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Biomedical subjects

D McCloskey

Publications and source records attributed to D McCloskey.

26 records · Page 2Linked to original sources

Different HLA associated gene combinations contribute to susceptibility for coeliac disease and dermatitis herpetiformis.

Forty two white patients of British or Irish descent with coeliac disease and 28 with dermatitis herpetiformis were typed for class I HLA-A, B, and C, and class II DR and DQ antigens. In coeliac disease there was a significant increase in the frequencies of A1, B8, DR3, DR7, and DQw2 compared with controls but no increase of DR2. In dermatitis herpetiformis there were similarly increased frequencies of A1, B8, DR3, and DQw2. In contrast with coeliac disease, however, the frequency of DR7 (18%) was no different from the control group but there was an increased frequency of DR2.

Adolescent↗

HLA and rheumatoid arthritis: an analysis of multicase families.

In a study of multicase RA families, significantly raised frequencies of the HLA antigens DR4, DR1, Bw62, Cw3, A2, A31 and significantly lower frequencies of DR2, DR3, and B8 were found in probands compared to normal controls. When haplotype frequencies were compared between probands and controls, two haplotypes A2-B44-DR4 and A2-Bw62-DR4 were at higher frequency in probands. These differences no longer reached significance when only DR4-containing haplotypes were compared between probands and controls. A significantly lower haplotype frequency of A1-B8-DR3 was observed in probands compared to controls. This difference did not remain significant when only non-DR4 haplotypes were compared. Using an affected sibling pair ratio method, significant linkage between HLA and RA was found (P less than 0.01). Significant linkage was also observed between HLA and seropositivity. Analysis of Hardy-Weinberg equilibrium for the DR locus did not support the suggestion that DR4-associated RA susceptibility was inherited as a dominant trait. In addition it did not support the notion of an additive effect of DR4 and DR1 in RA susceptibility as these antigens were not found together more frequently than predicted by their individual gene frequencies.

Arthritis, Rheumatoid↗

HLA frequency and haplotype analysis in a family study of adult onset rheumatoid arthritis.

Twenty-five families with probands who have rheumatoid arthritis (RA) were studied for clinical evidence of disease and for HLA status. This confirmed an association between RA and DR4 in 19/25 probands (76 per cent, p = 0.008). These 19 probands carried 24 haplotypes which contained DR4. There was no significant increase of DR4 haplotypes bearing B15(Bw62) or B44 when compared with published control haplotype data. The rare complement allele C4 B3 was detected as part of the extended haplotype A2 Cw3 B15(Bw62) DR4 C4 A*3B*3 in three probands with severe RA. Further studies to examine disease severity and autoantibody expression are in progress.

Arthritis, Rheumatoid↗

Experimental subglottic stenosis: histopathologic and bronchoscopic comparison of electrosurgical, cryosurgical, and laser resection.

Controversy continues over the optimal method of resecting subglottic stenosis. Electrosurgery, cryosurgery and laser resection have all had some clinical success. We sought to compare these treatment methods in experimentally-created subglottic stenosis. Subglottic strictures were created transbronchoscopically in newborn lambs by electrocoagulating a rim of mucosa. Four weeks later, all had 20 to 90% occlusion documented bronchoscopically. Control animals were found to have dense submucosal fibrosis in the cricoid area. Remaining experimental animals were treated with: (1) electrosurgical resection; (2) cryosurgical treatment; (3) Neodymium-yag (Nd:Yag) laser at 20 watts; (4) Nd:Yag laser with 40 watts; or (5) carbon dioxide laser at 10 watts. Animals from each group were sacrificed at 5 and 30 days postresection and the tracheas were examined grossly and microscopically. Animals sacrificed at 30 days postresection were bronchoscoped at weekly intervals. Cryosurgical and electrosurgical resection resulted in 1-3 mm of thermal damage adjacent to the margin of resection at 5 days post-treatment. Mucosal ingrowth and healing were rapid and there was no development of stenosis or damage to underlying structures. Use of the Nd:Yag laser resulted in 10-20 mm of surrounding damage in animals sacrificed at 5 days. At 30 days posttreatment, there was mucosal healing but extreme underlying damage and redevelopment of stenosis at the level of treatment. The carbon dioxide laser-treated animals showed thermal damage present up to 2 mm in depth from resected areas at 5 days post-treatment. Mucosal regeneration proceeded rapidly. This study indicates that electrosurgical and cryosurgical resection for experimental subglottic stenosis create minimal thermal damage and are associated with comparably acceptable rates of mucosal ingrowth and healing. The carbon dioxide laser created comparable to slightly decreased thermal damage but suffers at present from lack of optimal visualization of the subglottic lesion.

Animals↗

Anatomy and techniques in segmental splenectomy.

Accumulating clinical experience indicates the desirability of retention of splenic tissue and function. Results of angiographic studies in human and canine spleens demonstrate that intrasplenic vessels are lobar, segmental and, generally, without intersegmental communication. In the dog, bleeding from peripheral region vessels--penicilli, venules and sinuses--is well controlled by either microfibrillar collagen or the neodymium yttrium aluminum garnet laser. However, larger segmental vessels in the intermediate or hilar regions cannot be controlled by microfibrillar collagen or the neodymium yttrium aluminum garnet laser and require ligation. Identification of these vessels is greatly facilitated by laser or microfibrillar collagen coagulation of the surrounding splenic tissue. Results of histologic studies at ten, 20 and 30 day healing intervals disclosed no delayed sloughs, hemorrhage or cyst formation. With knowledge of segmental vascular anatomy and the techniques of microfibrillar collagen, neodymium yttrium aluminum garnet laser incision and coagulation plus aspiration and vessel ligation, segmental or subtotal splenic resection can be readily accomplished in dogs with minimal blood loss.

Angiography↗

Adult hemolytic uremic syndrome with renal arteriolar deposition of IgM andC3.

Two cases of idiopathic adult hemolytic uremic syndrome in which deposits of IgM and C3 were identified in renal arterioles showing fibrinoid necrosis are reported. Fibrin was also identified in the lumina of the involved vessels, but there was no laboratory evidence of disseminated intravascular coagulation. In both cases, serum C3 was decreased and C4 was normal, suggesting involvement of the alternate pathway of complement activation. These two cases suggest that in some instances the adult hemolytic uremic syndrome may be immunologically mediated, and that renal vascular thrombosis is a secondary phenomenon.

Antigen-Antibody Complex↗

Transampullary septectomy for post-cholecystectomy pain.

Twenty-eight patients with chronic, incapacitating upper abdominal pain after cholecystectomy had excision of the common wall between the terminal bile duct and duct of Wirsung (ampullary septum). Twenty-two also had a sphincteroplasty: six had had this procedure previously. Pancreatic function studies, scintiscans, ultrasound and pancreatograms were non-diagnositic. Hyperamylasemia was an uncommon finding. Eight patients were found to have evidence of mild pancreatitis at exploration. There was gross scarring of the ampullary septum in 22 cases. Histologic examination revealed inflammation in 12 septa; the degree of fibrosis could not be assessed since 14 control septa from autopsy material free from biliary tract disease revealed a comparable degree of collagen and smooth muscle. There were no deaths, and minimal morbidity. In follow-up from seven to 59 months (mean = 26), 16 patients are relatively free of pain, five have occasional episodes which require non-narcotic analgesics, and seven have gained no relief from the operative procedure. A randomized controlled trial is recommended.

Adult↗

HLA class I and class II antigen associations in acute leukaemias.

HLA-A,B,C and DR antigen frequencies were determined in a group of 188 patients suffering from acute myeloid (AML) and acute lymphoid leukaemia (ALL). These antigen frequencies were compared with those obtained on a panel of normal individuals (n = 109) of the same ethnic origin. The significance of the differences in the antigen distribution and the strength of the associations between particular HLA antigens and the disease were then calculated. The results obtained show a decreased frequency of HLA-Aw19 in the overall group of patients and the group of patients with ALL. In addition, the antigen frequency of the HLA-B18 and DR5(DRw11) antigens was also decreased in the overall group of patients and in those patients with AML but not in the patients with ALL. The results suggest that the antigen Aw19 may confer some degree of resistance to the development of ALL and that the HLA-B18 and/or DR5 antigens may be resistance factors for the development of AML.

Adolescent↗