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Biomedical subjects

A H Balk

Publications and source records attributed to A H Balk.

At least 127 records · Page 7Linked to original sources

Intracranial hemorrhage in association with thrombolytic therapy: incidence and clinical predictive factors.

In a period of 18 months, 2,469 patients with acute myocardial infarction treated with a thrombolytic agent were prospectively registered in 61 hospitals. Most patients (73%) were treated with streptokinase. Intracranial hemorrhage was observed in 24 patients, corresponding to an incidence rate of 1% (95% confidence interval 0.6% to 1.3%). The median time interval between the start of thrombolytic therapy and the first clinical signs of intracranial bleeding was 16 h (range 3 to 36). In total, 16 (66%) of the 24 patients died as a result of cerebral hematoma. To determine clinical predictive factors, a case-control study was conducted. For every patient with intracranial hemorrhage, two control patients who received thrombolytic therapy because of acute infarction in the same hospital and in the same period were selected. Detailed clinical characteristics of 22 of the 24 patients as well as of 7 other patients with documented intracerebral bleeding from the European Cooperative Study Group and of 2 patients who sustained intracranial hemorrhage outside the registry period were compared with 62 control patients. The results of multivariate logistic regression analysis indicate that patients taking an oral anticoagulant before admission, patients with a body weight less than 70 kg and those greater than 65 years old are at higher risk for intracranial hemorrhage during thrombolytic therapy.

Aged↗

Too early for cardiac transplantation--the right decision?

In 109 out of 479 patients who were referred for cardiac transplantation it was considered to be too early to put them on the waiting list for a donor heart. The clinical course of these 109 patients was analysed in order to verify whether this decision had been right. The mean age of the patients was 43 years, half of them suffered from ischaemic heart disease. The systolic left ventricular function of the patients was severely depressed (mean left ventricular ejection fraction 21%) and the left ventricular cavity was markedly dilated (mean echocardiographic end diastolic dimension 73 mm). Functional capacity, measured by bicycle ergometry, was low: mean maximal workload 62% of the expected load for gender, height and age. The median follow-up duration was 31 months. The survival rate of the patients was better than that of 175 patients who were accepted for transplantation after referral, 92%, 87%, 81%, 71% and 73%, 73%, 71%, 68% after 1, 2, 3 and 4 years respectively. Re-assessment was necessary in 29% of the patients within 1 year and in 52% within 3 years. Twenty patients died: 12 patients died before re-assessment had been initiated (eight sudden deaths), six patients because of progressive heart failure before heart transplantation could be performed and two patients died after heart transplantation. Left ventricular ejection fraction, pulmonary capillary wedge pressure and transpulmonary gradient were not reliable predictors of the course of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Acute rejection in heart transplant patients is associated with the presence of committed donor-specific cytotoxic lymphocytes in the graft but not in the blood.

In vivo-activated, committed donor-specific cytotoxic lymphocytes (cCTL) can be propagated and expanded from endomyocardial biopsies (EMB) in IL-2-enriched medium especially during an acute rejection episode. We report here our efforts to detect these cCTL by the same technique in peripheral blood at the moment of rejection and when no rejection was diagnosed. During or just before rejection, significantly less frequent (P less than 0.01) donor reactive cCTL were found in PBL samples (two out of 20) than in the simultaneously taken EMB samples (13 out of 19). Donor B-LCL and/or third-party B-LCL were lysed by 15 PBL samples. Inhibition studies revealed that this lysis was due to LAK-like cytotoxicity. The results show that peripheral blood does not reflect intra-graft events, which is probably the reason for the irreproducible results of diagnosis of rejection by monitoring immunological parameters in the peripheral blood.

Biopsy↗

Changes in left ventricular function and wall thickness in heart transplant recipients and their relation to acute rejection: an assessment by digitised M mode echocardiography.

OBJECTIVE: Assessment of changes in left ventricular diastolic function and wall thickness after heart transplantation to verify whether these changes predicted acute rejection assessed by endomyocardial biopsy. DESIGN: Follow up according to a predefined protocol of consecutive patients from the first week after transplantation. SETTING: Heart transplantation unit of the Thoraxcentre, University Hospital Rotterdam Dijkzigt, The Netherlands. PATIENTS: All 32 patients undergoing orthotopic heart transplantation from 1 January 1989 to 31 March 1990 were examined. Two were excluded from the analysis. Patients were treated with cyclosporin and low dose steroids. MAIN OUTCOME MEASURES: Data obtained by digitised M mode echocardiography were compared with the results of endomyocardial biopsy (Billingham classification). Mean values for left ventricular wall thickness, internal dimension, and their standardised rates of change and fractional shortening were determined from 4-6 consecutive expiratory beats. Mean values and individual trends during follow up were also investigated for each ultrasound variable. The results of these average values were compared with values in a group of 10 healthy volunteers. RESULTS: Median follow-up was 177 days (range 10-399). Two hundred and sixty three consecutive M mode studies were examined in relation to concurrent biopsy results. No significant differences were observed between the ultrasound variables at the time of moderate acute rejection (Billingham class 2, n = 37) and other biopsy classes (n = 226). Nor did changes in individual patients predict (moderate) acute rejection episodes. Twenty six of the 30 patients had an abnormal (slow) left ventricular relaxation pattern throughout follow up. CONCLUSIONS: Digitised left ventricular M mode echocardiography did not predict the presence of acute rejection. In most patients there was a persistent slow left ventricular relaxation pattern.

Acute Disease↗

Diffusion capacity in heart transplant recipients.

Preoperative diffusion capacity per liter alveolar volume (Kco) in cardiac transplant recipients with an intrinsic normal lung is within the normal range. In the first postoperative year, Kco showed a significant mean decrease of 12 percent (p less than 0.004). Lung function (TLC, VC, FEV1) tended to normalize after heart transplantation. Ventilation distribution remained stable before and after heart transplantation. Preoperatively, weak correlations were found between Kco and diastolic pulmonary arterial pressure (dPAP) and mean pulmonary capillary wedge pressure (PCWP). Postoperatively, correlation between Kco and PCWP was weak, and between Kco and dPAP it was not significant at all. These pressures determine the capillary blood volume before and after transplantation. Probably these weak correlations indicate that intrapulmonary factors, not cardiac factors, are of primary importance in the regulation of blood distribution. The percentage of decrease in Kco in the first postoperative year correlated with the change in dPAP and PCWP, but also with the cyclosporine level in the first posttransplant year. No correlation was found between cyclosporine level and pulmonary vascular resistance. It is suggested that higher levels of cyclosporine influence the alveolar capillary membrane, so that Kco decreases. The percentage of decrease in Kco was significantly more outspoken in patients who had rales on auscultation preoperatively. Using multiple regression analysis, we found that the factors most strongly related to the percentage of change in Kco in the first posttransplant year were the preoperative Kco, the cyclosporine level in the first postoperative year, and the change in dPAP in that year.

Adult↗

Phenotypic and functional analysis of T cell receptor gamma delta-bearing cells isolated from human heart allografts.

Endomyocardial biopsies from human heart transplant recipients were investigated with respect to the occurrence of in vivo activated, alloreactive TCR-gamma delta+ cells. More than one year after transplantation, 30% of the biopsy-derived T cell cultures contained TCR-gamma delta+ cells, whereas in the first year after heart transplant in only 8% of the culture TCR-gamma delta+ cells were found. Such an increase of TCR-gamma delta+ cells was not observed in the peripheral blood of the patient. In most biopsy-derived cultures, the gamma delta cells were delta-TCS1+. No donor-specific cytotoxic activity could be demonstrated for TCR-gamma delta+ cells tested, whereas non-MHC-restricted cytotoxicity was found in several cultures. The occurrence of nonalloreactive TCR-gamma delta+ cells late after transplantation, when acute cellular rejection episodes are rare, suggests a role in the down-regulation of the allo-Ir.

Cells, Cultured↗

Alloreactive lymphoid infiltrates in human heart transplants. Loss of class II-directed cytotoxicity more than 3 months after transplantation.

From 535 endomyocardial biopsies (87 heart transplant recipients) 283 cell cultures could be generated. All cultures tested contained T lymphocytes and in most cases CD4 was the predominant phenotype at any time posttransplant. A significantly higher proportion of CD8-dominated cultures was found among cultures from biopsies without myocytolysis. In the first 3 months post transplant 57% of cultures showed cytotoxicity against both class I and class II mismatched donor major histocompatibility complex (MHC) antigens, changing to an incidence of 33% at greater than 90 days. This proved to be due to a significant decrease in the number of cultures with human leukocyte antigen class II-directed cytotoxicity. This study shows that early after transplantation a heart transplant is infiltrated with activated donor-specific cytotoxic T cells which recognize a broad spectrum of mismatched donor MHC antigens, and that in time this spectrum becomes more restricted.

Antigens, Differentiation, T-Lymphocyte↗

[Psychosocial aspects of heart transplantation; 4-year experience].

The psychosocial aspects of heart transplantation are described on the basis of the experience gained with these patients in the University Hospital Rotterdam (Dijkzigt) from 1984 to 1988. Quality of life before and after heart transplantation was determined using a comprehensive patient questionnaire. This questionnaire was presented by means of a personal computer. Forty-eight patients completed the pretransplant questionnaire. Data on the quality of life 4 and 13 months after transplantation were available for 33 and 20 patients, respectively, mainly due to the limited observation time. Severe anxiety and depressive mood were the predominant features of patients before transplantation. After transplantation the level of anxiety returns to normal within four months. However, sleep disturbances and depressive feelings may persist. Despite physical recovery, only few return to full or partial employment. Our findings confirm international experience and suggest appropriate psychosocial support in the period following the transplantation procedure.

Anxiety↗

Cytomegalovirus seronegative heart transplant recipients. Prophylactic use of anti-CMV immunoglobulin.

Thirty-two CMV seronegative heart transplant patients received prophylactic anti-CMV immunoglobulin during the first three posttransplant months. One of the 16 recipients of a heart from a seronegative donor acquired CMV infection and developed CMV disease. In eight of the 16 recipients of a heart from a seropositive donor, CMV infection was observed. Viremia was diagnosed in seven of them, but only two of these patients developed CMV disease. The incidence of CMV infection and of CMV disease in the globulin-treated CMV seronegative recipients of a heart from a seropositive donor was comparable to the incidence of CMV infection and of CMV disease in 31 nonglobulin-treated CMV seropositive recipients. This was significantly lower (percentage difference 69 percent, 95 percent CI 42-97 percent, p less than 0.001) than expected on the basis of the data from the literature and indicates that passive immunization with anti-CMV immunoglobulins induces the same protection against CMV disease as natural acquired anti-CMV resistance. This protective effect was temporary, as one patient developed symptomatic CMV infection four months after transplantation at a time when the anti-CMV immunoglobulin levels had decreased to pretransplantation values.

Cytomegalovirus↗

Indirect enzyme-linked immunosorbent assay for immunoglobulin G and four immunoassays for immunoglobulin M to Toxoplasma gondii in a series of heart transplant recipients.

Toxoplasma gondii infections in heart transplant recipients were monitored by indirect enzyme-linked immunosorbent assay for immunoglobulin G (ELISA-IgG), indirect ELISA-IgM in serum IgM fractions, antibody capture ELISA-IgM, IgM-immunosorbent agglutination assay (ISAGA), and IgM immunoblotting. Basic immunosuppression consisted of cyclosporine and low-dose steroids. Before transplantation, 26 of 43 recipients showed serological evidence of infection. In serum samples from 15 (35%) recipients, specific antibodies were not detected. Approximately 50% of the heart donors, were toxoplasma seropositive. Eight of the fifteen seronegative recipients received hearts from toxoplasma-seropositive donors. In four of the eight recipients, seroconversion could be demonstrated with all tests used. In three of these four patients, clinical disease developed. One patient with strong serological evidence of toxoplasmosis died, but toxoplasma parasites and antigens were not detected at autopsy. In two patients, toxoplasma cysts were found in cardiac biopsies. Seroconversion was not prevented by the use of spiramycin prophylaxis in two recipients. Reactivations of latent infections or reinfections were detected by indirect ELISA in six (23%) seropositive recipients, but symptoms and signs of active T. gondii infection were not seen. Seroconversion and reactivation of infection were readily found by a combined use of indirect ELISA-IgG and ELISA-IgM and antibody capture ELISA-IgM. Discrepancies in results could be examined by immunoblotting. IgM-ISAGA retained stable positive values longer than IgM-ELISAs did. Cyclosporine treatment did not hamper detection of seroconversion but could cause antibody levels to remain relatively low in primary infections. Seronegative recipients should receive antitoxoplasma treatment on seroconversion.

Agglutination Tests↗