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Biomedical subjects

R J Howard

Publications and source records attributed to R J Howard.

At least 199 records · Page 11Linked to original sources
PubMed1989

Renal transplantation: a 20-year experience at the University of Florida.

Substantial gains have been made in both patient and graft survival during 20 years of transplanting kidneys at the University of Florida. The number of transplant recipients yearly has increased from six in 1966 to more than 100 in 1986. The use of immunosuppression reflects our evolving understanding of transplant immunology, with current morbidity and mortality rates considerably improved over those of the early years. This paper summarizes our transplantation experience over the past two decades.

Adolescent↗
PubMed1989

Incidental and purposeful random donor blood transfusion. Sensitization and transplantation.

We conducted a prospective study to gauge the frequency and degree of sensitization by transfusion and/or pregnancy in 797 candidates for first renal transplants. Sensitization was proportional to the number of blood transfusions. Multiple transfusions or a history of pregnancy without transfusions had similar effects on sensitization. The combination of transfusion and prior pregnancy resulted in sensitization of 1/3 of the candidates. Patients who were not sensitized and were accepted for 1-haplotype living-related donor grafts or first-cadaver donor grafts were transfused to receive a total of 5 units of packed red blood cells. Parous patients had an undue rate of antibody formation and alternate means of selecting and managing parous women are described. Nonparous candidates had a low rate of sensitization (8%) that did not prove an impediment to obtaining a transplant. Only 2% of prospective LRD graft recipients developed antibody against their intended donor. Transplant patients were generally managed with azathioprine and prednisone. One-haplotype LRD graft survival of protocol patients was 93.7% one year posttransplant, and 82.1% at 5 years. One-year CD graft survival was 77%. There was no reduction in graft survival when the interval between transfusion and transplantation exceeded one year. Random donor transfusion is effective in improving renal graft survival. Some recent multiinstitutional reports indicate a reduction or absence of the transfusion effect with current immunosuppression. Discarding blood transfusion as a preparation for transplantation may be ill-advised pending a prospective study.

Blood Transfusion↗
PubMed1989

Posttransplant antidonor antibodies and graft rejection. Evaluation by two-color flow cytometry.

The posttransplant production of antibodies against cryopreserved donor cells was studied in 50 consecutive cadaveric kidney graft recipients and in 23 additional patients selected for acute rejection. Serum was obtained twice weekly during the first 3 weeks posttransplant and then monthly for 6 months. IgM and IgG anti-T cell Abs were measured by 2-color flow cytometry. Results were analyzed in conjunction with the patients' demographics, previous sensitization, HLA-matching, posttransplant blood transfusions, incidence of delayed function, rejection episodes, and biopsy results. Antidonor antibodies, predominantly IgG, were detected in 19/48 (40%) of the patients proximate to the time of rejection. In contrast, antibodies were seen in only 2/22 (9%) of nonrejecting patients, and these antibodies were exclusively IgM. Younger patients were more likely to have antibody-mediated rejections. Cytotoxic antibody reactivity against panel cells developed or increased posttransplant in some patients, but it did not correlate with rejection. Previous sensitization and posttransplant transfusions favored the development of posttransplant panel reactivity but not of antidonor antibodies. Most rejections, including those associated with antidonor antibodies, were reversed by antirejection therapy. We conclude that antidonor antibodies are involved in a significant proportion of rejection episodes and that the damage induced does not necessarily culminate with loss of the graft.

Adult↗
PubMed1989

Prevention of transfusion-induced broad sensitization in renal transplant candidates.

Blood transfusions can induce broadly reactive anti-HLA cytotoxic antibodies, particularly in patients who have had previous transplants or pregnancies. To evaluate if HLA-matched transfusions were less immunogenic, renal transplant candidates at high risk of becoming sensitized were transfused with blood from partially or totally HLA-matched donors. The study was performed in multiparous patients who in addition had low level antilymphocyte antibodies detected by flow cytometry. Only 1/24 patients (4.2%) developed cytotoxic antibodies. Crossover studies were possible in 3 patients. In 2 patients the HLA-matched transfusions did not elicit a response, but the patients produced cytotoxic antibodies of broad reactivity when they were subsequently transfused with random donor blood. The third patient developed cytotoxic antibodies after transfusions mismatched for only one HLA-A,B antigen. Subsequent transfusions mismatched for a different antigen did not, in contrast, result in sensitization. These results demonstrate that HLA-matched transfusions, unlike regular and leukocyte-free transfusions evaluated in previous studies, can prevent sensitization in patients with a high probability of becoming untransplantable if transfused with random donor blood.

Antibodies↗
PubMed1989

Hospital patients who wear tinted spectacles--physical sign of psychoneurosis: a controlled study.

The wearing of tinted spectacles by patients is often said to be a marker of psychopathology but without supportive evidence. To investigate the validity of this observation the personalities of 20 medical hospital patients who wore tinted spectacles were compared, by means of a self-report inventory, with those of 20 controls who were age, sex, and diagnosis matched. There was a significant increase in the level of psychopathology in the tinted spectacle group, both in terms of an index of global psychological distress; the General Severity Index, and nine primary symptom dimensions measured by the inventory.

Adult↗
PubMed1989

Studies of the receptors on melanoma cells for Plasmodium falciparum infected erythrocytes.

We investigated whether thrombospondin plays a role in the binding of Plasmodium falciparum parasitized erythrocytes to C32 melanoma cells. Twelve patient isolates bound variably to melanoma cells, with good correlation between the degree of binding to cells and binding to thrombospondin. With a synchronous preparation of asexual parasites, acquisition of the capacity to bind to thrombospondin occurred at the same parasite stage as binding to melanoma cells. Development of parasites to trophozoites and schizonts correlated with binding of parasitized erythrocytes to thrombospondin and melanoma cells. The infected erythrocyte receptor for thrombospondin was destroyed by mild trypsinization, as was the receptor for melanoma cells. Although these results suggest similarity in the melanoma cell receptor and thrombospondin receptor for infected cells, other results showed that thrombospondin cannot alone be the melanoma cell receptor. Binding to other melanoma cell lines did not correlate with thrombospondin secretion: the RPMI 8252 and G361 cell lines bound few or no infected cells, yet secreted 50-100% as much thrombospondin as C32 cells. Iodinated thrombospondin bound in similar amounts to C32 cells and to noncytoadherent C361 melanoma cells. Binding and nonbinding melanoma cells did not differ in quantity of surface thrombospondin by radioimmunoassay. Thus, although purified, immobilized, thrombospondin binds parasitized erythrocytes, expression of thrombospondin alone on melanoma cells is not sufficient to mediate adherence.

Animals↗
PubMed1988

Two approximately 300 kilodalton Plasmodium falciparum proteins at the surface membrane of infected erythrocytes.

Two very large Plasmodium falciparum proteins are identified as constituents of the infected erythrocyte membrane. Sera were obtained from Aotus monkeys that had been repeatedly infected with asexual P. falciparum from one of four strains. The capacity of these sera to block in vitro cytoadherence of infected erythrocytes and agglutinate intact infected cells was determined. The sera were also used to immunoprecipitate protein antigens from detergent extracts of 125I-surface labeled or biosynthetically radiolabeled infected erythrocytes. For each serum/antigen combination, precipitation of only one protein correlated with the ability of the serum to interfere with cytoadherence and agglutinate infected cells. This malarial protein, denoted Pf EMP 1 (P. falciparum-erythrocyte-membrane-protein 1) bore strain-specific epitope(s) on the cell surface and displayed size heterogeneity (Mr approximately 220,000-350,000). Pf EMP 1 was strongly labeled by cell-surface radioiodination but was a quantitatively very minor malarial protein. Pf EMP 1 was distinguished by its size, surface accessibility and antigenic properties from a more predominant malarial protein in the same size range (Pf EMP 2) that is under the infected erythrocyte membrane at knobs. Monoclonal antibodies and rabbit antisera raised against Pf EMP 2 were used to show that this size heterogeneous antigen was indistinguishable from the previously described MESA (mature parasite infected erythrocyte surface antigen), identified by precipitation with rabbit antisera raised against the MESA hexapeptide repeats. Antibodies raised against Pf EMP 2/MESA did not precipitate Pf EMP 1. We conclude that Pf EMP 1 is either directly responsible for the cytoadherence phenomenon, or is very closely associated with another as yet unidentified functional molecule. Pf EMP 2/MESA must have a structural property/function that is important under the host cell membrane.

Animals↗
PubMed1988

Soft-tissue infections caused by halophilic marine vibrios.

Marine Vibrio bacteria can cause illness and occasionally death to people who are exposed to seawater. These gram-negative bacteria can be found in ocean water and estuaries and in uncooked marine animals; they can cause primary sepsis, gastroenteritis, and soft-tissue infections. During a five-year period from 1981 to 1986, we encountered 51 patients with primary soft-tissue infections caused by marine vibrios. Thirty-nine patients developed cellulitis after direct exposure to ocean water, nine had eaten raw oysters, and three had no obvious exposure to seawater. Twenty-two patients (44%) had an underlying illness that might have made them compromised hosts and predisposed them to infection. Twelve patients developed necrotizing infections. Thirteen patients ultimately died. These infections are susceptible to many antibiotics. Débridement is necessary when tissue necrosis occurs. Surgeons should suspect a marine vibrio infection if cellulitis occurs in a patient who has been near ocean water or has eaten raw oysters. These infections may not become apparent until a traveler has returned home, a place that may be far from the ocean.

Cellulitis↗
PubMed1988

Effects of cardiopulmonary bypass on pulmonary leukostasis and complement activation.

We measured white blood cell counts and complement component (C3a, C4a, and C5a) and prostacyclin levels, and studied lung biopsy specimens, in 16 patients undergoing cardiopulmonary bypass and compared them with four patients undergoing other pulmonary procedures. Bypass caused no significant elevation in peripheral venous white blood cell counts. Higher counts were present in the right atrium compared with the left atrium. Patients who underwent bypass had elevated complement component and prostacyclin concentrations before operation and these levels increased further during operation. Trapping of polymorphonuclear leukocytes occurred in pulmonary alveolar capillaries and venules after bypass. We conclude that bypass activates complement components primarily of the alternative pathway and leads to increased blood prostacyclin levels. These changes are accompanied by polymorphonuclear leukocyte accumulation in the lungs and may be important in initiation of the adult respiratory distress syndrome in these patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Loss of corticomedullary demarcation on magnetic resonance imaging: an index of biopsy-proven acute renal transplant dysfunction.

A prospective study of 19 cadaveric renal allograft recipients with suspected graft rejection was undertaken to compare the histological findings of the renal transplant biopsy with the results of magnetic resonance imaging (MRI). All 19 patients underwent a biopsy of the transplant allograft. Biopsy results included acute cellular rejection, acute vascular rejection, chronic vascular rejection (CVR), and acute tubular necrosis (ATN). Recipients of cadaveric renal allografts with normal function served as controls. The control showed distinct corticomedullary demarcation (CMD) on T1-weighted imaging. In contrast, CMD was absent or diminished in all the patients with suspected allograft rejection. Unfortunately, the loss of CMD did not correlate with a specific biopsy diagnosis. Patients with biopsy evidence of acute and chronic rejection or ATN demonstrated loss of CMD with similar image patterns. In conclusion, MRI is capable of detecting renal allograft dysfunction, but does not permit the determination of a specific cause.

Adult↗
PubMed1988

A portion of the Pf155/RESA antigen of Plasmodium falciparum is accessible on the surface of infected erythrocytes.

An investigation of antigens accessible to lactoperoxidase-catalysed cell surface iodination on intact Plasmodium falciparum-infected red blood cells (RBC) has identified a 125I-labelled antigen with an apparent size of about 155 kD. This labelled protein was specifically immunoprecipitated by the following antibodies: a rabbit antiserum and a mouse monoclonal antibody raised against a synthetic peptide comprising the 3',8-mer repeat EENVEHDA of the Pf155/RESA protein; a rabbit antiserum raised against a synthetic octapeptide comprising two copies of the 3',4-mer repeat EENV of the Pf155/RESA protein; and rabbit antisera against another synthetic peptide C(MYSNNNVED)2. The last antibody shows a strong reaction in asexual blood stage parasites with the Pf155/RESA antigen. While this antigen has been described previously as a submembrane component of the outer membrane of infected RBC, this report shows that at least part of its is accessible to the surface of both ring and late trophozoite-infected erythrocytes.

Amino Acid Sequence↗
PubMed1988

Evaluation of antibody synthesis in broadly sensitized patients.

This study was conducted to evaluate the rate of lymphocyte antibody synthesis in broadly sensitized patients. Antibody synthesis was estimated utilizing two approaches. In one, the time required by the antibodies to reach half their original values was determined by quantitating their levels by flow cytometry over periods of several months. In the other approach we measured the rate at which antibodies rose after inducing an artificial reduction by means of plasma exchanges. Patients not previously transplanted and not transfused during the study period showed low antibody synthesis and decreasing panel reactivity. In most previously transplanted patients panel reactivity did not change during the observation period. However, some patients displayed low antibody synthesis activity whereas others produced antibodies at a high rate. Extensive studies in one patient demonstrated active antibody synthesis even though he had not been transfused for more than two years. The results suggest that while frequent plasma exchanges can reduce antibody concentrations, concomitant use of immunosuppression may be needed only in patients shown to be actively producing antibodies.

Antibody Formation↗
PubMed1988

Late results of renal transplantation.

A total of 315 (64%) of 491 primary cadaver and living-related donor transplants performed from 1975 through 1984 were still functioning at 24 months. These selected patients were examined further to assess the impact of several risk factors on late graft and patient survival. Black recipients, patients with underlying diabetes mellitus or hypertension, patients with poor renal function at 24 months, and recipients of cadaver grafts had significantly poorer long-term graft survival. Age greater than or equal to 40, diabetes or hypertension, poor 24-month function, and cadaver donor transplantation were associated with poorer long-term patient survival. Considerable improvement in graft survival at 24 months was seen in 1980-1984 compared with the earlier period, coincident with our adoption of routine pretransplant random donor blood transfusion. In contrast, long-term graft survival in patients with functioning graft at two years did not improve significantly over the same period. Although living-related donor transplants showed greater graft and patient survival than cadaver donor grafts by univariate analysis, no such advantage was demonstrated by multivariate analysis.

Actuarial Analysis↗