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R Chapman

Publications and source records attributed to R Chapman.

At least 73 records · Page 4Linked to original sources
PubMed1996

Antineutrophil cytoplasmic antibodies in chronic liver diseases: prevalence, titre, specificity and IgG subclass.

BACKGROUND/AIMS: Antineutrophil cytoplasmic antibodies are reported in patients with chronic liver disease, but controversy exists about their prevalence and specificity. We aimed to find the prevalence and specificity of antineutrophil cytoplasmic antibodies in chronic liver diseases by determination of antineutrophil cytoplasmic antibody titre and IgG subclass. METHODS: One hundred and eight-four sera were studied: 63 primary sclerosing cholangitis, 28 autoimmune hepatitis, 34 primary biliary cirrhosis, 12 alcoholic liver disease, five large duct obstruction, four haemochromatosis, one chronic cholestatic syndrome, one cryptogenic cirrhosis and 36 normal individuals. Antineutrophil cytoplasmic antibodies were detected on alcohol-fixed neutrophils using an alkaline phosphatase technique. The IgG subclass of antineutrophil cytoplasmic antibodies was determined using monoclonal antibodies: HP 6001 for IgG1, HP 6002 for IgG2, HP 6050 for IgG3 and SK 44 for IgG4 (Sigma Immunochemicals). RESULTS: Antineutrophil cytoplasmic antibodies were detected in 65% of primary sclerosing cholangitis patients at a serum dilution of 1:5, dropping to 49% at 1:50. For autoimmune hepatitis, antineutrophil cytoplasmic antibodies were detected in 49% at 1:5, dropping to 11% at 1:50. Only 6% of primary biliary cirrhosis patients were antineutrophil cytoplasmic antibody-positive at 1:5, dropping to 3% at 1:50. All other controls were antineutrophil cytoplasmic antibody negative at 1:5. The presence of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis correlated with involvement of the intra- and extrahepatic biliary tree (p = 0.016, Fisher's exact test), but no other clinical parameters. Determination of the IgG subclass of antineutrophil cytoplasmic antibody in 33 primary sclerosing cholangitis and 11 autoimmune hepatitis patients revealed a predominance of IgG1 in both groups (94% and 82% of all IgG antineutrophil cytoplasmic antibodies, respectively), with a similar distribution of IgG2, IgG3 and IgG4 antineutrophil cytoplasmic antibodies between the groups. CONCLUSIONS: Antineutrophil cytoplasmic antibodies are specific to the autoimmune liver diseases, particularly primary sclerosing cholangitis and autoimmune hepatitis. Titres are highest in primary sclerosing cholangitis, with a diagnostic sensitivity of 49% and specificity of 89% at 1:50, making it a useful serological marker for this disease. The lack of correlation with any marker of activity and the association of antineutrophil cytoplasmic antibody with extent of biliary tract involvement suggest that antineutrophil cytoplasmic antibodies arises as a result of the disease or related process rather than being a cause of it. The detection of antineutrophil cytoplasmic antibodies in autoimmune hepatitis, together with a similar IgG subclass distribution of primary sclerosing cholangitis and autoimmune hepatitis antineutrophil cytoplasmic antibodies, may reflect similar mechanisms of immune regulation and a possible overlap syndrome. Future identification of the antigens against which this antineutrophil cytoplasmic antibody are directed should help to clarify this point, as well as allowing the development of a more sensitive and specific serological test for diagnostic purposes.

Adult↗
PubMed1996

Empirical reconstruction of the renal artery: long-term outcome.

PURPOSE: Unequivocal indications for renal artery reconstruction remain the presence of significant underlying renal insufficiency or severe hypertension. Thus surgical intervention for renal artery stenosis in the absence of this clinical picture may well be considered empirical and, as a consequence, treatment recommendations are ill-defined. Our experience with reconstruction of the minimally symptomatic or asymptomatic renal artery lesion in association with primary aortic repair over a 10-year period was reviewed. METHODS: Thirty-two patients who had atherosclerotic renal artery stenosis > or = 70% underwent prophylactic renal revascularization between 1982 and 1992. The patients' median age was 63 years (range, 44 to 79 years); 23 (72%) were men and nine (28%) were women. All had preoperative serum creatinine levels < or = 1.7 mg/dl (1.29 +/- 0.24 mg/dl) and were receiving either no antihypertensive medication (22%) or only a single agent (78%). Aortoiliac occlusive disease was present in 38% of this population, and aortic aneurysmal disease either alone or in combination with occlusive disease was found in 62%. RESULTS: Operative management included unilateral renal artery repair in 21 patients (66%) and bilateral renal revascularization in the remaining 11 (34%). The median decrease in postoperative serum creatinine level (> or = 7 days after operation) was 0.81 +/- 0.05% (mean postoperative serum creatinine level 1.27 +/- 0.07 mg/dl). The 30-day operative mortality rate was 3.1% (1 of 32). Late follow-up was available for 96% of patients (30 of 31; median, 64 months). Kaplan-Meier life table analysis revealed a 5-year probability of survival of 90.2% (95% confidence interval, 0.802 to 1.00). Stability of renal function was assessed by modeling the change in serum creatinine level over time with the intraclass correlation model. A serum creatinine level (mg/dl) = 1.3348 + 0.0011 x time (months) demonstrated minimal deterioration of excretory function during the observation period. Furthermore, the blood pressure of the majority of patients (75%) remained normal either with a single agent or without medication. Recurrent stenosis in one patient required treatment by percutaneous transluminal angioplasty. CONCLUSIONS: Adjunctive repair of the renal artery may be an appropriate option in selected patients who undergo simultaneous aortic surgery, even in the absence of severe hypertension or renal insufficiency. Surgical intervention can be accomplished with acceptable perioperative morbidity rates, and stability of renal function is sustainable in the majority of patients.

Adult↗
PubMed1996

Some factors associated with mortality in perforated peptic ulcer: a case-control study.

This study examined the associations of individual coexisting illnesses, septicaemia, intra-abdominal abscess, marital status, smoking and alcohol use, with mortality following perforation of peptic ulcer without pre-operative evidence of haemorrhage. Patients who died in hospital following ulcer perforation (cases; n = 300) were compared with patients who survived following ulcer perforation (controls; n = 276). The controls were frequency-matched to the cases on age, sex and perforation site. Data were analysed by logistic regression. Cardiac, respiratory, cerebrovascular, renal, liver and malignant diseases, and septicaemia and intra-abdominal abscess were associated with mortality and the coexisting illnesses were significantly increased in cases compared to controls both on admission and at the end of hospital stay. During hospitalization, the odds of pneumonia decreased in cases, otherwise there was little change in strengths of associations over this period. Being widowed or never married was positively associated with mortality, and moderate alcohol use was negatively associated. In conclusion, this study identifies several coexisting illnesses, septicaemia and intra-abdominal abscess as risk factors for mortality following ulcer perforation. The results suggest that, with little exception, the same level of mortality risk is associated with coexisting illnesses whether the beginning or end of hospital stay is used as the index time point.

Abdominal Abscess↗
PubMed1995

Adhesion molecule expression in primary sclerosing cholangitis and primary biliary cirrhosis.

There are conflicting reports regarding intercellular adhesion molecule-1 (ICAM-1) expression in primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Expression of adhesion molecules ICAM-1, lymphocyte adhesion molecule-1 (LFA-1), vascular cell adhesion molecule (VCAM), and E-selectin was examined together with HLA-DR in 16 liver biopsy specimens showing PSC and 12 specimens showing PBC. These were compared with biopsy specimens showing large duct obstruction (n = 7), chronic active hepatitis (n = 4), alcoholic liver disease (n = 4), and normal liver histological results (n = 5). ICAM-1 was detected on biliary epithelium in five of seven PSC specimens of histological stage 3 or 4, but not in nine early PSC specimens or in specimens from disease controls. In PBC, ICAM-1 was positive on three of 12 cases, two stage 2, and one stage 3. Nine of 16 PSC specimens (three of nine early, six of seven late disease) and six of 10 PBC specimens (three early, three late disease) were positive for HLA-DR. LFA-1 stained infiltrating inflammatory cells in PSC, PBC, and disease controls. In conclusion, ICAM-1 expression on biliary epithelium in PSC occurs mainly in late stage disease and therefore may be secondary to previous events inducing inflammation rather than of primary pathogenic importance. ICAM-1 expression in PBC is less common and not clearly associated with a particular disorder. Previous reports of ICAM-1 prevalence may have been biased towards end stage, pre-transplantation biopsy specimens.

Cell Adhesion Molecules↗
PubMed1995

Preparing for and handling agency inspections for the United Kingdom Department of Health.

This paper indicates some known differences in approach adopted by the United Kingdom Department of Health (DoH) Good Laboratory Practice (GLP) Monitoring Authority from that of other agencies and offers guidance to quality assurance (QA) professionals in dealing effectively with a DoH inspection. The UK GLP Programme contains, at present, just over 100 member laboratories, ranging from one-man pathology outfits to major companies with perhaps over 1000 staff working in compliance. Laboratories in the GLP program are subject to routine inspection every 2 years; without a satisfactory inspection and continued membership in the GLP program, UK laboratories cannot make a formal claim of compliance. Routine inspections occur at 2-year intervals, with a formal period of notice, allowing some preparation to occur. Routine inspections comprise the selection of a small number of studies for audit and inspection of all the facilities. Inspectors look critically at QA and management systems and routinely interview staff to get a feel for the skills, knowledge, competence, and attitude of those who work on nonclinical studies. Study directors are constant targets for the inspectors' inquisition. Throughout the inspection process, inspectors are accompanied by senior QA staff, whose notes are used to ensure that nothing in the final meeting is reported incorrectly or out of context. The inspectors leave after verbal discussion with management of any significant findings. A full written report is typically provided within 3 weeks, to which a written response from management is required within 4 weeks. There is no Freedom of Information program in the UK.

Appointments and Schedules↗
PubMed1994

Treatment of cancer-associated hypercalcemia. Double-blind comparison of rapid and slow intravenous infusion regimens of pamidronate disodium and saline alone.

BACKGROUND: We assessed the effects of 60-mg single doses of pamidronate disodium compared with saline alone in the treatment of cancer-associated hypercalcemia. METHODS: After pretreatment hydration, patients with corrected serum calcium concentrations of 3.0 mmol/L (12 mg/dL) or greater secondary to cancer were randomized to double-blind treatment with a single infusion of pamidronate disodium, 60 mg, over either 4 or 24 hours or continued infusions of 0.9% saline alone (n = 23 per group). Corrected serum calcium levels were measured daily for 7 days of inpatient evaluation. RESULTS: Response rates for both of the pamidronate regimens were significantly (P < .05) higher than that for saline alone. A complete response to treatment (corrected serum calcium concentration normalized) was observed for five (22%), 18 (78%), and 14 (61%) patients, respectively, who received saline alone, 4-hour infusion of pamidronate, and 24-hour infusion of pamidronate. There were no significant differences between the two pamidronate regimens. Median durations of complete response were 6, 6, and 11 days, respectively, and median times to relapse (includes complete plus partial responders and nonresponders) were 0, 7, and 7 days, respectively. Pamidronate was well tolerated as assessed by all clinical and laboratory measures, regardless of the time of infusion. CONCLUSIONS: A 4-hour infusion of pamidronate disodium, 60 mg, was as safe and effective as a 24-hour infusion, and both were superior to saline alone in lowering corrected serum calcium concentrations in patients with cancer-associated hypercalcemia.

Adult↗
PubMed1994

BCL2 translocations in leukemias of mature B cells.

Although translocations of the BCL2 gene are frequent in B-cell non-Hodgkin's lymphomas (B-NHL) the incidence, nature, and prognostic significance of similar translocations in the phenotypically related chronic leukemias of mature B cells are unknown. Therefore, we examined 170 cases of B-cell chronic lymphocytic leukemia (B-CLL), 7 cases of B-cell prolymphocytic leukemia (B-PLL), 25 cases of hairy cell leukemia (HCL) and 22 cases of splenic lymphoma with villous lymphocytes (SLVL) with defined cytogenetic abnormalities by DNA blot using both 5' and 3' BCL2 probes to search for rearrangement of the BCL2 locus. Translocation t(14;18) (q32.3;q21.3) was detected cytogenetically in 3 cases of B-CLL. All had breakpoints in the 3' region of BCL2, mapping between the major breakpoint region (MBR) and the minor cluster region (mcr), the breakpoint clusters commonly detected in B-NHL. In 2 of the 3 cases, the breakpoint within BCL2 was mapped to a 1.0-kb EcoRI-HindIII fragment indicating a clustering of breakpoints. Two cases of B-CLL had cytogenetically detectable t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). Both had rearranged the 5' region of the BCL2 gene to the corresponding lg light-chain gene. Molecular cloning of the t(18;22)(q21.3;q11) showed that the translocation disrupted the BCL2 promoter region and the first untranslated BCL2 exon. Nevertheless, high levels of BCL2 protein were seen in this case. Only 2 other cases in whom cytogenetic analysis was not successful showed rearrangement of the 5' region of BCL2, an overall incidence of 2.3%. No cases of B-PLL, HCL, or SLVL showed either 5' or 3' BCL2 rearrangement. These data confirm the cytogenetic observations that translocations involving the BCL2 locus in all forms of leukemia of mature B cells are rare, and limited to a minor subset of B-CLL. BCL2 translocations in B-CLL involve hot spots of recombination of both the 5' and 3' regions of the BCL2 gene, which are distinct from those commonly seen in B-NHL, suggesting distinct pathogenic mechanisms.

Aged↗
PubMed1994

Inappropriate expression of blood group antigens in hepatic allografts.

We examined the expression of blood group antigens of the ABO, Lewis and Kell antigen systems using monoclonal antibodies and immunohistochemical study on 42 liver allograft specimens from 33 patients who underwent liver transplantation between 1986 and 1991 to learn whether altered blood group antigen expression might have a bearing on the immunopathogenesis of transplant rejection. Specimens were obtained at intervals of 0 days to 3 yr after transplant; they yielded the following histological diagnoses; time zero (n = 4), acute rejection (n = 4), pure cholestasis (n = 4), biliary obstruction (n = 4), early chronic rejection (n = 4), end-stage chronic rejection (n = 15) and miscellaneous late posttransplant biopsies (n = 7). Aberrant expression of blood group antigens was observed in 5 of 15 patients with chronic rejection. Two transplants into the same group O patient showed aberrant expression of AB antigens on hepatocytes, with a canalicular pattern, in group O-transplanted livers. In all three cases in which a group O liver was transplanted into a group A recipient and histological signs of chronic rejection were present, antibody staining showed acquisition of recipient blood phenotype by the donor liver bile ducts, endothelium or both. Aberrant expression of ABO antigens was seen only in chronic rejection. In seven cases we noted canalicular staining of periportal hepatocytes with the Lewis antibodies, normally confined to ducts and ductules. This was associated with severe cholestasis in six of the seven cases and may have represented early ductular metaplasia. These changes in carbohydrate cell surface phenotype may play a role in regulation of hepatic allograft susceptibility to immune-mediated damage.

Adolescent↗
PubMed1993

A phase II trial of piroxantrone in adenocarcinoma of the pancreas. A Southwest Oncology Group study.

Thirty-five evaluable patients with advanced adenocarcinoma of the pancreas were treated with piroxantrone at a dose of 150 mg/m2 intravenously every 21 days. No objective responses were observed (95% confidence interval 0%-10%). Toxicities of grade > or = 3 were primarily hematologic and were seen in 28 patients. Piroxantrone is inactive in pancreatic cancer and no further investigation of this agent in this tumor is recommended.

Adenocarcinoma↗
PubMed1993

Single-dose intravenous therapy with pamidronate for the treatment of hypercalcemia of malignancy: comparison of 30-, 60-, and 90-mg dosages.

PURPOSE: To determine the efficacy, dose-response relationship, and safety of 30, 60, and 90 mg of a single intravenous dose of an aminobisphosphonate, pamidronate (APD), for the treatment of moderate to severe hypercalcemia of malignancy. PATIENTS AND METHODS: Patients with histologically proven cancer and a corrected serum calcium level of at least 12.0 mg/dL after 48 hours of normal saline hydration were enrolled in a double-blind, multicenter, randomized clinical trial. Pamidronate in 30-, 60-, or 90-mg doses was administered as a single 24-hour infusion. Serum calcium corrected for albumin, urine hydroxyproline, and calcium excretion, and serum parathyroid hormone (PTH) (1-84) were determined before and after pamidronate therapy. RESULTS: Thirty-two men and 18 women entered the study. A dose-response relationship for normalization of corrected serum calcium was seen after pamidronate administration. Corrected serum calcium normalized in 40% of patients who received 30 mg, in 61% of patients who received 60 mg, and in 100% of patients who received 90 mg of pamidronate. The decline in the serum calcium level was associated with decreased osteoclastic skeletal resorption evidenced by a decrease in urine calcium and hydroxyproline excretion. Among those with a normalized corrected serum calcium level, the mean (median) duration of normalization of the corrected serum calcium value was 9.2 (4), 13.3 (5), and 10.8 (6) days in the 30-, 60-, and 90-mg treatment groups, respectively. The response of hypercalcemia to pamidronate was not significantly influenced by the presence of skeletal metastases. PTH 1-84, suppressed in patients on entry into this study, increased to a greater extent in those patients with osteolytic skeletal metastases compared with those with humoral hypercalcemia of malignancy. Clinical improvement, including improved mental status and decreased anorexia, accompanied the decline in the corrected serum calcium level in all three treatment groups. Side effects included low-grade fever, asymptomatic hypocalcemia, hypomagnesemia, and hypophosphatemia. CONCLUSIONS: A single-dose infusion of 60 to 90 mg of pamidronate was highly effective and well tolerated and normalized corrected serum calcium in nearly all patients (61% to 100%) with hypercalcemia of malignancy.

Aged↗
PubMed1993

Vasoactive intestinal peptide, but not pituitary adenylate cyclase-activating peptide, modulates the responsiveness of the gonadotroph to LHRH in man.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are hypothalamic peptides sharing considerable sequence homology which are postulated to be hypophysiotrophic releasing factors. When infused into man, PACAP has no effect on anterior pituitary hormone levels, while VIP causes a significant increase in circulating prolactin concentrations. However, PACAP has recently been shown to augment the release of LH and FSH in response to LHRH in rat anterior pituitary cell culture. In order to ascertain if either peptide has a similar effect in man, PACAP and VIP were infused at 3.6 pmol/kg per min into six healthy male volunteers, and an LHRH test was performed 30 min after the infusion was commenced. Infusion of PACAP did not alter the gonadotrophin response to LHRH significantly. However, VIP augmented the release of LH significantly, both during the infusion and for 30 min thereafter, although there was no effect on FSH release. Thus VIP, but not PACAP, potentiates the release of LH after LHRH injection in man.

Follicle Stimulating Hormone↗
PubMed1993

Primary biliary cirrhosis: contribution of HLA class II allele DR8.

Primary biliary cirrhosis is a chronic cholestatic disease of unknown aetiology which predominantly affects middle-aged women. It is thought to be autoimmune in nature, but unlike many autoimmune diseases no clear HLA association has been described. Several studies have suggested conflicting associations with HLA class II, although a DR8 association is most frequently described. To test the hypothesis that primary biliary cirrhosis is associated with a certain HLA class II locus we genotyped 130 patients with the disease from the north-east region of England and 363 local healthy controls. HLA-DRB1 and confirmatory DQA and DQB genotypes were determined by TaqI restriction fragment DNA length polymorphism analysis. In addition, a polymerase chain reaction technique (double ARMS) was used to investigate the DRB3 locus (DR52) in 98 primary biliary cirrhosis patients and 107 local controls. We found an increased frequency of HLA-DR8 (18.5% vs 9.2%, p < 0.005, relative risk of 2.0 [1.3-3.1]) in the primary biliary cirrhosis group. HLA-DR8-positive primary biliary cirrhosis patients had a higher serum bilirubin level (p = 0.03) than DR8-negative patients. There was no difference in the DR52 frequencies and no association with markers of disease severity. These results support earlier serological findings, although the association between primary biliary cirrhosis and DR8 is weaker than previously described. In addition, DR8-positivity may identify a clinical subgroup with a worse prognosis.

Adult↗