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Biomedical subjects

A Vail

Publications and source records attributed to A Vail.

At least 55 records · Page 3Linked to original sources
PubMed1997

The effect of rhGH in vitro on donor-specific hyporesponsiveness in pediatric transplantation.

Recombinant human growth hormone (rhGH) improves growth in children after renal transplantation, but may be associated with augmented immune responses. To understand the effect of rhGH in transplantation, we evaluated the role of rhGH in a mixed leukocyte culture (MLC) in vitro. We demonstrated that PBMC isolated from normal adult volunteers cultured in an MLC in the presence of rhGH develop an augmented proliferative (25-400%) and cytotoxic (50-600%) response. Using in situ hybridization (ISH), we demonstrated that the frequency of cells expressing mRNA for IFNgamma increased in the presence of rhGH (100-800%). In vitro responses of PBMC from adults in an MLC may only loosely reflect responses in vivo during pediatric transplantation. After transplantation, adults develop decreased responses to donor-specific antigens in an MLC (donor-specific hyporesponsiveness - DSH). We evaluated the donor-specific responses of 20 pediatric patients who had each received a renal allograft from one parent. Pediatric patients developed DSH similarly to adults; however, no correlation was seen between the amount of DSH and graft function. We also evaluated the expression/production of IFNgamma and IL4 in response to donor-specific alloantigens. Patients exhibit marked DSH of IFNgamma expression and production. However, IL4 production was seen in 8 out of 10 patients with normal renal function, but only 1 out of 7 patients with biopsy proven chronic rejection. Finally, we evaluated the effect of rhGH in vitro on DSH. Only 3 out of 20 patients developed augmented donor-specific responses in the presence of rhGH in vitro. rhGH augments proliferation, cytotoxicity and IFNgamma expression during an MLC. After renal transplantation, rhGH augments donor-specific responses during an MLC in some pediatric patients.

Adolescent↗
PubMed1996

The effect of recombinant human growth hormone on responses to alloantigens in the pediatric transplant patient.

Recombinant human growth hormone (rhGH) improves growth in children after renal transplantation, but may be associated with augmented immune responses. We previously demonstrated that rhGH augments proliferative and cytotoxic responses and interferon-gamma (IFN-gamma) mRNA expression during a mixed leukocyte culture (MLC). In this study, we evaluated 12 pediatric patients after receiving a renal allograft from one of their parents. Peripheral blood mononuclear cells (PBMC) were isolated from patients and cultured with either donor or unrelated third-party PBMC in an MLC. Patients developed significant donor-specific hyporesponsiveness (DSH), however, no correlation was seen between the amount of DSH and graft function. Of the 12 patients, 2 developed augmented responses in the presence of rhGH. rhGH augments proliferation, cytotoxicity, and IFN-gamma expression during an MLC. Some patients develop increased responses to donor-specific alloantigens after renal transplantation. Further study is needed to better determine the significance of this finding.

Adolescent↗
PubMed1996

Clinical and surgical factors influencing corneal graft survival, visual acuity, and astigmatism. Corneal Transplant Follow-up Study Collaborators.

PURPOSE: To quantify clinical and operative factors that influence corneal graft outcome. METHODS: A multifactorial analysis was done on 2242 corneal grafts registered by the United Kingdom Transplant Service from July 1987 to June 1991. RESULTS: There was an increased risk of graft failure in patients with preoperative diffuse and other noncentral stromal edema, less-common eye diseases, small trephine size, difference in donor and recipient sizes greater than 0.25 mm, and use of mixed continuous and interrupted sutures. Visual acuity 3 months after surgery was poorer in patients who had glaucoma and low visual acuity preoperatively, small trephine size, and combined vitreous surgery. Use of interrupted sutures resulted in higher astigmatism at 3 months. CONCLUSIONS: After allowing for the effects of recipient factors, surgical factors significantly affected corneal graft outcome. No factors that showed significant benefits for graft survival also adversely affected visual performance. Details of medical history, clinical condition, and surgical method failed to predict more than a small proportion of observed variability in visual performance of functioning grafts.

Astigmatism↗
PubMed1996

An audit of the management of malignant hypercalcaemia.

A protocol was designed to help junior doctors to manage patients with malignant hypercalcaemia (MH). Seventy-five patients received 30 mg, 60 mg or 90 mg doses of pamidronate, depending on their initial serum calcium level. Fifty-four (72%) patients achieved normocalcaemia (NC) within 5 days after a single infusion of pamidronate. A further ten (13%) patients reached NC after a second dose, and 11 (15%) remained hypercalcaemic until death. NC was maintained for a median duration of 24 days. Patients received, on average, 30 mg less pamidronate than that given in the manufacturer's dosing schedule. The protocol was considered effective, economical and practical in the routine management of MH.

Adult↗
PubMed1996

Risk factor analysis of data from assessment clinics in the UK breast screening programme: a case-control study in Portsmouth and Southampton.

STUDY OBJECTIVES: The aim was to quantify the influence of demographic and reproductive factors on breast cancer. The subjects' path through the screening clinic, the inherent differences between the control groups, and the possible biases when using screening programmes were also considered. DESIGN: A case-control study using both personal contact and postal questionnaires to gather demographic and reproductive information. SETTING: Women attending two breast screening recall clinics in Portsmouth and Southampton over the period 1990-92. PARTICIPANTS: Altogether 1813 subjects between the ages of 50 and 65 years. The subjects' disease status was ascertained using a mammography and classified into four categories: 253 breast cancer (cases); 207 benign breast disease (BD); 410 requiring early rescreen (ER); and 943 for standard recall (SR). The BD, ER, and SR groups were used as separate controls. MAIN RESULTS: Of the factors considered here, the only two that showed a consistently significant effect on the risk of breast cancer were age and body mass index (BMI). Odds ratios were calculated for five yearly age groups and four groups of BMI using the youngest and lightest group as the baseline, respectively. There seemed to be an increase in the risk of breast cancer for increasing age for each comparison made (for cases v SR:OR (95% CI) = 1.60 (1.10, 2.34), 2.54 (1.76, 3.68)). All subjects above the lowest quartile of BMI experienced increased risk, although a trend was not clear (for cases v SR: OR (95% CI) = 1.66 (1.03, 2.66), 1.37 (0.86, 2.20), 1.98 (1.24, 3.15)). CONCLUSIONS: Various other potential risk factors were found to be inconsistently significant depending on choice of control group. This may help in understanding the differences between the three control groups used.

Age Factors↗
PubMed1996

Non-prescribed drug use during methadone treatment by clinic- and community-based patients.

We investigated the efficacy of methadone maintenance treatment in clinic-based (n = 10) and community-based (n = 10) patients by studying the relationships between dose, plasma concentrations of methadone and non-prescribed drug-use using logistic regression. We found that clinic-based patients had significantly reduced odds of having a urine sample test positive for illicit drugs when compared to community-based patients (OR = 0.20; 95% confidence interval 0.10-0.38: p < 0.001). There was no relationship between either methadone dose or plasma methadone concentration and testing positive for non-prescribed drugs (including cocaine, cannabis, amphetamine, ecstasy, benzodiazepines). We looked specifically at the misuse of opiate drugs. Location was again important and clinic-based patients had significantly reduced odds of having a urine sample test positive for opiate drugs (OR = 0.36, 95% confidence interval 0.18-0.71: p approximately 0.004). Opiate drug use in our patients was also significantly related to plasma methadone concentration, increasing noticeably when the drug concentration < 0.48 nmol/L (p approximately 0.04). We found no relationship between methadone dose and odds of having a positive urine drug test in either clinic- or community-based patients.

Adult↗
PubMed1995

A randomised trial of three methods of giving information about prenatal testing.

OBJECTIVE: To test the effect of extra non-directive information about prenatal testing, given individually or in a class. SETTING: Antenatal clinics in a district general hospital and a university hospital. DESIGN: Randomised controlled trial; participants allocated to control group or offer of extra information individually or in class. SUBJECTS: 1691 women booking antenatal care before 15 weeks' gestation. INTERVENTIONS: All participants received the usual information about prenatal tests from hospital staff. Individual participants were offered a separate session with a research midwife in which prenatal screening was described in detail. Class participants were offered the same extra information in an early prenatal class. MAIN OUTCOME MEASURES: Attendance at extra information sessions; uptake rates of prenatal tests; levels of anxiety, understanding, and satisfaction with decisions. RESULTS: Attendance at classes was lower than at individual sessions (adjusted odds ratio 0.45; 95% confidence interval 0.35 to 0.58). Ultrasonography was almost universally accepted (99%) and was not affected by either intervention. Uptake of cystic fibrosis testing, high in controls (79%), was lowered in the individual group (0.44; 0.20 to 0.97) and classes (0.39; 0.18 to 0.86). Uptake of screening for Down's syndrome, already low (34%) in controls, was not further depressed by extra information in classes (0.99; 0.70 to 1.39) and was slightly higher in the individual group (1.45; 1.04 to 2.02). Women offered extra information had improved understanding and were more satisfied with information received; satisfaction with decisions about prenatal testing was unchanged. The offer of individual information reduced anxiety later in pregnancy. CONCLUSIONS: Ultrasonography is valued for non-medical reasons and chosen even by fully informed people who eschew prenatal diagnosis. The offer of extra information has no overall adverse effects on anxiety and reduces uptake of blood tests when background uptake rate is high (but not when it is already low). High uptake of prenatal blood tests suggests compliant behaviour and need for more information.

Anxiety↗
PubMed1995

Avoiding unsuspected respiratory side-effects of topical timolol with cardioselective or sympathomimetic agents.

Topical timolol given for the treatment or chronic simple glaucoma may cause unrecognised bronchospasm among elderly people. We recruited 80 patients aged over 60 years, who were without a history of airways disease and already used timolol, into a randomised crossover study comparing the effects on spirometry and exercise tolerance of changing to betaxolol or dipivefrine therapy. Results showed an increase of 13% and 8% in mean peak flow rate and forced expiratory volume in 1 s (FEV1), respectively, when using betaxolol; and of 14% and 11% when using dipivefrine. There was also improved exercise tolerance with both agents. More than a quarter of the patients showed at least a 15% improvement in FEV1 when changed from timolol. Analysis of enrolment symptoms and response to nebulised salbutamol failed to produce a method of identifying these patients. Timolol may impair respiratory function and exercise tolerance of elderly patients even if they have no history of reversible airways disease.

Aged↗
PubMed1995

Maternal levels of serum-soluble CD8 and IL-2R are not significantly elevated in idiopathic preterm labour.

OBJECTIVE: To search for evidence of immune activation in idiopathic preterm term labour by measuring the soluble markers of T cell activation, CD8 (sCD8) and interleukin-2 receptor (sIL2R). DESIGN: Serum sCD8 and sIL-2R were measured by commercial ELISA in subjects undergoing idiopathic preterm labour (PTL; n = 15) and normal term labour (TL; n = 17). Two gestationally equivalent non-labouring groups were also included representing preterm (PTC; n = 10) and term (TC; n = 10) controls. Possible delayed responses in soluble activation markers were monitored in blood samples taken 48 h after delivery in both labouring groups (PTLp; n = 9: TLp; n = 9). RESULTS: (1) Excluding the 48 h postpartum samples, no statistically significant differences were revealed following a Kruskall-Wallis analysis of variance (ANOVA) for levels of sIL-2R (P = 0.093) and sCD8 (P = 0.098). Including the postpartum samples, however, gave statistically significant differences for each (sIL-2R: P = 0.033; sCD8: P = 0.006). (2) No statistically significant difference was revealed by direct comparison of the two labouring groups alone (Wilcoxon-Mann-Whitney test: P > 0.05). (3) Significantly lower levels of sCD8 were found in the PTL subgroup which had histological evidence of inflammation (Wilcoxon-Mann-Whitney: P = 0.003). CONCLUSIONS: Statistical analysis of our data suggests that idiopathic preterm labour is not commonly associated with significant elevations in circulating sCD8 or sIL-2R levels compared with normal term labour. Where significant changes in the levels of these markers do arise, our evidence points to a delayed effect of labour per se rather than infection as the most probable cause.

Analysis of Variance↗
PubMed1994

Influence of donor and histocompatibility factors on corneal graft outcome.

The Corneal Transplant Follow-up Study has followed 2311 penetrating keratoplasties for up to 450 days after transplant. A total of 207 failures were observed, including 65 classical rejections and 35 endothelial decompensations. At 12 months, graft survival was 89%, and survival free from rejection was 87%. For surviving grafts, risk of failure reduced from 4.8% in the first 75 days and stabilized after 5 months at 1.2% in each 75-day interval. Risk of rejection initially followed a similar pattern, but then increased after 12 months. Multifactorial analyses accounted for differences in recipient characteristics and interrelationships of donor factors. Donor age, sex, cause of death, and method of corneal storage were not found to influence significantly either time to graft failure or time to first rejection. Grafts in prospectively tissue-typed donor-recipient pairs were generally considered before surgery to be at increased risk of either graft failure or rejection. With due allowance, increasing risk of rejection was associated with increasing numbers of mismatches at HLA-A and HLA-B broad antigens. The opposite was true at HLA-DR broad antigens, where increased risk of rejection was observed with no mismatches.

Adult↗
PubMed1994

A meta-analysis of the therapeutic role of oil soluble contrast media at hysterosalpingography: a surprising result?

OBJECTIVE: To evaluate the therapeutic effect of oil-soluble contrast media compared with water-soluble contrast media after hysterosalpingography (HSG) in infertile couples. DESIGN: Meta-analysis of four randomized clinical trials (RCTs) and six nonrandomized controlled studies evaluating pregnancy rates after the use of oil- or water-soluble contrast media during HSG. SETTING: Institute of Epidemiology and Health Services Research, Leeds, United Kingdom. PATIENTS: Four identified RCTs studied 800 patients and six nonrandomized studies comprised an additional 1,806 patients, all experiencing primary or secondary infertility. INTERVENTION: Hysterosalpingography as part of infertility investigation. MAIN OUTCOME MEASURE: Pregnancy rates after HSG. RESULTS: Pregnancy rates were significantly higher in the oil-soluble contrast media group compared with the water-soluble contrast media group in the RCTs. Inclusion of the six nonrandomized studies did not alter this conclusion. This apparent benefit was greatest for patients with unexplained infertility. CONCLUSIONS: Oil-soluble contrast media have a therapeutic effect compared with water-soluble media and this effect is greatest for patients who have been diagnosed as having unexplained infertility. New techniques for the evaluation of tubal patency support the hypothesis that tubal "plugs" may be involved in proximal tubal blockage.

Clinical Trials as Topic↗
PubMed1994

Corneal graft survival and visual outcome. A multicenter Study. Corneal Transplant Follow-up Study Collaborators.

PURPOSE: The Corneal Transplant Follow-up Study has followed 2385 corneal transplants performed in the United Kingdom and the Republic of Ireland for up to 450 days to quantify factors influencing corneal graft survival and visual outcome 3 and 12 months postoperatively. METHODS: Multifactorial analyses of grafts registered by United Kingdom Transplant Support Service from July 1987 to June 1990 were used. Corrected visual acuity of functioning grafts was assessed at 3 and 12 months. RESULTS: Of 2385 corneal transplants followed, 214 failures were observed: graft survival was 95% at 3 months and 89% at 1 year. Similar factors affected outcome at each time. Decreased risk of failure was associated with surgeons reporting most grafts, and increased risk was associated with regrafts, patients younger than 10 years of age, nonvisual reasons for grafting, endothelial failure, and deep vascularization. Visual outcome was worse in older patients and was associated with cosmetic reasons for grafting, superficial vascularization preoperatively, and secondary endothelial failure. Visual acuity was better when the other eye had been grafted previously, or when the diagnosis was keratoconus or stromal dystrophy. CONCLUSIONS: Primary endothelial failure was associated with high failure rates but good visual results when functioning. Most other factors had similar effects on both outcome measures. Improved outcome under highest-reporting surgeons was slight, and indicated possible differences in postoperative care.

Adolescent↗
PubMed1993

Corneal transplantation in the United Kingdom and Republic of Ireland.

The Corneal Transplant Follow up Study has registered 4560 corneal grafts performed in the United Kingdom and Republic of Ireland from July 1987 to June 1991. Rates of reported grafts doubled during that time. This increase was greater for surgeons and regions reporting fewer grafts, but was consistent across patient factors. Eleven of 428 consultants were responsible for over 25% of grafts, and their patients' characteristics differed significantly from others. Overall, reasons for grafting were visual only (77%), visual and other (16%), and non-visual (7%). Most frequent diagnoses were endothelial failure (38%), inflammation (26%), and keratoconus (20%). Age ranged from 2 months to 97 years, and differed markedly with diagnosis. Eighteen per cent of transplants were regrafts, and 40% were vascularised preoperatively.

Adolescent↗
PubMed1993

Penetrating keratoplasty in the United Kingdom: an interim analysis of the corneal transplant follow-up study.

1. Clinical corneal transplantation has been performed for over a century, but many elements leading to a successful outcome have yet to be identified. 2. Because there are limitless supplies of tissue, the supply of corneas need never fall short of demand. Nevertheless, retrieval rates vary widely among regions in the UK due to uneven organization of services. 3. Organ culture of corneas improves the quality of transplanted tissues because it allows time for substandard material to be discarded. The outcome appears to equal other storage methods. 4. Between 1987 and 1991, 4,560 corneal transplants were performed by 428 surgeons at 216 centers in the UK and were registered with CTFS. Of these, 3,213 were evaluable for graft survival, rejection, and other measures of visual outcome. 5. Unifactorial analysis revealed that the percentage of graft survival at one year was 89% and rejection-free survival was 87%. However, the hazard of rejection appeared to increase at or after the time of suture removal. 6. The percentage of recipients in whom CVA was 6/24 or better (able to read normal text with correction) improved from 16% preoperatively to 59% at 3 and 70% at 12 months postoperatively overall. In patients transplanted purely for visual reasons, improvement was 78% and 83% at 3 and 12 months, respectively. 7. Interim results of multifactorial analysis suggest that the risk of graft failure, rejection, and decreased CVA increased in association with the following factors: surgeons who reported fewer than 50 transplants to the study; recipients under 10 years of age; previously failed grafts (the more failed grafts, the greater the risk); grafting for nonvisual reasons; certain diagnoses; and vascularization of the corneal bed prior to transplantation. 8. Astigmatism was investigated in 880 cases at 3 months postoperatively. Preliminary analysis indicated that the risk of severe astigmatism was influenced by suturing technique and large differences between (> 0.25 mm) donor and recipient trephine size. 9. The effects of HLA matching were evaluated in 542 transplants. HLA-A and B matching reduced the risk of rejection during the first 450 days posttransplant, but HLA-DR matching appeared to increase the risk of rejection. 10. A rat model designed to simulate clinical corneal grafting was used to investigate the interaction between immunosuppression and matching. Whereas MHC mismatching could be overcome with topical dexamethasone, non-MHC mismatching appeared resistant.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1992

Mortality from melanoma in migrants to Australia: variation by age at arrival and duration of stay.

All death records in Australia during the period 1964-1985 were analyzed to compare mortality from melanoma in immigrants and Australian-born individuals, and to investigate changes in risk in the immigrants according to their duration of stay and age at arrival. About 450,000 deaths were from cancer, and risks of melanoma were estimated by logistic regression relative to those of the Australian-born, with deaths from other cancers used as controls. Estimates were adjusted for age at death, time period, birth cohort, and state of registration of death in Australia. Region of birth was defined as New Zealand, other Oceania, England, Ireland/Scotland/Wales (including Northern Ireland and the Republic of Ireland), Central Europe, Eastern Europe, Southern Europe, Western Asia, or Eastern Asia, bearing in mind that many migrants born in Asia were of European descent. Overall, migrants from outside Oceania were at lower risk than the Australian-born, and the lowest risks in males were in Southern Europeans and Eastern Asians, reflecting the protective effect of a darker complexion. Risk of melanoma was related both to duration of stay in Australia and to age at arrival; although their relative importance cannot be measured, the patterns of change suggested that childhood migration may be more important in determining risk than number of years in Australia. The authors believe this study to be based on the largest data set ever used in migrant studies, and note that the previously found differences in melanoma risk between immigrants and Australian-born remained after adjustment for major temporal and geographic confounders. The results confirm the importance of the interaction between environmental and genetic risk factors in the etiology of melanoma.

Age Factors↗