Management of Atopic Eczema in primary care.

Introduction : Atopic eczema (AE) is a common inflammatory skin dermatosis that is increasing in prevalence. However, it can present in various clinical presentations, which leads to challenges in the diagnosis and treatment of the condition, especially in a primary care setting. The Clinical Practice Guidelines on the Management of Atopic Eczema was developed by a multidisciplinary development group and approved by the Ministry of Health Malaysia in 2018. It covers the aspects of diagnosis, severity assessment, treatment, and referral.

Ambulance response time and emergency medical dispatcher program: a study in Kelantan, Malaysia.

This study provided data by a simple method of acquiring information related to ambulance response time (ART) and determined whether it met the international standards of ART. Additionally, this paper also compared the duration of ART at this hospital before and after the implementation of an Emergency Medical Dispatcher (EMD) program. The ART, which started when details like phone number of the caller, exact location of the incident and the nature of the main complaint were received and ended when the emergency team arrived at the scene of the incident. The parameters recorded include call processing time, time taken to prepare the team and time taken to travel to the scene. The results of the study revealed that the ART for the university hospital (HUSM) was at 913.2 +/- 276.5 seconds (mean +/- SD) and it was far below the international standard of ART as a benchmark of a good ambulance service. However, the study suggested that the EMD program that was recently implemented at the HUSM gave a significantly improvement to the ART score.

The effect of propranolol in malay patients with liver cirrhosis - a pharmacodynamic evaluation.

The pharmacodynamics of propranolol were studied in 12 cirrhotic Malay patients. Fifteen healthy Malay volunteers were selected and several clinical parameters were obtained. The effects of three doses of propranolol in reducing the heart rate (HR) of these patients were observed to be significantly different. These differences were seen at dosing of 10 mg vs 20 mg and 10 mg vs 30 mg (P<0.001 and P<0.01, respectively). However, no significant difference was seen for doses between 20 mg vs 30 mg. At 20 mg the reduction in HR is more pronounced than the effect seen with the other two doses. The effects of propranolol in reducing V(max) and V(mean) of portal vein blood flow were found to be not significant at doses of 10 mg vs 30 mg, but between 10 mg vs 20 mg and 20 mg vs 30 mg there was significant difference (P<0.05 and P<0.01, respectively). Reduction of V(max) of more than 10% of baseline was achieved at doses of 10 mg and 20 mg. However, at a dose of 20 mg a more significant reduction was observed than at a dose of 10 mg. Dose-concentration-effect relationship was seen to be significantly different between HR reduction and propranolol concentration of the three steady-state levels (P<0.001). Similar results were obtained with V(max) and V(mean). The V(max) was found to be a reliable parameter for the assessment of therapeutic effect of the drugs in conferring changes in portal haemodynamics of liver cirrhotic patients. Further, Child-Pugh score is thought to be an important supporting factor in evaluating prognosis. The results of this pharmacodynamics studies suggest that the optimal dose of propranolol may be 20 mg propranolol thrice daily for cirrhotic Malay patients.

The Pharmacokinetics of Single Dose vs Steady-State Doses of Propranolol in Cirrhotic Malay Patients.

Pharmacokinetics of propranolol (PRN) given orally were studied in twelve cirrhotic Malay patients [10 males, 2 females], aged 33-62 years [49.83±9.17], body weight 39-72 kg [58.0±8.46] and height 142-168 cm [158.8±7.89] following single 20 mg and steady-state 20 mg tds for 7 days dosing of PRN. Blood samples were withdrawn hourly up to 48 hours. PRN concentrations in the plasma were assayed by HPLC with oxprenolol as the internal standard. Pharmacokinetic parameters were analysed using a non-linear regression program MultiForte. Area under the curve (AUC) as performed using the linear trapezoidal rule. Student's t-test was used to test for statistical significance and AUC in Malay cirrhotic patients was found to be much bigger than that observed in Caucasians. Steady-state AUC was significantly increased following multiple dosing (961.31±7.47 vs 2954.19±1153.34 ng.hr/ml), however, the volume of distribution (V(d)) declined (543.89±292.91 vs 224.14±1003.12 L) significantly compared to that of a single dose. The apparent systemic clearance (CL) was significantly reduced at steady-state (436.04±209.4 vs 129.51±48.42 ml/min) in comparison to single dose therapy. The peak plasma concentration (Cp(max)) was greatly increased at steady-state (54.32±22.37 vs 136.10±38.63 ng/ml). Based on the AUC, PRN bioavailability was greater in cirrhotic Malay patients compared to Caucasians who took only 20 mg instead of 80 mg doses. The decline in drug clearance following steady-state was due to saturation of the metabolizing capacity of hepatic enzymes and a decreased portal blood flow. Reduced V(d) was believed to be caused by increased drug-receptor interactions and decreased tissue/protein binding of PRN in these patients.

Essential role of kallikrein-kinin system in suppression of blood pressure rise during the developmental stage of hypertension induced by deoxycorticosterone acetate-salt in rats.

Deoxycorticosterone acetate (DOCA)-salt hypertension was induced in Brown Norway (BN) kininogen-deficient rats (BN-Ka) and normal rats from the same strain (BN-Ki) after nephrectomy. Systolic blood pressure, which was determined by the tail-cuff method, of BN-Ki increased gradually during this treatment. In contrast, the blood pressure of mutant BN-Ka increased rapidly 2 weeks after the onset of the treatment. Urinary excretion of active kallikrein and prokallikrein increased at the same degree in rats of both strains during this treatment. Significant increase in urinary sodium excretion was observed with a tendency to increase in urine volume during the treatment in normal BN-Ki rats, whereas both parameters were essentially not increased in mutant BN-Ka rats, which could not generate urinary kinin. Aprotinin infusion by osmotic minipump to normal BN-Ki rats during the DOCA-salt treatment resulted in significant further increase in the systolic blood pressure.

Influence of a kinin antagonist on acute hypotensive responses induced by bradykinin and captopril in spontaneously hypertensive rats.

We have evaluated the effects of a B2 receptor antagonist (B5630) of kinins on BK and captopril-induced acute hypotensive responses in anaesthetized SHR. Intravenous treatment of BK (1.0 microgram) and captopril (0.3 mg/kg) caused significant (p < 0.05) fall in the SBP and DBP. Whereas BK caused greater fall in the SBP (p < 0.05), DBP (p < 0.01) and duration of hypotension (p < 0.05) when administered after captopril (Fig 1 and 2). All the hypotensive effects of BK and captopril were significantly antagonised (p < 0.05) in the presence of B5630 (2.0 mg/kg). Further, the duration of hypotensive responses of BK and captopril were blocked (p < 0.05) by B5630. The agonists and BK-antagonist did not cause significant (p > 0.05) alterations in HR during the entire investigation. These findings provide evidence to support the suggestion that B2 receptor might be involved in the regulation of the hypotensive actions of BK and captopril. Kinins should also have valuable functions in the antihypertensive property of captopril-like drugs.

Suppression of rat deoxycorticosterone-salt hypertension by kallikrein-kinin system.

Brown Norway kininogen-deficient rats had very low levels of plasma kininogens and lower levels of plasma prekallikrein, compared with those of normal rats of the same strain. Systolic blood pressure, determined by the tail-cuff method, of 5-week-old kininogen-deficient rats (106 +/- 0.4 mm Hg, n = 7) and the rate of systolic blood pressure increase with age were not different from those in normal rats. Weekly injections of deoxycorticosterone acetate (5 mg/kg s.c.) with 1% sodium chloride solution in drinking water after uninephrectomy at 7 weeks of age caused a gradual increase in the blood pressure of normal rats, reaching a plateau at 18 weeks of age, whereas that of deficient rats rose rapidly to 158 +/- 6 mm Hg 2 weeks after the start of treatment and continued to increase slightly, becoming significantly higher than normal rats at 8, 9, 10, 11, and 12 weeks of age (p less than 0.05 or 0.01). The levels of urinary prokallikrein and active kallikrein were slightly higher in deficient rats before deoxycorticosterone acetate-salt treatment but were not significantly increased after this treatment, whereas these levels in normal rats were increased 3.6- and 4.7-fold by this treatment. Urinary free kinin, collected from the ureter in untreated deficient rats, was below the detection limit. The plasma level of low molecular weight kininogen, the substrate of glandular kallikrein, was decreased in normal rats during the treatment. Continuous subcutaneous injection of aprotinin by an osmotic pump to normal rats induced significant increase in blood pressure. These results indicate that glandular kallikrein may play a suppressive role in deoxycorticosterone acetate-salt hypertension.

The role of chemical mediators in the pathogenesis of inflammation with emphasis on the kinin system.

In recent years, numerous agents have been recognized as inflammatory mediators. In this review, however, we discuss only those having direct relevance to human inflammatory diseases These mediators are clinically important due to their proinflammatory properties such as vasodilatation, increased vascular permeability, pain and chemotaxis. They may lead to the fifth cardinal sign, loss of function in inflammatory diseases. Agonists and non-specific antagonists are used as pharmacological tools to investigate the inflammatory role of PGs, LTs, PAF, IL-1, histamine, complement, SP, PMN-leukocytes, and kallikrein-kininogen-kinin systems. Unfortunately, no compound is known which concurrently abolishes all actions and interactions of inflammatory mediators. Therefore it would be highly useful to promote efforts in developing selective and competitive antagonists against proinflammatory actions of these chemical mediators. This may help to a better understanding of the pathogenesis of inflammatory reactions, and it may also be useful for the therapy of inflammatory diseases.