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Biomedical subjects

L Gennari

Publications and source records attributed to L Gennari.

At least 55 records · Page 3Linked to original sources

Treatment of post-menopausal osteoporosis with recombinant human growth hormone and salmon calcitonin: a placebo controlled study.

OBJECTIVE: The usefulness of GH in the treatment of post-menopausal osteoporosis (PMO) is still debated. We have studied the effects of recombinant human GH (rhGH) given alone or in combination with salmon calcitonin (sCT) in the treatment of PMO. PATIENTS: Thirty women with established PMO (aged 61.1 +/- 4.4 years) were divided into 3 groups of 10 and randomly assigned to 3 treatment sequences: rhGH (12IU/day) s.c. for 7 days, followed by sCT (50 IU/day) s.c. for 21 days and by 61 days without treatment (group 1); placebo for 7 days, followed by sCT for 21 days and by 61 days without treatment (group 2); rhGH for 7 days, followed by placebo for 21 days, and by 61 days without treatment (group 3). Each cycle was repeated 8 times (24 months). MEASUREMENTS: At days 0, 8, 29 and 90 of each cycle, serum IGF-I, calcium, phosphate, osteocalcin, alkaline phosphatase and urinary excretion of calcium, hydroxyproline and pyridinoline cross-links (Pyr) were measured. At months 0, 6, 12, 18 and 24, bone mineral density (BMD) was measured by dualphoton absorptiometry (DPA), at lumbar spine (LS), femoral shaft (F) and distal radius (DR). RESULTS: A significant increase in serum osteocalcin and urinary calcium, hydroxyproline and Pyr was detected after each rhGH period. In group 1, BMD at lumbar spine increased by 2.5% at year 2; in contrast, significant (P < 0.05) decreases in BMD-LS values were found in patients treated with CT and placebo (group 2) and with GH and placebo (group 3). BMD-F did not show any significant change in patients of group 2, but a significant (P < 0.05) decrease was found in groups 1 and 3. BMD-DR did not show any significant change with respect to baseline in any of the three groups. No significant difference between the three groups was found in bone mass at the three different regions. CONCLUSIONS: Our study demonstrates that treatment with rhGH increases bone turnover in postmenopausal osteoporotic women. Combined treatment with rhGH and CT over a period of 24 months is able to maintain bone mass at lumbar spine and distal radius, but induces a decline at femoral shaft; therefore, it does not seem particularly useful in the therapy of post-menopausal osteoporosis.

Amino Acids↗

Total versus subtotal gastrectomy: surgical morbidity and mortality rates in a multicenter Italian randomized trial. The Italian Gastrointestinal Tumor Study Group.

OBJECTIVE: The purpose of this study was to analyze postoperative morbidity and mortality of patients included in a randomized trial comparing total versus subtotal gastrectomy for gastric cancer. SUMMARY BACKGROUND DATA: There is controversy as to whether the optimal surgery for gastric cancer in the distal half of the stomach is subtotal or total gastrectomy. Although only a randomized trial can resolve this oncologic dilemma, the first step is to demonstrate whether the two procedures are penalized by different postoperative morbidity and mortality rates. METHODS: A total of 624 patients with cancer in the distal half of the stomach were randomized to subtotal gastrectomy (320) or total gastrectomy (304), both associated with a second-level lymphadenectomy, in a multicenter trial aimed at assessing the oncologic outcome after the two procedures. The end points considered were the occurrence of a postoperative event, complication, or death and length of postoperative stay. RESULTS: Nonfatal complications and death occurred in 9% and 1% of subtotal gastrectomy patients and in 13% and 2% of total gastrectomy patients, respectively. Multivariate analysis of postoperative events showed that splenectomy or resection of adjacent organs was associated with a twofold risk of postoperative complications. Random surgery and extension of surgery influenced the length of stay. The mean length of stay, adjusted for extension of surgery, was 13.8 days for subtotal gastrectomy and 15.4 days for total gastrectomy. CONCLUSIONS: Our data show that subtotal and total gastrectomies, with second-level lymphadenectomy, performed as an elective procedure have a similar postoperative complication rate and surgical outcome. A conclusive long-term evaluation of the two operations and an accurate estimate of the oncologic impact of surgery on long-term survival, not penalized by excess surgical risk of one of the two operations, are consequently feasible.

Aged↗

Cell proliferation-related markers in colorectal liver metastases: correlation with patient prognosis.

PURPOSE: We analyzed the relation between phenotypic (DNA ploidy) and functional markers (S-phase cell fraction, p53, and bcl-2 protein expression) and defined their relevance on clinical outcome on a retrospective series of radically resected liver metastases from colorectal cancer. PATIENTS AND METHODS: Among 104 patients with resectable liver metastases from colorectal cancer, DNA ploidy was determined by flow cytometry, 3H-thymidine labeling index (TLI) by autoradiography, and expression of p53 and bcl-2 by immunohistochemistry. RESULTS: TLI was a significant indicator for relapse at 4 years from radical surgery, DNA ploidy was a suggestive indicator of clinical outcome, and p53 and bcl-2 expression provided no clinical information. By multivariate analysis, cell proliferation rate and Dukes' stage remained independent prognostic parameters. In the most representative subgroup of patients with H1 liver lesions (86 cases), TLI was always associated with relapse, and DNA ploidy and p53 expression provided discriminant information within slowly proliferating liver lesions. CONCLUSION: Tumor-cell proliferation of liver lesions should be used with stage of the primary colorectal cancer for a more accurate prognosis in patients submitted to curative hepatic resection.

Adult↗

The combined use of ultrasound and densitometry in the prediction of vertebral fracture.

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density for evaluating the probability of vertebral fracture. 397 postmenopausal women (59.1 +/- 6.0 years) with (n = 178) or without (n = 219) atraumatic vertebral fractures were studied. In all women, bone mineral density (BMD) of the lumbar spine was evaluated by dual X-ray absorptiometry (DXA) and speed of sound (SOS); broadband ultrasound attenuation (BUA) and Stiffness in the calcaneus were evaluated by an Achilles unit (Lunar Corporation). Ultrasonographic parameters and BMD were compared by examining the magnitude of the odds ratios, to determine which produces the highest estimate of the probability of odds of fracture, and by examining widths of the respective confidence intervals (CI) to show which estimate of odd ratio is the most precise. The relative risk of vertebral fracture, after adjusting for potential confounders, was 3.5 (CI 2.6-4.8) for BUA; 4.5 (CI 3.2-6.2) for SOS; 5.8 (CI 4.0-8.4) for Stiffness and 7.5 (CI 4.8-11.5) for BMD. Ultrasound (US) parameters were still significant independent predictors of vertebral fracture, even after adjusting for BMD. The relative risk of fracture for a simultaneous decrease by 1 SD of BMD and by 1 SD of each ultrasound parameter was 17.3 (CI 9.4-39.6) for BMD and SOS; 18.3 (CI 8.4-30.6) for BMD and BUA and 22.1 (CI 8.9-52.7) for BMD and Stiffness. Our data suggest that US and BMD provide complementary information which can be combined to improve estimates of vertebral fracture risk.

Age Factors↗

Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus.

The intraportal injection of human pancreatic islets has been indicated as a possible alternative to the pancreas transplant in insulin-dependent diabetic patients. Aim of the present work was to study the effect of intraportal injection of purified human islets on: (a) the basal hepatic glucose production; (b) the whole body glucose homeostasis and insulin action; and (c) the regulation of insulin secretion in insulin-dependent diabetes mellitus patients bearing a kidney transplant. 15 recipients of purified islets from cadaver donors (intraportal injection) were studied by means of the infusion of labeled glucose to quantify the hepatic glucose production. Islet transplanted patients were subdivided in two groups based on graft function and underwent: (a) a 120-min euglycemic insulin infusion (1 mU/kg/min) to assess insulin action; (b) a 120-min glucose infusion (+75 mg/di) to study the pattern of insulin secretion. Seven patients with chronic uveitis on the same immunosuppressive therapy as grafted patients, twelve healthy volunteers, and seven insulin-dependent diabetic patients with combined pancreas and kidney transplantation were also studied as control groups. Islet transplanted patients have: (a) a higher basal hepatic glucose production (HGP: 5.1 +/- 1.4 mg/kg/ min; P < 0.05 with respect to all other groups) if without graft function, and a normal HGP (2.4 +/- 0.2 mg/kg/min) with a functioning graft; (b) a defective tissue glucose disposal (3.9 +/- 0.5 mg/kg/min in patients without islet function and 5.3 +/- 0.4 mg/kg/min in patients with islet function) with respect to normals (P < 0.01 for both comparisons); (c) a blunted first phase insulin peak and a similar second phase secretion with respect to controls. In conclusion, in spite of the persistence of an abnormal pattern of insulin secretion, successful intraportal islet graft normalizes the basal HGP and improves total tissue glucose disposal in insulin-dependent diabetes mellitus.

Adult↗

Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.

BACKGROUND: The role of orthotopic liver transplantation in the treatment of patients with cirrhosis and hepatocellular carcinoma is controversial, and determining which patients are likely to have a good outcome after liver transplantation is difficult. METHODS: We studied 48 patients with cirrhosis who had small, unresectable hepatocellular carcinomas and who underwent liver transplantation. In 94 percent of the patients, the cirrhosis was related to infection with hepatitis B virus, hepatitis C virus, or both. The presence of tumor was confirmed by biopsy or serum alpha-fetoprotein assay. The criteria for eligibility for transplantation were the presence of a tumor 5 cm or less in diameter in patients with single hepatocellular carcinomas and no more than three tumor nodules, each 3 cm or less in diameter, in patients with multiple tumors. Thirty-three patients with sufficient hepatic function underwent treatment for the tumor, mainly chemoembolization, before transplantation. After liver transplantation, the patients were followed prospectively for a median of 26 months (range, 9 to 54). No anticancer treatment was given after transplantation. RESULTS: The overall mortality rate was 17 percent. After four years, the actuarial survival rate was 75 percent and the rate of recurrence-free survival was 83 percent. Hepatocellular carcinoma recurred in four patients (8 percent). The overall and recurrence-free survival rates at four years among the 35 patients (73 percent of the total) who met the predetermined criteria for the selection of small hepatocellular carcinomas at pathological review of small hepatocellular carcinomas at pathological review of the explanted liver wer 85 percent and 92 percent, respectively, whereas the rates in the 13 patients (27 percent) whose tumors exceeded these limits were 50 percent and 59 percent, respectively (P=0.01 for overall survival; P=0.002 for recurrence-free survival). In this group of 48 patients with early-stage tumors, tumor-node-metastasis status, the number of tumors, the serum alphafetoprotein concentration, treatment received before transplantation, and 10 other variables were not significantly correlated with survival. CONCLUSIONS: Liver transplantation is an effective treatment for small, unresectable hepatocellular carcinomas in patients with cirrhosis.

Adult↗

Cancer of the low and middle rectum: local and distant recurrences, and survival in 350 radically resected patients.

The purpose of this study was to compare local recurrence, distant metastases, and survival rate in 350 patients with cancer of the middle and low rectum who underwent a radical abdominoperineal resection (APER) or a sphincter-saving resection (SSR) in our Institute. There were 257 APER patients and 93 SSR patients, with a median follow-up of 77 months. At 5 years, the estimates in APER and SSR patients were respectively 11% and 30% for the incidence of pelvic recurrence, 18% and 8% for the incidence of distant metastases, and 64% and 73% for overall survival. In the multivariate analysis it was found that Dukes' stage significantly affected pelvic recurrences, distant metastases rate and overall survival; histologic type affected only the pelvic recurrence rate. However, the final outcome of patients following APER or SSR was similar, suggesting that local failure per se does not affect long-term survival.

Adult↗

Preoperative radiotherapy for resectable cancer of the middle-distal rectum: its effect on the primary lesion as determined by endorectal ultrasound using flexible echo colonoscope.

20 patients with rectal cancer within 8 cm of the anal verge were studied. Endoscopic endosonography was carried out before and after pre-operative radiotherapy (45 Gy over three weeks). The local extent (tumour stage and diameter) was compared with the results of histopathological examination of the resected specimen after anterior resection or total rectal excision. The Tumour Regression Grade (TRG) and lymph node status were also estimated. Two patients were not evaluated endosonographically. Two (11%) of the remaining 18 patients showed ultrasound evidence of down staging (14/18 uT3/4 pre-radiotherapy: 12/18 uT3/4 after) and tumour diameter was significantly reduced. Tumour Regression Grade estimation showed evidence of response to treatment, showing regression of more than 50% in 13 (65%) of cases. Involved nodes were less than 5 mm in diameter in 45% of cases. Histopathological evidence of nodal metastatic regression was seen in 13 (28%) of all involved nodes found. The ultrasonically determined response to radiotherapy may offer useful information in predicting outcome and possibly in selecting surgery.

Adenocarcinoma↗

Total nutritional manipulation in humans: report of a cancer patient.

We report here on a patient requiring home total parenteral nutrition (TPN) for a huge intra-abdominal desmoid associated with chronic small bowel pseudo-obstruction who was kept on a special lipid-based calorie regimen for 5 months. The rationale was to attempt to feed the host with a minimal stimulation of tumour growth by using lipid as caloric substrate instead of glucose which is utilized by the tumour. Gluconeogenesis was tentatively inhibited at the level of phosphoenolpyruvate-carboxy-kinase through the oral intake of hydrazine sulphate. The regimen consisted of 28 non-protein lipid Kcal/kg/day plus 1.5 g amino acid per kg/day. Only a small amount of glucose (approx. 40 g/day) was allowed. Tolerance to the regimen was good and body weight maintained. Liver enzymes remained within the normal range and liver sonography was normal throughout the 5 months' therapy and there were no episodes of symptomatic hypoglycaemia. The tumour volume did not substantially change.

Journal Article↗

Membrane binding sites and non-genomic effects of estrogen in cultured human pre-osteoclastic cells.

Besides functional estrogen receptors, the presence of signalling cell surface binding sites for 17beta-estradiol (17betaE2) has been reported in osteoblast- and osteoclast-like cells, suggesting that 17betaE2 may influence bone remodelling by a dual mechanism of action: to affect gene expression mediated by the nuclear activity of the steroid-receptor complex, and to initiate rapid responses triggered by a signal-generating receptor on the cell surface. Recently, we demonstrated that the human pre-osteoclastic cell line FLG 29.1 bears functional estrogen receptors. In this study we examined FLG 29.1 cells for the presence of cell surface binding sites for 17betaE2, and whether 17betaE2 could elicit cell signalling. Using a cell-impermeant and fluorescent estrogen conjugate, 17beta-estradiol-6-carboxymethyloxime-bovine serum albumin-fluorescein isothiocyanate, we demonstrated the presence of specific plasma membrane binding sites for 17betaE2. Stimulation of FLG 29.1 cells with low (1 nM) and high (1 microM) doses of 17betaE2 induced a prompt and significant (P < 0.05) increase of cellular pH, as measured in single cells using an image analysis system. In addition, both cAMP and cGMP were significantly increased by 17betaE2 with a dose-dependent response. Finally, a rapid increase of intracellular calcium ion concentration [Ca2+] was also induced by 1 nM 17betaE2, as measured in single cells using an image analysis system. Our findings strongly suggest a non-genomic action of 17betaE2 on osteoclast precursors.

Calcium↗

Risk of HBV reinfection after liver transplantation in HBsAg-positive cirrhosis. Primary hepatocellular carcinoma is not a predictor for HBV recurrence. The European Cooperative Study Group on Liver Cancer and Transplantation.

Two hundred and twenty-eight patients who underwent orthotopic liver transplantation for hepatitis B-related cirrhosis in 11 European Liver Transplant Centers were collected. The male/female ratio was 184/44, with a median age of 41 years (13-66). In 55 patients (24%) hepatocellular carcinoma was associated with liver disease. All cases were stratified for pre-orthotopic liver transplantation viral characteristics: HBV-DNA neg/HBeAg neg: 106 patients (47%), HBV-DNA neg/Delta pos: 80 (35.5%), HBV-DNA pos/HBeAg pos: 28 (12.5%), other 14 (5%). In 49 patients (21.4%) post-orthotopic liver transplantation passive prophylaxis with anti-HBs immunoglobulins was not followed, while in 179 patients the anti-HBs serum titer was kept above 100-200 mU/ml. Overall 5-year actuarial survival of the series was 54%. One hundred and eighty-five patients were evaluable for HBsAg reappearance in the serum at various intervals after orthotopic liver transplantation. Overall 3-year HBV-free survival of these patients was 55%. There was a significant difference in 3-year HBV-free survival between HBV-DNA neg (52%), HBV-DNA pos (13%) and Delta pos (73%) patients (p: 0.03). Sixty-three percent of patients in the prophylaxis group were HBV-free, compared to only 25% of untreated patients (p < 0.001). Three-year HBV-free survival in patients with or without HCC was 44% and 59%, respectively. Cox-multivariate analysis revealed that only post-transplantation prophylaxis (p: 0.003) and pre-transplantation viral activity (p: 0.004) can be considered as independent factors affecting HBV recurrence. Candidates with hepatocellular carcinoma in HBV-cirrhosis should not be excluded from orthotopic liver transplantation, supporting the idea of a higher risk of post-transplantation viral reactivation.

Adolescent↗

Comparing reconstruction with Roux-en-Y to a pouch following total gastrectomy.

BACKGROUND: Although more than 50 methods of gastric replacement after total gastrectomy have been used, none of them has demonstrated a substantial nutritional advantage. The Roux-en-Y esophagojejunostomy is still the preferred type of reconstruction, more because of its simplicity than the lack of postprandial disturbances. STUDY DESIGN: A randomized controlled trial was conducted to compare two reconstructive procedures, Roux-en-Y esophagojejunostomy (n = 24) and Hunt-Rodino-Lawrence pouch (HRL, n = 24), by evaluating nutritional status (body weight, arm circumference, and serum nutritional parameters), nutritional habits (number of meals, energy intake, and postprandial disturbances), and emptying time of the jejunal loop. RESULTS: Twenty-seven patients were studied two years after operation (12 had undergone Roux-en-Y and 15 had undergone HRL). No difference was found in either postoperative morbidity or mortality, emptying time, frequency of meals, or variation of body weight. Postprandial disturbances were more frequent in patients having Roux-en-Y. In a subset of patients, there was a correlation between nutrient intake and change of body weight, but not between nutrient intake and type of reconstruction. CONCLUSIONS: The simple use of a reservoir such as the HRL pouch after total gastrectomy is of no benefit to the patient as compared with the Roux-en-Y reconstruction.

Anastomosis, Roux-en-Y↗

Morbidity and mortality after hepatic resection of metastases from colorectal cancer.

A review was carried out of morbidity and mortality after hepatic resection for metastatic colorectal cancer in 208 consecutive patients who underwent this procedure between 1980 and 1992. Overall postoperative morbidity and mortality rates were 35 and 2.4 per cent respectively. The major morbidity rate was 18 per cent, the main complications being intra-abdominal sepsis, biliary fistula and haemorrhage. Of the different factors examined, morbidity was significantly related to the extent of liver resection (53 versus 21 per cent after major and minor resections respectively), amount of blood transfused (18 versus 52 per cent for no transfusion and more than 300 ml transfused respectively) and the date of the operation (53 versus 24 per cent before and after 1986 respectively). Multivariate analysis showed that only the extent of hepatic resection and the period at which surgery was performed retained their statistical significance. These data support the opinion that surgical treatment of hepatic metastases from colorectal cancer is an effective procedure with acceptable mortality and morbidity rates. An extensive experience of hepatic surgery is, however, necessary to optimize results.

Adenocarcinoma↗

Comparison of radioimmunodetection with other imaging methods in evaluating local relapses of colorectal carcinoma.

BACKGROUND: The prognosis for colorectal cancer patients is related closely to the extent of tumor at the time of diagnosis, and early detection of metastatic or recurrent disease is an important prerequisite for successful treatment. Radioimmunodetection is a relatively new technique to image colorectal cancer using radiolabelled monoclonal antibodies (MoAb). The goal of this study was to evaluate the clinical use of radioimmunodetection with the anti-carcinoembryonic antigen MoAb FO23C5, radiolabelled with 131I, in patients submitted to surgery for colorectal cancer and with suspected local recurrences. The results of radioimmunodetection were compared with those of computed tomography, ultrasonography, magnetic resonance imaging, and other diagnostic techniques (gastrointestinal x-ray, endoscopy, and, in selected cases, a surgical second look). METHODS: Fifty-nine patients with a rise in carcinoembryonic antigen serum levels or a clinical suspicion of recurrences entered the study. Scintigraphy was performed at multiple interval times (4-100 hours) after an intravenous injection of radiolabelled FO23C5 F(ab')2 fragments. RESULTS: The cumulative results showed the high sensitivity (89%), specificity (78%), and accuracy (86%) of radioimmunodetection. Of the radiologic methods, only magnetic resonance imaging had the same accuracy (86%), with lower specificity (64%) and higher sensitivity (93%). Computed tomographic scan and ultrasonography displayed the poorest accuracy (68% and 47%, respectively). CONCLUSIONS: Radioimmunodetection is an important imaging technique that can be used in clinical practice for the follow-up of the patient with colorectal carcinoma.

Antibodies, Monoclonal↗

Combined liver and pancreatic islets transplantation in man using cyclosporin immunosuppression.

We report a 1-year patient and graft survival after combined liver-pancreatic islet transplantation. The patient was affected by a pancreatic neuroendocrine carcinoma with extensive liver metastasis. Native pancreas and total liver removal was undertaken after a good response to chemotherapy, and the patient was still cancer-free 1 year later. Normal liver function and insulin independence was achieved, although islet response to glucose challenge remained delayed. Immunosuppression was maintained with cyclosporin monotherapy.

Cyclosporine↗

[The surgical treatment of hepatocarcinoma].

At the National Cancer Institute of Milan, 118 patients underwent surgical resection and 35 had liver transplants for HCC (hepatocarcinoma). Postoperative mortality was 14% and 17% after resection and transplantation respectively. The five-year survival was 35% for resected patients and 83% at 30 months for transplanted patients. Analysis of the literature shows that patients receiving a liver transplant for HCC stage I-II survive longer than those resected at the same stage.

Actuarial Analysis↗