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Sample records for high-dose intravenous metronidazole

  1. Human pharmacokinetics and toxicity of high-dose metronidazole administered orally and intravenously

    SciTech Connect

    Urtasun, R.C.; Rabin, H.R.; Partington, J.

    1983-01-01

    This study is part of a clinical program to assess the use of nitroimidazoles as radiosensitizers of hypoxic tumor cells. A total of 37 patients with malignant tumors have been entered into the study to receive oral high-dose metronidazole in conjunction with radiation. Twenty-eight patients with malignant brain tumors received 6 gm/m2 three times a week for 3 weeks (a mean total dose of 5.3 gm/m2). Maximum mean plasma drug concentration of 1 mM was obtained at 4 hours after drug ingestion with a mean half-life of 13 hours. Tissue and cerebrospinal fluid levels of 80% to 90% of the plasma levels were obtained at 4 to 6 hours. A linear relationship between increased drug dose and increased plasma concentration was observed at doses of 2.5 gm/m2 up to 6 gm/m2. Acute gastrointestinal and central nervous system toxicity was the dose-limiting factor (50% and 25%, respectively, at total doses of 5.3 gm/m2). Pharmacokinetic studies of intravenous metronidazole were performed in eight consenting patients. Single doses of 0.5, 1, 1.5, and 2 gm were administered intravenously by zero-order infusion pump. Seven of the eight patients received a second identical dose orally 1 week later and the results were compared. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion rate equations, by use of a nonlinear least-squares regression analysis program (NONLIN). The mean (+/- SD) for alpha half-life was 1.2 +/- 1.3 hours, and that for the beta half-life was 9.8 +/- 5.9 hours. The absolute oral bioavailability was estimated to approximate 100%.

  2. High-dose vaginal maintenance metronidazole for recurrent bacterial vaginosis: a pilot study.

    PubMed

    Aguin, Tina; Akins, Robert A; Sobel, Jack D

    2014-05-01

    The purpose of this study was to explore the benefit of high-dose intravaginal metronidazole as a maintenance therapy in reducing recurrence rates of bacterial vaginosis (BV). Eighteen women with a history of recurrent BV and symptomatic BV were treated with metronidazole 750 mg suppository intravaginally daily for 7 days. Those in remission by Amsel criteria received metronidazole 750 mg twice weekly for 3 months with further follow-up for 3 months. High-dose metronidazole intravaginally was associated with rare clinical recurrence during the period of use. After cessation of suppression therapy, recurrence was high.

  3. Concentrations and in vivo antibacterial activity of spiramycin and metronidazole in patients with periodontitis treated with high-dose metronidazole and the spiramycin/metronidazole combination.

    PubMed

    Poulet, Pierre-Pascal; Duffaut, Danielle; Barthet, Pierre; Brumpt, Ivan

    2005-03-01

    Previous studies have shown that metronidazole, alone or in combination with spiramycin (250 mg/1 500 000 units, three times/day), is an effective treatment for active periodontitis, although the dose of metronidazole currently used (750 mg/day) could provide concentrations in gingival crevice fluid that are too low for the MICs of the involved pathogens. This study tested the in vivo antibacterial efficacy of the currently used metronidazole dose (as contained in the fixed spiramycin/metronidazole combination) in patients with an active periodontitis, and of a high dose (1500 mg/day) of metronidazole alone. We measured the MICs of spiramycin and metronidazole for the recovered pathogens and the gingival crevice fluid antibiotic concentrations of both antibiotics, and attempted to correlate them with bacterial eradication. The concentrations of metronidazole consistently exceeded the MICs for the pathogens isolated in the corresponding sites, even at the usual metronidazole (250 mg three times/day) dose. All the bacterial species were eradicated during treatment and at follow-up, although Fusobacterium spp. eradicated during treatment reappeared in a majority of the cases at follow-up, 30 days after treatment, in both groups. The results of antibiotic therapy with metronidazole or the spiramycin/metronidazole combination are consistent with their in vitro antibacterial activity and with the local antibiotic concentrations; they suggest that the currently used metronidazole dose (250 mg, three times/day) alone or as part of the spiramycin/metronidazole combination, could be sufficient for the treatment of active periodontitis.

  4. High-dose vaginal metronidazole for recurrent bacterial vaginosis--a pilot study.

    PubMed

    Aguin, Tina J; Akins, Robert A; Sobel, Jack D

    2014-04-01

    The purpose of this study was to evaluate high-dose intravaginal metronidazole, with or without miconazole, in enhancing cure rates in women with recurrent BV. A total of 43 women with symptomatic recurrent BV were enrolled in a 4-arm study comparing 500 mg versus 750 mg of metronidazole, with or without miconazole, intravaginally for 7 days. Test of cure by saline wet mount and 10% potassium chloride microscopy, pH, Gram stain for Nugent score, and yeast culture were performed 3 times after treatment: 3 to 7 days, 30 to 35 days, and 60 to 70 days. Overall cure rate for the entire group was 92.6% at visit 2, 62.1% at visit 3, and 51.4% at visit 4. At visit 2, there was no difference in cure rates among patients who received metronidazole 750 mg ± miconazole daily (90.5%) compared with metronidazole 500 mg ± miconazole daily (85%). At visit 3, there was a significant improvement in cure rates among patients who received metronidazole 750 mg ± miconazole daily (78.9%) compared with metronidazole 500 mg ± miconazole daily (44.4%) (p < .05). At visit 4, a significant difference in clinical cure rates persisted among patients who received metronidazole 750 mg ± miconazole daily (68.4%) compared with of metronidazole 500 mg ± miconazole daily (33.3%; p < .05). Poor responses (Nugent score > 4 or pH > 4.4) at the first visit alter treatment-predicted recurrence. The addition of miconazole did not enhance BV response rates. Cure rates for BV were high in this refractory cohort and seemed dose dependent.

  5. Successful treatment of refractory Trichomonas vaginalis infection using intravenous metronidazole.

    PubMed

    Hawkins, Isobel; Carne, Christopher; Sonnex, Christopher; Carmichael, Andrew

    2015-08-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in a vulvo-vaginitis and altered vaginal discharge in symptomatic women. Since its introduction in the 1960 s, metronidazole has been the first-line drug for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or reinfection, although metronidazole resistance has previously been documented. Sensitivity testing is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. This case looks at a patient with refractory disease over an 18-month period, where intravenous infusion of metronidazole resulted in cure after multiple previous therapy failures. There is limited evidence to endorse the use of intravenous metronidazole, and this case report provides further support for its efficacy. © The Author(s) 2014.

  6. Pharmacokinetics of high-dose intravenous melatonin in humans.

    PubMed

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette M; Fenger, Andreas Q; Petersen, Marian C; Rosenberg, Jacob; Gögenur, Ismail

    2016-03-01

    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5-326,175.0) pg/mL and 1,251,500.0 (864,375.0-1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0- ∞ , 8,997,633.0 (6,071,696.2-11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6-105,779,612.0) pg · min/mL. High-dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.

  7. Fourteen-day high-dose esomeprazole, amoxicillin and metronidazole as third-line treatment for Helicobacter pylori infection.

    PubMed

    Puig, Ignasi; González-Santiago, Jesús M; Molina-Infante, Javier; Barrio, Jesús; Herranz, Maria Teresa; Algaba, Alicia; Castro, Manuel; Gisbert, Javier P; Calvet, Xavier

    2017-09-01

    The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole. Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or (13) C-UBT both before and after treatment. A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred. Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens. © 2017 John Wiley & Sons Ltd.

  8. Comparison of sequential intravenous/oral ciprofloxacin plus metronidazole with intravenous ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections.

    PubMed

    Wacha, Hannes; Warren, Brian; Bassaris, Harry; Nikolaidis, Paul

    2006-08-01

    Intra-abdominal infections are a substantial clinical problem and an important cause of morbidity and death in the hospital. Optimal treatment requires both source control and antibiotic therapy. Sequential intravenous (IV) to oral therapy may improve patient convenience and reduce total health care costs. In this randomized, double-blind trial, the efficacy of sequential IV-to-oral ciprofloxacin plus metronidazole was compared with ceftriaxone plus metronidazole in adult patients with complicated intra-abdominal infections. The trial enrolled 531 patients, who began with IV therapy. Patients who improved clinically were switched to oral therapy on day three or later. The clinical and bacteriological responses four to six weeks after the end of therapy and the safety of the two regimens were assessed. To maintain blinding, the patients received placebo IV in the ciprofloxacin group or placebo orally in the ceftriaxone group. A total of 475 patients (235 ciprofloxacin plus metronidazole, 240 ceftriaxone plus metronidazole) were valid for evaluation of efficacy. All patients were included in the safety analysis. Of the patients valid for efficacy, 78% of the ciprofloxacin plus metronidazole group and 81% of the ceftriaxone plus metronidazole group were eligible for a switch to oral therapy. The clinical success rates were 98.9% and 96.9%, respectively, which were statistically equivalent. The clinical success rates for all patients, including those on continuous IV therapy, were 90.6% and 87.9%. Source control was achieved in more than 90% of the patients. The bacteriological eradication rates were similar in the two groups. Bacterial complications (e.g., surgical site infections, abscesses) were encountered more often in the ceftriaxone plus metronidazole group. Sequential ciprofloxacin plus metronidazole IV-to-oral therapy was statistically equivalent to ceftriaxone plus metronidazole. The switch to oral therapy with ciprofloxacin plus metronidazole was as

  9. "Half-half" blisters in bullous pemphigoid successfully treated with adjuvant high-dose intravenous immunoglobulin.

    PubMed

    Pacheco, David; Lopes, Leonor; Soares-Almeida, Luis; Marques, Manuel Sacramento; Filipe, Paulo

    2012-09-01

    Bullous pemphigoid is a rare, autoimmune blistering disease. Its clinical presentation is tense blisters that may arise on normal-appearing or erythematous skin. Bullous pemphigoid refractory to systemic corticosteroids in combination with immunosuppressants such as azathioprine and mycophenolate mofetil may benefit from adjuvant high-dose intravenous immunoglobulin (IVIg). We describe a particular case with an unusual clinical presentation unresponsive to systemic corticosteroids plus azathioprine, in which the addition of high-dose IVIg was successful. The combined therapy of systemic corticosteroids and azathioprine plus high-dose IVIg can be an option in refractory cases due to its efficiency and tolerability.

  10. A quantity survey of intravenous administration of metronidazole in its different forms in a tertiary teaching hospital.

    PubMed

    Lee, L L; Rowland, J; Ling, C H Y; Fiakos, E

    2010-08-01

    The aim of this paper is to examine the prescribing patterns and cost of various formulations of metronidazole in a hospital setting over a 3-month period. Oral metronidazole has high bioavailability (98.9%) with peak plasma concentrations averaged at 2.3 h after dosing. Despite the high bioavailability of oral metronidazole, many patients continue to receive metronidazole intravenously when they are suitable for oral preparation. An audit of 120 consecutive patients prescribed metronidazole was conducted at the Liverpool Hospital, NSW, from March to July 2005. There were 65 men and 55 women (age 18-93). Of the 120 patients, 16 were on oral, 1 on rectal and 103 were on intravenous metronidazole. Treatment was initiated based on clinical diagnoses. Potential pathogens were subsequently identified on only 21 occasions. The use of metronidazole as an oral preparation was contraindicated in 27 patients (22.5%) who were nil-by-mouth. Of these, rectally administered metronidazole was contraindicated in only eight patients. The average course of intravenous metronidazole was 8.0 +/- 9.7 days (mean +/- SD). The total number of intravenous metronidazole treatment days was 824. Oral metronidazole would have been possible in 618 out of the 824 days. The estimated cost to administer each dose of oral, suppository and intravenous forms of metronidazole is $A0.11, $A1.34 and $A6.09 respectively. Thus, substantial savings could be achieved if oral metronidazole were to be administered whenever possible. The early use of oral or rectal metronidazole should be encouraged when there are no clinical contraindications.

  11. High-dose intravenous IgG treatment and renal function.

    PubMed

    Schifferli, J; Leski, M; Favre, H; Imbach, P; Nydegger, U; Davies, K

    1991-02-23

    In an open trial of high dose intravenous IgG (IVIG) treatment in nephrotic patients with glomerulonephritis, the first six patients so far studied showed a transient rise in plasma creatinine. This increase was not associated with any symptoms and the urinary deposit remained unchanged. Two other patients with pre-existing renal impairment but without nephrotic syndrome had a transient and reversible rise in plasma creatinine immediately after IVIG. These observations suggest that high-dose IVIG infusion can produce short-lived disturbances in renal function in patients with kidney diseases.

  12. [A case of primary erythromelalgia successfully treated with high-dose intravenous immunoglobulin therapy].

    PubMed

    Kuroda, Takeshi; Sugimoto, Azusa; Ishigaki, Seiichirou; Murakami, Hidetomo; Kawamura, Mitsuru

    2014-02-01

    Erythromelalgia is a rare condition characterized by constant or paroxysmal burning pain, erythema, and the elevation of skin temperature in the extremities. Recently, the impairment of C-fiber function due to autoimmune system involvement is considered as the primary cause of erythromelalgia. However, a successful treatment has yet not been established. We report a case of a 39-year-old woman with primary erythromelalgia accompanied by high cerebrospinal fluid protein concentration and axonal neuropathy. She received various antiepileptic and anti-inflammatory drugs, but failed to improve. She finally underwent high-dose intravenous immunoglobulin therapy, which dramatically improved her symptoms and normalized cerebrospinal fluid protein concentration. This result demonstrates the effectiveness of high-dose intravenous immunoglobulin therapy for the treatment of primary erythromelalgia and the possibility of autoimmune system involvement.

  13. [Metronidazole].

    PubMed

    Martinez, V; Caumes, E

    2001-09-01

    Metronidazole was first introduced for the treatment of trichomoniasis. Now, its therapeutics use has subsequently been expanded to include protozoal and anaerobic infections. Oral administration is recommended: rosacea, perioral dermatitis, Helicobacter pylori, Trichomonas vaginalis and Giardia lamblia infections and bacterial vaginosis. Metronidazole given orally is absorbed almost completely. Metronidazole has limited plasma protein binding but can reach very favourable tissue distribution, including central nervous system and placenta. This drug is extensively metabolised by the liver to form 5 oxydative metabolites. The majority of this drug and metabolites are excreted in urine and feces. The half-life is 6 to 10 hours. The recommended dose is 500 mg three time per day and an adaptation is necessary in renal insufficiency. Metronidazole is well tolerated when administered in dosages of less than 2 g per day. Some adverse reactions appear to be related to the high dosages and treatment duration. Drug interactions with alcohol, warfarin and phenytoin have been reported. Mutagenesis and cancerogenesis is only described in mouse. Resistance, both clinical and microbiological, has been described only rarely.

  14. Visual Outcome after Treatment with High Dose Intravenous Methylprednisolone in Indirect Traumatic Optic Neuropathy.

    PubMed

    Pokharel, S; Sherpa, D; Shrestha, R; Shakya, K; Shrestha, R; Malla, O K; Pradhananga, C L; Pokhrel, R P; Shrestha, P

    2016-01-01

    Traumatic optic neuropathy is an acute injury of the optic nerve due to trauma. It is an ocular emergency, requiring early treatment though there is no proven standard treatment protocol for the condition. Various studies have shown improvement in vision after intravenous steroids, but not statistically significant. Studies have revealed even optical decompression surgery is not the ultimate treatment because of no significant improvement of vision. Our study aims to assess visual outcome after high dose (1 gram) of intravenous methylprednisolone in cases with indirect optic neuropathy. This was a non-randomized interventional study carried out in Kathmandu Medical College Teaching Hospital from May 1st 2013- June 1st 2014. There were 10 cases with indirect traumatic optic neuropathy included in the study. Four cases received IV methylprednisolone and six cases were observed without steroid treatment. Traumatic optic neuropathy was observed more in males[8 (80%)]with higher number in age group 21-30 years old. The visual recovery after intravenous steroid treatment was rapid and beneficial in cases with vision better than Non Perception of Light (NPL), even in cases presented 4 days after the trauma. There was rapid and beneficial improvement in visual acuity after high dose of intravenous steroid treatment in cases with indirect traumatic optic neuropathy with vision better than Non Perception of Light (NPL).

  15. When is high-dose intravenous iron repletion needed? Assessing new treatment options

    PubMed Central

    Gozzard, David

    2011-01-01

    High doses of intravenous iron have a role in the treatment of a number of clinical situations associated with iron deficiency, iron deficiency anemia, and blood loss. In the presence of functioning erythropoiesis, iron supplementation alone may be adequate to replenish iron stores and restore blood loss. Where hormone replacement with an erythropoiesis-stimulating agent is required, iron adequacy will optimize treatment. Intravenous iron offers a rapid means of iron repletion and is superior to oral iron in many circumstances, especially in the presence of anemia of chronic disease, where it appears to overcome the block to absorption of iron from the gastrointestinal tract and immobilization of stored iron. The clinical situations where high doses of iron are commonly required are reviewed. These include nondialysis-dependent chronic kidney disease, inflammatory bowel disease, obstetrics, menorrhagia, and anemia associated with cancer and its treatment. The literature indicates that high doses of iron are required, with levels of 1500 mg in nondialysis-dependent chronic kidney disease and up to 3600 mg in inflammatory bowel disease. New formulations of intravenous iron have recently been introduced that allow clinicians to administer high doses of iron in a single administration. Ferumoxytol is available in the US, has a maximum dose of 510 mg iron in a single administration, but is limited to use in chronic kidney disease. Ferric carboxymaltose can be rapidly administered in doses of 15 mg/kg body weight, up to a ceiling dose of 1000 mg. A test dose is not required, and it can be used more widely across a spectrum of iron deficiency and iron deficiency anemia indications. The latest introduction is iron isomaltoside 1000. Again, a test dose is not required, and it can be delivered rapidly as an infusion (in an hour), allowing even higher doses of iron to be administered in a single infusion, ie, 20 mg/kg body weight with no ceiling. This will allow clinicians to

  16. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  17. Effect of high-dose intravenous eletriptan on coronary artery diameter.

    PubMed

    Goldstein, J A; Massey, K D; Kirby, S; Gibson, M; Hettiarachchi, J; Rankin, A J; Jackson, N C

    2004-07-01

    The goal of this study was to evaluate the coronary vasoconstrictive effects of high doses of eletriptan compared with a standard dose of sumatriptan. Patients with no clinically significant coronary artery disease were randomized to receive high-dose intravenous eletriptan (n = 24) vs a standard dose of sumatriptan (n = 18; 6 mg subcutaneously) vs placebo (n = 18). Serial angiograms were obtained. The primary non-inferiority analysis found equivalence between the mean maximum change in left anterior descending coronary artery diameter for eletriptan, -22%[95% confidence interval (CI) -26, -19], and sumatriptan, -19% (95% CI -22, -16). The change due to placebo was -16% (95% CI -20, -12). No individual cases of clinically significant vasoconstriction were observed. The results confirm that eletriptan has a broad cardiovascular safety margin, with plasma concentrations comparable to three to five times the Cmax of an oral 80-mg dose associated with modest vasoconstriction equivalent to standard therapeutic doses of sumatriptan.

  18. Review of high-dose intravenous vitamin C as an anticancer agent.

    PubMed

    Wilson, Michelle K; Baguley, Bruce C; Wall, Clare; Jameson, Michael B; Findlay, Michael P

    2014-03-01

    In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high-dose intravenous (IV) vitamin C (L-ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well-designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high-dose oral vitamin C. Marked differences are now recognized in the pharmacokinetics of vitamin C with oral and IV administration, opening the issue of therapeutic efficacy to question. In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant but may have pro-oxidant activity at high concentrations. The mechanism of its pro-oxidant action is not fully understood, and both intra- and extracellular mechanisms that generate hydrogen peroxide have been proposed. It remains to be proven whether vitamin C-induced reactive oxygen species occur in vivo and, if so, whether this will translate to a clinical benefit. Current clinical evidence for a therapeutic effect of high-dose IV vitamin C is ambiguous, being based on case series. The interpretation and validation of these studies is hindered by limited correlation of plasma vitamin C concentrations with response. The methodology exists to determine if there is a role for high-dose IV vitamin C in the treatment of cancer, but the limited understanding of its pharmacodynamic properties makes this challenging. Currently, the use of high-dose IV vitamin C cannot be recommended outside of a clinical trial. © 2014 Wiley Publishing Asia Pty Ltd.

  19. High Dose versus Low Dose Intravenous Pantoprazole in Bleeding Peptic Ulcer: A Randomized Clinical Trial

    PubMed Central

    Masjedizadeh, Abdol Rahim; Hajiani, Eskandar; Alavinejad, Pezhman; Hashemi, Seyed Jalal; Shayesteh, Ali Akbar; Jamshidian, Noordin

    2014-01-01

    BACKGROUND The appropriate dose of proton pump inhibitors for treatment of patients with upper (GI) bleeding remains controversial. This study compares high-dose versus low-dose intravenous proton pump inhibitor (PPI) infusion for prevention of GI bleeding complications. METHODS A total of 166 patients with bleeding peptic ulcers underwent therapeutic endoscopy using concomitant therapy by argon plasma coagulation (APC) and diluted epinephrine injection. Patients were randomly divided into two groups: high-dose pantoprazole (80 mg bolus, 8 mg per hour) and low-dose pantoprazole (40 mg bolus, 4 mg per hour) infused for three days. Initial outcomes were rebleeding, need for surgery, hemoglobin drop more than two units, and hospitalization for more than five days. Secondary outcome included mortality rate. RESULTS Overall, 166 patients (83 patients per group) enrolled in the study. The average age of patients in the high-dose group was 59.5±15.6 years and 52.3±13.3 years in the low-dose group (p=0.58). Males comprised 69.7% of patients. In the high-dose group, the mean number of units of transfused blood was 3.3±1.71 and in the low-dose group, it was 2.82±1.73 (p=0.50). There were 36 (43.37%) patients in the high-dose group and 40 (48.19%) in the low-dose group who were hospitalized for more than 5 days (p=0.53). Rebleeding was observed in 27 (32.53%) patients in the high-dose group and in 21 (25.30%) in the low-dose group (p=0.30). There were no significant differences observed in drop in hemoglobin of more than two units (p=0.15), mortality (p=0.99) and surgery (p=0.75) between the two groups. CONCLUSION For controlling peptic ulcer bleeding, there is no difference between high dose and low dose pantoprazole infusion. PMID:25093061

  20. Population pharmacokinetic modeling and Monte Carlo simulation of varying doses of intravenous metronidazole.

    PubMed

    Sprandel, Kelly A; Drusano, George L; Hecht, David W; Rotschafer, John C; Danziger, Larry H; Rodvold, Keith A

    2006-08-01

    Population pharmacokinetic modeling and Monte Carlo simulation (MCS) are approaches used to determine probability of target attainment (PTA) of antimicrobial therapy. The objectives of this study were 1) to determine a population pharmacokinetic model (PPM) using metronidazole and hydroxy-metronidazole concentrations from healthy subjects and critically ill patients, and 2) to determine the probability of attaining the pharmacodynamic target area under the plasma concentration (AUC)/MIC ratio >or=70 against 218 clinical isolates of Bacteroides fragilis using MCS. Eighteen healthy subjects were randomized to 3 dosages of intravenous metronidazole (500 mg every 8 h, 1000 mg day(-1), 1500 mg day(-1)) in an open-label 3-way crossover fashion. Serial blood samples were collected over 25.5 h on the 3rd day of each study period. An additional of 8 critically ill patients received intravenous metronidazole 500 mg every 8 h. Serial blood samples were collected over 8 h after the 2nd day of dosing. Plasma metronidazole and hydroxy-metronidazole concentrations were analyzed using a high-performance liquid chromatographic assay. The 834 plasma concentrations from 62 data sets were simultaneously modeled with Non-Parametric Adaptive Grid population modeling program. A 4-compartment model with a metabolite and zero-order infusion into the central compartment was used. The mean parameter vector and covariance matrix from PPM were inserted into the simulation module of ADAPT II. A 10,000-subject MCS was performed to determine the probability of PTA for a total drug AUC to MIC ratio >or=70 against 218 isolates of B. fragilis (MIC range, 0.125-2.0 mg L(-1)). Mean parameter values were CL(non-OH), 3.08 L h(-1); Vc, 35.4 L; K(OH), 0.04 h(-1); CL(OH), 2.78 L h(-1); and V(OH), 9.66 L. The regression values of the observed versus predicted concentrations (r2) of metronidazole and hydroxy-metronidazole were 0.972 and 0.980, respectively. The PTA for metronidazole 1500 mg day(-1) or 500 mg

  1. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids

    PubMed Central

    Gorlin, Andrew W; Rosenfeld, David M; Maloney, Jillian; Wie, Christopher S; McGarvey, Johnathan; Trentman, Terrence L

    2016-01-01

    The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted. PMID:27703394

  2. Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids.

    PubMed

    Gorlin, Andrew W; Rosenfeld, David M; Maloney, Jillian; Wie, Christopher S; McGarvey, Johnathan; Trentman, Terrence L

    2016-01-01

    The conversion of high-dose intravenous (IV) opioids to an equianalgesic epidural (EP) or intrathecal (IT) dose is a common clinical dilemma for which there is little evidence to guide practice. Expert opinion varies, though a 100 IV:10:EP:1 IT conversion ratio is commonly cited in the literature, especially for morphine. In this study, the authors surveyed 724 pain specialists to elucidate the ratios that respondents apply to convert high-dose IV morphine, hydromorphone, and fentanyl to both EP and IT routes. Eighty-three respondents completed the survey. Conversion ratios were calculated and entered into graphical scatter plots. The data suggest that there is wide variation in how pain specialists convert high-dose IV opioids to EP and IT routes. The 100 IV:10 EP:1 IT ratio was the most common answer of survey respondent, especially for morphine, though also for hydromorphone and fentanyl. Furthermore, more respondents applied a more aggressive conversion strategy for hydromorphone and fentanyl, likely reflecting less spinal selectivity of those opioids compared with morphine. The authors conclude that there is little consensus on this issue and suggest that in the absence of better data, a conservative approach to opioid conversion between IV and neuraxial routes is warranted.

  3. Safety and Efficacy of Intermittent Intravenous Administration of High-Dose Micafungin

    PubMed Central

    Neofytos, Dionysis; Huang, Yao-Ting; Cheng, Kimberly; Cohen, Nina; Perales, Miguel-Angel; Barker, Juliet; Giralt, Sergio; Jakubowski, Ann; Papanicolaou, Genovefa

    2015-01-01

    Background. The use of mold-active azoles for antifungal prophylaxis after allogeneic stem cell transplantation (SCT) is hindered by adverse events and drug–drug interactions. Higher doses of echinocandins administered intermittently may be an alternative in this setting. Methods. This was a single-center, observational 5-year study to characterize the safety and efficacy of intermittent administration of high-dose intravenous micafungin (≥5 doses of ≥300 mg micafungin 2–3 times weekly) in patients with acute leukemia and allogeneic SCT recipients. Results. A total of 104 patients (84 allogeneic SCT recipients and 20 patients with leukemia) received intermittent high-dose intravenous micafungin, 83 (79.8%) as prophylaxis. Large variability in the micafungin dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg micafungin 3 times weekly. Liver function tests decreased from baseline to end of treatment (EOT; P < .001). Patients with normal baseline liver function (n = 55 [52%]) maintained similar enzyme levels throughout the study. For patients with abnormal baseline liver function (n = 49 [47%]), liver function tests significantly improved from baseline to EOT (P ≤ .005). Duration and/or micafungin dosing algorithms were not associated with liver toxicity at EOT. There were no significant changes in renal function, and infusion-related reactions or deaths were not observed. Five of 83 (6.0%) patients in the prophylaxis group developed a breakthrough fungal infection. Conclusions. In this largest cohort of patients to date, intermittent administration of high-dose micafungin was well tolerated, without any associated liver or renal function abnormalities, and may be considered an alternative antifungal prophylactic strategy. Prospective studies are needed to further validate these findings. PMID:26567284

  4. Effect of high-dose intravenous vitamin C on inflammation in cancer patients

    PubMed Central

    2012-01-01

    Background An inflammatory component is present in the microenvironment of most neoplastic tissues. Inflammation and elevated C-reactive protein (CRP) are associated with poor prognosis and decreased survival in many types of cancer. Vitamin C has been suggested as having both a preventative and therapeutic role in a number of pathologies when administered at much higher-than-recommended dietary allowance levels. Since in vitro studies demonstrated inhibition of pro-inflammatory pathways by millimolar concentrations of vitamin C, we decided to analyze the effects of high dose IVC therapy in suppression of inflammation in cancer patients. Methods 45 patients with prostate cancer, breast cancer, bladder cancer, pancreatic cancer, lung cancer, thyroid cancer, skin cancer and B-cell lymphoma were treated at the Riordan Clinic by high doses of vitamin C (7.5 g -50 g) after standard treatments by conventional methods. CRP and tumor markers were measured in serum or heparin-plasma as a routine analysis. In addition, serum samples were collected before and after the IVCs for the cytokine kit tests. Results According to our data positive response to treatment, which was demonstrated by measurements of C- reactive protein, was found in 75% of patients and progression of the inflammation in 25% of patients. IVC treatments on all aggressive stage cancer patients showed the poor response of treatment. There was correlation between tumor markers (PSA, CEA, CA27.29 and CA15-3) and changes in the levels of C-reactive protein. Our test of the effect of IVC on pro-inflammatory cytokines demonstrated that inflammation cytokines IL-1α, IL-2, IL-8, TNF-α, chemokine eotaxin and CRP were reduced significantly after treatments. Conclusions The high dose intravenous ascorbic acid therapy affects C-reactive protein levels and pro-inflammation cytokines in cancer patients. In our study, we found that modulation of inflammation by IVC correlated with decreases in tumor marker levels. In

  5. High-dose intravenous therapy with immune globulin before delivery for idiopathic thrombocytopenic purpura.

    PubMed Central

    Adderley, R. J.; Rogers, P. C.; Shaw, D.; Wadsworth, L. D.

    1984-01-01

    A 15-year-old girl with a 9-year history of idiopathic thrombocytopenic purpura resistant to high-dose steroid therapy and to splenectomy was admitted to hospital at 35 weeks' gestation with a platelet count of 10 X 10(9)/L. The bleeding time was normal, and measures of platelet aggregation were nearly so. Treatment with high intravenous doses of polyvalent immune globulin led to a rise in the platelet count to more than 110 X 10(9)/L within 5 days. An elective cesarean section was performed through the lower uterine segment with good hemostasis. After delivery the platelet count fell to its former level, but no postpartum bleeding occurred. There was a brief episode of thrombocytopenia in the infant, with some petechiae but no other hemorrhagic manifestations. No untoward effects of the immune globulin infusion were observed in either mother or daughter. PMID:6423252

  6. High-dose metronidazole: pharmacokinetics and bioavailability using an iv preparation and application of its use as a radiosensitizer

    SciTech Connect

    Rabin, H.R.; Urtasun, R.C.; Partington, J.; Koziol, D.; Sharon, M.; Walker, K.

    1980-10-01

    As an extension of studies on the clinical use of nitroimidazoles as radiosensitizers, single-dose pharmacokinetic studies of iv metronidazole (500 mg/100-ml vials) were performed in eight consenting patients. Single doses of 0.5, 1.0, 1.5, and 2.0 g (0.29 to 1.21 g/m2) were administered iv by a zero-order infusion pump. Serial timed blood and urine samples were assayed for metronidazole and its two metabolites (acetic acid and ethoxy compounds) using a high-pressure liquid chromatographic assay. Open two-compartment kinetic characteristics of metronidazole were computed from simultaneous plasma infusion and urine excretion-rate equations using a nonlinear least-squares regression analysis program (NONLIN). Means of the four kinetic parameters were (h-1): k12, 1.18; k21, 0.86; k10, 0.22; and k'e, 0.46 x 10(-4). Means of the apparent volumes of distribution were (liters/kg): Vc, 0.41; VB, 1.02; and Vss, 0.75. The mean (+- SD) for alpha-half-life was 1.2 +- 1.3 hours, and that for beta-half-life was 9.8 +- 5.9 hours. Seven of the eight patients received a second identical dose orally 1 week later, and the absolute bioavailability was estimated to approximate 100%. Unless the oral route is not feasible and if immediate high peak blood levels are not necessary, oral metronidazole is the preferred route of administration of metronidazole for its radiosensitizing effects.

  7. High-dose intravenous desferrioxamine (DFO) delivery in four thalassemic patients allergic to subcutaneous DFO administration.

    PubMed

    Lombardo, T; Ferro, G; Frontini, V; Percolla, S

    1996-01-01

    To test the hypothesis that allergy to desferrioxamine is not an immunologic mechanism, but arises from a local effect on the dermal mast cell, we have treated four patients who were not receiving chelation therapy because of hypersensitivity to standard subcutaneous (SC) therapy, with high-dose desferrioxamine (DFO) by the intravenous (IV) route. Three patients had central venous access ports implanted on the anterior chest wall. The fourth patient had the therapy delivered by the peripheral vein route. All patients had the drug delivered via an elastomeric infusor. Intravenous therapy was successful for all patients. During one year of therapy no local or systemic allergic manifestations were noted. In addition, no impairment of hearing or vision or any catheter complications were reported. A very high level of patient compliance to the therapy resulted in dramatically decreased iron stores and ferritin levels (2,759 ng/ml to 717.5 ng/ml) and a significant improvement in the clinical status of all patients. The absence of allergic episodes in this patient group after 1 year of i.v. therapy would strongly support the hypothesis that SC DFO allergy is related to a direct effect on dermal mast cells and is not an immunological reaction. This study suggests that patients with severe allergy to SC DFO can therefore safely receive their chelation therapy via the i.v. route.

  8. Usefulness of high-dose intravenous human immunoglobulins treatment for refractory recurrent pericarditis.

    PubMed

    Moretti, Michele; Buiatti, Alessandra; Merlo, Marco; Massa, Laura; Fabris, Enrico; Pinamonti, Bruno; Sinagra, Gianfranco

    2013-11-01

    The management of refractory recurrent pericarditis is challenging. Previous clinical reports have noted a beneficial effect of high-dose intravenous human immunoglobulins (IvIgs) in isolated and systemic inflammatory disease-related forms. In this article, we analyzed retrospectively our clinical experience with IvIg therapy in a series of clinical cases of pericarditis refractory to conventional treatment. We retrospectively analyzed 9 patients (1994 to 2010) with refractory recurrent pericarditis, who received high-dose IvIg as a part of their medical treatment. Nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, or colchicine treatment was not discontinued during IvIg treatment. No patients had a history of autoimmune or connective tissue diseases. During an average period of 11 months from the first recurrence, patients had experienced a mean of 5 relapses before the first IvIg treatment. In 4 cases, patients showed complete clinical remission with no further relapse after the first IvIg cycle. Two patients experienced a single minor relapse, responsive to short-term nonsteroidal anti-inflammatory drugs. In 2 patients, we performed a second cycle of IvIg after a recurrence of pericarditis, with subsequent complete remission. One patient did not respond to 3 cycles of IvIg and subsequently underwent pericardial window and long-term immunosuppressive treatment. No major adverse effect was observed in consequence of IvIg administration in all the cases. In conclusion, although IvIg mode of action is still poorly understood in this setting, this treatment can be considered as an option in patients with recurrent pericarditis refractory to conventional medical treatment and, in our small series, has proved to be effective in 8 of 9 cases. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. [Treatment of iron deficiency in predialysis state by low molecular weight iron dextran high doses intravenously].

    PubMed

    Fievet, Patrick; Coppin, Mathilde; Brazier, François; Lefèvre, Magali; Stephan, Robin; Demontis, Renato

    2012-02-01

    Anemia is a common complication of chronic kidney disease (CKD) in predialysis stage. Iron deficiency is more common than in normal patients and plays a key role in the genesis of anemia. Its correction avoids the use of erythropoiesis stimulating agents (ESA) or reduces their dosage. Treatment with oral iron is often poorly tolerated and ineffective, necessitating the use of intravenous iron. New forms of injectable iron allow the use of high doses and correct iron deficiency in a single administration with consequent preservation of venous capital and lower costs. We studied the effectiveness of iron dextran of low molecular weight (LMWID) in high doses to correct iron deficiency and treat anemia in predialysis CKD patients. Twenty-nine doses of 500 to 1600 mg were administered to 25 patients followed for CKD (GFR between 60 and 10 ml/min per 1.73 m(2)), selected on biological criteria of iron deficiency defined by a ratio of transferrin saturation (TSAT) <20% and/or serum ferritin of less than 100 μg/L. Patients received treatment by ESA in 16 cases out of 29. One month after treatment, hemoglobin (Hb) increased significantly (11.4±1.6 vs 10.4±1.4 g/dL, P=0.0003) along with a significant increase in TSAT (21.3±7.3 vs 13.3±3.8%, P=0.000003) and serum ferritin (286±253 vs 91±60 μg/L, P=0.00005). Six patients had a serum ferritin greater than 500 μg/L after treatment, which may put them at risk of iron overload. Their serum ferritin was higher than the rest of the population before treatment, while the TSAT was no different, reflecting a functional deficiency. Their hemoglobin did not increase after treatment in contrast to the rest of the population suggesting the unavailability of iron for erythropoiesis with accumulation in the reticuloendothelial system. Renal function did not change significantly and there were no cases of acute renal failure. No immediate side effect was observed. Three patients presented delayed reactions to such self

  10. Postoperative high-dose intravenous iron sucrose with low dose erythropoietin therapy after total hip replacement.

    PubMed

    Yoon, Jiyeol; Kim, Sungmin; Lee, Soo Chan; Lim, Hongsub

    2010-12-01

    Erythropoietin combined with parenteral iron sucrose therapy is an alternative to blood transfusion in anemic patients. It was shown to be effective in surgical patients in several previous studies when used in conjunction with other methods. However, there are no guidelines about safety limits in dosage amounts or intervals. In this study, we report a case of significant postoperative hemorrhage managed with high dose parenteral iron sucrose, low dose erythropoietin, vitamin B(12), vitamin C, and folic acid. An 80-year-old female patient presented for severe anemia after a total hip arthroplasty and refused an allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2 g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of intravenous iron sucrose was given postoperatively for 6 consecutive days. Erythropoietin was also administered at 2,000 IU every other day for a total of 12,000 IU. The patient was discharged in good condition on the twelfth postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL on the twentieth postoperative day.

  11. Similar biological effect of high-dose oral versus intravenous methylprednisolone in multiple sclerosis relapses.

    PubMed

    Grau-López, L; Teniente-Serra, A; Tintoré, M; Rovira, A; Ramió-Torrenta, L; Brieva, L; Saiz, A; Cano, A; Carmona, O; Hervás, J V; Martínez-Cáceres, E M; Ramo-Tello, C

    2015-04-01

    Our aim was to investigate differences in immune mechanisms in multiple sclerosis (MS) relapse, after high-dose oral methylprednisolone (oMP) or intravenous methylprednisolone (ivMP). We measured serum cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFN-γ) in 39 of 49 MS patients with moderate-severe relapse, whom were treated with ivMP or oMP in a placebo-controlled, non-inferiority clinical trial. We assessed these cytokine levels at baseline and at 1 and 4 weeks post-treatment. The cytokine levels between oMP and ivMP were similar at any time. Proinflammatory cytokines (IL-6 and IFN-γ) were significantly decreased in both groups at week 1 (p = 0.05 / p = 0.03) and at week 4 (p = 0.04 / p = 0.05). This study provides further confirmatory evidence that oMP is not inferior to ivMP. clinicaltrials.gov identifier: NCT00753792. © The Author(s), 2014.

  12. Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

    PubMed Central

    Zhao, Wei; Qi, Tengfei; Shi, Mei; Guan, Zhifang; Lu, Haikong; Long, Fuquan; Gao, Zixiao; Zhang, Sufang; Zhou, Pingyu

    2017-01-01

    Background Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai. Methodology/Principal findings Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38–4.13%) and 0.35% (95% CI: 0.06–1.39%), respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients), fatigue (2 patients), cough (1 patient), sore throat (1 patient), diarrhea (1 patient) and erythematous rash (1 patient). The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05). Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia. Conclusions/Significance Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use

  13. False-Photosensitivity and Transient Hemiparesis Following High-Dose Intravenous and Intrathecal Methotrexate for Treatment of Acute Lymphoblastic Leukemia

    PubMed Central

    Shah, Nilay; Zambidis, Elias T.

    2011-01-01

    We describe a patient who was treated with high-dose intravenous and intrathecal methotrexate for acute lymphoblastic leukemia, and who manifested a false photosensitivity reaction with no prior evidence of sun exposure. This patient later experienced delayed transient hemiparesis following methotrexate administration, although without long-term sequelae. The etiology of these events is obscure, but suggestive of a vasculitic or immune-mediated reaction to methotrexate. PMID:19326416

  14. Efficacy of high-dose intravenous immunoglobulins in two patients with idiopathic recurrent pericarditis refractory to previous immunosuppressive treatment.

    PubMed

    Tona, Francesco; Bellotto, Fabio; Laveder, Francesco; Meneghin, Alessia; Sinagra, Gianfranco; Marcolongo, Renzo

    2003-01-01

    Although idiopathic acute pericarditis is usually a self-limiting disease, in many patients it may recur over a period of months or years. Even if some evidence seems to suggest the possible role of a deranged immune reactivity in the pathogenesis of idiopathic recurrent pericarditis, the etiology of the disease is still unknown. Furthermore, while some trial data confirm the usefulness of colchicine, its medical treatment is not yet clearly established. We here report the clinical history of 2 patients with idiopathic recurrent pericarditis resistant to prednisone, colchicine and other immunosuppressive drugs, who have been successfully treated with high-dose intravenous immunoglobulins.

  15. Adverse effects of high doses of intravenous alpha lipoic Acid on liver mitochondria.

    PubMed

    Vigil, Michael; Berkson, Burton M; Garcia, Ana Patricia

    2014-01-01

    Alpha lipoic acid (ALA, thioctic acid), among other actions, is an essential coenzyme in the conversion of pyruvate to acetyl co-enzyme A. Therefore, it is necessary for the production of energy for aerobic organisms. Scientists have found that it can be used medically to help regenerate liver tissue, reverse the complications of diabetes mellitus, slow or stop the growth of cancer cells, and chelate heavy metals, among other actions. In this article, the authors describe the cellular mitochondrial damage from excessively high doses of this beneficial agent.

  16. May early intervention with high dose intravenous immunoglobulin pose a potentially successful treatment for severe cases of tick-borne encephalitis?

    PubMed Central

    2013-01-01

    Background Arthropod-borne viral encephalitis of diverse origins shows similar clinical symptoms, histopathology and magnetic resonance imaging, indicating that the patho mechanisms may be similar. There is no specific therapy to date. However, vaccination remains the best prophylaxis against a selected few. Regardless of these shortcomings, there are an increasing number of case reports that successfully treat arboviral encephalitis with high doses of intravenous immunoglobulins. Discussion To our knowledge, high dose intravenous immunoglobulin has not been tested systematically for treating severe cases of tick-borne encephalitis. Antibody-dependent enhancement has been suspected, but not proven, in several juvenile cases of tick-borne encephalitis. Although antibody-dependent enhancement during secondary infection with dengue virus has been documented, no adverse effects were noticed in a controlled study of high dose intravenous immunoglobulin therapy for dengue-associated thrombocytopenia. The inflammation-dampening therapeutic effects of generic high dose intravenous immunoglobulins may override the antibody-dependent enhancement effects that are potentially induced by cross-reactive antibodies or by virus-specific antibodies at sub-neutralizing levels. Summary Analogous to the increasing number of case reports on the successful treatment of other arboviral encephalitides with high dose intravenous immunoglobulins, we postulate whether it may be possible to also treat severe cases of tick-borne encephalitis with high dose intravenous immunoglobulins as early in the course of the disease as possible. PMID:23822550

  17. Pharmacokinetics and effects after intravenous administration of high-dose boron to rat.

    PubMed

    Tagawa, T; Kono, K; Dote, T; Usuda, K; Nishiura, H; Koizumi, C; Saito, M; Nakaya, H; Nagaie, H

    2000-06-01

    Boron (B) compounds have been widely used in the chemical industry, agriculture, and environmental science. The kinetics and toxicity of B were studied by analyzing several serum and urine parameters after a single intravenous injection of sodium tetraborate solution (B: 85.7 mg/kg) in Wistar male rats. Blood samples were removed at 0, 1, 2, 4, and 6 h after injection. The serum parameters studied included: B, Na, Ca, K, P, Mg, gamma-GTP, AST, ALT, BUN, Cr, CK, LDH and ALD. Plasma concentration-time profiles of B were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Urine samples were collected from the bladder following infusion. The urinary parameters that were studied included urine volume and excretion of B, Cr and NAG. Results indicated that a two-compartment model could describe the elimination of B from plasma after intravenous administration. Urine volume significantly increased. A diuretic effect of B was noted.

  18. New Advances in the Treatment of Neurological Diseases Using High Dose Intravenous Immunoglobulins

    PubMed Central

    2008-01-01

    Since the incidental discovery in 1981 that intravenous immunoglobulins (IVIg) are immunomodulatory, they have been investigated in a large number of putative autoimmune diseases. This has led to licensing for idiopathic thrombocytopenic purpura, Kawasaki disease, and in neurological disorders for Guillain-Barré syndrome (GBS). Although not licensed, randomized controlled trials have also shown IVIg efficacy in other neuroimmunological diseases such as multifocal motor neuropathy (MMN), chronic inflammatory demyelinating neuropathy (CIDP), myasthenia gravis, dermatomyositis, and stiff-person syndrome. However, other indications are currently being explored including Alzheimer's disease, postpolio syndrome, and narcolepsy. There are even reports from experimental studies in stroke. The results of recently published clinical trials in both the classical neuroimmunological disorders as well as for new indications are reported and their role in clinical practice is discussed. PMID:21180569

  19. Pharmacokinetics of high doses of cyanocobalamin administered by intravenous injection for 26 weeks in rats.

    PubMed

    Nava-Ocampo, Alejandro A; Pastrak, Aleksandra; Cruz, Tony; Koren, Gideon

    2005-01-01

    1. High doses of vitamin B12 (cyanocobalamin) may be therapeutically effective to treat neurological alterations secondary to a wide range of disease states. The aim of the present study was to evaluate the effect of dose and repeated administration on the pharmacokinetics of cyanocobalamin in rats. 2. Forty-eight rats were randomly assigned to receive 1, 5, 25 or 100 mg/kg cyanocobalamin for 182 days (26 weeks). Cyanocobalamin plasma levels were quantified by HPLC on days 1, 85 and 182 of treatment and were analysed by means of non-compartment pharmacokinetic (PK) analysis. In addition, population PK analysis was used to fit cyanocobalamin plasma concentrations to time by means of a two-compartment model for intravascular administration. 3. The half-life of cyanocobalamin ranged from approximately 20 to 50 min, clearance ranged from 4.5 to 9 mL/min and the volume of distribution at steady state ranged from 140 to 470 mL. A statistically significant negative relationship existed between the dose of cyanocobalamin and the normalized area under the plasma concentration-time curve (AUC). This non-linearity was not exhibited in population PK analysis. No evidence of toxicity was observed. 4. At very high and prolonged doses (up to 100 mg/kg for 26 weeks), intravascular administration of cyanocobalamin in rats follows a two-compartment kinetic model and cyanocobalamin undergoes extensive extravascular distribution. The negative relationship between dose and normalized AUC is compatible with possible saturation of tubular reabsorption, thus increasing renal clearance at higher doses.

  20. A case of anorexia nervosa with Marchiafava-Bignami Disease that responded to high-dose intravenous corticosteroid administration.

    PubMed

    Tao, Hiroki; Kitagawa, Nobuki; Kako, Yuki; Yamanaka, Hiroyoshi; Ito, Koichi; Denda, Kenzo; Koyama, Tsukasa

    2007-11-15

    We report the first known case of anorexia nervosa (AN) with Marchiafava-Bignami Disease (MBD) that responded to high-dose intravenous corticosteroid administration. A 16-year-old Japanese female with AN was diagnosed with MBD after rapid weight loss. During the acute stage, she suffered from a sudden onset of coma. After regaining consciousness, she presented with lack of movement, apathy, labile affect, and poverty of speech. On admission, magnetic resonance imaging showed an area of demyelination in the splenium of the corpus callosum. Positron emission tomography obtained 7 days after admission showed areas of hypoperfusion in the medial temporal lobe and in regions anterior and posterior to the central sulcus.

  1. Long-term outcome of Graves' orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy.

    PubMed

    Sisti, E; Menconi, F; Leo, M; Profilo, M A; Mautone, T; Mazzi, B; Rocchi, R; Latrofa, F; Nardi, M; Vitti, P; Marcocci, C; Marinò, M

    2015-06-01

    Intravenous (iv) glucocorticoids (GC) (ivGC) and orbital radiotherapy (ORT) are commonly used in active Graves' orbitopathy (GO), with favorable outcomes in up to 80% of patients. However, little is known on the factors that may affect GO outcome in the long term, an issue that we investigated here. We studied retrospectively 96 untreated patients with GO, identified out of 787 consecutive patients who came to our GO Clinic for a follow-up visit between September 2010 and June 2013. After the first observation, patients were treated with ivGC and ORT and were then re-examined after a median period of 55.5 months. The primary end-point was the possible relation between GO outcome and several individual variables. Exophthalmometry, eyelid aperture, CAS, diplopia and visual acuity (the latter only in patients with an initial reduction) improved significantly after treatment. Overall, 67.7% of patients had improved and were considered as responders, whereas the remaining (29.1% stable and 4.5% worsened) were considered as non-responders. Age, smoking, thyroid volume, thyroid treatment, serum anti-TSH receptor autoantibodies and individual GO features at first observation did not affect the outcome of GO, which, in contrast, was affected by gender and by the time elapsed between first and last observation. Thus, the prevalence of responders was higher in females (76.4 vs 48% in males, P = 0.02) and the time elapsed between first and last observation was greater in responders (58 vs 39 months in non-responders, P = 0.02). Whereas the prevalence of responders and non-responders was similar up to 36 months, there was an increase in responders beginning between 37 and 48 months and reaching a peak of ~80% between 61 and 72 months, to plateau thereafter. Given the limitations of retrospective investigations, our study confirms that the combination of GC and ORT is effective in GO and shows that females have greater chances to respond to treatment. The notorious tendency of

  2. Effect of Intravenous High Dose Vitamin C on Postoperative Pain and Morphine Use after Laparoscopic Colectomy: A Randomized Controlled Trial

    PubMed Central

    Jeon, Younghoon; Park, Jun Seok; Moon, Suyoung

    2016-01-01

    Background and Objective. Vitamin C has antioxidant, neuroprotective, and neuromodulating effects. Recently, it showed antinociceptive effect as a result of the antioxidant properties. Therefore, we designed this study to assess the effect of intravenous vitamin C on opiate consumption and pain in patients undergoing laparoscopic colectomy. Methods. A total of 100 patients were enrolled and allocated to receive 50 mg/kg vitamin C or placebo by intravenous infusion immediately after induction of anesthesia. Morphine consumption and scores of pain were assessed at 2, 6, and 24 h after completion of surgery. Results. There were 97 patients included in the analysis. Patients who received vitamin C had higher plasma concentrations of vitamin C at the end of surgery, significantly lower morphine consumption at the 2 h after end of surgery, and significantly lower pain scores at rest during first 24 h postoperatively. There was no significant difference between groups in side effects, fatigue score, or pain score during cough. Conclusion. This study shows high dose vitamin C infusion decreased postoperative pain during the first 24 h and reduced morphine consumption in the early postoperative period. Additional research needed to examine whether higher doses of vitamin C and longer infusion times can amplify these effects. PMID:27872555

  3. Four-times-daily Dosing of Rabeprazole with Sitafloxacin, High-Dose Amoxicillin, or Both for Metronidazole-Resistant Infection with Helicobacter pylori in Japan.

    PubMed

    Sugimoto, Mitsushige; Sahara, Shu; Ichikawa, Hitomi; Kagami, Takuma; Ban, Hiromitsu; Otsuka, Taketo; Andoh, Akira; Furuta, Takahisa

    2017-02-01

    The bacterial resistance of Helicobacter pylori to antimicrobial agents such as clarithromycin and metronidazole has been increasing worldwide, leading to the failure of eradication treatment. Here, we present an eradication regimen consisting of four-times-daily dosing (q.i.d.) of rabeprazole with potent acid inhibition. To investigate the efficacy of eradication therapy with rabeprazole q.i.d. and amoxicillin or sitafloxacin in Japanese infected with a metronidazole-resistant strain. We retrospectively investigated the efficacy of eradication regimens with rabeprazole q.i.d. for 7 days in 111 Japanese pooled patients infected with a metronidazole-resistant strain of H. pylori at Hamamatsu University School of Medicine Hospital or the Shiga University of Medical Science Hospital: 1, with sitafloxacin 100 mg twice daily (b.i.d.) (n = 82); 2, with amoxicillin 500 mg q.i.d. (n = 15); and 3, with amoxicillin q.i.d. and sitafloxacin b.i.d.-combined regimen (n = 14). Eradication status was assessed at 8 weeks via a (13) C-urea breath test. Eradication rate on intention-to-treat analysis was 93.7% (95% confidence interval: 87.4-97.4%, 104/111), irrespective of the high prevalence of strains resistant to clarithromycin (81.1%, 90/111) and levofloxacin (42.3%, 47/111). No significant differences in eradication rates were observed among the different treatment regimens (p = .408), eradication history (p = .096) and different CYP2C19 genotypes (p = .789). On multivariate analysis, no significant risk factor for eradication failure by therapy with potent acid inhibition was seen. In Japanese patients infected with metronidazole-resistant strains of H. pylori, eradication rates exceeding 90% can be achieved using appropriate dosing of antibiotic agents with strain susceptibility (amoxicillin q.i.d. and/or sitafloxacin b.i.d.) together with acid inhibition for a full 24 h and rabeprazole 10 mg q.i.d. These findings may be further evidence for dual therapy with rabeprazole q

  4. Intravenous lipid emulsion and high-dose insulin as adjunctive therapy for propranolol toxicity in a pediatric patient.

    PubMed

    Thompson, Amanda M; Franco Palacios, Carlos R; Henriksen, Maria N

    2016-06-15

    The concurrent use of intravenous lipid emulsion (ILE) and high-dose insulin (HDI) for the management and treatment of propranolol toxicity in a pediatric patient is described. A seven-month-old infant (weight, 6.1 kg) was admitted to a hospital emergency department with lethargy and bradycardia after an unintentional overdose of propranolol suspension, which had been prescribed several days previously for treatment of a scalp hemangioma. Notable physical examination and laboratory findings were as follows: blood pressure, 121/84 mm Hg (normal range, 90 ± 30/60 ± 10 mm Hg); heart rate, 62 beats/min (normal range, 100-150 beats/min); respiratory rate, 24 breaths/min (normal range, 25-35 breaths/min); oxygen saturation, 100% on room air; and rectal temperature, 35.7 °C (normal range, 36.6-38.0 °C). The patient was lethargic. Treatment included i.v. fluid boluses of 0.9% sodium chloride injection and i.v. boluses and continuous infusions of HDI, dextrose, and ILE. After the completion of these treatments, hemodynamic stability was regained. The case is believed to be the first reported case in which a pediatric patient less than one year of age regained hemodynamic stability after administration of ILE and HDI rescue therapy. Monitoring blood glucose frequently with HDI is essential to avoid hypoglycemia. The rationale for using ILE and HDI for reversal of drug toxicities is discussed. A symptomatic pediatric patient with acute propranolol toxicity exhibited clinical improvement with the administration of ILE in conjunction with HDI. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  5. Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women

    PubMed Central

    McClelland, R. Scott; Balkus, Jennifer E.; Lee, Jeannette; Anzala, Omu; Kimani, Joshua; Schwebke, Jane; Bragg, Vivian; Lensing, Shelly; Kavak, Lale

    2015-01-01

    Background. Vaginal infections are common, frequently recur, and may increase women's risk for sexually transmitted infections (STIs). We tested the efficacy of a novel regimen to prevent recurrent vaginal infections. Methods. Human immunodeficiency virus (HIV)–negative women 18–45 years old with 1 or more vaginal infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or Trichomonas vaginalis (TV), were randomly assigned to receive vaginal suppositories containing metronidazole 750 mg plus miconazole 200 mg or matching placebo for 5 consecutive nights each month for 12 months. Primary endpoints, evaluated every 2 months, were BV (Gram stain) and VVC (positive wet mount and culture). Results. Participants (N = 234) were randomly assigned to the intervention (N = 118) or placebo (N = 116) arm. Two hundred seventeen (93%) women completed an end-of-study evaluation. The intervention reduced the proportion of visits with BV compared to placebo (21.2% vs 32.5%; relative risk [RR] 0.65, 95% confidence interval [CI] .48–.87). In contrast, the proportion of visits with VVC was similar in the intervention (10.4%) versus placebo (11.3%) arms (RR 0.92, 95% CI .62–1.37). Conclusions. Monthly treatment with intravaginal metronidazole plus miconazole reduced the proportion of visits with BV during 12 months of follow-up. Further study will be important to determine whether this intervention can reduce women's risk of STIs. PMID:25526757

  6. Comparison of effectiveness of high-dose intracoronary adenosine versus intravenous administration on the assessment of fractional flow reserve in patients with coronary heart disease.

    PubMed

    López-Palop, Ramón; Carrillo, Pilar; Frutos, Araceli; Cordero, Alberto; Agudo, Pilar; Mashlab, Samer; Bertomeu-Martínez, Vicente

    2013-05-01

    Intravenous adenosine is considered the drug of choice to obtain maximum hyperemia in the measurement of the fractional flow reserve (FFR). However, comparative studies performed between intravenous and intracoronary administration have not used high doses of intracoronary adenosine. The present study compared the efficacy and safety of high doses of intracoronary adenosine to intravenous administration when calculating the FFR. Intracoronary bolus doses of 60, 180, 300, and 600 μg adenosine were compared to an intravenous administration of 140 μg/kg/min, 200 μg/kg/min, and 140 μg/kg/min plus an intracoronary bolus of 120 μg. All the cases were performed using the radial approach. FFR was assessed in 102 patients with 108 intermediate lesions by an intracoronary pressure wire. The intracoronary dose of 60 μg was associated with a significantly greater FFR compared to the intravenous infusion (0.02 ± 0.03, p = 0.001). The intracoronary doses of 300 (-0.01 ± 0.00; p = 0.006) and 600 μg (-0.02 ± 0.00; p <0.0005) were significantly associated with a smaller FFR compared to the intravenous infusion. An intracoronary dose of 600 μg revealed a significantly greater percentage of lesions with an FFR <0.80 compared to intravenous infusion at 140 μg/kg/min (37.6 vs 31.5%; p <0.05) and 200 μg/kg/min (37.6 vs 32.4%; p <0.05) and compared to intracoronary doses of 60 (26.9%) and 180 μg (31.5%). In conclusion, an intracoronary bolus dose >300 μg can be equal to or more effective than an intravenous infusion of adenosine in achieving maximum hyperemia when calculating the FFR. Its use could simplify these procedures without having an effect on safety.

  7. Intracoronary versus intravenous high-dose bolus plus maintenance administration of tirofiban in patients undergoing primary percutaneous coronary intervention for acute ST elevation myocardial infarction.

    PubMed

    Candemir, Basar; Kilickap, Mustafa; Ozcan, Ozgur Ulas; Kaya, Cansin Tulunay; Gerede, Menekse; Ozdemir, Aydan Ongun; Ozdol, Cagdas; Kumbasar, Deniz; Erol, Cetin

    2012-07-01

    We aimed to examine whether intracoronary high-dose bolus of tirofiban plus maintenance would result in improved clinical outcome in STEMI patients undergoing primary PCI in this pilot trial. A total of 56 patients were enrolled to receive either intracoronary high-dose bolus plus maintenance (n = 34) or intravenous high-dose bolus plus maintenance (n = 22) of tirofiban. Pre and post intervention TIMI flow grades, myocardial blush grades, peak CKMB and troponin levels, time to peak CKMB and troponin, time to 50% ST resolution and major composite adverse cardiac event rates at 30 days were recorded. Although incidence of major adverse cardiac events was not different, post intervention TIMI flow and TIMI blush grades, peak CKMB and troponin levels, and time to peak CKMB and time to peak troponin were significantly different, favoring intracoronary strategy. In conclusion, this regimen improved myocardial reperfusion and coronary flow, and reduced myocardial necrosis, but failed to improve clinical outcomes at 30 days.

  8. Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women.

    PubMed

    McClelland, R Scott; Balkus, Jennifer E; Lee, Jeannette; Anzala, Omu; Kimani, Joshua; Schwebke, Jane; Bragg, Vivian; Lensing, Shelly; Kavak, Lale

    2015-06-15

    Vaginal infections are common, frequently recur, and may increase women's risk for sexually transmitted infections (STIs). We tested the efficacy of a novel regimen to prevent recurrent vaginal infections. Human immunodeficiency virus (HIV)-negative women 18-45 years old with 1 or more vaginal infections, including bacterial vaginosis (BV), vulvovaginal candidiasis (VVC), or Trichomonas vaginalis (TV), were randomly assigned to receive vaginal suppositories containing metronidazole 750 mg plus miconazole 200 mg or matching placebo for 5 consecutive nights each month for 12 months. Primary endpoints, evaluated every 2 months, were BV (Gram stain) and VVC (positive wet mount and culture). Participants (N = 234) were randomly assigned to the intervention (N = 118) or placebo (N = 116) arm. Two hundred seventeen (93%) women completed an end-of-study evaluation. The intervention reduced the proportion of visits with BV compared to placebo (21.2% vs 32.5%; relative risk [RR] 0.65, 95% confidence interval [CI] .48-.87). In contrast, the proportion of visits with VVC was similar in the intervention (10.4%) versus placebo (11.3%) arms (RR 0.92, 95% CI .62-1.37). Monthly treatment with intravaginal metronidazole plus miconazole reduced the proportion of visits with BV during 12 months of follow-up. Further study will be important to determine whether this intervention can reduce women's risk of STIs. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Comparison of high-dose and low-dose insulin by continuous intravenous infusion in the treatment of diabetic ketoacidosis in children.

    PubMed

    Burghen, G A; Etteldorf, J N; Fisher, J N; Kitabchi, A Q

    1980-01-01

    We studied the efficacy of low-dose (0.1 U/kg/h) and high-dose (1..0 U/kg/h) insulin, given randomly to children with diabetic ketoacidosis (DKA) by continuous intravenous infusion without a loading dose. Plasma glucose reached 250 mg/dl in 3.4 +/- 0.4 h with the high-dose insulin group compared with 5.4 +/- 0.5 h with the low-dose insulin group (P < 0.01). During the first 12 h of therapy, plasma glucose fell below 100 mg/dl in 2 of 16 in the low-dose compared with 12 of 16 in the high-dose patients. The decrement of ketone bodies, cortisol, and glucagon was similar in both groups. The number of hours required for HCO3(-) greater than or equal to meq/l and arterial blood pH greater than or equal to 7.30 were not significantly different in the two groups. Hypokalemia (K < 3.4 meq/L) occurred in 3 of 16 low-dose and 10 of 16 high-dose patients. The data show that low-dose insulin, with a slower rate of glucose decrease, is as effective as a high dose for the treatment of DKA in children with less incidence of hypokalemia and decreased potential for hypoglycemia.

  10. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura.

    PubMed

    Kane, Ian; Ragucci, Dominic; Shatat, Ibrahim F; Bussel, James; Kalpatthi, Ram

    2010-04-01

    This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high-dose, anti-D immune globulin (anti-D) (75 microg/kg) as initial treatment for childhood immune thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high-dose anti-D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti-D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti-D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high-dose anti-D are effective first-line therapies for childhood ITP. However, we observed increased ADRs in the high-dose anti-D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high-dose anti-D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure.

  11. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial.

    PubMed

    Le Page, Emmanuelle; Veillard, David; Laplaud, David A; Hamonic, Stéphanie; Wardi, Rasha; Lebrun, Christine; Zagnoli, Fabien; Wiertlewski, Sandrine; Deburghgraeve, Véronique; Coustans, Marc; Edan, Gilles

    2015-09-05

    High doses of intravenous methylprednisolone are recommended to treat relapses in patients with multiple sclerosis, but can be inconvenient and expensive. We aimed to assess whether oral administration of high-dose methylprednisolone was non-inferior to intravenous administration. We did this multicentre, double-blind, randomised, controlled, non-inferiority trial at 13 centres for multiple sclerosis in France. We enrolled patients aged 18-55 years with relapsing-remitting multiple sclerosis who reported a relapse within the previous 15 days that caused an increase of at least one point in one or more scores on the Kurtzke Functional System Scale. With use of a computer-generated randomisation list and in blocks of four, we randomly assigned (1:1) patients to either oral or intravenous methylprednisolone, 1000 mg, once a day for 3 days. Patients, treating physicians and nurses, and data and outcome assessors were all masked to treatment allocation, which was achieved with the use of saline solution and placebo capsules. The primary endpoint was the proportion of patients who had improved by day 28 (decrease of at least one point in most affected score on Kurtzke Functional System Scale), without need for retreatment with corticosteroids, in the per-protocol population. The trial was powered to assess non-inferiority of oral compared with intravenous methylprednisolone with a predetermined non-inferiority margin of 15%. This trial is registered with ClinicalTrials.gov, number NCT00984984. Between Jan 29, 2008, and June 14, 2013, we screened 200 patients and enrolled 199. We randomly assigned 100 patients to oral methylprednisolone and 99 patients to intravenous methylprednisolone with a mean time from relapse onset to treatment of 7·0 days (SD 3·6) and 7·4 days (3·9), respectively. In the per-protocol population, 66 (81%) of 82 patients in the oral group and 72 (80%) of 90 patients in the intravenous group achieved the primary endpoint (absolute treatment

  12. Reduction of circulating regulatory T cells by intravenous high-dose interferon alfa-2b treatment in melanoma patients.

    PubMed

    Mozzillo, Nicola; Ascierto, Paolo

    2012-10-01

    High-dose interferon alfa-2b (IFNα-2b) is the only approved adjuvant systemic therapy for resected, high risk melanoma in the United States (Fecher and Flaherty, in Natl Compr Cancer Netw 7:295-304, 2009). Recently, two important meta-analyses of randomized trials (Wheatley et al., in J Clin Oncol, 2007; Mocellin et al. in J Natl Cancer Inst, 2010) investigating IFNα-2b versus observation in high risk melanoma patients, showed that adjuvant IFNα-2b has an impact both on relapse-free survival (RFS) and overall survival (OS) independently by dosage, duration and route compared with observation in high risk melanoma patients. Despite of an absolute benefits of 3 % (Wheatley et al., in J Clin Oncol, 2007), this treatment is associated with significant toxicity, which impacts on patient quality of life. A better understanding of the mechanism of action may help to potentiate the clinical efficacy and reduce the toxicity of IFNα-2b/Peg-IFNα-2b. Numerous studies suggest that interferon's mechanism of action in melanoma is primarily immunomodulatory (Table 1) (de La Salmoniere, in Clin Cancer Res 6:4713-4718, 2000; Stuckert, in J Clin Oncol 25:8506, 2007; Gogas et al., in N Engl J Med 354:709-718, 2006; Moschos et al., in J Clin Oncol 24:3164-3171, 2006; Ascierto and Kirkwood, in J Transl Med 6:62, 2008) Recent efforts to elucidate the mechanism of action for interferon have focused upon signal transducers and activators of transcription (STAT) (Simons et al., in J Transl Med 9:52, 2011) signaling and immunoregulatory responses mediated by regulatory T cells (Tregs) (Wang et al., in Clin Cancer Res 13:1523-1531, 2007; Clin Cancer Res 14:8314-8320, 2008). Tregs are a suppressive CD4+ T cell population that is present, along with primed effector T cells, in tumor and tumor-draining lymph nodes (Hiura et al. in J Immunol 175:5058-5066, 2005). Tregs express high levels of surface antigens such as CD25, cytotoxic T lymphocyte associated antigen 4 (CTLA-4), and

  13. Population Pharmacokinetics of High-dose Methotrexate After Intravenous Administration in Chinese Osteosarcoma Patients from a Single Institution

    PubMed Central

    Zhang, Wei; Zhang, Qing; Tian, Xiaohuang; Zhao, Haitao; Lu, Wei; Zhen, Jiancun; Niu, Xiaohui

    2015-01-01

    Background: High-dose methotrexate (HD-MTX) with folinic acid (leucovorin) rescue is the gold standard therapy in the treatment of osteosarcoma. The plasma concentration of MTX is closely related to efficacy and toxicity. There are large individual differences. Many authors have described the pharmacokinetic (PK) profile of MTX regarding osteosarcoma under a variety of circumstances. However, no data concerning Chinese osteosarcoma patient PKs using the nonlinear mixed effects models (NONMEM) have been previously reported. The goals of this study were to establish the population pharmacokinetics (PPK) of HD-MTX treatment in Chinese osteosarcoma patients, and to explore the influence of patient covariates and between-occasion variability on drug disposition. Methods: An intravenous HD-MTX solution (10 g/m2) was given 274 times to 148 osteosarcoma patients. MTX plasma concentrations were measured at 0, 6, 12, 24, 48 and 72 h after commencement of the infusion, and the fluorescence polarization immunoassay was used to determine MTX plasma concentrations. The PPK model and parameters were estimated using NONMEM software. The effects of fixed-effect factors were evaluated, and the final regression model was obtained. Results: The following population parameters were obtained using a two-compartment model: CL1 (clearance of central compartment): (CL1)i = CL1TV × [1- θCL1 −MTXNUM × MTXNUM]×[1-θCL1 −CrCI1 × (CrCl1 −1.89)]×eηCL1i (L/h). V1 (central volume): (V1)i = V1TV × eηV1i (L). CL2 (clearance of peripheral compartment): (CL2)i = CL2TV ×[1- θCL2 −BODYAREA × (bodyarea − 1.62)]×eηCL2i (L/h). V2(peripheral compartment): (V2)i = V2TV ×[1 − θV2−bodyarea × (bodyarea-1.62)]× eηV2i (L). The PPK parameters (RSD%) were CL1, V1, CL2 and V2 with values of 6.20 L/h (8.48%), 19.6 L (extremely small), 0.0172 L/h (50.9%) and 0.515 L (39.1%), respectively. Creatinine clearance and the number of methotrexate chemotherapy cycles before MTX infusion had a

  14. Folliculitis et perifolliculitis capitis abscedens et suffodiens controlled with a combination therapy: systemic antibiosis (metronidazole plus clindamycin), dermatosurgical approach, and high-dose isotretinoin.

    PubMed

    Tchernev, Georgi

    2011-05-01

    Folliculitis et perifolliculitis capitis abscedens et suffodiens is a rare disease of unknown etiology. It is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. The condition is also known as 'acne necrotica miliaris' or 'Proprionibacterium' folliculitis. Most often the disease affects men of African-American or African-Caribbean descent between 20 and 40 years of age. The clinical picture is determined by fluctuating painful fistule-forming conglomerates of abscesses in the region of the occipital scalp. The cause of scalp folliculitis is not well understood. It is generally considered to be an inflammatory reaction to components of the hair follicle, particularly the micro-organisms. These include: bacteria (especially Propionibacterium acnes, but in severe cases, also Staphylococcus aureus), Yeasts (Malassezia species) and mites (Demodex folliculorum). The initial histopathologic finding is an exclusively neutrophilic infiltration followed by a granulomatous infiltrate. The treatment of the disease is usually difficult and often disappointing. Successful treatment with isotretinoin 1 mg/kg body mass could be achieved only after regular systematic administration in the course of 3-4 months. Here we describe a patient with eruptive purulent form of the disease, which has been controlled with combination therapy: systemic antibiosis with metronidazole and clindamycin, dermatosurgical removal of single nodular formations, and isotretinoin 1 mg/kg body mass for 3-5 months.

  15. Therapeutic equivalence requires pharmaceutical, pharmacokinetic, and pharmacodynamic identities: true bioequivalence of a generic product of intravenous metronidazole.

    PubMed

    Agudelo, M; Vesga, O

    2012-05-01

    Animal models of infection have been used to demonstrate the therapeutic failure of "bioequivalent" generic products, but their applicability for this purpose requires the accurate identification of those products that are truly bioequivalent. Here, we present data comparing one intravenous generic product of metronidazole with the innovator product in a neutropenic mouse thigh anaerobic infection model. Simultaneous experiments allowed comparisons (generic versus innovator) of potency and the concentration of the active pharmaceutical ingredient (API), analytical chemistry (liquid chromatography/mass spectrometry [LC/MS]), in vitro susceptibility testing, single-dose serum pharmacokinetics (PK) in infected mice, and in vivo pharmacodynamics (PD) against Bacteroides fragilis ATCC 25825 in synergy with Escherichia coli SIG-1 in the neutropenic mouse thigh anaerobic infection model. The Hill dose-response model followed by curve-fitting analysis was used to calculate and compare primary and secondary PD parameters. The generic and the innovator products were identical in terms of the concentration and potency of the API, chromatographic and spectrographic profiles, MIC and minimal bactericidal concentrations (MBC) (2.0 mg/liter), and mouse PK. We found no differences between products in bacteriostatic doses (BD) (15 to 22 mg/kg of body weight per day) or the doses needed to kill 1 log (1LKD) (21 to 29 mg/kg per day) or 2 logs (2LKD) (28 to 54 mg/kg per day) of B. fragilis under dosing schedules of every 12 h (q12h), q8h, or q6h. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the best PD index to predict the antibacterial efficacy of metronidazole (adjusted coefficient of determination [AdjR(2)] = 84.6%), and its magnitude to reach bacteriostasis in vivo (56.6 ± 5.17 h) or to kill the first (90.8 ± 9.78 h) and second (155.5 ± 22.2 h) logs was the same for both products. Animal models of infection

  16. Therapeutic Equivalence Requires Pharmaceutical, Pharmacokinetic, and Pharmacodynamic Identities: True Bioequivalence of a Generic Product of Intravenous Metronidazole

    PubMed Central

    Agudelo, M.

    2012-01-01

    Animal models of infection have been used to demonstrate the therapeutic failure of “bioequivalent” generic products, but their applicability for this purpose requires the accurate identification of those products that are truly bioequivalent. Here, we present data comparing one intravenous generic product of metronidazole with the innovator product in a neutropenic mouse thigh anaerobic infection model. Simultaneous experiments allowed comparisons (generic versus innovator) of potency and the concentration of the active pharmaceutical ingredient (API), analytical chemistry (liquid chromatography/mass spectrometry [LC/MS]), in vitro susceptibility testing, single-dose serum pharmacokinetics (PK) in infected mice, and in vivo pharmacodynamics (PD) against Bacteroides fragilis ATCC 25825 in synergy with Escherichia coli SIG-1 in the neutropenic mouse thigh anaerobic infection model. The Hill dose-response model followed by curve-fitting analysis was used to calculate and compare primary and secondary PD parameters. The generic and the innovator products were identical in terms of the concentration and potency of the API, chromatographic and spectrographic profiles, MIC and minimal bactericidal concentrations (MBC) (2.0 mg/liter), and mouse PK. We found no differences between products in bacteriostatic doses (BD) (15 to 22 mg/kg of body weight per day) or the doses needed to kill 1 log (1LKD) (21 to 29 mg/kg per day) or 2 logs (2LKD) (28 to 54 mg/kg per day) of B. fragilis under dosing schedules of every 12 h (q12h), q8h, or q6h. The area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) was the best PD index to predict the antibacterial efficacy of metronidazole (adjusted coefficient of determination [AdjR2] = 84.6%), and its magnitude to reach bacteriostasis in vivo (56.6 ± 5.17 h) or to kill the first (90.8 ± 9.78 h) and second (155.5 ± 22.2 h) logs was the same for both products. Animal models of infection

  17. Influence of high-dose intraoperative remifentanil with intravenous ibuprofen on postoperative morphine consumption in patients undergoing pancreaticoduodenectomy: a randomized trial.

    PubMed

    Koo, Chang-Hoon; Cho, Youn Joung; Hong, Deok Man; Jeon, Yunseok; Kim, Tae Kyong

    2016-12-01

    High-dose remifentanil during surgery paradoxically increases postoperative pain intensity and morphine consumption. Cyclooxygenase inhibitors decrease prostaglandin synthesis, thereby antagonizing N-methyl-d-aspartate receptor activation, and may reduce hyperalgesia. This study was performed to evaluate whether postoperative morphine consumption increased following intraoperative continuous remifentanil infusion and whether this could be prevented by intravenous ibuprofen pretreatment. A randomized controlled study. Single university hospital, study period from September 2014 to March 2015. One hundred and twenty patients undergoing pancreaticoduodenectomy. After induction of anesthesia, patients received remifentanil target-controlled infusion (effect site concentration of 4 ng/mL or 1 ng/mL) with or without intravenous ibuprofen (800 mg). Postoperative cumulative total morphine consumption and pain intensity were assessed. Intraoperative remifentanil use in patients receiving high-dose remifentanil was more than 3-fold higher than that in patients receiving low-dose remifentanil (2666.8 ± 858.4 vs 872.0 ± 233.3 μg, respectively; P< .001). However, cumulative total morphine consumption at postoperative 1, 3, 6, 12, 24, and 48 hours did not differ among the groups. There were no differences among the groups in the self-administered analgesic dose by the patients using a controlled analgesia device, number of self-administration attempts, numerical rating scale for pain, or analgesic side effects. We found no influence on postoperative pain after high-dose remifentanil in patients undergoing pancreaticoduodenectomy. Addition of intravenous ibuprofen did not reduce postoperative morphine consumption or pain intensity. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. High-Dose Intravenous Vitamin C Treatment of a Child with Neurofibromatosis Type 1 and Optic Pathway Glioma: A Case Report

    PubMed Central

    Mikirova, Nina; Hunnunghake, Ronald; Scimeca, Ruth C.; Chinshaw, Charles; Ali, Faryal; Brannon, Chris; Riordan, Neil

    2016-01-01

    Patient: Male, 1 Final Diagnosis: Optic glioma Symptoms: Visual problems Medication: — Clinical Procedure: Intravenous vitamin C Specialty: Oncology Objective: Unusual clinical course Background: In neurofibromatosis type 1 (NF1) disease, the loss of the tumor suppressor function of the neurofibromin gene leads to proliferation of neural tumors. In children, the most frequently identified tumor is the optic pathway glioma. Case Report: We describe the case of a 5-year-old child who was diagnosed with NF1 and optic pathway tumor onset at the age of 14 months. Because of the tumor progression, chemotherapy with carboplatin and vincristine was prescribed at this early age and continued for one year. As the progression of disease continued after chemotherapy, the child, at the age of 2.8 years, was started on high-dose intravenous vitamin C (IVC) treatment (7–15 grams per week) for 30 months. After 30 months, the results of IVC treatments demonstrated reduction and stabilization of the tumors in the optic chiasm, hypothalamus, and left optic nerve according to radiographic imaging. The right-sided optic nerve mass seen before IVC treatment disappeared by the end of the treatment. Conclusions: This case highlights the positive effects of treating NF1 glioma with IVC. Additional studies are necessary to evaluate the role of high-dose IVC in glioma treatment. PMID:27773919

  19. High-dose intravenous pulse steroid therapy for optic disc swelling and subretinal fluid in non-arteritic anterior ischemic optic neuropathy

    PubMed Central

    Takayama, Kei; Kaneko, Hiroki; Kachi, Shu; Ra, Eimei; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    ABSTRACT Non-arteritic anterior ischemic optic neuropathy (NAION) is a disease with microvascular abnormality that causes acute optic disc swelling (ODS) and, in severe cases, subretinal fluid (SRF) accumulation. ODS causes compartment syndrome and subsequent axonal degeneration and loss of retinal ganglion cells by apoptosis. No treatment modalities have been effective, although some cases improved after the intake of oral systemic steroids. We reported a case of a 72-year-old man who was referred due to a visual defect in the right eye. At first presentation, visual acuity and visual field were disturbed; critical flicker frequency (CFF) was decreased; and optic coherence tomography (OCT) showed ODS and SRF. Microscopic examination revealed parapapillary hemorrhage and fluorescence angiography showed non-filling, temporal-superior choroidal lesion adjacent to the optic disc at an early phase. After high-dose intravenous steroid treatment, SRF and ODS were decreased, and completely resolved after 30 days. Visual acuity and CFF were improved, and visual field was enlarged. High-dose intravenous steroids could possibly resolve SRF and ODS and improve visual function of patients with NAION. Some cases in NAION improved visual acuity and visual function in natural course, more cases were needed to evaluate the efficiency. PMID:28303068

  20. Prolonged high-dose intravenous magnesium therapy for severe tetanus in the intensive care unit: a case series

    PubMed Central

    2010-01-01

    Introduction Tetanus rarely occurs in developed countries, but it can result in fatal complications including respiratory failure due to generalized muscle spasms. Magnesium infusion has been used to treat spasticity in tetanus, and its effectiveness is supported by several case reports and a recent randomized controlled trial. Case presentations Three Caucasian Greek men aged 30, 50 and 77 years old were diagnosed with tetanus and admitted to a general 12-bed intensive care unit in 2006 and 2007 for respiratory failure due to generalized spasticity. Intensive care unit treatment included antibiotics, hydration, enteral nutrition, early tracheostomy and mechanical ventilation. Intravenous magnesium therapy controlled spasticity without the need for additional muscle relaxants. Their medications were continued for up to 26 days, and adjusted as needed to control spasticity. Plasma magnesium levels, which were measured twice a day, remained in the 3 to 4.5 mmol/L range. We did not observe hemodynamic instability, arrhythmias or other complications related to magnesium therapy in these patients. All patients improved, came off mechanical ventilation, and were discharged from the intensive care unit in a stable condition. Conclusion In comparison with previous reports, our case series contributes the following meaningful additional information: intravenous magnesium therapy was used on patients already requiring mechanical ventilation and remained effective for up to 26 days (significantly longer than in previous reports) without significant toxicity in two patients. The overall outcome was good in all our patients. However, the optimal dose, optimal duration and maximum safe duration of intravenous magnesium therapy are unknown. Therefore, until more data on the safety and efficacy of magnesium therapy are available, its use should be limited to carefully selected tetanus cases. PMID:20356376

  1. Incidence and risk factors of acute kidney injury associated with continuous intravenous high-dose vancomycin in critically ill patients

    PubMed Central

    Lacave, Guillaume; Caille, Vincent; Bruneel, Fabrice; Palette, Catherine; Legriel, Stéphane; Grimaldi, David; Eurin, Mathilde; Bedos, Jean-Pierre

    2017-01-01

    Abstract For vancomycin therapy of severe infections, the Infectious Diseases Society of America recommends high vancomycin trough levels, whose potential for inducing nephrotoxicity is controversial. We evaluated the incidence and risk factors of acute kidney injury (AKI) in critically ill patients given continuous intravenous vancomycin with target serum vancomycin levels of 20 to 30 mg/L. We retrospectively studied 107 continuous intravenous vancomycin treatments of ≥48 hours’ duration with at least 2 serum vancomycin levels ≥20 mg/L in critically ill patients. Nephrotoxicity was defined according to the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for AKI (ie, serum creatinine elevation by ≥26.5 μmoL/L or to ≥1.5 times baseline). Risk factors for AKI were identified by univariate and multivariate analyses. AKI developed in 31 (29%) courses. Higher serum vancomycin levels were associated with AKI (P < 0.01). Factors independently associated with AKI were highest serum vancomycin ≥40 mg/L (odds ratio [OR], 3.75; 95% confidence interval [CI], 1.40–10.37; P < 0.01), higher cumulative number of organ failures (OR, 2.63 95%CI, 1.42–5.31; P < 0.01), and cirrhosis of the liver (OR, 5.58; 95%CI, 1.08–31.59; P = 0.04). In this study, 29% of critically ill patients had AKI develop during continuous intravenous vancomycin therapy targeting serum levels of 20 to 30 mg/L. Serum vancomycin level ≥40 mg/L was independently associated with AKI. PMID:28207512

  2. Salvage therapy with high dose Intravenous Immunoglobulins in acquired Von Willebrand Syndrome and unresponsive severe intestinal bleeding

    PubMed Central

    2014-01-01

    A 91-year-old woman affected with acquired Von Willebrand (VW) syndrome and intestinal angiodysplasias presented with severe gastrointestinal bleeding (hemoglobin 5 g/dl). Despite replacement therapy with VW factor/factor VIII concentrate qid, bleeding did not stop (eleven packed red blood cell units were transfused over three days). High circulating levels of anti-VW factor immunoglobulin M were documented immunoenzimatically. Heart ultrasound showed abnormalities of the mitral and aortic valves with severe flow alterations. When intravenous immunoglobulins were added to therapy, prompt clinical and laboratory responses occurred: complete cessation of bleeding, raise in hemoglobin, VW factor antigen, VW ristocetin cofactor and factor VIII levels as well as progressive reduction of the anti-VWF autoantibody levels. PMID:24926417

  3. Cognitive and Affective Symptoms Experienced by Cancer Patients Receiving High-Dose Intravenous Interleukin 2 Therapy: An Integrative Literature Review.

    PubMed

    Mann, Tara K; Dail, Robin B; Bailey, Donald E

    2016-01-01

    Alterations in cognitive/affective functioning are among the most challenging adverse effects experienced by 80% of patients with metastatic melanoma and metastatic renal cell carcinoma undergoing high-dose interleukin 2 (IL-2) therapy. The purpose of this literature review is to describe what is known about IL-2-induced cognitive/affective symptoms, their prevalence, and level of severity and synthesize findings to determine areas for future research to address symptom management challenges. This review describes the IL-2 patient experience and the pathophysiology leading to these changes. An online electronic search using PubMed was performed to identify relevant literature published between 1992 and 2015. Of the original 113 articles, information was extracted from 9 articles regarding cognitive symptoms, affective symptoms, sample size, research design, reliability, and validity. Our review suggests that the trajectories, breadth, and depth of cognitive/affective symptoms have yet to be described. Despite intervention studies designed to address the psychosocial complications of IL-2, an understanding of the level of altered cognitive/affective symptoms experienced by IL-2 patients remains unclear. Our literature review reveals a lack of standardization when assessing, reporting, and managing cognitive/affective symptoms. Patients/family members have reported cognitive/affective symptoms to be the most alarming and difficult symptoms, yet these symptoms are not adequately screened for, and patients were not informed about potential changes. Assessing patients for cognitive/affective alterations is important to reduce anxiety while improving outcomes. Education about the illness trajectory (what to expect during/after treatment) can help care partners/patients set realistic shared expectations and increase coping.

  4. Increased BK viremia and progression to BK-virus nephropathy following high-dose intravenous immunoglobulin for acute cellular rejection.

    PubMed

    Boonyapredee, Maytee; Knight, Kendral; Little, Dustin

    2014-06-01

    BK virus nephropathy and cellular rejection are common causes of allograft dysfunction in renal transplant recipients. The two can be difficult to distinguish on allograft biopsy and can be present simultaneously. Management of the patient with coexistent BK infection and rejection is complicated by the conflicting ideals of decreasing immunosuppression to treat the former and increasing immunosuppression to treat the latter. The authors present the case of a 57-year-old renal transplant recipient who underwent allograft biopsy 8 weeks post-transplant for evaluation of increased serum creatinine in the setting of BK viremia (BKV). Biopsy revealed Banff classification 1b acute cellular rejection, with insufficient evidence to diagnose BK virus-associated nephropathy. The patient was administered intravenous immune globulin (IVIG), with no other changes in immunosuppressive therapy. Plasma and urine BK increased exponentially following IVIG administration, and allograft function further deteriorated. Repeat biopsy showed overt BK viral nephropathy, and BKV and creatinine decreased only after reduction in immunosuppression and initiation of leflunomide. Although case series have suggested a potential role for IVIG in the setting of BK infection, further study is needed to define the safety and efficacy of this approach. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  5. Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

    PubMed Central

    Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

    1995-01-01

    In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality. PMID:7621588

  6. Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin.

    PubMed

    Richter, C; Schnabel, A; Csernok, E; De Groot, K; Reinhold-Keller, E; Gross, W L

    1995-07-01

    In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30 g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab')2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25-70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.

  7. Rapid excretion of gallium-67 isotope in an iron-overloaded patient receiving high-dose intravenous deferoxamine

    SciTech Connect

    Baker, D.L.; Manno, C.S.

    1988-12-01

    A 23 year-old black male with homozygous sickle cell disease (Hb SS disease) and transfusional iron overload was admitted for evaluation of response to intravenous deferoxamine (DFO) therapy. Soon after admission, the patient suffered an intraventricular hemorrhage and during his subsequent hospitalization developed a persistent fever of undetermined origin (f.u.o.). Included in the diagnostic evaluation of fever was a gallium 67 scan (Ga-67), which was initially nondiagnostic because of Ga-67 citrate's preferential chelation by DFO. After DFO was discontinued, a repeat scan demonstrated a lesion above the left kidney. To our knowledge the unusual interaction in vivo of DFO with Ga-67 citrate has not been reported in the clinical literature. With the anticipated increased use of chelation therapy for patients with transfusional iron overload, this interaction may be encountered more frequently. DFO should be discontinued before the use of Ga-67 scanning in this clinical situation, or an alternative isotopic scan, such as indium-labelled white cells, should be considered.

  8. Infusion of high-dose intravenous immunoglobulin fails to lower the strength of human leukocyte antigen antibodies in highly sensitized patients.

    PubMed

    Alachkar, Nada; Lonze, Bonnie E; Zachary, Andrea A; Holechek, Mary J; Schillinger, Karl; Cameron, Andrew M; Desai, Niraj M; Dagher, Nabil N; Segev, Dorry L; Montgomery, Robert A; Singer, Andrew L

    2012-07-27

    Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100% and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. Whereas 12.8% of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41% of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.

  9. High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial.

    PubMed

    Vial, Pablo A; Valdivieso, Francisca; Ferres, Marcela; Riquelme, Raul; Rioseco, M Luisa; Calvo, Mario; Castillo, Constanza; Díaz, Ricardo; Scholz, Luis; Cuiza, Analia; Belmar, Edith; Hernandez, Carla; Martinez, Jessica; Lee, Sang-Joon; Mertz, Gregory J

    2013-10-01

    Andes virus (ANDV)-related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. NCT00128180.

  10. High-Dose Intravenous Methylprednisolone for Hantavirus Cardiopulmonary Syndrome in Chile: A Double-Blind, Randomized Controlled Clinical Trial

    PubMed Central

    Vial, Pablo A.; Valdivieso, Francisca; Ferres, Marcela; Riquelme, Raul; Rioseco, M. Luisa; Calvo, Mario; Castillo, Constanza; Díaz, Ricardo; Scholz, Luis; Cuiza, Analia; Belmar, Edith; Hernandez, Carla; Martinez, Jessica; Lee, Sang-Joon; Mertz, Gregory J.; Abarca, Juan; Tomicic, Vinko; Aracena, M. Eugenia; Rehbein, Ana Maria; Velásquez, Soledad; Lavin, Victoria; Garrido, Felipe; Godoy, Paula; Martinez, Constanza; Chamorro, Juan Carlos; Contreras, Jorge; Hernandez, Jury; Pino, Marcelo; Villegas, Paola; Zapata, Viviana; León, Marisol; Vega, Ivonne; Otarola, Irisol; Ortega, Carlos; Daube, Elizabeth; Huecha, Doris; Neira, Alda; Ruiz, Ines; Nuñez, M. Antonieta; Monsalve, Luz; Chabouty, Henriette; Riquelme, Lorena; Palma, Samia; Bustos, Raul; Miranda, Ruben; Mardones, Jovita; Hernandez, Nora; Betancur, Yasna; Sanhueza, Ligia; Inostroza, Jaime; Donoso, Solange; Navarrete, Maritza; Acuña, Lily; Manriquez, Paulina; Castillo, Fabiola; Unzueta, Paola; Aguilera, Teresa; Osorio, Carola; Yobanolo, Veronica; Mardones, Jorge; Aranda, Sandra; Carvajal, Soledad; Sandoval, Moisés; Daza, Soraya; Vargas, Felipe; Diaz, Violeta; Riquelme, Mauricio; Muñoz, Miriam; Carriel, Andrea; Lanino, Paola; Hernandez, Susana; Schumacher, Patricia; Yañez, Lia; Marco, Claudia; Ehrenfeld, Mildred; Delgado, Iris; Rios, Susana; Vial, Cecilia; Bedrick, Edward

    2013-01-01

    Background. Andes virus (ANDV)–related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. Methods. Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. Results. Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. Conclusions. Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. Clinical Trials Registration. NCT00128180. PMID:23784924

  11. The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection.

    PubMed

    Rokas, Kristina E E; Johnson, James W; Beardsley, James R; Ohl, Christopher A; Luther, Vera P; Williamson, John C

    2015-09-15

    The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy). A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores. Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups. Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Pharmacokinetics and pharmacodynamics of high doses of pharmaceutically prepared heroin, by intravenous or by inhalation route in opioid-dependent patients.

    PubMed

    Rook, Elisabeth J; van Ree, Jan M; van den Brink, Wim; Hillebrand, Michel J X; Huitema, Alwin D R; Hendriks, Vincent M; Beijnen, Jos H

    2006-01-01

    A pharmacokinetic-pharmacodynamic study was performed in opioid-dependent patients in the Netherlands, who were currently treated with high doses of pharmaceutically prepared heroin on medical prescription. Besides intravenous heroin, heroin was prescribed for inhalation by "chasing the dragon" method. In this technique, heroin base is heated on aluminium foil, and heroin vapours are inhaled into the lungs. Not much is known about the pharmacokinetics profile and bioavailability of this specific administration method. Therefore, a study was performed on pharmacokinetics and pharmacodynamics of heroin inhalation and intravenous use. Eleven patients who injected heroin and 9 patients who inhaled heroin entered the study. They were on steady-state heroin treatment for at least 12 months. For safety reasons, there was no crossing-over between heroin injection or inhalation. In a double-blind randomised study, 67-100-150% of the regular heroin maintenance dose was administered to each patient. Maximal single heroin dose was 450 mg. Plasma concentrations of heroin and its metabolites 6-monoacetylmorphine, morphine and morphine-glucuronides were analysed using LC-MS-MS. Blood pressure, heart rate, skin temperature and reaction time were assessed. Furthermore, visual analogue scales regarding craving and appreciation of heroin effect were scored by the subjects. Both in inhaling and injecting patients, the areas under curve of heroin and all measured metabolites were linearly related to heroin dose. Mean C(max) of heroin and its metabolites were 2-6 times lower after inhalation, than after intravenous injection. Bioavailability (F) of heroin inhalation was estimated as 52% (95% CI 44-61%). Heroin was rapidly cleared from plasma. Cl/F was 930 l/hr (95% CI 799-1061 l/hr) after intravenous administration, and 1939 l/hr (95% CI 1661-2217 l/hr) after inhalation. Heroin Cl and Vd were correlated to body weight (R(2) 15-19%). Morphine-glucuronides levels were inversely related to

  13. Effects of intravenous administration of high dose-diethylstilbestrol diphosphate on serum hormonal levels in patients with hormone-refractory prostate cancer.

    PubMed

    Kitahara, S; Umeda, H; Yano, M; Koga, F; Sumi, S; Moriguchi, H; Hosoya, Y; Honda, M; Yoshida, K

    1999-10-01

    The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.

  14. Patient-reported adverse effects of high-dose intravenous methylprednisolone treatment: a prospective web-based multi-center study in multiple sclerosis patients with a relapse.

    PubMed

    Jongen, Peter Joseph; Stavrakaki, Ioanna; Voet, Bernard; Hoogervorst, Erwin; van Munster, Erik; Linssen, Wim H; Sinnige, Ludovicus G; Verhagen, Wim I; Visser, Leo H; van der Kruijk, Ruud; Verheul, Freek; Boringa, Jan; Heerings, Marco; Gladdines, Werner; Lönnqvist, Fredrik; Gaillard, Pieter

    2016-08-01

    In a prospective multi-center observational study, we evaluated the frequency, severity, and impact on activities of daily living (ADL) of adverse effects (AEs) of high-dose intravenous methylprednisolone (IVMP) in relapsing remitting multiple sclerosis (MS) patients with a relapse. Online self-report questionnaires stating IVMP's most common AEs were completed at baseline, the 2nd day of treatment, and 1 day and 1 week after treatment. Eighty-five patients were included, 66 completed the baseline questionnaire, and 59 completed at least one post-baseline questionnaire. Patients reported on average 4 (median) AEs; two (3.4 %) reported no AE. Most frequent was change in taste (61 %), facial flushing (61 %), sick/stomach pain (53 %), sleep disturbance (44 %), appetite change (37 %), agitation (36 %), and behavioral changes (36 %). Of all AEs, 34.3 % were severe and 37.9 % impacted on ADL. A 3-day course resulted in 4 (median) AEs and a 5-day course in 7. All patients with high disease impact had two or more AEs, compared with 79 % of those with low impact (p < 0.01). Of patients with high disability, 45 % had severe AEs, compared with 16 % of those with low disability. Severe central nervous system (CNS)-related AEs occurred two times more frequently in patients with high disease impact, and two-and-a-half times more frequently in patients with high disability. Therefore, in virtually all patients, high-dose IVMP leads to AEs, with about one of three AEs being severe with impact on ADL. Patients with high disease impact or high disability may experience more (severe) AEs, due to a higher occurrence of severe CNS-related AEs.

  15. Metronidazole Oral

    MedlinePlus

    Metronidazole eliminates bacteria and other microorganisms that cause infections of the reproductive system, gastrointestinal tract, skin, vagina, ... Metronidazole comes as a tablet to take by mouth. It is usually taken two or three times ...

  16. High-dose insulin and intravenous lipid emulsion therapy for cardiogenic shock induced by intentional calcium-channel blocker and Beta-blocker overdose: a case series.

    PubMed

    Doepker, Bruce; Healy, William; Cortez, Eric; Adkins, Eric J

    2014-04-01

    Recently, high-dose insulin (HDI) and intravenous lipid emulsion (ILE) have emerged as treatment options for severe toxicity from calcium-channel blocker (CCB) and beta blocker (BB). Our aim was to describe the use and effectiveness of HDI and ILE for the treatment of CCB and BB overdose. We describe 2 patients presenting to the emergency department after intentional ingestions of CCBs and BBs. A 35-year-old man presented in pulseless electrical activity after ingesting amlodopine, verapamil, and metoprolol. A 59-year-old man presented with cardiogenic shock (CS) after ingesting amlodopine, simvastatin, lisinopril, and metformin. Both patients were initially treated with glucagon, calcium, and vasopressors. Shortly after arrival, HDI (1 unit/kg × 1; 1 unit/kg/h infusion) and ILE 20% (1.5 mL/kg × 1; 0.25 mL/kg/min × 60 min) were initiated. This led to hemodynamic improvement and resolution of shock. At the time of hospital discharge, both patients had achieved full neurologic recovery. HDI effectively reverses CS induced by CCBs and BBs due to its inotropic effects, uptake of glucose into cardiac muscle, and peripheral vasodilatation. ILE is theorized to sequester agents dependent on lipid solubility from the plasma, preventing further toxicity. To our knowledge, these are the first two successful cases reported using the combination of HDI and ILE for reversing CS induced by intentional ingestions of CCBs and BBs. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

    PubMed Central

    Hoffer, L. John; Robitaille, Line; Zakarian, Robert; Melnychuk, David; Kavan, Petr; Agulnik, Jason; Cohen, Victor; Small, David; Miller, Wilson H.

    2015-01-01

    Background Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail. Methods and Findings We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement. Conclusions Despite IVC’s biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC’s value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify

  18. [A case of anaphylactoid shock occurring immediately after the initiation of second intravenous administration of high-dose immunoglobulin (IVIg) in a patient with Crow-Fukase syndrome].

    PubMed

    Takahashi, Teruyuki; Ono, Shin-ichi; Ogawa, Katuhiko; Tamura, Masato; Mizutani, Tomohiko

    2003-06-01

    We report a case of anaphylactoid shock occurring immediately after the initiation of second intravenous administration of high-dose immunoglobulin (IVIg) in a patient with Crow-Fukase syndrome. The patient was a 57-year-old woman, who was admitted to our hospital because of numbness and muscle weakness in the four extremities, difficulty in walking, and foot edema. On admission, her skin was dry and rough, and also showing scattered pigmentation, small hemangiomas, and hypertrichosis in both legs. She had distal dominant muscle weakness, more prominent in her legs, and was not able to walk. Deep tendon reflexes in her four extremities were markedly diminished or absent. She had a glove and stocking type of paresthesia, severe impairment of vibration, and absence of joint position sensation in her four extremities. On laboratory data, serum vascular endothelial growth factor (VEGF) was markedly elevated to 5,184 pg/ml (normal: below 220 pg/ml). Cerebrospinal fluid examination revealed cell counts of 2/microliter and protein level of 114 mg/dl. Abdominal echo showed marked hepatosplenomegaly. On peripheral nerve conduction study, both motor and sensory conduction velocity were undetectable in her legs. We diagnosed her condition as Crow-Fukase syndrome, and started IVIg of polyethyleneglycol-treated gamma-globulin (PEG-glob) at 400 mg/kg/day for 5 consecutive days for polyneuropathy. Since the first IVIg mildly improved muscle weakness, we tried the second IVIg of PEG-glob. However, immediately after the initiation of second IVIg of PEG-glob, she developed hypotention, dyspnea, cold sweating, cyanosis, and became lethargic. We immediately stopped IVIg and started first-aid treatment with epinephrine and corticosteroid for these symptoms. This treatment was successful and the patient fully recovered without any sequelae. Since serum IgE level remained unchanged and lymphocyte stimulation test (LST) was positive against the same rot number of PEG-glob, we diagnosed

  19. Safety and efficacy of high-dose enteral, intravenous, and transdermal clonidine for the acute management of severe intractable childhood dystonia and status dystonicus: An illustrative case-series.

    PubMed

    Nakou, V; Williamson, K; Arichi, T; Lumsden, D E; Tomlin, Steve; Kaminska, M; Lin, J-P

    2017-07-28

    Acute dystonia in children is distressing, painful and can progress to life-threatening status dystonicus. Typical management involves benzodiazepines which can result in respiratory depression requiring PICU admission. Clonidine is less respiratory-depressant, and by facilitating sleep, switches dystonia off. It can also be administered via enteral, continuous intravenous infusion, and transdermal slow release routes. We describe the dose range and safety profile of clonidine management in a case-series of children with severe acute exacerbation of dystonia in a tertiary hospital setting. The management of 5 children (3 female, age range 8-14 years) suffering from an acute exacerbation of secondary dystonia requiring hospital admission at the Evelina London Children's Hospital was reviewed. The average and maximum dose of clonidine in mcg/kg/h and routes of administration were recorded for each day of hospital admission. Co-administration of any other medical treatments for dystonia and their route of administration were also recorded. Cardiovascular and respiratory clinical status were measured by recording the daily mean and maximum Paediatric Early Warning Scores (PEWS). Clonidine was administered via enteral, intravenous, and transdermal routes at a median dose of 2.5 mcg/kg/h (range 0.1-9 mcg/kg/h). Administration of high dose clonidine was associated with decreased use of benzodiazepines, morphine, and propofol: avoiding invasive respiratory support for ¾ cases during admission. Clonidine doses via all routes of administration did not correlate with poorer PEWS scores (p = 0.839). Both high dose intravenous and transdermal clonidine where found to be effective. High dose clonidine administered via different routes can be used in the acute management of severe exacerbations of dystonia. Its use in our cohort was not associated with significant cardio-respiratory depression even at doses as high as 9 mcg/kg/h. Copyright © 2017. Published by Elsevier

  20. Metronidazole Topical

    MedlinePlus

    ... a moisturizer (if your skin is dry) and cosmetics. Ask your doctor for advice on what cosmetics to use.Metronidazole gel for the vagina comes ... not swallow it. Do not apply dressings, bandages, cosmetics, lotions, or other skin medications to the area ...

  1. Incidence and risk factors of acute kidney injury associated with continuous intravenous high-dose vancomycin in critically ill patients: A retrospective cohort study.

    PubMed

    Lacave, Guillaume; Caille, Vincent; Bruneel, Fabrice; Palette, Catherine; Legriel, Stéphane; Grimaldi, David; Eurin, Mathilde; Bedos, Jean-Pierre

    2017-02-01

    For vancomycin therapy of severe infections, the Infectious Diseases Society of America recommends high vancomycin trough levels, whose potential for inducing nephrotoxicity is controversial. We evaluated the incidence and risk factors of acute kidney injury (AKI) in critically ill patients given continuous intravenous vancomycin with target serum vancomycin levels of 20 to 30 mg/L.We retrospectively studied 107 continuous intravenous vancomycin treatments of ≥48 hours' duration with at least 2 serum vancomycin levels ≥20 mg/L in critically ill patients. Nephrotoxicity was defined according to the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for AKI (ie, serum creatinine elevation by ≥26.5 μmoL/L or to ≥1.5 times baseline). Risk factors for AKI were identified by univariate and multivariate analyses.AKI developed in 31 (29%) courses. Higher serum vancomycin levels were associated with AKI (P < 0.01). Factors independently associated with AKI were highest serum vancomycin ≥40 mg/L (odds ratio [OR], 3.75; 95% confidence interval [CI], 1.40-10.37; P < 0.01), higher cumulative number of organ failures (OR, 2.63 95%CI, 1.42-5.31; P < 0.01), and cirrhosis of the liver (OR, 5.58; 95%CI, 1.08-31.59; P = 0.04).In this study, 29% of critically ill patients had AKI develop during continuous intravenous vancomycin therapy targeting serum levels of 20 to 30 mg/L. Serum vancomycin level ≥40 mg/L was independently associated with AKI.

  2. High-dose intravenously administered iron versus orally administered iron in blood donors with iron deficiency: study protocol for a randomised, controlled trial.

    PubMed

    Macher, Susanne; Drexler, Camilla; Lindenau, Ines; Sareban, Nazanin; Schlenke, Peter; Amrein, Karin

    2016-10-28

    About 2-3 % of the population participates in blood donation programmes. Each whole blood donation or ten apheresis donations cause a loss of 200-250 mg of iron. As a result, one of the most common risks of regular blood donors is iron deficiency. Although this has been known for decades, in most countries, iron status is currently not assessed or treated in this population. Premenopausal women are particularly affected, as they have lower iron reserves and higher daily requirements. Besides anaemia, iron deficiency may lead to fatigue and impaired cognitive and physical performance. Current iron preparations for intravenous administration are well tolerated and allow for application of large doses up to 1 g in one visit. Our hypothesis is that in blood donors with iron deficiency, intravenously administered iron is more efficient and as safe as oral iron supplementation. Since anaemia is one of the most frequent reasons for permanent or intermittent donor deferral, maintaining an iron-replete donor pool may help to prevent shortages in blood supply and to avoid iron deficiency-related comorbidities. In this randomised clinical trial we include male and female blood donors aged ≥18 and ≤65 years with a ferritin value of ≤30 ng/ml. Stratified by gender, participants are randomized with a web-based randomisation tool in a 1:1 ratio to either 1 g of intravenously administered ferric carboxymaltose or 10 g of iron fumarate supplements at one to two daily doses of 100 mg each. Eight to 12 weeks after the first visit, iron status, blood count and symptoms are assessed in both groups. The primary endpoint is the difference in transferrin saturation (%) following the intervention between both groups. Secondary endpoints include other parameters of iron metabolism and red blood cell count, the number of patients with drug-related adverse events, and subjective symptoms including those of the restless legs syndrome, quality of life, and fatigue. Iron

  3. Treatment with high-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins in patients with juvenile dermatomyositis who are intolerant to intravenous immune globulins: a report of 5 cases.

    PubMed

    Speth, Fabian; Haas, Johannes-Peter; Hinze, Claas H

    2016-09-13

    High-dose intravenous immune globulins (IVIg) are frequently used in refractory juvenile dermatomyositis (JDM) but are often poorly tolerated. High-dose recombinant human hyaluronidase-facilitated subcutaneous immune globulins (fSCIg) allow the administration of much higher doses of immune globulins than conventional subcutaneous immune globulin therapy and may be an alternative to IVIg. The safety and efficacy of fSCIg therapy in JDM is unknown. In this retrospective case series, five patients with steroid-refractory severe JDM were treated with high-dose fSCIg due to IVIg adverse effects (severe headaches, nausea, vomiting, difficult venous access). Peak serum IgG levels, muscle enzymes, the childhood myositis assessment scale and adverse effects were retrieved for at least 6 months following intiation of fSCIg. Data were analyzed by descriptive statistics. Patients initially received fSCIg 1 g/kg every 14 days, resulting in median IgG peak levels of 1901 mg/dl (1606-2719 mg/dl), compared to median IgG peak and trough levels while previously receiving IVIg of 2741 mg/dl (2429-2849 mg/dl) and 1351 mg/dl (1156-1710 mg/dl). Additional antirheumatic therapies consisted of low-dose glucocorticoid therapy, methotrexate, mycophenolate mofetil and/or rituximab. Two patients maintained clinically inactive disease and three patients had only a partial treatment response. In the three patients with partial treatment response, fSCIg 1 g/kg was then given on days 1 and 6 of every 28-day cycle resulting in IgG peak levels of between 2300-2846 mg/dl (previously 1606-1901 mg/dl on the biweekly regimen), resulting in clinically inactive disease in two of the three patients. There were no relevant adverse effects that limited continuation of fSCIg treatment. High-dose fSCIg is well-tolerated in patients with JDM and high peak serum IgG levels can be achieved which may be important for treatment success. High-dose fSCIg may therefore be an alternative to high-dose IVIg

  4. Clinicopathologic features of late-onset veno-occlusive disease/sinusoidal obstruction syndrome after high dose intravenous busulfan and hematopoietic cell transplant.

    PubMed

    Pai, Rish K; van Besien, Koen; Hart, John; Artz, Andrew S; O'Donnell, Peter H

    2012-08-01

    Most cases of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occur <21 days after allogeneic hematopoietic stem cell transplant (HCT). Rarely, however, VOD/SOS can occur later, and can be confused with other causes. We report the clinicopathologic features of eight patients with advanced hematologic malignancies developing VOD/SOS >30 days after dose-escalated busulfan/fludarabine/alemtuzumab and HCT. Median time to diagnosis was 52 days (range: 33-77). For seven patients, VOD/SOS was confirmed by liver biopsies showing classical features including reticulin deposition within sinusoids, central vein occlusions, hepatocyte atrophy/necrosis, sinusoidal/perivenular hemorrhage and sparing of portal tracts. VOD/SOS risk was directly related to higher busulfan plasma exposures. Two patients died from VOD/SOS, and in another two patients VOD/SOS was contributory to death. Late-onset VOD/SOS may be underrecognized and should be considered in the differential diagnosis of patients undergoing HCT, particularly after high dose busulfan. Liver biopsy should be entertained even late in the course if appropriate signs/symptoms exist.

  5. [Superior sagittal sinus thrombosis after intrathecal chemotherapy and intravenous high-dose cytarabine in an acute myeloid leukemia case with t(8;21)(q22;q22)].

    PubMed

    Kawakami, Keiki; Ito, Ryugo; Kageyama, Yuki; Nagaharu, Keiki; Yamaguchi, Takanori; Ito, Nobuo

    2016-04-01

    Superior sagittal sinus thrombosis (SSST) is a very rare but life-threatening complication in leukemia patients. SSST is very rare in acute myeloid leukemia (AML). In leukemia patients, several risk factors for SSST have been reported such as administration of L-asparaginase, disseminated intravascular coagulation, congenital thrombophilia, meningeal leukemia, and intrathecal chemotherapy (IT). Lumbar puncture itself and corticosteroid administration have also been acknowledged as risk factors. We describe herein our clinical experience with SSST in a 29-year-old Japanese man suffering from AML with t(8;21)(q22;q22), who presented with abrupt onset of loss of consciousness, left hemiplegia, and seizure soon after IT and high-dose cytarabine (HD-AraC) with dexamethasone for post remission consolidation. Despite the presence of intracranial hemorrhage (ICH) due to SSST rupture, we conducted anticoagulant therapy with heparin. Although ICH worsened temporarily, his clinical condition gradually improved with resolution of the SSST, and he eventually became fully ambulatory. There were no deficiencies of natural anticoagulants. Three additional cycles of HD-AraC without IT therapy were conducted, but no neurological complications recurred with the concomitant use of warfarin. He was discharged free of neurological deficits. In our case, there is a possibility that IT and the administration of corticosteroids along with HD-AraC triggered SSST.

  6. High-dose intravenous treatment in iron deficiency anaemia in inflammatory bowel disease: early efficacy and impact on quality of life

    PubMed Central

    García-López, Santiago; Bocos, Judith Millastre; Gisbert, Javier P.; Bajador, Eduardo; Chaparro, María; Castaño, Carlos; García-Erce, José A.; Gomollón, Fernando

    2016-01-01

    Background Anaemia and iron deficiency are very common in inflammatory bowel disease. Clinical trials have shown intravenous iron to be effective and well tolerated. However, published experience in clinical practice with specific evaluation of the effect on quality of life is limited. Material and methods We carried out a prospective, multicentre, observational study on the effects of ferric carboxymaltose in the treatment of iron deficiency anaemia in inflammatory bowel disease. Anaemia and iron deficiency were defined according to World Health Organization criteria. Efficacy and safety were evaluated at infusion, at 2 weeks and at 12 weeks. Quality of life was evaluated according to the SIBDQ-9 index. Complete response was defined as anaemia correction or more tan 2 g/dL increase in haemoglobin. Results A total of 88 courses of ferric carboxymaltose in 72 patients were evaluated. Complete response was observed in 46% of patients at week 2, and 81.2% at week 12. Quality of life improved significatively at week 2 in both complete responders and partial responders (p<0.0005); complete responders showed siginficantly better response (p=0.016). No predictive factor was identified. Only one transient adverse effect was observed; however, this was severe. Discussion Ferric carboxymaltose showed comparable efficacy to that demonstrated in clinical trials. After only two weeks of treatment, there was a significant improvement in quality of life, with a greater effect observed in those patients with a complete haematologic response. Intravenous iron can very quickly improve quality of life in inflammatory bowel disease. PMID:27177405

  7. High dose Intravenous Anti-D Immune Globulin is More Effective and Safe in Indian Paediatric Patients of Immune Thrombocytopenic Purpura

    PubMed Central

    Jena, Rabindra Kumar; Swain, Kali Prasanna

    2016-01-01

    Introduction Immune Thrombocytopenia (ITP) is characterised by an autoimmune antibody-mediated destruction of platelets and impaired platelet production. Few controlled trials exist to guide management of patients with ITP in Indian scenario for which patients require an individualized approach. Anti-D (Rho (D) immune globulin) at a higher dose can prove to be a cost effective and safe alternative for Indian patients with ITP. Aim To compare the safety and efficacy of higher dose (75μg/kg) intravenous Anti-D immune globulin against the standard dose of 50μg/kg for the management of ITP in Indian patients. Materials and Methods One hundred and sixty four children with newly diagnosed ITP between 4-14 years were randomly selected for inclusion and were treated with 50μg/kg (standard dose) or 75μg /kg (higher dose) of Anti-D to compare the efficacy and safety of higher dose intravenous anti-D immune globulin. Efficacy of Anti-D was measured in terms of rate of response and median time to response for increase in platelet counts. Any adverse event was noted. A decrease in haemoglobin concentration suggested accompanying haemolysis. Results Seventy one out of 84 patients treated with Anti-D at 75μg/kg produced complete response (85%) with median time of response being 2.5 days. On the contrary, 45 patients (70%) patients treated with 50μg/kg had complete response. However, there was no significant increase in haemolysis with higher dose. A significant correlation was found between dose and peak increase in platelet count measured at 7th day following administration. However, there was no relationship between the decrease in haemoglobin and the dose given, or between the increase in platelet count and fall in haemoglobin. Conclusion A 75μg/kg dose of Anti-D is more effective with acceptable side effect in comparison to 50μg dose for treatment of newly diagnosed Indian patients of ITP. PMID:28208873

  8. Decreased vitamin B12 and folate levels in cerebrospinal fluid and serum of multiple sclerosis patients after high-dose intravenous methylprednisolone.

    PubMed

    Frequin, S T; Wevers, R A; Braam, M; Barkhof, F; Hommes, O R

    1993-05-01

    Twenty-one patients (15 women, 6 men) with definite multiple sclerosis (MS) were treated with 1000 mg intravenous methylprednisolone-succinate (MP) daily for 10 days. Before MP treatment there was a negative correlation (r = 0.59, P = 0.0084) between serum vitamin B12 and progression rate, defined as the ratio of the score on Kurtzke's Expanded Disability Status Scale and disease duration. A significant decrease was demonstrated in the cerebrospinal fluid (CSF) and serum levels of folate and in the CSF level of vitamin B12 after MP treatment. The decrease in serum B12 was not statistically significant. After MP treatment all median levels of vitamin B12 and folate were below the reference medians. We hypothesize that low or reduced vitamin B12/folate levels found in MS patients may be related to previous corticosteroid treatments. Otherwise a more causal relationship between low vitamin B12/folate and MS cannot be excluded. Further studies may be required to clarify the vitamin B12 and folate metabolism in patients with MS.

  9. Metronidazole. A therapeutic review and update.

    PubMed

    Freeman, C D; Klutman, N E; Lamp, K C

    1997-11-01

    The nitroimidazole antibiotic metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment. Anaerobic bacteria which are typically sensitive are primarily Gram-negative anaerobes belonging to the Bacteroides and Fusobacterium spp. Gram-positive anaerobes such as peptostreptococci and Clostridia spp. are likely to test sensitive to metronidazole, but resistant isolates are probably encountered with greater frequency than with the Gram-negative anaerobes. Gardnerella vaginalis is a pleomorphic Gram-variable bacterial bacillus that is also susceptible to metronidazole. Helicobacter pylori has been strongly associated with gastritis and duodenal ulcers. Classic regimens for eradicating this pathogen have included metronidazole, usually with acid suppression medication plus bismuth and amoxicillin. The activity of metronidazole against anaerobic bowel flora has been used for prophylaxis and treatment of patients with Crohn's disease who might develop an infectious complication. Treatment of Clostridium difficile-induced pseudomembraneous colitis has usually been with oral metronidazole or vancomycin, but the lower cost and similar efficacy of metronidazole, coupled with the increased concern about imprudent use of vancomycin leading to increased resistance in enterococci, have made metronidazole the preferred agent here. Metronidazole has played an important role in anaerobic-related infections. Advantages to using metronidazole are the percentage of sensitive Gram-negative anaerobes, its availability as oral and intravenous dosage forms, its rapid bacterial killing, its good tissue penetration, its considerably lower chance of inducing C. difficile colitis, and expense. Metronidazole has notable

  10. Intravenous high-dose interferon with or without maintenance treatment in melanoma at high risk of recurrence: meta-analysis of three trials.

    PubMed

    Malczewski, Agnieszka; Marshall, Andrea; Payne, Miranda J; Mao, Lili; Bafaloukos, Dimitrios; Si, Lu; Pectasides, Dimitrios; Fountzilas, George; Guo, Jun; Gogas, Helen; Middleton, Mark R

    2016-01-01

    Resected stage IIB-IIIC malignant melanoma has a poor prognosis with a high risk of relapse and death. Treatment with adjuvant interferon alfa-2b (IFN-α-2b) is associated with improved relapse-free and overall survivals (OS), but the most appropriate dose and duration of treatment are unknown. In this article, we present an individual patient data random effects meta-analysis of melanoma patients from the U.K., Greek, and Chinese randomized trials. All patients were randomized either to IFN-α-2b 15-20 MIU/m(2) IV daily 5 days per week for 4 weeks (IV) or to the same regimen followed by IFN-α-2b 9-10 MIU/m(2) administered three times per week for 48 weeks (IV and SC). Allowing for dose interruptions and reductions, an equivalent total dose of IFN-α-2b was delivered in all three studies. We assessed whether IV was noninferior to IV and SC in terms of relapse-free survival (RFS) and investigated tumor and patient characteristics that impacted on outcomes. Median follow-up of 716 stage IIB-IIIC patients was 5.4 years. Noninferiority of IV compared to IV and SC could not be conferred for RFS (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.89-1.52; noninferior P = 0.17). Stage (P < 0.0001), site (acral vs. other, P < 0.0001), and Breslow thickness (P = 0.02) were significant predictors of RFS. The HR for death was 1.13 for IV compared to IV and SC, (95% CI 0.91-1.39). Stage (P < 0.0001) and Breslow thickness (P = 0.001) were significant independent predictors of OS. The available data suggest that where adjuvant high-dose interferon is being considered there is no evidence to deviate from the year long regimen described in the Eastern Cooperative Oncology Group and Intergroup studies.

  11. Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study).

    PubMed

    Nam, J L; Villeneuve, E; Hensor, E M A; Conaghan, P G; Keen, H I; Buch, M H; Gough, A K; Green, M J; Helliwell, P S; Keenan, A M; Morgan, A W; Quinn, M; Reece, R; van der Heijde, D M; Wakefield, R J; Emery, P

    2014-01-01

    In disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis (RA), to compare the efficacy of methotrexate (MTX) and infliximab (IFX) with MTX and intravenous corticosteroid for remission induction. In a 78-week multicentre randomised controlled trial, double-blinded to week 26, 112 treatment-naive RA patients (1987 American College of Rheumatology classification criteria) with disease activity score 44 (DAS44)>2.4 were randomised to MTX + IFX or MTX + single dose intravenous methylprednisolone 250 mg. A treat-to-target approach was used with treatment escalation if DAS44>2.4. In the IFX group, IFX was discontinued for sustained remission (DAS44<1.6 for 6 months). The primary outcome was change in modified total Sharp-van der Heijde score (mTSS) at week 50. The mean changes in mTSS score at week 50 in the IFX and intravenous steroid groups were 1.20 units and 2.81 units, respectively (adjusted difference (95% CI) -1.45 (-3.35 to 0.45); p=0.132). Radiographic non-progression (mTSS<2.0) occurred in 81% vs 71% (OR 1.77 (0.56 to 5.61); p=0.328). DAS44 remission was achieved at week 50 in 49% and 36% (OR 2.13 (0.91 to 5.00); p=0.082), and at week 78 in 48% and 50% (OR 1.12 (0.47 to 2.68); p=0.792). Exploratory analyses suggested higher DAS28 remission at week 6 and less ultrasound synovitis at week 50 in the IFX group. Of the IFX group, 25% (14/55) achieved sustained remission and stopped IFX. No substantive differences in adverse events were seen. In DMARD-naive early RA patients, initial therapy with MTX+high-dose intravenous steroid resulted in good disease control with little structural damage. MTX+IFX was not statistically superior to MTX+intravenous steroid when combined with a treat-to-target approach.

  12. Bismuth, Metronidazole, and Tetracycline

    MedlinePlus

    Helidac® (as a kit containing Bismuth Subsalicylate, Metronidazole, Tetracycline) ... Bismuth, metronidazole, and tetracycline is used along with other ulcer medications to treat duodenal ulcers. It is in a ...

  13. Metronidazole (Flagyl) and Pregnancy

    MedlinePlus

    Metronidazole (Flagyl®) In every pregnancy, a woman starts out with a 3-5% chance of having a ... risk. This sheet talks about whether exposure to metronidazole may increase the risk for birth defects over ...

  14. Metronidazole (Flagyl) and Pregnancy

    MedlinePlus

    ... than 40 years, and is sold under the brand name Flagyl®. Can taking metronidazole during early pregnancy ... previously raised some concerns. Older studies suggested an association between metronidazole and an increase in various birth ...

  15. Plasma hydroxy-metronidazole/metronidazole ratio in hepatitis C virus-induced liver disease.

    PubMed

    Marchioretto, M A M; Ecclissato, C; da Silva, C M F; Cassiano, N M; Calafatti, S A; Mendonça, S; Ribeiro, M L; Bernasconi, G C R; Degger, M F; Piovesan, H; Pedrazzoli, J

    2005-03-01

    It has been suggested that the measurement of metronidazole clearance is a sensitive method for evaluating liver function. The aim of this study was to evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole ratios as indicators of dynamic liver function to detect changes resulting from the various forms of chronic hepatitis C virus (HCV) infection. A total of 139 individuals were studied: 14 healthy volunteers, 22 healthy, asymptomatic, consecutive anti-HCV-positive HCV-RNA negative subjects, 81 patients with chronic hepatitis C (49 with moderate/severe chronic hepatitis and 34 with mild hepatitis), and 20 patients with cirrhosis of the liver. HCV status was determined by the polymerase chain reaction. Plasma concentrations of metronidazole and its hydroxy-metabolite were measured by reverse-phase high-performance liquid chromatography with ultraviolet detection in a blood sample collected 10 min after the end of a metronidazole infusion. Anti-HCV-positive HCV-RNA-negative individuals demonstrated a significantly reduced capacity to metabolize intravenously infused metronidazole compared to healthy individuals (0.0478 +/- 0.0044 vs 0.0742 +/- 0.0232). Liver cirrhosis patients also had a reduced plasma hydroxy-metronidazole/metronidazole ratio when compared to the other groups of anti-HCV-positive individuals (0.0300 +/- 0.0032 vs 0.0438 +/- 0.0027 (moderate/severe chronic hepatitis) vs 0.0455 +/- 0.0026 (mild chronic hepatitis) and vs 0.0478 +/- 0.0044 (anti-HCV-positive, HCV-RNA-negative individuals)). These results suggest an impairment of the metronidazole metabolizing system induced by HCV infection that lasts after viral clearance. In those patients with chronic hepatitis C, this impairment is paralleled by progression of the disease to liver cirrhosis.

  16. Metronidazole-induced encephalopathy in a patient with Crohn's disease

    PubMed Central

    Kim, Jihye; Park, Jae Yong; Hong, Seung Wook; Lee, Joo Young; Kang, Jin Woo; Hwang, Seongjun; Ko, Sang-Bae; Im, Jong Pil; Kim, Joo Sung

    2017-01-01

    Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy. PMID:28239323

  17. Genotoxic effects of metronidazole.

    PubMed

    Elizondo, G; Gonsebatt, M E; Salazar, A M; Lares, I; Santiago, P; Herrera, J; Hong, E; Ostrosky-Wegman, P

    1996-09-13

    Metronidazole (MTZ) is an effective agent used in the treatment of parasitic infections. Its genotoxic effects have been shown in a variety of prokaryotic systems; however, negative results have been reported in human in vivo studies. Due to its wide spread use, a study was performed to evaluate the chromosomal aberration frequencies in peripheral blood lymphocyte cultures from 10 individuals, before and after metronidazole treatment. A significant increase in the percentage of cells with chromatid and isochromatid breaks was observed after metronidazole treatment (1500 mg per day for 10 days). The percentages of cells with aberrations did not correlate with the levels of MTZ found in plasma. Individual variability was observed with respect to both the induction of aberrations and the concentration of MTZ in plasma. They could represent differences at the metabolic level, since metronidazole is known to be biotransformed by a polymorphic P450 cytochrome, and its metabolites have shown mutagenic activity.

  18. [Perioperative metronidazole-prophylaxis for cesarian section (author's transl].

    PubMed

    Gerstner, G; Kofler, E; Huber, J

    1980-12-01

    A prospective, randomized clinical trial was conducted in 103 patients undergoing cesarian section to assess the efficacy of prophylactic, intravenously administered Metronidazole on the infectious morbidity. A group of 53 patients with perioperative Metronidazol-prophylaxis was compared to a similar controll-group without prophylaxis. Bacteriologic swabs were taken from the cervix pre- and postoperatively, using anaerobic transport media. Prophylactic Metronidazole reduced postoperative fever of more than 38 degrees C on two subsequent days from 60% in the controll-group to 30,2% in the Metronidazole-group (p less than 0,01) wound infections were reduced from 18% without to 5,7% with prophylaxis (p less than 0,05) and Endometritis from 30% without to 13,2% with prophylaxis (p less than 0,05). An additional antibiotic therapy was necessary in 44% of the cases in the controllgroup, compared to 24,5% of the cases in the Metronidazolegroup (p less than 0,05). The mean duration of hospitalisation was reduced from 12,1 +/- 3,2 days in the controll-group to 11,2 +/- 2,1 in the Metronidazole-group (p less than 0,01). Anaerobic bacteria were isolated from the servical swabs in 60% preoperatively, with a still increasing incidence to 72% postoperatively, compared to 7% in the Metronidazole-group. Our results suggest, that prophylactic, intravenously administered Metronidazol reduces the infectious morbidity following cesarian section due to the reduction of the anaerobic flora at the female genital-tract.

  19. Glioblastoma multiforme: treatment by large dose fraction irradiation and metronidazole

    SciTech Connect

    Kapp, D.S.; Wagner, F.C.; Lawrence, R.

    1982-03-01

    In an attempt to overcome the possible radioresistance of glioblastoma multiforme related to the large shoulder on the in vitro survival curves and to sensitize hypoxic tumor cells, a treatment protocol was instituted at Yale University Medical Center and affiliated hospitals, using large dose fraction irradiation therapy in conjunction with the hypoxic cell sensitizer metronidazole. Nineteen patients with biopsy-confirmed, previously untreated, cerebral grade IV glioblastoma multiforme were, following surgery, irradiated once a week at 600 rad per fraction, 3.5 to 4 hours after ingestion of metronidazole, 6 gm/m/sup 2/. A total of 7 treatments were employed, with all patients maintained on antiseizure medications and corticosteroids. Metronidazole levels were determined prior to each treatment and patients were followed closely clinically and with serial computerized tomography (CT) scans. The treatment was well tolerated, in general, with no untoward side effects related to the high dose fraction irradiation. The majority of the patients experienced varying degrees of gastrointestinal upset lasting up to several hours following metronidazole administration. Three patients died of pulmonary emboli. One patient experienced moderately severe ototoxicity. A median survival of 9.4 months was obtained for all 19 patients, suggestive of a prolongation of survival compared to historical controls treated with conventionally fractionated radiation or with unconventional radiation fractionation schemes and metronidazole or misonidazole.

  20. Metronidazole-induced encephalopathy: not always a reversible situation.

    PubMed

    Hobbs, Kyle; Stern-Nezer, Sara; Buckwalter, Marion S; Fischbein, Nancy; Finley Caulfield, Anna

    2015-06-01

    Metronidazole is a nitroimidazole antimicrobial drug prescribed to treat infections caused by anaerobic bacteria and protozoa. Uncommonly, it causes central nervous system (CNS) toxicity manifesting as metronidazole-induced encephalopathy (MIE). Case report. A 65-year-old woman with hepatitis B cirrhosis (Child-Pugh class C, MELD 21) developed progressive encephalopathy to GCS 4 during a 3-week course of metronidazole for cholecystitis. Initial MRI was consistent with CNS metronidazole toxicity, with symmetrical T2 hyperintensity and generally restricted diffusion in bilateral dentate nuclei, corpus callosum, midbrain, superior cerebellar peduncles, internal capsules, and cerebral white matter. Laboratory values did not demonstrate significant electrolyte shifts, and continuous EEG was without seizure. High-dose thiamine was empirically administered. Lumbar puncture was not performed due to coagulopathy and thrombocytopenia. Despite discontinuation of metronidazole and keeping ammonia levels near normal, the patient did not improve. MRI was repeated 1 week after discontinuation of metronidazole. Although there was decreased DWI hyperintensity in the dentate nuclei, diffuse T2 hyperintensity persisted and even progressed in the brainstem, basal ganglia, and subcortical white matter. Petechial hemorrhages developed in bilateral corticospinal tracts and subcortical white matter. T1 hypointensity appeared in the corpus callosum. She was transitioned to comfort measures only and died 12 days later. MIE is an uncommon adverse effect of treatment with metronidazole that characteristically affects the dentate nuclei but may also involve the brainstem, corpus callosum, subcortical white matter, and basal ganglia. While the clinical symptoms and neuroimaging changes are usually reversible, persistent encephalopathy with poor outcome may occur.

  1. Topical Metronidazole for Odor Control in Pressure Ulcers.

    PubMed

    Lyvers, Elizabeth; Elliott, David P

    2015-09-01

    There are many remedies that have been recommended for the treatment of foul odor associated with pressure ulcers. This article seeks to review the literature surrounding the use of metronidazole as a safe and effective solution to an oftentimes stubborn and frustrating problem. Other tools used to control odor include bleach-based solutions and charcoal dressings. Metronidazole, with its antianaerobic properties, appears to have a useful role in therapy when applied topically to a pressure ulcer. Commercially available products include 0.75% and 1% creams, gels, lotions, and intravenous solutions. Of the 59 cases viewed throughout several publications, 56 reported nearly complete odor resolution in two to seven days when metronidazole was applied to the wound two or three times daily. Virtually no systemic adverse events have been reported in the literature, despite the risk for systemic absorption. A need remains to monitor for toxicities such as nausea, gastrointestinal distress, and neural toxicities from long-term use.

  2. Busulfan and metronidazole: an often forgotten but significant drug interaction.

    PubMed

    Gulbis, Alison M; Culotta, Kirk S; Jones, Roy B; Andersson, Borje S

    2011-07-01

    To report the case of a clinically significant drug interaction between intravenous busulfan and oral metronidazole observed through busulfan therapeutic drug monitoring (TDM). A 7-year-old boy with a history of myelodysplasia that progressed to acute myeloid leukemia received busulfan with therapeutic drug monitoring (TDM), clofarabine, and thiotepa as a pretransplant conditioning regimen for a cord blood transplant. The patient received metronidazole the day after a busulfan test dose of 0.5 mg/kg was administered. On the day of the first busulfan therapeutic dose, TDM was performed and the clearance of busulfan was significantly decreased by 46%. After 2 doses of busulfan therapy, the course area under the curve was exceeded, requiring discontinuation of busulfan. Metronidazole is not known to affect glutathione or the glutathione S-transferase A1 (GSTA1) enzyme system or cytochrome P450 (CYP) 3A4. Busulfan is a bifunctional alkylating agent widely used in pretransplant conditioning regimens in patients undergoing stem cell transplantation for hematologic malignancies. Busulfan metabolism is best described by hepatic conjugation to glutathione by GSTA1, although some CYP-dependent pathways have been described. Currently there is 1 publication describing the drug interaction between oral busulfan and oral metronidazole, in which concomitant use of metronidazole resulted in higher busulfan trough concentrations and higher risk of veno-occlusive disease. Our case represents a possible drug interaction based on the Horn Drug Interaction Probability Scale. Though the mechanistic basis for this interaction is unknown, the risks and benefits of using metronidazole during and in close proximity to busulfan should be carefully considered and therapeutic alternatives to metronidazole should be used when appropriate.

  3. Metronidazole for the treatment of Tritrichomonas foetus in bulls.

    PubMed

    Love, David; Fajt, Virginia R; Hairgrove, Thomas; Jones, Meredyth; Thompson, James A

    2017-04-14

    Tritrichomonas foetus is a sexually transmitted protozoon that causes reproductive failure, among cattle, so disruptive that many western US states have initiated control programs. Current control programs are based on the testing and exclusion of individual bulls. Unfortunately, these programs are utilizing screening tests that are lacking in sensitivity. Blanket treatment of all the exposed bulls and adequate sexual rest for the exposed cows could provide a more viable disease control option. The objectives of this study were twofold. The first objective was to demonstrate effectiveness for metronidazole treatment of a bull under ideal conditions and with an optimized treatment regime. This type of study with a single subject is often referred to as an n-of-1 or single subject clinical trial. The second objective of the current study was to review the scientific basis for the banning of metronidazole for use in Food Animals by the Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA). Results from an antimicrobial assay indicated that metronidazole at a concentration of 0.5 μg/mL successfully eliminated in vitro protozoal growth of bovine Tritrichomonas foetus. The estimated effective intravenous dose was two treatments with 60 mg/kg metronidazole, 24 h apart. A bull that had tested positive for Tritrichomonas foetus culture at weekly intervals for 5 weeks prior to treatment was negative for Tritrichomonas foetus culture at weekly intervals for five consecutive weeks following this treatment regimen. An objective evaluation of the published evidence on the potential public health significance of using metronidazole to treat Tritrichomonas foetus in bulls provides encouragement for veterinarians and regulators to consider approaches that might lead to permitting the legal use of metronidazole in bulls. The study demonstrated successful inhibition of Tritrichomonas foetus both in vitro and in vivo with metronidazole. The current status of metronidazole

  4. Metronidazole-Induced Cerebellar Toxicity

    PubMed Central

    Agarwal, Amit; Kanekar, Sangam; Sabat, Shyam; Thamburaj, Krishnamurthy

    2016-01-01

    Metronidazole is a very common antibacterial and antiprotozoal with wide usage across the globe, including the least developed countries. It is generally well-tolerated with a low incidence of serious side-effects. Neurological toxicity is fairly common with this drug, however majority of these are peripheral neuropathy with very few cases of central nervous toxicity reported. We report the imaging findings in two patients with cerebellar dysfunction after Metronidazole usage. Signal changes in the dentate and red nucleus were seen on magnetic resonance imaging in these patients. Most of the cases reported in literature reported similar findings, suggesting high predilection for the dentate nucleus in metronidazole induced encephalopathy. PMID:27127600

  5. Pharmacokinetics of metronidazole, tetracycline and bismuth in healthy volunteers after oral administration of compound tablets containing a combination of metronidazole, tetracycline hydrochloride and bismuth oxide.

    PubMed

    Wu, Y; Ding, L; Huang, N-Y; Wen, A-D; Liu, B; Li, W-B

    2015-02-01

    To eradicate Helicobacter pylori in human pylorus and to heal duodenal ulcers, recently, a new formulation of combination tablets containing metronidazole 125 mg, tetracycline hydrochloride 125 mg and bismuth oxide 40 mg has been developed. To investigate the pharmacokinetics of metronidazole, tetracycline and bismuth in healthy Chinese volunteers after oral administration of the test formulation. A one-sequence, 3-period study was conducted in 12 Chinese healthy volunteers (6 male, 6 female). Volunteers each received single low dose (1 tablet) under fed condition in period 1, single high dose (3 tablets) under fasted condition in period 2, and single high dose (3 tablets) and multiple doses (3 tablets at once, 4 times daily for 7 consecutive days) under fed condition in period 3. Blood samples were collected and determined over 48 h in every period. After single high dose administration under fed condition, the C max of metronidazole, tetracycline and bismuth were 6.833 ± 0.742 μg/mL, 0.8513 ± 0.1253 μg/mL and 3.32 ± 1.89 ng/mL, respectively. The C max and AUC 0-48 of metronidazole increased in proportion to the doses within the tested dose range, but tetracycline and bismuth did not. Food caused 10% and 80% decrease of the C max for metronidazole and bismuth, respectively, but did not affect tetracycline. No gender effect was found on the pharmacokinetics of the 3 ingredients. In the steady state, the C av of metronidazole, tetracycline and bismuth were 20.75 ± 3.52 μg/mL, 1.900 ± 0.243 μg/mL and 5.61 ± 1.34 ng/mL, respectively. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Pharmacokinetics of high-dose metoclopramide in cancer patients.

    PubMed

    McGovern, E M; Grevel, J; Bryson, S M

    1986-01-01

    The introduction of new cytotoxic drug regimens has been associated with an increase in the incidence and severity of adverse effects. This in turn has highlighted the need for more effective adjuvant therapy. The use of metoclopramide for the prophylaxis of nausea and vomiting, in high intravenous doses (50 to 1000 mg), has become established since 1981. As a lipid-soluble drug, metoclopramide has a large volume of distribution. The reported mean values after high doses range between 2.8 and 4.6 L/kg. The mean values for total body clearance and terminal half-life range from 0.31 to 0.69 L/kg/h and from 4.5 to 8.8 hours, respectively. The values of these pharmacokinetic parameters are essentially similar to those obtained after conventional doses (less than 50mg). Pharmacokinetic parameters appear unaffected by age, although no high-dose study has been conducted in children. Bodyweight is apparently correlated with clearance. An influence of renal function indices on terminal half-life and clearance has been shown, which is rather surprising since renal clearance accounts for only 20% of the total clearance. No thorough investigations exist which examine the influence of hepatic disease, cancer type and cytotoxic drug regimen on the disposition of metoclopramide. A relationship between dose (or concentration) and therapeutic or adverse effects of metoclopramide is outlined. The therapeutic benefit of high doses (up to 14 mg/kg) may be dependent on age, and on the combination of cytotoxic drugs. The advantages of high doses of metoclopramide are most apparent when the drug is used as protection against the adverse effects of high doses of cisplatin (greater than 60 mg/m2). Despite considerable pharmacokinetic variability, intravenous administration of high doses of metoclopramide is relatively safe due to its large therapeutic index.

  7. Metronidazole neurotoxicosis in two cats.

    PubMed

    Caylor, K B; Cassimatis, M K

    2001-01-01

    Two cats were presented for neurological dysfunction from suspected metronidazole toxicity. One cat was receiving 111 mg/kg body weight per day of metronidazole for 9 weeks. After 9 weeks, the dose was increased to 222 mg/kg body weight per day, and 2 days later the cat began to experience progressive neurological signs that culminated in generalized seizures. The second cat was receiving metronidazole at a total dose of 58 mg/kg body weight per day for 6 months. This cat experienced acute onset of ataxia and alteration in mentation. Laboratory evaluations in both cases were without significant findings. The neurological signs in both cats resolved within days of initiating supportive therapy and withdrawal of the drug. This report describes the two cases and discusses the etiology of metronidazole neurotoxicosis.

  8. Progressive muscle weakness after high-dose steroids in two children with CIDP.

    PubMed

    Rostasy, Kevin M; Diepold, Katharina; Buckard, Johannes; Brockmann, Knut; Wilken, Bernd; Hanefeld, Folker

    2003-09-01

    Corticosteroids and intravenous immunoglobulins belong to the first line of treatment in chronic inflammatory demyelinating polyneuropathy. In patients with a progressive course, plasma exchange and immunomodulatory drugs are added to the regimen. To reduce the side effects of long-term oral prednisolone, high-dose pulsatile intravenous methylprednisolone treatment has been advocated. We report two children with chronic inflammatory demyelinating polyneuropathy who, after high-dose intravenous pulsatile methylprednisolone, experienced a significant clinical deterioration with profound loss of muscle strength. Both patients improved after changing treatment to immunoglobulins in one and cyclosporine combined with immunoglobulins and oral prednisolone in the other.

  9. Optimization of Metronidazole Emulgel

    PubMed Central

    Rao, Monica; Sukre, Girish; Aghav, Sheetal; Kumar, Manmeet

    2013-01-01

    The purpose of the present study was to develop and optimize the emulgel system for MTZ (Metronidazole), a poorly water soluble drug. The pseudoternary phase diagrams were developed for various microemulsion formulations composed of Capmul 908 P, Acconon MC8-2, and propylene glycol. The emulgel was optimized using a three-factor, two-level factorial design, the independent variables selected were Capmul 908 P, and surfactant mixture (Acconon MC8-2 and gelling agent), and the dependent variables (responses) were a cumulative amount of drug permeated across the dialysis membrane in 24 h (Y 1) and spreadability (Y 2). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equations were generated for responses Y 1 and Y 2. The statistical validity of the polynomials was established, and optimized formulation factors were selected. Validation of the optimization study with 3 confirmatory runs indicated a high degree of prognostic ability of response surface methodology. Emulgel system of MTZ was developed and optimized using 23 factorial design and could provide an effective treatment against topical infections. PMID:26555982

  10. Randomized pharmacokinetic and drug–drug interaction studies of ceftazidime, avibactam, and metronidazole in healthy subjects

    PubMed Central

    Das, Shampa; Li, Jianguo; Armstrong, Jon; Learoyd, Maria; Edeki, Timi

    2015-01-01

    We assessed pharmacokinetic and safety profiles of ceftazidime–avibactam administered ± metronidazole, and whether drug–drug interactions exist between ceftazidime and avibactam, or ceftazidime-avibactam and metronidazole. The first study (NCT01430910) involved two cohorts of healthy subjects. Cohort 1 received ceftazidime–avibactam (2000–500 mg) as a single infusion or as multiple intravenous infusions over 11 days to evaluate ceftazidime–avibactam pharmacokinetics. Cohort 2 received ceftazidime, avibactam, or ceftazidime–avibactam over 4 days to assess drug–drug interaction between ceftazidime and avibactam. The second study (NCT01534247) assessed interaction between ceftazidime–avibactam and metronidazole in subjects receiving ceftazidime–avibactam (2000–500 mg), metronidazole (500 mg), or metronidazole followed by ceftazidime–avibactam over 4 days. In all studies, subjects received a single-dose on the first and final days, and multiple-doses every 8 h on intervening days. Concentration-time profiles for ceftazidime and avibactam administered as single- or multiple-doses separately or together with/without metronidazole were similar. There was no evidence of time-dependent pharmacokinetics or accumulation. In both interaction studies, 90% confidence intervals for geometric least squares mean ratios of area under the curve and maximum plasma concentrations for each drug were within the predefined interval (80–125%) indicating no drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. There were no safety concerns. In conclusion, pharmacokinetic parameters and safety of ceftazidime, avibactam, and metronidazole were similar after single and multiple doses with no observed drug–drug interaction between ceftazidime and avibactam, or ceftazidime–avibactam and metronidazole. PMID:26516584

  11. Intestinal Fatty-Acid Binding Protein and Metronidazole Response in Premature Infants

    PubMed Central

    Sampson, Mario R.; Bloom, Barry T.; Arrieta, Antonio; Capparelli, Edmund; Benjamin, Daniel K.; Smith, P. Brian; Kearns, Gregory L.; van den Anker, John; Cohen-Wolkowiez, Michael

    2014-01-01

    Objectives In premature infants with suspected intra-abdominal infection, biomarkers for treatment response to antimicrobial therapy are lacking. Intestinal fatty acid-binding protein (I-FABP) is specific to the enterocyte and is released in response to intestinal mucosal injury. I-FABP has not been evaluated as a surrogate marker of disease response to antimicrobial therapy. We examined the relationship between metronidazole exposure and urinary I-FABP concentrations in premature infants with suspected intra-abdominal infection. Study design We conducted an intravenous metronidazole pharmacokinetic study, collecting ≤3 urine samples per infant for I-FABP concentration measurements. We analyzed the relationship between I-FABP concentrations and measures of metronidazole exposure and pharmacokinetics, maturational factors, and other covariates. Results Twenty-six samples from 19 premature infants were obtained during metronidazole treatment. When analyzed without regard to presence of necrotic gastrointestinal disease, there were no significant associations between predictor variables and I-FABP concentrations. However, when the sample was limited to premature infants with necrotic gastrointestinal disease, an association was found between average predicted metronidazole concentration and I-FABP concentration (p=0.006). Conclusion While a predictive association between urinary I-FABP and metronidazole systemic exposure was not observed, the data suggest the potential of this endogenous biomarker to serve as a pharmacodynamic surrogate for antimicrobial treatment of serious abdominal infections in neonates and infants. PMID:25318626

  12. High dose of ascorbic acid induces cell death in mesothelioma cells.

    PubMed

    Takemura, Yukitoshi; Satoh, Motohiko; Satoh, Kiyotoshi; Hamada, Hironobu; Sekido, Yoshitaka; Kubota, Shunichiro

    2010-04-02

    Malignant mesothelioma is an asbestos-related fatal disease with no effective cure. Recently, high dose of ascorbate in cancer treatment has been reexamined. We studied whether high dose of ascorbic acid induced cell death of four human mesothelioma cell lines. High dose of ascorbic acid induced cell death of all mesothelioma cell lines in a dose-dependent manner. We further clarified the cell killing mechanism that ascorbic acid induced reactive oxygen species and impaired mitochondrial membrane potential. In vivo experiment, intravenous administration of ascorbic acid significantly decreased the growth rate of mesothelioma tumor inoculated in mice. These data suggest that ascorbic acid may have benefits for patients with mesothelioma.

  13. Induced liver injury after high-dose methylprednisolone in a patient with multiple sclerosis.

    PubMed

    Oliveira, Ana Torres; Lopes, Sandra; Cipriano, Maria Augusta; Sofia, Carlos

    2015-07-21

    A 33-year-old woman with multiple sclerosis, medicated with high doses of methylprednisolone, cyclophosphamide and glatiramer acetate, was referred to our department due to acute liver injury. The laboratory investigation was normal except for weakly positive antinuclear antibodies. Cyclophosphamide and glatiramer acetate were suspended, and intravenous immunoglobulin with maintenance of high doses of methylprednisolone was initiated. The patient developed another episode of acute hepatitis so the immunoglobulin was stopped. After that, she had three more episodes of elevation of liver enzymes with no hepatic insufficiency while medicated only with high doses of methylprednisolone. At this time, liver biopsy showed focal centrilobubar hepatocyte necrosis with minimal interface hepatitis. After the high doses of methylprednisolone were suspended, the patient remained asymptomatic, with normal hepatic enzymes. This case emphasises that, although rare, induced liver injury after high doses of methylprednisolone can occur. 2015 BMJ Publishing Group Ltd.

  14. Metronidazole and the immune system.

    PubMed

    Shakir, L; Javeed, A; Ashraf, M; Riaz, A

    2011-06-01

    Metronidazole (MTZ) is a nitroimidazole antibiotic used mainly for the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. Distinct from its antibiotic, amoebicidal, and antiprotozoal effects, MTZ displays immunopharmacological behaviour. This review outlines multiple effects of MTZ on different aspects of immunity, including innate and acquired immunity, and also highlights the immunopharmacological behaviour of MTZ in terms of its relevance to inflammation, delayed type hypersensitivity (DTH) and graft versus host disease (GVHD).

  15. Fluzone High-Dose Seasonal Influenza Vaccine

    MedlinePlus

    ... Address What's this? Submit What's this? Submit Button Influenza Types Seasonal Avian Swine/Variant Pandemic Other Fluzone High-Dose Seasonal Influenza Vaccine Questions & Answers Language: English (US) Español ...

  16. Liquid chromatographic assay for metronidazole and tinidazole: pharmacokinetic and metabolic studies in human subjects.

    PubMed Central

    Nilsson-Ehle, I; Ursing, B; Nilsson-Ehle, P

    1981-01-01

    We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase high-pressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected. PMID:7294765

  17. Treatment of trichomoniasis with metronidazole rectal suppositories

    PubMed Central

    Panja, S K

    1982-01-01

    Since a single dose of metronidazole in suppository form is very effective in the prevention of postoperative Gram-negative anaerobic infections, 84 patients with vaginal trichomoniasis were treated with metronidazole suppositories (two 1-g suppositories in a single dose). The cure rate in this series was 94%. PMID:7104657

  18. Toxic metronidazole-induced MRI changes.

    PubMed

    Horlen, C K; Seifert, C F; Malouf, C S

    2000-11-01

    To report a case of changes documented by magnetic resonance imaging (MRI) of the head probably due to accumulation of metronidazole in a patient with liver dysfunction. A 34-year-old Hispanic man with cirrhosis and hepatitis C being treated with metronidazole for Bacteroides fragilis meningitis and bacteremia developed ataxia, disorientation, and peripheral neuropathy. An MRI at the time meningitis was diagnosed was negative. After the patient received > 60 g of metronidazole, an MRI revealed increased signal intensity below, behind, and lateral to the fourth ventricle. Concomitant metronidazole serum concentration was toxic at 35.1 micrograms/mL. This is the second reported case of metronidazole-induced MRI changes. Metronidazole is known to accumulate in patients with liver dysfunction and can cause peripheral neuropathy and central nervous system (CNS) dysfunction; these effects may take up to two years to completely resolve. Metronidazole dosages should be reduced in patients with liver dysfunction to prevent the accumulation of metronidazole, which can lead to CNS dysfunction and peripheral neuropathy.

  19. [Is combining metronidazole and alcohol really hazardous?].

    PubMed

    Fjeld, Hilde; Raknes, Guttorm

    2014-09-16

    It is common practice to warn against intake of alcohol (ethanol) when taking metronidazole because of the risk of an effect similar to disulfiram (Antabuse). In this article we investigate whether such a warning has any real basis. KNOWLEDGE BASE: The article is based on a review of relevant literature retrieved through a search in PubMed. A search was also made in the WHO's database on adverse effects. No in-vitro studies, animal models, reports of adverse effects or clinical studies provide any convincing evidence of a disulfiram-like interaction between ethanol and metronidazole. The warning against simultaneous use of alcohol and metronidazole appear to be based on laboratory experiments and individual case histories in which the reported reactions are equally likely to have been caused by ethanol alone or by adverse effects of metronidazole. Recent research does not confirm a clinically relevant interaction between ethanol and metronidazole.

  20. Giardia, Entamoeba, and Trichomonas enzymes activate metronidazole (nitroreductases) and inactivate metronidazole (nitroimidazole reductases).

    PubMed

    Pal, Dibyarupa; Banerjee, Sulagna; Cui, Jike; Schwartz, Aaron; Ghosh, Sudip K; Samuelson, John

    2009-02-01

    Infections with Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, which cause diarrhea, dysentery, and vaginitis, respectively, are each treated with metronidazole. Here we show that Giardia, Entamoeba, and Trichomonas have oxygen-insensitive nitroreductase (ntr) genes which are homologous to those genes that have nonsense mutations in metronidazole-resistant Helicobacter pylori isolates. Entamoeba and Trichomonas also have nim genes which are homologous to those genes expressed in metronidazole-resistant Bacteroides fragilis isolates. Recombinant Giardia, Entamoeba, and Trichomonas nitroreductases used NADH rather than the NADPH used by Helicobacter, and two recombinant Entamoeba nitroreductases increased the metronidazole sensitivity of transformed Escherichia coli strains. Conversely, the recombinant nitroimidazole reductases (NIMs) of Entamoeba and Trichmonas conferred very strong metronidazole resistance to transformed bacteria. The Ehntr1 gene of the genome project HM-1:IMSS strain of Entamoeba histolytica had a nonsense mutation, and the same nonsense mutation was present in 3 of 22 clinical isolates of Entamoeba. While ntr and nim mRNAs were variably expressed by cultured Entamoeba and Trichomonas isolates, there was no relationship to metronidazole sensitivity. We conclude that microaerophilic protists have bacterium-like enzymes capable of activating metronidazole (nitroreductases) and inactivating metronidazole (NIMs). While Entamoeba and Trichomonas displayed some of the changes (nonsense mutations and gene overexpression) associated with metronidazole resistance in bacteria, these changes did not confer metronidazole resistance to the microaerophilic protists examined here.

  1. [Hopes of high dose-rate radiotherapy].

    PubMed

    Fouillade, Charles; Favaudon, Vincent; Vozenin, Marie-Catherine; Romeo, Paul-Henri; Bourhis, Jean; Verrelle, Pierre; Devauchelle, Patrick; Patriarca, Annalisa; Heinrich, Sophie; Mazal, Alejandro; Dutreix, Marie

    2017-04-01

    In this review, we present the synthesis of the newly acquired knowledge concerning high dose-rate irradiations and the hopes that these new radiotherapy modalities give rise to. The results were presented at a recent symposium on the subject. Copyright © 2017. Published by Elsevier Masson SAS.

  2. Possible nephotoxic interaction of lithium and metronidazole

    SciTech Connect

    Teicher, M.H.; Altesman, R.I.; Cole, J.O.; Schatzberg, A.F.

    1987-06-26

    Several classes of drugs can promote renal retention of lithium and, occasionally, can induce lithium intoxication. The antimicrobial agent metronidazole hydrochloride (Flagyl I.V.) was also implicated in producing such a reaction in one woman. The authors describe two patients who experienced toxic reactions to lithium following brief use of metronidazole. However, in these two patients, in contrast to the previous case, the degree of acute intoxication was less severe and treatment with metronidazole was completed without apparent suspicion, but persistent signs of renal damage later emerged.

  3. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis.

    PubMed

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-16

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection.

  4. Metronidazole-induced encephalopathy after prolonged metronidazole course for treatment of C. difficile colitis

    PubMed Central

    Godfrey, Mark S; Finn, Arkadiy; Zainah, Hadeel; Dapaah-Afriyie, Kwame

    2015-01-01

    A 65-year-old woman with a diagnosis of Clostridium difficile colitis undergoing prolonged treatment with metronidazole was admitted to hospital for altered mentation, slurred speech and weakness. She was diagnosed with metronidazole-induced encephalopathy, confirmed with brain MRI and improved when the offending agent was removed. This case report highlights encephalopathy as a complication of prolonged metronidazole treatment, which has become more common in clinical practice for the treatment of C. difficile infection. PMID:25596288

  5. High-dose neutron detector project update

    SciTech Connect

    Menlove, Howard Olsen; Henzlova, Daniela

    2016-08-10

    These are the slides for a progress review meeting by the sponsor. This is an update on the high-dose neutron detector project. In summary, improvements in both boron coating and signal amplification have been achieved; improved boron coating materials and procedures have increased efficiency by ~ 30-40% without the corresponding increase in the detector plate area; low dead-time via thin cell design (~ 4 mm gas gaps) and fast amplifiers; prototype PDT 8” pod has been received and testing is in progress; significant improvements in efficiency and stability have been verified; use commercial PDT 10B design and fabrication to obtain a faster path from the research to practical high-dose neutron detector.

  6. High dose Nutrizym 22 in cystic fibrosis.

    PubMed

    Shah, A; Dinwiddie, R; Madge, S; Prescott, P; Hudson, G

    1993-09-01

    New high dose pancreatic enzyme preparations could be potentially helpful to cystic fibrosis (CF) patients. The purpose of this study was to compare the efficacy of the new high dose pancreatic enzyme preparation, Nutrizym 22 with the standard preparation Nutrizym GR. Twenty-five CF children (aged 7-16 years) entered the study and 22 completed it; 3 did not, due to non-compliance. All were taking Nutrizym GR for at least 2 weeks before entering the study. A randomised double blind, crossover method using standard Nutrizym GR or double strength Nutrizym 22 capsules was carried out over two consecutive 14-day periods. Crossover analyses of variance showed no statistically significant differences in actual weight gain, appetite, abdominal pain, stool consistency or faecal fat during the prestudy and study periods. It is concluded that half the capsule numbers of the high strength preparation are just as effective as the standard capsule dosage.

  7. A pilot clinical trial comparing an acid-buffering formulation (ACIDFORM gel) with metronidazole gel for the treatment of symptomatic bacterial vaginosis.

    PubMed

    Simoes, Jose A; Bahamondes, Luis G; Camargo, Rodrigo P S; Alves, Valeria M N; Zaneveld, Lourens J D; Waller, Donald P; Schwartz, Jill; Callahan, Marianne M; Mauck, Christine K

    2006-02-01

    To compare the effectiveness of an acid-buffering formulation gel (ACIDFORM) with metronidazole gel in the treatment of symptomatic bacterial vaginosis (BV). After a confirmed diagnosis of BV according to the criteria established by Nugent and Amsel, 30 nonpregnant women were enrolled in a randomized, double-blind clinical study. The women were randomly assigned to receive either 5 g ACIDFORM gel (n = 13) or 10% metronidazole gel (n = 17) intravaginally once daily for five consecutive days. Participants were evaluated in two follow-up visits (7-12 days and 28-35 days after treatment). Therapeutic success was defined as the presence of less than three of Amsel's criteria. If three or more criteria were present at first or second follow-up visit, the woman was excluded from the study and treated orally with metronidazole. Nugent scores were recorded at each visit but these were not used to define cure. At the first follow-up visit, 15 (88%) of the women in the metronidazole group were cured compared with only three (23%) in the ACIDFORM group (P < 0.001). The remaining 12 women (10 of the ACIDFORM group and two of the metronidazole group) were considered as failure and were treated orally with metronidazole. At the second follow-up visit, two of the ACIDFORM-treated women and six of the metronidazole-treated women presented recurrent BV. Four women in the ACIDFORM group and one in the metronidazole group reported occasional burning and itching during product use. ACIDFORM gel was significantly less effective than high-dose metronidazole gel for the treatment of symptomatic BV.

  8. A pilot clinical trial comparing an acid-buffering formulation (ACIDFORM gel) with metronidazole gel for the treatment of symptomatic bacterial vaginosis

    PubMed Central

    Simoes, Jose A; Bahamondes, Luis G; Camargo, Rodrigo P S; Alves, Valeria M N; Zaneveld, Lourens J D; Waller, Donald P; Schwartz, Jill; Callahan, Marianne M; Mauck, Christine K

    2006-01-01

    Aim To compare the effectiveness of an acid-buffering formulation gel (ACIDFORM) with metronidazole gel in the treatment of symptomatic bacterial vaginosis (BV). Methods After a confirmed diagnosis of BV according to the criteria established by Nugent and Amsel, 30 nonpregnant women were enrolled in a randomized, double-blind clinical study. The women were randomly assigned to receive either 5 g ACIDFORM gel (n = 13) or 10% metronidazole gel (n = 17) intravaginally once daily for five consecutive days. Participants were evaluated in two follow-up visits (7–12 days and 28–35 days after treatment). Therapeutic success was defined as the presence of less than three of Amsel's criteria. If three or more criteria were present at first or second follow-up visit, the woman was excluded from the study and treated orally with metronidazole. Nugent scores were recorded at each visit but these were not used to define cure. Results At the first follow-up visit, 15 (88%) of the women in the metronidazole group were cured compared with only three (23%) in the ACIDFORM group (P < 0.001). The remaining 12 women (10 of the ACIDFORM group and two of the metronidazole group) were considered as failure and were treated orally with metronidazole. At the second follow-up visit, two of the ACIDFORM-treated women and six of the metronidazole-treated women presented recurrent BV. Four women in the ACIDFORM group and one in the metronidazole group reported occasional burning and itching during product use. Conclusion ACIDFORM gel was significantly less effective than high-dose metronidazole gel for the treatment of symptomatic BV. PMID:16433875

  9. Influence of early high-dose steroid treatment on Bell's palsy evolution.

    PubMed

    Lagalla, G; Logullo, F; Di Bella, P; Provinciali, L; Ceravolo, M G

    2002-09-01

    The objective of this double-blind, randomized, placebo-controlled study was to test the efficacy of high-dose prednisone, administered as early as possible, in modifying the natural progression of Bell's palsy. Sixty-two consecutive patients, enrolled within 72 hours of facial palsy onset, were assigned to high dose intravenous prednisone in combination with intramuscular polyvitaminic therapy (group A) or polyvitaminic therapy alone (group B). Clinical grading of facial muscle strength and length of absence from work were evaluated. An early worsening of facial muscle strength was observed in controls, leading to the divergence in the trends of the grading scores in the two groups; this result was not confirmed in the long-term follow-up. Treated patients returned to work earlier than controls. In conclusion, early treatment based on high-dose corticosteroids slightly accelerates spontaneous improvement in Bell's palsy.

  10. Pregnancy under high-dose buprenorphine.

    PubMed

    Simmat-Durand, Laurence; Lejeune, Claude; Gourarier, Laurent

    2009-02-01

    This study was first conducted to compare the consequences of the use of methadone and high-dose buprenorphine in pregnancy in France and secondly to describe the heterogeneity of women under high-dose buprenorphine. This paper focuses on the second point only. From October 1998 to September 1999, data on pregnancy, delivery outcomes and neonatal parameters were collected for 251 addicted women on methadone or high-dose buprenorphine (HDB) substitution followed in 35 hospitals and clinics in continental France. Then the data of 159 women who had been taking HDB during pregnancy and had delivered 160 live infants were analyzed. Most of these women were treated as outpatients by general practitioners. 43% of them belong to what we considered a "hidden population" of drug users: most of them were native French citizens, who lived with the future fathers in their own homes, had at least some secondary education, and were usually not followed in specialized centers for drug addicts. Almost all the women smoked every day during their pregnancies; 20% used heroin during the last 4 weeks preceding delivery; 16% admitted having injected HDB at least once. Notably, neither the severity nor the duration of the neonatal abstinence syndrome (NAS) seemed to be related to the daily doses of the substitution agent. Half of the newborns were treated for NAS, mainly with morphine hydrochloride. Although two different populations of women were clearly identified, 64 with no social disadvantage and 95 socially disadvantaged, there was no difference between the groups as for the severity of NAS which was only related to the mothers' compliance with a programme of treatment against addiction.

  11. Immune reactivity after high-dose irradiation

    SciTech Connect

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-03-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient.

  12. High-dose fenretinide in oral leukoplakia.

    PubMed

    William, William N; Lee, J Jack; Lippman, Scott M; Martin, Jack W; Chakravarti, Nitin; Tran, Hai T; Sabichi, Anita L; Kim, Edward S; Feng, Lei; Lotan, Reuben; Papadimitrakopoulou, Vassiliki A

    2009-01-01

    We previously showed that low-dose fenretinide (200 mg/d) had limited activity in retinoid-resistant oral leukoplakia (34% response rate) possibly because serum drug levels were insufficient to induce retinoid receptor-independent apoptosis. Therefore, we designed the single-arm phase II trial reported here to investigate whether higher-dose fenretinide would improve leukoplakia response over that of our previous study. Leukoplakia patients received fenretinide (900 mg/m(2) twice daily) in four 3-week cycles (1 week on drug followed by 2 weeks off). At week 12, clinical responses were determined and blood samples were collected for serum drug level assessments. A planned interim futility analysis led to early trial closure after the initial 15 (of 25 planned) patients because only 3 (20%) had a partial response (stopping rule: high-dose fenretinide inhibited the growth of head and neck cancer cells more and oral leukoplakia cells less than did lower doses of fenretinide. This result is consistent with our clinical finding that high-dose fenretinide did not improve on the historical response rate of lower-dose fenretinide in our previous oral leukoplakia trial.

  13. Metronidazole for the treatment of vaginal infections.

    PubMed

    Sobel, Ryan; Sobel, Jack D

    2015-05-01

    Metronidazole , undoubtedly the most widely known and used member of the nitroimidazole drug class, remains not only first line therapy for bacterial vaginosis (BV) and trichomoniasis, but serves as drug of first choice. Available and used both orally and topically with high efficacy rates, especially for trichomoniasis, nevertheless numerous unanswered questions remain regarding mechanism of action. Given the extraordinary global frequency of vaginitis due to BV and trichomoniasis, especially the high recurrence rate observed in BV, it is timely to critically examine the therapeutic role of metronidazole in management decisions. Search methodology used PUBMED literature review. In spite of many years of successful use, multiple questions exist regarding optimal dose and duration of therapy especially in the management of BV. Antimicrobial drug resistance remains uncommon in spite of extensive use. The use of metronidazole for vaginitis is reviewed in this article together with challenges to improving its more effective administration. Currently metronidazole or the family of nitroimidazoles, represent the drugs of first choice for trichomonas vaginitis and first line therapy for BV. Drug resistance for both entities remains uncommon; however, in contrast to trichomoniasis where relapse is rare, high recurrence rates are common in women with BV. Metronidazole appears to allow persistence of vaginal microbiome microorganisms which translate into frequent relapses. In the absence of new therapeutic alternatives, strategies are being developed to enhance drug cure rates.

  14. Artifactual Depression of Serum Glutamic Oxaloacetic Transaminase by Metronidazole

    PubMed Central

    Rissing, J. Peter; Newman, Cheryl; Moore, William L.

    1978-01-01

    Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay. PMID:214030

  15. Bacteremia Caused by a Metronidazole-Resistant Prevotella sp. Strain

    PubMed Central

    Mory, Francine; Carlier, Jean-Philippe; Alauzet, Corentine; Thouvenin, Maxime; Schuhmacher, Hélène; Lozniewski, Alain

    2005-01-01

    Metronidazole resistance among Prevotella spp. is rare. We report here the first case of bacteremia due to a high-level metronidazole-resistant Prevotella sp. responsible for treatment failure. PMID:16208024

  16. Metronidazole in prevention and treatment of bacteroides infections after appendicectomy.

    PubMed Central

    Willis, A T; Ferguson, I R; Jones, P H; Phillips, K D; Tearle, P V; Berry, R B; Fiddian, R V; Graham, D F; Harland, D H; Innes, D B; Mee, W M; Rothwell-Jackson, R L; Sutch, I; Kilbey, C; Edwards, D

    1976-01-01

    The frequency of non-clostridial anaerobic infection was studied in 95 patients who had undergone acute appendicectomy: 49 received prophylactic metronidazole and 46 received placebo. Anaerobic infection did not develop in any of the metronidazole-treated patients, but infections did develop in nine (19%) of the 46 controls. Metronidazole is conveniently administered by suppository to patients who cannot take oral drugs. Five patients with intra-abdominal infections caused by non-clostridial anaerobes were successfully treated with metronidazole. PMID:764935

  17. Putative metronidazole neurotoxicosis in a cat.

    PubMed

    Olson, E J; Morales, S C; McVey, A S; Hayden, D W

    2005-09-01

    A presumptive case of metronidazole toxicity in a 3.4-kg adult cat is described. The cat had been treated for suspected inflammatory bowel disease with an anti-inflammatory dose of prednisone and metronidazole (73.5-147 mg/kg PO q24h) for approximately 40 days prior to presentation. Clinical signs were primarily related to the central nervous system, including acute tetraparesis, unresponsiveness, tremors, and vocalization. The patient was euthanatized after 12 days of supportive care. Necropsy revealed no significant macroscopic lesions. Histologic evaluation revealed multifocal, fairly well-demarcated foci of necrosis in the brainstem, extending from the diencephalon to the medulla oblongata. To our knowledge, this is the first report to document histologic lesions associated with metronidazole administration in a cat.

  18. Mechanical and thermal studies of metronidazole crystals

    NASA Astrophysics Data System (ADS)

    Ramukutty, S.; Jeyasudha, R.; Ramachandran, E.

    2013-10-01

    Single crystals of metronidazole have been synthesized natural evaporation method. The grown crystal has been confirmed using single crystal X-ray diffraction analysis. Mechanical behavior has been determined using Vickers hardness measurement. Work-hardening coefficient and Newtonian resistance pressure of the crystal have been estimated. Kinetic analysis of the thermogravimetric data has been carried out by using Coats-Redfern relation. Activation energy, frequency factor and order of reaction have been also calculated. The Arrhenius equation for metronidazole is k = 0.38 × 108 e-76.679/ RT mol-1 s-1. Thermodynamic parameters have been also determined.

  19. Very high dose phenobarbital for refractory status epilepticus.

    PubMed

    Tiamkao, Somsak; Mayurasakorn, Nattakarn; Suko, Panit; Jitpimolmard, Suthipun; Arunpongpaisal, Suwanna; Phuttharak, Warinthorn; Auevitchayapat, Narong; Vannaprasaht, Suda; Tiamkao, Siriporn; Phunikhom, Kutcharin; Chaiyakum, Aporanee; Saengsuwan, Jiamjit

    2007-12-01

    Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to first, second and third-line therapy. The RSE is associated with high morbidity and mortality. Treatment guidelines of RSE give a spectrum of options, such as, continuous intravenous (i.v.) midazolam (MDL), or continuous i.v. propofol (PRO) as alternatives to phenobarbital (PB) or continuous i.v. pentobarbital (PTB). To study the efficacy of very-high-dose phenobarbital (VHDPB) for treatment RSE. Retrospective study The authors collected and analyzed data from adult patients who were diagnosed with RSE. The authors present 10 patients with RSE who were treated with VHDPB. All of them were generalized convulsive status epilepticus (GCSE). Ages ranged from 16-86 years old (mean.: 43 years). PB dosage ranged 40-140 mg/kg/day (mean: 70 mg/kg/day). The duration of status epilepticus (SE) varied widely, ranged 1-44 days (mean: 7 days). PB level ranged 35.29-218.34 ug/mL (mean 88.1 ug/mL). RSE was controlled by VHDPB 70%, 30% were not controlled. VHDPB were considered as alternative treatment for RSE.

  20. Wernicke's encephalopathy in a child with high dose thiamine therapy

    PubMed Central

    Park, So Won; Yi, Yoon Young; Han, Jung Woo; Kim, Heung Dong; Lee, Joon Soo

    2014-01-01

    Wernicke's encephalopathy is an acute neurological disorder characterized by mental confusion, oculomotor dysfunction, and ataxia. It has been reported in individuals with alcohol dependence, hyperemesis gravidarum, and prolonged parenteral nutrition without vitamin supplementation. Here we present the case of a 13-year-old male patient with neuroblastoma and a history of poor oral intake and nausea for 3 months. After admission, he showed gait disturbances, nystagmus, and excessive dizziness; his mental state, however, indicated he was alert, which did not fit the classical triad of Wernicke's encephalopathy. A diagnosis of Wernicke's encephalopathy was made only after brain magnetic resonance imaging and serum thiamine level analyses were performed. The patient's symptoms remained after 5 days of treatment with 100-mg thiamine once daily; thus, we increased the dosage to 500 mg 3 times daily, 1,500 mg per day. His symptoms then improved after 20 days of replacement therapy. This case report describes a pediatric patient who was promptly diagnosed with Wernicke's encephalopathy, despite only 2 suspicious symptoms, and who completely recovered after high doses of thiamine were given intravenously. PMID:25550705

  1. In vitro activity of nitazoxanide against some metronidazole-resistant and susceptible Trichomonas vaginalis isolates.

    PubMed

    Abdel-Magied, Aida A; Hammouda, Marwa M; Mosbah, Alaa; El-Henawy, Abeer A

    2017-04-01

    Trichomonas vaginalis cases refractory to metronidazole (MTZ) treatment had been reported. This study aimed to the assessment of in vitro metronidazole resistance among Trichomonas positive cases with treatment failure by determination of metronidazole minimal lethal concentration (MLC), and to the evaluation of the in vitro efficacy of nitazoxanide (NTZ) as compared to metronidazole (MTZ) in both resistant and susceptible isolates. Drug testing was carried out by an aerobic tube assay where suspension of Trichomonas trophozoites was exposed for 24 and 48 h to serial dilution of metronidazole and nitazoxanide. In refractory isolates n = 30, median MLC conc. for MTZ was 100 μg/ml versus 50 μg/ml for NTZ (P < .0001). After 48 h median MLC conc. for MTZ was 25 μg/ml versus 12 μg/ml for NTZ (P < .0001). NTZ against resistant isolates was twice as active as MTZ at 24 h and increased to 2.5 times at 48 h while in susceptible isolates, NTZ was twice as active as MTZ at both 24 h and 48 h. MTZ was about 8 times more active in susceptible than in resistant isolates. So, high doses of metronidazole in resistant cases will likely increase side effects. The study proved the activity of NTZ against trichomoniasis especially in cases with MTZ resistance. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. Intravenous Therapy.

    ERIC Educational Resources Information Center

    Galliart, Barbara

    Intended for teaching licensed practical nurses, this curriculum guide provides information related to the equipment and skills required for nursing care of patients needing intravenous (IV) therapy. It also explains the roles and responsibilities of the licensed practical nurse with regard to intravenous therapy. Each of the 15 instructional…

  3. Intravenous Therapy.

    ERIC Educational Resources Information Center

    Galliart, Barbara

    Intended for teaching licensed practical nurses, this curriculum guide provides information related to the equipment and skills required for nursing care of patients needing intravenous (IV) therapy. It also explains the roles and responsibilities of the licensed practical nurse with regard to intravenous therapy. Each of the 15 instructional…

  4. [Metronidazole-induced reversible cerebellar lesions and peripheral neuropathy].

    PubMed

    Toumi, S; Hammouda, M; Essid, A; Medimagh, L; Slamia, L Ben; Laouani-Kechrid, C

    2009-12-01

    Metronidazole is a widely prescribed treatment for amoebic and anaerobic germ infections. Its neurologic toxicity is rare but can be serious. We report the case of a 27-year-old male patient, treated with metronidazole for a cerebral abscess. He presented with a cerebellar syndrome and peripheral neuropathy at a cumulative metronidazole dose of 60g. The MRI aspect of the cerebellar lesions in addition to their reversibility after treatment cessation led to the diagnosis of metronidazole induced neurologic toxicity. The occurrence of neurologic disorders in patients treated with metronidazole must suggest drug toxicity and lead to cessation of treatment.

  5. Metronidazole: newly recognized cause of autonomic neuropathy.

    PubMed

    Hobson-Webb, Lisa D; Roach, E Steve; Donofrio, Peter D

    2006-05-01

    Metronidazole is a commonly used antibiotic prescribed for the treatment of anaerobic and protozoal infections of the gastrointestinal and genitourinary tracts. It is associated with numerous neurologic complications, including peripheral neuropathy. Neuropathy is typically detected in patients on chronic therapy, although it has been documented in those taking large doses for acute infections. Numerous case reports have been published describing motor and sensory neuropathy, yet autonomic neuropathy has not been described with metronidazole use. A previously healthy 15-year-old girl presented with complaints of burning pain in her feet following a short course of metronidazole for vaginitis. She could obtain pain relief only by submerging her feet in ice water. Examination revealed cold and swollen lower extremities that became erythematous and very warm when removed from the ice water. Temperature perception was reduced to the upper third of the shin bilaterally. Deep tendon reflexes and strength were preserved. Nerve conduction studies demonstrated a peripheral neuropathy manifested by reduced sensory nerve and compound muscle action potentials. Reproducible sympathetic skin potential responses could not be obtained in the hand and foot, providing evidence of a concurrent autonomic neuropathy. A thorough evaluation revealed no other cause for her condition. Repeated nerve conduction studies and sympathetic skin potentials returned to normal over the course of 6 months, paralleling the patient's clinical improvement. Metronidazole is a potential cause of reversible autonomic neuropathy.

  6. Metronidazole-triazole conjugates: activity against Clostridium difficile and parasites.

    PubMed

    Jarrad, Angie M; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X; Kaeslin, Geraldine; Elliott, Alysha G; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A T; Cooper, Matthew A

    2015-08-28

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  7. Metronidazole-triazole conjugates: Activity against Clostridium difficile and parasites

    PubMed Central

    Jarrad, Angie M.; Karoli, Tomislav; Debnath, Anjan; Tay, Chin Yen; Huang, Johnny X.; Kaeslin, Geraldine; Elliott, Alysha G.; Miyamoto, Yukiko; Ramu, Soumya; Kavanagh, Angela M.; Zuegg, Johannes; Eckmann, Lars; Blaskovich, Mark A.T.; Cooper, Matthew A.

    2015-01-01

    Metronidazole has been used clinically for over 50 years as an antiparasitic and broad-spectrum antibacterial agent effective against anaerobic bacteria. However resistance to metronidazole in parasites and bacteria has been reported, and improved second-generation metronidazole analogues are needed. The copper catalysed Huigsen azide-alkyne 1,3-dipolar cycloaddition offers a way to efficiently assemble new libraries of metronidazole analogues. Several new metronidazole-triazole conjugates (Mtz-triazoles) have been identified with excellent broad spectrum antimicrobial and antiparasitic activity targeting Clostridium difficile, Entamoeba histolytica and Giardia lamblia. Cross resistance to metronidazole was observed against stable metronidazole resistant C. difficile and G. lamblia strains. However for the most potent Mtz-triazoles, the activity remained in a therapeutically relevant window. PMID:26117821

  8. Cervix cancer brachytherapy: high dose rate.

    PubMed

    Miglierini, P; Malhaire, J-P; Goasduff, G; Miranda, O; Pradier, O

    2014-10-01

    Cervical cancer, although less common in industrialized countries, is the fourth most common cancer affecting women worldwide and the fourth leading cause of cancer death. In developing countries, these cancers are often discovered at a later stage in the form of locally advanced tumour with a poor prognosis. Depending on the stage of the disease, treatment is mainly based on a chemoradiotherapy followed by uterovaginal brachytherapy ending by a potential remaining tumour surgery or in principle for some teams. The role of irradiation is crucial to ensure a better local control. It has been shown that the more the delivered dose is important, the better the local results are. In order to preserve the maximum of organs at risk and to allow this dose escalation, brachytherapy (intracavitary and/or interstitial) has been progressively introduced. Its evolution and its progressive improvement have led to the development of high dose rate brachytherapy, the advantages of which are especially based on the possibility of outpatient treatment while maintaining the effectiveness of other brachytherapy forms (i.e., low dose rate or pulsed dose rate). Numerous innovations have also been completed in the field of imaging, leading to a progress in treatment planning systems by switching from two-dimensional form to a three-dimensional one. Image-guided brachytherapy allows more precise target volume delineation as well as an optimized dosimetry permitting a better coverage of target volumes.

  9. High dose insulin in toxic cardiogenic shock.

    PubMed

    Holger, Joel S; Engebretsen, Kristin M; Marini, John J

    2009-04-01

    To report the successful use of high dose insulin (HDI) in previously unreported insulin dosing ranges in a patient with severe myocardial toxicity due to an amitriptyline and citalopram overdose. A 65-year-old female presented in respiratory arrest, which was followed by bradycardic pulseless electrical activity after ingesting multiple medications. After a prolonged resuscitation, the patient was maintained only on infusions of norepinephrine (40 mcg/min), vasopressin (4 units/h), insulin (80 units/h), and sodium bicarbonate. Due to a deteriorating clinical condition and limited prognosis, the insulin infusion was titrated incrementally upwards to 600 units/h (6 units/kg/h) over a 5 h time period while simultaneously completely weaning off both vasopressors. She developed brisk pulses and warm extremities, and her cardiac output nearly tripled. After 2 days of stabilization the insulin was slowly tapered, and the patient recovered. HDI as a single cardiovascular agent significantly improved clinical and cardiovascular parameters after the failure of vasopressor therapy in severe cardiovascular toxicity. Higher doses of insulin than previously recommended may be needed in toxic poisonings when severe myocardial depression is present.

  10. High dose rate brachytherapy for oral cancer

    PubMed Central

    YamazakI, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. PMID:23179377

  11. [Clinical Characteristics of Metronidazole-induced Encephalopathy: A Report of Two Cases and a Review of 32 Japanese Cases in the Literature].

    PubMed

    Kato, Hideaki; Sosa, Hiroko; Mori, Masaaki; Kaneko, Takeshi

    2015-09-01

    Metronidazole is an antibiotic classically used against most anaerobic bacteria and protozoa. Because an intravenous form of metronidazole has recently entered the market, the use of this antibiotic is attracting renewed interest in many clinical settings in Japan. However, neurotoxicity is a major adverse event: in the central nervous system metronidazole-induced encephalopathy is a rare but serious condition. We performed a literature review of 34 cases including 2 of our cases, 25 from domestic conference abstracts, and 7 cases presented in full research papers. The mean patient age was 64.7 years. The conditions most commonly treated with metronidazole were brain abscess (35.3%), liver abscess (17.6%), and Clostridium difficile infection (14.7%). The most common predisposing conditions were liver dysfunction (26.5%), diabetes and other metabolic disorders (20.6%), and hematologic or solid organ malignancy (14.7%). The mean period of administration before the onset of encephalopathy symptoms was 61.3 days, and the mean total dose was 95.9g. The initial chief complaints were dysarthria (in 70.6% of the cases) and ataxia (61.8%); 82.4% of the cases were diagnosed on the basis of MRI (T2-weighted or FLAIR imaging). The key imaging finding was high intensity in the dentate nucleus bilaterally (82.4%). Stopping the metronidazole led to symptom remission within 8.5 days, but the MRI changes remained longer than the clinical symptoms. Two patients (6.0%) developed irreversible disturbance of consciousness. Although the mechanisms of this type of encephalopathy have not yet been elucidated, localized nerve-cell edema is likely caused by decreased metronidazole metabolism associated with liver and metabolic dysfunction. Careful observation for neurologic signs should be conducted during the treatment of brain abscesses associated with metronidazole administration, because patients with brain abscesses are naturally at high risk of metronidazole-induced encephalopathy.

  12. Refractory metabolic acidosis as a complication of high-dose midazolam infusion for pediatric status epilepticus.

    PubMed

    Federman, Myke D; Kelly, Robert; Harrison, Rick E

    2009-01-01

    The use of midazolam for the treatment of status epilepticus in children has generally been shown to be well tolerated and safe. Furthermore, encouraging efficacy has been observed when pediatric patients with status epilepticus have received continuous intravenous infusions of midazolam. A 9-year-old girl was treated with high-dose, continuous intravenous infusion of midazolam for the management of refractory status epilepticus. The patient developed a severe hyperchloremic, non-anion gap metabolic acidosis and resultant hemodynamic compromise, necessitating significant inotropic support and the initiation of a vasopressor infusion. We speculate that this complication was due to the preparation of parenteral midazolam with hydrochloric acid. The midazolam infusion was stopped, and, in less than 5 hours, the patient's metabolic acidosis resolved. The patient's inotropic and vasopressor infusions could only be weaned after discontinuing the use of high-dose midazolam. Although this complication was observed in only 1 pediatric patient with cortical dysplasia, caution and close clinical and laboratory surveillance should be exercised when administering continuous intravenous infusions of midazolam to pediatric patients.

  13. Modulation of the proteolytic cascade systems by high dose corticosteroids.

    PubMed

    Aasen, A O; Ruud, T E; Pillgram-Larsen, J; Röise, O; Stadaas, J

    1985-01-01

    The effects of high-dose corticosteroids (HDC) on activities within the proteolytic cascade systems were studied in vitro and in vivo using chromogenic peptide substrate assays. In in vitro experiments 20 mg methylprednisolone sodium succinate (Solu-Medrol) per ml plasma significantly inhibited activation of plasma prekallikrein, prothrombin and plasminogen and reduced functional plasma kallikrein inhibition, antithrombin and antiplasmin activities. The effects of HDC on activities within these proteolytic cascade systems were further evaluated in experimental acute pancreatitis in pigs. Acute pancreatitis was induced by injection of Na-taurocholate into the pancreatic duct. Seven test animals received methylprednisolone sodium succinate 30 mg per kg intravenously for 30 minutes before the induction of pancreatitis as pretreatment. Eight animals remained untreated. Trypsin (TRY), plasma prekallikrein (PKK), plasma kallikrein (KK) and functional plasma kallikrein inhibition capacity (KKI) were studied in the peritoneal exudate. Cardiac output (CO) and mean arterial pressure (MAP) were monitored regularly before and during a 6 hour observation period. During untreated pancreatitis a reduction of PKK levels of about 40% were found, paralleled by an increased KK activity and a reduction of KKI capacity. Several of the animals experienced high TRY activities. The mortality rate was 63% (5 out of 8 animals). In the pretreated groups, all animals survived the observation period. CO and MAP were significantly less reduced than the untreated group at 6 hours. HDC was also found to reduce significantly plasma kallikrein activities in the peritoneal exudate compared with untreated animals. No changes in TRY activities were found in pretreated animals. Furthermore, plasma prekallikrein and functional plasma kallikrein inhibition values in the exudate were elevated significantly in HDC treated animals compared with untreated animals.

  14. Continuous spinal anesthesia with high dose of local anesthetics.

    PubMed

    Imbelloni, Luiz Eduardo; Neto, Savino Gasparini; Ganem, Eliana Marisa

    2010-01-01

    Better control of the level, intensity, and duration of spinal analgesia represents the greatest advantages of continuous spinal anesthesia. With the advent of intermediate catheters (over-the-needle catheter) and its low incidence of headaches and neurological symptoms, the technique has been gaining credibility. The objective of this paper is to report the possible safety of the new catheter with a large dose of hyperbaric 0.5% bupivacaine with 1.6% glucose associated with hyperbaric 2% lidocaine with 1.6% glucose. Male patient, 78 years old, 85 kg, 168 cm, physical status ASA III, with hypertension, coronary artery disease, and chronic renal failure. The patient was candidate for surgery for huge bilateral inguinal and umbilical hernias, being submitted to preoperative pneumoperitoneum for one week to stretch abdominal cavity. After venoclysis with an 18G catheter, he was monitored with cardioscope, non-invasive blood pressure, and pulse oximetry; he was sedated with 1 mg of midazolam and 100 μg of fentanyl intravenously, and placed in left lateral decubitus. He underwent continuous spinal anesthesia by a median puncture in L₃-L₄ with a set with a 27G cut-bevel needle and 22G catheter. The total dose of anesthetic used was 25mg of 0.5% bupivacaine (hyperbaric, with 1.6% glucose), 160 mg of 2% lidocaine (hyperbaric, with 1.6% glucose), and morphine (100 μg). The patient was followed-up until the 30th postoperative day without neurological complaints. Recently, the poor distribution of the local anesthetic through the microcatheter was attributed as the cause of cauda equina syndrome. This case report showed that, with the administration of high doses of hyperbaric anesthetics through the new catheter, poor distribution or risk of cauda equina syndrome were not observed. Copyright © 2010 Elsevier Editora Ltda. All rights reserved.

  15. High-dose fluoroscopy: the administrator's responsibilities.

    PubMed

    Archer, Benjamin R

    2002-01-01

    During the past 15 years, developments in x-ray technologies have substantially improved the ability of practitioners to treat patients using fluoroscopically guided interventional techniques. Many of these procedures require a greater use of fluoroscopy and serial imaging (cine). This has increased the potential for radiation-induced dermatitis, epilation and severe radiation-induced burns to patients. Radiology administrators must realize that these high-dose procedures increase the risk for radiation injury and radiation-induced cancer in personnel as well as in patients. This article discusses particular clinical cases and describes positive, pro-active steps that practitioners and administrators can take to help prevent such injuries in their facilities. Unfortunately, with the exception of radiologists, a large proportion of physicians who use fluoroscopy have effectively no training or credentials in management of radiation or the biological effects associated with its use. In 1994, an FDA advisory warned that training of physicians for modern-day use of the fluoroscope was for the most part insufficient and needed to be expanded. Many prominent medical organizations such as the American College of Cardiology (14) and the American Heart Association (15) have published strongly worded position papers agreeing that there is an urgent need for such training. The consensus is that "rubber-stamp" privileges (16,17) to perform fluoroscopic procedures should no longer be granted. At present, the JCAHO is considering the implementation of a statement regarding JCAHO standards and privileges for practitioners to use fluoroscopic x-ray equipment. Whether or not the JCAHO becomes involved, it is becoming increasingly clear that all practitioners who use fluoroscopic radiation should be required to complete focused training in radiation physics, radiation biology and radiation safety. Training should include the pertinent aspects of radiation management in the clinical

  16. Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial.

    PubMed

    Sanchez, Sixto; Garcia, Patricia J; Thomas, Katherine K; Catlin, Mary; Holmes, King K

    2004-12-01

    We compared metronidazole 0.75% gel (containing 37.5 mg metronidazole per dose) with ovules containing metronidazole 500 mg and nystatin 100,000 U, for intravaginal treatment of bacterial vaginosis (BV). In a single-blinded trial, symptomatic women with BV by both Amsel and Nugent criteria were randomly assigned to gel or ovules, once nightly for 5 nights, and asked to return 3 times after treatment. Analyses were intent-to-treat. Of 151 women with BV by both criteria at enrollment, 138 (91%) returned at least once. Product limit estimates for persistence or recurrence of BV at 14, 42, and 104 days were 20% (95% CI 10%-29%), 38% (95% CI 25%-48%), and 52% (95% CI 37%-63%) after gel treatment, and 4% (95% CI 0%-9%), 17% (95% CI 7%-26%), and 33% (95% CI 21%-46%) after ovule treatment ( P = .01). Among women without BV at first follow-up, subsequent intercourse without condoms independently predicted subsequent recurrence ( P Metronidazole/nystatin ovules were significantly more effective than metronidazole gel. Unprotected sex predicted recurrence after initial improvement.

  17. Metabolism and metronidazole uptake in Trichomonas vaginalis isolates with different metronidazole susceptibilities.

    PubMed Central

    Müller, M; Gorrell, T E

    1983-01-01

    Three Trichomonas vaginalis isolates with low in vivo susceptibilities to metronidazole (95% curative dose, greater than 3 X 100 mg kg-1 in subcutaneous infections in mice) were compared with strain ATCC 30001 and with four isolates exhibiting high in vivo susceptibilities (95% curative dose, less than 3 X 15 mg kg-1). Activity of pyruvate:ferredoxin oxidoreductase, anaerobic fermentation, and anaerobic intracellular accumulation of [14C]metronidazole label showed no significant isolate-dependent differences which could be correlated with drug susceptibility. The results suggest that processes providing electrons for metronidazole activation are not defective in the resistant strains. Aerobiosis, known to inhibit the antimicrobial action of metronidazole, inhibited accumulation of label more strongly in resistant isolates than in susceptible ones. No differences were detected, however, between resistant and susceptible isolates in respiration, aerobic fermentation, and the specific activity of NADH and NADPH oxidases, the main terminal oxidases of T. vaginalis. These findings suggest that the production of electrons is not diminished under aerobic conditions. The inhibitory effect of aerobic conditions on metronidazole activation, possibly due to competition for the electrons, is markedly enhanced in the resistant isolates compared to the susceptible ones. The mechanism of this effect, however, remains unknown. PMID:6607028

  18. Outcomes of Patients with Alcohol Withdrawal Syndrome Treated with High-Dose Sedatives and Deferred Intubation.

    PubMed

    Stewart, Robert; Perez, Ricardo; Musial, Bogdan; Lukens, Carrie; Adjepong, Yaw Amoateng; Manthous, Constantine A

    2016-02-01

    High doses of sedating drugs are often used to manage critically ill patients with alcohol withdrawal syndrome. To describe outcomes and risks for pneumonia and endotracheal intubation in patients with alcohol withdrawal syndrome treated with high-dose intravenous sedatives and deferred endotracheal intubation. Observational cohort study of consecutive patients treated in the intensive care unit (ICU) of a university-affiliated, community hospital for alcohol withdrawal syndrome, where patients were not routinely intubated to receive high-dose or continuously infused sedating medications. We studied 188 patients hospitalized with alcohol withdrawal syndrome from 2008 through 2012 at one medical center. The mean age (SD) of the subjects was 50.8 ± 9.0 years and their mean ICU admission APACHE (Acute Physiology and Chronic Health Evaluation) II score was 6.2 ± 3.4. Thirty subjects (16%) developed pneumonia, and 38 (20.2%) required intubation. All of the 188 patients received lorazepam (median total dose, 42.5 mg), and 170 of 188 received midazolam, all but 2 by continuous intravenous infusion (median total dose, 527 mg; all administered in ICU); 19 received propofol (median total dose, 6,000 mg); and 19 received dexmedetomidine (median total dose, 1,075 mg). Intubated patients received substantially more benzodiazepine (median total dose, 761 mg of lorazepam equivalent vs. 229 mg for subjects in the nonintubated group; P < 0.0001). Endotracheal intubation was associated with pneumonia and higher acuity of illness (APACHE II score, >10). Intubated patients had a longer duration of hospital stay (median, 15 d vs. 6 d; P ≤ 0.0001). One patient did not survive hospitalization. In this single-center, observational study, where endotracheal intubation was deferred until aspiration or cardiopulmonary decompensation, treatment of alcohol withdrawal syndrome with high-dose, continuously infused sedating medications was not associated with excess morbidity

  19. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients.

    PubMed

    Albacker, Turki; Carvalho, George; Schricker, Thomas; Lachapelle, Kevin

    2008-07-01

    Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that is implicated in the pathogenesis of several postoperative complications. Studies have shown that proinflammatory cytokines are increased by acute hyperglycemia. Recent evidence suggests that insulin has antiinflammatory properties. Therefore, we hypothesized that high-dose insulin therapy would attenuate the systemic inflammatory response to cardiopulmonary bypass and surgery in coronary artery bypass patients while maintaining normoglycemia. A total of 52 patients who presented for elective coronary artery bypass were randomized to receive intraoperative intravenous insulin infusion, titrated to maintain blood glucose concentrations less than 180 mg/dL (group I, n = 25), or receive intraoperative fixed high dose of intravenous insulin infusion (5 mU/kg/min) with dextrose 20% infused separately to maintain a blood glucose level between 70 and 110 mg/dL (group II, n = 27). Blood samples were collected at different time points to determine tumor necrosis factor alpha (TNFalpha), interleukin 6 and 8 (IL6 and IL8), and complement factor 3 and 4 (C3 and C4). Patients in both groups had similar preoperative characteristics. Patients in the high-dose insulin group had higher blood insulin concentrations and tighter blood glucose control. There were lower levels of IL6 (150 pg/dL vs 245 pg/dL, p = 0.03), IL-8 (49 pg/dL vs 74 pg/dL, p = 0.05), and TNFalpha (2.2 pg/dL vs 3.0 pg/dL, p = 0.04) in group II in the early postoperative period. High-dose insulin therapy blunts the early postoperative surge in inflammatory response to CPB as reflected by decreased levels of IL6, IL8, and TNFalpha.

  20. High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study

    PubMed Central

    Zullo, Angelo; Ridola, Lorenzo; Francesco, Vincenzo De; Gatta, Luigi; Hassan, Cesare; Alvaro, Domenico; Bellesia, Annamaria; de Nucci, Germana; Manes, Gianpiero

    2015-01-01

    Background The prevalence of resistance to clarithromycin and metronidazole has considerably increased, with a corresponding decrease in the eradication rate for Helicobacter pylori (H. pylori) infection. Primary resistance to amoxicillin is extremely low, and esomeprazole was found to exert a noteworthy antimicrobial activity in vitro against H. pylori. A dual therapy with high-dose of esomeprazole coupled with high-dose amoxicillin might be therefore an ideal first-line treatment for H. pylori eradication. We aimed to assess the efficacy of a first-line 10-day, high-dose dual therapy consisting of amoxicillin and esomeprazole to eradicate H. pylori infection. Methods Consecutive naïve H. pylori-infected patients, who underwent an upper endoscopy in 4 Italian hospitals due to dyspeptic symptoms and found to be infected at routine histological assessment, were invited to participate. Patients enrolled received a 10-day, high-dose dual therapy comprising esomeprazole (40 mg t.i.d) and amoxicillin (1 g t.i.d.). At least 4 weeks after the end of the treatment a 13C-urea breath test was performed to evaluate the eradication. Results A total of 56 patients agreed to participate in the study and were all followed-up. The overall eradication was 87.5% (95% CI=78.8•96.2), without a statistically significant difference among centres. Overall, 5 (8.9%; 1.5•16.4%) patients complained of side-effects. Conclusions The 10-day, high-dose dual therapy with esomeprazole and amoxicillin might be an effective and safe first-line regimen. The efficacy of a longer 14-day regimen should be tested. PMID:26423014

  1. Metronidazole-induced encephalopathy in a patient with liver cirrhosis

    PubMed Central

    Cheong, Hyeong Cheol; Jeong, Taek Geun; Cho, Young Bum; Yang, Bong Joon; Kim, Tae Hyeon; Kim, Haak Cheoul

    2011-01-01

    Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis. PMID:21757988

  2. Interaction of metronidazole with DNA repair mutants of Escherichia coli.

    PubMed Central

    Yeung, T C; Beaulieu, B B; McLafferty, M A; Goldman, P

    1984-01-01

    It has been proposed that one of metronidazole's partially reduced intermediates interacts either with DNA to exert a bactericidal effect or with water to form acetamide. To test this hypothesis we have examined the effect of metronidazole on several mutants of Escherichia coli that are defective in DNA repair. UV-susceptible RecA- and UvrB- point mutants have an increased susceptibility to metronidazole as manifested by both a decreased minimal inhibitory concentration and a greater bactericidal response to metronidazole in resting cultures. By these criteria, however, we find that UvrB- deletion mutants, which lack the ability to reduce nitrate and chlorate, are no more susceptible to metronidazole than is the wild type. We find, however, that these deletion mutants also lack the ability to reduce metronidazole and thus possibly to form its reactive species. When metronidazole's bactericidal effect is expressed in terms of the concurrent accumulation of acetamide derived from metronidazole, then all RecA- and UvrB- mutants are killed more efficiently than their wild types. The data are consistent, therefore, with metronidazole's lethal effect being mediated by a partially reduced intermediate on the metabolic pathway between metronidazole and acetamide. Defects in other aspects of the DNA repair system do not confer this increased susceptibility to the proposed intermediate. A Tag- mutant, for example, which is defective in 3-methyl-adenine-DNA glycosylase, does not have this increased susceptibility to the presumed precursor of acetamide. Thus, these results provide further support for the hypothesis that the bactericidal effect of metronidazole is mediated by a partially reduced intermediate in the metabolic conversion of metronidazole to acetamide and suggest that this intermediate interacts with DNA to produce a lesion similar to that caused by UV light. PMID:6367636

  3. 78 FR 19271 - Draft Guidance for Industry on Bioequivalence Recommendations for Metronidazole Vaginal Gel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-29

    ... Recommendations for Metronidazole Vaginal Gel; Availability AGENCY: Food and Drug Administration, HHS. ACTION... guidance for industry entitled ``Bioequivalence Recommendations for Metronidazole Vaginal Gel.'' The... abbreviated new drug applications (ANDAs) for metronidazole vaginal gel. DATES: Although you can comment on...

  4. Uptake of metronidazole in Artemia at different developmental life stages.

    PubMed

    Rodriguez, Loretta; Livengood, Elisa J; Miles, Richard D; Chapman, Frank A

    2011-06-01

    The purpose of this study was to examine the capacity of live brine shrimp Artemia spp. to accumulate metronidazole at different developmental life stages. Metronidazole is used in fish as an antiparasitic medication. An effective drug delivery method is to enrich the Artemia with metronidazole and offer them as live feed to the infected fish, usually ornamental species and other small fishes. Artemia cysts were hatched and then soaked in a metronidazole solution (0.05%) at instars 1-3 of larval development. Our findings indicated that Artemia were able to accumulate metronidazole at levels considered therapeutic to other animals and humans (25-100 mg/kg). However, the levels varied depending on the stage of larval development. Artemia accumulated the highest levels of metronidazole (137-143 mg/kg) when they started filter feeding (instar 2), whereas newly hatched Artemia (instar 1) contained the lowest level (85 mg/kg). Based on this study and a review of the literature, a new protocol recommended for enriching Artemia with metronidazole consists of soaking the Artemia in a 0.05% metronidazole solution for 3 h at room temperature. Because metronidazole is relatively insoluble in water, it must first be dissolved in warm water with continuous stirring.

  5. [Anaphylactic shock during the use of high doses of aprotinin in cardiac surgery].

    PubMed

    Cottineau, C; Moreau, X; Drouet, M; De Brux, J L; Brenet, O; Delhumeau, A

    1993-01-01

    A 77-year-old man was admitted for mitral valve replacement, 46 days after a failed conservative mitral surgery where he received high-dose aprotinin. Twenty minutes after induction of anaesthesia, 250 UPh E of aprotinin were infused intravenously; before the end of this infusion, bronchospasm, systemic hypotension and generalized rash were noted. Immediate treatment included intravenous adrenaline and methylprednisolone; cardiovascular stability was restored after 10 minutes. Immediate histamine liberation was confirmed by the analysis of the time course of the clinical events, a previous contact and positive skin tests. Aprotinin has the antigenic molecular structure of natural proteins. Since 1987, it is used in cardiac surgery to reduce postoperative blood loss: to prevent serious allergic reactions to aprotinin, it is necessary, in patients known to have had previous aprotinin therapy, to perform skin testing with diluted aprotinin before infusion.

  6. Impact of high dose vitamin C on platelet function

    PubMed Central

    Mohammed, Bassem M; Sanford, Kimberly W; Fisher, Bernard J; Martin, Erika J; Contaifer Jr, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S; Chalfant, Charles E; Brophy, Donald F; Fowler III, Alpha A; Natarajan, Ramesh

    2017-01-01

    both baseline and day 8 saline controls. Platelet aggregation studies, showed uniform declines in collagen and ADP-induced platelet aggregations over the 8-d study period in all three groups (P > 0.05). Collagen and ADP-induced ATP secretion was also not different between the three groups (P > 0.05). Finally, VitC at the higher dose (3 mmol/L) also induced the release of several eicosanoids including thromboxane B2 and prostaglandin E2, as well as products of arachidonic acid metabolism via the lipoxygenases pathway such as 11-/12-/15-hydroxyicosatetraenoic acid (P < 0.05). CONCLUSION Alterations in PLT function by exposure to 3 mmol/L VitC for 8 d suggest that caution should be exerted with prolonged use of intravenous high dose VitC. PMID:28224106

  7. High dose anakinra for treatment of severe neonatal Kawasaki disease: a case report

    PubMed Central

    2014-01-01

    We report an 11-week-old female who presented with Kawasaki disease (KD) complicated by macrophage activation syndrome (MAS). The infant presented to the hospital with persistent fever, cough, diarrhea, and emesis, among other symptoms. Her condition quickly began to decompensate, and she developed classic features (conjunctivitis, rash, cracked lips, distal extremity edema) prompting a diagnosis of acute KD. The patient was treated with standard therapy for KD including three doses of intravenous immunoglobulin (IVIG), aspirin, and high dose glucocorticoids with no change in her condition. Due to a high suspicion for MAS, high dose anakinra therapy was initiated resulting in dramatic clinical improvements. She also received one dose of infliximab for concern for coronary artery changes, and over the course of several months, anakinra and high dose glucocorticoids were tapered. Nearly complete reversal of echocardiogram changes were observed after 8 months, and the infant is now off all immunosuppressive therapy. In this case report, we briefly review the importance of early recognition of MAS in pediatric patient populations with rheumatic diseases, and we suggest early initiation of anakinra therapy as a rapid and effective treatment option. PMID:25045337

  8. High dose cyclophosphamide performs better than monthly dose cyclophosphamide in quality of life measures.

    PubMed

    Dussán, K B; Magder, L; Brodsky, R A; Jones, R J; Petri, M

    2008-12-01

    In spite of current therapies, the overall health status of patients with SLE is poor. High-dose cyclophosphamide (50 mg/kg for 4 days) with or without stem-cell rescue has been introduced as a new therapy for severe SLE, including renal and central nervous system (CNS)-SLE. Long-term durable responses have been found to be 40%. A randomised clinical trial was completed comparing high-dose cyclophosphamide with monthly intravenous cyclophosphamide (750 mg/m squared bovine serum albumin) in patients with SLE who need cyclophosphamide for the first time. The primary outcome of the trial was complete clinical response. In this report, we compare the treatment groups with respect to quality of life. The patients in this study had a mean age of 35.3 +/- 10.1 years, were of Caucasian (35%), African-American (51%), Hispanic (8%) and Asian (6%) people, and 88% were women. The organ leading to treatment was renal lupus in 29%, CNS-lupus in 45% and other organs in 26%. Quality of life was measured at each visit using the Medical Outcome Study Short-Form 36 (SF-36). At 6 months, the patients in the high-dose cyclophosphamide trial arm had significantly greater improvement than patients in the monthly intravenous cyclophosphamide arm (P = 0.026; P = 0.0082, respectively) in the categories of general health and social functioning. At 18 months, the improvement in the role-physical score was significantly greater in the high-dose cyclophosphamide trial arm than in the monthly-dose cyclophosphamide arm (P = 0.025). At the end of the two and a half-year study, there were no significant differences between the groups with respect to changes in SF-36. By pooling the groups, at 30 months, there was a statistically significant (P < 0.05) improvement over baseline in 6 of the 8 SF-36 domains. This study shows earlier improvement in SF-36 measures at 6 months in the high-dose cyclophosphamide group but equal improvement in both arms at two and one and a half years. Eventual improvements

  9. High-dose immunosuppressant alters the immunological status of New Zealand white rabbits following skin transplantation.

    PubMed

    Cheng, Peilun; Zhong, Liming; Jiang, Zesheng; Wang, Yan; Pan, Mingxin; Gao, Y I

    2015-09-01

    The aim of this study was to investigate the effect of an immunosuppressant on the immunological status of New Zealand white rabbits after skin grafting, and to evaluate a method for monitoring the immunological status of subjects with skin transplants. The rabbits were randomly divided into allograft rejection, autograft tolerance, nontransplant, allograft low-dose immunosuppressant and allograft high-dose immunosuppressant groups. The rabbits in the low- and high-dose immunosuppressant groups were treated with cyclosporine A intravenously 8 h prior to skin transplantation and once daily following transplantation at doses of 2 and 25 mg/kg, respectively. At 12 days after skin transplantation, the spleens of donor (female) rabbits and recipient (male) rabbits were harvested for the preparation of single-cell suspensions. The splenocytes from recipient and donor rabbits were labeled with 0.3 or 6 µM carboxy fluorescein diacetate succinimidyl ester, respectively, and a mixed cell suspension was prepared. The final preparation was intravenously injected into recipient New Zealand white rabbits. The ratio of the two fluorescently labeled cell populations in the peripheral blood was measured using flow cytometry at 1, 2, 4 and 8 h after the injection, and the cell death rate was calculated. Histological analysis was also performed on samples collected at the time of splenectomy. The cell death rates of the allograft rejection and low-dose immunosuppressant groups reached their highest levels 8 h after the injection of spleen cell suspension. Allogeneic spleen cells from donor male rabbits were almost completely removed within 8 h of injection. The cell death rate increased slowly in the nontransplant, autograft and high-dose immunosuppressant groups without specificity. This study provides a specific method for the in vivo monitoring of the immunological status of patients after skin grafting. This method can quickly and accurately detect the immunological status of

  10. Preparation and Cyclodextrin Solubilization of the Antibacterial Agent Benzoyl Metronidazole

    PubMed Central

    Yang, Shuo

    2013-01-01

    A one-pot method for the preparation of benzoyl metronidazole was achieved by using N,N′-carbonyldiimidazole as a coupling reagent. Moreover, it was found that the byproduct imidazole as the catalyst promoted the reaction. In addition, the β-cyclodextrin solubilization of benzoyl metronidazole was investigated by phase-solubility method. The phase-solubility studies indicated that the solubility of benzoyl metronidazole (S = 0.1435 g/L) was substantially increased 9.7-fold (S′ = 1.3881 g/L) by formation of 1 : 1 benzoyl metronidazole/β-cyclodextrin complexes in water, and the association constant K a value was determined to be 251 (±23) dm3/mol. Therefore, β-cyclodextrin can work as a pharmaceutical solubilizer for benzoyl metronidazole and may improve its oral bioavailability. PMID:23970831

  11. [Reversible neurotoxicity secondary to metronidazole: report of one case].

    PubMed

    Retamal-Riquelme, Eva; Soto-San Martín, Hernán; Vallejos-Castro, José; Galdames-Poblete, Daniel

    2014-03-01

    Metronidazole can cause adverse effects both in the central and peripheral nervous system. We report a 34-year-old female who presented a reversible cerebellar syndrome and peripheral neuropathy as an adverse effect associated with the use of metronidazole. Brain magnetic resonance imaging (MRI) showed hyperintense T2 and FLAIR bilateral symmetrical cerebellar lesions, without contrast enhancement or mass effect, isointense in diffusion-weighted imaging and hypointense in apparent diffusion coefficient sequences. Also, electrophysiological evaluation was consistent with axonal polyneuropathy. She had received metronidazole for a liver abscess during 49 days. After discontinuation of metronidazole, she had rapid regression of cerebellar symptoms and normalization of MRI, with subsequent disappearance of peripheral symptoms. The brain MRI, electromyography and nerve conduction studies performed at 35 months later showed complete resolution of the lesions. Although metronidazole neurotoxicity is a rare event, it must be borne in mind because the prognosis is usually favorable after stopping the drug.

  12. Pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis.

    PubMed

    Wang, Xin; Nanovskaya, Tatiana N; Zhan, Ying; Abdel-Rahman, Susan M; Jasek, Marlo; Hankins, Gary D V; Ahmed, Mahmoud S

    2011-03-01

    The present study was undertaken to investigate the pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis. Twenty patients received metronidazole (Flagyl ®, Pfizer, 235 East 42nd Street, NY, NY 10017) oral dose 500 mg twice a day for 3 consecutive days. Pharmacokinetic analyses of metronidazole were performed after a single oral dose on the morning of day 4. Although absolute estimates of metronidazole total body exposure were highest in women during early term pregnancy, weight-corrected estimates of exposure maximum plasma drug concentration (C(max)) and the area under the plasma concentration-versus-time curve (AUC(0-12)), along with apparent oral clearance and distribution volume, were not significantly different between women at early, middle, and late stages of pregnancy and were in the range of reported values for nonpregnant patients receiving a similar dose. The pharmacokinetic profile of metronidazole did not change at the different time points assessed during pregnancy.

  13. Pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis

    PubMed Central

    Wang, Xin; Nanovskaya, Tatiana N.; Zhan, Ying; Abdel-Rahman, Susan M.; Jasek, Marlo; Hankins, Gary D.V.; Ahmed, Mahmoud S.

    2010-01-01

    Objective The present study was undertaken to investigate the pharmacokinetics of metronidazole in pregnant patients with bacterial vaginosis. Methods Twenty patients received metronidazole (Flagyl,® Pfizer, 235 East 42nd Street, NY, NY 10017) oral dose 500 mg twice a day for 3 consecutive days. Pharmacokinetic analyses of metronidazole were performed after a single oral dose on the morning of the day 4. Results Although absolute estimates of metronidazole total body exposure were highest in women during early term pregnancy, weight-corrected estimates of exposure maximum plasma drug concentration (Cmax, ) and the area under the plasma concentration-versus-time curve (AUC0-12), along with apparent oral clearance and distribution volume, were not significantly different between women at early, middle, and late stages of pregnancy and were in the range of reported values for nonpregnant patients receiving a similar dose. Conclusions The pharmacokinetic profile of metronidazole did not change at the different time points assessed during pregnancy. PMID:20608802

  14. Intravenous Pyelogram (IVP)

    MedlinePlus

    ... News Physician Resources Professions Site Index A-Z Intravenous Pyelogram (IVP) Intravenous pyelogram (IVP) is an x- ... the limitations of IVP exams? What is an Intravenous Pyelogram (IVP)? An intravenous pyelogram (IVP) is an ...

  15. Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period.

    PubMed

    Swain, E A; Magdesian, K G; Kass, P H; Edman, J E; Knych, H K

    2015-06-01

    Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics within the neonatal period. Blood samples were collected at serial time points after metronidazole administration. Metronidazole concentration in plasma was measured using LC-MS. Pharmacokinetic parameters were determined using noncompartmental analysis and compared between age groups. At 1-2.5 days of age, the mean peak plasma concentration after IV infusion was 18.79 ± 1.46 μg/mL, elimination half-life was 11.8 ± 1.77 h, clearance was 0.84 ± 0.13 mL/min/kg and the volume of distribution (steady-state) was 0.87 ± 0.07 L/kg. At 10-12 days of age, the mean peak plasma concentration after IV infusion was 18.17 ± 1.42 μg/mL, elimination half-life was 9.07 ± 2.84 h, clearance was 1.14 ± 0.21 mL/min/kg and the volume of distribution (steady-state) was 0.88 ± 0.06 L/kg. Oral approximated bioavailability was 100%. Cmax and Tmax after oral dosing were 14.85 ± 0.54 μg/mL and 1.75 (1-4) h, respectively. The elimination half-life was longer and clearance was reduced in neonatal foals at 1-2.5 days as compared to 10-12 days of age (P = 0.006, P = 0.001, respectively). This study warrants consideration for altered dosing recommendations in foals, especially a longer interval (12 h). © 2014 John Wiley & Sons Ltd.

  16. Cumulative irritation potential among metronidazole gel 1%, metronidazole gel 0.75%, and azelaic acid gel 15%.

    PubMed

    Colón, Luz E; Johnson, Lori A; Gottschalk, Ronald W

    2007-04-01

    Topical therapy for rosacea aims to reduce inflammatory lesions and decrease erythema but can carry side effects such as stinging, pruritus, and burning. Metronidazole and azelaic acid gel 15% are U.S. Food and Drug Administration-approved for the treatment of rosacea. The current study was conducted to assess the cumulative irritation potential of 2 formulations of metronidazole 0.75% gel and 1% gel--and azelaic acid gel 15% over 21 days (N=36). Results of this study demonstrated a significantly greater poten tial for irritation from azelaic acid compared with metronidazole gel 0.75% (P < .0001), which had significantly greater potential for irritation compared with metronidazole gel 1% (P = .0054). Metronidazole gel 1% had a similar profile to white petrolatum.

  17. High-dose insulin: a consecutive case series in toxin-induced cardiogenic shock.

    PubMed

    Holger, Joel S; Stellpflug, Samuel J; Cole, Jon B; Harris, Carson R; Engebretsen, Kristin M

    2011-08-01

    Cardiovascular medication overdoses can be difficult to treat. Various treatment modalities are currently recommended. To describe patient outcomes and adverse events of high-dose insulin therapy in consecutive overdose patients in cardiogenic shock after implementation of a high-dose insulin protocol (1-10 U/kg/h, while avoiding or tapering off vasopressors). This is an observational consecutive case series of patients identified from a registry. Data were collected by retrospective chart review of patients treated by our toxicology service with this protocol from February 2007 until March 2010. Twelve patients were treated with high-dose insulin. The mean age was 36.5 years (SD 11.7). Seven patients had pre-existing vasopressor therapy, and all were tapered off vasopressors while on insulin. Two patients experienced pulseless electrical activity cardiac arrest prior to high-dose insulin therapy. Intravenous fat emulsion was given to two patients. The mean maximum insulin infusion rate was 8.35 U/kg/h (mean = 8.35, SD 6.34). The mean duration of insulin infusion was 23.5 h (SD 19.7). The mean duration of glucose infusion post-insulin was 25.2 h (SD 17.7). The primary toxins were β-blocker in five, calcium channel blocker in two, combined β-blocker/calcium channel blocker in two, tricyclic antidepressant in one, and polydrug in 2. CLINICAL OUTCOMES: Eleven of 12 patients survived. One patient expired 9 h into insulin therapy from cardiac arrest shortly after the insulin was stopped and a vasopressor re-initiated (protocol deviation). Six patients experienced a total of 19 hypoglycemic events. Hypokalemia (defined as < 3.0 mEq/L) developed in eight patients. ADVERSE SEQUELAE: Necrotic digits occurred in one patient with known clotting disorder after receiving high-dose norepinephrine and INR reversal with fresh frozen plasma prior to insulin therapy. One patient was discharged with mild anoxic injury thought due to pulseless electrical activity arrest prior to

  18. Purpura and dermal thinning associated with high dose inhaled corticosteroids.

    PubMed Central

    Capewell, S; Reynolds, S; Shuttleworth, D; Edwards, C; Finlay, A Y

    1990-01-01

    OBJECTIVE--To assess the effect of high dose inhaled corticosteroids on skin. DESIGN--Cross sectional study of patients receiving treatment for chest diseases. SETTING--Outpatient chest clinic in a teaching hospital. PATIENTS--68 Patients divided into four groups of similar age--namely, 15 receiving long term oral prednisolone, 21 receiving high dose inhaled corticosteroids, 15 receiving low dose inhaled corticosteroids, and 17 controls. MAIN OUTCOME MEASURES--Skin thickness at three sites measured by A scan ultrasound and clinical assessment of purpura. RESULTS--Compared with controls patients in both the oral prednisolone treated group and the high dose inhaled corticosteroid treated group had significantly thinner skin at all three sites (group median thicknesses: prednisolone treated group 28-33% less than controls; high dose inhaled corticosteroid treated group 15-19% less than controls). Differences in skin thicknesses between the low dose inhaled corticosteroid treated group and the controls were trivial. The prevalence of purpura was significantly greater in patients receiving oral prednisolone (12/15 patients) and high dose inhaled corticosteroids (10/21) than in controls (2/17). CONCLUSION--Skin thinning and purpura represent further evidence of systemic effects of high dose inhaled corticosteroids. PMID:2372620

  19. The use of metronidazole during pregnancy: a review of evidence.

    PubMed

    Sheehy, Odile; Santos, Fabiano; Ferreira, Ema; Berard, Anick

    2015-01-01

    To review the available evidence concerning the relationship between the exposure to metronidazole during pregnancy and the risk of preterm delivery and birth defects. Studies investigating the association between gestational use of oral metronidazole on human subjects and the risk of preterm birth or/and birth defects were systematically retrieved from MEDLINE and EMBASE databases. We selected studies published in English or French between 1964 and 2012. Where effect estimates were not reported, crude ORs along with 95% confidence intervals were calculated. We selected 17 studies investigating the association between exposure to oral metronidazole and the risk of preterm birth, from which 12 were randomized clinical trials. In addition, we identified 13 studies devoted to the relationship between metronidazole and birth defects, from which 10 were cohort studies, 1 was a case-control study and 2 were meta-analysis. During pregnancy, treating bacterial vaginosis and trichomoniasis with metronidazole is effective and offers no teratogen risk. Benefit of metronidazole in the reduction of preterm birth was demonstrated for the combination of this medication with other antibiotics. Additional information is needed when metronidazole is used in association with other agents.

  20. Metronidazole with Lactacyd vaginal gel in bacterial vaginosis.

    PubMed

    Decena, Ditas Cristina D; Co, Jennifer T; Manalastas, Ricardo M; Palaypayon, Evelyn P; Padolina, Christia S; Sison, Judith M; Dancel, Louella A; Lelis, Marievi A

    2006-04-01

    To assess the efficacy and tolerability of lactic acid (Lactacyd vaginal gel; LVG) when given as an adjunct to metronidazole in the treatment of bacterial vaginosis (BV) among Filipino patients. A multicenter, open-labeled, controlled, randomized, three-arm comparative study on 90 women aged 18 years or over with clinically and microbiologically proven BV. The lactobacilli colony count significantly increased over time in all three arms. At day 14, growth of lactobacilli was significantly higher among patients in the lactic acid gel and combination treatment arms. Significant reduction of malodorous vaginal discharge (whiff test) and lowest recurrence of BV were noted in the metronidazole plus lactic acid gel arm. Regarding disappearance of signs of BV, there was significant decrease in the pH level and frequency of clue cell positive patients across time but was not significantly different across treatment groups. Only one patient (3%, 1/60) among those who received lactic acid gel complained of increased curd-like discharge. Six patients (10%, 6/60) who received metronidazole complained of epigastric pain/discomfort, dizziness and dyspnea. Lactic acid gel (LVG) is safe and as efficacious as metronidazole in the treatment of BV. There is evidence that LVG when combined with metronidazole is superior to metronidazole alone in promoting lactobacilli colonization. LVG as an adjunct to metronidazole, having the least number of recurrent BV, appears to result in better long-term treatment effect on bacterial vaginosis.

  1. A rare adverse effect of metronidazole: nervous system symptoms.

    PubMed

    Kafadar, Ihsan; Moustafa, Fatma; Yalçın, Koray; Klç, Betül Aydn

    2013-06-01

    Metronidazole, as a 5-nitroimidazole compound, is effective on anaerobic bacteria and protozoon diseases. Mostly, metronidazole is a tolerable drug but rarely presents serious adverse effects on the nervous system. In case of these adverse effects, treatment must be stopped.In this report, a 3-year-old child hospitalized because of diarrhea is presented. During the metronidazole treatment, loss of sight, vertigo, ataxia, and headache occurred as the adverse effects. By this report, we want to express the rare adverse effects of drugs in the differential diagnoses of nervous system diseases.

  2. DNA breakage due to metronidazole treatment.

    PubMed

    Menéndez, D; Rojas, E; Herrera, L A; López, M C; Sordo, M; Elizondo, G; Ostrosky-Wegman, P

    2001-07-01

    The mutagenicity of metronidazole [1-(hidroxyethyl)-2-methyl-5-nitroimidazole] (MTZ) has been shown in different prokaryotic systems. However, data on human cells are still contradictory. In this study DNA damage was determined by the single cell gel electrophoresis (SCGE) assay, in lymphocytes from 10 healthy subjects treated with therapeutic doses of this drug. Samples were obtained before treatment, as well as 1 and 15 days after ending treatment. Results showed a significant increase of DNA strand breaks 1 day after ending treatment, although, an inverse correlation between the amount of DNA damage and plasma concentrations of MTZ was obtained. Thus, the observed damage may be induced by some MTZ metabolite rather than by the parent drug. Interestingly, the amount of DNA damage returned to basal levels 15 days after ending treatment, except in two individuals. This persistent damage should be further investigated.

  3. Vulvoperineal Crohn's disease responsive to metronidazole*

    PubMed Central

    Rosmaninho, Aristóteles; Sanches, Madalena; Salgado, Marta; Alves, Rosário; Selores, Manuela

    2013-01-01

    Crohn's disease is a multisystem chronic granulomatous inflammatory disease that primarily affects the gastrointestinal tract. In the majority of the cases, the cutaneous manifestations follow the intestinal disease, but occasionally dermatological lesions are the inaugural event and may constitute the only sign of the disease. Vulvoperineal involvement is rare, may precede bowel symptoms by months to years and may go unrecognized. Due to the paucity of reports of Crohn's disease at this location and in the absence of randomized trials, there are no standard treatments for the cutaneous disease. We describe the case of a 47 year-old woman with vulvoperineal Crohn's disease without digestive involvement, that was successfully managed with metronidazole. PMID:24346884

  4. Juvenile dermatomyositis: treatment with intravenous gammaglobulin.

    PubMed

    Collet, E; Dalac, S; Maerens, B; Courtois, J M; Izac, M; Lambert, D

    1994-02-01

    High-dose intravenous gammaglobulin (IVGG) has proved to be effective in the treatment of a number of immune disorders. We report two patients with juvenile dermatomyositis (DM) who improved with IVGG therapy. These patients had become refractory to corticosteroids and had developed unacceptable steroid toxicity. We suggest that IVGG can be useful in the treatment of juvenile DM, by reducing steroid requirements, and replacing immunosuppressive drugs.

  5. Relevance of high-dose chemotherapy in solid tumours.

    PubMed

    Nieboer, P; de Vries, E G E; Mulder, N H; van der Graaf, W T A

    2005-05-01

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.

  6. Key Technologies for Ultra High Dose CMOS Applications

    SciTech Connect

    Jeon, Y.; Koo, I.; Singh, V.; Oh, J.; Jin, S.; Lee, J.; Rouh, K.; Ju, M.; Jeon, S.; Ku, J.; Lee, S. B.; Lee, S. W.; Ok, M. T.; Butterbaugh, J.; Lee, A.; Kim, K.; Lee, S. W.; Ju, K. J.; Park, J. W.

    2008-11-03

    The trend towards shrinking advanced microelectronic Logic and DRAM devices will require ultra high dose implantation. One ultra high dose application in DRAM, being rapidly adopted in production is Dual Poly Gate (DPG). Three main challenges existed for the adoption of this high dose dual poly gate (DPG) doping applications: monitoring of high dose implantation, photoresist stripping and maintaining high throughput. In this paper we present how these challenges have been addressed. VSEA's plasma doping (PLAD) tool offers several unique advantages for DPG applications. When compared to conventional or molecular beam line implanters or other immersion techniques, PLAD delivers 3 to 7 times higher throughput (compared to traditional ion implanter) without dopant penetration through the thin doped polysilicon layer into the gate oxide. It also improves P{sup +} poly silicon DPG device properties at superior throughput. In this work we demonstrate how hot spray photoresist strip processing eliminates the need for multiple-tools required for wet+ash+wet process. In addition to PLAD's patented in-situ dose control metrology we also demonstrate an ex-situ high dose implantation metrology using spectroscopic ellipsometer (SE) and spectroscopic reflectometer (SR). The technique shows good correlation (R{sup 2}{approx}0.99) between implant dose and damaged layer thickness.

  7. Pharyngo-cutaneous fistulae after laryngectomy. Influence of previous radiotherapy and prophylactic metronidazole

    SciTech Connect

    Johansen, L.V.; Overgaard, J.; Elbrond, O.

    1988-02-15

    The development of a pharyngocutaneous fistulae is a major complication after total laryngectomy. In Denmark radiotherapy is the primary treatment for all laryngeal carcinomas. Based on the experience with conventional daily irradiation, a split-course radiation schedule was introduced in 1978. The charts of 106 consecutive patients laryngectomized for recurrence in the years 1975 to 1984 were examined. Thirty-four patients developed a fistula. An evaluation of the different radiotherapy schedules used during this period allowed a dose-response curve to be constructed. It showed a pronounced increase of fistulae with high doses of radiotherapy. Split-course radiotherapy caused a rise in late complications and did not improve tumor control. Large field sizes increased the number of fistulae. High-dose fractions showed a surprisingly high incidence of late complications. Prophylactic metronidazole (introduced in 1980) resulted in a highly significant decrease in the frequency of postoperative fistulae. Patients in whom fistula formed were hospitalized for an average of 54 days, patients without, for 22 days.

  8. Metronidazole Toxicity in Cockayne Syndrome: A Case Series.

    PubMed

    Wilson, Brian T; Strong, Andrew; O'Kelly, Sean; Munkley, Jennifer; Stark, Zornitza

    2015-09-01

    Cockayne syndrome (CS) is a rare genetic disorder characterized by small stature, intellectual disability, and accelerated pathologic aging. Through the Cockayne Syndrome Natural History Study, we have identified 8 cases of acute hepatic failure after metronidazole administration (8% of our cohort), 3 of which were fatal. The interval between initial administration and death was 6 to 11 days. Two of these patients also experienced acute neurologic deficit. Both hepatotoxicity and acute neurologic deficit have been reported previously as extremely rare adverse events after metronidazole administration. However, we have not identified any patients with CS who have received metronidazole without serious adverse effects. We recommend that a diagnosis of CS be considered an absolute contraindication to the use of metronidazole.

  9. Tinidazole versus Metronidazole for the Treatment of Bacterial Vaginosis

    PubMed Central

    SCHWEBKE, Jane R.; DESMOND, Renee A.

    2010-01-01

    Objective To compare the efficacy of two different doses of tinidazole with metronidazole for treatment of bacterial vaginosis and compare side effects of the drugs. Study design Women were randomized to metronidazole 500 mg BID, tinidazole 500 mg BID, or tinidazole 1 gm BID all for 7 days. Follow-up visits were conducted at day 14 and day 28. Results 593 women were enrolled. There were no significant differences between the treatment arms. Overall cure rates were 76.8% at 14 days and 64.5% at one month. Women who admitted to engaging in sexual intercourse during the study were significantly more likely to have BV at follow-up. There were no significant differences in adverse events across treatment arms. Conclusions There were no differences in cure rates between metronidazole and either of the tinidazole dosing regimens studied. In addition, there were no important differences in the side effect profiles of metronidazole and tinidazole. PMID:21167471

  10. High-Dose Subcutaneous Immunoglobulin in Patients With Multifocal Motor Neuropathy: A Nursing Perspective.

    PubMed

    Rasutis, Vilija M; Katzberg, Hans D; Bril, Vera

    Multifocal motor neuropathy (MMN), an immune neuromuscular condition causing progressive weakness, usually responds to immune-mediated treatments, including intravenous immunoglobulin (IVIG). Fifteen patients with MMN receiving IVIG were enrolled in an open-label, single-center trial and switched to 20% subcutaneous immunoglobulin (SCIG) using a smooth transition protocol (ie, changing the therapy without interruption or impact on the intended outcome of the therapy). Patients received individualized training and support based on motivation and ability to learn, follow directions, and maintain compliance. Although some patients required assistance during the training phase, most managed self-infusion and reported satisfaction in managing therapy autonomously. Educating patients with neuropathies to self-infuse high-dose SCIG at home and with flexibility in dosing schedules was successfully demonstrated in this patient group.

  11. Distributive shock due to systemic capillary leak syndrome treated with high-dose immunosuppression

    PubMed Central

    Sheehan, James Robert; Keating, Liza; Chan, Antoni; Walden, Andrew

    2013-01-01

    A female patient in her 60s presented with a history of malaise, chills, headache and vomiting. She was in shock on presentation with a high haematocrit and a low albumin with evidence of rhabdomyolysis. Severe limb and truncal oedema developed with worsening hypotension leading to intensive care unit admission for multiple organ support. Extensive radiological, microbiological and immunological work up was negative with the exception of a monoclonal gammopathy. A review of patient investigations led to a diagnosis of Clarkson's disease. Treatment with high-dose methylprednisolone and intravenous immunoglobulins led to a rapid decline in the creatine kinase (CK) level and vasopressor requirements. The patient was discharged home on long-term terbutaline and has made a good recovery. PMID:23576661

  12. Distributive shock due to systemic capillary leak syndrome treated with high-dose immunosuppression.

    PubMed

    Sheehan, James Robert; Keating, Liza; Chan, Antoni; Walden, Andrew

    2013-04-09

    A female patient in her 60s presented with a history of malaise, chills, headache and vomiting. She was in shock on presentation with a high haematocrit and a low albumin with evidence of rhabdomyolysis. Severe limb and truncal oedema developed with worsening hypotension leading to intensive care unit admission for multiple organ support. Extensive radiological, microbiological and immunological work up was negative with the exception of a monoclonal gammopathy. A review of patient investigations led to a diagnosis of Clarkson's disease. Treatment with high-dose methylprednisolone and intravenous immunoglobulins led to a rapid decline in the creatine kinase (CK) level and vasopressor requirements. The patient was discharged home on long-term terbutaline and has made a good recovery.

  13. Indirect electroreduction as pretreatment to enhance biodegradability of metronidazole.

    PubMed

    Saidi, I; Soutrel, I; Floner, D; Fourcade, F; Bellakhal, N; Amrane, A; Geneste, F

    2014-08-15

    The removal of metronidazole, a biorecalcitrant antibiotic, by coupling an electrochemical reduction with a biological treatment was examined. Electroreduction was performed in a home-made flow cell at -1.2V/SCE on graphite felt. After only one pass through the cell, analysis of the electrolyzed solution showed a total degradation of metronidazole. The biodegradability estimated from the BOD5/COD ratio increased from 0.07 to 0.2, namely below the value usually considered as the limit of biodegradability (0.4). In order to improve these results, indirect electrolysis of metronidazole was performed with a titanium complex known to reduce selectively nitro compounds into amine. The catalytic activity of the titanium complex towards electroreduction of metronidazole was shown by cyclic voltammetry analyses. Indirect electrolysis led to an improvement of the biodegradability from 0.07 to 0.42. To confirm the interest of indirect electroreduction to improve the electrochemical pretreatment, biological treatment was then carried out on activated sludge after direct and indirect electrolyses; different parameters were followed during the culture such as pH, TOC and metronidazole concentration. Both electrochemical processes led to a more efficient biodegradation of metronidazole compared with the single biological treatment, leading to an overall mineralization yield for the coupling process of 85%. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Subjective adverse reactions to metronidazole in patients with amebiasis.

    PubMed

    Ohnishi, Kenji; Sakamoto, Naoya; Kobayashi, Ken-Ichiro; Iwabuchi, Sentaro; Nakamura-Uchiyama, Fukumi; Ajisawa, Atsushi; Yamauchi, Yuko; Takeshita, Nozomi; Yamamoto, Yasuyuki; Tsunoda, Takafumi; Yoshimura, Yukihiro; Tachikawa, Natsuo; Uehira, Tomoko

    2014-10-01

    Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Metronidazole activation and isolation of Clostridium acetobutylicum electron transport genes.

    PubMed Central

    Santangelo, J D; Jones, D T; Woods, D R

    1991-01-01

    An Escherichia coli F19 recA, nitrate reductase-deficient mutant was constructed by transposon mutagenesis and shown to be resistant to metronidazole. This mutant was a most suitable host for the isolation of Clostridium acetobutylicum genes on recombinant plasmids, which activated metronidazole and rendered the E. coli F19 strain sensitive to metronidazole. Twenty-five E. coli F19 clones containing different recombinant plasmids were isolated and classified into five groups on the basis of their sensitivity to metronidazole. The clones were tested for nitrate reductase, pyruvate-ferredoxin oxidoreductase, and hydrogenase activities. DNA hybridization and restriction endonuclease mapping revealed that four of the C. acetobutylicum insert DNA fragments on recombinant plasmids were linked in an 11.1-kb chromosomal fragment. DNA sequencing and amino acid homology studies indicated that this DNA fragment contained a flavodoxin gene which encoded a protein of 160 amino acids that activated metronidazole and made the E. coli F19 mutant very sensitive to metronidazole. The flavodoxin and hydrogenase genes which are involved in electron transfer systems were linked on the 11.1-kb DNA fragment from C. acetobutylicum. Images PMID:1991710

  16. Absence of Strand Breaks in Deoxyribonucleic Acid Treated with Metronidazole

    PubMed Central

    LaRusso, Nicholas F.; Tomasz, Maria; Kaplan, David; Müller, Miklós

    1978-01-01

    The deoxyribonucleic acid (DNA)-degrading potential of metronidazole was evaluated in vitro by three techniques: determination of melting curve, measurement of viscosity, and centrifugation in neutral or alkaline sucrose gradients. Studies were performed on calf thymus DNA and on 3H-labeled or unlabeled pneumococcal and T7 phage DNA after treatment with metronidazole alone or metronidazole reduced by sodium dithionite in the presence of DNA. This latter process is known to elicit covalent binding of metronidazole to DNA. Reduced or unreduced metronidazole had no effect on the melting properties, viscosity, or sedimentation velocity of the nucleic acids studied. Sodium dithionite alone, however, caused a 25% decrease in the intrinsic viscosity of pneumococcal DNA, and decreased the sedimentation velocity of pneumococcal and T7 phage DNA in both neutral and alkaline sucrose gradients. These data suggest that degradation of DNA is not important in the interaction of metronidazole with nucleic acids, an interaction assumed relevant to the cytotoxic, radiosensitizing, and mutagenic activities of this compound. PMID:626487

  17. High-dose methylprednisolone and endothelial glycocalyx in paediatric heart surgery.

    PubMed

    Pesonen, E; Keski-Nisula, J; Andersson, S; Palo, R; Salminen, J; Suominen, P K

    2016-11-01

    Corticosteroids are used in paediatric heart surgery to attenuate systemic inflammatory response. Glycocalyx regulates vascular permeability, shear stress and cell adhesion on the endothelium. Syndecan-1 serves as a biomarker of glycocalyx degradation. Hydrocortisone decreased endothelial glycocalyx degradation in an experimental model. Our hypothesis was that high-dose methylprednisolone decreases glycocalyx degradation as measured by plasma sydecan-1 concentration in children undergoing cardiac surgery. Two double-blinded, randomized, placebo-controlled trials were conducted. In the first trial ('neonatal trial'), 40 neonates undergoing open heart surgery received either 30 mg/kg intravenous methylprednisolone (n = 20) or placebo (n = 20). In the second trial ('VSD trial'), 45 infants and very young children, undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone intravenously after anaesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15) or placebo (n = 15). Plasma syndecan-1 concentrations were measured. Results were expressed both as absolute concentrations and in relative concentrations as multiples of the baseline values of syndecan-1. There were no statistically significant differences between the neonate trial groups for absolute syndecan-1 concentrations. However, operative administration of methylprednisolone to neonates significantly reduced the relative increases of syndecan-1 at weaning from cardiopulmonary bypass (P = 0.008) and at 6 h post-operatively (P = 0.018). There were no statistically significant differences in absolute or relative increases of syndecan-1 between the VSD trial study groups. High-dose methylprednisolone reduces shedding of glycocalyx in neonates after complex cardiac surgery but not in older infants after repair of VSD/AVSD with shorter ischaemia times. © 2016 The Acta Anaesthesiologica

  18. High-dose immunosuppressant alters the immunological status of New Zealand white rabbits following skin transplantation

    PubMed Central

    CHENG, PEILUN; ZHONG, LIMING; JIANG, ZESHENG; WANG, YAN; PAN, MINGXIN; GAO, YI

    2015-01-01

    The aim of this study was to investigate the effect of an immunosuppressant on the immunological status of New Zealand white rabbits after skin grafting, and to evaluate a method for monitoring the immunological status of subjects with skin transplants. The rabbits were randomly divided into allograft rejection, autograft tolerance, nontransplant, allograft low-dose immunosuppressant and allograft high-dose immunosuppressant groups. The rabbits in the low- and high-dose immunosuppressant groups were treated with cyclosporine A intravenously 8 h prior to skin transplantation and once daily following transplantation at doses of 2 and 25 mg/kg, respectively. At 12 days after skin transplantation, the spleens of donor (female) rabbits and recipient (male) rabbits were harvested for the preparation of single-cell suspensions. The splenocytes from recipient and donor rabbits were labeled with 0.3 or 6 µM carboxy fluorescein diacetate succinimidyl ester, respectively, and a mixed cell suspension was prepared. The final preparation was intravenously injected into recipient New Zealand white rabbits. The ratio of the two fluorescently labeled cell populations in the peripheral blood was measured using flow cytometry at 1, 2, 4 and 8 h after the injection, and the cell death rate was calculated. Histological analysis was also performed on samples collected at the time of splenectomy. The cell death rates of the allograft rejection and low-dose immunosuppressant groups reached their highest levels 8 h after the injection of spleen cell suspension. Allogeneic spleen cells from donor male rabbits were almost completely removed within 8 h of injection. The cell death rate increased slowly in the nontransplant, autograft and high-dose immunosuppressant groups without specificity. This study provides a specific method for the in vivo monitoring of the immunological status of patients after skin grafting. This method can quickly and accurately detect the immunological status of

  19. Metronidazole loaded pectin microspheres for colon targeting.

    PubMed

    Vaidya, Ankur; Jain, Aviral; Khare, Piush; Agrawal, Ram K; Jain, Sanjay K

    2009-11-01

    A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit(R) S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

  20. Montmorillonite nanodevices for the colon metronidazole delivery.

    PubMed

    Calabrese, Ilaria; Cavallaro, Gennara; Scialabba, Cinzia; Licciardi, Mariano; Merli, Marcello; Sciascia, Luciana; Turco Liveri, Maria Liria

    2013-11-30

    The adsorption profiles of the antibiotic metronidazole (MNE) into the K10-montmorillonite (MMT-K10) clay and the subsequent release have been investigated as a function of pH and MNE/MMT-K10 ratio, in order to evaluate the potential of the MNE/MMT-K10 hybrids as controlled drug delivery system. The adsorption mechanism has been first elucidated by performing complementary equilibrium and kinetic studies and through the X-ray diffractometry (XRD) characterization of the obtained composite materials. The gathered results allowed us to propose a mechanism consisting of a multi-step pathway involving the neutral and the cationic form of the drug, which interact with different sites of the clay surfaces, i.e. the interlayer region and the faces of the lamella. In a second step the drug release kinetics has been studied under physiological pH mimicking conditions simulating the oral drug administration and delivery. For the sake of comparison the commercial formulation has also been employed for the release studies. The investigation of the release profiles and the comparison with the commercial formulation of the drug reveal that the new-tailor made formulation could be fruitful exploited for successfully prolonged the action of drug in the desired site. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Metronidazole-induced central nervous system toxicity: a systematic review.

    PubMed

    Kuriyama, Akira; Jackson, Jeffrey L; Doi, Asako; Kamiya, Toru

    2011-01-01

    To assess patient and medication factors that contribute to metronidazole toxicity. We searched PUBMED from 1965 through April 7, 2011, and performed a hand search of bibliographies. Case reports or case series reporting metronidazole-induced central nervous toxicity. Two authors independently abstracted demographics, metronidazole indication, dose and duration, neurological manifestations, and outcomes as well as brain imaging findings. Among 64 patients, 48 (77%) had cerebellar dysfunction, 21 (33%) had altered mental status, and 8 (15%) had seizures. Patients' ages averaged 53.3 years (range, 12-87 years), and 64% were male. The median duration of metronidazole was 54 days, although 26% had taken it less than a week and 11% had taken it less than 72 hours. Among cases with outcome data, most patients either improved (n = 18 [29%]) or had complete resolution of their symptoms with discontinuation of metronidazole (n = 41 [65%]). There was no difference in resolution of symptom by age (P = 0.71) or sex (P = 0.34). The patients with cerebellar dysfunction were less likely to experience complete resolution than those with mental status changes or seizures (relative risk, 0.67; 95% confidence interval (CI), 0.49-0.92). Nearly all patients (n = 55 [86%]) underwent imaging of the brain: 44 (69%) underwent magnetic resonance imaging (MRI) and 12 (19%) underwent computed tomographic studies. All patients with cerebellar dysfunction had abnormalities on imaging: 93% (n = 39) had a cerebellar lesion, although numerous areas in the brain were affected. On follow-up MRIs, 25 patients (83%) had complete resolution of abnormalities. Metronidazole can rarely cause central nervous system toxicity; it does not seem to be a dose- or duration-related phenomenon. Most patients will have MRI abnormalities. Prognosis is excellent with metronidazole cessation.

  2. Effect of high-dose paracetamol on needle procedures in children with cancer--an RCT.

    PubMed

    Hedén, L; von Essen, L; Ljungman, G

    2014-03-01

    The aim was to investigate whether children experience less pain, fear and/or distress when they receive high-dose paracetamol compared with placebo, using a needle insertion in a subcutaneously implanted intravenous port as a model. Fifty-one children ranging from 1 to 18 years of age being treated in a paediatric oncology setting were included consecutively when undergoing routine needle insertion into a subcutaneously implanted intravenous port. All children were subjected to one needle insertion following topical anaesthetic (EMLA) application in this double-blind, placebo-controlled RCT, comparing orally administered paracetamol (n = 24) 40 mg/kg body weight (max 2000 mg) with placebo (n = 27). The patients' pain, fear and distress were reported by parents, nurses and children (≥7 years of age) using 0- to 100-mm visual analogue scales (VAS). In addition, pain observation, procedure time and cortisol reduction were assessed. No differences between the paracetamol and the placebo group were found with respect to demographic characteristics. According to VAS reports, paracetamol did not reduce pain, fear and distress compared with placebo. Pain observation, cortisol reduction and procedure time did not differ between the study groups. Paracetamol provides no additive effect in reducing pain, fear and distress when combined with topical anaesthesia in children undergoing port needle insertion. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  3. Synthesis and evaluation of sulfate conjugated metronidazole as a colon-specific prodrug of metronidazole.

    PubMed

    Kim, Hyunjeong; Lee, Yonghyun; Yoo, Hansun; Kim, Jihye; Kong, Hyesik; Yoon, Jeong-Hyun; Jung, Yunjin; Kim, Young Mi

    2012-04-01

    For an effort to improve therapeutic property of metronidazole (MTZ) which is a drug of choice for protozoal infections such as luminal amoebiasis, sulfate conjugated metronidazole (MTZS) was prepared and evaluated as a colon-specific prodrug of MTZ. The apparent partition coefficient of MTZ was greatly reduced by the sulfate conjugation. While (bio)chemically stable in the contents of the upper intestine, MTZS was rapidly cleaved to liberate MTZ on incubation with the cecal contents of rats. MTZ liberated from MTZS metabolized quickly at least partly by a microbial nitroreductase, suggesting the relevance of the metabolism to bioactivation of MTZ for antimicrobial action. Consistent with the hypothesis, MTZS elicited antibacterial activity in the cecal contents, which was as potent as free MTZ. The systemic absorption of MTZS was very low after oral administration of MTZS. In parallel with this, whereas MTZ disappeared mostly during the transit of the proximal small intestine, a substantial amount of MTZS remained in the small intestine, moving down to the large intestine where it metabolized rapidly. In addition to the efficient colonic delivery of MTZS, MTZS markedly reduced the systemic absorption of MTZ. Taken together, MTZS may be a potential colon-specific prodrug of MTZ which possesses improved therapeutic and toxicological properties.

  4. Reduced cerebral glucose metabolism and increased brain capillary permeability following high-dose methotrexate chemotherapy: a positron emission tomographic study

    SciTech Connect

    Phillips, P.C.; Dhawan, V.; Strother, S.C.; Sidtis, J.J.; Evans, A.C.; Allen, J.C.; Rottenberg, D.A.

    1987-01-01

    Regional glucose metabolic rate constants and blood-to-brain transport of rubidium were estimated using positron emission tomography in an adolescent patient with a brain tumor, before and after chemotherapy with intravenous high-dose methotrexate. Widespread depression of cerebral glucose metabolism was apparent 24 hours after drug administration, which may reflect reduced glucose phosphorylation, and the influx rate constant for /sup 82/Rb was increased, indicating a drug-induced alteration in blood-brain barrier function. Associated changes in neuropsychological performance, electroencephalogram, and plasma amino acid concentration were identified in the absence of evidence of systemic methotrexate toxicity, suggesting primary methotrexate neurotoxicity.

  5. Addition of Ceftriaxone and Amikacin to a Ciprofloxacin plus Metronidazole Regimen for Preventing Infectious Complications of Transrectal Ultrasound-Guided Prostate Biopsy: A Randomized Controlled Trial

    PubMed Central

    Izadpanahi, Mohammad-Hossein; Majidi, Seyed Mahmood; Khorrami, Mohammad-Hatef; Mohammadi-Sichani, Mehrdad

    2017-01-01

    Background. The objective of this study was to evaluate the efficacy of adding single doses of ceftriaxone and amikacin to a ciprofloxacin plus metronidazole regimen on the reduction of infectious complications following transrectal ultrasound-guided prostate biopsy (TRUS Bx). Materials and Methods. Four hundred and fifty patients who were candidates for TRUS Bx were divided into two groups of 225 each. The control group received ciprofloxacin 500 mg orally every 12 hours together with metronidazole 500 mg orally every 8 hours from the day prior to the procedure until the fifth postoperative day. In the second group, single doses of ceftriaxone 1 g by intravenous infusion and amikacin 5 mg/kg intramuscularly were administered 30–60 minutes before TRUS Bx in addition to the oral antimicrobials described for group 1. The incidence of infection was compared between the groups. Results. The incidence of infectious complications in the intervention group was significantly lower than that in the control group (4.6% versus 0.9%, p = 0.017). Conclusion. The addition of single doses of intramuscular amikacin and intravenously infused ceftriaxone to our prophylactic regimen of ciprofloxacin plus metronidazole resulted in a statistically significant reduction of infectious complications following TRUS Bx. PMID:28167960

  6. High-dose diazepam facilitates core cooling during cold saline infusion in healthy volunteers.

    PubMed

    Hostler, David; Northington, William E; Callaway, Clifton W

    2009-08-01

    Studies have suggested that inducing mild hypothermia improves neurologic outcomes after traumatic brain injury, major stroke, cardiac arrest, or exertional heat illness. While infusion of cold normal saline is a simple and inexpensive method for reducing core temperature, human cold-defense mechanisms potentially make this route stressful or ineffective. We hypothesized that intravenous administration of diazepam during a rapid infusion of 30 mL.kg-1 of cold (4 degrees C) 0.9% saline to healthy subjects would be more comfortable and reduce core body temperature more than the administration of cold saline alone. Fifteen subjects received rapidly infused cold (4 degrees C) 0.9% saline. Subjects were randomly assigned to receive, intravenously, 20 mg diazepam (HIGH), 10 mg diazepam (LOW), or placebo (CON). Main outcomes were core temperature, skin temperature, and oxygen consumption. Data for the main outcomes were analyzed with generalized estimating equations to identify differences in group, time, or a group x time interaction. Core temperature decreased in all groups (CON, 1.0 +/- 0.2 degrees C; LOW, 1.4 +/- 0.2 degrees C; HIGH, 1.5 +/- 0.2 degrees C), while skin temperature was unchanged. Mean (95% CI) oxygen consumption was 315.3 (253.8, 376.9) mL.kg-1.min-1 in the CON group, 317.9 (275.5, 360.3) in the LOW group, and 226.1 (216.4, 235.9) in the HIGH group. Significant time and group x time interaction was observed for core temperature and oxygen consumption (p < 0.001). Administration of high-dose diazepam resulted in decreased oxygen consumption during cold saline infusion, suggesting that 20 mg of intravenous diazepam may reduce the shivering threshold without compromising respiratory or cardiovascular function.

  7. Dosimetric characteristics of jasper samples for high dose dosimetry.

    PubMed

    Teixeira, Maria Inês; Caldas, Linda V E

    2012-07-01

    Different colored jasper samples from Brazilian mines were powdered and mixed with teflon (composites jasper-teflonTM). This paper describes a preliminary study of a thermoluminescent method (TL) to verify the possibility of their use as high dose dosimeters or irradiation indicators in industrial areas. The jasper samples were exposed to different radiation doses, using the gamma-cell 220 system (60Co) of IPEN. The TL emission curves of samples presented two peaks at 130 °C and 190 °C. Calibration curves were obtained for the jasper samples between 50 Gy and 20 kGy. All five types of jasper samples showed their usefulness as irradiation indicators and as high-dose dosimeters.

  8. High-dose secondary calibration laboratory accreditation program

    SciTech Connect

    Humphreys, J.C.

    1993-12-31

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

  9. High-dose thiamine as initial treatment for Parkinson's disease

    PubMed Central

    Costantini, Antonio; Pala, Maria Immacolata; Compagnoni, Laura; Colangeli, Marco

    2013-01-01

    Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23986125

  10. High-dose allergen exposure leads to tolerance.

    PubMed

    Woodfolk, Judith A

    2005-02-01

    Reports of decreased sensitization to cat allergen (Fel d 1) among individuals living with a cat or subjects exposed to high-dose cat allergen may be explained by the development of a form of high-dose tolerance resulting from natural exposure to an inhalant allergen. Although the epidemiological data regarding the relationship between exposure and sensitization to Fel d 1 are conflicting, the ability for high-dose Fel d 1 to induce a characteristic nonallergic immune response with a distinctive serum antibody profile has been established. Definition of this modified T-helper (Th)2 response to cat allergen, coupled with the renewed interest in regulatory T cells within the immunology field, has provided an avenue for exploring the mechanism by which IgE antibody-mediated responses are controlled. There is mounting evidence to suggest that the modified Th2 response is a variation of the allergic response and that the modified Th2-allergic axis is influenced by allergen dose and genetics. This article discusses putative immune mechanisms of tolerance within the context of an allergen-specific system. The relevance of high-dose allergen exposure and alternate factors such as endotoxin to the development of tolerance is considered. Fel d 1 exhibits unique molecular and immunological characteristics that may contribute to its tolerogenic properties. Major T-cell epitopes of Fel d 1 that preferentially induce regulatory factors have been defined. Furthermore, high-titer IgE antibody responses associated with atopic dermatitis are characterized by a defect in the T-cell repertoire that is specific to these epitopes. Identification of Fel d 1 epitopes that induce interleukin-10 may provide new targets for treatment.

  11. Retinal risks of high-dose ornithine supplements: a review.

    PubMed

    Hayasaka, Seiji; Kodama, Tatsuo; Ohira, Akihiro

    2011-09-01

    We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH(3) detoxification in the hyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 μmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 μmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Blood ornithine levels below 250 μmol/l do not produce retinal alteration. We concluded that short-term, low-dose or transient high-dose ornithine intake is safe for the retina; its nutritional usefulness and effect on NH(3) detoxification are supported by many researchers, but the effect may be limited; and long-term, high-dose ornithine intake may be risky for the retina. Patients with GA should avoid taking ornithine; amino acid supplementation should be administered carefully for patients with the HHH syndrome, relatives of patients with GA (heterozygotes) and subjects with RPE lesions; and blood ornithine levels and retinal conditions should be evaluated in individuals taking long-term, high-dose ornithine.

  12. Effects of metronidazole and its metabolites on histamine immunosuppression activity.

    PubMed

    Elizondo, G; Ostrosky-Wegman, P

    1996-01-01

    We have previously reported that metronidazole treatment increases human lymphocyte proliferation showing individual differences. This drug and its metabolites are imidazole compounds like histamine and cimetidine. The first is an endogenous amine that inhibits T-helper lymphocyte proliferation, and the second is a histamine antagonist. We presently report the in vitro effects of histamine, cimetidine, imidazole, metronidazole and its two principal metabolites (the acetic acid and hydroxy forms), on the mitogenic response to phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes. Histamine decreased lymphocyte proliferation while (in order of potency) cimetidine, the hydroxy metabolite of metronidazole, imidazole and metronidazole, increased the mitogenic response to PHA in a dose-response fashion. The acetic acid metabolite lacked immunomodulatory effects. Competitive studies showed that cimetidine, metronidazole, and the hydroxy metabolite blocked the inhibitory effect of histamine on lymphocyte proliferation in a dose-related manner. This blockage was non-competitive, suggesting that the target of the imidazole compounds was not the active site of the H2 receptor.

  13. Identification of intrinsically metronidazole-resistant clades of Gardnerella vaginalis.

    PubMed

    Schuyler, Jessica A; Mordechai, Eli; Adelson, Martin E; Sobel, Jack D; Gygax, Scott E; Hilbert, David W

    2016-01-01

    Gardnerella vaginalis is associated with bacterial vaginosis (BV), the most common cause of vaginal discharge. Metronidazole is a front-line therapy for BV, and treatment failure and recurrent disease are common problems. Whole-genome sequencing studies have revealed that G. vaginalis has a population structure that consists of 4 clades: clades 1 and 3 are associated with BV, whereas clades 2 and 4 are not. To determine if metronidazole susceptibility is associated with population structure, we analyzed 87 clinical isolates and found that metronidazole resistance (MIC ≥32 μg/mL) was highly associated with clade (P<0.0001), as 14/14 clade 3 isolates (100%) and 22/22 clade 4 isolates (100%) exhibited resistance, compared to only 16/37 clade 1 isolates (35%) and 1/14 clade 2 isolates (7.1%). The identification of intrinsically metronidazole-resistant G. vaginalis clades will facilitate future studies on the relationship between metronidazole resistance and BV treatment failure. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Prevalence of metronidazole-resistant Helicobacter pylori in dyspeptic patients.

    PubMed

    Xia, H X; Daw, M A; Beattie, S; Keane, C T; O'Morain, C A

    1993-03-01

    Susceptibility to metronidazole of 213 clinical strains of H. pylori from dyspeptic patients was determined by a plate dilution method. Seventy two (33.8%) of the strains were resistant to metronidazole (MIC > 8 mg/L), 20 of these were from 24 patients who had received previously metronidazole (83.3%), giving a primary (pretreatment) resistance rate of 27.5% (52/189). The resistance rate was higher in women than in men, especially aged 50 to 59 years old (43.6% vs 23.3%, p < 0.001). The resistance rate was lower in patients at 60 or over (9.8%), but similar between the younger patients groups (38.8% - 49.0%). There was no difference in the resistance rate between peptic ulcer disease (32.6%) and nonulcer dyspepsia (34.7%). These data indicated that metronidazole resistance in H. pylori is absolutely associated with previous use of the drug, and the higher resistance rate in women may be due to the more frequent prescription of the drug for their gynaecological infection or operation. Therefore, testing of susceptibility of H. pylori to metronidazole is important. A new susceptibility testing technique, the E-test was evaluated in this study and found to give comparable results to the plate dilution method and also had the advantage of being simple to perform.

  15. Preventing and Managing Toxicities of High-Dose Methotrexate.

    PubMed

    Howard, Scott C; McCormick, John; Pui, Ching-Hon; Buddington, Randall K; Harvey, R Donald

    2016-12-01

    : High-dose methotrexate (HDMTX), defined as a dose higher than 500 mg/m(2), is used to treat a range of adult and childhood cancers. Although HDMTX is safely administered to most patients, it can cause significant toxicity, including acute kidney injury (AKI) in 2%-12% of patients. Nephrotoxicity results from crystallization of methotrexate in the renal tubular lumen, leading to tubular toxicity. AKI and other toxicities of high-dose methotrexate can lead to significant morbidity, treatment delays, and diminished renal function. Risk factors for methotrexate-associated toxicity include a history of renal dysfunction, volume depletion, acidic urine, and drug interactions. Renal toxicity leads to impaired methotrexate clearance and prolonged exposure to toxic concentrations, which further worsen renal function and exacerbate nonrenal adverse events, including myelosuppression, mucositis, dermatologic toxicity, and hepatotoxicity. Serum creatinine, urine output, and serum methotrexate concentration are monitored to assess renal clearance, with concurrent hydration, urinary alkalinization, and leucovorin rescue to prevent and mitigate AKI and subsequent toxicity. When delayed methotrexate excretion or AKI occurs despite preventive strategies, increased hydration, high-dose leucovorin, and glucarpidase are usually sufficient to allow renal recovery without the need for dialysis. Prompt recognition and effective treatment of AKI and associated toxicities mitigate further toxicity, facilitate renal recovery, and permit patients to receive other chemotherapy or resume HDMTX therapy when additional courses are indicated.

  16. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    SciTech Connect

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  17. High-dose methylprednisolone for veno-occlusive disease of the liver in pediatric hematopoietic stem cell transplantation recipients.

    PubMed

    Myers, Kasiani C; Lawrence, Julia; Marsh, Rebecca A; Davies, Stella M; Jodele, Sonata

    2013-03-01

    Veno-occlusive disease (VOD) of the liver is a well-recognized serious complication of hematopoietic stem cell transplantation (HSCT), with few successful treatment modalities available for severe disease. Some reports have demonstrated success in adults with the use of high-dose steroid therapy, but experience in the pediatric population is lacking. We retrospectively reviewed HSCT patients treated at our institution since 2003 and identified 15 (2.4%) who developed VOD. Of these, nine (60%) were treated with intravenous high-dose methylprednisolone (500 mg/m(2) per dose every 12 hours for six doses). Steroid therapy was initiated at or before first ultrasound evidence of reversal of portal venous flow and before meeting criteria for initiation of defibrotide therapy. Four patients were also treated with defibrotide starting 2 to 5 days after initiation of steroids. Eight of nine patients (88%) with VOD were diagnosed with multiorgan failure. Response to high-dose steroid therapy as defined by decrease in bilirubin by 50% in 10 days from therapy initiation was noted in six of nine patients (67%), occurring within 3 to 6 days of steroid therapy. Two patients died from multiorgan failure due to VOD. Seven survivors of VOD recovered at the median 6 days (range, 5 to 38) from VOD diagnosis. Overall, VOD survival as a group was 78%; however, survival among responders was 100%. No serious toxicities related to high-dose steroid therapy were observed. We conclude that high-dose steroid therapy if initiated early may reverse VOD of the liver in pediatric HSCT patients, abrogating the need for defibrotide therapy with its associated toxicities and regulatory difficulties.

  18. High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies.

    PubMed

    Zohar, Joseph; Yahalom, Hila; Kozlovsky, Nitsan; Cwikel-Hamzany, Shlomit; Matar, Michael A; Kaplan, Zeev; Yehuda, Rachel; Cohen, Hagit

    2011-11-01

    High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100-140 mg) or placebo within 6 h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as expressed by the reduced risk of the development of PTSD post-trauma. In parallel, a comparative study of morphological arborization in dentate gyrus and its modulating molecules was performed in stress-exposed animals treated with high-dose hydrocortisone. Steroid-treated stressed animals displayed significantly increased dendritic growth and spine density, with increased levels of brain-derived neurotrophic factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal study provided insights into the potential mechanism of this intervention, as it identified relevant morphological and biochemical associations to the clinical observations. Thus, evidence from clinical and animal studies suggests that there is a "window of opportunity" in the early aftermath of trauma to help those who are vulnerable to the development of chronic PTSD.

  19. [Metronidazole-resistant trichomoniasis and successful therapy following high dosage].

    PubMed

    Weihe, J; Metelmann, C; Borner, K; Meingassner, J; Orfanos, C E

    1988-04-01

    A patient is reported who suffered for several months from a Trichomonas vaginalis infection that was resistant to the usual low-dose treatment with 5-nitro-imidazole derivatives. Following various ineffective therapeutic trials, the agent was isolated in order to determine its sensitivity to 5-nitro-imidazole. The resistance of the isolate to metronidazole was confirmed in vitro and in an animal experiment; the patient was therefore treated with high daily doses of metronidazole, 3 x 750 mg orally as well as 2 x 100 mg topically for 14 days. Substitution therapy with zinc was administered in order to normalize the patient's relatively low zinc serum levels. These measures finally led to a clinical cure and elimination of the pathogenic agent. This is the first confirmed case of a metronidazole-resistant Trichomonas vaginalis infection reported in the Federal Republic of Germany.

  20. Metronidazole-Induced Bullous Pemphigoid: A Case Report

    PubMed Central

    Moitra, Saibal; Banerjee, Indranil; Sikder, Ayan; Das, Prasanta

    2015-01-01

    Bullous pemphigoid is an autoimmune cutaneous blistering disorder, the exact pathogenesis of which is still not fully elucidated. Drug-induced bullous pemphigoid eruptions are rare but have been reported earlier with the use of frusemide, psoralens, ibuprofen, galantamine hydrobromide, ACE inhibitors like captopril, spironolactone, penicillin, ampicillin, levofloxacin, penicillamine. We hereby report a case of metronidazole induced bullous pemphigoid (BP) in a 52-year-old male patient suffering from liver abscess following 4 days of drug administration. The skin biopsy findings obtained from the patient were consistent with the diagnosis of bullous pemphigoid (BP). Metronidazole was discontinued and symptomatic treatment was offered to the patient. Following withdrawal of metronidazole, the bullae subsided in the next 7-10 days without any significant residual scarring. The causality assessment performed as per the Naranjo algorithm revealed the case to be probable (Naranjo score 7). PMID:26816913

  1. Tolerability of high doses of lercanidipine versus high doses of other dihydropyridines in daily clinical practice: the TOLERANCE Study.

    PubMed

    Barrios, Vivencio; Escobar, Carlos; de la Figuera, Mariano; Llisterri, Jose Luis; Honorato, Jesus; Segura, Julián; Calderón, Alberto

    2008-01-01

    The TOLERANCE study was aimed to compare the tolerability of high doses of lercanidipine (20 mg) with that of other frequently used dihydropyridines (amlodipine 10 mg/nifedipine GITS 60 mg) in the treatment of essential hypertension in daily clinical practice. It was an observational, transversal, multicentre study performed in a Primary Care Setting. A total of 650 evaluable patients with essential hypertension and age > or = 18 years were included. They had been treated with high doses of lercanidipine (n= 446) or amlodipine/nifedipine GITS (n= 204) during at least 1 month and previously with low doses (10 mg, 5 mg, and 30 mg, respectively) of the same drugs. The main objective was to compare the rates of vasodilation-related adverse events between both groups. Rates of signs and symptoms related to vasodilation were significantly higher (P < 0.001) in the amlodipine/nifedipine GITS group (76.8%, CI 95%[70.7; 82.9]) than in lercanidipine group (60.8%, [56.1;65.5]). Blood pressure control (< 140/90 mmHg or <130/80 for diabetics) and type of concomitant antihypertensive medications were similar in both groups. Treatment compliance was good (around 93%) and fairly comparable in both groups. Most adverse events with lercanidipine were mild (74.5% vs. 64% in amlodipine/nifedipine GITS group, P= 0.035) whereas severe adverse event rates did not differ significantly between groups (2.8% vs. 3.6%). In conclusion, treatment with lercanidipine at high doses is associated with a lower rate of adverse events related to vasodilation compared to high doses of amlodipine or nifedipine GITS in clinical practice.

  2. Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial.

    PubMed

    Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid; Markova, Veronika; Michaelsen, Kim F; Langhoff-Roos, Jens

    2017-02-01

    We compared the iron concentration in breast milk after a single high dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. In this randomised controlled trial, the women were allocated a single dose of intravenous 1200 mg iron isomaltoside or oral iron at a mean daily dose of 70.5 mg. We included 65 women with sufficient breast milk three days after inclusion - 30 from the intravenous iron group and 35 from the oral iron group - and collected breast milk and maternal blood samples three days and one week after allocation. The mean (±SD) iron concentration in breast milk in the intravenous and oral groups was 0.72 ± 0.27 and 0.40 ± 0.18 mg/L at three days (p < 0.001) and 0.47 ± 0.17 and 0.44 ± 0.25 mg/L after one week (p = 0.64). Baseline samples were not available that soon after birth. A single high dose of intravenous iron isomaltoside for postpartum haemorrhage led to a transient increase in the iron concentration in breast milk three days after treatment compared with oral iron. The difference disappeared one week after treatment, and mean iron concentrations were within the normal range in all samples. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  3. High-dose methylprednisolone pulse therapy for treatment of refractory intestinal involvement caused by Henoch-Schönlein purpura: a case report.

    PubMed

    Kang, Hyun Sik; Chung, Hee Sup; Kang, Ki-Soo; Han, Kyoung Hee

    2015-03-24

    Henoch-Schönlein purpura is an immunoglobulin A-mediated, small vascular inflammatory disease that can be associated with palpable purpura, arthralgia, abdominal pain, or nephritis. The presence of purpura facilitates the diagnosis of Henoch-Schönlein purpura at the onset of associated symptoms, whereas the absence of purpura makes the diagnosis challenging. It is important to diagnose Henoch-Schönlein purpura with delayed-onset skin purpura to avoid unnecessary surgery for acute abdomen. Most cases of Henoch-Schönlein purpura with severe abdominal pain are treated with low-dose steroids and intravenous immunoglobulin. A 15-year-old Korean girl complained of severe abdominal pain and delayed-onset purpura on admission. Henoch-Schönlein purpura was diagnosed based on endoscopic findings of hemorrhagic duodenitis and duodenal vasculitis and abdominal computed tomography findings of edematous bowels. Two common initial treatments, a low-dose steroid and intravenous immunoglobulin, were administered, but there was no improvement for 1 month. Subsequently, we used high-dose intravenous methylprednisolone pulse therapy (30 mg/kg/day, with a maximum of 1g/day), which dramatically alleviated her abdominal symptoms. High-dose intravenous methylprednisolone pulse therapy can be used as the ultimate treatment for delayed-onset Henoch-Schönlein purpura with severe abdominal pain when symptoms do not improve after low-dose steroid and intravenous immunoglobulin treatments.

  4. [Mycoplasma hominis symbiosis and Trichomonas vaginalis metronidazole resistance].

    PubMed

    Wang, Pin-Jia; Xie, Cheng-Bin

    2012-06-30

    To investigate the relation of Mycoplasma hominis symbiosis and the resistance of Trichomonas vaginalis to metronidazole. From November 2010 to July 2011, 160 isolates of T. vaginalis were collected from the genital tract secretion of gynecological out-patients at the Sichuan Provincial Hospital for Women and Children. The minimum lethal concentration (MLC) to metronidazole of these isolates was determined by an in vitro sensitivity assay with different concentration gradients of metronidazole (from 1 to 1 024 microg/ml), and M. hominis DNA in T. vaginalis was detected by polymerase chain reaction (PCR) technique with specific 16S rRNA primers. After clearance of M. hominis from the parasites by 32 microg/ml doxycycline, MLC was determined and compared with that before clearance. MLC of metronidazole in T. vaginalis ranged from 1 to 256 microg/ml, with 61.3% isolates (98/160) ranging from 1 to 8 microg/ml, 26.3% isolates (42/160) ranging from 16 to 32 microg/ml, and 12.5% isolates (20/160) ranging from 64 to 256 microg/ml. 61 isolates were PCR positive for M. hominis DNA in the 160 isolates of T. vaginalis. The M. hominis DNA positive rate was significantly higher in the T. vaginalis isolates with higher MLC than those isolates with lower MLC (P<0.01). However, when M. hominis was cleared by doxycycline from 8 isolates among the 61 ones, no change was observed in sensitivity of the isolates to metronidazole. M. hominis symbiosis might be associated with the metronidazole-resistance of T. vaginalis. However, it needs direct evidence.

  5. High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes.

    PubMed

    Kim, Keunyoung; Bae, Ok-Nam; Koh, Sung-Hee; Kang, Seojin; Lim, Kyung-Min; Noh, Ji-Yoon; Shin, Sue; Kim, Inho; Chung, Jin-Ho

    2015-10-01

    Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited.

  6. Metronidazole hydrazone conjugates: Design, synthesis, antiamoebic and molecular docking studies.

    PubMed

    Ansari, Mohammad Fawad; Siddiqui, Shadab Miyan; Agarwal, Subhash M; Vikramdeo, Kunwar Somesh; Mondal, Neelima; Azam, Amir

    2015-09-01

    Metronidazole hydrazone conjugates (2-13) were synthesized and screened in vitro for antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Six compounds were found to be better inhibitors of E. histolytica than the reference drug metronidazole. These compounds showed greater than 50-60% viability against HeLa cervical cancer cell line after 72 h treatment. Also, molecular docking study was undertaken on E. histolytica thioredoxin reductase (EhTHRase) protein which showed significant binding affinity in the active site. Out of the six actives, some of the compounds showed lipophilic characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. High-dose, conventionally fractionated thoracic reirradiation for lung tumors.

    PubMed

    Griffioen, Gwendolyn H M J; Dahele, Max; de Haan, Patricia F; van de Ven, Peter M; Slotman, Ben J; Senan, Suresh

    2014-03-01

    Loco-regional recurrences and second primary lung tumors are not uncommon after high-dose thoracic radiotherapy. The availability of improved radiotherapy techniques increases options for reirradiation. We describe a single-institutional experience with high-dose conventional thoracic reirradiation for both loco-regional recurrences and new primary tumors. Retrospective chart review of patients undergoing reirradiation between February 2004 and February 2013. Of 24 patients identified, 54% had a loco-regional recurrence, and 46% a new primary tumor. The majority (63%) had stage III NSCLC at both initial and second treatment; median interval between treatments was 51 months (5-189), median follow-up after reirradiation was 19.3 months (95% CI: 2.8-35.9). Median overall survival (OS) after reirradiation was 13.5 months, with 1-year survival 51%. Median event-free survival (EFS) was 8.4 months. Median time between reirradiation and local progression (n=8) or distant progression (n=8) was 6.7 and 11.8 months, respectively. Three patients died with possible grade 5 bleeding. Other toxicities were uncommon. Planning target volume (PTV) at reirradiation was the most important prognostic factor; PTV <300 versus ≥300cc was significantly associated with median OS (17.4 vs 8.2 months, p=0.03) and EFS (14.1 vs 5.5 months, p=0.03). Magnitude of overlap between the initial and subsequent PTVs, and between dose distributions, did not influence survival. Thoracic reirradiation with high dose conventional radiotherapy appears to deliver a meaningful survival benefit in low volume new primary or recurrent lung cancer. Further studies are needed to confirm these findings, and to establish reliable normal tissue tolerance doses for reirradiation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. [Neurological disturbances in patient who ingested high doses of simvastatin].

    PubMed

    Schetz, Daria; Sein Anand, Jacek

    2014-01-01

    We presented a case of 54-year old man, with dyslipidemia who, during his work, was exposed to prolonged electromagnetic radiation. Because of his concerns about the development of atherosclerosis, higher doses of simvastatin than recommended by the doctor, were used by him. After five weeks of such therapy the central nervous system symptoms such as: memory loss, cognitive disorders, sleeplessness, nervousness were presented. It is probable that the mentioned above symptoms were caused by high doses of drug took by the patient, and increased in blood-brain barrier permeability caused by electromagnetic radiation which lasted for about eight years.

  9. High-dose gallium-67 therapy in patients with relapsed acute leukaemia: a feasibility study.

    PubMed Central

    Jonkhoff, A. R.; Plaizier, M. A.; Ossenkoppele, G. J.; Teule, G. J.; Huijgens, P. C.

    1995-01-01

    Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia. Images Figure 2 PMID:8519674

  10. Safety of high-dose doripenem in adult patients with cystic fibrosis.

    PubMed

    Strawbridge, Seth; Nailor, Michael D

    2016-06-01

    High doses of β-lactam antibiotics have been advocated for acute pulmonary exacerbations caused by Pseudomonas aeruginosa in patients with cystic fibrosis (CF) secondary to high minimum inhibitory concentrations (MIC) of the infecting organisms. Some β-lactam antibiotics have increased elimination in CF patients. This case series examines the safety of high-dose doripenem (HDD), 2 g intravenously every 8 hours, which is 4 times the labeled dose, in CF patients. This was a retrospective, single site, chart review of all CF patients given HDD during a 3-year period. Adverse events were prospectively defined using labeled definitions within the package insert and the medical literature. A standard case report form was used to collect demographic details, antibiotic lengths of therapy and adverse events. A total of 17 patients (9 males), with a median age of 24 years, contributed 43 unique visits and 382 HDD exposure days. Mean duration of inpatient doripenem use was 8.9 days. Concurrent antibiotics were common, with a median number of additional antibiotics per admission of three. The median number of adverse effects documented was two. The most common adverse event was anemia, which was identified in 41 of 43 visits, but was present on admission in 31 instances. One patient developed leukopenia for 1 day, but returned to normal without dose adjustment. There were three instances of Clostridium difficile infection. One patient was documented to have an allergic reaction that led to discontinuation, but was ultimately rechallenged without adverse effect. Other common adverse events were gastrointestinal in origin. No other possible adverse effects led to discontinuation of the drug. In adult patients with CF, HDD in combination with other antibiotics did not lead to adverse effects necessitating discontinuation. HDD should be considered in this selected patient population, particularly when high MIC organisms are identified.

  11. High-dose immunoglobulin therapy in renal transplant recipients with hemophagocytic histiocytic syndrome.

    PubMed

    Asci, Gulay; Toz, Huseyin; Ozkahya, Mehmet; Cagirgan, Seckin; Duman, Soner; Sezis, Meltem; Ok, Ercan

    2006-01-01

    Hemophagocytic histiocytic syndrome (HHS) generally occurs in immunocompromised patients and often has a rapidly fatal course. HHS may be cured by treatment of the underlying disorder, especially when it is triggered by an infection. If no cause has been found, no therapy is known and outcome is poor. The aim of this study was to investigate the clinical course and response to intravenous immunoglobulin treatment in renal transplant patients diagnosed with HHS. Thirteen patients who were diagnosed with HHS between 1995 and 2003 were retrospectively assessed. The mean age of HHS patients was 38.6 +/- 10 years (5 women, 8 men). Median time to onset of symptoms after renal transplantation was 15.1 +/- 12.1 months (range 0.5-30 months). The first 2 patients in whom no etiologic factor was found were seen before 1998 and died due to multiorgan failure. HHS was related to an infectious etiology in 6 of 13 patients: tuberculosis (n=3), cytomegalovirus (CMV) infection (n=2), Escherichia coli (E. coli)-associated septicemia (n=1), but HHS was cured by antimicrobial therapy in only 2 of them (1 with tuberculosis, the other with E. coli-associated septicemia). After June 1998, high-dose immunoglobulin (IVIg) therapy was used in 6 patients. HHS was related to an infectious etiology in 2 patients unresponsive to antimicrobial treatment, and of unknown etiology in 4 patients. All of them completely recovered. Before 1998, 2 patients unresponsive to antimicrobial therapy (1 with tuberculosis, the other with CMV) died. They were not given IVIg. We concluded that when HHS does not respond to treatment of the underlying infection, or is of unknown etiology in immunocompromised patients, high-dose IVIg therapy should be administered.

  12. Effect of high-dose Ascorbic acid on vasopressor's requirement in septic shock

    PubMed Central

    Zabet, Mohadeseh Hosseini; Mohammadi, Mostafa; Ramezani, Masoud; Khalili, Hossein

    2016-01-01

    Objective: Effects of ascorbic acid on hemodynamic parameters of septic shock were evaluated in nonsurgical critically ill patients in limited previous studies. In this study, the effect of high-dose ascorbic acid on vasopressor drug requirement was evaluated in surgical critically ill patients with septic shock. Methods: Patients with septic shock who required a vasopressor drug to maintain mean arterial pressure >65 mmHg were assigned to receive either 25 mg/kg intravenous ascorbic acid every 6 h or matching placebo for 72 h. Vasopressor dose and duration were considered as the primary outcomes. Duration of Intensive Care Unit (ICU) stay and 28-day mortality has been defined as secondary outcomes. Findings: During the study period, 28 patients (14 in each group) completed the trial. Mean dose of norepinephrine during the study period (7.44 ± 3.65 vs. 13.79 ± 6.48 mcg/min, P = 0.004) and duration of norepinephrine administration (49.64 ± 25.67 vs. 71.57 ± 1.60 h, P = 0.007) were significantly lower in the ascorbic acid than the placebo group. No statistically significant difference was detected between the groups regarding the length of ICU stay. However, 28-day mortality was significantly lower in the ascorbic acid than the placebo group (14.28% vs. 64.28%, respectively; P = 0.009). Conclusion: High-dose ascorbic acid may be considered as an effective and safe adjuvant therapy in surgical critically ill patients with septic shock. The most effective dose of ascorbic acid and the best time for its administration should be determined in future studies. PMID:27162802

  13. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation.

    PubMed

    Nielsen, Torben K; Højgaard, Martin; Andersen, Jon T; Poulsen, Henrik E; Lykkesfeldt, Jens; Mikines, Kári J

    2015-04-01

    Treatment with high-dose intravenous (IV) ascorbic acid (AA) is used in complementary and alternative medicine for various conditions including cancer. Cytotoxicity to cancer cell lines has been observed with millimolar concentrations of AA. Little is known about the pharmacokinetics of high-dose IV AA. The purpose of this study was to assess the basic kinetic variables in human beings over a relevant AA dosing interval for proper design of future clinical trials. Ten patients with metastatic prostate cancer were treated for 4 weeks with fixed AA doses of 5, 30 and 60 g. AA was measured consecutively in plasma and indicated first-order elimination kinetics throughout the dosing range with supra-physiological concentrations. The target dose of 60 g AA IV produced a peak plasma AA concentration of 20.3 mM. Elimination half-life was 1.87 hr (mean, S.D. ± 0.40), volume of distribution 0.19 L/kg (S.D. ±0.05) and clearance rate 6.02 L/hr (100 mL/min). No differences in pharmacokinetic parameters were observed between weeks/doses. A relatively fast first-order elimination with half-life of about 2 hr makes it impossible to maintain AA concentrations in the potential cytotoxic range after infusion stop in prostate cancer patients with normal kidney function. We propose a regimen with a bolus loading followed by a maintenance infusion based on the calculated clearance. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  14. Safety of high-dose doripenem in adult patients with cystic fibrosis

    PubMed Central

    Strawbridge, Seth; Nailor, Michael D.

    2016-01-01

    Background: High doses of β-lactam antibiotics have been advocated for acute pulmonary exacerbations caused by Pseudomonas aeruginosa in patients with cystic fibrosis (CF) secondary to high minimum inhibitory concentrations (MIC) of the infecting organisms. Some β-lactam antibiotics have increased elimination in CF patients. This case series examines the safety of high-dose doripenem (HDD), 2 g intravenously every 8 hours, which is 4 times the labeled dose, in CF patients. Methods: This was a retrospective, single site, chart review of all CF patients given HDD during a 3-year period. Adverse events were prospectively defined using labeled definitions within the package insert and the medical literature. A standard case report form was used to collect demographic details, antibiotic lengths of therapy and adverse events. Results: A total of 17 patients (9 males), with a median age of 24 years, contributed 43 unique visits and 382 HDD exposure days. Mean duration of inpatient doripenem use was 8.9 days. Concurrent antibiotics were common, with a median number of additional antibiotics per admission of three. The median number of adverse effects documented was two. The most common adverse event was anemia, which was identified in 41 of 43 visits, but was present on admission in 31 instances. One patient developed leukopenia for 1 day, but returned to normal without dose adjustment. There were three instances of Clostridium difficile infection. One patient was documented to have an allergic reaction that led to discontinuation, but was ultimately rechallenged without adverse effect. Other common adverse events were gastrointestinal in origin. No other possible adverse effects led to discontinuation of the drug. Conclusions: In adult patients with CF, HDD in combination with other antibiotics did not lead to adverse effects necessitating discontinuation. HDD should be considered in this selected patient population, particularly when high MIC organisms are identified

  15. High-dose Parenteral Thiamine in Treatment of Wernicke’s Encephalopathy: Case Series and Review of the Literature

    PubMed Central

    NISHIMOTO, ANDREW; USERY, JUSTIN; C. WINTON, JOHN; TWILLA, JENNIFER

    2017-01-01

    Background: Thiamine deficiency can lead to Wernicke’s encephalopathy (WE), an acute and potentially life-threatening neurological disorder. Even though the main treatment modality for WE consists of thiamine replacement, evidence supporting an optimal dosing strategy and duration is unclear. Patients and Methods: We present a single-center case series of eleven patients that were admitted with possible WE and treated with high-dose parenteral thiamine. Results: Patients with suspected WE were treated with ≥500 mg intravenous thiamine for a median of 3 days with 73% of patients (eight out of eleven) displaying symptom resolution or improvement after treatment. No significant correlation between symptom resolution and timing of high-dose thiamine initiation (median=92 h) was identified. In patients whose symptoms resolved compared to those whose symptoms did not, there were no differences in patient variables nor adverse effects related to thiamine treatment. Conclusion: High-dose thiamine (≥500 mg) appears safe and efficacious for use in patients with suspected WE. PMID:28064230

  16. Involvement of NADPH oxidase in high-dose phenolic acid-induced pro-oxidant activity on rat mesenteric venules.

    PubMed

    Du, Wen-Yuan; Xiao, Ying; Yao, Jian-Jing; Hao, Zhe; Zhao, Yu-Bin

    2017-01-01

    In the present study, we investigated the potential role of phenolic acids in initiating oxidative damage to microvascular endothelial cells and the underlying mechanism mediating the pro-oxidant action. Male Wistar rats received high doses of phenolic acid [caffeic acid (CA), salvianolic acid B (SAB), chlorogenic acid (ChA) or ferulic acid (FA)]. The creation of reactive oxygen species in mesenteric microcirculation endothelial cells and adherent leukocytes along with venules were assessed using intravital microscopy. The expression levels of NADPH oxidase subunits (Nox4 and p22(phox)) in terminal ileum tissues were determined by western blot analysis. Intravenous injection of high-dose ChA or CA (7 mg/kg) markedly increased the peroxide production in the venular walls and upregulated the protein expression levels of Nox4 and p22(phox) in the ileum tissues, while the same dose of CA and SAB made no difference within the observation period. No changes were observed in the number of leukocytes adhering to the venular walls. High-dose ChA and FA led to an imbalance between the oxidant and antioxidant mechanism by boosting the expression levels of NADPH oxidase. Thus, we clarified the rationale behind the adverse effects of a herbal injection containing high levels of phenolic acid compounds.

  17. Effect of high dose of steroid on plateletcount in acute stage of dengue Fever with thrombocytopenia.

    PubMed

    Shashidhara, K C; Murthy, K A Sudharshan; Gowdappa, H Basavana; Bhograj, Abhijith

    2013-07-01

    Dengue infection is the most rapidly spreading mosquito-borne viral disease in the world and an estimated 50 million dengue infections reported annually. The pathogenesis of Thrombocytopenia in dengue fever (DF) is not clearly understood. Increased peripheral destruction of antibody coated platelets and acute bone marrow suppression were strongly suspected as the possible mechanism. This often leads to life threatening dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Steroids are used in the treatment of Idiopathic thrombocytopenic purpura to increase the platelet count which is mediated by auto antibodies .This hypothesis would support the use of steroids in dengue fever. The objective of this study was to test whether an intravenous high dose dexamethasone was efficacious in increasing the platelet count in acute stage of dengue fever with thrombocytopenia. During the study period between June 2010 - 2011 in JSS Hospital Mysore, 127 patients were screened for dengue fever with thrombocytopenia (<50000/cumm) and 61patients were randomly allocated, 30 to the study group and 31 to the control group, in an open labeled study. The study group received intravenous dexamethasone 8mg initially followed by 4 mg every 8 h thereafter for 4 days and IV fluids whenever required. The control Group received only IV fluids and antipyretics whenever it was indicated. The daily measurement of platelet count was carried out in all patients from the day of enrolment to the fourth day of post treatment. The baseline data (age, sex, and the mean duration of the illness, Hb%, haematocrit, and platelets) were similar in both the groups. The analysis of variance (ANOVA) statistics showed a significant linear association of the mean platelet counts with the days in either group. The mean platelet counts increased steadily in both the groups from days 1 to 4: day1 (0.687), day2 (0.34), day3 (0.530) and day4 (0.844). There was no significant difference between the two groups

  18. High-dose hydroxocobalamin administered after H2S exposure counteracts sulfide-poisoning-induced cardiac depression in sheep.

    PubMed

    Haouzi, Philippe; Chenuel, Bruno; Sonobe, Takashi

    2015-01-01

    Severe H2S poisoning leads to death by rapid respiratory and cardiac arrest, the latter can occur within seconds or minutes in severe forms of intoxication. To determine the time course and the nature of H2S-induced cardiac arrest and the effects of high-dose hydroxocobalamin administered after the end of sulfide exposure. NaHS was infused in 16 sedated mechanically ventilated sheep to reach concentrations of H2S in the blood, which was previously found to lead to cardiac arrest within minutes following the cessation of H2S exposure. High-dose hydroxocobalamin (5 g) or saline solution was administered intravenously, 1 min after the cessation of NaHS infusion. All animals were still alive at the cessation of H2S exposure. Three animals (18%) presented a cardiac arrest within 90 s and were unable to receive any antidote or vehicle. In the animals that survived long enough to receive either hydroxocobalamin or saline, 71% (5/7) died in the control group by cardiac arrest within 10 min. In all instances, cardiac arrest was the result of a pulseless electrical activity (PEA). In the group that received the antidote, intravenous injection of 5 g of hydroxocobalamin provoked an abrupt increase in blood pressure and blood flow; PEA was prevented in all instances. However, we could not find any evidence for a recovery in oxidative metabolism in the group receiving hydroxocobalamin, as blood lactate remained elevated and even continued to rise after 1 h, despite restored hemodynamics. This, along with an unaltered recovery of H2S kinetics, suggests that hydroxocobalamin did not act through a mechanism of H2S trapping. In this sheep model, there was a high risk for cardiac arrest, by PEA, persisting up to 10 min after H2S exposure. Very high dose of hydroxocobalamin (5 g), injected very early after the cessation of H2S exposure, improved cardiac contractility and prevented PEA.

  19. High-dose desvenlafaxine in outpatients with major depressive disorder.

    PubMed

    Ferguson, James M; Tourian, Karen A; Rosas, Gregory R

    2012-09-01

    This study investigated the safety and efficacy of long-term treatment with high-dose desvenlafaxine (administered as desvenlafaxine succinate) in major depressive disorder (MDD). In this multicenter, open-label study, adult outpatients with MDD aged 18-75 were treated with flexible doses of desvenlafaxine (200-400 mg/d) for ≤ 1 year. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs), patient discontinuations due to adverse events, electrocardiograms, vital signs, and laboratory determinations. The primary efficacy measure was mean change from baseline in the 17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score. The mean daily desvenlafaxine dose range over the duration of the trial was 267-356 mg (after titration). The most frequent TEAEs in the safety population (n = 104) were nausea (52%) and headache (41%), dizziness (31%), insomnia (29%), and dry mouth (27%). All TEAEs were mild or moderate in severity. Thirty-four (33%) patients discontinued from the study because of TEAEs; nausea (12%) and dizziness (9%) were the most frequently cited reasons. The mean change in HAM-D(17) total score for the intent-to-treat population (n = 99) was -9.9 at the last on-therapy visit in the last-observation-carried-forward analysis and -14.0 at month 12 in the observed cases analysis. Conclusion High-dose desvenlafaxine (200-400 mg/d) was generally safe and effective in the long-term treatment of MDD.

  20. Comparative pharmacokinetics of low- and high-dose ticarcillin.

    PubMed Central

    Guglielmo, B J; Flaherty, J F; Batman, R; Barriere, S L; Gambertoglio, J G

    1986-01-01

    Certain antipseudomonal penicillins, such as mezlocillin, exhibit a nonlinear pharmacokinetic disposition with increasing doses. We evaluated the effect of a single low dose (50 mg/kg) compared with a high dose (80 mg/kg) on the pharmacokinetics of ticarcillin in a crossover trial of eight healthy volunteers. No significant alteration in plasma clearance (130.1 +/- 36.5 versus 120.5 +/- 38.0 ml/min), nonrenal clearance (36.5 +/- 8.4 versus 33.4 +/- 18.5 ml/min), or volume of distribution at steady state (12.8 +/- 3.5 versus 12.3 +/- 4.5 liters) was observed between the low- and high-dose regimens, respectively. The elimination half-life remained unchanged between the two doses (67.9 +/- 14.3 versus 68.0 +/- 12.2 min). Unlike other newer antipseudomonal penicillins, ticarcillin did not display dose-dependent pharmacokinetic behavior with the range of doses used in the clinical setting. PMID:3777901

  1. Spectroscopic gamma camera for use in high dose environments

    NASA Astrophysics Data System (ADS)

    Ueno, Yuichiro; Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi; Fujishima, Yasutake; Kometani, Yutaka; Suzuki, Yasuhiko; Umegaki, Kikuo

    2016-06-01

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  2. Formation of titanium silicides by high dose ion implantation

    NASA Astrophysics Data System (ADS)

    Salvi, V. P.; Vidwans, S. V.; Rangwala, A. A.; Arora, B. M.; Kuldeep; Jain, Animesh K.

    1987-09-01

    We have investigated titanium silicide formation using high dose (˜ 2 × 10 21 ions/m 2) ion implantation of 30 keV, 48Ti + ions a room temperature into two different types of Si substrates: (a) n-type <111> single crystals and (b) amorphous Si films (˜ 200 nm thick) vacuum deposited onto a thermally grown SiO 2 layer. XRD and RBS techniques were employed to characterize various silicide phases and their depth distribution in as-implanted as well as in annealed samples. We find that a mixture of TiSi, TiSi 2 and Ti 5Si 4 silicides is formed by high dose implantation. Out of these, TiSi; was found to be the dominant phase. The composition of these silicide layers is practically uniform with depth and remains unaltered on heat treatment up to 750° C. The electrical properties of silicide layers have also been investigated using sheet resistance measurements. The resistivity of as-implanted layers is rather high ( ˜ 10 μΩ m), but drops sharply by nearly a factor of 20 after a post-implantation anneal above 800° C. The resistivity of silicide layers thus obtained compare well with silicides prepared by other techniques.

  3. ELDRS Characterization for a Very High Dose Mission

    NASA Technical Reports Server (NTRS)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  4. ELDRS Characterization for a Very High Dose Mission

    NASA Technical Reports Server (NTRS)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  5. Regulatory T Cell Responses to High-Dose Methylprednisolone in Active Systemic Lupus Erythematosus

    PubMed Central

    Chader, Driss; Cohen-Aubart, Fleur; Haroche, Julien; Fadlallah, Jehane; Claër, Laetitia; Musset, Lucile; Gorochov, Guy; Amoura, Zahir; Miyara, Makoto

    2015-01-01

    Background/Purpose A slight increase in the proportion of circulating regulatory T (Treg) cells has been reported in systemic lupus erythematosus (SLE) patients taking oral prednisone. The effects of intravenous (IV) high dose methylprednisolone (MP) on Tregs have not yet been described, especially in active SLE. Methods We prospectively analyzed the proportion of circulating CD4+ Treg cell subsets defined as follows: (1) naïve Treg (nTreg) FoxP3lowCD45RA+ cells; (2) effector Treg (eTreg) FoxP3highCD45RA− cells; and (3) non-suppressive FoxP3lowCD45RA− cells (non-regulatory Foxp3low T cells). Peripheral blood mononuclear cells of patients with active SLE were analyzed before the first infusion of IV high dose MP (day 0) and the following days (day 1, day 2, ±day 3 and ±day 8). The activity of SLE was assessed by the SLEDAI score. Results Seventeen patients were included. Following MP infusions, the median (range) percentage of eTregs significantly increased from 1.62% (0.53–8.43) at day 0 to 2.80% (0.83–14.60) at day 1 (p = 0.003 versus day 0), 4.64% (0.50–12.40) at day 2 (p = 0.06 versus day 1) and 7.50% (1.02–20.70) at day 3 (p = 0.008 versus day 2), and declined to baseline values at day 8. Expanding eTreg cells were actively proliferating, as they expressed Ki-67. The frequency of non-regulatory FoxP3low T cells decreased from 6.39% (3.20–17.70) at day 0 to 4.74% (1.03–9.72) at day 2 (p = 0.005); nTreg frequency did not change. All patients clinically improved immediately after MP pulses. The absence of flare after one year of follow up was associated with a higher frequency of eTregs at day 2. Conclusion IV high dose MP induces a rapid, dramatic and transient increase in circulating regulatory T cells. This increase may participate in the preventive effect of MP on subsequent flares in SLE. PMID:26629828

  6. Investigation of Metronidazole Use during Pregnancy and Adverse Birth Outcomes

    PubMed Central

    Koss, Catherine A.; Baras, Dana C.; Lane, Sandra D.; Aubry, Richard; Marcus, Michele; Markowitz, Lauri E.

    2012-01-01

    To assess whether treatment with metronidazole during pregnancy is associated with preterm birth, low birth weight, or major congenital anomalies, we conducted chart reviews and an analysis of electronic data from a cohort of women delivering at an urban New York State hospital. Of 2,829 singleton/mother pairs, 922 (32.6%) mothers were treated with metronidazole for clinical indications, 348 (12.3%) during the first trimester of pregnancy and 553 (19.5%) in the second or third trimester. There were 333 (11.8%) preterm births, 262 (9.3%) infants of low birth weight, and 52 infants (1.8%) with congenital anomalies. In multivariable analysis, no association was found between metronidazole treatment and preterm birth (odds ratio [OR], 1.02 [95% confidence interval [CI], 0.80 to 1.32]), low birth weight (OR, 1.05 [95% CI, 0.77 to 1.43]), or treatment in the first trimester and congenital anomalies (OR, 0.86 [0.30 to 2.45]). We found no association between metronidazole treatment during the first or later trimesters of pregnancy and preterm birth, low birth weight, or congenital anomalies. PMID:22751543

  7. Sudden death due to metronidazole/ethanol interaction.

    PubMed

    Cina, S J; Russell, R A; Conradi, S E

    1996-12-01

    Metronidazole (Flagyl), a commonly prescribed antimicrobial agent, can produce a reaction similar to that of disulfiram (Antabuse) when administered to patients drinking ethanol. This drug/chemical interaction results in accumulation of acetaldehyde in the blood. Acetaldehyde is hepatotoxic, cardiotoxic, and arrythmogenic; no lethal serum acetaldehyde level has been established. Sudden death has been reported in patients taking disulfiram while using ethanol; no fatalities have been reported due to ethanol/ metronidazole interactions. Described is a case of a 31-year-old woman who died moments after an assault by a male companion, during which he inflicted minor physical trauma to her upper arm. Toxicologic analysis yielded elevated concentrations of serum ethanol (162 mg/d), acetaldehyde (4.6 mg/d), and metronidazole (0.42 mg/L). The cause of death was reported to be cardiac dysrhythmia due to acetaldehyde toxicity due to an ethanol/ metronidazole interaction. Autonomic stress associated with the assault is likely to have contributed to this woman's death. The mechanism of death is examined.

  8. Metronidazole in the treatment of non-specific vaginitis (NSV).

    PubMed Central

    Jerve, F; Berdal, T B; Bohman, P; Smith, C C; Evjen, O K; Gjønnaess, H; Gaasemyr, M; Hausken, L; Hesla, K; Hoftvedt, E

    1984-01-01

    In a large multicentre study of 429 patients with the usual signs and symptoms of non-specific vaginitis (NSV), we studied the effect of different doses of metronidazole. The patients were divided into five treatment groups as follows: group A was given 400 mg metronidazole three times daily for seven days, group B 2000 mg as a single dose, group C 2000 mg on days 1 and 2, group D 2000 mg on days 1 and 3, and group E was given 1200 mg metronidazole once daily for five days. At follow up examination four weeks from the start of treatment, patients in groups D and E showed the best clinical results with cure rates of 94.0% and 93.6% respectively. In addition the rate of reisolation of Gardnerella vaginalis was lowest in group D. We therefore recommend metronidazole 2000 mg on days 1 and 3 as routine treatment for non-specific or vaginitis associated with gardnerella. PMID:6375804

  9. [Metronidazole effect on active oxygen production by human blood neutrophils].

    PubMed

    Shchepetkin, I A

    1997-01-01

    The in vitro effect of metronidazole on production of active oxygen by neutrophila and in the enzymatic system of glucose-glucose oxidase-peroxidase was studied by luminol-dependent chemiluminescence. An increase in the spontaneous and zymozan-stimulated chemiluminescence and a decrease in the phorbolmyristate acetate (PMA)-stimulated chemiluminescence after 2-hour preincubation of the neutrophils with 8.5 mM of metronidazole were observed. In concentrations of 0.9 to 8.7 mM metronidazole (without washing) dose-dependently lowered the neutrophil chemiluminescence in response to the effect of PMA and ionophore A23187 and to a lesser degree to that of zymozan. In doses of 20 to 100 mM the drug had an insignificant effect on production of active oxygen by the neutrophils in response to the cell stimulation by PMA, ionophore A23187 and zymozan. The data are in conformity with the scavenger effect of metronidazole on active oxygen radicals generating in the cell-free enzymatic system both in the presence and in the absence of superoxide dismutase.

  10. A Redox Basis for Metronidazole Resistance in Helicobacter pylori▿

    PubMed Central

    Kaakoush, N. O.; Asencio, C.; Mégraud, F.; Mendz, G. L.

    2009-01-01

    Metronidazole resistance in Helicobacter pylori has been attributed to mutations in rdxA or frxA. Insufficient data correlating RdxA and/or FrxA with the resistant phenotype, and the emergence of resistant strains with no mutations in either rdxA or frxA, indicated that the molecular basis of H. pylori resistance to metronidazole required further characterization. The rdxA and frxA genes of four matched pairs of metronidazole-susceptible and -resistant strains were sequenced. The resistant strains had mutations in either rdxA, frxA, neither gene, or both genes. The reduction rates of five substrates suggested that metabolic differences between susceptible and resistant strains cannot be explained only by mutations in rdxA and/or frxA. A more global approach to understanding the resistance phenotype was taken by employing two-dimensional gel electrophoresis combined with tandem mass spectrometry analyses to identify proteins differentially expressed by the matched pair of strains with no mutations in rdxA or frxA. Proteins involved in the oxireduction of ferredoxin were downregulated in the resistant strain. Other redox enzymes, such as thioredoxin reductase, alkyl hydroperoxide reductase, and superoxide dismutase, showed a pI change in the resistant strain. The data suggested that metronidazole resistance involved more complex metabolic changes than specific gene mutations, and they provided evidence of a role for the intracellular redox potential in the development of resistance. PMID:19223619

  11. Tinidazole vs metronidazole for the treatment of bacterial vaginosis.

    PubMed

    Schwebke, Jane R; Desmond, Renee A

    2011-03-01

    The purpose of this study was to compare the efficacy of 2 different doses of tinidazole with metronidazole for the treatment of bacterial vaginosis and to compare the side effects of the drugs. Women were assigned randomly to receive metronidazole 500 mg twice daily, tinidazole 500 mg twice daily, or tinidazole 1 g twice, all for 7 days. Follow-up visits were conducted at days 14 and 28. Five hundred ninety-three women were enrolled. There were no significant differences between the treatment arms. Overall cure rates were 76.8% at 14 days and 64.5% at 1 month. Women who admitted to engaging in sexual intercourse during the study were significantly more likely to have bacterial vaginosis at the follow-up visit. There were no significant differences in adverse events across treatment arms. There were no differences in cure rates between metronidazole and either of the tinidazole dosing regimens that were studied. In addition, there were no important differences in the side-effect profiles of metronidazole and tinidazole. Copyright © 2011 Mosby, Inc. All rights reserved.

  12. Efficacy of New 5-Nitroimidazoles against Metronidazole-Susceptible and -Resistant Giardia, Trichomonas, and Entamoeba spp.

    PubMed Central

    Upcroft, Jacqueline A.; Campbell, Raymond W.; Benakli, Kamel; Upcroft, Peter; Vanelle, Patrice

    1999-01-01

    The efficacies of 12 5-nitroimidazole compounds and 1 previously described lactam-substituted nitroimidazole with antiparasitic activity, synthesized via SRN1 and subsequent reactions, were assayed against the protozoan parasites Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica. Two metronidazole-sensitive lines and two metronidazole-resistant lines of Giardia and one line each of metronidazole-sensitive and -resistant Trichomonas were tested. All except one of the compounds were as effective or more effective than metronidazole against Giardia and Trichomonas, but none was as effective overall as the previously described 2-lactam-substituted 5-nitroimidazole. None of the compounds was markedly more effective than metronidazole against Entamoeba. Significant cross-resistance between most of the drugs tested and metronidazole was evident among metronidazole-resistant lines of Giardia and Trichomonas. However, some drugs were lethal to metronidazole-resistant Giardia and had minimum lethal concentrations similar to that of metronidazole for drug-susceptible parasites. This study emphasizes the potential in developing new nitroimidazole drugs which are more effective than metronidazole and which may prove to be useful clinical alternatives to metronidazole. PMID:9869568

  13. The aerobic activity of metronidazole against anaerobic bacteria.

    PubMed

    Dione, Niokhor; Khelaifia, Saber; Lagier, Jean-Christophe; Raoult, Didier

    2015-05-01

    Recently, the aerobic growth of strictly anaerobic bacteria was demonstrated using antioxidants. Metronidazole is frequently used to treat infections caused by anaerobic bacteria; however, to date its antibacterial activity was only tested in anaerobic conditions. Here we aerobically tested using antioxidants the in vitro activities of metronidazole, gentamicin, doxycycline and imipenem against 10 common anaerobic and aerobic bacteria. In vitro susceptibility testing was performed by the disk diffusion method, and minimum inhibitory concentrations (MICs) were determined by Etest. Aerobic culture of the bacteria was performed at 37°C using Schaedler agar medium supplemented with 1mg/mL ascorbic acid and 0.1mg/mL glutathione; the pH was adjusted to 7.2 by 10M KOH. Growth of anaerobic bacteria cultured aerobically using antioxidants was inhibited by metronidazole after 72h of incubation at 37°C, with a mean inhibition diameter of 37.76mm and an MIC of 1μg/mL; however, strains remained non-sensitive to gentamicin. No growth inhibition of aerobic bacteria was observed after 24h of incubation at 37°C with metronidazole; however, inhibition was observed with doxycycline and imipenem used as controls. These results indicate that bacterial sensitivity to metronidazole is not related to the oxygen tension but is a result of the sensitivity of the micro-organism. In future, both culture and antibiotic susceptibility testing of strictly anaerobic bacteria will be performed in an aerobic atmosphere using antioxidants in clinical microbiology laboratories. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  14. High-dose ambroxol reduces pulmonary complications in patients with acute cervical spinal cord injury after surgery.

    PubMed

    Li, Qiang; Yao, Gaiqi; Zhu, Xi

    2012-04-01

    Ambroxol has a very high affinity for lung tissues; its concentration is approximately 20 times higher in the lung than in the serum. We aimed to evaluate the effectiveness of high-dose ambroxol (990 mg/day) in the improvement of oxygenation and prevention of postoperative respiratory complications in the patients with acute cervical spinal cord injury (CSCI). A total of 61 acute CSCI patients admitted to the Intensive Care Unit (ICU) of our hospital between January 2009 and June 2011 were included in the study. They were graded as ASIA A and ASIA B according to the classification of the American Spinal Injury Association (ASIA) and were randomly divided into two groups: one group received intravenous ambroxol at 990 mg/day for 5 consecutive days after operation; the other group treated without ambroxol served as control. The results of arterial blood gas analysis on postoperative day 3 and 5 and occurrence of pulmonary complications within 5 days after operation were evaluated. The group treated with high-dose ambroxol showed a lower rate of postoperative pneumonia and hypoxemia within 5 days after operation. On the 3rd and 5th days, the oxygenation index in the high-dose ambroxol group (291.02 ± 34.96 and 301.28 ± 37.69) was significantly higher than in the control group (230.08 ± 26.25 and 253.82 ± 26.26), with significant differences between the two groups (P = 0.045 and 0.041). Administration of high-dose ambroxol should be considered as an alternative and effective approach to reduce the postoperative respiratory complications and improve the oxygenation status in acute CSCI patients.

  15. Intravenous immunoglobulin in pediatrics: A review

    PubMed Central

    Prasad, A.N.; Chaudhary, Sanjay

    2013-01-01

    There has been a rapid expansion of the use of intravenous immunoglobulin (IVIG) for an ever-growing number of conditions. IVIG is used at a ‘replacement dose’ (400–600 mg/kg/month) in antibody deficiencies and is used at a high dose (2 g/kg) as an ‘immunomodulatory’ agent in an increasing number of immune and inflammatory disorders.1 The limitations for IVIG are the cost of the preparation and the need for intravenous infusions. Due to the cost, shortages and growing use of IVIG there have been attempts to develop evidence-based guidelines for the use of IVIG in a wide variety of immune disorders in children and neonates. This commentary provides the recommendations and recent publication regarding the use of IVIG in various conditions in children. PMID:25378784

  16. Intravenous immunoglobulin therapy for refractory recurrent pericarditis.

    PubMed

    del Fresno, M Rosa; Peralta, Julio E; Granados, Miguel Ángel; Enríquez, Eugenia; Domínguez-Pinilla, Nerea; de Inocencio, Jaime

    2014-11-01

    Recurrent pericarditis is a troublesome complication of idiopathic acute pericarditis and occurs more frequently in pediatric patients after cardiac surgery (postpericardiotomy syndrome). Conventional treatment with nonsteroidal antiinflammatory drugs, corticosteroids, and colchicine is not always effective or may cause serious adverse effects. There is no consensus, however, on how to proceed in those patients whose disease is refractory to conventional therapy. In such cases, human intravenous immunoglobulin, immunosuppressive drugs, and biological agents have been used. In this report we describe 2 patients with refractory recurrent pericarditis after cardiac surgery who were successfully treated with 3 and 5 monthly high-dose (2 g/kg) intravenous immunoglobulin until resolution of the effusion. Our experience supports the effectiveness and safety of this therapy. Copyright © 2014 by the American Academy of Pediatrics.

  17. EPR/Homotaurine: A possible dosimetry system for high doses

    NASA Astrophysics Data System (ADS)

    Maghraby, A.; Salama, E.; Mansour, A.

    2011-12-01

    An EPR investigation of radiation induced radicals in Homotaurine revealed that there are two types of radicals produced after exposure to gamma radiation (60Co). EPR spectra were recorded and analyzed; also the microwave power saturation curves for both radicals were studied. The effect of change in modulation amplitude on peak-to-peak signal height and line width was investigated; this is in addition to the evaluation of energy dependence parameters compared to soft tissue and alanine dosimeters. Response of Homotaurine to different radiation doses (0.5 kGy-50 kGy) was studied and found to follow a linear relationship. Radiation induced radicals in Homotaurine persisted and showed a noticeable stability over 30 days following irradiation. It was found that Homotaurine possesses good dosimetric properties using EPR spectroscopy in high doses and is characterized by its simple spectrum.

  18. High-dose thiamine improves the symptoms of fibromyalgia.

    PubMed

    Costantini, Antonio; Pala, Maria Immacolata; Tundo, Silvia; Matteucci, Pietro

    2013-05-20

    Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients' history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms.

  19. High dose bystander effects in spatially fractionated radiation therapy

    PubMed Central

    Asur, Rajalakshmi; Butterworth, Karl T.; Penagaricano, Jose A.; Prise, Kevin M.; Griffin, Robert J.

    2014-01-01

    Traditional radiotherapy of bulky tumors has certain limitations. Spatially fractionated radiation therapy (GRID) and intensity modulated radiotherapy (IMRT) are examples of advanced modulated beam therapies that help in significant reductions in normal tissue damage. GRID refers to the delivery of a single high dose of radiation to a large treatment area that is divided into several smaller fields, while IMRT allows improved dose conformity to the tumor target compared to conventional three-dimensional conformal radiotherapy. In this review, we consider spatially fractionated radiotherapy approaches focusing on GRID and IMRT, and present complementary evidence from different studies which support the role of radiation induced signaling effects in the overall radiobiological rationale for these treatments. PMID:24246848

  20. High-dose thiamine improves the symptoms of Friedreich's ataxia.

    PubMed

    Costantini, Antonio; Giorgi, Rafaela; D'Agostino, Sonia; Pala, Maria Immacolata

    2013-05-22

    Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3-5 days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease.

  1. High dose thiamine improves fatigue in multiple sclerosis

    PubMed Central

    Costantini, Antonio; Nappo, Agostino; Pala, Maria Immacolata; Zappone, Antonietta

    2013-01-01

    The majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations. PMID:23861280

  2. Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma.

    PubMed

    Anderson, Peter M; Wiseman, Gregory A; Erlandson, Linda; Rodriguez, Vilmarie; Trotz, Barbara; Dubansky, Stephen A; Albritton, Karen

    2005-10-01

    Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.

  3. Assessments for High Dose Radionuclide Therapy Treatment Planning

    SciTech Connect

    Fisher, Darrell R.

    2003-10-01

    Advances in the biotechnology of cell-specific targeting of cancer, and the increased number of clinical trials involving treatment of cancer patients with radiolabeled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high-dose radionuclide therapy procedures. Optimized radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose-limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential time points using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organs tissues of concern, for the whole body, and sometimes for selected tumors. Patient-specific factors often require that dose estimates be customized for each patient. The Food and Drug Administration regulates the experimental use of investigational new drugs and requires reasonable calculation of radiation absorbed dose to the whole body and to critical organs using methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high-dose studies in the U.S. and elsewhere shows that 1) some studies are conducted with minimal dosimetry, 2) the marrow dose is difficult to establish and is subject to large uncertainties, and 3) despite the general availability of MIRD software, internal dosimetry methods are often inconsistent from one clinical center to another.

  4. Appearance of a metronidazole-resistant Helicobacter pylori strain in an infected-ICR-mouse model and difference in eradication of metronidazole-resistant and -sensitive strains.

    PubMed Central

    Matsumoto, S; Washizuka, Y; Matsumoto, Y; Tawara, S; Ikeda, F; Yokota, Y; Karita, M

    1997-01-01

    We tested whether antibiotic-resistant strains appeared in vivo after the failure of treatment using the Helicobacter pylori-infected euthymic mouse model. The numbers of colonies isolated from 56 ICR mice 2 weeks after 4 days of treatment with metronidazole (3.2, 10, or 32 mg/kg of body weight) or amoxicillin (1, 3.2 or 10 mg/kg), with treatment started 4 days after H. pylori CPY2052 inoculation, were counted, and the isolated strains were tested for their sensitivities to two antibiotics to rule out the presence of antibiotic-resistant strains. One metronidazole-resistant strain was detected in a mouse treated with 10 mg of metronidazole per kg, and the MIC of metronidazole for this strain was 25 microg/ml, compared to a MIC of 1.56 microg/ml for the original strain. However, no resistant strain was detected in the amoxicillin treatment group. After the examination described above, mice challenged with a metronidazole-resistant or -sensitive strain isolated from the stomach of a mouse were treated with metronidazole or amoxicillin. The metronidazole-resistant strain was more difficult to eradicate in vivo than the sensitive strain after treatment with metronidazole but not after treatment with amoxicillin. Thus, a metronidazole-resistant H. pylori strain was selected by insufficient treatment, but no resistant strain was selected with amoxicillin. Eradication of a metronidazole-resistant H. pylori strain in vivo required a higher dosage than eradication of a metronidazole-sensitive H. pylori strain. These results may explain one of the reasons for H. pylori treatment failure. PMID:9420026

  5. High-dose insulin therapy for neurogenic-stunned myocardium after stroke

    PubMed Central

    Devos, Justine; Peeters, André; Wittebole, Xavier; Hantson, Philippe

    2012-01-01

    A 44-year-old woman with a history of complicated type 2 diabetes mellitus presented with a diagnosis of right-hemispheric ischaemic stroke. She developed acute respiratory distress with radiological evidence of pulmonary oedema. The ECG showed poorly significant ST-segment changes, with a minimal increase of cardiac biomarkers. Echocardiography showed a severely depressed left ventricular function, with also low values of cardiac output at invasive monitoring. The possibility of neurogenic-stunned myocardium was discussed and a metabolic resuscitation with high-dose insulin was proposed. An intravenous bolus of 80 units of insulin (0.72 IU/kg) was followed by a continuous infusion at the rate of 160 IU/h (1.45 IU/kg/h). The treatment led to a rapid and sustained improvement of the haemodynamic condition and was well tolerated. In comparison with dobutamine, insulin had significant inotropic effects without tachycardia. The patient unfortunately died on day 35, from respiratory complications after poor neurological recovery. PMID:23175002

  6. Intracranial hypertension secondary to high dose cytosine arabinoside - A case study.

    PubMed

    Nurgat, Z A; Alzahrani, H; Lawrence, M; Mannan, A; Ashour, M; Rasheed, W; Aljurf, M

    2017-05-01

    We report a rare case of intracranial hypertension following high dose cytosine arabinoside (HiDAC) in a 20-year-old man, with precursor B-cell acute lymphoblastic leukemia (ALL). A five drug induction protocol for ALL was initiated; post induction consolidation was with HiDAC (3 g/m(2) IV every 12 h on days 1, 3 and 5). Post consolidation, cytogenetic remission was attained and he received an intensification and maintenance regimen for ALL, for a period of approximately 24 months. Four months following the completion of his treatment, the patient relapsed within the central nervous system (CNS). Intravenous salvage chemotherapy was initiated using a combination of fludarabine 30 mg/m(2), followed by cytarabine 2 g/m(2) 4 h later on days 1 through 5 (FA). On day # 23 of FA, he developed a severe headache. A gadolinium-enhanced brain magnetic resonance imaging (MRI) revealed increased intracranial pressure. On day # 25, ophthalmology examination suggested bilateral papilledema. He was started on acetazolamide 250 mg twice daily. He had spontaneous resolution of his symptoms. The patient had no recurrence of papilledema or any other neurological symptoms. Intracranial hypertension secondary to HiDAC, is an exceedingly rare complication and is not regularly associated as a common side effect of cytarabine administration. Prompt action in diagnosing and treating intracranial hypertension will save the patient from consequences, such as loss of vision, that are prevalent in this condition.

  7. Should high-dose interleukin-2 still be the preferred treatment for patients with metastatic melanoma?

    PubMed

    Dillman, Robert O; Barth, Neil M; VanderMolen, Louis A; Mahdavi, Khosrow; McClure, Stephanie E

    2012-08-01

    For more than 20 years interleukin-2 (IL2) was the preferred treatment for medically fit metastatic melanoma patients, but recently two new agents, ipilimumab and vemurafenib, were approved for stage IV disease. Single-institution data were used to determine the long-term survival rate for IL2-treated melanoma patients, and whether use of inpatient IL2 had declined recently. Between May 1987 and April 2010, 150 patients were hospitalized for high-dose, intravenous (i.v.) IL2. The average number of IL2 patients increased from 5.4 per year during 1987-1991 to 5.8 during 1992-1997 after regulatory approval of IL2, to 8.3 during 1998-2006 after a marketing indication in metastatic melanoma was granted, but dropped to 3.0 during 2007-2010. At the time of treatment, median age was 52 years; 27% were 60 years of age or older. At the time of analysis 122 patients were deceased. Median survival from the start date of IL2 treatment was 15.6 months, with a 20% 5-year survival. Among patients enrolled in clinical trials, there were as many nonresponders who survived 5 years as responders, which is consistent with a delayed immunotherapy benefit. In the absence of long-term survival data for these newer agents, IL2 probably should still be the preferred initial treatment for most patients with metastatic melanoma who are medically fit.

  8. High-Dose Vitamin D Failed to Curb Heart Disease in Study

    MedlinePlus

    ... medlineplus.gov/news/fullstory_164472.html High-Dose Vitamin D Failed to Curb Heart Disease in Study ... 5, 2017 (HealthDay News) -- Taking high doses of vitamin D once a month won't lower your ...

  9. High Doses of Vitamin D Fail to Cut Cancer Risk, Study Finds

    MedlinePlus

    ... gov/news/fullstory_164325.html High Doses of Vitamin D Fail to Cut Cancer Risk, Study Finds ... March 28, 2017 (HealthDay News) -- High doses of vitamin D supplements may not lower older women's risk ...

  10. Efficacy of Levofloxacin Based Triple and High-Dose PPI-Amoxicillin Dual Eradication Therapy for Helicobacter pylori after Failures of First- and Second-Line Therapies

    PubMed Central

    Okimoto, Kenichiro; Arai, Makoto; Saito, Keiko; Minemura, Shoko; Maruoka, Daisuke; Matsumura, Tomoaki; Nakagawa, Tomoo; Katsuno, Tatsuro; Ishii, Chisato; Murata, Shota; Watanabe, Masaharu; Nomura, Fumio; Yokosuka, Osamu

    2014-01-01

    Objectives. The aim of this study was to investigate and compare the eradication rate of Helicobacter pylori as the third-line triple therapy with rabeprazole (RPZ) + amoxicillin (AMPC) + levofloxacin (LVFX) and high-dose RPZ + AMPC. Methods. 51 patients who failed Japanese first-line (proton pump inhibitor (PPI) + AMPC + clarithromycin) and second-line (PPI + AMPC + metronidazole) eradication therapy were randomly assigned at a 1 : 1 ratio to one of the following third-line eradication groups: (1) RAL group: RPZ 10 mg (b.i.d.), AMPC 750 mg (b.i.d.), and LVFX 500 mg (o.d.) for 10 days; (2) RA group: RPZ 10 mg (q.i.d.) and AMPC 500 mg (q.i.d.) for 14 days. Patients who failed to respond to third-line eradication therapy received salvage therapy. Results. The rates of eradication success, based on intention to treat (ITT) analysis, were 45.8% in the RAL group and 40.7% in the RA group. The overall eradication rates were 73.9% in the RAL group and 64.0% in the RA group. There was no significant difference between the two groups. Conclusions. The third-line triple therapy with RPZ, AMPC, and LVFX was as effective as that with high-dose RPZ and AMPC. PMID:27379339

  11. A comparison of the efficacy of metronidazole vaginal gel and Myrtus (Myrtus communis) extract combination and metronidazole vaginal gel alone in the treatment of recurrent bacterial vaginosis

    PubMed Central

    Masoudi, Mansoureh; Rafieian Kopaei, Mahmoud; Miraj, Sepideh

    2017-01-01

    Objective: Due to the high incidence of bacterial vaginosis (BV) and its resistance to chemical medications and considering the anti-bacterial and anti-fungal effects of Myrtus communis, the present study aimed to compare the therapeutic effects of the vaginal gel of M. communis 2% (in metronidazole base) with metronidazole vaginal gel 0.75% alone on BV. Materials and Methods: This research was a randomized controlled clinical trial conducted on 80 women of 18-40 years old with BV. Patients were divided into two groups of 40 women. Diagnostic criteria were Amsel's criteria and Gram staining. The first group received vaginal gel of metronidazole plus M. communis 2% and the second group received metronidazole vaginal gel alone for five consecutive nights. Therapeutic effects and Amsel’s criteria were assessed after one week. Finally, the data were analyzed by SPSS 16 using t-test and Chi square tests. Results: There was a significant difference in the therapeutic response between the two groups. The results demonstrated that the combination of metronidazole and M. communis had a higher efficiency (p<0.05). The patients receiving M. communis in metronidazole gel base did not experience any recurrent BV, but 30% of patients taking metronidazole alone faced recurrent BV after three weeks of follow up. Conclusion: Findings of the study suggested that adding M. communis extract to metronidazole increases the efficiency of BV treatment. PMID:28348968

  12. A comparison of the efficacy of metronidazole vaginal gel and Myrtus (Myrtus communis) extract combination and metronidazole vaginal gel alone in the treatment of recurrent bacterial vaginosis.

    PubMed

    Masoudi, Mansoureh; Rafieian Kopaei, Mahmoud; Miraj, Sepideh

    2017-01-01

    Due to the high incidence of bacterial vaginosis (BV) and its resistance to chemical medications and considering the anti-bacterial and anti-fungal effects of Myrtus communis, the present study aimed to compare the therapeutic effects of the vaginal gel of M. communis 2% (in metronidazole base) with metronidazole vaginal gel 0.75% alone on BV. This research was a randomized controlled clinical trial conducted on 80 women of 18-40 years old with BV. Patients were divided into two groups of 40 women. Diagnostic criteria were Amsel's criteria and Gram staining. The first group received vaginal gel of metronidazole plus M. communis 2% and the second group received metronidazole vaginal gel alone for five consecutive nights. Therapeutic effects and Amsel's criteria were assessed after one week. Finally, the data were analyzed by SPSS 16 using t-test and Chi square tests. There was a significant difference in the therapeutic response between the two groups. The results demonstrated that the combination of metronidazole and M. communis had a higher efficiency (p<0.05). The patients receiving M. communis in metronidazole gel base did not experience any recurrent BV, but 30% of patients taking metronidazole alone faced recurrent BV after three weeks of follow up. Findings of the study suggested that adding M. communis extract to metronidazole increases the efficiency of BV treatment.

  13. A case of metronidazole-resistant Trichomonas vaginalis in pregnancy.

    PubMed

    Forbes, Georgina L; Drayton, Rachel; Forbes, Gavin D

    2016-09-01

    Trichomonas vaginalis is a sexually transmitted protozoan infection resulting in vulvo-vaginitis and altered vaginal discharge in symptomatic women. Trichomoniasis has been implicated in causing adverse pregnancy outcomes such as low birth weight and pre-term labour. Metronidazole is the recommended first-line treatment for trichomonal infection. Other nitroimidazoles, such as tinidazole, are used as alternative regimens with similar activity but at a greater expense. Treatment failure usually represents patient non-compliance or re-infection, although metronidazole resistance has previously been documented. Antimicrobial susceptibility testing for T. vaginalis is currently not available in the UK. Patients with disease unresponsive to first-line treatments pose a major challenge, as therapeutic options are limited. We present the case of a patient with presumed resistant infection during pregnancy, and the additional treatment issues that this presented. © The Author(s) 2015.

  14. Crystal growth by solvent evaporation and characterization of metronidazole

    NASA Astrophysics Data System (ADS)

    Ramukutty, S.; Ramachandran, E.

    2012-07-01

    Single crystals of metronidazole were crystallized by the slow solvent evaporation method and used as seeds to grow bulk crystals of size 8.0×6.5×2.0 mm3 using top-seeded submerged solution growth. The crystals were characterized using single crystal X-ray diffraction. Fourier transform infrared spectral analysis was made for the absorption bands of various functional groups present in the crystal. UV-vis absorption spectrum was used to identify the presence of nitroimidazole in metronidazole. Morphology study revealed that the growth is prominent along the c-axis and the prominent face is {010}. Thermal stability and thermal decomposition were analyzed using thermo calorimetry.

  15. Mummification of the infarcted myocardium by high dose corticosteroids.

    PubMed

    Kloner, R A; Fishbein, M C; Lew, H; Maroko, P R; Braunwald, E

    1978-01-01

    There is evidence that glucocorticoids reduce infarct size but their use in myocardial infarction remains controversial because of their potential adverse effects on healing of the infarct. To investigate the healing process, rats received either four parenteral doses of 50 mg/kg of methylprednisolone (MP) or saline 5 min, 3,6 and 24 hr after coronary occlusion and their hearts were examined by light and electron microscopy 48 hr and seven days after occlusion. At 48 hr, in five untreated rats, only 12 +/- 7% of injured myocytes showed the persistence of striations and a relatively intact sarcolemma despite loss of nuclei and hence appeared "mummified" whereas in six MP-treated rats 72 +/- 8% of myocytes exhibited this appearance (P less than 0.001). In treated rats there were fewer phagocytes than in controls. At seven days, in seven MP-rats, mummified cells were still more prominent than in five untreated rats and there were fewer phagocytes and less collagen. In conclusion, high dose of MP delays the inflammatory process and retards the disintegration of necrotic myocytes, resulting in impaired healing.

  16. High-dose naltrexone therapy for cocaine-alcohol dependence.

    PubMed

    Schmitz, Joy M; Lindsay, Jan A; Green, Charles E; Herin, David V; Stotts, Angela L; Moeller, F Gerard

    2009-01-01

    This randomized, double-blind, placebo-controlled study compared the effects of high-dose (100 mg/d) naltrexone versus placebo in a sample of 87 randomized subjects with both cocaine and alcohol dependence. Medication conditions were crossed with two behavioral therapy platforms that examined whether adding contingency management (CM) that targeted cocaine abstinence would enhance naltrexone effects compared to cognitive behavioral therapy (CBT) without CM. Primary outcome measures for cocaine (urine screens) and alcohol use (timeline followback) were collected thrice-weekly during 12 weeks of treatment. Retention in treatment and medication compliance rates were low. Rates of cocaine use and drinks per day did not differ between treatment groups; however naltrexone did reduce frequency of heavy drinking days, as did CBT without CM. Notably, adding CM to CBT did not enhance treatment outcomes. These weak findings suggest that pharmacological and behavioral interventions that have shown efficacy in the treatment of a single drug dependence disorder may not provide the coverage needed when targeting dual drug dependence.

  17. High-dose processing and application to Korean space foods

    NASA Astrophysics Data System (ADS)

    Song, Beom-Seok; Park, Jin-Gyu; Park, Jae-Nam; Han, In-Jun; Choi, Jong-il; Kim, Jae-Hun; Byun, Myung-Woo; Kang, Sang-Wook; Choi, Gi-Hyuk; Lee, Ju-Woon

    2009-07-01

    Nutrition bar, Ramen (ready-to-cook noodle), and two Korean traditional foods ( Kimchi, fermented vegetable; Sujeonggwa, cinnamon beverage) have been developed as space foods using high-dose gamma irradiation. Addition of calcium lactate and vitamin C, a mild heating, deep-freezing, and gamma irradiation at 25 kGy were conducted to prepare Kimchi as a ready-to-eat space food. Sterilization of Space Kimchi (SK) was confirmed by a microbiological test. The hardness of the Space Kimchi was lower than the untreated Kimchi (CON), but higher than the irradiated only Kimchi. Sensory attributes of the SK were similar to CON, and maintained during preservation at 35 °C for 30 days. The optimal doses for eliminating the contaminated microbes and maintaining the qualities of the Nutrition bars, Ramen, and Sujeonggwa were determined at 15, 10 and 6 kGy, respectively. All the Korean space food were certificated for use in space flight conditions of 30 days by the Russian Institute for Biomedical Problems.

  18. High-dose radiation sensor with wireless optical detection

    NASA Astrophysics Data System (ADS)

    Knapkiewicz, Paweł; Augustyniak, Izabela; Sareło, Katarzyna; Gorecka-Drzazga, Anna; Dziuban, Jan

    2017-05-01

    We present a miniature silicon-glass MEMS sensor for measurement of high doses of ionizing radiation (above 10 kGy) using a novel wireless optical detection method. The radiation sensor is a miniaturized version of the so-called hydrogen dosimeter. An amount of high-density polyethylene, located inside the MEMS sensor, degrades under ionizing radiation, releasing gaseous hydrogen. The increasing pressure deflects the thin silicon membrane. The sensor’s destructive and proportional modes of work are also proposed. In the destructive mode, sensors provide in situ information on excessive and discrete levels of radiation. The optical detection method is based on an optical head consisting of a moving membrane and a silicon screen with a matrix of micro-holes. Laser light is reflected from the membrane and scattered when the membrane is deflected, in the process illuminating the holes on the silicon screen. The number of illuminated holes is a function of the degree of membrane deflection; the transformation of the holes to the deflection allows for the calculation of pressure and eventually the dose of ionizing radiation.

  19. Theoretically required urinary flow during high-dose methotrexate infusion.

    PubMed

    Sasaki, K; Tanaka, J; Fujimoto, T

    1984-01-01

    The renal excretion of methotrexate (MTX) and its major metabolite 7-hydroxymethotrexate (7-OH-MTX) was analysed in 12 children with malignancies during 52 courses of high-dose methotrexate (H-D-MTX) infusion at dosages ranging from 0.7 to 8.4 g/m2. The peak concentrations of both MTX and 7-OH-MTX exceeded the aqueous solubilities of these compounds at low pH (less than or equal to 6.0). The cumulative MTX excretion in urine was 75%-98% of the administered amount of MTX, and the cumulative 7-OH-MTX excretion in the urine was 3%-15%. The theoretically required urinary flow (TRUF) was estimated as the minimum urine volume needed for complete resolution of MTX and its metabolites in urine. TRUF during MTX infusion from 0 to 6 h and from 6 to 12 h was correlated with the dosage of MTX, and these values were 0.1-1.8 ml/min/m2 at pH 7.0, 0.5-11.1 ml/min/m2 at pH 6.0, and 1.9-42.2 ml/min/m2 at pH 5.0 with dosages of 0.7 to 8.4 g/m2. The value of the theoretically required urinary flow is important to ensure adequate hydration and the optimum alkalinization schedule for massive MTX infusion.

  20. Shelf-stable food through high dose irradiation

    NASA Astrophysics Data System (ADS)

    Plaček, V.; Svobodová, V.; Bartoníček, B.; Rosmus, J.; Čamra, M.

    2004-09-01

    Irradiation of food with high doses (radappertization) is a way, how to prepare shelf-stable ready-to-eat food. The radappertization process requires that the food be heated at first to an internal temperature of at least 75°C to inactivate autolytic enzyme, which could cause the spoilage during storage without refrigeration. In order to prevent radiation induced changes in sensory properties (off flavors, odors, undesirable color change, etc.) the food was vacuum packed and irradiated in frozen state at -30°C or less to a minimum dose of 35 kGy. Such products have characteristics of fresh food prepared for eating even if they are stored for long time under tropical conditions. The wholesomeness (safety for consumption) has been confirmed during 40 years of testing. Within the NRI Řež 10 kinds of shelf-stable meat products have been prepared. The meat was cooked, vacuum packed in SiO x-containing pouch, freezed in liquid nitrogen and irradiated with electron beam accelerator. The microbial, chemical, and organoleptic properties have been tested.

  1. Effects of high-dose isoflavones on rat uterus.

    PubMed

    Carbonel, Adriana Aparecida Ferraz; Simões, Ricardo Santos; Santos, Regiane Helena Barros Rabelo; Baracat, Maria Cândida Pinheiro; Simões, Manuel de Jesus; Baracat, Edmund Chada; Soares Júnior, José Maria

    2011-01-01

    To evaluate the effects of high-dose isoflavones on the uterus of castrated adult rats. Adult, ovariectomized virgin rats (n = 40) were treated by gavage during 30 consecutive days with vehicle (propylene glycol, group GCtrl) or different doses of genistein: 42 (group GES42), 125 (GES125), or 250 (GES250) µg/g body weight per day. Animals were killed, weighed, vaginal and uterine samples were taken for cytologic evaluation, and serum levels of 17 β-estradiol and progesterone were determined. The middle third of the uterine horns was dissected, fixed in 10% formaldehyde and processed for paraffin inclusion; 5-µm thick sections were obtained and stained with HE for further histological study under light microscopy. The endometrial morphology and area, number and area of glands, and number of eosinophils in the lamina propria were analyzed. ANOVA and the Tukey-Kramer test were used for statistical analyses. Uterine weight, endometrial glandular area, and number of glands and eosinophils were all higher in GES250 > G125 than in the other groups (GES250 > GES125 > GES42 = GCtrl; p < 0.05). Morphological data showed signs of endometrial proliferation upon treatment with genistein, especially in animals in GES125 and GES250 compared to other groups. In all animals in GES250, signs of uterine squamous metaplasia were observed. A short treatment period with high daily doses of isoflavones can promote endometrial squamous metaplasia in ovariectomized rats.

  2. Survival After Shock Requiring High-Dose Vasopressor Therapy

    PubMed Central

    Lanspa, Michael J.; Jones, Jason P.; Kuttler, Kathryn G.; Li, Yao; Carlson, Rick; Miller, Russell R.; Hirshberg, Eliotte L.; Grissom, Colin K.; Morris, Alan H.

    2013-01-01

    Background: Some patients with hypotensive shock do not respond to usual doses of vasopressor therapy. Very little is known about outcomes after high-dose vasopressor therapy (HDV). We sought to characterize survival among patients with shock requiring HDV. We also evaluated the possible utility of stress-dose corticosteroid therapy in these patients. Methods: We conducted a retrospective study of patients with shock requiring HDV in the ICUs of five hospitals from 2005 through 2010. We defined HDV as receipt at any point of ≥ 1 μg/kg/min of norepinephrine equivalent (calculated by summing norepinephrine-equivalent infusion rates of all vasopressors). We report survival 90 days after hospital admission. We evaluated receipt of stress-dose corticosteroids, cause of shock, receipt of CPR, and withdrawal or withholding of life support therapy. Results: We identified 443 patients meeting inclusion criteria. Seventy-six (17%) survived. Survival was similar (20%) among the 241 patients with septic shock. Among the 367 nonsurvivors, 254 (69%) experienced withholding/withdrawal of care, and 115 (31%) underwent CPR. Stress-dose corticosteroid therapy was associated with increased survival (P = .01). Conclusions: One in six patients with shock survived to 90 days after HDV. The majority of nonsurvivors died after withdrawal or withholding of life support therapy. A minority of patients underwent CPR. Additionally, stress-dose corticosteroid therapy appears reasonable in patients with shock requiring HDV. PMID:22911566

  3. Possible pharmacokinetic interaction with quinidine: ciprofloxacin or metronidazole?

    PubMed

    Cooke, C E; Sklar, G E; Nappi, J M

    1996-04-01

    To discuss a potential pharmacokinetic interaction between quinidine, ciprofloxacin, and metronidazole. A 51-year-old black woman was admitted for shortness of breath, abdominal pain, and atrial fibrillation. Procainamide and diltiazem were begun for the atrial fibrillation and ciprofloxacin and metronidazole for suspected diverticulitis. The therapy was switched to quinidine on day 5 because of adverse events associated with procainamide. A trough serum quinidine concentration (SQC) on day 7 was 6.3 micrograms/mL (normal 2-5) with normal QT and QTc intervals. On day 8, the patient was discharged in normal sinus rhythm. She took her last doses of antibiotics on day 15 and a follow-up SQC on day 18 was 2.3 micrograms/mL. The possible explanations for the changes in SQCs include: (1) laboratory error, (2) compliance with medication regimen, and (3) altered hepatic metabolism. The first two are not likely in this case. The laboratory verified the elevated SQC and the patient had her prescriptions refilled within appropriate time limits. The third explanation seems more plausible. Quinidine is metabolized by the hepatic mixed-function oxidase system, specifically cytochrome P450 (CYP) 3A4. We found that metronidazole has been shown to inhibit CYP3A activity and ciprofloxacin has been shown to inhibit certain isozymes in the cytochrome P450 system as well. When metronidazole and ciprofloxacin are administered concomitantly with quinidine, clinicians should be aware of this potential interaction. Quinidine concentrations should be monitored and patients should be assessed for signs and symptoms of quinidine toxicity.

  4. Biowaiver monographs for immediate release solid oral dosage forms: metronidazole.

    PubMed

    Rediguieri, Camila F; Porta, Valentina; G Nunes, Diana S; Nunes, Taina M; Junginger, Hans E; Kopp, Sabine; Midha, Kamal K; Shah, Vinod P; Stavchansky, Salomon; Dressman, Jennifer B; Barends, Dirk M

    2011-05-01

    Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing metronidazole are reviewed. Metronidazole can be assigned to Biopharmaceutics Classification System Class I. Most BE studies that were identified reported the investigated formulations to be bioequivalent, indicating the risk of bioinequivalence to be low. Formulations showing differences in bioavailability showed dissimilarities in in vitro dissolution profiles. Furthermore, metronidazole has a wide therapeutic index. It is concluded that a biowaiver for solid IR formulations is justified, provided: (a) the test product and its comparator are both rapidly dissolving; (b) meet similarity of the dissolution profiles at pH 1.2, 4.5, and 6.8; (c) the test product contains only excipients present in IR drug products approved in International Conference on Harmonisation (ICH) or associated countries in the same dosage form; and (d) if the test product contains sorbitol, sodium laurilsulfate, or propylene glycol, the test product needs to be qualitatively and quantitatively identical to its comparator with respect to these excipients [corrected]..

  5. Effects of metronidazole on hepatic CYP3A4 activity.

    PubMed

    Haas, C E; Kaufman, D C; DiCenzo, R C

    2001-10-01

    To evaluate the effect of a short course of oral metronidazole, commonly used for bowel-preparation regimens, on hepatic cytochrome P450 (CYP) 3A4 activity, as measured by the [14C N-methyl]-erythromycin breath test (ERMBT) in healthy volunteers. Prospective, nonrandomized, interventional study University-affiliated, community, teaching hospital. Five healthy male volunteers. Subjects underwent a baseline ERMBT in the morning before receiving three oral doses of metronidazole 500 mg administered at 3 P.M., 7 P.M., and 11 P.M. Repeat ERMBTs were performed at 24, 72, and 96 hours after the initial ERMBT. Changes in ERMBT values were compared with baseline results using Freidman's repeated-measures analysis of variance on ranks. The ERMBT values did not change significantly compared with baseline (p=0.82). Median (range) ERMBT values expressed as a percentage of baseline at 24, 72, and 96 hours were 110.3 (96.2-136.9), 101.3 (99.3-115.0), and 101.8 (95.5-116.3), respectively A short course of oral metronidazole does not result in a significant change in hepatic CYP3A4 activity as measured by the ERMBT.

  6. [Good response of scleromyxedema and dermato-neuro syndrome to treatment with intravenous immunoglobulins].

    PubMed

    Bielsa, I; Benvenutti, F; Guinovart, R M; Ferrándiz, C

    2012-05-01

    Scleromyxedema is a potentially serious disease that can have various systemic complications. One of the most frequent forms of central nervous system involvement is dermato-neuro syndrome. High-dose intravenous immunoglobulins are among the drug treatments that have been used for this syndrome. We describe 2 patients with scleromyxedema, one of whom developed dermato-neuro syndrome. Both patients responded well to treatment with high-dose intravenous immunoglobulins. We suggest this therapy as a suitable first-line treatment for scleromyxedema and for its neurological complications.

  7. Draft Genome Sequence of a Metronidazole-Resistant Gardnerella vaginalis Isolate

    PubMed Central

    Schuyler, Jessica A.; Chadwick, Sean G.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the draft genome sequence of a Gardnerella vaginalis strain (3549624) isolated from a vaginal specimen. G. vaginalis is associated with bacterial vaginosis, the most common cause of vaginal discharge, which is often treated with metronidazole. This isolate is highly resistant to metronidazole (MIC, 500 µg/ml) and may be useful for comparative genomic studies to determine the molecular basis of metronidazole resistance in this species. PMID:26337887

  8. Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen).

    PubMed

    Gianni, Alessandro M; Magni, Michele; Martelli, Maurizio; Di Nicola, Massimo; Carlo-Stella, Carmelo; Pilotti, Silvana; Rambaldi, Alessandro; Cortelazzo, Sergio; Patti, Caterina; Parvis, Guido; Benedetti, Fabio; Capria, Saveria; Corradini, Paolo; Tarella, Corrado; Barbui, Tiziano

    2003-07-15

    Mantle cell lymphoma (MCL) is rarely cured with standard-dose chemotherapy. From January 1997 to February 2000, 28 previously untreated advanced-stage MCL patients younger than 61 years of age were treated at 9 Italian hematologic departments with 3 cycles of standard-dose debulking chemotherapy followed by a high-dose rituximab-supplemented sequence (R-HDS) including intravenous administration of high-dose cyclophosphamide, high-dose cytarabine, high-dose melphalan, and high-dose mitoxantrone plus melphalan. Study end points included toxicity, clinical and molecular response rates, long-term event-free survival (EFS), and overall survival (OS) rates, as well as the ability to harvest tumor-free peripheral blood stem cells. Optimal amounts of polymerase chain reaction-negative (PCR-negative) CD34+ cells were collected from all 20 informative patients. One patient died of toxicity. All 27 patients assessable for response achieved a complete response (CR), of which 24 remain in continuous complete remission (CCR) after a median follow-up of 35 months. Three patients had transient evidence of PCR-detectable disease in the bone marrow. The OS and EFS rates at 54 months were 89% and 79%, respectively. These results compare with the 42% OS rate and the 18% EFS rate observed in 35 age-matched historic controls treated with standard-dose chemotherapy at the participating centers. The use of rituximab in combination with high-dose chemotherapy represents a very effective in vivo purging method. The R-HDS regimen can be safely applied in a multicenter hematology setting and leads to long-term EFS and OS in the majority of patients with an otherwise incurable disease.

  9. Ethnicity association of Helicobacter pylori virulence genotype and metronidazole susceptibility

    PubMed Central

    Alfizah, Hanafiah; Rukman, Awang Hamat; Norazah, Ahmad; Hamizah, Razlan; Ramelah, Mohamed

    2013-01-01

    AIM: To characterise the cag pathogenicity island in Helicobacter pylori (H. pylori) isolates by analysing the strains’ vacA alleles and metronidazole susceptibilities in light of patient ethnicity and clinical outcome. METHODS: Ninety-five H. pylori clinical isolates obtained from patients with dyspepsia living in Malaysia were analysed in this study. Six genes in the cagPAI region (cagE, cagM, cagT, cag13, cag10 and cag67) and vacA alleles of the H. pylori isolates were identified by polymerase chain reaction. The isolates’ metronidazole susceptibility was also determined using the E-test method, and the resistant gene was characterised by sequencing. RESULTS: More than 90% of the tested isolates had at least one gene in the cagPAI region, and cag67 was predominantly detected in the strains isolated from the Chinese patients, compared with the Malay and Indian patients (P < 0.0001). The majority of the isolates (88%) exhibited partial deletion (rearrangement) in the cagPAI region, with nineteen different patterns observed. Strains with intact or deleted cagPAI regions were detected in 3.2% and 8.4% of isolates, respectively. The prevalence of vacA s1m1 was significantly higher in the Malay and Indian isolates, whereas the isolates from the Chinese patients were predominantly genotyped as vacA s1m2 (P = 0.018). Additionally, the isolates from the Chinese patients were more sensitive to metronidazole than the isolates from the Malay and Indian patients (P = 0.047). Although we attempted to relate the cagPAI genotypes, vacA alleles and metronidazole susceptibilities to disease outcome, no association was observed. The vacA alleles were distributed evenly among the strains with intact, partially deleted or deleted cagPAI regions. Interestingly, the strains exhibiting an intact cagPAI region were sensitive to metronidazole, whereas the strains with a deleted cagPAI were more resistant. CONCLUSION: Successful colonisation by different H. pylori genotypes is

  10. Tolerance of the Brachial Plexus to High-Dose Reirradiation.

    PubMed

    Chen, Allen M; Yoshizaki, Taeko; Velez, Maria A; Mikaeilian, Argin G; Hsu, Sophia; Cao, Minsong

    2017-05-01

    To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus-related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). The development of brachial plexus-related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Painful peripheral neuropathy after treatment with high-dose ifosfamide.

    PubMed

    Frisk, P; Stålberg, E; Strömberg, B; Jakobson A

    2001-10-01

    Ifosfamide is successfully employed in the treatment of bone and soft tissue sarcomas in children and young adults. Used at high doses (HDI) the drug may cause severe multiorgan toxicity. Peripheral neuropathy is a less well-known side effect that may limit its use. We describe a 16-year-old girl with a Ewing sarcoma who was given post-operative treatment with HDI (15 mg/m(2) infused over 5 days). After the second course she experienced paresthesias in both feet. After the third course she developed signs of severe toxicity in the CNS, kidneys, heart, and severe pain in her feet. Neurologic and neurophysiologic investigations, including neurographic studies of motor and sensory nerves, EMG, and thermotest, were performed in the acute phase and after 6 and 21 months, respectively. Renal and cardiac function was also assessed. She developed generalized weakness of the arms and legs and an extremely painful hyperesthesia of the soles. The symptoms improved gradually during follow-up but remained to some extent even after more than 2 years. Serial neurophysiologic investigations indicated classical signs of axonal neuropathy, which tended to improve during follow-up. After 18 months the glomerular filtration rate and the effective renal plasma flow were 30 and 12% of normal, respectively, while other organ functions had returned to baseline. Symptoms of peripheral neuropathy after HDI may herald severe multiorgan toxicity, if continued. Early administration of anesthetics through the intrathecal route should be considered in case of ifosfamide-induced painful peripheral neuropathy. Copyright 2001 Wiley-Liss, Inc.

  12. High-dose neutron irradiation performance of dielectric mirrors

    DOE PAGES

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; ...

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation tolerance. Alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of I and 4 displacements per atom (dpa) at 458 ± 10 K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa result in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to I dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failingmore » at 4 dpa. Transmission electron microscopy (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects, which increase in size with irradiation dose. The typical size of each defect was approximate to 8 nm in 1-dpa specimens and ≈ 42 nm in 4-dpa specimens. Buckling-type delamination of the interface between the substrate and first layer was typically observed in both 1- and 4-dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high-resolution-scanning-TEM mode using energy dispersive spectroscopy. Lastly, a significant interdiffusion between the film layers was observed in the Al2O3/SiO2 mirror, although it was less evident in the HfO2/SiO2 system. The ultimate goal of this work is to provide insight into the radiation-induced failure mechanisms of these mirrors.« less

  13. Molecular mechanisms linking high dose medroxyprogesterone with HIV-1 risk.

    PubMed

    Irvin, Susan C; Herold, Betsy C

    2015-01-01

    Epidemiological studies suggest that medroxyprogesterone acetate (MPA) may increase the risk of HIV-1. The current studies were designed to identify potential underlying biological mechanisms. Human vaginal epithelial (VK2/E6E7), peripheral blood mononuclear (PBMC), and polarized endometrial (HEC-1-A) cells were treated with a range of concentrations of MPA (0.015-150 μg/ml) and the impact on gene expression, protein secretion, and HIV infection was evaluated. Treatment of VK2/E6E7 cells with high doses (>15 μg/ml] of MPA significantly upregulated proinflammatory cytokines, which resulted in a significant increase in HIV p24 levels secreted by latently infected U1 cells following exposure to culture supernatants harvested from MPA compared to mock-treated cells. MPA also increased syndecan expression by VK2/E6E7 cells and cells treated with 15 μg/ml of MPA bound and transferred more HIV-1 to T cells compared to mock-treated cells. Moreover, MPA treatment of epithelial cells and PBMC significantly decreased cell proliferation resulting in disruption of the epithelial barrier and decreased cytokine responses to phytohaemagglutinin, respectively. We identified several molecular mechanisms that could contribute to an association between DMPA and HIV including proinflammatory cytokine and chemokine responses that could activate the HIV promoter and recruit immune targets, increased expression of syndecans to facilitate the transfer of virus from epithelial to immune cells and decreased cell proliferation. The latter could impede the ability to maintain an effective epithelial barrier and adversely impact immune cell function. However, these responses were observed primarily following exposure to high (15-150 μg/ml) MPA concentrations. Clinical correlation is needed to determine whether the prolonged MPA exposure associated with contraception activates these mechanisms in vivo.

  14. Cloning of Bacteroides fragilis plasmid genes affecting metronidazole resistance and ultraviolet survival in Escherichia coli

    SciTech Connect

    Wehnert, G.U.; Abratt, V.R.; Goodman, H.J.; Woods, D.R. )

    1990-03-01

    Since reduced metronidazole causes DNA damage, resistance to metronidazole was used as a selection method for the cloning of Bacteroides fragilis genes affecting DNA repair mechanisms in Escherichia coli. Genes from B. fragilis Bf-2 were cloned on a recombinant plasmid pMT100 which made E. coli AB1157 and uvrA, B, and C mutant strains more resistant to metronidazole, but more sensitive to far uv irradiation under aerobic conditions. The loci affecting metronidazole resistance and uv sensitivity were linked and located on a 5-kb DNA fragment which originated from the small 6-kb cryptic plasmid pBFC1 present in B. fragilis Bf-2 cells.

  15. Differential Expression and Immunolocalization of Antioxidant Enzymes in Entamoeba histolytica Isolates during Metronidazole Stress

    PubMed Central

    Iyer, Lakshmi Rani; Singh, Nishant; Verma, Anil Kumar; Paul, Jaishree

    2014-01-01

    Entamoeba histolytica infections are endemic in the Indian subcontinent. Five to eight percent of urban population residing under poor sanitary conditions suffers from Entamoeba infections. Metronidazole is the most widely prescribed drug used for amoebiasis. In order to understand the impact of metronidazole stress on the parasite, we evaluated the expression of two antioxidant enzymes, peroxiredoxin and FeSOD, in Entamoeba histolytica isolates during metronidazole stress. The results reveal that, under metronidazole stress, the mRNA expression levels of these enzymes did not undergo any significant change. Interestingly, immunolocalization studies with antibodies targeting peroxiredoxin indicate differential localization of the protein in the cell during metronidazole stress. In normal conditions, all the Entamoeba isolates exhibit presence of peroxiredoxin in the nucleus as well as in the membrane; however with metronidazole stress the protein localized mostly to the membrane. The change in the localization pattern was more pronounced when the cells were subjected to short term metronidazole stress compared to cells adapted to metronidazole. The protein localization to the cell membrane could be the stress response mechanism in these isolates. Colocalization pattern of peroxiredoxin with CaBp1, a cytosolic protein, revealed that the membrane and nuclear localization was specific to peroxiredoxin during metronidazole stress. PMID:25013795

  16. Bioadhesive Controlled Metronidazole Release Matrix Based on Chitosan and Xanthan Gum

    PubMed Central

    Eftaiha, Ala’a F.; Qinna, Nidal; Rashid, Iyad S.; Al Remawi, Mayyas M.; Al Shami, Munther R.; Arafat, Tawfiq A.; Badwan, Adnan A.

    2010-01-01

    Metronidazole, a common antibacterial drug, was incorporated into a hydrophilic polymer matrix composed of chitosan xanthan gum mixture. Hydrogel formation of this binary chitosan-xanthan gum combination was tested for its ability to control the release of metronidazole as a drug model. This preparation (MZ-CR) was characterized by in vitro, ex vivo bioadhesion and in vivo bioavailability study. For comparison purposes a commercial extended release formulation of metronidazole (CMZ) was used as a reference. The in vitro drug-release profiles of metronidazole preparation and CMZ were similar in 0.1 M HCl and phosphate buffer pH 6.8. Moreover, metronidazole preparation and CMZ showed a similar detachment force to sheep stomach mucosa, while the bioadhesion of the metronidazole preparation was higher three times than CMZ to sheep duodenum. The results of in vivo study indicated that the absorption of metronidazole from the preparation was faster than that of CMZ. Also, MZ-CR leads to higher metronidazole Cmax and AUC relative to that of the CMZ. This increase in bioavailability might be explained by the bioadhesion of the preparation at the upper part of the small intestine that could result in an increase in the overall intestinal transit time. As a conclusion, formulating chitosan-xanthan gum mixture as a hydrophilic polymer matrix resulted in a superior pharmacokinetic parameters translated by better rate and extent of absorption of metronidazole. PMID:20559494

  17. Differential expression and immunolocalization of antioxidant enzymes in Entamoeba histolytica isolates during metronidazole stress.

    PubMed

    Iyer, Lakshmi Rani; Singh, Nishant; Verma, Anil Kumar; Paul, Jaishree

    2014-01-01

    Entamoeba histolytica infections are endemic in the Indian subcontinent. Five to eight percent of urban population residing under poor sanitary conditions suffers from Entamoeba infections. Metronidazole is the most widely prescribed drug used for amoebiasis. In order to understand the impact of metronidazole stress on the parasite, we evaluated the expression of two antioxidant enzymes, peroxiredoxin and FeSOD, in Entamoeba histolytica isolates during metronidazole stress. The results reveal that, under metronidazole stress, the mRNA expression levels of these enzymes did not undergo any significant change. Interestingly, immunolocalization studies with antibodies targeting peroxiredoxin indicate differential localization of the protein in the cell during metronidazole stress. In normal conditions, all the Entamoeba isolates exhibit presence of peroxiredoxin in the nucleus as well as in the membrane; however with metronidazole stress the protein localized mostly to the membrane. The change in the localization pattern was more pronounced when the cells were subjected to short term metronidazole stress compared to cells adapted to metronidazole. The protein localization to the cell membrane could be the stress response mechanism in these isolates. Colocalization pattern of peroxiredoxin with CaBp1, a cytosolic protein, revealed that the membrane and nuclear localization was specific to peroxiredoxin during metronidazole stress.

  18. Outcome of metronidazole therapy for Clostridium difficile disease and correlation with a scoring system.

    PubMed

    Belmares, Jaime; Gerding, Dale N; Parada, Jorge P; Miskevics, Scott; Weaver, Frances; Johnson, Stuart

    2007-12-01

    To determine the response rate of Clostridium difficile disease (CDD) to treatment with metronidazole and assess a scoring system to predict response to treatment with metronidazole when applied at the time of CDD diagnosis. Retrospective review of patients with CDD who received primary treatment with metronidazole. We defined success as diarrhea resolution within 6 days of therapy. A CDD score was defined prospectively using variables suggested to correlate with disease severity. Among 102 evaluable patients, 72 had a successful response (70.6%). Twenty-one of the remaining 30 patients eventually responded to metronidazole, but required longer treatment, leaving 9 'true failures'. The mean CDD score was higher among true failures (2.89+/-1.4) than among all metronidazole responders (0.77+/-1.0) (p<.0001). The score was greater than 2 in 67% of true failures and 2 or less in 94% of metronidazole responders. Leukocytosis and abnormal CT scan findings were individual factors associated with a higher risk of metronidazole failure. Only 71% of CDD patients responded to metronidazole within 6 days, but the overall response rate was 91%. A CDD score greater than 2 was associated with metronidazole failure in 6 of 9 true failures. The CDD score will require prospective validation.

  19. Furazolidone- and Nitrofurantoin-Resistant Helicobacter pylori: Prevalence and Role of Genes Involved in Metronidazole Resistance

    PubMed Central

    Kwon, Dong H.; Lee, Miae; Kim, J. J.; Kim, J. G.; El-Zaatari, F. A. K.; Osato, M. S.; Graham, D. Y.

    2001-01-01

    The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant. rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection. PMID:11120984

  20. Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

    PubMed

    Armstrong, Eliana S; Mikulca, Janelle A; Cloutier, Daniel J; Bliss, Caleb A; Steenbergen, Judith N

    2016-11-25

    Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.gov, NCT01345929 and NCT01345955 , both registered April 28, 2011) provided an opportunity to test this hypothesis by examining the clinical and microbiological outcomes of high-dose levofloxacin treatment by levofloxacin minimum inhibitory concentration. Patients were randomly assigned 1:1 to ceftolozane/tazobactam (1.5 g intravenous every 8 h) or levofloxacin (750 mg intravenous once daily) for 7 days of therapy. The ASPECT-cUTI study provided data on 370 patients with at least one isolate of Enterobacteriaceae at baseline who were treated with levofloxacin. Outcomes were assessed at the test-of-cure (5-9 days after treatment) and late follow-up (21-42 days after treatment) visits in the microbiologically evaluable population (N = 327). Test-of-cure clinical cure rates above 90% were observed at minimum inhibitory concentrations ≤4 μg/mL. Microbiological eradication rates were consistently >90% at levofloxacin minimum inhibitory concentrations ≤0.06 μg/mL. Lack of eradication of causative pathogens at the test-of-cure visit increased the likelihood of relapse by the late follow-up visit. Results from this study do not support levofloxacin therapy for complicated urinary tract infections caused by organisms with levofloxacin minimum inhibitory concentrations ≥4 μg/mL. ClinicalTrials.gov, NCT01345929 and NCT01345955.

  1. High-dose versus low-dose oxytocin infusion regimens for induction of labour at term.

    PubMed

    Budden, Aaron; Chen, Lily J Y; Henry, Amanda

    2014-10-09

    When women require induction of labour, oxytocin is the most common agent used, delivered by an intravenous infusion titrated to uterine contraction strength and frequency. There is debate over the optimum dose regimen and how it impacts on maternal and fetal outcomes, particularly induction to birth interval, mode of birth, and rates of hyperstimulation. Current induction of labour regimens include both high- and low-dose regimens and are delivered by either continuous or pulsed infusions, with both linear and non-linear incremental increases in oxytocin dose. Whilst low-dose protocols bring on contractions safely, their potentially slow induction to birth interval may increase the chance of fetal infection and chorioamnionitis. Conversely, high-dose protocols may cause undue uterine hyperstimulation and fetal distress. To determine the effectiveness and safety of high- versus low-dose oxytocin for induction of labour at term We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2014) and the reference lists of relevant papers. Randomised controlled trials and quasi-randomised controlled trials that compared oxytocin protocol for induction of labour for women at term, where high-dose oxytocin is at least 100 mU oxytocin in the first 40 minutes, with increments delivering at least 600 mU in the first two hours, compared with low-dose oxytocin, defined as less than 100 mU oxytocin in the first 40 minutes, and increments delivering less than 600 mU total in the first two hours. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. Data were checked for accuracy. We have included nine trials, involving 2391 women and their babies in this review. Trials were at a moderate to high risk of bias overall.Results of primary outcomes revealed no significant differences in rates of vaginal delivery not achieved within 24 hours (risk ratio (RR) 0.94, 95% confidence interval

  2. Intravenous paracetamol (acetaminophen).

    PubMed

    Duggan, Sean T; Scott, Lesley J

    2009-01-01

    Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery. Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication. In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies. In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy. Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10 000). [table: see text].

  3. Toxicity and feasibility of adjuvant high-dose interferon alpha-2b in patients with melanoma in clinical oncologic practice

    PubMed Central

    Ravaud, A; Bedane, C; Geoffrois, L; Lesimple, T; Delaunay, M

    1999-01-01

    To assess the feasibility and toxicity profile of high-dose interferon alpha-2b (IFN-α-2b) in the adjuvant treatment of patients with cutaneous malignant melanoma outside the reference ECOG 1684 clinical trial, we conducted a prospective follow-up in an identical population of patients (cutaneous melanoma, T4 and/or N1) treated by intravenous IFN-α-2b:20 MIU m−2, 5 days a week for 4 weeks; and subcutaneous:10 MIU m−2, 3 times a week for 11 months. Thirty-six consecutive patients were considered in four different institutions. The frequency and severity of side-effects related to IFN-α, as well as the percentage of the planned dose given to patients, were identical to those reported in the initial report by ECOG. Fifty per cent and 47% of patients had a grade 3/4 WHO toxicity in the induction and consolidation phase respectively. A dose modification was necessary for 47.2% and 55.8% of the patients in the induction and consolidation phase respectively. The schedule and dose of high-dose IFN-α-2b in the adjuvant treatment of cutaneous malignant melanoma, as reported by ECOG 1684, is feasible. The significant toxicity reported in ECOG 1684 was also seen in our patients. Nevertheless, this protocol will not be a ‘standard’ treatment until the publication of the ECOG 1690 trial. © 1999 Cancer Research Campaign PMID:10468294

  4. High doses of cobalt induce optic and auditory neuropathy.

    PubMed

    Apostoli, Pietro; Catalani, Simona; Zaghini, Anna; Mariotti, Andrea; Poliani, Pietro Luigi; Vielmi, Valentina; Semeraro, Francesco; Duse, Sarah; Porzionato, Andrea; Macchi, Veronica; Padovani, Alessandro; Rizzetti, Maria Cristina; De Caro, Raffaele

    2013-09-01

    The adverse biological effects of continuous exposure to cobalt and chromium have been well defined. In the past, this toxicity was largely an industrial issue concerning workers exposed in occupational setting. Nevertheless, recent reports have described a specific toxicity mediated by the high levels of cobalt and chromium released by metallic prostheses, particularly in patients who had received hip implants. Clinical symptoms, including blindness, deafness and peripheral neuropathy, suggest a specific neurotropism. However, little is known about the neuropathological basis of this process, and experimental evidence is still lacking. We have investigated this issue in an experimental setting using New Zealand White rabbits treated with repeated intravenous injections of cobalt and chromium, alone or in combination. No evident clinical or pathological alterations were associated after chromium administration alone, despite its high levels in blood and tissue while cobalt-chromium and cobalt-treated rabbits showed clinical signs indicative of auditory and optic system toxicity. On histopathological examination, the animals showed severe retinal and cochlear ganglion cell depletion along with optic nerve damage and loss of sensory cochlear hair cells. Interestingly, the severity of the alterations was related to dosages and time of exposure. These data confirmed our previous observation of severe auditory and optic nerve toxicity in patients exposed to an abnormal release of cobalt and chromium from damaged hip prostheses. Moreover, we have identified the major element mediating neurotoxicity to be cobalt, although the molecular mechanisms mediating this toxicity still have to be defined.

  5. 4-week treatment of streptococcal native valve endocarditis with high-dose teicoplanin.

    PubMed Central

    Venditti, M; Gelfusa, V; Serra, P; Brandimarte, C; Micozzi, A; Martino, P

    1992-01-01

    The efficacy and safety of a 4-week course of intravenous teicoplanin (500 mg every 12 h for the first 2 days and 10 mg/kg of body weight every 24 h thereafter) in the treatment of streptococcal native valve endocarditis in 20 patients were evaluated. All blood isolates were inhibited by a concentration of 0.12 micrograms of teicoplanin per ml. Serum bactericidal activity levels were measured 1/2 and 24 h after antibiotic infusion on days 5 to 7 of therapy in 19 patients, and titers of greater than or equal to 1:32 and greater than or equal to 1:8, respectively, were obtained with 17 patients (89%). On the other hand, for two patients who were infected with teicoplanin-tolerant Streptococcus bovis, serum bactericidal activity levels of less than 1:2 were found. Of 20 patients, 4 were excluded from further analysis because of protocol violation or prosthetic valve infection. Of the remaining 16 patients, 6 did not complete teicoplanin therapy because of early death (1 patient) or drug fever (5 patients). Among patients who developed drug fever, three who discontinued teicoplanin by day 15 were switched to penicillin therapy, whereas the remaining two, who discontinued teicoplanin on day 22 and 25, respectively, did not receive any further therapy and have shown no relapse during the follow-up. Of 10 patients who completed trial therapy, 9 were cured and 1 relapsed. It is concluded that a 4-week course of high-dose teicoplanin may be a useful regimen for home treatment of selected cases of streptococcal native valve endocarditis. However, drug fever and infection with teicoplanin-tolerant S. bovis may be factors of concern with this therapeutic approach. PMID:1386972

  6. Improved closure of patent ductus arteriosus with high doses of ibuprofen.

    PubMed

    Meißner, Udo; Chakrabarty, Raktima; Topf, Hans-Georg; Rascher, Wolfgang; Schroth, Michael

    2012-04-01

    The patent ductus arteriosus (PDA) is associated with various complications of prematurity. Cyclooxygenase-inhibitors are the first-line intervention for closure of the PDA. However, the rates of PDA closure still are unsatisfactory. Therefore, an individual trial was performed by changing the strategy for treating neonates with ibuprofen to induce the closure of PDA. In a retrospective study, patients receiving 20, 10, and 10 mg/kg bodyweight ibuprofen (group 1) were compared by chart review with those receiving 10, 5, 5 mg/kg (group 2). The rate of PDA closure, the incidence of side effects related to the use of ibuprofen, and the need for surgical intervention for closure of the PDA were analyzed. A higher rate of closure after three doses in group 1 could be observed (60.9 vs 52.6%; p = 0.75), which was not significant but indicated a clear positive trend. If closure of the PDA was unsuccessful, intravenous ibuprofen was continued for an additional 2 days. After 5 days, 91.3% of PDA in group 1 was closed compared with 68.4% PDA in group 2. In summary, only 8.7% of the group 1 neonates needed surgical closure of PDA after insufficient medicamentous closure compared with 31.6% in group 2 (p = 0.25). Although not statistically significant, a clear positive trend for using the higher-dose medication can be seen. More work dealing with the limitations of a retrospective study must be done. Based on the data from this study, high-dose ibuprofen seems able to increase the rate of effective medicamentous PDA closure without any further unwanted side effects.

  7. High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

    PubMed Central

    Jindani, Amina; Harrison, Thomas S.; Nunn, Andrew J.; Phillips, Patrick P.J.; Churchyard, Gavin J.; Charalambous, Salome; Hatherill, Mark; Geldenhuys, Hennie; McIlleron, Helen M.; Zvada, Simbarashe P.; Mungofa, Stanley; Shah, Nasir A.; Zizhou, Simukai; Magweta, Lloyd; Shepherd, James; Nyirenda, Sambayawo; van Dijk, Janneke H.; Clouting, Heather E.; Coleman, David; Bateson, Anna L.E.; McHugh, Timothy D.; Butcher, Philip D.; Mitchison, Denny A.

    2014-01-01

    BACKGROUND Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS The 6-month regimen that included weekly administration of high-dose rifapentine and

  8. Dosimetry modeling for focal high-dose-rate prostate brachytherapy.

    PubMed

    Mason, Josh; Al-Qaisieh, Bashar; Bownes, Peter; Thwaites, David; Henry, Ann

    2014-01-01

    The dosimetry of focal high-dose-rate prostate brachytherapy was assessed. Dose volume histogram parameters, robustness to source position errors, and Monte Carlo (MC) simulations were compared for whole-gland (WG), hemi-gland (HEMI), and ultra-focal (UF) treatment plans. Tumor volumes were delineated based on MRI and template biopsy results for 9 patients. WG, HEMI, and UF plans were produced assuming 19 Gy single fraction monotherapy treatments. For UF plans, a 6-mm margin was applied to the visible tumor to create a focal-planning target volume (F-PTV). Systematic source position shifts of 1-4 mm were applied to assess plan robustness. The dosimetric impact of steel catheters was assessed using MC simulation. Mean D90 and V100 were 20.4 Gy and 97.9% for prostate in WG plans, 22.2 Gy and 98.1% for hemi-prostate in HEMI plans, and 23.0 Gy and 98.2% for F-PTV in UF plans. Mean urethra D10 was 20.3, 19.7, and 9.2 Gy in WG, HEMI, and UF plans, respectively. Mean rectal D2cc was 12.5, 9.8, and 4.6 Gy in WG, HEMI, and UF plans, respectively. Focal treatment plans were sensitive to source position errors-2 mm systematic shifts reduced mean prostate D90 by 0.7%, hemi-prostate D90 by 2.6%, and F-PTV D90 by 8.3% in WG, HEMI, and UF plans, respectively. MC simulation results were similar for all plan types with most dose volume histogram parameters reduced by <2%. HEMI and UF treatments can achieve higher D90 values compared with WG treatments with reduced organ at risk dose. Focal treatments are more sensitive to systematic source position errors than WG treatments. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  9. Cauda equina tolerance to high-dose fractionated irradiation

    SciTech Connect

    Pieters, Richard S.; Niemierko, Andrzej; Fullerton, Barbara C.; Munzenrider, John E. . E-mail: jmunzenrider@partners.org

    2006-01-01

    Purpose: To report late neurologic toxicity rates and clinical outcomes for patients treated with high dose fractionated radiation therapy using three-dimensional treatment planning and combined proton and photon beams to portions of the cauda equina (L2-coccyx). Methods and Materials: Medical records of 53 patients treated to fields encompassing the cauda equina were reviewed for the onset of neurologic symptoms in the absence of local failure. All doses were normalized to equivalent dose delivered in 2-Gy fractions. Median cauda dose was 65.8 cobalt Gray equivalents (CGE) (range, 31.9-85.1). Median follow-up was 87 months (range, 14-217 months). Results: Nineteen patients experienced local recurrences, and 13 others had neurologic toxicity. A total of 54% (i.e., 7/13) of the toxicities occurred 5 years or more after treatment. Median caudal dose was 73.7 CGE in the group with neurologic toxicity, and 55.6 CGE in those without. On multivariate actuarial analysis, cauda dose and gender were statistically significant for neurotoxicity at p = 0.002 and p = 0.017, respectively. The estimated tolerance doses 5 years from treatment, TD 5/5 and TD 50/5, were 55 CGE and 72 CGE, respectively, for males and 67 CGE and 84 CGE for females. The tolerance doses were about 8 CGE lower when estimated at 10 years from treatment. Disease-free survival rates at 5 and 10 years were 66% and 53%, respectively. Conclusions: This study suggests that the probability of neurotoxicity is a relatively steep function of dose to cauda equina (slope {gamma}{sub 5} = approximately 3). The cauda equina tolerance is greater for females than males by about 11 CGE (at 2 CGE per fraction). Extended follow-up is necessary to accurately assess neurologic damage and then differentiate that phenomenon from local recurrence; the traditional 5-year assessment has limited meaning in this population. Local control remains an issue for these patients, even with the radical doses used.

  10. High-dose neutron irradiation performance of dielectric mirrors

    SciTech Connect

    Nimishakavi Anantha Phani Kiran Kumar; Leonard, Keith J.; Jellison, Jr., Gerald Earle; Snead, Lance Lewis

    2015-05-01

    The study presents the high-dose behavior of dielectric mirrors specifically engineered for radiation tolerance. Alternating layers of Al2O3/SiO2 and HfO2/SiO2 were grown on sapphire substrates and exposed to neutron doses of I and 4 displacements per atom (dpa) at 458 ± 10 K in the High Flux Isotope Reactor (HFIR). In comparison to previously reported results, these higher doses of 1 and 4 dpa result in a drastic drop in optical reflectance, caused by a failure of the multilayer coating. HfO2/SiO2 mirrors failed completely when exposed to I dpa, whereas the reflectance of Al2O3/SiO2 mirrors reduced to 44%, eventually failing at 4 dpa. Transmission electron microscopy (TEM) observation of the Al2O3/SiO2 specimens showed SiO2 layer defects, which increase in size with irradiation dose. The typical size of each defect was approximate to 8 nm in 1-dpa specimens and ≈ 42 nm in 4-dpa specimens. Buckling-type delamination of the interface between the substrate and first layer was typically observed in both 1- and 4-dpa HfO2/SiO2 specimens. Composition changes across the layers were measured in high-resolution-scanning-TEM mode using energy dispersive spectroscopy. Lastly, a significant interdiffusion between the film layers was observed in the Al2O3/SiO2 mirror, although it was less evident in the HfO2/SiO2 system. The ultimate goal of this work is to provide insight into the radiation-induced failure mechanisms of these mirrors.

  11. Efficacy and safety of metronidazole injection for the treatment of infectious peritonitis, abdominal abscess and pelvic inflammatory diseases in Japan.

    PubMed

    Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Nagashima, Masahito

    2015-02-01

    Although metronidazole (MNZ) has been used worldwide for more than 4 decades as a standard therapy for trichomoniasis, anaerobic and amebic infections, resistance to MNZ is still low. MNZ is available as oral, intravenous, and vaginal formulations, but the intravenous formulation of MNZ has not been approved in Japan. We conducted a phase 3 study to evaluate the efficacy and safety of intravenous MNZ combined with ceftriaxone (CTRX) in Japanese subjects with infectious peritonitis, abdominal abscess or pelvic inflammatory diseases (PIDs) to obtain regulatory approval. A combination of MNZ/CTRX at doses of 500 mg 3 or 4 times a day/1 or 2 g twice a day was administered intravenously to a total of 38 hospitalized subjects. MNZ/CTRX was well tolerated and exhibited excellent clinical and bacteriological efficacy with clinical efficacy rates of 100% (20/20) in infectious peritonitis or abdominal abscess subjects and 90.0% (9/10) in PID subjects, and the eradication rates in infectious peritonitis or abdominal abscess subjects and PID subjects were 100% (16/16) and 100% (4/4), respectively, at the test of cure. MNZ/CTRX was effective in 1 subject in whom a metallo-β-lactamase-producing Bacteroides fragilis strain (MIC of MNZ, 2 μg/ml) was identified. The most common treatment-related adverse event was diarrhea (23.7%), followed by nausea (5.3%). No new safety signals were identified. MNZ/CTRX demonstrated excellent efficacy and was well tolerated in Japanese infectious peritonitis, abdominal abscess and PID subjects. This treatment regimen can be useful for anaerobic infections. Clinical registration number: NCT01473836. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Sense and nonsense of high-dose cytarabine for acute myeloid leukemia.

    PubMed

    Löwenberg, Bob

    2013-01-03

    High-dose cytarabine applied during remission induction or as consolidation after attainment of a complete remission has become an established element in the treatment of adults with acute myeloid leukemia. Recent evidence has challenged the need for these exceptionally high-dose levels of cytarabine. In this review, we present a reappraisal of the usefulness of high-dose cytarabine for acute myeloid leukemia treatment.

  13. High-dose-rate brachytherapy in uterine cervical carcinoma

    SciTech Connect

    Patel, Firuza D. . E-mail: patelfd@glide.net.in; Rai, Bhavana; Mallick, Indranil; Sharma, Suresh C.

    2005-05-01

    Purpose: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment of cervical cancer. The American Brachytherapy Society has recommended that the individual fraction size be <7.5 Gy and the range of fractions should be four to eight; however, many fractionation schedules, varying from institution to institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in patients with carcinoma of the uterine cervix. We found that our results and toxicity were comparable to those reported in the literature and hereby present our experience with this fractionation schedule. Methods and Materials: A total of 121 patients with Stage I-III carcinoma of the uterine cervix were treated with HDR brachytherapy between 1996 and 2000. The total number of patients analyzed was 113. The median patient age was 53 years, and the histopathologic type was squamous cell carcinoma in 93% of patients. The patients were subdivided into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor size <4 cm, and preserved cervical anatomy underwent simultaneous external beam radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and interdigitated with external beam radiotherapy. The 95 patients in Group 2, who had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range was 3-7 years (median, 36.4 months). Late toxicity was graded according to the Radiation Therapy Oncology Group criteria. Results: The 5-year actuarial local control and disease-free survival rate was 74.5% and 62.0%, respectively. The actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II, and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate was 88.8% for

  14. [Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

    PubMed

    Yokoyama, Yuka; Asaoka, Katsuyuki; Sugiyama, Taku; Uchida, Kazuki; Shimbo, Daisuke; Kobayashi, Satoshi; Itamoto, Koji

    2015-10-01

    Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

  15. Microparticles containing propolis and metronidazole: in vitro characterization, release study and antimicrobial activity against periodontal pathogens.

    PubMed

    de Souza Ferreira, Sabrina Barbosa; de Assis Dias, Bruno Rafael; Obregón, Clarissa Silva; Gomes, Carla Carolina; de Araújo Pereira, Raphaela Regina; Ribeiro Godoy, Janine Silva; Estivalet Svidzinski, Terezinha Inez; Bruschi, Marcos Luciano

    2014-03-01

    Ethylcellulose microparticles containing metronidazole and propolis extractive solution were prepared and evaluated in vitro against periodontal pathogens. Scanning electron microscopy, particle size analysis, drug entrapment efficiency and drug release of microparticles were determined. The antimicrobial activity of microparticles was evaluated against microorganisms of periodontal importance (Enterococcus faecalis, Streptococcus pyogenes, Streptococcus mutans, Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli). It was obtained particles with regular morphology, mean diameter of 1.23 µm, and entrapment efficiency for propolis and metronidazole were 91.41% and 22.23%, respectively. In vitro release studies of propolis and metronidazole from microparticles showed prolonged drug release and controlled by Fickian diffusion. Both propolis and metronidazole displayed activity against the tested strains. Moreover, the results showed that the strains of E. faecalis, S. pyogenes and S. mutans were more susceptible to the propolis and E. faecalis to the metronidazole. It was also observed that the amount of metronidazole to inhibit the microorganism strains in the physical mixture with propolis was smaller than in the metronidazole alone, suggesting potentiation effect between propolis and metronidazole. These microparticles would be useful for developing intermediary or eventual dosage form to be administered into the periodontal pocket more easily and safely.

  16. Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient.

    PubMed

    Graves, Tracey D; Condon, Marie; Loucaidou, Marina; Perry, Richard J

    2009-10-15

    Metronidazole-induced central nervous system (CNS) toxicity causes a spectrum of neurological symptoms including ataxia, encephalopathy and peripheral neuropathy. It is associated with characteristic MRI changes of high signal intensity in the dentate nuclei. Given the increasing use of metronidazole, it is import to recognise this drug as a cause of ataxia, as it is entirely reversible on drug withdrawal.

  17. Universal high-level primary metronidazole resistance in Helicobacter pylori isolated from children in Egypt.

    PubMed

    Sherif, May; Mohran, Zaynab; Fathy, Hanan; Rockabrand, David M; Rozmajzl, Patrick J; Frenck, Robert W

    2004-10-01

    Antimicrobial susceptibility testing was performed on 48 isolates of Helicobacter pylori recovered from Egyptian children undergoing routine endoscopies. The isolates were universally highly resistant to metronidazole, but resistance to other tested antimicrobial agents was rare (4% for clarithromycin, erythromycin, and azithromycin resistance versus 2% for ciprofloxacin and ampicillin resistance). Use of metronidazole for the treatment of H. pylori in Egypt should be avoided.

  18. Anti-emetic effect of high-dose metoclopramide vs alizapride--a randomised crossover study.

    PubMed Central

    Seng, K T; Tiong, C E; Hiang, T C

    1994-01-01

    A randomised double-blind crossover study was undertaken to compare the anti-emetic efficacy of alizapride against high dose metoclopramide. A total of 32 patients on cisplatin were randomised to receive either high dose metoclopramide (7 mg kg-1 day-1) or alizapride (5 mg kg-1 day-1). Anti-emetic responses in terms of control of vomiting episodes were similar in both regimens (59%). However, patients showed a statistically significant preference for high dose metoclopramide (P = 0.02). Side effects of both regimens were minimal. We conclude that alizapride is not superior to high dose metoclopramide in controlling cisplatin induced vomiting. PMID:7826833

  19. High-dose daptomycin plus fosfomycin is safe and effective in treating methicillin-susceptible and methicillin-resistant Staphylococcus aureus endocarditis.

    PubMed

    Miró, José M; Entenza, José M; Del Río, Ana; Velasco, Maria; Castañeda, Ximena; Garcia de la Mària, Cristina; Giddey, Marlyse; Armero, Yolanda; Pericàs, Juan M; Cervera, Carlos; Mestres, Carlos A; Almela, Manuel; Falces, Carlos; Marco, Francesc; Moreillon, Philippe; Moreno, Asuncion

    2012-08-01

    We describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptible Staphylococcus aureus [MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistant S. aureus [MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was tested in vitro against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistant S. aureus isolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.

  20. Comparison between the efficacy of metronidazole vaginal gel and Berberis vulgaris (Berberis vulgaris) combined with metronidazole gel alone in the treatment of bacterial vaginosis

    PubMed Central

    Masoudi, Mansoure; Kopaei, Mahmoud Rafieian; Miraj, Sepideh

    2016-01-01

    Background Bacterial vaginosis is one of the most prevalent complications among reproductive-aged women. Antibacterial and antifungal effects of Berberis vulgaris have been demonstrated in vitro and in vivo. Objectives This study aimed to compare the therapeutic effects of the vaginal gel of Berberis vulgaris 5% (in metronidazole base) with metronidazole vaginal gel 0.75% on bacterial vaginosis on 80 patients referred to the Hajar Hospital from January 2012 to April 2013. Methods This study was a randomized clinical trial research on 80 women affected by bacterial vaginosis, who were randomly divided into two groups of 40 participants. Diagnostic criteria were Amsel’s criteria and Gram stain. Berberis vulgaris 5% (in metronidazole gel base) or metronidazole vaginal gel for five-night usage was prescribed to each group, and after two to seven days therapeutic effects and Amsel criteria were assessed. Data analysis was performed by SPSS 16 using Student t-test, chi-square, and ANOVA tests. Results Findings of the study showed a statistically significant difference with regard to treatment response between the study groups (p<0.001), and the Berberis vulgaris group had a better response than the metronidazole gel group. The patients in groups of Berberis vulgaris in a metronidazole gel base did not experience any relapse, but, in the metronidazole group, 30% of patients experienced relapse during three weeks’ follow-up. Conclusions Findings of the study showed that adding Berberis vulgaris fruit extract on metronidazole improve the efficacy of bacterial vaginosis therapy. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT201411102085N13. Funding Shahrekord University of Medical Sciences supported this research. PMID:27757195

  1. Comparison between the efficacy of metronidazole vaginal gel and Berberis vulgaris (Berberis vulgaris) combined with metronidazole gel alone in the treatment of bacterial vaginosis.

    PubMed

    Masoudi, Mansoure; Kopaei, Mahmoud Rafieian; Miraj, Sepideh

    2016-08-01

    Bacterial vaginosis is one of the most prevalent complications among reproductive-aged women. Antibacterial and antifungal effects of Berberis vulgaris have been demonstrated in vitro and in vivo. This study aimed to compare the therapeutic effects of the vaginal gel of Berberis vulgaris 5% (in metronidazole base) with metronidazole vaginal gel 0.75% on bacterial vaginosis on 80 patients referred to the Hajar Hospital from January 2012 to April 2013. This study was a randomized clinical trial research on 80 women affected by bacterial vaginosis, who were randomly divided into two groups of 40 participants. Diagnostic criteria were Amsel's criteria and Gram stain. Berberis vulgaris 5% (in metronidazole gel base) or metronidazole vaginal gel for five-night usage was prescribed to each group, and after two to seven days therapeutic effects and Amsel criteria were assessed. Data analysis was performed by SPSS 16 using Student t-test, chi-square, and ANOVA tests. Findings of the study showed a statistically significant difference with regard to treatment response between the study groups (p<0.001), and the Berberis vulgaris group had a better response than the metronidazole gel group. The patients in groups of Berberis vulgaris in a metronidazole gel base did not experience any relapse, but, in the metronidazole group, 30% of patients experienced relapse during three weeks' follow-up. Findings of the study showed that adding Berberis vulgaris fruit extract on metronidazole improve the efficacy of bacterial vaginosis therapy. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT201411102085N13. Shahrekord University of Medical Sciences supported this research.

  2. A novel metronidazole fluorescent nanosensor based on graphene quantum dots embedded silica molecularly imprinted polymer.

    PubMed

    Mehrzad-Samarin, Mina; Faridbod, Farnoush; Dezfuli, Amin Shiralizadeh; Ganjali, Mohammad Reza

    2017-06-15

    A novel optical nanosensor for detection of Metronidazole in biological samples was reported. Graphene quantum dots embedded silica molecular imprinted polymer (GQDs-embedded SMIP) was synthesized and used as a selective fluorescent probe for Metronidazole detection. The new synthesized GQDs-embedded SMIP showed strong fluorescent emission at 450nm excited at 365nm which quenched in presence of Metronidazole as a template molecule.. The quenching was proportional to the concentration of Metronidazole in a linear range of at least 0.2μM to 15μM. The limit of detection for metronidazole determination was obtained 0.15μM. The nanosensor successfully worked in plasma matrixes. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. D-allose and D-psicose reinforce the action of metronidazole on trichomonad.

    PubMed

    Harada, Masakazu; Kondo, Emi; Hayashi, Hiromi; Suezawa, Chigusa; Suguri, Setsuo; Arai, Meiji

    2012-04-01

    The effects of D-allose and D-psicose on Tritrichomonas foetus were examined. They were cultured in F-bouillon medium including glucose, but had never increased when glucose was substituted to those sugars. When cultured in a medium including a dose of ED(50) metronidazole and those sugars, trichomonad density was significantly less than that in a medium with metronidazole only. D-Allose remarkably reinforced the action of metronidazole. This means there are some interactions between metronidazole and those sugars. Although the mechanism is not clear, by using those sugars for treatment with metronidazole, the drug dosage could be lowered and the development of drug resistance of trichomonad parasites might be prevented.

  4. [Helicobacter pylori resistance against metronidazole in Switzerland: implications for eradication therapy?].

    PubMed

    Sieber, C C; Frei, R; Beglinger, C; Mossi, S; Binek, J; Schaufelberger, H; Fried, R; Stalder, G A

    1994-08-09

    Gastroduodenal ulcers are strongly associated with Helicobacter pylori (HP) infection. Successful eradication drastically diminishes ulcer recurrence. Most of the eradication schemes include metronidazole (Flagyl). The present study was designed to establish the metronidazole resistance rate in Switzerland. Antral biopsies were taken in 153 patients with suspected ulcers (115 men, 38 women, mean age 46 +/- 16 [SD] years) during upper endoscopy for bacteriological testing. Metronidazole resistance (> 8 micrograms/ml) was found in 47/153 (31%) of the isolates. Resistance was found in no case to amoxicillin (Clamoxyl) (0/104 = 0%) and only in 3% (2/66) to clarithromycin (Klazid). Metronidazole resistance of HP in a third of the isolates studied is comparable to numbers found in other European countries. These findings raise the question whether eradication schemes including metronidazole without prior sensitivity testing are justified. Amoxicillin and clarithromycin appear to be valid alternatives.

  5. Clindamycin vaginal cream vs oral metronidazole in the treatment of bacterial vaginosis.

    PubMed

    Arredondo, J L; Higuera, F; Hidalgo, H; Narcio, L; Casanova, G; Beltran, M; Sanchez, C J

    1992-01-01

    This study was designed to compare the safety/efficacy of the treatment of 2% clindamycin vaginal cream and oral metronidazole in 184 women with bacterial vaginosis. This was a randomized, prospective, multicenter, double-blind, controlled study. Patients were randomized to either Clindamycin phosphate vaginal cream 2%, 5 gm intravaginally at bedtime, and placebo oral metronidazole capsules taken twice daily, or oral metronidazole capsules, 500 mg, taken twice daily, and placebo clindamycin vaginal cream, 5 gm to be administered intravaginally at bedtime. All treatments were for 7 days. Patients were seen for followup at 4-13 days and 20-43 days after completion of protocol therapy. 2 investigators in Mexico City enrolled a total of 184 patients (91 clindamycin and 93 metronidazole). 1 patient never received drugs after enrollment, leaving 183 valuable for safety. A total of 114 were valuable for efficacy. Protocol regimens were comparable in efficacy (p=0.22) and the percentage of cure/improvement was 87% in the clindamycin group compared to 79% in the metronidazole group. No relapse was observed in the clindamycin group, as opposed to 7% in the metronidazole group. The clindamycin group had a failure of 13% while this was 15% in the metronidazole group. Both treatments were well-tolerated. Most of the events were either vulvovaginal irritation upon application of the study drug, or the development of vaginitis/cervicitis. The 1 event classified as serious in this study (metronidazole group) was generalized rash which, in the opinion of the investigator, was related to the study drug. There were 4 nongenital tract side effects (1 gastrointestinal, 2 dermatologic, and 1 allergy) all in the metronidazole group. The authors can conclude that clindamycin 2% vaginal cream is at least as effective as orally administered metronidazole for the treatment of bacterial vaginosis in nonpregnant women.

  6. A prospective study of risk factors and historical trends in metronidazole failure for Clostridium difficile infection

    PubMed Central

    Hu, Mary Y.; Maroo, Seema; Kyne, Lorraine; Cloud, Jeffrey; Tummala, Sanjeev; Katchar, Kianoosh; Dreisbach, Valley; Noddin, Laura; Kelly, Ciarán P.

    2009-01-01

    Background & Aims Recent studies of C. difficile infection (CDI) indicate a dramatic increase in metronidazole failure. The aims of this study were to compare current and historical rates of metronidazole failure and identify risk factors for metronidazole failure. Methods 89 patients with CDI in 2004–2006 were followed for 60 days. Data were compared to a historical cohort of 63 CDI patients studied prospectively in 1998. Metronidazole failure was defined as persistent diarrhea after 10 days of therapy or a change of therapy to vancomycin. Stool samples were analyzed for the presence of NAP-1 strain. Results Metronidazole failure rates were 35% in both the 1998 and 2004–2006 cohorts. There was no difference in the median time to resolution of diarrhea (8 vs. 5 days, p = 0.52) or the proportion with more than 10 days of diarrhea (35% vs. 29%, p = 0.51). Risk factors for metronidazole failure included recent cephalosporin use (OR 32, 95% CI 5–219), CDI on admission (OR 23, 95% CI 3–156), and transfer from another hospital (OR 11, 95% CI 2–72). The frequency of NAP-1 infection in patients with and without metronidazole failure was similar (26% vs. 21%, p = 0.67). Conclusions We found no difference in metronidazole failure rates in 1998 and 2004–2006. Patients with recent cephalosporin use, CDI on admission, and transfer from another hospital were more likely to fail metronidazole and may benefit from early aggressive therapy. Infection with the epidemic NAP-1 strain was not associated with metronidazole failure in endemic CDI. PMID:19081526

  7. High-dose cyclophosphamide and adriamycin with DTIC maintenance for metastatic soft tissue sarcomas.

    PubMed

    Clamon, G; Sinkey, C; Jochimsen, P

    1983-08-01

    Intensive chemotherapy with high-dose cyclophosphamide and adriamycin with DTIC maintenance was given to 12 patients with metastatic soft tissue sarcomas. A partial response rate of 25% was seen; this is no better than can be achieved with single-agent therapy. Because of substantial toxicity without improved efficacy, the trial of high dose therapy was halted.

  8. Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

    PubMed

    Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

    2016-04-01

    We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (aged<15 years) with focal seizures treated with high-dose phenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. Potential intravenous drug incompatibilities in a pediatric unit

    PubMed Central

    Leal, Karla Dalliane Batista; Leopoldino, Ramon Weyler Duarte; Martins, Rand Randall; Veríssimo, Lourena Mafra

    2016-01-01

    ABSTRACT Objective To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. Methods A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student’s t test and ANOVA; the level of significance was set at 5% (p<0.05). Relative risks were calculated for each drug involved in potential incompatibility with 95% confidence interval. Results A total of 222 children participated in the study; 132 (59.5%) children were male and 118 (53.2%) were aged between 0 and 2 years. The mean length of stay was 7.7±2.3 days. Dipyrone, penicillin G and ceftriaxona were the most commonly prescribed drugs. At least one potential incompatibility was detected in about 85% of children (1.2 incompatibility/patient ratio). Most incompatibilities detected fell into the non-tested (93.4%), precipitation (5.5%), turbidity (0.7%) or chemical decomposition (0.4%) categories. The number of drugs and prescription of diazepam, phenytoin, phenobarbital or metronidazole were risk factors for potential incompatibility. Conclusion Most pediatric prescriptions involved potential incompatibilities, with higher prevalence of non-tested incompatibilities. The number of drugs and prescription of diazepam, phenobarbital, phenytoin or metronidazole were risk factors for potential incompatibilities. PMID:27462891

  10. Cytogenetic study of metronidazole and three metronidazole analogues in cultured human lymphocytes with and without metabolic activation.

    PubMed

    Gómez-Arroyo, Sandra; Melchor-Castro, Sara; Villalobos-Pietrini, Rafael; Camargo, Estela Meléndez; Salgado-Zamora, Héctor; Campos Aldrete, Maria Elena

    2004-06-01

    Metronidazole (MTZ) and other nitroimidazole derivatives have been extensively used to treat infections caused by protozoa and anaerobic bacteria. However, the need for new derivatives with similar therapeutic activity but lower toxicity to human beings prevails. On this purpose, three metronidazole analogues were synthesized, namely: 1-(p-methylphenacyl)-2-methyl-4-nitro imidazole (CPMe), 1-(p-methoxyphenacyl)-2-methyl-4-nitroimidazole (CPMeO), and 1-(p-fluorphenacyl)-2-methyl-4-nitroimidazole (CPF), which at low concentrations (0.5-2 microg/ml) showed a higher activity against Entamoeba histolytica than MTZ (3-6 microg/ml). The aim of this work was to investigate the cytogenetic effect of the three MTZ analogues on human lymphocyte cultures with and without metabolic activation in vitro, using the sister chromatid exchange test (SCE), comparatively with MTZ. The effect of the compounds on the cell proliferation kinetics (CPK) measured by the replication index (RI) and the cytotoxic effect in the mitotic index (MI) was evaluated as well. The SCE frequencies with and without S9 metabolic activation in treated and control lymphocytes showed no significant statistical differences. However when metabolic activation was involved a significant increase in the amount of third division metaphases provoked the CPK increased significantly with all the tested compounds. The RI showed similar behaviour, except for compound CPF.

  11. Subinhibitory concentrations of metronidazole increase biofilm formation in Clostridium difficile strains.

    PubMed

    Vuotto, Claudia; Moura, Ines; Barbanti, Fabrizio; Donelli, Gianfranco; Spigaglia, Patrizia

    2016-03-01

    Resistance mechanism to metronidazole is still poorly understood, even if the number of reports on Clostridium difficile strains with reduced susceptibility to this antibiotic is increasing. In this study, we investigated the ability of the C. difficile strains 7032994, 7032985 and 7032989, showing different susceptibility profiles to metronidazole but all belonging to the PCR ribotype 010, to form biofilm in vitro in presence and absence of subinhibitory concentrations of metronidazole. The quantitative biofilm production assay performed in presence of metronidazole revealed a significant increase in biofilm formation in both the susceptible strain 7032994 and the strain 7032985 exhibiting a reduced susceptibility to this antibiotic, while antibiotic pressure did not affect the biofilm-forming ability of the stable-resistant strain 7032989. Moreover, confocal microscopy analysis showed an abundant biofilm matrix production by the strains 7032994 and 7032885, when grown in presence of metronidazole, but not in the stable-resistant one. These results seem to demonstrate that subinhibitory concentrations of metronidazole are able to enhance the in vitro biofilm production of the above-mentioned PCR ribotype 010 C. difficile strains, susceptible or with reduced susceptibility to this antibiotic, suggesting a possible role of biofilm formation in the multifactorial mechanism of metronidazole resistance developed by C. difficile. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Effect of metronidazole use on tacrolimus concentrations in transplant patients treated for Clostridium difficile.

    PubMed

    Early, C R; Park, J M; Dorsch, M P; Pogue, K T; Hanigan, S M

    2016-10-01

    Two case reports suggest that metronidazole treatment for Clostridium difficile infections (CDI) increases tacrolimus (TAC) trough levels. The primary objective of this study was to determine the clinical significance of this potential interaction in transplant patients receiving CDI treatment. Currently, no robust literature exists to estimate a magnitude of pharmacokinetic interaction between metronidazole and TAC. In this retrospective study, the effects of CDI and metronidazole treatment on TAC levels in 52 adult solid organ transplant patients were investigated. The primary outcome was to determine the difference in dose-normalized TAC levels between baseline and symptom resolution in patients treated with metronidazole or vancomycin. The secondary outcome was to determine the difference in dose-normalized TAC levels at baseline and CDI diagnosis. The average change in log-transformed dose-normalized TAC levels from baseline to symptom resolution was 0.99 for metronidazole (n = 35) and 1.04 for vancomycin (n = 17) treatment. The mean difference between the groups was 0.96 (95% confidence interval: 0.74-1.24). No significant difference was found between dose-normalized TAC levels at CDI diagnosis and baseline (P = 0.37). CDI treatment with metronidazole was not associated with a >30% increase in TAC levels compared with vancomycin. Both treatment groups required TAC dose adjustments to maintain goal TAC levels and those treated with metronidazole did not require a significantly greater dose adjustment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Characterization of a Stable, Metronidazole-Resistant Clostridium difficile Clinical Isolate

    PubMed Central

    Lynch, Tarah; Chong, Patrick; Zhang, Jason; Hizon, Romeo; Du, Tim; Graham, Morag R.; Beniac, Daniel R.; Booth, Timothy F.; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Mulvey, Michael R.

    2013-01-01

    Background Clostridium difficile are Gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15–35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. Methodology/Principal Findings Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP) level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. Conclusions/Significance This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described. PMID:23349739

  14. Characterization of a stable, metronidazole-resistant Clostridium difficile clinical isolate.

    PubMed

    Lynch, Tarah; Chong, Patrick; Zhang, Jason; Hizon, Romeo; Du, Tim; Graham, Morag R; Beniac, Daniel R; Booth, Timothy F; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Mulvey, Michael R

    2013-01-01

    Clostridium difficile are gram-positive, spore forming anaerobic bacteria that are the leading cause of healthcare-associated diarrhea, usually associated with antibiotic usage. Metronidazole is currently the first-line treatment for mild to moderate C. difficile diarrhea however recurrence occurs at rates of 15-35%. There are few reports of C. difficile metronidazole resistance in the literature, and when observed, the phenotype has been transient and lost after storage or exposure of the bacteria to freeze/thaw cycles. Owing to the unstable nature of the resistance phenotype in the laboratory, clinical significance and understanding of the resistance mechanisms is lacking. Genotypic and phenotypic characterization was performed on a metronidazole resistant clinical isolate of C. difficile. Whole-genome sequencing was used to identify potential genetic contributions to the phenotypic variation observed with molecular and bacteriological techniques. Phenotypic observations of the metronidazole resistant strain revealed aberrant growth in broth and elongated cell morphology relative to a metronidazole-susceptible, wild type NAP1 strain. Comparative genomic analysis revealed single nucleotide polymorphism (SNP) level variation within genes affecting core metabolic pathways such as electron transport, iron utilization and energy production. This is the first characterization of stable, metronidazole resistance in a C. difficile isolate. The study provides an in-depth genomic and phenotypic analysis of this strain and provides a foundation for future studies to elucidate mechanisms conferring metronidazole resistance in C. difficile that have not been previously described.

  15. Topical metronidazole can reduce pain after surgery and pain on defecation in postoperative hemorrhoidectomy.

    PubMed

    Ala, Shahram; Saeedi, Majid; Eshghi, Fariborz; Mirzabeygi, Parastou

    2008-02-01

    Topical metronidazole (10 percent) has been previously demonstrated to decrease postoperative pain after hemorrhoidectomy. The aim of this study was to evaluate the effect of topical metronidazole (10 percent) in reducing postoperative and after-defecation pain of hemorrhoidectomy. A double-blind, randomized trial was conducted to compare posthemorrhoidectomy pain with use of topical metronidazole (10 percent) vs. placebo carrier, applied to surgical site. Forty-seven patients were randomly allocated to receive metronidazole (n=25) or placebo (n=22). Pain was assessed using a visual analog scale preoperatively and on postoperative hours 6 and 12 and at days 1, 2, 7, and 14. The use of narcotic, additional analgesics, and complications were recorded. (Pain scores were calculated and compared with baseline values and control group (t test, SPSS ver.10). Patients in the topical metronidazole group had significantly less postoperative pain than those in the placebo group up to day 14 (P metronidazole group, after-defecation pain was ranked significantly lower at day 2 (P=0.016) and patients required fewer additional analgesics postoperatively on days 2 and 7 (P metronidazole significantly reduce posthemorrhoidectomy discomfort, and postoperative defecation pain is reduced compared with that of the placebo control group.

  16. Helicobacter pylori infection treated with a tripotassium dicitrato bismuthate and metronidazole combination.

    PubMed

    Weil, J; Bell, G D; Powell, K; Morden, A; Harrison, G; Gant, P W; Jones, P H; Trowell, J E

    1990-12-01

    Seventy-two patients with H. pylori infection in their antral mucosa took part in the study. Forty-three received metronidazole 400 mg t.d.s. for two weeks, plus De-Nol tabs 2 b.d. for four weeks, and the remaining 29 patients received metronidazole 400 mg t.d.s. for two weeks plus De-Nol liquid 5 ml q.d.s. for four weeks. Seven of 57 H. pylori isolates were found to have pre-treatment metronidazole resistance. Success, in terms of eradication of H. pylori, was assessed using a one-month post-treatment 14C urea breath test. Successful eradication of H. pylori was achieved in 72% and 79%, respectively, of the metronidazole/De-Nol tablet and metronidazole/De-Nol liquid groups. These figures increased to 87% and 84%, respectively, if the patients whose organisms were known to be metronidazole-sensitive were considered in isolation. H. pylori was successfully eradicated in only one of seven patients with a metronidazole-resistant organism.

  17. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis.

    PubMed

    Sobel, Jack D; Ferris, Daron; Schwebke, Jane; Nyirjesy, Paul; Wiesenfeld, Harold C; Peipert, Jeffrey; Soper, David; Ohmit, Suzanne E; Hillier, Sharon L

    2006-05-01

    Efficacy study of suppressive vaginal metronidazole in reducing recurrent symptomatic episodes of bacterial vaginosis. Multicenter prospective study with initial 10-day open-label metronidazole gel in which asymptomatic responders randomly assigned to receive twice weekly metronidazole vaginal gel or placebo for 16 weeks and off therapy for 12 weeks. Of 157 eligible women with recurrent bacterial vaginosis, 112 of 127 returning evaluable women (88.2%) responded clinically and were randomly assigned. During suppressive therapy, recurrent bacterial vaginosis occurred in 13 women (25.5%) receiving metronidazole and 26 (59.1%) receiving placebo (MITT analysis, relative risk [RR] 0.43, CI = 0.25-0.73, P = .001). During the entire 28-week follow-up, recurrence occurred in 26 (51.0%) on treatment compared with 33 (75%) on placebo (RR 0.68, CI = 0.49-0.93, P = .02). Probability for remaining cured was 70% for metronidazole compared with 39% on placebo, which declined to 34% and 18%, respectively, by 28 weeks follow-up. Adverse effects were uncommon; however, secondary vaginal candidiasis occurred significantly more often in metronidazole-treated women (P = .02). Suppressive therapy with twice-weekly metronidazole gel achieves a significant reduction in the recurrence rate of bacterial vaginosis; however, secondary vaginal candidiasis is common.

  18. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation

    PubMed Central

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-01-01

    Abstract Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate. This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2 g/kg), a single dose of rituximab (375 mg/m2), and 4 doses of bortezomib (1.3 mg/m2). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients. There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83 ± 16.0 (14952 ± 5820) and 63 ± 36.0 (10321 ± 7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468–634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group. In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients. PMID:26844479

  19. Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation.

    PubMed

    Jeong, Jong Cheol; Jambaldorj, Enkthuya; Kwon, Hyuk Yong; Kim, Myung-Gyu; Im, Hye Jin; Jeon, Hee Jung; In, Ji Won; Han, Miyeun; Koo, Tai Yeon; Chung, Junho; Song, Eun Young; Ahn, Curie; Yang, Jaeseok

    2016-02-01

    Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2  g/kg), a single dose of rituximab (375  mg/m), and 4 doses of bortezomib (1.3  mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83  ±  16.0 (14952  ±  5820) and 63  ±  36.0 (10321  ±  7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor-specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients.

  20. Pharmacokinetics of moxifloxacin and high-dose levofloxacin in severe lower respiratory tract infections.

    PubMed

    Kontou, Paschalina; Manika, Katerina; Chatzika, Kalliopi; Papaioannou, Maria; Sionidou, Maria; Pitsiou, Georgia; Kioumis, Ioannis

    2013-09-01

    This study evaluated the pharmacokinetics of intravenous moxifloxacin 400 mg once and levofloxacin 500 mg twice daily in patients with lower respiratory tract infections (LRTIs) and assessed their pharmacodynamic adequacy against common respiratory pathogens. Eighteen patients with LRTIs hospitalised in general wards were included. Serial blood samples were obtained at steady state and concentrations were determined using HPLC. Pharmacokinetic variables were estimated by a two-compartment model. The characteristic pharmacodynamic parameter for fluoroquinolones (AUC(0-24)/MIC) was calculated. Peak and trough concentrations were, respectively, 4.81 ± 1.03 and 0.59 ± 1.13 mg/L for moxifloxacin and 6.42 ± 1.08 and 0.79 ± 0.39 mg/L for levofloxacin. Pharmacokinetic data for moxifloxacin and levofloxacin, respectively, were: CL, 10.27 ± 1.24 and 22.66 ± 6.62 L/h; t1/2, 13.43 ± 5.12 and 6.75 ± 1.34 h; Vss, 163.03 ± 53.88 and 170.73 ± 39.59 L; and AUC(0-24), 39.38 ±5.28 and 47.06 ± 14.09 mg·h/L. The pharmacodynamic target was attained in all patients by both antibiotics against the majority of respiratory pathogens. Moxifloxacin proved to be pharmacodynamically efficacious against Gram-positive bacteria with MICs ≤ 0.79 mg/L and Gram-negative bacteria with MICs ≤ 0.32 mg/L. These MIC thresholds for levofloxacin were 1.1 mg/L and 0.38 mg/L, respectively. Moxifloxacin and high-dose levofloxacin show a favourable pharmacokinetic profile in plasma of patients with severe LRTIs, without significant interpatient variability. They ensure optimal pharmacodynamic exposure against the majority of microbes involved in these infections. However, the predicted efficacy against Gram-negative bacteria with MICs ≥ 0.5 mg/L appears to be low.

  1. Proteomic Analysis of a NAP1 Clostridium difficile Clinical Isolate Resistant to Metronidazole

    PubMed Central

    Chong, Patrick M.; Lynch, Tarah; McCorrister, Stuart; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Westmacott, Garrett R.; Mulvey, Michael R.

    2014-01-01

    Background Clostridium difficile is an anaerobic, Gram-positive bacterium that has been implicated as the leading cause of antibiotic-associated diarrhea. Metronidazole is currently the first-line treatment for mild to moderate C. difficile infections. Our laboratory isolated a strain of C. difficile with a stable resistance phenotype to metronidazole. A shotgun proteomics approach was used to compare differences in the proteomes of metronidazole-resistant and -susceptible isolates. Methodology/Principal Findings NAP1 C. difficile strains CD26A54_R (Met-resistant), CD26A54_S (reduced- susceptibility), and VLOO13 (Met-susceptible) were grown to mid-log phase, and spiked with metronidazole at concentrations 2 doubling dilutions below the MIC. Peptides from each sample were labeled with iTRAQ and subjected to 2D-LC-MS/MS analysis. In the absence of metronidazole, higher expression was observed of some proteins in C. difficile strains CD26A54_S and CD26A54_R that may be involved with reduced susceptibility or resistance to metronidazole, including DNA repair proteins, putative nitroreductases, and the ferric uptake regulator (Fur). After treatment with metronidazole, moderate increases were seen in the expression of stress-related proteins in all strains. A moderate increase was also observed in the expression of the DNA repair protein RecA in CD26A54_R. Conclusions/Significance This study provided an in-depth proteomic analysis of a stable, metronidazole-resistant C. difficile isolate. The results suggested that a multi-factorial response may be associated with high level metronidazole-resistance in C. difficile, including the possible roles of altered iron metabolism and/or DNA repair. PMID:24400070

  2. Search for novel candidate mutations for metronidazole resistance in Helicobacter pylori using next-generation sequencing.

    PubMed

    Binh, Tran Thanh; Suzuki, Rumiko; Trang, Tran Thi Huyen; Kwon, Dong Hyeon; Yamaoka, Yoshio

    2015-04-01

    Metronidazole resistance is a key factor associated with Helicobacter pylori treatment failure. Although this resistance is mainly associated with mutations in the rdxA and frxA genes, the question of whether metronidazole resistance is caused by the inactivation of frxA alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible H. pylori strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant H. pylori strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in frxA (hp0642), rdxA (hp0954), and rpsU (hp0562) were confirmed by the Sanger method. The mutated sequence in rdxA was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in rdxA showed a low MIC (16 mg/liter), while those containing mutations in both rdxA and frxA showed a higher MIC (48 mg/liter). No transformants containing a single mutation in frxA or rpsU were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in rdxA are mainly associated with metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance only in the presence of rdxA mutations. Moreover, mutations in rpsU may play a role in metronidazole resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Metronidazole-Induced Encephalopathy in Alcoholic Liver Disease: A Diagnostic and Therapeutic Challenge.

    PubMed

    Sonthalia, Nikhil; Pawar, Sunil V; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Rathi, Pravin M; Contractor, Qais

    2016-10-01

    Acute encephalopathy in a patient with alcoholic liver disease (ALD) is a commonly encountered emergency situation occurring most frequently due to liver failure precipitated by varying etiologies. Acute reversible cerebellar ataxia with confusion secondary to prolonged metronidazole use has been reported rarely as a cause of encephalopathy in patients with ALD. We describe a decompensated ALD patient with recurrent pyogenic cholangitis associated with hepatolithiasis who presented to the emergency department with sudden-onset cerebellar ataxia with dysarthria and mental confusion after prolonged use of metronidazole. Magnetic resonance imaging (MRI) of the brain was suggestive of bilateral dentate nuclei hyper intensities on T2 and fluid-attenuated inversion recovery sections seen classically in metronidazole-induced encephalopathy (MIE). Decompensated liver cirrhosis resulted in decreased hepatic clearance and increased cerebrospinal fluid concentration of metronidazole leading to toxicity at a relatively low total cumulative dose of 22 g. Both the clinical symptoms and MRI brain changes were reversed at 7 days and 6 weeks, respectively, after discontinuation of metronidazole. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with ALD presenting with encephalopathy creates a diagnostic dilemma for the emergency physician regarding whether to continue metronidazole and treat for hepatic encephalopathy or to suspect for MIE and withhold the drug. Failure to timely discontinue metronidazole may worsen the associated hepatic encephalopathy in these patients. Liver cirrhosis patients have higher mean concentration of metronidazole and its metabolite in the blood, making it necessary to keep the cumulative dose of metronidazole to < 20 g in them. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Search for Novel Candidate Mutations for Metronidazole Resistance in Helicobacter pylori Using Next-Generation Sequencing

    PubMed Central

    Binh, Tran Thanh; Suzuki, Rumiko; Trang, Tran Thi Huyen; Kwon, Dong Hyeon

    2015-01-01

    Metronidazole resistance is a key factor associated with Helicobacter pylori treatment failure. Although this resistance is mainly associated with mutations in the rdxA and frxA genes, the question of whether metronidazole resistance is caused by the inactivation of frxA alone is still debated. Furthermore, it is unclear whether there are other mutations involved in addition to the two genes that are associated with resistance. A metronidazole-resistant strain was cultured from the metronidazole-susceptible H. pylori strain 26695-1 by exposure to low concentrations of metronidazole. The genome sequences of both susceptible and resistant H. pylori strains were determined by Illumina next-generation sequencing, from which putative candidate resistance mutations were identified. Natural transformation was used to introduce PCR products containing candidate mutations into the susceptible parent strain 26695-1, and the metronidazole MIC was determined for each strain. Mutations in frxA (hp0642), rdxA (hp0954), and rpsU (hp0562) were confirmed by the Sanger method. The mutated sequence in rdxA was successfully transformed into strain 26695-1, and the transformants showed resistance to metronidazole. The transformants containing a single mutation in rdxA showed a low MIC (16 mg/liter), while those containing mutations in both rdxA and frxA showed a higher MIC (48 mg/liter). No transformants containing a single mutation in frxA or rpsU were obtained. Next-generation sequencing was used to identify mutations related to drug resistance. We confirmed that the mutations in rdxA are mainly associated with metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance only in the presence of rdxA mutations. Moreover, mutations in rpsU may play a role in metronidazole resistance. PMID:25645832

  5. Evaluation of Nitrofurantoin Combination Therapy of Metronidazole-Sensitive and -Resistant Helicobacter pylori Infections in Mice

    PubMed Central

    Jenks, Peter J.; Ferrero, Richard L.; Tankovic, Jacques; Thiberge, Jean-Michel; Labigne, Agnès

    2000-01-01

    The main objectives of this study were to determine whether the nitroreductase enzyme encoded by the rdxA gene of Helicobacter pylori was responsible for reductive activation of nitrofurantoin and whether a triple-therapy regimen with nitrofurantoin was able to eradicate metronidazole-sensitive and -resistant H. pylori infections from mice. The susceptibilities to nitrofurantoin of parent and isogenic rdxA mutant strains (three pairs), as well as a series of matched metronidazole-sensitive and -resistant strains isolated from mice (30) and patients (20), were assessed by agar dilution determination of the MIC. Groups of mice colonized with the metronidazole-sensitive H. pylori SS1 strain or a metronidazole-resistant rdxA SS1 mutant were treated with either metronidazole or nitrofurantoin as part of a triple-therapy regimen. One month after the completion of treatment the mice were sacrificed and their stomachs were cultured for H. pylori. The nitrofurantoin MICs for all strains tested were between 0.5 and 4.0 μg/ml. There was no significant difference between the susceptibility to nitrofurantoin of the parental strains and those of respective rdxA mutants or between those of matched metronidazole-sensitive and -resistant H. pylori isolates. The regimen with metronidazole eradicated infection from all eight SS1-infected mice and from one of eight mice inoculated with the rdxA mutant (P ≤ 0.001). The regimen with nitrofurantoin failed to eradicate infection from any of the six SS1-infected mice (P ≤ 0.001) and cleared infection from one of seven mice inoculated with the rdxA mutant. These results demonstrate that, despite the good in vitro activity of nitrofurantoin against H. pylori and the lack of cross-resistance between metronidazole and nitrofurantoin, eradication regimens involving nitrofurantoin are unable to eradicate either metronidazole-sensitive or -resistant H. pylori infections from mice. PMID:10991835

  6. Proteomic analysis of a NAP1 Clostridium difficile clinical isolate resistant to metronidazole.

    PubMed

    Chong, Patrick M; Lynch, Tarah; McCorrister, Stuart; Kibsey, Pamela; Miller, Mark; Gravel, Denise; Westmacott, Garrett R; Mulvey, Michael R

    2014-01-01

    Clostridium difficile is an anaerobic, Gram-positive bacterium that has been implicated as the leading cause of antibiotic-associated diarrhea. Metronidazole is currently the first-line treatment for mild to moderate C. difficile infections. Our laboratory isolated a strain of C. difficile with a stable resistance phenotype to metronidazole. A shotgun proteomics approach was used to compare differences in the proteomes of metronidazole-resistant and -susceptible isolates. NAP1 C. difficile strains CD26A54_R (Met-resistant), CD26A54_S (reduced- susceptibility), and VLOO13 (Met-susceptible) were grown to mid-log phase, and spiked with metronidazole at concentrations 2 doubling dilutions below the MIC. Peptides from each sample were labeled with iTRAQ and subjected to 2D-LC-MS/MS analysis. In the absence of metronidazole, higher expression was observed of some proteins in C. difficile strains CD26A54_S and CD26A54_R that may be involved with reduced susceptibility or resistance to metronidazole, including DNA repair proteins, putative nitroreductases, and the ferric uptake regulator (Fur). After treatment with metronidazole, moderate increases were seen in the expression of stress-related proteins in all strains. A moderate increase was also observed in the expression of the DNA repair protein RecA in CD26A54_R. This study provided an in-depth proteomic analysis of a stable, metronidazole-resistant C. difficile isolate. The results suggested that a multi-factorial response may be associated with high level metronidazole-resistance in C. difficile, including the possible roles of altered iron metabolism and/or DNA repair.

  7. High Dose Vaginal Misoprostol Versus Concentrated Oxytocin + Low Dose Vaginal Misoprostol for Mid-Trimester Labor Induction: A Randomized Trial

    PubMed Central

    Nuthalapaty, Francis S.; Ramsey, Patrick S.; Biggio, Joseph R.; Owen, John

    2013-01-01

    Objective To compare the efficacy and side effects of a high-dose vaginal misoprostol regimen to concentrated intravenous oxytocin plus low-dose vaginal misoprostol for mid-trimester labor induction. Study Design Women at 14-24 weeks, with obstetric or fetal indications for delivery and no prior cesarean, were randomly assigned to receive either vaginal misoprostol 600 μg ×1, then 400 μg q 4 hr × 5 (Group 1) or escalating-dose concentrated oxytocin infusions (277-1667 mU/min) plus vaginal misoprostol 400 μg × 1, then 200 μg q 6 hr × 2, then 100 μg × 1 (Group 2). Analysis was by intent to treat. Primary outcomes were live birth rate and induction-to-delivery interval. Results The intended sample size was 70 women per group; however, the trial was terminated at the initial interim analysis due to a highly significant difference in one of the primary study outcomes. Twenty women were assigned to Group 1 and 18 were assigned to the Group 2. Median induction-to-delivery interval was significantly shorter in Group 1 (12 hr, range 4 - 44 hr) versus Group 2 (18 hr, range 7 - 36 hr; p=0.01). Induction success rate at 12 hours was significantly higher in the Group 1 (60%), compared to Group 2 (22%, p=.02). No significant difference was noted in the live birth rate between Group 1 and 2 (13%, 0%, p = 0.16). The incidence of retained placenta requiring curettage, chorioamnionitis, intrapartum fever, nausea, emesis, and diarrhea were similar between both groups. Conclusion Compared to concentrated oxytocin plus low-dose vaginal misoprostol, high-dose vaginal misoprostol significantly shortens mid-trimester labor inductions. PMID:16157113

  8. CDP-choline at high doses is as effective as i.v. thrombolysis in experimental animal stroke.

    PubMed

    Gutiérrez-Fernández, María; Leciñana, María Alonso de; Rodríguez-Frutos, Berta; Ramos-Cejudo, Jaime; Roda, José María; Díez-Tejedor, Exuperio

    2012-09-01

    Use of thrombolysis in acute ischaemic stroke may be limited by a narrow benefit/risk ratio. Pharmacological inhibition of the ischaemic cascade may constitute an effective and safer approach to stroke treatment. This study compared the effects of high doses of cytidine diphosphate-choline (CDP-choline; 1000 mg/kg) with recombinant tissue plasminogen activator (rt-PA; 5 mg/kg) in an experimental animal model of embolic stroke. Fifteen rats were embolized in the right internal carotid artery with an autologous clot and were divided into three groups: (1) infarct; (2) intravenous rt-PA 5 mg/kg 30 minutes post-embolization; and (3) CDP-choline 1000 mg/kg, intraperitoneal, three doses, 30 minutes, 24 hours, and 48 hours post-embolization. Functional evaluation scores were evaluated using Rogers test, lesion volume by haematoxylin and eosin staining, cell death with transferase-mediated dUTP nick-end labelling, and plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha with enzyme-linked immunosorbent assay. In this study, CDP-choline and rt-PA produced a significant reduction in brain damage considering infarct volume, cell death, and inflammatory cytokines (tumour necrosis factor-alpha and IL-6) compared with the infarct group. Additionally, CDP-choline significantly decreased infarct volume, cell death, and IL-6 levels with respect to the rt-PA group. From these results, we conclude that high-dose CDP-choline may be an effective treatment for acute ischaemic stroke even in absence of thrombolysis.

  9. High-Dose Vincristine Sulfate Liposome Injection for Advanced, Relapsed, and Refractory Adult Philadelphia Chromosome–Negative Acute Lymphoblastic Leukemia

    PubMed Central

    O'Brien, Susan; Schiller, Gary; Lister, John; Damon, Lloyd; Goldberg, Stuart; Aulitzky, Walter; Ben-Yehuda, Dina; Stock, Wendy; Coutre, Steven; Douer, Dan; Heffner, Leonard T.; Larson, Melissa; Seiter, Karen; Smith, Scott; Assouline, Sarit; Kuriakose, Philip; Maness, Lori; Nagler, Arnon; Rowe, Jacob; Schaich, Markus; Shpilberg, Ofer; Yee, Karen; Schmieder, Guenter; Silverman, Jeffrey A.; Thomas, Deborah; Deitcher, Steven R.; Kantarjian, Hagop

    2013-01-01

    Purpose Relapsed adult acute lymphoblastic leukemia (ALL) is associated with high reinduction mortality, chemotherapy resistance, and rapid progression leading to death. Vincristine sulfate liposome injection (VSLI), sphingomyelin and cholesterol nanoparticle vincristine (VCR), facilitates VCR dose-intensification and densification plus enhances target tissue delivery. We evaluated high-dose VSLI monotherapy in adults with Philadelphia chromosome (Ph) –negative ALL that was multiply relapsed, relapsed and refractory to reinduction, and/or relapsed after hematopoietic cell transplantation (HCT). Patients and Methods Sixty-five adults with Ph-negative ALL in second or greater relapse or whose disease had progressed following two or more leukemia therapies were treated in this pivotal phase II, multinational trial. Intravenous VSLI 2.25 mg/m2, without dose capping, was administered once per week until response, progression, toxicity, or pursuit of HCT. The primary end point was achievement of complete response (CR) or CR with incomplete hematologic recovery (CRi). Results The CR/CRi rate was 20% and overall response rate was 35%. VSLI monotherapy was effective as third-, fourth-, and fifth-line therapy and in patients refractory to other single- and multiagent reinduction therapies. Median CR/CRi duration was 23 weeks (range, 5 to 66 weeks); 12 patients bridged to a post-VSLI HCT, and five patients were long-term survivors. VSLI was generally well tolerated and associated with a low 30-day mortality rate (12%). Conclusion High-dose VSLI monotherapy resulted in meaningful clinical outcomes including durable responses and bridging to HCT in advanced ALL settings. The toxicity profile of VSLI was predictable, manageable, and comparable to standard VCR despite the delivery of large, normally unachievable, individual and cumulative doses of VCR. PMID:23169518

  10. Short duration, high dose, alternating chemotherapy in metastatic neuroblastoma. (ENSG 3C induction regimen). The European Neuroblastoma Study Group.

    PubMed Central

    Pinkerton, C. R.; Zucker, J. M.; Hartmann, O.; Pritchard, J.; Broadbent, V.; Morris-Jones, P.; Breatnach, F.; Craft, A. E.; Pearson, A. D.; Wallendszus, K. R.

    1990-01-01

    Fifty-one children, aged from 15 months to 13 years 5 months with metastatic neuroblastoma presenting sequentially at the participating institutions received four 3 to 4 weekly courses of high dose multiagent chemotherapy. High dose cisplatin (200 mg m-2) combined with etoposide (500 mg m-2), HIPE, was alternated with ifosfamide (9 g m-2), vincristine (1.5 mg m-2), and adriamycin (60 mg m-1), IVAd. Disease status was re-evaluated 3 to 4 weeks after the fourth course and the response classified according to the International Neuroblastoma Response Criteria (INRC). The overall response rate in evaluable patients was 55% and response rates by site were: bone marrow 67% (complete response 47%); bone scan 68%; primary tumour 61%, and urinary catecholamine metabolites (VMA/HVA) 95%. Serial 51Cr EDTA renal clearance studies showed a glomerular filtration rate (GFR) decline in 40% of patients but in only seven cases to below 50% of the pretreatment value. There was no instance of renal failure during induction, though two patients developed severe renal failure following 'megatherapy' given to consolidate remission. Serial audiometry showed a significant decline in hearing at frequencies above 2,000 Hz in 37% of children but at or below 2,000 Hz in only 17%. Neutropenia and thrombocytopenia were severe and intravenous antibiotics were required after 30% of courses. Each of two treatment-related deaths occurred during pancytopenia following courses of IVAd. Complete, or greater than 90%, removal of primary site tumour was possible in 70% of cases following this induction regimen and 75% of patients proceeded to elective megatherapy within a median time of 24 weeks after diagnosis. This short intensive induction programme is highly effective at achieving cytoreduction, enabling early surgery and early megatherapy procedures. It is, however, too early to draw firm conclusions about the impact of this approach to treatment on the cure rate. PMID:2386751

  11. [Investigation of in vitro metronidazole resistance in the clinical isolates of Trichomonas vaginalis].

    PubMed

    Ertabaklar, Hatice; Yaman Karadam, Senem; Malatyalı, Erdoğan; Ertuğ, Sema

    2016-10-01

    Trichomonas vaginalis, a flagellated, urogenital anaerobic protozoon is reported as an important cause of vaginitis with a global distribution. Although metronidazole is the primary choice of drug for the treatment of trichomoniasis, the presence of resistant isolates from many different countries highlights the need of novel drugs for the treatment. Many studies from Turkey mostly dealing with the in vitro effects of compounds and natural products against T.vaginalis have been reported, however, only one study has been encountered searching the metronidazole resistance in a single T.vaginalis isolate. The aim of this study was to determine the in vitro metronidazole resistance and minimum lethal concentrations (MLCs) of the isolates from symptomatic cases. T.vaginalis strains isolated from vaginal discharge samples of symptomatic women that were sent to Adnan Menderes University Faculty of Medicine, Research and Training Hospital Parasitology Laboratory, between 2009-2014 period, were included in the study. The strains were isolated by the inoculation of samples into trypticase-yeast-maltose medium supplemented with 10% fetal calf serum. A total of 40 T.vaginalis isolates stored by cryopreservation were revived before the experiments. T.vaginalis trophozoites were incubated with different concentrations of metronidazole (200, 100, 50, 25, 12.5, 6.25, 3.12, 1.56 μg/ml) and the viability of cells were examined in both aerobic and anaerobic conditions under phase contrast microscope. Additionally, non-motile isolates were further inoculated into fresh media and viability was checked. The wells containing motile trophozoites after 48 hours of incubation with 15 µg/ml and/or higher metronidazole concentration in anaerobic condition and 75 µg/ml and/or higher metronidazole concentration in aerobic conditions were determined as resistant isolates. Of the 40 T.vaginalis isolates three (7.5%) were resistant to metronidazole. MLC mean values of metronidazole

  12. The role of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea.

    PubMed

    Tart, Serina B

    2013-10-01

    For the treatment of Clostridium difficile-associated diarrhea (CDAD), metronidazole and vancomycin remain the most commonly used agents. The major advantage of metronidazole is its low cost, while the advantage of oral vancomycin is a more favorable pharmacokinetic profile. The epidemiology and clinical severity of CDAD have changed due to the emergence of a hypervirulent strain (BI/NAP1/027). In 2010, the Infectious Diseases Society of America/Society for Health Care Epidemiology of America expert panel defined severe CDAD and recommended oral vancomycin to treat these patients. Metronidazole remains the preferred agent for treatment of mild to moderate CDAD.

  13. Draft Genome Sequence of a Metronidazole-Susceptible Atopobium vaginae Isolate

    PubMed Central

    Schuyler, Jessica A.; Mordechai, Eli; Adelson, Martin E.; Gygax, Scott E.

    2015-01-01

    We report the draft genome sequence of a vaginal isolate of Atopobium vaginae vaginae (strain 44061), an organism linked to bacterial vaginosis (BV), the most common gynecological infection in the United States. This species is often highly resistant to metronidazole, which is a front-line therapy for BV. Strain 44061 is a metronidazole-susceptible isolate (MIC, 16 µg/ml), and its genome sequence will be useful for comparative studies to elucidate the molecular basis of metronidazole resistance in this species. PMID:26337886

  14. Regional Differences in Metronidazole Resistance and Increasing Clarithromycin Resistance among Helicobacter pylori Isolates from Japan

    PubMed Central

    Kato, Mototsugu; Yamaoka, Yoshio; Kim, Jae J.; Reddy, Rita; Asaka, Masahiro; Kashima, Kei; Osato, Michael S.; El-Zaatari, Fouad A. K.; Graham, David Y.; Kwon, Dong H.

    2000-01-01

    The patterns of antibiotic resistance in Helicobacter pylori were assessed in two different regions in Japan. Overall, prevalences of resistance to metronidazole and clarithromycin were 12.4 and 12.9%, respectively. While there was no difference in clarithromycin resistance, the prevalence of metronidazole resistance was significantly higher in Kyoto (23.8%) than in Sapporo (8.1%). From 1996 to 1999, the prevalence of metronidazole resistance did not change but the prevalence of clarithromycin resistance doubled (from 9.1 to 18.7%). PMID:10898707

  15. Determinants of Quality of Life in High-Dose Benzodiazepine Misusers

    PubMed Central

    Tamburin, Stefano; Federico, Angela; Faccini, Marco; Casari, Rebecca; Morbioli, Laura; Sartore, Valentina; Mirijello, Antonio; Addolorato, Giovanni; Lugoboni, Fabio

    2017-01-01

    Benzodiazepines (BZDs) are among the most widely prescribed drugs in developed countries, but they have a high potential for tolerance, dependence and misuse. High-dose BZD misuse represents an emerging addiction phenomenon, but data on quality of life (QoL) in high-dose BZD misusers are scant. This study aimed to explore QoL in high-dose BZD misuse. We recruited 267 high-dose BZD misusers, compared the QoL scores in those who took BZD only to poly-drug misusers, and explored the role of demographic and clinical covariates through multivariable analysis. Our data confirmed worse QoL in high-dose BZD misusers and showed that (a) QoL scores were not negatively influenced by the misuse of alcohol or other drugs, or by coexisting psychiatric disorders; (b) demographic variables turned out to be the most significant predictors of QoL scores; (c) BZD intake significantly and negatively influenced QoL. Physical and psychological dimensions of QoL are significantly lower in high-dose BZD misusers with no significant effect of comorbidities. Our data suggest that the main reason for poor QoL in these patients is high-dose BZD intake per se. QoL should be considered among outcome measures in these patients. PMID:28054975

  16. Variation in long-term antipsychotic polypharmacy and high-dose prescribing across physicians and hospitals.

    PubMed

    Latimer, Eric A; Naidu, Adonia; Moodie, Erica E M; Clark, Robin E; Malla, Ashok K; Tamblyn, Robyn; Wynant, Willy

    2014-10-01

    This study had two aims: to measure the prevalence of long-term prescribing of high doses of antipsychotics and antipsychotic polypharmacy in a large Canadian province and to estimate the relative contributions of patient-, physician-, and hospital-level factors. Government hospital discharge, physician, and pharmaceutical claims data were linked to identify individuals with schizophrenia who in 2004 had antipsychotics available to them for at least 11 months. Individuals on a high dose throughout that period, as well as individuals on multiple concurrent antipsychotics (polypharmacy), were identified. Logistic and generalized linear mixed models using patient-, physician-, and hospital-level predictors were estimated. Among the 12,150 individuals identified, 11.9% were on a high dose and 10.4% on antipsychotic polypharmacy continually, with 3.7% in both groups. After adjustment for potential confounders, analyses showed that systematic propensity for physicians to prescribe high doses accounted for 10.9% of the remaining unexplained variance, and physicians as a group who prescribed high doses across a hospital or psychiatry department accounted for 3.0%. For antipsychotic polypharmacy the corresponding percentages were 9.7% and 6.2%. Even after adjustment, the variation in high-dose prescribing and antipsychotic polypharmacy remained substantial. Long-term high-dose and antipsychotic polypharmacy prescribing appeared partly driven by some physicians' and some hospitals' propensities to prescribe in this way independently of patient characteristics. Given the weight of the evidence against high-dose prescribing and antipsychotic polypharmacy, measures addressed to physicians and hospitals most likely to prescribe high doses, antipsychotic polypharmacy, or both should be considered.

  17. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis

    PubMed Central

    TURNER, Abigail Norris; REESE, Patricia CARR; FIELDS, Karen S.; ANDERSON, Julie; ERVIN, Melissa; DAVIS, John A.; FICHOROVA, Raina N.; ROBERTS, Mysheika Williams; KLEBANOFF, Mark A.; JACKSON, Rebecca D.

    2014-01-01

    Objective Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence. Study design This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban STD clinic (clinicaltrials.gov registration NCT01450462). All participants received 500mg oral metronidazole twice daily for seven days. Intervention participants (n=59) also received nine doses of 50,000 international units of cholecalciferol (vitamin D3) over 24 weeks; control women (n=59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12 and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period. Results Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (<20 ng/mL). BV prevalence among women randomized to vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm. Conclusions Women receiving vitamin D experienced significant increases in serum 25

  18. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis.

    PubMed

    Turner, Abigail Norris; Carr Reese, Patricia; Fields, Karen S; Anderson, Julie; Ervin, Melissa; Davis, John A; Fichorova, Raina N; Roberts, Mysheika Williams; Klebanoff, Mark A; Jackson, Rebecca D

    2014-11-01

    Low serum vitamin D levels have been associated with increased prevalence of the reproductive tract condition bacterial vaginosis (BV). The objective of this trial was to evaluate the effect of high-dose vitamin D supplementation on BV recurrence. This randomized, placebo-controlled, double-blinded trial enrolled 118 women with symptomatic BV from an urban sexually transmitted disease clinic (clinicaltrials.gov registration NCT01450462). All participants received 500 mg of oral metronidazole twice daily for 7 days. Intervention participants (n = 59) also received 9 doses of 50,000 IU of cholecalciferol (vitamin D3) over 24 weeks; control women (n = 59) received matching placebo. Recurrent BV was assessed via Nugent scoring after 4, 12, and 24 weeks. We assessed the effect of the intervention using an intention-to-treat approach, fitting Cox proportional hazards models to evaluate recurrent BV over the follow-up period. Most participants (74%) were black, with a median age of 26 years. Median presupplementation serum 25-hydroxyvitamin D [25(OH)D] was similar across randomization arms: 16.6 ng/mL in the vitamin D arm and 15.8 ng/mL in the control arm. At trial completion, median 25(OH)D among women receiving vitamin D was 30.5 ng/mL, vs 17.8 ng/mL in control women; 16% of women receiving vitamin D and 57% receiving placebo remained vitamin D deficient (<20 ng/mL). BV prevalence among women randomized to vitamin D was very similar to those randomized to placebo at the 4- and 12-week visits, but by the 24-week visit, BV prevalence was 65% among women in the vitamin D arm and 48% among control women. BV recurrence was not reduced by vitamin D supplementation (intention-to-treat hazard ratio, 1.11; 95% confidence interval, 0.68-1.81). Among women experiencing recurrent BV, median time to recurrence was 13.7 weeks in the vitamin D arm and 14.3 weeks in the control arm. Women receiving vitamin D experienced significant increases in serum 25(OH)D, but this increase was not

  19. Intravenous self-injection of four novel phenethylamines in baboons.

    PubMed

    Sannerud, C.A.; Kaminski, B.J.; Griffiths, R.R.

    1996-08-01

    The present study evaluated the intravenous self-administration of four substituted phenethylamines, using a substitution procedure in baboons. Baboons were trained to self-inject 0.32mg/kg/injection cocaine under a fixed-ration (FR) schedule, with a 3h timeout following each injection. Doses of (+/-)-N-ethyl-3, 4-methylenedioxyamphetamine HCI (MDE), (+/-)-N-hydroxy-3, 4-methylendioxyamphetamine HCI (N-OH-MDA), (+)-N-N-dimethylamphetamine HCI (NNDMA), and 4-bromo-2,5-dimethyoxy-beta-phenethylamine (BDMPEA) and their vehicles were substituted for cocaine for 15 or more successive days. High doses of MDE and N-OH-MDA maintained self-injection; however, NNDMA and BDMPEA self-injection was less consistent. NNDMA did not reliably maintain self-injection, whereas one or more doses of BDMPEA maintained self-injection in each of three baboons. Intermediate to high doses of all four compounds decreased food pellet intake maintained under a FR schedule of reinforcement on a different lever. In some baboons, high doses of N-OH-MDA, NNDMA and BDMPEA produced signs of behavioral toxicity (e.g. cyclic pattern of self-injection, behavioral agitation, stereotypical movements) that were similar to those previously observed after administration of high doses of classic psychomotor stimulants such as d-amphetamine; however, the severity and profile of this behavioral toxicity differed between compounds. Thus, the present study documents both similarities and differences in the behavioral profiles of these four phenethylamines.

  20. Novel aryl carbamate derivatives of metronidazole as potential antiamoebic agents.

    PubMed

    Hayat, Faisal; Wahedi, Hussain Mustatab; Park, Seonghyeok; Tariq, Saba; Azam, Amir; Shin, Dongyun

    2016-01-01

    A series of novel aryl carbamate derivatives of metronidazole (MNZ) were designed, synthesized, and screened for antiamoebic activity. As compared to MNZ, most of the derivatives exhibited moderate to excellent activity against the HM1:IMSS strain of Entamoeba histolytica. Compounds 7, 14, 16, 19, and 21 exhibited the most promising antiamoebic activity with IC50 values of 0.24, 0.08, 0.26, 0.26, and 0.15 μM, respectively, compared to that of MNZ (1.78 μM). Moreover, from the toxicological studies of these compounds on human melanocytes, the melan-a cell line revealed that the potent compounds are nontoxic at concentrations ranging from 2.5 to 50 μM.

  1. Discriminative Dissolution Method for Benzoyl Metronidazole Oral Suspension.

    PubMed

    da Silva, Aline Santos; da Rosa Silva, Carlos Eduardo; Paula, Fávero Reisdorfer; da Silva, Fabiana Ernestina Barcellos

    2016-06-01

    A dissolution method for benzoyl metronidazole (BMZ) oral suspensions was developed and validated using a high-performance liquid chromatography (HPLC) method. After determination of sink conditions, dissolution profiles were evaluated using different dissolution media and agitation speeds. The sample insertion mode in dissolution media was also evaluated. The best conditions were obtained using a paddle, 50 rpm stirring speed, simulated gastric fluid (without pepsin) as the dissolution medium, and sample insertion by a syringe. These conditions were suitable for providing sink conditions and discriminatory power between different formulations. Through the tested conditions, the results can be considered specific, linear, precise, accurate, and robust. The dissolution profiles of five samples were compared using the similarity factor (f 2) and dissolution efficiency. The dissolution kinetics were evaluated and described by the Weibull model. Whereas there is no monograph for this pharmaceutical formulation, the dissolution method proposed can be considered suitable for quality control and dissolution profile comparison of different commercial formulations.

  2. Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

    PubMed

    Hussein, Rola; El-Halabi, Mustapha; Ghaith, Ola; Jurdi, Nawaf; Azar, Cecilio; Mansour, Nabil; Sharara, Ala I

    2011-03-01

    Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.

  3. Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer

    DTIC Science & Technology

    2015-02-01

    AWARD NUMBER: W81XWH-14-1-0014 TITLE: Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer PRINCIPAL INVESTIGATOR: Peter Maxim...TITLE AND SUBTITLE ery High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0014 5c...1 Contract number: W81XWH-14-1-0014 Title: Very High Dose-Rate Radiobiology and Radiation Therapy for Lung Cancer Principal Investigator: Peter G

  4. [Development of a perforated peptic ulcer in a child during high dose prednisolone treatment].

    PubMed

    Moll Harboe, Kirstine; Midtgaard, Helle; Wewer, Vibeke; Cortes, Dina

    2012-09-24

    Since perforated peptic ulcer is uncommon in children proton pump inhibitor prophylaxis is not routinely recommended when children are treated with high dose steroids. We describe a case of perforated ulcer in a six-year-old patient with nephrotic syndrome treated with high dose prednisolone. Initially, ulcer was not suspected due to uncharacteristic symptoms. The child developed peritoneal signs and surgery revealed a perforated peptic ulcer in the stomach. We recommend treatment with proton pump inhibitors if children, who are treated with high dose steroids develop abdominal symptoms, which can be caused by an ulcus.

  5. Lessons learned from administration of high-dose methylprednisolone sodium succinate for acute pediatric spinal cord injuries.

    PubMed

    Caruso, Michelle C; Daugherty, Margot C; Moody, Suzanne M; Falcone, Richard A; Bierbrauer, Karin S; Geis, Gary L

    2017-10-06

    OBJECTIVE Methylprednisolone sodium succinate (MPSS) has been studied as a pharmacological adjunct that may be given to patients with acute spinal cord injury (ASCI) to improve neurological recovery. MPSS treatment became the standard of care in adults despite a lack of evidence supporting clinical benefit. More recently, new guidelines from neurological surgeon groups recommended no longer using MPSS for ASCI, due to questionable clinical benefit and known complications. However, little information exists in the pediatric population regarding MPSS use in the setting of ASCI. The aim of this paper was to describe steroid use and side effects in patients with ASCI at the authors' Level 1 pediatric trauma center in order to inform other hospitals that may still use this therapy. METHODS A retrospective chart review was conducted to determine adherence in ordering and delivery according to the guideline of the authors' institution and to determine types and frequency of complications. Inclusion criteria included age < 17 years, blunt trauma, physician concern for ASCI, and admission for ≥ 24 hours or treatment with high-dose intravenous MPSS. Exclusion criteria included penetrating trauma, no documentation of ASCI, and incomplete medical records. Charts were reviewed for a predetermined list of complications. RESULTS A total of 602 patient charts were reviewed; 354 patients were included in the study. MPSS was administered in 59 cases. In 34 (57.5%) the order was placed correctly. In 13 (38.2%) of these 34 cases, MPSS was administered according to the recommended timeline protocol. Overall, only 13 (22%) of 59 patients received the therapy according to protocol with regard to accurate ordering and administration. Among the patients with ASCI, 20 (55.6%) of the 36 who received steroids had complications, which was a significantly higher rate than in those who did not receive steroids (8 [24.2%] of 33, p = 0.008). Among the patients without ASCI, 10 (43.5%) of the 23

  6. Pharmacokinetic and anti-cancer properties of high dose ascorbate in solid tumours of ascorbate-dependent mice.

    PubMed

    Campbell, Elizabeth J; Vissers, Margreet C M; Wohlrab, Christina; Hicks, Kevin O; Strother, R Matthew; Bozonet, Stephanie M; Robinson, Bridget A; Dachs, Gabi U

    2016-10-01

    Despite recent evidence for an anti-tumour role for high-dose ascorbate, potential mechanisms of action are still unclear. At mM concentrations that are achieved with high-dose intravenous administration, autoxidation of ascorbate can generate cytotoxic levels of H2O2. Ascorbate is also a required co-factor for the hydroxylases that suppress the transcription factor hypoxia-inducible factor (HIF-1). HIF-1 supports an aggressive tumour phenotype and is associated with poor prognosis, and previous studies have shown that optimizing intracellular ascorbate levels down-regulates HIF-1 activation. In this study we have simultaneously measured ascorbate concentrations and the HIF-1 pathway activity in tumour tissue following high dose ascorbate administration, and have studied tumour growth and physiology. Gulo(-/-) mice, a model of the human ascorbate dependency condition, were implanted with syngeneic Lewis lung tumours, 1g/kg ascorbate was administered into the peritoneum, and ascorbate concentrations were monitored in plasma, liver and tumours. Ascorbate levels peaked within 30min, and although plasma and liver ascorbate returned to baseline within 16h, tumour levels remained elevated for 48h, possibly reflecting increased stability in the hypoxic tumour environment. The expression of HIF-1 and its target proteins was down-regulated with tumour ascorbate uptake. Elevated tumour ascorbate levels could be maintained with daily administration, and HIF-1 and vascular endothelial growth factor protein levels were reduced in these conditions. Increased tumour ascorbate was associated with slowed tumour growth, reduced tumour microvessel density and decreased hypoxia. Alternate day administration of ascorbate resulted in lower tumour levels and did not consistently decrease HIF-1 pathway activity. Levels of sodium-dependent vitamin C transporters 1 and 2 were not clearly associated with ascorbate accumulation by murine tumour cells in vitro or in vivo. Our results support

  7. High-dose weekly AmBisome antifungal prophylaxis in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic study.

    PubMed

    Mehta, Parinda; Vinks, Alexander; Filipovich, Alexandra; Vaughn, Gretchen; Fearing, Deborah; Sper, Christine; Davies, Stella

    2006-02-01

    Disseminated fungal infection causes significant morbidity and mortality in children undergoing hematopoietic stem cell transplantation (HSCT). The widespread use of prophylactic oral triazoles has limitations of poor absorption, interindividual variability in metabolism, and hepatic toxicity. AmBisome (amphotericin B liposomal complex) has a better safety profile than the parent drug amphotericin B and produces higher plasma and tissue concentrations. We hypothesized that once-weekly high-dose AmBisome therapy could provide adequate fungal prophylaxis for immunocompromised children undergoing HSCT. We performed a pharmacokinetic pilot study to determine whether once-weekly high-dose AmBisome administration would result in effective concentrations throughout the dosing interval. A total of 14 children (median age, 3 years, 1 month; range, 4.5 months-9 years, 9 months) undergoing HSCT received once-weekly intravenous AmBisome prophylaxis (10 mg/kg as a 2-hour infusion). Blood samples for pharmacokinetic measurements were drawn around the first and the fourth weekly doses. The concentration of non-lipid-complexed amphotericin in plasma was determined by a validated bioassay. Pharmacokinetic parameters after single doses and during steady state were calculated using standard noncompartmental methods. AmBisome was well tolerated at this dose. Complete pharmacokinetic profiles for weeks 1 and 4 were obtained in 12 patients. The half-life calculated in this pediatric population was shorter on average than reported in adults (45 hours vs 152 hours). The volume of distribution correlated best with body weight (R(2) = .55), and clearance was best predicted by initial serum creatinine level (R(2) = .19). Mean (+/- standard deviation) individual plasma trough concentrations were 0.23 (0.13) mg/L after single doses and 0.47 (0.41) mg/L after multiple doses. Mean steady-state area under the curve was higher at week 4 than after a single dose (P < .05). Single-dose and steady

  8. Intravenous clonazepam in eclampsia.

    PubMed

    Harding, D L; Leong, C M

    1988-02-01

    A case of postpartum eclampsia is reported, controlled by intravenous clonazepam, a benzodiazepine anticonvulsant. Clonazepam was effective in controlling the myoclonic jerks, which were a feature in this patient, without producing excessive sedation. The literature reveals several reports on the use of clonazepam in severe preeclampsia, but its use in Australia has not been widely employed.

  9. Changes in dendritic cell phenotype after a new high-dose weekly schedule of interleukin-2 therapy for kidney cancer and melanoma.

    PubMed

    Finkelstein, Steven E; Carey, Timothy; Fricke, Ingo; Yu, Daohai; Goetz, Dawn; Gratz, Megan; Dunn, Mary; Urbas, Patricia; Daud, Adil; DeConti, Ronald; Antonia, Scott; Gabrilovich, Dmitry; Fishman, Mayer

    2010-10-01

    High-dose intravenous interleukin-2 (IL-2) therapy (14 doses/course, 2 courses/cycle) for metastatic melanoma or kidney cancer induces infrequent, although major responses. In this trial, we evaluated a new schedule (dose of 600,000 IU/kg, 8 h between doses, 5 doses/course, 4 courses at weekly intervals/cycle) of high-dose IL-2, in which we inserted more planned breaks while maintaining high cumulative dose delivery, and investigated the relationship between dendritic cells (DC) and response to treatment. Target dose delivery was attained: median IL-2 cumulative dose per patient was 11.4 and 10.8 million units/kg (cycles 1 and 2, respectively). Major responses were observed in patients with kidney cancer (n=20; 3 complete and 2 partial responses) and melanoma (n=16; 1 partial response). Adverse events appeared comparable with those typically associated with high-dose IL-2. From this data set, we introduce the hypothesis-generating observation that patients who had more favorable outcomes had high pretreatment DC-to-myeloid-derived suppressor cell (MDSC) ratios, similar to the ratio observed in healthy individuals. However, even in patients with the most favorable outcome, after treatment, there were IL-2-induced changes in the DC-to-MDSC ratio, specifically increases in MDSCs. This modified IL-2 schedule is a feasible option, with a more uniform dose delivery over the treatment cycle, a similar toxicity profile, and observed complete, durable response in patients with renal cancer. Pretreatment assessment of DC phenotypic or maturational status may be a starting point to predicting response to high-dose IL-2 cytokine immunotherapy in patients with melanoma and kidney cancer.

  10. High-Dose Flu Shot May Help Nursing Home Residents Avoid Hospital

    MedlinePlus

    ... medlineplus.gov/news/fullstory_167348.html High-Dose Flu Shot May Help Nursing Home Residents Avoid Hospital ... July 21, 2017 (HealthDay News) -- Nobody wants the flu, but it can prove deadly for frail residents ...

  11. High-dose monoclonal antibodies via the subcutaneous route: challenges and technical solutions, an industry perspective.

    PubMed

    Narasimhan, Chakravarthy; Mach, Henryk; Shameem, Mohammed

    2012-07-01

    This review summarizes the various challenges in product development involved in subcutaneous administration of high-dose monoclonal antibodies and attempts to provide an industry perspective of some of the available technologies and potential avenues to overcome these challenges.

  12. An Alternative to the Use of High-Dose Estrogens for Postcoital Contraception.

    ERIC Educational Resources Information Center

    Schilling, Lee H.

    1979-01-01

    Research is reported on the use of ethinyl estradiol and norgestrel for contraception after intercourse. This treatment is offered as an alternative to high doses of estrogen and appears to be successful in preventing unwanted pregnancies. (JMF)

  13. EVALUATION OF ALGINATE MICROSPHERES WITH METRONIDAZOLE OBTAINED BY THE SPRAY DRYING TECHNIQUE.

    PubMed

    Szekalska, Marta; Winnicka, Katarzyna; Czajkowska-Kośnik, Anna; Sosnowska, Katarzyna; Amelian, Aleksandra

    2015-01-01

    In the present study, nine formulations (F1-F9) of alginate microspheres with metronidazole were prepared by the spray drying technique with using different drug:polymer ratio (1:2, 1:1, 2:1) and different sodium alginate concentration (1, 2, 3%). The obtained microspheres were characterized for size, morphology, drug loading, (potential and swelling degree. Mucoadhesive properties were examined using texture analyzer and three different models of adhesive layers--gelatin discs, mucin gel and porcine vaginal mucosa. In vitro drug release, mathematical release profile and physical state of microspheres were also evaluated. The obtained results indicate that sodium alginate is a suitable polymer for developing mucoadhesive dosage forms of metronidazole. The optimal formulation F3 (drug:polymer ratio 1:2 and 1% alginate solution) was characterized by the highest metronidazole loading and sustained drug release. The results of this study indicate promising potential of ALG microspheres as alternative dosage forms for metronidazole delivery.

  14. One-Gram, Single-Dose Metronidazole (Flagyl) for Trichomonal Vaginitis.

    ERIC Educational Resources Information Center

    Moore, Jennifer R.

    1979-01-01

    Effective single-dose treatment of trichomonal vaginitis is reported. Large single-dose treatment with metronidazole was found to be effective and avoided the side effects occurring with multidose treatment. (MJB)

  15. One-Gram, Single-Dose Metronidazole (Flagyl) for Trichomonal Vaginitis.

    ERIC Educational Resources Information Center

    Moore, Jennifer R.

    1979-01-01

    Effective single-dose treatment of trichomonal vaginitis is reported. Large single-dose treatment with metronidazole was found to be effective and avoided the side effects occurring with multidose treatment. (MJB)

  16. Metronidazole-resistant clinical isolates of Trichomonas vaginalis have lowered oxygen affinities.

    PubMed

    Yarlett, N; Yarlett, N C; Lloyd, D

    1986-05-01

    Oxygen affinities of metronidazole susceptible and resistant isolates of the parasitic flagellate protozoon Trichomonas vaginalis were determined by mass spectrometric methods. Apparent O2Km values for the respiration of non-proliferating cell suspensions were about 10-fold higher for metronidazole resistant strains than for the susceptible strains C1-NIH or NYH-286. Simultaneous monitoring of hydrogen evolution in the presence of increasing O2 tensions enabled apparent Ki values for H2 to be determined; and this function was independent of metronidazole susceptibility. Apparent O2 affinities of the hydrogenosomal and non-sedimentable fractions were determined for the strains CDC 85 (metronidazole resistant) and C1-NIH, which showed the deficiency in the O2 scavenging capacity by the resistant strain to be associated with the hydrogenosome-containing fraction.

  17. Down-regulation of flavin reductase and alcohol dehydrogenase-1 (ADH1) in metronidazole-resistant isolates of Trichomonas vaginalis

    PubMed Central

    Leitsch, David; Drinić, Mirjana; Kolarich, Daniel; Duchêne, Michael

    2012-01-01

    The microaerophilic parasite Trichomonas vaginalis is a causative agent of painful vaginitis or urethritis, termed trichomoniasis, and can also cause preterm delivery or stillbirth. Treatment of trichomoniasis is almost exclusively based on the nitroimidazole drugs metronidazole and tinidazole. Metronidazole resistance in T. vaginalis does occur and is often associated with treatment failure. In most cases, metronidazole-resistant isolates remain susceptible to tinidazole, but cross resistance between the two closely related drugs can be a problem. In this study we measured activities of thioredoxin reductase and flavin reductase in four metronidazole-susceptible and five metronidazole-resistant isolates. These enzyme activities had been previously found to be downregulated in T. vaginalis with high-level metronidazole resistance induced in the laboratory. Further, we aimed at identifying factors causing metronidazole resistance and compared the protein expression profiles of all nine isolates by application of two-dimensional gel electrophoresis (2DE). Thioredoxin reductase activity was nearly equal in all strains assayed but flavin reductase activity was clearly down-regulated, or even absent, in metronidazole-resistant strains. Since flavin reductase has been shown to reduce oxygen to hydrogen peroxide, its down-regulation could significantly contribute to the impairment of oxygen scavenging as reported by others for metronidazole-resistant strains. Analysis by 2DE revealed down-regulation of alcohol dehydrogenase 1 (ADH1) in strains with reduced sensitivity to metronidazole, an enzyme that could be involved in detoxification of intracellular acetaldehyde. PMID:22449940

  18. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

    DTIC Science & Technology

    2008-06-01

    computed tomography –based high dose rate brachytherapy of prostate cancer, Journal of Applied Clinical Medical Physics, Vol. 8, No. 4, Fall 2007...Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy PRINCIPAL INVESTIGATOR: Jean Pouliot, Ph.D. I-Chow Hsu, M.D...response, including the time for reviewing instructions, searching existing data sources , gathering and maintaining the data needed, and completing and

  19. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy. Addendum

    DTIC Science & Technology

    2009-06-01

    Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy PRINCIPAL INVESTIGATOR: Jean Pouliot, Ph.D. I-Chow Hsu...data sources , gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this...NUMBER Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy 5b. GRANT NUMBER W81XWH-04-1-0262

  20. Targeting MRS-Defined Dominant Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy

    DTIC Science & Technology

    2010-06-01

    Intraprostatic Lesions with Inverse-Planned High Dose Rate Brachytherapy PRINCIPAL INVESTIGATOR: Jean Pouliot, Ph.D. I-Chow Hsu...data sources , gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this...Intraprostatic lesions with Inverse-Planned 5a. CONTRACT NUMBER W81XWH-04-1-0262 High Dose Rate Brachytherapy 5b. GRANT NUMBER

  1. High-dose fractionated radiation therapy for select patients with brain metastases

    SciTech Connect

    Pezner, R.D.; Lipsett, J.A.; Archambeau, J.O.; Fine, R.M.; Moss, W.T.

    1981-08-01

    Four patients with metastases to the brain were treated by high-dose fractionated radiation therapy. In all four cases, a complete response and prolonged disease-free survival could be documented. Unlike the standard therapy for such patients (i.e., craniotomy and postoperative irradiation), high-dose fractionated radiation therapy carries no operative risk and can encompass multiple brain metastases and metastases in deep or critical intracranial sites. The risk of radiotherapy side effects in the brain is discussed.

  2. Metronidazole-but not IL-10 or prednisolone-rescues Trichuris muris infected C57BL/6 IL-10 deficient mice from severe disease.

    PubMed

    Kopper, Jamie J; Patterson, Jon S; Mansfield, Linda S

    2015-09-15

    Trichuris muris infected C57BL/6 mice are a frequently studied model of immune mediated resistance to helminths. Our objective was to characterize dose-dependent gastrointestinal (GI) disease and pathology due to Trichuris in C57BL/6 mice with varying degrees of IL-10 sufficiency. These mice can serve as a model for other animals (dogs, cattle) and humans where IL-10 polymorphisms have been associated with disease susceptibility and may affect susceptibility to whipworm. C57BL/6 IL-10(+/+), IL-10(+/-) and IL-10(-/-) mice were infected with T. muris (J strain) in a dose response study. T. muris produced dose-dependent disease in IL-10(-/-) mice. Ninety percent of mice receiving the high dose (75 ova) had severe disease necessitating early euthanasia, while the medium dose (50 ova) resulted in 100% early euthanasia of males/75% of females, and the low dose (25 ova) in 100% early euthanasia of males/25% of females. Having some IL-10 as in heterozygotes did not rescue all infected mice from effects of the high dose. 2/21 IL-10(-/-), 1/17 IL-10(+/-), and 0/17 IL-10(+/+) mice in the high dose group had severe peritonitis and extra-intestinal bacteria confirmed by fluorescent 16S rDNA analysis of peritoneal organ surfaces. Three of twenty one IL-10(-/-) had demonstrable extra-intestinal T. muris adults. Although free from viral pathogens, 12/21 IL-10(-/-), 6/17 IL-10(+/-), and 4/17 IL-10(+/+) infected mice had hepatitis, while control mice of all genotypes did not. Mice had evidence of inflammation of serosal surfaces of liver, spleen and GI tract even when extraintestinal Trichuris were not found. Blinded histopathology scoring revealed that even when infected IL-10(-/-) mice displayed few, if any, clinical signs, levels of gut inflammation did not vary significantly from those mice euthanized early due to severe disease. To examine whether antibiotics or corticosteroids could reverse severe disease and lesions, IL-10(-/-) mice infected with T. muris were treated with

  3. Efficacy and Safety of Metronidazole for Pulmonary Multidrug-Resistant Tuberculosis

    PubMed Central

    Carroll, Matthew W.; Jeon, Doosoo; Mountz, James M.; Lee, Jong Doo; Jeong, Yeon Joo; Zia, Nadeem; Lee, Myungsun; Lee, Jongseok; Via, Laura E.; Lee, Soyoung; Eum, Seok-Yong; Lee, Sung-Joong; Goldfeder, Lisa C.; Cai, Ying; Jin, Boyoung; Kim, Youngran; Oh, Taegwon; Chen, Ray Y.; Dodd, Lori E.; Gu, Wenjuan; Dartois, Veronique; Park, Seung-Kyu; Kim, Cheon Tae

    2013-01-01

    Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens. PMID

  4. PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

    PubMed

    Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

    2016-03-01

    Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

  5. Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis.

    PubMed

    Carroll, Matthew W; Jeon, Doosoo; Mountz, James M; Lee, Jong Doo; Jeong, Yeon Joo; Zia, Nadeem; Lee, Myungsun; Lee, Jongseok; Via, Laura E; Lee, Soyoung; Eum, Seok-Yong; Lee, Sung-Joong; Goldfeder, Lisa C; Cai, Ying; Jin, Boyoung; Kim, Youngran; Oh, Taegwon; Chen, Ray Y; Dodd, Lori E; Gu, Wenjuan; Dartois, Veronique; Park, Seung-Kyu; Kim, Cheon Tae; Barry, Clifton E; Cho, Sang-Nae

    2013-08-01

    Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.

  6. Clinical relevance of metronidazole and peripheral neuropathy: a systematic review of the literature.

    PubMed

    Goolsby, Tiffany A; Jakeman, Bernadette; Gaynes, Robert P

    2017-09-05

    The objective of this paper was to review and evaluate the literature on metronidazole-associated peripheral neuropathy and determine the relevance in clinical practice. MEDLINE/PubMed, EBSCO, and Google Scholar were searched through February 2017 using the search terms metronidazole and peripheral neuropathy, or polyneuropathy, or paresthesia, or neurotoxicity. Relevant case reports, retrospective studies, surveys, and review articles were included. Bibliographies of all relevant articles were reviewed for additional sources. Overall, metronidazole is generally well tolerated but serious neurotoxicity, including peripheral neuropathy, has been reported. The overall incidence of peripheral neuropathy associated with metronidazole is unknown. Our review found 36 case reports (40 unique patients) of metronidazole-associated peripheral neuropathy with the majority of cases receiving >42 total grams (>4 weeks) of therapy (31 out of 40). In addition, we reviewed 13 clinical studies and found varying rates of peripheral neuropathy from 0-50%. Within these clinical studies, we found a higher incidence of peripheral neuropathy in patients receiving >42 total grams (>4 weeks) of metronidazole compared to those patients receiving ≤ 42 total grams (17.9% vs 1.7%). Nearly all patients had complete resolution of symptoms. In conclusion, peripheral neuropathy is exceedingly rare in patients who receive ≤ 42 total grams of metronidazole. Patients who receive larger total doses may be at higher risk of peripheral neuropathy but most patients have resolution of symptoms after discontinuing therapy. Antimicrobial stewardship programs may consider use of antibiotic combinations that include metronidazole over broad-spectrum alternatives when treating with ≤42 grams of the drug (≤4 weeks). Copyright © 2017. Published by Elsevier B.V.

  7. Anti-anaerobic activity of levofloxacin alone and combined with clindamycin and metronidazole.

    PubMed

    Credito, K L; Jacobs, M R; Appelbaum, P C

    2000-11-01

    Microdilution MICs of levofloxacin against twelve anaerobes ranged between 0.5-8.0 microg/ml and those of clindamycin and metronidazole between 0.008-2.0 and 0.25->16.0 microg/ml, respectively. Combination of levofloxacin with clindamycin and/or metronidazole in time-kill tests led to synergy at levofloxacin concentrations at or below the MIC in 7/12 strains.

  8. [The risk-benefit of high doses of botulinum toxin injections for muscle spasticity ].

    PubMed

    Rousseaux, M; Daveluy, W

    2007-01-01

    To bring general elements of reflection on the use of the high doses of botulinum toxin in spastic children and adults. Review of the literature on the high doses and the benefit-risk associated with botulinum toxin injections. The medical literature exclusively relates to the use of the high doses in children and adolescents. Comparative work with conventional doses suggests a relative interest, but with a risk of increased side effects. Several articles report on treatments with high and even very high doses in series of patient, with a documented effectiveness. But their justification remains partial and the study of the possible side effects is limited. Reflections are brought to contribute to the debate on the use of high doses, taking into account the local physiological effect of botulinum toxin, the risk of regional and general diffusion, the need for a progressive strategy, the variability of effects, the cost of the treatment and the need for obtaining an informed consent of the patient and of significant others. The use of high doses of botulinum toxin increases progressively, but must remain very careful.

  9. High-dose immunoglobulin infusion for thrombotic thrombocytopenic purpura refractory to plasma exchange and steroid therapy.

    PubMed

    Park, Seh Jong; Kim, Seok Jin; Seo, Hee Yun; Jang, Moon Ju; Oh, Doyeun; Kim, Byung Soo; Kim, Jun Suk

    2008-09-01

    The outcomes of the treatment of thrombotic thrombocytopenic purpura (TTP) have been shown to be improved by the administration of plasma exchange. However, treatment options are currently limited for cases refractory to plasma exchange. The autoantibodies that block the activity of ADAMTS13 have been demonstrated to play a role in the pathogenesis of TTP; therefore, high-dose immunoglobulin, which can neutralize these autoantibodies, may be useful for refractory TTP. However, successful treatment with high-dose immunoglobulin for TTP refractory to plasma exchange and corticosteroids has yet to be reported in Korea. Herein, we describe a refractory case which was treated successfully with high-dose immunoglobulin. A 29-year-old male diagnosed with TTP failed to improve after plasma exchange coupled with additional high-dose corticosteroid therapy. As a salvage treatment, we initiated a 7-day regimen of high-dose immunoglobulin (400 mg/kg) infusions, which resulted in a complete remission, lasting up to the last follow-up at 18 months. High-dose immunoglobulin may prove to be a useful treatment for patients refractory to plasma exchange; it may also facilitate recovery and reduce the need for plasma exchange.

  10. Challenges in oral administration of metronidazole dissolved in drinking water to rhesus monkeys (Macaca mulatta).

    PubMed

    Labberton, Linda; Bakker, Jaco; Klomp, Rianne; Langermans, Jan A M; van Geijlswijk, Ingeborg M

    2013-06-01

    Intestinal pathogens such as Entamoeba spp. and Giardia spp. protozoans are not uncommon among rhesus macaques (Macaca mulatta) in research facilities. These infections affect the health of the macaques, potentially causing severe diarrhea, and also pose a risk of zoonotic transmission to human caretakers. Infections must therefore be treated, but no standard treatment for intestinal protozoans in macaques has been developed. Metronidazole is commonly used to treat infections with Giardia spp. and Entamoeba spp. in veterinary medicine, but evidence-based information on effectiveness and dosages for nonhuman primates is lacking, and administration of drugs to nonhuman primates is challenging. The authors designed a study to determine whether oral administration of metronidazole dissolved in drinking water would be successful in rhesus macaques. They monitored daily fluid intake of macaques given water with or without metronidazole and with or without flavored syrup. Metronidazole addition, with or without flavored syrup, resulted in a decrease in fluid intake. Although it was possible to administer metronidazole in drinking water to some macaques, the authors conclude that this strategy is not a practical clinical method because of variation in the amount of water and metronidazole ingested by the macaques.

  11. Evaluation of polycaprolactone matrices for the intravaginal delivery of metronidazole in the treatment of bacterial vaginosis.

    PubMed

    Pathak, Meenakshi; Turner, Mark; Palmer, Cheryn; Coombes, Allan G A

    2014-09-01

    Microporous, poly (ɛ-caprolactone) (PCL) matrices loaded with the antibacterial, metronidazole were produced by rapidly cooling suspensions of drug powder in PCL solutions in acetone. Drug incorporation in the matrices increased from 2.0% to 10.6% w/w on raising the drug loading of the PCL solution from 5% to 20% w/w measured with respect to the PCL content. Drug loading efficiencies of 40-53% were obtained. Rapid 'burst release' of 35-55% of the metronidazole content was recorded over 24 h when matrices were immersed in simulated vaginal fluid (SVF), due to the presence of large amounts of drug on matrix surface as revealed by Raman microscopy. Gradual release of around 80% of the drug content occurred over the following 12 days. Metronidazole released from PCL matrices in SVF retained antimicrobial activity against Gardnerella vaginalis in vitro at levels up to 97% compared to the free drug. Basic modelling predicted that the concentrations of metronidazole released into vaginal fluid in vivo from a PCL matrix in the form of an intravaginal ring would exceed the minimum inhibitory concentration of metronidazole against G. vaginalis. These findings recommend further investigation of PCL matrices as intravaginal devices for controlled delivery of metronidazole in the treatment and prevention of bacterial vaginosis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  12. Effect of temperature on the metronidazole BSA interaction: Multi-spectroscopic method

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Jiang, Xin Yu; Chen, Xiao Qing; Chen, Yue

    2008-03-01

    The interaction between metronidazole and bovine serum albumin (BSA) was investigated using fluorescence spectroscopy (FS) and resonance light scattering spectroscopy (RLS). The apparent binding constants ( Ka) between metronidazole and BSA were 3.42 × 10 4 (20 °C), 5.78 × 10 4 (30 °C) and 8.23 × 10 4 L mol -1 (40 °C), and the binding sites values ( n) were 1.48 ± 0.03. The experimental results showed that the metronidazole could be inserted into the BSA, quenching the inner fluorescence by forming the metronidazole-BSA complex. The addition of increasing metronidazole to BSA solution leads to the gradual enhancement in RLS intensity, exhibiting the formation of the aggregate in solution. It was found that both static quenching and non-radiation energy transfer were the main reasons for the fluorescence quenching. The entropy change and enthalpy change were positive, which indicated that the interaction of metronidazole and BSA was driven mainly by hydrophobic forces. The process of binding was a spontaneous process in which Gibbs free energy change was negative.

  13. Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates.

    PubMed

    Korosh, Travis; Bujans, Emmanuel; Morada, Mary; Karaalioglu, Canan; Vanden Eynde, Jean Jacques; Mayence, Annie; Huang, Tien L; Yarlett, Nigel

    2017-10-01

    A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH2 to C10 H20 ) containing a meta- (m) or para (p)-benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole-susceptible (C1) and metronidazole-refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2'-[α,ω-propanediylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, displayed a 5.5-fold lower minimum inhibitory concentration (MIC) toward T. vaginalis isolate 085 than metronidazole under aerobic growth conditions, (26 μm compared to 145 μm). A dose of 25 mg/kg per day for four days of compound 3m cured a subcutaneous mouse model infection using T. vaginalis isolates 286 (metronidazole susceptible) and 085 (metronidazole refractory). Compound 3m was weakly reduced by pyruvate:ferredoxin oxidoreductase, but unlike metronidazole was not dependent upon added ferredoxin. It is concluded from structure-activity relationships that there was no obvious trend based on the length of the central aliphatic chain, or the steric position of the bisbenzimidazole enabling prediction of biological activity. The compounds generally fulfill Lipinski's rile of five, indicating their potential as drug leads. © 2017 John Wiley & Sons A/S.

  14. Trichomonas vaginalis Flavin Reductase 1 and its Role in Metronidazole Resistance

    PubMed Central

    Leitsch, David; Janssen, Brian D.; Kolarich, Daniel; Johnson, Patricia J.; Duchêne, Michael

    2015-01-01

    Summary The enzyme flavin reductase 1 (FR1) from Trichomonas vaginalis, formerly known as NADPH oxidase, was isolated and identified. Flavin reductase is part of the antioxidative defense in T. vaginalis and indirectly reduces molecular oxygen to hydrogen peroxide via free flavins. Importantly, a reduced or absent flavin reductase activity has been reported in metronidazole-resistant T. vaginalis, resulting in elevated intracellular oxygen levels and futile cycling of metronidazole. Interestingly, FR1 has no close homologue in any other sequenced genome, but seven full-length and three truncated isoforms exist in the T. vaginalis genome. However, out of these, only FR1 has an affinity for flavins, i.e. FMN, FAD, and riboflavin, which is high enough to be of physiological relevance. Although there are no relevant changes in the gene sequence or any alterations of the predicted FR1-mRNA structure in any of the strains studied, FR1 is not expressed in highly metronidazole-resistant strains. Transfection of a metronidazole-resistant clinical isolate (B7268), which does not express any detectable amounts of FR, with a plasmid bearing a functional FR1 gene nearly completely restored metronidazole sensitivity. Our results indicate that FR1 has a significant role in the emergence of metronidazole resistance in T. vaginalis. PMID:24256032

  15. ASSOCIATION OF CALCIUM HYDROXIDE AND METRONIDAZOLE IN THE TREATMENT OF DOG'S TEETH WITH CHRONIC PERIAPICAL LESION

    PubMed Central

    Panzarini, Sônia Regina; Souza, Valdir; Holland, Roberto; Dezan, Eloi

    2006-01-01

    One of the primary objectives of endodontic treatment of teeth with pulp necrosis is the elimination of microorganisms from the root canal system, as effectively as possible, especially in cases with chronic periapical lesions. AIM: The purpose of this study was to analyze the response of the periapical tissue of dogs' teeth with chronic periapical lesions to endodontic treatment performed with utilization of metronidazole, calcium hydroxide, and an association of both as root canal dressings. METHODOLOGY: Forty root canals were submitted to pulpectomy and the root canals were kept exposed to the oral environment for 6 months. Then, they were submitted to biomechanical preparation and divided into 4 study groups with 10 specimens: group I – no root canal dressing; group II – calcium hydroxide; group III – metronidazole; group IV – calcium hydroxide associated to metronidazole. After 15 days, the root canals were filled with Fill Canal sealer. After 90 days, the animals were killed and the especimens processed for histological analysis. RESULTS: Calcium hydroxide dressing provided a significantly better outcome compared to other experimental groups (α = 0.01). Also, the results of the association of metronidazole and calcium hydroxide were similar to those observed for the metronidazole group. The worst results were obtained by the no root canal dressing group. CONCLUSION: The use of metronidazole alone or associated with Calcium hydroxide, did not improve periapical healing when compared to Calcium hydroxide dressing. PMID:19089054

  16. Electrochemical Determination of Metronidazole in Tablet Samples Using Carbon Paste Electrode

    PubMed Central

    Nikodimos, Yosef

    2016-01-01

    Cyclic voltammetric investigation of metronidazole at carbon paste electrode revealed an irreversible reduction peak centered at about −0.4 V. Observed peak potential shift with pH in the range 2.0 to 8.5 indicated the involvement of protons during the reduction of metronidazole, whereas the peak potential shift with scan rate in the range 10–250 mV/s confirmed the irreversibility of the reduction reaction. A better correlation coefficient for the dependence of peak current on the scan rate than on the square root of scan rate indicated an adsorption controlled kinetics. Under the optimized method and solution parameters, an excellent linearity between the reductive peak current and the concentration of metronidazole was observed in the concentration range 1.0 × 10−6 to 5.0 × 10−4 M with a correlation coefficient, method detection limit (based on s = 3σ), and limit of quantification of 0.999, 2.97 × 10−7 M and 9.91 × 10−7 M, respectively. Good recovery results for spiked metronidazole in tablet samples and selective determination of metronidazole in tablet formulations in the presence of selected potential interferents such as rabeprazole, omeprazole, and tinidazole confirmed the potential applicability of the developed method for the determination of metronidazole in real samples like pharmaceutical tablets. PMID:27119041

  17. The mutation of the rdxA gene in metronidazole-resistant Helicobacter pylori clinical isolates.

    PubMed

    Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rahimi, Ebrahim; Safaei, Hajieh Ghasemian

    2014-01-01

    Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is consequential for efficient treatment of bacterial infections. Although metronidazole has been frequently used in treatment regimens for H. pylori infection, but antibiotic resistance is now a major contributing factor in treatment failure. Nevertheless metronidazole has been greatly used as a critical component of combination therapies for H. pylori infection. This study is trying to describe the mutational mechanisms of metronidazole resistance in H. pylori in our clinical isolates in Isfahanian patients, Iran and compare with the findings of previous studies in world. MIC values of metronidazole for H. pylori strains were determined by E- test. Both rdxA and glmM genes used for confirmation of isolates as H. pylori and then amplification of another rdxA oligonucleotide pair was done. Finally, the six resistant strains were sent to sequencing for other processing and further analysis was done by software. The result of six clinical isolates in comparison with 26695, J99 and 69A as a sensitive and resistant reference strains showed plenty of mutations. No frame shift and nonsense mutation was seen in our clinical isolates. An interesting finding in metronidazole-resistant strains in our study was the detection of one mutation not previously described in the literature in the rdxA gene and this W(209)R substitution presumably plays a role in inducing metronidazole resistance.

  18. The mutation of the rdxA gene in metronidazole-resistant Helicobacter pylori clinical isolates

    PubMed Central

    Mirzaei, Nasrin; Poursina, Farkhondeh; Moghim, Sharareh; Rahimi, Ebrahim; Safaei, Hajieh Ghasemian

    2014-01-01

    Backgrounds: Antibiotic resistance is an increasing problem throughout the developed world, and knowledge about different resistance mechanisms is consequential for efficient treatment of bacterial infections. Although metronidazole has been frequently used in treatment regimens for H. pylori infection, but antibiotic resistance is now a major contributing factor in treatment failure. Nevertheless metronidazole has been greatly used as a critical component of combination therapies for H. pylori infection. Objective: This study is trying to describe the mutational mechanisms of metronidazole resistance in H. pylori in our clinical isolates in Isfahanian patients, Iran and compare with the findings of previous studies in world. Materials and Methods: MIC values of metronidazole for H. pylori strains were determined by E- test. Both rdxA and glmM genes used for confirmation of isolates as H. pylori and then amplification of another rdxA oligonucleotide pair was done. Finally, the six resistant strains were sent to sequencing for other processing and further analysis was done by software. Results: The result of six clinical isolates in comparison with 26695, J99 and 69A as a sensitive and resistant reference strains showed plenty of mutations. No frame shift and nonsense mutation was seen in our clinical isolates. Conclusion: An interesting finding in metronidazole-resistant strains in our study was the detection of one mutation not previously described in the literature in the rdxA gene and this W(209)R substitution presumably plays a role in inducing metronidazole resistance. PMID:24761398

  19. Metronidazole prodrugs: synthesis, physicochemical properties, stability, and ex vivo release studies.

    PubMed

    Mura, Carla; Valenti, Donatella; Floris, Costantino; Sanna, Roberta; De Luca, Maria Antonietta; Fadda, Anna Maria; Loy, Giuseppe

    2011-09-01

    The aim of the present study was to develop a colon targeted delivery system for metronidazole using polymeric prodrug formulation. Two chitosan amide conjugates of metronidazole were prepared by using two different spacers to covalently link the drug to the amino group of the chitosan glucosamine units. Glutaric and succinic hemiesters of metronidazole were thus prepared and then coupled to chitosan to obtain metronidazole-glutaryl- and metronidazole-succinyl-chitosan conjugates. Polymeric prodrugs were characterized by solid state NMR method, namely carbon 13 cross polarization magic angle spinning ((13)C NMR CPMAS). Prodrug stability study was carried out in acid (pH = 1.2) and in alkaline (pH = 7.4) buffers in a thermostatic bath at 37 °C. Drug release from the two prodrugs was studied by incubating each of them with 10% w/v cecal and colonic content of rats. Obtained results showed that both prodrugs were adequately stable in acid environment, while the succinyl conjugate was more stable than the glutaryl one in alkaline buffer. Both the prodrugs released the drug in cecal and colonic content, showing that the two systems could serve as colon specific delivery systems of metronidazole. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  20. High Helicobacter pylori resistance to metronidazole and clarithromycin in Brazilian children and adolescents.

    PubMed

    Ogata, Silvio K; Godoy, Anita P Ortiz; da Silva Patricio, Francy R; Kawakami, Elisabete

    2013-06-01

    The aim of the present study was to assess the primary and secondary resistance of Helicobacter pylori strains to clarithromycin, amoxicillin, furazolidone, tetracycline, and metronidazole, the conventional antibiotics presently used in Brazilian children and adolescents. Seventy-seven consecutive H pylori strains, 71 of 77 strains obtained from patients without previous eradication treatment for H pylori infection, and 6 strains from patients in whom previous eradication treatment had failed. Global rate of resistance was 49.3% (38/77): 40% of strains were resistant to metronidazole, 19.5% to clarithromycin, and 10.4% to amoxicillin. All of the tested H pylori strains were susceptible to furazolidone and tetracycline. Multiple resistance were detected in 18.2% (14/77 patients) of the strains: 6 of 14 (43%) simultaneously resistant to clarithromycin and metronidazole; 5 of 14 (36%) to amoxicillin and metronidazole; 2 of 14 (14%) to amoxicillin, clarithromycin, and metronidazole; and 1 of 14 (7%) to clarithromycin and amoxicillin. The high resistance rate to metronidazole and clarithromycin observed in clinical H pylori isolates can exclude these antimicrobials in empirical eradication treatment in Brazil. Otherwise, furazolidone and tetracycline presented no resistance. Properly assessing the risks and benefits, these 2 antimicrobials and their derivatives could be used in empirical eradication schedules, both associated with amoxicillin, which showed a low resistance rate despite its wide use in pediatric patients.

  1. Resistance of Helicobacter pylori to tetracycline, amoxicillin, clarithromycin and metronidazole in Israeli children and adults.

    PubMed

    Peretz, Avi; Paritsky, Maya; Nasser, Omar; Brodsky, Diana; Glyatman, Tatyana; Segal, Sofia; On, Avi

    2014-08-01

    The aim of this study was to examine Helicobacter pylori-resistance rate to different antibiotics: tetracycline, amoxicillin, clarithromycin and metronidazole, and to compare eradication rates in adults and children in Israel. The study was based on the hypothesis of high-resistance rates to clarithromycin and metronidazole especially in adults and overall low-resistance rates to tetracycline and amoxicillin. One seventy six biopsies from patients with dyspeptic symptoms were cultured of which 100 were from adults (19-79 years) and 76 from children (7-17 years). All positive cultures were examined by Epsilometer test for MIC determination against tetracycline, amoxicillin, clarithromycin and metronidazole. 48.3% (85 out of 176) were H. pylori positive, of which 44% were from adults and 54% from children. Antibiotic resistance was seen in 31 out of 44 (70.5%) for metronidazole, 1 out of 44 (2.3%) for amoxicillin, 10 out of 44 (22.3%) for clarithromycin and 1 out of 44 (2.3%) for tetracycline among adults. Antibiotic resistance was seen in 10 out of 41 (24.4%) for metronidazole, 5 out of 41 (12.2%) for amoxicillin, 10 out of 41 (24.4%) for clarithromycin and 1 out of 41 (2.4%) for tetracycline among children. High rates of H. pylori resistance to metronidazole and clarithromycin was found especially among adults. Therefore, to increase the success rate of anti-H. pylori treatment, other classes of antibiotics need to be considered.

  2. Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance.

    PubMed

    Leitsch, David; Janssen, Brian D; Kolarich, Daniel; Johnson, Patricia J; Duchêne, Michael

    2014-01-01

    The enzyme flavin reductase 1 (FR1) from Trichomonas vaginalis, formerly known as NADPH oxidase, was isolated and identified. Flavin reductase is part of the antioxidative defence in T. vaginalis and indirectly reduces molecular oxygen to hydrogen peroxide via free flavins. Importantly, a reduced or absent flavin reductase activity has been reported in metronidazole-resistant T. vaginalis, resulting in elevated intracellular oxygen levels and futile cycling of metronidazole. Interestingly, FR1 has no close homologue in any other sequenced genome, but seven full-length and three truncated isoforms exist in the T. vaginalis genome. However, out of these, only FR1 has an affinity for flavins, i.e. FMN, FAD and riboflavin, which is high enough to be of physiological relevance. Although there are no relevant changes in the gene sequence or any alterations of the predicted FR1-mRNA structure in any of the strains studied, FR1 is not expressed in highly metronidazole-resistant strains. Transfection of a metronidazole-resistant clinical isolate (B7268), which does not express any detectable amounts of FR, with a plasmid bearing a functional FR1 gene nearly completely restored metronidazole sensitivity. Our results indicate that FR1 has a significant role in the emergence of metronidazole resistance in T. vaginalis.

  3. Metronidazole for bacterial vaginosis. A comparison of vaginal gel vs. oral therapy.

    PubMed

    Hanson, J M; McGregor, J A; Hillier, S L; Eschenbach, D A; Kreutner, A K; Galask, R P; Martens, M

    2000-11-01

    To compare the efficacy and safety of 0.75% metronidazole vaginal gel with oral metronidazole for the treatment of bacterial vaginosis (BV). Nonpregnant women with BV were enrolled in a multicenter, randomized, investigator-blind treatment trial. Patients were randomly assigned to either 0.75% metronidazole vaginal gel (5 g twice daily for five days) or oral metronidazole (500 mg twice daily for seven days). Follow-up visits occurred approximately two and five weeks after initiation of therapy. BV was clinically eliminated at the first follow-up visit in 83.7% (36/43, 95% CI 72.3-95.1%) of the intravaginal group and 85.1% (40/47, 95% CI 74.6-95.6%) of the oral group. At the final visit, BV was eliminated in 70.7% (29/41, 95% CI 56.3-85.1%) of the intravaginal group and 71.1% (32/45, 95% CI 57.4-84.8%) of the oral group. Significantly more patients in the oral treatment group (51.8%) reported gastrointestinal complaints as compared to the intravaginal treatment group (32.7%, P = .04). The efficacy of 0.75% metronidazole vaginal gel twice daily for five days in treating BV was similar to that of standard oral metronidazole treatment and was associated with fewer gastrointestinal complaints.

  4. Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers

    PubMed Central

    Comer, Sandra D.; Sullivan, Maria A.; Vosburg, Suzanne K.; Manubay, Jeanne; Amass, Leslie; Cooper, Ziva D.; Saccone, Phillip; Kleber, Herbert D.

    2012-01-01

    BACKGROUND Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, crossover study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs). METHODS Intravenous heroin users (n=12) lived in the hospital for 8–9 weeks and were maintained on each of 3 different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin, and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the 3 buprenorphine maintenance dose conditions. RESULTS Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of “drug liking” and “desire to take the drug again” were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient. CONCLUSIONS These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, it is lower than for buprenorphine alone, particularly when participants received higher maintenance dosages and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment. PMID

  5. Miconazole mucoadhesive buccal tablet in high-dose therapy with autologous stem cell transplantation (HDT/ASCT)-induced mucositis.

    PubMed

    Orvain, C; Moles-Moreau, M P; François, S; Mercier, M; Moal, F; Hamel, J F; Parot-Schinkel, E; Ifrah, N; Hunault-Berger, M; Tanguy-Schmidt, A

    2015-02-01

    Oral mucositis is a major cause of morbidity in high-dose therapy/autologous stem cell transplantation (HDT/ASCT), where microbial colonization has an important pathological implication. In this study, we evaluated the impact of miconazole mucoadhesive buccal tablet (MBT) on mucositis-related complications. During two consecutive 34-month periods, patients treated with HDT/ASCT in our hematology department received either miconazole MBT (60 patients) or conventional oral amphotericin B suspensions three times a day (44 patients) in order to prevent or decrease chemotherapy-induced mucositis. The use of miconazole MBT is associated with less infectious complications as indicated by shorter antibiotic use (7.8 vs. 12.3 days; p < 0.0001), shorter intravenous antifungal use (1.4 vs. 3.6 days; p = 0.02), and a trend towards less yeast contamination in stool samples. Less patients required any analgesic drugs during hospitalization in the miconazole MBT group (18 vs. 7 %; p = 0.09). Indirect indicators of chemotherapy-induced mucositis (duration of hospitalization, morphine use) were in favor of miconazole MBT in patients with multiple myeloma (MM) but not for those with lymphoma. This study suggests that miconazole MBT provides a valid alternative to oral amphotericin B suspensions in regards to mucositis-related complications. A prospective and randomized study is warranted to establish the definite role of miconazole MBT.

  6. High-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone for remission induction in refractory adult acute leukemia.

    PubMed

    Guthrie, T H

    1987-04-01

    Fifteen consecutive patients with refractory adult acute leukemia (RAAL) were treated with a combination of high-dose, continuous-infusion cyclophosphamide, cytarabine, vincristine, and prednisone (Hi-COAP). The initial nine patients received cyclophosphamide 350 mg/m2 as a 24-hour intravenous (IV) infusion over 5 days; cytarabine, 100 mg/m2 IV bolus every 12 hours for ten doses; vincristine, 2.0 mg IV bolus on day 1; and prednisone, 100 mg orally for 7 days. The last six patients had the cyclophosphamide infusion lengthened to 7 days, and the cytarabine increased to 14 doses. All patients were evaluable for toxicity and response. Seven patients (47%) obtained a complete remission and six patients (40%) a partial remission. Median duration of all remissions has been 7.0 months with a range of 1 to 32 months. Toxicity has been limited to primarily myelosuppression with no hemorrhagic cystitis, central nervous system (CNS), hepatic, or pulmonary toxicity noted. Gastrointestinal toxicity was mild, with no effect on nutritional status noted. Median duration of complete responders was 8.5 months. Thus, Hi-COAP demonstrates promising efficacy with minimal toxicity in RAAL and warrants further exploration in multiinstitutional trials.

  7. Scurvy in an alcoholic patient treated with intravenous vitamins

    PubMed Central

    Ong, John; Randhawa, Rabinder

    2014-01-01

    Vitamin C deficiency is rare in developed countries but there is an increased prevalence in chronic alcohol abusers. In the UK, it is common practice to treat patients with chronic alcoholism who are admitted to hospital with intravenous vitamins B1, B2, B3, B6 and C for 2–3 days, followed by oral thiamine and vitamin B-compound tablets. This is a case of a 57-year-old man with a history of chronic alcoholism and chronic obstructive lung disease who was admitted to the intensive care unit for pneumonia requiring ventilatory support. He was given high doses of intravenous vitamins B1, B2, B3, B6 and C for 3 days then oral thiamine and vitamin B compound tablets but developed scurvy 4 days later. He was restarted on oral vitamin C supplementation and showed signs of improvement within 3 days of treatment. PMID:24728889

  8. Scurvy in an alcoholic patient treated with intravenous vitamins.

    PubMed

    Ong, John; Randhawa, Rabinder

    2014-04-11

    Vitamin C deficiency is rare in developed countries but there is an increased prevalence in chronic alcohol abusers. In the UK, it is common practice to treat patients with chronic alcoholism who are admitted to hospital with intravenous vitamins B1, B2, B3, B6 and C for 2-3 days, followed by oral thiamine and vitamin B-compound tablets. This is a case of a 57-year-old man with a history of chronic alcoholism and chronic obstructive lung disease who was admitted to the intensive care unit for pneumonia requiring ventilatory support. He was given high doses of intravenous vitamins B1, B2, B3, B6 and C for 3 days then oral thiamine and vitamin B compound tablets but developed scurvy 4 days later. He was restarted on oral vitamin C supplementation and showed signs of improvement within 3 days of treatment.

  9. [Adult-onset Still's disease with pulmonary and cardiac involvement and response to intravenous immunoglobulin].

    PubMed

    Neto, Nilton Salles Rosa; Waldrich, Leandro; de Carvalho, Jozélio Freire; Pereira, Rosa Maria Rodrigues

    2009-01-01

    Cardiopulmonary manifestations of adult-onset Still's disease (AOSD) include pericarditis, pleural effusion, transient pulmonary infiltrates, pulmonary interstitial disease and myocarditis. Serositis are common but pneumonitis and myocarditis are not and bring elevated risk of mortality. They may manifest on disease onset or flares. Previously reported cases were treated with high-dose glucocorticoids and immunosupressants and, when refractory, intravenous immunoglobulin (IVIG). We report an AOSD patient whose flare presented with severe pleupneumonitis and myopericarditis and, following nonresponse to a methylprednisolone pulse, high dose of prednisone and cyclosporine A, recovered after a 2-day 1g/kg/day IVIG infusion.

  10. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH-DOSE

  11. Formulation development and evaluation of metronidazole magnetic nanosuspension as a magnetic-targeted and polymeric-controlled drug delivery system

    NASA Astrophysics Data System (ADS)

    Latha, Subbiah; Selvamani, Palanisamy; Kumar, Chelladurai Senthil; Sharavanan, Palaniappan; Suganya, Govindan; Beniwal, Vijender Singh; Rao, Poduri Rama

    2009-05-01

    A nanosuspension of magnetically tagged metronidazole was developed by the solvent displacement method coupled with ultrasonication and was evaluated for its physicochemical properties. The drug release from metronidazole magnetic nanosuspension at pH 1.2 and 7.0 shows maximum correlation coefficient for zero order and Higuchi model, respectively. The anthelmintic activity of the formulated metronidazole magnetic nanosuspension was evaluated on Indian earthworms (Pheretima poi). Metronidazole magnetic nanosuspension at a dose of 10 and 50 mg/ml shortened by 31% and 34%, respectively, the mean time to death of the earthworms when compared against a non-magnetic metronidazole suspension. Thus, the developed metronidazole magnetic nanosuspension showed potent, controlled and targeted drug action and might be a good therapeutic avenue in combating infectious GI disorders.

  12. Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 2. Cerebrospinal Fluid Concentration Measurements in Patients with External Ventricular Drain

    PubMed Central

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William

    2014-01-01

    This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0–τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0–τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF. PMID:24277050

  13. Metronidazole and hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain.

    PubMed

    Frasca, Denis; Dahyot-Fizelier, Claire; Adier, Christophe; Mimoz, Olivier; Debaene, Bertrand; Couet, William; Marchand, Sandrine

    2014-01-01

    This study explored metronidazole and hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and hydroxymetronidazole in CSF.

  14. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome.

    PubMed

    Fowler Iii, Alpha A; Kim, Christin; Lepler, Lawrence; Malhotra, Rajiv; Debesa, Orlando; Natarajan, Ramesh; Fisher, Bernard J; Syed, Aamer; DeWilde, Christine; Priday, Anna; Kasirajan, Vigneshwar

    2017-02-04

    We report a case of virus-induced acute respiratory distress syndrome (ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth University with vitamin C and with the very positive results of a previously performed phase I safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation (ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient's recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.

  15. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome

    PubMed Central

    Fowler III, Alpha A; Kim, Christin; Lepler, Lawrence; Malhotra, Rajiv; Debesa, Orlando; Natarajan, Ramesh; Fisher, Bernard J; Syed, Aamer; DeWilde, Christine; Priday, Anna; Kasirajan, Vigneshwar

    2017-01-01

    We report a case of virus-induced acute respiratory distress syndrome (ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth University with vitamin C and with the very positive results of a previously performed phase I safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation (ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient’s recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes. PMID:28224112

  16. Potential intravenous drug incompatibilities in a pediatric unit.

    PubMed

    Leal, Karla Dalliane Batista; Leopoldino, Ramon Weyler Duarte; Martins, Rand Randall; Veríssimo, Lourena Mafra

    2016-01-01

    To investigate potential intravenous drug incompatibilities and related risk factors in a pediatric unit. A cross-sectional analytical study conducted in the pediatric unit of a university hospital in Brazil. Data on prescriptions given to children aged 0-15 years from June to October 2014 were collected. Prescriptions that did not include intravenous drugs and prescriptions with incomplete dosage regimen or written in poor handwriting were excluded. Associations between variables and the risk of potential incompatibility were investigated using the Student's t test and ANOVA; the level of significance was set at 5% (p<0.05). Relative risks were calculated for each drug involved in potential incompatibility with 95% confidence interval. A total of 222 children participated in the study; 132 (59.5%) children were male and 118 (53.2%) were aged between 0 and 2 years. The mean length of stay was 7.7±2.3 days. Dipyrone, penicillin G and ceftriaxona were the most commonly prescribed drugs. At least one potential incompatibility was detected in about 85% of children (1.2 incompatibility/patient ratio). Most incompatibilities detected fell into the non-tested (93.4%), precipitation (5.5%), turbidity (0.7%) or chemical decomposition (0.4%) categories. The number of drugs and prescription of diazepam, phenytoin, phenobarbital or metronidazole were risk factors for potential incompatibility. Most pediatric prescriptions involved potential incompatibilities, with higher prevalence of non-tested incompatibilities. The number of drugs and prescription of diazepam, phenobarbital, phenytoin or metronidazole were risk factors for potential incompatibilities. Avaliar o potencial de incompatibilidade dos medicamentos intravenosos, identificando possíveis fatores de risco em uma unidade pediátrica. Trata-se de um estudo observacional analítico do tipo transversal realizado na unidade de pediatria de um hospital de ensino no Brasil. Os dados foram coletados de junho a outubro de

  17. Scavenging properties of metronidazole on free oxygen radicals in a skin lipid model system.

    PubMed

    Narayanan, Sabrina; Hünerbein, Andreas; Getie, Melkamu; Jäckel, Andreas; Neubert, Reinhard H H

    2007-08-01

    Reactive oxygen species (ROS) play a vital role in the pathophysiology of the skin disease rosacea, a chronic, genetically-determined and UV-triggered disease, leading to facial redness and blemishes and exhibiting a deep impact on a patient's self-esteem and quality of life. ROS can cause oxidative damage to nucleic acids, sugars, proteins and lipids, thereby contributing to adverse effects on the skin. Metronidazole has been the first-line topical agent therapy for many years; nevertheless the mechanism of action is still not well understood. The therapeutic efficacy of metronidazole has been attributed to its antioxidant effects, which can involve two pathways: decreased generation of ROS within tissues or scavenging and inactivation of existing ROS. Previous investigations have shown that metronidazole reduces ROS by decreasing ROS production in cellular in-vitro systems. The aim of the following study was to demonstrate that metronidazole additionally exhibits antioxidative properties in a cell-free system, by acting as an antioxidant scavenger. A simple skin lipid model (oxidative) system and a complex skin adapted lipid system in conjunction with thiobarbituric acid (TBA) test, a quantitative assay for the detection of malondialdehyde (MDA) and therefore lipid peroxidation, were used to determine the antioxidative properties of metronidazole after UV irradiation. Results clearly show that metronidazole has antioxidative properties in a cell-free environment, acting as a free radical scavenger. Simple skin lipid model: in the presence of 10, 100 and 500 microg mL(-1)metronidazole the MDA concentration was reduced by 25, 36 and 49%, respectively. Complex skin lipid system: in the presence of 100 and 500 microg mL(-1)metronidazole the MDA concentration was reduced by 19 and 34%, respectively. The results obtained in this study and from previous publications strongly suggest that metronidazole exhibits antioxidative effects via two mechanisms: decrease in ROS

  18. Effects of metronidazole (Flagyl) on the determination of serum ASAT on the SMA 12/60 Auto Analyser.

    PubMed

    Karlsen, R L; Kristiansen, G; Solberg, J H

    1983-04-01

    Therapeutic serum concentrations of metronidazole will lead to under-estimation of ASAT activity when a SMA 12/60 Auto Analyser is used. This interference is due to metronidazole entering the colorimeter through the dialyser membrane in the SMA 12/60 Auto Analyser. This drug is one of the few with a relatively high therapeutic serum concentration, absorbing light in the 340 nm range. Metronidazole will similarily affect other 340 nm methods (LDH, ALAT) available on the SMA 12/60. This interference with metronidazole on the SMA 12/60 can easily be solved by the introduction of a separate serum blank channel for the 340 nm methods.

  19. A Simple Low-dose X-ray CT Simulation from High-dose Scan.

    PubMed

    Zeng, Dong; Huang, Jing; Bian, Zhaoying; Niu, Shanzhou; Zhang, Hua; Feng, Qianjin; Liang, Zhengrong; Ma, Jianhua

    2015-10-01

    Low-dose X-ray computed tomography (CT) simulation from high-dose scan is required in optimizing radiation dose to patients. In this study, we propose a simple low-dose CT simulation strategy in sinogram domain using the raw data from high-dose scan. Specially, a relationship between the incident fluxes of low- and high- dose scans is first determined according to the repeated projection measurements and analysis. Second, the incident flux level of the simulated low-dose scan is generated by properly scaling the incident flux level of high-dose scan via the determined relationship in the first step. Third, the low-dose CT transmission data by energy integrating detection is simulated by adding a statistically independent Poisson noise distribution plus a statistically independent Gaussian noise distribution. Finally, a filtered back-projection (FBP) algorithm is implemented to reconstruct the resultant low-dose CT images. The present low-dose simulation strategy is verified on the simulations and real scans by comparing it with the existing low-dose CT simulation tool. Experimental results demonstrated that the present low-dose CT simulation strategy can generate accurate low-dose CT sinogram data from high-dose scan in terms of qualitative and quantitative measurements.

  20. Metronidazole decreases viability of DLD-1 colorectal cancer cell line.

    PubMed

    Sadowska, Anna; Krętowski, Rafał; Szynaka, Beata; Cechowska-Pasko, Marzanna; Car, Halina

    2013-10-01

    The aim of our study was to evaluate the impact of metronidazole (MTZ) on DLD-1 colorectal cancer cell (CRC) line. Toxicity of MTZ was determined by MTT test. Cells were incubated with MTZ used in different concentrations for 24, 48, and 72 hours. The effect of MTZ on DNA synthesis was measured as [3H]-thymidine incorporation. The morphological changes in human DLD-1 cell line were defined by transmission electron microscope OPTON 900. The influence of MTZ on the apoptosis of DLD-1 cell lines was detected by flow cytometry and fluorescence microscopy, while cell concentration, volume, and diameter were displayed by Scepter Cell Counter from Millipore. Our results show that cell viability was diminished in all experimental groups in comparison with the control, and the differences were statistically significant. We did not find any significant differences in [3H]-thymidine incorporation in all experimental groups and times of observation. Cytofluorimetric assays demonstrated a statistically significant increase of apoptotic rate in MTZ concentrations 10 and 50 μg/mL after 24 hours; 0.1, 10, 50, and 250 μg/mL after 48 hours; and in all concentrations after 72 hours compared with control groups. In the ultrastructural studies, necrotic or apoptotic cells were occasionally seen. In conclusion, MTZ affects human CRC cell line viability. The reduction of cell viability was consistent with the apoptotic test.

  1. Implications of metronidazole pharmacodynamics for therapy of trichomoniasis.

    PubMed

    Larsen, B; Wilson, A H; Glover, D D; Charles, D

    1986-01-01

    A liquid chromatographic technique for the detection of metronidazole (MDZ) and its major metabolites, combined with a vaginal sampling technique employing extraction of drug from vaginal swabs, was used to evaluate the concentration of MDZ in the vaginal fluid during therapy. Wide variation in the absolute concentration of unchanged drug was noted, although the average vaginal levels were about half the serum concentration 2 h after treatment had been initiated and comparable to the serum levels 6 and 24 h after treatment. Oral administration of MDZ invariably resulted in the presence of the drug in the serum and urine but the drug was not always detected in the vaginal secretions. The presence of the relatively inactive acetyl metabolite in the vaginal fluid of patients who failed to respond to therapy for trichomoniasis suggested the possible role of drug modification as a contributing factor in the lack of therapeutic success. The presence of MDZ in women in whom the cervix had previously been surgically removed attests to the transport or transudation of the drug across the vaginal epithelium without involvement of the secretory activity of the cervix.

  2. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials.

    PubMed

    Johnson, Stuart; Louie, Thomas J; Gerding, Dale N; Cornely, Oliver A; Chasan-Taber, Scott; Fitts, David; Gelone, Steven P; Broom, Colin; Davidson, David M

    2014-08-01

    Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole. Patients with CDI were randomly assigned in a 2:1:1 ratio to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 2 consecutive days including day 10. In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P < .001), and metronidazole was inferior to vancomycin (P = .02; 44.2% [n = 534], 72.7% [n = 278], and 81.1% [n = 259], respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  3. Lon protease affects the RdxA nitroreductase activity and metronidazole susceptibility in Helicobacter pylori.

    PubMed

    Tu, I-Fan; Liao, Jiahn-Haur; Yang, Feng-Ling; Lin, Nien-Tsung; Chan, Hong-Lin; Wu, Shih-Hsiung

    2014-10-01

    The lon gene of Helicobacter pylori strains is constitutively expressed during growth. However, virtually nothing is understood concerning the role of Lon in H. pylori. This study examined the function and physiological role of Lon in H. pylori (HpLon) using a trapping approach to identify putative Lon binding partners in the bacterium. Protease-deficient Lon was expressed and served as the bait in trapping approach to capture the interacting partners in H. pylori. The antibiotic susceptibility of wild-type and lon derivative mutants was determined by the E test trips and the disc diffusion assay. The effect of HpLon on RdxA activity was detected the change in NADPH oxidation and metronidazole reduction by spectrophotometer. Lon in Helicobacter pylori (HpLon) interacting partners are mostly associated with metronidazole activation. lon mutant presents more susceptible to metronidazole than that of the wild type, and this phenotype is recovered by complementation of the wild-type Lon. We found that the ATPases associated with a variety of cellular activities (AAA(+) ) module of HpLon causes a decrease in both NADPH oxidase and Mtz reductase activity in RdxA, a major Mtz-activating enzyme in H. pylori. Metronidazole resistance of H. pylori causes the serious medical problem worldwide. In this study, HpLon is involved in metronidazole susceptibility among H. pylori strains. We provide the evidence that HpLon alters RdxA activity in vitro. The decrease in metronidazole activation caused by HpLon is possibly prior to accumulate mutation in rdxA gene before the metronidazole-resistant strains to be occurred. © 2014 John Wiley & Sons Ltd.

  4. Evaluation of mechanical and rheological properties of metronidazole gel as local delivery system.

    PubMed

    Jelvehgari, Mitra; Montazam, Hassan

    2011-06-01

    Rosacea is a chronic multifactorial vascular skin disorder that affects about 10 percent of the general population. Metronidazole is an effective antibiotic in the treatment of moderate-to severe rosacea. Metronidazole is a suitable drug in cases of resistance to tetracycline or erythromycin, but it has also been shown that oral metronidazole may increase the side effects (e.g., peripheral neuropathy). Oral metronidazole should not be used for more than three months, and hence topical metronidazole gel is the best therapeutic choice in rosacea (especially during pregnancy). This study examined the mechanical (adhesiveness, cohesiveness, extrudability, spreadability, homogeneity) and rheological (viscosity), skin irritant and drug release properties of different metronidazole gel formulations that contain anionic emulsifying wax, glycerin and lactic acid in different proportions. The release studies were conducted using Franz diffusion cells and Silastic membrane as a barrier. The results indicated that gel compressibility, hardness, and adhesiveness, are the factors that influence the ease of gel removal from the container, ease of gel application onto the mucosal membrane, and gel bioadhesion. The findings showed that there exists a strong negative correlation between the spreadability of a formulation and its cohesiveness, the spreadability of a formulation is inversely proportional to its cohesiveness. However, sorbitol solution (70%) concentration was not significantly correlated with drug release. In addition, drug release was significantly reduced as the concentration of anionic emulsifying wax increased and the concentration of lactic acid decreased. The maximum metronidazole release was achieved at a pH of 4-6. Data obtained from in vitro release studies were fitted to various kinetic models and high correlation was obtained in the Higuchi and first order models. The results showed that all the gel formulations showed good extrudability, viscosity

  5. An in vitro metronidazole susceptibility test for trichomoniasis using the InPouch TV test.

    PubMed

    Borchardt, K A; Li, Z; Zhang, M Z; Shing, H

    1996-04-01

    An efficient anaerobic culture system, the InPouch TV test, was used to determine the susceptibility of Trichomonas vaginalis to metronidazole. Glacial acetic acid was employed as a solvent for metronidazole. T vaginalis isolates were cultured from 16 symptomatic female patients. The 11 who responded to oral metronidazole, 250 mg tid for 7 days, were considered as having sensitive trichomonads; the 5 who remained infected after treatment were considered to have resistant organisms. All isolates were cultured for minimum lethal concentrations (MLC). Metronidazole was added to a series of pouches; two-fold dilution of the most concentrated was 50 micrograms/ml and the least was 0.4 micrograms/ml. The inoculum of viable trichomonads was 1 x 105/ml in each pouch. Pouches were incubated at 37 degrees C for 48 h, examined microscopically for motile trichomonads, and then 0.5 ml was subcultured to drug free pouches. After 5 days incubation at 37 degrees C, each subculture and culture were examined microscopically for viable trichomonads. Eleven isolates of T vaginalis from patients responding to metronidazole treatment had MLC between 0.4 to 3.1 micrograms/ml. The MLC from the 5 treatment failure patients were between 12.5 to 50 micrograms/ml. For the 16 patients in this study, the MLC values determined with the InPouch TV test differentiated between infection caused by metronidazole sensitive and resistant trichomonads. The mean MLC of clinically resistant isolates was approximately eleven fold higher than the mean MLC of clinically sensitive isolates (15 micrograms/ml vs 1.32 micrograms/ml). There was a significant difference between clinically resistant and sensitive isolates (t = 5.47, p < 0.0005). This study suggests that the InPouch TV test could be used for distinguishing between metronidazole resistant and sensitive isolates.

  6. Community intravenous therapy provision.

    PubMed

    O'Hanlon, Sue; McGrail, Pam; Hodgkins, Paul

    2017-03-08

    Many healthcare services that were once only available in acute settings are now common in the community. Intravenous (IV) therapy is increasingly available as a community service. Given the option, most patients would choose to receive their treatment in a community setting, rather than in hospital. This article describes several outpatient parenteral antimicrobial therapy services, including their advantages and disadvantages. It explores the ways one community NHS trust has developed its community IV therapy service over the past ten years and examines issues pertinent to effective service delivery.

  7. [Maintenance treatment with high-dose buprenorphine: are the recommendations being followed?].

    PubMed

    Seyer, D; Dif, C; Balthazard, G; Sciortino, V

    1998-01-01

    Since February 1996, high-dose buprenorphine has been approved for use in the treatment of opioid dependence. In addition, recommendations concerning indications, patient selection, prescribing information and patient delivery have been addressed to doctors and pharmacists. Between its date of approval for use and late 1996, the medical service of French National Health Insurance followed 149 illicit drug users who received high-dose buprenorphine. They all lived in the Vosges 'département' and were affiliated with French Social Security Health Insurance. In general, the recommendations (consultation with a specialist, psychosocial follow-up and dosage schedules) were not followed by prescribing physicians. Concomitant prescriptions with psychotropic drugs, mainly benzodiazepines, were frequently encountered. This raises considerable concern since there have been recent reports of lethal intoxications with high-dose buprenorphine.

  8. High dose of tigecycline for extremely resistant Gram-negative pneumonia: yes, we can

    PubMed Central

    2014-01-01

    Few antimicrobials are currently active to treat infections caused by extremely resistant Gram-negative bacilli (ERGNB), which represent a serious global public health concern. Tigecycline, which covers the majority of these ERGNB (with the exception of Pseudomonas aeruginosa), is not currently approved for hospital-acquired pneumonia, and several meta-analyses have suggested an increased risk of death in patients receiving this antibiotic. Other studies suggest that the use of high-dose tigecycline may represent an alternative in daily practice. De Pascale and colleagues report that the clinical cure rate in patients with ventilator-associated pneumonia is significantly higher with a high dose of tigecycline than with the conventional dose, although mortality was unaffected. This high dose is safe; no patients required discontinuation or dose reduction. PMID:25043402

  9. Bone metastasis in breast cancer is treated by high-dose tamoxifen.

    PubMed

    Stathopoulos, George P; Trafalis, Dimitrios; Kaparelou, Maria

    2016-01-01

    Bone metastases in breast cancer are quite common, and some patients may have no other site of metastasis. An effective treatment is often endocrine agents administration (tamoxifen or antiaromatases), given mainly to postmenopausal women. Radiation treatment is also effective, although difficult to perform in cases of extensive skeletal disease. Chemotherapy does not help. The purpose of this study was to investigate the effectiveness of high-dose tamoxifen in female patients with breast cancer and bone metastasis. 28 patients with breast cancer were treated with high-dose tamoxifen. All of them had been pretreated with hormonal therapy including low-dose tamoxifen. The results were extremely positive with clinical amelioration and also disappearance of osteolysis in some patients. Twenty six out of 28 patients responded to the treatment, the criteria being mainly pain reduction and body mobilization (an amelioration which lasted 8 months-4 years). Tamoxifen is efficient when readministered at high dose to breast cancer patient with bone metastasis.

  10. Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer

    PubMed Central

    Schöttle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Siobal, Maike; Florin, Alexandra; Rokitta, Dennis; Hinze, Yvonne; Dietlein, Felix; Plenker, Dennis; König, Katharina; Albus, Kerstin; Heuckmann, Johannes M.; Rauh, Daniel; Franz, Thomas; Neumaier, Bernd; Fuhr, Uwe; Heukamp, Lukas C.; Ullrich, Roland T.

    2015-01-01

    Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy. PMID:26540572

  11. Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer.

    PubMed

    Schöttle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Siobal, Maike; Florin, Alexandra; Rokitta, Dennis; Hinze, Yvonne; Dietlein, Felix; Plenker, Dennis; König, Katharina; Albus, Kerstin; Heuckmann, Johannes M; Rauh, Daniel; Franz, Thomas; Neumaier, Bernd; Fuhr, Uwe; Heukamp, Lukas C; Ullrich, Roland T

    2015-11-17

    Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy.

  12. Collagenous colitis: Requirement for high-dose budesonide as maintenance treatment.

    PubMed

    Fernandez-Bañares, Fernando; Piqueras, Marta; Guagnozzi, Danila; Robles, Virginia; Ruiz-Cerulla, Alexandra; Casanova, María José; Gisbert, Javier P; Busquets, David; Arguedas, Yolanda; Pérez-Aisa, Angeles; Fernández-Salazar, Luis; Lucendo, Alfredo J

    2017-09-01

    Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. High-dose nimotuzumab improves the survival rate of esophageal cancer patients who underwent radiotherapy

    PubMed Central

    Wang, Chunyu; Fu, Xiaolong; Cai, Xuwei; Wu, Xianghua; Hu, Xichun; Fan, Min; Xiang, Jiaqing; Zhang, Yawei; Chen, Haiquan; Jiang, Guoliang; Zhao, Kuaile

    2016-01-01

    Nimotuzumab (h-R3) is a humanized monoclonal antibody that is safe to use against epidermal growth factor receptor (EGFR). However, the available information is insufficient about the dose effect of monoclonal antibody against epidermal growth factor receptor for the treatment of esophageal squamous cell carcinoma (ESCC). We retrospectively recruited 66 patients with ESCC who were treated with h-R3 and chemoradiotherapy/radiotherapy. Patients who received more than 1,200 mg of h-R3 were classified as the high-dose group, and the remaining patients were classified as the low-dose group. The endpoint for efficacy was the overall survival. Differences in survival between the groups were analyzed using the log-rank test. The Cox proportional hazards model was used in multivariate analysis to identify independent prognostic factors. The low-dose and high-dose groups comprised 55 and eleven patients, respectively. The median follow-up time in the final analysis was 46 months. The high-dose group showed no increased incidence of toxicities compared to the low-dose group. The 1-, 2-, and 5-year overall survival rates in the low-dose and high-dose groups were 66.9%, 50.0%, 31.5% and 90.0%, 80.0%, 66.7%, respectively (P=0.04). Multivariate analyses showed that the high-dose group had better survival than the low-dose group (hazard ratio 0.28, 95% confidence interval 0.09–0.94, P=0.039). Taken together, high-dose h-R3 showed limited toxicity and improved survival in patients with ESCC. PMID:26766917

  14. Gene expression profiling in undifferentiated thyroid carcinoma induced by high-dose radiation

    PubMed Central

    Bang, Hyun Soon; Choi, Moo Hyun; Kim, Cha Soon; Choi, Seung Jin

    2016-01-01

    Published gene expression studies for radiation-induced thyroid carcinogenesis have used various methodologies. In this study, we identified differential gene expression in a human thyroid epithelial cell line after exposure to high-dose γ-radiation. HTori-3 cells were exposed to 5 or 10 Gy of ionizing radiation using two dose rates (high-dose rate: 4.68 Gy/min, and low-dose rate: 40 mGy/h) and then implanted into the backs of BALB/c nude mice after 4 (10 Gy) or 5 weeks (5 Gy). Decreases in cell viability, increases in giant cell frequency, anchorage-independent growth in vitro, and tumorigenicity in vivo were observed. Particularly, the cells irradiated with 5 Gy at the high-dose rate or 10 Gy at the low-dose rate demonstrated more prominent tumorigenicity. Gene expression profiling was analyzed via microarray. Numerous genes that were significantly altered by a fold-change of >50% following irradiation were identified in each group. Gene expression analysis identified six commonly misregulated genes, including CRYAB, IL-18, ZNF845, CYP24A1, OR4N4 and VN1R4, at all doses. These genes involve apoptosis, the immune response, regulation of transcription, and receptor signaling pathways. Overall, the altered genes in high-dose rate (HDR) 5 Gy and low-dose rate (LDR) 10 Gy were more than those of LDR 5 Gy and HDR 10 Gy. Thus, we investigated genes associated with aggressive tumor development using the two dosage treatments. In this study, the identified gene expression profiles reflect the molecular response following high doses of external radiation exposure and may provide helpful information about radiation-induced thyroid tumors in the high-dose range. PMID:27006382

  15. [High-dose daidzein affects growth and development of reproductive organs in male rats].

    PubMed

    Jiang, Chun-Xia; Pan, Lian-Jun; Feng, Yao; Xia, Xin-Yi; Huang, Yu-Feng

    2008-04-01

    To explore the effect of the phytoestrogen daidzein on the growth and development of the testis and epididymis in male SD rats. Thirty 10-week old (early adult) and 30 4-week old (pubertal) male SD rats were included in the study, each age group equally divided into 5 subgroups: normal control, positive control, low-dose, medium-dose and high-dose. The normal and positive control groups were given 1 ml distilled water and the same amount of distilled water containing diethylstilbestrol (DES) at the dose of 0.1 mg/kg, and the low-, medium- and high-dose groups administered daidzein in the dose of 2mg/kg, 20 mg/ kg and 100 mg/kg, respectively, all by gavage for 90 days. Observations were made on the changes in body weight and testicular and epididymal indexes, as well as on the structural changes of the testis and epididymis by H&E staining. The early adult rats showed no significant differences in body weight and testicular and epididymal indexes between the claiclzein groups and the control (P > 0.05), nor did the pubertal rats in epididymal index (P > 0.05). The testicular index differed significantly between the high-dose group (3.21 +/- 0.07) and the normal control (3.71 +/- 0.45) (P < 0.05). The body weight reduced markedly in the high-dose group (P < 0.05), but with no significant differences between the normal control and the other two dose groups (P > 0.05). No obvious changes were observed in epididymal morphology in all the daidzein groups of the early adult and pubertal rats, but high-dose daidzein resulted in smaller testes and impaired spermatogenesis. The phytoestrogen daidzein, administered in a high dose, could delay the growth and development of the testis and induce structural changes of testicular tissues in pubertal SD rats.

  16. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  17. Efficacy of High-Dose Baclofen for Alcohol Use Disorder and Comorbid Bulimia: A Case Report.

    PubMed

    Weibel, Sébastien; Lalanne, Laurence; Riegert, Myriam; Bertschy, Gilles

    2015-01-01

    High-dose baclofen is a promising treatment for alcohol use disorder, with a specific action on craving. A more general action on craving in other addictive disorders has been suggested based on the hypothesis of a common neurobiological pathway in addictions. We report the case of a woman with both alcohol use disorder and bulimia nervosa. There was a positive response to high-dose baclofen on alcohol craving, but no response on food craving. The case illustrates that craving could be differentially responsive to anti-craving drugs.

  18. Mucormycoses: serious complication of high-dose corticosteroid therapy for traumatic optic neuropathy.

    PubMed

    Dojcinovic, I; Richter, M

    2008-04-01

    Mucormycosis is harmless to a healthy person, but can cause opportunistic infections in immunocompromised patients, and once it has invaded internal organs is frequently fatal. Traumatic optic neuropathy is a rare complication of maxillofacial trauma. Management is controversial, and there are no treatment guidelines in the literature. The main methods of treatment of this condition employed today are high-dose corticosteroids and surgical optic nerve decompression, either alone or in combination. In this case, the patient was in good health, but received high-dose corticosteroids for 2 weeks, which temporarily diminished immune response and permitted the development of mucormycosis.

  19. High-Dose Magnesium Sulfate Infusion for Severe Asthma in the Emergency Department: Efficacy Study.

    PubMed

    Irazuzta, Jose E; Paredes, Fatima; Pavlicich, Viviana; Domínguez, Sara L

    2016-02-01

    To assess the efficacy of a high-dose prolonged magnesium sulfate infusion in patients with severe, noninfectious-mediated asthma. Prospective, randomized, open-label study. Twenty-nine-bed pediatric emergency department located in a children's hospital in Asuncion, Paraguay. All patients of 6-16 years old who failed to improve after 2 hours of standard therapy for asthma. Subjects were randomized to receive magnesium sulfate, 50 mg/kg over 1 hour (bolus) or high-dose prolonged magnesium sulfate infusion of 50 mg/kg/hr for 4 hours (max, 8.000 mg/4 hr). Patients were monitored for cardiorespiratory complications. Asthma severity was assessed via asthma scores and peak expiratory flow rates at 0-2-6 hours. The primary outcome was discharge to home at 24 hours. An analysis of the hospital length of stay and costs was a secondary outcome. Thirty-eight patients were enrolled, 19 in each group. The groups were of similar ages, past medical history of asthma, asthma score, and peak expiratory flow rate. There was a significant difference in the patients discharged at 24 hours: 47% in high-dose prolonged magnesium sulfate infusion (9/19) versus 10% (2/21) in the bolus group (p = 0.032) with an absolute risk reduction 37% (95% CI, 10-63) and a number needed to treat of 2.7 (95% CI, 1.6-9.5) to facilitate a discharge at or before 24 hours. The length of stay was shorter in the high-dose prolonged magnesium sulfate infusion group (mean ± SD in hr: high-dose prolonged magnesium sulfate infusion, 34.13 ± 19.54; bolus, 48.05 ± 18.72; p = 0.013; 95% CI, 1.3-26.5). The cost per patient in the high-dose prolonged magnesium sulfate infusion group was one third lower than the bolus group (mean ± SD: high-dose prolonged magnesium sulfate infusion, $603.16 ± 338.47; bolus, $834.37 ± 306.73; p < 0.016). There were no interventions or discontinuations of magnesium sulfate due to adverse events. The early utilization of high-dose prolonged magnesium sulfate infusion (50 mg/kg/hr/4

  20. Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

    PubMed

    Hannoun-Lévi, J-M; Peiffert, D

    2014-10-01

    Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations.

  1. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report.

    PubMed

    Herrlinger, Ulrich; Küker, Wilhelm; Uhl, Martin; Blaicher, Hans-Peter; Karnath, Hans-Otto; Kanz, Lothar; Bamberg, Michael; Weller, Michael

    2005-06-01

    The NOA-03 trial explored high-dose methotrexate alone in 37 patients with primary central nervous system lymphoma. The overall median survival was 25 months. After 4 years, the rate of leukoencephalopathy in patients surviving more than 12 months was 58% with and 10% without whole-brain radiotherapy given at relapse (p = 0.11). Attention deficits were found in all six tested patients, and memory deficits in four patients. Two patients had normal, three had moderately restricted, and one had markedly restricted quality of life. Thus, high-dose methotrexate with deferred radiotherapy had only moderate efficacy and was associated with significant neurotoxicity in long-term surviving patients.

  2. The safety and efficacy of high dose ferric carboxymaltose in patients with chronic kidney disease: A single center study

    PubMed Central

    Vikrant, S.; Parashar, A.

    2015-01-01

    Ferric carboxymaltose (FCM) is a parenteral, dextran-free iron formulation designed to overcome the limitations of existing intravenous (IV) iron preparations. We investigated the safety and efficacy of high dose administration of FCM in our anemic chronic kidney disease (CKD) patients. It was a prospective observational study from June 2011 to August 2013. FCM was administered as IV infusion 1000 mg in 250 ml of normal saline over 15-30 min. Efficacy was evaluated by comparing the Hb and/or serum iron status at the first follow-up visit after the infusion with that at the baseline. A total of 500 infusions were administered to 450 patients. All patients had a successful administration of the FCM. None of the patients had any serious drug-related AE. AE of mild to moderate severity observed or reported after the infusion were: accelerated hypertension (0.2%), feeling abnormal (0.6%), headache and bodyaches (0.6% each), and infusion site reaction (0.8%). 261 patients had a follow up Hb, which showed an increase of 1.7 ± 1.5 g/dl after a period of 11 ± 7.2 weeks (P = 0.001); 188 (72%) patients had a rise in Hb of ≥1 g/dl. The increase in Hb was observed uniformly across all stages of CKD. Proportions of patients with an Hb of above 10 and 11 g/dl increased from 30.2% to 62.8% and 16.1% to 37.9%, respectively (P = 0.001). Iron status evaluation done in 44 patients after a follow up period of 15.1 ± 11.5 weeks showed increases in Hb of 1.6 ± 2.2 g/dl (P = 0.001), transferrin saturation of 9.1 ± 16.9% (P = 0.001), and ferritin of 406 ± 449 ng/ml (P = 0.001). We conclude high dose administration of FCM is safe and well-tolerated. It was effective in the treatment of iron deficiency in nondialysis and peritoneal dialysis CKD patients. PMID:26199472

  3. Stability of high-dose insulin in normal saline bags for treatment of calcium channel blocker and beta blocker overdose.

    PubMed

    Laskey, Dayne; Vadlapatla, Rajesh; Hart, Katherine

    2016-11-01

    High-dose insulin has become a first-line therapy for treating severe calcium channel blocker and beta blocker toxicity. Insulin infusions used to treat other conditions (e.g., diabetic ketoacidosis) may be used, but this may lead to pulmonary compromise due to fluid volume overload. An obvious solution would be to use a more concentrated insulin infusion; however, data describing the stability of insulin in polyvinyl chloride bags at concentrations >1 unit/mL are not readily available. To determine the stability of insulin at 16 units/mL in 0.9% saline solution. Eight-hundred units of regular insulin (8 mL from a stock vial containing 100 units/mL) were added to 42 mL of 0.9% saline solution in a polyvinyl chloride bag to make a final concentration of 16 units/mL. Two bags were stored at 4 °C (refrigerated) and two at 25 °C (room temperature). Samples were withdrawn and tested for insulin concentration periodically over 14 days. Concentrated regular insulin in a polyvinyl chloride bag remained within 90% of equilibrium concentration at all time points, indicating the 16 units/mL concentration was sufficiently stable both refrigerated and at room temperature for 14 days. Administration of high-dose insulin can cause fluid volume overload when using traditional insulin formulations. The 16 units/mL concentration allows for the treatment of a patient with severe calcium channel blocker or beta blocker toxicity for a reasonable period of time without administering excessive fluid. Insulin at a concentration of 16 units/mL is stable for 14 days, the maximum timeframe currently allowed under US Pharmacopeia rules for compounding of sterile preparations. This stability data will allow institutions to issue beyond-use dating for intravenous fluids containing concentrated insulin and used for treating beta blocker and calcium channel blocker toxicity.

  4. Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

    PubMed

    Leyvraz, S; Herrmann, R; Guillou, L; Honegger, H P; Christinat, A; Fey, M F; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B

    2006-11-20

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

  5. Exposure to Metronidazole In Vivo Readily Induces Resistance in Helicobacter pylori and Reduces the Efficacy of Eradication Therapy in Mice

    PubMed Central

    Jenks, Peter J.; Labigne, Agnes; Ferrero, Richard L.

    1999-01-01

    The Helicobacter pylori SS1 mouse model was used to characterize the development of resistance in H. pylori after treatment with metronidazole monotherapy and to examine the effect of prior exposure to metronidazole on the efficacy of a metronidazole-containing eradication regimen. Mice colonized with the metronidazole-sensitive H. pylori SS1 strain were treated for 7 days with either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole once a day or three times per day (TID). In a separate experiment, H. pylori-infected mice were administered either peptone trypsin broth or the mouse equivalent of 400 mg of metronidazole TID for 7 days, followed 1 month later by either peptone trypsin broth or the mouse equivalent of 20 mg of omeprazole, 250 mg of clarithromycin, and 400 mg of metronidazole twice a day for 7 days. At least 1 month after the completion of treatment, the mice were sacrificed and their stomachs were cultured for H. pylori. The susceptibilities of isolates to metronidazole were assessed by agar dilution determination of the MICs. Mixed populations of metronidazole-resistant and -sensitive strains were isolated from 70% of mice treated with 400 mg of metronidazole TID. The ratio of resistant to sensitive strains was 1:100, and the MICs for the resistant strains varied from 8 to 64 μg/ml. In the second experiment, H. pylori was eradicated from 70% of mice treated with eradication therapy alone, compared to 25% of mice pretreated with metronidazole (P < 0.01). Mice still infected after treatment with metronidazole and eradication therapy contained mixed populations of metronidazole-resistant and -sensitive isolates in a ratio of 1:25. These results demonstrate that H. pylori readily acquires resistance to metronidazole in vivo and that prior exposure of the organism to metronidazole is associated with failure of eradication therapy. H. pylori-infected mice provide a suitable model for the study of resistance mechanisms in H. pylori

  6. In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control.

    PubMed

    McCarty, Mark F

    2016-10-01

    In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive. Alternatively, administration of high-dose biotin has potential for modulating hepatic enzyme expression in a favorable way. Studies in rodents and in cultured hepatocytes demonstrate that, in the context of low insulin exposure, supra-physiological levels of biotin induce increased expression of GK while suppressing that of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects may be a downstream consequence of the fact that biotin down-regulates mRNA expression of FOXO1; insulin's antagonism of the activity of this transcription factor is largely responsible for its modulatory impact on hepatic glycolysis and gluconeogenesis. Hence, high-dose biotin may compensate for subnormal insulin exposure by suppressing FOXO1 levels. High-dose biotin also has the potential to oppose hepatic steatosis by down-regulating SREBP-1 expression. Two pilot trials of high-dose biotin (16 or 2mg per day) in type 1 diabetics have yielded promising results. There is also some reason to suspect that high-dose biotin could aid control of diabetic neuropathy and nephropathy via its stimulatory effect on cGMP production. Owing to the safety, good tolerance, moderate expense, and current availability of high-dose biotin, this strategy merits more

  7. Carotid Artery Stenting for Acute Ischemic Stroke Patients after Intravenous Recombinant Tissue Plasminogen Activator Treatment

    PubMed Central

    Deguchi, Ichiro; Hayashi, Takeshi; Neki, Hiroaki; Yamane, Fumitaka; Ishihara, Shoichiro; Tanahashi, Norio; Takao, Masaki

    2016-01-01

    We herein report three ischemic stroke patients who underwent emergency carotid artery stenting after receiving intravenous tissue plasminogen activator (t-PA) treatment. All patients received antiplatelet medications immediately before stent placement for loading as well as dual antiplatelet therapy after stenting. Under high-dose and dual antiplatelet therapy, none of the three patients showed symptomatic intracranial hemorrhaging. However, one case showed reocclusion of the placed stent after acute thrombosis. As a result, new treatment strategies for the use of antiplatelet agents during emergency stent placement must be developed, particularly for patients who have received intravenous t-PA therapy. PMID:27725550

  8. Intravenous immunoglobulin in treatment of cardiac tamponade in a patient with systemic lupus erythematosus.

    PubMed

    Grenader, Tal; Shavit, Linda

    2004-12-01

    We describe a 23-year-old female patient with a history of systemic lupus erythematosus and pulmonary hypertension who developed a large pericardial effusion with cardiac tamponade. Invasive interventions such as pericardial window or pericardiectomy were ruled out because of the posterior localization of the effusion and high risk of general anesthesia in a patient with severe pulmonary hypertension. The patient received high-dose steroids intravenously with no response. A 5-day course of intravenous immunoglobulin resulted in gradual decrease of the pericardial effusion and resolution of cardiac tamponade within 2 weeks.

  9. Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis.

    PubMed

    Raja, Indu M; Basavareddy, Asha; Mukherjee, Deepali; Meher, Bikash Ranjan

    2016-01-01

    To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1(st) week and 4(th) week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4(th) week (P = 0.0013), but not at 1(st) week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile.

  10. Combinatorial effects of amoxicillin and metronidazole on selected periodontal bacteria and whole plaque samples.

    PubMed

    Kulik Kunz, Eva M; Lenkeit, Krystyna; Waltimo, Tuomas; Weiger, Roland; Walter, Clemens

    2014-06-01

    The aim of the present study was to analyze in vitro the combinatorial effects of the antibiotic combination of amoxicillin plus metronidazole on subgingival bacterial isolates. Aggregatibacter (Actinobacillus) actinomycetemcomitans, Prevotella intermedia/nigrescens, Fusobacterium nucleatum and Eikenella corrodens from our strain collection and subgingival bacteria isolated from patients with periodontitis were tested for their susceptibility to amoxicillin and metronidazole using the Etest. The fractional inhibitory concentration index (FICI), which is commonly used to describe drug interactions, was calculated. Synergy, i.e. FICI values ≤ 0.5, between amoxicillin and metronidazole was shown for two A. actinomycetemcomitans (FICI: 0.3), two F. nucleatum (FICI: 0.3 and 0.5, respectively) and one E. corrodens (FICI: 0.4) isolates. Indifference, i.e. FIC indices of >0.5 but ≤4, occurred for other isolates and the 14 P. intermedia/nigrescens strains tested. Microorganisms resistant to either amoxicillin or metronidazole were detected in all samples by Etest. Combinatorial effects occur between amoxicillin and metronidazole on some strains of A. actinomycetemcomitans, F. nucleatum and E. corrodens. Synergy was shown for a few strains only. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Evaluation of metronidazole-loaded poly(3-hydroxybutyrate) membranes to potential application in periodontitis treatment.

    PubMed

    da Silva, Marcio A C; Oliveira, Renata N; Mendonça, Roberta Helena; Lourenço, Talita G B; Colombo, Ana Paula V; Tanaka, Marcelo N; Tude, Elena M O; da Costa, Marysilvia F; Thiré, Rossana Mara S M

    2016-01-01

    Guided tissue regeneration is a technique used for periodontium reconstruction. This technique uses barrier membranes, which prevent epithelial growth in the wound site and may also be used to release antibiotics, to protect the wound against opportunistic infections. Periodontal poly(3-hydroxybutyrate) membranes containing metronidazole (a drug used to help in infection control) were produced and characterized. The kinetic mechanism of the metronidazole delivery of leached and nonleached membrane as well as its cytotoxicity and structural integrity were evaluated. Poly(3-hydroxybutyrate) membranes containing 0.5-2 wt % of the drug and 20 wt % of the plasticizer were manufactured via compression molding. Based on morphological analysis, membranes loaded with 2% metronidazole were considered for detailed studies. The results revealed that metronidazole delivery by the leached membranes seemed to follow the Fick's law. Membranes were noncytotoxic. The amount of metronidazole delivered was in the range of the minimal inhibitory concentration for Porphyromonas gingivalis, and the membranes inhibited the proliferation of these bacteria. Besides, they maintained their mechanical resistance after 30 days of immersion in phosphate buffer at pH 7.4. © 2015 Wiley Periodicals, Inc.

  12. Randomized, double-blind, comparative study of oral metronidazole and tinidazole in treatment of bacterial vaginosis

    PubMed Central

    Raja, Indu M.; Basavareddy, Asha; Mukherjee, Deepali; Meher, Bikash Ranjan

    2016-01-01

    Objective: To compare the efficacy and tolerability of oral metronidazole and tinidazole in patients with bacterial vaginosis (BV) using Amsel's criteria. Patients and Methods: This was a randomized double-blind study, conducted by the Departments of Pharmacology and Gynecology of a tertiary care teaching hospital. Patients diagnosed with BV received either tablet metronidazole 500 mg twice daily for 5 days or tablet tinidazole 500 mg once daily + one placebo for 5 days and instructed to come for follow-up at the 1st week and 4th week. They were categorized as cured, partially cured, and not cured based on Amsel's criteria at the end of the study and compared between two groups using Chi-square test. Results: A total 120 women were enrolled in the study, of which 114 completed the study. The treatment arms were comparable. The cure rate with low-dose tinidazole was significantly more compared to metronidazole at 4th week (P = 0.0013), but not at 1st week (P = 0.242). The adverse drug reactions were less with tinidazole compared to metronidazole. Conclusion: Tinidazole at lower dose offers a better efficacy than metronidazole in long-term cure rates and in preventing relapses with better side effect profile. PMID:28066102

  13. Effects of mesocaval shunt on the pharmacokinetics of metronidazole in young rats.

    PubMed

    Guillé, Beatriz E Perez; Alvarez, Fernando Villegas; Toledo López, Alejandra R; Bravo-Luna, Miguel A Jiménez; Soriano-Rosales, Rosa E; Lares-Asseff, Ismael; Arrellin, Gerardo; Guillé, Maria G Pérez

    2005-01-01

    Prophylactic and therapeutic management of portosystemic encephalopathies is based on protein restriction in the diet, and the use of lactulose and antibiotics such as metronidazole. These actions intend to reduce the main source of intestinal ammonia production and release into the systemic circulation. The aim of this study was to evaluate the medium-term effects of mesocaval shunt on the pharmacokinetics of metronidazole in rats with healthy livers. Male Lewis rats were divided into two groups. The first group was subjected to mesocaval shunt (MCS) and the other employed as a control. The following tests were carried out in both groups: metronidazole pharmacokinetics, determination of ALT, AST, albumin, urea and ammonium, liver weight and histomorphology. A loss in body and liver weight was registered in rats subjected to MCS. AST levels also increased compared to controls. Significant differences in almost all pharmacokinetic parameters were detected between MCS and control rats, especially in Kel, AUC and Cmax. Modifications in metronidazole pharmacokinetics and liver weight changes without microstructural modification secondary to MCS were found. We suggest that individual drug-monitoring and pharmacokinetic analysis must be carried out in metronidazole medicated patients with modifications in portal circulation with or with out macro or micro liver structural alterations.

  14. [MRI and SPECT findings in a case of metronidazole-induced reversible acute cerebellar ataxia].

    PubMed

    Takase, Kei-ichiro; Santa, Yo; Ohta, Sumio; Yoshimura, Takeo

    2005-05-01

    A 69-year-old man was referred to our department because of acute onset nausea, vomiting, dysphagia, dysarthria and gait disturbance. He had a 50-day-history of amebic dysentery and had been treated with 1,500 mg metronidazole per day. Neurological examination revealed dysphagia, ataxic speech, ataxia of the left extremities and the trunk, and hyperactive deep tendon reflexes in all extremities. Sensory impairment of all modalities was apparent in a glove and stocking pattern, with mild paresthesia. Brain MRI showed T2 high signal lesions in the bilateral cerebellar dentate nuclei, more markedly on the left. On brain SPECT, obvious low blood perfusion was observed in the left cerebellar hemisphere. These findings well explained the ataxia of the left limbs. One month after discontinuing metronidazole, the cerebellar ataxia, dysphagia and MRI abnormalities completely cleared. Therefore, central nervous system damage induced by metronidazole is considered reversible. In spite of the presence of the MRI lesion in the right dentate nucleus, the patient had no ataxia of the right extremities and there was no hypoperfusion in the right cerebellar hemisphere. Thus, metronidazole does not appear to have a direct neurotoxic effect on the central nervous system. On the other hand, nerve conduction studies showed axonal polyneuropathy, which was not improved one month after cessation of the drug; thus metronidazole seems to exert more damage on peripheral nerves.

  15. Pyruvate Decarboxylase, the Target for Omeprazole in Metronidazole-Resistant and Iron-Restricted Tritrichomonas foetus

    PubMed Central

    Sutak, Róbert; Tachezy, Jan; Kulda, Jaroslav; Hrdý, Ivan

    2004-01-01

    The substituted benzimidazole omeprazole, used for the treatment of human peptic ulcer disease, inhibits the growth of the metronidazole-resistant bovine pathogen Tritrichomonas foetus in vitro (MIC at which the growth of parasite cultures is inhibited by 50%, 22 μg/ml [63 μM]). The antitrichomonad activity appears to be due to the inhibition of pyruvate decarboxylase (PDC), which is the key enzyme responsible for ethanol production and which is strongly upregulated in metronidazole-resistant trichomonads. PDC was purified to homogeneity from the cytosol of metronidazole-resistant strain. The tetrameric enzyme of 60-kDa subunits is inhibited by omeprazole (50% inhibitory concentration, 16 μg/ml). Metronidazole-susceptible T. foetus, which expresses very little PDC, is only slightly affected. Omeprazole has the same inhibitory effect on T. foetus cells grown under iron-limited conditions. Similarly to metronidazole-resistant cells, T. foetus cells grown under iron-limited conditions have nonfunctional hydrogenosomal metabolism and rely on cytosolic PDC-mediated ethanol fermentation. PMID:15155220

  16. Metronidazole and spiramycin therapy of mixed Bacteroides spp. and Neisseria gonorrhoeae infection in mice.

    PubMed

    Brook, I

    1989-01-01

    The in vitro and in vivo activity of metronidazole and spiramycin, used singly or in combination, was tested in the eradication of infection caused by Bacteroides spp. and Neisseria gonorrhoeae alone or in combination. The in vitro tests consisted of determinations of the minimal inhibitory concentrations (MIC), carried out with or without the addition of a constant amount of the other antimicrobials. The MIC of both Bacteroides bivius and Bacteroides fragilis for metronidazole were significantly reduced by the addition of spiramycin (from 0.5 to 0.125 micrograms/ml). The in vivo tests were carried out in mice and consisted of measurements of the effects of the antimicrobial agents on the bacterial contents of abscesses induced by subcutaneous injection of bacterial suspension. Synergism between metronidazole and spiramycin was noted against Bacteroides spp. in abscesses caused by either Bacteroides spp. alone, or in combination with N. gonorrhoeae. Furthermore, an additional reduction in the number of N gonorrhoeae was noted in mixed infection with Bacteroides that was treated with metronidazole alone. This study demonstrates the in vitro and in vivo efficacy of the combination of metronidazole and spiramycin in the treatment of infections caused by either Bacteroides spp. alone or in combination with N. gonorrhoeae.

  17. Effects of high-dose methadone maintenance on cocaine place conditioning, cocaine self-administration, and mu-opioid receptor mRNA expression in the rat brain.

    PubMed

    Leri, Francesco; Zhou, Yan; Goddard, Benjamin; Cummins, Erin; Kreek, Mary Jeanne

    2006-07-01

    Methadone maintenance at appropriate doses can effectively reduce cocaine abuse in heroin-dependent individuals. In the present studies, we investigated the effect of high-dose methadone maintenance cocaine conditioned place preference (CPP) and cocaine intravenous self-administration. Rats implanted with methadone-filled osmotic mini-pumps (20 and 55 mg/kg/day, SC) and conditioned with cocaine (1, 5, and 20 mg/kg, i.p.) did not express cocaine CPP. Similarly, rats implanted with methadone pumps (55 mg/kg/day) after cocaine conditioning (20 mg/kg) displayed neither spontaneous nor cocaine-precipitated (20 mg/kg, i.p.) CPP. In contrast, methadone maintenance (30 and 55 mg/kg/day, SC) did not alter the intravenous self-administration (continuous schedule of reinforcement) of various doses of cocaine (0.1, 0.5, and 2.0 mg/kg/inf). To explore neuropharmacological interactions between methadone maintenance and cocaine conditioning, we quantitatively measured mRNA levels of mu-opioid receptor (MOR) and proopiomelanocortin genes 10 days after methadone maintenance. MOR mRNA levels in both the nucleus accumbens core and frontal cortex were significantly elevated in rats exposed to cocaine during CPP conditioning. However, upregulation of MOR mRNA levels in the nucleus accumbens core were reduced by methadone maintenance in a dose-dependent manner. In conclusion, our results suggest that high-dose methadone maintenance does not alter the direct reinforcing effect of cocaine, but blocks spontaneous and cocaine-precipitated cocaine-seeking, possibly by preventing MOR alterations in the nucleus accumbens core induced by cocaine conditioning.

  18. Depletion of metronidazole in brook trout (Salvelinus fontinalis).

    PubMed

    Watson, Lynn; MacNeil, James D; Potter, Ross; Hellou, Jocelyne

    2015-01-01

    Metronidazole (MNZ), which is effective in the treatment of intestinal infections in fish, is also a suspected carcinogen and has been banned in numerous jurisdictions for use in any food-producing animal, including fish. Few reports have been published on the depletion of MNZ in fish. A depletion study was therefore undertaken using MNZ in feed provided to trout under controlled conditions. The water was maintained at 17.5 ± 0.9°C throughout the medication and depletion periods in the study. Following a 20-day acclimatisation period in the holding tanks, the trout (approximately 150-200 g bodyweight at the start of the study) were subjected to two separate medication and withdrawal periods: (A) 5 day medication/5 day withdrawal and (B) 5 day medication/16 day withdrawal. This simulated a potential multiple dosing in an aquaculture setting. In both medication periods, the trout were dosed with medicated feed containing 3 g MNZ kg(-1) fish. Fish were sacrificed in accordance with accepted animal care protocols and tissue samples were analysed by UPLC-MS/MS. Analyte concentrations in trout muscle ranged from a high of 27,000 ± 10,000 ng g(-1) for MNZ and 830 ± 570 ng g(-1) for MNZ-OH on day 1 of withdrawal period A to a low of 1.8 ± 2.3 ng g(-1) for MNZ and < 0.4 ng g(-1) for MNZ-OH on day 16 of withdrawal period B. The results demonstrate that when using the UPLC-MS/MS method, residues of MNZ may be detected in fish treated with MNZ after 16 days of withdrawal.

  19. The use of urinary and kidney SILAM proteomics to monitor kidney response to high dose morpholino oligonucleotides in the mdx mouse.

    PubMed

    Zhang, Aiping; Uaesoontrachoon, Kitipong; Shaughnessy, Conner; Das, Jharna R; Rayavarapu, Sree; Brown, Kristy J; Ray, Patricio E; Nagaraju, Kanneboyina; van den Anker, John N; Hoffman, Eric P; Hathout, Yetrib

    Phosphorodiamidate morpholino oligonucleotides (PMO) are used as a promising exon-skipping gene therapy for Duchenne Muscular Dystrophy (DMD). One potential complication of high dose PMO therapy is its transient accumulation in the kidneys. Therefore new urinary biomarkers are needed to monitor this treatment. Here, we carried out a pilot proteomic profiling study using stable isotope labeling in mammals (SILAM) strategy to identify new biomarkers to monitor the effect of PMO on the kidneys of the dystrophin deficient mouse model for DMD (mdx-23). We first assessed the baseline renal status of the mdx-23 mouse compared to the wild type (C57BL10) mouse, and then followed the renal outcome of mdx-23 mouse treated with a single high dose intravenous PMO injection (800 mg/kg). Surprisingly, untreated mdx-23 mice showed evidence of renal injury at baseline, which was manifested by albuminuria, increased urine output, and changes in established urinary biomarker of acute kidney injury (AKI). The PMO treatment induced further transient renal injury, which peaked at 7 days, and returned to almost the baseline status at 30 days post-treatment. In the kidney, the SILAM approach followed by western blot validation identified changes in Meprin A subunit alpha at day 2, then returned to normal levels at day 7 and 30 after PMO injection. In the urine, SILAM approach identified an increase in Clusterin and γ-glutamyl transpeptidase 1 as potential candidates to monitor the transient renal accumulation of PMO. These results, which were confirmed by Western blots or ELISA, demonstrate the value of the SILAM approach to identify new candidate biomarkers of renal injury in mdx-23 mice treated with high dose PMO. Chemical compounds studied in this article: Phosphorodiamidate morpholino (PubChem CID: 22140692); isoflurane (PubChem CID: 3763); formic acid (PubChem CID: 284); acetonitrile (PubChem CID: 6342); acetone (PubChem CID: 180); methanol (PubChem CID: 887).

  20. The use of urinary and kidney SILAM proteomics to monitor kidney response to high dose morpholino oligonucleotides in the mdx mouse

    PubMed Central

    Zhang, Aiping; Uaesoontrachoon, Kitipong; Shaughnessy, Conner; Das, Jharna R.; Rayavarapu, Sree; Brown, Kristy J; Ray, Patricio E.; Nagaraju, Kanneboyina; van den Anker, John N.; Hoffman, Eric P; Hathout, Yetrib

    2015-01-01

    Phosphorodiamidate morpholino oligonucleotides (PMO) are used as a promising exon-skipping gene therapy for Duchenne Muscular Dystrophy (DMD). One potential complication of high dose PMO therapy is its transient accumulation in the kidneys. Therefore new urinary biomarkers are needed to monitor this treatment. Here, we carried out a pilot proteomic profiling study using stable isotope labeling in mammals (SILAM) strategy to identify new biomarkers to monitor the effect of PMO on the kidneys of the dystrophin deficient mouse model for DMD (mdx-23). We first assessed the baseline renal status of the mdx-23 mouse compared to the wild type (C57BL10) mouse, and then followed the renal outcome of mdx-23 mouse treated with a single high dose intravenous PMO injection (800 mg/kg). Surprisingly, untreated mdx-23 mice showed evidence of renal injury at baseline, which was manifested by albuminuria, increased urine output, and changes in established urinary biomarker of acute kidney injury (AKI). The PMO treatment induced further transient renal injury, which peaked at 7 days, and returned to almost the baseline status at 30 days post-treatment. In the kidney, the SILAM approach followed by western blot validation identified changes in Meprin A subunit alpha at day 2, then returned to normal levels at day 7 and 30 after PMO injection. In the urine, SILAM approach identified an increase in Clusterin and γ-glutamyl transpeptidase 1 as potential candidates to monitor the transient renal accumulation of PMO. These results, which were confirmed by Western blots or ELISA, demonstrate the value of the SILAM approach to identify new candidate biomarkers of renal injury in mdx-23 mice treated with high dose PMO. Chemical compounds studied in this article: Phosphorodiamidate morpholino (PubChem CID: 22140692); isoflurane (PubChem CID: 3763); formic acid (PubChem CID: 284); acetonitrile (PubChem CID: 6342); acetone (PubChem CID: 180); methanol (PubChem CID: 887) PMID:26213685

  1. High-dose omeprazole infusion compared with scheduled second-look endoscopy for prevention of peptic ulcer rebleeding: a randomized controlled trial.

    PubMed

    Chiu, Philip Wai Yan; Joeng, Henry Kin Ming; Choi, Catherine Lai Yin; Tsoi, Kelvin Kam Fai; Kwong, Kwok Hung; Lam, Siu Ho; Sung, Joseph Jao Yiu

    2016-08-01

    Previous studies have shown that both scheduled second-look endoscopy and high-dose continuous omeprazole infusion are effective in preventing peptic ulcer rebleeding. The aim of this noninferiority trial was to compare the efficacy of these two strategies for the prevention of rebleeding following primary endoscopic hemostasis. Consecutive patients who received endoscopic treatment for bleeding peptic ulcers (actively bleeding, with nonbleeding visible vessels) were randomized to two treatment groups following hemostasis. One group (second-look endoscopy group) received the proton pump inhibitor (PPI) omeprazole as an intravenous bolus every 12 hours for 72 hours and a second endoscopy within 16 - 24 hours with retreatment for persistent stigmata of bleeding. The other group (PPI infusion group) received continuous high-dose omeprazole infusion for 72 hours. Patients who developed rebleeding underwent surgery if repeat endoscopic therapy failed. The primary outcome was the rebleeding rate within 30 days after initial hemostasis. The margin for noninferiority was set at 5 %. A total of 153 patients were randomized to the PPI infusion group and 152 to the second-look endoscopy group. Rebleeding occurred within 30 days in 10 patients (6.5 %) in the PPI infusion group and in 12 patients (7.9 %) in the second-look endoscopy group (P = 0.646). Surgery was required for rebleeding in six patients from the PPI infusion group and three patients in the second-look endoscopy group (P = 0.32). Intensive care unit stay, transfusion requirements, and mortality were not different between the groups. Patients in the second-look endoscopy group were discharged 1 day earlier than those in the PPI infusion group (P < 0.001). After endoscopic hemostasis, high-dose PPI infusion was not inferior to second-look endoscopy with bolus PPI in preventing peptic ulcer rebleeding. ClinicalTrials.gov (NCT: 00164931). © Georg Thieme Verlag KG Stuttgart · New York.

  2. Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial.

    PubMed

    Prunier, Fabrice; Bière, Loïc; Gilard, Martine; Boschat, Jacques; Mouquet, Frédéric; Bauchart, Jean-Jacques; Charbonnier, Bernard; Genée, Olivier; Guérin, Patrice; Warin-Fresse, Karine; Durand, Eric; Lafont, Antoine; Christiaens, Luc; Abi-Khalil, Wissam; Delépine, Stéphane; Benard, Thomas; Furber, Alain

    2012-02-01

    Preclinical studies and pilot clinical trials have shown that high-dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in pat