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Biomedical subjects

D Bernstein

Publications and source records attributed to D Bernstein.

At least 109 records · Page 6Linked to original sources

Heart, heart-lung, and lung transplantation in the first year of life.

Seventeen infants less than 1 year of age have undergone heart (12), heart-lung (3), and lung (2) transplantation for end-stage cardiopulmonary disease. The infants undergoing heart transplantation had a mean age of 4.5 months (range, 19 days to 12 months) with the diagnosis of cardiomyopathy in 4 and congenital heart disease in 8. Four of the 8 patients (50%) had hypoplastic left heart syndrome. Actuarial survival at 1 and 2 years was 74% and compared favorably with the survival of older children at 1 and 2 years of 82% and 69%. The linearized rejection rate was less in infants as compared with children more than 1 year of age (0.61 versus 1.48 episodes per 100 patient days). In intermediate follow-up, no graft atherosclerosis has been noted. Immunosuppression has included a three-drug protocol of cyclosporine, azathioprine, and prednisone. A steroid taper to alternate day steroids or off completely by 6 months has been the goal and has been accomplished in 6 of 12 infants. Heart-lung and lung transplantation has been performed in 5 infants. One infant in each group died: 1 infant secondary to airway complications and sepsis and another due to pulmonary sepsis. A pulmonary lobe from a larger and older donor was transplanted into a 4-week-old infant as a single-lung transplant with good outcome. The 3 surviving infants are well 24, 18, and 2 months after transplantation. Obliterative bronchiolitis has not been clinically apparent in this group. These data support the clinical efficacy of heart, heart-lung, and lung transplantation in the first year of life.

Actuarial Analysis↗

Noradrenergic responses to clonidine in acute and remitted depressed male patients.

To investigate noradrenergic function in depression, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma norepinephrine (NE), mean arterial pressure (MAP), and heart rate responses to intravenous clonidine (2 micrograms/kg), an alpha 2-adrenergic agonist, were measured in 27 acutely depressed patients, 18 remitted depressed patients, and 27 normal control subjects; a placebo infusion was administered to a subgroup. Clonidine compared with placebo, over a 150-minute time course, decreased plasma NE, MAP, and heart rate, but not plasma MHPG, in the control subjects. Plasma MHPG, plasma NE, MAP, and heart rate at baseline or in response to clonidine and placebo over 150 minutes did not indicate any group differences. The only significant plasma MHPG response to clonidine in the normal control subjects occurred 60 minutes after the infusion. A significantly diminished plasma MHPG response to clonidine at 60 minutes was found in the acutely depressed group compared with the normal control subjects. These results suggest that peripheral inhibitory noradrenergic responses to clonidine are normal in depressed patients, while plasma MHPG responses to clonidine, which have a limited central contribution, appear to be a weak reflection of central noradrenergic function and appear insufficiently robust for a meaningful evaluation of hypothetical group differences in central inhibitory alpha 2-adrenergic activity in this population.

Acute Disease↗

Prevalence of dust mites in the homes of people with asthma living in eight different geographic areas of the United States.

The density and species prevalence of dust mites were determined at various times over a 5-year-period in 252 homes of dust mite sensitive people with asthma who lived in eight geographic areas of the United States (Cincinnati, Ohio; New Orleans, La.; Memphis, Tenn.; Galveston, Texas; Greenville, N.C.; Delray Beach, Fla.; San Diego and Los Angeles, Calif.). The most common dust mites found in the homes were Dermatophagoides farinae (DF), D. pteronyssinus (DP), Euroglyphus maynei (EM), and Blomia tropicalis. All homes in all locations contained Dermatophagoides spp. mites, but few homes were populated exclusively by either DF or DP alone. Most homes (81.7%) were coinhabitated by both DF and DP. In coinhabited homes one species was predominant and usually made up at least 75% of the total mite population. Prevalence of the dominant or only species present varied between homes within a geographic area. EM occurred in significant numbers in 35.7% of homes in New Orleans, Memphis, Galveston, Delray Beach, and San Diego. Blomia tropicalis occurred in these same cities but in low densities. For all dust samples, only 13 homes of the 252 sampled had 100 or fewer mites/gm dust, which is considered to be the threshold for sensitivity. Most homes had average mite densities of 500 or more mites/gm dust. The results of the present study suggest a significant and widespread occurrence of both DF and DP. Therefore extracts of both mite species should be considered for diagnostic tests and immunotherapy. Significant levels of EM were present in some areas. Thus sensitivity to EM should be considered in these areas.

Adolescent↗

Kiddie-Infant Descriptive Instrument for Emotional States (KIDIES): use in children with developmental disorders.

The Kiddie-Infant Descriptive Instrument for Emotional States (KIDIES) was used to overcome the limitations of microanalytic facial observations and subjective assessments in the diagnosis of childhood developmental disorders. The KIDIES quantifies eight behavioral and eight affective dimensions by evaluating facial, vocal, gestural, and postural displays. In a sample of 42 subjects, KIDIES ratings distinguished between children with pervasive developmental disorder and a comparison group with mixed developmental diagnoses, and demonstrated sensitivity to emotional changes as a result of environmental shift. The results suggest that the KIDIES has potential as a reliable instrument for evaluating emotional and behavioral patterns in young developmentally disordered children.

Affective Symptoms↗

Cardiac growth after pediatric heart transplantation.

BACKGROUND: To assess whether normal cardiac growth occurs after heart transplantation in the pediatric age group, we performed a study of 13 infants and children who underwent orthotopic heart transplantation at Stanford. METHODS AND RESULTS: The echocardiographic data from a population of 93 normal children were analyzed to determine estimates of the fifth, 25th, 50th, 75th, and 95th percentiles of the normal pediatric population. Growth curves for each of the cardiac dimensions were stratified into six classes representing each of the percentile bands, and dimensions for the 13 patients were tracked between early postoperative (early) and point of maximal follow-up (late). Results were compared by Student's paired t test to determine whether normal growth was occurring. The mean age at transplant was 5.0 +/- 1.3 years (mean +/- SEM) (range, 0.4-12.8 years), duration of follow-up was 3.1 +/- 0.4 years (1.3-5.8 years), and change in body surface area was 0.24 +/- 0.03 m2 (0.12-0.50 m2). Both right ventricular (RV) and left ventricular (LV) chamber dimensions were within the normal range at both early and late time points and grew normally as assessed by a lack of class changes. Early wall thickness measurements were above the 95th percentile in seven of 13 patients (LV), 12 of 13 patients (septum), and four of 13 patients (RV). Wall thickness measurements remained above normal, and there were no significant class changes at late follow-up. Histological examination in five patients showed markedly increased septal myocyte width, indicating myocyte hypertrophy. Atrial and great vessel anastomotic sites showed no evidence of obstruction by Doppler and catheterization studies. CONCLUSIONS: These data demonstrate that normal cardiac chamber dimensional growth occurs at greater than 3 years' follow-up after pediatric heart transplantation. Significant LV and septal (and to a lesser extent RV) hypertrophy persists and may have implications for long-term allograft growth and function.

Body Surface Area↗

Transcriptional regulation of left ventricular beta-adrenergic receptors during chronic hypoxia.

beta-Adrenergic receptor downregulation is the end result of cellular adaptation to prolonged agonist exposure. The factors mediating receptor downregulation include receptor phosphorylation, receptor movement from the plasma membrane to intracellular sites, and alterations in nascent receptor synthesis. We have previously demonstrated a downregulation of the left ventricular beta-receptor during chronic hypoxia in vivo. To determine the mechanism of this downregulation, we produced chronic hypoxia in seven newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 weeks. Six lambs served as normoxic controls. Sarcolemmal membrane and cytosolic fractions were prepared from left ventricular free wall samples. beta-Receptor density in each fraction was determined with the radioligand [125I]iodocyanopindolol. Steady-state levels of beta-receptor mRNA were determined by Northern blot analysis using a beta 1-adrenergic receptor cDNA probe. During chronic hypoxia, left ventricular membrane beta-adrenergic receptor density decreased by 55% (153 +/- 28 fmol/mg for hypoxic lambs versus 342 +/- 79 fmol/mg for control lambs, p < 0.05). There was no corresponding increase in beta-receptor density in the cytosolic fraction (23 +/- 3 fmol/mg for hypoxic lambs versus 33 +/- 9 fmol/mg for control lambs, p = NS), nor was there a significant change in the ratio of beta 1-receptor/beta 2-receptor subtypes as assessed by radioligand binding (beta 1 subtype, 84.1 +/- 10.1% for hypoxic lambs versus 93.2 +/- 8.8% for control lambs; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Decreased serum insulin-like growth factor-I associated with growth failure in newborn lambs with experimental cyanotic heart disease.

To determine whether chronic hypoxemia results in alterations in endocrine function that may contribute to growth failure, we measured growth hormone (GH), somatomedins (insulin-like growth factors I and II, IGF-I and IGF-2), hepatic growth hormone receptors, and circulating IGF-binding proteins IGFBP-3 and IGFBP-2 in 12 newborn lambs with surgically created pulmonic stenosis and atrial septal defect, and in 10 controls. During chronic hypoxemia (oxygen saturation of 60-74% for 2 wk), weight gain was 60% of control (hypoxemic, 135 +/- 20 vs. control, 216 +/- 26 g/d, P less than 0.02). IGF-I was decreased by 43% (hypoxemic 253.6 +/- 29.3 SE vs. control 448.0 +/- 75.5 ng/ml, P = 0.01), whereas GH was unchanged (19.9 +/- 5.1 vs. 11.9 +/- 3.0 ng/ml, NS). The increase in IGF-1 was associated with a decrease in IGFBP-3 (hypoxemic, 5.09 +/- 1.25 vs. control, 11.2 +/- 1.08 arbitrary absorbency units per mm (Au.mm), P less than 0.01), and increase in IGFBP-2 (0.47 +/- 0.03 vs. 0.19 +/- 0.13 Au.mm, P less than 0.05), but no significant downregulation of hepatic GH receptors (hypoxemic, 106.1 +/- 20.1 vs. control, 147.3 +/- 25.9 fmol/mg, NS). Thus, chronic hypoxemia in the newborn is associated with a decrease in IGF-I and IGFBP-3 in the face of normal GH. This suggests peripheral GH unresponsiveness, similar to protein-calorie malnutrition or GH receptor deficiency dwarfism, but mediated at a level distal to the hepatic GH receptor.

Animals↗

Neuropsychological and neurological manifestations of HIV-1 dementia in drug users.

The cognitive and motor deficits associated with human immunodeficiency virus-1 (HIV-1) infection have been studied using neurological examination and neuropsychological tests. However, drug users with HIV-1 infection generally have been excluded from such studies. Forty-four well-characterized drug users stratified by Centers for Disease Control staging were administered a standardized neurological examination and a battery of neuropsychological tests under single-blind conditions designed to minimize the acute effects of psychoactive substances. The results of the blind neurological examination were consistent with the previously ascertained clinical staging of HIV-1 infection. The pattern of neuropsychological deficits across HIV-1 states was similar to those found in cohorts of homosexual men.

AIDS Dementia Complex↗

Alterations in postnatal intestinal function during chronic hypoxemia.

Growth failure is a major complication of chronic hypoxemia, as seen in infants and children with cyanotic congenital heart disease. To determine whether chronic hypoxemia during infancy affects the gastrointestinal tract, we examined small intestinal growth and digestive enzyme activities in chronically hypoxemic newborn lambs and in age-matched controls. Chronic hypoxemia was produced by placing an inflatable occluder around the main pulmonary artery and performing a balloon atrial septostomy. Aortic oxygen saturation was reduced to 60-74% for 2 wk, after which the small intestine was removed for analysis. During chronic hypoxemia, somatic growth rate was decreased to 60% of control (hypoxemic, 135 +/- 20 versus control, 216 +/- 26 g/d, p less than 0.02). No differences in caloric intake were found (hypoxemic, 129 +/- 4 versus control, 128 +/- 4 kcal/kg/d). Chronic hypoxemia did not alter small intestinal growth, as measured by jejuno-ileal weight, jejuno-ileal length, mucosal weight, or mucosal protein or DNA contents. However, sp act of lactase, the principal disaccharidase of the infant lamb intestine, were significantly decreased (hypoxemic, 0.08 +/- 0.01 versus control, 0.146 +/- 0.03 units of enzyme activity/mg DNA, p less than 0.05), as were the total small intestinal contents of lactase (hypoxemic, 61.7 +/- 7.0 versus control, 120.6 +/- 21.7 units of enzyme activity, p less than 0.01). There also were decreases in specific and total activities of other digestive enzymes such as maltase, amino-oligopeptidase, and alkaline phosphatase in hypoxemic intestine that did not achieve statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Current approach to hypoplastic left heart syndrome. Palliation, transplantation, or both?

Over the past 3 years, 35 newborn infants have been referred for surgical management of hypoplastic left heart syndrome. Surgical palliation (first-stage Norwood) or cardiac transplantation was offered. Twenty-four families (68%) chose palliation and 11 families (32%) chose cardiac transplantation. Of the 11 infants listed for cardiac transplantation, five underwent transplantation. Because of a lack of donors after an average wait of 25 days (19 to 31), the remaining six infants underwent palliation, with no perioperative deaths. Of the 30 infants undergoing palliation, including crossovers, 20 (67%) survived the first operative stage. Among the last 19 infants undergoing palliation in 1990, the early survival was 84%. Risk factors determined for poor outcome were year of operation (p less than 0.001) and circulatory arrest time greater than 50 minutes (p less than 0.001). Among the 13 infants undergoing palliation with a circulatory arrest time of less than 50 minutes, there were 12 survivors (92%); among 12 having a circulatory arrest time of more than 50 minutes, there were four survivors (33%). At intermediate follow-up, six infants have undergone second-stage procedures (Glenn), with five survivors. There were eight late deaths, four caused by respiratory infections and four caused by cardiac problems, including a thrombosed shunt in one infant. Three of five infants are alive and doing well after cardiac transplantation. Size of aorta, tricuspid regurgitation, and ventricular wall thickness did not prove to be risk factors. Given the existing data, we believe these infants should be managed selectively on the basis of donor availability and family wishes.

Actuarial Analysis↗

Adult-child interaction during invasive medical procedures.

Adult-child interactions during stressful medical procedures were investigated in 43 pediatric patients videotaped during a venipuncture procedure in the course of cancer treatment. Relations among six adult behavior categories (explain, distract, command to engage in coping behavior, give control to the child, praise, and criticize/threat/bargain) and three child behavior categories (momentary distress, cry/scream, and cope) were examined using correlational and sequential analysis. Results indicated that adult distraction resulted in increased child coping and reduced momentary distress and crying. Adult explanations, although a likely response to child distress and crying, did not result in a reduction of these behaviors. Attempts to give the child control reduced child crying. Implications for clinical interventions during painful medical procedures are discussed.

Adaptation, Psychological↗

The growth hormone response to clonidine in acute and remitted depressed male patients.

The growth hormone (GH) response to clonidine was evaluated in 28 acutely depressed male patients, 17 remitted depressed patients, and 26 normal control subjects. The GH response to clonidine was blunted (delta less than 4 ng/ml) in a significantly increased proportion of both acute and remitted patients compared to control subjects. Covarying for age effects, the GH response to clonidine (as area-under-the-curve) was not significantly different between any of the three groups, but was significantly diminished in both the acute and remitted depressed patients who were ever hospitalized for an episode of depression, compared to control subjects. Six patients studied in both the acute and remitted states were blunted in both states. These findings could not be accounted for by other clinical and demographic variables including weight, time off antidepressants, severity of current depressive symptoms, and subtype of depression. These results raise the possibility that the blunted GH response to clonidine may represent a state-independent correlate of some forms of severe depression. Issues regarding the specificity and interpretation of this finding require further clarification.

Acute Disease↗

Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study.

The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.

Animals↗

Regulation of atrial autonomic receptors in experimental cyanotic heart disease.

During chronic hypoxemia, left ventricular beta-adrenergic receptor density is decreased and a dissociation occurs between increased chronotropic and decreased inotropic responses to chronically elevated sympathetic tone. To determine whether this dissociation was related to alterations in autonomic receptor populations in the right atrium, we studied right atrial cholinergic and beta-adrenergic receptors in chronically hypoxemic newborn lambs and in normoxemic controls. Heart rate response was determined by infusing isoproterenol at 0.1 or 0.5 microgram.kg-1.min-1. Muscarinic receptors were quantified with [3H]quinuclidinyl benzilate and beta-adrenergic receptors with [125I]iodocyanopindolol. Competition with ICI 118,551 was used to determine beta 1- vs. beta 2-receptor subtypes. In the hypoxemic lambs, isoproterenol resulted in a lesser percentage increase in heart rate (hypoxemic, 46 +/- 6% vs. control, 89 +/- 17%, P less than 0.05); however, because baseline heart rate was higher in the hypoxemic lambs (213 +/- 7 vs. 177 +/- 12 beats/min, P less than 0.05), maximal heart rate responses were similar (310 +/- 7 vs. 326 +/- 6 beats/min, NS). There was no change in receptor density or affinity of either muscarinic or beta-adrenergic receptors and no change in the proportion of beta 1- vs. beta 2-receptor subtypes. Thus the dissociation between the chronotropic and inotropic responses to chronic hypoxemia may be in part secondary to a differential regulation of beta-adrenergic receptors between the left ventricle and the right atrium.

Animals↗