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Biomedical subjects

T C Shope

Publications and source records attributed to T C Shope.

At least 19 recordsLinked to original sources

Respiratory syncytial virus morbidity and mortality estimates in congenital heart disease patients: a recent experience.

OBJECTIVE: To determine recent morbidity and mortality rates from respiratory syncytial virus infection in a pediatric congenital heart disease population. DESIGN: Retrospective cohort study design. SETTING: The C. S. Mott Children's Hospital, University of Michigan Medical Center. PATIENTS: A total of 740 pediatric patients hospitalized at the University of Michigan Medical Center for symptomatic respiratory syncytial virus infection, of whom, 79 patients had clinically important congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We retrospectively examined the charts of 740 patients hospitalized at our children's hospital from July 1, 1983 to June 30, 1990 with symptomatic respiratory syncytial virus infection to assess morbidity and mortality outcomes. Seventy-nine patients had congenital heart disease and 40 of these patients had pulmonary hypertension. For the entire cohort and a subset of patients with community-acquired infection, those patients with congenital heart disease had longer durations of hospitalization and greater need for, and days of, both intensive care and mechanical ventilation than patients without congenital heart disease. Mortality risk for respiratory syncytial virus community-acquired infection was not different for congenital heart disease vs. noncongenital heart disease patients (0.0% vs. 0.2%; p = 1.00). When examining only patients with congenital heart disease, those patients with pulmonary hypertension had increased hospital days and greater intensive care and mechanical ventilation durations compared with patients without this diagnosis. The overall mortality rate was low and was equally low for congenital heart disease groups with or without pulmonary hypertension (2.5 vs. 2.6). For community-acquired illness, no mortality was found in either congenital heart disease group. When the cohort of congenital heart disease patients was divided into pre- and postribavirin administration eras, no differences in mean hospital duration, ICU days, and mechanical ventilation days were noted. Of the 79 congenital heart disease patients, only two died during their hospitalization in which respiratory syncytial virus infection occurred. Both patients had nosocomial-acquired respiratory syncytial virus and both were from the postribavirin administration cohort. One of these two patients had received antiviral therapy. Neither death was secondary to respiratory syncytial virus respiratory failure (based on pathologic examination). CONCLUSIONS: We conclude that respiratory syncytial virus mortality risk in pediatric patients with congenital heart disease is less than the risk reported a decade ago. Respiratory syncytial virus infection in congenital heart disease patients with pulmonary hypertension is associated with increased morbidity but not increased mortality rates. The markedly decreased respiratory syncytial virus mortality risk in patients with congenital heart disease currently experienced is likely secondary to improvements in intensive care management and advances in the surgical correction in this population rather than antiviral therapy.

Academic Medical Centers

Serum isocitrate dehydrogenase activity in Reye's syndrome.

Serum levels of isocitrate dehydrogenase was determined in 12 Reye's syndrome patients and the enzyme levels were compared with serum ornithine carbamyl phosphate, glutamic oxaloacetic transaminase (aspartate aminotransferase), ammonia, and the stages of the disorder. Isocitrate dehydrogenase was elevated in 8 of the 12 patients and there was no direct correlation between elevated serum isocitrate dehydrogenase level and other clinical parameters.

Adolescent

A measles outbreak at university medical settings involving health care providers.

In 1985, a measles outbreak involved 14 students and non-student contacts in Michigan. Eight transmissions occurred at university medical facilities; five of these were likely airborne transmissions. Medical students and a medical resident were involved in the outbreak's propagation. Health care providers need to be immune to measles. Measles should be suspected in young adults with compatible illnesses; persons suspected to have measles should be placed in stringent respiratory isolation to preclude airborne transmission.

Academic Medical Centers

Intranasal interferon-alpha 2b for seasonal prophylaxis of respiratory infection.

Efficacy of intranasal recombinant alpha interferon (IFN-alpha 2b) was evaluated over a four-week period. The first 400 participants received either 1,500,000 IU of IFN-alpha 2b or placebo twice daily. Rhinovirus infections were prevented (protective efficacy, 76%). Parainfluenza infections were not prevented, but symptoms in associated episodes of disease were significantly reduced. The medication was generally well tolerated, but side effects were often observed. The most commonly reported symptom was blood-tinged mucus. A pilot study of IFN-alpha 2b or placebo administered on a once-daily dose schedule was also carried out in 150 participants. There was a suggestion of continued efficacy with reduced side effects. Overall, these findings would limit the use of IFN-alpha 2b on the twice-daily schedule to shorter time periods or to special situations in which the efficacy clearly outweighs side effects, and they encourage further examination of other dosage schedules.

Administration, Intranasal

Natural killer cells inhibit outgrowth of autologous Epstein-Barr virus-infected B lymphocytes.

To determine whether natural killer (NK) cells are the cells responsible for inhibition of outgrowth of Epstein-Barr virus (EBV)-infected autologous B lymphocytes, NK-enriched or NK-depleted populations were prepared by Percoll density gradient fractionation and complement lysis depletion of cells reacting with NK-specific monoclonal antibody HNK-1. These cells were then examined in parallel for NK activity and inhibition of outgrowth. NK-enriched low density cells inhibited outgrowth whereas NK-depleted high density cells did not. Low density cells treated with monoclonal antibodies HNK-1 and DR plus complement had little NK activity and failed to inhibit EBV-induced outgrowth, whereas these same cells treated with monoclonal antibodies OKT3 and DR plus complement had strong NK activity and caused marked inhibition of outgrowth. These findings indicate that NK cells rather than mature T cells, monocytes, or B cells, are responsible for inhibition of EBV-induced B cell outgrowth.

Adult

Free fatty acids in an animal model of Reye's syndrome.

Recent studies have indicated that viral infections, aspirin treatment and hyperammonemia are associated with Reye's syndrome. It has also been reported that free fatty acids in serum and total lipids in the liver of Reye's syndrome patients are elevated during illness. The role of the lipid changes in the development of the disorder cannot be optimally studied in human patients, because infection and aspirin ingestion occur prior to the earliest symptoms of Reye's syndrome. Effects of influenza B infection, aspirin treatment and hyperammonemia on the level of free fatty acids, total lipids and triacylglycerols in serum and liver of an animal model of Reye's syndrome are reported here. Hyperammonemia was produced in young, male ferrets either by feeding them small amounts of an arginine-deficient diet after overnight fasting or by an intraperitoneal injection of jackbean urease. The ferret model resembled Reye's syndrome in developing increased levels of individual and total serum free fatty acids, liver triacylglycerol and total lipids. The results also indicate that influenza infection or aspirin treatment, or both, while increasing the severity of encephalopathy in the deficient ferrets, did not cause a significant change in the level of serum free fatty acids. Other results suggest that elevation of serum ammonia, serum free fatty acid or liver lipids, either singly or in various combinations, does not provide conditions that can explain the rapidly developing encephalopathy in the arginine-deficient ferrets.

Ammonia

Pharmacokinetics of vidarabine in the treatment of infants and children with infections due to herpesviruses.

The pharmacokinetics of vidarabine were studied on 22 occasions in nine infants and three older children with herpesvirus infection. The drug was administered for 10 days in doses of 15-30 mg/kg per day. Vidarabine was not detected in the serum of any patient, although small quantities were detected in the urine of two of the older children. Peak serum concentrations of arabinosyl hypoxanthine, the major metabolite of vidarabine, ranged from 2.3 to 11.4 micrograms/ml. Concentrations of this metabolite were higher in two preterm infants than in full-term infants receiving comparable doses. The mean elimination half-life estimated from cumulative urinary excretion was 2.4 hr in a preterm infant, 3.1 hr in full-term infants, and 2.8 hr in older children. Neither clearance nor half-life changed when multiple doses were administered. Vidarabine and arabinosyl hypoxanthine did not accumulate during therapy. The rates of recovery of drug from the urine and of renal clearance of arabinosyl hypoxanthine were directly related to the age and maturity of the patient. Arabinosyl hypoxanthine readily diffused into cerebrospinal fluid.

Arabinonucleosides

Arginine requirement and ammonia toxicity in ferrets.

Hyperammonemia of varying magnitude was produced in young, male ferrets by either feeding them a purified diet containing low amounts of arginine or by intraperitoneal injections of jackbean urease. The responses were different depending on the method used to produce hyperammonemia. When hyperammonemia was produced by feeding a synthetic diet containing less than 0.2% arginine, ferrets developed encephalopathy soon after eating the diet and recovered after 4 hours. Although intraperitoneal injection of jackbean urease (100 IU/kg) caused severe hyperammonemia, ferrets did not become sick. Ferrets injected with 450 IU/kg of jackbean urease developed hyperammonemia but developed encephalopathy only after 15 hours. Ferrets showed remarkable capacity to tolerate elevated blood ammonia levels.

Ammonia

Epstein-Barr virus antibody in childhood Hodgkin's disease.

Fifteen patients with childhood onset of Hodgkin's disease were studied for prevalence and quantity of Epstein-Barr virus (EBV) antibody to learn about the relationship between infection with EBV and Hodgkin's disease. Findings indicated that, compared with normal child control subjects, prevalence of EBV antibody is not increased in Hodgkin's disease, but the quantity of antibody increases as the duration of Hodgkin's disease increases. It seems that EBV plays no role in the cause of Hodgkin's disease and that production of greater amounts of antibody relates to immunoregulatory defects associated with Hodgkin's disease.

Adolescent

Human newborns are deficient in natural killer activity.

The peripheral blood natural killer (NK) activity of newborns was found to be significantly less than that of adults. In mixing experiments newborn cells inhibited adult NK activity in only one of nine instances. Interferon treatment in vitro increased newborn NK activity to an even greater degree than adult NK activity. These findings imply that diminished newborn NK activity is due not to inhibitory cells or lack of pre-NK cells but rather to deficient in vivo activation of pre-NK cells. This deficiency may be a major factor in the increased susceptibility of newborns to certain virus infections.

Adult

Infections in leukemic children: a prospective analysis.

A 28-month prospective study of 54 leukemic children was carried out to determine the incidence and type of infection associated with febrile episodes. Fever was caused by infections in 84 of 199 episodes (71%). Two-thirds of the febrile episodes and 57% of the documented infections occurred when leukemic activity was demonstrable. However, only nine of 29 febrile episodes which occurred at the time of initial diagnosis of acute leukemia were due to infection. All serious bacterial infections occurred in children with absolute granulocyte counts less than 500/mm3. Septicemia was responsible for seven of the 17 deaths which occurred during the period of observation. The five children with Pseudomonas infections were colonized 10 to 30 days before they developed their infection. The majority of viral infections occurred in patients in remission, and were principally caused by cytomegalovirus, varicella-zoster virus, or Epstein-Barr virus. With the exception of one patient who died with a complex infection (CMV and Pneumocystis carinii), the children in this study responded well to viral infections.

Acute Disease

Inhibition of the in vitro outgrowth of Epstein-Barr virus-infected lymphocytes by TG lymphocytes.

Human T lymphocytes subpopulations from subjects not acutely infected with EBV have been selected and examined for ability to inhibit the outgrowth of autologous B lymphocytes that have undergone in vitro infection with EB virus. The results show that only TG lymphocytes are inhibitory. TG lymphocytes from subjects who are EBV antibody-negative inhibit as well as those from subjects who have EBV antibody. TG lymphocyte populations, as well as other T cell fractions obtained from neonatal subjects, fail to inhibit the outgrowth of infected, autologous lymphocytes under the conditions tested. We propose that NK cells are responsible for the inhibitory effects described in this report.

Adolescent

Epidemic measles in a highly vaccinated population.

During November, 1975, to May, 1976, measles occurred at a rate of 20.3 cases per 1000 in a purported immunized population, of whom historical and serologic survey revealed that 9 per cent had no history of either measles illness or vaccination and 18 per cent did not have detectable measles antibody. Antibody was detectable in 92 per cent of those vaccinated at greater than or equal to 13 months, 80 per cent at 12 months and 67 per cent of those vaccinated when less than one year old (P less than 0.001), but no significant differences existed with increasing years since vaccination (P greater than 0.1). A second vaccination increased detectable antibody prevalence only in those originally vaccinated when less than nine months old (42 to 80 per cent, P less than 0.02). During a measles outbreak, more cases occurred in those receiving vaccine when less than 12 months old than in those vaccinated at greater than or equal to 12 months (37 per cent vs. 9 per cent, P less than 0.001). A second vaccination protected those originally vaccinated at less than 12 months (35 per cent ill without a second vaccination vs. 2 per cent with, P less than 0.001). Thus, a single measles vaccination of children less than 12 months old does not protect; a second vaccination will protect this group.

Age Factors

EB virus: malignant lymphoma in cottontop marmosets following inoculation and recovery of the virus from cells of an experimental tumor maintained in organ culture.

The oncogenic potential of Epstein-Barr virus (EBV) was investigated in cottontop marmosets. Neoplasia resembling human malignant lymphomas, reticulum cell sarcoma type, occurred following inoculation of materials containing EBV. One of 4 monkeys that received autologous cells transformed in vitro by EBV developed lymphoma in mesenteric lymph nodes seven and one-half months after inoculation. Three of 4 marmosets inoculated with cell-free EBV developed lymphoma. The latent period for given with EBV accelerated the course of disease. Nevertheless malignant lymphoma occurred in an animal given only cell-free virus. Six of 8 marmosets inoculated with EBV demonstrated antibodies to the virus. Four marmosets not exposed to the virus, of which 2 received immunosuppressive drugs, have not developed tumors, nor EBV antibodies. EBV antigen detectable by immunofluorescences has been found in 2% of cells shed from one tumor maintained in organ culture. These results imply that EBV is capable of inducing malignant lymphoma in at least one primate species. Additional experimental evidence is required, however, before its oncogenic capacity in this host can be accepted without reservation.

Animals