Effects of intranasal 17beta-estradiol and raloxifene on lipid profile and fibrinogen in hypercholesterolemic postmenopausal women: a randomized, placebo-controlled clinical trial.

AIM: To compare the effects of 17beta-estradiol given intranasally (intranasal E2) and raloxifene on serum lipid profile and fibrinogen in hypercholesterolemic postmenopausal women. METHODS: The study population consisted of 46 women after menopause. The placebo group (n = 11) was given calcium, while the intervention groups were given intranasal E2 (Aerodiol; Servier, Chambray-les-Tours, France) (n = 16) or raloxifene (Evista; Lilly SA, Madrid, Spain) (n = 19). Blood lipids and fibrinogen were compared between groups at baseline and after 3 months of treatment. RESULTS: The group receiving intranasal E2 showed a significant decrease in triglyceride levels (p<0.05) and a marked increase in high-density lipoprotein cholesterol levels (p<0.05). No changes in lipid profile were observed in the raloxifene and placebo groups. Raloxifene caused a significant decrease in fibrinogen levels (p<0.05). CONCLUSION: Intranasal E2 exerts significant effects on lipid profile in hypercholesterolemic postmenopausal women. Raloxifene has a greater impact on fibrinogen than intranasal E2 application.     

N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

Neuropeptides in idiopathic chronic constipation (slow transit constipation)

Tissue specimens from the large bowel of 18 patients with long-standing slow transit constipation were investigated to determine the distribution and density of several neuropeptides and amines in the enteric nerve system, and also of endocrine cells in comparison to normal individuals. CGRP (calcitonin gene-related peptide), galanin, glucagon, GRP (gastrin-releasing peptide), metenkephalin, motilin, neuropeptide Y (NPY), PACAP, peptide YY (PYY), serotonin, somatostatin, substance P and VIP were studied by immunohistochemistry. Tissue concentrations of VIP, substance P and galanin were also measured by radioimmunoassay. Significantly increased VIP, SP and galanin contents were found in specimens from the ascending colon. Levels of VIP and galanin were also increased in the transverse colon. Immunohistochemistry revealed only marginal changes with an increased density of PACAP nerve fibres in the smooth muscle and of VIP and PACAP nerves in the myenteric plexus of the transverse colon. In the descending colon substance P and NPY immunoreactivity were also increased in the myenteric plexus while the density of VIP nerve fibres was reduced in the mucosa/submucosa. The frequency of PYY-containing cells and the 5-HT-containing cells in the ascending colon was significantly increased in the constipated patients.     

How to assess fetal metabolic acidosis from cord samples.

The degree of metabolic acidosis at birth has been calculated in cord artery and vein samples from 21 term fetuses with cord artery pH less than 7.20. The aim of the study was to compare base deficit values calculated from either Siggaard-Andersen alignment nomogram (BD blood) or the Acid-Base chart (BD extra cellular fluid, BDecf). BDblood was found to be consistently higher in the cord artery as compared with BDecf, 13.2 +/- 3.5 and 9.9 +/- 2.9 mmol/l (Mean +/- SD), respectively. A significant correlation was found between cord artery PCO2 and BDblood whereas BDecf appeared unaffected by PCO2. In cases with cord entanglement BDecf a-v differences were increased to 3.4 +/- 2.3 mmol/l as compared with the small a-v difference noted in acidotic cases without cord entanglement, 1.1 +/- 1.25 mmol/l. It is speculated that with acutely emerging, intermittent asphyxia due to cord compression, a cord artery and vein difference in metabolic acidosis may exist and where the vein captures the basal level and the artery the acute changes. It is concluded that BDecf in both cord artery and vein add valuable information on the mechanisms behind metabolic acidosis.     

Stoma Adjustable Silicone Gastric Banding versus Vertical Banded Gastroplasty for the Treatment of Morbid Obesity

Background: Among gastric restrictive operations, the procedure of choice is still controversial. The aim of this study is to compare the results of two different gastric restrictive procedures: vertical banded gastroplasty (VBG) and stoma adjustable silicone gastric banding (ASGB). Methods: Between 1991 and 1996, 51 patients were treated surgically for morbid obesity: 27 underwent VBG and 24 underwent ASGB. Preoperative body weight (BW), body mass index (BMI) and percentage of ideal body weight (% IBW) were (mean ± SD): 145.7 ± 45.3 kg; 53.9 ± 15.9 kg/m²; 249.1 ± 73.5% respectively in the VBG group. Corresponding figures for the ASBG group were 132.5 ± 22.7 kg; 46.9 ± 7.8 kg/m² and 207.2 ± 35.0%. Results: In the VBG group, the median follow-up period was 26 months (range: 7-47). Eighteen months after the operation BW, BMI, % IBW and percentage of excess weight loss (% EWL) were 85.5 ± 26.8 kg, 31.9 ± 9.8 kg/m², 145.4 ± 43.9% and 74 ± 1% respectively. Complications included incisional hernia (n = 1), and bowel obstruction (n = 1). One patient died of acute myocardial infarction on the third postoperative day. In the ASGB group, median follow-up time was 19.7 months (range: 18-26). At 18 months postoperation BW, BMI, % IBW and % EWL values were 86.6 ± 20.6 kg 30.6 ± 6.6 kg/m2 140.6 ± 29.3% and 64 ± 1% respectively. Gastric wall erosion occurred in two patients and the bands had to be removed. These patients underwent VBG 6 months later. Complications encountered in this group were incisional hernia (n = 1), outlet stenosis and reflux esophagitis (n = 1), reservoir leakage (n = 1) and gastrointestinal bleeding (n = 1). Two patients died of pulmonary embolism and acute gastrointestinal bleeding. Conclusions: Weight reduction was not statistically significant between the two groups. ASGB was easier to perform and less invasive than VBG.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.     

Effect of venom from Cerastes cerastes (Egyptian sand viper) on luminol-dependent chemiluminescence of human blood phagocyte cells

Cerastes cerastes venom added in vitro to human whole blood caused a marked inhibitory effect on the luminol-dependent chemiluminescence induced by phorbol myristate acetate (PMA) or opsonized zymosan on phagocyte cells. The inhibitory effect produced by the venom was both dose- and time-dependent when PMA was used as the stimulant of the oxidative burst. Similarly, the venom produced a significant inhibitory effect when added to isolated polymorphonuclear leukocytes (PMNs). Incubation of the isolated PMNs with the highest concentration of the venom used (1000 micrograms/ml), however, did not result in any significant disruption of the membranes of these cells. The effect of the venom on the isolated PMNs was also reversible following washing of the venom-treated cells with phosphate-buffered saline. The scavenger of reactive oxygen species such as superoxide dismutase, catalase and dimethyl sulphoxide potentiated the effect of the venom on the luminol-dependent chemiluminescence of human phagocyte cells. Sodium azide, the myeloperoxidase inhibitor, and sodium benzoate produced a similar potentiating effect. The results suggest that some of the toxicity of the venom may be mediated by an action on the phagocytic immune system.