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PubMedDate not supplied

Clinical comparison of cefotaxime with gentamicin plus clindamycin in the treatment of peritonitis and other soft-tissue infections.

The efficacy and safety of cefotaxime were compared with the efficacy and safety of gentamicin plus clindamycin in the treatment of peritonitis and soft-tissue infection in 112 patients. Patients received 20 mg of intravenous cefotaxime/kg of body weight every 6 hr or 1 mg of gentamicin/kg every 8 hr plus 5 mg of clindamycin/kg every 6 hr (both intravenously). Therapy was continued for five to 10 days. The overall clinical cure rate was 82%, with no significant difference between cure rates in the two groups. Both antibiotic regimens were effective against aerobic and anaerobic isolates, although Pseudomonas aeruginosa, an occasional isolate of Enterobacter, and some anaerobes were resistant to cefotaxime. All clinical failures involved patients who had septicemia or who had received inadequate surgical treatment. Six (11%) of the patients who received combination therapy developed impaired renal function, as indicated by a rise in serum creatinine of 30%. No reduction in renal function was noted in patients given cefotaxime. The clinical efficacy of cefotaxime was equal to that of gentamicin plus clindamycin, and less nephrotoxicity was encountered with cefotaxime.

Adolescent↗
PubMed2006

Vancomycin-induced elevation of liver enzyme levels.

OBJECTIVE: To report a case of oral vancomycin-induced elevation of liver enzyme levels. CASE SUMMARY: A 57-year-old man with multiple medical conditions requiring systemic antibiotic therapy developed numerous Clostridium difficile-associated enterocolitis episodes. The patient did not respond adequately to oral metronidazole, as evidenced by his continuing diarrhea. He was treated with oral vancomycin on 5 separate occasions (with doses from 125 to 500 mg/day), each of which resulted in significant elevations in alanine aminotransferase (to 371 U/L) and aspartate aminotransferase (to 203 U/L) levels. The elevations resolved on each occasion with discontinuation of vancomycin. DISCUSSION: Vancomycin, a glycopeptide antibiotic, has primary activity against gram-positive bacteria. Oral vancomycin can be used for the treatment of C. difficile-associated enterocolitis in patients who fail to respond to or are intolerant to metronidazole therapy. Oral vancomycin has very poor bioavailability and, as of May 4, 2006, has not been associated with hepatic toxicity. Inflammatory bowel disease processes can result in increased absorption of oral vancomycin. CONCLUSIONS: This is the first reported case of oral vancomycin-induced elevation of hepatic enzyme levels. Use of the Naranjo probability scale indicated that this was a probable adverse drug-associated event.

Alanine Transaminase↗
PubMed1987

Developing an occupational therapy curriculum at a small college.

Small colleges and universities are increasingly turning to new program development to increase enrollments, stem decline, and ensure survival. Occupational therapy is an increasingly popular curriculum among small college and university administrators in view of its potential for attracting students, enhancing the organization's profile and mission, and generating revenue. This study examined the development of the occupational therapy curriculum at College Misericordia, Dallas, Pennsylvania, from 1981 to 1984. Interviews and pertinent documents, such as financial records, curricular materials, and enrollment statistics, were analyzed. The results demonstrate that the occupational therapy curriculum was instrumental in increasing enrollments and generating revenues at this small college. It can be concluded that curriculum development in occupational therapy can have a positive effect on an organization's ability to remain viable in an increasingly competitive market.

Curriculum↗
PubMed2002

Transmyocardial laser revascularization: a review of basic and clinical aspects.

Transmyocardial laser revascularization (TMR or TMLR) is a surgical therapy developed to treat patients with debilitating, medically refractory angina pectoris due to epicardial coronary artery disease that is not amenable to treatment using the traditional methods of percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). This technique can also be applied percutaneously [percutaneous myocardial revascularization (PMR) or direct myocardial revascularization (DMR)]. The original hypotheses which motivated development of TMR were that: (i) oxygenated blood could flow directly from the left ventricle and perfuse the myocardium; and (ii) such artificially created channels would remain patent. However, experimental data have refuted both hypotheses. In the face of early reports of marked clinical benefits in terms of relief of anginal symptoms, alternate hypotheses to explain the mechanism have been pursued, including TMR-associated neoangiogenesis and cardiac denervation. Clinically, numerous reports of reduction in frequency and severity of anginal symptoms, improved exercise tolerance and improved quality of life have appeared from nonblind registry-type studies as well as nonblind randomized clinical trials of TMR or PMR versus continued medical therapy. TMR was not associated with a significant improvement in survival compared with medical therapy alone in randomized trials. For example, the prospective, randomized Angina Treatments-Lasers and Normal Therapies in Comparison (ATLANTIC) trial found a 1-year mortality of 5% in 92 TMR-treated patients and 10% in 90 patients treated with medication only. No proof of improved myocardial blood flow in hearts of treated patients is currently available. The first randomized study of PMR was the Potential Angina Class Improvement From Intramyocardial Channels (PACIFIC) trial which found significantly greater improvements in anginal symptoms and exercise tolerance with PMR plus medical therapy, compared with medical therapy alone. The preliminary results of two double-blind studies with PMR/DMR have been presented but have not yet been published in full. Whereas PMR-treated patients did significantly better than sham-treated control groups after 6 months in the Blinded Evaluation of Laser Intervention Electively For angina pectoris (BELIEF) trial, there was no difference after 1 year between DMR-treated patients and those treated with medication only in the DMR In Regeneration of Endomyocardial Channels Trial (DIRECT). Different devices used for revascularization in these two trials may explain the disparity in the results, and therefore the efficacy and tolerability of each device should be judged upon data collected with that particular device.

Angina Pectoris↗
PubMed1991

Treatment of high-risk solid tumors of childhood with intensive therapy and autologous bone marrow transplantation.

Autologous bone marrow transplantation (ABMT) allows delivery of intensive, marrow-ablative chemotherapy or chemoradiotherapy to children with high-risk solid tumors. Results from several studies of neuroblastoma suggest that outcome is improved by ABMT; however, relapses can occur months to years after complete clinical remission. Other high-risk tumors including peripheral neuroepithelioma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, and brain tumors also appear to be responsive to intensive marrow-ablative therapy, although few studies have been reported. For tumors that can metastasize to marrow, a sensitive method is necessary for detecting tumor cell contamination. Immunocytologic analysis with monoclonal antibodies can identify one neuroblastoma cell per 10(5) normal marrow cells; this method also is applicable to other tumors with appropriate antibodies. Ex vivo removal (purging) of tumor cells decreases the probability of infusing tumorigenic cells with the ABMT. There is considerable experience in tumor detection and purging for neuroblastoma, but little has been done for other childhood solid tumors. Future investigations of ABMT will aim to further increase disease-free survival by intensifying induction and marrow-ablative regimens and by developing therapies to be given after ABMT that are directed at minimal residual disease. As pilot investigations mature, the efficacy of ABMT and conventional chemotherapy will be compared in multi-institution randomized studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Rechallenge of patients who had discontinued alendronate therapy because of upper gastrointestinal symptoms.

BACKGROUND: There have been reports from physicians in clinical practice that up to 30% of patients taking bisphosphonate therapy develop upper gastrointestinal (UGI) symptoms, many or most of which they assume to be related to the drug. However, in several large placebo-controlled clinical trials of bisphosphonates, the incidence of UGI symptoms has been > or =30%, even among patients receiving placebo, perhaps reflecting a high background incidence of UGI events in osteoporotic patients. OBJECTIVE: To assess the relationship between alendronate treatment and UGI complaints in patients who had discontinued treatment with alendronate in clinical practice because of UGI symptoms, we compared the incidence of such events on rechallenge with alendronate or placebo. METHODS: This was a multicenter, double-blind trial in which postmenopausal women with osteoporosis who had previously discontinued alendronate therapy because of a UGI adverse experience were randomized to daily treatment with either alendronate 10 mg or matching placebo (1:1 ratio) for 8 weeks. The primary end point was the cumulative incidence of discontinuations due to any UGI adverse experience. Secondary end points were the incidence of any clinical adverse experiences and the percentage change from baseline in urinary N-telopeptide adjusted for urinary creatinine at week 8. RESULTS: A total of 172 women were included in the study. They were a mean of 20.9 years past menopause, ranging in age from 41 to 90 years (mean, 67.0 years); 90.7% were white. On rechallenge, 14.8% (13/88) of patients in the alendronate group and 16.7% (14/84) in the placebo group discontinued treatment because of UGI adverse experiences. CONCLUSION: The results of this study suggest that many UGI adverse experiences reported during therapy with alendronate may reflect a high background incidence of UGI complaints and an increased sensitivity to detection of such complaints, rather than a causal relationship to therapy.

Alendronate↗
PubMed2005

Prevention of central cell damage to isolated islets of Langerhans in hamsters by low temperature preconditioning.

BACKGROUND: The efficacy of clinical islet transplantation has been demonstrated with autografts, and although islet allografts have established insulin independence in a small number of IDDM patients, the treatment is confounded by the necessity of central cell damage immunosuppression, the lack of donor tissue, and recurring islet immunogenicity. These limitations underscore a need to develop therapies to serve the large population of diabetic patients. This study was designed to document central cell damage to isolated islets of Langerhans in hamsters and its prevention. METHODS: Islets were cultured at 37 degree centigrade for 7-14 days after isolation, and then at 26 degree centigrade for 2,4 and 7 days before additional culture at 37 degree centigrade for an additional 7 days. Central cell damage in the isolated islets was monitored by video-microscopy and analyzed quantitatively by a computer-assisted image analysis system. The analysis included daily measurement of the diameter and the area of the isolated islets and the area of the central cell damage that developed in those islets over time during culture. Histological examination and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to characterize cell damage and to monitor islet function. RESULTS: Microscopic analysis showed that during the 7 to 14 days of culture at 37 degree centigrade, central cell damage appeared in the larger islets with diameters greater than 200 microm, which included both necrotic and apoptotic cell death. Low temperature (26 degree centigrade) culture prevented central cell damage of isolated islets. The 7-day culture procedure at 26 degree centigrade could inhibit most of the central cell (excluding diameters greater than 300 microm) damage when the islets were rewarmed to 37 degree centigrade. CONCLUSIONS: Our results indicate that central cell damage to isolated islets of Langerhans correlates with the size of the islets. Low temperature (26 degree centigrade) culture can prevent central cell damage to the isolated islets, and is capable to successfully precondition these islets for 37 degree centigrade culture. These novel findings may help to understand the pathophysiology of early loss of islet tissue after transplantation, and may provide a new strategy to improve graft function in the clinical setting of islet transplantation.

Animals↗
PubMed2004

Pocket hematoma after pacemaker or implantable cardioverter defibrillator surgery: influence of patient morbidity, operation strategy, and perioperative antiplatelet/anticoagulation therapy.

STUDY OBJECTIVES: Pocket hematoma is a common complication after pacemaker or implantable cardioverter defibrillator (ICD) implantation. Thus, we investigated the influence of patient comorbidity, implantation strategy, operator experience, antiplatelet therapy, and anticoagulation therapy on hematoma rate. DESIGN: Between 1990 and 2002, a total of 3,164 devices (pectoral pacemakers, 2,792; ICDs, 372) were implanted at our institution. Predictors of hematoma occurrence were determined prospectively and were analyzed by multivariate regression analysis. Operator experience was graded by individual implantation number, as follows: low, < 50; medium, 50 to 100; and high, > 100. RESULTS: The incidence of pocket hematoma was 4.9%, leading to prolonged hospitalization in 2.0% of all patients. Reoperation for pocket hematoma was required in 1.0% of patients. High-dose heparinization (hazard ratio [HR], 4.2), combined acetylsalicylic acid (ASA)/thienopyridine treatment after coronary stenting (HR, 5.2), and low operator experience (HR, 1.6) were independently predictive of hematoma development. Therapy with ASA alone did not increase the hematoma rate compared to patients who did receive antiplatelet or anticoagulation therapy (3.1% vs 2.5%, respectively; difference not significant). In patients with nonvalvular atrial fibrillation, postoperative high-dose heparinization substantially increased the hematoma rate (10.7% vs 2.9%, respectively; p < 0.001) without reducing the rate of arterial embolism within the first month after implantation (0.18% vs 0.21%, respectively; difference not significant). The infection rate (0.28% within 3 months after implantation) was not influenced by the presence of the pocket hematoma. CONCLUSIONS: The use of high-dose heparinization and combined ASA/thienopyridine treatment are highly predictive for the occurrence of intraoperative bleeding and pocket hematoma in patients who have undergone pacemaker and ICD surgery. We propose recommendations for the management of antiplatelet and anticoagulation therapy in patients undergoing these interventions.

Aged↗
PubMed2006

Enhanced 11beta-hydroxysteroid dehydrogenase activity, the metabolic syndrome, and systemic hypertension.

Metabolic syndrome, with its attendant cardiovascular complications, is reaching epidemic proportions worldwide; hence, there is intense interest in understanding the pathogenesis of and developing therapy for these common disorders. Recent studies have suggested that metabolic syndrome may be a stress response, with an underlying abnormality in the enzyme 11beta-hydroxysteroid dehydrogenase. At the cellular level, the enzyme hydroxysteroid dehydrogenase type 1 (HSD1) locally regenerates active cortisol from inactive cortisone, amplifying glucocorticoid receptor activation and promoting preadipocyte differentiation and adipocyte hypertrophy. Although initial studies in transgenic mice and humans are encouraging, more data are required to conclusively prove the hypothesis that the adipose-tissue-specific overexpression of HSD1 and the resultant increase in tissue-specific cortisol concentrations result in human obesity, insulin resistance, high blood pressure, and metabolic syndrome. Currently, selective inhibitors of HSD1 are not available for human use; however, their development is under way. The use of potent and selective HSD1 inhibitors will finally confirm or refute this hypothesis and may turn out to be an effective strategy for combating these common maladies.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

A clinical nude mouse metastatic model for highly malignant human pancreatic cancer.

Pancreatic cancer is a highly aggressive and treatment-refractory cancer. A clinically-relevant animal model is necessary to develop therapy for metastatic pancreatic cancer. In this study we evaluated the efficacy of mitomycin C (MMC) and 5-FU against the human pancreatic adenocarcinoma cell line PAN-12 in an orthotopic human metastatic pancreatic cancer nude mice model. The model is constructed by surgical orthotopic implantation (SOI) of histologically intact tumor tissue in the tail portion of the pancreas near the spleen. PAN-12 grew very aggressively in the control group of nude mice with extensive local invasion and distant metastasis to various organs with a propensity for the lung but to other organs as well, including the liver, kidney and regional and distant lymph nodes. In a striking effect none of the mice in the MMC-treated group developed tumor. Although mice in the 5-FU treated group survived statistically significantly longer than those in the untreated control, the overall incidence of metastasis in these mice was equivalent to those in the control. However no liver or kidney metastases were found in the 5-FU treated animals perhaps accounting in part for their longer survival. This "clinical" nude mouse model of highly metastatic pancreatic cancer can now be used to discover new effective agents for this disease.

Adenocarcinoma↗
PubMed1998

[Genetic therapy for the nervous system: a trend in modern neurology].

INTRODUCTION: Genetic therapy is in itself a new type of treatment, of potential use in many neurological conditions currently considered to be resistant to conventional treatment. Great advances have been made in the construction of vectors of expression and carriers of viral genes, thus work is starting on the characterization of target cells for neuronal genetic therapy. DEVELOPMENT: As a result of advances in this field, two methods of genetic transference have evolved. One, 'in vivo', involves transfection of genetic material by means of chemical or viral agents. The 'ex vivo' variant depends on manipulation of culture cells to subsequently inject them into the host organism with a view to correcting the cell phenotype. Both methods have been used in preliminary experiments designed to test the efficacy of genetic transference for improvement of dysfunction of the nervous system. At the present time there is much experimentation with the use of genetic transference using modified cells to synthetize growth factors or key enzymes of the neurotransmission process in biomodels of Parkinsonism and Alzheimer amongst other conditions. CONCLUSIONS: Genetic therapy, as is shown in this review, has great therapeutic potential for nervous diseases which are very severe and complex. There is certainly a long way to go to perfect these techniques, particularly with regard to biological security and regulation of the element transferred. However, when it is used it will mean a major qualitative change in the treatment of nervous system disorders which are at present a cause of severe handicap and have little chance of treatment.

Animals↗
PubMed2006

Multiple sclerosis, natalizumab therapy, and progressive multifocal leukoencephalopathy.

PURPOSE OF REVIEW: Multiple sclerosis affects many people, often in early adulthood, and causes significant disability. Natalizumab is a novel agent to be evaluated for multiple sclerosis and Crohn's disease that has demonstrated unique efficacy but has unfortunately been implicated in three cases of progressive multifocal leukoencephalopathy. This review covers the mechanism of action of natalizumab and efficacy for multiple sclerosis, the three cases of natalizumab-associated progressive multifocal leukoencephalopathy, our understanding of progressive multifocal leukoencephalopathy, and the mechanisms that may account for these events. RECENT FINDINGS: Natalizumab, an anti-alpha4-integrin antibody, binds to T-cell surface receptors to prevent migration from the circulation into the brain tissue. Phase II and III trials have been completed and demonstrate previously unseen efficacy in preventing relapses and disease progression. The cases of progressive multifocal leukoencephalopathy, two fatal and one disabling, resulted in the voluntary suspension of natalizumab and bring this entire class of agents into doubt. It is important to determine what led to the development of progressive multifocal leukoencephalopathy in the natalizumab-associated cases and to advance understanding and continue to develop therapies for the treatment of multiple sclerosis. SUMMARY: With ongoing safety evaluations, natalizumab is being reevaluated by the US Food and Drug Administration for possible reapproval and return to the market. If natalizumab is reapproved, challenging questions and issues will remain in treating patients with multiple sclerosis.

Adult↗
PubMed1999

Exposure of expanded polytetrafluoroethylene-wrapped hydroxyapatite orbital implant: a report of two patients.

PURPOSE: Hydroxyapatite (HA) spheres used to replace volume after an enucleation are often wrapped with autologous tissue before orbital implantation. Man-made materials are less expensive and pose no risk for viral transmission. The use of expanded polytetrafluoroethylene (ePTFE) to wrap HA spheres was evaluated. METHODS: The medical records of 2 consecutive patients who underwent uncomplicated implantation of an HA sphere wrapped in ePTFE were reviewed. RESULTS: An unusual reaction to the ePTFE material that was nonresponsive to topical or systemic antibiotic therapy developed in these 2 patients. Eventual wound erosion and bacterial infection of the implant necessitated its removal. CONCLUSIONS: Although well tolerated in other surgeries, ePTFE, when used to wrap HA spheres and placed into the orbit, may cause persistent conjunctival discharge, pyogenic granuloma formation, and eventual wound erosion. Therefore, the use of this material to wrap HA spheres is not recommended.

Aged↗
PubMedDate not supplied

Renal allograft rupture caused by acute tubular necrosis.

Renal allograft rupture is a rare but potentially lethal complication of kidney transplantation. A renal allograft recipient receiving quadruple immunosuppressive therapy developed a spontaneous allograft rupture 13 days after kidney transplantation. Warm ischaemia time during the transplant was 80 minutes. The ruptured kidney graft could not be salvaged because of the patient's haemodynamic instability. The histopathological examination showed interstitial oedema with severe acute tubular necrosis with no signs of acute rejection. The most common causes of renal graft rupture are acute rejection and vein thrombosis, while acute tubular necrosis may only rarely be responsible for this complication. Renal graft rupture may be the result of interstitial damage attributed both to the prolonged warm ischaemia time during the transplant and to post-transplant acute tubular necrosis in the absence of graft rejection. In those patients whose haemodynamic status cannot be stabilized by appropriate aggressive haemodynamic support therapy, graft nephrectomy should be considered the only definitive treatment.

Female↗
PubMed1985

Accelerated recovery from immune-mediated thrombocytopenia with plasmapheresis.

Autoimmune thrombocytopenia unresponsive to corticosteroid therapy developed in a 16-year-old female with long-standing Sjögren's syndrome. Serial plasma exchange caused a linear decrease in platelet antibody titer associated with a concomitant rise in platelet count. Statistical analysis of sequential platelet counts revealed an increase with plasmapheresis and immunosuppression that was significantly greater than that achieved with immunosuppression alone (p less than 0.005).

Adolescent↗
PubMed2000

A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication.

BACKGROUND: Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia. Although the cumulative evidence is strong, early controlled trials showed methodological limitations. METHODS: A randomized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention. Both interventions were delivered by 2 experienced nurses who received regular supervision. Patients were assessed by blind raters at baseline, after treatment (lasting up to 9 months), and at a 9-month follow-up evaluation. Patients continued to receive routine care throughout the study. An assessor blind to the patients' treatment groups rated the technical quality of audiotaped sessions chosen at random. Analysis was by intention to treat. RESULTS: Ninety patients received a mean of 19 individual treatment sessions over 9 months, with no significant between-group differences in treatment duration. Both interventions resulted in significant reductions in positive and negative symptoms and depression. At the 9-month follow-up evaluation, patients who had received cognitive therapy continued to improve, while those in the befriending group did not. These results were not attributable to changes in prescribed medication. CONCLUSION: Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to standard antipsychotic drugs, with its efficacy sustained over 9 months of follow-up.

Adult↗
PubMed1995

Cefazolin is inferior to cefotetan as single-dose prophylaxis for women undergoing elective total abdominal hysterectomy.

The purpose of this prospective, randomized, double-blind clinical trial was to compare the efficacy of 1-g doses of intravenous cefazolin with that of 1-g doses of intravenous cefotetan in preventing major operative site infections after elective abdominal hysterectomy. A major operative site infection requiring parenteral antimicrobial therapy developed in 46 (9%) of 511 evaluable women: 30 (11.6%) of 258 women given cefazolin prophylaxis and 16 (6.3%) of 253 women given cefotetan prophylaxis (relative risk, 1.84; 95% confidence interval, 1.03 to 3.29; P < .05). Risk factors for major operative site infection were younger age, lower postoperative hemoglobin concentration, and a proliferative endometrium. Ten (3.9%) of 258 women given cefazolin prophylaxis had a postoperative pelvic abscess; two of these women required additional surgical procedures, compared with two (0.8%) of 253 women given cefotetan prophylaxis who had an abscess but did not require surgery (relative risk, 4.9; 95% confidence interval, 1.09 to 22.16; P = .04). A greater number of infections and more serious infections occurred following cefazolin prophylaxis; this treatment resulted in 234 additional hospital days for administration of parenteral antimicrobial therapy.

Adult↗
PubMed2002

[Delivery of "suicide" thymidine kinase gene of herpes virus in the complex with cationic peptide into human hepatoma cells in vitro].

The delivery of "suicide" herpes simplex virus type-1 thymidine kinase gene (tk) into tumor cells, followed by treatment with synthetic nucleotide analogues (gancyclovir, acyclovir), is a perspective approach to cancer therapy. Serious limitations in employment of the existing means of gene delivery into target cells constitute the main obstacle for cancer gene therapy development. In the present work a possibility to use a nonviral gene delivery system is shown based on the employment of lysine rich peptide K8 and amphipathic peptide JTS-1 for transferring tk gene into human hepatoma HepG2 cells. Cationic peptide K8 forms compact complexes with plasmid DNA, and JTS-1 acts as a pH-dependent endosomal releasing agent. Transfection of HepG2 cells by tk expression vector coupled with K8/JTS-1 peptides, followed by acyclovir administration (50-100 micrograms/ml) for 24 h leads to cell cycle arrest in the G1/S checkpoint of some cells, which eventually die through apoptosis. Treatment of HepG2 cells with higher acyclovir concentration (200 micrograms/ml) additionally results in a nonspecific toxic effect. The above results demonstrate the efficacy of K8/JTS-1 delivery system for the "suicide" cancer gene therapy, and may be regarded as a basis for further elaboration of "suicide" cancer approaches in vivo.

Acyclovir↗