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Biomedical subjects

R Goldin

Publications and source records attributed to R Goldin.

At least 19 recordsLinked to original sources
PubMed2005

Aberrations of early trophoblast differentiation predispose to pregnancy failure: lessons from the anti-phospholipid syndrome.

OBJECTIVES: The epithelium of the human placenta comprises an inner cytotrophoblast (CT) which proliferates and fuses with the outer differentiated syncytiotrophoblast (ST). Turnover has been studied focussing on second and third trimester placentas but with a paucity of data describing the normal first trimester trophoblast. The aim of this study was to compare the nuclear CT:ST ratio in normal and pathological pregnancy and thus establish the relationship between cytotrophoblast and syncytiotrophoblast nuclear number during early gestation. METHODS: Archival first trimester material from placentas from healthy pregnancy and recurrent miscarriage (anti-phospholipid syndrome) was stained with H&E, cytokeratin-7 and Mib-1. The area of trophoblast as a fraction of total villous area was calculated and the number of sectioned cytotrophoblast and syncytiotrophoblast nuclei as well as the number of proliferating cytotrophoblast was evaluated. RESULTS: Normal features of trophoblast development during the first trimester (rise in trophoblast area, increase in number of syncytiotrophoblast nuclei, increase in number of proliferating cytotrophoblast, decrease in the nuclear CT:ST ratio) are absent/reversed in tissues from recurrent miscarriage (decreasing trophoblast area, constant number of syncytiotrophoblast nuclei, decreasing number of proliferating trophoblast, constant nuclear CT:ST ratio). CONCLUSIONS: Proliferation of cytotrophoblast in early gestation provides a pool of trophoblast stem cells critical for ongoing placental development. Premature cytotrophoblast differentiation in favour of syncytial fusion results in deficiencies of cytotrophoblast and rarification of villous trophoblast. Abnormal trophoblast differentiation in early gestation may be due to a premature onset of maternal perfusion of the placenta and may be a likely antecedent for conditions associated with failure of placentation such as recurrent miscarriage.

Abortion, Habitual↗
PubMed2005

Treatment of histologically mild hepatitis C virus infection with interferon and ribavirin: a multicentre randomized controlled trial.

Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing alpha-interferon (3 MU thrice weekly) + ribavirin (1000-1200 mg/day) for 48 weeks with no treatment in treatment naive, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with alpha-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% vs 49% P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.

Adult↗
PubMed2004

Concurrent granulomatous Pneumocystis carinii and Mycobacterium xenopi pneumonia: an unusual manifestation of HIV immune reconstitution disease.

This report of concurrent granulomatous Pneumocystis carinii pneumonia (GPCP) and Mycobacterium xenopi pneumonia (MXIP) in a patient with advanced HIV disease 3-5 weeks after commencing antiretroviral therapy (ART) fits the syndrome of HIV immune reconstitution/restoration disease (IRD). It may also be a unique window into the immunology of granulomatous inflammation.

AIDS-Related Opportunistic Infections↗
PubMed2003

Measurement and determinants of the natural history of liver fibrosis in hepatitis C virus infection: a cross sectional and longitudinal study.

INTRODUCTION: The rate of development of liver fibrosis in hepatitis C virus (HCV) infection varies between individuals. This accounts for the variation in duration of progression to cirrhosis. The aims of this study were: (1) to determine whether fibrosis progresses linearly through the grading scales and (2) to identify factors which influence the rate of fibrosis. METHODS: HCV infected patients who had undergone at least one liver biopsy were identified. Biopsies were scored using the modified HAI (Ishak) and METAVIR systems, which were compared. Patients were treatment naïve at first biopsy. Demographic features were examined for their relationship to fibrosis rate (defined as fibrosis stage/infection duration) using univariate and multivariate analysis. A subgroup of patients with two biopsies was examined to test the assumption that fibrosis progresses in a linear fashion. RESULTS: A total of 917 patients were included. Male sex (p<0.00001), older age at infection (p</=0.00001), and viral genotype non-1 (p=0.005) were all associated with a rapid rate of fibrosis. On multiple linear regression they accounted for 29.5% of the variability in fibrosis rate (r(2)=0.295). METAVIR and Ishak scores were highly correlated (r=0.935, p<0.0001). In 137 patients who had two biopsies, the predicted probability for an increase of 1 on the fibrosis score was too low to assess linearity. CONCLUSIONS: Demographic features account for a minority of fibrosis rate variability. The Ishak and METAVIR scoring systems are equivalent. Linearity of fibrosis progression cannot be assessed in biopsies only a few years apart.

Adult↗
PubMed2003

Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection.

BACKGROUND: The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects. METHODS: We studied the relationship between rate of fibrosis (calculated by dividing the fibrosis stage by duration of infection) and genotypes of specific coagulation pathway genes in 352 White European patients infected with HCV. Genotyping was performed using reverse line blot hybridisation. RESULTS: The rate of fibrosis was significantly higher in patients with the factor V Leiden genotype (Arg560Gln) (ANOVA, p=0.004). In disease association studies, a significant association was seen (Fisher's exact test, p=0.029; odds ratio 3.28 for fast progression to cirrhosis (expected to reach cirrhosis in less than 30 years) if heterozygous for factor V Leiden). No associations were seen between factor II genotype and fibrosis rate. CONCLUSIONS: Possession of the factor V Leiden polymorphism significantly increases the risk of rapid disease progression in HCV, suggesting a role for the coagulation system in the pathogenesis of fibrotic liver disease.

Adult↗
PubMed2003

Pneumocystis carinii pneumonia with pleurisy, platypnoea and orthodeoxia.

We present a patient who collapsed with chest pain and dyspnoea on a transatlantic flight. She was found to have Pneumocystis carinii pneumonia (PCP) and human immunodeficiency virus infection. Platypnoea and orthodeoxia, which have not been previously reported in association with PCP, were major features of her illness. The PCP predominantly affected her lung bases and it is likely that gravity increased intrapulmonary blood flow through poorly ventilated lung bases with failure of pulmonary vasoconstriction to increase upper zone perfusion, exacerbating desaturation on sitting up. The partial DNA sequence of the infecting P carinii was identical to previously described isolates.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Chlamydia pneumoniae in infrequently examined blood vessels.

AIM: To determine the prevalence of Chlamydia pneumoniae DNA in infrequently examined blood vessels. METHODS: Vessels obtained from 15 men and six women at coronary artery bypass surgery were tested by a nested polymerase chain reaction (PCR) assay for C pneumoniae DNA. RESULTS: Chlamydia pneumoniae DNA was detected in four of six atheromatous ascending aorta specimens but in none of eight non-atheromatous aorta specimens, in six of 11 atheromatous internal mammary artery specimens but in none of seven non-atheromatous internal mammary artery specimens, in five of seven long saphenous vein specimens showing evidence of disease but in none of 12 specimens without evidence of disease, and in two of three previously grafted veins. Overall, C pneumoniae occurred significantly more often in diseased than in normal vessels (p = < 0.00001). CONCLUSIONS: Chlamydia pneumoniae is often present in diseased areas of arteries, including the internal mammary arteries, and even in diseased areas of veins. It is not present in apparently healthy areas of either type of vessel.

Aged↗
PubMed2001

Purification of woodchuck hepatitis surface antigen using a monoclonal antibody raised against the antigen.

Woodchuck hepatitis virus (WHV) is closely related to the human hepatitis B virus (HBV) and infection of woodchucks with WHV creates a useful model for studies of immunity, pathogenesis and therapy of HBV infection. To increase the usefulness of this model, monoclonal antibodies were raised to woodchuck hepatitis surface antigen (WHsAg) and one of these antibodies was used to purify the antigen by affinity chromatography from serum, a simpler and quicker method of purification than the current ultracentrifugation methods. The bands found by SDS-polyacrylamide gel electophoresis of WHsAg were the major 25 and 29 kilodalton (kDa) bands and a triplet of 45, 51 and 55 kDa which are thought to be the glycosylated and unglycosylated middle and large WHsAg. Both the antibody and the antigen are valuable reagents for the study of WHV infection.

Animals↗
PubMed2000

Selective in vivo transfection of murine biliary epithelia using polycation-enhanced adenovirus.

We have investigated the use of polycations to increase adenovirus-mediated expression of transgenic protein to the biliary epithelia with a view to gene therapy for hepatobiliary disease in CF. We have shown that adenovirus carrying the beta-galactosidase transgene transfect both human and mouse biliary epithelia in primary culture and that in both instances adenovirus transfection can be significantly increased by co-complexing with polycation. In vivo administration of 1 x 109 p.f.u. adenovirus co-complexed with the polyamine polyethyenimine (PEI) into the mouse biliary duct leads to >80% positively stained biliary epithelia while adenovirus alone at the same titre infected <5% biliary epithelia. We suggest that the use of low titre polycation enhanced adenoviral delivery to the biliary tree of CF patients could be of therapeutic significance. As a prelude to an extensive in vivo functional investigation in CF null mice we have shown that Ad5/polycation complexes deliver functional CFTR to non-CFTR expressing cells in vitro more efficiently than Ad5 alone.

Adenoviridae↗
PubMed2000

Disseminated Mycoplasma fermentans in AIDS patients: several case reports.

We describe the clinical course of 2 HIV-positive patients in whom Mycoplasma fermentans was disseminated and persistent. We identified individuals in whom M. fermentans had been detected in a peripheral blood mononuclear cell (PBMC) or bronchoalveolar lavage (BAL) specimen. Of this group a number had archival specimens of interest: liver and/or bone marrow, taken to investigate a systemic illness, and a few had M. fermentans positive tissues. Two patients, NC and DP, had recurrent episodes of lower respiratory tract infection and fever and both had been investigated by bronchoscopy on 4 occasions. M. fermentans was detected in specimens taken 18 and 27 months apart for NC and DP respectively, and in between, and repeatedly in respiratory tract tissues of DP. Granuloma were identified in the liver of NC that was M. fermentans positive but no further evidence of opportunistic infection was found during his illness. Both patients had M. fermentans positive bone marrow specimens. Assessment of the patients' records suggested that in one patient M. fermentans may have contributed to the respiratory disease and in the other to the systemic disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Hepatitis C virus replication in hepatocellular carcinoma.

Hepatitis C virus (HCV) replication is reported in both tumour and non-tumour tissue in a case of hepatocellular carcinoma. Viral replication was established by showing the presence of minus strand HCV RNA by PCR amplification, after excluding residual reverse transcriptase activity of Taq polymerase. No minus strand was found in serum derived virion RNA. PCR amplified products from both tumour and non-tumour parenchyma were sequenced in the 5' non-coding region and shown to be identical. The genotype of this Indonesian patient was found to be 1b (or II), the most prevalent type in the Far East.

Base Sequence↗
PubMed1993

Partial control of hepatitis delta virus superinfection by immunisation of woodchucks (Marmota monax) with hepatitis delta antigen expressed by a recombinant vaccinia or baculovirus.

We have successfully limited the level of hepatitis delta viraemia occurring after superinfection of hepadna-virus infected woodchucks by prior immunisation with the short form of the hepatitis delta virus antigen expressed by a recombinant baculovirus or vaccinia virus. This phenomenon occurred in the absence of detectable circulating antibody to hepatitis delta virus antigen and in the absence of evidence of priming of the humoral immune response and may reflect the induction of a cytotoxic T-cell response. The latter would control viraemia by rapid lysis of delta antigen expressing hepatocytes. It is suggested that the T-cell epitopes involved may be located on the carboxyl end of the delta protein (amino acids 77-195).

Animals↗
PubMed1993

High-energy shock waves pyrotherapy. A new concept in extracorporeal tumour therapy.

High-intensity shock waves (HISW) waves can produce rapid and intense tissue heating. We have studied a novel device capable of simultaneous shock wave generation, focusing and extracorporeal delivery along with imaging of the proposed target. Shock waves are generated by piezo-electric crystals and target a focal point of 10 x 2 mm. In a preliminary study, three groups of land race pigs received HISW to discrete points on the liver parenchyma. There was no mortality in any group. Cardiovascular monitoring revealed that HISW did not induce any haemodynamic changes during treatment and that core temperatures and liver function tests were unaffected by this therapy. Ultrasound monitoring during treatment demonstrated discreet hyperechoic areas with acoustic shadowing suggesting cavitation. Animals killed immediately after 48 h of HISW therapy had discrete necrotic cylinders within the liver with a mean diameter of 2 cm (+0.21 SD). Histological examination revealed a pattern of necrosis and vascular changes suggestive of ischaemia. In addition, there were areas of coagulative necrosis consistent with thermal injury. Animals killed at 2 months had necrotic cavities which had become surrounded by mature fibrosis. These early results indicate that high energy shock waves delivered extracorporeally can cause specific destruction of liver tissue by focused hyperthermia and cavitation. Clinical studies of this device are required to assess the possible virtue of HISW in the treatment of liver and other tumours.

Animals↗