Evaluation of complement fixation procedures for the diagnosis of visceral leishmaniasis

Three complement fixation (CF) procedures were evaluated for their ability to detect serum antibodies to visceral leishmaniasis. These tests differ in their use of buffers, volumes of complement and sensitized erythrocyte concentrations, incubation times and percentage haemolysis endpoints. Freeze-thawed sonicates of Leishmania donovani promastignotes were used as antigen. Test sensitivity was determined using sera from 46 Kenyans with parasitologically proven leishmaniasis. The frequencies of positive reactions in all three tests were 96-97% and positive antibody titres ranged from 1:16 to 1:4096. Specificity was determined with 20 sera from healthy individuals with no known exposure to leishmaniasis. The frequencies of false positive reactions were 0-10% in the control sera, with titres up to 1:16. No cross-reactions were observed with sera from patients with bacterial, fungal and other parasitic diseases. In replicate experiments, 99-100% of the sera tested were within one titre dilution of each other. All three CF procedures provide very good sensitivity, specificity and low cross-reactivity and are statistically similar in their capacity to diagnose visceral leishmaniasis.     

Isosorbide dinitrate and intra-aortic balloon pumping in preinfarctional angina. Effects on central circulatory dynamics.

The dynamics of the central circulation were measured by a radionuclidic technique in 18 men with high-risk preinfarctional angina who received therapy with isosorbide dinitrate (n equals 18), intra-aortic balloon pumping (n equals 8), or both (n equals 8). Administration of 5 mg of isosorbide dinitrate sublinqually was associated with a reduction in stroke volume index (SVI), cardiac index (CI), systemic arterial blood pressure, and left ventricular end-diastolic volume (LVEDV) and with increased left ventricular ejection fraction (LVEF). Intra-aortic balloon pumping did not alter SVI or CI, but decreased systolic blood pressure and LVEDV and increased LVEF and diastolic blood pressure. The combination of therapy with isosorbide dinitrate and intraaortic balloon pumping resulted in decreased SVI, systolic blood pressure, and LVEDV and increased LVEF. Thus, therapy with isosorbide dinitrate reduced left ventricular preload, and intra-aortic balloon pumping reduced blood pressure, which resulted in a decreased LVEDV and an increase in LVEF. Therapy with isosorbide dinitrate and intra-aortic balloon pumping act to alter central circulatory dynamics in favor of reducing myocardial oxygen demand.     

Treatment of refractory unstable angina in geographically isolated areas without cardiac surgery. Invasive versus conservative strategy (TRUCS study).

AIMS: We compared invasive (on-site coronary angioplasty or emergency air-ambulance transfer for bypass grafting surgery) vs conservative (persistent medical treatment) strategies in the management of refractory unstable angina in geographically isolated hospitals without cardiac surgical facilities. METHODS AND RESULTS: One hundred and forty eight randomized patients with refractory unstable angina were compared on an intention-to-treat basis. Outcomes (invasive vs conservative): (a) in hospital: stabilization (96% vs 43%, P=0.0001), non-fatal myocardial infarction (2.6% vs 4.2%, P=ns), death (1.3% vs 8.3%, P=0.046), combined outcome (3.9% vs 12.5%, P=0.053) and hospitalization (11.4+/-6.3 vs 12.4+/-8.0 days, P=ns). (b) 30-days follow-up: non-fatal myocardial infarction (2.6% vs 4.2%, P=ns), death (2.6% vs 11.1%, P=0.030) and combined outcome (5.3% vs 15.3%, P=0.031). (c) 12 month follow-up: non-fatal myocardial infarction (3. 9% vs 4.2%, P=ns), death (3.9% vs 12.5%, P=0.053), combined outcome (7.9% vs 16.7%, P=ns), re-admissions for unstable angina: (17.1% vs 23.6%, P=ns), late coronary angioplasty: (15.8% vs 11.1%, P=ns) and (d) late coronary bypass grafting: (7.9% vs 12.5%, P=ns). CONCLUSION: Invasive treatment of patients with refractory angina in remote areas without surgical back-up results in significant in-hospital stabilization and a reduction in major events in-hospital and at 30 days. Coronary angioplasty in stand-alone units and air-transfer of these patients seems safe.     

Colocalization of integrin receptors and reelin in dendritic spine postsynaptic densities of adult nonhuman primate cortex

The expression of telencephalic reelin (Reln) and glutamic acid decarboxylase mRNAs and their respective cognate proteins is down-regulated in postmortem brains of schizophrenia and bipolar disorder patients. To interpret the pathophysiological significance of this finding, immunoelectron microscopic experiments are required, but these cannot be carried out in postmortem human brains. As an alternative, we carried out such experiments in the cortex of rats and nonhuman primates. We found that Reln is expressed predominantly in layer I of both cortices and is localized to bitufted (double-bouquet), horizontal, and multipolar gamma-aminobutyric acid-ergic interneurons, which secrete Reln into extracellular matrix. Reln secretion is mediated by a constitutive mechanism that depends on the expression of a specific signal peptide present in the Reln carboxy-terminal domain. Extracellular matrix Reln is found to aggregate in proximity of postsynaptic densities expressed in apical dendrite spines, which include also the alpha(3) subunit of integrin receptors. Most pyramidal neurons of various cortical layers express the mouse-disabled 1 (Dab1) protein, which, after phosphorylation by a soluble tyrosine kinase, functions as an adapter protein, probably mediating a modulation of cytoskeleton protein expression. We hypothesize that the decrease of neuropil and dendritic spine density reported to exist in the neocortex of psychiatric patients may be related to a down-regulation of Reln-integrin interactions and the consequent decrease of cytoskeleton protein turnover.     

Sagittal spine shape literacy in the general adult population,assessed by a novel,simple graphical tool

[Purpose] The sagittal shape of the spine is associated with back-pain, balance and quality of life. We developed, evaluated and report the responses of a graphical tool to assess sagittal spine shape knowledge (literacy). [Participants and Methods] Two hundred and fifty adults were randomly assigned, in a cross-sectional crossover study, to free-hand draw and select the “ideal” sagittal spine shape. We evaluated the inter and intra-rater reliability and agreement between tests and the sagittal and lordotic spine literacy between the drawing and selection test versions. [Results] Drawing test inter- and intra-rater agreement was 79% and 80% respectively. Drawing vs. selection agreement was 43%. More participants drew than selected the correct spine (30% vs. 21%) (p<0.001) and lumbar lordosis shape (56% vs. 42%) (p<0.001). Test order did not affect spine shape literacy scores. A significantly poorer literacy trend was observed with spine pain presence (p=0.02). [Conclusion] We developed a reliable method to evaluate spine shape literacy and established that only 21% and 42% of our sample demonstrated correct sagittal spine and lordotic spine shape literacy, respectively. The low literacy scores suggests that consideration of including spine shape literacy in health literacy and self-management programs may be warranted, especially in ageing populations.     

Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation

Most radiotherapy (RT) involves the use of high doses (>50 Gy) to treat malignant disease. However, low to intermediate doses (approximately 3–50 Gy) can provide effective control of a number of benign conditions, ranging from inflammatory/proliferative disorders (e.g. Dupuytren''s disease, heterotopic ossification, keloid scarring, pigmented villonodular synovitis) to benign tumours (e.g. glomus tumours or juvenile nasopharyngeal angiofibromas). Current use in UK RT departments is very variable. This review identifies those benign diseases for which RT provides good control of symptoms with, for the most part, minimal side effects. However, exposure to radiation has the potential to cause a radiation-induced cancer (RIC) many years after treatment. The evidence for the magnitude of this risk comes from many disparate sources and is constrained by the small number of long-term studies in relevant clinical cohorts. This review considers the types of evidence available, i.e. theoretical models, phantom studies, epidemiological studies, long-term follow-up of cancer patients and those treated for benign disease, although many of the latter data pertain to treatments that are no longer used. Informative studies are summarized and considered in relation to the potential for development of a RIC in a range of key tissues (skin, brain etc.). Overall, the evidence suggests that the risks of cancer following RT for benign disease for currently advised protocols are small, especially in older patients. However, the balance of risk vs benefit needs to be considered in younger adults and especially if RT is being considered in adolescents or children.     

Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe

Objectives

The aim of the study was to evaluate the long‐term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)‐, darunavir/ritonavir (DRV/r)‐, and lopinavir/ritonavir (LPV/r)‐containing regimens.

Methods

Data were analysed for 5678 EuroSIDA‐enrolled patients starting a DRV/r‐, ATZ/r‐ or LPV/r‐containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART‐naïve subjects (8%) at ritonavir‐boosted protease inhibitor (PI/r) initiation; (2) ART‐experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV‐1 RNA copies/mL; and (3) ART‐experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan–Meier and multivariable Cox models were used to compare risks of failure by PI/r‐based regimen. The main analysis was performed with intention‐to‐treat (ITT) ignoring treatment switches.

Results

The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log‐rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART‐naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment‐experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r‐based ART.

Conclusions

Although confounding by indication and calendar year cannot be completely ruled out, in ART‐experienced subjects the long‐term effectiveness of DRV/r‐containing regimens appears to be greater than that of ATZ/r and LPV/r.

     

Current concepts in the management of fungal peritonitis

Fungal pathogens are uncommon isolates in the setting of peritonitis. Secondary peritonitis results from a breach in the gastrointestinal tract with gross contamination of the peritoneum. Peritonitis in patients undergoing peritoneal dialysis represents a unique form of secondary peritonitis often caused by nosocomial bacteria and fungi. Regardless of the clinical circumstances, most cases of fungal peritonitis are caused by Candida species, however, other yeasts and filamentous fungi have been uncommonly reported. Treatment of secondary peritonitis consists of appropriate surgical intervention and systemic antifungal therapy. Systemic antifungals such as amphotericin B or fluconazole are also essential for the treatment of fungal peritonitis in patients who are peritoneal dialysis dependent. Salvage of the peritoneal dialysis catheter may be attempted, however, removal is usually required to achieve cure. Prophylaxis with fluconazole in patients with recurrent gastrointestinal perforations or anastomotic leakages has reduced the incidence of Candida peritonitis. Benefit of nystatin for fungal peritonitis prophylaxis in peritoneal dialysis patients is questionable.