Hirschsprung''s disease: a search for etiology

Expression of proliferating cell nuclear antigen (PCNA) as well as p53, bcl-2 and C-erb B-2 genes protein products on Reed-Sternberg/Hodgkin's (R-S/H) cells was analyzed by immunohistochemistry in 65 patients with Hodgkin's disease (HD). Their significance as markers of clinical malignancy and prognostic factors was evaluated. Positive reaction for PCNA was present in 57 cases (87.7%), for p53 in 42 (64.6%), for bcl-2 in 41 (63.1%), and for C-erb B-2 in 38 cases (58.5%) of HD. The high proliferate PCNA index and high expression of p53 and bcl-2 correlated with poor response to the treatment. Expression of both p53 and bcl-2 oncoproteins negatively influenced overall survival and disease free survival. Indexes of PCNA, p53 and bcl-2 were significantly higher in patients with advanced disease then in early clinical stages. In LP type of HD the lowest indexes of PCNA or bcl-2, and even lack of bcl-2 expression on R-S/H cells were observed. There was no correlation between expression of C-erb B-2 and response to the treatment, time of survival, clinical stage or histopathological types of HD. Statistical analysis let us to the conclusion, that indexes of PCNA, p53 and bcl-2 expression can be taken into consideration as a new prognostic factors in Hodgkin's disease. C-erb B-2 protein expression seems to be of no value for prognosis in HD.     

Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and body weight

Recent evidence suggests that the central melanocortin (MC) system is a prominent contributor to food intake and body weight control. MC receptor (MC-R) populations in the arcuate and paraventricular nuclei are considered probable sites of action mediating the orexigenic effects of systemically or intracerebroventricularly administered ligands. Yet, the highest MC4-R density in the brain is found in the dorsal motor nucleus of the vagus nerve, situated subjacent to the commissural nucleus of the solitary tract, a site of pro-opiomelanocortin mRNA expression. We evaluated the contribution of the caudal brainstem MC system by (1) performing respective dose-response analyses for an MC-R agonist (MTII) and antagonist (SHU9119) delivered to the fourth ventricle, (2) comparing, in the same rats, the fourth intracerebroventricular dose-response profiles to those obtained with lateral intracerebroventricular delivery, and (3) delivering an effective dose of MTII or SHU9119 to rats before a 24 hr period of food deprivation. Fourth intracerebroventricular agonist treatment yielded a dose-dependent reduction of short-term (2 and 4 hr) and longer-term (24 hr) food intake and body weight. Fourth intracerebroventricular antagonist treatment produced the opposite pattern of results: dose-related increases in food intake and corresponding increases in body weight change for the 24-96 hr observation period. Comparable dose-response functions for food intake and body weight were observed when these compounds were delivered to the lateral ventricle. Results from deprived rats (no effect of MTII or SHU9119 on weight loss) support the impression derived from the dose-response analyses that the body weight change that follows MC treatments is secondary to their respective effects on food intake. Results support the relevance of the brainstem MC-R complement to the control of feeding.     

Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination after stent implantation

OBJECTIVE: To explore the basis of the gender-based differences in endocrine and surgical findings in patients with prolactinoma (prolactin cell adenoma) as well as in their clinical outcome. MATERIAL AND METHODS: In young or reproductive-age female patients, older women (beyond 40 years of age), and male patients, we systematically studied the following factors: operative and endocrine features (tumor size, invasiveness, preoperative serum prolactin level, and biochemical outcome), specific biologic variables (mitotic index, MIB-1 labeling index, and p27 immunoreactivity), and hormone receptor status (estrogen and progesterone receptor proteins as well as dopamine D2 receptor messenger RNA). RESULTS: Of the various factors assessed, the preoperative prolactin level and MIB-1 labeling index were lower in young female patients in comparison with older female and particularly male patients. Hormone levels were also positively associated with mitotic activity as well as the MIB-1 labeling index. Although invasion was infrequent in microadenomas of young female patients, no statistically significant differences in tumor size or invasiveness were noted among the three patient groups. Absence of differences in invasiveness may, in part, be explained by artifacts of case selection. CONCLUSION: The basis for the observed differences in proliferative activities in tumors of the three study groups is not readily apparent but may reflect differences in the endocrine milieu or the effect of sex steroid hormone receptors, tumoral vascularity, or specific growth factors.     

Feeding colostrum increases circulating insulin-like growth factor I in newborn pigs independent of endogenous growth hormone secretion

Our objective was to examine the influence of feeding and endogenous GH secretion on circulating IGF-I in colostrum-deprived newborn pigs fed colostrum (n = 4), formula (control, n = 4), or water (n = 4). In another four formula-fed pigs, GH was ablated (GRF-A) with two intravenous injections of a GH releasing-factor antagonist (N-Ac-Tyr1,D-Arg2)-GRF(1-29)-NH2. Blood was serially sampled in all pigs to measure plasma IGF-I and GH profiles. Feeding increased plasma IGF-I concentration two- to fourfold and decreased GH secretion. Despite a more than 80% decrease in the plasma GH in GRF-A pigs, the circulating IGF-I concentration was similar to that in control pigs. In colostrum-fed pigs, plasma IGF-I was higher than that in control pigs, despite equal nutrient intake and lower circulating GH. There were no differences in plasma IGF binding protein (IGFBP)-3 levels among the treatment groups. However, the relative abundance of plasma IGFBP-4 was lower, and that of IGFBP-1 higher, in unfed pigs than in any of the three fed groups. The plasma insulin concentration was not different among fed pigs, but it was lower in unfed pigs. Our results indicate that the circulating IGF-I concentration is more dependent on nutrient intake than on GH in newborn pigs, despite relatively high GH concentrations. However, because the nutrient content in the formula was designed to match that of colostrum, a factor other than nutrient intake and GH was responsible for the maximal increase in circulating IGF-I concentration observed in colostrum-fed pigs.     

Low-dose oral etoposide monotherapy in adult Langerhans cell histiocytosis

BACKGROUND: The purpose of this study was to test the disease-controlling effect of low-dose oral etoposide monotherapy in adult-onset multisystem Langerhans cell histiocytosis. There are no previous reports of low-dose etoposide monotherapy for this condition. OBSERVATIONS: A 27-year-old man with a 7-year history of multifocal chronic Langerhans cell histiocytosis presented with severe disabling ulcers in intertriginous areas. He had previously been treated with 2 different regimens of antitumoral chemotherapy; one had to be discontinued due to myelosuppression and the other had proved ineffective. We treated with oral etoposide monotherapy at 50 mg/d (22 mg/m2 per day) for 21 days. The treatment was repeated at 28-day intervals for a total of 6 cycles. A rapid initial response with subtotal diminution of the involved skin area was found. No adverse effects were observed. The clinical picture has remained stable during the 7 months following cessation of therapy. CONCLUSION: Low-dose oral etoposide treatment is an adequate therapeutic measure for prolonged disease control in adult-type Langerhans cell histiocytosis.