Role of CRH in the pathogenesis of dementia of Alzheimer's type and other dementias

This review focuses on the role of corticotrophin-releasing hormone (CRH) in the pathogenesis of Alzheimer's disease (AD) and briefly discusses its role in other dementias, including Parkinson's disease (PD), progressive supranuclear palsy (PSP) and Huntington's disease (HD). During aging the hypothalamic-pituitary-adrenal (HPA) axis changes, which has repercussions on hormonal levels in the brain. The significance of these changes has been examined by many researchers, but the relationship between CRH and other neurotransmitters needs to be further explored.     

Can fine-needle aspiration biopsy of thyroid nodule help in determining the extent of surgery in follicular and Hurthle cell neoplasm at a community teaching institution?

Fine-needle aspiration biopsy (FNAB) was used to evaluate cold thyroid nodules in 179 patients treated between 1990 and 1998. The purpose of this study was to see whether FNAB findings of follicular or Hurthle cells could help in planning the extent of thyroid surgery. Group I patients (47) had findings suggestive of follicular or Hurthle cell neoplasm. Group II patients (132) had inconclusive results. In group I FNAB was 100 per cent correct in diagnosing follicular or Hurthle cell neoplasm with a high percentage of malignant findings (malignancy 85 per cent and benign adenoma 15 per cent). In Group II malignancy was found in 16 per cent and benign pathology in 84 per cent. Women were more likely to have malignancy than men. The average age was over 50 years in patients with either malignant or benign nodules. In addition there was no significant difference in average size of benign or malignant nodules (2.9 vs 2.6 cm respectively). When an FNAB finding was suggestive of neoplasm malignancy was found in 85 per cent. On the other hand when an FNAB was inconclusive malignancy was present in 16 per cent. Thus we conclude that using FNAB finding can guide surgical resection and recommend performing total or subtotal thyroidectomy when FNAB is suggestive of neoplasm and lobectomy when FNAB is inconclusive.     

A new teaching model for resident training in regional anesthesia

The adequacy of resident education in regional anesthesia is of national concern. A teaching model to improve resident training in regional anesthesia was instituted in the Anesthesiology Residency in 1996 at Duke University Health System. The key feature of the model was the use of a CA-3 resident in the preoperative area to perform regional anesthesia techniques. We assessed the success of the new model by comparing the data supplied by the Anesthesiology Residency to the Residency Review Committee for Anesthesiology for the training period July 1992-June 1995 (pre-model) and the training period July 1998-June 2001 (post-model). During the 3-yr training period, the pre-model CA-3 residents (n = 12) performed a cumulative total of 80 (58-105) peripheral nerve blocks (PNBs), 66 (59-74) spinal anesthetics, and 133 (127-142) epidural anesthetics. The CA-3 post-model residents (n = 10) performed 350 (237-408) PNBs, 107 (92-123) spinal anesthetics, and 233 (221-241) epidural anesthetics (P < 0.0001). All results are reported as median (interquartile range). We conclude that our new teaching model using our CA-3 residents as block residents in the preoperative area has increased their clinical exposure to PNBs. IMPLICATIONS: Inadequate exposure to peripheral nerve blocks has been a national problem. A teaching model instituted at Duke University Health System has resulted in a fourfold increase in exposure to peripheral nerve blocks compared with the national averages.     

Value of early systematic transoesophageal ultrasonography after mitral valve replacement by Saint-Jude prosthesis

The aim of this study was to assess the value of the routine multiplane transoesophageal echocardiography (TEE) in the early postoperative period after mitral valve replacement with a Saint Jude Médical (SJM) mechanical prosthesis. This prospective work enrolled 56 patients who have been operated between September 1999 and September 2001, all these patients had a multiplan TEE after 14.7 days (8-29 days) of post-operative. The effect of peri-prosthetic leaks was 59%. They were always minimal and asymptomatic. 68% of them disappeared at the late exam. An asymptomatic intermittent blockage of an leaflet had been noted in one patient. It appears to us today indispensable to achieve a systematic TEE in the early post operative period after mitral valve replacement. This exam remains little aggressive and comfortably supportable by the patient in look of information brought.     

Myocardial infarction by complete thrombosis of the common coronary trunk. Two case reports

Complete thrombosis of the left main coronary artery is a rare angiographic finding. It carries a very high mortality rate related to cardiogenic shock; malignant arrhythmia or sudden death. We report two case of a 37 and 65 years old women, admitted to our hospital with complete occlusion of the left main coronary responsible of anteroseptal myocardial infarct. The revascularisation consisted in surgical treatment in one case and percutaneous angioplasty in the second patient. The aim of our study is to discuss the different therapeutic approaches and the prognosis of this affection.     

Heparin use during pregnancy

The use of anticoagulants in pregnancy is problematic. In this focus, the authors reviewed the problems associated with the use of vitamin K antagonist during pregnancy. Then, they presented the general considerations on the use of unfractioned heparin and low molecular weight heparin during pregnancy. Finally they established the therapeutic recommendations for anticoagulation during pregnancy including treatment and prophylaxis of venous thromboembolism, anticoagulation of pregnant women with mechanical heart valves and the management of pregnant women with antiphospholipid antibodies and multiple pregnancy losses.     

Substituted acrylophenones and related mannich bases as possible spermicides and inhibitors of HIV envelope glycoprotein-CD4 interaction

Several appropriately substituted 4-(dialkylamino-alkyl)-substituted-styryl-alkyl ketones or acetophenones were prepared and subjected to the Mannich reaction to yield compounds that would incorporate both alpha,beta-unsaturated keto groups and a substituted aminomethyl function with or without another olefinic moiety at position 4. The spermicidal activity of the prepared compounds was evaluated. Several compounds 2d, 4a and 4e were found to possess spermicidal activity at 0.005% concentration, while compounds 2a, 2c, 2f, 3a and 4b were active at 0.01% concentration. Compounds 2a, 2c, 3a, 4a and 4e also inhibited the interaction between recombinant HIV Env and CD4. Out of these, compound 2c was found to be most active.     

Cardiovascular risk factors in an Iranian urban population: Tehran lipid and glucose study (phase 1)

OBJECTIVES: Coronary artery disease is becoming more prevalent in developing countries, particularly in urban areas. This study was conducted to determine the prevalence of cardiovascular risk factors among Tehran urban population. METHODS: The prevalence and distribution of high blood pressure, cigarette smoking, dyslipoproteinemia, diabetes mellitus, and obesity was determined in 15,005 subjects, aged three years and over, selected by cluster random sampling in Tehran urban district-13 between February 1999 to August 2001. Total energy intake, percent of energy derived from protein, carbohydrate, and fat were assessed in a subsidiary of 1,474 persons by means of two 24-hour dietary recalls. RESULTS: In adults, 78% of men and 80% of women presented at least one CVD risk factor. The percentage of adult women with two or more risk factors was significantly greater than the one for men. Prevalence of DM, hypertension, obesity, high TC, low HDL, high TGs, and smoking was 9.8, 20.4, 14.4, 19.3, 32, 5.3, and 22.3%, respectively. In children and adolescents, two or more CVD risk factors were found in 9% of boys and 7% of girls. Prevalence of hypertension, obesity, high TC, low HDL, and high TGs, was 12.7, 5.2, 5.1, 10.2, and 5%, respectively. The mean percentage values of energy intake derived from carbohydrate, protein, and fat were 57.8 +/- 6.9, 11.1 +/- 1.8, and 30.9 +/- 7.2, respectively. CONCLUSION: The prevalence of cardiovascular risk factors among Tehran urban population is high; particularly of high total cholesterol, low HDL cholesterol levels, and high waist to hip ratio. An effective strategy for life style modification is a cornerstone of a population approach to the cardiovascular risk factors. Moreover, these results will serve as a baseline for assessment of future trends in the risk factors studied.     

Assessment of growth inhibition and morphological changes in in vitro and in vivo hepatocellular carcinoma models post treatment with dl1520 adenovirus

BACKGROUND AND AIMS: E1B-deleted virus dl1520 (ONYX-015) has been previously used in clinical trials mainly for treatment of head and neck tumors, and has been shown to have beneficial effects independent of p53 status. The main aim of this investigation was to carry out a preclinical study for assessment of the use of dl1520 in in vitro and in vivo hepatocellular carcinoma (HCC) models with various p53 status (deleted, mutant, and wild type), and study the ultrastructural changes in the carcinoma cells during and following treatment with dl1520. METHODS: dl1520 (ONYX-015) virus was used for treatment of three HCC cell lines in culture, then for treatment of developed xenografts in SCID mice. The effects of dl1520 on HCC cell growth and accompanied morphological changes were assessed by various techniques including transmission electron microscopy. dl1520 infection was confirmed using polymerase chain reaction and immunolabeling at transmission electron microscopy level. RESULTS: dl1520 was effective in killing cells and inhibiting HCC cell growth both in vitro and in vivo. The cell killing was at higher levels in cells possessing abnormal p53. Survival rates in SCID mice treated with dl1520 were statistically significantly higher in HCC tumors with deleted and mutant p53, than in tumors with wild-type p53. CONCLUSIONS: The findings in this study suggest that dl1520 could be safely and effectively used for treatment of HCC dependent on the p53 status of the cells in vivo. Characteristic morphological changes that took place in the dl1520-treated HCC cells/tumors were distinct at transmission electron microscopy level and are the first of their kind to be reported.     

Adenovirus replication-competent vectors (KD1, KD3) complement the cytotoxicity and transgene expression from replication-defective vectors (Ad-GFP,Ad-Luc)

The successful clinical application of adenovirus (Ad) in cancer control has been of limited success because of the current inability to infect the majority of cancer cells with a large amount of vector. In this study, we show that when human lung tumors growing in immunodeficient nude mice were coinfected with a replication-defective (RD) Ad vector expressing green fluorescent protein and a replication-competent (RC) Ad vector named KD3, KD3 enhanced the expression of green fluorescent protein throughout the tumor. Also, KD3 and another RC vector named KD1 complemented the expression of luciferase from a RD vector in a human liver tumor xenotransplant in nude mice. Altogether, these results suggest that the combination of a RD vector with a RC vector might be a more effective treatment for cancer than either vector alone due to more widespread dissemination of the virus.