Prevalence of chronic viral hepatitis in people of south Asian ethnicity living in England: the prevalence cannot necessarily be predicted from the prevalence in the country of origin.

The prevalence of hepatitis B and hepatitis C in immigrant communities is unknown. Immigrants from south Asia are common in England and elsewhere, and the burden of viral hepatitis in these communities is unknown. We aimed to determine the prevalence of viral hepatitis in immigrants from south Asia living in England, and we therefore undertook a community-based testing project in such people at five sites in England. A total of 4998 people attending community centres were screened for viral hepatitis using oral fluid testing. The overall prevalence of anti-hepatitis C virus (HCV) in people of south Asian origin was 1.6% but varied by country of birth being 0.4%, 0.2%, 0.6% and 2.7% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. The prevalence of hepatitis B surface antigen was 1.2%-0.2%, 0.1%, 1.5% and 1.8% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. Analysis of risk factors for HCV infection shows that people from the Pakistani Punjab and those who have immigrated recently are at increased risk of infection. Our study suggests that migrants from Pakistan are at highest risk of viral hepatitis, with those from India at low risk. As prevalence varies both by country and region of origin and over time, the prevalence in migrant communities living in western countries cannot be easily predicted from studies in the country of origin.

Dose-dependent relationship between acidosis at birth and likelihood of death or cerebral palsy.

BACKGROUND: The acid-base status of infants around birth can provide information about their past, current and future condition. Although umbilical cord blood pH <7.0 or base deficit ≥12 mmol/L is associated with increased risk of adverse outcome, there is uncertainty about the prognostic value of degree of acidosis as previous studies have used different variables, thresholds, outcomes and populations. METHODS: Retrospective review of routinely collected clinical data in all live-born inborn infants of 35 weeks gestation or more delivered between January 2005 and December 2013 at the Simpson Centre for Reproductive Health, Edinburgh, UK. Infants were included if their lowest recorded pH was <7 and/or highest base deficit ≥12 mmol/L on either umbilical cord blood and/or neonatal blood gas within 1 hour of birth. Neurodevelopmental outcome of the infants with encephalopathy was collected from the targeted follow-up database. RESULTS: 56 574 infants were eligible. 506 infants (0.9%) met inclusion criteria. Poor condition at birth and all adverse outcomes increased with worsening acidosis. Combined outcome of death or cerebral palsy was 3%, 10% and 40% at lowest pH of 6.9-6.99, 6.8-6.89 and <6.8, respectively, and 8%, 14% and 59% at a base deficit of 12-15.9, 16-19.9 and 20 mmol/L or more, respectively. CONCLUSIONS: There is a dose-dependent relationship between the degree of acidosis within an hour of delivery, and the likelihood of adverse neonatal and later neurodevelopmental outcome in infants born at 35 weeks gestation or more.

Accuracy of frozen section in the diagnosis of liver mass lesions.

OBJECTIVE: To evaluate the diagnostic accuracy of intraoperative frozen sections diagnosis of liver lesions thought to be malignant tumours. METHODS: 285 frozen sections of liver from 173 patients were reviewed. The examinations were done between 1998 and 2004. RESULTS: Final histological diagnosis was divided into positive (32%) and negative (68%) for malignancy. In four cases (2%), diagnosis was deferred to paraffin section. There was one false positive and two false negative diagnoses. Sensitivity was 96.9% and specificity was 99.1%, and the overall accuracy to determine the lesions was 95%. The cases were further analysed to ascertain the nature of diagnostic difficulties, which comprised pathological misinterpretation, sampling error, and technical imperfections. Biliary hamartoma was the most common entity that was confused with malignant tumours in frozen sections. CONCLUSIONS: The data are in accordance with those of similar studies in other sites, and confirm that the frozen section is an accurate and reliable method for intraoperative diagnosis of suspected liver lesions.

Patients' perspective of pathology specimens. A prospective study.

AIM: To determine the degree of patients' interest in surgical pathology specimens. To assess the impact of patients' involvement in surgical pathology on their understanding of (and confidence in) the storage and use of pathology specimens. METHODS: Forty seven patients were invited to visit the pathology department and view their specimens postoperatively. Those who visited were asked to complete a questionnaire to assess the effect of the visit. RESULTS: Thirty three of the 47 patients wished to view their specimens, but only 14 actually made the visit. All those who visited indicated that it made them better able to understand the reason for surgery and tissue retention issues, and more likely to consent to the use of excess tissue for research. CONCLUSION: In general, patients are keen to know what happens to and what is wrong with the organs removed at surgery, and their involvement in surgical pathology can have positive and beneficial effects both for themselves and the profession.

Outcome of women with inadequate cervical smears followed up for five years.

BACKGROUND: The clinical and prognostic significance of "inadequate" cervical smear is unknown, even though women with repeated inadequate smears are referred for colposcopy in the National Health Service (NHS) Cervical Screening Programme. AIM: To follow up a cohort of women with inadequate cervical smears over the following five years to examine outcomes, including detection of high grade cervical intraepithelial neoplasia (CIN). METHODS: The study comprised 1972 women with an inadequate cervical smear reported at Walsall Hospitals NHS Trust between 1 April 1995 and 31 March 1996. Results of cervical smears and biopsies taken over the following five years were reviewed to confirm the outcome. FINDINGS: Within five years, 2.2% of women with an inadequate cervical smear developed histologically confirmed high grade CIN, which was higher than the 1.3% seen among all women with cervical smear tests reported at the same laboratory over the same period, although the difference was not significant at the 95% level of confidence. Where inadequacy resulted from or was contributed to by "polymorphs obscuring", the risk of subsequent development/detection of high grade CIN was 2.6%. CONCLUSIONS: Women with inadequate cervical smears had an increased risk of detection of high grade CIN in the following five years compared with "all women". This increased risk was not significant, although if a larger number of women had been studied significance may have been reached, so that further studies are needed. The increased risk appeared to be at least partially dependent on the reason for inadequacy.

Temporal changes in tissue repair permit survival of diet-restricted rats from an acute lethal dose of thioacetamide.

Although, diet restriction (DR) has been shown to substantially increase longevity while reducing or delaying the onset of age-related diseases, little is known about the mechanisms underlying the beneficial effects of DR on acute toxic outcomes. An earlier study (S. K. Ramaiah et al., 1998, Toxicol. Appl. Pharmacol. 150, 12-21) revealed that a 35% DR compared to ad libitum (AL) feeding leads to a substantial increase in liver injury of thioacetamide (TA) at a low dose (50 mg/kg, i.p.). Higher liver injury was accompanied by enhanced survival. A prompt and enhanced tissue repair response in DR rats at the low dose (sixfold higher liver injury) occurred, whereas at equitoxic doses (50 mg/kg in DR and 600 mg/kg in AL rats) tissue repair in AL rats was substantially diminished and delayed. The extent of liver injury did not appear to be closely related to the extent of stimulated tissue repair response. The purpose of the present study was to investigate the time course (0-120 h) of liver injury and liver tissue repair at the high dose (600 mg TA/kg, i.p., lethal in AL rats) in AL and DR rats. Male Sprague-Dawley rats (225-275 g) were 35% diet restricted compared to their AL cohorts for 21 days and on day 22 they received a single dose of TA (600 mg/kg, i.p.). Liver injury was assessed by plasma ALT and by histopathological examination of liver sections. Tissue repair was assessed by [3H]thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) immunohistochemistry during 0-120 h after TA injection. In AL-fed rats hepatic necrosis was evident at 12 h, peaked at 60 h, and persisted thereafter until mortality (3 to 6 days). Peak liver injury was approximately twofold higher in DR rats compared to that seen in AL rats. Hepatic necrosis was evident at 36 h, peaked at 48 h, persisted until 96 h, and returned to normal by 120 h. Light microscopy of liver sections revealed progression of hepatic injury in AL rats whereas injury regressed completely leading to recovery of DR rats by 120 h. Progression of injury led to 90% mortality in AL rats vs 30% mortality in DR group. In the surviving AL rats, S-phase DNA synthesis was evident at 60 h, peaked at 72 h, and declined to base level by 120 h, whereas in DR rats S-phase DNA synthesis was evident at 36 h and was consistently higher until 96 h reaching control levels by 120 h. PCNA studies showed a corresponding increase in cells in S and M phase in the AL and DR groups. DR resulted in abolition of the delay in tissue repair associated with the lethal dose of TA in ad libitum rats. Temporal changes and higher tissue repair response in DR rats (earlier and prolonged) are the conduits that allow a significant number of diet restricted rats to escape lethal consequence.

The impact of arterial collateralization on outcome after intra-arterial therapy for acute ischemic stroke.

BACKGROUND AND PURPOSE: Although intra-arterial therapy for acute ischemic stroke is associated with superior recanalization rates, improved clinical outcomes are inconsistently observed following successful recanalization. There is emerging concern that unfavorable arterial collateralization, though unproven, predetermines poor outcome. We hypothesized that poor leptomeningeal collateralization, assessed by preprocedural CTA, is associated with poor outcome in patients with acute ischemic stroke undergoing intra-arterial therapy. MATERIALS AND METHODS: We retrospectively analyzed patients with acute ischemic stroke with intracranial ICA and/or MCA occlusions who received intra-arterial therapy. The collaterals were graded on CTA. Univariate and multivariate analyses were used to investigate the association between the dichotomized leptomeningeal collateral score and functional outcomes at 3-months mRS ≤2, mortality, and intracranial hemorrhages. RESULTS: Eighty-seven patients were included. The median age was 66 years (interquartile range, 54-76 years) and the median NIHSS score at admission was 18 (interquartile range, 14-20). The leptomeningeal collateral score 3 was found to have significant association with the good functional outcome at 3 months: OR = 3.13; 95% CI, 1.25-7.825; P = .016. This association remained significant when adjusted for the use of IV tissue plasminogen activator: alone, OR = 2.998; 95% CI, 1.154-7.786; P = .024; and for IV tissue plasminogen activator and other confounders (age, baseline NIHSS score, and Thrombolysis in Cerebral Infarction grades), OR = 2.985; 95% CI, 1.027-8.673; P = .045. CONCLUSIONS: We found that poor arterial collateralization, defined as a collateral score of <3, was associated with poor outcome, after adjustment for recanalization success. We recommend that future studies include collateral scores as one of the predictors of functional outcome.

Higher neutrophil infiltration mediated by osteopontin is a likely contributing factor to the increased susceptibility of females to alcoholic liver disease.

Alcoholic liver disease (ALD) is a major public health problem in the United States and women are known to be more susceptible to ALD. However, the precise mechanism for increased susceptibility of females to ALD is not completely understood. The present study is based on the hypothesis that induction of osteopontin (OPN), a matricellular protein, is the likely contributing factor for higher neutrophil recruitment in females during alcoholic steatohepatitis (ASH). ASH was induced in male and female Sprague-Dawley rats by feeding them a Lieber-DeCarli diet containing ethanol (EtOH) for 6 weeks, followed by a single injection of lipopolysaccharide (LPS, 10 mg/kg, ip). Liver injury, measured by plasma transaminase elevations and confirmed by haematoxylin and eosin-stained liver sections, revealed approximately 25-fold higher liver injury in the female ASH model compared with the males. Although steatosis, necrosis, and neutrophil infiltration were evident in both male and female rats, hepatic neutrophilic necrotic foci were noted as early as 2 h after LPS injection in the EtOH-treated female rats. Hepatic neutrophil infiltration correlated with higher expression of cleaved (cOPN) and uncleaved OPN in the EtOH + LPS-treated female rats compared with the males. OPN secretion was localized predominantly in the biliary epithelium and females had significantly higher OPN mRNA than their male counterparts in the ASH model. The ability of OPN to attract neutrophils was further confirmed in vivo, in a peritonitis rat model, and by neutralizing OPN (nOPN) antibody experiments. Hepatic neutrophil infiltration was largely inhibited ( approximately 50%) by nOPN antibody. Flow cytometry experiments revealed OPN-mediated up-regulation of the CD11b neutrophil adhesion molecule. In conclusion, these data suggest that higher hepatic expression of OPN is the likely reason for higher and early hepatic neutrophil infiltration making females more susceptible to ALD during ASH.

GPs and contracting for secondary health care.

Publication of the NHS White Paper Working for Patients and subsequent legislation has introduced the requirement for district health authorities to assess the health and health care needs of their resident populations. Sam Ramaiah and colleagues describe their experience in South Tees of working with GPs to fulfil this objective.