Comparison of a parasite lactate dehydrogenase-based immunochromatographic antigen detection assay (OptiMAL) with microscopy for the detection of malaria parasites in human blood samples

Microscopic examination of blood smears remains the gold standard for malaria diagnosis, but is labor-intensive and requires skilled operators. Rapid dipstick technology provides a potential alternative. A study was conducted in The Gambia to compare the performance of OptiMAL, an immunochromatographic antigen detection assay for the diagnosis of malaria using parasite lactate dehydrogenase, against standard microscopy in patients with suspected malaria. For initial diagnosis of Plasmodium falciparum, irrespective of stage, this assay had a sensitivity of 91.3%, a specificity of 92%, a positive predictive value of 87.2%, and a negative predictive value of 94.7%. The sensitivity of the test decreased markedly at parasitemias < 0.01%. This assay can be used for the diagnosis of malaria in areas where microscopy is not available and for urgent malaria diagnosis at night and at weekends, when routine laboratories are closed and when relatively inexperienced microscopists may be on duty.     

Novel erythropoiesis stimulating protein (darbepoetin alfa) alleviates anemia associated with chronic inflammatory disease in a rodent model

OBJECTIVE: We developed a rodent model of noninfectious systemic inflammation to examine the pathogenesis of the associated anemia of chronic disorders (ACD), to evaluate the similarity of this ACD model to human ACD, and to evaluate the potential efficacy of novel erythropoiesis stimulating protein (darbepoetin alfa) as an ACD therapy. METHODS: Lewis rats were immunized with peptidoglycan-polysaccharide polymers (PG-APS), the chronic inflammation and associated ACD were characterized, and the effects of darbepoetin alfa treatment on complete blood counts (CBC), red blood cell (RBC) indices, and iron metabolism were analyzed weekly. RESULTS: Acutely inflamed rats had reduced peripheral blood (PB) RBC counts and hemoglobin (Hb) concentrations and increased reticulocyte counts. PB RBC numbers normalized during chronic inflammation, but RBC remained hypochromic and microcytic. Consequently, the rats remained chronically anemic. Anemic rats had fluctuating serum erythropoietin (EPO) concentrations, but mean EPO concentrations never varied significantly from baseline control levels. Histology of anemic rat spleen sections revealed reticuloendothelial siderosis. Total serum iron concentrations were chronically low. Peritoneal exudate cells (PEC) isolated from anemic rats and stimulated with PG-APS in vitro produced more interleukin (IL)-1alpha and interferon (IFN)-gamma, and significantly more tumor necrosis factor (TNF)-alpha and IL-10 than control cultures. Darbepoetin alfa restored Hb concentrations to baseline levels within 2 to 7 weeks, depending on dosage. A refined treatment strategy restored Hb to baseline and maintained those levels with reduced dosing. CONCLUSION: ACD in this rodent model closely replicates human ACD. Darbepoetin alfa treatment reversed ACD in this model by increasing RBC production and RBC hemoglobinization while reducing siderosis and hypoferremia.     

Detection of dimeric inhibin throughout the human menstrual cycle by two-site enzyme immunoassay

OBJECTIVE We have developed and validated a two-site immunoassay for the measurement of dimeric inhibin in plasma and subsequently measured dimeric inhibin levels in plasma through the normal female menstrual cycle. DESIGN Recombinant inhibin added to plasma samples was quantitatively recovered in both follicular and luteal phase, and serial dilutions of samples were tested for parallelism to similar dilutions of recombinant 32kDa inhibin. Daily samples were assayed from four women through a menstrual cycle. PATIENTS (a) Four groups of six women who (i) were in the follicular phase of a normal menstrual cycle, (ii) were in the luteal phase of a normal menstrual cycle, (iii) were post-menopausal and (iV) who had received hMG to induce superovulation. (b) Four healthy female volunteers aged 25–33. RESULTS Post-menopausal women had less than 2ng/l of inhibin whereas six women treated with hMG had dimeric inhibin concentrations up to 1125ng/l. During the early follicular phase, at the time of onset of menstruation, extremely low levels of dimeric inhibin were found (3-4ng/l (CI 2.2-5.0)) while in the late follicular phase, there was a marked increase in dimeric inhibin concentration. The concentration of dimeric inhibin was maximal (65.6 ng/l (CI 53.1-81,1)) in the mid-luteal phase. The overall pattern of dimeric inhibin concentration during the menstrual cycle was similar to that observed with previous inhibin assays although the magnitude of change was considerably greater. CONCLUSION The human ovary, In particular the corpus luteum, secretes significant amounts of dimeric and therefore biologically active inhibin.     

Prevalence and Comorbidity of Insomnia and Effect on Functioning in Elderly Populations

A good night's sleep is often more elusive as we age, because the prevalence of insomnia in older people is high. Insufficient sleep can have important effects on daytime function by increasing the need to nap, reducing cognitive ability including attention and memory, slowing response time, adversely affecting relationships with friends and family, and contributing to a general sense of being unwell. However, rather than aging per se, circadian rhythm shifts, primary sleep disorders, comorbid medical/psychiatric illnesses, and medication use cause sleep difficulties in older people, which psychosocial factors may also affect. Clinicians should ask elderly patients about satisfaction with sleep. Any sleep complaints warrant careful evaluation of contributing factors and appropriate treatment.     

Risk factors for diagnostic delay in acute aortic dissection

In acute aortic dissection (AAD), timely diagnosis is challenging. However, dedicated studies of the entity and determinants of delay are currently lacking. We surveyed pre-/in-hospital time to diagnosis and explored risk factors for diagnostic delay. We analyzed the dedicated database of a metropolitan AAD network (161 patients diagnosed since 1996; 115 Stanford type A) in terms of hospital arrival times (from pain to presentation at any hospital) and in-hospital diagnostic times (presentation to final diagnosis). Median (interquartile range) in-hospital diagnostic times were approximately twofold greater than hospital arrival times (177 minutes, 644, vs 75 minutes, 124, p = 0.0001, Wilcoxon test). Median annual in-hospital diagnostic times were most often approximately 3 hours (spread was wide, but decreased after 2001; rho = -0.94, p = 0.005). Risk factors (univariate analysis) for in-hospital diagnostic time >75th percentile (12 hours) included pleural effusion (odds ratio 3.96, 95% confidence interval 1.80 to 8.69), dyspneic presentation (odds ratio 3.33, 95% confidence interval 1.93 to 8.59), and age <70 years (odds ratio 2.34, 95% confidence interval 1.03 to 5.36). Systolic arterial pressure < or =105 mm Hg decreased the likelihood of lengthy diagnosis (odds ratio 0.08, 95% confidence interval 0.01 to 0.59). In patients (n = 82) with routine values (since 2000), troponin positivity (odds ratio 3.63, 95% confidence interval 1.12 to 11.84) and an acute coronary syndrome-like electrocardiogram (odds ratio 2.88, 95% confidence interval 1.01 to 8.17) were also risk factors. In conclusion, in a metropolitan setting, most of the diagnostic delay may occur in hospital. At presentation, pleural effusion, troponin positivity, acute coronary syndrome-like electrocardiogram, and dyspnea are possible "clinical confounders" associated with particularly long in-hospital diagnostic times.     

Asymptomatic glomerulonephritis after nonstreptococcal upper respiratory infections.

Two hundred forty previously healthy military personnel with nonstreptococcal upper respiratory infections were prospectively studied to define the incidence and clinicopathologic characteristics of possible virus-associated glomerulonephritis. Nine patients without preceding streptococcal infection had erythrocyte casts on urinalysis and glomerulonephritis on biopsy. Of these nine, four had a reduction in total hemolytic complement and five had serologic evidence of infection with adenovirus, influenza A, or influenza B. Initial renal biopsy showed either focal or diffuse mesangial proliferation in all nine, with mesangial C3 deposits in six specimens. Repeat biopsy in three showed histologic improvement or loss of immunofluorescent staining, or both. Sequential creatinine clearances were reduced to 74 to 90 mL/min.1.73 m2 in five patients for the duration of follow-up. We conclude that nonstreptococcal upper respiratory infection is frequently associated with glomerulonephritis and that abnormal glomerular structure and decreased creatinine clearances may persist for at least 2 to 8 months.     

The diagnosis and treatment of adults with obstructive airways disease in general practice

Two hundred and one patients diagnosed by their general practitioners as having asthma and 113 as having chronic bronchitis were compared by symptomatology and airways reversibility. Though the majority of patients given these two diagnoses could be separated by symptom complex, in about one-third such differentiation was difficult. There was no significant difference in bronchodilator reversibility between the asthmatics and chronic bronchitics. Nine out of 15 (60%) asthmatics and four out of 18 (22%) chronic bronchitics responded by 15% or more to a course of oral corticosteroid drugs. The majority of corticosteroid responders had been undertreated. The problems arising from the poor correlation between airways reversibility and symptomatic diagnosis are discussed.