COMPLEMENT C4 NULL ALLELES AS A MARKER OF GOLD OR D-PENICILLAMINE TOXICITY IN THE TREATMENT OF RHEUMATOID ARTHRITIS

C4 null alleles and HLA-DR antigens were defined in 48 rheumatoidarthritis (RA) subjects who had developed renal or haematologicalside effects to gold or penicillamine, as compared to 33 RAsubjects who had received the drugs for similar time periodswithout developing side effects. A C4A null allele was foundin 56% of subjects with and 31% of those with out side effects(P = 0.027, relative risk 2.8). A similar but statisticallynon-significant trend was observed with the C4B null allele(P = 0.64) resulting in a higher risk of drug toxicity in rheumatoidpatients bearing either a C4A or C4B null allele (relative risk5.7). Frequencies of DR3 and DR4 were similar in the two groups. KEY WORDS: HLA, Complement C4     

Expression of BCL-2 in the developing human fetal and infant breast

The expression of BCL-2 protein was analysed in 10 fetal and 45 infant breast specimens by immunocytochemical staining of methacarn-fixed, paraffin-embedded tissue. In the developing fetal breast bud, BCL-2 was expressed in the basal cell layer and in the surrounding mesenchyme. Basal cells of epithelial buds destined to become hair follicles also expressed BCL-2 while the basal cell layer of the epidermis was negative. In infant breasts studied (aged 0–2 years), there was heterogeneous staining of the luminal epithelial cells of the ducts and lobules and no staining of myoepithelial cells or fibroblasts. The intensity of staining had a strong positive correlation with the age of the infant. Although the function of the bcl -2 gene in epithelial cells is unknown, these findings suggest that bcl -2 has a role in the morphogenesis of the human breast, and may help to sustain active epithelial-mesenchymal interaction by inducing longevity of certain cells.     

HLA ASSOCIATIONS IN SUBJECTS WITH RHEUMATOID ARTHRITIS AND BRONCHIECTASIS BUT NOT WITH OTHER PULMONARY COMPLICATIONS OF RHEUMATOID DISEASE

We have examined HLA-DR, DQA and DQB variants in 72 controls,153 subjects with RA without extra-articular features and insubjects with the rheumatoid pulmonary complications of interstitialfibrosis (23) peripheral airways disease (13) and in 41 subjectswith RA and bronchiectasis. Subjects with RA alone showed theexpected association with HLA-DR4 (79%) but those with RA andco-existent pulmonary fibrosis were less likely to be DR4 positive(61%). No other HLA-DR variants were significantly increasedin the different disease groups. HLA which types serologicallyas DQw1 was increased in subjects with RA and peripheral airwaysdisease as compared to rheumatoid subjects with normal lungfunction, but these differences were not statistically significant.DQBI*0601 was increased in subjects with bronchiectasis withor without RA (but only significantly so in RA-BR subjects)DQBI*0301, DQBI*020l and DQAI*0501 frequencies were also increasedin subjects with RA and bronchiectasis as compared to thosewith RA alone. KEY WORDS: Rheumatoid arthritis, Pulmonary fibrosis, Obstructive airways disease, Bronchiectasis, HLA-DR, HLA-DQ, HLA-Dw, C4     

HYPOFIBRINOGENEMIA DUE TO INCREASED FIBRINOLYSIS IN TWO PATIENTS WITH ACUTE PROMYELOCYTIC LEUKEMIA

Two patients with acute promyelocytic leukemia and severe bleeding associated with hypofibrinogenemia were studied. The markedly shortened whole blood clot lysis time and dilute clot lysis time suggested that the defect was an increase in fibrinolysis. Although disseminated intravascular coagulation could not be totally excluded as an alternative mechanism, excessive fibrinolysis was confirmed as the pathogenic cause by the prompt response to the administration of tranexamic acid. The low circulating plasminogen, α₂ plasmin inhibitor level and the presence of α₂ plasmin inhibitor-protease complex in both patients suggested that the increased fibrinolysis probably resulted from the liberation of plasminogen activator from the promyelocyte.     

Acute effects of atrial natriuretic peptide on left ventricular diastolic function: A pulsed wave Doppler study in man

Doppler echocardiographic indices of diastolic function andsystemic haemodynamics were studied in response to infusionsof atrial natriuretic peptide (0.5, 1, 2, 5 pmol.kg^–1.min^–1)and placebo (0.9%(w/v) saline) in ten normal male subjects.Compared with placebo, atrial natriuretic peptide infusion produceda significant and dose-related reduction in the isovolumic relaxationtime [(mean and 95% CI) –5.9 (–9.2 To –2.6)ms (P<0.01) at 5pg. kg^–1 min^–1 and a significantincrease in the ratio between early and late transmitral peakvelocities [0.46 (0.02 to 0.89) (P<0.05) at 5 pg. kg^–1min^–1]. No significant changes in heart rate, blood pressureor aortic stroke distance were observed with infusion of atrialnatriuretic peptide compared with placebo. These data suggestthat pathophyisological plasma concentrations of atrial natriureticpeptide improve diastolic function by increasing the rate ofmyocardial relaxation.     

Dexmedetomidine: perioperative applications in children

Dexmedetomidine is a highly specific and selective alpha‐2‐adrenergic agonist with sedative, anxiolytic, and organ protective effects. Its clinical applications in children include premedication, prevention of emergence delirium, as part of multimodal anesthetic regimen and sedation in the pediatric intensive care unit. Its role in neuroprotection in children undergoing anesthesia should be explored. In this review, various uses of dexmedetomidine are discussed in detail.     

Linked electronic medication systems in community pharmacies for preventing pseudoephedrine diversion: A review of international practice and analysis of results in Australia

Introduction and Aims. Pseudoephedrine is a precursor often diverted into the illegal manufacture of amphetamine type substances (ATS). The aim of this study was to evaluate the effectiveness of a linked electronic medication recording system (LEMS) established in Australian pharmacies in 2005 for preventing the diversion of pseudoephedrine. Design and Methods. The number of illegal ATS laboratories detected in each jurisdiction of Australia from 1996–1997 to 2004–2005 were analysed by linear regression nationally and by each jurisdiction. The statistical significance of seizures in 2005–2006 was based on the comparison of the observed value to the 95% prediction confidence intervals calculated from the historical data for each jurisdiction and nationally. Results. Pharmacies in Queensland commenced an LEMS in late 2005 to minimise retail pseudoephedrine diversion. The number of ATS laboratories seized in 2005–2006 in Queensland was significantly lower (P < 0.05) than predicted by historical data. For all other jurisdictions and nationally the totals of laboratories seized in 2005–2006 were not significantly different from predicted values. Discussion and Conclusions. The significant decline in ATS illegal laboratories seized in Queensland in 2005–2006 suggests the effective use of LEMS in pharmacies to minimise pseudoephedrine diversion. In order to evaluate a national LEMS, more frequent data on numbers of linked pharmacies, ATS laboratories seized and indicators of pseudoephedrine sales and misuse are required. Testing the use of LEMS by pharmacies for preventing the diversion of other medicines seems appropriate.[Berbatis CG, Sunderland VB, Dhaliwal SS. Linked electronic medication systems in community pharmacies for preventing pseudoephedrine diversion: A review of international practice and analysis of results in Australia. Drug Alcohol Rev 2009]