosis. A review of the clinical manifestations, diagnostic studies and treatment are discussed so that leptospirosis will be considered more carefully in the initial evaluation and management of similar patients.

Long-term outcomes of Gamma Knife radiosurgery in patients with vestibular schwannomas.

PubMed

Murphy, Erin S; Barnett, Gene H; Vogelbaum, Michael A; Neyman, Gennady; Stevens, Glen H J; Cohen, Bruce H; Elson, Paul; Vassil, Andrew D; Suh, John H

2011-02-01

The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS). One hundred seventeen patients with VS underwent GKRS between January 1997 and February 2003. At the time of analysis, at least 5 years had passed since GKRS in all patients. The mean patient age was 60.9 years. The mean maximal tumor diameter was 1.77 ± 0.71 cm. The mean tumor volume was 1.95 ± 2.42 ml. Eighty-two percent of lesions received 1300 cGy and 14% received 1200 cGy. The median dose homogeneity ratio was 1.97 and the median dose conformality ratio was 1.78. Follow-up included MR imaging or CT scanning approximately every 6-12 months. Rates of progression to surgery were calculated using the Kaplan-Meier method. Of the 117 patients in whom data were analyzed, 103 had follow-up MR or CT images and 14 patients were lost to follow-up. Fifty-three percent of patients had stable tumors and 37.9% had a radiographically documented response. Imaging-documented tumor progression was present in 8 patients (7.8%), but in 3 of these the lesion eventually stabilized. Only 5 patients required a neurosurgical intervention. The estimated 1-, 3-, and 5-year rates of progression to surgery were 1, 4.6, and 8.9%, respectively. One patient (1%) developed trigeminal neuropathy, 4 patients (5%) developed permanent facial neuropathy, 3 patients (4%) reported vertigo, and 7 patients (18%) had new gait imbalance following GKRS. Gamma Knife radiosurgery results in excellent local control rates with minimal toxicity for patients with VS. The authors recommend standardized follow-up to gain a better understanding of the long-term effects of GKRS.

Osimertinib reactivated immune-related colitis after treatment with anti-PD1 antibody for non-small cell lung cancer.

PubMed

Takenaka, Tomoyoshi; Yamazaki, Koji; Miura, Naoko; Harada, Naohiko; Takeo, Sadanori

2017-12-01

We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea. We diagnosed immune-related colitis and started oral prednisolone. However, the steroid therapy was ineffective, so the patient was administered infliximab and an increased dose of prednisolone. Her symptoms subsequently resolved, and her mucosal lesions improved. Six months after the last administration of nivolumab, osimertinib was initiated as fourth-line therapy, but 3 days later, the patient developed blood in the stool and frequent diarrhea. Osimertinib treatment was discontinued, given the possibility that it had reactivated the patient's immune-related colitis. We subsequently re-administered oral prednisolone (2 mg/kg/day), and the colitis resolved within a few weeks.

Intensive symptom control of opioid-refractory dyspnea in congestive heart failure: Role of milrinone in the palliative care unit.

PubMed

Silvestre, Julio; Montoya, Maria; Bruera, Eduardo; Elsayem, Ahmed

2015-12-01

We describe an exemplary case of congestive heart failure (CHF) symptoms controlled with milrinone. We also analyze the benefits and risks of milrinone administration in an unmonitored setting. We describe the case of a patient with refractory leukemia and end-stage CHF who developed severe dyspnea after discontinuation of milrinone. At that point, despite starting opioids, she had been severely dyspneic and anxious, requiring admission to the palliative care unit (PCU) for symptom control. After negotiation with hospital administrators, milrinone was administered in an unmonitored setting such as the PCU. A multidisciplinary team approach was also provided. Milrinone produced a dramatic improvement in the patient's symptom scores and performance status. The patient was eventually discharged to home hospice on a milrinone infusion with excellent symptom control. This case suggests that milrinone may be of benefit for short-term inpatient administration for dyspnea management, even in unmonitored settings and consequently during hospice in do-not-resuscitate (DNR) patients. This strategy may reduce costs and readmissions to the hospital related to end-stage CHF.

Analysis of Predictors of Resection and Survival in Locally Advanced Stage III Pancreatic Cancer: Does the Nature of Chemotherapy Regimen Influence Outcomes?

PubMed

Bednar, Filip; Zenati, Mazen S; Steve, Jennifer; Winters, Sharon; Ocuin, Lee M; Bahary, Nathan; Hogg, Melissa E; Zeh, Herbert J; Zureikat, Amer H

2017-05-01

Locally advanced unresectable pancreatic cancer (LAPC) historically portends a poor prognosis. FOLFIRINOX and gemcitabine/nab-paclitaxel have proven effective in the metastatic setting. We sought to evaluate the outcomes of these regimens compared with older regimens in LAPC. A retrospective, single institutional review of all consecutive LAPC treated with "new" (FOLFIRINOX and/or gemcitabine/nab-paclitaxel) and "old" (gemcitabine or 5-FU) chemotherapy from 2010 to 2014 was performed. Univariate and multivariate predictors of resection and survival were determined. A total of 92 patients (new chemotherapy = 61, old chemotherapy = 31) were analyzed, of which 19 (21%) underwent eventual resection (median overall survival [OS] = 32 vs. 14.3 months for unresected patients, P = 0.0002). For the overall cohort, resection (hazard ratio [HR] 0.261, P = 0.014), radiation therapy (HR 0.458, P = 0.004), number of lines of chemotherapy (HR 0.486, P = 0.012), and new chemotherapy (HR 0.593 vs. old regimens, P = 0.065) were independent predictors of OS on multivariate analyses (MVA). On MVA, predictors of eventual resection were head and neck tumors (OR 0.307, P = 0.033) or SMA involvement (OR 0.285, P = 0.023). In nonresected patients (73), MVA showed treatment with new chemotherapy (HR 0.452, P = 0.006), radiation (HR 0.459, P = 0.006), and number of lines of CT (HR 0.705, P = 0.013) to be predictors of survival. In LAPC, use of FOLFIRNOX and/or gemcitabine/nab-paclitaxel is associated with improved survival compared with older chemotherapy regimens, regardless of eventual resection. Tumor location and relationship to certain vasculature are important determinants of resection in this cohort.

Lead toxicity masquerading as sickle cell crisis.

PubMed

Nelson, M S; Chisolm, J J

1986-06-01

We recently saw a 12-year-old black boy with known sickle cell disease who had been seen many times for abdominal pain thought to be secondary to a vasoocclusive crisis. The patient eventually was admitted, after a seizure and the onset of obtundation. The etiology of his acute encephalopathy remained unclear until bone films of his knees fortuitously revealed "lead lines." The patient was treated and did well subsequently. This case emphasizes the importance of considering other diagnoses when a sickle cell patient presents with a crisis.

Neuropathic pain in the orofacial region: The role of pain history. A retrospective study.

PubMed

Dieb, W; Moreau, N; Chemla, I; Descroix, V; Boucher, Y

2017-06-01

Orofacial neuropathic pain is often difficult to treat, mostly because of still unclear underlying mechanisms. The occurrence of such neuropathic pain varies depending on different factors, of which preexisting preoperative pain seems to be of high importance. The aim of this study was thus to test the hypothesis that prior history of pain could indeed be considered a risk factor for the development of orofacial neuropathic pain in the same region. The study was performed in the dental department of the Groupe Hospitalier Pitié-Salpêtrière (GHPS) in Paris, France. We investigated the presence of prior inflammatory pain before development of orofacial neuropathic pain in 56 patients. For each patient file, the following items were collected: age, gender; medical history; diagnosis; description of the pain (at time of consultation); presence or absence of prior dental treatment; date and type of dental treatment received. 41 patients (73%) of orofacial neuropathic pain patients had a history of pain compatible with an inflammatory condition; 4% (n=2) did not report any prior pain and 23% (n=13) could not remember. Among the patients with documented history of pain prior to neuropathy, 88% (n=36) received surgical treatment; 61%, (n=25) endodontic treatment and 22%, (n=9) restorative treatment. All eventually received endodontic treatment or tooth extraction. These dental treatments are compatible with the hypothesis of prior inflammatory pain in these patients. These results support the hypothesis that prior inflammatory pain could favor the development of orofacial neuropathic pain. Prevention and treatment of inflammatory trigeminal pain may therefore play a key role in preventing future neuropathic pain development. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Altered Th17 cells and Th17/regulatory T-cell ratios indicate the subsequent conversion from undifferentiated connective tissue disease to definitive systemic autoimmune disorders.

PubMed

Szodoray, Peter; Nakken, Britt; Barath, Sandor; Csipo, Istvan; Nagy, Gabor; El-Hage, Fadi; Osnes, Liv T; Szegedi, Gyula; Bodolay, Edit

2013-12-01

A shift in the balance between Th17-cells and regulatory T-cells (Treg) is an important feature of systemic autoimmune diseases (SAID), and may also contribute to their development. Hereby, we assessed the distribution of peripheral Th17 and Treg-cells in patients with undifferentiated connective tissue disease (UCTD), the forerunner of SAIDs and followed these parameters during the development towards definitive SAIDs. Fifty-one UCTD patients were investigated and followed-up for 3 years. Flow cytometry was used to identify and follow three cell-populations: Th17-cells (CD4+IL-17+ T-cells), natural regulatory T-cells (CD4(+)CD25(bright)FoxP3(+); nTregs) and IL-10 producing Type-1 regulatory T-cells (CD4+IL-10+ T-cells; Tr1). Altogether 37.3% of these patients progressed into SAIDs. Th17-cells were increased in UCTD vs. controls, which further increased in those, whom developed SAIDs eventually. The Th17/nTreg ratio gradually increased from controls through UCTD patients, reaching the highest values in SAID-progressed patients. Regarding the Th17/Tr1 ratios, a similar tendency was observed moreover Th17/Tr1 could distinguish between UCTD patients with, or without subsequent SAID progression in a very early UCTD stage. Various immunoserological markers showed association with Th17 and Th17/nTreg at baseline, indicating the consecutive development of a distinct SAID. The derailed Th17/Treg balance may contribute to disease progression therefore could function as a prognostic marker. Copyright © 2013 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Psychosocial predictors of health outcomes in colorectal cancer: a comprehensive review.

PubMed

Sales, Paulo M G; Carvalho, André F; McIntyre, Roger S; Pavlidis, Nicholas; Hyphantis, Thomas N

2014-07-01

A diagnosis of colorectal cancer (CRC) and its long-term treatment may lead to significant psychological distress and impaired health-related quality of life (HRQoL) for a significant proportion of patients. We searched the PubMed/MEDLINE electronic database for available literature on the associations between personality characteristics, depression, psychological distress and HRQoL in CRC. Additional references were identified through the citation tracking of the included articles. Recent evidence indicates that Type-D (distressed) personality may predict distress among CRC patients. Additionally, other personality traits, such as specific ego defense mechanisms, influence the coping responses and HRQoL. Although the presence of a stoma has been linked to the development of depressive symptoms and impairment in HRQoL in CRC patients, more prospective studies are necessary to confirm these associations. Sense of coherence (SOC) has both a moderating and mediating effect on health (especially mental health and HRQoL), and preliminary data indicate that SOC may be an independent predictor of CRC survival. The interplay between personality variables during the elaboration of "the impaired role" is complex, and the assessment of personality traits may be incorporated into a comprehensive psychosomatic evaluation of CRC patients. More well-designed prospective investigations are necessary to establish the contributory role of personality dimensions for the development of and protection from distress and impairment in the HRQoL of CRC patients, which could eventually lead to the development of psychosocial interventions that are personalized to this patient population (for example, manual-based psychotherapies). Copyright © 2014 Elsevier Ltd. All rights reserved.

Comprehensive Approaches to Managing Delirium in Patients with Advanced Cancer

PubMed Central

Kang, Jung Hun; Shin, Seong Hoon; Bruera, Eduardo

2013-01-01

Delirium is a frequently under-recognized complication in patients with advanced cancer. Uncontrolled delirium eventually leads to significant distress to patients and their families. However, delirium episodes can be reversed in half of these patients by eliminating precipitating factors and using appropriate interventions. The purpose of this narrative review is to discuss the most recent updates in the literature on the management of delirium in patients with advanced cancer. This article addresses the epidemiology, cause, pathophysiology, clinical characteristics, and assessment of delirium as well as various treatment options, including nonpharmacologic intervention and palliative sedation. PMID:22959227

Drug-Coated Balloon Angioplasty: A Novel Treatment for Pulmonary Artery In-Stent Stenosis in a Patient with Williams Syndrome.

PubMed

Cohen, Jennifer L; Glickstein, Julie S; Crystal, Matthew A

2017-12-01

A 20-month-old boy with Williams syndrome had undergone multiple surgical and catheter-based interventions for resistant peripheral pulmonary arterial stenoses with eventual bilateral stent placement and conventional balloon angioplasty. He persistently developed suprasystemic right ventricular (RV) pressure. Angioplasty with a drug-coated balloon (DCB) was performed for in-stent restenosis and to remodel his distal pulmonary vessels bilaterally. This resulted in immediate improvement in the in-stent stenosis and resultant decrease in RV pressure. Follow-up catheterization two months later continued to show long-lasting improvement in the in-stent stenosis. We hypothesize that the anti-proliferative effects of DCBs may be of benefit in the arteriopathy associated with Williams syndrome. We report this as a novel use of a DCB in the pulmonary arterial circulation in a patient with Williams syndrome.

Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency

PubMed Central

Non, Lemuel; Brito, Daniel; Anastasopoulou, Catherine

2015-01-01

Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI. PMID:25612752

Neurosarcoidosis-associated central diabetes insipidus masked by adrenal insufficiency.

PubMed

Non, Lemuel; Brito, Daniel; Anastasopoulou, Catherine

2015-01-22

Central diabetes insipidus (CDI) is an infrequent complication of neurosarcoidosis (NS). Its presentation may be masked by adrenal insufficiency (AI) and uncovered by subsequent steroid replacement. A 45-year-old woman with a history of NS presented 2 weeks after abrupt cessation of prednisone with nausea, vomiting, decreased oral intake and confusion. She was diagnosed with secondary AI and intravenous hydrocortisone was promptly begun. Over the next few days, however, the patient developed severe thirst and polyuria exceeding 6 L of urine per day, accompanied by hypernatraemia and hypo-osmolar urine. She was presumed to have CDI due to NS, and intranasal desmopressin was administered. This eventually normalised her urine output and serum sodium. The patient was discharged improved on intranasal desmopressin and oral prednisone. AI may mask the manifestation of CDI because low serum cortisol impairs renal-free water clearance. Steroid replacement reverses this process and unmasks an underlying CDI. 2015 BMJ Publishing Group Ltd.

Mild traumatic brain injury: is diffusion imaging ready for primetime in forensic medicine?

PubMed

Grossman, Elan J; Inglese, Matilde; Bammer, Roland

2010-12-01

Mild traumatic brain injury (MTBI) is difficult to accurately assess with conventional imaging because such approaches usually fail to detect any evidence of brain damage. Recent studies of MTBI patients using diffusion-weighted imaging and diffusion tensor imaging suggest that these techniques have the potential to help grade tissue damage severity, track its development, and provide prognostic markers for clinical outcome. Although these results are promising and indicate that the forensic diagnosis of MTBI might eventually benefit from the use of diffusion-weighted imaging and diffusion tensor imaging, healthy skepticism and caution should be exercised with regard to interpreting their meaning because there is no consensus about which methods of data analysis to use and very few investigations have been conducted, of which most have been small in sample size and examined patients at only one time point after injury.

[Anesthetic complications in sequential bipulmonary transplantation in patients with cystic fibrosis. Apropos of 6 cases].

PubMed

López, L M; Vicente, R; Ramos, F; Palacios, L; Calvo, A; Hernández, S; Borro, J M; Morales, P; Montero, R

1996-03-01

Cystic fibrosis (CF) is a disease characterized mainly by altered exocrine gland function that eventually produces irreversible dysfunction of the pancreas and lungs. The respiratory insufficiency that develops in CF patients in the advanced stages of disease can only be corrected at this time by lung or heart-lung transplantation. We describe our experience with 6 terminal phase CF patients who underwent sequential double lung transplantation (SDLT). Anesthesia was intravenous, with exhaustive hemodynamic and respiratory monitoring. During surgery the most frequently encountered hemodynamic complications were low minute volume, arterial hypotension and irregular heart rate. The main respiratory complications were hypoxemia, hypercapnia and pulmonary edema of the implanted lung, which developed in all cases to varying degrees related to the organ's state of preservation and duration of ischemia. Other complications were the need for extracorporeal circulation in 1 case, oliguria and blood loss requiring multiple transfusions. The most critical moments were at the time of clamping the pulmonary artery, the period after revascularization of the donated lung, and at the start of patient ventilation through the first implanted lung so that the second could be implanted. Although our series is small, it is of interest given the limited Spanish experience with lung transplantation in CF patients, and the good early results obtained, which are similar to those reported for other diseases.

Adverse clinical sequelae after skin branding: a case series.

PubMed

Raza, Shahzad; Mahmood, Khalid; Hakeem, Abdul; Polsky, Sylvie; Haemel, Anna; Rai, Soniya; Ali Baig, Mahadi

2009-01-23

Branding refers to a process whereby third degree burns are inflicted on the skin with a hot iron rod or metallic object. Branding employs the phenomenon of "counter irritation," and is widely used by faith healers in developing countries for therapeutic purposes. Some methods, which are very crude and inhuman, carry a large risk of complications. The purpose of this study is to present a series of complications and to familiarize clinicians with this dangerous method of treatment. Four Pakistani patients, three male and one female, ranging from 25 to 60 years of age "branded" with a red hot iron rod for various medical reasons presented with severe medical complications to our tertiary care hospital. The mean duration between the procedure and presentation to the hospital was 6 days. At the time of admission, two patients had septic shock, one patient had cavernous sinus thrombosis and one patient had multiple splenic abscesses. All patients received standard care for wound management and systemic infections. Two patients eventually died during the course of treatment. Severe complications from branding are troublesome and the potential risks of this treatment outweigh its benefits. Globally, there is a great need for heightened awareness about the dangers of branding among patients and physicians, as this will have an important effect on patients who seek branding for various medical conditions.

Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

PubMed Central

Arango, Celso

2014-01-01

Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

Overactivating CAR T cells interferes with their ability to fight cancer in mice | Center for Cancer Research

Cancer.gov

CAR T-cell therapy, in which a patient’s T cells are reprogrammed in the lab to boost their ability to recognize and destroy cancer cells when they are returned to the body, has led to dramatic responses for many patients with certain blood cancers. Not all patients respond to the treatment, however, and many who do eventually relapse. Read more…

Small Molecule Inhibitors in Acute Myeloid Leukemia: From the Bench to the Clinic

PubMed Central

Al-Hussaini, Muneera; DiPersio, John F.

2014-01-01

Many patients with acute myeloid leukemia (AML) will eventually develop refractory or relapsed disease. In the absence of standard therapy for this population, there is currently an urgent unmet need for novel therapeutic agents. Targeted therapy with small molecule inhibitors (SMIs) represents a new therapeutic intervention that has been successful for the treatment of multiple tumors (e.g., gastrointestinal stromal tumors, chronic myelogenous leukemia). Hence, there has been great interest in generating selective small molecule inhibitors targeting critical pathways of proliferation and survival in AML. This review highlights a selective group of intriguing therapeutic agents and their presumed targets in both preclinical models and in early human clinical trials. PMID:25025370

Sudden Death: An Uncommon Occurrence in Dementia with Lewy Bodies.

PubMed

Molenaar, Joery P; Wilbers, Joyce; Aerts, Marjolein B; Leijten, Quinten H; van Dijk, Jan G; Esselink, Rianne A; Bloem, Bastiaan R

2016-01-01

We present a 75-year-old woman with dementia and parkinsonism who developed severe orthostatic hypotension and eventually died. Autopsy revealed extensive Lewy body formation in the midbrain, limbic system, intermediate spinal cord, and medulla oblongata. Furthermore, a vast amount of Lewy bodies was seen in the paravertebral sympathetic ganglia which likely explained the severe autonomic failure. We speculate that this autonomic failure caused sudden death through dysregulation of respiration or heart rhythm, reminiscent of sudden death in multiple system atrophy (MSA). Clinicians should be aware of this complication in patients presenting with parkinsonism and autonomic dysfunction, and that sudden death may occur in dementia with Lewy bodies (DLB) as it does in MSA.

Scleroderma renal crisis and ovarian hyperstimulation syndrome related to the use of clomiphene in a patient with scleroderma.

PubMed

Kobak, Senol; Hacivelioglu, Servet; Gungor, Selen

2014-01-01

This paper presented a 28-year-old female with systemic sclerosis who developed scleroderma renal crisis and ovarian hyperstimulation syndrome following clomiphene administration. Urgent therapy including angiotensin-converting enzyme (ACE) inhibitors and supportive care resulted in regression and eventually resolution of all the clinical and laboratory symptoms. Although scleroderma renal crisis is a fatal complication of high-dose corticosteroids, rarely is this seen with the use of ACE inhibitors. This case report aimed to investigate the potential capacity of the selective oestrogen receptor modulator clomiphene to induce scleroderma renal crisis as well as corticosteroids. Copyright © 2012 Elsevier España, S.L. All rights reserved.

[Cystic echinococcosis mimicking tuberculosis in childhood].

PubMed

Pekcan, Sevgi; Kiper, Nural; Köse, Mehmet; Cobanoğlu, Nazan; Yalçın, Ebru; Doğru, Deniz; Ozçelik, Uğur

2011-01-01

Both cystic echinococcosis (CE) and tuberculosis (Tbc) are important health problems in developing countries. Pulmonary CE and Tbc have to be differentiated from other diseases as they have increased the risk of morbidity and mortality. Besides, these two diseases can mimic each other. Here, we discuss a 7 year-old patient admitted with fever, cough who was unresponsive to nonspecific antibiotic treatment given for pneumonia, had Tbc treatment due to a positive tuberculin skin test and radiologic appearance consistent with Tbc and on follow-up. He was eventually diagnosed as CE based on a cystic lesion consistent with CE in the liver and echinococcosis specific IgE positivity and was succesfully treated with anti-parasitic therapy.

[Myxedema coma].

PubMed

Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D; Wartofsky, Leonard

2017-01-01

Hypothyroidism is a frequently diagnosed and simply treated disease. If not recognised, however, in time it may develop into the most severe manifestation of hypothyroidism known as myxedema coma. The term "myxedema coma" is generally seen as misleading since most patients do not initially present in a coma. The typical progression is lethargy evolving into stupor and, eventually, into coma with respiratory failure and hypothermia. It mainly affects elderly women, often occurring in winter and is relatively rare. It can be considered a form of decompensated hypothyroidism often triggered by a variety of non-thyroid conditions or diseases provoking an extremely severe condition of multiple system failure with lethal consequences unless an early diagnosis is made and an aggressive treatment is administered.

The moral relevance of personal characteristics in setting health care priorities.

PubMed

Olsen, Jan Abel; Richardson, Jeff; Dolan, Paul; Menzel, Paul

2003-10-01

This paper discusses the moral relevance of accounting for various personal characteristics when prioritising between groups of patients. After a review of the results from empirical studies, we discuss the ethical reasons which might explain-and justify-the views expressed in these studies. The paper develops a general framework based upon the causes of ill health and the consequences of treatment. It then turns to the question of the extent to which a personal characteristic-and the eventual underlying ethical justification of its relevance-could have any relationships to these causes and consequences. We attempt to disentangle those characteristics that may reflect a potentially relevant justification from those which violate widely accepted principles of social justice.

[Therapy of the peromelic form of symbrachydactyly by double second-toe transplantation].

PubMed

Hülsemann, W; Preisser, P; Habenicht, R; Partecke, B-D

2002-09-01

From 1989 to 2001 eleven children with the peromelic type of symbrachydactyly underwent a staged double second toes transplantation for restoration of two finger rays. The second toe of the feet were transplanted first to the small finger position and in the second step to the thumb position. One failure occurred in the first toe transplantation and another developed a venous thrombosis with partial necrosis and eventually a useless ray. Eight children were reviewed retrospectively in a mean follow-up of 5.3 years. The ability to pinch was restored in four children. In all patients without complications the function of the hand improved and the sensitivity was good.

Molecular diagnostics of neurodegenerative disorders.

PubMed

Agrawal, Megha; Biswas, Abhijit

2015-01-01

Molecular diagnostics provide a powerful method to detect and diagnose various neurological diseases such as Alzheimer's and Parkinson's disease. The confirmation of such diagnosis allows early detection and subsequent medical counseling that help specific patients to undergo clinically important drug trials. This provides a medical pathway to have better insight of neurogenesis and eventual cure of the neurodegenerative diseases. In this short review, we present recent advances in molecular diagnostics especially biomarkers and imaging spectroscopy for neurological diseases. We describe advances made in Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), and finally present a perspective on the future directions to provide a framework for further developments and refinements of molecular diagnostics to combat neurodegenerative disorders.

Narcolepsy and cataplexy: a pediatric case report.

PubMed

Savaş, Tülin; Erol, Ilknur; Saygı, Semra; Habeşoğlu, Mehmet Ali

2016-12-01

Narcolepsy is characterized by excessive sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis during the rapid eye movement period of sleep. Herein, we present a boy aged eight years who was diagnosed as having narcolepsy and cataplexy about thirteen months after his first presentation. He was admitted with symptoms of daytime sleepiness. In the follow-up, cataplexy in the form of head dropping attacks developed seven months after the first admission. The patient was investigated for different prediagnoses and was eventually diagnosed as having narcolepsy and cataplexy through polysomnography and multiple sleep latency tests thirteen months after the first presentation. He is being followed up and is under drug therapy; his symptoms have improved substantially.

Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis.

PubMed

Cahen, Djuna L; Gouma, Dirk J; Laramée, Philippe; Nio, Yung; Rauws, Erik A J; Boermeester, Marja A; Busch, Olivier R; Fockens, Paul; Kuipers, Ernst J; Pereira, Stephen P; Wonderling, David; Dijkgraaf, Marcel G W; Bruno, Marco J

2011-11-01

A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Analysis of medical litigation among patients with medical disputes in cosmetic surgery in Taiwan.

PubMed

Lyu, Shu-Yu; Liao, Chuh-Kai; Chang, Kao-Ping; Tsai, Shang-Ta; Lee, Ming-Been; Tsai, Feng-Chou

2011-10-01

This study aimed to investigate the key factors in medical disputes (arguments) among female patients after cosmetic surgery in Taiwan and to explore the correlates of medical litigation. A total of 6,888 patients (3,210 patients from two hospitals and 3,678 patients from two clinics) received cosmetic surgery from January 2001 to December 2009. The inclusion criteria specified female patients with a medical dispute. Chi-square testing and multiple logistic regression analysis were used to analyze the data. Of the 43 patients who had a medical dispute (hospitals, 0.53%; clinics, 0.73%), 9 plaintiffs eventually filed suit against their plastic surgeons. Such an outcome exhibited a decreasing annual trend. The hospitals and clinics did not differ significantly in terms of patient profiles. The Chi-square test showed that most patients with a medical dispute (p < 0.05) were older than 30 years, were divorced or married, had received operations under general anesthesia, had no economic stress, had a history of medical litigation, and eventually did not sue the surgeons. The test results also showed that the surgeon's seniority and experience significantly influenced the possibility of medical dispute and nonlitigation. Multiple logistical regression analysis further showed that the patients who did decide to enter into litigation had two main related factors: marital stress (odds ratio [OR], 10.67; 95% confidence interval [CI], 1.20-94.73) and an education level below junior college (OR, 9.33; 95% CI, 1.01-86.36). The study findings suggest that the key characteristics of patients and surgeons should be taken into consideration not only in the search for ways to enhance pre- and postoperative communication but also as useful information for expert testimony in the inquisitorial law system.

Does a foamy-block mattress system prevent pressure sores ? A prospective randomised clinical trial in 1729 patients.

PubMed

Berthe, J V; Bustillo, A; Mélot, C; de Fontaine, S

2007-01-01

Pressure ulcers are a frequent complication of bed rest. The development of an efficient and low cost pressure relieving system for the prevention of bed-sores would be of considerable hospital health and economic interest. Our study was designed to determine the effectiveness in pressure-sore prevention of an interface pressure-decreasing mattress, the Kliniplot mattress, used in our institution since 1978. In a prospective randomised controlled 7-month clinical trial we compared the Kliniplot mattress with our standard hospital mattress in 1729 patients admitted to medical and surgical departments (neurology, cardiology, oncology-haematology, neurosurgery, thoracic surgery and orthopaedic surgery). Two groups (Klinipot mattress and standard hospital mattress) were monitored for the prevention of pressure sores. The patients were evaluated on a daily basis from their admission until the eventual occurrence of a bed-sore. Patients' characteristics and pressure-sore risk factors were similar at the baseline in both groups. Patients presenting with a pressure sore at the time of admission were excluded. Forty-two of the 1729 patients (2.4%) who entered the study developed at least one pressure sore. Twenty-one of the 657 patients (3.2%) nursed on the Kliniplot mattress, and 21 of the 1072 patients (1.9%) on the standard mattress developed bed-sores (p = 0.154). The median time for the occurrence of pressure sores was 31 days (range 6-87) with the Kliniplot mattress and 18 days (range 2 to 38) with the standard mattress (p < 0.001). The risk categories for developing bed-sores using the modified Ek's scale were no different at the baseline between both groups (p = 0.764). The severity of the pressure sores was no different between both groups (p = 0.918). Our results show that the occurrence of pressure sores is not reduced but is delayed when patients are nursed on a Kliniplot pressure-decreasing mattress.

An upper limb robot model of children limb for cerebral palsy neurorehabilitation.

PubMed

Pathak, Yagna; Johnson, Michelle

2012-01-01

Robot therapy has emerged in the last few decades as a tool to help patients with neurological injuries relearn motor tasks and improve their quality of life. The main goal of this study was to develop a simple model of the human arm for children affected with cerebral palsy (CP). The Simulink based model presented here shows a comparison for children with and without disabilities (ages 6-15) with normal and reduced range of motion in the upper limb. The model incorporates kinematic and dynamic considerations required for activities of daily living. The simulation was conducted using Matlab/Simulink and will eventually be integrated with a robotic counterpart to develop a physical robot that will provide assistance in activities of daily life (ADLs) to children with CP while also aiming to improve motor recovery.

Breaking Hepatitis B Virus Tolerance and Inducing Protective Immunity Based on Mimicking T Cell-Independent Antigen.

PubMed

Li, Xiaoyan; Ni, Runzhou

2016-11-01

There are over 350 million chronic carriers of hepatitis B virus (HBV) in the world, of whom about a third eventually develop severe HBV-related complications. HBV contributes to liver cirrhosis and hepatocellular carcinoma development. Remarkable progress has been made in selective inhibition of HBV replication by nucleoside analogs. However, how to generate protective antibody of HBsAb in HBV-infected patients after HBV-DNA becomes negative still remains a challenge for scientists. In this study, we show that OmpC-HBsAg 'a' epitope chimeric protein vaccine can break HBV tolerance and induce protective immunity in HBV transgenic mice based on mimicking T cell-independent antigen to bypass T cells from the adaptive immune system. The antibodies induced by the vaccine have the ability to prevent HBV virion infection of human hepatocytes.

Robotics and neurosurgery.

PubMed

Nathoo, Narendra; Pesek, Todd; Barnett, Gene H

2003-12-01

Ultimately, neurosurgery performed via a robotic interface will serve to improve the standard of a neurosurgeon's skills, thus making a good surgeon a better surgeon. In fact, computer and robotic instrumentation will become allies to the neurosurgeon through the use of these technologies in training, diagnostic, and surgical events. Nonetheless, these technologies are still in an early stage of development, and each device developed will entail its own set of challenges and limitations for use in clinical settings. The future operating room should be regarded as an integrated information system incorporating robotic surgical navigators and telecontrolled micromanipulators, with the capabilities of all principal neurosurgical concepts, sharing information, and under the control of a single person, the neurosurgeon. The eventual integration of robotic technology into mainstream clinical neurosurgery offers the promise of a future of safer, more accurate, and less invasive surgery that will result in improved patient outcome.

Anterolateral ankle impingement in adolescents: outcomes of nonoperative and operative treatment.

PubMed

Edmonds, Eric W; Chambers, Reid; Kaufman, Elizabeth; Chambers, Henry G

2010-03-01

Ankle sprains in adolescents usually resolve with conservative management but a few patients may develop ankle impingement syndrome. There have been adult studies addressing surgical treatment of this pathology, but our study evaluated the surgical management of anterolateral ankle impingement in adolescents by comparing their outcomes after nonoperative treatment and subsequent surgical intervention. Thirteen patients (children and adolescents) diagnosed with ankle impingement by history, physical examination, and magnetic resonance imaging during a 9-year period at our institution underwent eventual arthroscopic debridement. A retrospective chart review of these patients was performed and they were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) functional rating scale on 3 separate occasions: (1) initial presentation, (2) termination of nonoperative management, and (3) final postoperative follow-up visit. Thirteen adolescents (11 girls and 2 boys; 14 ankles) with a mean age of 15.6 (11.9-18.3) years met the inclusion criteria; of these, all had arthroscopic surgery. Mean duration of reported symptoms was 9.6 (4-15) months and mean duration of nonoperative management (physical therapy, activity modifications) was 6.9 (2-12) months. The mean AOFAS rating (out of 100 total) at initial presentation was 68.4 (40-84) and after nonoperative management was no better with a mean of 68.2 (63-76). The mean AOFAS rating at final follow-up was 90.6 (52-100), which was statistically significant (P

Magnetic resonance imaging in evaluating workers' compensation patients.

PubMed

Babbel, Daniel; Rayan, Ghazi

2012-04-01

We studied the utility of magnetic resonance imaging (MRI) studies for workers' compensation patients with hand conditions in which the referring doctor obtained the images. We compared the MRI findings with the eventual clinical findings. We also investigated the approximate cost of these MRI studies. We retrospectively reviewed the charts of all workers' compensation patients seen in a hand and upper extremity practice over the course of 3 years. We selected patients who had MRI studies of the affected upper extremities before referral to the senior author (G.R.). We reviewed the charts for information regarding demographics, referral diagnoses, MRI diagnoses made by the radiologist, the area of the upper extremity studied, and eventual clinical diagnoses by the senior author. We made a determination as to whether a hand surgeon could have adequately diagnosed and treated the patients' conditions without the imaging studies. We also investigated the cost associated with these MRIs. We included 62 patients with a total of 67 MRI scans in this study. The MRI studies did not contribute to clinically diagnosing the patients' conditions in any of the cases we reviewed. The hand surgeon's clinical diagnosis disagreed with the radiologist's MRI diagnosis in 63% of patients. The MRI was unnecessary to arrive at the clinical diagnosis and did not influence the treatment offered for any of the 62 patients. The total cost for the 67 non-contrast MRI studies was approximately $53,000. Costly imaging studies are frequently done to determine the validity of a patient's reported problems; unfortunately, these tests are frequently unnecessary and waste resources. Magnetic resonance imaging scans may not be the standard for accurate diagnosis and can misdirect care. Therapeutic III. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Magnetic Resonance Imaging Assessment of Squamous Cell Carcinoma of the Anal Canal Before and After Chemoradiation: Can MRI Predict for Eventual Clinical Outcome?

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

Goh, Vicky, E-mail: vicky.goh@stricklandscanner.org.u; Gollub, Frank K.; Liaw, Jonathan

2010-11-01

Purpose: To describe the MRI appearances of squamous cell carcinoma of the anal canal before and after chemoradiation and to assess whether MRI features predict for clinical outcome. Methods and Materials: Thirty-five patients (15 male, 20 female; mean age 60.8 years) with histologically proven squamous cell cancer of the anal canal underwent MRI before and 6-8 weeks after definitive chemoradiation. Images were reviewed retrospectively by two radiologists in consensus blinded to clinical outcome: tumor size, signal intensity, extent, and TNM stage were recorded. Following treatment, patients were defined as responders by T and N downstaging and Response Evaluation Criteria inmore » Solid Tumors (RECIST). Final clinical outcome was determined by imaging and case note review: patients were divided into (1) disease-free and (2) with relapse and compared using appropriate univariate methods to identify imaging predictors; statistical significance was at 5%. Results: The majority of tumors were {<=}T2 (23/35; 65.7%) and N0 (21/35; 60%), mean size 3.75cm, and hyperintense (++ to +++, 24/35 patients; 68%). Following chemoradiation, there was a size reduction in all cases (mean 73.3%) and a reduction in signal intensity in 26/35 patients (74.2%). The majority of patients were classified as responders (26/35 (74.2%) patients by T and N downstaging; and 30/35 (85.7%) patients by RECIST). At a median follow-up of 33.5 months, 25 patients (71.4%) remained disease-free; 10 patients (28.6%) had locoregional or metastatic disease. Univariate analysis showed that no individual MRI features were predictive of eventual outcome. Conclusion: Early assessment of response by MRI at 6-8 weeks is unhelpful in predicting future clinical outcome.« less

Clinical trials with velnacrine: (PROPP) the physician reference of predicted probabilities--a statistical model for the estimation of hepatotoxicity risk with velnacrine maleate.

PubMed

Hardiman, S; Miller, K; Murphy, M

1993-01-01

Safety observations during the clinical development of Mentane (velnacrine maleate) have included the occurrence of generally asymptomatic liver enzyme elevations confined to patients with Alzheimer's disease (AD). The clinical presentation of this reversible hepatocellular injury is analogous to that reported for tetrahydroaminoacridine (THA). Direct liver injury, possibly associated with the production of a toxic metabolite, would be consistent with reports of aberrant xenobiotic metabolism in Alzheimer's disease patients. Since a patient related aberration in drug metabolism was suspected, a biostatistical strategy was developed with the objective of predicting hepatotoxicity in individual patients prior to exposure to velnacrine maleate. The method used logistic regression techniques with variable selection restricted to those items which could be routinely and inexpensively accessed at screen evaluation for potential candidates for treatment. The model was to be predictive (a marker for eventual hepatotoxicity) rather than a causative model, and techniques employed "goodness of fit", percentage correct, and positive and negative predictive values. On the basis of demographic and baseline laboratory data from 942 patients, the PROPP statistic was developed (the Physician Reference Of Predicted Probabilities). Main effect variables included age, gender, and nine hematological and serum chemistry variables. The sensitivity of the current model is approximately 49%, specificity approximately 88%. Using prior probability estimates, however, in which the patient's likelihood of liver toxicity is presumed to be at least 30%, the positive predictive value ranged between 64-77%. Although the clinical utility of this statistic will require refinements and additional prospective confirmation, its potential existence speaks to the possibility of markers for idiosyncratic drug metabolism in patients with Alzheimer's disease.

Prognostic significance of ventricular late potentials in patients with pulmonary sarcoidosis.

PubMed

Yodogawa, Kenji; Seino, Yoshihiko; Ohara, Toshihiko; Iwasaki, Yu-Ki; Hayashi, Meiso; Miyauchi, Yasushi; Azuma, Arata; Shimizu, Wataru

2018-06-01

Early detection of cardiac involvement in sarcoidosis is difficult but essential to achieve optimal treatment. Signal-averaged electrocardiography (SAECG) can detect subtle cardiac electrical abnormalities termed late potentials (LPs) and would be useful for the early diagnosis of cardiac involvement. This study aims to investigate the prognostic significance of LP in patients with pulmonary sarcoidosis. We prospectively studied 74 patients with pulmonary sarcoidosis without overt electrocardiographic abnormalities. All participants underwent SAECG, cardiac echocardiography, and 24-hour ambulatory Holter monitoring. Serum angiotensin-converting enzyme and B-type natriuretic peptide levels were also evaluated. We followed these patients for the evaluation of incidence of cardiac events including cardiac death, arrhythmias, and heart failure requiring hospital admission. Of the studied population, 29 patients (39.2%) had detectable LP. During a mean follow-up period of 9.8 years, 8 patients with LPs had cardiovascular events, including development of complete atrioventricular block (n = 4), ventricular tachycardia (n = 2), and heart failure (n = 2). Meanwhile, only 1 of 45 patients without LP developed cardiac event (heart failure). Multivariate analyses revealed that LPs were associated with an increased risk of developing cardiac events (hazard ratio 9.66; 95% confidence interval 1.20-78.01; P = .033) whereas age, sex, serum angiotensin-converting enzyme and B-type natriuretic peptide levels, number of premature ventricular contractions on 24-hour Holter monitoring, and echocardiographic parameters were not associated with subsequent cardiac events. SAECG might possibly be useful for the early detection of cardiac sarcoidosis and, if independently validated, could eventually be considered as a screening test for further risk stratification. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Towards numerical simulations of fluid-structure interactions for investigation of obstructive sleep apnea

NASA Astrophysics Data System (ADS)

Huang, Chien-Jung; White, Susan M.; Huang, Shao-Ching; Mallya, Sanjay; Eldredge, Jeff D.

2014-11-01

Obstructive sleep apnea(OSA) is a medical condition characterized by repetitive partial or complete occlusion of the airway during sleep. The soft tissues in the airway of OSA patients are prone to collapse under the low pressure loads incurred during breathing. The numerical simulation with patient-specific upper airway model can provide assistance for diagnosis and treatment assessment. The eventual goal of this research is the development of numerical tool for air-tissue interactions in the upper airway of patients with OSA. This tool is expected to capture collapse of the airway in respiratory flow conditions, as well as the effects of various treatment protocols. Here, we present our ongoing progress toward this goal. A sharp-interface embedded boundary method is used on Cartesian grids for resolving the air-tissue interface in the complex patient-specific airway geometries. For the structure simulation, a cut-cell FEM is used. Non-linear Green strains are used for properly resolving the large tissue displacements in the soft palate structures. The fluid and structure solvers are strongly coupled. Preliminary results will be shown, including flow simulation inside the 3D rigid upper airway of patients with OSA, and several validation problem for the fluid-structure coupling.

Review of behavioral health integration in primary care at Baylor Scott and White Healthcare, Central Region

PubMed Central

Fluet, Norman R.; Reis, Michael D.; Stern, Charles H.; Thompson, Alexander W.; Jolly, Gillian A.

2016-01-01

The integration of behavioral health services in primary care has been referred to in many ways, but ultimately refers to common structures and processes. Behavioral health is integrated into primary care because it increases the effectiveness and efficiency of providing care and reduces costs in the care of primary care patients. Reimbursement is one factor, if not the main factor, that determines the level of integration that can be achieved. The federal health reform agenda supports changes that will eventually permit behavioral health to be fully integrated and will allow the health of the population to be the primary target of intervention. In an effort to develop more integrated services at Baylor Scott and White Healthcare, models of integration are reviewed and the advantages and disadvantages of each model are discussed. Recommendations to increase integration include adopting a disease management model with care management, planned guideline-based stepped care, follow-up, and treatment monitoring. Population-based interventions can be completed at the pace of the development of alternative reimbursement methods. The program should be based upon patient-centered medical home standards, and research is needed throughout the program development process. PMID:27034543

Radiomics: Images Are More than Pictures, They Are Data

PubMed Central

Kinahan, Paul E.; Hricak, Hedvig

2016-01-01

In the past decade, the field of medical image analysis has grown exponentially, with an increased number of pattern recognition tools and an increase in data set sizes. These advances have facilitated the development of processes for high-throughput extraction of quantitative features that result in the conversion of images into mineable data and the subsequent analysis of these data for decision support; this practice is termed radiomics. This is in contrast to the traditional practice of treating medical images as pictures intended solely for visual interpretation. Radiomic data contain first-, second-, and higher-order statistics. These data are combined with other patient data and are mined with sophisticated bioinformatics tools to develop models that may potentially improve diagnostic, prognostic, and predictive accuracy. Because radiomics analyses are intended to be conducted with standard of care images, it is conceivable that conversion of digital images to mineable data will eventually become routine practice. This report describes the process of radiomics, its challenges, and its potential power to facilitate better clinical decision making, particularly in the care of patients with cancer. PMID:26579733

Nonsyndromic tooth agenesis patterns and associated developmental dental anomalies: a literature review with radiographic illustrations.

PubMed

Agarwal, P; Vinuth, D P; Dube, G; Dube, P

2013-01-01

Tooth agenesis is one of the most intriguing phenomena, because it is frequently associated with other oral anomalies, structural variations and malformations of other teeth, late eruption, transposition and crowding. The diagnosis can be quite challenging as radiographic examination is critical for the diagnosis but not always possible and the late developing teeth may be sometimes scored developmentally missing. Accurate diagnosis therefore requires radiographic, clinical, and dental cast examinations. It is an important clinical and public health problem. Patients with missing permanent teeth may suffer from a reduced chewing ability, inarticulate pronunciation, and an unfavorable aesthetic appearance. Clinically, early diagnosis of a dental anomaly can alert the clinician to the possible development of other associated dental anomalies in the same patient or family, and avoid the possible sequelae. Understanding of tooth agenesis patterns and their impact on diagnosis, prevention, and eventually therapeutics are becoming integral parts of comprehensive dental care. Dental examination with radiographic screening of hypodontia in early childhood should be emphasized as part of public oral health policy to allow early diagnosis and timely intervention.

[Treatment and prevention of cancer treatment related oral mucositis].

PubMed

Ruiz-Esquide, Gonzalo; Nervi, Bruno; Vargas, Alex; Maíz, Alberto

2011-03-01

One of the most common and troublesome complications of modern intensive anticancer treatments is oral mucositis. The purpose of this review is to summarize current evidence and clinical guidelines regarding its prevention and therapy. The use of keratinocyte growth factor-1, supplementary glutamine and other recently developed treatment modalities are discussed. The injury of the oral mucosa caused by antineoplastic agents promotes the local expression of multiple pro-inflammatory and pro-apoptotic molecules and eventually leads to the development of ulcers. Such lesions predispose patients to several infectious and nutritional complications. Also, they lead to modification of treatment schedules, potentially affecting overall prognosis. Local cryotherapy with ice chips and phototherapy with low energy laser may be useful as preventive measures. Mouthwashes with allopurinol and phototherapy with low energy laser can be used as treatment. In radiotherapy, special radiation administration techniques should be used to minimize mucosal injury. Pain control should always be optimized, with the use of patient controlled analgesia and topical use of morphine. Supplemental glutamine should not be used outside of research protocols. Lastly, thorough attention should be paid to general care and hygiene measures.

Gastrointestinal Hemorrhage Related to Fluoxetine in a Patient With Stroke.

PubMed

Wee, Tze Chao

2017-11-01

We report on a patient who developed massive gastrointestinal hemorrhage related to the use of fluoxetine in combination with aspirin and clopidogrel. A 58-year-old man was admitted with a posterior circulation infarct with significant weakness in all four limbs and dysarthria. Aspirin and clopidogrel were started. Fluoxetine was started for pharmacological neurostimulation to promote motor recovery and for low mood. He developed gastrointestinal hemorrhage a week after fluoxetine was started. Fluoxetine was suspended and investigations failed to reveal the source of the bleeding. He was then restarted on fluoxetine along with dual antiplatelets, and gastrointestinal hemorrhage recurred after 1 week. He was extensively investigated for a source of gastrointestinal hemorrhage, and again no source could be identified. Eventually, fluoxetine was switched to mirtazapine with no further gastrointestinal hemorrhage. He remained on dual antiplatelets. A number of case-control and cohort studies had identified the association of gastrointestinal hemorrhage with the use of selective serotonin reuptake inhibitor (SSRI). We hope to raise awareness of this association in physical medicine and rehabilitation physicians as the use of SSRI is expected to rise.

Modified Puestow procedure for the management of chronic pancreatitis in children.

PubMed

Laje, Pablo; Adzick, N Scott

2013-11-01

To present our experience with the modified Puestow procedure in the management of children with chronic pancreatitis. Retrospective chart review of patients treated between 2003 and 2012. Six patients underwent a modified Puestow procedure (lateral pancreaticojejunostomy) for the management of chronic pancreatitis, three females and three males. Four patients had hereditary pancreatitis (three with confirmed N34S mutation in the SPINK1 gene), one patient had chronic pancreatitis of unknown etiology, and one patient with annular pancreas developed obstructive chronic pancreatitis. The pancreatic duct was dilated in all cases, with a maximum diameter of 5 to 10mm. Median time between onset of pain and surgery was 4 years (range: 1-9). Median age at surgery was 7.5 years (range: 5-15). Median hospital stay was 12 days (range: 9-28). Median follow up was 4.5 years (range: 5 months to 9 years). All patients had temporary postoperative improvement of their abdominal pain. In two patients the pain recurred at 6 months and 2 years postoperatively and eventually required total pancreatectomy to treat intractable pain, 3 and 8 years after surgery. Two patients were pain free for two years and subsequently developed occasional episodes of pain. The two most recent patients are pain free at 1 year (obstructive chronic pancreatitis) and 5 months (hereditary pancreatitis) follow-up. Two patients developed type I diabetes mellitus 10 and 12 months postoperatively (one with hereditary and one with idiopathic chronic pancreatitis). We conclude that the modified Puestow procedure in children is feasible and safe. It seems to provide definitive pain control and prevent further damage to the pancreas in patients with obstructive chronic pancreatitis. However, in patients with hereditary pancreatitis, pain control outcomes are variable and the operation may not abrogate the progression of disease to pancreatic insufficiency. Copyright © 2013 Elsevier Inc. All rights reserved.

Designing and Implementation of a Heart Failure Telemonitoring System.

PubMed

Safdari, Reza; Jafarpour, Maryam; Mokhtaran, Mehrshad; Naderi, Nasim

2017-09-01

The aim of this study was to identify patients at-risk, enhancing self-care management of HF patients at home and reduce the disease exacerbations and readmissions. In this research according to standard heart failure guidelines and Semi-structured interviews with 10 heart failure Specialists, a draft heart failure rule set for alerts and patient instructions was developed. Eventually, the clinical champion of the project vetted the rule set. Also we designed a transactional system to enhance monitoring and follow up of CHF patients. With this system, CHF patients are required to measure their physiological measurements (vital signs and body weight) every day and to submit their symptoms using the app. additionally, based on their data, they will receive customized notifications and motivation messages to classify risk of disease exacerbation. The architecture of system comprised of six major components: 1) a patient data collection suite including a mobile app and website; 2) Data Receiver; 3) Database; 4) a Specialists expert Panel; 5) Rule engine classifier; 6) Notifier engine. This system has implemented in Iran for the first time and we are currently in the testing phase with 10 patients to evaluate the technical performance of our system. The developed expert system generates alerts and instructions based on the patient's data and the notify engine notifies responsible nurses and physicians and sometimes patients. Detailed analysis of those results will be reported in a future report. This study is based on the design of a telemonitoring system for heart failure self-care that intents to overcome the gap that occurs when patients discharge from the hospital and tries to accurate requirement of readmission. A rule set for classifying and resulting automated alerts and patient instructions for heart failure telemonitoring was developed. It also facilitates daily communication among patients and heart failure clinicians so any deterioration in health could be identified immediately.

Allografts about the Knee in Young Patients with High-Grade Sarcoma.

PubMed

Brigman, Brian E; Hornicek, Francis J; Gebhardt, Mark C; Mankin, Henry J

2004-04-01

Reconstruction after resections for high-grade sarcomas about the knee in children and adolescents is a challenging problem because of the large soft tissue and skeletal defects, the effects of adjuvant therapy, and the potential for long-term use of the limb. One hundred sixteen patients, all 18 years or younger, with osteosarcoma or Ewing's sarcoma located between the middle femur and middle tibia, were treated with chemotherapy, resection, and allograft reconstruction. One hundred three patients with osteosarcoma and 13 patients with Ewing's sarcoma had 105 Stage II and 11 Stage III tumors. There were 72 osteoarticular grafts (39 femur, 33 tibia), 28 intercalary grafts (19 femur), seven allograft-prosthetic composites (all femur,) and nine allograft-arthrodeses (seven femur, two tibia). At latest followup, 49% of all of the allograft reconstructions were rated good or excellent, 14% were rated as fair, and 37% were failures. Sixteen percent had an infection develop. Twenty-seven percent of patients had a fracture, 34% had a nonunion, and 14 patients eventually required amputation. Reconstruction of large bone defects about the knee in young patients who are being treated with chemotherapy is difficult. Although complications significantly affect outcome, allografts are a viable option for reconstruction in children with high-grade sarcomas about the knee.

The Hospital for the Ruptured and Crippled: Knight to Gibney, 1870–1887

PubMed Central

2006-01-01

In 1870, R&C moved to its second site on the corner of Lexington Avenue and 42nd Street. A newly constructed building designed by a specialist in ecclesiastical architecture became the home of a 200-bed children's hospital planned entirely by Dr. James Knight, founder of the hospital and its first Surgeon-in-Chief. Expansion of the facilities and of the professional staff, although needed and welcomed, brought new challenges, changes, and conflicts. The root of these was to lie in the complex character of James Knight with his dogmatic approach to patient care vs the open nature of his newly appointed assistant, Virgil Gibney, who was to become his successor and eventually the second Surgeon-in-Chief. How these two personalities worked together for 13 years, abruptly parted, and then after Knight's death, the reappearance of Gibney, is a fascinating story of the early development of the first orthopedic hospital in this country. It was a period after the Civil War described as the “Gilded Age,” where not only the country, but the city, was going through its own challenges, changes and conflicts. Emerging was a new era for R&C introducing surgery, postgraduate medical education, and eventually, clinical and basic research. PMID:18751838

The Hospital for the Ruptured and Crippled: Knight to Gibney, 1870-1887.

PubMed

Levine, David B

2006-02-01

In 1870, R&C moved to its second site on the corner of Lexington Avenue and 42nd Street. A newly constructed building designed by a specialist in ecclesiastical architecture became the home of a 200-bed children's hospital planned entirely by Dr. James Knight, founder of the hospital and its first Surgeon-in-Chief. Expansion of the facilities and of the professional staff, although needed and welcomed, brought new challenges, changes, and conflicts. The root of these was to lie in the complex character of James Knight with his dogmatic approach to patient care vs the open nature of his newly appointed assistant, Virgil Gibney, who was to become his successor and eventually the second Surgeon-in-Chief. How these two personalities worked together for 13 years, abruptly parted, and then after Knight's death, the reappearance of Gibney, is a fascinating story of the early development of the first orthopedic hospital in this country. It was a period after the Civil War described as the "Gilded Age," where not only the country, but the city, was going through its own challenges, changes and conflicts. Emerging was a new era for R&C introducing surgery, postgraduate medical education, and eventually, clinical and basic research.

Prediction of two month modified Rankin Scale with an ordinal prediction model in patients with aneurysmal subarachnoid haemorrhage

PubMed Central

2010-01-01

Background Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with a frequently disabling outcome. Our aim was to develop a prognostic model to predict an ordinal clinical outcome at two months in patients with aSAH. Methods We studied patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomized multicentre trial to compare coiling and clipping in aSAH patients. Several models were explored to estimate a patient's outcome according to the modified Rankin Scale (mRS) at two months after aSAH. Our final model was validated internally with bootstrapping techniques. Results The study population comprised of 2,128 patients of whom 159 patients died within 2 months (8%). Multivariable proportional odds analysis identified World Federation of Neurosurgical Societies (WFNS) grade as the most important predictor, followed by age, sex, lumen size of the aneurysm, Fisher grade, vasospasm on angiography, and treatment modality. The model discriminated moderately between those with poor and good mRS scores (c statistic = 0.65), with minor optimism according to bootstrap re-sampling (optimism corrected c statistic = 0.64). Conclusion We presented a calibrated and internally validated ordinal prognostic model to predict two month mRS in aSAH patients who survived the early stage up till a treatment decision. Although generalizability of the model is limited due to the selected population in which it was developed, this model could eventually be used to support clinical decision making after external validation. Trial Registration International Standard Randomised Controlled Trial, Number ISRCTN49866681 PMID:20920243

Tics, Tourette Syndrome, and OCD

MedlinePlus

... AAP Find a Pediatrician Health Issues Conditions Abdominal ADHD Allergies & Asthma Autism Cancer Chest & Lungs Chronic Conditions ... In children who eventually develop tic disorders and ADHD, the ADHD usually develops 2 to 3 years ...

THE PATHOMECHANICAL ETIOLOGY OF POST-TRAUMATIC OSTEOARTHRITIS FOLLOWING INTRAARTICULAR FRACTURES

PubMed Central

Anderson, Donald D; Marsh, J Lawrence; Brown, Thomas D

2011-01-01

Many intra-articular fracture patients eventually experience significant functional deficits, pain, and stiffness from post-traumatic osteoarthritis (PTOA). Over the last several decades, continued refinement of surgical reconstruction techniques has failed to markedly improve patient outcomes. New treatment paradigms are needed - ideally, bio/pharmaceutical. Progress in that direction has been impeded because the pathomechanical etiol-ogy of PTOA development is poorly understood. In particular, the relative roles and pathomechanisms of acute joint injury (from the initial trauma) versus chronic contact stress elevation (from residual incongruity) are unknown, primarily because there have been no objective methods for reliably quantifying either of these insult entities. Over the past decade, novel enabling technologies have been developed that provide objective biomechanical indices of injury severity and of chronic contact stress challenge to fractured joint surfaces. The severity of the initial joint injury is indexed primarily on the basis of the energy released in fracture, obtained from validated digital image analysis of CT scans. Chronic contact stress elevations are indexed by patient-specific finite element stress analysis, using models derived from post-reduction CT scans. These new measures, conceived in the laboratory, have been taken through the stage of validation, and then have been applied in studies of intra-articular fracture patients, to relate these biomechanical indices of cartilage insult to the incidence and severity of PTOA This body of work has provided a novel framework for developing and testing new approaches to forestall PTOA following intra-articular fractures. PMID:22096414

Spontaneous subarachnoid haemorrhage and outcome--results from Tan Tock Seng Hospital, Singapore.

PubMed

Wong, S H; Yeo, T T; Seow, W T; Tan, K K; Ong, P L

1999-07-01

To ascertain the number of cases of spontaneous (aneurysmal) subarachnoid haemorrhage presenting to Tan Tock Seng Hospital, Singapore, over a one year period, the demographics of the patients involved, their treatment and their eventual outcome. A retrospective study from June 1995 to June 1996. There were 62 patients admitted over this period with an average of 5 patients per month. Their ages ranged from 9 to 85 years with a mean of 54 years. All 62 patients underwent 4-vessel cerebral angiograms. Forty-three patients (69%) underwent clipping of their aneurysms. Twelve patients (19%) had negative angiograms. Four patients (6%) underwent coiling of their aneurysms via interventional neuroradiology techniques. Patients with subarachnoid haemorrhage of Grades 1 to 3 on the WFNS (World Federation of Neurological Surgeons) grading had a favourable outcome (Glasgow Outcome Score of 4 and 5) in 85% of the cases. The overall mortality rate for the operated group (all grades) was 11%. However for the group with good WFNS grading, namely the Grade 1 to 2 groups, there were no deaths. Twenty-four percent of patients developed clinically symptomatic vasospasm. Eighteen percent of patients required ventriculo-peritoneal shunting for hydrocephalus secondary to the subarachnoid haemorrhage. The overall management mortality (operated and non-operated cases) was 14% for proven aneurysmal and angiographically-negative spontaneous subarachnoid haemorrhage. These results are comparable to that of other reputable centers reported in the literature.

Evaluation of patients' education on foot self-care status in diabetic patients.

PubMed

Kafaie, Parichehr; Noorbala, Mohamad Taghi; Soheilikhah, Sedigheh; Rashidi, Maryam

2012-12-01

Skin problems caused by neuropathy and antipathy are common manifestations of diabetes. The most serious about such problem is the diabetic foot, which may lead to eventual ulceration and amputation, and will decrease a patient's quality of life dramatically. The aim of this study is to assess the level of foot self-care and foot conditions in diabetic patients, and to demonstrate the role of self-care education in diabetic foot care. A total of 80 diabetic patients were included in the study, all of whom had referred to "Yazd Diabetic Research Center." The levels of their foot self-care were recorded in pre-test questionnaires, and then all of the patients were visited and educated by a Dermatologist for their foot self-care on a monthly basis, after which their post-test results were recorded through a second administration of the same questionnaire. Eventually, data from the pre and post-test questionnaires were analyzed to identify the possible effects of education. A total of 80 diabetic patients (34 males, 46 females) with a mean average age of 53.53 ± 10.19 and mean average duration of diabetes 12.42 ± 6.73 years were assessed. A significant increase in foot self-care through education was observed (baseline 27.06 ± 8.77, vs. post education 43.12 ± 8.77; P = 0.0001). After education, foot and nail lesions improved completely in 84% and 62.8%. Moreover, 77.8% of patients had suitable shoes and 79.6% had suitable socks. Our findings showed that foot self-care education could improve knowledge and performance of patients about various foot problems, and was significantly important in preventing ulcers.

Psychiatric patient disposition agreement between the emergency physician and the psychiatry consultant.

PubMed

Chakravarthy, Bharath; Menchine, Michael; Thompson, Daniel E; Rajeev, Sindhya; Santos, Barbara-Jean

2013-01-01

Mental illness is prevalent, disabling, and costly. Emergency department (ED) visits for mental health-related reasons are on the increase. Determine the level of agreement between emergency physicians and psychiatrists regarding psychiatric patient disposition. We conducted a prospective, observational study at a private university hospital ED from October 2008-April 2009 using a convenience sample of patients of all ages with psychiatric complaints who received formal psychiatric consultation during their ED visit. The emergency physician completed a data sheet prior to psychiatric consultation, assessing the likelihood of admission for psychiatric evaluation. We evaluated the positive predictive value (PPV) and negative predictive value (NPV) of the emergency physician admission decision for all patients before psychiatric consultation, compared with the patients' actual disposition as determined by the consulting psychiatrist. The study captured 230 subjects, 53% of whom were suicidal patients. 74% of patients were eventually admitted. The emergency physician decision to admit for inpatient psychiatric evaluation had a PPV of 87.3% (CI 81.4-91.9%) and an NPV of 66.7% (CI 52.9-78.6%) compared to the psychiatrist decision for the total sample, and a PPV of 90% (CI 82.4-95.1%) and an NPV of 69.6% (CI 47.1-86.8%) for suicidal patients. Additionally, the κ score, a measure of agreement between emergency physician disposition decision and psychiatrist disposition decision, was 0.530 (Cl 0.404-0.656). 95% of patients with an ED assessment of "definitely admit" were eventually admitted by the psychiatrist. Emergency physician disposition has a high PPV (87.3%) and a moderate NPV (66.7%) compared to psychiatrist disposition.

Patient and family physician preferences for care and communication in the eventuality of anthrax terrorism.

PubMed

Kahan, Ernesto; Fogelman, Yacov; Kitai, Eliezer; Vinker, Shlomo

2003-08-01

The threat of bioterrorism consequent to the September 11, 2001 attack in the USA generated suggestions for improved medical response mainly through hospital preparedness. The aim of the present study was to investigate the impact of this period of tension on patients' first choice for care and for receiving relevant information, and on primary care doctors' feelings of responsibility in the eventuality of an anthrax attack. During October 11-31, 2001, 500 patients from 30 clinics throughout Israel were asked to complete a questionnaire on their awareness of the anthrax threat, measures taken to prepare for it, and preferred sources of care and information. Their 30 physicians, and an additional 20, completed a questionnaire on knowledge about anthrax and anthrax-related patient behaviours and clinic visits. The outstanding finding was the low rate (30%) of patients who chose the hospital emergency department as their first choice for care or information if they were worried about an anthrax attack or the media communicated that an attack was in progress. The other two-thirds preferred their family doctor or the health authorities. Most of the physicians (89%) felt it was their responsibility to treat anthrax-infected patients and that they should therefore be supplied with appropriate guidelines. This study suggests that in Israel, a country with a high degree of awareness of civil defence aspects, both patients and primary care doctors believe that family physicians should have a major role in the case of bioterrorist attacks. This must be seriously considered during formulation of relevant health services programmes.

Anti-α-galactosidase A antibody response to agalsidase beta treatment: data from the Fabry Registry.

PubMed

Wilcox, William R; Linthorst, Gabor E; Germain, Dominique P; Feldt-Rasmussen, Ulla; Waldek, Stephen; Richards, Susan M; Beitner-Johnson, Dana; Cizmarik, Marta; Cole, J Alexander; Kingma, Wytske; Warnock, David G

2012-03-01

Agalsidase beta, a form of recombinant human α-galactosidase A (αGAL), is approved for use as enzyme replacement therapy (ERT) for Fabry disease. An immunogenic response against a therapeutic protein could potentially impact its efficacy or safety. The development of anti-αGAL IgG antibodies was evaluated in 571 men and 251 women from the Fabry Registry who were treated with agalsidase beta. Most men developed antibodies (416 of 571, 73%), whereas most women did not (31 of 251, 12%). Women were also significantly more likely to tolerize than men; whereas 18 of 31 women tolerized (58%, 95%CI: 52%-64%), only 47 of 416 men tolerized during the observation period (11%, 95% CI: 8%-15%). Patients who eventually tolerized had lower median peak anti-αGAL IgG antibody titers than patients who remained seropositive at their most recent assessment (400 versus 3200 in men, 200 versus 400 in women, respectively). Patients with nonsense mutations in the GLA gene were more likely to develop anti-αGAL IgG antibodies than patients with missense mutations. Approximately 26% of men (151 of 571) reported infusion-associated reactions (IARs), compared to 11% of women (27 of 251). Men who developed anti-αGAL IgG antibodies were more likely to experience IARs compared to those who remained seronegative. Nine percent of seronegative men and women (34 of 375) reported IARs. The majority of IARs occurred during the first 6 to 12 months of agalsidase beta treatment and decreased over time, in both seroconverted and seronegative patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Designing and Implementation of a Heart Failure Telemonitoring System

PubMed Central

Safdari, Reza; Jafarpour, Maryam; Mokhtaran, Mehrshad; Naderi, Nasim

2017-01-01

Introduction: The aim of this study was to identify patients at-risk, enhancing self-care management of HF patients at home and reduce the disease exacerbations and readmissions. Method: In this research according to standard heart failure guidelines and Semi-structured interviews with 10 heart failure Specialists, a draft heart failure rule set for alerts and patient instructions was developed. Eventually, the clinical champion of the project vetted the rule set. Also we designed a transactional system to enhance monitoring and follow up of CHF patients. With this system, CHF patients are required to measure their physiological measurements (vital signs and body weight) every day and to submit their symptoms using the app. additionally, based on their data, they will receive customized notifications and motivation messages to classify risk of disease exacerbation. The architecture of system comprised of six major components: 1) a patient data collection suite including a mobile app and website; 2) Data Receiver; 3) Database; 4) a Specialists expert Panel; 5) Rule engine classifier; 6) Notifier engine. Results: This system has implemented in Iran for the first time and we are currently in the testing phase with 10 patients to evaluate the technical performance of our system. The developed expert system generates alerts and instructions based on the patient’s data and the notify engine notifies responsible nurses and physicians and sometimes patients. Detailed analysis of those results will be reported in a future report. Conclusion: This study is based on the design of a telemonitoring system for heart failure self-care that intents to overcome the gap that occurs when patients discharge from the hospital and tries to accurate requirement of readmission. A rule set for classifying and resulting automated alerts and patient instructions for heart failure telemonitoring was developed. It also facilitates daily communication among patients and heart failure clinicians so any deterioration in health could be identified immediately. PMID:29114106

[Bioethical aspects of the Health Care Reform in Chile. The problems of access and costs of resources ].

PubMed

Rosselot, Eduardo

2003-09-01

During the process of health reforms there is always the concern that patients rights might be harmed. The bill that is being discussed in the Chilean Parliament contains an special issue dedicated to patient's obligations and rights. However, on the author's opinion, the best protection for patient rights rests on adequate financing and access to a reasonably, good and qualified health care. A thorough revision of the proposals contained in the reform will allow an objective assessment of the eventual ethical problems that it might imply.

Mirtazapine for anorexia nervosa with depression.

PubMed

Jaafar, Nik Ruzyanei Nik; Daud, Tuti Iryani Mohd; Rahman, Fairuz Nazri Abdul; Baharudin, Azlin

2007-09-01

To report the use of Mirtazapine in the treatment of anorexia nervosa with depression primarily regarding its propensity for weight gain. We present an outpatient case report of anorexia nervosa with depression. The patient's subsequent progress was recorded. The patient gained 2.5 kg within 3 months to eventually attain a body mass index of 15 after 5 months. Her depression achieved full remission at 6 weeks of treatment. Mirtazapine is the choice medication in this case. However, treating depression requires caution, given these patients' physical vulnerability. Controlled trials of Mirtazapine for anorexia nervosa are needed.

[Providing regular relief; considerations for palliative care in the Netherlands].

PubMed

Crul, B J; van Weel, C

2001-10-20

Over the last few decades the attention devoted to the palliative aspects of medicine, particularly those in hospital care, has declined due to the emphasis on medical technology. In Anglo-Saxon countries a review of this development resulted in structured palliative care that benefited terminally ill patients with a progressive fatal disease, especially cancer patients. Due to increasing national and international criticism of both the practice of euthanasia (assumed to be too liberal) and the lack of attention devoted to structured palliative care in the Netherlands, the Dutch government decided to improve the structure of palliative care. The government's viewpoint is based on the assumption that good palliative care that includes adequate pain control benefits patient care and might eventually lead to fewer requests for euthanasia. The improvements to palliative care should be realised by means of improvements in the structure, training and knowledge. Six academic medical clusters have been designated as Centres for the Development of Palliative Care (Dutch acronym: COPZ) for a 5-year period. Each COPZ must develop the various aspects needed to improve palliative care within the region it serves and ensure that its activities are carefully coordinated with those in the other centres. Research will focus on measuring the efficacy of palliative care as well as ethical and epidemiological aspects. A government committee will assess the appropriateness of the activities undertaken by each of the centres.

Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland.

PubMed

Tran, Simon D; Sugito, Takayuki; Dipasquale, Giovanni; Cotrim, Ana P; Bandyopadhyay, Bidhan C; Riddle, Kathryn; Mooney, David; Kok, Marc R; Chiorini, John A; Baum, Bruce J

2006-10-01

There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjögren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.

Analysis of volumetric response of pituitary adenomas receiving adjuvant CyberKnife stereotactic radiosurgery with the application of an exponential fitting model

PubMed Central

Yu, Yi-Lin; Yang, Yun-Ju; Lin, Chin; Hsieh, Chih-Chuan; Li, Chiao-Zhu; Feng, Shao-Wei; Tang, Chi-Tun; Chung, Tzu-Tsao; Ma, Hsin-I; Chen, Yuan-Hao; Ju, Da-Tong; Hueng, Dueng-Yuan

2017-01-01

Abstract Tumor control rates of pituitary adenomas (PAs) receiving adjuvant CyberKnife stereotactic radiosurgery (CK SRS) are high. However, there is currently no uniform way to estimate the time course of the disease. The aim of this study was to analyze the volumetric responses of PAs after CK SRS and investigate the application of an exponential decay model in calculating an accurate time course and estimation of the eventual outcome. A retrospective review of 34 patients with PAs who received adjuvant CK SRS between 2006 and 2013 was performed. Tumor volume was calculated using the planimetric method. The percent change in tumor volume and tumor volume rate of change were compared at median 4-, 10-, 20-, and 36-month intervals. Tumor responses were classified as: progression for >15% volume increase, regression for ≤15% decrease, and stabilization for ±15% of the baseline volume at the time of last follow-up. For each patient, the volumetric change versus time was fitted with an exponential model. The overall tumor control rate was 94.1% in the 36-month (range 18–87 months) follow-up period (mean volume change of −43.3%). Volume regression (mean decrease of −50.5%) was demonstrated in 27 (79%) patients, tumor stabilization (mean change of −3.7%) in 5 (15%) patients, and tumor progression (mean increase of 28.1%) in 2 (6%) patients (P = 0.001). Tumors that eventually regressed or stabilized had a temporary volume increase of 1.07% and 41.5% at 4 months after CK SRS, respectively (P = 0.017). The tumor volume estimated using the exponential fitting equation demonstrated high positive correlation with the actual volume calculated by magnetic resonance imaging (MRI) as tested by Pearson correlation coefficient (0.9). Transient progression of PAs post-CK SRS was seen in 62.5% of the patients receiving CK SRS, and it was not predictive of eventual volume regression or progression. A three-point exponential model is of potential predictive value according to relative distribution. An exponential decay model can be used to calculate the time course of tumors that are ultimately controlled. PMID:28121913

Unravelling the spirits’ message: a study of help-seeking steps and explanatory models among patients suffering from spirit possession in Uganda

PubMed Central

2014-01-01

As in many cultures, also in Uganda spirit possession is a common idiom of distress associated with traumatic experiences. In the DSM-IV and -5, possession trance disorders can be classified as dissociative disorders. Dissociation in Western countries is associated with complicated, time-consuming and costly therapies. Patients with spirit possession in SW Uganda, however, often report partial or full recovery after treatment by traditional healers. The aim of this study is to explore how the development of symptoms concomitant help-seeking steps, and explanatory models (EM) eventually contributed to healing of patients with spirit possession in SW Uganda. Illness narratives of 119 patients with spirit possession referred by traditional healers were analysed using a mixed-method approach. Treatments of two-thirds of the patients were unsuccessful when first seeking help in the medical sector. Their initially physical symptoms subsequently developed into dissociative possession symptoms. After an average of two help-seeking steps, patients reached a healing place where 99% of them found satisfactory EM and effective healing. During healing sessions, possessing agents were summoned to identify themselves and underlying problems were addressed. Often-mentioned explanations were the following: neglect of rituals and of responsibilities towards relatives and inheritance, the call to become a healer, witchcraft, grief, and land conflicts. The results demonstrate that traditional healing processes of spirit possession can play a role in restoring connections with the supra-, inter-, intra-, and extra-human worlds. It does not always seem necessary to address individual traumatic experiences per se, which is in line with other research in this field. The study leads to additional perspectives on treatment of trauma-related dissociation in Western countries and on developing effective mental health services in low -and middle-income countries. PMID:24940355

Unravelling the spirits' message: a study of help-seeking steps and explanatory models among patients suffering from spirit possession in Uganda.

PubMed

van Duijl, Marjolein; Kleijn, Wim; de Jong, Joop

2014-01-01

As in many cultures, also in Uganda spirit possession is a common idiom of distress associated with traumatic experiences. In the DSM-IV and -5, possession trance disorders can be classified as dissociative disorders. Dissociation in Western countries is associated with complicated, time-consuming and costly therapies. Patients with spirit possession in SW Uganda, however, often report partial or full recovery after treatment by traditional healers. The aim of this study is to explore how the development of symptoms concomitant help-seeking steps, and explanatory models (EM) eventually contributed to healing of patients with spirit possession in SW Uganda. Illness narratives of 119 patients with spirit possession referred by traditional healers were analysed using a mixed-method approach. Treatments of two-thirds of the patients were unsuccessful when first seeking help in the medical sector. Their initially physical symptoms subsequently developed into dissociative possession symptoms. After an average of two help-seeking steps, patients reached a healing place where 99% of them found satisfactory EM and effective healing. During healing sessions, possessing agents were summoned to identify themselves and underlying problems were addressed. Often-mentioned explanations were the following: neglect of rituals and of responsibilities towards relatives and inheritance, the call to become a healer, witchcraft, grief, and land conflicts. The results demonstrate that traditional healing processes of spirit possession can play a role in restoring connections with the supra-, inter-, intra-, and extra-human worlds. It does not always seem necessary to address individual traumatic experiences per se, which is in line with other research in this field. The study leads to additional perspectives on treatment of trauma-related dissociation in Western countries and on developing effective mental health services in low -and middle-income countries.

"Joven & Fuerte": Program for Young Women with Breast Cancer in Mexico - Initial Results.

PubMed

Villarreal-Garza, Cynthia; Castro-Sánchez, Andrea; Platas, Alejandra; Miaja, Melina; Mohar-Betancourt, Alejandro; Barragan-Carrillo, Regina; Fonseca, Alan; Vega, Yoatzin; Martinez-Cannon, B Alejandra; Aguilar, Dione; Bargalló-Rocha, Enrique; Cardona-Huerta, Servando; Peña-Curiel, Omar; Matus-Santoso, Juan

2017-01-01

Despite the high rates of breast cancer among young Mexican women, their special needs and concerns have not been systematically addressed. To fulfill these unsatisfied demands, we have developed "Joven & Fuerte: Program for Young Women with Breast Cancer in Mexico," the first program dedicated to the care of young breast cancer patients in Latin America, which is taking place at the National Cancer Institute of Mexico and the two medical facilities of the Instituto Tecnológico y de Estudios Superiores de Monterrey. The program was created to optimize the complex clinical and psychosocial care of these patients, enhance education regarding their special needs, and promote targeted research, as well as to replicate this program model in other healthcare centers across Mexico and Latin America. From November 2013 to February 2017, the implementation of the "Joven & Fuerte" program has delivered specialized care to 265 patients, through the systematic identification of their particular needs and the provision of fertility, genetic, and psychological supportive services. Patients and families have engaged in pedagogic activities and workshops and have created a motivated and empowered community. The program developed and adapted the first educational resources in Spanish dedicated for young Mexican patients, as well as material for healthcare providers. As for research, a prospective cohort of young breast cancer patients was established to characterize clinicopathological features and psychosocial effects at baseline and during follow-up, as a guide for the development of specific cultural interventions addressing this vulnerable group. Eventually, it is intended that the program's organization and structure can reach national and international interactions and serve as a platform for other countries.

The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features.

PubMed

Ruggieri, M; Polizzi, A; Spalice, A; Salpietro, V; Caltabiano, R; D'Orazi, V; Pavone, P; Pirrone, C; Magro, G; Platania, N; Cavallaro, S; Muglia, M; Nicita, F

2015-05-01

Spinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271). © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Frequency of EGFR T790M mutation and multimutational profiles of rebiopsy samples from non-small cell lung cancer developing acquired resistance to EGFR tyrosine kinase inhibitors in Japanese patients.

PubMed

Ko, Ryo; Kenmotsu, Hirotsugu; Serizawa, Masakuni; Koh, Yasuhiro; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Naito, Tateaki; Murakami, Haruyasu; Isaka, Mitsuhiro; Endo, Masahiro; Nakajima, Takashi; Ohde, Yasuhisa; Yamamoto, Nobuyuki; Takahashi, Kazuhisa; Takahashi, Toshiaki

2016-11-08

The majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs. We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs. We analyzed 27 practicable samples using a tumor genotyping panel to assess 23 hot-spot sites of genetic alterations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, and HER2), gene copy number of EGFR, MET, PIK3CA, FGFR1, and FGFR2, and ALK, ROS1, and RET fusions. Additionally, 34 samples were analyzed by commercially available EGFR mutation tests. Sixty-one patients underwent rebiopsy. Twenty-seven samples were analyzed using our tumor genotyping panel, and 34 samples were analyzed for EGFR mutations only by commercial clinical laboratories. Twenty-one patients (34 %) had EGFR T790M mutation. Using our tumor genotyping panel, MET gene copy number gain was observed in two of 27 (7 %) samples. Twenty patients received continuous treatment with EGFR-TKIs even after disease progression, and 11 of these patients had T790M mutation in rebiopsy samples. In contrast, only 10 of 41 patients who finished EGFR-TKI treatment at disease progression had T790M mutation. The frequency of T790M mutation in patients who received continuous treatment with EGFR-TKIs after disease progression was significantly higher than that in patients who finished EGFR-TKI treatment at disease progression (55 % versus 24 %, p = 0.018). The frequency of T790M mutation in this study was lower than that in previous reports examining western patients. These results suggest that continuous treatment with EGFR-TKI after disease progression may enhance the frequency of EGFR T790M mutation in rebiopsy samples.

The Space Station Prototype Program - The development of a regenerative life support system for extended-duration missions.

NASA Technical Reports Server (NTRS)

Willis, N. C., Jr.; Neel, J. M.

1972-01-01

Design concepts and test philosophies which may contribute to the development of a low-cost maintainable environmental control/life support system are examined. It is shown that the concept of producing flight prototype equipment during a developmental program can reduce the eventual cost of a flight system by incorporating realistic flight-type design requirements without imposing exacting design features and stringent controls. A flight prototype design is one that can be converted readily into an actual flight design without any conceptual change. Modularity of subsystems provides the system and the program a degree of flexibility relative to the eventual vehicle configuration and technological improvements.

The Treatment of Obesity in Cardiac Rehabilitation

PubMed Central

Ades, Philip A.; Savage, Patrick D.; Harvey-Berino, Jean

2010-01-01

Obesity is an independent risk factor for the development of coronary heart disease (CHD). At entry into cardiac rehabilitation (CR) over 80% of patients are overweight and over 50% have the metabolic syndrome. Yet, CR programs do not generally include weight loss programs as a programmatic component and weight loss outcomes in CR have been abysmal. A recently published study outlines a template for weight reduction based upon a combination of behavioral weight loss counseling and an approach to exercise that maximized exercise-related caloric expenditure. This approach to exercise optimally includes walking as the primary exercise modality and eventually requires almost daily longer distance exercise to maximize caloric expenditure. Additionally, lifestyle exercise such as stair climbing and avoidance of energy-saving devices should be incorporated into the daily routine. Risk factor benefits of weight loss and exercise training in overweight patients with coronary heart disease are broad and compelling. Improvements in insulin resistance, lipid profiles, blood pressure, clotting abnormalities, endothelial-dependent vasodilatory capacity, and measures of inflammation such as C-reactive protein have all been demonstrated. CR/secondary prevention programs can no longer ignore the challenge of obesity management in patients with CHD. Individual programs need to develop clinically effective and culturally sensitive approaches to weight control. Finally, multicenter randomized clinical trials of weight loss in CHD patients with assessment of long-term clinical outcomes need to be performed. PMID:20436355

Use of Cox's Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response.

PubMed

Asano, Junichi; Hirakawa, Akihiro; Hamada, Chikuma; Yonemori, Kan; Hirata, Taizo; Shimizu, Chikako; Tamura, Kenji; Fujiwara, Yasuhiro

2013-01-01

In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically "cured." Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.

Why the general dentist needs to know how to manage oral lichen planus.

PubMed

Price, Stephanie M; Murrah, Valerie A

2015-01-01

Oral lichen planus (OLP) is a frequently mismanaged chronic disease that requires care throughout a patient's life, and therefore a condition the general dentist must know how to manage. Patients with OLP often suffer considerable physical discomfort and an inability to perform proper oral hygiene, eventually resulting in poor periodontal health. In addition, these patients are confronted with the psychological stress of knowing that OLP is not curable. This is accompanied by a fear of other negative health developments, particularly oral cancer. The objective of this study was to identify major issues surrounding the management of OLP by the general dentist. A literature review of over 1100 articles was performed. An eclectic compilation of the issues revealed 12 major areas of concern. This article reviews those concerns and presents strategies for coping with the myriad signs, symptoms, and complications associated with this disease, as well as educational approaches and legal considerations. A rationale is provided to place the responsibility for the management of these patients under the person best positioned to coordinate care for this condition--the general dentist. A general dentist can contribute to the overall oral health of an OLP patient with timely diagnosis, effective treatment, thorough patient education, and the orchestration of efforts by a team of health care providers.

Radiation recall gastritis secondary to combination of gemcitabine and erlotinib in pancreatic cancer and response to PPI - a case report.

PubMed

Choi, Seong Ji; Kim, Hyo Jung; Kim, Jae Seon; Bak, Young-Tae; Kim, Jun Suk

2016-08-02

Radiation recall gastritis is rare but can be induced after concurrent chemoradiation for pancreatic cancer. We report a patient with pancreatic cancer who developed radiation-recall gastritis related to a combination of gemcitabine and erlotinib. A 54-year-old female with unresectable pancreatic cancer received gemcitabine in combination with radiation therapy followed by chemotherapy with gemcitabine and erlotinib. After completing 2 cycles of chemotherapy, the patient had epigastric pain, nausea, and vomiting. Abdominal computed tomography (CT) scan revealed diffuse wall thickening of the stomach, and esophagogastroduodenoscopy (EGD) showed multiple gastric ulcers. The patient was treated with proton pump inhibitors (PPI) and was continued on maintenance chemotherapy. Two months later, the patient presented with the similar symptoms and persistent gastric ulcers were observed during subsequent EGD. Nevertheless, the patient's symptom had resolved with PPI therapy. Thus, the patient underwent maintenance chemotherapy with gemcitabine and erlotinib for additional 4 cycles. Eventually, follow-up abdominal CT Scan and EGD at 6 months demonstrated resolution of the gastric ulcers. Physicians should be aware of the possibility of radiation recall gastritis associated with a combination of gemcitabine and erlotinib. Administration of PPIs may mitigate the adverse effects of gemcitabine and erlotinib in the presence of radiation recall gastritis; however further studies are warranted.

GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects

PubMed Central

Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M; Mefford, Heather C; Myers, Candace T; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette; Scheffer, Ingrid E; Brilstra, Eva; van Haelst, Mieke M; van der Smagt, Jasper J; Bok, Levinus A; Møller, Rikke S; Jensen, Uffe B; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H; Jamra, Rami Abou; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R

2017-01-01

Background We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Methods Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. Results Overall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated. Conclusions In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies. PMID:28377535

Successful treatment of IgM paraproteinaemic neuropathy with fludarabine

PubMed Central

Wilson, H.; Lunn, M.; Schey, S.; Hughes, R

1999-01-01

OBJECTIVES—To evaluate the response of four patients with IgM paraproteinaemic neuropathy to a novel therapy—pulsed intravenous fludarabine.
BACKGROUND—The peripheral neuropathy associated with IgM paraproteinaemia usually runs a chronic, slowly progressive course which may eventually cause severe disability. Treatment with conventional immunosuppressive regimens has been unsatisfactory. Fludarabine is a novel purine analogue which has recently been shown to be effective in low grade lymphoid malignancies.
METHODS—Four patients were treated with IgM paraproteinaemic neuropathy with intravenous pulses of fludarabine. Two of the four patients had antibodies to MAG and characteristic widely spaced myelin on nerve biopsy and a third had characteristic widely spaced myelin only. The fourth had an endoneurial lymphocytic infiltrate on nerve biopsy and a diagnosis of Waldenström's macroglobulinaemia.
RESULTS—In all cases subjective and objective clinical improvement occurred associated with a significant fall in the IgM paraprotein concentration in three cases. Neurophysiological parameters improved in the three patients examined. The treatment was well tolerated. All patients developed mild, reversible lymphopenia and 50% mild generalised myelosuppression, but there were no febrile episodes.
CONCLUSION—Fludarabine should be considered as a possible treatment for patients with IgM MGUS paraproteinaemic neuropathy.

 PMID:10209166

Management of pediatric postoperative chylothorax.

PubMed

Bond, S J; Guzzetta, P C; Snyder, M L; Randolph, J G

1993-09-01

Questions persist about the management of postoperative chylothorax in infants and children. Our experience with postoperative chylothorax over the most recent decade (1980 to 1990) has been reviewed. The type and amount of drainage, data from cardiac catheterization and echocardiography, operative decisions and details, and eventual outcomes have been cataloged. All patients were initially treated with total gut rest, with operation reserved for unabated drainage. Chylothorax developed postoperatively in 15 infants and 11 children (18 with a cardiac procedure and 8 with a noncardiac procedure). The average age was 3.1 years. Spontaneous cessation and cure occurred in 19 (73.1%) of these 26 patients, with an average drainage duration of 11.9 days (range, 4 to 30 days). Those for whom operation was chosen drained preoperatively for an average of 29.2 days (range, 25 to 40 days). There were no deaths in either group. Complications were lymphopenia (2 patients) and fungal sepsis (1 patient). The amount of drainage per day was not significantly different between patients treated operatively and those treated nonoperatively. Failure of nonoperative management was associated with venous hypertension from increased right-sided cardiac pressures or central venous thrombosis (p < 0.05, Fisher's exact test). Presumably this increased pressure is transmitted to the lymphatic system. These patients should be identified early and considered for thoracic duct suture or pleuroperitoneal shunting.

Dietetic treatment with hypercaloric and hyperprotein intake in patients following severe brain injury.

PubMed

Balzola, F; Boggio Bertinet, D; Solerio, A; Rizzonato, P; Urciuoli, R; Piazza, A

1980-01-01

Sixty four patients, following severe acute brain injury were fed according to a strict dietetic therapy at the Intensive Care Unit at the Institute of Neurological Surgery, University of Turin. We used mixtures composed of simple nutritional elements consisting of carbohydrate as glucose polymers from 7 to 15 units, free aminoacids and MCT oil, integrated with natural elements. The solutions were administered via a nasogastric tube with the maximum caloric intake of 6.000 Kcal and 186 grams proteins/24 hr. After recording a series of hematochemical and clinical parameters we obtained the following results: 1) the average blood sugar level was always found to be pathological among the 11 patients who eventually died during their hospitalization, while 30% of the discharged patients had normal blood sugar values; 2) kidney function was significantly more affected among eventually deceased patients than among discharged ones; 3) the hospitalization time had a negative influence on the hepatic functions. Total serum albumins and proteins cease their decline respectively at average values of 2 and 5.5% gr, cholesterol maintains a constant level between 180 and 200% gr, calcium between 8 and 9 mg% and phosphorous around 3 mg%. Alkaline phosphatase in all patients rose significantly to pathological values only after a week of hospitalization. All other tests presented an irregular course. The survival period of our group of patients was significantly longer than that of control group. Within our group the survival rate was better among patients who received, within 10 days from cerebral damages, a hypercaloric and hyperprotein diet of more than 5.000 Kcal and 120 grams of proteins in 24 h, as compared to those whom the same diet was administered more gradually or following a longer period of time after having sustained cerebral damage.

Redox Regulation in Bone Marrow Failure

DTIC Science & Technology

2012-06-01

Fanconi anemia mutation for hematopoietic senescence. J Cell Sci, 2007. 120(Pt 9): p. 1572-83. 2. Aylon, Y. and M. Oren, Living with p53, dying of p53...aplastic anemia patients with a p38 MAPK inhibitor can restore defective hematopoietic activity, suggesting the critical role of p38 in bone marrow...hematopoietic stem cells, and eventually leading to bone marrow failure [7, 8] [9] [10]. On the other hand, treating aplastic anemia patients with a p38

Dynamic value assessments in oncology supported by the PACE Continuous Innovation Indicators.

PubMed

Paddock, Silvia; Goodman, Clifford; Shortenhaus, Scott; Grainger, David; Zummo, Jacqueline; Thomas, Samuel

2017-10-01

Several recently developed frameworks aim to assess the value of cancer treatments, but the most appropriate metrics remain uncertain. We use data from the Patient Access to Cancer care Excellence Continuous Innovation Indicators to examine the relationship between hazard ratios (HRs) from clinical trials and dynamic therapeutic value accumulating over time. Our analysis shows that HRs from initial clinical trials poorly predict the eventual therapeutic value of cancer treatments. Relying strongly on HRs from registration trials to predict the long-term success of treatments leaves a lot of the variance unexplained. The Continuous Innovation Indicators offer a complementing, dynamic method to track the therapeutic value of cancer treatments and continuously update value assessments as additional evidence accumulates.

Breast necrosis secondary to vasopressor extravasation: management using indocyanine green angiography and omental flap closure.

PubMed

Hagopian, Thomas M; Ghareeb, Paul A; Arslanian, Brian H; Moosavi, Benjamin L; Carlson, Grant W

2015-01-01

Extravasation is a rare but serious complication of vasopressor administration. A 60-year-old female who underwent ascending and hemiarch repair of the aorta along with aortic valve replacement developed extensive right breast and chest wall necrosis after vasopressor extravasation from an internal jugular vein central line. The patient underwent a total mastectomy due to deep tissue necrosis detected by laser-assisted indocyanine green dye angiography, and eventually required omental flap reconstruction to obtain adequate sternal coverage. This case represents a previously unreported complication of internal jugular central line extravasation of vasopressors with resultant breast and chest wall necrosis, and highlights the utility of the omentum in chest wall reconstruction. © 2015 Wiley Periodicals, Inc.

Tube thoracostomy: the struggle to the "standard of care".

PubMed

Monaghan, Sean F; Swan, Kenneth G

2008-12-01

Tube thoracostomy for thoracic injuries has been standard for only the last 40 years. Its theoretic roots trace back to World War II, where the goal of treatment was restoration of intrathoracic organ function. Thoracentesis was used to evacuate the hemopneumothorax resulting from chest trauma and that compromised pulmonary function. Experience gained in military and civilian hospitals contributed to the development of tube thoracostomy as an alternative treatment for patients with chest trauma. Progress stalled due to technologic problems and unacceptable complications associated with tube thoracostomy use during the Korean War. Technology improved, however, as did the success of thoracostomy, and it eventually become the standard of care, first in the civilian community and, ultimately, in the Vietnam War.

Amyotrophic lateral sclerosis: update and new developments

PubMed Central

Pratt, Ashley J; Getzoff, Elizabeth D; Perry, J Jefferson P

2012-01-01

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease. It is typically characterized by adult-onset degeneration of the upper and lower motor neurons, and is usually fatal within a few years of onset. A subset of ALS patients has an inherited form of the disease, and a few of the known mutant genes identified in familial cases have also been found in sporadic forms of ALS. Precisely how the diverse ALS-linked gene products dictate the course of the disease, resulting in compromised voluntary muscular ability, is not entirely known. This review addresses the major advances that are being made in our understanding of the molecular mechanisms giving rise to the disease, which may eventually translate into new treatment options. PMID:23019386

A new evidence-based risk stratification system for cutaneous squamous cell carcinoma into low, intermediate, and high risk groups with implications for management.

PubMed

Baum, Christian L; Wright, Adam C; Martinez, Juan-Carlos; Arpey, Christopher J; Brewer, Jerry D; Roenigk, Randall K; Otley, Clark C

2018-01-01

Most primary cutaneous squamous cell carcinomas are cured with surgery. A subset, however, may develop local and nodal metastasis that may eventuate in disease-specific; death. This subset has been variably termed high risk. Herein, we review; an emerging body of data on the risks of these outcomes and propose an evidence-based; risk stratification for low-, intermediate-, and high-risk tumors that takes into; account both tumor and patient characteristics. Finally, we discuss a framework for; management of these tumors on the basis of data, when available, and our; recommendations when data are sparse. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Pancytopenia after low dose methotrexate therapy in a hemodialysis patient: case report and review of literature.

PubMed

Yang, Ching-Ping; Kuo, Mei-Chuan; Guh, Jinn-Yuh; Chen, Hung-Chun

2006-01-01

Methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis (RA) with a side effect of pancytopenia. However, only a few cases of severe pancytopenia caused by low-dose MTX therapy have been reported, and the condition is rarely reported in uremic patients on dialysis therapy. We thereby report a hemodialysis patient who developed severe pancytopenia after oral treatment with low-dose MTX for RA. A 55-year-old woman who had been on regular hemodialysis treatment for 7 yr suffered from RA for 10 yr. She was regularly treated with celecoxib, prednisolone, and sulfasalazine in the past year. Because of the increasing arthralgia, 7.5 mg per week MTX was prescribed 3 months before admission. Stomatitis, fever, general fatigue, multiple skin carbuncles, and easy bruising developed after a cumulative dose of 90 mg. Pancytopenia was found at admission and the nadir of white blood cell count was 250/microL with 28% neutrophils, hematocrit was 22%, and platelet count was 6000/microL. Eosinophil counts increased from 11.5% initially to 26.1% on the sixth admission day. Transfusion with red blood cells and platelets, and appropriate antibiotics and folic acid were prescribed. She continued receiving regular hemodialysis and eventually recovered within 3 weeks.

The evolution of tumor metastases during clonal expansion.

PubMed

Haeno, Hiroshi; Michor, Franziska

2010-03-07

Cancer is a leading cause of morbidity and mortality in many countries. Solid tumors generally initiate at one particular site called the primary tumor, but eventually disseminate and form new colonies in other organs. The development of such metastases greatly diminishes the potential for a cure of patients and is thought to represent the final stage of the multi-stage progression of human cancer. The concept of early metastatic dissemination, however, postulates that cancer cell spread might arise early during the development of a tumor. It is important to know whether metastases are present at diagnosis since this determines treatment strategies and outcome. In this paper, we design a stochastic mathematical model of the evolution of tumor metastases in an expanding cancer cell population. We calculate the probability of metastasis at a given time during tumor evolution, the expected number of metastatic sites, and the total number of cancer cells as well as metastasized cells. Furthermore, we investigate the effect of drug administration and tumor resection on these quantities and predict the survival time of cancer patients. The model presented in this paper allows us to determine the probability and number of metastases at diagnosis and to identify the optimum treatment strategy to maximally prolong survival of cancer patients. 2009 Elsevier Ltd. All rights reserved.

Awake craniotomy for glioma resection: Technical aspects and initial results in a single institution.

PubMed

Trimble, Gillian; McStravick, Clodagh; Farling, Peter; Megaw, Katie; McKinstry, Steven; Smyth, Graham; Law, Gillian; Courtney, Heather; Quigley, Gavin; Flannery, Thomas

2015-01-01

Although variations in the technique of awake craniotomy (AC) have been widely reported, a key member of this interdisciplinary procedure is the healthcare professional performing assessments of neurological function during resection. The expertise of the latter will depend on the neurological function to be tested and on available resources of the institution. This report details our initial experience of an AC service utilizing the expertise of a speech and language therapist (SLT) and an experienced neuro-physiotherapist (NP) to monitor patient function during glioma resection. Forty-five patients underwent 50 AC procedures for eloquently located gliomas over a 3-year period. Patients with a glioma involving speech or sensorimotor areas were assessed preoperatively by the SLT/NP respectively. The same therapist monitored the patient's neurological function intraoperatively and executed a rehabilitation program tailored to the needs of the patient in the postoperative period. Three patients underwent biopsy only, due to intraoperative seizures precluding intraoperative mapping (2 cases) or speech arrest on stimulation of a small recurrent tumor. The remaining 47 cases were suitable for repetitive neurological assessment "awake" during tumor debulking. One patient with a large sensorimotor tumor developed intraoperative hemiparesis due to outward brain herniation (which recovered postoperatively). Ten patients developed a new or worsened neurological deficit in the initial postoperative period (6 were detected intraoperatively), of which 5 eventually had resolution and returned to baseline function within 2 weeks. In our initial experience based anecdotally on a previous similar "non-awake" caseload, we have found AC with the input of the SLT/NP to be a key component in ensuring optimal functional outcomes for patients with gliomas in eloquently located areas.

Mortality and Its Risk Factors in Patients with Rapid Eye Movement Sleep Behavior Disorder.

PubMed

Zhou, Junying; Zhang, Jihui; Lam, Siu Ping; Mok, Vincent; Chan, Anne; Li, Shirley Xin; Liu, Yaping; Tang, Xiangdong; Yung, Wing Ho; Wing, Yun Kwok

2016-08-01

To determine the mortality and its risk factors in patients with rapid eye movement (REM) sleep behavior disorder (RBD). A total of 205 consecutive patients with video-polysomnography confirmed RBD (mean age = 66.4 ± 10.0 y, 78.5% males) were recruited. Medical records and death status were systematically reviewed in the computerized records of the health care system. Standardized mortality ratio (SMR) was used to calculate the risk ratio of mortality in RBD with reference to the general population. Forty-three patients (21.0%) died over a mean follow-up period of 7.1 ± 4.5 y. The SMR was not increased in the overall sample, SMR (95% confidence interval [CI]) = 1.00 (0.73-1.33). However, SMR (95% CI) increased to 1.80 (1.21-2.58) and 1.75 (1.11-2.63) for RBD patients in whom neurodegenerative diseases and dementia, respectively, eventually developed. In the Cox regression model, mortality risk was significantly associated with age (hazard ratio [HR] = 1.05; 95% CI, 1.01-1.10), living alone (HR = 2.04; 95% CI, 1.39-2.99), chronic obstructive pulmonary disease (HR = 3.38; 95% CI, 1.21-9.46), cancer (HR = 10.09; 95% CI, 2.65-38.42), periodic limb movements during sleep (HR = 3.06; 95% CI, 1.50-6.24), and development of neurodegenerative diseases (HR = 2.84; 95% CI, 1.47-5.45) and dementia (HR = 2.66; 95% CI, 1.39-5.08). Patients with RBD have a higher mortality rate than the general population only if neurodegenerative diseases develop. Several risk factors on clinical and sleep aspects are associated with mortality in RBD patients. Our findings underscore the necessity of timely neuroprotective interventions in the early phase of RBD before the development of neurodegenerative diseases. © 2016 Associated Professional Sleep Societies, LLC.

A better prediction model for patient surges from influenza? New Internet-based tool shows promise, say researchers.

PubMed

2012-03-01

In a study focused on Baltimore, MD, researchers have found that data culled from Google Flu Trends, a free Internet-based influenza surveillance system, shows strong correlation with hikes in ED visits from patients with flu-like symptoms. While the approach has yet to be validated in other cities or regions, experts recommend that ED administrators and providers familiarize themselves with the new surveillance tool and stay abreast of developments regarding similar surveillance mechanisms. Google Flu Trends (www.google.org/flutrends/) is a free Internet-based tool that monitors Internet-based searches for flu information. Users can customize their search by location (city, state, country). Researchers say the advantage of this approach over traditional surveillance methods is that it provides real-time data about flu-related activity in a city or region. Traditional approaches, which rely on case reports from the Centers for Disease Control and Prevention, are delayed. Researchers hope to eventually leverage this tool, and perhaps other surveillance data, into a powerful early-warning mechanism that EDs can use to better plan for patient surges due to influenza.

The role of the pediatric nephrologist in the care of children with diabetes mellitus.

PubMed

Lane, P; Steffes, M; Mauer, S M

1991-05-01

The pediatric nephrologist has traditionally not been involved in the care of the diabetic child since diabetic nephropathy presents in adulthood. Recent studies suggest that diabetic kidney disease develops silently during childhood. Measurement of urinary albumin excretion (UAE) allows earlier detection of patients at risk of nephropathy, often in adolescence. In addition to diabetic nephropathy, diabetic children are at risk of urinary tract infections, renal papillary necrosis, and various forms of glomerulonephritis. The role of the pediatric nephrologist in the care of the child with diabetes might include advising on the administration and interpretation of screening for UAE and the measurement and interpretation of glomerular filtration rate, and blood pressure. Children with evidence of renal dysfunction should be evaluated and treated by the pediatric nephrologist. Frequently, renal biopsy will be necessary in these patients. Future research may allow the detection of diabetic kidney disease earlier in childhood, further expanding the role of the pediatric nephrologist. In particular, early renal biopsy may eventually be used to select those patients at risk of diabetic nephropathy for specific treatment alterations.

Physician-perceived contradictions in end-of-life communication: toward a self-report measurement scale.

PubMed

Amati, Rebecca; Hannawa, Annegret F

2015-01-01

Communication is undoubtedly a critical element of competent end-of-life care. However, physicians commonly lack communication skills in this particular care context. Theoretically grounded, evidence-based guidelines are needed to enhance physicians' communication with patients and their families in this important time of their lives. To address this need, this study tests and validates a Contradictions in End-of-Life Communication (CEOLC) scale, which disentangles the relational contradictions physicians commonly experience when communicating with end-of-life patients. Exploratory factors analysis confirmed the presence of eight physician-perceived dialectical tensions, reflecting three latent factors of (1) integration, (2) expression, and (3) dominance. Furthermore, a number of significant intercultural differences were found in cross-cultural comparisons of the scale in U.S., Swiss, and Italian physician samples. Thus, this investigation introduces a heuristic assessment tool that aids a better understanding of the dialectical contradictions physicians experience in their interactions with end-of-life patients. The CEOLC scale can be used to gather empirical evidence that may eventually support the development of evidence-based guidelines and skills training toward improved end-of-life care.

A New Technique in Surgical Management of the Giant Cerebral Hydatid Cysts.

PubMed

Aydin, Mehmet Dumlu; Karaavci, Nuh Cagri; Akyuz, Mehmet Emin; Sahin, Mehmet Hakan; Zeynal, Mete; Kanat, Ayhan; Altinors, Mehmet Nur

2018-05-01

In hydatid disease, the central nervous system is affected approximately in 2% to 3% of patients. Surgical management in these patients is important. To develop a surgical technique to avoid the formation of great volume of cavity after hydatid cyst removal and prevent complications associated with brain collapse and cortical convolution. In 2 patients, hydatid cysts were delivered by this new technique. A balloon filled with 150 cc of sterile air/distilled water was placed in the cavity until the balloon filled the entire cavity. Air/distilled water evacuation was continued at a rate of 20 cc/d and, after a week, eventually, the balloons were removed RESULTS:: All cysts were delivered without rupture. Neurologic outcomes were good. No complications were observed related to usage of the system such as balloon rupture, evacuation problems, and infection. The authors believe that the balloon insertion technique may be a useful method to prevent brain collapse, cortical convolution, and complications associated with this condition. Further technical refinements of the system are needed for better results.

The double auditory meatus--a rare first branchial cleft anomaly: clinical presentation and treatment.

PubMed

Stokroos, R J; Manni, J J

2000-11-01

To discuss the embryology, classification, clinical experience with, and management of first branchial cleft anomalies. Retrospective case review. Tertiary referral center. Patients with a first branchial cleft anomaly. Surgery or revision surgery. Classifications according to Work, Olsen, Chilla; previous diagnostic and therapeutic pitfalls; outcome of intervention (including facial nerve function). Between 1984 and 1999, first branchial cleft anomalies were diagnosed in 18 patients. Surgical treatment was the treatment of choice. The authors' approach in Work type I and type 2 lesions is described, and surgical aspects of revision surgery are discussed. The importance of early establishment of the relationship of the anomaly to the facial nerve is stressed. In 8 patients, previous surgical attempts had been undertaken without establishment of the diagnosis first. After intervention, the outcome was favorable. First branchial cleft anomalies occur sporadically in ordinary clinical practice. They may go unrecognized or may be mistaken for tumors or other inflammatory lesions of in the periauricular region. However, the distinct clinical features, which can be derived from embryologic development, usually lead to the correct diagnosis. This avoids both treatment delay and eventual failure.

A favorable outcome despite a 39-hour treatment delay for arterial gas embolism: case report.

PubMed

Covington, Derek; Bielawski, Anthony; Sadler, Charlotte; Latham, Emi

2016-01-01

Cerebral arterial gas embolism (CAGE) occurs when gas enters the cerebral arterial vasculature. CAGE can occur during sitting craniotomies, cranial trauma or secondary to gas embolism from the heart. A far less common cause of CAGE is vascular entrainment of gas during endoscopic procedures. We present the case of a 49-year-old male who developed a CAGE following an esophagoduodenoscopy (EGD) biopsy. Due to a delay in diagnosis, the patient was not treated with hyperbaric oxygen (HBO₂) therapy until 39 hours after the inciting event. Despite presenting to our institution non-responsive and with decorticate posturing, the patient was eventually discharged to a rehabilitation facility, with only mild left upper extremity weakness. This delay in HBO₂ treatment represents the longest delay in treatment to our knowledge for a patient suffering from CAGE secondary to EGD. In addition to the clinical case report, we discuss the etiology of CAGE and the evidence supporting early HBO₂ treatment, as well as the data demonstrating efficacy even after considerable treatment delay. Copyright© Undersea and Hyperbaric Medical Society.

The use of acrylic resin oral prosthesis in radiation therapy of oral cavity and paranasal sinus cancer

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

Cheng, V.S.T.; Oral, K.; Aramamy, M.A.

1982-07-01

In radiation therapy of cancer of the oral cavity and the paranasal sinuses, the extent to which the tissues of the oral cavity are included in the radiation treatment portals will determine the severity of the oral discomfort during treatment. This will affect the nutritional status of the patients, and may eventually affect the total dose of radiation which the patients can receive for treatment of their cancers. In cooperation with the Maxillofacial Prosthetic Department, an acrylic resin oral prosthesis was developed. This prosthesis is easy to use and can be made for each individual patient within 24 hours. Itmore » allows for maximum sparing of the normal tissues in the oral cavity and can be modified for shielding of backscattered electrons from heavy metals in the teeth. We have also found that acrylic resin extensions can be built onto the posterior edge of post-maxillectomy obturators; this extension can be used as a carrier for radioactive sources to deliver radiation to deep seated tumor modules in the paranasal sinuses.« less

Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

PubMed Central

Rinaldi, Leonardo; Selman, Helmy

2016-01-01

A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice.

PubMed

Soulard, Valérie; Bosson-Vanga, Henriette; Lorthiois, Audrey; Roucher, Clémentine; Franetich, Jean-François; Zanghi, Gigliola; Bordessoulles, Mallaury; Tefit, Maurel; Thellier, Marc; Morosan, Serban; Le Naour, Gilles; Capron, Frédérique; Suemizu, Hiroshi; Snounou, Georges; Moreno-Sabater, Alicia; Mazier, Dominique

2015-07-24

Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Humanized mice offer a means to overcome this and further provide the opportunity to observe the parasites in vivo. Here we improve on previous protocols to achieve efficient double engraftment of TK-NOG mice by human primary hepatocytes and red blood cells. Thus, we obtain the complete hepatic development of P. falciparum, the transition to the erythrocytic stages, their subsequent multiplication, and the appearance of mature gametocytes over an extended period of observation. Furthermore, using sporozoites derived from two P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG mice sustain maturation of the liver stages, and the presence of late-developing schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG mice are highly suited for in vivo observations on the Plasmodium species of humans.

Adverse clinical sequelae after skin branding: a case series

PubMed Central

2009-01-01

Introduction Branding refers to a process whereby third degree burns are inflicted on the skin with a hot iron rod or metallic object. Branding employs the phenomenon of "counter irritation," and is widely used by faith healers in developing countries for therapeutic purposes. Some methods, which are very crude and inhuman, carry a large risk of complications. The purpose of this study is to present a series of complications and to familiarize clinicians with this dangerous method of treatment. Case presentation Four Pakistani patients, three male and one female, ranging from 25 to 60 years of age "branded" with a red hot iron rod for various medical reasons presented with severe medical complications to our tertiary care hospital. The mean duration between the procedure and presentation to the hospital was 6 days. At the time of admission, two patients had septic shock, one patient had cavernous sinus thrombosis and one patient had multiple splenic abscesses. All patients received standard care for wound management and systemic infections. Two patients eventually died during the course of treatment. Conclusion Severe complications from branding are troublesome and the potential risks of this treatment outweigh its benefits. Globally, there is a great need for heightened awareness about the dangers of branding among patients and physicians, as this will have an important effect on patients who seek branding for various medical conditions. PMID:19166615

Reconstructive Management of Devastating Electrical Injuries to the Face.

PubMed

Janis, Jeffrey E; Khansa, Ibrahim; Lehrman, Craig R; Orgill, Dennis P; Pomahac, Bohdan

2015-10-01

Devastating fourth-degree electrical injuries to the face and head pose significant reconstructive challenges. To date, there have been few peer-reviewed articles in the literature that describe those reconstructive challenges. The authors present the largest case series to date that describes the management of these injuries, including the incorporation of face transplantation. A retrospective case series was conducted of patients with devastating electrical injuries to the face who were managed at two level-1 trauma centers between 2007 and 2011. Data describing patient injuries, initial management, and reconstructive procedures were collected. Five patients with devastating electrical injuries to the face were reviewed. After initial stabilization and treatment of life-threatening injuries, all five underwent burn excision and microsurgical reconstruction using distant flaps. Two of the patients eventually underwent face transplantation. The authors describe differences in management between the two trauma centers, one of which had the availability for composite tissue allotransplantation; the other did not. Also described is how initial attempts at traditional reconstruction affected the eventual face transplantation. The care of patients with complex electrical burns must be conducted in a multidisciplinary fashion. As with all other trauma, the initial priority should be management of the airway, breathing, and circulation. Additional considerations include cardiac arrhythmias and renal impairment attributable to myoglobinuria. Before embarking on aggressive reconstruction attempts, it is advisable to determine early whether the patient is a candidate for face transplantation in order to avoid antigen sensitization, loss of a reconstructive "lifeboat," surgical plane disruption, and sacrifice of potential recipient vessels. Therapeutic, V.

Early treatment with intravenous lipid emulsion in a potentially lethal hydroxychloroquine intoxication.

PubMed

Ten Broeke, R; Mestrom, E; Woo, L; Kreeftenberg, H

2016-06-01

This case report describes the possible benefit of intravenous lipid emulsion in two patients surviving a severe intoxication with hydroxychloroquine in a dose that was previously considered to be lethal. The first case involves a 25-year-old female who ingested 17.5 grams of hydroxychloroquine, approximately one hour before presentation. An ECG showed QRS widening and the lab results showed hypokalaemia. She became unconscious, and developed hypotension and eventually apnoea. After intubation, supportive care consisted of norepinephrine and supplementation of potassium. Moreover, sodium bicarbonate and intravenous lipid emulsion were started to prevent cardiac toxicity. After these interventions, haemodynamic stability was established within a few hours. Although cardiomyopathy was confirmed, the patient recovered after two weeks. The second case concerns a 25-year-old male who took 5 grams of hydroxychloroquine. At presentation, two hours after intake, he showed QTc prolongation and hypokalaemia. The patient was treated with the usual supportive care and, although presentation to hospital was later, with intravenous lipid emulsion. Also this patient recovered. In conclusion, these cases show the benefit of supplemental intravenous lipid emulsion to prevent cardiac toxicity after a severe intoxication with hydroxychloroquine.

Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis.

PubMed

Qiao, Yong-Chao; Shen, Jian; Hong, Xue-Zhi; Liang, Ling; Bo, Chao-Sheng; Sui, Yi; Zhao, Hai-Lu

2016-09-01

Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) have implicated in the development of type 1 diabetes mellitus (T1DM), yet the existing evidence remains unclear. Hereby we performed a systematic review and meta-analysis to characterize the changes in T1DM patients. A total of 1407 T1DM patients and 1373 healthy controls from 40 case-control studies were eventually included in the pooling analysis. Compared with the controls, T1DM patients had decreased frequency of CD4(+)CD25(+)Treg (p=0.0003), CD4(+)CD25(+)Foxp3(+)Treg (p=0.020), and the level of TGF-β (p=0.030). Decrease in IL-10 (p=0.14) was not significant. All the changes remained significant when the studies with low NOS scores and publication bias were excluded. In conclusion, peripheral Treg and serum TGF-β are reduced in type 1 diabetes mellitus whereas changes in serum IL-10 are not significant. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of sulfatides in dried blood and urine spots from metachromatic leukodystrophy patients by liquid chromatography/electrospray tandem mass spectrometry.

PubMed

Barcenas, Mariana; Suhr, Teryn R; Scott, C Ronald; Turecek, Frantisek; Gelb, Michael H

2014-06-10

Treatments are being developed for metachromatic leukodystrophy (MLD), suggesting the need for eventual newborn screening. Previous studies have shown that sulfatide molecular species are increased in the urine of MLD patients compared to samples from non-MLD individuals, but there is no data using dried blood spots (DBS), the most common sample available for newborn screening laboratories. We used ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) to quantify sulfatides in DBS and dried urine spots from 14 MLD patients and 50 non-MLD individuals. Several sulfatide molecular species were increased in dried urine samples from all MLD samples compared to non-MLD samples. Sulfatides, especially low molecular species, were increased in DBS from MLD patients, but the sulfatide levels were relatively low. There was good separation in sulfatide levels between MLD and non-MLD samples when dried urine spots were used, but not with DBS, because DBS from non-MLD individuals have measurable levels of sulfatides. Sulfatide accumulation studies in urine, but not in DBS, emerges as the method of choice if newborn screening is to be proposed for MLD. Copyright © 2013 Elsevier B.V. All rights reserved.

Endometrial fluid associated with Essure implants placed before in vitro fertilization: Considerations for patient counseling and surgical management

PubMed Central

Walsh, David J; Jones, Christopher A; Wood, Samuel H

2015-01-01

Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices. PMID:26473113

Immunotherapy for Prostate Cancer Enters Its Golden Age

PubMed Central

Boikos, Sosipatros A.; Antonarakis, Emmanuel S.

2012-01-01

In the United States, prostate cancer is the most frequent malignancy in men and ranks second in terms of mortality. Although recurrent or metastatic disease can be managed initially with androgen ablation, most patients eventually develop castration-resistant disease within a number of years, for which conventional treatments (eg, chemotherapy) provide only modest benefits. In the last few years, immunotherapy has emerged as an exciting therapeutic modality for advanced prostate cancer, and this field is evolving rapidly. Encouragingly, the US Food and Drug Administration (FDA) has recently approved two novel immunotherapy agents for patients with advanced cancer: the antigen presenting cell-based product sipuleucel-T and the anti-CTLA4 (cytotoxic T-lymphocyte antigen 4) antibody ipilimumab, based on improvements in overall survival in patients with castration-resistant prostate cancer and metastatic melanoma, respectively. Currently, a number of trials are investigating the role of various immunological approaches for the treatment of prostate cancer, many of them with early indications of success. As immunotherapy for prostate cancer enters its golden age, the challenge of the future will be to design rational combinations of immunotherapy agents with each other or with other standard prostate cancer treatments in an effort to improve patient outcomes further. PMID:22844202

Using beliefs and magical thinking to fight cancer distress-a case study.

PubMed

Salander, P

2000-01-01

This case relates to the way in which a young patient developed serious difficulties in coping with her life in the years following a successful bone-marrow transplant. By means of an illustrative metaphor, she revealed her existential position and the way in which she attempted to deal with her anxiety. Being diseased implied that life's order was replaced by disorder and a loss of basic trust. She tried to re-establish order by establishing beliefs that attributed specific regularities to life, and to influence the risk of recurrence by living according to these beliefs. Unfortunately, this meant that she had to tread a very thin line over a course mined with anxiety and eventually, she became a prisoner of her own creation. The author claims that we can learn from this case, as it clearly illustrates psychological dimensions commonly seen in cancer patients: the way anxiety is related to disorder and the way patients try to regain control of their lives through constructing belief-systems. The case also features a discussion of how we, as clinicians, may be able to help these patients. Copyright 2000 John Wiley & Sons, Ltd.

Right heart dysfunction and failure in heart failure with preserved ejection fraction: mechanisms and management. Position statement on behalf of the Heart Failure Association of the European Society of Cardiology.

PubMed

Gorter, Thomas M; van Veldhuisen, Dirk J; Bauersachs, Johann; Borlaug, Barry A; Celutkiene, Jelena; Coats, Andrew J S; Crespo-Leiro, Marisa G; Guazzi, Marco; Harjola, Veli-Pekka; Heymans, Stephane; Hill, Loreena; Lainscak, Mitja; Lam, Carolyn S P; Lund, Lars H; Lyon, Alexander R; Mebazaa, Alexandre; Mueller, Christian; Paulus, Walter J; Pieske, Burkert; Piepoli, Massimo F; Ruschitzka, Frank; Rutten, Frans H; Seferovic, Petar M; Solomon, Scott D; Shah, Sanjiv J; Triposkiadis, Filippos; Wachter, Rolf; Tschöpe, Carsten; de Boer, Rudolf A

2018-01-01

There is an unmet need for effective treatment strategies to reduce morbidity and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Until recently, attention in patients with HFpEF was almost exclusively focused on the left side. However, it is now increasingly recognized that right heart dysfunction is common and contributes importantly to poor prognosis in HFpEF. More insights into the development of right heart dysfunction in HFpEF may aid to our knowledge about this complex disease and may eventually lead to better treatments to improve outcomes in these patients. In this position paper from the Heart Failure Association of the European Society of Cardiology, the Committee on Heart Failure with Preserved Ejection Fraction reviews the prevalence, diagnosis, and pathophysiology of right heart dysfunction and failure in patients with HFpEF. Finally, potential treatment strategies, important knowledge gaps and future directions regarding the right side in HFpEF are discussed. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

p.Arg82Leu von Hippel-Lindau (VHL) Gene Mutation among Three Members of a Family with Familial Bilateral Pheochromocytoma in India: Molecular Analysis and In Silico Characterization

PubMed Central

John, Anulekha Mary; C, George Priya Doss; Ebenazer, Andrew; Seshadri, Mandalam Subramaniam; Nair, Aravindan; Rajaratnam, Simon; Pai, Rekha

2013-01-01

Various missense mutations in the VHL gene have been reported among patients with familial bilateral pheochromocytoma. However, the p.Arg82Leu mutation in the VHL gene described here among patients with familial bilateral pheochromocytoma, has never been reported previously in a germline configuration. Interestingly, long-term follow-up of these patients indicated that the mutation might have had little impact on the normal function of the VHL gene, since all of them have remained asymptomatic. We further attempted to correlate this information with the results obtained by in silico analysis of this mutation using SIFT, PhD-SNP SVM profile, MutPred, PolyPhen2, and SNPs&GO prediction tools. To gain, new mechanistic insight into the structural effect, we mapped the mutation on to 3D structure (PDB ID 1LM8). Further, we analyzed the structural level changes in time scale level with respect to native and mutant protein complexes by using 12 ns molecular dynamics simulation method. Though these methods predict the mutation to have a pathogenic potential, it remains to be seen if these patients will eventually develop symptomatic disease. PMID:23626751

HIP collapse. Don't blame doctors & patients.

PubMed

Sinagra, J

1999-11-01

While HIP's eventual insolvency was the culmination of several years of financial deterioration, certain events caused this to accelerate. This event is a long overdue impetus for change. The state has learned some hard lessons from the HIP/PHP debacle. The authors proposes a package of bills that will avoid a repeat of this issue.

Severity of Mental Health Impairment and Trajectories of Improvement in an Integrated Primary Care Clinic

ERIC Educational Resources Information Center

Bryan, Craig J.; Corso, Meghan L.; Corso, Kent A.; Morrow, Chad E.; Kanzler, Kathryn E.; Ray-Sannerud, Bobbie

2012-01-01

Objective: To model typical trajectories for improvement among patients treated in an integrated primary care behavioral health service, multilevel models were used to explore the relationship between baseline mental health impairment level and eventual mental health functioning across follow-up appointments. Method: Data from 495 primary care…

Confidentiality, Informed Consent, and Ethical Considerations in Reviewing the Client's Psychotherapy Records

ERIC Educational Resources Information Center

Blunt, David R.

2006-01-01

Ethical dilemmas that break the confidentiality of the client eventually test the psychologist's boundaries such that not taking action may place the patient in a position where they suffer, hurt themselves, or others. The effectiveness in obtaining a valid informed consent might depend upon the therapists training, experience, and sound judgment…

Subliminal (latent) processing of pain and its evolution to conscious awareness

PubMed Central

Borsook, David; Youssef, Andrew M.; Barakat, Nadia; Sieberg, Christine B.; Elman, Igor

2018-01-01

By unconscious or covert processing of pain we refer to nascent interactions that affect the eventual deliverance of pain awareness. Thus, internal processes (viz., repeated nociceptive events, inflammatory kindling, re-organization of brain networks, genetic) or external processes (viz., environment, socioeconomic levels, modulation of epigenetic status) contribute to enhancing or inhibiting the presentation of pain awareness. Here we put forward the notion that for many patients, ongoing sub-conscious changes in brain function are significant players in the eventual manifestation of chronic pain. In this review, we provide clinical examples of nascent or what we term pre-pain processes and the neurobiological mechanisms of how these changes may contribute to pain, but also potential opportunities to define the process for early therapeutic interventions. PMID:29476771

Subliminal (latent) processing of pain and its evolution to conscious awareness.

PubMed

Borsook, David; Youssef, Andrew M; Barakat, Nadia; Sieberg, Christine B; Elman, Igor

2018-05-01

By unconscious or covert processing of pain we refer to nascent interactions that affect the eventual deliverance of pain awareness. Thus, internal processes (viz., repeated nociceptive events, inflammatory kindling, reorganization of brain networks, genetic) or external processes (viz., environment, socioeconomic levels, modulation of epigenetic status) contribute to enhancing or inhibiting the presentation of pain awareness. Here we put forward the notion that for many patients, ongoing sub-conscious changes in brain function are significant players in the eventual manifestation of chronic pain. In this review, we provide clinical examples of nascent or what we term pre-pain processes and the neurobiological mechanisms of how these changes may contribute to pain, but also potential opportunities to define the process for early therapeutic interventions. Copyright © 2018. Published by Elsevier Ltd.

Developing treatments for cognitive deficits in schizophrenia: The challenge of translation

PubMed Central

Young, J.W.; Geyer, M.A.

2015-01-01

Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. Whilst antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition. PMID:25516372

Vancomycin-resistant Enterococcus in pediatric oncology patients: balancing infection prevention and family-centered care.

PubMed

Singh, Jasjit; Esparza, Samuel; Patterson, Melanie; Vogel, Kate; Patel, Bijal; Gornick, Wendi

2013-04-01

In February 2007, we experienced an abrupt 8-fold increase in vancomycin-resistant Enterococcus (VRE)-positive pediatric hematology/oncology patients in isolation per day, peaking at 12 patients in isolation per day in June 2007. We enforced and expanded infection prevention practices and initiated a rigorous 6-month clearance process. After noting an eventual decrease, we modified clearance to a 3-month process, maintaining <1 patient/day in isolation by June 2009, subjectively improving family and staff satisfaction after this 2-year process. VRE infection was relatively uncommon (7.8%), although continued VRE colonization portended an overall poorer prognosis.

GPR98 mutations cause Usher syndrome type 2 in males.

PubMed

Ebermann, I; Wiesen, M H J; Zrenner, E; Lopez, I; Pigeon, R; Kohl, S; Löwenheim, H; Koenekoop, R K; Bolz, H J

2009-04-01

Mutations in the large GPR98 gene underlie Usher syndrome type 2C (USH2C), and all patients described to date have been female. It was speculated that GPR98 mutations cause a more severe, and eventually lethal, phenotype in males. We describe for the first time two male patients with USH2 with novel GPR98 mutations. Clinical characterization of a male patient and his affected sister revealed a typical USH2 phenotype in both. GPR98 may have been excluded from systematic investigation in previous studies, and the proportion of patients with USH2C probably underestimated. GPR98 should be considered in patients with USH2 of both sexes.

LINC00857 expression predicts and mediates the response to platinum-based chemotherapy in muscle-invasive bladder cancer.

PubMed

Dudek, Aleksandra M; van Kampen, Jasmijn G M; Witjes, J Alfred; Kiemeney, Lambertus A L M; Verhaegh, Gerald W

2018-06-01

Approximately 20% of patients with bladder cancer are diagnosed with muscle-invasive disease (MIBC). The treatment involves radical cystectomy, but almost 50% of patients with MIBC eventually relapse and develop metastasis. The use of platinum-based chemotherapy in the neoadjuvant setting or for metastatic patients has been shown to improve the overall survival in a subset of patients. Unfortunately, no biomarkers are available to select patients with MIBC who will benefit from chemotherapy or to monitor the efficacy of the treatment. Recently, long noncoding RNAs (lncRNAs) were shown to regulate a variety of processes involved in the development and progression of cancer, including bladder cancer. Moreover, several lncRNAs have been shown to play a role in chemotherapy resistance. Here, we analyzed lncRNA expression associated with response to platinum-based chemotherapy in metastatic MIBC using data from the MiTranscriptome lncRNA expression database. Expression of the lncRNA, LINC00857, was found to be upregulated in tumors from patients that did not respond to platinum-based chemotherapy. Moreover, high expression of LINC00857 is correlated with shorter recurrence-free and overall survival of patients with MIBC. Knockdown of LINC00857 significantly decreased cell viability of bladder cancer cell lines through the induction of apoptosis. Furthermore, LINC00857 knockdown sensitized UM-UC-3 and T24 bladder cancer cells to cisplatin, via the negative regulation of the LMAN1 gene. Our data indicate that LINC00857 plays an important role in the regulation of response to platinum-based chemotherapy. LINC00857 potentially could serve as a novel prognostic and predictive biomarker and might be a therapeutic target to overcome cisplatin resistance in patients with MIBC. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Advances in Age-related Macular Degeneration Understanding and Therapy

PubMed Central

Miller, Joan W; Bagheri, Saghar; Vavvas, Demetrios G

2017-01-01

While the development of anti-vascular endothelial growth factor (anti-VEGF) as a therapy for neovascular age-related macular degeneration (AMD) was a great success, the pathologic processes underlying dry AMD that eventually leads to photoreceptor dysfunction, death, and vision loss remain elusive to date, with a lack of effective therapies and increasing prevalence of the disease. There is an overwhelming need to improve the classification system of AMD, to increase our understanding of cell death mechanisms involved in both neovascular and non-neovascular AMD, and to develop better biomarkers and clinical endpoints to eventually be able to identify better therapeutic targets—especially early in the disease process. There is no doubt that it is a matter of time before progress will be made and better therapies will be developed for non-neovascular AMD. PMID:29142592

Frequency of seizures and epilepsy in neurological HIV-infected patients.

PubMed

Kellinghaus, C; Engbring, C; Kovac, S; Möddel, G; Boesebeck, F; Fischera, M; Anneken, K; Klönne, K; Reichelt, D; Evers, S; Husstedt, I W

2008-01-01

Infection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy. The database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined. Of 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on anticonvulsant therapy (gabapentin: 14 patients, carbamazepine: 9 patients, valproate: 2 patients, phenytoin: 1 patient, lamotrigine: 1 patient). Patients with only provoked seizures had no epilepsy risk factors except HIV infection, and were less likely to be infected via intravenous drug abuse. Seizures are a relevant neurological symptom during the course of HIV infection. Although in some patients seizures only occur provoked by acute disease processes, the majority of patients with new onset seizures eventually develops epilepsy and require anticonvulsant therapy. Intravenous drug abuse and the presence of non-HIV-associated risk factors for epilepsy seem to be associated with the development of chronic seizures in this patient group.

Stereotactic Radiosurgery for Patients With Brain Metastases From Small Cell Lung Cancer

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

Wegner, Rodney E.; Olson, Adam C.; Kondziolka, Douglas

2011-11-01

Background: Patients with small-cell lung cancer have a high likelihood of developing brain metastases. Many of these patients will have prophylactic cranial irradiation (PCI) or eventually undergo whole brain radiation therapy (WBRT). Despite these treatments, a large number of these patients will have progression of their intracranial disease and require additional local therapy. Stereotactic radiosurgery (SRS) is an important treatment option for such patients. Methods: We retrospectively reviewed the charts of 44 patients with brain metastases from small-cell lung cancer treated with gamma knife SRS. Multivariate analysis was used to determine significant prognostic factors influencing survival. Results: The median follow-upmore » from SRS in this patient population was 9 months (1-49 months). The median overall survival (OS) was 9 months after SRS. Karnofsky performance status (KPS) and combined treatment involving WBRT and SRS within 4 weeks were the two factors identified as being significant predictors of increased OS (p = 0.033 and 0.040, respectively). When comparing all patients, patients treated with a combined approach had a median OS of 14 months compared to 6 months if SRS was delivered alone. We also compared the OS times from the first definitive radiation: WBRT, WBRT and SRS if combined therapy was used, and SRS if the patient never received WBRT. The median survival for those groups was 12, 14, and 13 months, respectively, p = 0.19. Seventy percent of patients had follow-up magnetic resonance imaging available for review. Actuarial local control at 6 months and 12 months was 90% and 86%, respectively. Only 1 patient (2.2%) had symptomatic intracranial swelling related to treatment, which responded to a short course of steroids. New brain metastases outside of the treated area developed in 61% of patients at a median time of 7 months; 81% of these patients had received previous WBRT. Conclusions: Stereotactic radiosurgery for small-cell lung carcinoma brain metastases provided safe and effective local tumor control in the majority of patients.« less

Familial Churg-Strauss Syndrome in a Sister and Brother.

PubMed

Alyasin, Soheyla; Khoshkhui, Maryam; Amin, Reza

2015-06-01

Churg-Strauss syndrome (CSS) is a granulomatous small vessel vasculitis. It is characterized by asthma, allergic granulomatosis and vasculitis. This syndrome is rare in children. A 5 years old boy was admitted with cough, fever and dyspnea for 2 weeks. On the basis of laboratory data (peripheral eosinophilia), associated with skin biopsy, and history of CSS in his sister, this disease was eventually diagnosed. The patient had good response to corticosteroid. In every asthmatic patient with prolonged fever, eosinophilia and multisystemic involvment, CSS should be considered.

[Fibromyalgia syndrome after comprehensive treatment of breast cancer: a case report].

PubMed

Ding, Xia; Li, Yan; Cui, Yiyi; Shen, Yingying; Gu, Jianzhong; Guo, Yong

2016-05-25

Fibromyalgia syndrome after comprehensive treatment of breast cancer is rare and seldom reported. Here we present a case of a 50-year-old female patient,who was admitted to the hospital because of generalized fibromyalgia for 3 months and brain metastasis after the right breast carcinoma surgery for 1 month, and the clinical diagnosis was brain metastasis from breast carcinoma combined with fibromyalgia syndrome. The fibromyalgia were relieved with proper symptomatic treatment but the patient eventually died of tumor progression.

Predicted versus executed surgical orthognathic treatment.

PubMed

Falter, B; Schepers, S; Vrielinck, L; Lambrichts, I; Politis, C

2013-10-01

This study aimed to analyse combined surgical-orthodontic treatment plans, compare them with the actual surgery performed, and define factors resulting in changes of the original plan during orthodontic pre-surgical preparation. The clinical files of 312 orthognathic surgery patients, operated between January 2008 and December 2010, were retrospectively reviewed. Of these 312 patients, 129 had a bimaxillary operation. One hundred sixty patients had osteotomy of the lower jaw only and 23 had osteotomy of the upper jaw only. Factors analysed in the study include Angle Class malocclusion, patient sex, and age. Lip-to-incisor relationship, overjet, overbite and midline deviations of the upper and lower jaw were recorded. Effects of surgical assisted rapid palatal expansion (SARPE) on the eventual surgery were also investigated. Reasons for changing the original treatment plan at the time of the finished pre-surgical-orthodontic alignment were analysed. The original treatment plan was changed in 42 of the 312 patients (13.5%). Changes occurred generally in case of a larger interval between set-up of the first treatment plan and the eventual operation (average 22.4 versus 16.4 months for patients with changed versus unchanged treatment plan, respectively). All Class I patients had surgery performed as planned. Class III patients had a significantly higher rate of altered treatment plan (27.3%) than Class II patients (7.6%). More men (52.4%) saw their treatment plan changed, although there were more women than men in the study population (59.6 versus 40.4%). One in seven patients (13.5%) had a different operation than was planned at the start of treatment. Class III patients with small overjet and overbite commonly have a treatment plan for a monomaxillary operation that, after decompensation, needs to be adapted to a bimaxillary operation. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Flap reconstruction for soft-tissue defects with exposed hardware following deep infection after internal fixation of ankle fractures.

PubMed

Ovaska, Mikko T; Madanat, Rami; Tukiainen, Erkki; Pulliainen, Lea; Sintonen, Harri; Mäkinen, Tatu J

2014-12-01

The aim of the present study was to determine the outcome for patients treated with flap reconstruction following deep ankle fracture infection with exposed hardware. Out of 3041 consecutive ankle fracture operations in 3030 patients from 2006 to 2011, we identified 56 patients requiring flap reconstruction following deep infection. Thirty-two of these patients could be examined at a follow-up visit. Olerud-Molander Ankle (OMA) score, 15D score, Numeric Rating Scale (NRS), and clinical examination were used to assess the outcome. A total of 58 flap reconstructions were performed in 56 patients with a mean age of 57 years (range 25–93 years) and mean follow-up time of 52 months. The most commonly used reconstruction was a distally based peroneus brevis muscle flap with a split-thickness skin graft. A microvascular free flap was required in only one patient. 22 (39%) patients required subsequent surgical interventions because of a flap-related complication. With flap reconstruction, hardware could eventually be salvaged in 53% of patients with a non-consolidated fracture. The mean OMA score was fair or poor in 53% of the patients, and only 56% had recovered their pre-injury level of function. Half of the patients had shoe wear limitations. The 15D score showed a significantly poorer health-related quality of life compared to an age-standardised sample of the general population. The mean pain NRS was 2.1 (range 0–6), and the mean satisfaction NRS was 6.6 (range 0–10). Our study showed that successful treatment of a soft-tissue defect with exposed hardware following ankle fracture infections can be achieved with local flaps. Despite eventual reconstructive success, complications are common. Patients perceive a poorer health-related quality of life, have shoe wear limitations, and only half of them achieve their pre-injury level of function.

Anti-Jk3 in a Filipino man.

PubMed

McCaskill, Shaina; Wise, Scott; Tinsley, Sheila

2015-01-01

A 62-year-old Filipino man with a history of chronic obstructive pulmonary disease, hypertension, and hyperlipidemia was admitted to the emergency department at Hospital A with recurrent fevers, weakness, and jaundice. The patient was evaluated and eventually discharged with a diagnosis of possible drug-induced hepatitis. One month later, the patient was admitted to Hospital B for recurrent fevers and weakness. The patient's hemoglobin was 3.8 g/dL. Six units of packed red blood cells (RBCs) were ordered for transfusion. The patient's sample typed as group B, D+, and the antibody screen was negative. All six units of packed RBCs appeared compatible (at immediate spin) and were transfused to the patient. His hemoglobin level 4 days post-transfusion was 9.3 g/dL, and the patient was discharged. The patient returned after a week for follow-up and his hemoglobin was found to have dropped to 8.5 g/dL, which continued to fall until it reached 7.0 g/dL. Additional packed RBCs were ordered for transfusion. during subsequent pre-transfusion compatibility testing, the antibody screen was found to be positive (all screening cells reactive at the antihuman globulin phase). An antibody identification panel was performed.The patient's serum was found to react with all panel cells tested, including the autocontrol tube. A direct antiglobulin test revealed the presence of both anti-IgG and anti-C3 coating the patient's RBCs. The specimen was then sent to a reference laboratory for further testing. Results from the reference lab testing revealed the presence of anti-Jk3 in the patient's serum. the patient was placed on steroids, and his reticulocyte count increased with no further signs of extravascular hemolysis. No additional transfusions were necessary. he was eventually discharged with a hemoglobin of 13.6 g/dL. the purpose of this case study is to report the findings of an extremely rare but clinically significant antibody, anti-Jk3.

A Convex Hull-Based New Metric for Quantification of Bladder Wall Irregularity in Pediatric Patients With Congenital Anomalies of the Kidney and Urinary Tract.

PubMed

Stember, Joseph N; Newhouse, Jeffrey; Behr, Gerald; Alam, Shumyle

2017-11-01

Early identification and quantification of bladder damage in pediatric patients with congenital anomalies of the kidney and urinary tract (CAKUT) is crucial to guiding effective treatment and may affect the eventual clinical outcome, including progression of renal disease. We have developed a novel approach based on the convex hull to calculate bladder wall trabecularity in pediatric patients with CAKUT. The objective of this study was to test whether our approach can accurately predict bladder wall irregularity. Twenty pediatric patients, half with renal compromise and CAKUT and half with normal renal function, were evaluated. We applied the convex hull approach to calculate T, a metric proposed to reflect the degree of trabeculation/bladder wall irregularity, in this set of patients. The average T value was roughly 3 times higher for diseased than healthy patients (0.14 [95% confidence interval, 0.10-0.17] versus 0.05 [95% confidence interval, 0.03-0.07] for normal bladders). This disparity was statistically significant (P < .01). We have demonstrated that a convex hull-based procedure can measure bladder wall irregularity. Because bladder damage is a reversible precursor to irreversible renal parenchymal damage, applying such a measure to at-risk pediatric patients can help guide prompt interventions to avert disease progression. © 2017 by the American Institute of Ultrasound in Medicine.

Impaired math achievement in patients with acute vestibular neuritis.

PubMed

Moser, Ivan; Vibert, Dominique; Caversaccio, Marco D; Mast, Fred W

2017-12-01

Broad cognitive difficulties have been reported in patients with peripheral vestibular deficit, especially in the domain of spatial cognition. Processing and manipulating numbers relies on the ability to use the inherent spatial features of numbers. It is thus conceivable that patients with acute peripheral vestibular deficit show impaired numerical cognition. Using the number Stroop task and a short math achievement test, we tested 20 patients with acute vestibular neuritis and 20 healthy, age-matched controls. On the one hand, patients showed normal congruency and distance effects in the number Stroop task, which is indicative of normal number magnitude processing. On the other hand, patients scored lower than healthy controls in the math achievement test. We provide evidence that the lower performance cannot be explained by either differences in prior math knowledge (i.e., education) or slower processing speed. Our results suggest that peripheral vestibular deficit negatively affects numerical cognition in terms of the efficient manipulation of numbers. We discuss the role of executive functions in math performance and argue that previously reported executive deficits in patients with peripheral vestibular deficit provide a plausible explanation for the lower math achievement scores. In light of the handicapping effects of impaired numerical cognition in daily living, it is crucial to further investigate the mechanisms that cause mathematical deficits in acute PVD and eventually develop adequate means for cognitive interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

The use of antigravity suits in the treatment of idiopathic orthostatic hypotension

NASA Technical Reports Server (NTRS)

Landmark, K.; Kravik, S.

1980-01-01

Idiopathic orthostatic hypotension is an uncommon disease characterized by a drop in blood pressure when going from a recumbent to a standing position. Treatment by medication generally produces poor results. Three patients at the Royal Hospital in Oslo were treated with antigravity suits and all were able to maintain adequate blood pressures in the standing position. One patient improved dramatically and was able to take short walks while wearing the suit. The two other patients, however, felt that wearing the suits eventually became uncomfortable. This treatment represents a useful treatment alternative for intractable cases.

Binge Eating among Women Veterans in Primary Care: Comorbidities and Treatment Priorities.

PubMed

Rosenbaum, Diane L; Kimerling, Rachel; Pomernacki, Alyssa; Goldstein, Karen M; Yano, Elizabeth M; Sadler, Anne G; Carney, Diane; Bastian, Lori A; Bean-Mayberry, Bevanne A; Frayne, Susan M

2016-01-01

Little is known about the clinical profile and treatment priorities of women with binge eating disorder (BED), a diagnosis new to the fifth edition of Diagnostic and Statistical Manual of Mental Disorders. We identified comorbidities and patients' treatment priorities, because these may inform implementation of clinical services. Data were collected from women veteran primary care patients. Analyses compared those who screened positive for BED (BED+), and those without any binge eating symptoms (BED-). Frequencies of comorbid medical and psychological disorders were high in the BED+ group. The BED+ group's self-identified most common treatment priorities were mood concerns (72.2%), weight loss (66.7%), and body image/food issues (50%). Among those with obesity, a greater proportion of the BED+ group indicated body image/food issues was their top treatment priority (12.9% vs. 2.8%; p < .01), suggesting that these patients may be more apt to seek treatment beyond weight management for their problematic eating patterns. Women primary care patients with BED demonstrate high medical and psychological complexity; their subjective treatment priorities often match objective needs. These findings may inform the development of targeted BED screening practices for women with obesity in primary care settings, and the eventual adoption of patient-centered BED treatment resources. Published by Elsevier Inc.

One stage vertical rectus muscle recession using adjustable sutures under local anaesthesia.

PubMed Central

Rauz, S; Govan, J A

1996-01-01

AIMS: To assess the results of visual axis alignment following one stage adjustable suture surgery to correct vertical diplopia. METHOD: Eight patients with a mean age of 44.9 years (range 16-80 years) complaining of vertical diplopia underwent rectus muscle recession under local anaesthesia with intraoperative adjustment of sutures. Diplopia was secondary to superior oblique paresis in four patients, dysthyroid eye disease in two patients, superior rectus paresis in one patient, and one developed a consecutive deviation after previous squint surgery. The surgery consisted of seven single muscle recessions (six inferior recti and one superior rectus) and one two muscle recession (inferior and lateral recti). The surgery was performed under topical anaesthesia supplemented with a subconjunctival injection of local anaesthetic over the muscle insertions. RESULTS: The patients remained comfortable throughout their surgery. All had a reduction in their vertical deviation. Six were asymptomatic and were eventually discharged. One had residual diplopia which was well tolerated without further intervention. One had persistent troublesome diplopia which was corrected by temporary Fresnel prisms. He became asymptomatic after further surgery of a 1 mm inferior rectus advancement. CONCLUSION: One stage adjustable suture surgery is recommended in all cases of strabismus surgery when postoperative results would otherwise be unpredictable. PMID:8949715

Effectiveness of heat moisture exchangers (hmes) in preventing perioperative hypothermia among adult patients undergoing abdominal surgery under general endotracheal anaesthesia.

PubMed

Anaegbu, Nc; Olatosi, Oj; Tobi, Ku

2013-01-01

Heat Moisture Exchangers (HMEs) conserve heat and moisture during expiration and make this available to inspired gases during subsequent inspiration. We sought to evaluate the effectiveness of HMEs in the prevention of perioperative hypothermia in patients scheduled for abdominal surgery under general anaesthesia relaxant technique with endotrachael intubation (GART.) Lagos University Teaching Hospital, in Modular theatre, Anaesthesia unit. The study was a randomized, controlled, longitudinal, interventional study Methods: 100 ASA I, II and III patients aged 18 to 65 years scheduled for abdominal surgery under GART were randomly assigned to 2 groups, groups H and C. Group H had HMEs, while group C served as controls. Core temperature measured using tympanic probe was every 10 minutes till end of anaesthesia Data from total 99 patients, 49 in group H and 50 in group C were eventually analysed. Although patients in both groups developed hypothermia in the course of anaesthesia, core temperature was significantly lower p< 0.05 after one hour in the control group than the intervention group. The use of HMEs during general anaesthesia with endotrachael intubation did not prevent hypothermia but resulted in higher core temperature and should be part of a multimodal approach in the prevention of perioperative hypothermia. Heat Moisture Exchangers, General endotracheal anaesthesia, Hypothermia, abdominal surgery.

Acquired resistance of EGFR-mutant lung adenocarcinomas to afatinib plus cetuximab is associated with activation of mTORC1

PubMed Central

Pirazzoli, Valentina; Nebhan, Caroline; Song, Xiaoling; Wurtz, Anna; Walther, Zenta; Cai, Guoping; Zhao, Zhongming; Jia, Peilin; de Stanchina, Elisa; Shapiro, Erik M.; Gale, Molly; Yin, Ruonan; Horn, Leora; Carbone, David P.; Stephens, Philip J; Miller, Vincent; Gettinger, Scott; Pao, William; Politi, Katerina

2014-01-01

SUMMARY Patients with EGFR-mutant lung adenocarcinomas (LUADs) who initially respond to first-generation TKIs develop resistance to these drugs. A combination of the irreversible TKI afatinib and the EGFR antibody cetuximab can be used to overcome resistance to first-generation TKIs; however, resistance to this drug combination eventually emerges. We identified activation of the mTORC1 signaling pathway as a mechanism of resistance to dual inhibition of EGFR in mouse models. Addition of rapamycin reversed resistance in vivo. Analysis of afatinib+cetuximab-resistant biopsy specimens revealed the presence of genomic alterations in genes that modulate mTORC1 signaling including NF2 and TSC1. These findings pinpoint enhanced mTORC1 activation as a mechanism of resistance to afatinib+cetuximab and identify genomic mechanisms that lead to activation of this pathway, revealing a potential therapeutic strategy for treating patients with resistance to these drugs. PMID:24813888

Laparoscopic and ultrasound assisted management of gallstone ileus after biliointestinal bypass Case report and a review of literature.

PubMed

Zago, Mauro; Bozzo, Samantha; Centurelli, Andrea; Giovanelli, Alessandro; Vasino, Michele Ciocca

2016-05-24

To report about an additional case of biliary ileus after bariatric surgery is reported and extensively reviewing the literature on this topic. We reviewed the literature and found three cases of gallstone ileus (GI) that occurred after bariatric surgery. A 41 year old patient presented a GI eight years after a biliointestinal bypass (BIB) for morbid obesity. The patient complained of abdominal pain for two weeks. Computed tomography (CT) and abdominal ultrasound (US) allowed a preoperative diagnosis of GI and planning of surgical strategy. Surgical treatment was carried out through laparoscopic-assisted enterolithotomy alone procedure. This choice is supported discussing the related issues: morbidity, potential recurrence, eventual developing of gallbladder carcinoma. It is the first reported case of GI after BIB preoperatively diagnosed through CT scan and US, and treated with a laparoscopic assisted approach. Additional considerations concerning preoperative diagnosis, surgical strategy, technical details and follow-up can be usefully applied even in non post-bariatric biliary ileus. Biliointestinal bypass, Gallstone ileus, Laparoscopy, Ultrasonography.

The pathogenesis of steroid-induced osteonecrosis of the femoral head: A systematic review of the literature.

PubMed

Wang, Ao; Ren, Ming; Wang, Jincheng

2018-05-30

Steroid (glucocorticoid)-induced osteonecrosis of the femoral head (SONFH) is a metabolic disease that occurs due to the use of glucocorticoid drugs, leading to impaired blood supply to the femoral head and death of bone cells and bone marrow composition, which in turn lead to structural change, collapse of the femoral head, and articular dysfunction. SONFH is a challenging disorder to treat in adults due to frequent collapse of the femoral head and dysfunction of the hip joint. Eventually, patients require joint arthroplasty surgery, which severely impairs the patients' quality of life. However, the exactly pathogenesis of SONFH is still not clear. Recently, as the development of precision medicine and lucubrating on stem cell and molecular biology, the exact pathogenesis of SONFH is being investigated and more new treatments are being explored. This review article discusses five major theories about the pathogenesis of SONFH. Copyright © 2017. Published by Elsevier B.V.

Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells.

PubMed

Tanimoto, Azusa; Yamada, Tadaaki; Nanjo, Shigeki; Takeuchi, Shinji; Ebi, Hiromichi; Kita, Kenji; Matsumoto, Kunio; Yano, Seiji

2014-07-15

Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4)--anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.

Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells

PubMed Central

Tanimoto, Azusa; Yamada, Tadaaki; Nanjo, Shigeki; Takeuchi, Shinji; Ebi, Hiromichi; Kita, Kenji; Matsumoto, Kunio; Yano, Seiji

2014-01-01

Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK. PMID:24952482

Posterior capsular rent: Prevention and management.

PubMed

Chakrabarti, Arup; Nazm, Nazneen

2017-12-01

This review article deals with a potentially sight threatening complication - rupture of the posterior capsule - during cataract surgery. Cataract surgery is the most commonly performed surgical procedure in ophthalmology and despite tremendous technical and technological advancements, posterior capsular rent (PCR) still occurs. PCR occurs both in the hands of experienced senior surgeons and the neophyte surgeons, although with a higher frequency in the latter group. Additionally, certain types of cataracts are prone to this development. If managed properly in a timely manner the eventual outcome may be no different from that of an uncomplicated case. However, improper management may lead to serious complications with a higher incidence of permanent visual disability. The article covers the management of posterior capsular rent from two perspectives: 1. Identifying patients at higher risk and measures to manage such patients by surgical discipline, and 2. Intraoperative management of posterior capsular rent and various case scenarios to minimize long-term complications.This review is written for experienced and not-so-experienced eye surgeons alike to understand and manage PCR.

Gait analysis of young male patients diagnosed with primary bladder neck obstruction.

PubMed

Zago, Matteo; Camerota, Tommaso Ciro; Pisu, Stefano; Ciprandi, Daniela; Sforza, Chiarella

2017-08-01

Primary bladder neck obstruction (PBNO) represents an inappropriate or inadequate relaxation of the bladder neck during micturition. Based on the observation of an increased rate of postural imbalances in male patients with PBNO, we hypothesized a possible role of an unbalanced biomechanics of the pelvis on urethral sphincters activity. Our aim was to identify kinematic imbalances, usually disregarded in PBNO patients, and which could eventually be involved in the etiopathogenesis of the disease. Seven male adult patients (39.6±7.1years) were recruited; in all patients, PBNO was suspected at bladder diary and uroflowmetry, and was endoscopically confirmed with urethroscopy. Participants gait was recorded with a motion capture system (BTS Spa, Italy) to obtain three-dimensional joint angles and gait parameters. Multivariate statistics based on a Principal Component model allowed to assess the similarity of patients' gait patterns with respect to control subjects. The main finding is that patients with PBNO showed significant discordance in the observations at the ankle and pelvis level. Additionally, 6/7 patients demonstrated altered trunk positions compared to normal curves. We suggest that the identified postural imbalances could represent the cause for an anomalous activation of pelvic floor muscles (hypertonia). The consequent urinary sphincters hypercontraction may be responsible for the development of voiding dysfunction in male patients with no significant morphological alterations. Results reinforced the hypothesis of an etiopathogenetic role of postural imbalances on primary bladder neck obstruction in male patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Acetabular labral tears with underlying chondromalacia: a possible association with high-level running.

PubMed

Guanche, Carlos A; Sikka, Robby S

2005-05-01

The use of hip arthroscopy has helped delineate intra-articular pathology and has enabled clinicians to further elucidate the factors responsible for injuries, such as running. The subtle development of degenerative changes may be a result of repetitive impact loading associated with this sport. This study presents a population of runners with common pathologic acetabular changes. Case series. Eight high-level runners with an average age of 36 years (range, 19 to 45 years) were seen for complaints of increasing hip pain with running without any history of macrotrauma. All of the patients had either run several marathons (4), were triathletes (1), Olympic middle distance runners (1), or had run more than 10 miles per week for longer than 5 years (2). Plain radiographic analysis revealed no degenerative changes and an average center-edge (CE) angle of 36.7 degrees (range, 28 degrees to 44 degrees). All patients underwent hip arthroscopy with labral debridement. In 6 patients (75%), a chondral injury of the acetabular cartilage underlying the labral tear was noted. In addition, 3 patients had ligamentum teres disruptions. It is possible that the development of these tears is the result of subtle instability, which may be exacerbated by running, eventually leading to labral tearing and possible ligamentum teres disruption. While perhaps concurrently, subtle acetabular dysplasia may play a role. Although this study does not confirm an association between running and the development of labral tears or chondral lesions in the hip, it certainly questions whether there is an injury pattern common to this population, a "runner's hip." Level IV.

PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system.

PubMed

Alonso-Alconada, L; Barbazan, J; Candamio, S; Falco, J L; Anton, C; Martin-Saborido, C; Fuster, G; Sampedro, M; Grande, C; Lado, R; Sampietro-Colom, L; Crego, E; Figueiras, S; Leon-Mateos, L; Lopez-Lopez, R; Abal, M

2018-05-01

Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.

Refractory open-angle glaucoma after neodymium-yttrium-aluminum-garnet laser lysis of vitreous floaters.

PubMed

Cowan, Lisa A; Khine, Kay T; Chopra, Vikas; Fazio, Doreen T; Francis, Brian A

2015-01-01

To illustrate 3 cases of chronic open-angle glaucoma secondary to the neodymium-yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis procedure for symptomatic vitreous floaters. Observational case series. Location of the study was the Doheny Eye Institute. Three eyes of 2 patients who developed chronic open-angle glaucoma after Nd:YAG vitreolysis for symptomatic floaters presenting with very high intraocular pressure (IOP >40 mm Hg) were selected. The time from the laser treatment to the onset of elevated pressure ranges from 1 week to 8 months. There was no associated inflammation, steroid use, or other identifiable cause of chronic IOP elevation. All eyes were treated initially with glaucoma medication, followed by selective laser trabeculoplasty (SLT) and eventually glaucoma surgery (Trabectome) in 2 eyes for disease management. In all eyes, intraocular pressures were eventually stabilized within a normal pressure range from 18 to 38 months following Nd:YAG vitreolysis. At the latest follow-up post surgery, all eyes had intraocular pressures of 22 mm Hg or less with or without medications. Secondary open-angle glaucoma is a complication of Nd:YAG vitreolysis for symptomatic floaters that may present with an increase in intraocular pressure immediately, or many months after the surgery. Furthermore this complication may be permanent and require chronic medical therapy or glaucoma surgery. Copyright © 2015 Elsevier Inc. All rights reserved.

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

PubMed

Wahie, S; Meggitt, S J

2013-09-01

The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multicentre prospective study using a validated disease activity measure. © 2013 British Association of Dermatologists.

Biobehavioral Development. From Cells to Selves.

ERIC Educational Resources Information Center

National Inst. of Child Health and Human Development (NIH), Bethesda, MD.

Key to the mission of the National Institute of Child Health and Human Development (NICHD) is answering fundamental questions about how a single fertilized cell eventually develops into a fully functional adult human being and how a multitude of genetic and environmental factors influence that process. This document details part of NICHD's…

DNA methylation/demethylation programming during peach flower bud dormancy release, development and blooming

USDA-ARS?s Scientific Manuscript database

Peach flower bud development undergoes a long, complex and temperature-dependent regulation process with cessation of growth in response to cool temperatures in late fall, a slow but gradual development during the chilling period in winter, and eventually blooming in early spring. It has been demon...

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

Understanding the T cell immune response in SARS coronavirus infection

PubMed Central

Janice Oh, Hsueh-Ling; Ken-En Gan, Samuel; Bertoletti, Antonio; Tan, Yee-Joo

2012-01-01

The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development. PMID:26038429

Understanding the T cell immune response in SARS coronavirus infection.

PubMed

Janice Oh, Hsueh-Ling; Ken-En Gan, Samuel; Bertoletti, Antonio; Tan, Yee-Joo

2012-09-01

The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.

Relevance of the Measles Virus Expression in Cancer - an Update.

PubMed

Benharroch, Daniel; Ariad, Samuel; Tadmor, Noa; Nalbandyan, Karen; Lazarev, Irena

2016-10-01

Evidence of an association between classical Hodgkin lymphoma and the measles virus has previously been presented by our group. Arguments held against our thesis were reevaluated. Substantiation of a relationship between the measles virus and additional solid tumors was submitted. Moreover, a pathogenic pathway was suggested to support a possible contribution of the measles virus to the development of classical Hodgkin lymphoma. We have chosen to exclude a discussion of measles virotherapy, since this carries distinct implications. We now add new evidence regarding the expression of the measles virus phosphoprotein in a few cancers. We also suggest a role in this context for atypical measles syndrome in malignant tumors. Last, we propose a collaboration which may make the best, on the one hand of our cohort of classical Hodgkin lymphoma, half of which carry the measles virus expression in their tumor cells. The planned study will also look into the patients vaccination records and into a previous history of the measles disease. On the other hand, cohorts of patients diagnosed with late onset measles will be assessed for the eventual diagnosis of atypical measles syndrome and will be followed up for the subsequent development of a malignant tumor.

Molecular diagnostics of inflammatory disease: New tools and perspectives.

PubMed

Garzorz-Stark, Natalie; Lauffer, Felix

2017-08-01

This essay reviews current approaches to establish novel molecular diagnostic tools for inflammatory skin diseases. Moreover, it highlights the importance of stratifying patients according to molecular signatures and revising current outdated disease classification systems to eventually reach the goal of personalized medicine. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents

PubMed Central

Seki, J.T.; Sakurai, N.; Lam, W.; Reece, D.E.

2017-01-01

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients. Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient’s advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients. Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient’s safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure. PMID:28874903

Indications, retrieval rate, and complications of inferior vena cava filters: Single-center experience in Saudi Arabia.

PubMed

Shabib, Abdullah Bin; Alsayed, Fahad; Aldughaythir, Saad; Habeeb, Hanan; Al Tamimi, Sumayyah; Masuadi, Emad; Alzahrani, Mohsen; Alaklabi, Ali; Alotaibi, Azzam; Rajendram, Rajkumar; Almegren, Mosaad

2018-01-01

Inferior vena cava (IVC) filter is indicated in patients with acute venous thromboembolism (VTE) in whom therapeutic anticoagulation is contraindicated. While prophylactic insertion of an IVC filter may be considered for patients at high risk of VTE, there are significant differences between clinical guidelines on the role of IVC filters. These discrepancies have arisen predominantly because of the paucity of data on the efficacy and safety of IVC filters. We, therefore, evaluated the indications for filter insertion, the rate of filter retrieval and complications in patients who received IVC filters at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. A descriptive, retrospective review of electronic- and paper-based medical records was performed. Consecutive sampling was used to study all adult patients who received an IVC filter at KAMC between 2007 and 2016 and met the inclusion criteria. A total of 382 IVC filters were inserted. 113 patients (30%) had an acute VTE and a contraindication to anticoagulation while 53 patients (14%) received an IVC filter in the absence of VTE (i.e., prophylactic). Only 124 (32.5%) IVC filters were eventually retrieved. The most common reason for nonretrieval was the need for permanent filtration (155, 60%). Thrombotic complications developed in 72 (19%) patients; nine patients had fatal pulmonary embolism. The insertion of IVC filters in this cohort was associated with low retrieval rate and relatively high incidence of thrombotic complications. Follow-up of patients is required to detect IVC filter-related complications and to increase retrieval rate.

Meningitis due to Moraxella nonliquefaciens in a paediatric patient: a case report and review of the literature

PubMed Central

Szymczak, Wendy; Munjal, Iona

2017-01-01

Introduction. Moraxella nonliquefaciens is an unusual organism to be isolated from cerebral spinal fluid (CSF) and there exists only one case report of M. nonliquefaciens meningitis from a neonate. Moraxella species normally exist as part of the human upper respiratory tract flora and rarely cause invasive human disease. There are only a handful of case reports implicating the organism as a cause of endocarditis, bacteraemia, septic arthritis and endophthalmitis. Identification to the species level based on routine laboratory techniques has been challenging, with final identification often made through 16S rRNA sequencing. With the use of a newer diagnostic tool, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) MS, we were able to rapidly identify the organism and initiate appropriate treatment. Case presentation. We present a rare care of M. nonliquefaciens meningitis in a paediatric patient with an underlying cranial anatomical defect due to Crouzon syndrome. She had been admitted to hospital 3 months previously with Streptococcus pneumoniae meningitis and mastoiditis, and returned to the emergency department with meningismus. CSF culture grew M. nonliquefaciens. She was treated with ceftriaxone with rapid improvement and eventually was taken for endoscopic surgical repair of a right encephalocele defect. Conclusion. The use of MALDI-TOF MS allowed for the rapid identification of the organism. The patient recovered with appropriate antimicrobial therapy and eventual surgical correction. An underlying anatomical defect should be considered in all patients who present with meningitis due to this unusual organism. PMID:28348808

Paclitaxel stimulates chromosomal fusion and instability in cells with dysfunctional telomeres: Implication in multinucleation and chemosensitization

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

Park, Jeong-Eun; Woo, Seon Rang; Department of Biochemistry, College of Medicine, Korea University, Seoul 136-705

Research highlights: {yields} Paclitaxel serves as a stimulator of chromosomal fusion in cells in which telomeres are dysfunctional. {yields} Typical fusions involve p-arms, but paclitaxel-induced fusions occur between both q- and p-arms. {yields} Paclitaxel-stimulated fusions in cells in which telomeres are dysfunctional evoke prolonged G2/M cell cycle arrest and delay multinucleation. {yields} Upon telomere erosion, paclitaxel promotes chromosomal instability and subsequent apoptosis. {yields} Chromosomal fusion enhances paclitaxel chemosensitivity under telomere dysfunction. -- Abstract: The anticancer effect of paclitaxel is attributable principally to irreversible promotion of microtubule stabilization and is hampered upon development of chemoresistance by tumor cells. Telomere shortening, andmore » eventual telomere erosion, evoke chromosomal instability, resulting in particular cellular responses. Using telomerase-deficient cells derived from mTREC-/-p53-/- mice, here we show that, upon telomere erosion, paclitaxel propagates chromosomal instability by stimulating chromosomal end-to-end fusions and delaying the development of multinucleation. The end-to-end fusions involve both the p- and q-arms in cells in which telomeres are dysfunctional. Paclitaxel-induced chromosomal fusions were accompanied by prolonged G2/M cell cycle arrest, delayed multinucleation, and apoptosis. Telomere dysfunctional cells with mutlinucleation eventually underwent apoptosis. Thus, as telomere erosion proceeds, paclitaxel stimulates chromosomal fusion and instability, and both apoptosis and chemosensitization eventually develop.« less

Osimertinib for EGFR T790M mutation-positive non-small cell lung cancer.

PubMed

Soejima, Kenzo; Yasuda, Hiroyuki; Hirano, Toshiyuki

2017-01-01

Significant advances have been made since the development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFR mutations in non-small-cell lung cancer (NSCLC), however, lung cancer cells eventually acquire resistance to those agents. Osimertinib (AZD9291) has been developed as 3 rd generation EGFR-TKI with activities against sensitizing mutations and T790 M resistance mutation, which account for about 50% of the mechanisms of acquired resistance to 1 st or 2 nd generation EGFR-TKIs. A recent phase I/II clinical trial with osimertinib for advanced NSCLC patients with known sensitizing EGFR mutations and documented disease progression on prior EGFR-TKIs revealed promising effect with acceptable toxicities. Areas covered: This article summarizes current understanding and available preclinical and clinical data on osimertinib and also discusses future directions. The literature search included PubMed and the latest articles from international conferences. Expert commentary: The development of osimertinib has provided new therapeutic options for NSCLC patients harboring T790 M. Compared with other EGFR-TKIs including rociletinib, osimertinib seems to possess an advantage with respect to the effect and safety profile among existing EGFR-TKIs. However, tumor progression still occurs even when treating with osimertinib. A further understanding of the mechanisms of resistance is eagerly anticipated in order to develop next generation EGFR-TKIs.

Regeneration of the lung: Lung stem cells and the development of lung mimicking devices.

PubMed

Schilders, Kim A A; Eenjes, Evelien; van Riet, Sander; Poot, André A; Stamatialis, Dimitrios; Truckenmüller, Roman; Hiemstra, Pieter S; Rottier, Robbert J

2016-04-23

Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology. However, the use of different model systems, experimental approaches and readout systems may generate somewhat conflicting or contradictory results. In an effort to summarize the latest developments in the lung epithelial stem cell biology, we provide an overview of the current status of the field. We first describe the different stem cells, or progenitor cells, residing in the homeostatic lung. Next, we focus on the plasticity of the different cell types upon several injury-induced activation or repair models, and highlight the regenerative capacity of lung cells. Lastly, we summarize the generation of lung mimics, such as air-liquid interface cultures, organoids and lung on a chip, that are required to test emerging hypotheses. Moreover, the increasing collaboration between distinct specializations will contribute to the eventual development of an artificial lung device capable of assisting reduced lung function and capacity in human patients.

Second branchial cleft anomaly with an ectopic tooth: a case report.

PubMed

Alyono, Jennifer C; Hong, Paul; Page, Nathan C; Malicki, Denise; Bothwell, Marcella R

2014-09-01

Branchial cleft cysts, sinuses, and fistulas are the most common congenital lateral neck lesions in children. They arise as a result of an abnormal development of the branchial arches and their corresponding ectoderm-lined branchial clefts. Of these diverse anomalies, second branchial cleft lesions are the most common, accounting for approximately 95% of all branchial arch pathologies. We describe what is to the best of our knowledge the first reported case of an ectopic tooth in a branchial cleft anomaly. The patient was a young girl who had other congenital abnormalities and syndromic features and who was eventually diagnosed with Townes-Brocks syndrome. We describe the clinical presentation, management, pathologic analysis, and postoperative outcomes of this case, and we present a brief review of Townes-Brocks syndrome.

'Subarachnoid cyst' after evacuation of chronic subdural hematoma: Case report of an unusual postoperative morbidity.

PubMed

Sharon, Low Y Y; Wai Hoe, N G

2016-01-01

Burr-hole drainage of chronic subdural hematomas are routine operative procedures done by neurosurgical residents. Common postoperative complications include acute epidural and/or subdural bleeding, tension pneumocephalus, intracranial hematomas and ischemic cerebral infarction. We report an interesting post-operative complication of a 'subarachnoid cyst' after burr-hole evacuation of a chronic subdural hematoma. The authors hypothesize that the 'cyst' is likely secondary to the splitting of the adjacent neomembrane within its arachnoid-brain interface by iatrogenic irrigation of the subdural space. Over time, this 'cyst' develops into an area of gliosis which eventually causes long-term scar epilepsy in the patient. As far as we are aware, this is the first complication of such a 'subarachnoid cyst' post burr-hole drainage reported in the literature.

West Nile Meningoencephalitis Presenting as Isolated Bulbar Palsy With Hypercapnic Respiratory Failure: Case Report and Literature Review.

PubMed

Tso, Geoffrey; Kaldas, Kirsten; Springer, Joseph; Barot, Nikhil; Kamangar, Nader

2016-05-01

Since the outbreak of West Nile virus (WNV) in the United States in 1999, the WNV neuroinvasive disease has been increasingly reported with a wide spectrum of neuromuscular manifestations. We submit a case of a 46-year-old male with a history of alcohol abuse, diabetes, hypertension, and hepatitis C who presented with fever, nausea, shortness of breath, and dysphagia. The patient rapidly developed hypercapnic respiratory failure and was found to have WNV meningoencephalitis without obvious neuromuscular weakness. His hospital course was significant for repeated failures of extubation secondary to persistent bulbar weakness eventually requiring tracheotomy. This is a unique case of WNV meningoencephalitis with bulbar palsy without other neuromuscular manifestations resulting in recurrent hypercapnic respiratory failure. © The Author(s) 2015.

Iron in Multiple Sclerosis and Its Noninvasive Imaging with Quantitative Susceptibility Mapping

PubMed Central

Stüber, Carsten; Pitt, David; Wang, Yi

2016-01-01

Iron is considered to play a key role in the development and progression of Multiple Sclerosis (MS). In particular, iron that accumulates in myeloid cells after the blood-brain barrier (BBB) seals may contribute to chronic inflammation, oxidative stress and eventually neurodegeneration. Magnetic resonance imaging (MRI) is a well-established tool for the non-invasive study of MS. In recent years, an advanced MRI method, quantitative susceptibility mapping (QSM), has made it possible to study brain iron through in vivo imaging. Moreover, immunohistochemical investigations have helped defining the lesional and cellular distribution of iron in MS brain tissue. Imaging studies in MS patients and of brain tissue combined with histological studies have provided important insights into the role of iron in inflammation and neurodegeneration in MS. PMID:26784172

Future Perspectives for Management of Stage A Heart Failure.

PubMed

Tanaka, Hidekazu

2018-05-07

Patients with Stage A heart failure (HF) show no HF symptoms but have related comorbid diseases with a high risk of progressing to HF. Screening for comorbid diseases warrants closer attention because of the growing interest in addressing Stage A HF as the best means of preventing eventual progression to overt HF such as Stages C and D. The identification of individuals of Stage A HF is potentially useful for the implementation of HF-prevention strategies; however, not all Stage A HF patients develop left ventricular (LV) structural heart disease or symptomatic HF, which lead to advanced HF stages. Therefore, Stage A HF requires management with the long-term goal of avoiding HF development; likewise, Stage B HF patients are ideal targets for HF prevention. Although the early detection of subclinical LV dysfunction is, thus, essential for delaying the progression to HF, the assessment of subclinical LV dysfunction can be challenging. Global longitudinal strain (GLS) as assessed by speckle-tracking echocardiography has recently been reported to be a sensitive marker of early subtle LV myocardial abnormalities, helpful for the prediction of the outcomes for various cardiac diseases, and superior to conventional echocardiographic indices. GLS reflects LV longitudinal myocardial systolic function, and can be assessed usually by means of two-dimensional speckle-tracking. This article reviews the importance of the assessment of subclinical LV dysfunction in Stage A HF patients by means of GLS, and its current potential to prevent progression to later stage HF.

New therapeutic horizons: mapping the future of glycemic control with incretin-based therapy.

PubMed

Campbell, R Keith; Miller, Sara

2009-01-01

More than 24 million adults and children in the United States are living with diabetes, and the vast majority of those individuals have type 2 diabetes. The clinical benefits of good glycemic control have been well established. Most patients eventually require the use of multiple hyperglycemic drugs in combination to approach or achieve the American Diabetes Association's recommended target A1C value of 7%. The role of incretin-based therapies for both glycemic control and beta-cell protection has become an area of intense interest and development. Although current practice guidelines do not include specific recommendations about when and how to incorporate incretin-based agents, a consensus statement published by the American Diabetes Association/European Association for the Study of Diabetes suggests the addition of a glucagon-like peptide-1 (GLP-1) agonist for patients not at goal A1C with metformin and lifestyle changes. The goal of this article is to review this class of agents, discuss their role in the treatment of type 2 diabetes, and address the practical aspects of integrating incretin-based agents into the management of patients with diabetes. Currently, 3 incretin-based therapies are available and widely used in clinical practice. Several more agents are either under review by the Food and Drug Administration (FDA) or are in the very late stages of development. For diabetes educators trying to help their patients understand the differences among their antidiabetic medications, a comprehensive understanding of these agents and their role in therapy is imperative.

[(18)F]Choline PET/CT and stereotactic body radiotherapy on treatment decision making of oligometastatic prostate cancer patients: preliminary results.

PubMed

Pasqualetti, Francesco; Panichi, Marco; Sainato, Aldo; Matteucci, Fabrizio; Galli, Luca; Cocuzza, Paola; Ferrazza, Patrizia; Coraggio, Gabriele; Pasqualetti, Giuseppe; Derosa, Lisa; Sollini, Martina; Mannelli, Lorenzo; Ortori, Simona; Monzani, Fabio; Ricci, Sergio; Greco, Carlo; Fabrini, Maria Grazia; Erba, Paola Anna

2016-01-22

A new entity of patients with recurrent prostate cancer limited to a small number of active metastatic lesions is having growing interest: the oligometastatic patients. Patients with oligometastatic disease could eventually be managed by treating all the active lesions with local therapy, i.e. either surgery or ablative stereotactic body radiotherapy. This study aims to assess the impact of [(18)F]Choline ([(18)F]FMCH) PET/CT and the use stereotactic body radiotherapy (SBRT) in patients (pts) with oligometastatic prostate cancer (PCa). Twenty-nine pts with oligometastatic PCa (≤3 synchronous active lesions detected with [(18)F]FMCHPET/CT) were treated with repeated salvage SBRT until disease progression (development of > three active synchronous metastases). Primary endpoint was systemic therapy-free survival measured from the baseline [(18)F]FMCHPET/CT. A total of 45 lesions were treated with SBRT. After a median follow-up of 11.5 months (range 3-40 months), 20 pts were still in the study and did not receive any systemic therapy. Nine pts started systemic therapy, and the median time of the primary endpoint was 39.7 months (CI 12.20-62.14 months). No grade 3 or 4 toxicity was recorded. Repeated salvage [(18)F]FMCHPET/CT-guided SBRT is well tolerated and could defer the beginning of systemic therapy in selected patients with oligometastatic PCa.

Efficacy of Stereotactic Radiosurgery in Patients with Multiple Metastases: Importance of Volume Rather Than Number of Lesions.

PubMed

Dahshan, Basem A; Mattes, Malcolm D; Bhatia, Sanjay; Palek, Mary Susan; Cifarelli, Christopher P; Hack, Joshua D; Vargo, John A

2017-12-19

The role of stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases is controversial. While whole brain radiation therapy (WBRT) has historically been the mainstay of treatment, its value is increasingly being questioned as emerging data supports that SRS alone can provide comparable therapeutic outcomes for limited (one to three) intracranial metastases with fewer adverse effects, including neurocognitive decline. Multiple recent studies have also demonstrated that patients with multiple (> 3) intracranial metastases with a low overall tumor volume have a favorable therapeutic response to SRS, with no significant difference compared to patients with limited metastases. Herein, we present a patient with previously controlled breast cancer who presented with multiple recurrences of intracranial metastases but low total intracranial tumor volume each time. This patient underwent SRS alone for a total of 40 metastatic lesions over three separate procedures with good local control and without any significant cognitive toxicity. The patient eventually opted for enrollment in the NRG-CC001 clinical trial after multiple cranial recurrences. She received conventional WBRT with six months of memantine and developed significant neurocognitive side effects. This case highlights the growing body of literature supporting the role of SRS alone in the management of multiple brain metastases and the importance of maximizing neurocognition as advances in systemic therapies prolong survival in Stage IV cancer.

Efficacy of Stereotactic Radiosurgery in Patients with Multiple Metastases: Importance of Volume Rather Than Number of Lesions

PubMed Central

Mattes, Malcolm D; Bhatia, Sanjay; Palek, Mary Susan; Cifarelli, Christopher P; Hack, Joshua D; Vargo, John A

2017-01-01

The role of stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases is controversial. While whole brain radiation therapy (WBRT) has historically been the mainstay of treatment, its value is increasingly being questioned as emerging data supports that SRS alone can provide comparable therapeutic outcomes for limited (one to three) intracranial metastases with fewer adverse effects, including neurocognitive decline. Multiple recent studies have also demonstrated that patients with multiple (> 3) intracranial metastases with a low overall tumor volume have a favorable therapeutic response to SRS, with no significant difference compared to patients with limited metastases. Herein, we present a patient with previously controlled breast cancer who presented with multiple recurrences of intracranial metastases but low total intracranial tumor volume each time. This patient underwent SRS alone for a total of 40 metastatic lesions over three separate procedures with good local control and without any significant cognitive toxicity. The patient eventually opted for enrollment in the NRG-CC001 clinical trial after multiple cranial recurrences. She received conventional WBRT with six months of memantine and developed significant neurocognitive side effects. This case highlights the growing body of literature supporting the role of SRS alone in the management of multiple brain metastases and the importance of maximizing neurocognition as advances in systemic therapies prolong survival in Stage IV cancer. PMID:29492355

ALS Clinical Trials Review: 20 Years of Failure. Are We Any Closer to Registering a New Treatment?

PubMed Central

Petrov, Dmitry; Mansfield, Colin; Moussy, Alain; Hermine, Olivier

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating condition with an estimated mortality of 30,000 patients a year worldwide. The median reported survival time since onset ranges from 24 to 48 months. Riluzole is the only currently approved mildly efficacious treatment. Riluzole received marketing authorization in 1995 in the USA and in 1996 in Europe. In the years that followed, over 60 molecules have been investigated as a possible treatment for ALS. Despite significant research efforts, the overwhelming majority of human clinical trials (CTs) have failed to demonstrate clinical efficacy. In the past year, oral masitinib and intravenous edaravone have emerged as promising new therapeutics with claimed efficacy in CTs in ALS patients. Given their advanced phase of clinical development one may consider these drugs as the most likely near-term additions to the therapeutic arsenal available for patients with ALS. In terms of patient inclusion, CT with masitinib recruited a wider, more representative, less restrictive patient population in comparison to the only successful edaravone CT (edaravone eligibility criteria represents only 18% of masitinib study patients). The present manuscript reviews >50 CTs conducted in the last 20 years since riluzole was first approved. A special emphasis is put on the analysis of existing evidence in support of the clinical efficacy of edaravone and masitinib and the possible implications of an eventual marketing authorisation in the treatment of ALS. PMID:28382000

Long-term outcomes of fertility-sparing treatment of atypical polypoid adenomyoma with medroxyprogesterone acetate.

PubMed

Nomura, Hidetaka; Sugiyama, Yuko; Tanigawa, Terumi; Matoda, Maki; Kanao, Hiroyuki; Kondo, Eiji; Takeshima, Nobuhiro

2016-01-01

Our objective was to analyze the long-term oncologic outcomes of fertility-preserving hormonal treatment with medroxyprogesterone acetate (MPA) in patients with APA. In a retrospective chart review, we identified patients with APA who were treated with MPA for fertility preservation at our hospital between 2001 and 2011. Eighteen patients with histologically diagnosed APA were identified. Clinical data including treatment, obstetrical, and oncologic outcomes were recorded. The mean observation period was 77.6 months (median 73.5, range 22-142), and the mean age was 33.6 years. Four patients also developed well-differentiated endometrial carcinoma. After the treatment, 14 patients (77.8 %) achieved either a complete response or partial response. Eight patients experienced recurrence, while four experienced persistent disease. Ten patients (55.6 %) eventually underwent hysterectomy. The median time to hysterectomy was 40.3 months (range 24-68). Nine patients progressed to endometrial cancer, and one experienced persistent APA. Among younger patients (<35 years of age), four out of five patients who were married could have children. Seven patients (38.9 %) showed no evidence of the disease during the observation period (median 60 months, range 22-117 months). No one died because of the disease during the observation period. MPA yields a high response rate in APA, and if only younger patients are considered, a favorable pregnancy rate can be obtained. However, because recurrence rate is high, long-term follow-up under supervision of a trained gynecologic oncologist is required. To confirm MPA's utility, multi-center collaboration would be warranted.

Assessing head and neck cancer patient preferences and expectations: A systematic review.

PubMed

Blanchard, Pierre; Volk, Robert J; Ringash, Jolie; Peterson, Susan K; Hutcheson, Katherine A; Frank, Steven J

2016-11-01

To enhance the value of care, interventions should aim at improving endpoints that matter to patients. The preferences of head and neck cancer patients regarding treatment outcomes are therefore a major topic for patient-centered research. A systematic review (PROSPERO number CRD42016035692) was conducted by searching electronic databases (Medline, Embase, Cochrane, CINAHL) for articles evaluating patient or surrogate preferences in head and neck cancer. A qualitative review was performed but no quantitative synthesis. Of 817 references retrieved, 20full-text articles were eventually included in the qualitative analysis Disease sites included mixed head and neck tumor sites, n=9; larynx, n=6; oropharynx/oral cavity, n=5. Overall, patients prioritized survival over functional endpoints. However, preferences and utility scores varied greatly between patients and healthy subjects, and differences were less pronounced with spouses or healthcare providers. Findings from studies of laryngeal preservation are consistent and conclude that a subset of patients would be willing to compromise a certain amount of survival to avoid laryngectomy. On the other hand, studies of patients with oropharyngeal cancer are too heterogeneous to draw conclusions about acceptable functional trade-offs or priorities, and should be the focus of future research. Future research surrounding head and neck cancer patients will most likely be clinically applicable if the questions are focused on well-defined patient groups and treatment options. Gathering reliable and valid quality-of-life data, designing patient preference studies that use reliable and generalizable methods, and using the results to develop decision aids for shared decision-making strategies are recommended going forward. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acanthosis nigricans

MedlinePlus

... cause any symptoms other than skin changes. Eventually, dark, velvety skin with very visible markings and creases ... your provider if you develop areas of thick, dark, velvety skin. Alternative Names AN; Skin pigment disorder - ...

Ewing’s Sarcoma: Overcoming the Therapeutic Plateau

PubMed Central

Subbiah, Vivek; Kurzrock, Razelle

2013-01-01

The hallmark of Ewing’s sarcoma (EWS) is a translocation -- t(11;22)(q24;q12) -- that most frequently results in the EWS/FLI1 aberrant chimeric gene. Because EWS afflicts young patients, it stands out among the diverse sarcoma subtypes. The frontline, standard-of-care cytotoxic chemotherapy regimens produce minimal benefit in patients with metastases at presentation or those with relapsed disease. While the outcomes of chemorefractory EWS patients are poor, recent developments have led to the promising use of targeted therapy. Specifically, inhibition of insulin-like growth factor 1 receptor (IGF1R) signaling and the mammalian target of rapamycin (mTOR) pathways has emerged as a targeted therapy in EWS, with select patients experiencing dramatic therapeutic responses. However, targeted therapies in general, and these responders in particular, are faced with the ultimate conundrum of eventual resistance. To optimize response, combining IGF1R and mTOR inhibitor-based regimens with chemotherapy in the upfront setting in newly diagnosed high-risk EWS may clarify the true benefit of IGF1R inhibitors in these patients. Another option is to explore novel targeted multikinase inhibitors and poly(ADP-ribose) polymerase (PARP) inhibitors, which have experienced a surge in supporting preclinical data. Drugs inhibiting the downstream targets of EWS/FLI1 are also in preclinical development. However, ultimately, the underlying biomarker correlates of resistance and response must be delineated along with ways to overcome them. Novel agents, together with integration of advances in multimodal approaches (including surgery and radiation), as well as offering targeted therapies early in the disease course represent new strategies for confronting the challenges of EWS. PMID:22742646

Optimal management of immune-related adverse events resulting from treatment with immune checkpoint inhibitors: a review and update.

PubMed

Nagai, Hiroki; Muto, Manabu

2018-06-01

Over the last two decades, molecular-targeted agents have become mainstream treatment for many types of malignancies and have improved the overall survival of patients. However, most patients eventually develop resistance to these targeted therapies. Recently, immunotherapies such as immune checkpoint inhibitors have revolutionized the treatment paradigm for many types of malignancies. Immune checkpoint inhibitors have been approved for treatment of melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck squamous cell carcinoma, Hodgkin's lymphoma, bladder cancer and gastric cancer. However, oncologists have been faced with immune-related adverse events caused by immune checkpoint inhibitors; these are generally mild but can be fatal in some cases. Because immune checkpoint inhibitors have distinct toxicity profiles from those of chemotherapy or targeted therapy, many oncologists are not familiar with the principles for optimal management of immune-related adverse events, which require early recognition and appropriate treatment without delay. To achieve this, oncologists must educate patients and health-care workers, develop checklists of appropriate tests for immune-related adverse events and collaborate closely with organ specialists. Clinical questions that remain include whether immune checkpoint inhibitors should be administered to patients with autoimmune disease and whether patients for whom immune-related adverse events lead to delays in immunotherapy should be retreated. In addition, the predicted use of combination immunotherapies in the near future means that oncologists will face a higher incidence and severity of immune-related adverse events. This review provides an overview of the optimal management of immune-related adverse events attributed to immune checkpoint inhibitors.

Mortality and Its Risk Factors in Patients with Rapid Eye Movement Sleep Behavior Disorder

PubMed Central

Zhou, Junying; Zhang, Jihui; Lam, Siu Ping; Mok, Vincent; Chan, Anne; Li, Shirley Xin; Liu, Yaping; Tang, Xiangdong; Yung, Wing Ho; Wing, Yun Kwok

2016-01-01

Study Objectives: To determine the mortality and its risk factors in patients with rapid eye movement (REM) sleep behavior disorder (RBD). Methods: A total of 205 consecutive patients with video-polysomnography confirmed RBD (mean age = 66.4 ± 10.0 y, 78.5% males) were recruited. Medical records and death status were systematically reviewed in the computerized records of the health care system. Standardized mortality ratio (SMR) was used to calculate the risk ratio of mortality in RBD with reference to the general population. Results: Forty-three patients (21.0%) died over a mean follow-up period of 7.1 ± 4.5 y. The SMR was not increased in the overall sample, SMR (95% confidence interval [CI]) = 1.00 (0.73–1.33). However, SMR (95% CI) increased to 1.80 (1.21–2.58) and 1.75 (1.11–2.63) for RBD patients in whom neurodegenerative diseases and dementia, respectively, eventually developed. In the Cox regression model, mortality risk was significantly associated with age (hazard ratio [HR] = 1.05; 95% CI, 1.01–1.10), living alone (HR = 2.04; 95% CI, 1.39–2.99), chronic obstructive pulmonary disease (HR = 3.38; 95% CI, 1.21–9.46), cancer (HR = 10.09; 95% CI, 2.65–38.42), periodic limb movements during sleep (HR = 3.06; 95% CI, 1.50–6.24), and development of neurodegenerative diseases (HR = 2.84; 95% CI, 1.47–5.45) and dementia (HR = 2.66; 95% CI, 1.39–5.08). Conclusions: Patients with RBD have a higher mortality rate than the general population only if neurodegenerative diseases develop. Several risk factors on clinical and sleep aspects are associated with mortality in RBD patients. Our findings underscore the necessity of timely neuroprotective interventions in the early phase of RBD before the development of neurodegenerative diseases. Citation: Zhou J, Zhang J, Lam SP, Mok V, Chan A, Li SX, Liu Y, Tang X, Yung WH, Wing YK. Mortality and its risk factors in patients with rapid eye movement sleep behavior disorder. SLEEP 2016;39(8):1543–1550. PMID:27306273

Interactive videoconsultation is a feasible method for neurological in-patient assessment.

PubMed

Craig, J; Patterson, V; Russell, C; Wootton, R

2000-11-01

To evaluate the feasibility of interactive videoconsultation (IATV) as a means by which neurologists might assess patients admitted with neurological symptoms to hospitals distant from a neurological centre, we studied 25 unselected patients using interactive videoconsultation (IATV) and then validated the IATV diagnoses and management plans at a later face-to-face consultation. IATV consultation led to an eventual diagnosis in 23 out of 25 patients, with one diagnosis being changed and one remaining uncertain. The IATV management plans were felt to be appropriate for all patients in study. Twelve patients were able to be discharged from hospital on the same day as IATV on the advice of the neurologist. It is therefore practical to assess patients admitted with neurological symptoms to distant hospitals using IATV and this may result in more efficient use of in-patient resources.

[Seric 21-hydroxilase antibodies in patients with anti-microsomal fraction antibodies. Autoimmune polyendocrine syndrome].

PubMed

Botta, Silvia; Roveto, Silvana; Rimoldi, Daniel

2007-01-01

Autoimmune polyendocrine syndrome (APS) is the association of autoimmune endocrine diseases, with other autoimmune nonendocrine disorders. APS types 1, 2 and 4 include autoimmune adrenalitis; this suggests the presence of autoantibodies. A specific serological marker for these is the anti 21- hydroxilase autoantibody (a21-OH). APS type 2 is the association of autoimmune adrenalitis, to autoimmune thyroid disease and/or diabetes mellitus, all these are induced by autoantibodies. Alopecia, vitiligo, myasthenia and other manifestations can be minor components. We sought to establish the prevalence of seric a21-OH in patients with positive anti-microsomal fraction autoantibodies, autoimmune thyroid disease and/or non-endocrine autoimmune diseases. We also aimed to diagnose incomplete forms of APS and to follow up patients at risk of progression to complete forms of APS. A population of 72 patients and another of 60 controls with negative anti-microsomal fraction autoantibodies were studied. Elevated seric a21-OH were found in two patients. Patient A with 47 U/ml had autoimmune hypothyroidism and myasthenia; and patient B with 8.75 U/ml had autoimmune hypothyrodism and vitiligo; they both lacked adrenal insufficiency. Seric a21-OH had a prevalence of 2.8%. Regarding the adrenal component, patients A and B had an incomplete and latent APS type 2. Considering a21-OH as markers of latent endocrine autoimmune diseases and taking into account the eventual risk of developing clinical manifestations, periodic biochemical and clinical follow-ups are recommended.

Isolated central nervous system progression on Crizotinib

PubMed Central

Chun, Stephen G.; Choe, Kevin S.; Iyengar, Puneeth; Yordy, John S.; Timmerman, Robert D.

2012-01-01

Advanced non-small lung cancer (NSCLC) remains almost uniformly lethal with marginal long-term survival despite efforts to target specific oncogenic addiction pathways that may drive these tumors with small molecularly targeted agents and biologics. The EML4-ALK fusion gene encodes a chimeric tyrosine kinase that activates the Ras signaling pathway, and this fusion protein is found in approximately 5% of NSCLC. Targeting EML4-ALK with Crizotinib in this subset of NSCLC has documented therapeutic efficacy, but the vast majority of patients eventually develop recurrent disease that is often refractory to further treatments. We present the clinicopathologic features of three patients with metastatic NSCLC harboring the EML4-ALK translocation that developed isolated central nervous system (CNS) metastases in the presence of good disease control elsewhere in the body. These cases suggest a differential response of NSCLC to Crizotinib in the brain in comparison to other sites of disease, and are consistent with a previous report of poor CNS penetration of Crizotinib. Results of ongoing clinical trials will clarify whether the CNS is a major sanctuary site for EML4-ALK positive NSCLC being treated with Crizotinib. While understanding molecular mechanisms of resistance is critical to overcome therapeutic resistance, understanding physiologic mechanisms of resistance through analyzing anatomic patterns of failure may be equally crucial to improve long-term survival for patients with EML4-ALK translocation positive NSCLC. PMID:22986231

Epileptogenesis in experimental models.

PubMed

Pitkänen, Asla; Kharatishvili, Irina; Karhunen, Heli; Lukasiuk, Katarzyna; Immonen, Riikka; Nairismägi, Jaak; Gröhn, Olli; Nissinen, Jari

2007-01-01

Epileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another.

Machine learning for predicting the response of breast cancer to neoadjuvant chemotherapy

PubMed Central

Mani, Subramani; Chen, Yukun; Li, Xia; Arlinghaus, Lori; Chakravarthy, A Bapsi; Abramson, Vandana; Bhave, Sandeep R; Levy, Mia A; Xu, Hua; Yankeelov, Thomas E

2013-01-01

Objective To employ machine learning methods to predict the eventual therapeutic response of breast cancer patients after a single cycle of neoadjuvant chemotherapy (NAC). Materials and methods Quantitative dynamic contrast-enhanced MRI and diffusion-weighted MRI data were acquired on 28 patients before and after one cycle of NAC. A total of 118 semiquantitative and quantitative parameters were derived from these data and combined with 11 clinical variables. We used Bayesian logistic regression in combination with feature selection using a machine learning framework for predictive model building. Results The best predictive models using feature selection obtained an area under the curve of 0.86 and an accuracy of 0.86, with a sensitivity of 0.88 and a specificity of 0.82. Discussion With the numerous options for NAC available, development of a method to predict response early in the course of therapy is needed. Unfortunately, by the time most patients are found not to be responding, their disease may no longer be surgically resectable, and this situation could be avoided by the development of techniques to assess response earlier in the treatment regimen. The method outlined here is one possible solution to this important clinical problem. Conclusions Predictive modeling approaches based on machine learning using readily available clinical and quantitative MRI data show promise in distinguishing breast cancer responders from non-responders after the first cycle of NAC. PMID:23616206

Update on options for treatment of metastatic castration-resistant prostate cancer.

PubMed

Vishnu, Prakash; Tan, Winston W

2010-06-24

Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA) testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC), the median survival is about 1-2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC. Since the two landmark trials (TAX-327 and Southwest Oncology Group 99-16) in CRPC, several newer cytotoxic drugs (epothilones, satraplatin), targeted agents (abiraterone, MDV3100) and vaccines have been tested in phase II and III setting with promising results. The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, 'circulating tumor cells', have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.

Cancer cachexia, mechanism and treatment

PubMed Central

Aoyagi, Tomoyoshi; Terracina, Krista P; Raza, Ali; Matsubara, Hisahiro; Takabe, Kazuaki

2015-01-01

It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials. PMID:25897346

Coorientational Accuracy during Regional Development of Energy Resources: Problems in Agency-Public Communication.

ERIC Educational Resources Information Center

Bowes, John E.; Stamm, Keith R.

This paper presents a progress report from a research program aimed at elucidating communication problems which arise among citizens and government agencies during the development of regional environmental policy. The eventual objective of the program is to develop a paradigm for evaluative research in communication that will provide for the…

Do Pre-Service Science Teachers Have Understanding of the Nature of Science?: Explicit-Reflective Approach

ERIC Educational Resources Information Center

Örnek, Funda; Turkey, Kocaeli

2014-01-01

Current approaches in Science Education attempt to enable students to develop an understanding of the nature of science, develop fundamental scientific concepts, and develop the ability to structure, analyze, reason, and communicate effectively. Students pose, solve, and interpret scientific problems, and eventually set goals and regulate their…

Clinical, imaging, and follow-up observations of patients with anti-GABAB receptor encephalitis.

PubMed

Qiao, Song; Zhang, Yin-Xi; Zhang, Bi-Jun; Lu, Ru-Yi; Lai, Qi-Lun; Chen, Lin-Hui; Wu, Jiong

2017-05-01

Anti-gamma-aminobutyric acid B (anti-GABA B ) receptor encephalitis is a newly described type of autoimmune encephalitis. We report a case series of patients diagnosed with anti-GABA B receptor encephalitis in China, focusing on their presentations, laboratory and imaging results, and outcomes, as well as the treatment strategies which were employed. Data from patients diagnosed with anti-GABA B receptor encephalitis in the Second Affiliated Hospital, School of Medicine, Zhejiang University, from January 2014 to June 2015 were retrospectively collected and analyzed. Based on specific diagnostic criteria, seven cases were included. Six of the seven patients were males, and a median age at presentation of 56 years (range: 4-71 years). Seizures were the most common initial symptom, and all patients developed symptoms of typical limbic encephalitis during their disease course. Additional types of autoantibodies were identified in four patients. After presentation, three patients were found to have small cell lung cancer and one patient was eventually diagnosed with thymoma. All patients accepted first-line immune therapy, but only one chose tumor treatment. The three tumor-free patients had a good outcome, whereas those with tumors had a poor one. Finally, there were no relapses during follow-up. Anti-GABA B receptor encephalitis is a rare, unique autoimmune disease, and is often associated with tumors. It should be considered in the differential diagnosis for middle and senior-aged patients who present with predominantly limbic encephalitis symptoms. Importantly, earlier recognition of this potentially treatable condition could improve its overall prognosis.

The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family.

PubMed

Hensen, Erik F; Jansen, Jeroen C; Siemers, Maaike D; Oosterwijk, Jan C; Vriends, Annette Hjt; Corssmit, Eleonora Pm; Bayley, Jean-Pierre; van der Mey, Andel Gl; Cornelisse, Cees J; Devilee, Peter

2010-01-01

Germline mutations in SDHD predispose to the development of head and neck paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on the sex of the parent who transmits the mutation: paragangliomas only arise upon paternal transmission. In this study, both the risk of paraganglioma and phaeochromocytoma formation, and the risk of developing associated symptoms were investigated in 243 family members with the SDHD.D92Y founder mutation. By using the Kaplan-Meier method, age-specific penetrance was calculated separately for paraganglioma formation as defined by magnetic resonance imaging (MRI) and for paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated to be 54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70 years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in 8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one patient (3%). Although the majority of carriers of a paternally inherited SDHD mutation will eventually develop head and neck paragangliomas, we find a lower penetrance than previous estimates from studies based on predominantly index cases. The family-based study described here emphasizes the importance of the identification and inclusion of clinically unaffected mutation carriers in all estimates of penetrance. This finding will allow a more accurate genetic counseling and warrants a 'wait and scan' policy for asymptomatic paragangliomas, combined with biochemical screening for catecholamine excess in SDHD-linked patients.

A Unique Case of Malignant Pleuropericardial Effusion: HHV-8-Unrelated PEL-Like Lymphoma—A Case Report and Review of the Literature

PubMed Central

Mohammad, Farhan; Siddique, Muhammad Neaman; Siddiqui, Faraz; Popalzai, M.; Asgari, Masoud; Odaimi, Marcel

2014-01-01

Primary effusion lymphoma (PEL) or body cavity lymphoma is a rare type of extra nodal lymphoma of B-cell origin that presents as lymphomatous effusion(s) without any nodal enlargement or tumor masses. It belongs to the group of AIDS related non-Hodgkin's lymphomas. First described in 1996 in HIV infected individuals who were coinfected with Kaposi's sarcoma-associated herpesvirus (KSHV) or HHV-8 virus, it was included as a separate entity in WHO classification of tumors of hematopoietic and lymphoid tissue in the year 2001. The definition included association with HHV-8 virus as a mandatory diagnostic criterion. However, cases were later reported where PEL-like disease process was diagnosed in HHV-8 negative patients. This was eventually recognized as a rare but distinct entity termed as “HHV-8-unrelated PEL-like lymphoma”. Herein, we are reporting a case of an elderly patient who presented with a large pleuropericardial effusion and was eventually diagnosed with this entity. Till date, only around 50 cases of HHV-8-unrelated PEL-like lymphoma have been reported and our case being EBV, HIV, and Hepatitis C negative makes it very unique and rare occurrence. We are also presenting a review of relevant literature focused mainly on comparing outcomes in patients treated with and without chemotherapy. PMID:24716045

Hypersomnia as presenting symptom of anti-Ma2-associated encephalitis: case study.

PubMed

Rojas-Marcos, Iñigo; Graus, Francesc; Sanz, Gema; Robledo, Arturo; Diaz-Espejo, Carlos

2007-01-01

We describe a patient who presented with excessive daytime sleepiness (EDS) and was eventually diagnosed with anti-Ma2 encephalitis. Neurological examination disclosed somnolence, left palpebral ptosis, and vertical gaze paresis. A brain MRI showed high signal intensity in the hypothalamus and each hippocampus. Ma2 antibodies were found in the patient's serum, and fiberbronchoscopy disclosed a lung carcinoma. After three months of steroid treatment, the results of the patient's neurological exam became normal. We conclude that anti-Ma2 encephalitis may present with mostly isolated EDS and that it may respond to steroids despite old age and the presence of an untreated lung cancer.

Vascular complications of transcatheter aortic valve replacement: A concise literature review

PubMed Central

Chaudhry, Muhammad Ali; Sardar, Muhammad Rizwan

2017-01-01

Transcatheter aortic valve replacement (TAVR) is a relatively newer therapeutic modality which offers a promising alternative to surgical aortic valve replacement for patients with prohibitive, high and intermediate surgical risk. The increasing trend to pursue TAVR in these patients has also led to growing awareness of the associated potential vascular complications. The significant impact of these complications on eventual clinical outcome and mortality makes prompt recognition and timely management a critical factor in TAVR patients. We hereby present a concise review with emphasis on diverse vascular complications associated with TAVR and their effective management to improve overall clinical outcomes. PMID:28824787

[The clinical history in surgical processes. Bioethical aspects and basic professional ethics].

PubMed

Collazo Chao, Eliseo

2008-11-01

Surgeons are increasingly facing multiple civil liability claims from their patients. Against this background and taking any eventual liability claims into account, surgeons must be increasingly aware of the importance of maintaining patient medical histories, which raises numerous questions on the length of time and form of keeping them. Ethical and legal obligations need to be taken into account in order to identify the controversial aspects related to patients and their environment, as well as shedding light on the most appropriate behaviour in each case. We must never forget the case history is a clinical document, subjected to the medical art and medical ethics which regulate it.

Ethics in oncology: principles and responsibilities declared in the Italian Ragusa statement.

PubMed

Gori, Stefania; Pinto, Carmine; Caminiti, Caterina; Aprile, Giuseppe; Marchetti, Paolo; Perrone, Francesco; Di Maio, Massimo; Omodeo Salè, Emanuela; Mancuso, Annamaria; De Cicco, Maurizio; Di Costanzo, Francesco; Crispino, Sergio; Passalacqua, Rodolfo; Merlano, Marco; Zagonel, Vittorina; Fioretto, Luisa; Micallo, Giovanni; Labianca, Roberto; Bordonaro, Roberto; Comandone, Alessandro; Spinsanti, Sandro; Iacono, Carmelo; Nicolis, Fabrizio

2016-12-01

Cancer care involves many ethical issues. The need for more patient-centered healthcare together with the improved empowerment of every person diagnosed with cancer have been transposed by the Italian Association of Medical Oncology (AIOM) and eventually translated in the Ragusa statement. This position paper describes the philosophy that lies beneath this document and its fundamental principles.

Impaired Cognition in Rats with Cortical Dysplasia: Additional Impact of Early-Life Seizures

ERIC Educational Resources Information Center

Lucas, Marcella M.; Lenck-Santini, Pierre-Pascal; Holmes, Gregory L.; Scott, Rod C.

2011-01-01

One of the most common and serious co-morbidities in patients with epilepsy is cognitive impairment. While early-life seizures are considered a major cause for cognitive impairment, it is not known whether it is the seizures, the underlying neurological substrate or a combination that has the largest impact on eventual learning and memory. Teasing…

Hypothenar hammer syndrome and basilic bypass.

PubMed

Chander, R K; Phair, J; Oza, P; Patel, M; Balar, N

2014-12-01

We report a case of hypothenar hammer syndrome. The case presents necessary diagnostic measures and discusses the etiology of this syndrome. Additionally, the case reviews treatments, which culminated in the eventual use of ulnar artery bypass with autogenous basilica vein to treat and resolve the ischemic fingers of the patient. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Determinants of compliance with nasal continuous positive airway pressure treatment applied in a community setting.

PubMed

Ball, E M.; Banks, M B.

2001-05-01

Objectives: To assess determinants of nasal continuous positive airway pressure (CPAP) compliance when applied in a community setting.Background: One-third of obstructive sleep apnea patients eventually refuse CPAP therapy. Treatment outcomes may be improved by identifying predictors of CPAP failure, including whether management by primary care physicians without sleep consultation affects results.Methods: Polysomnogram, chart review, and questionnaire results for regular CPAP users (n=123) were compared with those returning the CPAP machine (n=26).Results: Polysomnographic data and the presence of multiple sleep disorders were only modestly predictive of CPAP compliance. Striking differences in questionnaire responses separated CPAP users from non-users, who reported less satisfaction with all phases of their diagnosis and management. Rates of CPAP use were not significantly different between patients managed solely by their primary care physician or by a sleep consultant.Conclusions: Polysomnographic findings are unlikely to identify eventual CPAP non-compliers in a cost-effective fashion. Improvements in sleep apnea management may result from addressing the role of personality factors and multiple sleep disorders in determining compliance. In this practice setting, management by primary care physicians did not significantly degrade CPAP compliance.

Bilateral endogenous necrotizing scleritis due to Aspergillus oryzae.

PubMed

Stenson, S; Brookner, A; Rosenthal, S

1982-01-01

A case of bilateral necrotizing scleritis due to Aspergillus oryzae is reported. The patient was a former addict of intravenous narcotics treated five years previously for meningitis due to the same organism. A seeding focus in the thoracic spine was eventually found. The patient responded well to combined local and systemic therapy with amphotericin B, flucytosine, and natamycin. This represents, to the best of our knowledge, both the first reported case of ocular disease due to this species of Aspergillus and of isolated scleral, nonintraocular involvement in endogenous oculomycosis.

Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics.

PubMed

Yoo, Joseph; Kistler, C Andrew; Yan, Linda; Dargan, Andrew; Siddiqui, Ali A

2016-12-01

Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer.

Endoscopic ultrasound in pancreatic cancer: innovative applications beyond the basics

PubMed Central

Yoo, Joseph; Kistler, C. Andrew; Yan, Linda; Dargan, Andrew

2016-01-01

Endoscopic ultrasound (EUS) has become a mainstay in assisting in the diagnosis and staging of pancreatic cancer. In addition, EUS provides a modality to treat chronic pain through celiac plexus neurolysis. Currently, there is growing data and utilization of EUS in more diverse and innovative applications aimed at providing more sophisticated diagnostic, prognostic and therapeutic options for patients with pancreatic cancer. EUS delivery of chemotherapy, viral and biological vectors and fiducial markers may eventually revolutionize the way clinicians approach the care of a patient with pancreatic cancer. PMID:28078128

The Evolving Treatment Landscape of Advanced Renal Cell Carcinoma in Patients Progressing after VEGF Inhibition

PubMed Central

Barata, Pedro C.; Ornstein, Moshe C.

2017-01-01

Despite significant changes in the therapeutic landscape of renal cell carcinoma, the majority of patients with metastatic disease eventually progress after first-line treatment with vascular endothelial growth factor receptors (VEGFR) tyrosine kinase inhibitor (TKI) therapy. Understanding existing data on subsequent therapies is crucial to define an optimal treatment sequence following first-line failure. This review examines the data supporting currently approved agents in this setting and provides a framework for decision-making regarding treatment sequencing beyond first-line therapy with VEGFR TKIs. PMID:28725539

A 17-Year-Old Girl With Acute Onset of Hemiparesis.

PubMed

Morrissey, Michael; Ciorciari, Anthony J; Cunningham, Sandra J

2016-06-01

The presentation of acute-onset hemiparesis in a teenager can be challenging and offers a wide differential diagnosis. We discuss the approach to the patient (which should begin with thorough history taking and physical examination) and advanced imaging as directed by the patient's signs and symptoms. We report the case of an otherwise well 17-year-old girl who presented to the pediatric emergency department with a 2-day history of left-sided weakness and difficulty ambulating. Her eventual diagnosis of Balo concentric sclerosis, a rare form of multiple sclerosis, is discussed.

Microarray gene expression analysis of uterosacral ligaments in uterine prolapse.

PubMed

Ak, Handan; Zeybek, Burak; Atay, Sevcan; Askar, Niyazi; Akdemir, Ali; Aydin, Hikmet Hakan

2016-11-01

Pelvic organ prolapse (POP) is a major health problem that impairs the quality of life with a wide clinical spectrum. Since the uterosacral ligaments provide primary support for the uterus and the upper vagina, we hypothesize that the disruption of these ligaments may lead to a loss of support and eventually contribute to POP. In this study, we therefore investigated whether there are any differences in the transcription profile of uterosacral ligaments in patients with POP when compared to those of the control samples. Seventeen women with POP and 8 non-POP controls undergoing hysterectomy for benign conditions were included in the study. Affymetrix® Gene Chip microarrays (Human Hu 133 plus 2.0) were used for whole genome gene expression profiling analysis. There was 1 significantly down-regulated gene, NKX2-3 in patients with POP compared to the controls (p=4.28464e-013). KIF11 gene was found to be significantly down-regulated in patients with ≥3 deliveries compared to patients with <3 deliveries (p=0.0156237). UGT1A1 (p=2.43388e-005), SCARB1 (p=1.19001e-006) and NKX2-3 (p=2.17966e-013) genes were found to be significantly down-regulated in the premenopausal patients compared to the premenopausal controls. UGT1A1 gene was also found to be significantly down-regulated in the post menopausal patients compared to the postmenopausal controls (p=0.0005). This study provides evidence for a significant down-regulation of the genes that take role in cell cycle, proliferation and embryonic development along with cell adhesion process on the development of POP for the first time. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The 200th anniversary of the stethoscope: Can this low-tech device survive in the high-tech 21st century?

PubMed

Bank, Ivan; Vliegen, Hubert W; Bruschke, Albert V G

2016-12-14

In 1816, Laennec discovered that auscultation of the heart and lungs could effectively be performed by placing a hollow cylinder (initially made of a roll of paper) between the chest of the patient and the ear of the examiner. This was the first step in the development of the stethoscope, which was a breakthrough in the diagnosis and management of cardiac and pulmonary patients. Technical improvements of the stethoscope followed and in cardiac patients auscultation soon became a major diagnostic tool. In the second half of the 20th century, new powerful non-invasive diagnostic modalities were developed and the interest in auscultation declined. As a result, the auscultatory skills of students and physicians at all levels of training decreased to a disappointingly low level. We now must decide whether we should stimulate the use of and proficiency in auscultation or if we should accept the further decline and eventual abolishment of this component of the physical examination. Reviewing the literature and taking into consideration the setting in which the patients are presented, including the availability of advanced diagnostic facilities, we conclude that the time-honoured stethoscope, in spite of its limitations, still has potential as a patient-friendly, effective, and economical instrument in medical practice. However, new initiatives are required to train students, physicians and allied health professionals in cardiac auscultation to avoid misinterpretations that may harm the patients and generate extra costs. To be successful such programs will require wide support from the medical community. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery.

PubMed

Winzeler, Bettina; Zweifel, Christian; Nigro, Nicole; Arici, Birsen; Bally, Martina; Schuetz, Philipp; Blum, Claudine Angela; Kelly, Christopher; Berkmann, Sven; Huber, Andreas; Gentili, Fred; Zadeh, Gelareh; Landolt, Hans; Mariani, Luigi; Müller, Beat; Christ-Crain, Mirjam

2015-06-01

Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation. The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery. This was a prospective multicenter observational cohort study. Three Swiss or Canadian referral centers were used. Consecutive pituitary surgery patients were included. Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI. Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1. Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points. In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.

Advancing a smart air cushion system for preventing pressure ulcers using projection Moiré for large deformation measurements

NASA Astrophysics Data System (ADS)

Cheng, Sheng-Lin; Tsai, Tsung-Heng; Lee, Carina Jean-Tien; Hsu, Yu-Hsiang; Lee, Chih-Kung

2016-03-01

A pressure ulcer is one of the most important concerns for wheelchair bound patients with spinal cord injuries. A pressure ulcer is a localized injury near the buttocks that bear ischial tuberosity oppression over a long period of time. Due to elevated compression to blood vessels, the surrounding tissues suffer from a lack of oxygen and nutrition. The ulcers eventually lead to skin damage followed by tissue necrosis. The current medical strategy is to minimize the occurrence of pressure ulcers by regularly helping patients change their posture. However, these methods do not always work effectively or well. As a solution to fundamentally prevent pressure ulcers, a smart air cushion system was developed to detect and control pressure actively. The air cushion works by automatically adjusting a patient's sitting posture to effectively relieve the buttock pressure. To analyze the correlation between the dynamic pressure profiles of an air cell with a patient's weight, a projection Moiré system was adopted to measure the deformation of an air cell and its associated stress distribution. Combining a full-field deformation imaging with air pressure measured within an air cell, the patient's weight and the stress distribution can be simultaneously obtained. By integrating a full-field optical metrology with a time varying pressure sensor output coupled with different active air control algorithms for various designs, we can tailor the ratio of the air cells. Our preliminary data suggests that this newly developed smart air cushion has the potential to selectively reduce localized compression on the tissues at the buttocks. Furthermore, it can take a patient's weight which is an additional benefit so that medical personnel can reference it to prescribe the correct drug dosages.

Pathologic Markers Determining Prognosis in Patients with Treated or Healing Giant Cell Arteritis.

PubMed

Sultan, Harris; Smith, Stacy V; Lee, Andrew G; Chévez-Barrios, Patricia

2018-06-08

To provide quantitative evidence linking the Cluster of Differentiation-68 (CD68)+ macrophage-marker found on temporal artery biopsies (TABs) with disease prognosis. Retrospective, cross-sectional study METHODS: We examined 42 consecutive patients who had undergone unilateral TABs at a single hospital in 2015. Clinical data, laboratory data, and histopathologic features of TABs were recorded. clinical diagnosis of giant cell arteritis (GCA) with TAB performed at the same center. CD68 immunohistochemistry was used to label macrophages in the TABs. multiple logistic regression and bivariate comparisons to measure the association between CD68+ cells per histologic section with placement on immunomodulatory therapy (IMT). Twenty seven patients were females (64%), with a mean age of 72 (standard deviation [S.D.] ±7.7). Eleven patients (26%) were placed on IMT, 17 (40%) had disease recurrence during steroid taper, and 25 (60%) were referred to rheumatology. Of 42 biopsies, 35 underwent staining with CD68 to confirm active inflammation in suspicious, but not diagnostic, specimens. Patients eventually placed on IMT had increased CD68+ cells/slice compared to those not on IMT (median 5.00 [25-75 th quartile 2.00-7.15] vs 1.21 [0.38-2.57], p=0.031, respectively). A receiver operating characteristics (ROC) curve demonstrates that 2.17 CD68+ cells/slice predicts placement on IMT with an odds ratio of 1.54 (95% C.I. 1.02-2.33, p=0.038). Patients refractory to initial steroid tapers and those eventually placed on IMT had increased CD68 cells/section. CD68+ macrophages and their location on the internal elastic lamina may predict disease severity in patients with presumed GCA. Our results suggest that this marker may expedite patient triaging to alternate treatment to the usual steroid therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel Immunotherapies for Autoimmune Hepatitis

PubMed Central

Cassim, Shamir; Bilodeau, Marc; Vincent, Catherine; Lapierre, Pascal

2017-01-01

Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent. Lifelong immunosuppression is not without risks, especially in the pediatric population; 4% of patient with type 1 AIH will eventually develop hepatocellular carcinoma with a 2.9% probability after 10 years of treatment. Therefore, future treatments should aim to restore tolerance to hepatic autoantigens and induce long-term remission. Promising new immunotherapies have been tested in experimental models of AIH including T and B cell depletion and regulatory CD4+ T cells infusion. Clinical studies on limited numbers of patients have also shown encouraging results using B-cell-depleting (rituximab) and anti-TNF-α (infliximab) antibodies. A better understanding of key molecular targets in AIH combined with effective site-specific immunotherapies could lead to long-term remission without blanket immunosuppression and with minimal deleterious side effects. PMID:28184367

The modern staged repair of classic bladder exstrophy: a detailed postoperative management strategy for primary bladder closure.

PubMed

Stec, Andrew A; Baradaran, Nima; Schaeffer, Anthony; Gearhart, John P; Matthews, Ranjiv I

2012-10-01

Successful primary bladder closure of classic bladder exstrophy sets the stage for development of adequate bladder capacity and eventual voided continence. The postoperative pathway following primary bladder closure at the authors' institution is quantitatively and qualitatively detailed. Sixty-five consecutive newborns (47 male) undergoing primary closure of classic bladder exstrophy were identified and data were extracted relating to immediate postoperative care. Overall success rate was utilized to validate the pathway. Mean age at time of primary closure was 4.6 days and mean hospital stay was 35.8 days. Osteotomy was performed in 19 patients (mean age 8.8 days), and was not required in 39 infants (mean age 2.9 days). All patients were immobilized for 4 weeks. Tunneled epidural analgesia was employed in 61/65 patients. All patients had ureteral catheters and a suprapubic tube, along with a comprehensive antibiotic regimen. Postoperative total parenteral nutrition was commonly administered, and enteral feedings started around day 4.6. Our success rate of primary closure was 95.4%. A detailed and regimented plan for bladder drainage, immobilization, pain control, nutrition, antimicrobial prophylaxis, and adequate healing time is a cornerstone for the postoperative management of the primary closure of bladder exstrophy. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

PubMed Central

Tefera, Tesfaye W.; Borges, Karin

2017-01-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS. PMID:28119559

Current state of type 2 diabetes management.

PubMed

Molitch, Mark E

2013-06-01

Type 2 diabetes mellitus (T2DM) and its associated comorbidities are a major public health issue in the United States. Although a sizable pharmacotherapeutic armamentarium exists to combat this disease and several sources have published evidence-based management guidelines, the management of patients with T2DM remains complex and suboptimal. Currently available medications target various organs in an attempt to normalize hyperglycemia; however, newer agents targeting additional organ systems are in development. Among these, a class of medications that inhibit the sodium glucose cotransporter 2 (SGLT2) in the kidney show promise in their ability to decrease glucose reabsorption and increase glucose excretion. In particular, one of these compounds, canagliflozin, recently was approved by the US Food and Drug Administration. Despite such advances, the natural course of T2DM often eventually leads to the initiation of insulin therapy. A working knowledge of management guidelines, particularly concerning when and how to initiate monotherapies, combination therapies, and complex insulin regimens, is essential for optimal patient management. Insulin therapies should mimic normal physiologic levels of insulin through the use of both basal and bolus insulin analogues. Recognition of the various factors influencing therapeutic choices is also critical for improved patient management.

A new method to improve the clinical evaluation of cystic fibrosis patients by mucus viscoelastic properties.

PubMed

Tomaiuolo, Giovanna; Rusciano, Giulia; Caserta, Sergio; Carciati, Antonio; Carnovale, Vincenzo; Abete, Pasquale; Sasso, Antonio; Guido, Stefano

2014-01-01

In cystic fibrosis (CF) patients airways mucus shows an increased viscoelasticity due to the concentration of high molecular weight components. Such mucus thickening eventually leads to bacterial overgrowth and prevents mucus clearance. The altered rheological behavior of mucus results in chronic lung infection and inflammation, which causes most of the cases of morbidity and mortality, although the cystic fibrosis complications affect other organs as well. Here, we present a quantitative study on the correlation between cystic fibrosis mucus viscoelasticity and patients clinical status. In particular, a new diagnostic parameter based on the correlation between CF sputum viscoelastic properties and the severity of the disease, expressed in terms of FEV1 and bacterial colonization, was developed. By using principal component analysis, we show that the types of colonization and FEV1 classes are significantly correlated to the elastic modulus, and that the latter can be used for CF severity classification with a high predictive efficiency (88%). The data presented here show that the elastic modulus of airways mucus, given the high predictive efficiency, could be used as a new clinical parameter in the prognostic evaluation of cystic fibrosis.

A case of McCune-Albright syndrome associated with pituitary GH adenoma: therapeutic process and autopsy.

PubMed

Liu, Fuyi; Li, Wenting; Yao, Yong; Li, Guilin; Yang, Yi; Dou, Wanchen; Zhong, Dingrong; Wang, Lin; Zhu, Xiangdong; Hu, Hua; Zhang, Jianmin; Wang, Renzhi; Chen, Gao

2011-01-01

McCune-Albright syndrome (MAS) is a clinical syndrome with low incidence, and its concurrence with pituitary GH adenoma is rare. Little of the history, treatment and outcome has been studied. Follow-up of a 37-year-old male patient of MAS associated with pituitary GH adenoma was performed continuously recording the disease development and the treatment process until death, after which an autopsy was performed. Radiation therapy (RT) efficaciously controlled GH hypersecretion, however, it may have been the cause of the malignant transformation of the dysplastic bone tissue, which eventually caused brain hernia and death; autopsy demonstrated that the cranium had significant thickening (as much as 10 cm), the pathological diagnosis was fibrous dysplasia of bone associated with chondrosarcoma; and undifferentiated chondrosarcoma with malignant fibrous histocytoma subtype in the sellar region; nodular goiter with the thyroid gland, one nodus was pathologically demonstrated as papillary carcinoma. GH adenoma, present in a patient with MAS, might be cured by RT; but the risk of malignant transformation of the dysplastic bone tissue in the field of irradiation make it controversial. Lessons from the case reported here told us that we should take great caution when recommending RT for patients like this.

Therapeutic options for carotid in-stent restenosis: review of the literature.

PubMed

van Haaften, Anne C; Bots, Michiel L; Moll, Frans L; de Borst, Gert J

2010-10-01

To critically evaluate published evidence on therapeutic options for in-stent restenosis (ISR) after carotid artery stent (CAS) placement, a systematic analysis of studies reporting interventions for ISR after CAS placement was conducted. In total 20 studies were found, describing 100 interventions after carotid ISR in 96 patients. The interventions most performed were repeat percutaneous transluminal angioplasty (PTA; n = 54), repeat CAS placement (n = 31), and carotid endarterectomy with stent removal (n = 9). No periprocedural complications were identified in any of the studies evaluated. Recurrent restenosis after intervention for ISR occurred in 12 of 84 cases (14%). All 12 patients received tertiary treatment. Two patients developed a third recurrence and eventually disabling stroke, one of whom died. In the other 10 interventions, no further follow-up was described. In conclusion, several treatment strategies for ISR after CAS placement have been reported, with acceptable short-term results. The quality of the currently available data is still limited by the variability of results and study designs. Therefore, no recommendation can be made for any specific therapy. This argues for better study design and more consistency of reporting standards. Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.

ACY-1215 accelerates vemurafenib induced cell death of BRAF-mutant melanoma cells via induction of ER stress and inhibition of ERK activation.

PubMed

Peng, Ueihuei; Wang, Zhihao; Pei, Sa; Ou, Yunchao; Hu, Pengchao; Liu, Wanhong; Song, Jiquan

2017-02-01

BRAFV600E mutation is found in ~50% of melanoma patients and BRAFV600E kinase activity inhibitor, vemurafenib, has achieved a remarkable clinical response rate. However, most patients treated with vemurafenib eventually develop resistance. Overcoming primary and secondary resistance to selective BRAF inhibitors remains one of the most critically compelling challenges for these patients. HDAC6 has been shown to confer resistance to chemotherapy in several types of cancer. Few studies focused on the role of HDAC6 in vemurafenib resistance. Here we showed that overexpression of HDAC6 confers resistance to vemurafenib in BRAF-mutant A375 cells. ACY-1215, a selective HDAC6 inhibitor, inhibits the proliferation and induces the apoptosis of A375 cells. Moreover, ACY-1215 sensitizes A375 cells to vemurafenib induced cell proliferation inhibition and apoptosis induction, which occur partly through induction of endoplasmic reticulum (ER) stress and inactivation of extracellular signal-regulated kinase (ERK). Taken together, our results suggest that the inhibition of HDAC6 may be a promising strategy for the treatment of melanoma and overcoming resistance to vemurafenib.

Development of the Next Generation Air Quality Modeling System

EPA Science Inventory

A next generation air quality modeling system is being developed at the U.S. EPA to enable modeling of air quality from global to regional to (eventually) local scales. We envision that the system will have three configurations: 1. Global meteorology with seamless mesh refinemen...

The spontaneous return of sensibility in breasts reconstructed with autologous tissues.

PubMed

Shaw, W W; Orringer, J S; Ko, C Y; Ratto, L L; Mersmann, C A

1997-02-01

Some spontaneous return of sensibility following autologous tissue breast reconstruction is often suspected but not well documented. In the present study, objective touch-pressure, pain, temperature, and vibratory sensibilities were recorded in 33 autologous breast reconstructions at an average of 25.2 months postoperatively. Correlation of the sensory return with patients' satisfaction toward reconstruction was done by a detailed questionnaire. All except one patient regained a variety of sensibilities touch pressure in 97 percent of patients (averaging 81.05 gm/mm2 versus control of 7.98 gm/mm2), pain in 88 percent of patients, heat in 64 percent of patients (45 percent of quadrants), cold in 82 percent of patients (67 percent of quadrants), and high- and low-frequency vibration in 100 percent of patients (high in 90 percent of quadrants, low in 96 percent). Subjectively, 94 percent considered their chest comfortable to touch following reconstruction compared with 34 percent following mastectomy. On a scale from 1 to 10, patients rated their reconstructions an average of 9.3. Our findings confirm the spontaneous return of sensibility following a variety of autologous tissue breast reconstructions. The value of the sensory return is suggested by the high degree of satisfaction in nearly all patients. Further attempts to correlate the degree of sensory return with the degree of satisfaction were inconclusive because of the uniformly high satisfaction reported by the patients. The mechanism of reinnervation appears to come both from the skin margins and from the deep surface of the flap. Future developments in breast reconstruction should take into consideration the eventual quality of sensory return.

Twenty years of the Italian Fanconi Anemia Registry: where we stand and what remains to be learned.

PubMed

Risitano, Antonio M; Marotta, Serena; Calzone, Rita; Grimaldi, Francesco; Zatterale, Adriana

2016-03-01

The natural history of Fanconi anemia remains hard to establish because of its rarity and its heterogeneous clinical presentation; since 1994, the Italian Fanconi Anemia Registry has collected clinical, epidemiological and genetic data of Italian Fanconi Anemia patients. This registry includes 180 patients with a confirmed diagnosis of Fanconi anemia who have either been enrolled prospectively, at diagnosis, or later on. After enrollment, follow-up data were periodically collected to assess the clinical course, possible complications and long-term survival; the median follow up was 15.6 years. The main goal of the study was to describe the natural history of Fanconi anemia, focusing on the following variables: family history, disease presentation, development of hematological manifestations, development of malignancies, occurrence of hematopoietic stem cell transplantation and survival. Typical morphological and/or hematological abnormalities and/or growth retardation were the most common manifestations at diagnosis; the majority of patients (77%) exhibited hematological abnormalities at the initial presentation, and almost all (96%) eventually developed hematological manifestations. More than half of the patients (57%) underwent a bone-marrow transplant. The occurrence of cancer was quite rare at diagnosis, whereas the cumulative incidence of malignancies at 10, 20 and 30 years was 5%, 8% and 22%, respectively, for hematological cancers and 1%, 15% and 32%, respectively, for solid tumors. Overall survival at 10, 20 and 30 years were 88%, 56% and 37%, respectively; the main causes of death were cancer, complications of the hematological presentation and complications of transplantation. These data clearly confirm the detrimental outcome of Fanconi anemia, with no major improvement in the past decades. Copyright© Ferrata Storti Foundation.

The Onset of Type 2 Diabetes: Proposal for a Multi-Scale Model

PubMed Central

Tieri, Paolo; De Graaf, Albert; Franceschi, Claudio; Liò, Pietro; Van Ommen, Ben; Mazzà, Claudia; Tuchel, Alexander; Bernaschi, Massimo; Samson, Clare; Colombo, Teresa; Castellani, Gastone C; Capri, Miriam; Garagnani, Paolo; Salvioli, Stefano; Nguyen, Viet Anh; Bobeldijk-Pastorova, Ivana; Krishnan, Shaji; Cappozzo, Aurelio; Sacchetti, Massimo; Morettini, Micaela; Ernst, Marc

2013-01-01

Background Type 2 diabetes mellitus (T2D) is a common age-related disease, and is a major health concern, particularly in developed countries where the population is aging, including Europe. The multi-scale immune system simulator for the onset of type 2 diabetes (MISSION-T2D) is a European Union-funded project that aims to develop and validate an integrated, multilevel, and patient-specific model, incorporating genetic, metabolic, and nutritional data for the simulation and prediction of metabolic and inflammatory processes in the onset and progression of T2D. The project will ultimately provide a tool for diagnosis and clinical decision making that can estimate the risk of developing T2D and predict its progression in response to possible therapies. Recent data showed that T2D and its complications, specifically in the heart, kidney, retina, and feet, should be considered a systemic disease that is sustained by a pervasive, metabolically-driven state of inflammation. Accordingly, there is an urgent need (1) to understand the complex mechanisms underpinning the onset of this disease, and (2) to identify early patient-specific diagnostic parameters and related inflammatory indicators. Objective We aim to accomplish this mission by setting up a multi-scale model to study the systemic interactions of the biological mechanisms involved in response to a variety of nutritional and metabolic stimuli and stressors. Methods Specifically, we will be studying the biological mechanisms of immunological/inflammatory processes, energy intake/expenditure ratio, and cell cycle rate. The overall architecture of the model will exploit an already established immune system simulator as well as several discrete and continuous mathematical methods for modeling of the processes critically involved in the onset and progression of T2D. We aim to validate the predictions of our models using actual biological and clinical data. Results This study was initiated in March 2013 and is expected to be completed by February 2016. Conclusions MISSION-T2D aims to pave the way for translating validated multilevel immune-metabolic models into the clinical setting of T2D. This approach will eventually generate predictive biomarkers for this disease from the integration of clinical data with metabolic, nutritional, immune/inflammatory, genetic, and gut microbiota profiles. Eventually, it should prove possible to translate these into cost-effective and mobile-based diagnostic tools. PMID:24176906

[Intrathecal baclofen therapy for spastic paraparesis due to aortic dissecting aneurysm; recent progress in treatment strategy].

PubMed

Nakajima, T; Akagawa, H; Ochiai, T; Hayashi, M; Goto, S; Taira, T; Okada, Y

2009-11-01

A 48-year-old man suffered from acute dissection of thoracic aortic aneurysm which eventually led to replacement of the ascending aorta with a tube graft. During this clinical course, circulatory failure in intercostal artery resulted in spinal cord infarction followed by moto-sensory disturbance below Th7 dermatomic area. Seven months later, spasticity with pain in both lower extremities became conspicuous that was uncontrollable by any oral medication. Eventually the patient underwent the implantation of continuous infusion pump for intrathecal baclofen therapy (ITB). The clinical condition was remarkably improved and now has been well controlled. ITB, authorized by Japanese Ministry of Health Labour and Welfare in 2006, has notable therapeutic effects on spasticity derived from any sort of central nervous disorder. More promotive enlightenment if ITB is indispensable for enhancement of its medical benefit in Japan.

Everolimus affects vasculogenic mimicry in renal carcinoma resistant to sunitinib

PubMed Central

Serova, Maria; Tijeras-Raballand, Annemilaï; Santos, Celia Dos; Martinet, Matthieu; Neuzillet, Cindy; Lopez, Alfred; Mitchell, Dianne C.; Bryan, Brad A.; Gapihan, Guillaume; Janin, Anne; Bousquet, Guilhem; Riveiro, Maria Eugenia; Bieche, Ivan; Faivre, Sandrine

2016-01-01

Angiogenesis is hallmark of clear cell renal cell carcinogenesis. Anti-angiogenic therapies have been successful in improving disease outcome; however, most patients treated with anti-angiogenic agents will eventually progress. In this study we report that clear cell renal cell carcinoma was associated with vasculogenic mimicry in both mice and human with tumor cells expressing endothelial markers in the vicinity of tumor vessels. We show that vasculogenic mimicry was efficiently targeted by sunitinib but eventually associated with tumor resistance and a more aggressive phenotype both in vitro and in vivo. Re-challenging these resistant tumors in mice, we showed that second-line treatment with everolimus particularly affected vasculogenic mimicry and tumor cell differentiation compared to sorafenib and axitinib. Finally, our results highlighted the phenotypic and genotypic changes at the tumor cell and microenvironment levels during sunitinib response and progression and the subsequent improvement second-line therapies bring to the current renal cell carcinoma treatment paradigm. PMID:27509260

[Staging gastritis with the OLGA system: prevalence of advanced stages of gastric atrophy in Mexican patients].

PubMed

Ramírez-Mendoza, P; Ruiz-Castillo, S A; Maroun-Marun, C; Trujillo-Benavides, O; Baltazar-Montúfar, P; Méndez del Monte, R; Angeles-Garay, U

2011-01-01

Gastric adenocarcinoma of intestinal type is preceded by inflammation, which produces mucosal atrophy and intestinal metaplasia, progressing eventually to dysplasia and invasive cancer. Recently an international group, the Operative Link on Gastritis Assessment (OLGA) proponed a staging system for gastric biopsies. To recognize the distribution of advanced stages of gastric mucosal atrophy in Mexican patients with dyspepsia according to the OLGA system. We apply the OLGA system for cancer risk (Stages 0 to IV) to 322 gastric biopsies from consecutive patients with dyspepsia. Using the Sydney protocol, we recorded the presence of atrophy, dysplasia and the relationship with ulcer disease. We report the stage of atrophy for each region and the Helicobacter pylori infection status. We documented 72 (22.4%) cases with atrophy, 50 of them (69.4%) were metaplastic-type. Overall, nine biopsies (2.78%) were stage III (all of them with metaplastic-type atrophy) and there was not stage IV cases. We did not find high-grade dysplasia or intramucosal carcinoma. In 8 of subjects with stage III, we observed low-grade dysplasia. We documented gastric ulcer in 5 patients with stage II, 60% of them with associated low-grade dysplasia. Five patients with duodenal ulcer were found in stages 0 and I. We found low prevalence of advanced stages of mucosal gastric atrophy among patients with dyspepsia. However we recognized 9 patients with stage III according to OLGA system worthy of follow-up because the high risk for developing gastric cancer.

The effect of silicone implants on the diagnosis, prognosis, and treatment of breast cancer.

PubMed

Handel, Neal

2007-12-01

Because of the prevalence of breast cancer, many augmented women eventually will develop the disease. This article reviews what is known about the effect of implants on the detection, prognosis, and treatment of carcinoma of the breast. Observations were made on 4082 breast cancer patients (3953 nonaugmented and 129 augmented) treated over a 23-year time span. Findings in the two groups were compared and differences analyzed statistically. Mammograms of all women with palpable lesions were reviewed to assess mammographic sensitivity in patients with and without implants. Cosmetic outcomes in augmented patients treated with breast conservation therapy were reviewed. Augmented patients presented more frequently with palpable lesions, invasive tumors, axillary nodal metastases, and false-negative mammograms. However, there was no significant difference in stage of disease, tumor size, recurrence rates, or survival between the two groups. Augmented patients treated with breast conservation therapy often experienced poor cosmetic results and frequently required reoperation. Despite the diminished sensitivity of mammography in women with implants, augmented and nonaugmented patients are diagnosed at a similar stage of disease and have a comparable prognosis. Implants may impair mammography but appear to facilitate tumor detection on physical examination. Magnetic resonance imaging and breast ultrasound may be useful adjuncts, but conventional mammography remains the most reliable tool for diagnosing early breast cancer in augmented patients. Breast implants do not interfere with mastectomy or breast reconstruction but may compromise the outcome of breast conservation therapy.

A Dose Escalation and Pharmacodynamic Study of Triapine and Radiation in Patients With Locally Advanced Pancreas Cancer

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

Martin, Ludmila Katherine; Grecula, John; Jia, Guang

2012-11-15

Purpose: Triapine, a novel inhibitor of the M2 subunit of ribonucleotide reductase (RR), is a potent radiosensitizer. This phase 1 study, sponsored by the National Cancer Institute Cancer Therapy Evaluation Program, assessed the safety and tolerability of triapine in combination with radiation (RT) in patients with locally advanced pancreas cancer (LAPCA). Methods and Materials: We evaluated 3 dosage levels of triapine (24 mg/m{sup 2}, 48 mg/m{sup 2}, 72 mg/m{sup 2}) administered with 50.4 Gy of RT in 28 fractions. Patients with LAPCA received triapine thrice weekly, every other week during the course of RT. Dose-limiting toxicity (DLT) was assessed duringmore » RT and for 4 weeks after its completion. Dynamic contrast-enhanced magnetic resonance imaging and serum RR levels were evaluated as potential predictors for early response. Results: Twelve patients were treated. Four patients (1 nonevaluable) were enrolled at dosage level 1 (DL1), 3 patients at DL2, and 5 patients (2 nonevaluable) at DL3. No DLTs were observed, and the maximum tolerated dose was not reached. Two patients (17%) achieved partial response, and 6 patients (50%) had stable disease. One patient underwent R0 resection after therapy. Ninety-two percent of patients (100% at DL3) experienced freedom from local tumor progression. In 75% of patients who eventually experienced progression, metastases developed without local progression. RR levels did not seem to predict outcome. In 4 patients with available data, dynamic contrast-enhanced magnetic resonance imaging may predict early response or resistance to therapy. Conclusion: The combination of triapine at 72 mg/m{sup 2} 3 times weekly every other week and standard RT is tolerable with interesting activity in patients with LAPCA.« less

Renal impairment in stroke patients: A comparison between the haemorrhagic and ischemic variants.

PubMed

Shrestha, Pratyush; Thapa, Shalima; Shrestha, Shikher; Lohani, Subash; Bk, Suresh; MacCormac, Oscar; Thapa, Lekhjung; Devkota, Upendra Prasad

2017-01-01

Background: Renal impairment is regularly seen in hospitalized stroke patients, affecting the outcome of patients, as well as causing difficulties in their management. A prospective cohort study was conducted to assess the trend of renal function in hospitalized ischemic and haemorrhagic stroke patients. The incidence of renal impairment in these subgroups, the contributing factors and the need for renal replacement in renal impaired patients was evaluated. Methods: Alternate day renal function testing was performed in hospitalized stroke patients. Estimated glomerular filtration rate (e-GFR) was calculated and the trend of renal function in the two stroke subgroups (haemorrhagic and ischemic) was assessed, with renal impairment defined as e-GFR < 60mL/ minute per 1.73m 2 . Results: Among 52 patients, 25 had haemorrhagic stroke (mean age 59.81 ± 14.67) and 27 had ischemic stroke (mean age 56.12 ± 13.08). The mean e-GFR (mL/minute per 1.732m 2 ) at admission in the haemorrhagic stroke subgroup was 64.79 ± 25.85 compared to 86.04 ± 26.09 in the ischemic stroke subgroup (p=0.005). Sixteen out of 25 (64%) patients in the haemorrhagic stroke subgroup and 9 out of 27 (33.3%) patients in the ischemic subgroup developed renal impairment (p=0.027). The location of the bleed (p=0.8), volume of hematoma (p=0.966) and surgical intervention (p=0.4) did not predispose the patients to renal impairment. One out of 16 patients with haemorrhagic stroke (who eventually died), and 2 out of 9 patients with ischemic stroke required renal replacement. Conclusion : Renal impairment is commonly seen in stroke patients, more so in patients who suffered haemorrhagic strokes.  The impairment, however, is transient and rarely requires renal replacement therapy.

An Algorithmic Approach to Operative Management of Complex Pediatric Dog Bites: 3-Year Review of a Level I Regional Referral Pediatric Trauma Hospital

PubMed Central

Shayesteh, Ali; Xu, Min Li

2017-01-01

Background: Incidence of dog bites continues to rise among the pediatric population and serves as a public health threat for the well-being of children. Plastic surgeons are at the forefront of initial management and eventual outcome of these devastating injuries. This study set out to determine the nature of dog bite injuries treated over a 3-year period at a large level 1 pediatric trauma center. Methods: A retrospective review of emergency room records of all pediatric patients (age, 0–18 years old) who sustained dog bites between January 2012 and December 2014 were gathered. All details about age of patient, location and severity of dog bites, type of dog breed, antibiotics given, and emergency versus operative treatment were recorded and analyzed. Results: One hundred eight patients aged 5 months to 18 years old were treated in the emergency department after suffering dog bite injuries during the study period. The highest incidence of dog bites occurred in preschool children. The mean age for patients who required operative repair was lower than the mean age for patients who underwent primary closure in the emergency department. The location of injury was most commonly isolated to the head/neck region. Of the 56 cases that had an identified dog breed, pit bulls accounted for 48.2% of the dog bites, and 47.8% of pit bull bites required intervention in the operating room. Conclusion: Children with large dog bite injuries require more immediate care in a level 1 pediatric trauma hospitals in order to optimize their hospitalization course and eventual outcome. PMID:29184724

Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia.

PubMed

Palm, Catrin; Pistrosch, Frank; Herbrig, Kay; Gross, Peter

2006-07-01

Hyponatremia is the most frequent electrolyte disorder encountered in hospitalized patients. It is a state of relative water excess due to stimulated arginine vasopressin (AVP) and fluid intake greater than obligatory losses. This kind of hyponatremia occurs in the syndrome of inappropriate antidiuretic hormone secretion, congestive heart failure, and liver cirrhosis. Fluid restriction is the presently recommended treatment for hyponatremia. However, fluid restriction may be very difficult for patients to achieve, is slow to work, and does not allow a graded therapeutic approach. More efficient and specific treatments of hyponatremia are needed. In this respect, pharmacologic research has yielded a number of compounds exhibiting antagonistic qualities at the vasopressin V2 receptor. Among these agents, peptidic derivatives of AVP turned out to have intrinsic antidiuretic properties in vivo when given over days or weeks. The development of such agents for use in patients has not been pursued. However, several promising nonpeptide, vasopressin receptor antagonists have been described; these agents are VPA-985 (lixivaptan), YM-087 (conivaptan), OPC-41061 (tolvaptan), and SR-121463. Prospective, randomized, placebo-controlled trials performed with these agents found that they corrected hyponatremia efficiently and safely. Most of the studies were conducted over a 4- to 28-day period. Long-term studies will be needed in the future to address such issues as the eventual benefit to patients and the effects of vasopressin antagonists on morbidity and mortality of patients with hyponatremia.

Veno-venous extracorporeal membrane oxygenation using a double-lumen bi-caval cannula for severe respiratory failure post total artificial heart implantation.

PubMed

Miessau, J; Yang, Q; Unai, S; Entwistle, J W C; Cavarocchi, N C; Hirose, H

2015-07-01

We report a unique utilization of a double-lumen, bi-caval Avalon cannula for veno-venous (VV) extracorporeal membrane oxygenation (ECMO) during placement of a total artificial heart (TAH, SynCardia, Tucson, AZ). A 22-year-old female with post-partum cardiomyopathy was rescued on veno-arterial (VA) ECMO because of cardiogenic shock. The inability to wean ECMO necessitated implantation of the TAH as a bridge to transplant. In addition, the patient continued to have respiratory failure and concomitant VV ECMO was planned with the implant. During TAH implantation, the Avalon cannula was placed percutaneously from the right internal jugular vein into the inferior vena cava (IVC) under direct vision while the right atrium was open. During VV ECMO support, adequate flows on both ECMO and TAH were maintained without adverse events. VV ECMO was discontinued, without reopening the chest, once the patient's respiratory failure improved. However, the patient subsequently developed a profound respiratory acidosis and required VV ECMO for CO2 removal. The Avalon cannula was placed in the femoral vein to avoid accessing the internal jugular vein and risking damage to the TAH. The patient's oxygenation eventually improved and the cannula was removed at the bedside. The patient was supported for 22 days on VV ECMO and successfully weaned from the ventilator prior to her orthotropic heart transplantation. © The Author(s) 2014.

A Rare Case of Psychomotor Disturbances Linked to the Use of an Adulterated Dietary Supplement Containing Sibutramine.

PubMed

Shapira, Barak; Goldstein, Lee; Reshef, Amikam; Poperno, Alina

2016-01-01

Sibutramine, an oral anorexiant, is often found as an adulterant in various counterfeit herbal slimming products and dietary supplements. The use of sibutramine has been associated with various cardiovascular and psychiatric symptoms. Here, we report a rare case of psychomotor disturbances, in a patient with no previously diagnosed movement disorders. A 26-year-old woman developed abnormal behavior, visual hallucinations, hyperkinesia, facial flushing, and dizziness after taking a counterfeit dietary supplement which contained undeclared sibutramine and phenolphtalein. Laboratory work-up revealed microcytic anemia; leucopenia; and elevated erythrocyte sedimentation rate, C-reactive protein levels, and antistreptolysin O titer, but rheumatic fever was ruled out. After a neurologic examination, involuntary movements were classified as chorea. The psychiatric examination result was unremarkable. The patient responded well to haloperidol therapy. Body temperature, erythrocyte sedimentation rate, and C-reactive protein levels eventually normalized. The patient was discharged. This is the first report we are aware of about a transient, chorea-like psychomotor movement disorder associated with sibutramine. Although the causal relationship between sibutramine and the patient's symptoms cannot be proven definitely, the temporal dimension does suggest sibutramine initiation and termination led to onset and resolution of symptoms, respectively. Furthermore, because of the widespread availability of adulterated food supplements containing sibutramine, physicians should be more aware of their implications for patients.

Centile-based early warning scores derived from statistical distributions of vital signs.

PubMed

Tarassenko, Lionel; Clifton, David A; Pinsky, Michael R; Hravnak, Marilyn T; Woods, John R; Watkinson, Peter J

2011-08-01

To develop an early warning score (EWS) system based on the statistical properties of the vital signs in at-risk hospitalised patients. A large dataset comprising 64,622 h of vital-sign data, acquired from 863 acutely ill in-hospital patients using bedside monitors, was used to investigate the statistical properties of the four main vital signs. Normalised histograms and cumulative distribution functions were plotted for each of the four variables. A centile-based alerting system was modelled using the aggregated database. The means and standard deviations of our population's vital signs are very similar to those published in previous studies. When compared with EWS systems based on a future outcome, the cut-off values in our system are most different for respiratory rate and systolic blood pressure. With four-hourly observations in a 12-h shift, about 1 in 8 at-risk patients would trigger our alerting system during the shift. A centile-based EWS system will identify patients with abnormal vital signs regardless of their eventual outcome and might therefore be more likely to generate an alert when presented with patients with redeemable morbidity or avoidable mortality. We are about to start a stepped-wedge clinical trial gradually introducing an electronic version of our EWS system on the trauma wards in a teaching hospital. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Using stem cell biology to study and treat ophthalmologic and oculoplastic diseases

PubMed Central

Wu, Albert Y.; Daniel, Michael G.

2017-01-01

With the rapid growth of the stem cell biology field, the prospect of regenerative medicine across multiple tissue types comes closer to reality. Several groundbreaking steps paved the way for applying stem cell biology to the several subfields within ophthalmology and oculoplastic surgery. These steps include the use of stem cell transplants as well as studies of various ophthalmologic pathologies at the molecular level. The necessity of stem cell transplant is readily apparent, having already been used for several studies such as artificial lacrimal gland design and eyelid reconstruction. Investigating the stem cell biology behind oncological diseases of the eye has also developed recently, such as with the identification of specific markers to label cancer stem cells in orbital adenoid cystic carcinoma. The advent of induced pluripotent stem cells led to a burst of productivity in the field of regenerative medicine, making it possible to take a patient's own cells, reprogram them, and use them to either study patient-specific pathology in vitro or use them for eventual patient specific therapeutics. Patient-specific adipose-derived stem cells (ASCs) have been used for a variety of treatments, such as wound healing and burn therapies. As the fields of stem cell biology and regenerative medicine continue to progress, its use will become a mainstay of patient-specific cell therapies in the future. PMID:29018761

The management of acute and chronic pancreatitis.

PubMed

Banks, Peter A; Conwell, Darwin L; Toskes, Phillip P

2010-02-01

Pancreatitis, which is most generally described as any inflammation of the pancreas, is a serious condition that manifests in either acute or chronic forms. Chronic pancreatitis results from irreversible scarring of the pancreas, resulting from prolonged inflammation. Six major etiologies for chronic pancreatitis have been identified: toxic/ metabolic, idiopathic, genetic, autoimmune, recurrent and severe acute pancreatitis, and obstruction. The most common symptom associated with chronic pancreatitis is pain localized to the upper-to-middle abdomen, along with food malabsorption, and eventual development of diabetes. Treatment strategies for acute pancreatitis include fasting and short-term intravenous feeding, fluid therapy, and pain management with narcotics for severe pain or nonsteroidal anti-inflammatories for milder cases. Patients with chronic disease and symptoms require further care to address digestive issues and the possible development of diabetes. Dietary restrictions are recommended, along with enzyme replacement and vitamin supplementation. More definitive outcomes may be achieved with surgical or endoscopic methods, depending on the role of the pancreatic ducts in the manifestation of disease.

Temporal characteristics of botulinum neurotoxin therapy

PubMed Central

Lebeda, Frank J; Cer, Regina Z; Stephens, Robert M; Mudunuri, Uma

2010-01-01

Botulinum neurotoxin is a pharmaceutical treatment used for an increasing number of neurological and non-neurological indications, symptoms and diseases. Despite the wealth of clinical reports that involve the timing of the therapeutic effects of this toxin, few studies have attempted to integrate these data into unified models. Secondary reactions have also been examined including the development of adverse events, resistance to repeated applications, and nerve terminal sprouting. Our primary intent for conducting this review was to gather relevant pharmacodynamic data from suitable biomedical literature regarding botulinum neurotoxins via the use of automated data-mining techniques. We envision that mathematical models will ultimately be of value to those who are healthcare decision makers and providers, as well as clinical and basic researchers. Furthermore, we hypothesize that the combination of this computer-intensive approach with mathematical modeling will predict the percentage of patients who will favorably or adversely respond to this treatment and thus will eventually assist in developing the increasingly important area of personalized medicine. PMID:20021324

The HPV Vaccine | Center for Cancer Research

Cancer.gov

Two researchers leveraged CCR’s unique environment of investigator-driven inquiry to pursue studies of two cancer-causing genes that eventually led to the development of a vaccine against two forms of human papillomavirus.

Fingernails Yield Clues to Limb Regeneration

MedlinePlus

... in mice. The findings, published in the journal Nature, could eventually lead to the development of novel ... Nail Epithelium Couples Nail Growth to Digit Regeneration. Nature 2013 Jul 11;499(7457):228-32. doi: ...

An Overview of the Naval Enlisted Professional Development Information System (NEPDIS). Focus on the Trained Person.

ERIC Educational Resources Information Center

Ansbro, Thomas M.

This is the first in a series of reports describing the origin, development, and applications of the Naval Enlisted Professional Development Information System (NEPDIS). The NEPDIS was designed to be a fully computerized information assembly and analysis system that would eventually support manpower, personnel, and training management. This report…

[Patient with B-CLL with a history of unrelated hematopoietic cells donation--retrospective analysis of CLL development and implication for the recipient].

PubMed

Jindra, P; Žejšková, L; Peková, S; Navrátilová, J; Schutzová, M; Vokurka, S; Koza, V

2012-01-01

Donor cell leukemia (DCL) is a relatively rare but well documented complication of hematopoietic stem cell transplantation. So far, publications described only DCL arising de novo in the recipient. In this study, we describe a case of chronic lymphocytic leukemia (B-CLL) developing in a volunteer unrelated donor from the Czech National Marrow Donors Registry (CNMDR) several years after donation. From archival DNA sample, we have retrospectively found that subclinical CLL clone was already present at the time of donation but early death of recipient prevented eventual development of DCL. This case documents well the long period between detection of B-CLL clone and full development of clinical-laboratory symptomatology. The medical and ethical questions posed by an isolated case of detection of hematological malignancy present either only in the donor or only in the recipient are discussed. The case demonstrates the increasing risk of development of various forms of DCL and thus highlights the need for long-term monitoring of stem cell donor, not only in terms of health of donor but also in terms of potential risks for the recipient.

Protecting the normal in order to better kill the cancer

PubMed Central

Liu, Bingya; Ezeogu, Lewis; Zellmer, Lucas; Yu, Baofa; Xu, Ningzhi; Joshua Liao, Dezhong

2015-01-01

Chemotherapy is the only option for oncologists when a cancer has widely spread to different body sites. However, almost all currently available chemotherapeutic drugs will eventually encounter resistance after their initial positive effect, mainly because cancer cells develop genetic alterations, collectively coined herein as mutations, to adapt to the therapy. Some patients may still respond to a second chemo drug, but few cases respond to a third one. Since it takes time for cancer cells to develop new mutations and then select those life-sustaining ones via clonal expansion, “run against time for mutations to emerge” should be a crucial principle for treatment of those currently incurable cancers. Since cancer cells constantly change to adapt to the therapy whereas normal cells are stable, it may be a better strategy to shift our focus from killing cancer cells per se to protecting normal cells from chemotherapeutic toxicity. This new strategy requires the development of new drugs that are nongenotoxic and can quickly, in just hours or days, kill cancer cells without leaving the still-alive cells with time to develop mutations, and that should have their toxicities confined to only one or few organs, so that specific protections can be developed and applied. PMID:26177855

Telerehabilitation for patients with heart failure.

PubMed

Tousignant, Michel; Mampuya, Warner Mbuila

2015-02-01

Heart failure is a chronic and progressive condition that is associated with high morbidity and mortality rates. Even though cardiac rehabilitation (CR) has been shown to be beneficial to heart failure patients, only a very small proportion of them will actually be referred and eventually participate. The low participation rate is due in part to accessibility and travel difficulties. Telerehabilitation is a new approach in the rehabilitation field that allows patients to receive a complete rehabilitation program at home in a safe manner and under adequate supervision. We believe that by increasing accessibility to CR, telerehabilitation programs will significantly improve heart failure patients' functional capacity and quality of life. However, it is crucial to provide policy makers with evidence-based data on cardiac telerehabilitation if we want to see its successful implementation in heart failure patients.

Extracorporeal shock wave lithotripsy for obstructing pancreatic duct calculi.

PubMed

Matthews, K; Correa, R J; Gibbons, R P; Weissman, R M; Kozarek, R A

1997-08-01

A review was done to determine the effectiveness of extracorporeal shock wave lithotripsy (ESWL) in the treatment of impacted pancreatic duct calculi. A total of 19 patients, who were potential candidates for radical pancreatic surgery after unsuccessful endoscopic retrograde cholangiopancreatography, sphincterotomy and attempted stone extraction from the pancreatic ducts, underwent ESWL of the calculi. Followup ranged from 6 months to 6 years. Of the 19 patients 14 avoided a major operation and 6 have remained pain-free for the long term. Two patients died of causes not related to ESWL or endoscopic retrograde cholangiopancreatography. Five patients eventually underwent a Whipple or Puestow procedure for relief of symptoms or persistent obstruction. Complications were minimal. ESWL is a valuable adjunct in patients with impacted pancreatic duct calculi unretrievable by primary endoscopic retrograde cholangiopancreatography.

A comparative analysis of high-speed rail station development into destination and multi-use facilities : the case of San Jose Diridon.

DOT National Transportation Integrated Search

2017-02-01

As a burgeoning literature on high-speed rail development indicates, good station-area planning is a very important prerequisite for the eventual successful operation of a high-speed rail station; it can also trigger opportunities for economic develo...

METHODS DEVELOPMENT AT THE NEAR LAB ECOLOGICAL RESEARCH AREA (NLERA) LOCATED IN THE NEUSE RIVER BASIN.

EPA Science Inventory

This task supports the Agency's efforts on developing a proper risk assessment tools to address Ecological and eventually Human exposures. The Agency needs to be able to identify, measure and estimate ecosystem exposure to multiple stressors. The research under this task suppor...

ERTS-A: a new apogee for mineral finding

USGS Publications Warehouse

Carter, William D.

1971-01-01

The EROS Program will continue investigations to select or develop optimum, economical airborne and space systems that will expand man's ability to observe and profit from natural resources. It is to be hoped that several of these systems will eventually prove useful supplements to current and developing mineral exploration technology.

A medical oncologist's approach to immunotherapy for advanced renal tumors: is nephrectomy indicated?

PubMed

Cooney, Matthew M; Remick, Scot C; Vogelzang, Nicholas J

2004-02-01

Metastatic renal cell carcinoma is highly resistant to systemic therapy. Although interleukin-2 and interferon remain the most active agents for this disease, long-term survival rates remain poor. Two phase 3 trials, European Organization Research and Treatment of Cancer 30947 and Southwest Oncology Group 8949, have demonstrated a survival benefit of nephrectomy followed by interferon versus interferon alone in patients having an excellent performance status (PS 0 and 1). Removal of the primary tumor followed by interferon is not recommended for patients with a moderate or poor PS (PS 2-4). Even with this aggressive approach, most patients eventually will die from their kidney cancer; therefore, every patient with metastatic disease should be considered for enrollment into clinical trials.

Bridging the gap. The separate worlds of evidence-based medicine and patient-centered medicine.

PubMed

Bensing, J

2000-01-01

Modern medical care is influenced by two paradigms: 'evidence-based medicine' and 'patient-centered medicine'. In the last decade, both paradigms rapidly gained in popularity and are now both supposed to affect the process of clinical decision making during the daily practice of physicians. However, careful analysis shows that they focus on different aspects of medical care and have, in fact, little in common. Evidence-based medicine is a rather young concept that entered the scientific literature in the early 1990s. It has basically a positivistic, biomedical perspective. Its focus is on offering clinicians the best available evidence about the most adequate treatment for their patients, considering medicine merely as a cognitive-rational enterprise. In this approach the uniqueness of patients, their individual needs and preferences, and their emotional status are easily neglected as relevant factors in decision-making. Patient-centered medicine, although not a new phenomenon, has recently attracted renewed attention. It has basically a humanistic, biopsychosocial perspective, combining ethical values on 'the ideal physician', with psychotherapeutic theories on facilitating patients' disclosure of real worries, and negotiation theories on decision making. It puts a strong focus on patient participation in clinical decision making by taking into account the patients' perspective, and tuning medical care to the patients' needs and preferences. However, in this approach the ideological base is better developed than its evidence base. In modern medicine both paradigms are highly relevant, but yet seem to belong to different worlds. The challenge for the near future is to bring these separate worlds together. The aim of this paper is to give an impulse to this integration. Developments within both paradigms can benefit from interchanging ideas and principles from which eventually medical care will benefit. In this process a key role is foreseen for communication and communication research.

Heart rate variability in epilepsy: A potential biomarker of sudden unexpected death in epilepsy risk.

PubMed

Myers, Kenneth A; Bello-Espinosa, Luis E; Symonds, Joseph D; Zuberi, Sameer M; Clegg, Robin; Sadleir, Lynette G; Buchhalter, Jeffrey; Scheffer, Ingrid E

2018-06-06

Sudden unexpected death in epilepsy (SUDEP) is a tragic and devastating event for which the underlying pathophysiology remains poorly understood; this study investigated whether abnormalities in heart rate variability (HRV) are linked to SUDEP in patients with epilepsy due to mutations in sodium channel (SCN) genes. We retrospectively evaluated HRV in epilepsy patients using electroencephalographic studies to study the potential contribution of autonomic dysregulation to SUDEP risk. We extracted HRV data, in wakefulness and sleep, from 80 patients with drug-resistant epilepsy, including 40 patients with mutations in SCN genes and 40 control patients with non-SCN drug-resistant epilepsy. From the SCN group, 10 patients had died of SUDEP. We compared HRV between SUDEP and non-SUDEP groups, specifically studying awake HRV and sleep:awake HRV ratios. The SUDEP patients had the most severe autonomic dysregulation, showing lower awake HRV and either extremely high or extremely low ratios of sleep-to-awake HRV in a subgroup analysis. A secondary analysis comparing the SCN and non-SCN groups indicated that autonomic dysfunction was slightly worse in the SCN epilepsy group. These findings suggest that autonomic dysfunction is associated with SUDEP risk in patients with epilepsy due to sodium channel mutations. The relationship of HRV to SUDEP merits further study; HRV may eventually have potential as a biomarker of SUDEP risk, which would allow for more informed counseling of patients and families, and also serve as a useful outcome measure for research aimed at developing therapies and interventions to reduce SUDEP risk. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Dissociative identity disorder and the process of couple therapy.

PubMed

Macintosh, Heather B

2013-01-01

Couple therapy in the context of dissociative identity disorder (DID) has been neglected as an area of exploration and development in the couple therapy and trauma literature. What little discussion exists focuses primarily on couple therapy as an adjunct to individual therapy rather than as a primary treatment for couple distress and trauma. Couple therapy researchers have begun to develop adaptations to provide effective support to couples dealing with the impact of childhood trauma in their relationships, but little attention has been paid to the specific and complex needs of DID patients in couple therapy (H. B. MacIntosh & S. Johnson, 2008 ). This review and case presentation explores the case of "Lisa," a woman diagnosed with DID, and "Don," her partner, and illustrates the themes of learning to communicate, handling conflicting needs, responding to child alters, and addressing sexuality and education through their therapy process. It is the hope of the author that this discussion will renew interest in the field of couple therapy in the context of DID, with the eventual goal of developing an empirically testable model of treatment for couples.

Development, Feasibility, and Small-Scale Implementation of a Web-Based Prognostic Tool—Surveillance, Epidemiology, and End Results Cancer Survival Calculator

PubMed Central

2017-01-01

Background Population datasets and the Internet are playing an ever-growing role in the way cancer information is made available to providers, patients, and their caregivers. The Surveillance, Epidemiology, and End Results Cancer Survival Calculator (SEER*CSC) is a Web-based cancer prognostic tool that uses SEER data, a large population dataset, to provide physicians with highly valid, evidence-based prognostic estimates for increasing shared decision-making and improving patient-provider communication of complex health information. Objective The aim of this study was to develop, test, and implement SEER*CSC. Methods An iterative approach was used to develop the SEER*CSC. Based on input from cancer patient advocacy groups and physicians, an initial version of the tool was developed. Next, providers from 4 health care delivery systems were recruited to do formal usability testing of SEER*CSC. A revised version of SEER*CSC was then implemented in two health care delivery sites using a real-world clinical implementation approach, and usage data were collected. Post-implementation follow-up interviews were conducted with site champions. Finally, patients from two cancer advocacy groups participated in usability testing. Results Overall feedback of SEER*CSC from both providers and patients was positive, with providers noting that the tool was professional and reliable, and patients finding it to be informational and helpful to use when discussing their diagnosis with their provider. However, use during the small-scale implementation was low. Reasons for low usage included time to enter data, not having treatment options in the tool, and the tool not being incorporated into the electronic health record (EHR). Patients found the language in its current version to be too complex. Conclusions The implementation and usability results showed that participants were enthusiastic about the use and features of SEER*CSC, but sustained implementation in a real-world clinical setting faced significant challenges. As a result of these findings, SEER*CSC is being redesigned with more accessible language for a public facing release. Meta-tools, which put different tools in context of each other, are needed to assist in understanding the strengths and limitations of various tools and their place in the clinical decision-making pathway. The continued development and eventual release of prognostic tools should include feedback from multidisciplinary health care teams, various stakeholder groups, patients, and caregivers. PMID:28729232

Does a normalizing electroencephalogram in benign childhood epilepsy with centrotemporal spikes abort attention deficit hyperactivity disorder?

PubMed

Schneebaum-Sender, Nira; Goldberg-Stern, Hadassa; Fattal-Valevski, Aviva; Kramer, Uri

2012-10-01

This retrospective study delineated the efficacy of antiepileptic drugs in preventing the need for methylphenidate in patients with benign childhood epilepsy with centrotemporal spikes and attention deficit hyperactivity disorder. Seventeen patients were identified. A reduction of electroencephalogram pathologic activity by more than 50% was achieved in some patients with the antiepileptic drugs levetiracetam, sulthiame, lamotrigine, clobazam, and valproic acid. Complete normalization was achieved in two patients with sulthiame. Improvement in attention along with the reduction of pathologic electroencephalogram activity was observed in four patients, two with sulthiame, and one each with lamotrigine and levetiracetam (which was ceased because of suicidal tendencies). However, this improvement in attention was either temporary or not significant enough to discontinue methylphenidate. Methylphenidate was eventually prescribed to all patients. Copyright © 2012 Elsevier Inc. All rights reserved.

A rapid method of toilet training the institutionalized retarded1

PubMed Central

Azrin, N. H.; Foxx, R. M.

1971-01-01

Incontinence is a major unsolved problem in the institutional care of the profoundly retarded. A reinforcement and social analysis of incontinence was used to develop a procedure that would rapidly toilet train retardates and motivate them to remain continent during the day in their ward setting. Nine profoundly retarded adults were given intensive training (median of four days per patient), the distinctive features of which were artificially increasing the frequency of urinations, positive reinforcement of correct toileting but a delay for “accidents”, use of new automatic apparatus for signalling elimination, shaping of independent toileting, cleanliness training, and staff reinforcement procedures. Incontinence was reduced immediately by about 90% and eventually decreased to near-zero. These results indicate the present procedure is an effective, rapid, enduring, and administratively feasible solution to the problem of incontinence of the institutionalized retarded. PMID:16795291

Dedifferentiated liposarcoma of the lower extremity with low-grade dedifferentiation and low-grade osteosarcomatous component.

PubMed

Zajicek, Anna K; Bridge, Julia A; Akers, Joshua W; McGarry, Sean V; Walker, Craig W

2017-02-01

Dedifferentiated liposarcoma can arise de novo or as a complication of a preexisting well-differentiated liposarcoma. We describe the radiologic and pathologic features of a long-standing liposarcoma with multiple recurrences in a 59-year-old male. Imaging demonstrated a heterogeneous fat-containing mass in the anterior thigh. The adjacent proximal femur showed irregular cortical new bone, eventually followed by intramedullary osteoblastic involvement and pathologic fracture. Histologic assessment at resection revealed dedifferentiated liposarcoma with low-grade osteosarcomatous component. The patient subsequently developed metastatic lesions in the lungs containing osteoid and osteoblastic bone metastases. We discuss the radiologic and pathologic features of this rare entity that, to our knowledge, has previously been reported to directly involve osseous structures in only one other case and discuss the potential pitfalls in diagnosis.

‘Subarachnoid cyst’ after evacuation of chronic subdural hematoma: Case report of an unusual postoperative morbidity

PubMed Central

Sharon, Low Y. Y.; Wai Hoe, NG

2016-01-01

Burr-hole drainage of chronic subdural hematomas are routine operative procedures done by neurosurgical residents. Common postoperative complications include acute epidural and/or subdural bleeding, tension pneumocephalus, intracranial hematomas and ischemic cerebral infarction. We report an interesting post-operative complication of a ‘subarachnoid cyst’ after burr-hole evacuation of a chronic subdural hematoma. The authors hypothesize that the ‘cyst’ is likely secondary to the splitting of the adjacent neomembrane within its arachnoid-brain interface by iatrogenic irrigation of the subdural space. Over time, this ‘cyst’ develops into an area of gliosis which eventually causes long-term scar epilepsy in the patient. As far as we are aware, this is the first complication of such a ‘subarachnoid cyst’ post burr-hole drainage reported in the literature. PMID:27366276

Cryosurgery and laser surgery in the treatment of malignant and benign laryngeal processes.

PubMed

Miehlke, A; Chilla, R; Vollrath, M

1979-01-01

Cryosurgery of the larynx is still in the stage of development. In the treatment of laryngeal papillomas cryosurgery has been quite successful. The use of cryosurgery in laryngo-hypopharyngeal carcinoma and in laryngeal stenosis is still restricted to special indications (old age, risk patients). A combination of cryosurgery and telecobalt irradiation has proven valuable in the management of tumors. After the basic physics of laser radiation are explained, the principle mechanisms of interaction between the CO2 laser on human tissue are mentioned. This is followed by the description of the different indications for laser surgery in the larynx. A chordectomy and the opening of a subglottic stenosis with the laser beam are described and documented with photographs. Finally, there is an outlook to an eventually broader spectrum of indications for laser surgery in the field of ent.

Synthesis and biological evaluation of guanylhydrazone coactivator binding inhibitors for the estrogen receptor.

PubMed

LaFrate, Andrew L; Gunther, Jillian R; Carlson, Kathryn E; Katzenellenbogen, John A

2008-12-01

Most patients with hormone-responsive breast cancer eventually develop resistance to traditional antiestrogens such as tamoxifen, and this has become a major obstacle in their treatment. We prepared and characterized the activity of a series of 16 guanylhydrazone small molecules that are designed to block estrogen receptor (ER) activity through a non-traditional mechanism, by directly interfering with coactivator binding to agonist-liganded ER. The inhibitory activity of these compounds was determined in cell-based transcription assays using ER-responsive reporter gene and mammalian two-hybrid assays. Several of the compounds gave IC(50) values in the low micromolar range. Two secondary assays were used to confirm that these compounds were acting through the proposed non-traditional mode of estrogen inhibitory action and not as conventional antagonists at the ligand binding site.

An independent jury-based consensus conference model for the development of recommendations in medico-surgical practice.

PubMed

Lesurtel, Mickaël; Perrier, Arnaud; Bossuyt, Patrick M M; Langer, Bernard; Clavien, Pierre-Alain

2014-03-01

There is an increasing demand for standardization in the choice of treatments for specific conditions, so-called personalized medicine. The task is far from trivial, because the perspectives from many stakeholders must be respected, including patients and health care providers, as well as payers or governments to better control costs while optimizing quality of care. One approach to provide widely accepted therapies is the consensus conference. We describe a novel methodology to achieve consensus in controversial areas with the main goal to minimize biases. The principle of this approach relies on a clear distinction between those who provide the evidence (experts) and those who draw the final recommendations (the jury). The jury consists of individuals with sufficient background knowledge to cover the perspectives of all stakeholders' without being involved directly in the topic under evaluation. The organizing committee, the experts, and the jury interact within 3 phases: Preparation, the actual consensus conference, and deliberations. Each question is addressed by a panel of experts, leading to the proposition of recommendations at the conference meeting, which are challenged by the jury and the audience. Based on all available information, the jury finalizes the consensus recommendations, which are eventually published and made available to all. This novel model of consensus conference allows the construction of consensual, evidence-based, explicit recommendations for therapies in a process that may also identify issues for further research, eventually fostering progress in the field. Copyright © 2014 Mosby, Inc. All rights reserved.

Molecular and cellular mechanisms of aortic stenosis.

PubMed

Yetkin, Ertan; Waltenberger, Johannes

2009-06-12

Calcific aortic stenosis is the most common cause of aortic valve replacement in developed countries, and this condition increases in prevalence with advancing age. The fibrotic thickening and calcification are common eventual endpoint in both non-rheumatic calcific and rheumatic aortic stenoses. New observations in human aortic valves support the hypothesis that degenerative valvular aortic stenosis is the result of active bone formation in the aortic valve, which may be mediated through a process of osteoblast-like differentiation in these tissues. Additionally histopathologic evidence suggests that early lesions in aortic valves are not just a disease process secondary to aging, but an active cellular process that follows the classical "response to injury hypothesis" similar to the situation in atherosclerosis. Although there are similarities with the risk factor and as well as with the process of atherogenesis, not all the patients with coronary artery disease or atherosclerosis have calcific aortic stenosis. This review mainly focuses on the potential vascular and molecular mechanisms involved in the pathogenesis of aortic valve stenosis. Namely extracellular matrix remodeling, angiogenesis, inflammation, and eventually osteoblast-like differentiation resulting in bone formation have been shown to play a role in the pathogenesis of calcific aortic stenosis. Several mediators related to underlying mechanisms, including growth factors especially transforming growth factor-beta1 and vascular endothelial growth factors, angiogenesis, cathepsin enzymes, adhesion molecules, bone regulatory proteins and matrix metalloproteinases have been demonstrated, however the target to be attacked is not defined yet.

Infantile spasms with periventricular nodular heterotopia, unbalanced chromosomal translocation 3p26.2 -10p15.1 and 6q22.31 duplication.

PubMed

Jones, Kevin; Weiss, Shelly K; Minassian, Berge

2016-07-01

Patients presenting with infantile spasms, dysmorphic features, and periventricular nodular heterotopia may benefit from genetic copy number variation microarray, or whole-exome sequencing to identify candidate genes. This will allow personalized diagnosis and prognostication and the eventual understanding of single and combined gene functions in brain health and disease.

Percutaneous tricuspid valvotomy for pacemaker lead-induced tricuspid stenosis

PubMed Central

Patil, Devendra V.; Nabar, Ashish A.; Sabnis, Girish R.; Phadke, Milind S.; Lanjewar, Charan P.; Kerkar, Prafulla G.

2015-01-01

Permanent pacemaker lead-induced tricuspid regurgitation is extremely uncommon. We report a patient with severe tricuspid stenosis detected 10 years after permanent single chamber pacemaker implantation in surgically corrected congenital heart disease. The loop at the level of the tricuspid valve may have caused endothelial injury and eventually led to stenosis. Percutaneous balloon valvotomy for such stenosis has not been reported from India. PMID:26995417

Clinical Spectrum of Disorders of Sexual Differentiation.

PubMed

Rehman, Urooj Lal; Ahsan, Tasnim; Jabeen, Rukhshanda; Zehra, Fatima

2016-03-01

To describe the mode of presentation and causes of the disorders of sexual differentiation in patients presenting in the Endocrine Clinic. Observational study. The Endocrine and Diabetes Unit of Jinnah Postgraduate Medical Centre (JPMC), Karachi, from July 2012 to July 2014. Patients with phenotypic, psychosocial gender confusion or absence of gender appropriate secondary sexual maturation were enrolled in the study. Patients having chronic systemic disease, as cause of delayed puberty, were excluded from the study. SPSS 13 was used to evaluate the data. A total of 48 patients registered in the study with mean age of 19.9 ±8 years. Female gender was assigned to 28 (58.3%) of which 8 (28.57%) had genital ambiguity. Male gender was assigned to 20 (41.66%) patients at the time of birth and 7 (35%) of them had ambiguous genitalia. Karyotyping could be done in 36 (75%) patients of which 17 (47.2%) were females and 19 (52.7%) were males. Karyotypic gender of the 19 (48.57%) male patients was 46 XX, 46 XY and 47 XXY; in 4 (21.05%), 5 (26.3%) and 10 (52.6%) patients, respectively with 9 Klinfelter syndrome. Karyotypic gender of 17 (47.42%) female patients were 46 XX, 46 XY and 45 X0; in 5 (29.4%), 3 (17.64%) and 9 (52.9%) patients, respectively. Disorder of sexual development constitutes a small but difficult area of endocrinology with disastrous consequences, especially if assigned wrong sex at birth. Mode of presentation of these cases was diverse ranging from delayed puberty, to gender confusion, to pregnancy in a male. Eventually in an adult patient assignment or reassignment of gender identity was primarily the patient's prerogative.

Antinuclear antibodies in patients with polymorphic light eruption: a long-term follow-up study.

PubMed

Tzaneva, S; Volc-Platzer, B; Kittler, H; Hönigsmann, H; Tanew, A

2008-05-01

Previous studies have shown elevated titres of antinuclear antibodies (ANA) in 2.9-19% of patients with polymorphic light eruption (PLE). A diagnosis of lupus erythematosus (LE) was finally established in some of these ANA-positive patients. To investigate whether the presence of ANA in patients with PLE merely represents an epiphenomenon or is associated with an increased risk of eventual progression to LE. We identified 472 patients with PLE who had received prophylactic photo(chemo)therapy between 1986 and 2003 and were routinely tested for the presence of ANA. All ANA-positive (ANA titre of>or=1:80) patients were asked to attend for a follow-up examination comprising a medical history, complete skin inspection and a detailed laboratory analysis including ANA and antibodies against extractable nuclear antigens. Of all the patients, 55 (11.7%) were found to be ANA positive on one or several occasions, and three (0.6%) also had antibodies to SS-A/Ro. Thirty-nine (71%) of all ANA-positive patients including all Ro+ subjects were available for follow-up after a median follow-up period of 8 years (interquartile range 5-11.5). Twenty-five patients showed persistence of ANA positivity with a median titre of 1:160 (range 1:80-1:640), whereas in 14 patients ANA titres had returned to normal levels. None of the patients revealed additional clinical, histopathological or laboratory abnormalities suggestive of LE. After a median follow-up period of 8 years none of the ANA-positive patients developed LE. Our findings indicate that PLE is a benign disease without tendency to progress to LE.

Is Hyperinsulinemia a Form of Diabetes?

MedlinePlus

... underlying problem. Hyperinsulinemia is most often caused by insulin resistance — a condition in which your body doesn't ... pancreas tries to compensate by making more insulin. Insulin resistance may eventually lead to the development of type ...

Progress Towards Treatment and Cure of Epidermolysis Bullosa: Summary of the DEBRA International Research Symposium EB2015

PubMed Central

Uitto, Jouni; Tuderman, Leena Bruckner; Christiano, Angela M.; McGrath, John A.; Has, Cristina; South, Andrew P.; Kopelan, Brett; Robinson, E. Clare

2015-01-01

Epidermolysis bullosa (EB), a group of complex heritable blistering diseases, is the topic of triennial research meetings organized by DEBRA International, the umbrella of patient advocacy organizations. The DEBRA 2015 Research Conference, held in May 2015, brought together investigators and clinicians from around the world working at the forefront of EB research. Discussing the state-of-the-art approaches from a wide range of disciplines, there was a palpable excitement at this conference brought about by the optimism about applying new sequencing techniques, genome editing, protein replacement, autologous and allogeneic stem cell therapy, innovations in cancer biology, revertant mosaicism and iPSC techniques, all of which are aimed at developing new therapies for EB. Many in the field who have participated in EB research for many years were especially enthusiastic and felt that, possibly for the first time, the field seems uniquely poised to bring these new tools to effectively tackle EB using multiple complementary approaches towards improved quality of life and eventually a cure for patients suffering from EB, a currently intractable disease. PMID:26802230

Management of inflammatory bowel disease.

PubMed

Nayar, M; Rhodes, J M

2004-04-01

Ulcerative colitis and Crohn's disease result from an interaction between genetic and environmental factors. Only one gene, NOD2/CARD15, has been clearly identified; a minority of people with alteration of this gene develop Crohn's disease. The NOD2/CARD15 protein is thought to be involved in defence against intracellular bacteria. This supports the idea that Crohn's disease and ulcerative colitis result from altered immunological responses to the normal intestinal flora. Life expectancy is normal in ulcerative colitis and nearly so in Crohn's disease, but both conditions cause considerable morbidity. Approximately 80% of patients with Crohn's disease eventually require surgery, and about 25% of patients with ulcerative colitis require colectomy. Treatment of ulcerative colitis is generally by corticosteroids for acute disease and mesalazine for maintenance, but the range of therapies for Crohn's disease is expanding. Alternative therapies include immunosuppressives, enteral nutrition, antibiotics, anti-TNF antibody (infliximab), corticosteroids, and surgery. High dosages of corticosteroids may provide symptomatic relief in Crohn's disease but do not affect the long term natural history of the disease, and management strategies should avoid using steroids whenever possible.

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

The protection of the patient's private life: the computer challenge. Second part.

PubMed

Van Overstraeten, M; Michel, Luc

2002-12-01

Today, medical practice is invaded by a growing number of technologies of all kinds, among which computer techniques have an important place. Although they have significant advantages, for instance in terms of medical record management, they give rise to several problems, particularly concerning the confidentiality of the patient's data with regards to third party. A great number of specific provisions, complementary to the general texts protecting private life (examined in the first part of this two parts article), endeavour to solve these problems. It is true that these provisions are recent, have various origins and often appear as rules difficult to understand. Yet, they are partially inspired by a common logic. Relying on these common features, the authors make two suggestions for the future, in order to avoid that the growing computerisation of medical practice eventually destabilises the health care relationship: a) Any dictatorship of confidentiality must be rejected b) Stimulating a sense of professionalism is most likely the way to avoid an anarchic and unrealistic development of rules aimed at regulating the health care relationship.

Evaluation of a computational model to predict elbow range of motion

PubMed Central

Nishiwaki, Masao; Johnson, James A.; King, Graham J. W.; Athwal, George S.

2014-01-01

Computer models capable of predicting elbow flexion and extension range of motion (ROM) limits would be useful for assisting surgeons in improving the outcomes of surgical treatment of patients with elbow contractures. A simple and robust computer-based model was developed that predicts elbow joint ROM using bone geometries calculated from computed tomography image data. The model assumes a hinge-like flexion-extension axis, and that elbow passive ROM limits can be based on terminal bony impingement. The model was validated against experimental results with a cadaveric specimen, and was able to predict the flexion and extension limits of the intact joint to 0° and 3°, respectively. The model was also able to predict the flexion and extension limits to 1° and 2°, respectively, when simulated osteophytes were inserted into the joint. Future studies based on this approach will be used for the prediction of elbow flexion-extension ROM in patients with primary osteoarthritis to help identify motion-limiting hypertrophic osteophytes, and will eventually permit real-time computer-assisted navigated excisions. PMID:24841799

Respiratory failure in a patient with antecedent poliomyelitis: amyotrophic lateral sclerosis or post-polio syndrome?

PubMed

Terao, Shin-ichi; Miura, Naofumi; Noda, Aiji; Yoshida, Mari; Hashizume, Yoshio; Ikeda, Hiroshi; Sobue, Gen

2006-10-01

We report a 69-year-old man who developed paralytic poliomyelitis in childhood and then decades later suffered from fatal respiratory failure. Six months before this event, he had progressive weight loss and shortness of breath. He had severe muscular atrophy of the entire right leg as a sequela of the paralytic poliomyelitis. He showed mild weakness of the facial muscle and tongue, dysarthria, and severe muscle atrophy from the neck to proximal upper extremities and trunk, but no obvious pyramidal signs. Electromyogram revealed neurogenic changes in the right leg, and in the paraspinal, sternocleidomastoid, and lingual muscles. There was a slight increase in central motor conduction time from the motor cortex to the lumbar anterior horn. Pulmonary function showed restrictive ventilation dysfunction, which was the eventual cause of death. Some neuropathological features were suggestive of amyotrophic lateral sclerosis (ALS), namely Bunina bodies. In patients with a history of paralytic poliomyelitis who present after a long stable period with advanced fatal respiratory failure, one may consider not only respiratory impairment from post-polio syndrome but also the onset of ALS.

Hyperinsulinemic hypoglycemia evolving to gestational diabetes and diabetes mellitus in a family carrying the inactivating ABCC8 E1506K mutation.

PubMed

Vieira, Teresa C; Bergamin, Carla S; Gurgel, Lucimary C; Moisés, Regina S

2010-11-01

Congenital hyperinsulinism of infancy (CHI) is the most common cause of hypoglycemia in newborns and infants. Several molecular mechanisms are involved in the development of CHI, but the most common genetic defects are inactivating mutations of the ABCC8 or KCNJ11 genes. The classical treatment for CHI has been pancreatectomy that eventually leads to diabetes. More recently, conservative treatment has been attempted in some cases, with encouraging results. Whether or not the patients with heterozygous ABCC8 mutations submitted to conservative treatment may spontaneously develop type 2 diabetes in the long run, is a controversial issue. Here, we report a family carrying the dominant heterozygous germ line E1506K mutation in ABCC8 associated with persistent hypoglycemia in the newborn period and diabetes in adulthood. The mutation occurred as a de novo germ line mutation in the mother of the index patient. Her hypoglycemic symptoms as a child occurred after the fourth year of life and were very mild, but she developed glucose metabolism impairment in adulthood. On the other hand, in her daughter, the clinical manifestations of the disease occurred in the neonatal period and were more severe, leading to episodes of tonic-clonic seizures that were well controlled with octreotide or diazoxide. Our data corroborate the hypothesis that the dominant E1506K ABCC8 mutation, responsible for CHI, predisposes to the development of glucose intolerance and diabetes later in life. © 2009 John Wiley & Sons A/S.

CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia.

PubMed

Wang, Jinghua; Chen, Siyu; Xiao, Wei; Li, Wende; Wang, Liang; Yang, Shuo; Wang, Weida; Xu, Liping; Liao, Shuangye; Liu, Wenjian; Wang, Yang; Liu, Nawei; Zhang, Jianeng; Xia, Xiaojun; Kang, Tiebang; Chen, Gong; Cai, Xiuyu; Yang, Han; Zhang, Xing; Lu, Yue; Zhou, Penghui

2018-01-10

Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ζ signaling domain. We further investigate the function of CLL-1 CAR-T cells. The CLL-1 CAR-T cells specifically lysed CLL-1 + cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1 + myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.

Exercise-Induced Neuroprotection of the Nigrostriatal Dopamine System in Parkinson's Disease

PubMed Central

Hou, Lijuan; Chen, Wei; Liu, Xiaoli; Qiao, Decai; Zhou, Fu-Ming

2017-01-01

Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen. Exercise may also minimize DA denervation-induced medium spiny neuron (MSN) dendritic atrophy and other abnormalities such as enlarged corticostriatal synapse and abnormal MSN excitability and spiking activity. Taken together, epidemiological studies, clinical observations, and animal research indicate that appropriately dosed physical activity and exercise may not only reduce the risk of developing PD in vulnerable populations but also benefit PD patients by potentially protecting the residual DA neurons or directly restoring the dysfunctional cortico-basal ganglia motor control circuit, and these benefits may be mediated by exercise-triggered production of endogenous neuroprotective molecules such as neurotrophic factors. Thus, exercise is a universally available, side effect-free medicine that should be prescribed to vulnerable populations as a preventive measure and to PD patients as a component of treatment. Future research needs to establish standardized exercise protocols that can reliably induce DA neuron protection, enabling the delineation of the underlying cellular and molecular mechanisms that in turn can maximize exercise-induced neuroprotection and neurorestoration in animal PD models and eventually in PD patients. PMID:29163139

Changes in laboratory test results and diagnostic imaging presentation before the detection of occupational cholangiocarcinoma.

PubMed

Kubo, Shoji; Takemura, Shigekazu; Sakata, Chikaharu; Urata, Yorihisa; Nishioka, Takayoshi; Nozawa, Akinori; Kinoshita, Masahiko; Hamano, Genya; Nakanuma, Yasuni; Endo, Ginji

2014-01-01

A cholangiocarcinoma outbreak among workers of an offset color proof-printing department in a printing company was recently reported. It is important to understand the clinical course leading to occupational cholangiocarcinoma development for investigation of the carcinogenesis process and for surveillance and early detection. We evaluated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma. We investigated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma in 2 patients because the data were available. Results The clinical courses observed in the 2 participating patients showed persistent elevation of serum γ-glutamyl transpeptidase levels with or without elevated serum levels of alanine aminotransferase and/or aspartate aminotransferase before cholangiocarcinoma detection. Dilatation of the bile ducts without tumor-induced stenosis was observed several years before cholangiocarcinoma detection and progressed gradually in both patients. The serum concentration of carbohydrate 19-9 also increased prior to cholangiocarcinoma detection in both patients. Eventually, observation of stenosis of the bile duct and a space-occupying lesion strongly suggested cholangiocarcinoma. Pathological examination of the resected specimens showed chronic bile duct injury and neoplastic lesions, such as "biliary intraepithelial neoplasia" and "intraductal papillary neoplasm of the bile duct" in various sites of the bile ducts, particularly in the dilated bile ducts. The changes in laboratory test results and diagnostic imaging might be related to the development of cholangiocarcinoma. It is important to monitor diagnostic imaging presentation and laboratory test results in workers with extended exposure to organic solvents.

Rare cancers: Challenges & issues.

PubMed

Pillai, Raveendran K; Jayasree, K

2017-01-01

Rare cancers account for about 22 per cent of all cancers diagnosed worldwide, disproportionately affecting some demographic groups, with an occurrence of less than 6 per 100,000 individuals annually. Many rare cancers in adults, adolescents and children are not curable, and patients and care providers have little option to take therapeutic decisions. The epidemiology of rare cancers is a challenging area of study but is inadequately addressed. Despite efforts mainly in some European nations, a few improvements have been observed in the management of rare cancers. Reasons for this obvious stagnation are multifactorial and are mainly inherent to logistical difficulties in carrying out clinical trials in very small patient populations, hesitation of the pharmaceutical industry to spend in small markets and complexity in creating adequate information for the development of cost-effective drugs. Rare cancers also face specific challenges that include late and incorrect diagnosis, lack of clinical expertise and lack of research interest and development of new therapies. The utilization of nationally representative study findings for the patients' evaluation may possibly offer chances to find out pathogenesis and prevalence, and this will eventually lead to control and prevention. Currently, advancing targeted therapies offer a great opportunity for the better management of rare cancers. Conducting clinical trials with small patient population, innovative clinical trial approach, prevailing controlling obstacles for international cooperation and financial support for research are the present challenges for rare cancers. The International Rare Cancers Initiative functions as a main platform for achieving new international clinical trials in rare tumours. This review delineates the current challenges and issues in the interpretation, management and research scenarios of rare cancers.

Histological transformation after acquired resistance to epidermal growth factor tyrosine kinase inhibitors.

PubMed

Shao, Yi; Zhong, Dian-Sheng

2018-04-01

Non-small-cell lung cancer patients with sensitive epidermal growth factor receptor mutations generally respond well to tyrosine kinase inhibitors (TKIs). However, acquired resistance will eventually develop place after 8-16 months. Several mechanisms contribute to the resistance including T790M mutation, c-Met amplification, epithelial mesenchymal transformation and PIK3CA mutation; however, histological transformation is a rare mechanism. The patterns and mechanisms underlying histological transformation need to be explored. We searched PubMed, EMBASE and search engines Google Scholar, Medical Matrix for literature related to histological transformation. Case reports, cases series, and clinical and basic medical research articles were reviewed. Sixty-one articles were included in this review. Cases of transformation to small-cell lung cancer, squamous cell carcinoma, large-cell neuroendocrine carcinoma and sarcoma after TKI resistance have all been reported. As the clinical course differed dramatically between cases, a new treatment scheme needs to be recruited. The mechanisms underlying histological transformation have not been fully elucidated and probably relate to cancer stem cells, driver genetic alterations under selective pressure or the heterogeneity of the tumor. When TKI resistance develops, we recommend that patients undergo a second biopsy to determine the reason, guide the next treatment and predict the prognosis.

Bilateral cataract formation via acute spontaneous fracture of the lens following treatment of hyperglycemic hyperosmolar syndrome.

PubMed

Sychev, Yevgeniy V; Zepeda, Emily M; Lam, Deborah L

2017-09-01

Acute development of cataracts that may be transient is known to occur during correction of diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome. Nettleship in 1885 was the first to describe the presence of a transient cataract in three diabetic patients that grew worse and eventually cleared with treatment. 1 We present a case of irreversible cataracts formed by nuclear fracture of the crystalline lens after hyperglycemia correction, an entity that has not yet been described. A 67 year-old Caucasian man presented with sudden bilateral vision loss one week after a week-long hospitalization in the intensive care unit for correction of hyperglycemia in the setting of hyperglycemic hyperosmolar syndrome requiring an insulin drip. This was caused by spontaneous fractures of the lens nuclei causing bilateral irreversible cataracts. The patient underwent uncomplicated bilateral cataract extraction resulting in restoration of normal vision. Acute transient cataracts that develop during correction of hyperglycemic hyperosmolar syndrome are thought to result from osmotic lens swelling. In this case report, internal fracture of the lens was produced by mechanical forces generated in the process of lens swelling occurring as a consequence of initial hyperglycemia and its subsequent correction. This case represents a rare ocular complication of hyperglycemia correction, and provides new evidence that mechanical forces can be part of diabetic cataractogenesis.

[Digitalization of radiological imaging information and consequences for patient care in the hospital ].

PubMed

den Heeten, G J; Barneveld Binkhuysen, F H

2001-08-25

Determining the rate at which radiology must be digitalised has been a controversial issue for many years. Much radiological information is still obtained from the film-screen combination (X-rays) with all of its known inherent restrictions. The importance of imaging information in the healthcare process continues to increase for both radiologists and referring physicians, and the ongoing developments in information technology means that it is possible to integrate imaging information and electronic patient files. The healthcare process can only become more effective and efficient when the appropriate information is in the right place at the right time, something that conventional methods, using photos that need to be physically moved, can scarcely satisfy. There is also a desire for integration with information obtained from nuclear medicine, pathology and endoscopy, and eventually of all stand-alone data systems with relevance for the individually oriented hospital healthcare. The transition from a conventional to a digital process is complex; it is accompanied by the transition from a data-oriented to a process-oriented system. Many years have already been invested in the integration of information systems and the development of digital systems within radiology, the current performance of which is such that many hospitals are considering the digitalisation process or are already implementing parts of it.

The origins, development, and passage of Medicare's revolutionary prospective payment system.

PubMed

Mayes, Rick

2007-01-01

This article explains the origins, development, and passage of the single most influential postwar innovation in medical financing: Medicare's prospective payment system (PPS). Inexorably rising medical inflation and deep economic deterioration forced policymakers in the late 1970s to pursue radical reform of Medicare to keep the program from insolvency. Congress and the Reagan administration eventually turned to the one alternative reimbursement system that analysts and academics had studied more than any other and had even tested with apparent success in New Jersey: prospective payment with diagnosis-related groups (DRGs). Rather than simply reimbursing hospitals whatever costs they charged to treat Medicare patients, the new model paid hospitals a predetermined, set rate based on the patient's diagnosis. The most significant change in health policy since Medicare and Medicaid's passage in 1965 went virtually unnoticed by the general public. Nevertheless, the change was nothing short of revolutionary. For the first time, the federal government gained the upper hand in its financial relationship with the hospital industry. Medicare's new prospective payment system with DRGs triggered a shift in the balance of political and economic power between the providers of medical care (hospitals and physicians) and those who paid for it--power that providers had successfully accumulated for more than half a century.

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

PubMed Central

Takahashi, Sanai; Sugimura, Yoshiki

2018-01-01

Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers. PMID:29614830

Severe hypokinesis caused by paraneoplastic anti-Ma2 encephalitis associated with bilateral intratubular germ-cell neoplasm of the testes.

PubMed

Matsumoto, Lumine; Yamamoto, Tomotaka; Higashihara, Mana; Sugimoto, Izumi; Kowa, Hisatomo; Shibahara, Junji; Nakamura, Koichiro; Shimizu, Jun; Ugawa, Yoshikazu; Goto, Jun; Dalmau, Josep; Tsuji, Shoji

2007-04-15

We report a 40-year-old man with severe hypokinesis as paraneoplastic manifestation of a microscopic "carcinoma in situ" of the testis. The young age of the patient, along with progressive neurologic deterioration, detection of anti-Ma2 antibodies, and ultrasound findings of bilateral microcalcifications, led to bilateral orchiectomy, revealing the tumor in both testes. After orchiectomy, neurological symptoms stabilized, but the patient eventually died of systemic complications caused by his severe neurological deficits. Anti-Ma2 paraneoplastic encephalitis should be considered in patients with severe hypokinesis, and intensive investigation and aggressive approach to treatment is encouraged to prevent progression of the neurological deficits.

Severe Hypokinesis Caused by Paraneoplastic Anti-Ma2 Encephalitis Associated with Bilateral Intratubular Germ-Cell Neoplasm of the Testes

PubMed Central

Matsumoto, Lumine; Yamamoto, Tomotaka; Higashihara, Mana; Sugimoto, Izumi; Kowa, Hisatomo; Shibahara, Junji; Nakamura, Koichiro; Shimizu, Jun; Ugawa, Yoshikazu; Goto, Jun; Dalmau, Josep; Tsuji, Shoji

2007-01-01

We report a 40-year-old man with severe hypokinesis as paraneoplastic manifestation of a microscopic “carcinoma in situ” of the testis. The young age of the patient, along with progressive neurologic deterioration, detection of anti-Ma2 antibodies, and ultrasound findings of bilateral microcalcifications, led to bilateral orchiectomy, revealing the tumor in both testes. After orchiectomy, neurological symptoms stabilized, but the patient eventually died of systemic complications caused by his severe neurological deficits. Anti-Ma2 paraneoplastic encephalitis should be considered in patients with severe hypokinesis, and intensive investigation and aggressive approach to treatment is encouraged to prevent progression of the neurological deficits. PMID:17269131

Rare extraskeletal Ewing's sarcoma mimicking as adenocarcinoma of the sigmoid.

PubMed

Mertens, Michelle; Haenen, Filip W N; Siozopoulou, Vasiliki; Van Cleemput, Marc

2017-06-01

Extraskeletal Ewing's sarcoma (EES) is a rare finding in comparison with Ewing's sarcoma of bone and usually manifests in young patients. However, even in older patients, one must consider the diagnosis. In this case, we describe a 52-year-old woman diagnosed with EES, mimicking as adenocarcinoma of the sigmoid. The tumor was not visualized by a multi-slice spiral computed tomography of the abdomen and pelvis with intravenous contrast, and eventually the diagnosis was made by positive immunohistochemical staining for CD99 and by molecular testing for EWSR1 translocation. This combination of the patient's age and the localization of the tumor mimicking an adenocarcinoma of the sigmoid has never been described before.

Ovulation induction in women with polycystic ovary syndrome.

PubMed

Perales-Puchalt, Alfredo; Legro, Richard S

2013-08-01

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. There are multiple ways to induce ovulation in PCOS patients, which will eventually provide a successful live birth. Each of these treatments varies in aggressiveness and effectiveness. Ranging from lifestyle modifications, through insulin-sensitizing agents, selective estrogen receptor modulators, aromatase inhibitors, gonadotropins, to laparoscopic ovarian drilling and assisted reproductive techniques, each method achieves ovulation induction through different mechanisms of action. This review provides a description and specific characteristics of the different methods used for ovulation induction which can help to design a personalized approach to each PCOS patient, and a general stepwise approach to ovulation induction in these patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Coblator Arytenoidectomy in the Treatment of Bilateral Vocal Cord Paralysis

PubMed Central

Googe, Benjamin; Nida, Andrew; Schweinfurth, John

2015-01-01

A 77-year-old female with bilateral vocal cord paralysis and dependent tracheostomy status after total thyroidectomy presented to clinic for evaluation of decannulation via arytenoidectomy. Preliminary data suggests coblation versus standard CO2 laser ablation in arytenoidectomy may provide benefits in terms of decreased tissue necrosis and patient outcome. The patient elected to proceed with arytenoidectomy by coblation. The initial procedure went well but postoperative bleeding required a return trip to the operating room for hemostasis. In the coming months the patient's tracheostomy tube was gradually downsized and eventually capped. She was decannulated eight months after surgery, speaking well and without complaints. Details of the surgical procedure and outcome will be discussed. PMID:26457217

Metabolic Bone Diseases and Total Hip Arthroplasty: Preventing Complications.

PubMed

Moya-Angeler, Joaquin; Lane, Joseph M; Rodriguez, Jose A

2017-11-01

Metabolic bone diseases are a diverse group of conditions characterized by abnormalities in calcium metabolism and/or bone cell physiology. These unbalanced processes can eventually lead to bony deformities and altered joint biomechanics, resulting in degenerative joint disease. Not infrequently, patients with metabolic bone diseases have restricting hip joint pain that ultimately necessitates hip arthroplasty. To minimize complications, the surgeon must consider the particular characteristics of these patients. The surgical and medical management of patients with metabolic bone diseases undergoing hip arthroplasty requires appropriate preoperative diagnosis, careful attention to the technical challenges of surgery, and strategies to maximize the long-term results of the surgical intervention, such as the use of bone anabolic and anticatabolic agents.

The role of exercise in amyotrophic lateral sclerosis.

PubMed

Chen, Amy; Montes, Jacqueline; Mitsumoto, Hiroshi

2008-08-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor nervous system. It causes progressive and cumulative physical disabilities in patients, and leads to eventual death due to respiratory muscle failure. The disease is diverse in its presentation, course, and progression. We do not yet fully understand the cause or causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. Currently, we rely on a multidisciplinary approach to symptomatically manage and care for patients who have ALS. In this article, the authors review the literature on the role of exercise in patients who have ALS, and briefly compare what is known about exercise in other neuromuscular diseases.

Current issues in malignant pleural mesothelioma evaluation and management.

PubMed

Ai, Jing; Stevenson, James P

2014-09-01

Malignant pleural mesothelioma (MPM) is an uncommon disease most often associated with occupational asbestos exposure and is steadily increasing in worldwide incidence. Patients typically present at an older age, with advanced clinical stage and other medical comorbidities, making management quite challenging. Despite great efforts, the prognosis of MPM remains poor, especially at progression after initial treatment. Macroscopic complete resection of MPM can be achieved through extrapleural pneumonectomy (EPP) or extended (ie, radical) pleurectomy (e-P/D) in selected patients and can result in prolonged survival when incorporated into a multimodality approach. Given the morbidity associated with surgical resection of MPM, optimizing identification of appropriate patients is essential. Unfortunately, most patients are not candidates for EPP or e-P/D due to advanced stage, age, and/or medical comorbidity. Pemetrexed and platinum combination chemotherapy has become the cornerstone of therapy for patients with unresectable disease because the combination is associated with improved survival and quality of life in treated patients. However, MPM eventually becomes resistant to initial therapy, and benefit to further lines of therapy has not been substantiated in randomized clinical trials. Translational research has provided exciting insights into tumorigenesis, biomarkers, and immune response in MPM, leading to the development of multiple novel therapeutic agents that are currently in clinical trials. These advances hold the promise of a new era in the treatment of MPM and suggest that this disease will not be left behind in the war on cancer. ©AlphaMed Press.

Arthrodesis of the knee with an intramedullary nail.

PubMed

Donley, B G; Matthews, L S; Kaufer, H

1991-07-01

The cases of twenty patients who had an arthrodesis in which an intramedullary nail was used for stabilization were reviewed at an average follow-up of six years. The predominant indications were infection after total knee arthroplasty and post-traumatic pain and instability. Other indications included aseptic loosening of the components of a total knee arthroplasty, reconstruction after resection of a giant-cell tumor, non-union of a fracture of the distal part of the femur or the proximal part of the tibia, and failed external-compression arthrodesis. Success was achieved in seventeen patients (85 per cent), and functional stability immediately postoperatively was gained in all twenty. Of the three patients in whom the arthrodesis failed, all had sustained an intraoperative fracture, and infection eventually developed. Of the twelve nails that were secured to the greater trochanter with a loop of stainless-steel wire, none showed evidence of proximal migration. Of the eight nails that were not thus secured, two migrated proximally, necessitating removal of the nail. Two drawbacks to this operation are the long duration and the large amount of blood that is lost. The major advantage is that a high percentage of patients have progression to a stable fusion despite serious problems. Furthermore, all but seven patients (including the six who had a tumor or who had sustained an intraoperative fracture) were able to bear full weight by the second postoperative week. Only a few patients needed an external support for walking.

GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects.

PubMed

Platzer, Konrad; Yuan, Hongjie; Schütz, Hannah; Winschel, Alexander; Chen, Wenjuan; Hu, Chun; Kusumoto, Hirofumi; Heyne, Henrike O; Helbig, Katherine L; Tang, Sha; Willing, Marcia C; Tinkle, Brad T; Adams, Darius J; Depienne, Christel; Keren, Boris; Mignot, Cyril; Frengen, Eirik; Strømme, Petter; Biskup, Saskia; Döcker, Dennis; Strom, Tim M; Mefford, Heather C; Myers, Candace T; Muir, Alison M; LaCroix, Amy; Sadleir, Lynette; Scheffer, Ingrid E; Brilstra, Eva; van Haelst, Mieke M; van der Smagt, Jasper J; Bok, Levinus A; Møller, Rikke S; Jensen, Uffe B; Millichap, John J; Berg, Anne T; Goldberg, Ethan M; De Bie, Isabelle; Fox, Stephanie; Major, Philippe; Jones, Julie R; Zackai, Elaine H; Abou Jamra, Rami; Rolfs, Arndt; Leventer, Richard J; Lawson, John A; Roscioli, Tony; Jansen, Floor E; Ranza, Emmanuelle; Korff, Christian M; Lehesjoki, Anna-Elina; Courage, Carolina; Linnankivi, Tarja; Smith, Douglas R; Stanley, Christine; Mintz, Mark; McKnight, Dianalee; Decker, Amy; Tan, Wen-Hann; Tarnopolsky, Mark A; Brady, Lauren I; Wolff, Markus; Dondit, Lutz; Pedro, Helio F; Parisotto, Sarah E; Jones, Kelly L; Patel, Anup D; Franz, David N; Vanzo, Rena; Marco, Elysa; Ranells, Judith D; Di Donato, Nataliya; Dobyns, William B; Laube, Bodo; Traynelis, Stephen F; Lemke, Johannes R

2017-07-01

We aimed for a comprehensive delineation of genetic, functional and phenotypic aspects of GRIN2B encephalopathy and explored potential prospects of personalised medicine. Data of 48 individuals with de novo GRIN2B variants were collected from several diagnostic and research cohorts, as well as from 43 patients from the literature. Functional consequences and response to memantine treatment were investigated in vitro and eventually translated into patient care. Overall, de novo variants in 86 patients were classified as pathogenic/likely pathogenic. Patients presented with neurodevelopmental disorders and a spectrum of hypotonia, movement disorder, cortical visual impairment, cerebral volume loss and epilepsy. Six patients presented with a consistent malformation of cortical development (MCD) intermediate between tubulinopathies and polymicrogyria. Missense variants cluster in transmembrane segments and ligand-binding sites. Functional consequences of variants were diverse, revealing various potential gain-of-function and loss-of-function mechanisms and a retained sensitivity to the use-dependent blocker memantine. However, an objectifiable beneficial treatment response in the respective patients still remains to be demonstrated. In addition to previously known features of intellectual disability, epilepsy and autism, we found evidence that GRIN2B encephalopathy is also frequently associated with movement disorder, cortical visual impairment and MCD revealing novel phenotypic consequences of channelopathies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Recurrent genital herpes treatments and their impact on quality of life.

PubMed

Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

2003-01-01

Herpes genitalis is one of the most common viral sexually transmitted diseases in the world, with an estimated seroprevalence in the US of greater than 20%. Two viruses of the same family cause herpes genitalis: herpes simplex virus 1 and 2. After the resolution of primary infection, the virus persists in the nerve roots of the sacral plexus, often causing recurrent (though generally less severe) outbreaks. These outbreaks, as well as the infectious potential to the patient's sexual partners, results in significant psychological stress on the patient, and has a tremendous negative impact on QOL. Current treatment modalities may result in a reduction in the number of outbreaks and viral shedding, but no cure exists. Although studies have clearly demonstrated the negative impact of recurrent genital herpes on QOL, an assessment scale specific to herpes was not developed until recently. Earlier studies indicated that patients did not perceive a significant benefit from episodic treatment with antivirals, but studies using the Recurrent Genital Herpes Quality of Life Questionnaire (RGHQoL) have now demonstrated that suppressive antiviral therapy improves quality of life in patients with frequent recurrences of genital herpes. However, not all patients with recurrent genital herpes need suppressive therapy, and proposed factors to consider include frequency of recurrence, physical and psychological distress caused by recurrences, and the potential for transmission to the patient's sexual partner. Newer therapeutic modalities, including the topical immune response modifier resiquimod and herpes vaccines, may eventually be shown to further decrease the psychological morbidity of recurrent genital herpes.

AGGRESSIVE RETINAL ASTROCYTOMAS IN FOUR PATIENTS WITH TUBEROUS SCLEROSIS COMPLEX

PubMed Central

Shields, Jerry A; Eagle, Ralph C; Shields, Carol L; Marr, Brian P

2004-01-01

ABSTRACT Objective To report the clinical and histopathologic findings of retinal astrocytic tumors that showed progressive growth in four patients with tuberous sclerosis complex (TSC). Methods Four young children each developed an enlarging retinal neoplasm that eventually necessitated enucleation of the affected eye. The systemic findings, clinical course, and histopathologic findings were reviewed. Results Each patient had a progressively enlarging retinal mass associated with a total exudative retinal detachment and neovascular glaucoma. Enucleation was necessary in each case because the affected eye became blind and painful. The mean patient age at enucleation was 7 years, and the median age was 3 years. At the time of enucleation the tumors ranged from 10 to 20 mm in basal diameter and from 10 to 25 mm in thickness. Histopathologic studies of each eye revealed a giant cell astrocytoma that had produced a total exudative retinal detachment. The tumor cells showed positive immunoreactivity to neuron-specific enolase and glial fibrillary acidic protein. The retinal neoplasms in these cases were identical histopathologically to the subependymal giant cell astrocytoma that typifies TSC in the brain. One tumor filled the entire eye and perforated the globe. Although the lesions simulated retinoblastoma clinically, each patient had ocular and systemic findings of TSC, supporting the diagnosis of astrocytic hamartoma. Conclusions Although retinal astrocytic lesions of TSC generally are stationary, they can sometimes grow relentlessly and cause severe ocular complications. Patients with retinal astrocytic hamartomas should have serial ophthalmic evaluations because of this possibility. PMID:15747752

Anomalous aortic origin of a coronary artery: a report from the Congenital Heart Surgeons Society Registry.

PubMed

Poynter, Jeffrey A; Williams, William G; McIntyre, Susan; Brothers, Julie A; Jacobs, Marshall L

2014-01-01

Anomalous aortic origin of a coronary artery (AAOCA) is a common congenital heart lesion that may be rarely associated with myocardial ischemia and sudden death in the young. Evidence-based criteria for managing young patients with AAOCA are lacking. The Congenital Heart Surgeons Society (CHSS) established a multicenter registry of patients with AAOCA aged ≤30 years to develop these criteria. All institutional members of the CHSS are eligible to enroll patients. Patients were enrolled retrospectively if diagnosis of AAOCA occurred between January 1, 1998, and January 20, 2009, and prospectively from January 20, 2009 forward. The first phase of analysis explored possible associations between demographics, symptoms, coronary anatomy, and management using correlation analysis and logistic regression. As of June 2012, 198 patients were enrolled from CHSS member institutions (median age at diagnosis = 10.2 years; 64% male). Data were extracted from clinical records. Fifty-four percent were symptomatic at presentation (most commonly chest pain, N = 78). The AAOCA was diagnosed at autopsy in two patients who presented with sudden death (one with anomalous aortic origin of the left coronary artery [AAOLCA]; one with a single ostium above a commissure giving rise to both left and right coronary arteries). Imaging reports documented anomalous aortic origin of the right coronary artery (AAORCA) in 144 patients, AAOLCA in 51 patients, and AAOLCA/AAORCA in 1 patient. Surgery or autopsy without surgery was performed in 106 patients (71 AAORCA [67%]; 31 AAOLCA [29%]; and 4 AAORCA/AAOLCA [4%]) at a median age of 12.6 years. Overall, 52% of patients with AAORCA versus 67% with AAOLCA had surgery. Most surgical operative reports described an intramural segment of the coronary artery with anomalous origin. Surgery correlated with symptoms, older age, and presence of an intramural segment in the setting of AAOLCA. Management decisions, including surgical referral, are associated with patient symptoms and coronary morphology. Information derived from annual follow-up of surgically and nonsurgically managed patients enrolled in the registry will eventually form the basis for development of evidence-based protocols to address the spectrum of risk and inform clinical decision making in this heterogeneous population of young patients.

Local morbidity from red-bellied black snake (Pseudechis porphyriacus, Elapidae) envenoming: Two cases and a brief review of management.

PubMed

Weinstein, Scott A; Mirtschin, Peter J; Tristram, Hamish; Lawton, Luke; White, Julian

2018-02-01

The red-bellied black snake (Pseudechis porphyriacus, Elapidae) is one of several species of venomous snakes most commonly implicated in human and domestic animal envenoming in Australia. Human systemic envenoming can present with myotoxicity that may include myoglobinuria; hemoglobinuria and intravascular hemolysis; thrombocytopenia, anticoagulant coagulopathy, and, rarely, mild cranial nerve palsies. Pseudechis porphyriacus envenoming can also feature significant local morbidity such as ecchymoses, bleeding, pain and necrosis. Some envenomed patients may develop progressive thickness necrosis independent of secondary infection, and occasionally require surgical debridement. Uncommonly, some digital envenoming may cause more severe deeper tissue pathology that justifies dermotomy and/or distal phalangeal amputation. Presented are two patients with significant local morbidity from P. porphyriacus envenoming. An 18-month old girl received a protracted envenoming on her right foot, while a 38-year old male professional zoologist was envenomed on the third digit of his right hand. Each patient experienced myotoxicity, one had anticoagulant coagulopathy, and both developed clinically significant local morbidity including persistent bleeding, ecchymoses, local necrosis and pain; each required extensive treatment and variably prolonged admission. Noted also were transiently elevated D-dimer with low-normal or normal fibrinogen levels. The progressive necrosis and subsequent chronic pathologic changes with ischemia of the latter patient's digit eventually required a dermotomy and amputation of the distal phalanx. The pediatric patient did not require extensive wound debridement, but experienced prolonged difficulty in ambulation because of slowly resolving wound discomfort. Factors that may contribute to the severity of local morbidity of P. porphyriacus envenoming are considered, and management of envenoming by this taxon is briefly reviewed. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Iatrogenic Cushing syndrome in patients receiving inhaled budesonide and itraconazole or ritonavir: two cases and literature review.

PubMed

Blondin, Marie-Christine; Beauregard, Hugues; Serri, Omar

2013-01-01

To present two cases of iatrogenic Cushing syndrome caused by the interaction of budesonide, an inhaled glucocorticoid, with ritonavir and itraconazole. We present the clinical and biochemical data of two patients in whom diagnosis of Cushing syndrome was caused by this interaction. We also reviewed the pertinent literature and management options. A 71-year-old man was treated with inhaled budesonide for a chronic obstructive pulmonary disease and itraconazole for a pulmonary aspergillosis. The patient rapidly developed a typical Cushing syndrome complicated by bilateral avascular necrosis of the femoral heads. Serum 8:00 AM cortisol concentrations were suppressed at 0.76 and 0.83 μg/dL on two occasions. The patient died 4 days later of a massive myocardial infarction. The second case is a 46-year-old woman who was treated for several years with inhaled budesonide for asthma. She was put on ritonavir, a retroviral protease inhibitor, for the treatment of human immunodeficiency virus (HIV). In the following months, she developed typical signs of Cushing syndrome. Her morning serum cortisol concentration was 1.92 μg/dL. A cosyntropin stimulation test showed values of serum cortisol of <1.10, 2.65, and 5.36 μg/dL at 0, 30, and 60 minutes, respectively, confirming an adrenal insufficiency. Because the patient was unable to stop budesonide, she was advised to reduce the frequency of its administration and eventually taper the dose until cessation. Clinicians should be aware of the potential occurrence of iatrogenic Cushing syndrome and secondary adrenal insufficiency due to the association of inhaled corticosteroids with itraconazole or ritonavir.

Prognostic Estimation of Advanced Heart Failure With Low Left Ventricular Ejection Fraction and Wide QRS Interval.

PubMed

Oh, Changmyung; Chang, Hyuk-Jae; Sung, Ji Min; Kim, Ji Ye; Yang, Wooin; Shim, Jiyoung; Kang, Seok-Min; Ha, Jongwon; Rim, Se-Joong; Chung, Namsik

2012-10-01

Cardiac resynchronization therapy (CRT) has been known to improve the outcome of advanced heart failure (HF) but is still underutilized in clinical practice. We investigated the prognosis of patients with advanced HF who were suitable for CRT but were treated with conventional strategies. We also developed a risk model to predict mortality to improve the facilitation of CRT. Patients with symptomatic HF with left ventricular ejection fraction ≤35% and QRS interval >120 ms were consecutively enrolled at cardiovascular hospital. After excluding those patients who had received device therapy, 239 patients (160 males, mean 67±11 years) were eventually recruited. During a follow-up of 308±236 days, 56 (23%) patients died. Prior stroke, heart rate >90 bpm, serum Na ≤135 mEq/L, and serum creatinine ≥1.5 mg/dL were identified as independent factors using Cox proportional hazards regression. Based on the risk model, points were assigned to each of the risk factors proportional to the regression coefficient, and patients were stratified into three risk groups: low- (0), intermediate-(1-5), and high-risk (>5 points). The 2-year mortality rates of each risk group were 5, 31, and 64 percent, respectively. The C statistic of the risk model was 0.78, and the model was validated in a cohort from a different institution where the C statistic was 0.80. The mortality of patients with advanced HF who were managed conventionally was effectively stratified using a risk model. It may be useful for clinicians to be more proactive about adopting CRT to improve patient prognosis.

Five-year course and outcome of dysthymic disorder: A prospective, naturalistic follow-up study.

PubMed

Klein, D N; Schwartz, J E; Rose, S; Leader, J B

2000-06-01

There have been few naturalistic follow-up studies of dysthymic disorder. This study describes the 5-year course and outcome of dysthymic disorder. The authors conducted a prospective, longitudinal follow-up study of 86 outpatients with early-onset dysthymic disorder and 39 outpatients with episodic major depressive disorder. Follow-ups, conducted 30 and 60 months after entry into the study, rated patients on the Longitudinal Interval Follow-Up Evaluation and the Modified Hamilton Rating Scale for Depression. The estimated 5-year recovery rate from dysthymic disorder was 52.9%. Among patients who recovered, the estimated risk of relapse was 45.2% during a mean of 23 months of observation. Patients with dysthymic disorder spent approximately 70% of the follow-up period meeting the full criteria for a mood disorder. During the course of the follow-up the patients with dysthymic disorder exhibited significantly greater levels of symptoms and lower functioning and were significantly more likely to attempt suicide and to be hospitalized than were patients with episodic major depressive disorder. Finally, among patients with dysthymic disorder who had never experienced a major depressive episode before entry into the study, the estimated risk of having a first lifetime major depressive episode was 76.9%. Dysthymic disorder is a chronic condition with a protracted course and a high risk of relapse. In addition, almost all patients with dysthymic disorder eventually develop superimposed major depressive episodes. Although patients with dysthymic disorder tend to show mild to moderate symptoms, from a longitudinal perspective, the condition is severe.

A qualitative analysis of the nutritional requirements of palliative care patients.

PubMed

Muir, C I; Linklater, G T

2011-10-01

The National Health Servive (NHS) Quality Improvement Scotland developed nutritional Clinical Standards to address the problem of malnutrition in hospitals. NHS palliative care units are obliged to incorporate these standards into nutritional aspects of care. The nutritional needs of this patient population are under-researched. The present study aimed to explore patients' views of nutrition, to begin to understand their concerns and to determine whether such standards meet the needs of patients in the palliative care setting. A qualitative study was conducted in 2009 in an NHS Palliative Care Unit. Six inpatients were involved in one-to-one interviews, which were audiotaped and transcribed verbatim. The transcripts were subject to qualitative data analysis in accordance with a previous framework. A recurring theme that emerged was that of change and uncertainty. Four main areas subject to change were: disease state, symptoms, oral dietary intake and weight. Each change could exert control over, or be controlled by, the patient. When patients were eventually unable to exert control, they accepted the change, either willingly or enforced, thereby unintentionally setting their own targets. The present study enables a deeper understanding of the concerns that palliative care patients have regarding their oral dietary intake and weight. Their 'malnutrition' not only refers to physical malnutrition alone, but also incorporates psychological and social 'malnutrition'. When applying standards or protocols regarding nutritional care, these wider issues must be taken into account to meet patients' nutritional needs. © 2011 The Authors. Journal of Human Nutrition and Dietetics © 2011 The British Dietetic Association Ltd.

New-onset neonatal pulmonary hypertension associated with a rhinovirus infection.

PubMed

Patel, Nishit; The, Tiong G

2012-01-01

A 3.5-week-old male neonate who developed an upper and lower respiratory tract rhinovirus infection that was temporally associated with the development of severe pulmonary hypertension is described. Rhinovirus has not previously been associated with pulmonary hypertension. This child developed severe pulmonary hypertension with right ventricular failure, requiring mechanical ventilation, nitric oxide inhalation and, eventually, extracorporeal membrane oxygenation.

Treatment patterns and survival in patients with ALK-positive non-small-cell lung cancer: a Canadian retrospective study.

PubMed

Kayaniyil, S; Hurry, M; Wilson, J; Wheatley-Price, P; Melosky, B; Rothenstein, J; Cohen, V; Koch, C; Zhang, J; Osenenko, K; Liu, G

2016-12-01

Crizotinib was the first agent approved for the treatment of anaplastic lymphoma kinase ( ALK )-positive (+) non-small-cell lung cancer (nsclc), followed by ceritinib. However, patients eventually progress or develop resistance to crizotinib. With limited real-world data available, the objective of the present work was to evaluate treatment patterns and survival after crizotinib in patients with locally advanced or metastatic ALK + nsclc in Canada. In this retrospective study at 6 oncology centres across Canada, medical records of patients with locally advanced or metastatic ALK + nsclc were reviewed. Demographic and clinical characteristics, treatments, and outcomes data were abstracted. Analyses focused on patients who discontinued crizotinib treatment. Of the 97 patients included, 9 were crizotinib-naïve, and 39 were still receiving crizotinib at study end. The 49 patients who discontinued crizotinib treatment were included in the analysis. Of those 49 patients, 43% received ceritinib at any time, 20% subsequently received systemic chemotherapy only (but never ceritinib), and 37% received no further treatment or died before receiving additional treatment. Median overall survival from crizotinib discontinuation was shorter in patients who did not receive ceritinib than in those who received ceritinib (1.7 months vs. 20.4 months, p < 0.001). In a multivariable analysis, factors associated with poorer survival included lack of additional therapies (particularly ceritinib), male sex, and younger age, but not smoking status; patients of Asian ethnicity showed a nonsignificant trend toward improved survival. A substantial proportion of patients with ALK + nsclc received no further treatment or died before receiving additional treatment after crizotinib. Treatment with systemic agents was associated with improved survival, with ceritinib use being associated with the longest survival.

Tumour suppressor menin is essential for development of the pancreatic endocrine cells.

PubMed

Fontanière, Sandra; Duvillié, Bertrand; Scharfmann, Raphaël; Carreira, Christine; Wang, Zhao-Qi; Zhang, Chang-Xian

2008-11-01

Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene predispose patients to MEN1 that affects mainly endocrine tissues, suggesting important physiological functions of the gene in adult endocrine cells. Homozygous disruption of Men1 in mice causes embryonic lethality, whereas the eventual involvement of the gene in embryonic development of the endocrine cells remains unknown. Here, we show that homozygous Men1 knockout mice demonstrate a reduced number of glucagon-positive cells in the E12.5 pancreatic bud associated with apoptosis, whereas the exocrine pancreas development in these mice is not affected. Our data suggest that menin is involved in the survival of the early pancreatic endocrine cells during the first developmental transition. Furthermore, chimerism assay revealed that menin has an autonomous and specific effect on the development of islet cells. In addition, using pancreatic bud culture mimicking the differentiation of alpha- and beta-cells during the second transition, we show that loss of menin leads to the failure of endocrine cell development, altered pancreatic structure and a markedly decreased number of cells expressing neurogenin 3, indicating that menin is also required at this stage of the endocrine pancreas development. Taken together, our results suggest that menin plays an indispensable role in the development of the pancreatic endocrine cells.

[Automatic mechanical chest compression during helicopter transportation].

PubMed

Kyrval, Helle S; Ahmad, Khalil

2010-11-15

We describe a case story with a drowned, hypothermic trauma patient treated with an automatic mechanical chest compression device during helicopter transportation to a trauma center. After falling from a 25 meter high bridge into 2 °C water, she was rescued lifeless 17 minutes later. Advanced life support was initiated. During transport by a rescue helicopter, chest compressions were effectively provided by Lund University Cardiopulmonary Assist System (LUCAS). Upon arrival to a trauma centre approx. 60 minutes later, the patient was treated with extracorporal circulation and rewarmed. She was eventually discharged to her home with minor loss of cerebral function.

Paracoccidioidomycosis: case report and review.

PubMed

Manns, B J; Baylis, B W; Urbanski, S J; Gibb, A P; Rabin, H R

1996-11-01

A previously well 59-year-old man presented with paracoccidioidomycosis, more than 15 years after leaving South America. He failed to respond to conventional therapies, first with oral itraconazole and then with amphotericin B plus sulfadiazine, and eventually died of recurrent arterial emboli possibly due to paracoccidioidomycotic aortitis. This patient's presentation demonstrates the difficulties that may be encountered in diagnosing and managing this disease. Paracoccidioidomycosis should be suspected in patients with an appropriate travel history who experience weight loss and have pulmonary, mucosal, and cutaneous lesions. This article comprehensively reviews the literature, with emphasis on epidemiology, clinical presentation, diagnosis, and therapy with imidazole antifungal medications.

A crisis of the heart: an acute reversible cardiomyopathy bridged to recovery in a patient with Addison's disease.

PubMed

Krishnamoorthy, Arun; Mentz, Robert J; Hyland, Kristen A; McMillan, Edward B; Patel, Chetan B; Milano, Carmelo A; Hernandez, Adrian F

2013-01-01

Primary adrenal insufficiency or Addison's disease is a rare disorder often difficult to diagnose on presentation by the nature of its associated nonspecific symptoms, such as nausea or weakness. Cardiovascular complications of the condition are usually limited to hypovolemic hypotension; however, we highlight here a rare, dramatic case of a fulminant adrenal crisis in a young man primarily marked by acute biventricular systolic failure and cardiogenic shock. The patient was successfully treated with corticosteroid replacement and bridged with temporary mechanical circulatory support to eventual complete the recovery of native myocardial function.

Mycobacterium tuberculosis osteomyelitis in a patient with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): a case report.

PubMed

Mannepalli, Supriya; Mitchell-Samon, Levonne; Guzman, Nilmarie; Relan, Manish; McCarter, Yvette S

2010-02-23

The incidence of tuberculosis is increasing in the United States. Extra-pulmonary involvement is more common in patients with HIV/AIDS. The diagnosis of Tuberculosis osteomyelitis requires a high degree of suspicion for accurate and timely diagnosis.We present a case of a 49 year old Caucasian male with HIV/AIDS who presented with a four-month history of soft tissue swelling in the left proximal thigh unresponsive to various broad spectrum antibiotics who was eventually diagnosed with Mycobacterium tuberculosis osteomyelitis of the left proximal femur.

Current progress in patient-specific modeling

PubMed Central

2010-01-01

We present a survey of recent advancements in the emerging field of patient-specific modeling (PSM). Researchers in this field are currently simulating a wide variety of tissue and organ dynamics to address challenges in various clinical domains. The majority of this research employs three-dimensional, image-based modeling techniques. Recent PSM publications mostly represent feasibility or preliminary validation studies on modeling technologies, and these systems will require further clinical validation and usability testing before they can become a standard of care. We anticipate that with further testing and research, PSM-derived technologies will eventually become valuable, versatile clinical tools. PMID:19955236

A comparative analysis of high speed rail station development into destination and/or multi-use facilities : the case of San Jose Diridon.

DOT National Transportation Integrated Search

2017-02-01

As a burgeoning literature on high-speed rail development indicates, good station-area planning is a very important prerequisite for the : eventual successful operation of a high-speed rail station; it can also trigger opportunities for economic deve...

Discovering Geography: Teacher Created Activities for High School and Middle School.

ERIC Educational Resources Information Center

Petersen, James F., Ed.

This guide contains 20 classroom activities designed by teachers to study topics in geography with the eventual goal of aiding in the development of geographic literacy in students. The various activities involve map reading skills, climatology, current events, urban development, and community planning. Each activity presentation includes an event…

Plant Development and Genetics Experiment

NASA Technical Reports Server (NTRS)

2003-01-01

Aboard the International Space Station (ISS), the Russian Lada greenhouse provides home to an experiment that investigates plant development and genetics. Space grown peas have dried and 'gone to seed.' The crew of the ISS will soon harvest the seeds. Eventually some will be replanted onboard the ISS, and some will be returned to Earth for further study.

Design, development, test, and evaluation of an automated analytical electrophoresis apparatus

NASA Technical Reports Server (NTRS)

Bartels, P. A.; Bier, M.

1977-01-01

An Automated Analytical Electrophoresis Apparatus (AAEA) was designed, developed, assembled, and preliminarily tested. The AAEA was demonstrated to be a feasible apparatus for automatically acquiring, displaying, and storing (and eventually analyzing) electrophoresis mobility data from living blood cells. The apparatus and the operation of its major assemblies are described in detail.

Commerical Crew Astronauts Evaluate Crew Dragon Controls

NASA Image and Video Library

2017-01-10

Astronaut Bob Behnken, work in a mock-up of the SpaceX Crew Dragon flight deck at the company's Hawthorne, California, headquarters as development of the crew systems continues for eventual missions to the International Space Station.