Evaluation of occult acetaminophen hepatotoxicity in hospitalized children receiving acetaminophen. Pediatric Pharmacology Research Unit Network

The safety of repeated doses of acetaminophen in ill children with the potential of reduced glutathione stores has been questioned. This study measured hepatic transaminases in children and adolescents (n=100) who received > or = 6 therapeutic doses of acetaminophen over a 48-hour period of hospitalization. Acetaminophen-protein adducts were measured in a cohort of subjects with hepatic transaminase elevation (n=8) and in those (n=10) receiving concurrent drug therapy with agents that induce the cytochrome P450 enzymes involved in acetaminophen metabolism. Acetaminophen-protein adducts were not detected in this cohort of 18 subjects. Based on this pilot study, the routine use of acetaminophen at therapeutic doses in ill, hospitalized children and adolescents appears safe.     

Fifty landmark discoveries in gastroenterology during the past 50 years. A brief history of modern gastroenterology at the millennium: Part II. Gastrointestinal motility, nutrition, and diseases of the lower gastrointestinal tract, liver, and pancreas

During the last half century, many outstanding discoveries have revolutionized the clinical practice and science of gastroenterology. Although the scientific results are widely disseminated, the discoverers have received inadequate recognition and the history of their discoveries is largely unstudied and unknown. At the millennium, a committee selected 50 landmark discoveries in gastroenterology during the past 50 years. A brief history of each landmark discovery is presented. Part I was presented in the previous issue of Gastroenterology Clinics of North America. Part II presents landmark discoveries in gastrointerintal (GI) motility, clinical trials, nutrition, and diseases of the lower GI tract, liver, biliary tree, and pancreas.     

Pilot study of rosiglitazone therapy in women with breast cancer: effects of short-term therapy on tumor tissue and serum markers.

PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARgamma is associated with antiproliferative effects on human breast cancer cells in preclinical studies. The purpose of this study was to test the hypothesis that PPARgamma ligand therapy might inhibit tumor growth and progression in human breast cancer. EXPERIMENTAL DESIGN: We conducted a pilot trial of short-term (2-6 weeks) treatment with the thiazolidinedione rosiglitazone in 38 women with early-stage (T(is)-T(2), N(0-1), M(0)) breast cancer, administered between the time of diagnostic biopsy and definitive surgery. RESULTS: Short-term treatment with rosiglitazone (8 mg/d) did not elicit significant effects on breast tumor cell proliferation using Ki67 expression as a measure of cell proliferation and surrogate marker of tumor growth and progression. In pretreatment tumors notable for nuclear expression of PPARgamma by immunohistochemistry, down-regulation of nuclear PPARgamma expression occurred following rosiglitazone administration (P = 0.005). No PPARG mutations were identified, and the incidence of P12A and H446H polymorphisms did not differ relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in increased serum adiponectin (P < 0.001), decreased insulin levels (P = 0.005), and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated without serious adverse events. CONCLUSION: Our data indicate that short-term rosiglitazone therapy in early-stage breast cancer patients leads to local and systemic effects on PPARgamma signaling that may be relevant to breast cancer.     

Scarf osteotomy in the management of symptomatic adolescent hallux valgus

Purpose  

This study was designed to assess the utility of the scarf osteotomy in the management of symptomatic adolescent hallux valgus.     

The conservative management of patients with symptoms of stress incontinence: a randomized, prospective study comparing weighted vaginal cones and interferential therapy

Sixty-nine female patients with symptoms of stress urinary incontinence were randomized to treatment with either interferential therapy or weighted vaginal cones. Fifty-four patients completed treatment (interferential therapy, 30 patients; weighted vaginal cones, 24 patients). Patients were assessed by subjective response, pad testing, continence charts, and the maximum weight of cone that could be held actively and passively. Forty-seven patients were reassessed at 6 months (19 cones; 28 interferential), five patients (9.26%) required surgery, and two patients (3.7%) could not be reassessed. Subjective response to treatment was good, with 80% to 90% of patients cured or improved after treatment. After 6 months, 41.67% in the cone group and 40% in the interferential group were subjectively cured, with improvement in 50% and 30%, respectively. Of those patients initially referred for treatment, greater than 30% in each group were cured of symptoms. There was an objective improvement in both groups. In the cone group 50% had improved after treatment and greater than 60% had improved at 6 months as assessed by pad testing, while in the interferential group 76% had improved after treatment and 73% had improved at 6 months. There was no significant difference in improvement between the two groups in any of the methods of assessment. However, the cones require less supervision by trained staff and can be used at home by the patient. Their use results in a savings in time for the physiotherapy department. The use of the cones is recommended as a cost-effective method of treatment that can be added to the present therapy options available to the physiotherapist.     

An evaluation of the Tono-Pen for the measurement of diurnal intraocular pressure

We evaluated the Oculab Tono-Pen for potential value in the measurement of diurnal intraocular pressure. Repeated recordings every ten minutes on the same eyes suggested that the instrument provides reproducible information. However, comparisons with Goldmann applanation tonometric measurements, in both single determinations and eight-hour diurnal recordings, showed considerable variation. Correction factors, using either the mean difference in paired readings from the single measurement study or individual differences from the initial set of diurnal recordings, did not eliminate this lack of correlation between measurements with the two instruments.     

Structural and functional rescue of murine rod photoreceptors by human rhodopsin transgene.

Mice carrying a targeted disruption of the rhodopsin gene develop a severe degenerative retinopathy, failing to elaborate rod photoreceptor outer segments (ROS), having no recordable rod electroretinogram (ERG) and losing all of their rod cells over a period of approximately 12 weeks. Murine and human rhodopsins differ in their amino acid sequences. Whether, or to what extent, such variability might influence the ability of human rhodopsin to serve as an adequate structural and functional substitute for the endogenous protein in mouse rod cells bears direct relevance to exploiting the full utility of Rho-/-animals as a model of degenerative retinal disease in man. We crossed Rho-/-mice with mice expressing a wild-type human rhodopsin transgene at levels approximating to those of the endogenous protein. Immunohistological examination of retinal selections from such animals demonstrated ROS of normal number and length and temporal expression of rhodopsin similar to that observed in wild-type animals; that is, immunoreactivity to an anti-rhodopsin antibody became clearly evident by day 3 post-partum. Whereas Rho-/-mice never display a rod ERG response, and even lose cone responses by 12 weeks of age, rescued mice showed 75% normal maximum amplitudes and had ERG b-wave thresholds (based on a 50 microV criterion) within 0.1 log unit of normal wild-type at 20 weeks, and cone amplitudes remained normal at this age. These data demonstrate very substantial structural and functional rescue of the rod photoreceptors of Rho-/-mice and long-term preservation by the human rhodopsin transgene.