Mumps orchitis; review of 8 cases]

The occurrence of secondary hypogonadism is a common finding in males who seek help with erectile dysfunction, although the relationship to diminished testosterone is unclear. Two possibilities exist regarding both the genesis and maintenance of the hypogonadotropic hypogonadal state. First, a defect in hypothalamic function, resulting in downregulation as well as in alterations of anterior pituitary function; second, estradiol inhibition of gonadotropin release, both of which result in decreased testosterone production. As testosterone levels decrease and estradiol levels increase, the ratio of free testosterone to estradiol reaches a critical point and the estrogenic gonadotropin suppressive effects predominate. This ratio may signal the biological point of no return and could become one of the criteria for defining the separation of the transitional hypogonadal state from the final 'end stage' hypogonadotropic hypogonadal state. As the aging process continues, there is a relative accumulation of fatty tissue, and aromatization accelerates the conversion of testosterone to estradiol. This additional secondary estradiol inhibition results in the maintenance of the testosterone deficient state, and the aging process continues uncontested.     

Oscillatory-sensitization model of repeated drug exposure: cocaine's effects on shock-induced hypoalgesia

1. The authors have recently proposed that the sensitization produced by repeated exposure to drugs or stress may give way to an alternating pattern of increases and decreases in the response to each subsequent exposure (i.e., oscillate), as the limits of the physiological system are approached. 2. Evidence for oscillation has been obtained for 6 drug/non-drug stressors and 9 neurochemical or endocrine endpoints. This paper extends the model to a behavioral outcome. 3. In the first experiment, rats were given 0, 1, 2 or 3 pretreatments with cocaine hydrochloride (COC; 12 mg/kg i.p.), separated by 1-week intervals, and then were tested for footshock-induced hypoalgesia (5-sec, 2-mA), as measured by withdrawal latencies from a hot-plate. 4. The second experiment replicated the first and extended the pretreatment sequence to 5 COC injections. 5. In both experiments, shock significantly increased latencies over the no-shock controls. COC enhanced shock-induced hypoalgesia and this sensitization reached its maximum after 2 COC pretreatments. Thereafter, oscillation developed such that the sensitization was attenuated by 3 as compared to 2 COC injections, enhanced by 4 injections, and reattenuated after 5 COC pretreatments. 6. These data complement other findings by demonstrating that the oscillation model extends to a stress-induced behavioral outcome.     

Growth and differentiation of bone marrow hematopoietic cells in mice bearing Ehrlich ascite tumor and treated with Dicyclopentadienildichlorotitanium (IV)

In this work we have investigated the growth and differentiation of bone marrow stem cells in mice bearing Ehrlich ascites tumor and treated with three dose-regimens of Dicyclopentadienyldichlorotitanium (IV) (DDCT). We also studied the presence of colony stimulating factors in the serum of DDCT-treated animals, as well as the effects of the drug on the survival of the tumor-bearing mice. The results demonstrated that the myelosuppression developed in the tumor-bearing animals is prevented by the administration of 1, 2 or 3 doses of 15 mg/kg DDCT. In the treatment with three doses, however, 23% of the animals died. Moreover, DDCT treatment in normal animals resulted in increased numbers of CFU-GM. We observed the presence of stimulating factors in the serum of drug-treated animals which induced the growth and differentiation of bone marrow progenitor cells from normal animals in vitro. On the other hand, in vitro addition of the drug to these cultures had no effect. Thus, we conclude that the drug protects against the myelosuppression induced by the tumor and that this protection may be related to an indirect action of the drug.     

Active Wegener's granulomatosis is associated with HLA-DR+ CD4+ T cells exhibiting an unbalanced Th1-type T cell cytokine pattern: reversal with IL-10

Wegener's granulomatosis (WG) is a granulomatous vasculitis that affects the upper respiratory tract, lung, and kidney. Since T cells make up a significant proportion of cells infiltrating granulomatous lesions in WG, we investigated the proliferative response and cytokine profile of T cells from these patients. PBMCs were isolated from 12 patients with active WG, 7 patients with inactive disease, and 12 healthy normal donors. PBMCs from clinically active WG patients exhibited increased proliferation following stimulation with either PMA/ionomycin or anti-CD2 and anti-CD28, when compared with normal donors. In addition, these PBMCs exhibited increased secretion of IFN-gamma, but not of IL-4, IL-5, or IL-10. Furthermore, TNF-alpha production from PBMCs and CD4+ T cells isolated from patients with WG was elevated, when compared with healthy donors. In further studies, we investigated the ability of WG patients' monocytes to produce IL-12 and showed that both inactive and active patients produced increased amounts of IL-12. Finally, the in vitro IFN-gamma production by WG PBMC is inhibited in a dose-dependent manner by exogenous IL-10. These data suggest that T cells from WG patients overproduce IFN-gamma and TNF-alpha, probably due to dysregulated IL-12 secretion, and that IL-10 may therefore have therapeutic implications for this disease.     

Surgical treatment of cicatricial biliary strictures

BACKGROUND/AIMS: Cicatricial biliary strictures are usually associated with high morbidity and mortality rates, frequently related to technical difficulties of their surgical repair, mainly in hilar lesions. Interference with bile duct blood supply during surgical attempts for correction is a major factor for unsuccessful results. The aim of this study is to evaluate, after an extended follow-up period, the results obtained with a modified technique for surgical correction of cicatricial biliary strictures. METHODOLOGY: The medical records of 57 patients surgically treated for cicatricial biliary strictures between January 1984 and July 1995 were reviewed and the immediate and long term results retrospectively analyzed. Patients consisted of 46 females and 11 males. The average age was 43 years. The etiology of the biliary lesion was: cholecystectomy alone (23); cholecystectomy with duct exploration (8); T tube CBD drainage (6); Biliary-enteric anastomosis stricture (16); choledochoplasty (2) and trauma (2). In 28 cases (49.1%) the stricture was located in the upper third of the bile duct, in 28 (49.1%) in the middle third and in one case (1.7%) it was low. All patients were submitted to longitudinal Roux-en-Y hepaticojejunostomy with mucosa apposition after dissection of the anterior aspect of the biliary tract. No transanastomotic stents were used. RESULTS: Ten patients (17.5%) presented 11 postoperative complications: biliary fistula (4), duodenal fistula (1), wound infection (5), and acute pancreatitis (1). Average hospital stay was 11 days and there were no postoperative mortalities. The follow-up study was possible in 54 patients and ranged from one to ten years, with an average of 2.9 years. Four patients of 28 (14%) with hilar lesions developed stricture recurrence and cholangitis episodes, whereas no patients bearing lesions below the biliary junction had such complications. CONCLUSION: Roux-en-Y hepaticojejunostomy with mucosa apposition without transanastomotic stent performed after minimal dissection of the biliary duct, thus avoiding major interference with the bile duct blood supply, is a safe and efficient method for the surgical repair of cicatricial biliary strictures. Using this technique excellent results can be obtained in the lesions below the biliary junction and acceptable results may be achieved in patients with hilar lesions.     

CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology

The purpose of this study was (1) to investigate the efficacy of chemotherapy regimens designed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma (ALCL) and (2) to identify prognostic factors in these children. Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies, HM89 and HM91. The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation. Treatment consisted of 2 courses of COPADM (methotrexate, cyclophosphamide, doxorubicin, vincristine, and prednisone) and a maintenance treatment of 5 to 7 months. Seventy-eight patients (95%) achieved a complete remission and 21 relapsed. The probability of survival and event-free survival at 3 years was of 83% (72% to 90%) and 66% (54% to 76%), respectively, with a median follow-up of 49 months. In multivariate analysis, visceral involvement, mediastinal involvement, and lacticodeshydrogenase (LDH) level >/=800 UI/L were shown to be predictive of a higher risk of failure. In conclusion, this type of regimen demonstrated efficacy in childhood ALCL. However, therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level.     

Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer

Intravenous injection of stearoyl vanillylamide (C18-VA), a nonpungent capsaicin (CAP) analog, enhances adrenaline secretion significantly and as effectively as CAP in rats. Because swimming capacity was enhanced by CAP in mice due to CAP-induced adrenal catecholamine secretion, we investigated the effects of oral administration of C18-VA on swimming capacity using an adjustable-current water pool. Male Std ddY 6-wk-old mice were fed a commercial diet for this study and one group was orally administered C18-VA via a stomach tube. Treated mice were able to swim longer before exhaustion than the control mice (62.9 +/- 5.6 vs. 49.6 +/- 7. 0 min, P < 0.05). The swimming capacity of two groups administered C18-VA (0.02 and 0.033 mmol/kg) was significantly greater than that of those administered vehicle alone, (P < 0.05). Substance P concentration in cerebrospinal fluid, which is involved in pain transmission and is the first direct measure of pungency, was not affected by C18-VA administration. In an experiment examining the effects of C18-VA on serum adrenaline concentration, adrenaline was significantly greater in C18-VA treated mice than in controls at 2-h post-dose (C18-VA group, 26.09 +/- 2.82; control group 13.29 +/- 0. 96 microg/L, P < 0.01). In a separate study free fatty acids in serum were elevated in treated mice at 2-h post-dose (P < 0.01). While serum glucose concentration was not affected. These results suggest that C18-VA increased swimming capacity of mice via adrenaline release, independent of pungency. In addition, the present study suggests the usefulness of its application to humans.     

Cardiovascular events and mortality in newly and chronically depressed persons > 70 years of age

The role of duration of depressed mood in the prediction of cardiovascular disease (CVD) requires further study, as it has been suggested that emerging depressive symptoms may be a better predictor than persistent depressive symptoms. This prospective cohort study of 3,701 men and women aged > 70 years uses 3 measurement occasions of depressive symptomatology (Center for Epidemiologic Studies-Depression Scale) during a 6-year period to distinguish persons who were newly (depressed at baseline but not at 3 and 6 years before baseline) and chronically depressed (depressed at baseline and at 3 or 6 years before baseline). Their risk of subsequent CVD events and all-cause mortality was compared with that of subjects who were never depressed during the 6-year period. Outcome events were based on death certificates and Medicare hospitalization records. During a median follow-up of 4.0 years, there were 732 deaths (46.2/1,000 person-years) and 933 new CVD events (64.7/1,000 person-years). In men, but not in women, newly depressed mood was associated with an increased risk of CVD mortality (relative risk 1.75, 95% confidence interval [CI] 1.00 to 3.05), new CVD events (relative risk 2.07, 95% CI 1.44 to 2.96), and new coronary heart disease events (relative risk 2.03, 95% CI 1.28 to 3.24) after adjustment for traditional CVD risk factors. The association between newly depressed mood and all-cause mortality was smaller (relative risk 1.40, 95% CI 0.95 to 2.07). Chronic depressed mood was not associated with new CVD events or all-cause mortality. Our findings suggest that newly depressed older men, but not women, were approximately twice as likely to have a CVD event than those who were never depressed. In men, recent onset of depressed mood is a better predictor of CVD than long-term depressed mood.