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Biomedical subjects

D Phelan

Publications and source records attributed to D Phelan.

At least 19 recordsLinked to original sources
PubMed1994

Induction immunosuppression with antilymphocyte globulin or OKT3 in cadaver kidney transplantation. Results of a single institution prospective randomized trial.

Improved cadaver kidney allograft survival rates, shorter duration of acute tubular necrosis, and a reduction in the incidence of rejection have been achieved using "quadruple sequential therapy"--AZA, prednisone, and antilymphocyte globulin (ALG) induction followed by the delayed addition of CsA. OKT3 has been shown to be effective in preventing and treating rejection, including steroid- and ALG-resistant rejection episodes. A single institution prospective randomized trial comparing ALG and OKT3 prophylaxis in first cadaver kidney allograft recipients was performed to assess their relative advantages and disadvantages. First cadaver kidney allograft recipients were prospectively randomized to receive 7 days of either ALG (n = 58) or OKT3 (n = 59) as part of a quadruple therapy protocol that included AZA, prednisone, and oral CsA. Patient characteristics, patient survival and causes of death, graft survival and causes of graft loss, incidence of and time to rejection and response to treatment, incidence of infections and their type, renal function, and antibody formation to ALG and OKT3 were examined. The 1-, 2-, and 3-year actuarial patient survival rates were 96% in the ALG group and 98% in the OKT3 group. The graft survival rates were 81.1%, 78.4%, and 78.4% in the ALG group and 84.1%, 78.7%, and 78.7% in the OKT3 group. In ALG-treated patients, 63% never had rejection, compared with 49% in the OKT3 patients (P = NS). In the ALG group 31% had a single rejection, 6% had 2 rejections, and none had 3 rejections, compared with 37%, 12%, and 2% in the OKT3 group. In the ALG group, 43% were steroid responsive compared with 65% in the OKT3 group (P = 0.08). There were 1.44 infections per patient in the ALG group compared with 0.76 in the OKT3 group (P = 0.0004). In the ALG group, 37% of patients developed CMV disease compared with 10% in the OKT3 group (P = 0.001). In donor-positive/recipient-negative patients, 8/10 (80%) in the ALG group developed CMV infection, of which 6 (75%) had severe or moderate CMV disease, compared with 2/15 (13%) patients in the OKT3 group (P = 0.002), of whom only one (6.7%) developed moderate disease. In donor-positive/recipient-positive patients, 8/23 (35%) in the ALG group developed CMV infection, of whom 5/8 (62.5%) developed severe or moderate disease compared with 1/21 (4.8%) in the OKT3 group (P = 0.02). Antibody formation to ALG and OKT3 occurred in 11% and 8% of patients, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Cardiopulmonary resuscitation skills in non consultant hospital doctors--the Irish experience.

We assessed the Cardiopulmonary Resuscitation (CPR) skills in 30 Non Consultant Hospital Doctors (N.C.H.D.'s) chosen randomly from a total of 110 on the staff of a university associated teaching hospital. The candidates filled out a questionnaire and were asked to perform initial assessment and CPR on a mannikin for two minutes. None of the candidates followed the recognised airway, breathing and circulation ABC sequence and only one provided effective CPR. We suggest there is a need for encouragement for doctors to undergo CPR training with subsequent certification and ongoing refresher courses during their career.

Attitude of Health Personnel↗
PubMed1992

The relationship between a nutritional index and acute physiology score in critical illness.

Prognostic indices derived from available physiological data (SAPS), complex nutritional and biochemical tests (PNI), grip strength and serum albumin were calculated in 16 critically ill patients receiving intravenous nutrition over a six week period. The aim was to compare these independently derived prognostic indices, to assess their response to feeding, and to determine suitability for use in Irish intensive care units. Mean SAPS (7.6 +/- 0.92), PNI (3.1 +/- 0.29), serum albumin (30.3 +/- 1.03 g/l) and grip strength (17.9 +/- 1.3%) were all suggestive of an "at risk" group. Significant associations were found between the accepted SAPS index and both PNI (r = 0.6, p < 0.001, n = 35) and grip strength (r = -0.68, p < 0.001, n = 44) but not with serum albumin. No consistent improvement was seen in response to feeding in any of the derived indices. The close correlation between prognostic indices derived from either physiological, nutritional or grip strength data in this study and the failure of prognostic indices to improve during hyperalimentation would support a common mechanism, e.g. endogenous mediators, for metabolic and physiological disturbance in critical illness. It suggests that the role of hyperalimentation is supportive rather than therapeutic and re-iterates the importance of managing underlying disease processes. Simple grip strength may be a useful alternative to complex nutritional indices.

Critical Illness↗
PubMed1991

Antiidiotypic antibodies to HLA class I alloantibodies in normal individuals: a mechanism of tolerance to noninherited maternal HLA antigens.

Recent reports indicate that 25%-50% of transplant patients exhibit B-cell nonresponsiveness to their noninherited maternal HLA antigens (NIMAs). To test the hypothesis that tolerance of NIMAs is mediated by antiidiotypic antibodies, sera from seven normal human subjects were tested for the capacity to inhibit the reactivity of HLA alloantisera directed to NIMAs. Five of seven sera inhibited (50%-100%) the cytotoxicity of monospecific alloantisera directed to their NIMAs. This inhibition was specific in that antisera directed to third-party HLA antigens were not inhibited. Cytotoxicity inhibition by normal sera was selective for antisera directed to HLA-B locus antigens. Absorption with an antibody specific for an HLA class I framework determinant eliminated the inhibitory activity of three of the five sera, suggesting that the inhibition was mediated by soluble HLA antigens in these cases. However, two of the sera retained inhibitory activity following soluble antigen depletion, suggesting that, in these cases, inhibition is mediated by antiidiotypic antibodies. This hypothesis was confirmed by purifying the immunoglobulin (Ig) fraction of one of these sera by anti-Ig affinity chromatography; the column eluate (Ig fraction) but not the effluent (Ig-depleted serum) was capable of inhibition. These data are consistent with the hypothesis that tolerance of NIMAs is mediated, at least in part, by antiidiotypic antibodies.

Antibodies, Anti-Idiotypic↗
PubMed1990

Evaluation of putative cytoprotective properties of antiulcer drugs using quantitative histological techniques.

The capacity for cytoprotection has been claimed for a number of drugs that may have a place in the treatment of peptic ulcer disease. In this study we have used quantitative histological criteria to evaluate the ability of these drugs to be cytoprotective and have compared their effects with that of natural prostaglandin E2 (PG). The standard rat model, with injury by instillation of 1 ml of absolute ethanol, has been used. Putative cytoprotective agents were administered 15 min prior to ethanol. Each animal was sacrificed 15 min after ethanol exposure. The stomach was removed and studied using an established quantitative histological technique. This technique provides a measure of the surface area of mucosa damaged and of the volume of mucosa damaged. Ethanol alone caused damage to 76% of the area of the rat stomach and 14% of the volume of the rat gastric mucosa. Pretreatment by PG (25 micrograms/ml) resulted in reduction of the area of damage to 45% and reduction of the percentage volume damage to 2.2%. The synthetic analog of PGE2, Enprostil (1 microgram/ml) achieved similar protective effects. With pretreatment with colloidal bismuth subcitrate (10 mg/kg) or sucralfate (25 mg/kg), no protection against the surface area damaged by ethanol was seen, but there was a marked reduction of the volume of mucosa damaged. Indomethacin pretreatment augmented the damage caused by ethanol. The protective effects of colloidal bismuth subcitrate and sucralfate were not blocked by pretreatment with indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Lack of T-cell tolerance of noninherited maternal HLA antigens in normal humans.

Recent clinical reports of nonresponsiveness to noninherited maternal human leukocyte antigens have led to speculation that humans may acquire tolerance of noninherited maternal antigens through exposure to maternal cells neonatally or in utero. To test this hypothesis, we measured the responsiveness of normal subjects to their noninherited maternal and paternal antigens using cell-mediated lympholysis assays and mixed leukocyte reactions. All individuals exhibited cell-mediated lympholysis and mixed leukocyte reaction responses to the maternal cells that were comparable to those to the paternal cells. Limiting dilution analyses revealed significant cytotoxic T-lymphocyte precursor frequencies to both sets of parental antigens. To exclude the possibility that tolerance of individual noninherited maternal antigens was masked by the response to other antigens expressed on the same target cell, we raised cytotoxic T lymphocytes to the maternal cells and then tested for reactivity to a panel of targets that expressed single noninherited maternal HLA antigens. In all cases, each noninherited maternal antigen expressed on the maternal cells elicited a significant cell-mediated lympholysis response. An analysis of clinical data showed that pretransplant mixed lymphocyte reactions to maternal cells are not significantly lower than those to paternal cells. These data suggest that the reported B-cell tolerance of noninherited maternal antigens is not mediated by clonal deletion of T cells induced by exposure to the maternal cells neonatally or in utero.

Adolescent↗
PubMed1990

Septicaemia and the prevention of multiorgan failure--the intensive care perspective.

Septicaemia frequently presents without "classic" signs of infection--tachypnoea, hypotension and confusion are the commonest features. The mortality rate is 40 to 80% and in intensive care units, septicaemia accounts for 70% of all deaths. Despite the use of antimicrobial drugs to which the offending organism is sensitive, patients are still dying. Effects on distant organ systems are due to "Mediators". "Microvascular Failure" resulting in tissue hypoxia is the unifying hypothesis of multiple organ failure in septicaemia. Mortality is correlated with the number of organ system failures. Supportive management is aimed at prevention of organ failure--manipulation of the circulation being the central key. Intravascular volume expansion, vasoactive drugs, mechanical ventilation and invasive monitoring are the means. Antimicrobial therapy must be guided by 'best guess' approach with multiple agents until isolation of the offending organism can recommend specific therapy. Aggressive surgical drainage or excision, is particularly applicable in abdominal sepsis. Several adjunctive therapies aimed at mediators of sepsis, are as yet experimental.

Critical Care↗
PubMed1989

Massive pulmonary haemorrhage due to leptospirosis.

A young man with leptospirosis developed massive pulmonary haemorrhage. This was remarkable both in its severity and in its occurrence early in the clinical course - before the onset or presence of jaundice, renal failure or of a serological diagnosis. It occurred in the absence of a coagulopathy or thrombocytopenia and presumably was a consequence of the capillary fragility characteristic of the disease - perhaps precipitated in this instance by mechanical ventilation.

Adult↗
PubMed1989

Ketosis, a complication of theophylline toxicity.

A case of prolonged theophylline toxicity in a young non-diabetic female is reported. Blood gas analysis revealed a mixed respiratory alkalosis and metabolic acidosis. The metabolic acidosis was due to ketoacids, which were detected in the patient's breath and urine. The ketones cleared rapidly when theophylline elimination was increased with activated charcoal, i.v. metoprolol reduced excessive b-adrenergic stimulation and a 10% dextrose infusion repleted hepatic glycogen. Theophylline is known to increase free fatty acid levels. It is postulated that prolonged fasting led to depletion of hepatic glycogen and that ketones were generated by metabolism of elevated serum fatty acids. In previous reviews of the metabolic abnormalities associated with theophylline toxicity ketosis has not been described.

Acidosis↗
PubMed1989

Purtscher's retinopathy and fat embolism.

A 19-year-old woman who sustained multiple trauma but no head injury developed fulminant fat embolism syndrome (FES). Her neurological deterioration was associated with cerebral oedema and the concomitant Purtscher's type retinopathy. We suggest that the pathogenesis of the retinopathy and of the cerebral oedema are the same and that Purtscher's retinopathy and retinopathy of the FES are indistinguishable.

Adult↗
PubMed1987

Extra reactivities detected in flow-cytometry-positive, CDC-negative crossmatches are definable HLA specificities.

In this preliminary study, additional reactions were detected in sera that were not found by T-AHG-CDC. The reactions had definable HLA specificities. In our laboratory, the procedures described in this article had the following relative sensitivities for detecting class I HLA alloantibody specificities: FC = B-AHG-CDC greater than T-AHG-CDC greater than B-CDC greater than T-CDC. This study supports the concept that some FC-positive crossmatches, negative by T-AHG-CDC, can be associated with reduced renal allograft survival, since many of the additional reactions detected by FC appear to be due to HLA Class I antibodies.

B-Lymphocytes↗