Introduction of a novel self-injector for sumatriptan. A controlled clinical trial in general practice

A novel self-injector for the administration of subcutaneous sumatriptan in the treatment of migraine attacks was tested in 138 patients recruited by family physicians in Denmark; 108 patients completed the initial double-blind, crossover part of the study. Sumatriptan 6 mg s.c. was significantly better than placebo at 30, 60, 90 and 120 min after injection in relieving moderate or severe headache to mild or none as well as relieving any headache to none. At 60 min after injection, the treatment response rate was 61% for sumatriptan and 6% for placebo. During the following open-phase trial of four attacks treated with sumatriptan, treatment response rates were 68–74%. During the total of 538 attacks treated, 12 attempts at using the self-injector failed. In the double-blind and open phases, 81% and 90% of patients respectively found the device easy or very easy to use. Adverse effects were benign and short-lasting, but led seven patients to discontinue the study. In conclusion, subcutaneous sumatriptan administered with a novel self-injector is an effective treatment for migraine compared to placebo in patients treated by their family physician.     

Membrane protein interactions in sickle red blood cells: evidence of abnormal protein 3 function

The pattern of membrane abnormalities in sickle red blood cells suggests that sickle hemoglobin damages membrane proteins. We have previously shown a functional defect in sickle ankyrin, poor spectrin- binding ability. Here we examine the other major binding interactions of sickle membrane proteins including spectrin self-association, binding of ankyrin and protein 4.1 to protein 3, and the formation of the spectrin-actin-protein 4.1 complex. We found that sickle spectrin was normal in self-association and ability to participate in the spectrin-actin-protein 4.1 complex. Sickle protein 4.1 bound normally to protein 3 and formed normal complexes with actin and spectrin, even when sickle spectrin was used. The only major abnormality we found was a reduced ability of sickle protein 3 to bind ankyrin. This functional defect could not be explained experimentally on the basis of cysteine modification or enhanced tyrosine phosphorylation. We conclude that damage of sickle membrane proteins is not a diffuse scattershot process, but is largely confined to regions near membrane-associated hemoglobin, the spectrin-binding domain of ankyrin and the ankyrin- binding domain of protein 3. The mechanism and consequences of this damage continues to be investigated.     

Risk factors for bone loss in the hip of 75-year-old women: A 4-year follow-up study

Risk factors for bone loss among the elderly are largely unknown. The objective of the study was to examine longitudinal bone loss in the hip in one-hundred and sixty-two 75-year-old women. Bone mineral density (BMD, g/cm²) was measured with dual X-ray absorptiometry (DXA) at baseline and after 4 years. The relationship between changes in BMD during follow-up and the following factors; baseline BMD, baseline weight, weight change, baseline lean and fat body mass (measured with DXA), serum values of biochemical markers and hormones, nutritional and lifestyle factors according to a questionnaire was assessed.     

Serum FGF23 levels in normal and disordered phosphorus homeostasis.

We investigated if the circulating levels of the phosphaturic factor FGF23 are elevated in subjects with XLH. Although we failed to find a statistically significant increase, FGF23 levels were significantly correlated with the degree of hypophosphatemia in XLH. In contrast, FGF23 levels were markedly increased in subjects with ESRD and correlated inversely with the degree of hyperphosphatemia. INTRODUCTION: Inactivating mutations of PHEX cause renal phosphate wasting in X-linked hypophosphatemic rickets (XLH) because of the accumulation of a phosphaturic hormone called phosphatonin. The recent discovery that FGF23 is the circulating phosphaturic factor in autosomal dominant hypophosphatemia raises the possibility that FGF23 is phosphatonin. METHODS: Fasting serum FGF23 levels and serum biochemical parameters were measured using a human FGF23 (C-terminal) ELISA assay in 11 subjects with XLH and 42 age-matched controls, 5 subjects with hypophosphatemia of unknown cause, and 14 hyperphosphatemic subjects with end stage renal disease (ESRD). Associations between variables were examined using the Spearman's correlation coefficient and linear regression analysis. RESULTS AND CONCLUSIONS: FGF23 (RU/ml) concentrations were not different (p = 0.11) between control and hypophosphatemic XLH subjects, but were significantly increased in hyperphosphatemic subjects with ESRD (p < 0.001). Western blot analysis found the presence of both full-length and C-terminal FGF23 fragments in serum from ESRD subjects. There was a strong inverse correlation between FGF23 and serum phosphorus (r = -0.60) and calcium and phosphorus (Ca x P) product (r = -0.65) in XLH, and a strong positive relationship between FGF23 and Pi (r = 0.50) and Ca x P product (r = 0.62) in ESRD. FGF23 levels were variably elevated in subjects with hypophosphatemia of unknown cause, one of which had tumor-induced osteomalacia (TIO). Removal of the tumor resulted in rapid reduction in serum FGF23 levels. These findings suggest that FGF23 has a possible role in mediating hypophosphatemia in XLH and TIO, but the overlapping levels of FGF23 in hypophosphatemic disorders and normal subjects indicate that serum phosphorus and FGF23 can also be independently regulated.     

Age-related decline in bone mass measured by dual-energy X-ray absorptiometry and quantitative ultrasound in a population-based sample of both sexes: identification of useful ultrasound thresholds for osteoporosis screening.

Quantitative ultrasound (QUS) can be used as a screening tool for low bone mineral density (BMD), but clinical guidelines have not been set. The aim of this population-based, cross-sectional study was to compare age-related changes in bone mass measured by QUS (Lunar, Achilles Plus) and dual-energy X-ray absorptiometry (DXA) in a random sample of 1630 individuals (1041 females, 589 males) 30-85 yr of age. Individuals with DXA T-scores < or =-2.5 at the femoral neck or total hip were identified and receiver operating curves (ROCs) were used to calculate cutoff points for QUS. Sensitivity, specificity, and kappa statistics were calculated. Age-related bone loss was significantly larger with QUS than DXA at all sites in women. For men, the curves were similar for QUS and DXA in the hip. Similar correlations were found between QUS and DXA in different age groups of both sexes (0.36-0.60). For women aged 50-65 yr, a QUS T-score >-1.0 was found to be the most applicable for identifying normal BMD. In the 70-85 yr age group, a T-score <-2.5 for women and a T-score <-0.5 for men seemed reasonable cutoffs for identifying normal BMD (sensitivity: 86-93%; specificity: 28-44%; discordance: 33-73%). Calcaneal QUS cannot be used for the diagnosis of osteoporosis according to WHO criteria, but it can be of use to exclude osteoporosis in 30-40% of our cases.     

Prevalence of chronic kidney disease based on estimated glomerular filtration rate and proteinuria in Icelandic adults.

BACKGROUND: The purpose of this study was to compare three different equations to calculate estimated glomerular filtration rate (eGFR) based on serum creatinine (SCr) and to estimate the prevalence of chronic kidney disease (CKD) in the Icelandic population. METHODS: This was a cross-sectional study using data from the Reykjavik Heart Study. GFR was estimated with three equations: Equation I was based on 1/SCr; Equation II based on the Cockcroft-Gault equation; and Equation III was the modified MDRD equation. The eGFR calculated with Equation III and proteinuria were used to estimate the prevalence of CKD. The prevalence was age-standardized to the truncated world population. We used chi-square and ANCOVA to compare the group with low eGFR to age-matched controls. RESULTS: The subjects consisted of 9229 males and 10,027 females, aged 33-85 years. The equations performed very differently. Equation I showed women with higher eGFR than men and little change with age. Equation II showed men with higher eGFR than women and marked decline in eGFR with age. Equation III was similar to Equation II but the decline in eGFR with age was not as great. Regardless of the equation used, most subjects (63.7-80.7%) had an eGFR in the range of 60-89 ml/min/1.73 m2. Using Equation III, age-standardized prevalence of low eGFR for the population aged 35-80+ years was estimated to be 4.7 and 11.6% for men and women, respectively. The proportion of subjects with eGFR <60 ml/min/1.73 m2 increased with advancing age. An additional 2.39% of men and 0.89% of women had proteinuria. The prevalence of renal and cardiovascular risk factors including proteinuria, hypertension, lipid abnormalities and markers of inflammation was higher among those with low eGFR than age-matched controls. CONCLUSIONS: GFR estimates and the prevalence of CKD are dependent on the equation used to calculate eGFR. Unexpectedly, a low proportion of the Icelandic population had normal kidney function according to the eGFR regardless of the equation used. These equations may not be useful in epidemiological research.     

Brine Shrimp Toxicity Evaluation of Some Tanzanian Plants Used Traditionally for the Treatment of Fungal Infections

Plants which are used by traditional healers in Tanzania have been evaluated to obtain preliminary data of their toxicity using the brine shrimps test. The results indicate that 9 out of 44 plant species whose extracts were tested exhibited high toxicity with LC₅₀ values below 20µg/ml. These include Aloe lateritia Engl. (Aloaceae) [19.1µg/ml], Cassia abbreviata Oliv. (Caesalpiniaceae) [12.7µg/ml], Croton scheffleri Pax (Euphorbiaceae) [13.7µg/ml], Hymenodactyon parvifolium Brig (Rubiaceae) [13.4µg/ml], Kigelia Africana L. (Bignoniaceae) [7.2µg/ml], and Ocimum suave Oliv. (Labiatae) [16.7µg/ml]. Twelve plants gave LC₅₀ values between 21 and 50µg/ml, 11 plants gave LC₅₀ values between 50 and 100 µg/ml, and 18 plants gave LC₅₀ values greater than 100 µg/ml.     

Malaria and HIV co-infection and their effect on haemoglobin levels from three health-care institutions in Lagos,southwest Nigeria

Background

Malaria and human immunodeficiency virus (HIV) are two major infections with enormous public health consequence. Together, they are endemic in many developing countries with anaemia being the most frequent haematological consequence of the infections.

Objectives

To determine the prevalence of malaria and HIV co-infection as well as anaemia among selected patients from three health-care institutions in Lagos, Nigeria.

Methods

A cross-sectional study of 1080 patients was carried out to determine the prevalence of malaria and HIV co-infection as well as anaemia. Blood sera from each of the patients were screened for malaria parasites, HIV-1 and HIV-2 using Giemsa stain, Cambridge Biotech Recombigen HIV-1/HIV-2 rapid device, respectively while haemoglobin estimation was performed using cyanmethemoglobin method.

Results

Our data showed that the total number of malaria infected patients were significantly higher in HIV sero-positive patients 47.7% (31/65) when compared with their HIV sero-negative counterparts 25.8% (262/1015) P = 0.047. The result also revealed that 25.8% (8/31) of the patients co-infected with malaria and HIV had anaemia as compared to 11.1% (29/262) infected with malaria alone. Multivariable logistic regression analysis showed that patients with dual infection of malaria and HIV were twice likely to be anaemic than those infected with malaria alone [adjusted OR 2.4, 95% CI, 1.3 to 2.7, P = 0.014].

Conclusions

Our data indicated a higher prevalence of malaria in HIV infected patients and also revealed that patients co-infected with malaria and HIV were more likely to be anaemic.