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Biomedical subjects

D Bernstein

Publications and source records attributed to D Bernstein.

At least 55 records · Page 3Linked to original sources
PubMed1998

Alterations in dynamic heart rate control in the beta 1-adrenergic receptor knockout mouse.

beta 1-Adrenergic receptors (beta 1-ARs) are key targets of sympathetic nervous system activity and play a major role in the beat-to-beat regulation of cardiac chronotropy and inotropy. We employed a beta 1-AR gene knockout model to test the hypothesis that beta 1-AR function is critical for maintenance of resting heart rate and baroreflex responsiveness and, on the basis of its important role in regulating chronotropy and inotropy, is also required for maximal exercise capacity. Using an awake unrestrained mouse model, we demonstrate that resting heart rate and blood pressure are normal in beta 1-AR knockouts and that the qualitative responses to baroreflex stimulation are intact. Chronotropic reserve in beta 1-AR knockouts is markedly limited, with peak heart rates approximately 200 beats/min less than wild types. During graded treadmill exercise, heart rate is significantly depressed in beta 1-AR knockouts at all work loads, but despite this limitation, there are no reductions in maximal exercise capacity or metabolic indexes. Thus, in mice, the beta 1-AR is not essential for either maintenance of resting heart rate or for maximally stressed cardiovascular performance.

Adrenergic beta-Agonists↗
PubMed1998

Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus.

Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p < 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p < 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs.

Adolescent↗
PubMed1998

Relative abundance of organochlorine pesticides and polychlorinated biphenyls in adipose tissue and serum of women in Long Island, New York.

Some organochlorine pesticides (OCPs) and PCBs are under investigation as possible risk factors for breast cancer because of their estrogenic properties and widespread presence in the environment. It is important to know whether adipose tissue used by some investigators and serum assays used by others can provide comparable information on body burden. Concentrations of seven OCPs or their breakdown products as well as 14 PCB congeners were measured in the adipose tissue and serum of 293 women enrolled as controls in a case-control study of environmental factors for breast cancer in Long Island, New York, a high-risk region. Adipose OCP/PCB levels were measured using a supercritical fluid extraction method developed by the authors. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene (p,p'-DDE) was detected in all adipose and serum samples; two chlordane derivatives, beta-hexachlorocyclohexane (a lindane isomer) and hexachlorobenzene, were detected in at least 92% of adipose samples. The di-ortho hexachlorinated PCB congeners 2,4,5,2',4',5'-hexachlorobiphenyl and 2,3,4,2',4',5'-hexachlorobiphenyl were detected in all adipose and over 98% of serum samples. 1,1-Dichloro-2,2-di(4-chlorophenyl)ethylene comprised 77% of total pesticide residues in adipose and 71% in serum. 2,4,5,2',4',5'-Hexachlorobiphenyl comprised 24% of adipose and 21% of serum PCBs. The relative concentration patterns of the 14 PCB congeners were similar to those reported in other human studies and were also typical of patterns reported in environmental samples from various biota, including mammals and birds, but differed substantially from patterns reported in occupationally exposed workers. All adipose-serum correlations for pesticides and most PCBs were statistically significant. Either serum or adipose OCP/PCB levels of a variety of environmental organochlorine compounds may serve as useful biomarkers of body burden.

Adipose Tissue↗
PubMed1998

Pregnancy and delivery in a group of Israeli teenagers. A case-controlled study.

OBJECTIVE: To assess characteristics of an Israeli group of nulliparous teenagers and to compare selected variables of their course and outcome of pregnancy with controls. METHODS: Hospital records of 46 consecutive nulliparous teenagers younger than 17.5 years who delivered during a ten-year period and 84 matched adult controls were reviewed. RESULTS: The majority of the teenagers were older than 15 years, married and most were born in Israel or in the former Soviet Union with no obvious socio-economical deprivation. The rate of prenatal follow-up, hypertensive disorders, type of analgesia during labor and mode of delivery were similar in teenagers and controls. A statistically non-significant higher rate of anemia (hemoglobin, 10 gr%), preterm delivery and low birth weight were observed in teenagers. Only the rate of induction of labor and the rate of a hemoglobin level higher than 12 gr% were significantly lower in teenagers. CONCLUSIONS: The course and outcome of pregnancy were in most respects similar in this group of nulliparous teenagers and matched adult controls.

Adolescent↗
PubMed1997

A brain imaging (single photon emission computerized tomography) study of semantic and affective processing in psychopaths.

Psychopaths have been described as human predators who use charm, intimidation, and violence to control others and to satisfy their own needs. Underlying their propensity to violate social norms and expectations is a profound lack of empathy, guilt, or remorse, affective processes that have long resisted scientific investigation. Using brain imaging technology we found that psychopaths differed from nonpsychopaths in the pattern of relative cerebral blood flow during processing of emotional words. The results were consistent with the hypothesis that there are anomalies in the way psychopaths process semantic and affective information.

Adult↗
PubMed1997

Long-term survivors of pediatric heart transplantation: a multicenter report of sixty-eight children who have survived longer than five years.

OBJECTIVE: Short-term survival after pediatric heart transplantation is now excellent, but ultimately the efficacy of this procedure will depend on duration and quality of survival. We sought to evaluate the clinical course of long-term survivors of heart transplantation in childhood. METHODS: Patients who had undergone heart transplantation at the university hospitals of Stanford, Columbia, and Pittsburgh between 1975 and 1989 and survived longer than 5 years from transplantation were identified and their clinical courses retrospectively reviewed. RESULTS: Sixty eight children have survived more than 5 years from transplantation, and 60 (88%) are currently alive with a median follow-up of 6.8 years (5 to 17.9 years). Thirteen have survived more than 10 years from transplantation. Renal dysfunction caused by immunosuppressive agents was common, and two patients required late renal transplantation. Lymphoproliferative disease or other neoplasm occurred in 12 patients, but none resulted in death. Coronary artery disease was diagnosed in 13 patients (19%), leading to retransplantation in eight. Death after 5 years was related to acute or chronic rejection in 5 of 8 cases. Two of the deaths were directly related to noncompliance with immunosuppressive medication. All survivors are in New York Heart Association class 1. CONCLUSIONS: Long-term survival with good quality of life can be achieved after heart transplantation in childhood, though complications of immunosuppression remain common. Posttransplantation coronary artery disease is emerging as the main factor limiting long term graft and patient survival.

Adolescent↗
PubMed1997

Does the study of victimization revictimize the victims?

Although the number of questionnaire surveys examining the sequelae of prior sexual and physical victimization has increased over the last decade, little attention has been given to understanding the impact of such studies on participants. As part of a larger study of long-term effects of prior sexual and physical victimization, 500 randomly selected women in an HMO received a comprehensive questionnaire including multiple symptomatic distress measures and several items inquiring into previous history of sexual, physical, and emotional abuse and neglect. They also completed a short rating scale asking about their reactions to completing the questionnaire. Despite the sensitive content, the women who participated generally found the experience to be a positive one. Only a small number of women were more upset than they had anticipated, but the vast majority felt they would have completed the survey even if they had known in advance how they would feel. The subset of women who did express distress was significantly different from the group that did not, with respect to other measures of symptomatic distress and trauma exposure. These data suggest that surveys that inquire into prior episodes of childhood victimization are generally well tolerated by women who participate, and that, although a small number may be disturbed by these investigations, in general, adverse reactions may be less common than previously anticipated.

Adult↗
PubMed1997

Cardiovascular indexes in the mouse at rest and with exercise: new tools to study models of cardiac disease.

Manipulations of the murine genome that alter cardiovascular function have created the need for methods to study cardiovascular physiology in genetically altered animals in vivo. We adapted chronic physiological measurement techniques to the nonanesthetized, nonrestrained murine model, established strain-specific cardiovascular and metabolic norms, and evaluated responses to anesthesia, exercise, and adrenergic stimulation. Anesthesia resulted in alterations in heart rate (HR), blood pressure (BP), and O2 consumption (V(O2)) and CO2 production (V(CO2)) for up to 6 h postoperatively. There were significant interstrain differences in resting values of HR and BP Graded treadmill exercise resulted in linear increases in HR, V(O2), V(CO2), and respiratory exchange ratio (RER) similar to those seen in larger species. Response to beta-adrenergic stimulation showed a classic sigmoidal dose-response curve; however, there was very little tachycardiac response to vagal blockade, indicating low resting vagal tone. This study demonstrates the feasibility of performing chronic cardiovascular measurements in nonanesthetized mice and stresses the importance of allowing for anesthetic recovery and strain variability. Murine cardiovascular responses to exercise can be reliably measured and are qualitatively similar to those in humans.

Adrenergic Agents↗
PubMed1997

Developmental and afterload stress regulation of heat shock proteins in the ovine myocardium.

Heat shock proteins (hsps) are produced in the myocardium in response to stresses such as ischemia, hyperthermia, and increased afterload. The role of these stress proteins in the developing myocardium is unknown. Expression of the inducible (hsp 72) and cognate (hsc 73) hsps was determined in the immature ovine myocardium during the perinatal transition, and their role in subsequent myocardial growth was examined. hsp synthesis was also studied during acute afterload stress in newborns by aortic banding to a gradient of 50 torr for 4 h. Expression of the inducible (hsp 72) isoform is developmentally regulated in both right and left ventricles: low levels in the fetus, increasing throughout development, and peaking in the 14-25-d newborn and adult. The cognate (hsc 73) isoform remains unchanged during development in the left ventricle but decreases with age in the right ventricle. The inducible (hsp 72) isoform is also developmentally regulated in the lung, increasing postnatally to a peak in the 14-25-d-old and adult sheep. Finally, newborn myocardium demonstrated a rapid increase in hsp expression in response to afterload stress, similar to that seen in the adult.

Animals↗
PubMed1997

[Gynecologic problems of the lower genital tract in children and young adolescents].

Hospital records of 46 girls under the age of 17 years, hospitalized for lower genital tract problems in 1986-95 were reviewed. The most common conditions were results of unintentional injuries (43.5%), imperforate hymen (28.2%) and infections (19.6%). The median age for unintentional injuries was significantly lower than for other conditions (7.0 vs 11.4; p < 0.001). Most injuries were external and occurred during outdoor activities. Mean volume of estimated bloody fluid drained in those with imperforate hymen was greater when the diagnosis was made after the age of 12 (783 vs 433; not significant). It has been suggested that hematocolpos and hematometra should be prevented, but the possible unfavorable sequelae have not been documented. The relative order of frequency of the various diagnostic groupings and the diagnoses of labial adhesions and imperforate hymen are specific for the age of the study group.

Accidents↗
PubMed1996

Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c.

alpha2-Adrenergic receptors (alpha2ARs) are essential components of the neural circuitry regulating cardiovascular function. The role of specific alpha2AR subtypes (alpha2a, alpha2b, and alpha2c) was characterized with hemodynamic measurements obtained from strains of genetically engineered mice deficient in either alpha2b or alpha2c receptors. Stimulation of alpha2b receptors in vascular smooth muscle produced hypertension and counteracted the clinically beneficial hypotensive effect of stimulating alpha2a receptors in the central nervous system. There were no hemodynamic effects produced by disruption of the alpha2c subtype. These results provide evidence for the clinical efficacy of more subtype-selective alpha2AR drugs.

Adrenergic alpha-Agonists↗
PubMed1996

Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects.

At least three distinct beta-adrenergic receptor (beta-AR) subtypes exist in mammals. These receptors modulate a wide variety of processes, from development and behavior, to cardiac function, metabolism, and smooth muscle tone. To understand the roles that individual beta-AR subtypes play in these processes, we have used the technique of gene targeting to create homozygous beta 1-AR null mutants (beta 1-AR -/-) in mice. The majority of beta 1-AR -/- mice die prenatally, and the penetrance of lethality shows strain dependence. Beta l-AR -/- mice that do survive to adulthood appear normal, but lack the chronotropic and inotropic responses seen in wild-type mice when beta-AR agonists such as isoproterenol are administered. Moreover, this lack of responsiveness is accompanied by markedly reduced stimulation of adenylate cyclase in cardiac membranes from beta 1-AR -/- mice. These findings occur despite persistent cardiac beta 2-AR expression, demonstrating the importance of beta 1-ARs for proper mouse development and cardiac function, while highlighting functional differences between beta-AR subtypes.

Adenylyl Cyclases↗
PubMed1996

Evaluation of household dust mite exposure and levels of specific IgE and IgG antibodies in asthmatic patients enrolled in a trial of immunotherapy.

BACKGROUND: Monitoring the response to immunotherapy entails understanding exposure to relevant allergens. For the major indoor allergens, this requires sampling of dust from the patient's house. The objectives of this study were to measure indoor allergen levels during a controlled trial of dust mite immunotherapy for asthma and to relate these results to serum antibody levels. METHODS: Eighty-eight asthmatic patients with mite allergy from seven geographic areas in the United States were enrolled in and completed a course of immunotherapy with Dermatophagoides extract or placebo control. Sensitization was evaluated by quantitative measurements of IgG and IgE antibodies. Dust samples were assayed for group I mite (Der p 1 and Der f 1), cat (Fel d 1), and cockroach (Bla g 1) allergens by monoclonal antibody-based ELISA. RESULTS: Over the 4 years of the study, each of the houses had at least one sample that contained more than 2 micrograms of group I mite allergen per gram of dust. Mean mite allergen levels, however, varied over a wide range, from 0.2 microgram/gm or less to more than 50 micrograms/gm. IgE antibodies to mite were present in sera from 78% of the patients, whereas IgE antibodies to cat and cockroach allergens were found in sera from 34% and 11% of patients, respectively. Sixty-four percent of the patients had exposure and sensitization to mite, whereas the comparable figure for each of the other allergens was 5%. CONCLUSIONS: Examination of the results suggested that allergen exposure, relative to a trial of immunotherapy, could be expressed as (1) the maximum level found in the house, (2) the percentage of sites having greater than 2 micrograms/gm, or (3) the mean value at the site with the maximum level. This report provides a background for evaluating the clinical results of immunotherapy in these patients and a model for the way in which sensitization and exposure should be monitored in studies of this kind.

Adolescent↗
PubMed1996

Hepatitis C virus RNA quantification in right and left lobes of the liver in patients with chronic hepatitis C.

Quantification of hepatitis C virus RNA in liver tissue is likely to be useful in the study of the natural history, pathogenesis, progression and treatment of hepatitis C virus-associated liver disease. Quantitative measurements of hepatitis C virus RNA in liver biopsy samples using the branched DNA (bDNA) signal amplification assay were carried out. The aims of this study were threefold: first, to assess the level of hepatitis C virus RNA in biopsy samples from the right and left lobes of the liver; second, to evaluate the correlation between hepatitis C virus RNA levels in serum and liver; and third, to investigate the relationship between serum and liver hepatitis C virus RNA levels and the severity of hepatic histology in non-cirrhotic patients with chronic hepatitis C. There was a strong correlation (r = 0.92, P < 0.01) between hepatitis C virus RNA levels in the right and left lobes of the liver as well as a strong correlation between hepatitis C virus RNA levels in liver and serum (r = 0.82, P < 0.01). However, there was no significant correlation between the severity of hepatic histology and levels of hepatitis C virus RNA in serum and liver among patients with chronic active hepatitis classified according to Knodell's hepatic activity index (KI). Our results indicate that hepatitis C virus RNA quantification from a single liver biopsy is representative of both lobes in patients with chronic hepatitis, and suggest that serum hepatitis C virus RNA levels are a meaningful reflection of hepatitis C virus RNA levels in the liver.

Adult↗
PubMed1996

Admission criteria for inpatient substance abuse/dependence rehabilitation: implications for managed care.

In view of recent trends toward the replacement of traditional inpatient rehabilitation programs with nonresidential services, we examined the extent to which patients currently admitted to inpatient rehabilitation for alcohol or drug abuse/dependence met published criteria suggesting a preferential need for inpatient or residential care. Over 90% of almost 300 veterans with a primary DSM-III R diagnosis of alcohol or substance abuse/dependence, admitted to six New York Metropolitan Area Veterans Administration Medical Centers for inpatient rehabilitation, met at least one criterion dimension considered indicative of a need for such services, with over two-thirds meeting two or more dimensions. These findings suggest a continuing need for initial primary inpatient or residential rehabilitation for such patients.

Adult↗
PubMed1996

Malignancy in Crohn's disease.

The risk for the development of malignancy in Crohn's disease is not as well defined as it is with ulcerative colitis. The risk for the development of small bowel adenocarcinoma is greater in patients with Crohn's disease than in the general population although the magnitude of this increased risk is unclear. Risk factors associated with the development of small bowel carcinoma in Crohn's disease include male sex, duration of disease, associated fistulous disease, and the presence of surgically excluded loops of bowel. Crohn's colitis has been associated with an increased risk of colorectal carcinoma in patients with long-standing colitis, strictures, fistulae, and right-sided colonic disease. Secondary gastrointestinal carcinomas are rare in Crohn's disease. This article reviews the current literature regarding the association of various malignancies in Crohn's disease. Although concentrating on population based and case-control studies, it includes referral center studies as well as case reports.

Case-Control Studies↗