Effects of monensin on insulin release from isolated human islets.
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Biomedical subjects
Publications and source records attributed to F Mosca.
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We describe a case of renovascular hypertension accompanied by renal failure, arising in a young man with a solitary kidney 4 months after a blunt abdominal trauma. A giant haematoma was found around the right kidney and ultrasound-guided percutaneous drainage completely relieved the symptom complex. Nine years later, the patient is normotensive with normal renal function.
1. The aim was to investigate the possibility of interindividual variability of histamine N-methyltransferase (HNMT) in the human liver and renal cortex. The activity of HNMT was measured in 99 specimens of the human liver and in 75 specimens of the renal cortex. 2. In the liver the activity of HNMT was positively skewed. It ranged 2.9-fold with a median of 1.72 pmol/min/mg. In the renal cortex the activity of HNMT was normally distributed and ranged 2.6-fold with a mean and coefficient of variation of 1.35 pmol/min/mg and 21%, respectively. 3. The activities of catechol methyltransferase and thiopurine methyltransferase were measured in the renal cortex and any correlations with HNMT activity were assessed. There was a weak but significant correlation (r = 0.294, p = 0.010) between HNMT and catechol methyltransferase activities whereas HNMT activity was not correlated with thiopurine methyltransferase activity. 4. These results are consistent with the view that HNMT is well expressed in the human liver and renal cortex and that it varies among subjects.
We describe the cases of two premature infants carrying a central venous line who developed on the fourth day of life a catheter related intracardiac thrombus. Although they were clinically asymptomatic we opted for thrombolytic treatment considering the potential risks of this situation. Treatment with recombinant tissue plasminogen activator (rt-PA) was performed for one day in the first case and for three days in the second one, in association with fresh frozen plasma. Thrombus dissolution occurred in both patients and no adverse effects were noted. In our experience tissue plasminogen activator was a therapy acceptably safe and effective inducing clot lysis in very low birthweight neonates into critical situations.
OBJECTIVE: The study was conducted to determine whether the performance of an extended lymphadenectomy and retroperitoneal soft-tissue clearance in association with a pancreatoduodenal resection improves the long-term survival of patients with a potentially curable adenocarcinoma of the head of the pancreas. SUMMARY BACKGROUND DATA: The usefulness of performing an extended lymphadenectomy and retroperitoneal soft-tissue clearance in conjunction with a pancreatoduodenal resection in the treatment of ductal adenocarcinoma of the head of the pancreas is still unknown. Published studies suggest a benefit for the procedure in terms of better long-term survival rates; however, these studies were retrospective or did not prospectively evaluate large series of patients. MATERIALS AND METHODS: Eighty-one patients undergoing a pancreatoduodenal resection for a potentially curable ductal adenocarcinoma of the head of the pancreas were randomized to a standard (n = 40) or extended (n = 41) lymphadenectomy and retroperitoneal soft-tissue clearance in a prospective, multicentric study. The standard lymphadenectomy included removal of the anterior and posterior pancreatoduodenal, pyloric, and biliary duct, superior and inferior pancreatic head, and body lymph node stations. In addition to the above, the extended lymphadenectomy included removal of lymph nodes from the hepatic hilum and along the aorta from the diaphragmatic hiatus to the inferior mesenteric artery and laterally to both renal hila, with circumferential clearance of the origin of the celiac trunk and superior mesenteric artery. Patients did not receive any postoperative adjuvant therapy. RESULTS: Demographic (age, gender) and histopathologic (tumor size, stage, differentiation, oncologic clearance) characteristics were similar in the two patient groups. Performance of the extended lymphadenectomy added time to the procedure, although the difference did not reach statistical significance (397 +/- 50 minutes vs. 372 +/- 50 minutes, p > 0.05). Transfusion requirements, postoperative morbidity and mortality rates, and overall survival did not differ between the two groups. When subgroups of patients were analyzed, using an a posteriori analysis that was not planned at the time of study design, there was a significantly (p < 0.05) longer survival rate in node positive patients after an extended rather than a standard lymphadenectomy. The survival curve of node positive patients after an extended lymphadenectomy could be superimposed onto the curves of node negative patients. Survival curves in node negative patients did not differ according to the magnitude of the lymphadenectomy. Multivariate analysis of all patients showed that long-term survival was affected by tumor differentiation (well vs. moderately vs. poorly differentiated, p > 0.001), diameter (< or = 2.0 cm. vs. > 2.0 cm., p < 0.01), lymph node metastasis (absent vs. present, p < 0.01) and need for 4 or more units of transfused blood (< 4 vs. > or = 4, p <0.01). CONCLUSIONS: The addition of an extended lymphadenectomy and retroperitoneal soft-tissue clearance to a pancreatoduodenal resection does not significantly increase morbidity and mortality rates. Although the overall survival rate does not differ in the two groups, there appears to be a trend toward longer survival in node positive patients treated with an extended rather than a standard lymphadenectomy.
Post-reperfusion inflammation as well as anti-allograft response occur following kidney transplantation. We evaluated tissue damage by multiple renal indicators and searched for rejection predictors forewarning serum creatinine upturns. Twenty recipients (43 +/- 9 y; donors' age 35 +/- 16 y) of first renal grafts were studied. All through their hospital stay (35 +/- 18 d, range 17-75 d) we measured serum levels of urea, creatinine and electrolytes along with urinary excretion rates of total protein, albumin, enzymes (GGT, NAG, AAP) and electrolytes. During the period of observation, peaks were seen on the 1st day for serum creatinine, serum K+ and urine albumin output; on the 2nd day for urine Na+, GGT, AAP and protein excretion rates; on the 4th day for urea and creatinine outputs; on the 5th day for NAG output. On the 14th day, serum urea and creatinine as well as urine GGT, NAG, AAP, albumin and total protein were still elevated compared to 20 healthy control subjects. Delayed/slow graft function was observed in six recipients with higher pre-transplantation plasma lipids and lower donor HDL cholesterol. Hospital stay time was correlated with need for post-transplantation dialysis (p = 0.01) and recipient proteinuria by time 0 (TO) to day 3 (p = 0.02). Cold ischemia time was positively associated with 0-3 d serum creatinine, 0-3 d urinary urea and protein outputs (multiple r 0.9, p < 0.001). Multivariate analysis of longitudinal data showed that recipients' serum creatinine was positively correlated (p < 0.001) with urine AAP and negatively correlated with urine albumin, with diuresis volume and urine creatinine (p < 0.01). Serum creatinine elevations were preceded (previous 1-7 d) by increases in urinary indicators, the probability being higher in the presence of multiple simultaneous abnormalities. Useful parameters predictive of favorable graft outcome prior to transplantation included a brief cold ischemia time and a normal donor/recipient serum lipoprotein profile. Following transplantation, useful parameters were a high diuresis volume at time zero along with low urine NAG and high albumin outputs; early (first opst-graft 3 d) polyuria, low urea and GGT, high K, NAG and total protein excretions.
BACKGROUND: To evaluate anesthesia and Intensive Care Unit (ICU) costs for Orthotopic Liver Transplantation (OLT) through a point by point analysis of the entire process from anesthesia induction to ICU discharge. DESIGN: Retrospective analysis. SETTING: Regional Transplantation Centre participating to the Italian National Health Care System. METHODS: Anesthesia and ICU costs for each OLT performed during 1997 were estimated through the analysis of costs of the following categories: drugs, medical and nurse staff, blood bank, radiology, laboratory, haemoderivates. RESULTS: Forty OLTs were performed in 38 recipients during the study period. The total charges for the anesthesia and ICU management of these patients calculated in US dollars were 583.433,23 (considering the exchange rates valid in January 1998). ICU costs resulted approximately 2.5 times higher than those for anesthesia. Blood bank and drugs were the categories that had the greatest impact on the final expense whereas laboratory had the lowest. The charges referred to medical and nurse staff resulted higher in the ICU than for anesthesia. CONCLUSIONS: The Italian National Health Care System has to deal with limited resources; costs analysis of high-tech procedures as OLT is of basic importance to optimise resources allocation and to enforce money-saving actions.
BACKGROUND: Epidemiological data are fundamental to adequately plan the activity of a liver transplantation centre. AIM: To evaluate the ratio between need and supply of liver grafts in Tuscany and to develop a regional strategy aimed at increasing donor recruitment. METHODS: The need for liver grafts was estimated on the basis of an epidemiological study: 19 Medical Units were requested to fill in a questionnaire inquiring into all Tuscan patients evaluated for liver disease during three different periods of one month each in 1996. The information collected was matched with the selection criteria currently employed at our centre and the patients were classified into the following four categories: 1. current transplantation candidates; 2. future transplantation candidates; 3. candidates not suitable on account of age; 4. candidates not suitable on account of exclusion criteria. The number of liver donors was obtained from the donor registry. RESULTS: Questionnaires were returned for a total of 452 patients: 27 (5.97%) were classified as current transplantation candidates, 62 (13.72%) as future transplantation candidates and 19 (4.20%) as candidates not suitable on account of age. The annual incidence and prevalence of transplantation candidates were 14.7 and 30.6 cases per million inhabitants, respectively. If age (> or = 61 years) was not considered in the exclusion criteria, the annual prevalence of transplantation candidates reached 52.1 cases per million inhabitants. During the same period there were 44 organ donors (12.2 donors per million inhabitants) of whom 33 were suitable for liver donation (9.3 liver donors per million inhabitants). To reduce this discrepancy a new programme for organ recruitment, based upon the Spanish model, has been recently employed. CONCLUSIONS: The annual need for liver grafts in Tuscany largely exceeds the number of donors currently available. It is hoped that the new regional programme for organ recruitment will improve these figures.
BACKGROUND: Cyclosporine (CsA)-induced acute nephrotoxicity could be reduced by prevention of parenchymal accumulation of the drug itself. The objective of this prospective study was to evaluate whether cilastatin, an inhibitor of active tubular resorption of CsA, reduces CsA-induced acute nephrotoxicity in kidney graft recipients. METHODS: Sixty-nine kidney recipients with immediate graft functional recovery were randomly assigned to either the treatment group (imipenem/cilastatin, n=33) or the control group (ceftazidime, n=36). All patients followed a standard immunosuppressive regimen based on CsA and low-dose prednisone. Graft function and CsA levels were evaluated 3, 5, 10, 15, and 30 days after transplantation. RESULTS: Compared with the control group, imipenem/cilastatin administration reduced the serum creatinine level in the first 2 weeks after transplantation, reaching a significant effect on postoperative day 10 (P<0.05). No significant differences were demonstrated between the two groups for CsA levels, patient and graft survival, and all the other examined parameters. CONCLUSIONS: Our findings support the hypothesis that cilastatin administration can reduce CsA-induced acute nephrotoxicity after kidney transplantation.
Isolated human pancreatic islets were prepared by collagenase digestion and density gradient purification, and the effects of glibenclamide (0.5 and 5.0 mumol/l) and metformin (20 and 200 mumol/l), alone or in combination, on insulin release were evaluated at varying glucose concentrations. At 3.3 mmol/l glucose level, the addition of 5.0 mumol/l glibenclamide or 5.0 mumol/l glibenclamide plus 200 mumol/l metformin caused a significant increase of insulin release, compared with glucose alone. At 16.7 mmol/l glucose concentration, a significant increase of insulin secretion, compared with glucose alone, was produced by the addition of either 5.0 mumol/l glibenclamide, 200 mumol/l metformin, or both 5.0 mumol/l glibenclamide and 200 mumol/l metformin. The effect of the combination of the two drugs was significantly higher than that with either drug used alone. Thus, glibenclamide was shown to have an insulinotropic effect on human islets at both low and high glucose concentrations, and metformin at high glucose concentrations. A possible synergistic effect of glibenclamide and metformin at high glucose concentrations is also suggested.
OBJECTIVE: To compare the effects on cerebral perfusion and oxygenation of intravenous ibuprofen and indomethacin as treatment for patent ductus arteriosus in preterm infants. STUDY DESIGN: Sixteen infants receiving mechanical ventilation (< 31 weeks gestation) with patent ductus arteriosus received either 0.2 mg/kg indomethacin (n = 8) or 10 mg/kg ibuprofen (n = 8) infused over 1 minute. Near-infrared spectroscopy was used to measure changes in cerebral blood volume and in oxidized cytochrome oxidase concentration. Cerebral blood flow velocity in the pericallosal artery was measured using Doppler ultrasonography. RESULTS: Indomethacin caused a significant reduction of CBV (maximal changes in cerebral blood volume: -320 +/- 171 microL/100 gm) and, in four of eight patients, a fall in oxidized cytochrome oxidase concentration (maximal change in oxidized cytochrome oxidase concentration in the eight patients: -0.68 +/- 0.98 mumol/L, NS). Cerebral blood flow velocity fell significantly. Ibuprofen caused no significant reduction of cerebral blood volume, oxidized cytochrome oxidase concentration, or cerebral blood flow velocity, whereas a significant increase of cerebral blood volume (+207 +/- 200 microL/100 gm) was observed after 60 minutes. Ductus closure was seen in six of eight infants after the first dose of indomethacin and in five of eight infants after the first dose of ibuprofen. The therapeutic cycle involved administration of a second and third dose, provided no side effects occurred. Treatment was effective in all infants. CONCLUSION: Compared with indomethacin, treatment with ibuprofen does not significantly reduce cerebral perfusion and oxygen availability; the observed increase in cerebral blood volume requires further investigation.
BACKGROUND: This study compared long-term survival in pancreatic or periampullary cancer treated with Whipple pancreatoduodenectomy (PD) and pylorus-preserving pancreatoduodenectomy (PPPD). METHODS: Two hundred twenty-one patients with pancreatic head or periampullary cancer were treated. Prognostic variables included age, gender, type and period of operation, and tumor stage. In the ductal adenocarcinomas variables also included tumor and node status, type of lymphadenectomy, pathologic grade, and presence of microscopic residual tumor. The end point was death as a result of neoplastic recurrence. Survival curves were estimated by using the Kaplan-Meier method, and multifactorial analysis was also performed on the data from the ductal adenocarcinoma group. RESULTS: The mortality rate was 8.2% in the PD group versus 7.0% in the PPPD group. Morbidity rates were 34.4% for PD and 45.8% for PPPD. Five-year survival was 9.6% in the ductal adenocarcinoma and 63.8% in the periampullary carcinoma groups. Univariate analysis failed to show statistically significant differences in survival curves between the two treatments in either patient group. Correcting for multiple variables in the ductal adenocarcinoma group did not reveal any significant differences in survival rates between the two treatments. CONCLUSIONS: PPPD was as successful as classic PD in the treatment of ductal adenocarcinoma and periampullary cancer of the pancreas. Long-term survival was not influenced by the type of resection.
BACKGROUND: Recurrence of adrenal cortical carcinoma (ACC) after radical surgery is a common finding. Although successful reoperations have been reported with encouraging results, most published experiences are anecdotal and based on few cases. We report the results of surgical treatment for recurrent ACC in a multiinstitutional series. METHODS: One hundred eighty-eight cases of ACC were collected in a national registry. A complete follow-up was obtained in 179 cases. At initial diagnosis 92 patients had local disease (stage I or II). One hundred seventy patients underwent surgical treatment, considered radical in 140; in this group, recurrent disease was observed in 52 cases (37%) after a mean disease-free interval of 21.7 months. RESULTS: Adjuvant chemotherapy was ineffective in ameliorating the prognosis. The mean survival in 20 patients who underwent reoperation was significantly higher (15.85 +/- 14.9 months) than in nonreoperated cases (3.2 +/- 2.9 months). Five-year actuarial survival in reoperated patients is significantly better than in nonreoperated patients (49.7% versus 8.3%, respectively). CONCLUSIONS: Although the prognosis of this tumor is still poor, surgery is the only effective therapy; reoperation allows survival comparable to that observed in patients without recurrent disease. An aggressive strategy for recurrent ACC is advisable until prospective studies demonstrate a real effectiveness for chemotherapy.
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