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Biomedical subjects

G Dixon

Publications and source records attributed to G Dixon.

At least 55 records · Page 3Linked to original sources

Grafting of fetal pancreata into neonatal rat brain.

Undigested fetal pancreatic tissue has been previously shown to have immunogenic properties, even after transplantation into the adult rat brain, a relatively immunoprivileged site. In the present study, iso-, allo-, and xenografts of fetal pancreas were placed into neonatal rat brain parenchyma and ventricles in order to determine the extent and quality of its survival in this environment. Adult recipients of the same tissue types were used as controls. Selective survival of insulin-staining beta cells was observed in neonates (n = 33) over the 6-week period of the experiment. Ducts and acini were gradually destroyed in allo- and xenografts, disappearing completely by the 42nd day, while there were no such changes in the isografts. The absence of an acute inflammatory reaction was noted, but there were varying degrees of lymphocytic infiltration, though small (20 +/- 4 lymphocytes per average graft area of 0.16 mm2) in all but one graft. This infiltrate was greatest in allografts, with a significant increase observed after 14 days, corresponding to the time when the ducts started to disappear. Other structures present included fibroblasts and blood vessels. The latter increased significantly with time after transplantation. Unlike isografts placed in the parenchyma of adult rats, allo- and xenografts were rejected from the earliest time observed, 7 days postoperatively. In summary, these data show that beta cells in rat fetal pancreas will survive when grafted across major allogeneic and xenogeneic barriers for up to 6 weeks, without utilization of any form of immunosuppression, provided the recipients are neonates.

Age Factors↗

Human tolerance to 100% oxygen at 9.5 psia during five daily simulated 8-hour EVA exposures.

Extravehicular activity (EVA) currently involves decompression to 4.3 psia. This degree of decompression carries a significant potential for decompression sickness (DCS) which could be alleviated if a pressure of 9.5 psia could be maintained in the pressure suit. Previous studies have not evaluated the potential for oxygen toxicity at 9.5 psia. Twenty-one subjects were exposed to 100% oxygen at 9.5 psia for 5 consecutive days, 8 h.d-1 while performing moderate exercise to simulate a typical work-week in the proposed pressure suit environment. No DCS or venous gas bubbles were detected. Pulmonary function tests, physical exams, blood analyses, arterial oxygen saturation monitoring, and X-rays showed no evidence of oxygen toxicity under these conditions. These results suggest that a 100% oxygen, 9.5 psia pressure suit environment could avoid both DCS and oxygen toxicity during EVAs of comparable duration and physical activity.

Adult↗

Increased expression of adhesive proteins on leukocytes by TNF alpha.

To further elucidate the role of tumor necrosis factor alpha (TNF alpha) in cell adhesion, we investigated the effect of TNF alpha on the expression of surface adhesive protein. After treatment with TNF alpha for 1 h, the increased expression of surface adhesive proteins (beta subunit) was observed on granulocytes but not on monocytes or lymphocytes. The expression of Mac-1 (3,4-fold increase) was consistently enhanced more than p 150,95 (1.4-fold increase) and LFA-1 expression was unchanged. Dose-response and time course studies indicated a parallel relationship between TNF alpha-increased expression of surface adhesive proteins and TNF alpha-induced granulocyte adhesion. The anti-inflammatory drug Dexamethasone suppressed both TNF alpha-induced granulocyte adhesion and TNF alpha-induced expression of surface adhesive proteins. The inhibition of granulocyte adhesion correlated with the reduction of surface adhesive protein expression. The data suggest that one contributing factor in the mechanism by which Dexamethasone inhibited TNF alpha-induced granulocyte adhesion may be diminished expression of surface adhesive proteins.

Antigens, Surface↗

Effects of exposure to factor concentrates containing donations from identified AIDS patients. A matched cohort study.

We compared recipients of eight lots of factors VIII and IX voluntarily withdrawn from distribution because one donor was known to have subsequently developed the acquired immunodeficiency syndrome with a nonexposed cohort matched by age, sex, and factor use. The factor VIII recipient cohorts did not differ in prevalence of antibody to human immunodeficiency virus (HIV) (exposed, 75%; nonexposed, 86%), T-cell subset numbers (median: exposed, 619 T-helper cells per cubic millimeter; nonexposed, 659 T-helper cells per cubic millimeter), T-helper to T-suppressor ratios, or immunoglobulin levels. Exposed individuals had higher levels of immune complexes by C1q binding and staphylococcal binding assays and lower responses to phytohemagglutinin and concanavalin A. However, only the staphylococcal binding assay values were outside the normal range for our laboratory. Factor IX recipient cohorts did not differ in HIV antibody prevalence (exposed, 30%; nonexposed, 40%) or any immune tests. Although exposed and nonexposed individuals did not differ from each other in a clinically meaningful fashion at initial testing, both the exposed and nonexposed cohorts had high rates of HIV seroprevalence. Market withdrawals were clearly insufficient means of limiting the spread of HIV in hemophilic patients; however, the currently available methods of donor screening and viral inactivation of blood products will prevent continued exposure within this population.

Acquired Immunodeficiency Syndrome↗

HTLV-III/LAV antibody and immune status of household contacts and sexual partners of persons with hemophilia.

We evaluated the human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody and immune status of 88 persons living with and/or sexual partners of 43 hemophiliacs, 12 of whom had AIDS, five of whom had AIDS-related complex (ARC), 17 of whom were clinically well but HTLV-III/LAV antibody positive, and nine of whom were well and HTLV-III/LAV antibody negative. No nonhemophilic household contacts (0/50) of healthy hemophiliacs were HTLV-III/LAV antibody positive; two of 33 nonhemophilic AIDS/ARC contacts were positive. One was a spouse and one a sexual partner of a hemophiliac. One of these antibody-positive contacts herself had AIDS, and one had ARC. Antibody-negative, nonhemophilic contacts of AIDS/ARC and of antibody-positive hemophiliacs had significantly lower numbers of lymphocytes, T helper lymphocytes, and T suppressor lymphocytes than did contacts of antibody-negative hemophiliacs. We conclude that risk of HTLV-III/LAV transmission may exist for spouses and/or sexual contacts of hemophiliacs with AIDS/ARC, but we cannot now determine the risk for contacts of asymptomatic hemophiliacs.

Acquired Immunodeficiency Syndrome↗

Human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus antibody. Association with hemophiliacs' immune status and blood component usage.

We studied the human T-lymphotropic retrovirus type III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody status of 234 factor VIII concentrate recipients, 36 factor IX concentrate recipients, 69 long-term recipients of frozen packed red blood cells, and 47 persons not receiving routine transfusion therapy. Factor VIII concentrate recipients had a significantly higher rate of seropositivity (74%) than any other group. Factor IX concentrate recipients had a significantly higher rate (39%) than recipients of frozen packed red blood cells (4%) or nontransfused persons (4%). In factor VIII concentrate recipients, HTLV-III/LAV seropositivity was significantly associated with more severe hemophilia, greater factor dosage, elevated immunoglobulin and immune complex levels, lower T-helper lymphocyte numbers, and lower ratios of T-helper to T-suppressor lymphocytes. For factor IX concentrate recipients, seropositivity was associated with more severe hemophilia. Antibody-positive factor IX concentrate recipients had a lower rate of seropositivity to HTLV-III/LAV p41 membrane antigen than did antibody-positive factor VIII concentrate recipients, but factor VIII and factor IX concentrate recipients had similar rates of seropositivity to core antigens. We conclude that both factor VIII and factor IX concentrates may transmit HTLV-III/LAV. For factor VIII recipients, HTLV-III/LAV seropositivity is associated with altered immune test results.

Adolescent↗

Immune status of blood product recipients.

Persons with hemophilia are at risk of the acquired immunodeficiency syndrome (AIDS), and clinically asymptomatic hemophiliacs have shown a high incidence of AIDS-like immune abnormalities, facts leading to speculation that many hemophiliacs have been exposed to the AIDS agent through their blood products. We therefore evaluated the immune status of three groups of blood product recipients without AIDS in New York City, including 47 persons with hemophilia A receiving factor VIII concentrate, 50 persons with homozygous beta-thalassemia, and 27 persons with sickle cell anemia receiving frozen-packed RBCs and 20 healthy persons who had not received a transfusion. Hemophiliac participants had significantly lower lymphocyte counts (median, 1,826/cu mm) than did the thalassemic (6,110/cu mm) or anemic (4,443/cu mm) participants, had lower numbers of T-helper lymphocytes (median, 533 cells/cu mm v 1,733 cells/cu mm and 1,554 cells/cu mm), and had a lower T-helper/suppressor ratio (median, 0.8 v 1.8 and 2.1). These differences remained after adjustment for age and sex. Thus, AIDS-like immune abnormalities were found in patients receiving factor concentrate, but not in those receiving RBCs. These defects could be due to both an immunosuppressive effect of the lyophilized factor itself and to contact with the AIDS agent.

Acquired Immunodeficiency Syndrome↗

Inspiratory muscle conditioning using a threshold loading device.

We demonstrate the effectiveness of a new conditioning technique for increasing the strength and endurance of the inspiratory muscles. The technique employs a threshold loading device which allows for maximization of exercise intensity with a minimum of exercise duration. After ten weeks, with approximately 25 minutes of exercise time per week, four test subjects showed an average increase in maximum inspiratory pressure (PImax) of 50 (+/- 9 SD) cm H2O (p less than 0.02), whereas four control subjects undergoing submaximal inspiratory muscle exercise showed no significant change. The time the test subjects could endure 65 percent of their prestudy PImax increased from an average of 3.58 +/- 1.65 SD min to over 10 min in all four subjects. No significant change was seen in control subjects. Further testing showed the test subjects could endure 100 percent of their prestudy PImax after conditioning for an average duration 5.15 +/- 1.65 min. This technique should be useful for conditioning the inspiratory muscles in subjects with pulmonary disease.

Adolescent↗

Hypothalamic function in amenorrheic runners.

We have examined temperature regulation in eight amenorrheic runners and gonadotropin response to an opioid antagonist in seven amenorrheic runners, 18 to 29 years of age, running 20 to 70 miles a week. Following equilibration, oral temperature was measured continuously, first in a cold room at 39 degrees F and then in a sauna at 172 degrees F in eight amenorrheic runners, in eight eumenorrheic runners, and in eight control subjects in the early follicular phase of the menstrual cycle. Studies were terminated if a subject's temperature fell below 94 degrees F or rose above 102 degrees F, and all studies were conducted in the afternoon. The rates of temperature change, calculated from total net temperature change divided by elapsed time in the test chamber, were not significantly different among the three groups of women. Seven other amenorrheic runners failed to have any significant changes in luteinizing hormone or follicle-stimulating hormone levels in response to the opioid receptor antagonist naloxone administered as an intravenous infusion at 1.6 mg/hour for 4 hours. If opioids inhibit gonadotropin secretion in exercise-associated amenorrhea, an increase in gonadotropins in response to naloxone would have been anticipated. Although it is possible that the dose of naloxone selected was inappropriate and that temperature responses under other conditions might differ from those of normal women, these data suggest that endogenous opiates do not play a direct role in the amenorrhea associated with exercise and that temperature regulatory centers in the hypothalamus are intact in this disorder, compared with other causes of amenorrhea such as anorexia nervosa. Further studies of hypothalamic function are warranted to test these possibilities.

Adolescent↗

The pathogenesis of premature craniosynostosis in acrocephalosyndactyly (Apert's syndrome). A reconsideration.

A detailed examination of a stillborn fetus with Apert's syndrome showed several unexpected findings, which prompted a reevaluation of the heretofore generally accepted hypotheses regarding the cause of the dysmorphic craniofacial features in this syndrome. (1) The characteristic clinical features of Apert's syndrome were present at 24 to 26 weeks of gestation, and presumably much earlier. (2) However, there was no evidence, clinical or histological, of premature fusion of any of the cranial sutures or basilar synchondroses in this fetus. From our observations, and from a critical review of the literature, we conclude that the characteristic craniofacial malformations of Apert's syndrome are not caused by premature fusion of the cranial sutures, as has been commonly postulated. Rather, a malformation of the skull base is the most likely primary morphological event, and it leads to the characteristic dysmorphic facies, then secondarily to premature craniosynostosis. We believe the nature of the malformation is related to an abnormality in the bones which comprise the cranial base base (e.g. the sphenoid, ethmoid, and occipital bones) and to abnormal spatial relationships between the cribriform plate and the crista galli, resulting in a positional disarrangement of the points of basal attachment of the dura matter. The latter, then, precludes the normal response of the neurocranium to the forces produced by the growing brain. The synostosis is viewed as a symptom, rather than as a cause, of the dysmorphic craniofacial features typical of Apert's syndrome.

Acrocephalosyndactylia↗

Effects of legal termination on subsequent pregnancy.

Two hundred and eleven patients who had undergone vaginal termination and were pregnant again were investigated; 43-2% had become pregnant within one year of termination. The overall fetal loss in the 211 patients was 17-5% compared with 7-5% in a group matched for parity but consisting of patients who were pregnant after a spontaneous abortion. Altogether 4-3% of pregnancies after legal abortion ended as first trimester abortions, 8-5% as second trimester abortions, and 13-7% in premature delivery. Among 11 women whose cervices had been lacerated at the time of legal termination the fetal loss in subsequent pregnancy was 45-5%, and only one pregnancy went beyond 36 weeks. Routine Shirodkar suture may be beneficial when the cervix is known to have been damaged at legal abortion. Several patients had asked that their general practitioner should not be told of their termination, and such patients may not admit their termination during a subsequent pregnancy, which could thus be jeopardised. No evidence was found to suggest that infants of patients with a history of legal termination are small for dates.

Abortion, Induced↗