Biomedical subjects

A Griffiths

Publications and source records attributed to A Griffiths.

At least 37 records · Page 2Linked to original sources

PubMed1998

Panning phage antibody libraries on cells: isolation of human Fab fragments against ovarian carcinoma using guided selection.

The display of repertoires of human antibody (Ab) fragments on filamentous phages and selection by binding of the phage to antigen (Ag) have provided a ready means of deriving human Ab against purified Ag. However, it has been more difficult to obtain phage Ab against an individual Ag of a complex mixture, such as cell surface Ag. Using the technique of "guided selection," we generated human Ab against the high-affinity folate-binding protein (FBP), a cell surface Ag that is overexpressed in many human ovarian carcinomas. The guiding Ab template was provided by the light chain of mouse monoclonal Ab Mov19 (K[aff], 10[8] M[-1]) directed against FBP; this was paired with repertoires of human heavy chains displayed on phages, and the hybrid Ab fragments were selected by binding to an ovarian carcinoma cell line (OVCAR3). The selected human heavy chains were then paired with repertoires of human light chains. Further panning led to the isolation of a human Fab fragment, C4, with a binding affinity of 0.2 x 10(8) M(-1). This was highly specific for FBP, as demonstrated by ELISA and flow cytometry data and by immunoprecipitation of the relevant molecule from the cell surface of ovarian carcinoma cells. Moreover, C4 targeted the same or a closely related epitope of the Ag, as did the template rodent monoclonal Ab Mov19. These results suggest the usefulness of guided selection as a simple means to deriving human Ab against cell surface Ag for which a rodent Ab is available.

Amino Acid Sequence↗

PubMed1998

Absence of linkage between inflammatory bowel disease and selected loci on chromosomes 3, 7, 12, and 16.

BACKGROUND & AIMS: Linkage data derived from genome-wide scans of inflammatory bowel disease (IBD) sibling-pair families have identified 4 loci on chromosomes 3, 7, 12, and 16 as potential sites for IBD susceptibility genes. The aim of this study was to investigate whether linkage analysis of another independently collected set of sibling pairs with IBD would provide further evidence of linkage between these previously reported loci and IBD. METHODS: Using the MAPMAKER/SIBS program, the segregation of 21 microsatellite marker loci spanning the 4 putative IBD gene loci was analyzed in a study population comprising 161 families with 114 Crohn's disease, 36 ulcerative colitis, and 50 mixed IBD sibling pairs from the Greater Toronto area. RESULTS: The results of multipoint linkage analysis showed no evidence for linkage between IBD and each of the 21 marker loci studied; the logarithm of odds scores in all instances were less than 0.8. These linkage data were found, by exclusion mapping analysis, to exclude values of lambdas ranging from 1.5 to 3.0, depending on the locus evaluated. CONCLUSIONS: The loci previously suggested as representing IBD susceptibility loci are not linked to IBD in the Toronto population examined in this analysis.

Chromosome Mapping↗

PubMed1998

Outcome after ileoanal anastomosis in pediatric patients with ulcerative colitis.

BACKGROUND: To review the outcome after restorative proctocolectomy among children and adolescents with ulcerative colitis at a pediatric inflammatory bowel disease center. METHODS: The records of all patients with ulcerative colitis undergoing colectomy and ileoanal anastomosis at The Hospital for Sick Children, Toronto, Canada, were reviewed. Questionnaires concerning functional results were sent to patients with restored transanal defecation. RESULTS: Seventy three patients (mean age, 13.2 years; range, 2.6-18.8 years) underwent ileoanal anastomosis (19 straight ileoanal anastomosis, 41 J pouch, 13 S pouch) between January 1980 and June 1995 and were observed 5.8+/-3.3 years. The ileoanal anastomosis is nonfunctional in 19 (26%) patients. Excision rates according to type of restorative procedure were J pouch, 7% (3 of 41); S pouch, 32% (4 of 13); and straight ileoanal anastomosis, 32% (6 of 19). Failure was usually attributable to intractable diarrhea among patients with straight ileoanal anastomosis but was caused by anastomotic leak or pelvic-perianal sepsis among patients with pouch procedures. Failure rates did not vary with age at ileoanal anastomosis. Among patients retaining ileoanal continuity, continence problems reported in the questionnaire were frequent and tended to be more extreme among younger patients. Overall, 90% of respondents reported satisfaction with the functional outcome of the restorative operation. CONCLUSIONS: The success rate of the ileoanal anastomosis/J-pouch procedure is comparable to that in adult series. The ileoanal anastomosis/J-pouch procedure is the operation of choice for children and adolescents who want ileoanal continuity restored after colectomy for ulcerative colitis.

Adolescent↗

PubMed1998

Glycoprotein C-deficient mutants of two strains of herpes simplex virus type 1 exhibit unaltered adsorption characteristics on polarized or non-polarized cells.

Mutants of herpes simplex virus type 1 (HSV-1) strain SC16, lacking each of the dispensable glycoproteins C, G, E, I or J, were examined for their ability to infect the apical or basolateral surfaces of polarized human epithelial cells. None of the mutants was significantly different from the wild-type parent when assayed on either surface. Since a previous report had demonstrated that glycoprotein C (gC) was necessary for the infection of apical surfaces of polarized epithelium, a second gC-negative mutant was constructed on a background of HSV-1 strain HFEM. This mutant displayed no phenotype when assayed on the apical surface. Furthermore, neither gC-negative mutant differed from its wild-type parent in its adsorption kinetics or specific infectivity on non-polarized Vero cells, a result which is inconsistent with the view that interactions between gC and cell surface proteoglycans constitute the initial adsorption process. Our findings thus conflict with previous reports and suggest that proposed functions of HSV-1 gC in the infection of polarized and non-polarized cells may be strain-dependent.

Adsorption↗

PubMed1998

Dental education resources on the Web.

New methods of delivering educational material are being developed in order to improve effectiveness and efficiency of learning. They are not designed to replace conventional teaching methods, but to complement them and encourage self-directed learning among students. In the present technological age, the use of computers in teaching and learning is almost mandatory. This article describes the development of educational aids available on the World Wide Web through the project DERWeb (Dental Education Resources on the World Wide Web) and its expansion as a site for dental information for the whole dental community. Courses and demonstrations to various groups by the team have led to interest and uptake by those who were previously unaware of this form of information dissemination or were "afraid" to use computers. The project is expanding continually and projections for future development are discussed.

Computer Communication Networks↗

PubMed1998

Longitudinal lipid profiles on CAPD: their relationship to weight gain, comorbidity, and dialysis factors.

The dyslipidemia of chronic renal failure may worsen after the commencement of continuous ambulatory peritoneal dialysis (CAPD). The purpose of this study was to relate baseline and longitudinal changes in the lipid profile to anthropometrics (weight, mid-arm circumference), aspects of treatment (albumin, total protein losses, peritoneal solute transport [dialysate:plasma ratio of creatinine], dialysate caloric load), total calorie intake (cal/kg), preexisting cardiovascular comorbidity, and survival. Lipid profiles (triglycerides [TG], total cholesterol [TC], and HDL) were measured, along with the above factors, every 6 mo in an unselected prospective cohort of 124 patients who were not treated with lipid-lowering drugs, commencing CAPD between 1990 and 1993, until 1995. On univariate analysis, age, plasma albumin, cardiovascular disease, baseline TG, and TC:HDL ratio predicted survival. Simultaneous multiple Cox regression including all of the significant predictors demonstrated that either high TG or TC: HDL still predicted death, both in patients with and without clinically overt cardiovascular disease. Between 6 and 36 mo of treatment, TC, TG, and TC:HDL were elevated when compared with the baseline, more so in patients with preexisting cardiovascular disease (P < 0.05). Throughout this period, weight and mid-arm circumference correlated positively with TG and negatively with HDL. There were positive correlations between TC and albumin levels for 12 mo after commencement of treatment, but otherwise there were no significant or consistent relationships between lipid profiles and total protein losses, dialysate calorie load, or total cal/kg or solute transport. The worsening dyslipidemia associated with CAPD was not associated with aspects of treatment such as glucose load or protein losses. The strongest predictors of worsening lipid profiles were weight gain and preexisting cardiovascular comorbidity.

Adult↗

PubMed1998

Evaluation of facilitated communication.

Two case studies are presented to demonstrate the effectiveness of Facilitated Communication (FC). A wide variety of sources of data have been examined and consistent behaviour found within FC interactions. There are indications that changes in behaviour of both people resulted at least in part from the use of FC.

Adult↗

PubMed1998

Safety profile of WinRho anti-D.

WinRho anti-D is manufactured with multiple processes to minimize the risk of transmitting blood-borne diseases such as viruses. These safety features include donor selection, plasma testing, solvent-detergent viral inactivation, and nanofiltration. To date, there has not been any case of viral transmission in association with use of WinRho anti-D. Adverse drug reactions are infrequent and generally mild; the most common are headache, fever, and chills. Some degree of hemolysis is inevitable due to the mechanism of action of WinRho anti-D, but this is predictable and transient. A few cases of intravascular hemolysis have been reported; hypersensitivity reactions are very rare. WinRho anti-D has been shown in both clinical trials and postmarketing surveillance to be safe and effective in the treatment of idiopathic thrombocytopenic purpura (ITP) and in the prevention of Rh isoimmunization.

Drug Hypersensitivity↗

PubMed1998

Body mass index as a predictor of survival in adults with cystic fibrosis referred for lung transplantation.

BACKGROUND: The timing of referral and listing for lung transplantation in adults with cystic fibrosis is influenced by many factors including pulmonary function, body mass index (BMI), sex, and patient and physician choice. This study aimed to analyze the effect of these variables on waiting list and postoperative mortality rates. In particular, low BMI is suggested to portend a poor outcome after transplantation. METHODS: All patients with cystic fibrosis referred to our institution (n = 92) between 1989 and 1996 were reviewed, and the effect on survival of BMI, sex, and other covariates was analyzed by use of Cox proportional hazards regression. RESULTS: Forty-five transplantations were undertaken with a mean waiting time of 226 days (range 1 to 678). Fifteen of the 62 listed patients died before transplantation with a mean time to death of 160 days (range 8 to 533). Fifteen patients died after transplantation. BMI at the time of listing predicted waiting list mortality (P < .05). Female sex tended to increase waiting list mortality rates, such that the combination of BMI less than 18 kg/m2, and female sex was associated with a 21% 1-year waiting list survival without transplantation. Age, forced expiratory volume in 1 second, sex, BMI, and date of transplantation did not predict postoperative survival. CONCLUSION: Patients with cystic fibrosis (particularly women) referred for lung transplantation with a BMI less than 18 kg/m2 are at high risk of death over the next 12 months. With this in mind, they should not be denied transplantation unduly while attempts are made to increase weight, especially because pretransplantation BMI does not influence posttransplantation survival.

Adult↗

PubMed1997

The DERWeb project--dental education resources on the Internet.

The delivery of dental education, in common with other forms of higher education, has altered considerably over the last decade. The introduction of the World Wide Web enabled resources for dental education to be delivered in a new and innovative manner. DERWeb was funded by HEFC-JISC. The primary resource consists of a library of 1600 clinical dental images each with keywords and a description. Selected images were used to create teaching materials to demonstrate to dental educators world wide how the image library could be used by individual institutions. Hands-on courses were held to demonstrate the new resource and to evaluate computer skills in the dental community. Since the commencement of the project in September 1994 DERWeb has become one of the leading resources for dental education world wide. The site has been accessed by 79 countries with approximately 107000 accesses in October 1996. DERWeb also designs and maintains the British Dental Association pages together with other professional organisations. Its resources also include dental contact addresses and links to quality dental sites world wide. Further funding has enabled DERWeb to expand further and explore new technologies to develop interactivity on the Web.

Computer Communication Networks↗

PubMed1997

Psychosocial factors predicting employee sickness absence during economic decline.

Psychosocial factors such as work characteristics, life events, social support, and personality were examined as predictors of the change in medically certified sickness absence observed during a period of severe economic decline. Longitudinal data, derived from self-reports and register-based information relating to 763 local government employees, were collected at 3 points during a 5-year period: before the economic decline, during the nadir of that decline, and immediately after the nadir. After the effects of prior absence and demographic and lifestyle variables had been partialed out, the results of multiple Poisson regression analyses showed that work characteristics play a major role in forthcoming sickness absences. Negative life events and the personality trait sense of coherence (in women) also predicted forthcoming absence rate. Social support did not relate to absences either in men or in women.

Adult↗

PubMed1997

Energy expenditure and body composition in children with Crohn's disease: effect of enteral nutrition and treatment with prednisolone.

BACKGROUND: Malnutrition and growth retardation are common complications of Crohn's disease in children. The contribution of resting energy expenditure (REE) to malnutrition is unclear. AIMS: To characterise the REE and body composition in children with Crohn's disease and compare them with normal controls and patients with anorexia nervosa; to compare the effects of prednisolone and enteral nutrition on energy expenditure and body composition. SUBJECTS: Twenty four children with Crohn's disease, 19 malnourished females with anorexia nervosa, and 22 healthy control subjects were studied. METHODS: In children with Crohn's disease measurements were done when the disease was acute and repeated at one and three months after treatment with either prednisolone or enteral nutrition. Resting energy expenditure was measured by indirect calorimetry and body composition by anthropometry, bioelectrical impedance analysis, total body potassium, H218O, and bromide space studies. RESULTS: Body weight and ideal body weight were significantly lower in patients with Crohn's disease than in healthy controls. Lean tissue was depleted and there was an increase in extracellular water. Per unit of lean body mass, there was no difference between REE in patients with Crohn's disease and controls, whereas patients with anorexia nervosa had significantly reduced REE. With enteral nutrition all body compartments and REE increased significantly (p < 0.001). In a subgroup of age-matched men there was a significant increase in height after three months of enteral nutrition compared with prednisolone (p < 0.01). Those treated with steroids did not show a significant change in height but did show an increase in all body compartments. However, intracellular water as well as lean body mass accretion were significantly higher in the enteral nutrition group than in the prednisolone group. CONCLUSIONS: Despite being malnourished, children with Crohn's disease fail to adapt their REE per unit of lean body mass. This might be a factor contributing to their malnutrition. Lean tissue accretion is higher in patients treated with enteral nutrition than in those treated with prednisolone.

Adolescent↗

PubMed1996

Supplementary enteral nutrition maintains remission in paediatric Crohn's disease.

BACKGROUND: Liquid diets given enterally combined with "bowel rest' are efficacious in the treatment of active Crohn's disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS: This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn's disease in children. PATIENTS AND METHODS: Children and adolescents with active Crohn's disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS: Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn's disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn's Disease Activity Index, PCDAI to < or = 20) was achieved in 47 of 65 (72%) patients. Subsequently, 20 of these 47 (43%) relapsed by six months and 28 of 47 (60%) by 12 months. Patients who continued nasogastric supplementary feeding (n = 28) after resumption of an otherwise normal diet remained well longer than those who discontinued nocturnal supplements completely (n = 19) (p < 0.02). Furthermore, continued use of nasogastric supplements before completion of puberty was associated with improved linear growth. CONCLUSION: After successful treatment of active Crohn's disease by exclusive enteral nutrition, supplementary enteral nutrition without restriction of normal diet is associated with prolongation of remission and improved linear growth in children and adolescents.

Adolescent↗

PubMed1996

Pulmonary allograft ischemic time: an important predictor of survival after lung transplantation.

BACKGROUND: Traditionally organ availability in human lung transplantation has been limited by aiming to keep the graft ischemic time under 6 hours. To maximize organ supply in a country with a widely spread population, we have routinely procured organs beyond this time. Our experience outlines the clinical consequences of a prolonged allograft ischemic time. METHODS: Between 1990 and 1994 we performed 106 lung or heart-lung transplantations. The average graft ischemic time was 323 +/- 93 minutes. Lung preservation included a prostacyclin infusion (40 to 80 ng/kg/min for 10 minutes) and cold modified Euro-Collins solution flush. Organs were stored and transported on ice at 6 degrees to 10 degrees C. Graft ischemic time, transplant type, age, gender, cytomegalovirus status, and anesthetic time were subject to multivariate Cox regression analysis. RESULTS: Survival and graft ischemic times for heart-lung (n = 38), single lung (n = 33), and bilateral lung transplantation (n = 35) were not significantly different. Graft ischemic time was an independent predictor of survival (p < 0.01). Subgroup analysis notes the effect to be most pronounced beyond 5 hours (p = 0.02, hazard ratio 3.44, confidence interval 1.12 to 9.8). CONCLUSIONS: Pulmonary allograft ischemic time beyond 5 hours does not result in acceptable outcomes although survival is reduced. Attempts should be made to minimize graft ischemic times with careful coordination of transport and personnel.

Adult↗

PubMed1996

Reverse telescope anastomotic technique reduces the incidence of bronchial stricture.

BACKGROUND: Bronchial stricture remains a major problem after lung transplantation. We hypothesized that a "reverse" telescope anastomosis, where the donor bronchus is sleeved external to the recipient bronchus, would be associated with a lower incidence of anastomotic stricture. METHODS: Over a 12-month period our Unit performed 35 consecutive single and bilateral sequential lung transplantations. The 56 bronchial anastomoses were constructed as a conventional (n = 27) or as a reverse (n = 29) telescope. RESULTS: Bronchial strictures developed in 48% of the conventional anastomoses but in only 7% of the reverse anastomoses (p < or = 0.05). Furthermore, the reverse telescope anastomosis eliminated the need for stenting. CONCLUSIONS: This technique greatly reduced the need for dilatation, debridement, and stent placement and may reduce the morbidity and mortality associated with anastomotic complications.

Adult↗

PubMed1993

Slow-release 5-aminosalicylic acid therapy in children with small intestinal Crohn's disease.

Pharmacologic agents effective in the treatment of Crohn's disease confined to the small intestine are limited. The therapeutic efficacy of oral mesalazine in small bowel inflammation, although theoretically promising, remains unproven. In an open-labeled initial trial, timed-release 5-aminosalicylic acid (5-ASA), administered at a daily dosage of 30.6 +/- 9.0 mg/kg (mean +/- SEM) to children with active Crohn's disease involving the small intestine, was associated with improvement on the Harvey index in six of 12 patients treated for 8.1 +/- 3.9 weeks. In a subsequent prospective, double-blind study 14 children, ages 9.3 to 16.1 years, with active Crohn's disease limited radiologically in the small intestine were randomized to receive either timed-release 5-ASA [50 mg/kg/day (maximum 3 g/day)] or placebo for 8 weeks. Following a 4-week washout period, patients crossed over to receive the other study drug for a further 8 weeks. Six children completed the entire 20-week trial. The van Hees index improved among patients receiving 5-ASA for 8 weeks (delta = -18 +/- 6.4) but deteriorated among patients given placebo (delta = +14 +/- 4.1) (p < 0.05). Mean Crohn's Disease Activity Index (CDAI) decreased marginally after 8 weeks of 5-ASA treatment (delta = -48 +/- 38.2) but not with placebo (delta = -3.0 +/- 7.9) (p = 0.31). Of the eight noncompleters, more patients dropped out of the study because of lack of therapeutic response to placebo (n = 5) than to 5-ASA (n = 2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1993

An investigation of a nosocomial outbreak of Clostridium difficile by pyrolysis mass spectrometry.

Isolates from a presumptive nosocomial outbreak of Clostridium difficile infection at a large teaching hospital were typed by pyrolysis mass spectrometry (PMS) and antibiograms. One isolate, from the putative index case, was dissimilar from the outbreak strain, but 24 isolates from 16 patients were indistinguishable by both methods. The outbreak centred on two wards for the acute care of the elderly, with a few cases elsewhere. Transfer of patients appeared to be the route of transmission between wards. There was a significant fall in the incidence of cases following intervention by the Infection Control Unit. This included ward inspection, advice on antibiotic usage and advice on prevention of faecal-oral transfer, particularly by proper handwashing. Subsequent monitoring of C. difficile infection showed a background of sporadic, dissimilar isolates with occasional apparent cross-infection incidents limited to a few patients. In suspected outbreaks, patterns of antibiotic susceptibility may be useful in initial screening, before referral for more sophisticated typing. There was excellent correlation between PMS results, antibiograms and epidemiological information.

Aged↗

PubMed1993

Effects of zolpidem on saccadic eye movements and psychomotor performance: a double-blind, placebo controlled study in healthy volunteers.

1. Peak saccade velocity provides a valuable means of assessing the sedative effect of drugs in humans. The present study investigated the effects of zolpidem, an imidazopyridine hypnotic, on saccade velocity in healthy volunteers after single and repeated administration. 2. Zolpidem 5 mg, 10 mg and 20 mg significantly and dose dependently depressed peak saccade velocity during the 1.5 h after a single administration. On the morning after zolpidem administration, peak saccade velocity had returned towards pretreatment levels. Nitrazepam 10 mg also significantly depressed peak saccade velocity but the effect was maintained the following morning. The saccade response to zolpidem (5 and 10 mg) was undiminished after the seven nightly doses. 3. Nightly administration of zolpidem improved subjective sleep quality and there was no evidence of rebound insomnia following cessation of drug treatment.

Adult↗