Haptoglobin from psoriatic patients exhibits decreased activity in binding haemoglobin and inhibiting lecithin-cholesterol acyltransferase activity

Objective The aim of this work was to assess whether psoriasis is associated with phenotype prevalence and altered activity of haptoglobin (Hpt). Background Hpt is a plasma acute‐phase glycoprotein, displaying in humans three phenotypes. Phenotype prevalence or structure modification of Hpt was associated with several diseases. The Hpt main function is to bind and carry to the liver free haemoglobin for degradation and iron recycling. Hpt was recently found able to bind the apolipoprotein A‐I (ApoA‐I), thus impairing its stimulation on the activity of the enzyme lecithin‐cholesterol acyl‐transferase (LCAT). Study design Hpt was isolated from patients with psoriasis vulgaris, and its activity in haemoglobin or ApoA‐I binding and LCAT inhibition was compared with that of normal protein. Methods Two affinity chromatography steps, the first using resin‐coupled haemoglobin and the second anti‐Hpt antibodies, were used to purify Hpt. The protein phenotype was assessed by electrophoresis. Binding experiments were performed by Enzyme‐linked immunosorbent assay with stationary haemoglobin or ApoA‐I, Hpt in solution and anti‐Hpt antibodies for detection of bound Hpt. Standard LCAT assays were carried out in the presence of Hpt purified from patients or healthy subjects. Results Phenotype prevalence of Hpt in psoriasis was not found. After affinity chromatography by haemoglobin, albumin and ApoA‐I were routinely found heavily contaminating only Hpt from normal subjects. Isolated Hpt from patients had lower activity than normal protein in both haemoglobin binding and LCAT inhibition. Conclusions In psoriasis, Hpt displays some structure modification(s), which might be associated with the protein function in the disease.     

Growth hormone therapy for protein catabolism

GH and IGF-I have shown remarkable consistency of effect in a wide range of catabolic conditions. Doses of around 10 IU/m2/day of GH and 80 micrograms/kg/day of IGF-I over short periods of time can improve net protein synthesis and preserve lean body mass. Most studies have reported metabolic endpoints, but favorable clinical effects have included decreased hospital stay and mortality in burns, improved respiratory muscle function in COAD, preserved grip strength post- operatively, and improvements in cardiac and bowel failure. Adverse effects of GH treatment are uncommon and usually related to glycaemic control. GH and IGF-I have differential effects on insulin concentrations--increasing or decreasing concentrations, respectively. The hypoglycaemic effects of IGF-I are dependent on route of administration and are avoided by subcutaneous delivery. Occasional patients have needed to discontinue GH treatment due to hyperglycaemia, although the anabolic action of GH may be partially mediated by increased insulin levels. The co-administration of GH and IGF-I has theoretical advantages by both increasing IGF binding-protein concentrations and balancing glycaemic control. An initial study with combination therapy in calorically-restricted volunteers has shown anabolic effects greater than with either agent alone. This approach requires further study in catabolic patients. There is a need for large, well-designed trials with clinical rather than purely metabolic end-points, and some of these are already underway. Should these studies confirm the early findings, financial considerations will become paramount, although it remains possible that treatment may be self-financing if lengths of hospital admissions are shortened.      

EFFICACY OF TWICE-DAILY AMOXYCILLIN/CLAVULANATE (‘AUGMENTIN-DUO’ 400/57) IN MILD TO MODERATE LOWER RESPIRATORY TRACT INFECTION IN CHILDREN

SUMMARY A new amoxycillin/clavulanate regimen (‘Augmentin-Duo’ 400/57), to be given orally in two divided doses, has been proposed to overcome the inconvenience of tid dosing. This observer-blind, multicentre study randomised children aged two to 12 years with lower respiratory tract infection to seven days' treatment with either amoxycillin/clavulanate bid at a dose of 25/3.6mg/kg/day (221 patients) or the currently prescribed amoxycillin/clavulanate regimen of 20/5mg/kg/day tid (216 patients). Clinical success (cure) rates at follow up were 81.0% for the bid group and 77.8% for the tid group [difference 3.2%; 95% CI (-4.36, 10.80)], indicating that the regimens were of equivalent efficacy. Both regimens were well tolerated, and there was no statistically significant difference in the incidence of adverse experiences between the two groups. Compliance with study medication was high and similar for both groups (80% compliance: bid 90.0%; tid 87.0%).     

Meeting oxygen needs in Africa: an options analysis from the?Gambia

Objective

To compare oxygen supply options for health facilities in the Gambia and develop a decision-making algorithm for choosing oxygen delivery systems in Africa and the rest of the developing world.

Methods

Oxygen cylinders and concentrators were compared in terms of functionality and cost. Interviews with key informants using locally developed and adapted WHO instruments, operational assessments, cost-modelling and cost measurements were undertaken to determine whether oxygen cylinders or concentrators were the better choice. An algorithm and a software tool to guide the choice of oxygen delivery system were constructed.

Findings

In the Gambia, oxygen concentrators have significant advantages compared to cylinders where power is reliable; in other settings, cylinders are preferable as long as transporting them is feasible. Cylinder costs are greatly influenced by leakage, which is common, whereas concentrator costs are affected by the cost of power far more than by capital costs. Only two of 12 facilities in the Gambia were found suitable for concentrators; at the remaining 10 facilities, cylinders were the better option.

Conclusion

Neither concentrators nor cylinders are well suited to every situation, but a simple options assessment can determine which is better in each setting. Nationally this would result in improved supply and lower costs by comparison with conventional cylinders alone, although ensuring a reliable supply would remain a challenge. The decision algorithm and software tool designed for the Gambia could be applied in other developing countries.     

High-dose versus low-dose bovine surfactant treatment in very premature infants

The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24–29 weeks and birth weight 500–1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO₂) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO₂/ FiO₂) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25 % improvement in the endpoint. Oxygenation was improved significantly with high-dose ( n = 42) compared to low-dose treatment ( n =48): 30.9±15.0 kPa (231.5±112.7 mmHg) versus 24.1±15.7 kPa (180.6±118.0 mmHg) (mean ± SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.     

Immunological factors in milk from Brazilian mothers delivering small-for-date term neonates

Breast milk samples from three groups of Brazilian women were evaluated: G1, mothers delivering term babies of low birth weight (n=16); G2, mothers delivering preterm babies of appropriate birth weight (n = 20); G3, mothers delivering term babies of appropriate birth weight ( n = 30). Milk samples were obtained at 48 h and on the 7th, 15th, 30th and 60th days after delivery and they were analyzed for lysozyme and total IgA levels and for the presence of specific antibodies against Poliovirus types I, II, III, Rotavirus, Herpes simplex virus, Varicella zoster and Cytomegalovirus. The groups were not statistically different in relation to mother's age, parity, type of delivery or socio-economic levels. IgA levels were higher in both low-birth-weight groups (G1 & G2) compared to the control group (G3) throughout the study period. Lysozyme levels decreased up to the 15th day, increasing thereafter up to the 60th day in all groups. Specific antibodies were detected throughout the study period, with no differences among groups. We conclude that breast milk composition of mothers delivering low-birth-weight babies (G1 & G2) was similar despite the different gestational ages.     

IDEAL PAIN RELIEF FOLLOWING LAPAROSCOPIC CHOLECYSTECTOMY

In a previous report the effectiveness of intraperitoneal bupivacaine in reducing pain following laparoscopic cholecystectomy was demonstrated. Other methods of pain relief are commonly used but none has been compared following laparoscopic cholecystectomy. In two further studies we have compared the analgesic effect of intraperitoneal bupivacaine against wound infiltration with bupivacaine, and against intraperitoneal bupivacaine with the addition of a non-steroidal anti-inflammatory drug (NSAID) in patients undergoing laparoscopic cholecystectomy. Two consecutive studies were performed. In the first, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine injected into the trocar wounds. In the second study, patients in group 1 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity; patients in group 2 were given 20 ml of 0.25% bupivacaine into the peritoneal cavity and a diclofenac suppository (100 mg) one hour before surgery. Postoperative pain was assessed with a visual analogue pain scale. There was no difference in pain scores in the two groups in either study. Intraperitoneal bupivacaine is as effective as wound infiltration. The addition of an NSAID makes no difference in the reduction of postoperative pain following laparoscopic cholecystectomy.