Menopausal hot flushes and plasma beta-endorphins

Plasma beta-endorphin levels were measured in five women in physiologic menopause suffering from frequent episodes of hot flushes, recorded objectively by the measurement of finger temperature. Significantly lower levels of plasma beta-endorphin levels were found at the onset of the hot flushes than five to 20 minutes before (P less than .001). After the flush there was a significant rise of plasma beta-endorphin levels at five, ten, and 15 minutes (P less than .002).     

Papillary carcinoma of the thyroglossal duct cyst: a case report

The thyroglossal duct cyst is the most common anomaly in thyroid development. To date, approximately 250 cases have been reported, the majority being papillary thyroid carcinomas. In most cases the diagnosis is established only after excision of a clinically benign thyroglossal duct cyst. Controversies exist in relation to a rational and effective therapeutic approach. A further case of thyroglossal duct papillary carcinoma affecting a 52 years-old man is presented to highlight the clinicopathological features of this condition. FNAC resulted false negative. Surgery consisted in a Sistrunk procedure, followed by total thyroidectomy and central lymphectomy after definitive histological diagnosis. In view of the prolonged course of papillary carcinoma, long-term follow-up is mandatory.     

Nonocclusive intestinal ischemia in patients with acute aortic dissection

BACKGROUND: In aortic dissection, visceral complications that result from aortic branch compromise have been described extensively, whereas intestinal ischemia not associated with the false lumen anatomy has rarely been discussed. The aim of this report is to identify clinical factors that may contribute to the development of this form of acute mesenteric ischemia, to profile the patients at greatest risk, and to review diagnostic and treatment methods that emerged from our experience. METHODS: With a computerized database, we identified 371 patients who underwent treatment in our institution with a diagnosis of aortic dissection between July 15, 1985, and January 10, 2001. Mesenteric ischemia was present in 73 patients (19%). In 36 patients (9%), bowel ischemia was not associated with a false lumen anatomy or an extension of the dissection process. From a general analysis of the determinants of mesenteric ischemia in aortic dissection, we investigated, with univariate and multivariate analysis, the specific characteristics of these patients with nonocclusive ischemia. A retrospective analysis of the oxygen metabolic profile of patients who underwent operation also was performed. RESULTS: The mortality rate in patients with nonocclusive mesenteric ischemia was 86%; sepsis and multiple organ failure were the causes of death in all nonsurvivors. Surgical treatment was beneficial only in the early phases of the disease. The results of the multivariate analysis showed the multifactorial origin of nonocclusive mesenteric ischemia; cerebral ischemia, thrombosis of the false lumen, severe coagulation disorders, chronic obstructive pulmonary disease, aortic calcinosis, prolonged hypotension, chronic renal insufficiency, and low cardiac output were independent predictors of the condition. In patients who underwent operation, the significant risk factors were severe coagulation disorders, postoperative cerebral ischemia, maximal oxygen extraction rate of more than 0.40, aortic calcinosis, chronic obstructive pulmonary disease, thrombosis of the false lumen, inotropic support, and chronic renal insufficiency. An oxygen extraction rate of more than 0.4 at 6 hours after operation was found to be an index of intestinal damage sufficient to initiate an evaluation for visceral ischemia. Significant differences with occlusive ischemia also were evidenced with this study. CONCLUSION: In aortic dissection, nonocclusive mesenteric ischemia shows some unique clinical and individual predisposing factors. Most instrumental investigations are of poor diagnostic value, and prognosis is poor, especially when mesenteric gangrene had already taken place. Prevention can be exercised only with a heightening of our awareness of this condition and with timely correction of metabolic disturbances. In suspected cases, an aggressive surgical attitude may represent the only means for reducing mortality.     

Classification and prediction of the progression of thyroid-associated ophthalmopathy by an artificial neural network

OBJECTIVE: We have used an artificial neural network in an attempt to classify and predict the progression of thyroid-associated ophthalmopathy (TAO) at the first clinical examination. DESIGN: This retrospective comparative case series included a group of patients examined by the ophthalmologist only once because of the absence of signs of progressive disease (GR1), as subsequently monitored by an endocrinologist, and a group of patients on follow-up because of progressive disease (GR2). PARTICIPANTS AND METHODS: We examined 242 patients, of whom 207 were women and 35 were men. GR1 included 129 patients (257 eyes) who, on ophthalmologic assessment, were further classified as having no TAO (n = 53; GR1a) and only lid signs or inactive, stable TAO (n = 76; GR1b). GR2 included 113 patients (219 eyes). One hundred three normal subjects (205 eyes), 50 women and 53 men, were tested to provide normal ranges for proptosis values. We applied a model of back propagation neural network with 17 input variables, a training matrix of 414 observations, a randomly selected test group of 115 observations, and, as output, the progression of disease. The ophthalmologic assessment included (1) lid fissure measurement, (2) Hertel, (3) color vision, (4) cover test and Hess screen, (5) visual acuity, (6) tonometry, (7) fundus examination, (8) visual field, and (9) orbital computed tomography scan or ultrasonography. Other parameters included in the neural analysis were gender and age of the patients, their cigarette smoking, and the interval between follow-up visits. RESULTS: The prevalence of smokers among patients without TAO was significantly lower than that among those with TAO (P < 0.03). Mean proptosis values (Hertel) were significantly different in GR1, in GR2, and in a group of normal eyes (P < 0.0001), and the changes of values in consecutive measurements were associated with progression of the disease (P < 0.01). Differences of the proptosis values in the two groups of patients were not related to smoking. The neural network correctly classified 78.3% of 115 eyes (87 patients) and predicted TAO progression in 69.2% of 39 eyes (28 patients). CONCLUSIONS: In our opinion, neural network analysis can be successfully applied for classifying TAO and predicting progression at the first clinical examination.     

Raltitrexed plus oxaliplatin as first-line chemotherapy in metastatic colorectal carcinoma: a multicentric phase II trial

For advanced colorectal carcinoma, two new drugs, raltitrexed (TOM) and oxaliplatin (L-OHP), have recently shown interesting results. Preclinical and clinical studies suggest that this combination, because of its favorable toxicity profile, high response rate and convenient schedule of administration, can be administered successfully in this disease. In our phase II study, 37 non pre-treated patients with metastatic colorectal carcinoma were treated with TOM (3 mg/m(2)) and L-OHP (130 mg/m(2)) every 3 weeks. In total, 222 cycles were administered; all patients received at least 2 cycles (median 6, range 2-8). There were two complete and 14 partial responses for an overall response rate of 43% (95% CI 27-69%). The median time to response was 2.5 months (range 2-4) and the median duration was 10.3 months (range 5-18). Twelve of the 23 (52%) patients with symptomatic colorectal cancer were classified as clinical benefit responders for at least 4 weeks during the study period. Treatment was well tolerated, and both acute, essentially hematologic, and cumulative hepatic and neurologic toxicities were manageable and reversible. Response rate and toxic effects observed during this study warrant additional studies comparing this TOM-L-OHP regimen with CPT-11 and/or capacitebine-containing regimens in metastatic colorectal carcinoma.     

Phase II trial of weekly intravenous gemcitabine administration with interferon and interleukin-2 immunotherapy for metastatic renal cell cancer

PURPOSE: Since metastatic renal cell carcinoma has a poor prognosis and treatment strategies, including hormone therapy, chemotherapy and immunotherapy, have little impact on the quality of life and global survival statistics, new interest has recently focused on the combination of immuno-chemotherapy using pyrimidine analogues, such as gemcitabine. MATERIALS AND METHODS: In a phase II study 16 patients with metastatic renal cell carcinoma were treated with 1,000 mg./m. gemcitabine intravenously on days 1, 8, 15 and 28 for 6 months, 3 MU (1 MU = 1 x 10(6) IU) interferon (IFN)-alpha intramuscularly 3 times a week and 4.5 million IU interleukin (IL)-2 subcutaneously daily for 5 days a week for 2 consecutive weeks every month for 6 months. Responding and nonprogressing cases were maintained on immunotherapy consisting of IFN-alpha and IL-2 for further 6 months. RESULTS: In 15 evaluable patients overall response rate (1 complete response plus 3 partial response) was 28% while stable disease was achieved in 7 (47%). Median survival duration was 20 months (range, 9 to 26+) and median time to tumor progression was 14 months (6 to 26+). The complete response lasted 24+ months and partial response lasted 16 months. The regimen was well tolerated with only 1 case of neutropenia (WHO grade 3), while anorexia, fatigue and flu-like symptoms were the most common toxicity problems but were never greater than grade 2. CONCLUSIONS: Despite the small sample size, this study demonstrates that gemcitabine combined with standard doses of IFN-alpha and low doses of IL-2 is effective treatment for metastatic renal cell carcinoma. This biotherapy was well tolerated and resulted in an optimum objective response and relatively long-term survival.     

Intraportal hepatocyte transplantation in the pig: hemodynamic and histopathological study

BACKGROUND: Hepatocyte transplantation is an attractive treatment for various liver diseases. The intraportal route of transplantation is favored, but little information is available on the possible adverse effects in this technique. We investigated the influence of intraportal loads of hepatocytes on portal, pulmonary, and systemic hemodynamics in 13 pigs. METHODS: Under general anesthesia, pigs were provided with an arterial line, a Swan-Ganz catheter, and two intraportal catheters, one for cell infusion and one for heparin infusion and portal pressure measurement. Pig hepatocytes were infused at a rate of 25 million cells/min. RESULTS: The first six animals were used to develop the infusion technique. In the last seven animals, portal pressure increased linearly with cell load upon infusion of 400-2400 x 10(6) hepatocytes (r(2)=0.704;P<0.05). Portal flow measured by Doppler sonography decreased by 23-66% below basal values. An inverse linear relationship was found between portal pressure and portal flow (r(2)=0.679; P<0.05), portal flow approaching zero for portal pressure >40 mmHg. Pulmonary arterial pressure increased by 11-62%. AST increased up to 10-fold, and platelets decreased by 22-58%. Hepatocytes-containing thrombi were present in segmental and in smaller portal branches. Hepatocytes were always identified in lung sinusoids 48 hr after infusion, and a small basal pulmonary infarction was found in one animal. CONCLUSION:. These data suggest that up to 2.4% of total hepatocyte mass can be infused in this large animal model. However, the risk of significant thrombotic complications should be considered for clinical applications.     

Arteroportal fistulas between the accessory right hepatic, gastroduodenal and superior mesenteric arteries and portal vein: a difficult technical problem to overcome in liver transplantation

BACKGROUND: Fistulous communications between the accessory right hepatic (ARHA), gastroduodenal (GD), and superior mesenteric (SMA) arteries and the portal vein (PV) may represent a contraindication for liver transplantation (LT). MATERIAL: A patient with HCV-related liver cirrhosis and progressive liver decompensation underwent preoperative LT work-up. Doppler ultrasound (DU), Angiography and MRI revealed arteroportal fistulas (APF) and diversion of mesenteric-splenoportal flow through spontaneous splenorenal shunts (SSRS) in the systemic circulation. The patient was transplanted and the ARHA and GDA were distally sectioned; the HA was anastomosed to the donor HA; the superior mesenteric vein (SMV) was detached from the splenopancreatic venous bed by sectioning and ligating the Henle trunk, by ligating an posterior-inferior pancreatic vein and, finally, by positioning an iliac vein interposition graft between the SMV and the donor PV. The postanastomotic SMV trunk and recipient PV were ligated below and above the pancreatic head, respectively. RESULTS: Reperfusion and late liver function were good. DU and MRI studies showed an effective portal flow and the maintenance of a normal splenopancreatic vein outflow through the SSRS. DISCUSSION: APF represent a serious clinical problem, particularly in patients who need LT. The persistence of arterial flow into the PV is dangerous for the long-term liver function. A particular surgical strategy, strictly tailored to the hemodynamic conditions, has to be planned. CONCLUSIONS: Extrahepatic multiple APF would no longer to represent a contraindication to LT, although this claim needs to be confirmed in the light of further experience and a longer-term follow-up.     

Gemcitabine plus Epi-doxorubicin as first-line chemotherapy for bladder cancer in advanced or metastatic stage: a phase II

Combination chemotherapy with newer, more active drugs in patients with advanced and/or metastatic bladder cancer might show improved response rate and survival. Gemcitabine (GEM) and Epidoxorubicin (EPI) have demonstrated activity in this disease. In addition, experimental studies in vitro have shown that the two agents have additive-synergistic effects when used in combination. Our prior phase I dose-finding study in previously untreated patients with advanced or metastatic bladder cancer defined recommended doses for further trials of GEM 1000 mg/m2 and EPI 25 mg/m2 on days 1, 8 and 15 every 28 days. A phase II trial at this dose level was initiated in previously untreated patients to assess efficacy and toxicity. Eligible patients had measurable disease; Karnofsky performance status (PS) of > 40; no prior chemotherapy; and adequate bone marrow reserve, cardiac, hepatic and renal function. Thirty- one patients (22 males, 9 females) with median age of 64 (range 44-75) and median PS of 80 were accrued, and all were eligible. Twelve patients had T4N1-2 M0, 8 had lymph node only metastases, while 11 had visceral metastases (liver, bone, lung). A total of 181 cycles was administered (range 3-7 per patient). Major toxicities (WHO grade > or = 3) were: neutropenia in 5 patients, thrombocytopenia in 2 patients, and anemia in 2 patients. Three patients had febrile neutropenic episodes and only 3 patients required dose reduction. Grade 1-2 non-hematological toxicities included nausea/vomiting, stomatitis and alopecia. No cardiac toxicity was observed. Of the 30 response evaluable patients, 17 (57%) demonstrated a major response (3 complete and 14 partial) (95% CI: 39%-75%), 7 had stable disease (23%) and 6 progressed (20%). These preliminary results confirm the phase I observation that the combination of GEM--EPI is highly active in the treatment of advanced and metastatic bladder cancer with a favourable toxicity profile.     

Surgical treatment of abdominal aortic aneurysms associated with aortic valve incompetence: strategies and outcomes

BACKGROUND: The exact incidence of associated aortic valve incompetence (AVI) and abdominal aortic aneurysm (AAA) in the general population is not known. In recent years, we have observed this association with increasing frequency. This observation is probably due to the extensive preoperative screening of the cardiac and vascular status of patients who are candidates for surgical procedures. The choice of the optimal surgical strategy is needed to achieve low operative morbidity and mortality. The present study reviews our experience with a subset of patients suffering the association of AVI and large AAA. Surgical strategy, clinical management and outcome are presented.METHODS: Between January 1982 and May 2000, 76 patients with the association of AAA and AVI have been evaluated in our institution. Forty-four patients have been treated for both AAA and aortic valve (AV) regurgitation. These patients have been divided into three groups on the basis of the surgical strategy adopted. Group 1: combined procedure (16 patients); group 2: AAA repair prior to AV surgery (nine patients); group 3: AV surgery prior to aneurysm repair (19 patients).RESULTS: Hospital mortality was 4.5% (two patients); overall mortality was 6.8% (three patients).CONCLUSIONS: In patients with AAA and AVI, an accurate and complete preoperative evaluation is essential. Surgical strategy should be individualized on the basis of the cardiac preoperative status.