PubMed Health⌕ Search

Biomedical subjects

J C Underwood

Publications and source records attributed to J C Underwood.

At least 19 recordsLinked to original sources
PubMed2004

Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study.

BACKGROUND: The natural history of hepatitis C virus (HCV) infection remains uncertain. Previous data concerning rates of progression are from studies using estimated dates of infection and single liver biopsy scores. We prospectively studied the rate of progression of fibrosis in HCV infected patients by repeat liver biopsies without intervening treatment. PATIENTS: We studied 214 HCV infected patients (126 male; median age 36 years (range 5-8)) with predominantly mild liver disease who were prospectively followed without treatment and assessed for risk factors for progression of liver disease. Interbiopsy interval was a median of 2.5 years. Paired biopsies from the same patient were scored by the same pathologist. RESULTS: Seventy of 219 (33%) patients showed progression of at least 1 fibrosis point in the Ishak score; 23 progressed at least 2 points. Independent predictors of progression were age at first biopsy and any fibrosis on first biopsy. Factors not associated with progression were: necroinflammation, duration of infection, alcohol consumption, alanine aminotransferase levels, current or past hepatitis B virus infection, ferritin, HCV genotype, and steatosis or iron deposition in the initial biopsy. CONCLUSIONS: One third of patients with predominantly mild hepatitis C showed significant fibrosis progression over a median period of 30 months. Histologically, mild hepatitis C is a progressive disease. The overall rate of fibrosis progression in patients with hepatitis C was low but increased in patients who were older or had fibrosis on their index biopsy. These data suggest that HCV infection will place an increasing burden on health care services in the next 20 years.

Adolescent↗
PubMed2000

Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas.

Angiogenesis is essential to the growth and metastasis of solid tumours. Vascular endothelial growth factor (VEGF) is a potent pro-angiogenic cytokine that is overexpressed in malignant tumours such as invasive carcinoma of the breast. The low oxygen tensions (hypoxia) present in these tumours are known to up-regulate the expression of VEGF by tumour cells. Human macrophages also respond to hypoxia by increasing their release of VEGF in vitro, although the effect of hypoxia on VEGF expression by macrophages in vivo has yet to be demonstrated. The present study compared the expression of VEGF by macrophages in areas of low and high vascularity in 24 invasive breast carcinomas (12 lobular, 12 ductal). The cellular distributions of VEGF protein, CD31 (vessels), and CD68 (macrophages) were compared in sequential sections for each tumour. In ten tumours, both tumour cells and macrophages were immunoreactive for VEGF protein. Use of non-isotopic in situ hybridization to localize VEGF mRNA showed that these cell types also expressed VEGF mRNA. No significant differences in the cellular distribution of VEGF protein were found between lobular and ductal carcinomas. In all tumours, macrophages accumulated in higher numbers in poorly vascularized than in highly vascularized areas. In VEGF-positive tumours, macrophages were immunoreactive for VEGF only in avascular areas where tumour cells also expressed VEGF. This suggests that VEGF expression by these two cell types may be regulated by the same microenvironmental stimuli in breast carcinomas. In addition, significantly more macrophages were present in poorly vascularized areas of VEGF-positive than VEGF-negative tumours. This suggests that VEGF may exert a chemotactic action on macrophages in vivo and guide their migration into avascular tumour sites.

Adult↗
PubMed1999

Macrophage responses to hypoxia: relevance to disease mechanisms.

Macrophages are ubiquitous in the stromal compartment of tissues under normal physiological conditions and the number of these cells increases markedly with the onset and progression of many pathological states. The mechanisms underlying this response are well described in such conditions as wound healing and malignant tumors, where tissue-specific signals enhance the extravasation of blood monocytes and their subsequent differentiation into macrophages. Recent evidence suggests that macrophages may also be stimulated by microenvironmental factors present in diseased tissues to perform distinct, tissue-specific activities. One such factor, hypoxia (low oxygen tension), results from insufficient vascular perfusion of a given tissue. Various studies have shown that experimental hypoxia alters the morphology, expression of cell surface markers, viability, phagocytosis, metabolic activity, and release of cytokines by macrophages. Here we review the evidence for these macrophage responses to hypoxia, the involvement of co-stimuli, and their implications for the role of macrophages in various disease processes. Because the intracellular mechanisms mediating the effects of hypoxia on gene expression in other cell types have been characterized recently, we discuss their possible involvement in the effects of hypoxia on gene expression in macrophages.

Animals↗
PubMed1999

Low-dose methotrexate is ineffective in primary biliary cirrhosis: long-term results of a placebo-controlled trial.

BACKGROUND & AIMS: New treatments for primary biliary cirrhosis (PBC) need to be evaluated. We conducted a single-center double-blind, randomized trial of methotrexate, 7.5 mg/wk (n = 30), vs. placebo (n = 30) for up to 6 years in PBC. METHODS: Methods included three monthly symptom assessment and liver function tests and liver biopsy and gastroscopy at baseline, after 2 years, and after 4-6 years. RESULTS: Patients randomized to methotrexate had, compared with patients randomized to placebo, (1) significantly lower on-treatment serum alkaline phosphatase, gamma-glutamyltransferase, immunoglobulin (Ig) M, IgG, and (after 24 months) aspartate aminotransferase and alanine aminotransferase levels (P < 0.02-0.001 by analysis of covariance to adjust for baseline differences); (2) a nonsignificant trend toward lower on-treatment pruritus scores; (3) similar on-treatment Knodell inflammatory scores but nonsignificant trends toward lower Knodell fibrosis score and less ductopenia; (4) a trend toward greater increases in serum bilirubin level and Mayo score with time (both significant after 5 years of follow-up); and (5) a 2.9-fold (95% confidence interval, 0.85-10.25-fold) increase the rate of death or liver transplantation as a result of liver disease during or after the trial (P = 0.09) in a Cox multivariate regression analysis compared with patients randomized to placebo. CONCLUSIONS: These results do not support the clinical use of low-dose methotrexate in PBC.

Aged↗
PubMed1998

Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C Virus Study Group.

The frequencies of HLA class I antigens and class II haplotypes were compared in subjects with previous (polymerase chain reaction [PCR]-negative) or with persistent (PCR-positive) hepatitis C virus (HCV) infection and in HCV patients with mild versus severe histologic activity scores on liver biopsy. The DRB1*11 allele group was found in 11 (31.4%) of 35 subjects with previous infection and in 11 (8.2%) of 135 subjects with persistent infection (P < .001). The DQB1*0301 allele was found in 18 (51.4%) of 35 subjects with previous infection and in 33 (24.4%) of 135 patients with persistent infection (P < .002). Both observations remained significant after correction for multiple testing. No significant association was shown between severity of disease and any HLA class I or II type. Thus, the HLA class II alleles DRB1*11 and DQB1*0301 are associated with clearance of circulating HCV.

Adult↗
PubMed1997

Does funeral preference influence clinical necropsy request outcome?

Attitudes towards necropsy have been shown to be more favourable amongst those relatives preferring cremation as a method of disposal compared to those with a preference for burial. In a two-year retrospective study, no significant relationship was found between funeral preferences (burial or cremation) and clinical necropsy request outcome when age, sex and religion were taken into account. Potential religious objections to necropsy were infrequent and cremation was found to have become the most popular method of disposing of the dead during a period when local clinical necropsy rates have continued to decline. Funeral preference is unlikely to have been a significant factor in the decline in clinical necropsy rates.

Attitude to Health↗
PubMed1996

Ownership and uses of human tissue: does the Nuffield bioethics report accord with opinion of surgical inpatients?

OBJECTIVE: To compare opinion of surgical inpatients with the conclusions of the report of the Nuffield Council on Bioethics regarding the ownership and uses of human tissue. DESIGN: Survey of results of questionnaires completed by patients. SETTING: Large teaching hospital. SUBJECTS: 384 postoperative adult surgical patients. RESULTS: There was strong support among patients for the use of tissues in medical education, research, and science with the exception of those tissues which may transmit disease to others. Few patients (39; 10%) believed that they retained ownership of tissue removed at surgery. Most believed that the tissue belonged to the hospital (103; 27%), to nobody (103; 27%), or to the laboratory (77; 20%). Most patients had not been given any information about the possible uses of their tissues after removal. CONCLUSIONS: Surgical inpatients seem to endorse the conclusions of the Nuffield report regarding the ownership and uses of human tissue. The recommendations regarding patient information and consent procedures should be implemented at the earliest opportunity.

Adult↗
PubMed1996

The natural history of chronic hepatitis C in haemophiliacs.

Most haemophiliacs treated with non-virally-inactivated clotting factor concentrates have been infected with hepatitis C virus (HCV). We have studied the natural history of chronic HCV infection by following all 138 HCV-positive patients from our centre for periods of up to 28 years. As well as the clinical and biochemical characteristics, we studied 116 liver samples from 63 patients obtained at elective biopsy (n = 103) or autopsy (n = 13). 36 (26%) of the patients were HIV positive, and three were chronic carriers of hepatitis B. Evidence of previous exposure to hepatitis A and B was found in 37.2% and 48.1% respectively. Raised transaminase levels were found in 82.6% of patients. 11 of 15 patients with normal transaminases tested by PCR for HCV RNA were positive, indicating that most patients, even in this group, have chronic hepatitis C infection. Cirrhosis was diagnosed by liver histology in 19 patients, and nine patients developed liver failure. The incidence of cirrhosis rose rapidly 15 years after HCV infection to 15.6 per 1000 person-years. Multivariate analysis showed that HIV status, length of time since HCV infection and age at HCV infection were independently associated with both the development of cirrhosis and liver failure. Two patients developed hepatocellular carcinoma: one of these was exposed only to a single batch of FVIII concentrate 11 years earlier. Chronic hepatitis C is increasingly recognized as a major cause for morbidity and mortality in haemophiliacs, especially those who are HIV positive and who were infected at an older age.

Adolescent↗
PubMed1996

Funeral directors, mortuaries and necropsies: implications for necropsy consent rates and the prevention of infection.

AIM: To evaluate the attitudes and experiences of funeral directors in relation to necropsies. METHODS: All 1631 members of the National Association of Funeral Directors were surveyed by postal questionnaire about the purposes of necropsies, the technical and administrative problems associated with necropsied cases and their relations with relatives, mortuaries and pathology departments. RESULTS: In total, 123 funeral directors completed the questionnaire (8% response rate). Workload, proportion of cases necropsied and type of mortuary did not influence answers. Necropsies were considered important for the assessment of treatment outcome, identification of inherited disease and junior pathologist training, but not for medical audit. There was strong support for more education about necropsies. The areas of necropsy practice most frequently discussed with relatives related to concerns about funeral delay and the involvement of the coroner or equivalent authority. Funeral directors occasionally counselled relatives for or against giving necropsy consent. The commonest technical problems associated with necropsies were difficulties in embalming, leakage of body fluids and scalpel penetration in visible areas. Few administrative problems were reported; the commonest was inflexibility in body collection times. There was strong support for a national code of practice to cover relations between funeral directors and mortuaries despite general satisfaction with relations with local pathology departments. CONCLUSIONS: Although the relation among the funeral profession, mortuaries and pathology departments is largely satisfactory, a national code of practice for funeral directors and mortuaries is desirable.

Attitude↗
PubMed1995

Heterogeneity of hepatitis C virus genotypes in hemophilia: relationship with chronic liver disease.

In this study we have determined the hepatitis C virus (HCV) serotype and genotype in a cohort of 96 HCV-infected hemophiliacs and have examined the relationship between HCV genotype and severity of chronic liver disease as determined by liver biopsy. HCV serotype was determined by specific enzyme-linked immunosorbent assays (ELISAs) and genotype by restriction fragment length polymorphism (RFLP) and HCV viral sequencing. The pattern of genotype distribution was quite unlike that of HCV-infected United Kingdom (UK) blood donors in that five of the six known HCV genotypes were represented, 50% were type 1, 13% type 2, and 18% type 3. An unexpected observation was the presence of HCV genotype 4 in four patients and type 5 in two patients. An additional feature was the presence of mixed infection, detected in 14% and 7% by serotype and genotype analysis, respectively. Liver biopsies were available from 51 patients. Cirrhosis was present in five of 27 (19%) of individuals with type 1, in 2 of 9 (22%) with type 2, and 5 of 8 (63%) of those with type 3. The heterogeneous pattern of HCV genotype distribution in this cohort of patients and the observed relationship between the severity of the related liver disease and specific HCV genotype may have important implications with respect to the natural history and treatment of HCV-related chronic liver disease in infected hemophiliacs worldwide.

Alanine Transaminase↗
PubMed1995

Fractal and integer-dimensional geometric analysis of pigmented skin lesions.

Accurate in vivo diagnosis of pigmented skin lesions is required to identify and excise malignant melanomas but to avoid unnecessary excision of benign lesions; the published rates of clinical diagnostic accuracy are about 65%. This study investigates whether fractal geometric analysis of pigmented skin lesions can improve the rate of diagnostic accuracy. Forty-two pigmented skin lesions (15 malignant melanomas, 21 melanocytic naevi, and 6 basal cell papillomas) on patients attending a dermatology clinic were photographed, excised, and sent for histopathological examination. The fractal dimension of the boundary of the lesions was measured using a box-counting method implemented on a microcomputer-based image analysis system. Euclidean geometric parameters were also measured. The fractal dimension of all the lesions was greater than the topological dimension (one), indicating that there is a fractal element to their structure. Using all measured parameters together, multivariate linear discriminant analysis produced a confusion matrix in which 45% of the lesions were assigned to the correct diagnostic group with a kappa statistic of 0.33. There was no significant difference between the fractal dimension of melanocytic naevi and that of malignant melanomas (p = 0.18). Although pigmented skin lesions have a fractal element to their structure, the fractal dimension of their boundaries is not a useful morphometric discriminant between the diagnostic groups of malignant melanomas and benign melanocytic naevi.

Algorithms↗
PubMed1995

Cavitation of mesenteric lymph nodes: a rare complication of coeliac disease, associated with a poor outcome.

Five cases are presented, all of which showed peculiar cavitation of mesenteric lymph nodes. Clinically, three presented with abdominal symptoms, a mass or obstruction, warranting laparotomy. Two patients showed cavitating mesenteric lymph nodes at autopsy. Lymph nodes were enlarged with central, partly cystic degeneration; milky fluid exuded from the cut surface. In each case, investigation showed intestinal villous atrophy and splenic atrophy; coeliac disease was confirmed by response to gluten withdrawal. Three patients died, two from cachexia and the other from pneumonia; the other two are alive and well one year and six years after presentation. Review of the literature shows 12 previously reported cases, with a mortality of about 50%. The diagnosis is made by the histopathologist, alerting appropriate treatment. The pathogenesis is unknown.

Adult↗