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Biomedical subjects

C A Rogers

Publications and source records attributed to C A Rogers.

At least 19 recordsLinked to original sources
PubMed1997

Is subclinical ovarian failure an autoimmune disease?

Young women with unexplained infertility who exhibit elevated basal serum follicle stimulating hormone (FSH) concentrations (>10 IU/l) have poor outcomes in in-vitro fertilization. A subgroup of these women has regular menses, representing 'subclinical' ovarian failure, which may have an autoimmune basis and could potentially be treated by immunosuppression. To investigate this further, a range of immunological markers was used to assess autoimmune activity in 14 women aged <40 years with elevated FSH compared with 15 infertile women with normal FSH and 10 pre-menopausal, healthy controls. All samples were taken during natural menstrual cycles. Organ-specific antibodies against ovary, endometrium and thyroid, and non-organ-specific antibodies against histones and cardiolipin, were not significantly increased in elevated FSH patients compared with other control groups. Soluble CD23 and soluble intercellular adhesion molecule concentrations were not elevated in the sera of the women tested, and circulating T cell subsets remained unaltered. Significantly, increased concentrations of the complement breakdown product C3a and terminal complement complexes were detected in the elevated FSH group compared with the normal FSH group, although the latter also had significant complement activation compared with laboratory controls. Autoimmunity appears as an infrequent cause of 'subclinical' ovarian failure, but there is evidence of activation of complement in the sera of infertile women.

Adult↗
PubMed1997

Conclusions of the corneal transplant follow up study. Collaborating Surgeons.

AIM: On the basis of finalised data from the Corneal Transplant Follow up Study to identify and quantify factors influencing corneal graft outcome in terms of graft survival, rejection, visual acuity, and astigmatism. METHODS: Multifactorial analysis of 2777 grafts registered by the UK Transplant Support Service from July 1987 to June 1991. RESULTS: Several recipient factors influencing graft survival, rejection, and visual acuity were identified, but no donor factors. Of the operative factors amenable to change, mixed suturing was associated with reduced graft survival, and larger grafts with increased risk of rejection but better visual acuity when surviving. There was increased risk of rejection with poor matching at HLA class I antigens, but mismatched HLA-DR grafts suffered less rejection than those with zero HLA-DR mismatches. Recipient age below 10 years was associated with increased risk of both rejection and graft failure. However, whereas increasing age above 10 years was not associated with differential graft survival, it was significantly associated with decreasing risk of rejection. CONCLUSIONS: While confirming possible benefits of HLA-A and B matching, the expense and delay involved in awaiting matched HLA-DR tissue is unlikely to be justified. Other donor factors are unrelated to graft outcome following screening of tissue by eye banks. The highest rates of graft failure and rejection happen in the early postoperative period, and factors influencing visual outcome are also apparent at this stage.

Adolescent↗
PubMed1996

Cardiac transplantation in childhood cancer survivors in Great Britain.

The aim of this study was to identify patients treated in Great Britain for childhood cancer and subsequently referred for cardiopulmonary transplantation in order to assess diagnosis, cancer treatment, management and outcome. Computerised record linkage between the National Registry of Childhood Tumours and the national transplant database held and maintained by the United Kingdom Transplant Support Service Authority (UKTSSA) was used to identify patients. Verification and clinical details were then obtained from the oncology and transplant centres. 16 patients were identified from the 31992 cases of childhood malignancy diagnosed in Britain since 1970. These comprised 13 heart transplants, 2 heart/lung transplants and 1 patient who died while on the heart transplantation waiting list. All 14 potential heart transplant patients had cardiomyopathy presumed secondary to anthracycline therapy. The original diagnoses were acute myeloblastic leukaemia (3), Wilms' tumour (4), rhabdomyosarcoma (2) and one each of five different solid tumours. Median age at diagnosis was 44 months (range 4-165 months). Median anthracycline dose was 413 mg/m2 (range 240-680 mg/m2). 13 of the 14 potential cardiac transplantation patients were more than 2 years from end of their cancer treatment before requiring transplantation and the transplantation was performed 2-126 months after onset of cardiac failure at a median age of 163 months. Five year actuarial survival from transplantation was 74%. There was no recurrence of the original malignancy in any of these patients. Both heart/lung patients died, 3 and 11 months after the transplant. These heart transplantation data suggest that, in Britain, survival compares favourably with that of patients whose heart transplant was required for other causes of cardiomyopathy. This indicates that patients successfully treated for childhood cancer should not be excluded from transplant programmes.

Adolescent↗
PubMed1996

Effects of inhibition of complement activation using recombinant soluble complement receptor 1 on neutrophil CD11b/CD18 and L-selectin expression and release of interleukin-8 and elastase in simulated cardiopulmonary bypass.

The inflammatory response to cardiopulmonary bypass includes activation of complement and induction of several neutrophil activation pathways. A recombinant soluble form of complement receptor 1 was used as a specific inhibitor of complement activation in simulated cardiopulmonary bypass circuits. Substantial complement activation was observed in these circuits with progressive accumulation of both plasma C3a and terminal complement complex. Soluble complement receptor 1 resulted in a significant reduction in C3a levels (p < 0.01) but did not inhibit terminal complement complex generation. A marked rise in neutrophil CD11b/CD18 expression, simultaneous loss of L-selectin expression, and a progressive accumulation of plasma elastase-alpha 1-antitrypsin occurred and were not affected by soluble complement receptor. However, generation of interleukin-8 in the circuits was inhibited (p < 0.05) by pretreatment with soluble complement receptor. These data suggest that changes in neutrophil activation seen during cardiopulmonary bypass may not be induced directly by anaphylatoxin generation.

CD11 Antigens↗
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

Expression and function of membrane regulators of complement on rat astrocytes in culture.

Human astrocytes express CD59, decay accelerating factor and membrane cofactor protein to restrict the damaging effect of complement (C) activation on their cell surface. 5I2 antigen (5I2 Ag) is the functional analogue of the latter two proteins in rats. We here demonstrate the surface expression on rat astrocytes of CD59 and 5I2 Ag and use sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting to confirm their identity and to quantify expression. Rat CD59 (MW 20,000) was expressed at 720 x 10(3) molecules per cell and 5I2 Ag (MW 58,000 and 64,000) at 625 x 10(3) molecules per cell. Reverse transcription-polymerase chain reaction using specific oligonucleotide primers demonstrated expression of mRNA for each protein. Twenty-four-hour stimulation with inflammatory cytokines (interferon-gamma, tumour necrosis factor-alpha, interleukins-1 beta, -2 and -6) or phorbol myristate acetate had no significant effect on the level of expression of either protein as determined by Western blotting. Lysis caused by classical pathway activation of C in human or rat serum was enhanced by blocking the function of CD59 and 5I2 Ag on rat astrocytes with monoclonal antibodies.

Animals↗
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

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↗
PubMed1990

Renal transplantation in highly sensitized patients: five years of the SOS Scheme.

1. One-year graft survival of 218 patients transplanted through the SOS Scheme for highly sensitized recipients was 65%. There was significant improvement in the graft survival of 135 patients transplanted from 1986 to 1988, compared to the 83 patients transplanted from 1984 to 1985 (70% vs 56% at 1 year). 2. Of the 513 patients entered into the SOS Scheme, 218 (42%) received a graft, and of those 218, 179 were transplanted within 1 year. 3. Sex and previous graft history influenced the patient's sensitization status. Males with previously failed grafts and females waiting for their first transplant appeared at greater risk of becoming highly sensitized. 4. HLA matching improved graft survival in highly sensitized patients. The effect of matching was most evident for DR and for HLA-B and DR combined. The effect of matching for HLA-A was minimal. 5. HLA-DR1-positive individuals appeared to be at lower risk of becoming highly sensitized. In addition, DR1-positive highly sensitized patients had superior graft survival compared to DR1 negative recipients.

Graft Survival↗
PubMed1990

Identification, characterization, and photoaffinity labeling of the dihydropyridine receptor associated with the L-type calcium channel from bovine adrenal medulla.

The dihydropyridine receptor associated with the L-type Ca2+ channel in adrenal medulla membranes has been identified and characterized. [3H]PN200-110 binds in a stereoselective, saturable manner to a single class of high affinity sites in adrenal medulla membranes, with a Kd of 0.1 nM and a Bmax of 141 fmol/mg of protein. Dihydropyridines inhibited [3H]PN200-110 binding with the rank order (+)-PN200-110 greater than nifedipine greater than nimodipine greater than usoldipine greater than or equal to nitrendipine greater than BayK8644 greater than (-)-PN200-110. [3H] PN200-110 binding was sensitive to divalent cations, as examined by the effects of Ca2+, Mg2+, and the chelators ethylene glycol bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and EDTA. [3H]PN200-110 binding was modulated by various classes of L-type Ca2+ channel effectors. Benzothiazepines modulated binding of [3H]PN200-110 in a negative or positive manner that was temperature dependent, whereas phenylalkylamines weakly inhibited [3H]PN200-110 binding. Bepridil stimulated [3H] PN200-110 binding, whereas phencyclidine was without effect. The photoaffinity probe [3H]azidopine labeled a single polypeptide that migrated with an apparent molecular weight of 185,000-190,000 in sodium dodecyl sulfate gel electrophoresis. The dihydropyridine receptor was found to bind specifically to wheat germ agglutinin columns. These results demonstrate the presence of a Ca2+ channel blocker complex in adrenal medulla. The drug receptor sites reside on a glycoprotein complex in which a polypeptide analogous to the alpha 1-subunit of the L-type Ca2+ channel from skeletal muscle has been identified.

Adrenal Medulla↗