Frequency of urolithiasis in individuals seropositive for human immunodeficiency virus treated with indinavir is higher than previously assumed

PURPOSE: Indinavir was approved by the Food and Drug Administration in 1996 as a human immunodeficiency type 1 protease inhibitor to treat human immunodeficiency virus infection. Prompted by the high number of patients receiving indinavir who present with renal colic at our institution, we performed a detailed investigation of the true frequency of urolithiasis during indinavir treatment. MATERIALS AND METHODS: We evaluated 105 patients with a mean age of 38.1 years who were treated with indinavir from 1996 to 1997. Before indinavir treatment was initiated all patients underwent renal ultrasonography, urinalysis, and determination of serum sodium, potassium, calcium, uric acid and creatinine. It was recommended that all patients drink 2 l of fluids daily, and all remained under continuous surveillance. RESULTS: Metabolic evaluation and ultrasonography showed no abnormality in any case. A stone episode occurred in 13 men (12.4%) as renal colic during observation. Colic recurred in 1 patient after 2 and 5 months, and in 1 after 2 months. Median duration of indinavir treatment until an acute stone episode was 21.5 weeks (range 6 to 50). A total of 12 stones passed spontaneously. Three patients underwent ureteroscopic calculous removal and 1 was treated with extracorporeal shock wave lithotripsy. CONCLUSIONS: Despite adequate patient information and compliance the rate of nephrolithiasis during indinavir therapy was 12.4%.     

Inhibitory effect of melatonin on products of lipid peroxidation resulting from chronic ethanol administration

Despite decades of research, the role of free radicals in alcohol-induced organ injury is still a matter of debate. The present work was designed to investigate the potential protective effect of melatonin, a reported radical scavenger and antioxidant, on free radical toxicity induced by chronic ethanol administration. The major end-point of oxidative damage measured in this report was lipid peroxidation. Four groups of male Sprague-Dawley rats were used. The first group served as untreated controls and received a daily injection of alcoholic (<1% ethanol) saline. The second group of rats received daily at 18:00 a single subcutaneous injection of melatonin (10 mg/kg). Group 3 rats received only ethanol (3 g/kg) for 30 consecutive days; the ethanol was given at 18:30. The final group of rats was given both melatonin and ethanol with melatonin preceding ethanol by 30 min. Products of lipid peroxidation [malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)] were measured in the brain, heart, liver, lung and testes. At the conclusion of the study, MDA + 4-HDA levels were significantly increased in brains, hearts, lungs and testes, but not livers, of alcohol-treated compared with control rats. The percentage increases in lipid peroxidation products were 21.8%, 28.8%, 35.9% and 45.3% for brain, heart, lung and testes, respectively. In animals given melatonin 30 min before ethanol, the increases in MDA + 4-HDA levels were significantly reduced in all organs investigated, with levels not different from those in control rats. Based on these findings, it is speculated that melatonin's direct and indirect antioxidative actions inhibited alcohol-induced lipid peroxidation. These results suggest a new strategy for the treatment of alcohol-related diseases using melatonin as an antioxidant to reduce the damage inflicted by aggressive radical species.     

The HIV wasting syndrome

Wasting syndrome, one of the most common complications of HIV disease, is more often found in people of low socioeconomic status and women. The pathophysiology of wasting and its treatment are discussed. Perturbations of metabolism, malnutrition, androgen deficiency, treating underlying illnesses, nutritional considerations, and pharmacologic approaches are explored. The first step to treating HIV wasting syndrome is to provide appropriate antiretroviral therapy, including meticulous prophylaxis and treatment of opportunistic infections (OIs). Other treatments include using oral supplements or total parenteral feeding to maintain nutritional levels, approved appetite stimulants, such as Megestrol acetate and dronabinol, or the controversial use of anabolic steroids. Concerns about steroid use include potential for abuse, and the possibility of developing malignancies and severe gonadal dysfunction.     

Über die Entstehung von „Bolzengeschossen“ bei Verwendung präparierter Viehbetäubungsapparate

Zusammenfassung Einige gebräuchliche Modelle unter den Viehbetäubungsapparaten verfügen über Gummipuffer und Rückholfedern. Durch diese Bestandteile wird der vorschnellende Bolzen gebremst und in seine Ausgangsposition zurückgebracht. Wenn man den Gummipuffer und die Rückholfeder vor der Schußabgabe entfernt, kann der Bolzen abreißen und zu einem frei fliegenden Geschoß werden. In einem Suizidfall ist unter solchen Umständen ein 17 cm langes Bolzenstück durch die Stirn in die Schädelkapsel eingedrungen.     

Behandlung einer akuten monoblastären Leukämie bei einem Säugling mit einer Glutarazidurie Typ I

Glutaric aciduria type 1 (GA1) is caused by an inherited deficiency of the enzyme glutaryl coenzyme A dehydrogenase (GDH) involved in the degradation of lysine, hydroxylysine, and tryptophan. Affected infants develop unspecific neurological symptoms and macrocephaly. Deterioration of the neurological status, so-called encephalopathic crisis can be triggered by catabolism and is usually incompletely reversible. We report on a 4-year-old girl with GA1 who presented with acute monoblastic leukemia at the age of 8 months. She was treated with combination chemotherapy according to current standards. Despite the elevated risk of metabolic imbalance during infections in neutropenia, encephalopathy crises could be avoided by reduced intake of lysine and tryptophan, a high-energy diet, and supplementation with carnitine.     

Endocrine patterns in patients with benign and malignant prostatic diseases

BACKGROUND: The known importance of the endocrine system, particularly of steroid hormones, for development of the prostate gland and the fact that steroid hormones act as immunmodulators prompted us to compare hypophyseal, adrenal, and gonadal hormones, including cortisol, in patients with benign and malignant prostatic diseases. METHODS: Patients with newly diagnosed, untreated prostate cancer (PC) (n = 75) and, as a control population, those with untreated lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) (n = 159) entered this prospective study. In all patients, the following parameters were obtained by serum analysis: prostate-specific antigen (PSA), human luteinizing hormone (hLH), human follicle-stimulating hormone (hFSH), testosterone, estradiol (E2), cortisol, and dehydroepiandrosterone-sulphate (DHEA-S). Serum samples were collected of fasting patients between 7. 30-10.00 AM. RESULTS: Age was comparable in both groups (PC: 65.6 +/- 7.6 years (mean +/- standard deviation) vs. controls: 64.9 +/- 8. 1 years; P = 0.56). HFSH (PC: 6.6 +/- 3.9 mIU/ml; controls: 8.4 +/- 6.4 mIU/ml; P = 0.04), hLH (PC: 5.3 +/- 4.8mIU/ml; controls: 7.6 +/- 6.2 mIU/ml; P = 0.009), and estradiol (PC: 25.8 +/- 12.7 pg/ml; controls: 32.6 +/- 12.6 pg/ml; P = 0.0003) were significantly lower in PC patients than controls. Cortisol (PC: 16.7 +/- 4.2 microg/dl; controls: 13.5 +/- 4.3 microg/dl; P < 0.0001) was significantly higher in cases. The difference for cortisol and estradiol concentrations between PC patients and controls held true in all life-decades. Serum concentrations for DHEA-S and testosterone were comparable between PC and control patients. In PC patients, none of the endocrine parameters correlated to serum PSA or clinical/pathological stage. CONCLUSIONS: Patients with newly diagnosed, untreated PC yielded significantly higher cortisol and lower estradiol serum concentrations than controls. The known effect of cortisol on the immune status warrants further studies.     

Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer.

PURPOSE: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. EXPERIMENTAL DESIGN: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. Results and CONCLUSIONS: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.     

Quality of life outcomes after brachytherapy for early stage prostate cancer

PURPOSE: We compare general and disease specific health related quality of life in men undergoing brachytherapy for early stage prostate cancer to those undergoing radical prostatectomy and age matched healthy controls. MATERIALS AND METHODS: Cohorts consisted of 48 men treated with brachytherapy with and without pretreatment external beam radiation therapy (brachytherapy group), 74 who underwent radical prostatectomy (prostatectomy group) and age matched healthy controls from the literature. The RAND 36-item general health survey, University of California Los Angeles Prostate Cancer Index, American Urological Association symptom index, validated Cancer Interference with Life and Family Scales, and sociodemographic and co-morbidity questionnaires were completed 3 to 17 months after treatment. RESULTS: General health related quality of life did not differ greatly among the 3 groups. Urinary function (leakage) was worse in the brachytherapy group than in controls but better than in the prostatectomy group. Brachytherapy group patients had more irritative urinary symptoms and worse bowel function than controls. Sexual function and bother were worse in prostatectomy and brachytherapy groups than in healthy controls. Physical function, bodily pain, urinary function, and bother and American Urological Association symptom index scores improved with time after brachytherapy. Patients who underwent brachytherapy after external beam radiation performed worse in all general and disease specific health related quality of life domains compared to those who did not undergo pretreatment radiation therapy. CONCLUSIONS: At an average of 7.5 months after treatment the general health related quality of life of patients undergoing brachytherapy with and without pretreatment external beam radiation was similar to age matched controls, although urinary, bowel and sexual problems were reported. These problems appeared to improve during the first year after treatment. Much of the impairment in disease specific health related quality of life among patients undergoing brachytherapy may be attributed to pretreatment radiation.