Increased prevalence and risk of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China.

AIMS: To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes mellitus. METHODS: We recruited patients with Type 2 diabetes with a BMI ≥ 24 kg/m2 , who visited the diabetes clinics of 60 hospitals in 21 cities in Guangdong Province, China from August 2011 to March 2012. Anthropometric measurements, biochemical tests and abdominal ultrasonography were performed for all the patients. RESULTS: The study included 3861 patients (1860 men) with a mean ± sd (range) age of 58.91 ± 13.06 (18-90) years. Non-alcoholic fatty liver disease was found in 1751 patients (45.4%), with a significantly higher prevalence among men than women (48.0 vs 42.9%). The peak of non-alcoholic fatty liver disease prevalence was in patients with a BMI of 34-35 kg/m2 , those with a triglyceride/HDL cholesterol ratio of 5.5-6.0, men aged < 30 years and women aged 40-50 years. Assessment using the BARD (BMI, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score system showed that the prevalence of advanced fibrosis was 80.52% in all patients and that women had a higher prevalence than men (86.52 vs 74.16%). Multiple logistic regression analyses showed that dyslipidaemia, BMI and 2-h postprandial plasma glucose were independent risk factors for non-alcoholic fatty liver disease, while heart rate and female gender were protective factors. CONCLUSION: The prevalence of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China is high. Multiple metabolic disorders were significantly associated with non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes.

Effects of pioglitazone and glipizide on platelet function in patients with type 2 diabetes.

OBJECTIVE: Platelet hyper-reactivity is one of the most important causes of accelerated atherosclerosis and increased risk of thrombotic vascular events associated with type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of different add-on anti-diabetic therapies on platelet function in T2DM patients. PATIENTS AND METHODS: A three-group parallel study was conducted in 120 patients with T2DM (HbA1c > 7%) undergoing treatment with metformin. Patients were randomly assigned to receive add-on therapy with glipizide or pioglitazone. Markers of PF (platelet PAC-1 binding, p-selectin expression and adenosine diphosphate-induced platelet aggregation) were measured at weeks 0, 4 and 24. Primary outcome was effects of pioglitazone and glipizide on platelet aggregation. Secondary outcome was the related influencing factors of platelet aggregation. RESULTS: There were no significant differences in baseline characteristics between glipizide and pioglitazone groups. After 24 weeks, fasting blood glucose (p < 0.01) and HbA1c (p < 0.01) were higher in pioglitazone group than those in glipizide group. Fasting insulin (p < 0.01) and HOMA-IR (p < 0.01) were lower in pioglitazone group than that in glipizide group. Markers of platelet function were significantly decreased in both groups at 24 weeks (PAC-1: pioglitazone: -63.3%; glipizide: -45.9%; p-selectin: pioglitazone: -73.9%; glipizide: -54.9%; platelet aggregation: pioglitazone: -24.1%; glipizide: -13.4%; all p < 0.01 vs. baseline), but the decrease in platelet function was more significant in pioglitazone group (p < 0.05). Multiple linear regression analyses showed that platelet aggregation was independently associated with treatment groups (p < 0.001), Triglyceride (p = 0.009) and HDL-C (p = 0.015). CONCLUSIONS: Add-on therapy with pioglitazone may be more effective than glipizide for inhibiting platelet activation in T2DM.

Efficacy and safety of pregabalin for treating painful diabetic peripheral neuropathy: a meta-analysis.

BACKGROUND: Pregabalin is considered to be an effective treatment for painful diabetic peripheral neuropathy (DPN), but controversy exists about its efficacy and safety. We performed a meta-analysis to systematically assess the efficacy and safety of pregabalin for managing pain associated with DPN. METHODS: Medline, EMBASE, and the Cochrane Central Register were searched in July 2014 for randomized, double-blind, placebo-controlled trials published in English on the use of pregabalin to treat DPN-associated pain. Principal outcomes were mean pain score after pregabalin treatment and the proportions of patients showing a pain reduction of at least 50%. RESULTS: Nine trials involving a total of 2056 participants were identified. Pooled analysis showed that pregabalin was significantly superior to placebo for improving mean pain scores [mean difference (MD) = -0.79, P < 0.001]. Pregabalin reduced pain below baseline by at least 50% in a significantly greater proportion of patients than placebo did [relative risk = 1.54, P < 0.001]. Patients were more likely to self-report their status as 'improved' after taking pregabalin than placebo (relative risk = 1.38, P < 0.001). Pregabalin also improved sleep quality more than placebo (MD = -0.88, P < 0.001). On the other hand, patients receiving pregabalin were more likely to experience mild side effects than were patients receiving placebo. CONCLUSIONS: Our meta-analysis indicates that pregabalin is more effective than placebo for managing DPN-associated pain and other symptoms that reduce quality of life. The drug is also reasonably well tolerated.

Anterior development in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum: hunchback and orthodenticle expression.

In the dipteran Drosophila, the genes bicoid and hunchback work synergistically to pattern the anterior blastoderm during embryogenesis. bicoid, however, appears to be an innovation of the higher Diptera. Hence, in some non-dipteran insects, anterior specification instead relies on a synergistic interaction between maternally transcribed hunchback and orthodenticle. Here we describe how orthologues of hunchback and orthodenticle are expressed during oogenesis and embryogenesis in the parthenogenetic and viviparous form of the pea aphid, Acyrthosiphon pisum. A. pisum hunchback (Aphb) mRNA is localized to the anterior pole in developing oocytes and early embryos prior to blastoderm formation - a pattern strongly reminiscent of bicoid localization in Drosophila. A. pisum orthodenticle (Apotd), on the other hand, is not expressed prior to gastrulation, suggesting that it is the asymmetric localization of Aphb, rather than synergy between Aphb and Apotd, that regulates anterior specification in asexual pea aphids.

Transduction capabilities of neonatal ventricular afferent neurons in vivo.

We sought to determine the capacity of ventricular sensory nerve endings (neurites) associated with neonatal nodose ganglion afferent neurons to transduce mechanical and chemical stimuli in situ. Spontaneous activity generated by 17 nodose ganglion cardiac afferent neurons was identified in 8 anesthetized neonatal pigs (10-21 days old) using extracellular recording recording techniques. The activity generated by afferent neurons was studied when their ventricular sensory neurites were exposed to local mechanical or chemical stimuli, following systemic administration of specific chemicals or during brief periods of apnea. Gentle mechanical distortion of their ventricular sensory fields enhanced the activity generated by 6 spontaneously active afferent neurons, while suppressing the activity generated by another 3 neurons. Afferent neuronal activity was either enhanced or suppressed when the following chemicals were applied to identified ventricular epicardial sensory fields: the sodium channel modifier veratridine (92% of tested neurons); the P1-purinoceptor agonist adenosine (92%); the neuropeptides angiotensin II (100%), bradykinin (90%) and substance P (90%); and the nitric oxide donor S-nitroso-N-acetylpenicillamine (100%). Epicardial application of isoproternol or nicotine induced modest neuronal responses. Cardiac afferent neurons were also affected when these chemicals were administered systemically. Apnea of 60-100 s duration modified (enhanced, n = 2; suppressed, n = 5) the activity generated by most identified afferent neurons. The estimated average conduction velocity of afferent axons associated with these neurons was 1.0 +/- 0.2 m/s. It is concluded that neonatal nodose ganglion cardiac afferent neurons respond to many of the chemicals known to modify adult cardiac afferent neurons. That cardiac afferent neurons are capable of sensing the mechanical and chemical milieu of the neonatal heart should be taken into account when considering altered neonatal cardiovascular status such as occurs during apnea.

Auscultation of the heart: a trial of classroom teaching versus computer-based independent learning.

Declining skills in auscultation of the heart prompted an evaluation of teaching methods for medical students. A comparison of classroom teaching and computer-aided independent learning of auscultation was carried out with two groups of approximately 20 second-year medical students. Both groups used approximately 20 recorded normal and abnormal heart sounds and murmurs, chosen to illustrate learning issues. For the classroom group a cardiologist presented each case through multiple stethophones and led the discussion. The individual study group used a new CD-ROM collection of cases and recordings in quiz format, with a hypertext link to a comprehensive text on auscultation and additional recordings. Students were tested with 16 multiple choice and 5 open questions on eight selected recordings, and evaluated the teaching by questionnaire. The classroom-taught students scored higher on open questions than the CD-ROM-taught group, but in general performance by both groups was satisfactory and equivalent. Students of both groups repeatedly had difficulty classifying regurgitant and ejection murmurs and identifying characteristics of the second heart sound. Both CD-ROM and classroom teaching methods were highly rated by students but most students preferred a combination.

Paediatric echocardiography by telemedicine--nine years' experience.

In 1987 we established a realtime echocardiography service by telemedicine from the paediatric cardiology department of a tertiary-care hospital in Halifax. The service was initially provided to single regional hospital but was expanded to six regional hospitals in the three Canadian Maritime Provinces. The system used a dial-up broadband video-transmission service provided by the telephone companies. Records of all transmissions were kept prospectively and reviewed to January 1997. A total of 324 transmissions were made. During 1995-96 there were 135 studies: 69 (51%) were urgent examinations of newborn children and 30 (22%) were urgent examinations of older children; repeat studies and postoperative checks (usually for pericardial effusion) accounted for the other 36 studies (27%). The images were of broadcast quality except in five cases where problems with transmission or poor sedation occurred. A comparison of 26 transmitted studies with repeat, 'in person' studies showed no important discrepancies in diagnosis. During the two-year study period, the cost of the network (equipment leasing costs and telecommunications costs) was C$90,000. Use of the telemedicine network saved unnecessary patient transfer in 31 cases. The cost of the transportation avoided was C$100,000-C$118,000. This review confirms our preliminary findings that broadband echocardiography transmission provides a service comparable in availability and accuracy to that provided in our paediatric cardiology division.

A novel method to create atrial septal defect using a cutting balloon in piglets.

A new method of creating atrial septal defect, using a 3- or 4-blade cutting balloon catheter combined with conventional static balloon dilation, is discussed. Radially directed surgical cuts made in the atrial septum were enlarged by balloon angioplasty, producing defects measuring 3 to 8 mm, with a mean Qp/Qs of 1.96/L.

Transaortic balloon valvoplasty of the pulmonary valve.

An unconventional transaortic to transductal approach was performed to perforate and dilate the pulmonary valve in pulmonary atresia. Ductal arteriosus patency was maintained by prostaglandin.

Successful treatment of supraventricular tachycardia-induced cardiomyopathy with amiodarone: case report and review of literature.

Permanent junctional reciprocating tachycardia (PJRT) is a rare cause of supraventricular tachycardia in the pediatric population and is resistant to most pharmacological therapy. A case of supraventricular tachycardia that, on the basis of postnatal electrocardiographic and Holter monitor evidence, was diagnosed as PJRT and presented in utero as an atypical tachycardia with severe tachycardia-induced cardiomyopathy confirmed postnatally is presented. It is the only case of which the authors are aware that was controlled in the neonatal period by amiodarone and that resulted in complete resolution of systolic dysfunction. The literature discussing how tachycardia may induce cardiomyopathy and the use of amiodarone in treatment both pre- and postnatally are reviewed.

Autoregulation of pit-1 gene expression mediated by two cis-active promoter elements.

The pit-1 gene is a member of a large family of genes that encode proteins which are involved in development and which contain a highly homologous region, referred to as the POU domain. Pit-1, a pituitary-specific transcription factor, can activate the transcription of the growth hormone and prolactin promoters. It is expressed in mature thyrotroph, somatotroph and lactotroph cell types of the anterior pituitary which arise sequentially during development; somatotrophs and lactotrophs, which secrete growth hormone and prolactin, respectively, are the last to arise. Intriguingly, during ontogeny, pit-1 transcripts are observed in the rat neural tube and neural plate (embryonic day 10-11) and disappear thereafter (day 13), only to reappear exclusively in the anterior lobe of the pituitary gland (day 15) just before activation of prolactin and growth hormone. This biphasic pattern suggests a complex mechanism of initial activation of pit-1 gene expression. Transcription and transfection analyses in vitro using wild-type and mutated promoters indicate that Pit-1 can positively autoregulate the expression of the pit-1 promoter as a consequence of binding to two Pit-1-binding elements. Mutation of the 5' Pit-1-binding site abolished positive autoregulation, whereas mutation of the element located immediately 3' of the cap site markedly increased expression of the pit-1 promoter. These data are consistent with a positive, attenuated autoregulatory loop that seems to function in maintaining pit-1 gene expression.

A family of POU-domain and Pit-1 tissue-specific transcription factors in pituitary and neuroendocrine development.

The anterior pituitary gland provides a model for investigating the molecular basis for the appearance of phenotypically distinct cell types, within an organ, a central question in development. The rat prolactin and growth hormone genes are selectively expressed in distinct cell types (lactotrophs and somatotrophs) of the anterior pituitary gland, which reflect differential mechanisms of gene activation or restriction because of interactions of multiple factors binding to these genes. We find that the pituitary-specific 33,000 dalton transcription factor, Pit-1, normally expressed in somatotrophs, lactotrophs, and thyrotrophs, can bind to and activate both growth hormone and prolactin promoters in vitro at levels even tenfold lower than those normally present in pituitary cells. In the case of the prolactin gene, high levels of expression in transgenic animals required two cis-active regions; a distal enhancer (-1.8 to -1.5 kb) and a proximal region (-422 to +33 bp). Each of these regions alone can direct low levels of fusion gene expression to prolactin-producing cell types in transgenic mice, but a synergistic interaction between these regions is necessary for high levels of expression. The initial appearance of the prolactin transgene expression closely follows the appearance of high levels of Pit-1, but later increases in expression coincident with appearance of mature lactotrophs suggest the operation of additional, critical positive factor(s). Unexpectedly, transgenes containing the distal enhancer removed from its normal context are expressed in both the prolactin-producing lactotrophs and the TSH-producing thyrotrophs, thereby suggesting that sequences flanking this enhancer are necessary to restrict expression to the correct cell type within the pituitary. These data indicate that distinct processes of gene activation and restriction are necessary for the fidelity of cell-type specific expression within an organ. Consistent with this model, we find that lactotroph cell lines that cannot express the growth hormone gene contain high levels of functional Pit-1. We suggest a large, highly related POU-domain gene family, potentially exceeding 100 members, has been conserved and expanded in evolution to meet the increasing requirements for more intricate patterns of cell phenotypes. The POU-domain subgroup of the homeodomain gene family, in concert with other homeodomain proteins and with other classes of transcription factors, is likely to contribute to the establishment of the mammalian neuroendocrine system.

A tissue-specific transcription factor containing a homeodomain specifies a pituitary phenotype.

Multiple related cis-active elements required for cell-specific activation of the rat prolactin gene appear to bind a pituitary-specific positive transcription factor(s), referred to as Pit-1. DNA complementary to Pit-1 mRNA, cloned on the basis of specific binding to AT-rich cell-specific elements in the rat prolactin and growth hormone genes, encodes a 33 kd protein with significant similarity at its carboxyl terminus to the homeodomains encoded by Drosophila developmental genes. Pit-1 mRNA is expressed exclusively in the anterior pituitary gland in both somatotroph and lactotroph cell types, which produce growth hormone and prolactin, respectively. Pit-1 expression in heterologous cells (HeLa) selectively activates prolactin and growth hormone fusion gene expression, suggesting that Pit-1 is sufficient to confer a characteristic pituitary phenotype. The structure of Pit-1 and its recognition elements suggests that metazoan tissue phenotype is controlled by a family of transcription factors that bind to related cis-active elements and contain several highly conserved domains.

An evaluation of the hot plate technique to study narcotic antagonists.

The mouse hot plate model, with slight differences from the way it is used to study narcotic analgesics, was evaluated as a method for determining the oral effectiveness, relative potency and duration of action of two standard narcotic antagonists, naloxone and naltrexone, and a new agent, 6-desoxy-6-methylene-naltrexone (ORF 11676). Naltrexone and ORF 11676 were found to be more effective orally than naloxone. Naltrexone and ORF 11676 were equipotent by 3 routes of administration and both were more potent than naloxone. Naloxone produced a significantly shorter duration of action than the other two drugs. It was concluded that the mouse hot plate method, used to detect and characterize the activity of narcotic antagonists, provides information compatible with that obtained in other species, including man.