Prospective analysis of clinical and cytogenetic features of 435 cases of MDS diagnosed using the WHO (2001) classification: a prognostic scoring system for predicting survival in RCMD

We characterized the prevalence, clinical and cytogenetic characteristics and survival of 435 patients diagnosed with de novo MDS in a single laboratory according to WHO criteria, and compared the utility of different scoring systems to predict survival for individual subtypes of MDS. The mean follow-up period was 25.1 (5.5–53.2) months. Our results confirm major differences in the age-distribution and prevalence of individual subtypes of MDS between Asian and Western patients with a median age of 58 years and a predominance of RCMD (69.9%). Survival rates were similar to those reported in the West: the 3-year survival rate for MDS was 46.7% with a median survival time for RCMD of 38 months and RAEB, 10 months. We found that the IPSS and WPSS scoring systems, which are weighted heavily by blast cell count and karyotype, were not independent predictors for survival in RCMD patients. Multivariate analysis demonstrated that a scoring system based on age (≥60 years), ANC (<1.0 × 10⁹/L), Hb (<90 g/L), number of cytopenias and complex karyotype is a more useful predictor of survival in RCMD.     

Evidence of marked sexual behavior change associated with low HIV-1 seroconversion in 149 married couples with discordant HIV-1 serostatus: experience at an HIV counselling center in Zaire

To determine the effect of an HIV-1 counselling program on 149 married Zairian couples with discordant HIV-1 serology, the rates of HIV-1 seroconversion and reported condom utilization have been observed during 382.4 person-years of follow-up (minimum follow-up time per couple of 6 months). Before determination of HIV-1 serostatus and counselling, less than 5% of these couples had ever used a condom. One month after notification of HIV-1 serostatus and counselling, 70.7% of couples reported using condoms during all episodes of sexual intercourse. At 18 months follow-up, 77.4% of the 140 couples still being followed reported continued use of condoms during all episodes of sexual intercourse. At the time of notification of HIV-1 serostatus, 18 couples experienced acute psychological distress. Home-based counselling by trained nurses resolved these difficulties in all but three couples who subsequently divorced. Intensive counselling following notification of HIV-1 serostatus led to low rates of HIV-1 seroconversion (3.1% per 100 person-years of observation) in Zairian married couples with discordant HIV-1 serostatus who voluntarily attended an HIV counselling center.     

Changes in glucose transport and protein kinase Cβ2 in rat skeletal muscle induced by hyperglycaemia

Abstract Aims/hypothesis. We have previously reported that hyperglycaemia activates glucose transport in skeletal muscle by a Ca²⁺-dependent pathway, which is distinct from the insulin-signalling pathway. The aim of this study was to explain the signalling mechanism by which hyperglycaemia autoregulates glucose transport in skeletal muscle. Methods. Isolated rat soleus muscle was incubated in the presence of various concentrations of glucose or 3-O-methylglucose and protein kinase C and phospholipase C inhibitors. Glucose transport activity, cell surface glucose transporter 1 and glucose transporter 4 content and protein kinase C translocation was determined. Results. High concentrations of 3-O-methylglucose led to a concentration-dependent increase in [³H]-3-O-methylglucose transport in soleus muscle. Dantrolene, an inhibitor of Ca²⁺ released from the sarcoplasmic reticulum, decreased the V_max and the K_m of the concentration-response curve. Protein kinase C inhibitors (H-7 and GF109203X) inhibited the stimulatory effect of high glucose concentrations on hexose transport, whereas glucose transport stimulated by insulin was unchanged. Incubation of muscle with glucose (25 mmol/l) and 3-O-methylglucose (25 mmol/l) led to a three fold gain in protein kinase Cβ ₂ in the total membrane fraction, whereas membrane content of protein kinase Cα, β ₁, δ, ɛ and ϑ were unchanged. A short-term increase in the extracellular glucose concentration did not change cell surface recruitment of glucose transporter 1 or glucose transporter 4, as assessed by exofacial photolabelling with [³H]-ATB-BMPA bis-mannose. Conclusion/interpretation. Protein kinase Cβ ₂ is involved in a glucose-sensitive, Ca²⁺-dependent signalling pathway, which is possibly involved in the regulation of glucose transport in skeletal muscle. This glucose-dependent increase in 3-0-methylglucose transport is independent of glucose transporter 4 and glucose transporter 1 translocation to the plasma membrane and may involve modifications of cell surface glucose transporter activity. [Diabetologia (1999) 42: 1071–1079] Received: 1 March 1999 and in revised form: 20 April 1999     

Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge

BACKGROUND: Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure, persistently high rates of readmission, especially within the first month of discharge, continue to be documented. AIMS: As part of an ongoing randomized study on the value of multidisciplinary care in a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure population, we examined the effects of this intervention on previously high (20%) 1-month readmission rates. METHODS: Unlike previous studies of this approach, both multidisciplinary (MC) and routine care (RC) populations were cared for by the cardiology service, complied with adherence to clinical stability criteria prior to discharge (100% of patients) and received at least target dose angiotensin-converting enzyme (ACE) inhibition with perindopril prior to discharge (94% of indicated patients). We analysed death and unplanned readmission for heart failure at 1 month. RESULTS: This early report from the first 70 patients (67% male, 71% systolic dysfunction with a mean ejection fraction of 31.0+/-6.7%) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups. This unexpected result represents a dramatic improvement both for this patient cohort (20% 30-day readmission rate prior to enrollment reduced to 0% following the index admission in both care groups) and in comparison with available data. CONCLUSIONS: Critical contributors to this improvement appear to be specialist cardiology care, adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge. Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition.     

Insulin- and glucose-induced phosphorylation of the Na(+),K(+)-adenosine triphosphatase alpha-subunits in rat skeletal muscle.

Phosphorylation of the alpha-subunits of Na(+),K(+)-adenosine triphosphatase in response to insulin, high extracellular glucose concentration, and phorbol 12-myristate 13-acetate was investigated in isolated rat soleus muscle. All three stimuli increased alpha-subunit phosphorylation approximately 3-fold. Phorbol 12-myristate 13-acetate- and high glucose-induced phosphorylation of the alpha-subunit was completely abolished by the PKC inhibitor GF109203X, whereas insulin-stimulated phosphorylation was only partially reduced. Notably, insulin stimulation resulted in phosphorylation of the alpha-subunit on serine, threonine, and tyrosine residues, whereas high extracellular glucose or phorbol 12-myristate 13-acetate stimulation mediated phosphorylation only on serine and threonine residues. Insulin stimulation resulted in translocation of Na(+),K(+)-adenosine triphosphatase alpha(2)-subunit to the plasma membrane and increased Na(+),K(+)-adenosine triphosphatase activity in the same membrane fraction. High glucose had no effect on alpha-subunits distribution. Immunoprecipitation with antiphosphotyrosine antibody and subsequent Western blot analysis with anti-alpha(1)- and -alpha(2)-subunit antibodies revealed that both alpha(1)- and alpha(2)-subunit isoforms underwent phosphorylation on tyrosine residues in response to insulin, although with different time course and magnitude. Thus, we show that insulin-stimulated phosphorylation of Na(+),K(+)-adenosine triphosphatase alpha-subunit occurs via a PKC- and tyrosine kinase-dependent mechanism, whereas high glucose-induced phosphorylation is only PKC-dependent. Phosphorylation of Na(+),K(+)-adenosine triphosphatase alpha-subunits may be involved in regulation of Na(+),K(+)-adenosine triphosphatase activity by insulin or high extracellular glucose in skeletal muscle.     

Clinical assessment and core outcome variables are poor predictors of hip arthritis diagnosed by MRI in juvenile idiopathic arthritis

OBJECTIVES: To compare the diagnostic performance of clinical assessment against magnetic resonance imaging (MRI) diagnosed hip arthritis in a juvenile idiopathic arthritis (JIA) population. To determine the clinical and serological predictors of MRI diagnosed hip arthritis. METHODS: A total of 34 JIA patients with established disease (mean disease duration 6.3 yrs) had their hip MRIs scored for features of active hip arthritis and hip damage. Results were compared with clinical variables (disease subtype, history of hip pain, core outcome variables (COV)) and the clinician's assessment of active hip arthritis. RESULTS: MRI features of active hip arthritis were found in 45 hips (70%) and hip damage in 36 hips (56%). Clinical assessment had fair agreement with MRI scoring of active arthritis in patients with disease duration <4 yrs (kappa score 0.38, P = 0.045). Clinical assessment had a sensitivity of 25.7% and specificity of 91% for detecting MRI diagnosed arthritis. Of the core outcome variables only erythrocyte sedimentation rate predicted inflammation detected on MRI (r = 0.44, P = 0.014). CONCLUSIONS: The association between the clinician's assessment, core outcome variables and MRI findings in this study was limited. This indicates that clinical and laboratory findings are inadequate diagnostic tools for the assessment of hip arthritis when compared with MRI as the gold standard.     

功能性胃肠病的根源——脑肠轴神经系统记忆假说

功能性胃肠病(functionalgastrointestinaldisorders,FGID)以消化道动力与内脏感觉异常为主要病理生理特征并有多种症状重叠、多变或相互转换以及反复发作、较难治愈等特点;其病因和发病机制目前仍未完全清楚.本文将大脑记忆外延提出FGID的根源是脑肠轴神经系统记忆的假说,并用这个假说解释说明FGID的各种特点,以及治疗FGID的思路和方法.     

Male partner voluntary counselling and testing associated with the antenatal services in Kinshasa, Democratic Republic of Congo: a randomized controlled trial

Low male participation in voluntary counselling and testing (VCT) services at antenatal clinics (ANCs) represents a lost HIV-prevention opportunity. A three-arm randomized controlled trial (RCT) was conducted that offered VCT at a neighbourhood health centre, bar or church to the male partners of pregnant women attending a maternity unit in Kinshasa, Democratic Republic of Congo (DRC). The primary outcome was the proportion of male participation at VCT; secondary outcomes were uptake of couple counselling and determinants of male and couple participation. From a total of 2706 women included in the study, 591 male partners (22%) attended one of the three venues. Male participation was significantly higher in bars (26%, P < 0.001), and higher but not statistically significant in church-based VCT (21%, P = 0.163) compared with health centre VCT (18%). Male participation in VCT associated with ANCs was higher in non-health service settings, particularly in bars. A combination of different strategies rather than single targeted interventions will be needed to increase VCT uptake in male partners of women seeking VCT at ANCs.     

European Society of Cardiology Heart Failure Association Standards for delivering heart failure care

The management of heart failure (HF) is complex. As a consequence, most cardiology society guidelines now state that HF care should be delivered in a multiprofessional manner. The evidence base for this approach now means that the establishment of HF management programmes is a priority. This document aims to summarize the key elements which should be involved in, as well as some more desirable features which can improve the delivery of care in a HF management programme, while bearing in mind that the specifics of the service may vary from site to site. We envisage a situation whereby all patients have access to the best possible care, including improved access to palliative care services, informed by and responsive to advances in diagnosis management and treatment. The goal should be to provide a 'seamless' system of care across primary and hospital care so that the management of every patient is optimal, no matter where they begin or continue their health-care journey.