Evaluation of topical ibuprofen cream in the treatment of acute ankle sprains.

One hundred patients who presented to the accident and emergency (A&E) department with an acute ankle sprain were entered into a study to determine the efficacy of topical ibuprofen cream by using a double-blind placebo controlled design in a single type of soft-tissue injury. The subjects were given either topical ibuprofen cream or a placebo cream in addition to the standard management of the department. Patients kept diaries recording walking ability and pain visual analogue scales for resting, standing and walking. A total of 51 patients returned diaries that were suitable for analysis. Patients using the topical ibuprofen cream had significant reduction in pain scores over the first 48 h of treatment.     

Self-treatment of malaria in a rural area of western Kenya.

Reported are the results of a study of residents'' knowledge about malaria and antimalarial drugs and of their treatment-seeking behaviour in a rural area of western Kenya. The study subjects were generally well-informed about the symptoms of the disease. Malaria was perceived as a relatively mild illness, much less severe than acquired immunodeficiency syndrome (AIDS), measles, difficulty in breathing, and diarrhoea. Self-treatment was extremely common: of 138 episodes of febrile illness, 60% were treated at home with herbal remedies or medicines purchased at local shops, and only 18% received treatment at a health centre or hospital; no treatment was sought by the remainder. Commercially available chloroquine preparations were perceived as more effective than either antipyretics or herbal remedies for the treatment of malaria, and injections were regarded as more effective than oral medications. 4-Amino-quinolines were used to treat 58% of febrile illnesses but in only 12% of the cases was a curative dose of > or = 25 mg/kg body weight employed. Even attendance at a health centre did not ensure adequate treatment because of the common practice of sharing medication among family members. Greatly increased attention should be paid to the role of home treatment of malaria when policies are being developed for the management of febrile illnesses in sub-Saharan Africa.     

Modified Ultrafiltration Attenuates Dilutional Coagulopathy in Pediatric Open Heart Operations

Background. Extreme hemodilution caused by relatively large prime volumes required for cardiopulmonary bypass in infants causes a dilutional coagulopathy, characterized by low concentrations of fibrinogen and other circulating coagulation factors. Modified ultrafiltration results in hemoconcentration and is associated with decreases in postoperative bleeding and transfusion requirements in children. This study was undertaken to quantify the effect of modified ultrafiltration on concentrations of fibrinogen, plasma proteins, and platelets in infants and small children.

Methods. Twenty patients less than 15 kg were studied. Cardiopulmonary bypass circuits were primed with crystalloid solutions. Red blood cells were added during cardiopulmonary bypass for hematocrits less than 15%. Colloid solutions were not administered. Concentrations of fibrinogen, plasma proteins, and platelets, and hematocrit were measured before cardiopulmonary bypass, before modified ultrafiltration, and after modified ultrafiltration.

Results. Modified ultrafiltration was associated with significant (p < 0.001) increases in hematocrit (19% ± 6% to 31% ± 9%), fibrinogen (65 ± 29 to 101 ± 45 mg/dL), and total plasma proteins (2.7 ± 0.3 to 4.9 ± 0.7 g/dL), but no change (p = 0.129) in platelet count.

Conclusions. We conclude that modified ultrafiltration significantly attenuates the dilutional coagulopathy associated with cardiopulmonary bypass in infants.     

Organic anion transport in HepG2 cells: absence of the high-affinity, chloride-dependent transporter.

In previous studies, we identified a 55 kD organic anion-binding protein in liver cell sinusoidal plasma membrane subfractions. Other investigators identified another 55 kD bromosulfophthalein/bilirubin binding protein on the surface of rat hepatocytes and HepG2 cells and suggested that this protein served as a transporter for these ligands. In this study, transport of 35S-sulfobromophthalein by the human hepatoma cell line, HepG2, was quantified in the presence and absence of bovine serum albumin to further clarify the possible function of these plasma membrane binding proteins. In contrast to results in normal rat hepatocytes, virtually no uptake of 35S-sulfobromophthalein by HepG2 cells in the presence of bovine serum albumin was found. In the absence of albumin, HepG2 cells expressed temperature-dependent uptake of 35S-sulfobromophthalein. However, the high-affinity Cl(-)-dependent sulfobromophthalein transport that characterizes normal rat hepatocytes was absent, as indicated by an approximately 95-fold lower affinity and 170-fold higher capacity of HepG2 cells for sulfobromophthalein compared with previous results with rat hepatocytes. These results suggest that 55 kD sulfobromophthalein/bilirubin-binding protein on the liver cell surface differs from organic anion-binding protein and is not responsible for sulfobromophthalein extraction in the presence of albumin, although it may play some role in lower affinity transport by cells. Immunoblot analysis and metabolic labeling of HepG2 cells demonstrated synthesis of organic anion-binding protein. However, light microscopic immunocytochemistry and immunoprecipitation of surface iodinated rat hepatocytes and HepG2 cells with antibody to a recombinant organic anion-binding protein fusion protein indicated absence of organic anion-binding protein on the surface of HepG2 cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of morphogens in endochondral ossification

Summary The formation of bone occurs normally by one of two developmental processes: intramembranous or endochondral ossification. Endochondral ossification occurs in the morphogenesis of the limb buds and growth plates, and in the regeneration of bone following injury (fracture callus). Two classes of diffusible morphogen-like molecules (MLMs) involved in limb development are the bone morphogenetic proteins (BMPs) and retinoic acid (RA). These MLMs are associated, respectively, with the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) of the primitive limb bud. They function as potent regulators of pattern formation and are involved in tissue proliferation and differentiation. The presence of endochondral ossification in fracture callus suggests a role for MLMs in that process as well. To date, virtually nothing is known about the role of morphogens in the regeneration of bone (fracture healing). In this article, we review the current knowledge of MLMs in bone formation and propose a theory on their role in fracture healing. We hypothesize that MLMs involved in fracture healing may also express spatial and temporal information. A more complete understanding of the role of morphogens in both limb development and fracture healing is of major importance to practicing orthopedists and their patients.     

Antiarrhythmic activity of 17 beta-aminoestratrienes. Comparison of 3-ols and 3-acetates with the corresponding 3-(3-amino-2-hydroxypropyl) ethers

The antiarrhythmic efficacy of 17 beta-amino- and 17 beta-amino-16 alpha-hydroxyestratrien-3-ols and 3-acetates (group 1) was compared with the efficacy of corresponding 3-[2-hydroxy-3-(isopropylamino)propyl] and 3-[2-hydroxy-3-(tert-butylamino)propyl] ethers (group II), substituents which are usually associated with beta-adrenoceptor blocking activity. Group I compounds exerted potent antiarrhythmic activity against both aconitine-induced arrhythmias in mice and ischemia-induced arrhythmias in rats and reduced the maximum following frequency of isolated guinea pig atria. Electrophysiological studies indicated that their mechanism of action is due to an ability to reduce the fast inward sodium current in cardiac cells (class I antiarrhythmic action). Group II compounds were inactive in the aconitine and atrial tests and electrophysiological studies confirmed that they were devoid of class I activity. However, these compounds, like both class I antiarrhythmic and beta-adrenoceptor blocking drugs, were active against ischemia-induced arrhythmias. Group II compounds, unlike group I compounds, exerted nonspecific beta-adrenoceptor blocking actions, which may account for their activity in the rat test. It was concluded that introduction of the 3-substituted ether group did not confer any advantage over the parent 3-ol or 3-acetate compounds.     

Management of major colonic haemorrhage

Major colonic haemorrhage remains a difficult diagnostic and therapeutic problem. We propose that those patients who continue to bleed after resuscitation are best served by immediate laparotomy. High flow antegrade irrigation and intra-operative colonoscopy can then be used to localize the site of bleeding and allow appropriate excisional surgery rather than blind colonic resection.     

Acute interstitial nephritis: clinical features and response to corticosteroid therapy.

BACKGROUND: Acute interstitial nephritis (AIN) is a recognized cause of reversible acute renal failure characterized by the presence of an interstitial inflammatory cell infiltrate. METHODS: In order to evaluate the clinical characteristics and management of this disorder, we performed a retrospective study of all cases of AIN found by reviewing 2598 native renal biopsies received at our institution over a 12 year period. Presenting clinical, laboratory and histological features were identified, as was clinical outcome with specific regard to corticosteroid therapy response. RESULTS: AIN was found in 2.6% of native biopsies, and 10.3% of all biopsies performed in the setting of acute renal failure during the period analysed (n = 60). The incidence of AIN increased progressively over the period observed from 1 to 4% per annum. AIN was drug related in 92% of cases and appeared to be idiopathic in the remainder. The presenting symptoms included oliguria (51%), arthralgia (45%), fever (30%), rash (21%) and loin pain (21%). Median serum creatinine at presentation was 670 micromol/l [interquartile range (IQR) 431-1031] and 58% of cases required acute renal replacement therapy. Corticosteroid therapy was administered in 60% of cases. Serum creatinine at baseline was similar in the corticosteroid-treated and conservatively managed groups; 700 micromol/l (IQR 449-1031) vs 545 micromol/l (IQR 339-1110) P = 0.4. In this, the largest retrospective series to date, we did not detect a statistically significant difference in outcome, as determined by serum creatinine, between those patients who received corticosteroid therapy and those who did not, at 1, 6 and 12 months following presentation. CONCLUSION: The results of this study do not support the routine administration of corticosteroid therapy in the management of AIN.     

Central fat predicts deterioration of insulin secretion index and fasting glycaemia: 6-year follow-up of subjects at varying risk of Type 2 diabetes mellitus.

AIMS: To examine the relationships between body composition and changes in fasting glycaemia, and in indices of insulin secretion and insulin action over 6 years in females with a family history of Type 2 diabetes with or without prior gestational diabetes ('at risk' group, AR) and control females (control group, C). METHODS: At baseline and at follow-up, an oral glucose tolerance test and dual energy X-ray absorptiometry assessment of body composition were performed. Indices of insulin resistance (HOMA R') and insulin secretion (HOMA beta') were obtained from fasting insulin and glucose concentrations. RESULTS: At baseline, the groups were similar for age, body mass index, fasting levels of plasma glucose and insulin, HOMA R' and HOMA beta'. Despite similar total body fatness, AR had significantly greater waist circumference and central fat (both P < 0.02) compared with C. At follow-up there was a significant increase in central adiposity only in AR, and the fasting plasma glucose (FPG) level was higher in AR compared with C (5.0 +/- 0.2 vs. 4.3 +/- 0.2 mmol/l, P = 0.02). This rise in plasma glucose in AR was related to a decline in HOMA beta' (r = 0.45, P = 0.0065). Both the baseline and the increments in total and central abdominal fat mass were associated with the time-related decline in HOMA beta'. CONCLUSIONS: Six years after initial assessment, AR showed deterioration in FPG levels due predominantly to a decline in insulin secretion index without major change in insulin resistance index. Importantly, baseline body fatness (especially central adiposity), as well as increases in fatness with time, were the major predictors of the subsequent decline of insulin secretion index and the consequent rise in FPG.