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Ritonavir strongly inhibits cytochrome P450, thus altering the metabolism of other drugs. We report on an HIV-positive man who, on his 13th day of ritonavir therapy, developed severe ergotism after self-administration of low doses of ergotamine. Drug interactions, the degree of responsibility of the patient and the availability of over-the-counter medications must be considered when prescribing antiretroviral therapy.
OBJECTIVE: To describe the effect of soy milk on the international normalized ratio (INR) in a patient treated with warfarin. CASE SUMMARY: A 70-year-old white man who was stable on warfarin therapy developed subtherapeutic INR values after ingesting soy protein in the form of soy milk. The subtherapeutic INR values could not be explained by factors known to reduce the INR such as noncompliance, new medications, other alternative therapies, increased physical activity, changes in medication storage, or increased consumption of vitamin K. INR values returned to therapeutic concentrations within 2 weeks after discontinuation of the soy milk. Repeated coagulation test results during the next 2 months remained within the normal range. DISCUSSION: Impaired warfarin metabolism may be ascribed to various pharmacodynamic and pathologic factors. Subtherapeutic INR values may also be the result of concomitant administration of metabolic inducers resulting in drug-drug, drug-herb, or drug-food interactions. An objective causality assessment in this case revealed that INR decline in a warfarin-treated patient as a result of soy milk ingestion was in the range of possible to probable. Speculative mechanisms of soy milk-induced INR decline such as changes in warfarin absorption or metabolism resulting from alterations in the P-glycoprotein efflux system or organic anion-transporting polypeptides are discussed. CONCLUSIONS: The temporal relationship between the start of soy milk and subtherapeutic INR values in 1 patient suggests that soy milk may have possibly or probably caused a decline in INR. Soy protein food-drug interactions with warfarin may be more common than the literature suggests, and further studies are needed to determine the exact mechanism. Healthcare professionals should be alerted to the potential implications of this food-drug interaction.
An adult male with non-Hodgkin lymphoma, who had been admitted to the hospital for more than one month and had received previous antibiotic therapy, developed Corynebacterium jeikeium septicemia. The organism was isolated in four blood cultures and it was multirresistant, being only sensitive to vancomycin, ciprofloxacin, norfloxacin and rifampin. The patient improved clinically and was bacteriologically cured with intravenous vancomycin therapy.
Richter's syndrome (RS) is characterized by the development of high-grade non-Hodgkin's lymphoma (NHL) in a patient with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. At The University of Texas M.D. Anderson Cancer Center the incidence of RS is 3.9%. The large cells of RS may arise through transformation of the original CLL clone or represent a new neoplasm. RS may be triggered by viral infections, such as Epstein-Barr virus (EBV). Trisomy 12 and chromosome 11 abnormalities, as well as multiple genetic defects, have been described in patients with RS. These abnormalities may cause CLL cells to proliferate and, by facilitating the acquisition of new genetic abnormalities, to transform into RS cells. The therapeutic strategies for RS typically include therapies developed for NHL or acute lymphoblastic leukemia. The reported response rates with these therapies are 5% to 43%, and the median survival duration ranges from 5 to 8 months. The median overall survival duration at our institution of patients with RS is 9.1 months (95% confidence interval, 7.8 to 11 months), and the median failure-free survival duration is 7.1 months (95% confidence interval, 5.1 to 10.4 months). Patients appear to benefit from cytoreductive therapy consisting of chemotherapy and immunotherapy, followed by allogeneic stem cell transplantation, as postremission therapy. As part of a program aiming to cure RS, we are currently conducting a clinical trial of oxaliplatin, fludarabine, and cytarabine in combination with rituximab and recommend postremission therapy, including allogeneic stem cell transplantation in patients with available donors.
A conservation technique has been developed for the treatment of early breast cancer which involved removal of the tumor, axillary clearance, tumor site implantation with Iridium-192 wires for a boost dose and subsequent treatment of the breast with radical megavoltage external beam therapy. Although the cosmetic results were satisfactory in the majority of the patients, for some it was rated as fair or poor. One variable factor which could have carried some morbidity was the dose of radiation received by the skin. In 51 patients, doses were measured at several points over the treated breast using Thermoluminescent Dosimetry (TLD) at the time of the iridium implant and during the subsequent external beam therapy. Development of skin pigmentation, oedema, and fibrosis were unrelated to the dose received by the skin but the findings suggested that doses greater than 50 Gy to the skin increased the possibility of late (greater than 24 months) telangiectasia over the boosted area. Treatment of tumors in the lower half of the breast, or in large breasts, was associated with a higher incidence of poor cosmesis. This may have been the result of varying posture on the interstitial dose distribution from the Iridium-192 wires and comparison of dose distribution in both supine and erect positions was carried out.
Acquired immunodeficiency syndrome, a death sentence two decades ago, has been transformed into a chronic disease with a life expectancy of many years, due to the advent of highly active antiretroviral therapy. Despite virologic success, nearly 50 percent of patients on highly active antiretroviral therapy develop lipodystrophy with central and visceral fat accumulation and/or facial and limb fat atrophy. The changes are referred to as the human immunodeficiency virus lipodystrophy syndrome. The authors describe a series of five patients with antiretroviral therapy-induced lipodystrophy of the face who benefited from surgical correction of their typical stigmatizing malar atrophy. Dermafat grafts were transferred from the abdominal wall to malar pockets through a transoral approach. The aesthetic results were dramatic and stable, lasting the duration of the 1- to 2-year follow-up period.
OBJECTIVE: To investigate the antitumor effect of combined adenovirus encoding E. coli cytosine deaminase (AdCD) and adenovirus encoding murine interleukin 2 (AdIL-2) on murine melanoma. METHODS: C57BL/6 mice were inoculated s.c. with B16F10 melanoma cells and 3 days later received injections of AdCD and/or AdIL-2 at the site of tumor inoculation followed by administration of 5-flurocytosine (5FC) 300 mg/kg per day for 10 days. RESULTS: Mice receiving AdCD/5FC/AdIL2 therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5FC, AdIL2, AdlacZ/5FC, or PBS. Immunological analysis illustrated that combined treatment could enhance NK activity and CTL activity. Flow cytometry demonstrated that AdCD/5FC/AdIL2 therapy increased the expression of MHC-1 and CD80 molecules on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly after the combined therapy. CONCLUSIONS: Our data showed that combined transfer of CD suicide gene and IL-2 gene could inhibit the tumor growth more significantly. The increased specific and non-specific antitumor immunity might be responsible for the enhanced therapeutic effect.
Over the last decade, polyomavirus nephropathy (PVN) has emerged as an important cause of renal allograft dysfunction and graft loss. PVN occurs with a prevalence of 1%-8% in renal transplant recipients and is most commonly reported within the first 12 months posttransplant. The human polyomavirus, BK virus, is thought to be the primary etiologic agent of PVN. Risk factors for PVN are not well defined and are most likely a result of a complex interaction between multiple donor and recipient factors. Definitive diagnosis of PVN is made through histological assessment of a renal allograft biopsy. Recent studies have also evaluated noninvasive urine and serum markers for screening of BK virus replication and as adjunct tools in PVN diagnosis and monitoring. The principal treatment for PVN is immunosuppression reduction, but this must be balanced against the risks of rejection. If rejection occurs concurrently with PVN, a brief increase in immunosuppression to treat the rejection episode followed by a subsequent reduction in immunosuppression is recommended. No antiviral treatments for PVN have been approved by the Food and Drug Administration. Although the antiviral drug cidofovir has shown in vitro activity against murine polyomaviruses, and has been effective in some patients, it is associated with significant nephrotoxicity. Small series of patients treated with leflunomide and intravenous immune globulin therapy for PVN have also recently been reported. Retransplantation after graft loss due to PVN is feasible, but experience is limited. Current research is focusing on identifying PVN risk factors, refining screening, diagnostic and monitoring methods, and developing therapy for prophylaxis and treatment of PVN with the goals of decreasing the prevalence of PVN and improving allograft outcomes in renal transplant recipients diagnosed with PVN. This review will present recent advances in basic and clinical research related to PVN and renal transplantation.
A 32-year-old man with systemic lupus erythematosus controlled by steroid therapy developed multifocal cutaneous abscesses caused by Mycobacterium scrofulaceum. The distribution and evolution of the lesions suggested hematogenous dissemination, but he exhibited no pulmonary or other visceral manifestations of systemic mycobacterial disease. The patient completed nine months of therapy with isoniazid and rifampin, and the lesions resolved within five months of presentation.
The UKCC recognises that midwives may become qualified in non-traditional therapies. One of the major difficulties for a practitioner advancing into a new field of practice is determining her/his competence. As new therapies develop, there is not initially the expertise to determine the accepted standards of care and practice. Vicarious liability depends on whether the midwife is acting in the course of her employment when she is carrying out the therapy. The midwife has a legal duty to respect the mother's wishes and choices. It is essential for the midwife to keep comprehensive, clear records on any agreement with the mother over the use of complementary therapies.
This was a prospective study involving 27 patients with moderate symptoms of benign prostatic hyperplasia (BPH) treated continuously with 5 mg of finasteride daily for one year. There was improvement in clinical BPH symptoms in 22 patients (81.48%), increase in urinary flow rates by a mean of 2.2 mls/sec in 20 patients (74.07%) and a mean decrease in prostate volume of 20.9% in 25 patients (92.59%) comparable to the findings of the other investigators. No patient on finasteride therapy developed acute urinary retention suggesting reduced risk. The reversal in BPH progression stems from the ability of finasteride to reduce prostate volume thus relieving urinary obstruction and to decrease BPH symptoms and increase urinary flow rates. Finasteride therapy was well tolerated in this study. No adverse effect was observed except impotence in one patient (3.7%) and loss of libido in another patient (3.7%). For symptomatic relief in men with moderate obstructive symptoms of BPH, finasteride should be considered an effective alternative to watchful waiting. These findings warrant further investigations and may signal a positive change in the role of medical therapy in the future long term management of BPH.
OBJECTIVE: To assess whether the scale used affects levels of evidence inferred from a systematic review of studies on exercise therapy and chronic low back pain (LBP). DESIGN: Twenty trials previously analyzed in a systematic review were assessed by 2 readers using 16 different scales. SETTING: Tertiary care teaching hospital in France. PARTICIPANTS: Chronic LBP patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: For the scales allowing classification into high- and low-quality trials, a rating system with 4 levels of evidence was used to summarize conclusions drawn. The Spearman rank correlation coefficient was used to assess correlations between the scores obtained with the different scales. Interrater reliability of the scales was assessed with the intraclass correlation coefficient and the Bland and Altman method, and the degree of agreement between the readers was calculated using the kappa coefficient. RESULTS: Two of the 3 main results of the systematic review (conflicting evidence on the effectiveness of exercise therapy compared with inactive treatments; strong evidence that exercise therapy is more effective than usual care by a general practitioner) were influenced by the scale used. The range of the Spearman rank correlation coefficients between the different scales was wide (range,.49-.94), the interreader reliability of the scales was heterogeneous, and the interreader agreement was often low (kappa<or=.60 for 7/10 tests). CONCLUSIONS: The use of summary scores to identify physical therapy trials of high quality is questionable. Different quality assessment scales should probably be used to assess pharmacologic interventions and physical therapies. Development and validation of quality scales specific to physical treatments are needed.
This review aims to discuss recent developments in antithrombotic therapy. New and specific inhibitors of platelet dependent thrombosis appear to moderately improve the outcome in coronary vascular disease. Further studies will need to address the cost-benefit ratio of this additional intervention. Hirudin and analogues are potent inhibitors of thrombin, and are clinically efficious, but at current dosage levels still complicated by bleeding. Low molecular weight heparin have markedly improved the efficacy of prevention and treatment of venous thromboembolism.
This overview describes the development of interferon therapy in four different types of viral diseases. (1) Upper respiratory infections: despite extensive efforts interferons have not found a place in the treatment of these very common diseases. (2) Herpes keratitis: alpha interferons are highly active in combination therapy, but have gained only very limited clinical use. (3) Papillomavirus infections: alpha interferons have been approved for the treatment of papillomavirus infections of skin and mucous membranes and are in fairly wide clinical use. (4) Chronic hepatitis B, C and D: alpha interferons have become the treatment of choice and are used very extensively worldwide. The four examples illustrate both the clinical potentials and the limitations of alpha interferons and give some guidelines for future work. The overall conclusion is that chronic viral diseases lend themselves to interferon therapy more readily than acute viral infections. The general trend is toward the use of interferons in combination therapy.
Expanding knowledge about basic biology and a detailed understanding of the signaling pathways that participate in the growth and metastasis of breast cancer have identified opportunities for diagnostic and therapeutic intervention. Endocrine therapy represents the first and most successful example of targeted therapy in breast cancer. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) is now part of the management of metastatic disease and is under evaluation as adjuvant therapy. Other pathways have been targeted, and several candidate drugs are being developed. While these developments represent opportunities for better therapies, they have also identified limitations in identification of targets and development of targeted therapies. Validation of targets is critical, and it is also critical to determine whether the putative target can be identified in a consistent, practical, and inexpensive manner. Finally, it is imperative that targeted therapies are devoid of toxicities secondary to the ubiquitous nature of the target, and we must improve our understanding of interactions that provide specificity of signaling under physiologic conditions.
BACKGROUND: Stroke is one of the most significant potential complications in patients who are undergoing cardioversion for atrial fibrillation. To minimize the risk of stroke, the American College of Chest Physicians' (ACCP's) Third Consensus Conference on Antithrombotic Therapy developed specific recommendations regarding anticoagulation before and following elective cardioversion of patients with atrial fibrillation. OBJECTIVE: To determine if patients undergoing cardioversion for atrial fibrillation are administered anticoagulants according to the ACCP's Third Consensus Conference on Antithrombotic Therapy recommendations. DESIGN: A retrospective review of cases of atrial fibrillation at a tertiary care teaching hospital to determine if physicians are routinely following these recommendations. METHODS: Data were collected for the year 1994 for all patients admitted to a tertiary care teaching hospital with a diagnosis of atrial fibrillation (n = 111). The ACCP's recommendations that were evaluated included the following: patients undergoing elective cardioversion for atrial fibrillation should receive anticoagulation for 3 weeks before and 4 weeks following cardioversion except in cases of new-onset atrial fibrillation, and warfarin and heparin should be administered jointly for several days before discontinuation of heparin therapy. RESULTS: Of the 111 patients who presented with a diagnosis of atrial fibrillation, 51 underwent elective cardioversion. In 18 (35%) of 51 cases, physicians failed to follow at least one of ACCP's recommendations regarding anticoagulation. These included failing to (1) administer anticoagulants to patients for 3 weeks before elective cardioversion (n = 14); (2) administer anticoagulants to patients for 4 weeks following cardioversion (n = 6); and (3) overlap heparin and/or warfarin therapies for 72 hours (n = 4). Six cases failed to meet more than one of these recommendations. CONCLUSION: Physicians are not routinely following the ACCP's Third Consensus Conference on Antithrombotic Therapy recommendations regarding anticoagulation in elective cardioversion of atrial fibrillation, thus increasing patients' risk of stroke.
A brief review of up-date problems of neutron radiobiology, related to neutron therapy development and setting up of radiation safety standards for neutrons, is present. The main attention is paid to the effects of combined gamma-neutron irradiation, peculiarities of reactor neutrons biological action and new approaches in neutron capture therapy. On the basis of own and literature data the results of cellular and whole-body studies as well as the applicability of biophysical modelling for description and interpretation of experimental data are discussed.
A 54-year-old female with chronic renal failure who had undergone renal homotransplantation and who was being maintained for 3 months on immunosuppressive therapy, developed Candida pyarthrosis of the hip. The patient posed a management problem because of the nephrotoxicity of the antibiotics required to control Candida. The literature was of little help in resolving the treatment dilemma because only 4 other cases of Candida pyarthrosis in adults, and only one other on immunosuppressive therapy, have been reported. Surgical excision of the head and neck of the femur was elected because the combined use of Amphotericin B and 5-fluorocytosine posed an unacceptable risk of renal damage while the use of 5-fluorocytosine alone might allow development of step-wise resistance to the drug. Femoral head and neck resection and a 7-month course of 5-fluorocytosine brought the infection under control and allowed normal would healing. With increasing number of compromised susceptible patients, the frequency of serious infections caused by ordinarily saphrophytic organisms is likely to increase. There is a need for more case reports on management, including the consequences of surgical excision of Candida infected tissues.