Twelve-hour fasting compared with expedited oral intake in the initial inpatient management of hyperemesis gravidarum: a randomised trial.

OBJECTIVE: To evaluate fasting for 12 hours compared with expedited oral feeding in hospitalised women with hyperemesis gravidarum (HG). DESIGN: Randomised trial. SETTING: University Hospital, Malaysia: April 2016-April 2017. POPULATION: One hundred and sixty women hospitalised for HG. METHOD: Women were randomised upon admission to fasting for 12 hours or expedited oral feeding. Standard HG care was instituted. MAIN OUTCOME MEASURE: Primary outcome was satisfaction score with overall treatment at 24 hours (0-10 Visual Numerical Rating Scale VNRS), vomiting episodes within 24 hours and nausea VNRS score at enrolment, and at 8, 16 and 24 hours. RESULTS: Satisfaction score, median (interquartile range) 8 (5-9) versus 8 (7-9) (P = 0.08) and 24-hour vomiting episodes were 1 (0-4) versus 1 (0-5) (P = 0.24) for 12-hour fasting versus expedited feeding, respectively. Repeated measures analysis of variance of nausea scores over 24 hours showed no difference (P = 0.11) between trial arms. Participants randomised to 12-hour fasting compared with expedited feeding were less likely to prefer their feeding regimen in future hospitalisation (41% versus 65%, P = 0.001), to recommend to a friend (65% versus 84%, P = 0.01; RR 0.8, 95% CI 0.6-0.9) and to adhere to protocol (85% versus 95%, P = 0.04; RR 0.9, 95% CI 0.8-1.0). Symptoms profile, ketonuria status at 24 hours and length of hospital stay were not different. CONCLUSION: Advisory of 12-hour fasting compared with immediate oral feeding resulted in a non-significant difference in satisfaction score but adherence to protocol and fidelity to and recommendation of immediate oral feeding to a friend were lower. The 24-hour nausea scores and vomiting episodes were similar. TWEETABLE ABSTRACT: Women hospitalised for hyperemesis gravidarum could feed as soon, as much and as often as can be tolerated compared with initial fasting.

Immunogenicity and Safety of the AS04-adjuvanted Human Papillomavirus-16/18 Cervical Cancer Vaccine in Malaysian Women Aged 18-35 years: A Randomized Controlled Trial.

INTRODUCTION: Cervical cancer is the third most common cancer in women worldwide. The HPV-16/18 AS04- adjuvanted vaccine (Cervarix©) has previously been shown to be highly immunogenic with a clinically acceptable safety profile. This phase IIIb, double-blind, randomized (1:1) and placebo controlled trial (NCT00345878) was designed to evaluate the vaccine immunogenicity against HPV-16 and HPV-18 as well as its safety and reactogenicity in Malaysian women. METHODS: Healthy women aged 18-35 years received intramuscularly three doses of either the vaccine (HPV group) or aluminium hydroxide (ALU group) at 0, 1, and 6 months. Antibody titers were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: A total of 271 eligible subjects were enrolled and 266 subjects completed the study. Initially seronegative subjects in the HPV group showed 100% seroconversion one month post-dose-3 for anti HPV-16 and anti-HPV-18 antibodies with geometric mean titers of 11107.5 (95% CI: 9727.3-12683.4) EL.U/mL and 4273.5 (95% CI: 3771.8-4841.9) EL.U/mL, respectively. Over 96% of subjects in both groups received all three vaccine doses. Solicited local (pain) and general symptoms (myalgia, fatigue, arthralgia and headache) were commonly reported in both HPV and ALU groups. Eight serious adverse events were reported throughout the study (five in the HPV group; three in the ALU group), all considered by investigators to be unrelated to vaccination. CONCLUSION: The HPV-16/18 AS04-adjuvanted vaccine was immunogenic and generally well tolerated in Malaysian women aged 18-35 years.

Paraquat poisoning: experience in hospital taiping (year 2008 - october 2011).

INTRODUCTION: Paraquat is a quaternary nitrogen herbicide which is highly toxic to human. Death is usually from respiratory failure and may occur within days up to a month after exposure. It is easily available and commonly abused to commit suicide. METHODOLOGY: This is a retrospective study describing the demographic characteristics, clinical features and outcomes of paraquat poisoning cases admitted to Hospital Taiping from 1st January 2008 to 30th October 2011. Medical records of 79 patients were reviewed. RESULT: Majority were of the Indian ethnicity (72.2%) followed by Chinese (13.9%) and Malay (10.1%). Majority was male (73.4%) and between 20 to 29 years old (34.2%). The median age of the patients was 30 years old. The mean length of stay was 6.2 days. Most exposures were intentional (69.6%) and presented to the hospital early at less than 6 hours after exposure (72.2%). Patients with positive urine paraquat result had significantly higher mortality rate compared to patients with negative results (47.4% vs 15.2% respectively). We found that neither hemofiltration nor immunosuppressive therapies help to improve survival. CONCLUSION: The non-survivor characteristics of patients with paraquat poisoning are intentional exposure, delay from exposure to hospital admission, urine paraquat positivity and manifestation of respiratory failure. The demographic characteristics, reasons for exposure and mortality rate are similar to previous reports. Urine paraquat may be used to assess severity of the exposure as well as prognosis. Hemofiltration and immunosuppression therapy do not improve patients' survival and paraquat remains a lethal killer.

Significant resolution of tuberculous pleural effusion on chemotherapy alone.

BACKGROUND: As a standard, significant pleural effusion, whether tuberculous (TB) or not, requires therapeutic thoracocentesis. We tested the hypothesis that standard anti-TB chemotherapy alone can resolve significant pleural effusion. METHODS: 20 eligible patients with TB pleural effusion of at least 30% of the hemithorax (10 with moderate-size and 10 with large-size effusion, respectively) were retrospectively reviewed for radiological resolution of their effusions at two, six and 12 months after commencement of standard six-month therapy. RESULTS: The mean percentage resolutions in both groups were comparable (48% vs 46% at two months; 59% vs 85% at six months; 84% vs 95% at 12 months). The mean sizes of effusions were also comparable (18% vs 33% at two months; 14% vs 10% at six months; 6% vs 4% at 12 months). Cigarette smoking and Indian ethnicity were univariately associated with incomplete resolution of effusions. CONCLUSION: Standard anti-TB chemotherapy alone appears to be sufficient to resolve significant TB pleural effusion. An avoidance of therapeutic thoracocentesis may reduce the risk of infection exposure or allow better channelling of resources in certain clinical settings.

Optimization of Genotype by Sequencing data for phylogenetic purposes.

• Herein we propose a framework for assembling and analyzing Genotype by Sequencing (GBS) data to better understand evolutionary relationships within a group of closely related species using the mastiff bats (Molossus) as our model system. Many species within this genus have low-levels of genetic variation within and between morphologically distinct species, and the relationships among them remain unresolved using traditional Sanger sequencing methods. Given that both de novo and reference genome pipelines can be used to assemble next generation sequences, and that several tree inference methodologies have been proposed for single nucleotide polymorphism (SNP) data, we test whether different alignments and phylogenetic approaches produce similar results. We also examined how the process of SNP identification and mapping can affect the consistency of the analyses. Different alignments and phylogenetic inferences produced consistent results, supporting the GBS approach for answering evolutionary questions on a macroevolutionary scale when the genetic distance among phenotypically identifiable clades is low. We highlight the importance of exploring the relationships among groups using different assembly assumptions and also distinct phylogenetic inference methods, particularly when addressing phylogenetic questions in genetic and morphologically conservative taxa. • The method uses the comparison of several filter settings, alignments, and tree inference approaches on Genotype by Sequencing data. • Consistent results were found among several approaches. • The methodology successfully recovered well supported species boundaries and phylogenetic relationships among species of mastiff bats not hypothesized by previous methods.

Budesonide/formoterol combination therapy as both maintenance and reliever medication in moderate-to-severe asthma: a real-life effectiveness study of Malaysian patients.

Budesonide/Formoterol (Symbicort) combination therapy as both maintenance and reliever treatment (SMART) is a novel approach in asthma management. We examined its 'real-life effectiveness' in treating Malaysian patients with moderate-to-severe asthma in whom despite on combined inhaled corticosteroids and long-acting beta2-agonist, were still inadequately controlled. In a retrospective study, 22 eligible adult patients on SMART [mean (range) age: 49 (36-65) years; FEV1: 41 (21-74)% predicted] were identified from medical records of an urban-based university hospital chest clinic, and their clinical outcomes studied at three months. Another 16 patients [50 (14-66) years; 48 (20-91)% predicted] of similar severity and treatment (i.e. Symbicort maintenance treatment plus short-acting beta2-agonist as reliever), but not on SMART, were used as comparator over the same assessment period. In addition, the patients were separately interviewed with standard questionnaire on their satisfaction and compliance to the SMART approach. In SMART group, rescue treatment requirement (p<0.001) and FEV1 [median difference = 2.5%, p=0.015; mean difference: 90 ml, p=0.013] showed significant improvement while in comparator, there was significant improvement only in the requirement for rescue treatment (p=0.023). Hospital admission rates were significantly reduced in SMART group compared to the other (p=0.039), but not in emergency treatment. Five patients asked to discontinue SMART while all others were satisfied, compliant and perceived improvement of their asthma with SMART. The maximum daily doses of inhaled budesonide and formoterol were 1400 microg and 31.5 microg respectively. Our preliminary findings suggest that SMART approach can be attempted as an effective and safe treatment option for patients with inadequately controlled moderate-to-severe asthma in Malaysian setting.

High frequency of p16INK4A gene alterations in hepatocellular carcinoma.

The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations by: methylation-specific PCR (MSP) to determine the methylation status of the p16 promoter region; comparative multiplex PCR to detect homozygous deletion; PCR-SSCP and DNA sequencing analysis to identify mutation of the p16 gene. We found high frequency of hypermethylation of the 5' CpG island of the p16 gene in 30 of 48 cases (62.5%) of HCC tumors. Moreover, homozygous deletion at p16 region were present in five of 48 cases (10.4%); and missense mutation were detected in three of 48 cases (6.3%). The overall frequency of p16 alterations, including homozygous deletion, mutation and hypermethylation, in HCC tumors was 70.8% (34 of 48 cases). These findings suggest that: (a) the inactivation of the p16 is a frequent event in HCC; (b) the p16 gene is inactivated by multiple mechanisms including homozygous deletion, promoter hypermethylation and point mutation; (c) the most common somatic alteration of the p16 gene in HCC is de novo hypermethylation of the 5' CpG island; and (d) in contrast to other studies, high frequency of genomic alterations are not uncommon in the 9p21 of the p16 gene. Our results strongly suggest that the p16 gene plays an important role in the pathogenesis of HCC.

Effectiveness of ProFile .04 taper rotary instruments in endodontic retreatment.

This study investigated the retreatment effectiveness of .04 Taper nickel-titanium rotary ProFiles. Thirty extracted single-rooted anterior teeth were instrumented and obturated with gutta-percha/Roth's Sealer using lateral condensation. They were distributed into three groups of 10 each. Retreatment for group A was done using Profile alone, group B using Profile and chloroform, and group C using hand files with chloroform. The teeth were then split longitudinally into halves. The remaining gutta-percha/sealer on the root canal wall in the cervical, middle, apical thirds, and the whole canals were visually scored with the aid of light microscopes. The results showed that the mean scores in groups A and B were generally lower (better) than group C. Mean scores of the apical thirds tended to be higher (worse) than the middle and the cervical thirds, except in group A. ProFile with or without chloroform seemed to be a viable alternative retreatment method.

Mechanics of patterned helical Si springs on Si substrate.

The elastic response, including the spring constant, of individual Si helical-shape submicron springs, was measured using a tip-cantilever assembly attached to a conventional atomic force microscope. The isolated, four-turn Si springs were fabricated using oblique angle deposition with substrate rotation, also known as the glancing angle deposition, on a templated Si substrate. The response of the structures was modeled using finite elements, and it was shown that the conventional formulae for the spring constant required modifications before they could be used for the loading scheme used in the present experiment.

Umbilical vs peripheral vein catheterization for parenteral nutrition in sick premature neonates.

The efficacy and safety of using umbilical venous catheters vs. peripheral venous catheters for the delivery of parenteral nutrition was studied in 129 critically ill premature infants who were treated in a neonatal intensive care unit for the first 3 weeks of life. Infants who received parenteral nutrition by umbilical venous catheter had greater parenteral caloric intake, lower physiologic weight loss and greater weight gain during the study as compared to infants who received parenteral nutrition by peripheral vein. While the overall incidence of sepsis was comparable in both groups (19% vs 19.7%), benign and transient episodes of hyperglycemia were seen more commonly in infants receiving parenteral nutrition by umbilical catheters. None of the hyperglycemic infants, however, required insulin therapy. The incidence of other metabolic complication was comparable in both groups. At follow up, no evidence of portal hypertension was detected in any of the infants up to 66 months of age treated with umbilical venous catheters. We conclude that the use of umbilical venous catheter allows for a comparably safe and a more appropriate parenteral nutrition support than peripheral catheters in critically ill premature neonates.

Facial nerve paralysis associated with Kawasaki disease.

Kawasaki disease is a multisystem disorder with varying clinical expression. This is a report on one case of Kawasaki disease which during its clinical course developed facial nerve palsy and spontaneous recovery without specific treatment. It is hoped that this report will serve to remind physicians of the association of facial nerve paralysis with Kawasaki disease.

Screening soybeans for resistance to reniform nematode disease in the Philippines.

Sixty-five soybean varieties were tested in the field for resistance to Rotylenchulus reniformis. Criteria for resistance or susceptibility were root necrosis, nematode recovery from roots and soil, and egg production. Nine varieties were resistant, 13 moderately resistant, 26 moderately susceptible, and 17 susceptible. Linear correlations between resistance rating and each assessment parameter were highly significantly positive, suggesting that any of the parameters could be used to identify resistance. There were also highly significant positive linear correlations between any two combinations of parameters, indicating that they were reciprocally related.

DNA barcoding and genetic diversity of phyllostomid bats from the Yucatan Peninsula with comparisons to Central America.

The mitochondrial cytochrome c oxidase subunit I gene is the standard DNA barcoding region used for species identification and discovery. We examined the variation of COI (454 bp) to discriminate 20 species of bats in the family Phyllostomidae that are found in the Yucatan Peninsula of southeastern Mexico and northern Guatemala and compared them genetically to other samples from Central America. The majority of these species had low intraspecific variation (mean = 0.75%), but some taxa had intraspecific variation ranging to 8.8%, suggesting the possibility of cryptic species (i.e. Desmodus rotundus and Artibeus jamaicensis). There was a recurring biogeographic pattern in eight species with a separation of northern and southern Middle American localities. The Yucatan Peninsula was a discrete area identified in four species, whereas Panama was recovered in five species of phyllostomid bats. Our study establishes a foundation for further molecular work incorporating broader taxonomic and geographic coverage to better understand the phylogeography and genetic diversity that have resulted from the ecological constraints in this region and the remarkable differentiation of bats in the Neotropics.

A new species of Chiroderma (Chiroptera, Phyllostomidae) from Northeastern Brazil.

A new species of Chiroderma Peters, 1860 (Chiroptera, Phyllostomidae) from the State of Piauí in Northeastern Brazil is described based on mensural analysis, morphological data and geographical distribution. It is most similar morphologically to C. doriae Thomas, 1891 but differentiated by a smaller body size and by differences in cranial traits. In comparison to other members of the genus, the new species can be distinguished by a combination of characters, including size of the body, conspicuousness of facial and median dorsal stripes, ear length, and variation in cranial and dentition traits.

[ELISA of rat sera infected with Paragonimus iloktsuenensis].

Enzyme-linked immunosorbent assay (ELISA) of paragonimiasis iloktsuenensis rat sera was performed using crude antigens of Paragonimus iloktsuenensis (PIA), P. westermani (PWA) and Clonorchis sinensis (CSA). Three crude antigens (PIA, PWA, CSA) were prepared to saline homogenated supernatants of whole adult worms. Infected rat sera were obtained biweekly from the albino rats fed 50-80 metacercariae of P. iloktsuenensis through gastric catheter. Experimental groups were divided into 4 groups: GI (controls), GII, GIII and GIV according to 1-7 worms as GII, 10-19 worms as GIII and 22-40 worms as GIV, respectively. In ELISA, the mean OD values of each group for the homologous antigen (PIA) were increased significantly compared to the control sera at the 4th week of infection. With the progress of duration of infection, the mean OD values of infected sera of GII & GIV continuously increased up to the 12th week (last week), but in GIII the mean OD value increased until the 10th week. No significance was noted among the infection dose groups (GII, GIII and GIV), after the 6th week of infection. Also, the OD values of all infected rats did not show any proportional relationships to the number of worms recovered. In brief, the antibody productivity of individual rats were strongly different. The rat sera infected with P. iloktsuenensis cross-reacted with those infected with P. westermani or C. sinensis, as identified by OD values.

Eosinophil cationic protein in Henoch-Schönlein purpura and in IgA nephropathy.

In order to identify the relationship between eosinophil activation in Henoch-Schönlein purpura (HSP) and IgA nephropathy, serum eosinophil cationic protein (ECP) was analyzed in both conditions. The soluble interleukin-2 receptor (sIL-2R) was also analyzed. The levels of ECP were significantly higher in HSP patients (mean 9.7 +/- 1.8 microg/l) than in a control group (mean 4.6 +/- 0.7 microg/l). When the HSP patients were classified into two groups, one with normal urine and one with abnormal urine, the latter showed higher levels of ECP than the former. Levels of ECP were not significantly higher in IgA nephropathy patients than in a control group. The sIL-2R levels were elevated in the serum of HSP and IgA nephropathy patients compared with controls. In conclusion, eosinophil activation may be involved in the pathogenesis of HSP but not in IgA nephropathy.

The role of laparoscopic surgery in the management of endometrial cancer.

OBJECTIVE: To assess the place of laparoscopically assisted vaginal hysterectomy in the treatment of endometrial cancer. DESIGN: A retrospective uncontrolled case series. SETTING: Gynaecological Oncology Department, Queen Elizabeth Hospital, Gateshead. POPULATION: Women with endometrial cancer referred to this centre from August 1992 to August 1997. MAIN OUTCOME MEASURES: Success of laparoscopically assisted vaginal hysterectomy, operative morbidity, and the length of hospital stay. RESULTS: Laparoscopically assisted vaginal hysterectomy was successful in 35 of 40 women (88%). Five women required laparotomy. Two women sustained injury to the inferior epigastric vessels. One sustained injury to the small intestine requiring later laparotomy and three women required a blood transfusion. The mean hospital stay was 3 x 3 days (SD 1 x 5). Three women died of the disease within one year of their operation. CONCLUSION: Laparoscopically assisted vaginal hysterectomy is a feasible treatment for endometrial cancer. It can be performed successfully in high risk population who are medically unfit and overweight. However, a larger randomised study is required to assess the morbidity compared with the traditional open approach.

The ATP-dependent CodWX (HslVU) protease in Bacillus subtilis is an N-terminal serine protease.

HslVU is a two-component ATP-dependent protease, consisting of HslV peptidase and HslU ATPase. CodW and CodX, encoded by the cod operon in Bacillus subtilis, display 52% identity in their amino acid sequences to HslV and HslU in Escherichia coli, respectively. Here we show that CodW and CodX can function together as a new type of two-component ATP-dependent protease. Remarkably, CodW uses its N-terminal serine hydroxyl group as the catalytic nucleophile, unlike HslV and certain beta-type subunits of the proteasomes, which have N-terminal threonine functioning as an active site residue. The ATP-dependent proteolytic activity of CodWX is strongly inhibited by serine protease inhibitors, unlike that of HslVU. Replacement of the N-terminal serine of CodW by alanine or even threonine completely abolishes the enzyme activity. These results indicate that CodWX in B.subtilis represents the first N-terminal serine protease among all known proteolytic enzymes.

Frequent allelic loss on chromosome 9 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide and highly associated with chronic virus-B or -C infection and cirrhosis. Molecular studies have shown high frequency of loss of heterozygosity (LOH) in some specific chromosome regions, but LOH on chromosome 9 in HCC has not been thoroughly investigated. In our investigation of chromosome 9 with 19 polymerase-chain-reaction (PCR)-based polymorphic microsatellite markers, 30 of 48 HCC tissue samples (63%) had LOH, and a distinct common deletion region and a region of loss were identified. The first region was located at the 9p21 region and the minimal deletion region was located between loci D9S1747 and D9S1748. This is a region of approximately 200 kb which includes the p16 tumor-suppressor gene. A region of loss was located on 9p13 to 9q33. The putative tumor-suppressor gene for nevoid-basal-cell-carcinoma syndrome (NBCCS) at 9q22.3 resides within this region. In addition to LOH, 4 HCC cases showed possible homozygous deletions at 9p21 with markers D9S1748, D9S1752 and D9S171 by multiplex PCR analysis. In 3 cases, the minimal region of possible homozygous deletion was approximately 300 kb and was defined between markers D9S1747 and D9S1752. Since this deletion region includes both the p15 and the p16 tumor-suppressor genes, these genes were possibly inactivated by homozygous deletion in HCC. In addition, a second region of possible homozygous deletion was present on the centromeric side of 9p21. However, these changes are not associated with age, gender, size or tumor-cell differentiation. Our data also suggest that inactivation of the p16 and the p15 genes and the possibility of other unknown tumor-suppressor genes located on these defined deleted regions of chromosome 9 may be involved in the pathogenesis of HCC.