Visual Field Compromised In Patients Suffering From Severe Menorrhagia

Purpose: To evaluate menorrhagia as a risk factor for compromised visual field Design: A cross-sectional cohort study Participants: 25 Menorrhagic patients and 23 non-menorrhagic female subjects Methods: Patients were recruited from the Obstetrics and Gynaecology clinic and divided into two groups. Those suffering from active menorrhagia were allocated into the disease group while those had never suffered from menorrhagia constituted the control group. All subjects completed a pictorial blood assessment chart (PBAC) to quantify the severity of their menorrhagia. All subjects then underwent an eye examination and investigations including visual field and optical coherent tomography. Main Outcome Measures: The mean PBAC was compared between the disease group and the control group. Correlation analysis was tested between PBAC and visual field global indices. Results: Subjects suffering from menorrhagia have a compromised performance in visual field when compared with subjects with no menorrhagia. A positive association was observed between the severity of menorrhagia and a poorer visual field performance. Conclusions: Menorrhagia may be a risk factor for visual field defects. Further research is encouraged to evaluate whether it may be a risk factor for glaucoma development or progression.published_or_final_versio

Prevalence of occult hepatitis B infection in a highly endemic area for chronic hepatitis B: A study of a large blood donor population

Background and aims: The aim of the present study was to determine the population prevalence of occult hepatitis B (OHB) infection and its clinical profile in a highly endemic area of chronic hepatitis B virus disease. Methods: OHB was first identified by individual sample testing for hepatitis B surface antigen (HBsAg) followed by nucleic acid testing (NAT) and vice versa for 3044 (cohort 1, stored sera from donation within 1 year) and 9990 (cohort 2, prospective study) blood donors, respectively. OHB was confirmed meticulously by ≥2 out of 3 tests with detectable hepatitis B virus (HBV) DNA using a sensitive standardised assay. Detailed serology and viral load in the serum and liver were studied. Results: The prevalence of OHB was 0.13% (4/3044) and 0.11% (11/9967) for cohort 1 and 2, respectively. In cohort 2, 10 out of 11 OHB samples were positive for anti-HBc (hepatitis B core antigen) antibody (all were immunoglobulin G). Seven had detectable anti-HBs. The serum HBV DNA levels were extremely low (highest 14.1 IU/ml). Of the six donors who underwent liver biopsies, all had normal liver biochemistry, extremely low liver HBV DNA (highest 6.21 copies/cell) and nearly normal liver histology. For those with viral sequence generation, none had the common HBsAg mutant G145R. Conclusions: The prevalence of OHB in a highly endemic area of chronic HBV was very low, thus implying a low impact on transfusion services. To implement universal screening, the high cost of NAT should be taken into account. OHB blood donors had very low HBV replication, and normal liver biochemistry and histology, conferring a favourable prognosis.published_or_final_versio

Seven-Year Treatment Outcome of Entecavir in a Real-World Cohort: Effects on Clinical Parameters, HBsAg and HBcrAg Levels

published_or_final_versio

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

A BKCa to Kv switch during spermatogenesis in the rat seminiferous tubules

Spermatogenesis is a complex cellular event during which the diploid germ cells differentiate and divide by mitosis and meiosis at specific time points along the spermatogenic cycle to generate the haploid spermatozoa. For this complex event to go in an orderly manner, cell differentiation and division must be precisely controlled by signals arising from within and outside the seminiferous tubules. Changes in the membrane potential of the germ cells are likely to be an important part of the signaling mechanism. We have applied the whole-cell patch clamp technique to identify and characterize ion channels in different spermatogenic cells from immature and mature rat testes fractionated by discontinuous Percoll gradient. A voltage- and Ca2+-dependent, outwardly rectifying current with gating and pharmacologic properties resembling the large conductance K+ channels (BKCa) was recorded from the spermatogonia and primary spermatocytes. Another voltage-dependent, outwardly rectifying current that was sensitive to 4-aminopyridine, a Kv channel blocker, was detected in spermatocytes and early spermatids. This current is likely caused by the smaller conductance, voltage-sensitive K+ channels (Kv). In some spermatogonia, both the BKCa channels and the Kv channels could be simultaneously detected in the same cell. It appears that during the course of spermatogenesis, there is up-regulation of Kv but down-regulation of BKCa. Reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemistry further confirmed the differential expression of the ion channels in different spermatogenic cells. We conclude that these ion channels may play an important role in the control of spermatogenesis.link_to_subscribed_fulltex

Expression of the cystic fibrosis transmembrane conductance regulator in rat spermatids: Implication for the site of action of antispermatogenic agents

To establish whether cystic fibrosis transmembrane conductance regulator (CFTR) is functionally expressed in the testis, we subjected spermatogenic cells from rat testes to analysis of CFTR mRNA, protein and channel activity. CFTR mRNA was detected in the testes of mature but not immature rats using reverse transcription-polymerase chain reaction analysis. Western blot analysis performed with a CFTR specific antibody revealed immunoreactivity in the membrane extract of spermatogenic cells. Immunohistochemical studies localized CFTR in round and elongated spermatids, but not in the fully developed spermatozoa. Using a whole-cell patch clamp technique, we recorded an inward current activated by intracellular cAMP (100 μmol/l) in round spermatids. The current displayed a linear I/V relationship and was inhibited by diphenylamine-2-carboxylate (DPC), a chloride channel blocker. Transfection of the rat germ cell CFTR cDNA into human embryonic kidney (HEK) 293 cells caused the expression of a cAMP-activated chloride current with CFTR characteristics. The current was completely blocked by the antispermatogenic agents 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid, lonidamine (500 υmol/l) and 1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid, AF2785 (250 υmol/l). These results taken together provide evidence that CFTR is differentially expressed in spermatids during spermiogenesis. We speculate that CFTR may interact with aquaporin to bring about cytoplasmic volume contraction which is an essential feature of spermiogenesis.link_to_subscribed_fulltex

Rabbit sex hormone binding globulin: Primary structure, tissue expression, and structure/function analyses by expression in Escherichia coli

Sex hormone binding globulin (SHBG) is a homodimeric plasma protein found in mammals that binds sex steroids with high affinity and regulates their bioavailability. The protein is identical in structure and properties to the androgen binding protein (ABP) found in the male reproductive tract. We have isolated a 1245-base pair rabbit SHBG cDNA encoding a reading frame for a signal peptide followed by a protein of 367 amino acids, which shares 79.0, 68.1 and 63.2% amino acid identity with the corresponding human, rat and mouse proteins respectively. Northern blot and host-nested PCR analyses indicated that rabbit SHBG is produced from a 1.6 kilobase mRNA in the liver of both sexes and in the testis. The rabbit SHBG cDNA was inserted into pGEX- 1λT for expression of glutathione S-transferase/SHBG fusion protein in Escherichia coli. The bacterial product bound 5α-dihydrotestoterone (DHT) in the same manner as the corresponding protein in serum. The dissociation constants (K(d)) for rabbit and human SHBGs produced in E. coli were 11.1 ± 1.1 nM and 2.1 ± 0.6 nM respectively, and rabbit SHBG formed a less stable protein-steroid complex (t( 1/4 )= 5 min) that human SHBG (t( 1/4 )>60 min). Unlike human SHBG, rabbit SHBG does not bind estradiol with high affinity. To aid in the identification of differences in the sequences of rabbit and human SHBG, which determine species differences in steroid-binding affinity and specificity, chimeras containing the 5'-terminal half of SHBG from one species and 3'-terminal half of SHBG from the other species were constructed and expressed. It was found that the chimeric proteins assumed similar steroid-binding affinity and specificity as the wild-type proteins when the amino (N)-terminal half of SHBG was derived from the same species. Replacement of the carboxyl (C)-terminal half of rabbit SHBG by the corresponding region of the human molecule increased the integrity of its steroid-protein complex. This supports the concept that amino acids within the N-terminal half of SHBG constitute the steroid-binding domain while the C-terminal half of the molecule may provide structural stability to the protein and its steroid-binding site.link_to_subscribed_fulltex

Cerebral grey, white matter and csf in never-medicated, first-episode schizophrenia

We report the first voxel-based morphometric (VBM) study to examine cerebral grey and white matter and cerebrospinal fluid (CSF) using computational morphometry in never-medicated, first-episode psychosis (FEP). Region-of-interest (ROI) analysis was also performed blind to group membership. 26 never-medicated individuals with FEP (23 with DSM-IV schizophrenia) and 38 healthy controls had MRI brain scans. Groups were balanced for age, sex, handedness, ethnicity, paternal socio-economic status, and height. Healthy controls were recruited from the local community by advertisement. Grey matter, white matter, and CSF: global brain volume ratios were significantly smaller in patients. Patients had significantly less grey matter volume in L and R caudate nuclei, cingulate gyri, parahippocampal gyri, superior temporal gyri, cerebellum and R thalamus, prefrontal cortex. They also had significantly less white matter volume in the R anterior limb of the internal capsule fronto-occipital fasciculus and L and R fornices, and significantly greater CSF volume especially in the R lateral ventricle. Excluding the 3 subjects with brief psychotic disorder did not alter our results. Our data suggest that fronto-temporal and subcortical-limbic circuits are morphologically abnormal in never-medicated, schizophrenia. ROI analysis comparing the schizophrenia group (n = 23) with the healthy controls (n = 38) confirmed caudate volumes were significantly smaller bilaterally by 11%, and lateral ventricular volume was significantly larger on the right by 26% in the patients. Caudate nuclei and lateral ventricular volume measurements were uncorrelated (Pearson correlation coefficient 0.30, p = 0.10), ruling out the possibility of segmentation artefact. Ratio of lateral ventricle to caudate volume was bilaterally significantly increased (p < 0.005, 2-tailed), which could represent an early biomarker in first-episode, never-medicated schizophrenia. © 2006 Elsevier B.V. All rights reserved.link_to_subscribed_fulltex

Early psychosis services for rural, remote and coastal communities in Australia

BACKGROUND: An effective means of reducing disability from psychotic disorders is the provision of early detection and intervention targeted at the prodromal phase. Current research and clinical programs for early psychosis (EP) have failed to encapsulate the specific needs of rural and remote communities (RARC) such as limited availability of mental health providers and long distances to travel for care (Fox et al, 1995). This study investigated access to care and service delivery for rural youths experiencing EP. METHODS: Routine clinical mental health service data were analysed for 10–25 year old patients across three rural regions of New South Wales. A large data set (N=1562) for the Central West (CW) rural region was compared to smaller data sets for the Far West (FW) remote and the North Coast (NC) coastal regions. Demographic, clinical and service features were analysed against characteristics specific to RARC. Clinical measures included the HoNOSCA, HoNOS and SDQ. RESULTS: EP patients in the CW represented 10.4% of patients accessing mental health services, but utilised services twice as often as non EP patients and absorbed 37.6% of inpatient service encounters. While the median distance to access service for CW EP patients was 88km, an absence of inpatient services for FW resulted in FW EP patients travelling as far as 895km for hospitalisation. CONCLUSIONS: The results emphasise the importance of developing specific EP services to address the diversity across RARC. The lack of appropriate and timely treatment for rural youths is likely to increase the impairment associated with EP