Ultrasound prediction of fetal lung maturity

Amniocentesis for determination of fetal lung maturity and ultrasonographic (US) evaluation of the biparietal diameter (BPD) and placental grade were performed simultaneously in 261 nondiabetic pregnant women. A BPD of at least 9.3 cm and a grade 3 placenta were evaluated as predictors of fetal lung maturity using amniotic fluid phospholipids as indicators of a mature lung profile. The ability of the sonographic parameters to predict fetal lung maturity was closely related to menstrual age. Before 37 weeks, the false-positive prediction rate using a grade 3 placenta was 100%, and the false-positive prediction using the BPD was 85.6%. After 37 weeks, the false-positive rate using a grade 3 placenta was 5.9%, and the false-positive rate using the BPD was 9.5%. Thus menstrual age, and not these two US parameters, dictated fetal lung maturity. The authors conclude that the best use of US for predicting fetal lung maturity is in establishing menstrual age early in pregnancy.     

Sudden infant death syndrome in Brazil: fact or fancy?

CONTEXT AND OBJECTIVE: The true incidence of sudden infant death syndrome (SIDS) in Brazil is unknown. The aim here was to identify SIDS cases in the city of Ribeir?o Preto, State of S?o Paulo, between 2000 and 2005, in order to estimate its incidence. DESIGN AND SETTING: Retrospective analysis of data on live births and infant deaths in Ribeir?o Preto and from autopsies of infants performed at the Death Verification Service of the Interior (SVOI) between 2000 and 2005. RESULTS: There were 47,356 live births and 537 deaths, with infant mortality rates ranging from 12.9 to 10.9 of live births. Among the 24 infants who died possibly due to SIDS and who were autopsied at the SVOI, six were from families living in the municipality (0.13 of live births): three (50%) were diagnosed as SIDS, and one each (16.66%) as indeterminate cause, bronchoaspiration and cerebral edema. Two deaths occurred in the first month of life (33.33%) and one each (16.66%) at two, four, six and eight months. Two deaths each (33.33%) occurred in the months of February and December, one each in August and October (16.66%). Four cases (66.7%) occurred in the summer and one each (16.66%) in winter and spring. There was 5:1 predominance of males over females. CONCLUSIONS: The frequency of SIDS was lower than what has been reported worldwide and in the Brazilian literature, thus suggesting underdiagnosis, indicating the lack of any specific postmortem protocol for SIDS identification and showing the need to implement this.     

Cure of Helicobacter pylori-positive active duodenal ulcer patients: double-blind, multicentre, 12-month study comparing a two-week dual vs a one-week triple therapy

Aims. To compare a two-week dual therapy to a one-week triple therapy for the healing of duodenal ulcer and the eradication of the Helicobacter pylori infection.Patients and Methods. A total of 165 patients with active duodenal ulcer were enrolled in the study. At entry, endoscopy, clinical examination and laboratory tests were performed. Histology and the rapid urease test were used to diagnose Helicobacter pylori infection. Patients received either lansoprazole 30 mg plus amoxycillin 1 g bid for two weeks (two-week, dual therapy) or lansoprazole 30 mg plus amoxycillin 1 g plus tinidazole 500 mg bid for one week plus lansoprazole qd for an additional week (one-week, triple therapy). Two and twelve months after cessation of therapy, endoscopy and clinical assessments were repeated.Results. Duodenal ulcer healing and Helicobacter pylori eradication were both significantly greater (p<0. 0001) in the triple therapy group (healing: 98.6%; Helicobacter pylori cure rate: 72.6%) than in the dual therapy group (healing: 77.3%; Helicobacter pylori cure rate: 33.3%). Ulcers healed more frequently in Helicobacter pylori-cured than in Helicobacter pylori-not cured patients (94.9% vs. 77.2%; p<0.0022). After one year, Helicobacter pylori eradication was re-confirmed in 46/58 patients previously treated with the triple therapy and in 10/40 patients treated with the dual therapy (p<0.0001). Only three duodenal ulcer relapses were observed throughout follow-up: all were in Helicobacter pylori-not cured patients.Conclusions. Triple therapy was more effective than dual both in curing Helicobacter pylori infection and healing active duodenal ulcers. The speed of ulcer healing obtained after only 7 days of antibiotics and 14 days of proton pump inhibitors confirmed that longer periods of anti ulcer therapy were not necessary. Helicobacter pylori -not cured patients had more slowly healing ulcers which were more apt to relapse when left untreated.     

Pallidal stimulation for segmental dystonia: Long term follow up of 11 consecutive patients

Pallidal stimulation is a convincing and valid alternative for primary generalized dystonia refractory to medical therapy or botulinum toxin. However, the clinical outcome reported in literature is variable most likely because of heterogeneity DBS techniques employed and /or to clinical dystonic pattern of the patients who undergo surgery. In this study, we report the long term follow up of a homogeneous group of eleven subjects affected by segmental dystonia who were treated with bilateral stimulation of the Globus Pallidus pars interna (GPi) from the years 2000 to 2008. All the patients were evaluated, before surgery and at 6‐12‐24‐36 months after the treatment, in accordance with the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS). Our study indicates that DBS promotes an early and significant improvement at 6 months with an even and a better outcome later on. The analysis of specific sub items of the BFMDRS revealed an earlier and striking benefit not only as far as segmental motor function of the limbs but also for the complex cranial functions like face, (eyes and mouth), speech and swallowing, differently from results reported in primary generalized dystonia. Deep Brain Stimulation of GPi should be considered a valid indication for both generalized and segmental dystonia when other therapies appear ineffective. © 2009 Movement Disorder Society     

Inhibition of anti-IgE mediated human mast cell activation by NO donors is dependent on their NO release kinetics

Background and purpose:

Although the mast cell is a source of nitric oxide (NO), the effect of NO on human mast cells has not been defined. This study investigated if exogenous NO could affect human mast cell activation.

Experimental approach:

Effects of different NO donors on immunoglobulin E (IgE)-dependent activation of human-cultured mast cells (HCMC) derived from precursors in buffy coat were investigated by measuring histamine release. Intracellular NO in HCMC was monitored with confocal microscopy using the fluorescent NO indicator 4-amino-5-methylamino-2′, 7′-difluorofluorescein.

Key results:

Diethylamine NONOate (DEA/NO) and MAHMA NONOate (NOC-9), both have rapid NO release rates, only inhibited anti-IgE-induced histamine release when added to HCMC at the time of activation. NO donors with slower NO release kinetics were ineffective even after 30 min incubation. Confocal microscopy revealed that the effectiveness of NO donors was dependent on the availability of adequate NO inside HCMC during activation. The inhibitory action of DEA/NO was diminished by the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl but potentiated by the anti-oxidant, N-acetylcysteine (NAC). Furthermore, co-incubation with NAC allowed previously ineffective NO donors to suppress HCMC activation and thus suggested that NAC could increase the availability of NO from NO donors.

Conclusions and implications:

Our results demonstrated that NO was able to modulate human mast cell activation but only when enough NO was present at the time of cell activation. Our findings explain the controversy over the effectiveness of NO on mast cell degranulation and supports the possibility that NO donors could be beneficial for treating allergic inflammation.     

Amygdala gene expression of NMDA and GABAA receptors in patients with mesial temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common form of partial epilepsy and affects 40% of the patients. Seizures arising from the mesial temporal lobe structures (i.e., amygdala and hippocampus) are common, whereas neocortical seizures are rare. In recent years, many studies aimed to identify the pattern of gene expression of neurotransmitters involved in molecular mechanisms of epilepsy. We used real‐time PCR to quantify the expression of GABA_A (subunits α1, β1, β2) and NMDA (subunits NR1, NR2A, and NR2B) receptor genes in amygdalae of 27 patients with TLE and 14 amygdalae from autopsy controls. The NR1 subunit was increased in patients with epilepsy when compared with controls. No differences were found in expression of NMDA subunits NR2A and NR2B or in α1, β1, and β2 subunits of GABA_A receptors. Our results suggest that the NR1 subunit of NMDA receptors is involved in the amygdala hyperexcitability in some of the patients with TLE. © 2010 Wiley Periodicals, Inc., Inc.     

The role of circulating miRNAs and CA19-9 in pancreatic cancer diagnosis

Diagnosis and treatment of pancreatic ductal adenocarcinoma (PA) remains a challenge in clinical practice. The aim of this study was to assess the role of microRNAs (miRNAs-21, -23a, -100, -107, -181c, -210) in plasma and tissue as possible biomarkers in the diagnosis of PA. Samples of plasma (PAp-n = 13), pancreatic tumors (PAt-n = 18), peritumoral regions (PPT-n = 9) were collected from patients during the surgical procedure. The control group consisted of samples from patients submitted to pancreatic surgery for trauma or cadaveric organs (PC-n = 7) and healthy volunteers donated blood (PCp-n = 6). The expression profile of microRNAs was measured in all groups using RT-PCR, serum CA19-9 levels were determined in PA and PC. In tissue samples, there was a difference in the expression of miRNAs-21, -210 (p < 0.05) across the PAt, PC and PPT groups. The PAp showed overexpression of miRNAs-181c, -210 (p < 0.05) when compared to PCp. The combination of miRNAs-21, -210 tissue expression and serum CA19-9 showed 100% accuracy in the diagnosis of PA, as well as miR-181c expression in the plasma (PApxPCp). The expression of microRNAs in plasma proved to be a promising tool for a noninvasive detection test for PA, as well as further studies will evaluate the utility of microRNAs expression as biomarkers for prognostic and response to therapy in PA.     

Comparative analysis of the pathological events involved in immune and non‐immune TRALI models

Background and Objectives Transfusion‐related acute lung injury (TRALI) is characterized by leukocyte transmigration and alveolar capillary leakage shortly after transfusion. TRALI pathogenesis has not been fully elucidated. In some cases, the infusion of alloantibodies (immune model), whereas in others the combination of neutrophil priming by proinflammatory molecules with the subsequent infusion of biological response modifiers (BRMs) in the hemocomponent (non‐immune model) have been implicated. Our aim was to compare the pathological events involved in TRALI induced by antibodies or BRMs using murine models. Materials and Methods In the immune model, human HNA‐2⁺ neutrophils were incubated in vitro with a monoclonal antibody (anti‐CD177, clone 7D8) directed against the HNA‐2 antigen and injected i.v. in NOD/SCID mice. In the non‐immune model, BALB/c mice were treated with low doses of lipopolysaccharide (LPS) followed by platelet‐activating factor (PAF) infusion 2 h later. Forty minutes after PAF administration, or 6 h after neutrophil injection, lungs were isolated and histological analysis, determination of a variety of cytokines and chemokines including keratinocyte‐derived chemokine (KC), MIP‐2, the interleukins IL‐1β, IL‐6, IL‐8 as well as TNFα, cell influx and alveolar capillary leakage were performed. Results In both models, characteristic histological findings of TRALI and an increase in KC and MIP‐2 levels were detected. In contrast to the immune model, in the non‐immune model, there was a dramatic increase in IL‐1β and TNFα. However, capillary leakage was only detected if PAF was administrated. Conclusions Regardless of the triggering event(s), KC, MIP‐2 and integrins participate in TRALI pathogenesis, whereas PAF is essential for capillary leakage when two events are involved.     

A glycoprotein inhibitor of in vitro granulopoiesis associated with AIDS

Patients infected with the human immunodeficiency virus (HIV) often present with neutropenia. To elucidate the mechanism(s) of this HIV- related neutropenia, we assessed the proliferative capacity of the granulocyte-macrophage progenitor cell (CFU-GM) from the bone marrow (BM) of 78 patients within the AIDS spectrum manifesting symptoms or signs related to HIV infection. Of these, 70 had a significant deficit in the growth of this committed progenitor when compared with normal controls (P less than .01). Further analysis revealed that the nucleated bone marrow cells from AIDS and AIDS-related complex (ARC) patients inhibited the growth of CFU-GMs from normal individuals when cocultured in agar (P less than .001). Control CFU-GMs were also inhibited when they were cultured over feeder layers containing patients' BM cells (P less than .001). Conditioned media obtained from the liquid culture of patients' BM cells did not inhibit normal control CFU-GM growth to a degree different from that of the cells themselves (P greater than .4). Analysis of these conditioned media by polyacrylamide gel electrophoresis (PAGE) revealed a unique glycoprotein (gp) with a mol wt of 84 kd. Further studies revealed that this gp possessed the inhibitory activity. These data suggest that this gp may be an important factor in HIV-related neutropenia. The presence of gp84 was independent of drugs administered to the patients.     

Determinants of demand for total hip and knee arthroplasty: a systematic literature review

Background

Specialized drug shops such as pharmacies and drug shops are increasingly becoming important sources of treatment. However, knowledge on their regulatory performance is scarce. We set out to systematically review literature on the characteristics, knowledge and practices of specialized drug shops in Sub-Saharan Africa.

Methods

We searched PubMed, EMBASE, WEB of Science, CAB Abstracts, PsycINFO and websites for organizations that support medicine policies and usage. We also conducted open searches using Google Scholar, and searched manually through references of retrieved articles. Our search included studies of all designs that described characteristics, knowledge and practices of specialized drug shops. Information was abstracted on authors, publication year, country and location, study design, sample size, outcomes investigated, and primary findings using a uniform checklist. Finally, we conducted a structured narrative synthesis of the main findings.

Results

We obtained 61 studies, mostly from Eastern Africa, majority of which were conducted between 2006 and 2011. Outcome measures were heterogeneous and included knowledge, characteristics, and dispensing and regulatory practices. Shop location and client demand were found to strongly influence dispensing practices. Whereas shops located in urban and affluent areas were more likely to provide correct treatments, those in rural areas provided credit facilities more readily. However, the latter also charged higher prices for medicines. A vast majority of shops simply sold whatever medicines clients requested, with little history taking and counseling. Most shops also stocked popular medicines at the expense of policy recommended treatments. Treatment policies were poorly communicated overall, which partly explained why staff had poor knowledge on key aspects of treatment such as medicine dosage and side effects. Overall, very little is known on the link between regulatory enforcement and practices of specialized drug shops.

Conclusions

Evidence suggests that characteristics and practices of specialized drug shops differ across rural and urban locations, and that these providers are highly responsive to client demand. However, there is a dearth in knowledge on how regulatory enforcement influences their characteristics and practices, and what strategies can be employed to strengthen the governance of the retail pharmaceutical sector.