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Biomedical subjects

R Hong

Publications and source records attributed to R Hong.

At least 55 records · Page 3Linked to original sources
PubMed1991

The DiGeorge anomaly.

The DiGeorge anomaly, DGA (formerly termed DiGeorge syndrome), is now known to be a developmental field defect in which pharyngeal pouch derivatives do not arise, usually because of inadequate neural crest contributions. The conditions in which this occurs include exposure to teratogens, cytogenetic abnormalities, and Mendelian disorders. As a result, the facies and cardiovascular defects which occur are very characteristic. Two rare conotruncal anomalies, type B interrupted aortic arch and truncus arteriosus account for over half of the cardiac lesions seen in DGA. Failure of descent of the thymus is extremely common in DGA, but immunodeficiency which requires correction occurs only in approximately 25% of the cases. The term, complete DGA, should be reserved for those patients in need of reconstitution of the immune system. One can identify those patients requiring treatment of the thymic defect by T cell enumeration and in vitro proliferation assays. Two alternatives for therapy are thymus transplantation and bone marrow transplantation from a HLA matched sibling.

Branchial Region↗
PubMed1991

Effects of environmental toxins on lymphocyte function: studies in rhesus and man.

The immune system is a potential target of environmental toxins. Impairment of immune function could have a disastrous effect upon the affected individual. We had the unique opportunity to study the results of a prolonged exposure to TCDD (2,3,7,8-tetrachlorodibenzo-P-dioxin) in rhesus monkeys and their offspring. Subsequently, we performed similar studies on humans exposed to the nematode pesticide, Aldicarb. This report summarizes those previous studies. In the monkeys, no major deficits of the immune system were found and the animals did not have excessive numbers of infections. However, at higher doses of dietary TCDD (25 ppt), only 22% of the offspring survived to 1 year of age. Thus, the failure to demonstrate effects on the young may simply relate to the essential equivalence of the lethal to an immunosuppressive dose. In humans, exposure to the acetylcholinesterase inhibitor, Aldicarb, was received through contaminated well water. The known exposure was for at least 1 year and could have been as long as 5 years. Various tests of the immune system, including lymphocyte subset counts, proliferative responses, total immunoglobulin levels and specific antibody responses did not reveal immunodeficiency. Increases in the numbers of CD8 positive T lymphocytes was observed. There was no evidence of any increase in clinical illness in the exposed compared with the control group.

Adult↗
PubMed1991

Renal insufficiency after bone marrow transplantation in children.

Between 1975 and 1988, 92 pediatric patients have undergone bone marrow transplantation (BMT) at our institution for malignant or immune deficiency disease. We evaluated in a retrospective fashion 64 of these patients who survived beyond the first 60 days post-BMT. The clinical course was divided into: less than 60 days post-BMT (early) and greater than 60 days post-BMT (late). The presence or absence of renal insufficiency was noted as well as all known potential factors predisposing to insufficiency. Step-wise regression analysis was then performed to determine which of the factors were most significantly associated with renal dysfunction during the two periods. The follow-up period was 2 months to 11 years (mean 17.5 months). The mean age of the patients was 7.6 years (1 month-18 years). Fifty percent of the patients had renal insufficiency during the early period and 28% of the patients had insufficiency after the initial 60 days. Three major predictors of renal insufficiency were discovered. Cyclosporin A or amphotericin B early or late post-BMT was independently predictive of developing insufficiency during the same period. Conditioning with total body irradiation was a predictor for insufficiency in both periods. Early insufficiency was not predictive of late insufficiency. Hypertension was present in 31% of patients during the early period and in 16% during the late period. Hypertension was strongly associated with cyclosporin use and renal insufficiency. Renal insufficiency is a frequent sequela in children following BMT and likely results from a combination of radiation injury and drug toxicity.

Adolescent↗
PubMed1990

Monoclonal antibody T-cell-depleted HLA-haploidentical bone marrow transplantation for Wiskott-Aldrich syndrome.

Four patients with Wiskott-Aldrich syndrome received bone marrow transplants (BMT) using monoclonal antibody T cell-depleted HLA-haploidentical marrow from a family member donor. The patients did not receive a significantly larger inoculum of mature T cells than other recipients of T cell-depleted marrow transplants. All four patients achieved quick engraftment, and three of the four patients are alive and well today. The three living patients have all had a complete return of normal T-cell and B-cell function. Infectious complications in the surviving patients were minimal; however, all three experienced some degree of graft-versus-host disease (GVHD). Two of these three patients received GVHD prophylaxis. The patient not receiving GVHD prophylaxis experienced severe GVHD and had a difficult posttransplant course. The patient who did not survive was chronically ill before BMT, whereas the other patients were in relatively good health at the time of BMT. Since the majority of individuals with this disease lack a matched bone marrow donor, our results using partially matched donors suggest that a greater number of patients can be successfully treated for Wiskott-Aldrich syndrome and that outcome is related to control of GVHD and state of health before BMT. Marrow transplantation should be offered earlier in the disease course before the onset of major infectious problems.

Antibodies, Monoclonal↗
PubMed1990

Update on the immunodeficiency diseases.

Newer understanding of the development of the immune system and novel methods to repair these defects promise cures for previously fatal diseases. The advances stem from the ability to define the developmental stages and describe the diseases at the gene level. Coordinate with this progress, recombinant DNA technology may soon permit the precise correction of the defect. For the moment, gene replacement is accomplished at the cellular level by bone marrow transplantation. Here too, rapid clinical advances now permit the use of nonsibling donors. The long-term results are equivalent to those obtained in the past when only HLA-matched siblings could donate. There is now a support group that is of inestimable value to the families of those who suffer from immunodeficiency. Thus, there has been both technological and social progress in the area of primary immunodeficiency. The future is clearly brighter each year.

Child↗
PubMed1990

Day to day reproducibility of electrically inducible ventricular arrhythmias in survivors of acute myocardial infarction.

Day to day reproducibility of the response to programmed ventricular stimulation has not been evaluated in survivors of acute myocardial infarction. Programmed ventricular stimulation was performed prospectively on 2 consecutive days in 56 patients on an average of 12 +/- 5 days (range 7 to 29) after an acute myocardial infarction. No patient had a history of documented or suspected sustained ventricular tachycardia or fibrillation occurring greater than 48 h after infarction. During initial programmed ventricular stimulation, 21 patients had induction of sustained ventricular tachycardia or fibrillation (Group I), and 35 patients had induction of either nonsustained ventricular tachycardia or no ventricular tachycardia (Group II). Repeat programmed ventricular stimulation in Group I patients induced sustained ventricular tachycardia or fibrillation in 16 of 21 patients (reproducibility 76%); the maximal induced response in the other 5 patients was nonsustained ventricular tachycardia in 2 patients and fewer than six repetitive ventricular responses in 3 patients. The day to day reproducibility was significantly higher for inducible sustained ventricular tachycardia of cycle length greater than or equal to 240 ms compared with rapid sustained ventricular tachycardia of cycle length less than 240 ms (100% versus 44%, p less than 0.009) or ventricular fibrillation (100% versus 43%, p less than 0.009). Repeat programmed ventricular stimulation in Group II patients did not induce sustained ventricular arrhythmias in 31 of 35 patients (reproducibility 89%). Thus, in survivors of acute myocardial infarction, inducible slow sustained ventricular tachycardia was a highly reproducible finding, whereas inducibility of rapid sustained ventricular tachycardia and ventricular fibrillation showed a significant day to day variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effect of acute hemodynamic decompensation on electrical inducibility of ventricular arrhythmias in patients with dilated cardiomyopathy and complex nonsustained ventricular arrhythmias.

In patients with dilated cardiomyopathy, hemodynamic decompensation has been postulated to increase vulnerability to reentrant ventricular arrhythmias. To test this hypothesis, we performed programmed ventricular stimulation with three extrastimuli on nine patients with dilated cardiomyopathy and asymptomatic complex ventricular arrhythmias during a period of acute hemodynamic decompensation; programmed ventricular stimulation was then repeated following hemodynamic improvement with nitroprusside. These patients did not have a history of documented or suspected sustained ventricular tachycardia or fibrillation. The mean left ventricular ejection fraction was 0.21 +/- 0.04 (range 0.15 to 0.26). In the baseline state, mean right atrial pressure was 8 +/- 4 mm Hg, pulmonary artery wedge pressure was 20 +/- 3 mm Hg, and cardiac index was 3.2 +/- 0.5 L/min/m2. Following acute hemodynamic decompensation, mean right atrial pressure increased to 16 +/- 5 mm Hg and pulmonary artery wedge pressure to 33 +/- 8 mm Hg; cardiac index decreased to 2.1 +/- 0.5 L/min/m2. In this decompensated state, programmed ventricular stimulation failed to induce sustained or nonsustained ventricular arrhythmias in any patient. Following nitroprusside administration (mean dose 1.5 +/- 1.1 micrograms/kg/min), there were significant decreases in mean right atrial pressure (11 +/- 3 mm Hg) and pulmonary artery wedge pressure (16 +/- 3 mm Hg), and a significant increase in cardiac index (3.1 +/- 1.1 L/min/m2) (p less than 0.05 for all values versus the decompensated state). In the improved hemodynamic state, programmed ventricular stimulation induced nonsustained ventricular tachycardia (six beats) in only one patient, and sustained arrhythmias in none.(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗
PubMed1990

Changes in T-lymphocyte distribution associated with ingestion of aldicarb-contaminated drinking water: a follow-up study.

The carbamate pesticide, aldicarb, is the most commonly found man-made groundwater contaminant in Wisconsin. A 1985 study linked ingestion of aldicarb-contaminated drinking water with altered T-cell distributions, specifically an increase in the mean number of CD8+ (T8) T cells. To further evaluate this finding, a follow-up study was done in 1987. Of the 50 Portage County, Wisconsin, women who participated in the first study, 45 participated in the follow-up: 18 formerly exposed and 27 formerly unexposed. In our follow-up study, only 5 women were found to be currently exposed to aldicarb. This group of 5 women, compared to 39 unexposed women who had peripheral blood specimens taken, had an increased percentage of lymphocytes and an increased number of CD2+ T cells, due to an increased number of total CD8+ T cells. Although the number of exposed persons was small, the increases in percentage lymphocytes and absolute numbers of CD2+ and CD8+ T cells were consistent with a dose-response relationship. No identified drinking water contaminant other than aldicarb could explain these findings. These results support earlier evidence linking aldicarb exposure and lymphocyte distribution changes. Although adverse clinical effects have not been documented, the widespread use of this chemical and consequent potential for widespread exposure indicate a clear need for further research on this issue.

Adult↗
PubMed1990

X-linked severe combined immunodeficiency. Diagnosis in males with sporadic severe combined immunodeficiency and clarification of clinical findings.

Over 80% of infants with severe combined immunodeficiency (SCID) of unknown genetic etiology are males, yet less than a third of these affected males have a family history of X-linked disease. To help identify new mutations of the X-linked SCID gene and to provide genetic counseling, X chromosome inactivation patterns in T cells from 16 women who had sons with sporadic SCID were examined. Between 9 and 35 human/hamster hybrids that selectively retained the active human X chromosome were produced from the T cells of each woman and analyzed with an X-linked restriction fragment length polymorphism for which the woman in question was heterozygous. Exclusive use of a single X as the active X was seen in the T cell hybrids from 7 of the 16 women, identifying these women as carriers of X-linked SCID. Studies on additional family members confirmed the mutant nature of the inactive X and revealed the source of the new mutation in three families. To determine whether there were any laboratory characteristics that might differentiate the boys whose mothers were identified as carriers of X-linked SCID from those whose mothers were not, the clinical records of both groups were compared to each other and to a group of 14 boys with a family history of X-linked SCID. The most consistent finding in the 21 patients with X-linked SCID was an elevated proportion of B cells. These data demonstrate the high incidence of spontaneous mutation for the X-linked SCID gene and help clarify the characteristic presenting features of this disorder.

B-Lymphocytes↗
PubMed1990

Biological and clinical effects of the oral immunomodulator 3,6-bis(2-piperidinoethoxy)acridine trihydrochloride in patients with malignancy.

CL 246,738 is a synthetic heterocyclic of the acridine class that has immunomodulating, interferon (IFN)-inducing, and antitumor activity by the oral route in mice. We have completed a phase I ascending dose trial to determine the maximum tolerated oral dose and biologic modifying effects. Twenty-three patients received CL 246,738 orally at five dose levels, escalating from 5 to 50 mg/kg. The major side effects were gastrointestinal disturbances such as nausea, vomiting, and diarrhea. No hematologic, hepatic, or symptomatic dose-limiting toxicities were encountered. The mean half-life of CL 246,738 in whole blood was at least 300 h and remained relatively constant over the dose range studied. Higher doses resulted in increased whole blood levels. Biologic response modification included stimulation of the IFN-induced proteins, 2',5'-oligoadenylate synthetase and beta 2-microglobulin, at higher doses of CL 246,738, and enhanced T-cell proliferation to alloantigens at lower doses. Increases in lymphocytes bearing the Leu-7 phenotypic marker were observed and some patients had enhanced natural killer (NK) cell cytotoxicity. Enhanced NK cell cytotoxicity was demonstrated in vitro. Thus, CL 246,738 was orally relatively well tolerated and has immunomodulating properties in humans.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

Associations of the skeletal and immune systems.

Certain disorders of the immune system seem to be associated with skeletal defects. The association was first recorded by McKusick et al. (Bulletin of the Johns Hopkins Hospital 116:285-326, 1964). A number of relationships between lymphocytes and osteocytes can be proposed. These include a common environment for development, common metabolic needs and effects upon osteocytes by products (cytokines) elaborated from lymphocytes or monocytes during immune responses. Thus, bony defects of varying degrees of severity are seen in short-limb dwarfs, cartilage-hair hypoplasia, and adenosine deaminase (ADA) deficiency. Cytokine activation of osteoclasts accounts for the lytic lesions seen in malignancies and the excessive bone resorption which accompanies autoimmune disorders such as rheumatoid arthritis. Correction of primary immune deficiency is accomplished by bone marrow transplantation. If the bony abnormality is subtle (as in some cases of ADA deficiency) the skeletal problem is resolved; if the bone defect is major as in short-limb dwarfism, no improvement is seen.

Adenosine Deaminase↗
PubMed1989

Assessment of immunity.

An approach to the assessment of the immune system primarily from the vantage point of the general physician is presented, indicating the clinical situations where analysis is most likely to yield informative results. Preliminary screening by the primary physician is discussed, followed by a brief description of measures which are employed in referral centers. A definitive diagnosis should be possible in nearly all cases. With the rapid advances in recombinant DNA technology and bone marrow transplantation, a cure can be expected for most patients, particularly if the diagnosis is made early.

Child↗
PubMed1989

Prediction of persistent immunodeficiency in the DiGeorge anomaly.

To assess the natural history of the immune defect in DiGeorge anomaly, we reviewed serial immunologic studies in 18 patients. The diagnosis was made with criteria based on the concept of the DiGeorge anomaly as a field defect. Initial or early follow-up laboratory examination suggested moderate to normal T cell function in 14 patients. None of these patients have lost T cell capability; they have never had infections characteristic of T cell deficiency. Four patients had clinical and laboratory evidence of profound immunodeficiency. A decreased number of CD4+ cells (less than 400/microliters) and a decrease in phytohemagglutinin responsiveness (stimulation index less than 10) may be useful in discriminating patients with immunodeficiency; absolute lymphocyte count and immunoglobulin values were not informative. At the time of surgery, the thymus was not found in 11 of 14 patients; however, only two of these patients had immunodeficiency. Patients with a persistently low number of CD4+ cells and decreased phytohemagglutinin response are candidates for immunologic reconstitution.

Aging↗
PubMed1989

Prognostic significance of programmed ventricular stimulation in survivors of acute myocardial infarction.

The prognostic significance of the response to programmed ventricular stimulation was studied in 75 stable survivors of acute myocardial infarction. Programmed ventricular stimulation induced sustained ventricular arrhythmias in 33 (44%) patients and did not induce these arrhythmias in 42 (56%) patients. During a mean follow up of 18 months, four patients died suddenly and three developed spontaneous sustained ventricular tachycardia. The occurrence of arrhythmic events was not significantly different in patients with inducible sustained arrhythmias and those without, but such events were predicted by the presence of mild congestive heart failure. Although the inducibility of sustained ventricular tachycardia (but not ventricular fibrillation) seemed to identify a high risk subset with an arrhythmic event rate of 21% compared with 5.5% in others, it had a low sensitivity (57%) and a low positive predictive accuracy (21%) for arrhythmic events. Programmed ventricular stimulation is not helpful in identifying a subset of patients at high risk after an uncomplicated acute myocardial infarction.

Arrhythmias, Cardiac↗