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Biomedical subjects

J Rhodes

Publications and source records attributed to J Rhodes.

At least 19 recordsLinked to original sources
PubMed1992

Galactose oxidation in the design of immunogenic vaccines.

Potent immunological adjuvants are urgently required to complement recombinant and synthetic vaccines. However, it has not been possible to derive new principles for the design of vaccine adjuvants from knowledge of the mechanism of immunogenicity. Carbonyl-amino condensations, which are essential to the inductive interaction between antigen-presenting cells and T helper cells, were tested as a target for the enhancement of immune responses. Enzymic oxidation of cell-surface galactose to increase aminereactive carbonyl groups on murine lymphocytes and antigen-presenting cells provided a potent, noninflammatory method of enhancing the immunogenicity of viral, bacterial, and protozoal subunit vaccines in mice.

Adjuvants, Immunologic↗
PubMed1992

A pharmacokinetic study of sulphasalazine and two new formulations of mesalazine.

We have examined the pharmacokinetics of enteric coated sulphasalazine compared with two new formulations of mesalazine. These consisted of microgranules of mesalazine coated with Eudragit S in a concentration of either 20 or 25% dry lacquer substance; these in turn were enclosed in capsules coated with Eudragit L. In-vitro dissolution studies of coated microgranules showed that drug release was pH dependent. Studies in 7 normal volunteers showed median peak concentrations of 5-amino-salicylic acid and N-acetyl-5-amino-salicylic acid occurred at about 6 hours with both microgranular preparations, compared with sulphasalazine at 15 h. The microgranule formulation coated with 20% Eudragit S gave serum levels and overall systemic absorption similar to values with sulphasalazine. This new formulation may be of value for delivering mesalazine and other therapeutic agents to the colon.

Adult↗
PubMed1992

A comparison of upper gastrointestinal mucosal damage by standard and delayed-release indomethacin.

Forty-five patients taking long-term indomethacin and with endoscopic erosions or superficial ulcers in the oesophagus, stomach or duodenal bulb were randomized in a double-blind study to continue with standard indomethacin or receive a 'delayed-release' formulation. This consisted of microgranules of indomethacin coated with an acrylic resin, Eudragit L, which releases drug in the small intestine. Endoscopy was repeated after 8 weeks and biopsies taken on both occasions. Changes in endoscopic lesions and histological appearances were similar in both groups, although mucosal erythema was less in those given Eudragit L indomethacin. Systemic, rather than topical, effects of indomethacin may therefore be responsible for persistence of gastro-duodenal mucosal lesions in these patients. There is reason to question the clinical practice of using expensive, delayed-release preparations.

Adult↗
PubMed1992

Smoking habits in psoriasis: a case control study.

We have examined smoking habits in 108 patients with psoriasis, including some with palmoplantar distribution, and compared the results with matched controls from the community. There was a significant association between psoriasis, current smoking status (OR = 2.7, 95% CI 1.44-5.42, P less than 0.01) and smoking habits prior to the onset of disease (OR = 3.75, 95% CI 1.68-9.47, P less than 0.001). There was also a marked dose-response relationship; the relative risk of psoriasis in those currently smoking more than 20 cigarettes/day was significantly elevated (OR = 5.3, 95% CI 2.1-13.0, P less than 0.001). Separate analysis of patients without palmoplantar distribution of psoriasis showed a significant association with smoking prior to onset of psoriasis (OR = 3.6, 95% CI 1.5-9.8, P less than 0.001). Smoking may play a role in the aetiology of this common skin disorder.

Adolescent↗
PubMed1992

Incidence of ulcerative colitis in Cardiff over 20 years: 1968-87.

The annual incidence of ulcerative colitis in the city of Cardiff was examined over a 20 year period. In the decade 1968-77, the mean annual incidence was 6.4 per 10(5) of the population compared with 6.3 for the period 1978-87. There was no difference in the distribution or extent of the disease between decades or between sexes. This contrasts with the increased incidence of Crohn's disease during the same period. The study included a survey of family practitioners which identified a further 19 patients (11% of the total).

Adolescent↗
PubMed1992

Perceived discrimination in education and employment by people with Crohn's disease: a case control study of educational achievement and employment.

Eighty three patients in whom the diagnosis of Crohn's disease had been made before the age of 40 years and who had been resident in the city of Cardiff were asked to complete a detailed questionnaire about their educational and employment experiences. Responses were obtained from 58 patients (response rate = 70%), 23 buddy controls, and 27 community controls. The mean (SD) age of patients at the time of the survey was 31 (5) years. Twenty four of the patients were diagnosed before leaving secondary education, at a mean age of 17 years. They had lost significantly more days' schooling than controls (chi 2 = 14.3 p less than 0.001) but had achieved similar academic success as measured by examination passes and attendance at tertiary institutes of education. Similar numbers of patients and controls were employed at the time of the survey, although significantly more patients had experienced long term unemployment (z = 2.6 p less than 0.01). As a result of their experiences up to 30% actively concealed their illness from employers.

Adult↗
PubMed1992

Sexual dysfunction amongst women with Crohn's disease: a hidden problem.

The sexual problems of 50 women with Crohn's disease, of whom 45 had a stable relationship, were investigated by structured interview and compared with age-matched controls. Twenty-four percent patients had either infrequent or no intercourse compared with 4% of controls (chi 2 = 8.3, p < 0.005). However, amongst patients and controls who were sexually active, the frequency of intercourse was similar. Reasons for sexual inactivity included abdominal pain (24%), diarrhoea (20%) and fear of faecal incontinence (14%). Dyspareunia was common in patients (chi 2 = 6.5, p < 0.01) and this was irrespective of the site of disease (large vs. small bowel chi 2 = 0.85, NS). Women with perianal disease and fistulae were more likely to have dyspareunia than women with neither (chi 2 = 4.2, p < 0.05), although this was not so for less extensive involvement with only perianal disease (chi 2 = 2.8, NS) or fistulae (chi 2 = 0.8, NS). Vaginal candidiasis was more common in patients (chi 2 = 5.8, p < 0.02), and on occasions this may have contributed to dyspareunia. Women with Crohn's disease experience sexual problems much more than healthy controls and they need support, sympathetic investigation and management.

Adult↗
PubMed1992

Risk of ulceration with long-term indomethacin: endoscopic and histological changes in upper gastro-intestinal mucosa.

Twenty patients taking long-term indomethacin were chosen for the study because all had a normal endoscopic examination; biopsies, however, from the oesophagus, gastric antrum and duodenal bulb revealed histological inflammation in all patients in at least one site. After 8 weeks during which indomethacin therapy was continued, a further endoscopy revealed lesions in 5 patients--peptic ulcer in 3 and erosions in 2--but only 1 of these had any change in gastro-intestinal symptoms. Irrespective of whether mucosal lesions are seen on endoscopy in patients established on non-steroidal anti-inflammatory drug therapy, they remain in danger of developing both ulcers and erosions which are likely to be asymptomatic. At no time can one justifiably feel this patient group is not at risk of peptic ulceration.

Arthritis, Rheumatoid↗
PubMed1992

Longitudinal study of cortical bone loss in patients with inflammatory bowel disease.

Bone mineral density of the radius was measured by single-photon absorptiometry in 50 patients with inflammatory bowel disease. Thirty-three had Crohn's disease and 17 ulcerative colitis; 25 were women. The mean age was 45 years (range, 18-70 years). Measurements were repeated in 39 of them after a mean follow-up period of 7.9 years (range, 7.1-8.2 years). In female patients the mean (95% confidence interval) annual change in radial bone mineral density was -0.74% (-1.34% to -0.14%) (P = 0.022), the greatest bone loss occurring in postmenopausal women (mean, -1.16% (-2.01% to -0.30%)). In male patients the mean annual rate of bone loss was -0.07% (-0.41% to 0.28%) (P = NS). Patients with abnormally low values at the first measurement remained osteopenic at the second measurement, whilst some others with normal values initially showed increased rates of bone loss and had a subnormal bone mineral density after the follow-up period. These results show increased rates of cortical bone loss in some patients with inflammatory bowel disease and emphasize the need to monitor bone mass in these patients so that prophylactic measures can be instituted.

Absorptiometry, Photon↗
PubMed1992

Total parenteral nutrition-induced changes in gut mucosal function: atrophy alone is not the issue.

BACKGROUND: Total parenteral nutrition (TPN) has been implicated in gut atrophy and breakdown of barrier function leading to bacterial translocation (BT) in animals. BT during TPN, however, is not found consistently, and it has therefore been suggested that macromolecular permeability may occur independently of BT during TPN. METHODS: Male Sprague-Dawley rats were administered isocaloric standard TPN enterally, parenterally, or split equally between the two routes or allowed food ad lib. A second group of rats was administered isocaloric TPN with and without 4% lipids, and changes in gut barrier function were assessed by measuring lactulose permeability. RESULTS: Rats receiving TPN both enterally and parenterally maintained histologic intestinal structure to the same degree as rats fed enterally and those allowed food. Although parenteral feeding led to significant gut atrophy and cecal bacterial overgrowth, BT was not increased. Gut permeability to lactulose, however, was increased significantly in the TPN groups. Lipid content did not affect outcome. CONCLUSIONS: These results suggest that gut atrophy, BT, and permeability to macromolecules are not necessarily related. Gut-origin septic states during TPN or trauma may be caused by an increased escape of macromolecules from the gut, and BT may be an end result rather than a primary cause of such septic episodes.

Animals↗
PubMed1992

Are non-steroidal anti-inflammatory drugs always necessary? A general practice survey.

The number of patients receiving long-term 'repeat prescriptions' for non-steroidal anti-inflammatory drugs (NSAIDs) was examined in a General Practice; a group of them with osteoarthritis or musculoskeletal pain attempted to withdraw their NSAID treatment and substitute alternative analgesics. Thirty-eight randomly selected patients, with conditions other than rheumatoid arthritis, were interviewed and alternative analgesics prescribed to replace their NSAID therapy. After one month, 22 had very satisfactory pain relief without their NSAID but 16 had resumed therapy, with four of them on a reduced dosage; three others wished to try an alternative analgesic again. Five initially with gastro-intestinal symptoms were asymptomatic within a month of discontinuing their NSAID. After four months, 24 of the 38 had discontinued NSAIDs, including one who had an upper gastrointestinal haemorrhage during the study; two others were taking a reduced dosage.

Adult↗
PubMed1992

Inhibition of specific T-cell activation by monosaccharides is through their reactivity as aldehydes.

The effect of monosaccharides on the inductive interaction between antigen-presenting cells and T cells was investigated in a human system. Some monosaccharides, but not others, were found to inhibit antigen-specific T-cell activation. Responses to mitogen were unaffected. In order for inhibition to occur, a high concentration (approximately 50 mM) of monosaccharide was necessary. The role of monosaccharide aldehyde groups in inhibition was investigated using the alpha-methyl pyranoside and the alditol forms of inhibitory monosaccharides. Unlike the native monosaccharides, these molecular configurations possess the ring structure and the open chain structure respectively but do not contain aldehydes. Together they represent all the molecular characteristics of both forms of the monosaccharide except the possession of aldehyde groups. These two molecular species produced no significant inhibition. Modified forms of the sugar moiety of ribofuranosidoadenine (adenosine) were also tested. The periodate oxidized form of the molecule in which the ribose bears two aldehyde groups, was a potent inhibitor of antigen-induced T-cell activation whereas periodate-oxidized, borohydride-reduced ribofuranosidoadenine, in which the ribose aldehydes are converted to alcohols, produced no inhibition. The former was shown to form Schiff bases with ligands on peripheral blood mononuclear cells (PBMC) as predicted whereas the latter did not. Periodate oxidized dextran, but not native dextran, was also inhibitory. Together these data show that inhibition of T-cell activation by sugars requires reactive aldehydes and this is consistent with the Schiff base model of specific antigen-presenting cell (APC)-T cell inductive interaction in which exogenous aldehydes and other carbonyl donors prevent the necessary formation of Schiff bases between cellular ligands.

Aldehydes↗
PubMed1991

Human T cell recognition of influenza A nucleoprotein. Specificity and genetic restriction of immunodominant T helper cell epitopes.

The characterization of human T cell antigenic sites on influenza A nucleoprotein (NP) is important for subunit vaccine development for either antibody boosting during infection or to stimulate T cell-mediated immunity. To identify such sites, 31 synthetic peptides that cover more than 95% of the amino acid sequence from NP of influenza A/NT/60/68 virus were tested for their ability to stimulate PBL from 42 adult donors. The most frequently recognized region was covered by a peptide corresponding to residues 206-229 of NP, with 20/42 (48%) of responders. In many individuals this was also one of the peptides that stimulated the strongest T cell responses. Other regions that were also frequently recognized were 341-362 by 13/42 (30%), 297-318 by 10/42 (23%), and 182-205 by 9/42 (21%) of individuals. These peptides covered highly conserved regions in NP of influenza A viruses, suggesting that they could be useful in boosting cross-reactive immunity against the known type A virus strains. In order to define the class II restriction molecules used to present particular T cell epitopes, 22 persons from the donor panel were HLA-typed. The majority of persons who expressed DR2, and proliferated to NP also responded to the major immunodominant region 206-229. In addition, this peptide was also immunodominant in the one person expressing DRw13. The observation that recognition of this peptide is associated with DR2 was confirmed by using short term T cell lines and APC from a panel of typed donors. Further results with virus-specific T cell lines and clones and transfected L cells expressing DR molecules showed that DR1 could also present this peptide. Therefore the results suggest that recognition of 206-229 is associated with at least three different DR haplotypes and this may explain the high frequency with which this peptide is recognized in the population. The fine specificity of the response to peptide 206-229 was distinct when presented by DR1- or DR2-expressing APC. The DR1 response was dependent on the N terminus, and the DR2 response was directed to the C terminus of the peptide.

Adult↗
PubMed1991

Sensitivity and tolerance to nicotine in smokers and nonsmokers.

We studied the responses of smokers and lifelong non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n = 8), non-smokers on a 30 mg patch (n = 8) and smokers on a 30 mg patch (n = 8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD = 3.7), 10.9 (SD = 4.2) and 4.1 (SD = 2.7) ng/ml in the three groups, respectively (P less than 0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch (X Cmax 13.9 ng/ml, SD = 4.9; Tmax 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P less than 0.01) within the first hour, and seven dropped out (P less than 0.01) at 3-8 h due mainly to severe nausea, vomiting or headache (X Cmax 18.4 ng/ml, SD = 4.9; Tmax 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour (X Cmax 7.9 ng/ml, SD = 3.0; Tmax 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication.

Administration, Cutaneous↗
PubMed1991

Hemodynamic correlates of exercise function in patients with primary pulmonary hypertension.

The purpose of this investigation was to study the hemodynamic correlates of exercise function in patients with primary pulmonary hypertension and to further define the role of exercise testing in the evaluation of these individuals. Data from the progressive exercise tests and subsequent cardiac catheterization in 16 consecutive patients, aged 16.9 +/- 10.4 years (range 6 to 35), with primary pulmonary hypertension were prospectively collected and analyzed. Exercise capacity averaged 40 +/- 36% (range 0 to 117%) of that predicted for age, height and gender. Statistically significant correlations existed between exercise capacity and 10 invasively measured hemodynamic variables. Mean right atrial pressure, a variable previously noted to be one of the best predictors of survival in patients with primary pulmonary hypertension, correlated best with exercise capacity (r = -0.83, p less than 0.0001). Exercise capacity greater than 75% of the predicted value identified the two patients who had a positive response to acute pulmonary vasodilator drug testing. Poor exercise capacity (less than 10% of the predicted value) identified the three patients who died during or soon after cardiac catheterization. The ability of exercise testing to identify patients at high risk for cardiac catheterization was superior to that of other noninvasive variables. Results of exercise testing may help guide decisions regarding the optimal timing of heart-lung or single lung transplantation.

Adolescent↗