Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release

The involvement of metabolites of arachidonic acid in platelet-dense granule secretion and secondary platelet-platelet interactions is well characterized. However, their role in heterotypic interactions dependent on alpha-granule secretion is less well understood. Using platelet-surface expression of P-selectin as a marker of alpha-granule secretion, we have shown that: (1) aspirin treatment of platelets at doses that block dense granule secretion does not inhibit alpha-granule secretion to adenosine diphosphate (ADP); (2) synergism between epinephrine and ADP in the induction of P-selectin expression is similarly unaffected by aspirin; and (3) the ability of P-selectin to mediate adhesion of activated platelets to monocytes and polymorphonuclear lymphocytes in whole blood is also unchanged by aspirin treatment. To further explore the mechanisms responsible for platelet alpha-granule secretion, we have shown that inhibition of Na+/H+ exchange by either acidification of the extracellular medium or amiloride treatment blocked ADP-induced P-selectin expression. In contrast, incubation with the platelet lipoxygenase inhibitor 5,8,11- eicosatrynoic acid, by itself and with aspirin, did not decrease ADP- induced P-selectin expression. We conclude that platelet alpha-granule secretion in response to ADP is dependent on intact Na+/H+ exchange but is independent of the lipoxygenase- and cyclooxygenase-dependent metabolites of arachidonic acid.     

Expression of apoptosis regulatory proteins p53 and Bcl-2 in skin of patients with chronic renal failure on maintenance haemodialysis

BACKGROUND: Chronic renal failure results in multi-organ system derangement including cardiovascular, gastrointestinal, neurological, endocrinal, blood and dermatological abnormalities. Maintenance of skin homeostasis requires a delicate balance between proliferation, differentiation and apoptosis. p53 and Bcl-2 proteins play a central role in the regulation of apoptosis. OBJECTIVE: Evaluation of the expression of apoptosis regulatory proteins p53 and Bcl-2 in apparently normal skin of patients, with chronic renal failure on maintenance haemodialysis, with respect to their role in the apoptotic process. METHODS: Biopsy specimens were obtained from 10 patients with chronic renal failure on maintenance haemodialysis, as well as seven age-matched control subjects. Computer-assisted image analysis was employed to measure epidermal thickness in H&E-stained sections. Immunoperoxidase technique was also used to demonstrate p53 and Bcl-2 proteins and the TUNEL technique for detection of apoptotic cells in these specimens. RESULTS: The mean epidermal thickness was significantly higher (P < 0.0001) in patients than controls. Meanwhile, no apoptotic cells were detected in the epidermis of patients. On the other hand, a statistically significant difference was observed in both p53 (P = 0.0001) and Bcl-2 expression (P = 0.0003) when comparing patients and controls. Expression of p53 (2.74 +/- 0.84) and Bcl-2 (3.45 +/- 1.35) proteins was higher in skin samples obtained from patients with chronic renal failure and on maintenance haemodialysis than those from control cases (0.5 +/- 0.96 and 0.8 +/- 0.6, respectively). Moreover, Bcl-2 expression in patients was observed in basal as well as squamous cell layers of skin, whereas in control subjects it was confined to the basal cell layer only. CONCLUSION: These findings suggest that an alteration in the proliferation/apoptosis balance may be present in the skin of such patients.     

Patient controlled analgesia (PCA) in paediatric surgery: a prospective study following laparoscopic and open appendicectomy

Patient controlled analgesia (PCA) has not yet gained universal acceptance for the management of postoperative pain in paediatric surgery. In a prospective study we evaluated feasibility and complications of PCA following 90 cases of laparoscopic or open appendicectomy. PCA proved to be a safe and feasible method with few complications (2% of medical complications, no abort of application, 17 technical checks in a total running time of 4125 h). Acceptance by patients was high and children of all age groups worked the system properly. Assessment of application protocols showed, that the consumption of analgesics was significantly reduced following laparoscopic appendicectomy (P < 0.05). PCA is a safe and feasible method for the management of postoperative pain in children and PCA recording provides an excellent insight into the consumptional behaviour of patients, enabling staff to evaluate postoperative pain for various procedures.     

Effect of intravenous hydrocortisone on nocturnal airflow limitation in childhood asthma.

Low endogenous cortisol levels appear to contribute to the pathophysiology of nocturnal asthma. Lower cortisol levels are associated with lower forced expiratory volume in one second (FEV1) levels in children with asthma. The aim of the present study was to identify whether substitution of low serum cortisol with intravenous hydrocortisone decreases 24-h FEV1 variation and/or indirect measures of airway inflammation. Hydrocortisone was given over 24 h in a double-blind randomised crossover design to 26 subjects. FEV1 was measured every 4 h during 24 h; blood eosinophils and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured at 04:00 h and 16:00 h. Cortisol levels increased during the night and morning hours. FEV1 values were higher at all time points in children with nocturnal asthma (n=10; 24-h FEV1 variation > or = 15%) which was significant at 08:00 h, unlike in the non-nocturnal asthma (NA-) group (n=16). Numbers of eosinophils (10(9) x L(-1)) at 04:00 h decreased in the asthma group (median 0.61 (range 0.05-1.42) versus 0.52 (0.05-1.79)). Provocative dose causing a 20% fall in FEV1 (PD20) methacholine did not change, whereas PD20 AMP improved only at 16:00 h in the NA- group (72.0 (0.13-144.0) versus 144.0 (2.25-144.0) mg x mL(-1)). These results show that substitution of lower endogenous 24-h values of cortisol contribute to higher forced expiratory volume in one second values and a decrease of blood eosinophils as an inflammatory marker in more severe airway obstruction.     

The neuroendocrine challenge paradigm in headache research

The neuroendocrine challenge paradigm provides a "window" on central neurotransmitter function in vivo. This strategy is based on the premise that the sensitivity of certain central receptors can be inferred from the magnitude of the hormonal response to specific pharmacologic probes. For example, the serotonin (5HT) receptor agonist m-chlorophenylpiperazine (m-CPP) stimulates the release of cortisol and prolactin and induces migraine-like headaches. We have previously reported that the headache and cortisol responses to m-CPP are highly correlated, which may implicate a disturbance in central serotonergic neurotransmission in the pathogenesis of migraine. As pharmacologic probes with greater specificity for 5HT receptor subtypes become available, we may be able to elucidate these mechanisms with greater precision. The neuroendocrine challenge methodology is also applicable to the study of other neurotransmitter systems and other headache disorders.     

Spinning top urethra: not a normal variant

Spinning top urethra (STU) is a term used to describe a widened posterior urethra seen mainly in girls. It is commonly regarded as a normal variant. The authors studied 30 girls with STU using videourodynamics. Twenty-eight showed bladder instability; 21, a congenital wide bladder neck anomaly; and 20, both instability and a wide bladder neck. One patient had a sensitive bladder. All patients had a urodynamic abnormality. The authors believe that the STU is nearly always an indication of bladder instability or wide bladder neck anomaly. The most common mechanism for the dilatation of the posterior urethra is that unstable contractions are resisted by a voluntary increase in distal sphincter tension so as to prevent leakage of urine. The resulting pressure rise produces distention of the posterior urethra, which will be maximal in subjects with a weak bladder neck mechanism as in the congenital wide bladder neck anomaly. The authors believe that STU is seldom if ever a normal variant.