Disturbance of SHH signalling pathway during early embryogenesis in the cadmium-induced omphalocele chick model

Introduction

Administration of cadmium (Cd) after 60 h (H) incubation induces ventral body wall defect (VBWD) similar to the omphalocele phenotype in the chick embryo. In this model, the earliest histological changes have been observed in somites commencing at 4-h post-treatment (4H). The molecular mechanism by which Cd acts in this critical period of embryogenesis still remains unclear. Sonic hedgehog (SHH) signalling plays an important role in vertebrate development, including somitogenesis and thus ventral body wall formation. Patched (PTCH), a cell membrane receptor for SHH, is expressed in somites and Patched knockout mice display somite dysfunction. Another transmembrane receptor, Smoothened (SMO), is also expressed in somites and transduces the SHH signal regulated by PTCH. We designed this study to test the hypothesis that SHH signalling is downregulated during the critical period of early embryogenesis in the Cd-induced omphalocele chick model.

Methods

After 60 h of incubation, chicks were exposed to either chick saline or 50 μL of 50 μM cadmium acetate and divided into two groups: control and Cd (n = 24 for each group). Chicks were harvested 1, 4, and 8 h post-treatment. Real-time RT-PCR was performed to evaluate the relative mRNA expression level of SHH, PTCH and SMO. Immunofluorescence confocal microscopy was then performed to evaluate protein expression/distribution of SHH, PTCH and SMO.

Results

The relative mRNA expression levels of SHH, PTCH and SMO were significantly downregulated in the Cd group compared to controls at 4H post treatment, whereas, there were no significant differences at the other time points. Immunohistochemistry revealed that the intensity of SHH, PTCH and SMO was markedly diminished at 4 h in Cd-treated embryos compared to controls.

Conclusion

Disturbance of the SHH signalling pathway as evidenced by SHH, PTCH and SMO downregulation during the narrow window of early embryogenesis may result in somite maldevelopment, contributing to the omphalocele phenotype in the Cd chick model.     

The impact of video-assisted thoracic surgery (VATS) in patients with suspected advanced ovarian malignancies and pleural effusions

OBJECTIVES: We previously reported our initial experience of patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent video-assessed thoracic surgery (VATS) before planned abdominal exploration. The objective of this study was to report the surgical findings and management of patients who underwent VATS in an update of our experience. METHODS: We performed a retrospective review of all patients with suspected advanced ovarian cancer and moderate to large pleural effusions who underwent VATS for assessment of extent of intrathoracic disease at our institution between 6/01 and 8/05. RESULTS: Twenty-three patients with a median age of 61 years (range, 36-79) were identified. VATS was performed for right-sided effusions in 17 patients (74%), and a median of 1350 ml (400-3700 ml) of pleural fluid was drained. VATS demonstrated macroscopic disease in 15 (65%) patients, with nodules >1 cm in 11/15 (73%), and nodules <1 cm in 4/15 (27%). Macroscopic intrathoracic disease was found in 4/10 (40%) patients with negative cytology. Intrathoracic cytoreduction was performed in 3/11 patients (27%) with intrathoracic disease >1 cm. After VATS, 12/23 patients (52%) underwent primary surgical management, with cytoreduction to < or =1 cm achieved in 11/12 patients (92%). The other eleven patients received primary chemotherapy after undergoing diagnostic laparoscopy alone (4/11) or no further abdominal exploration (7/11). Nine of these patients proceeded to interval cytoreduction, while 2 had pathology demonstrating upper gastrointestinal and lymphoma primaries at the time of VATS. Final diagnosis of primary site of disease included: ovary, 14 (61%); endometrial, 2 (9%); dual ovarian/endometrial primaries, 1 (4%); fallopian tube, 1 (4%); primary peritoneal, 1 (4%); other, 4 (17%). Overall, findings at VATS altered primary surgical management in 11/23 (48%) patients. CONCLUSIONS: Sixty-five percent of patients with suspected advanced ovarian cancer and moderate to large pleural effusions had gross intrathoracic disease identified at VATS, with the majority (11/15, 73%) having disease >1 cm in diameter. Use of VATS allows for assessment of intrathoracic disease and may help identify candidates for primary cytoreductive surgery and possible intrathoracic cytoreduction versus neoadjuvant chemotherapy.     

Chronic splenomegaly in Nairobi, Kenya. II. Portal hypertension

Eighty-five patients with chronic splenomegaly and proven oesophageal varices were studied at Kenyatta National Hospital, Nairobi. The major defined groups were hepatosplenic schistosomiasis (24%), cirrhosis (20%) and portal vein occlusion (11%). Hyper-reactive malarial splenomegaly (tropical splenomegaly syndrome) was considered as the cause of oesophageal varices in only one patient. In 26% of cases liver biopsy was non-diagnostic and the extrahepatic portal vein was demonstrated radiologically to be patent. Such patients were thought to be suffering from idiopathic portal hypertension, not previously described elsewhere in Africa. Hepatitis B surface antigen was detected in 12% of controls and in 58% of patients with cirrhosis (p less than 0.001). Some serological marker of previous hepatitis B virus infection was present in 92% of patients with cirrhosis and in 79% of controls. Kamba patients from Machakos and Kitui Districts were significantly more prevalent than expected among these 85 cases of portal hypertension.     

Point-of-care hepatitis C screening with direct access referral to improve linkage to care among halfway house residents: a pilot randomised study

INTRODUCTIONLinkage to care among individuals with substance misuse remains a barrier to the elimination of the hepatitis C virus (HCV). We aimed to determine whether point-of-care (PoC) education, screening and staging for liver disease with direct access to hospitals would improve linkage to care among this group.METHODSAll participants were offered PoC education and HCV screening. HCV-positive participants were randomised to standard care (controls) or direct access, which provided a direct pathway to hospitals. Linkage to care was determined by reviewing electronic medical records. Linkage of care cascade was defined as attendance at the specialist clinic, confirmation of viraemia by HCV RNA testing, discussion about HCV treatment and initiation of treatment.RESULTS351 halfway house residents were screened. The overall HCV prevalence was 30.5% (n = 107), with 69 residents in the control group and 38 in the direct access group. The direct access group had a significantly higher percentage of cases linked to specialist review for confirmatory RNA testing (63.2% vs. 40.6%, p = 0.025), HCV treatment discussion (p = 0.009) and treatment initiation (p = 0.01) compared to the controls. Overall, only 12.6% (n = 13) had treatment initiation during follow-up. PoC HCV screening with direct access referral had significantly higher linkage to HCV treatment initiation (adjusted odds ratio 9.13, p = 0.005) in multivariate analysis.CONCLUSIONPoC HCV screening with direct access improves linkage to care and simplifies the HCV care cascade, leading to improved treatment uptake. PoC education, screening, diagnosis and treatment may be an effective strategy to achieving HCV micro-elimination in this population.     

Anomalous left anterior descending artery from pulmonary artery: An extremely rare coronary anomaly

We report a rare coronary artery anomaly–anomalous origin of the left anterior descending artery from the pulmonary artery in a 40-year-old woman. The uniqueness of this case is the absence of any significant morbidity from this condition in adulthood which is in contrast to other reported cases where patients present with myocardial infarction, congestive heart failure, and sometimes death during the early infantile period.¹     

Outcome of trabeculectomy in hospital Melaka, Malaysia

AIM: To study the success and outcome of trabeculectomy in Hospital Melaka. METHODS: Medical records of all patients who underwent trabeculectomy between January 1, 2007 and October 31, 2010 whom were followed up for at least 6 months postoperatively in Hospital Melaka were retrospectively reviewed. RESULTS: A total number of 117 eyes of 91 patients with the age range between 12 to 84 years underwent primary trabeculectomy (n=20, 17.1%), combine trabeculectomy with cataract surgery (n=90, 76.9%), repeat trabeculectomy (n=5, 4.3%), and combine repeat trabeculectomy with cataract surgery (n=2, 1.7%). The disease spectrum includes primary open-angle glaucoma (POAG) (54 patients, 59.3%), priamry angle-closure glaucoma (PACG) (14 patients, 15.4%), secondary glaucomas (19 patients, 20.9%) and juvenile glaucomas (4 patients, 4.4%). Preoperative mean intraocular pressure (IOP) was (24.69±8.67)mmHg as compared to postoperative mean IOP of (15.81±6.66)mmHg, (15.07±4.72)mmHg and (15.68 ±3.65)mmHg at 6-month, 12-month and 24-month respectively. Eighty-two point one percent of eyes (n=96) achieved complete success (CS), 12.8% (n=15) with qualified success (QS) and only 5.1% (n=6) failed at 6 month with two of them warrant other filtering surgery. At twelve months, trabeculectomy with CS was 71.6% (n=63), QS in 22.7% (n=20) and failure in 5.7% (n=5). Sixty-seven point five percent (n=27) attained CS, 20.0% (n=8) with QS while 12.5% (n=5) failed at 24 month postoperative. CONCLUSION: As the understanding of the lower the IOP, the better the patients retaining the visual function, trabeculectomy is significantly a choice of treatment in uncontrolled glaucoma. This study concluded that trabeculectomy performed in Hospital Melaka has produced significant success as compared to other studies.     

Importance of anemia and transferrin levels in the regulation of intestinal iron absorption in hypotransferrinemic mice.

The hypotransferrinemic mouse (trf (hpx)) is a mutant strain exhibiting transferrin deficiency, marked anemia, hyperabsorption of iron, and elevated hepatic iron stores. We set out to investigate the relative roles of anemia and of transferrin in the malregulation of intestinal iron absorption in these animals. Transfusion of erythrocytes obtained from littermate controls increased hemoglobin levels and reduced reticulocyte counts in recipient animals. Although mucosal to carcass (59)Fe transfer was reduced, total duodenal iron uptake was not significantly affected. Iron absorption in homozygotes, in contrast to littermate controls, was not reduced by hyperoxia. Mouse transferrin injections, in the short term, increased delivery of iron to the marrow and raised hemoglobin levels. Although mucosal transfer and total iron uptake were reduced at the higher transferrin doses, total uptake was still higher than in controls. Daily injections of mouse/human transferrin for 3 weeks from weaning, normalized hemoglobin values, and markedly reduced liver iron and intestinal iron absorption values in trf (hpx) animals. When such daily-injected mice were left for a week to allow transferrin clearance, iron absorption values were significantly enhanced; hemoglobin or hepatic iron levels were, however, not significantly altered. These data indicate that hyperabsorption of iron in trf (hpx) mice is not solely because of the anemia; transferrin levels per se do affect iron absorption, possibly via a direct effect on the intestinal mucosa.