Esophageal abnormalities in patients with chest pain and normal coronary angiograms

AIMS: To evaluate the frequency and the variety of esophageal abnormalities in patients with chest pain and normal coronary angiograms. PATIENTS AND METHODS:: We have conducted a prospective study including patients with noncardiac chest pain based on normal coronary angiograms. We performed for all patients an upper gastrointestinal endoscopy, 24-hour esophageal pH monitoring and stationary esophageal manometry. RESULTS: Fifty patients were studied on a 3-year period (24 men and 26 women, mean age: 51.5 years). Gastroesophageal reflux disease was found on 24-hour esophageal pH monitoring in 29 patients (58%), associated with a good symptomatic correlation in 17 patients (34%). Esophageal motor disorders as nutcracker esophagus and diffuse esophageal spasm were found in 6 patients (12%) associated with gastroesophageal reflux disease in two cases. Independent factors associated with gastroesophageal reflux disease and esophageal motor disorders were respectively presence of regurgitations (p = 0.005 : adjusted OR[IC95%] : 3.57 [1.28 - 16.66]) and age higher than 58 years (p = 0.01 : adjusted OR[IC95%]: 2.77 [1.33 - 12.50]). CONCLUSIONS: Gastroesophageal reflux disease is the most common esophageal abnormality n; patients with noncardiac chest pain. In the absence of regurgitations, 24-hour esophageal pH monitoring must be the first test to be performed.     

Sensitization of human neutrophil defense activities through activation of platelet-activating factor receptors by ginkgolide B, a bioactive component of the Ginkgo biloba extract EGB 761

Ginkgolide B (GKB, BN 52021) was described as a platelet-activating factor (Paf) receptor antagonist. However, it is not known whether all GKB biological effects are mediated through Paf receptor antagonism only. To gain insight into the drug mode of action, we investigated here the effects of GKB per se on functional and signaling activities in human polymorphonuclear leukocytes (PMN). Treatment of PMN with GKB (0.5-12 microM) stimulates a rapid and weak production of reactive oxygen species determined by chemiluminescence. ROS production required the activation of protein kinase C (PKC), tyrosine kinases and p38 mitogen-activated protein kinase as indicated by inhibitory effects of, respectively, GF 109203X (IC(50) of 0.5 microM), genistein (IC(50) of 0.5 microM) and SB 203580 (IC(50) of 0.2 microM) or SB 202190 (IC(50) of 1.1 microM). GKB stimulated a Pertussis toxin-sensitive PLD activity assessed by the formation of tritiated phosphatidic acid and choline. By contrast, GKB did prevent the Paf-mediated PLD activity and CL response (IC(50) of 2 microM). Interestingly, both GKB and Paf-induced CL response were prevented by selective Paf antagonists such as CV 6209 or WEB 2086 indicating that GKB may directly activate Paf receptors. Finally, GKB potentiated the CL response induced by fMet-Leu-Phe and zymosan. These results show that GKB is the first partial agonist of the Paf receptor described so far capable of priming the polymorphonuclear leukocyte function.     

Highly active antiretroviral therapy does not affect mitochondrial beta-oxidation of fatty acids: an in vitro study in fibroblasts.

Preeclampsia is a multifactorial pregnancy-specific disease. In some cases, severe preeclampsia and related disorders of acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, low platelets syndrome are associated with inherited defects in mitochondrial beta-oxidation of fatty acids, especially a deficiency of long-chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD). Recently, an unexplained increase in the incidence of preeclampsia has been documented in human immunodeficiency virus (HIV)-infected pregnant women on treatment with highly active antiretroviral therapy (HAART). We performed this study to determine if antiretroviral drugs affect mitochondrial beta-oxidation fatty acids in vitro. Two normal and 1 heterozygous LCHAD-deficient cell lines were exposed to up to 5 times the therapeutic concentrations of the following antiretroviral drugs: nevirapine, didanosine, lamivudine, and a combination of nelfinavir, zidovudine, and lamivudine. One homozygous LCHAD-deficient cell line served as the positive control. After exposure of the fibroblasts to these drugs for periods ranging from 2 to 10 days, accumulations of even-chain 3-hydroxy fatty acids (3-OH-C6 to 3-OH-C18) in the culture media were measured by stable-isotope dilution gas chromatography/mass spectrometry. Compared to the respective unexposed fibroblasts, there was no significant build-up of 3-hydroxy fatty acids in the culture media of normal or heterozygous LCHAD-deficient fibroblasts exposed to antiretroviral drugs. Our results show that the commonly used antiretroviral drugs do not adversely affect fatty acid oxidation in fibroblasts. Therefore, an altered fatty acid oxidation may not be the mechanism for the reported increased risk of preeclampsia in HIV-infected pregnant women on HAART.     

Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia

BACKGROUND: Pre-eclampsia is one of the most serious and common complications of pregnancy. Nifedipine, a calcium channel blocker, and the vasodilator hydralazine have both been used as antihypertensive agents in this condition. The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre-eclampsia. METHODS: One hundred and twenty-six pre-eclamptic patients with a gestational age of more than 20 weeks were randomized to receive either 8 mg nifedipine sublingually or 5-10 mg intravenous hydralazine. Women with a history of heart failure and women receiving antihypertensive treatment during the course of the current pregnancy were excluded. For each patient the following data were recorded; the number of drug administrations, the time needed to control blood pressure, mean urinary output, the time interval between effective control and a new hypertensive crisis after each drug administration and relevant adverse effects in mother or fetus. RESULTS: Effective control of blood pressure was achieved in both treatment arms. Data analysis indicated significantly fewer drug administrations in the nifedipine arm of the study. The time interval before a new hypertensive crisis following initial effective control of blood pressure was significantly longer in the nifedipine group when compared with hydralazine. Effective control of blood pressure was achieved more rapidly in multiparous patients receiving nifedipine (p=0.026). Mean urinary output before and after delivery was greater in the nifedipine arm of the study. There were no significant differences between the two groups in other variables. In addition, in neither group were there any serious adverse effects in mother or fetus. CONCLUSION: Nifedipine is safe and more effective than hydralazine in controlling blood pressure in severe pre-eclampsia. It has the added advantage of being cheaper and more widely available than the latter and is easily administered.     

Corticotherapy for asthma in the child

Corticosteriods have a puissant anti-inflammatory action and enjoyment a central role in the treatment for childhood asthma. Systemic steroids are used in resistant bronchodilatator exacerbations of asthma. Usually steroids are given for short courses, rarely for long term in severe asthma with high risk of side-effects. Inhaled corticosteroids have'nt changed the treatment for childhood asthma and are recommanded in persistent asthma. Inhaled steroids are well tolerant even at high doses, but it must always research the minimal effective dose. The aim of steroid's treatment is controlling asthma with minimal side-effects to give a normal life to the asthmatic children.     

Mortality in cirrhosis: prevalence,causes, and predictive factors

To determine the global mortality rate during cirrhosis, to point out its principal causes and to look for factors associated with a higher death risk in cirrhotic patients. We carried out a retrospective study on patients hospitalized for cirrhosis during a seven-year period. We indicated the number of deceased patients, as well as the cause and the time interval for death. Age, sex, Child's score, etiology and the state of the cirrhosis were considered in a univariate and a multivariate analysis to look for mortality predictive factors. 109 patients (49 males, 60 females) of average age 57 years (15-87) were studied. The average follow-up interval was 30 months (1-96). The global mortality rate was 24%, with a five-year survival rate of 66%. In univariate analysis, mortality was more frequent in the following cases: presence of an initial complication (p < 0.001), Child C cirrhosis (p = 0.02) and post-hepatitic B cirrhosis (p = 0.004). In multivariate analysis, only B viral etiology (five-year survival rate of 48%, p = 0.002) and the existence of an initial complication (five-year survival rate of 30%, p < 0.001) were independently associated with a higher mortality risk. Our study showed that cirrhosis is associated with an important mortality. Our results confirm the poor prognosis of a cirrhosis revealed by an inaugural complication and suggests that post-hepatitic B cirrhosis is more severe than post-hepatitic C cirrhosis.     

Reduced kallikrein excretion by liposome-encapsulated cyclosporin in the rat

Abstract— Different phospholipids and methods of preparation were used to produce cyclosporin encapsulated in liposomes. The optimal formulation of cyclosporin-liposome was compared to the oily cyclosporin after intraperitoneal administration of 25 mg kg^?1 body weight to rats. Urinary kallikrein excretion was significantly reduced with the liposomal form. The abrupt increase of kallikrein excretion after the tenth day with the control oil preparation suggests that cyclosporin toxicity could be present at the tubular level, and the encapsulation of cyclosporin in liposomes reduces tubular damage.     

Current issues in the management of advanced squamous cell carcinoma of the penis

Effective treatment of penile carcinoma incorporates three modalities: surgery, radiation and chemotherapy. Surgery alone may offer a high cure rate in early stages of the disease. In certain patients radiation therapy may be utilized to eradicate the tumor and allow organ preservation. For patients with locally advanced disease, multi-modality approaches incorporating adjuvant or neoadjuvant chemotherapy and radiation therapy need to be studied. This approach may confer a survival benefit to a group that would otherwise have a poor prognosis. Finally, in the setting of metastatic disease, less toxic and more effective combination chemotherapy are sought. Novel targeted therapies that have been successful in squamous cell carcinoma at other sites must also be studied in this disease. We believe that multi-institutional trials should be designed in order to obtain prospective benchmark data from which to make valid comparisons of outcome.     

Serology: recent developments, strengths, limitations and prospects: a state of the art overview

Specific antibodies can be used as a surrogate marker for bacterial load in leprosy. Tests to detect antibodies can be used for (i) the classification of patients for treatment purposes [most multibacillary (MB) patients are seropositive, most paucibacillary (PB) patients are not], (ii) the prediction of an increased risk of relapse and (iii) the identification of contacts having an increased risk of developing leprosy. With the advent of fast, robust and easy to perform serological tests such as lateral flow, agglutination and card tests, the application of serology in the field for these purposes becomes a feasible prospect. We hereby present an overview of the current knowledge and new developments in this area and discuss the strengths, limitations and possible applications of antibody detection in leprosy research and control.