Pancreaticoduodenectomy for selected periampullary neuroendocrine tumors: fifty patients

BACKGROUND: Most resectable pancreatic or peripancreatic neuroendocrine tumors are treated by enucleation or distal pancreatectomy. A minority of tumors may require pancreaticoduodenectomy for complete tumor excision because of their large size, location, or lymph node involvement. METHODS: This study reviews the management of 50 patients treated by pancreaticoduodenectomy for periampullary neuroendocrine tumors between 1962 and 1996 at a single institution. RESULTS: There were 30 men and 20 women with a mean age of 52 +/- 2 years. Functional tumors were resected in 17 patients: insulinoma, seven tumors; gastrinoma, eight tumors; vipoma, one tumor; and glucagonoma, one tumor. Tumors were classified as malignant in 29 patients and benign in 21. The median intraoperative blood loss was 800 ml, and the median number of units of blood transfused was zero. The postoperative length of stay was 20 +/- 2 days. Postoperative morbidity included 11 patients (24%) with a pancreatic fistula and four patients (8%) with a biliary fistula. There was one in-hospital death (2%), in 1967. The actuarial survival rates at 2, 5, and 7 years are 81%, 73%, and 65%, respectively. Patients with benign tumors had a significantly improved 5-year survival rate (94%) compared with those with malignant tumors (61%; p = 0.03). CONCLUSIONS: Selected patients with periampullary neuroendocrine tumors can be managed successfully by pancreaticoduodenectomy, with low mortality and acceptable morbidity rates.     

The effectiveness of ovarian cancer screening. A decision analysis model

OBJECTIVE: To estimate the effectiveness of ovarian cancer screening with CA 125 and transvaginal sonography. DESIGN: Decision analysis was used to examine the no-screen compared with the screen strategy. SETTING: Estimates of cancer incidence, survival, and life expectancy were derived from population-based data and clinical series. SUBJECTS: A cohort of 40-year-old women of all races and residing in the United States. INTERVENTIONS: A one-time screening intervention. The criterion standard for diagnosis of ovarian cancer was evaluation with exploratory laparotomy. MAIN OUTCOME MEASURE: Average years of life expectancy gained by women in the screened group. RESULTS: Screening for ovarian cancer with a combination of CA 125 and transvaginal sonography increases the average life expectancy in the population by less than 1 day. CONCLUSIONS: Given the limited effect on overall life expectancy, it is unlikely that mass screening for ovarian cancer with CA 125 and transvaginal sonography would be an effective health policy.     

Short-term handling of the slimming agent oleoyl-estrone in liposomes (Merlin-2) by the rat

Female adult rats were injected in the jugular vein with oleoyl-3H-estrone incorporated into liposomes. The label rapidly disappeared from the blood, being taken up by the tissues, mainly liver, spleen and lung, which filtered most of the label. However, many other tissues, such as the heart, brown adipose tissue, adrenals and visceral fat incorporated significant amounts of oleoyl-estrone. The analysis of the form in which the label remained 10 min after the injection showed that it was hydrolysed in a large proportion even in liver and lungs. However, in most tissues (brain, brown and white - periovaric - adipose tissues and ovaries), intact oleoyl-estrone accounted for less than one quarter of all tissue label, and less than 10% in the case of subcutaneous adipose tissue and uterus. This rapid destruction of oleoyl-estrone is in agreement with the active role of this compound in the control of body weight.     

Distribution of alpha 1A, alpha 1B and alpha 1E voltage-dependent calcium channel subunits in the human hippocampus and parahippocampal gyrus

The distribution of voltage-dependent calcium channel subunits in the central nervous system may provide information about the function of these channels. The present study examined the distribution of three alpha-1 subunits, alpha 1A, alpha 1B and alpha 1E, in the normal human hippocampal formation and parahippocampal gyrus using the techniques of in situ hybridization and immunocytochemistry. All three subunit mRNAs appeared to be similarly localized, with high levels of expression in the dentate granule and CA pyramidal layer. At the protein level, alpha 1A, alpha 1B and alpha 1E subunits were differentially localized. In general, alpha 1A-immunoreactivity was most intense in cell bodies and dendritic processes, including dentate granule cells, CA3 pyramidal cells and entorhinal cortex pre-alpha and pri-alpha cells. The alpha 1B antibody exhibited relatively weak staining of cell bodies but stronger staining of neuropil, especially in certain regions of high synaptic density such as the polymorphic layer of the dentate gyrus and the stratum lucidum and radiatum of the CA regions. The alpha 1E staining pattern shared features in common with both alpha 1A and alpha 1B, with strong immunoreactivity in dentate granule, CA3 pyramidal and entorhinal cortex pri-alpha cells, as well as staining of the CA3 stratum lucidum. These findings suggest regions in which particular subunits may be involved in synaptic communication. For example, comparison of alpha 1B and alpha 1E staining in the CA3 stratum lucidum with calbindin-immuno-reactivity suggested that these two calcium channels subunits may be localized presynaptically in mossy fibre terminals and therefore may be involved in neurotransmitter release from these terminals.     

Glucosamine-induced insulin resistance in 3T3-L1 adipocytes is caused by depletion of intracellular ATP

Glucosamine, which enters the hexosamine pathway downstream of the rate-limiting step, has been routinely used to mimic the insulin resistance caused by high glucose and insulin. We investigated the effect of glucosamine on insulin-stimulated glucose transport in 3T3-L1 adipocytes. The Delta-insulin (insulin-stimulated minus basal) value for 2-deoxyglucose uptake was dramatically inhibited with increasing concentrations of glucosamine with an ED50 of 1.95 mM. Subcellular fractionation experiments demonstrated that reduction in insulin-stimulated 2-deoxyglucose uptake by glucosamine was due to an inhibition of translocation of both Glut 1 and Glut 4 from the low density microsomes (LDM) to the plasma membrane. Analysis of the insulin signaling cascade revealed that glucosamine impaired insulin receptor autophosphorylation, insulin receptor substrate (IRS-1) phosphorylation, IRS-1-associated PI 3-kinase activity in the LDM, and AKT-1 activation by insulin. Measurement of intracellular ATP demonstrated that the effects of glucosamine were highly correlated with its ability to reduce ATP levels. Reduction of intracellular ATP using azide inhibited Glut 1 and Glut 4 translocation from the LDM to the plasma membrane, insulin receptor autophosphorylation, and IRS-1 tyrosine phosphorylation. Additionally, both the reduction in intracellular ATP and the effects on insulin action caused by glucosamine could be prevented by the addition of inosine, which served as an alternative energy source in the medium. We conclude that direct administration of glucosamine can rapidly lower cellular ATP levels and affect insulin action in fat cells by mechanisms independent of increased intracellular UDP-N-acetylhexosamines and that increased metabolism of glucose via the hexosamine pathway may not represent the mechanism of glucose toxicity in fat cells.     

Infant affect and affect regulation during the still-face paradigm with mothers and fathers: the role of infant characteristics and parental sensitivity

This laboratory study examined mothers' and fathers' sensitivity during face-to-face interactions with their infants as well as infants' affective and regulatory responses during mother-infant versus father-infant still face (SF). The degree to which infant gender and temperament as well as parental sensitivity predicted SF responses was also examined. Participants included 94 healthy, primarily White, middle-class 4-month-olds and their parents. Results indicated that mothers and fathers were equally sensitive toward their infants. Infants' affect and regulatory behaviors were also significantly stable across mother- and father-infant SF situations, although several differences in mean levels of regulation emerged. Finally, the extent to which exogenous and endogenous variables predicted infant SF responses differed as a function of which affect or regulatory variable was being examined and with which parent the infant was experiencing SF.     

Pharmacologic therapy for prostatism

Although the general approach to management of a sufficient degree of benign prostatic hyperplasia in the past was surgical intervention (transurethral resection of the prostate), the current availability of effective pharmacologic therapy has changed the initial management strategy. At present, two types of drugs are available for treatment of prostatism: (1) selective alpha-adrenergic blocking agents (terazosin, doxazosin, and tamsulosin) and (2) an inhibitor of the 5 alpha-reductase enzyme (finasteride). Pharmacologic blockade of the alpha(1)-adrenoceptors is thought to result in relaxation of the smooth muscle in the prostate and bladder neck, which reduces urethral resistance, improves voiding function, and minimizes the symptoms of prostatism. These effects may be noted by the patient within several weeks after initiation of treatment. The mechanism of action of finasteride is a blocking of the conversion of testosterone to dihydrotestosterone and an associated volume shrinkage of the prostate. On the average, a 25% reduction in prostate volume can be achieved, but a period of 12 months or longer of finasteride therapy is needed for maximal shrinkage and maximal decrease in symptoms of prostatism. The expanding population of middle-aged and elderly men with prostatism of moderate severity will undoubtedly prompt the development of additional pharmacologic options for treatment of prostatism and benign prostatic hyperplasia.     

The direct activating effect of a nonapeptide neurohormone (vasotocin) on the thyroid and interrenal glands of sturgeons in in-vitro experiments

An in-vitro effect of nonapeptide neurohormone vasotocin on thyroid and interrenal glands was studied in hybrid of Siberian and Lena sturgeons [correction of salmons] at light microscopy level using morphometric method. At a concentration of 0.1 and 1 nmol/l vasotocin was shown to exert undirectional stimulating effect on the thyroid and interrenal gland functions. In the presence of vasotocin at a concentration of 1 nmol/l in culture media the activity of glands is even more pronounced than under the influence of adenohypophyseal hormones, adrenocorticotropic (8 x 10 ng/ml) and thyrotropic (5 ng/ml).     

Methotrexate treatment of idiopathic granulomatous hepatitis

OBJECTIVE: To test the efficacy and safety of low-dose oral pulse methotrexate therapy in patients with idiopathic granulomatous hepatitis who had complications of, did not respond to, or refused glucocorticoid therapy. DESIGN: Prospective case study. SETTING: Academic medical center hospital. PATIENTS: Seven patients with biopsy-proven, idiopathic granulomatous hepatitis who could not tolerate or were unresponsive to glucocorticoid therapy. INTERVENTION: Low-dose oral pulse methotrexate, 15 mg/wk. MEASUREMENTS: Temperature, symptoms, dose of concurrent glucocorticoids, biochemical tests of liver function, side effects of methotrexate, and assessment of liver biopsy specimens. RESULTS: All six febrile patients became afebrile within 3 months of starting methotrexate. Fatigue and anorexia improved in all patients. Glucocorticoid therapy was successfully discontinued within 6 months of starting methotrexate in four patients receiving prednisone at entry. Liver biopsy specimens were obtained again after methotrexate therapy and showed absence of granulomas in four of four patients. The minimum effective dose of methotrexate was 0.20 mg/kg body weight per week. No serious adverse effects and no failures to respond to methotrexate therapy were noted in this group of patients. In three patients, methotrexate therapy has been successfully tapered without signs or symptoms of recurrent disease. CONCLUSIONS: Low-dose oral pulse methotrexate was effective in treating patients with granulomatous hepatitis.