Controlled-release codeine is equivalent to acetaminophen plus codeine for post-cholecystectomy analgesia

PURPOSE: Following ambulatory surgery, long-acting analgesics may provide advantages over short-acting analgesics. This study compared controlled-release codeine (CC) and acetaminophen plus codeine (A/C; 300 mg/30 mg) for pain control in the 48-hr period following laparoscopic cholecystectomy. METHODS: Eligible patients were randomized to CC or A/C in a double-blind, double-dummy parallel group study. Unrelieved pain in hospital was treated with fentanyl i.v. bolus. Pain [100 mm visual analogue scale (VAS)] was assessed before the first dose of medication; at 0.5, one, two, three, and four hours post-dose; at discharge; and three times a day for 48 hr. Adverse events were recorded and measures of patient satisfaction were assessed at the end of the study. RESULTS: Eighty-four patients were enrolled in the study; 42 patients in each group. There were no statistically significant differences between CC and A/C treatment. Mean VAS baseline pain was similar in both groups (P = 0.49) and there was no significant difference in the time to onset of analgesia (P = 0.17). At 0.5 hr, the mean VAS pain score was significantly reduced from baseline in both groups (P = 0.0001). The VAS pain scores at discharge were reduced 59% and 56% from baseline, respectively (P = 0.61). There was no difference between treatments in the incidence of adverse events and patients reported similar levels of satisfaction. CONCLUSIONS: Controlled-release codeine provides an equivalent onset of analgesia, reduction in postoperative pain, and level of patient satisfaction, to acetaminophen plus codeine, over 48 hr following cholecystectomy, with the advantage of less frequent dosing.     

In vivo and in vitro models demonstrate a role for caveolin-1 in the pathogenesis of ischaemic acute renal failure

Caveolae and their proteins, the caveolins, transport macromolecules; compartmentalize signalling molecules; and are involved in various repair processes. There is little information regarding their role in the pathogenesis of significant renal syndromes such as acute renal failure (ARF). In this study, an in vivo rat model of 30 min bilateral renal ischaemia followed by reperfusion times from 4 h to 1 week was used to map the temporal and spatial association between caveolin-1 and tubular epithelial damage (desquamation, apoptosis, necrosis). An in vitro model of ischaemic ARF was also studied, where cultured renal tubular epithelial cells or arterial endothelial cells were subjected to injury initiators modelled on ischaemia-reperfusion (hypoxia, serum deprivation, free radical damage or hypoxia-hyperoxia). Expression of caveolin proteins was investigated using immunohistochemistry, immunoelectron microscopy, and immunoblots of whole cell, membrane or cytosol protein extracts. In vivo, healthy kidney had abundant caveolin-1 in vascular endothelial cells and also some expression in membrane surfaces of distal tubular epithelium. In the kidneys of ARF animals, punctate cytoplasmic localization of caveolin-1 was identified, with high intensity expression in injured proximal tubules that were losing basement membrane adhesion or were apoptotic, 24 h to 4 days after ischaemia-reperfusion. Western immunoblots indicated a marked increase in caveolin-1 expression in the cortex where some proximal tubular injury was located. In vitro, the main treatment-induced change in both cell types was translocation of caveolin-1 from the original plasma membrane site into membrane-associated sites in the cytoplasm. Overall, expression levels did not alter for whole cell extracts and the protein remained membrane-bound, as indicated by cell fractionation analyses. Caveolin-1 was also found to localize intensely within apoptotic cells. The results are indicative of a role for caveolin-1 in ARF-induced renal injury. Whether it functions for cell repair or death remains to be elucidated.     

The occurrence of Chlamydia trachomatis in the semen of men participating in an IVF programme

Chlamydia trachomatis is one of the most common causative agentsof sexually transmitted diseases. The authors studied the occurrenceof C.trachomatis in the semen of 184 asymptomatic men participatingin the IVF programme. Twenty-six (14.1%) of the 184 tested werepositive for C.trachomatis, these patients and their wives receivingdoxycycline capsules twice, 100 mg on the first day and 100mg/day for the following 13 days. This treatment was effectivein 88.5% of the cases and in the rest, treatment continued witherithromycin 250 mg four times/day for 2 weeks. The authorscompared the semen parameters (cell count, motility, morphology,bovine mucus penetration and hypo-osmotic swelling test) inthe infected and non-infected groups and observed no significantdifference between these two groups     

Identification of histiocytic reticulum cells by the immunohistochemical demonstration of factor XIII (F-XIIIa) in human lymph nodes

Morphologically and enzyme histochemically distinguishable tissue macrophages and stromal cells of human reactive lymph nodes were characterized by the cytoplasmic presence of the subunit A of factor XIII and by the expression of surface antigenic determinants reacting with monoclonal antibodies directed against monocyte/macrophage populations (Mo 1, Leu M3) and HLA-DR antigens. The distribution of F-XIIIa positive cells was studied on formaldehyde-fixed paraffin-embedded sections with immunoperoxidase techniques. established on cryostat section with double immunofluorescence. Alpha-Naphthyl acetate esterase (ANAE) reaction was The immunophenotype was established on cryostat sections with double immunofluorescence. Alpha-Naphthyl acetate esterase (ANAE) reaction was carried out on these cryostat sections to identify tissue macrophages. The antibody against F-XIIIa detected histiocytes in both intra- and extra-sinusoidal locations which were ANAE+, Mo 1+, Leu M3+ and HLA-DR-. F-XIIIa was also present in fibroblast-like mesenchymal cells with the following phenotypic characteristics: ANAE-, Mo 1+, Leu M3+ and HLA-DR+. The anti F-XIIIa antibody did not stain lymphoid cells, granulocytes, epithelial cells, endothelial cells and mast cells. The immunohistochemical detection of F-XIIIa works on formaldehyde-fixed paraffin-embedded sections. The most promising application seems to be the identification of histiocytes in lymphoid and histiocytic proliferations.     

Gender, suicidality and bipolar mixed states in adolescents

BACKGROUND: The purpose of this study was to determine the relationship between mixed states and suicidality among adolescent outpatients presenting with a DSM-IV defined major depressive episode (MDE). METHODS: Two-hundred and forty-seven adolescents meeting the criteria for MDE were screened for the presence of concurrent, intra-MDE hypomania/mania (i.e., mixed states). All patients were asked whether they had current suicidal ideation or had recently attempted any self-destructive physical act associated with the thought of dying (i.e., a suicide attempt). The data were subjected to analysis using univariate logistic regression. RESULTS: One hundred of the 247 (40.5%) adolescents were bipolar type I or type II. Of these, 82% were in mixed states. Of the patients with suicidal ideation, 62.8% were girls, and of those with histories of a suicide attempt, 69.4% were girls. Girls had more than twice the risk of having suicidal ideation (OR=2.2, p=0.004) and nearly 3 times the risk of having histories of a suicide attempt than boys (OR=2.87, p<0.0001). Being in a mixed state per se did not predict either suicidal ideation or a suicide attempt among all of the 247 patients. However, mixed states apparently independently contributed to the risk of (non-fatal) suicidal behavior among girls only. Of the mixed states, girls had nearly 4 times the risk of having made a suicide attempt compared with those without mixed states (OR=3.9, p=0.003). Age, presence of psychotic features and family history of mood disorder had little or no bearing on suicidality. LIMITATIONS: Correlational chart review study, no data collection on Axis I and Axis II comorbidity and adverse life-events. CONCLUSIONS: This report of greater suicidality in adolescent girls in a mixed state parallels the well-known adult literature of high frequency of mixed states in women. The findings are of relevance to the controversy of antidepressants and suicidality in juvenile depressives in that they identify a vulnerable group. In line with earlier suggestions by the senior author [Akiskal, H.S., 1995. Developmental pathways to bipolarity: are juvenile-onset depressions pre-bipolar? J. Am. Acad. Child Adolesc. Psych. 34, 754-763], our data highlight the public health importance of the wider recognition of bipolar mixed states in juvenile patients masquerading as unipolar depression. Finally, it appears to us that it is the failure of our formal nosology on mixed states--rather than the antidepressants per se--which is the root problem in this controversy.     

Study of the renin-angiotensin system in essential hypertension

320 patients with essential hypertension divided into three groups (minor, medium and major severty) were studied against 50 normal controls. Plasma renin activity (PRA) was estimated in case of normal and low Na intake, furthermore, of low Na intake in association with administration of chlorothiazide, in the recumbent position as well as at the end of 4-hr walk. The hypertensive group of medium severity (Group II) revealed a significant decrease in PRA, compared with the controls and with the hypertensive group of minor severity (Group I), in each period of observation. A significant increase of PRA in response to insulin hypoglycaemia was demonstrable in all three groups and in the controls, but the increase was of significantly lesser degree in Group II than either in the controls or in Group I. The plasma catecholamine concentrations were found lower in Group II than in the controls and in Group I. An elevation of the plasma catecholamine levels was demonstrable in response to insulin hypeglycaemia, but it was of lesser degree in Group II than a Group I and in the controls. The poor responsiveness of the RAS in Group II is attributed to an inadequate adrenergic activity and to an increased mean arterial pressure in that group, but the higher age of patients and longer duration of hypertensive disease, both characteristic of the group of medium severity, may also effect the renin-angiotensin system.     

The gastric mucosal barrier: tight junction structure in gastritis and ulcer biopsies

Summary Tight junctions of the human gastric mucosa were examined using quantative freeze-fracture methods. Biopsies examined were from patients with gastric diseases including gastritis, ulcers, and pernicious anemia. No significant differences were seen in strand number or tight junction complex depth among the biopsies analyzed, however, anomalous tight junction structures were observed. Discontinuities in the tight junction complex and hyperplastic tight junctions (extensions of the apical tight junction strands radiating over the lateral plasma membrane) were seen. These alterations were not associated exclusively with either the diagnosis of gastritis or ulcers. However, a higher frequency of tight junction breaks was seen in stomach biopsies diagnosed as gastritis while those diagnosed as ulcers displayed a higher occurrence of hyperplastic tight junctions.     

Mechanisms of the inhibition of Shaker potassium channels by protons

Potassium channels are regulated by protons in various ways and, in most cases, acidification results in potassium current reduction. To elucidate the mechanisms of proton-channel interactions we investigated N-terminally truncated Shaker potassium channels (K_v1 channels) expressed in Xenopus oocytes, varying pH at the intracellular and the extracellular face of the membrane. Intracellular acidification resulted in rapid and reversible channel block. The block was half-maximal at pH 6.48, thus even physiological excursions of intracellular pH will have an impact on K⁺ current. The block displayed only very weak voltage dependence and C-type inactivation and activation were not affected. Extracellular acidification (up to pH 4) did not block the channel, indicating that protons are effectively excluded from the selectivity filter. Channel current, however, was reduced greatly due to marked acceleration of C-type inactivation at low pH. In contrast, inactivation was not affected in the T449V mutant channel, in which C-type inactivation is impaired. The pH effect on inactivation of the wild-type channel had an apparent pK of 4.7, suggesting that protonation of extracellular acidic residues in Kv channels makes them subject to pH regulation.     

Surgical treatment of renovascular hypertension

Unilateral stenosis of the renal artery was verified by angiography in 34 patients with hypertension. The cause-effect relationship between elevated blood pressure and stenosis of the renal artery was proved by detailed renin studies (basic plasma renin activity, plasma renin activity following orthostatic and diuretic stimulation, renal vein renin activity). Surgical treatment was applied in 39 cases: they were aortorenal bypass in 9, autotransplantation in 7, patch graft in 2, denervation in 2, decompression in 3 and nephrectomy in 16 cases. Six months following the operation, 68.4% of the patients were normotensive without drugs and 18.4% of them with a reduced dose of drugs. To achieve normotension preoperative treatment had to be continued only in 13.2% of the patients. Two to four years postoperatively, 29 patients were subjected to control examinations and in 23 cases also to angiography. Restenosis was observed in 4 patients (17.4%). As a result of surgical treatment, the increased response to hyperreninaemia and to various stimuli decreased. Based on the control examinations, 58.7% of the patients could be considered to be cured.