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Biomedical subjects

M J Boyle

Publications and source records attributed to M J Boyle.

41 records · Page 3Linked to original sources

Definition of two distinct types of AIDS-associated non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) in a human immunodeficiency virus (HIV)-infected person is an AIDS-defining condition. There is both an increased incidence of NHL and a poorer prognosis for the disease in these HIV-infected persons, compared with patients who spontaneously develop NHL. A series of 41 consecutive patients with HIV-associated NHL treated at St Vincent's Hospital, Sydney, between 1984 and September 1989 was assessed. Of these, 36 had NHL proven on biopsy and NHL was diagnosed clinically in the other five. On histologic examination 11 had high-grade malignant lymphoma, small non-cleaved cell (SNCC) type, similar to Burkitt lymphoma, 18 had high-grade lymphoma large cell immunoblastic (LCI) type, and seven could not be classified due to inadequate material for assessment. The clinical features of these two groups were compared. Those patients with LCI had advanced CD4+ immunodeficiency and poor survival (median = 6 weeks). The other group with SNCC had better preserved immune function, and longer survival (median = 18 weeks). Three patients had survived longer than 3 years all of whom had SNCC lymphoma as their first AIDS-defining illness. The clinical features and prognostic factors demonstrated in this study document heterogeneity of NHL in HIV-infected patients and should be used as a guide to treatment of these patients, by reserving more intensive treatment for those persons with better prognostic features.

Acquired Immunodeficiency Syndrome↗

Monolobar Caroli's disease.

Two cases of Caroli's disease confined to the left lobe of the liver are described. One patient is a 13-yr-old who presented with acute pancreatitis. The second patient presented with obstructive jaundice at age 60. In the latter case, the diagnosis was made by percutaneous transhepatic cholangiography, in the former by postoperative T-tube cholangiography. The diseased bile ducts were not resected in either patient. Both remain well at 4 and 5.5 yr postoperatively. Monolobar involvement in Caroli's disease has been described previously in only 34 published cases, and these are reviewed in detail.

Adolescent↗

Airflow measurement inaccuracies in aerosol imaging.

Aerosol production using inclined compressed air tanks may be subject to error caused by airflow meter variability and by the degree of inclination of the air-flow meter. Since most of these tanks are used in an inclined position, it is important for clinicians to be aware of these errors.

Aerosols↗

Intrasplenic liver parenchymal cells in conjunction with low-dose rapamycin and cyclosporine induce a unique and specific prolongation of rat cardiac and small bowel allograft survival.

These experiments investigated the immunosuppressive properties of liver tissue. Brown Norway (BN; RT1n) rat heart allografts survived in untreated control Wistar Furth (WFu; RTl(u)) rat recipients for 6.2 +/- 1.5 days, while allografts in animals that received rapamycin (RAPA) 0.0075 mg/kg/day and cyclosporine (CsA) 0.375 mg/kg/day delivered for 14 days by continuous intravenous infusion (civi) using osmotic pumps in conjunction with intrasplenic (i.s.) saline survived to 18.4 +/- 1.3 days. i.s. addition of 3 M-KCl extracted BN hepatic antigen or unpurified BN hepatocytes (liver parenchymal cells-5 x 10(7)/kg), which exhibited a 4.8% class II antigen expression, and which alone failed to prolong allograft survival (MST = 6.0 +/- 1.4 days), increased heart allograft survival to 25.3 +/- 2.3 and 27.2 +/- 1.9 days, respectively (p < 0.01). Hepatocyte purification using Dynabeads and Percoll reduced class II expression to 0.9% and increased allograft survival to 32.8 +/- 1.6 days (p < 0.01). In contrast, the effect of 5 x 10(8)/kg BN erythrocytes, exhibiting only 0.1% class II expression, was much less (23.8 +/- 1.9 days). Administration i.s. of BN splenocytes or nonparenchymal liver cells, demonstrated by flow cytometry to exhibit a 47.3 or 55.1% expression of class II antigen, respectively, failed to induce any significant increase in allograft survival (18.4 +/- 4.6 and 19.4 +/- 0.5 days, respectively). Survival of BN rat small bowel allografts was increased in Lewis (LEW; RTl1) rat recipients treated with RAPA, CsA, and unfractionated BN hepatocytes from 10.2 +/- 1.9 to 21.2 +/- 1.5 days. Pretreatment with i.s. BN hepatocytes, 14 days prior to harvesting, reduced WFu lymphocyte responses to allogeneic stimulation with BN or ACI spleen cells by 75 and 70%, respectively. Addition of 1 x 10(5) unpurified donor-specific BN or third-party Buffalo (BUF; RTl(b)) hepatocytes, but not supernatant, to the responder wells of MLCs resulted in a 61 and 40% suppression, respectively, of the WFu lymphocyte response induced by BN allogeneic stimulation. These findings suggest that while class I MHC expression has a significant role to play in exerting the immunosuppressive effects of hepatocytes, other influences more specific to liver may also prevail.

Animals↗

15AU81, a prostacyclin analog, enhances donor-specific hepatocytes to prolong the survival of rat heart but not small bowel allografts.

Prostacyclin analogs have previously been shown to have not only cytoprotective but also independent immunosuppressive effects. The effect of one such analog, 15AU81, to enhance the immunosuppressive effects of liver was investigated. We have previously demonstrated that cyclosporine (CsA) in conjunction with rapamycin (RAPA) potentiates class I+, class II- donor-specific hepatocytes to prolong rat cardiac and small bowel allograft survival. Brown Norway (BN; RT1n) hepatocytes alone (5 x 10(7)/kg, administered intrasplenically) failed to prolong the survival of BN heart allografts in Wistar Furth (WFu; RT1u) recipients, beyond that of untreated controls (MST = 7.2 +/- 0.8 days). Survival of BN hearts was increased to 11.4 +/- 1.7 days in WFu recipients treated with BN hepatocytes and 50 microg/kg/day 15AU81 administered by continuous s.c. infusion for 14 days using osmotic pumps (p < 0.05). The further addition of RAPA 0.0075 mg/kg/day and CsA 0.375 mg/kg/day delivered for 14 days by continuous i.v. infusion (CIVI) using osmotic pumps (a combination that alone prolonged BN heart allografts in WFu hosts to 18.4 +/- 1.3 days and in conjunction with BN hepatocytes prolonged survival to 27.2 +/- 1.9 days) prolonged allograft survival to 35.2 +/- 5.2 days. In contrast, the survival of small bowel allografts was not enhanced by 15AU81 administration. Survival of BN small bowel transplants in LEW recipients treated with hepatocytes alone (MST = 11.6 +/- 1.5 days) or hepatocytes plus 15AU81 (MST = 10.0 +/- 1.0 days) was similar to controls (MST = 10.2 +/- 1.9 days). Treatment with hepatocytes and RAPA/CsA increased survival to 21.2 +/- 1.5 days. The further addition of 15AU81 failed to augment this (MST = 17.0 +/- 1.9 days). In vitro WFu lymphocyte proliferative responses from animals pretreated with BN hepatocytes, 15AU81, or both treatments, for 2 weeks prior to harvesting, exhibited a reduction of at least 50%, compared to untreated controls upon allostimulation with irradiated BN or ACI spleen cells. These findings demonstrate that 15AU81 interacts favorably with hepatocytes either alone or in conjunction with RAPA and CsA to enhance their immunosuppressive effects on rat heart allograft survival. The failure to enhance small bowel allograft survival may be explained by the inability at this low dosage of 15AU81 to influence the intense graft versus host reaction elicited by small bowel transplants.

Animals↗