Successful treatment of medically refractory ventricular fibrillation with emergency cardiopulmonary bypass in an adolescent with corrected complex congenital heart disease.
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Biomedical subjects
Publications and source records attributed to B Davis.
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In this report the role played by human immunodeficiency virus type-1 (HIV-1) in the pathogenesis of HIV-1-related thrombocytopenia was investigated. CD34+ hematopoietic stem/progenitor cells were purified from the bone marrow (BM) of HIV-1(+) thrombocytopenic patients, HIV-1(+) nonthrombocytopenic individuals, HIV-1(-) patients with immune thrombocytopenic purpura, and HIV-1(-) normal donors. CD34+ cells from HIV-1(+) thrombocytopenic individuals alone showed a reduced capacity to give rise to megakaryocytic colonies (CFU-Meg) and also a progressive and significant decline in cell number when placed in liquid culture containing recombinant human interleukin-3 (rIL-3). This decline involved not only megakaryocyte but also erythroid and granulocyte/macrophage progenitors. The defects in megakaryocyte colony formation and CD34+ cell growth did not result from a productive HIV-1 infection of CD34+ cells. Moreover, HIV-1 DNA was absent from CD34+ cells in 10 of 12 thrombocytopenic patients examined. On the other hand, the decreased survival/proliferation of CD34+ cells in liquid culture, within the HIV-1(+) thrombocytopenic patients, was correlated with the presence of HIV-1 p24 antigen in BM plasma. These results demonstrate an impairment of CD34+ cells in HIV-1(+) individuals presenting thrombocytopenia as the only hematologic manifestation. Furthermore, these findings suggest that increased viral replication in the BM microenvironment may cause this impairment and possibly contributes to HIV-induced thrombocytopenia.
OBJECTIVE: Plasma renin activity was measured at baseline and 6 months in a trial of nonpharmacologic therapy of mild hypertension to determine whether plasma renin activity predicts the diastolic blood pressure (DBP) response to nonpharmacologic therapy. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial of volunteers from the general community with mild hypertension (DBP between 90 and 100 mm Hg), off all antihypertensive therapy at baseline, treated in special research clinics (n = 593). INTERVENTIONS: Subjects were randomly assigned to usual, weight loss, or low sodium/high potassium diet and then randomly assigned to receive placebo, chlorthalidone, or atenolol. MAIN OUTCOME MEASURES: Renin was analyzed as plasma renin activity and as a renin index (logarithm of 24-hour urinary sodium excretion times logarithm of plasma renin activity) (593 patients at baseline and 6 months) to correct for varied sodium intakes. The DBP was measured using the random zero device. RESULTS: Change in DBP at 6 months could be predicted from baseline plasma renin activity or renin index. The DBP was decreased after 6 months of therapy by 2 mm Hg for each unit increase in baseline plasma renin activity and by 0.16 mm Hg for each unit increase in baseline renin index. Patients in the highest renin index quartile had a greater DBP response to atenolol therapy, and patients in the lowest renin index quartile had a greater DBP response to chlorthalidone therapy. Weight loss diet achieved a greater reduction in DBP in patients with higher baseline renin index and had an additive effect on DBP response in both of the drug groups. Patients on a weight loss diet receiving placebo in the highest baseline renin index quartile had a reduction in DBP of 12.4 mm Hg, compared with 4.4 mm Hg in the lowest baseline renin index quartile (P = .009). A low sodium/high potassium diet had a lesser effect than a weight loss diet on pharmacologic therapy. As with the weight loss diet, patients on a low sodium/high potassium diet in the highest baseline renin index quartile had a greater reduction in DBP than patients in the lowest baseline renin index quartile. CONCLUSIONS: These data suggest a significant relationship between baseline levels of plasma renin index and the likelihood of success of nonpharmacologic treatment of hypertension.
The authors report on the incidence of myopia in a large group of premature infants with birth weights of less than 1251 g followed as part of the multicenter study of Cryotherapy for Retinopathy of Prematurity. None of the eyes reported here underwent cryotherapy. Eyes were refracted using cycloplegic retinoscopy at 3 months (n = 2916), 12 months (n = 2626), and 24 months (n = 961 at 5 of the 23 centers) after term. Myopia was observed in approximately 20% of the children at each test age. The percentage of high myopia (greater than or equal to 5 diopters) doubled from 2% to 4.6% between 3 and 12 months and remained stable thereafter. Lower birth weight and increasing severity of retinopathy of prematurity (ROP) were strong predictors of myopia and high myopia. In addition, anisometropia, astigmatism, and the presence of posterior pole residua from ROP also were associated with a higher incidence of myopia and high myopia.
The Trial of Antihypertensives Interventions and Management (TAIM) was a multicenter double-blind placebo-controlled clinical trial of drug and diet combinations for the treatment of mild hypertension among 878 participants, ages 21 to 65, 110% to 160% ideal weight, and with baseline diastolic blood pressure 90 to 100 mm Hg. The drugs used were placebo, chlorthalidone (25 mg/daily) or atenolol (50 mg/daily). The diets studied were usual, weight loss, sodium reduction/potassium increase. Trial end points were 6-month diastolic blood pressure change, cardiovascular risk change, and quality of life change. Either drug combined with weight loss produced the greatest blood pressure reduction of 15 mm Hg, compared to 8 mm Hg on placebo/usual diet. Adding sodium restriction to either drug did not enhance blood pressure lowering effect. Drugs outperformed diet in terms of antihypertensive effect. However, those on placebo and assigned to weight reduction who lost more than 4.5 kg and those on sodium restriction who reduced sodium to less than 70 mEq daily lowered blood pressure to a similar extent as those on either of the two drugs alone. Cardiovascular risk at 6 months relative to baseline ranged from 0.85 in weight loss/atenolol subgroup to 1.04 in the usual diet/chlorthalidone subgroup. Blacks were more responsive to chlorthalidone plus weight loss and whites to atenolol plus weight loss. Quality of life, as measured by scales of distress and well-being, was favorably affected by weight reduction. Although there were few side effects of the drugs and most patients improved on most parameters, sexual complaints were worsened among those on chlorthalidone and usual diet compared to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
Muslims abstain from food and drink from dawn to sunset during Ramadam, the ninth month of the Islamic calendar. The purpose of this study was to examine the changes that occurred in body composition and both resting and exercise metabolism during a 4 week Ramadan fast. Subjects consumed an average of 1220 kcal each day during Ramadan and lost a significant 1.92 kg body weight. The subjects also lost 2.8% fat. Fat-free mass did not change. Serum sodium, chloride, and protein increased during the first week of Ramadan and returned to the pre-fasting levels during the last week. This indicates a state of dehydratation existed during the first week of Ramadan. Consistent with this is first week 1.13 kg body weight loss with no change in percent fat. First week Ramadan tests showed a significant decrease in VO2max with a return to the pre-test levels in the last week. The lower resting afternoon VO2 suggests that during Ramadan the body's metabolism slows down during the day in order to conserve its energy stores, however, exercise economy as measured by submaximal VO2 in mk/kg/min is not affected.
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The interleukin-4 receptor (IL-4R) is expressed as a 140-Kd membrane glycoprotein that binds IL-4 with high affinity. Recently, cDNA clones for the murine IL-4R have been isolated. One clone encodes an integral membrane protein, while another encodes a protein in which translation is terminated before the transmembrane region, thus producing a soluble form of the IL-4R (sIL-4R). HeLa cell clones overexpressing sIL-4R were isolated using a novel filter-overlay and 125I-IL-4 ligand binding technique. Quantitative analysis demonstrated that the kinetics and affinity of IL-4 binding to the recombinant sIL-4R were similar to the native membrane-bound IL-4R. As low doses of sIL-4R specifically inhibited IL-4-induced proliferative responses in vitro, sIL-4R biodistribution and elimination parameters were evaluated to assess the pharmacokinetic potential of sIL-4R as a therapeutic agent. Pharmacokinetic studies demonstrated that radiolabeled sIL-4R had a distribution half-life of 9 minutes and an elimination half-life of 2.3 hours following intravenous (IV) administration. When administered by intraperitoneal or subcutaneous (SC) injection, the elimination half-lives were prolonged to 4.2 hours and 6.2 hours, respectively. Although the initial blood level of sIL-4R was reduced if administered by SC injection, the bioavailability was comparable with IV administration. The main sites of sIL-4R elimination were the liver and kidney.
To determine whether a general-purpose epidemiologic questionnaire can be used in childhood cancer hospitals to identify associations between environmental factors and the major types of childhood cancer, we report the results of the analysis of the data obtained from such a questionnaire. On admission to St. Jude Children's Research Hospital in Memphis, Tennessee, between 1979 and 1986 a questionnaire was administered to 1,270 mothers of patients diagnosed with childhood cancer. Approximately one-half of the children had acute leukemias (n = 629); the remainder had lymphomas (n = 237) or solid tumors (n = 404). Responses to questions regarding the patients' and parents' environmental and medical histories were compared across nine diagnostic categories. Only 5 of 232 variables remained nominally statistically significant (P less than 0.05) after adjusting for confounding by patient or maternal age, year of birth or diagnosis, patient's race, and social class. The variables identified were length of time the patient was breast-fed (chi 2 = 16.1, P = 0.04); having a garden with fertilizers, herbicides, and pesticides (chi 2 = 17.2, P = 0.03); maternal use of sex hormones during the year before the patient's birth (chi 2 = 18.2, P = 0.02); maternal cigarette consumption (chi 2 = 18.0, P = 0.02); and patient contact with persons with cancer (chi 2 = 20.7, P = 0.01). Despite the large number of patients studied, we identified fewer significant variables than would be expected, on the average, under the null hypothesis. We conclude that the data obtained from a general-purpose epidemiologic questionnaire do not provide a useful overview of the association between exposure to environmental factors and several types of childhood cancer.
The mainstay of therapy for pyoderma gangrenosum has been corticosteroids, but many patients respond poorly. During the past 2 years we have treated seven patients who had pyoderma gangrenosum with cyclosporine after their condition proved resistant to conventional therapy. No evidence of permanent toxicity from cyclosporine was detected and treatment with other immunosuppressive agents was discontinued in five of seven cases. Tuberculosis was reactivated in one patient. Three patients had a remission, three had an intermediate response, and one did not respond. These results indicate that cyclosporine is useful in the treatment of patients with refractory pyoderma gangrenosum and suggest an immune mechanism in the pathogenesis of this disorder.
Nasal and retrobulbar infection caused by the Oomycete Pythium insidiosum is described in a cat. The diagnosis was established on three criteria. The staining of broad, sparsely septate hyphal elements in biopsy tissue using a fluorescein-labelled antiglobulin specific for P. insidiosum, detection of antibodies to P. insidiosum by an immunodiffusion test, and isolation of the aetiological agent in pure culture from the biopsy tissue. Treatment with ketoconazole for 6 weeks resulted in clinical improvement, but proptosis of the left eye slowly appeared after the discontinuation of treatment. This case represents a new host for P. insidiosum, namely, a domestic, shorthaired cat, from North Carolina, U.S.A.
Stimulation of pulmonary C-fibers (PCs) by capsaicin and of rapidly adapting receptors (RARs) by reduced lung compliance reflexly increases airway submucosal gland secretion in dogs. Because both PCs and RARs are stimulated by cigarette smoke (nicotine being the primary stimulus), we performed experiments in anesthetized open-chest artificially ventilated dogs (with aortic nerves cut) to determine whether cigarette smoke reflexly stimulates airway secretion. We measured submucosal gland secretion by counting the hillocks in a 1.2-cm2 field of tracheal epithelium coated with tantalum dust. Secretion was stimulated by delivery of 40-320 ml smoke from high-nicotine cigarettes to the lower trachea, secretion rate increasing from 7.4 +/- 1.3 to 48.1 +/- 5.1 hillocks.cm-2.min-1. Results of cutting the pulmonary vagal branches or carotid sinus nerves or both indicated that the secretory response was initiated by stimulation of lower respiratory vagal afferents and augmented several seconds later by stimulation of carotid chemoreceptors. Results of cooling the cervical vagus nerves to 7 and 0 degrees C indicated that most of the vagally mediated increase in secretion was due to stimulation of afferent lung C-fibers.
To investigate how central and peripheral nerves affect lysozyme secretion from tracheal submucosal glands in ferrets we injected substance P (20 nmol/kg in 200 microliters) intracisternally or intravenously into anesthetized artificially ventilated ferrets. We collected 3-ml samples from a perfused (3 ml/5 min) segment of trachea in situ during 15 min before and 45 min after injection of substance P. Content of lysozyme, a specific marker of tracheal submucosal gland serous cell secretion in ferrets, was measured spectrophotometrically in each sample. Intracisternal substance P increased peak lysozyme output threefold compared with baseline. This increase was abolished completely by cutting both superior laryngeal nerves (SLN) and was partially inhibited by atropine, phentolamine, or propranolol. Intravenous substance P increased peak lysozyme output 10-fold compared with baseline. This increase was partly abolished by cutting both SLN. We concluded that intracisternal substance P stimulated the central nervous system (CNS) and activated cholinergic, adrenergic, and nonadrenergic noncholinergic secretomotor nerves to tracheal glands and that intravenous substance P increased lysozyme secretion both by acting directly on tracheal glands and indirectly on the CNS to activate secretomotor nerves.
The SHEP is a randomized, placebo-controlled trial that will follow standard clinical trial principles in analyzing data relating to its proposed hypotheses. The protocol has stated a priori the main objective as well as the secondary subgroup hypotheses. Sample size calculations for SHEP have accounted for dropins to and drop-outs from active therapy as well as for the risk of nonstroke death. The sample size achieved (4,736 participants) should be adequate to address the proposed questions. Monitoring procedures have been described and established. A data and safety monitoring board that uses these procedures is closely following the data from the trial. The board will periodically examine the data to determine whether termination of the study is warranted.
An animal model was used to evaluate the influence of residual lens cortex on postoperative inflammation and cellular deposits on intraocular lenses (IOLs). Eighteen New Zealand white rabbits underwent bilateral endocapsular phacoemulsification with placement of a one-piece polymethylmethacrylate (PMMA) IOL in the capsular bag. A predetermined amount (15 mg, 30 mg or 60 mg) of homogenized lens cortex was injected into the anterior chamber of one of the eyes of each rabbit after bilateral IOL implantation. The contralateral eye served as the control. The animals underwent slit-lamp examination postoperatively, and the anterior segment of each eye was examined by gross and light microscopy. On slit-lamp examination, the eyes which had received a 60-mg injection of cortex showed a significantly higher amount of posterior synechiae than their contralateral, control eyes. After 2 weeks of observation, the rabbits were sacrificed, the eyes were enucleated, and the IOLs were removed and examined by light microscopy and scanning electron microscopy (SEM). The number of cellular deposits on the IOLs removed from the eyes receiving a 30-mg injection of cortex was significantly larger than that found in their contralateral, control eyes (P less than 0.05), but the eyes in the 60-mg and 15-mg injection groups showed no significant difference between control eyes and IOL eyes in the number of cellular deposits on explanted IOLs. Observation by SEM determined that the filopodia on the epithelioid cells found on the IOLs removed from the eyes in the 60-mg injection group showed an increased number and length compared to their controls. The epithelioid cells on the IOLs of the 30-mg injection group showed an increased number of filopodia compared to their controls.
This chapter discusses international aspects of diseases resulting from exposure to chemical pollutants in the environment, with an emphasis on developing countries. These countries share many of the same problems of air, water, and pesticide pollution that face the more industrialized countries. In developing countries, however, the problems are compounded by a number of unique situations, viz., economic priorities, high burden of infectious diseases, impoverishment, and absence of a regulatory framework for the disposal of toxic chemicals. This discussion emphasizes the importance of interactions among toxicants, malnutrition, and infectious diseases for both urban and rural populations insofar as these interactions contribute to disease. Toxicants not only produce disease directly but also exacerbate diseases with other causes. Specific examples from developing countries demonstrate how human health effects from exposures to environmental chemicals can be assessed. While they do not strictly fall under the rubric of "developing countries," the public health consequences of inadequate control of environmental pollution in the East European countries should demonstrate the magnitude of the problem, except that in developing countries the public health consequence of environmental chemicals will be aggravated by the widespread malnutrition and high prevalence of infectious diseases. Much needs to be done before we can adequately quantify the contribution of environmental chemicals to morbidity and mortality in developing countries with the level of sophistication now evident in the charting of infectious diseases in these countries.