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J Rhodes

Publications and source records attributed to J Rhodes.

At least 145 records · Page 8Linked to original sources

Smoking, eicosanoids and ulcerative colitis.

In this study, which is the first of its kind using normal tissue samples that are very difficult to obtain, we have investigated the hypothesis that smoking protects against ulcerative colitis by altering the colonic mucosal formation of prostaglandins and related substances. Colonic mucosa biopsied from healthy young men produced prostaglandin E, 6-keto-PGF1 alpha (formed from PGI2), leukotriene B4 and leukotriene C4/D4/E4 as determined by radioimmunoassay. With each substance, the median yield was lower in the group of smokers who smoked 3 cigarettes in the 2 h before biopsy, than in the non-smokers. However, with each eicosanoid the statistical probability approached only the 10% level, but the fact that the trend was the same for all eicosanoids somewhat strengthens the possibility of a real difference between the groups.

6-Ketoprostaglandin F1 alpha↗

Squamous carcinoma in the liver.

Squamous carcinoma of the liver has only rarely been reported. We present a case which highlights not only the difficulties in diagnosis but also how it can closely mimic sclerosing cholangitis.

Aged↗

Effect of ulcerative colitis and smoking on rectal blood flow.

Rectal blood flow was measured by laser doppler flowmetry over 60 minutes in eight patients with colitis in remission and eight healthy male non-smokers. Ten smokers were also examined on two occasions, one of which included smoking a cigarette. Plasma nicotine concentrations were measured in smokers. All subjects showed a pronounced fall in rectal blood flow in the first 30 minutes and patients with colitis had significantly higher values compared with smokers (p less than 0.002; p less than 0.04) and non-smokers (p less than 0.007; p less than 0.002) during the first and second 30 minutes respectively. Values in smokers and non-smokers were similar, but smoking a cigarette was associated with a significant fall in blood flow (p less than 0.04) and this change was inversely related to the rise in plasma nicotine concentration (r = -0.63; p less than 0.05). The findings may be relevant to the association between colitis and the smoking history.

Adult↗

Effect of right ventricular anatomy on the cardiopulmonary response to exercise. Implications for the Fontan procedure.

Incorporation of the right ventricle (RV) into the pulmonary circulation of patients with tricuspid atresia undergoing a Fontan procedure has been advocated. The consequences of this approach on the exercise function of these patients was studied by examining the effects of progressive and steady-state bicycle exercise tests performed by 11 patients with right atrial (RA)-RV Fontan anastomoses, seven patients with RA-pulmonary artery (PA) Fontan anastomoses, 13 patients after repair of tetralogy of Fallot, and 34 normal control patients. All patients were in New York Heart Association class I. The exercise function of the patients undergoing RA-RV and RA-PA Fontan procedures were similar. The achieved peak work loads 60% and 67% of control and peak oxygen consumptions 60% and 64% of control, respectively. Both groups also displayed excessive ventilation, elevated dead space/tidal volume ratios, and depressed cardiac output during steady-state exercise. In contrast, tetralogy of Fallot patients achieved peak work loads and oxygen consumptions 83% of control and maintained normal cardiac outputs and dead space/tidal volume ratios during steady-state exercise. These results suggest that the presence of an RV within the pulmonary circulation of the Fontan patient does not result in improved exercise function. This may be due to the development of obstructive gradients across the RA-RV conduits during exercise or to the RV's negative effect on left ventricular compliance. Moreover, in contrast with the postoperative tetralogy of Fallot patient, the hypoplastic RV of tricuspid atresia may not have sufficient myocardium to assume the active pumping function required by exercise.

Adolescent↗

Phagocytosis of Histoplasma capsulatum yeasts and microconidia by human cultured macrophages and alveolar macrophages. Cellular cytoskeleton requirement for attachment and ingestion.

Phagocytosis of Histoplasma capsulatum (Hc) yeasts and microconidia by human macrophages (M phi) was quantified by a fluorescence quenching technique. Phagocytosis of unopsonized Hc yeasts by monocyte-derived M phi and human alveolar M phi (AM) was rapid. After 60 min, 79% of cultured M phi and 59% of AM had ingested an average of 9.8 and 11 yeasts/M phi, respectively. In contrast, only 26% of monocytes ingested 4.5 yeasts/cell after 60 min. Phagocytosis of unopsonized microconidia by cultured M phi and by AM was equivalent. Monoclonal antibodies specific for the alpha-chains and beta-chain of the CD18 family of adhesion receptors inhibited the binding of Hc yeasts and microconidia to cultured M phi and AM. Thus, the M phi CD18 complex mediates recognition of both phases of this dimorphic fungus. Disruption of actin microfilaments with cytochalasin D inhibited both attachment and ingestion of yeasts by M phi. In contrast, nocodazole, which prevents polymerization of microtubules, did not inhibit binding or ingestion. Both drugs inhibited ingestion, but neither drug inhibited binding of C3b- and C3bi-coated sheep erythrocytes to complement receptors type one (CR1) or type three (CR3), respectively. Therefore, different signal transducing mechanisms for phagocytosis appear to be triggered by the binding of Hc yeasts to CD18, and by the binding of EC3bi to CD11b/CD18, respectively.

Antibodies, Monoclonal↗

Oxygen consumption and cardiac response of short-leg and long-leg prosthetic ambulation in a patient with bilateral above-knee amputation: comparisons with able-bodied men.

This study measured oxygen uptake (VO2), minute ventilation (VE), and heart rate (HR) in a bilateral above-knee (AK) amputee and in three able-bodied controls during progressive treadmill exercise. Walking conditions for the amputee included using bilateral short-leg (SL) and long-leg (LL) prostheses. A progressive treadmill protocol to maximal capacity was used for the amputee and duplicated by the control subjects. An automated system was used to measure VO2, VE, and HR throughout exercise. Data analysis was restricted to the use of parameter averages and percentages to describe differences between experimental conditions. Maximal VO2 for the amputee averaged 23.3mL/kg-1/min-1 with the LL and 22.8mL/kg-1/min-1 with the SL prostheses, a negligible difference between conditions; however, exercise duration was 27% longer when using the SL prostheses. In addition, when averaged over the first four stages of exercise, VO2, VE, and HR were 24%, 32%, and 14% higher, respectively, when the LL prostheses were used. Treadmill walking by unimpaired controls averaged 47% and 79% more economical than walking with the SL or LL prostheses, respectively. These results demonstrate that the use of currently available AK prostheses requires significant energy expenditure, which limits their use to only the most physically fit individuals.

Adult↗

Epidemiological survey of coeliac disease and inflammatory bowel disease in first-degree relatives of coeliac patients.

One hundred and sixty-two of 182 patients with coeliac disease provided satisfactory details of family size and the prevalence of coeliac disease and inflammatory bowel disease among their first-degree relatives. Patients ranged in age from 11 months to 79 years with a mean age of 41 (+/- 23) years. Twenty patients had at least one first-degree relative with coeliac disease: a total of 25 of 861 relatives were affected (prevalence = 2904/100,000) compared with an expected 0.9 cases (prevalence = 100/100,000; p less than 0.001). Six relatives had inflammatory bowel disease (prevalence = 697/100,000) compared with an expected 1.3 cases (prevalence = 150/100,000; p less than 0.001). Five of these had ulcerative colitis, and one had Crohn's disease. The relative risk of ulcerative colitis is, therefore, five times greater for first-degree relatives of people with coeliac disease than for the general population (95 per cent confidence interval, 4.7-7.2). There is a clear association between coeliac disease and ulcerative colitis, which may point to factors involved in the aetiology of colitis.

Adolescent↗

Evidence for an intercellular covalent reaction essential in antigen-specific T cell activation.

The inductive interaction between class II+ APC and Th cell was investigated in a human system at the chemical level. The study set out to test the predictions of a model of Ag presentation in which epsilon-amino groups and carbonyl groups at the surface of APC and T cell react covalently to form reversible intercellular Schiff bases. In the experimental system of oxidative mitogenesis this process results in T cell activation. If oxidative mitogenesis is an experimental amplification of a physiologic process, and intercellular Schiff base formation is essential in Ag presentation, then it should be possible to inhibit Ag presentation by prior formation of Schiff bases on the surface of participating cells. In this situation Ag-induced T cell activation and T cell activation induced by periodate oxidation should invariably behave in the same way. It should also be possible to demonstrate Schiff base formation occurring between accessory cells and lymphocytes directly and definitively by means of specific reduction with sodium cyanoborohydride. Aldehyde treatment of accessory cells should prevent this intercellular Schiff base formation. In this study the following observations were made. 1) Both Ag-specific and periodate-induced T cell activation were inhibited by aldehyde treatment of class II+ accessory cells. 2) Noncross-linking donors of carbonyl groups other than aldehydes inhibited Ag-specific T cell activation. 3) Brief, low-dose treatment of T cells with aldehydes inhibited Ag-dependent T-cell activation. 4) Exogenous amino groups in the form of lysine and other amino acids inhibited both Ag-specific and periodate-induced T-cell activation. 5) The weak reducing agent sodium cyanoborohydride which is specific for Schiff bases at neutral pH inhibited both Ag-induced and periodate-induced T cell activation. Responses to PHA were markedly prolonged by this reagent. 6) Schiff base formation occurring between accessory cells and lymphocytes was detected directly and definitively by means of radiolabeling with NaCNB(3H)3 at neutral pH. These data are consistent with the view that the formation of reversible covalent Schiff bases between ligands on APC and T cell is an essential process in Ag-induced T cell activation.

Aldehydes↗

The histology of anal skin tags in Crohn's disease: an aid to confirmation of the diagnosis.

We have investigated excision biopsy of anal skin tags as an adjunct to rectal biopsy in the diagnosis of Crohn's disease. Twenty-six patients with proven Crohn's disease of the large and/or small bowel were studied. All had perianal skin tags removed under local anaesthesia as outpatients, when rectal biopsies were also obtained. Three sections from each skin tag and three from each rectal biopsy were examined for granulomas. The rectal biopsies were also examined for changes 'suggestive' of Crohn's disease. Anal skin tags from 26 patients without Crohn's disease acted as controls. Of the patients with Crohn's disease, granulomas were found in both anal skin tags and rectal biopsies in five patients, in anal skin tags only in four, and in rectal biopsies only in three. When present, granulomas were more plentiful in anal skin tags than in rectal biopsies, being seen in all 3 sections in 7 of 9 'positive' tags (i.e.: in 31% of 78 sections), compared to only 1 of 8 'positive' rectal biopsies (i.e.: in 13% of 78 sections). No granulomas were seen in control anal skin tags. The procedure provides a simple technique which is complementary to rectal biopsy, by which histological confirmation of Crohn's disease may be obtained.

Adult↗

Effect of ranitidine on gastroduodenal mucosal damage in patients on long-term non-steroidal anti-inflammatory drugs.

Twenty-four patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs) were followed in a double-blind placebo-controlled trial to assess the effect of ranitidine 300 and 600 mg daily on upper gastrointestinal mucosal damage and to assess methods of monitoring mucosal damage. Sixteen were given ranitidine and 8 had placebo throughout the study. Comparisons suggested that ranitidine reduced symptoms and endoscopic evidence of mucosal damage. Histological evidence of gastritis was present in only half of those on ranitidine but in all receiving placebo. Erosions and blood loss occurred intermittently during the study but faecal blood losses using 51Cr-labelled red cells failed to identify any difference between groups. Endoscopic observation of erosions and serial biopsies may provide simple, reliable measurements for future studies to assess the effect of therapy in reducing mucosal damage from long-term NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

Effect of nicotine and cotinine on the production of oxygen free radicals by neutrophils in smokers and non-smokers.

1. Neutrophils play a role in the pathogenesis of ulcerative colitis. Most of the patients with ulcerative colitis are non-smokers. 2. Neutrophil function was examined in healthy males, five smokers and five non-smokers, measuring production of oxygen free radicals by chemiluminescence. 3. The chemiluminescence was examined in the presence of nicotine and its main metabolite cotinine in various concentrations. 4. 10 mM nicotine inhibited production of oxygen free radicals (90.2% +/- 11.6) compared with controls (P less than 0.001), as did the same concentration of cotinine (58.9% +/- 34.2), (P less than 0.05). 5. 1 mM solutions had no effect and 3 mM nicotine was required to achieve 50% inhibition. 6. Smokers and non-smokers did not differ. 7. Since plasma concentrations of nicotine after a cigarette are only between 5 and 15 mM, the observed effects of nicotine and cotinine in much higher pharmacological concentrations in this system are unlikely to be of clinical relevance in ulcerative colitis.

Cotinine↗

Does smoking improve colitis?

In 14 of 30 patients with ulcerative colitis who resumed smoking there was an improvement in their symptoms over the subsequent median period of 6 weeks. This group smoked a median number of 20 cigarettes, compared with 10 by those who did not improve.

Adult↗

A study of the menopause, smoking, and contraception in women with Crohn's disease.

One hundred and ninety-six women with Crohn's disease from south-east Wales were asked to provide details of their menstrual cycles, age at menopause, history of surgery, smoking habits and use of oral contraceptives. One hundred and forty-six provided the information (response rate 77 per cent). Eighty-four were still menstruating, three were pregnant, 10 had undergone hysterectomy, one had a pharmacologically-induced menopause and 48 had had a physiological menopause. Of these 48 women, 33 were diagnosed as having Crohn's disease before the menopause. Twenty-five of these were smokers. The mean age at menopause was similar in smokers and non-smokers and in those diagnosed before and after the menopause. The mean age at menopause was between 46 and 47. A logistic analysis using the 'status quo' method showed that 50 per cent of women with Crohn's disease had the menopause at 47.6 years compared with 49.6 years in a group of healthy women from the same area. The two groups had similar smoking habits and it would seem that a premature menopause is associated with Crohn's disease.

Adult↗

Platelet number and size in relation to serum orosomucoid concentration in Crohn's disease.

The relationship between platelet size and platelet count was investigated in 41 patients with Crohn's disease. A high platelet count was associated with a decrease in platelet size, but an overall increase in the platelet crit. There was also a significant correlation between the patient's platelet count and serum orosomucoids, which have traditionally been used to assess disease activity.

Adolescent↗

Functional abolition of monocyte HLA-DR by aldehyde treatment. A novel approach to studies of class II restriction elements in antigen presentation.

The effect of low concentration aldehyde treatment (0.0012 to 0.005%) on the expression of HLA-DR Ag by human monocytes was investigated. This treatment was shown to selectively abolish the expression of HLA-DR determinants defined by a monomorphic mAb (YE2.36) in a rosette assay. The expression of class I MHC Ag and Fc gamma R remained unaffected. As a result, the presentation of the recall Ag tetanus toxoid and streptokinase-streptodornase (SK-SD) to freshly isolated autologous T cells and T cell clones was completely inhibited. Increasing the concentration of aldehyde to 0.05% consistently produced partial restoration of Ag-presenting capacity. Low dose aldehyde treatment did not affect monocyte viability or membrane turnover. Thus, aldehyde-treated monocytes produced a second generation of HLA-DR and expression was almost completely restored to normal after 24 h of culture. The presentation of monocyte class II Ag as alloantigens was also inhibited by low dose aldehyde treatment but inhibition was much less marked when monocytes were aldehyde treated at 2 h rather than at 24 h of culture. This is consistent with the reexpression of HLA-DR which occurred readily in the first 24 h of culture and much less readily thereafter. Low dose aldehyde treatment did not affect Ag uptake and processing. However, monocytes which had been pulsed with Ag, aldehyde-treated to abolish HLA-DR, and then cultured to allow regeneration of HLA-DR could present Ag only when given a second Ag pulse, suggesting that once the association between microbial Ag and HLA-DR had formed the Ag was not then free to reassociate with novel HLA-DR. Low dose aldehyde treatment did not affect monocyte IL-1 production, neither did it inhibit the detection of HLA-DR by soluble mAb in FACS analysis. These results are consistent with the view that low dose aldehyde treatment disrupts the tertiary structure of human Ia molecules such that allostimulatory determinants and restriction elements for exogenous Ag are rendered inaccessible to T lymphocyte receptors and to cell-bound anti-DR mAb in the rosette assay, although DR determinants may remain accessible to soluble mAb.

Aldehydes↗