Evaluation and management of metabolic and coagulative disorders in HIV-infected patients receiving highly active antiretroviral therapy

A number of metabolic disorders, including hypercholesterolemia, hypertriglyceridemia, insulin resistance, elevated fasting glucose and diabetes mellitus, were reported in a high proportion of HIV-infected patients receiving highly active antiretroviral therapy (HAART). Less frequently, coagulative disorders were described in patients receiving HAART. Since all these metabolic disorders may predispose to coronary heart disease, an early evaluation and treatment is advisable. Existing guidelines for uninfected patients may be applied, taking into account, however, the potential for drug interactions and accumulated toxicity. It may be helpful to stratify all patients in three risk groups to plan regular diagnostic screening. Treatment of dyslipidemia and diabetes mellitus should include a first-line approach with non-pharmacological interventions. Statins and fibrates are proposed for HIV-infected patients with HAART-related hyperlipidemia, but concern has been raised on their potential for interaction with antiretrovirals and hepatic and muscle toxicity. Metformin and thiazolidenediones (or glitazones), hypoglycemic agents that increase insulin sensitivity, are presently under evaluation in diabetic and glucose-intolerant HIV-infected patients treated with HAART. Glitazones also have a potential for ameliorating the lipodystrophic syndrome. The routine evaluation of coagulative parameters is probably not advisable until a benefit of widespread screening is assessed in prospective studies. A heightened awareness of the possiblity of coagulative disorders, together with controlled trials and basic research, is needed.     

Stem cell therapies in reparative medicine

The future implementation of stem cell therapies to treat conditions thus far considered incurable has been envisioned as logical consequence of the fast-paced progress in stem cell research over the last few years. Still, many practical obstacles stand in the way to the routine application of these novel technologies in medicine. The conference "Stem Cell Therapies in Reparative Medicine," held aboard the cruise vessel Majesty of the Seas (Miami, USA-Nassau, Bahamas, April 19-22, 2002), focused on the analysis of these problems from different perspectives, including developmental biology (cell proliferation, fate determination, and enrichment), immunology (allorejection and prevention of autoimmunity recurrence), and clinical therapy, emphasizing the impact of stem cell technologies on the emerging field of tissue engineering and the treatment of alpha-1 antitrypsin deficiency.     

Human Islet Transplantation: Update

New hope for the treatment of type 1 diabetes has recently emerged from the encouraging results of islet cell transplantation in humans during the last few years. Although still facing considerable problems, the challenge to achieving insulin independence has been overcome in some patients who received an islet graft. However, the success of clinical trials is still limited by the inability to transplant enough viable human islets to compensate for the insulin-deficient state, the number of islets that engraft following transplantation, the rejection process, and the recurrence of autoimmunity. The important advances in immunosuppressive regimens, organ procurement techniques, isolation techniques, and availability of defined collagenase blends have contributed to the continuing promise of making islet cell transplantation the treatment of choice for type 1 diabetes mellitus.     

Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone

BACKGROUND: Surgery is the standard treatment for patients with resectable esophageal carcinoma, but the long term prognosis of these patients is unsatisfactory. Some randomized trials of preoperative chemotherapy suggest that the prognosis of patients who respond may be improved. METHODS: This randomized, controlled trial compared patients with clinically resectable esophageal epidermoid carcinoma who underwent surgery alone (Arm A) with those who received preoperative chemotherapy (Arm B). Overall survival and the prognostic impact of major response to chemotherapy were analyzed. Forty-eight patients were enrolled in each arm. Chemotherapy consisted of two or three cycles of cisplatin (100 mg/m2 on Day 1) and 5- fluorouracil (1000 mg/m2 per day continuous infusion on Days 1-5). In both study arms, transthoracic esophagectomy plus two-field lymphadenectomy was performed. The two groups were comparable in terms of patient characteristics. RESULTS: Forty-seven patients were evaluable in each arm. The curative resection rate was 74.4% (35 of 47 patients) in Arm A and 78.7% (37 of 47 patients) in Arm B. Treatment-related mortality was 4.2% in both arms. The response rate to preoperative chemotherapy was 40% (19 of 47 patients), including 6 patients (12.8%) who achieved a pathologic complete responses. Overall survival was not improved significantly. The 19 patients in Arm B who responded to chemotherapy and underwent curative resection had significantly better 3-year and 5-year survival rates (74% and 60%, respectively) compared with both nonresponders (24% and 12%, respectively; P = 0.0002) and patients in Arm A who underwent complete resection (46% and 26%, respectively; P = 0.01): Patients who achieved a pathologic complete response (P = 0.01), but not those who achieved a partial response (P = 0.2), had significantly improved survival. CONCLUSIONS: Patients with resectable esophageal carcinoma who underwent preoperative chemotherapy and obtained a pathologic complete response had a significantly improved long term survival. Major efforts should be undertaken to identify patients before neoadjuvant treatments who are likely to respond.     

Thoracoscopic management of chylothorax complicating esophagectomy

BACKGROUND: Chylothorax is a relatively uncommon complication of esophageal surgery that may lead to severe respiratory, nutritional, and immunologic deficiencies. PATIENTS AND METHODS: Between 1992 and 2000, 3 of 316 patients (0.9%) undergoing transthoracic esophagectomy for carcinoma developed postoperative chylothorax. Two of them had previously been treated with neoadjuvant chemoradiation, and one had been submitted to esophagogastric resection through a left thoracotomy. After a 2-week trial of total parenteral nutrition and drainage, two patients underwent thoracic duct ligation via thoracotomy. In the last patient, the operation was completed by thoracoscopy. The azygos vein and the periaortic tissue above the diaphragm were encircled en bloc by a right-angled clamp, and a roticulating endostapler was applied. RESULTS: Reoperation was successful in all patients. The postoperative hospital stay was 4 days. CONCLUSION: Thoracoscopy is a safe and effective procedure for the treatment of chylothorax complicating esophagectomy. Given the minimal trauma to the patient, early thoracoscopic reoperation can be advocated in patients with high-output chyle loss in order to reduce the hospital stay.     

Studien über die Pest

Ohne ZusammenfassungHierzu Taf. I–IV.     

Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers

Ianez R F, Buim M E, Coutinho‐Camillo C M, Schultz R, Soares F A & Lourenço S V
(2010) Histopathology 57 , 410–417
Human salivary gland morphogenesis: myoepithelial cell maturation assessed by immunohistochemical markers Aims: Myoepithelial cells are important components of salivary gland structure, aiding the expulsion of saliva from acinar lobules. The aim was to evaluate the expression of smooth muscle actin (SMA), calponin, caldesmon, CD10, CD29, S100 protein, glial fibrillary acidic protein (GFAP) and p63 in myoepithelial cells during salivary gland morphogenesis to understand the maturation process of these cells and their possible use in the diagnosis of salivary gland lesions. Methods and results: Major and minor human salivary glands at various stages of development, derived from fetuses at 8–26 weeks of gestation, were studied immunohistochemically. Fully developed salivary glands were used as controls. The protein p63 was present in all stages of salivary gland morphogenesis from initial bud to terminal bud stage. CD29, S100 and calponin were detected increasingly as salivary gland structure matured and in fully developed salivary gland. Proteins GFAP, CD10 and caldesmon were not observed in myoepithelial cells of salivary glands. Conclusions: The proteins SMA, calponin, CD29, S100 and p63, which are present from the earliest stages of salivary gland maturation, are valuable myoepithelial markers but, although very specific, are not exclusive markers for this cell type.