The evaluation of gastrointestinal function in diabetic patients

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Incidence and determinants of moderate COPD (GOLD II) in male smokers aged 40–65 years: 5-year follow up

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major health problem with an estimated prevalence of 10-15% among smokers. The incidence of moderate COPD, as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), is largely unknown. AIM: To determine the cumulative incidence of moderate COPD (forced expiratory volume in 1 second/forced vital capacity ratio [FEV1/FVC] <0.7 and FEV1 <80% predicted) and its association with patient characteristics in a cohort of male smokers. DESIGN: Prospective cohort study. SETTING: The city of IJsselstein, a small town in the Netherlands. METHOD: Smokers aged 40-65 years who were registered with local GPs, participated in a study to identify undetected COPD. Baseline measurements were taken in 1998 of 399 smokers with normal spirometry (n = 292) or mild COPD (FEV1/FVC <0.7 and FEV1 >or=80% predicted, n = 107) and follow-up measurements were conducted in 2003. RESULTS: After a mean follow-up of 5.2 years, 33 participants developed moderate COPD (GOLD II). This showed an estimated cumulative incidence of 8.3% (95% CI = 5.8 to 11.4) and a mean annual incidence of 1.6%. No participant developed severe airflow obstruction. The risk of developing moderate COPD in smokers with baseline mild COPD (GOLD I) was five times higher than in those with baseline normal spirometry (one in five versus one in 25). CONCLUSIONS: In a cohort of middle-aged male smokers, the estimated cumulative incidence of moderate COPD (GOLD II) over 5 years was relatively high (8.3%). Age, childhood smoking, cough, and one or more GP contacts for lower respiratory tract problems were independently associated with incident moderate COPD.     

The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.      

Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer’s disease

The neurofibrillary tangles (NFT) and amyloid‐ß plaques (AP) that comprise Alzheimer’s disease (AD) neuropathology are associated with neurodegeneration and microglial activation. Activated microglia exist on a dynamic spectrum of morphologic subtypes that include resting, surveillant microglia capable of converting to activated, hypertrophic microglia closely linked to neuroinflammatory processes and AD neuropathology in amnestic AD. However, quantitative analyses of microglial subtypes and neurons are lacking in non‐amnestic clinical AD variants, including primary progressive aphasia (PPA‐AD). PPA‐AD is a language disorder characterized by cortical atrophy and NFT densities concentrated to the language‐dominant hemisphere. Here, a stereologic investigation of five PPA‐AD participants determined the densities and distributions of neurons and microglial subtypes to examine how cellular changes relate to AD neuropathology and may contribute to cortical atrophy. Adjacent series of sections were immunostained for neurons (NeuN) and microglia (HLA‐DR) from bilateral language and non‐language regions where in vivo cortical atrophy and Thioflavin‐S‐positive APs and NFTs were previously quantified. NeuN‐positive neurons and morphologic subtypes of HLA‐DR‐positive microglia (i.e., resting [ramified] microglia and activated [hypertrophic] microglia) were quantified using unbiased stereology. Relationships between neurons, microglia, AD neuropathology, and cortical atrophy were determined using linear mixed models. NFT densities were positively associated with hypertrophic microglia densities (P < 0.01) and inversely related to neuron densities (P = 0.01). Hypertrophic microglia densities were inversely related to densities of neurons (P < 0.01) and ramified microglia (P < 0.01). Ramified microglia densities were positively associated with neuron densities (P = 0.02) and inversely related to cortical atrophy (P = 0.03). Our findings provide converging evidence of divergent roles for microglial subtypes in patterns of neurodegeneration, which includes hypertrophic microglia likely driving a neuroinflammatory response more sensitive to NFTs than APs in PPA‐AD. Moreover, the accumulation of both NFTs and activated hypertrophic microglia in association with low neuron densities suggest they may collectively contribute to focal neurodegeneration characteristic of PPA‐AD.     

Osteometric Dimensions of the Laminas of the Spine

The present study was undertaken to evaluate the dimensions of the laminas from C2 to L5 by using adult human spine specimens for the objective of providing a set of quantitative data for the laminas from C2 to L5 vertebrae.There exists enormous amount of Anatomic data based on facet and pedicle parameters by different research workers, but it seems that the detailed studies based on measurements of laminar parameters from cervical to lumbar spines are almost nil.Forty spines (920 vertebrae) were considered for the present study. Anatomic evaluation of the laminas'included the laminar height, width, thickness, width angle & slope angle.The greatest laminar height was observed at T11 for males & females ( 22.8 ± 2.1 mm, 23.0 + 1.8mm) respectively. There was a marked change in pattern at L5 where there was a decrease in laminar height from that of preceding lumbar levels.The greatest laminar width was at-L5 for males & females (12.1 ± 2.4mm 11.5 ± 2.1 mm ) respectively. The laminar thickness was maximum at T3 for males and females (5:2 ± 0.7mm & 5.1 ± 0.2mm ) respectively. The maximum width angle was at T9 for males (99.2 ± 9.7mm) & at L4for females (100.6 ± 12.3mm). The-slope angle was maximum at L5 for males and females (113.5 ± 4.8mm & 118.0 ± 1.4mm) respectively.Thus, for the proper, understanding of the weight transmission through the spine and it related hypothesis the Anatomic parameters of the laminas provided by the present study are very important and also they provide an adequate database necessary for the surgical placement of sublaminar instruments in spine related surgeries.     

Effect of shared care on blood pressure in patients with chronic kidney disease: a cluster randomised controlled trial

Background

Chronic kidney disease (CKD) is highly prevalent in patients with diabetes or hypertension in primary care. A shared care model could improve quality of care in these patients

Aim

To assess the effect of a shared care model in managing patients with CKD who also have diabetes or hypertension.

Design and setting

A cluster randomised controlled trial in nine general practices in The Netherlands.

Method

Five practices were allocated to the shared care model and four practices to usual care for 1 year. Primary outcome was the achievement of blood pressure targets (130/80 mmHg) and lowering of blood pressure in patients with diabetes mellitus or hypertension and an estimated glomerular filtration rate (eGFR)<60ml/min/1.73m².

Results

Data of 90 intervention and 74 control patients could be analysed. Blood pressure in the intervention group decreased with 8.1 (95% CI = 4.8 to 11.3)/1.1 (95% CI = −1.0 to 3.2) compared to −0.2 (95% CI = −3.8 to 3.3)/−0.5 (95% CI = −2.9 to 1.8) in the control group. Use of lipid-lowering drugs, angiotensin-system inhibitors and vitamin D was higher in the intervention group than in the control group (73% versus 51%, 81% versus 64%, and 15% versus 1%, respectively, [P = 0.004, P = 0.01, and P = 0.002]).

Conclusion

A shared care model between GP, nurse practitioner and nephrologist is beneficial in reducing systolic blood pressure in patients with CKD in primary care.     

Decompensated cirrhosis-related admissions in a large urban hospital in Uganda: prevalence,clinical and laboratory features and implications for planning patient management

Background

Cirrhosis-related complications are a major cause of morbidity and mortality in areas where its risk factors are endemic.

Objective

We determined the prevalence of decompensated cirrhosis among patients on the gastroenterology service of Mulago Hospital and described the clinical and laboratory features of these patients.

Methods

All patients admitted to the unit were assessed and their diagnosis documented. Patients with cirrhosis had clinical features of decompensation recorded. History of alcohol consumption was taken and testing for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) performed.

Results

Between September 2010 and January 2011, we enrolled 482 patients. The majority (53.7%) were male, overall median age 38 years. Decompensated cirrhosis was diagnosed in 85 (17.6%) patients. Of the 85 patients, 47 (55.3%) gave a history of alcohol intake, HBsAg was positive in 23 (27.1%) and anti-HCV in 3 (3.5%). Decompensation was defined by ascites among 81 (95.3%) patients, variceal bleeding in 31 (36.5%), encephalopathy in 20 (23.5%).

Conclusion

Cirrhosis is common in Mulago hospital presenting mainly with ascites and variceal bleeding. Aside from controlling causes of liver diseases, especially alcohol and hepatitis B virus infection, in the interim it is necessary to manage complications in patients who already have cirrhosis.     

An electrophysiological index of stimulus unfamiliarity

This study investigated the functional significance of the N2 response to novel stimuli. In one condition, background, target, and deviant stimuli were simple geometric figures. In a second condition, all stimulus types were unfamiliar/unusual figures. In a third condition, background and target stimuli were unusual figures and deviant stimuli were simple shapes. Unusual figures, whether they were deviant, target, or background stimuli, evoked larger N2 responses than their simple, familiar counterparts. N2 elicited by an unusual background stimulus was larger than that evoked by simple, deviant stimuli, a pattern opposite that exhibited by the subsequent P3. Deviance from immediate context had limited influence over N2 amplitude. The results suggest that novelty N2 and novelty P3 reflect the processing of different aspects of "novel" visual stimuli. The novelty P3 is particularly sensitive to deviation from immediate context. In contrast, the novelty N2 is sensitive to deviation from long-term context that renders a stimulus unfamiliar and difficult to encode.