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Biomedical subjects

D Shapiro

Publications and source records attributed to D Shapiro.

At least 73 records · Page 4Linked to original sources
PubMed1995

The cardiovascular response to postural change as a function of race.

Little is known about racial differences in cardiovascular responses to postural change. The immediate and delayed change from sitting to standing was studied in 207 healthy young Asian, black, and white men and women by means of a noninvasive blood pressure tracking system. Whereas Asians and whites had decreased mean arterial pressure (MAP) 32-41 s after standing, blacks had an increase. During the delayed response (3 min after standing), compared to Asians and whites, blacks had greater increases in diastolic blood pressure and MAP. Their heart rate increase was also greater than Asians. For systolic blood pressure and pulse pressure there were Race x Family History interactions for the immediate response to orthostasis and Race x Gender interactions for the delayed response. Blacks generally displayed different cardiovascular patterns from the other two racial groups, possibly reflecting increased peripheral resistance and altered baroreceptor function.

Adolescent↗
PubMed1995

Effects of anger/hostility, defensiveness, gender, and family history of hypertension on cardiovascular reactivity.

In this study, we examined the combined effects of anger/hostility and defensiveness on reactivity to three stressors (math, handgrip, cold pressor) and how these effects are moderated by gender and family history of hypertension. The subjects were 209 college students. Low compared with high Spielberger anger-out scores were associated with greater diastolic blood pressure (DBP) reactivity in low- but not high-defensive women with a negative family history. High compared with low hostility scores were associated with greater heart rate reactivity in low-defensive men with an opposite effect in high-defensive men. Gender, family history, and defensiveness each affected differential DBP reactivity to the three tasks. Combined study of biological factors and coping styles can improve our understanding of cardiovascular reactivity and disease.

Adolescent↗
PubMed1995

Insurance coverage for experimental technologies.

As the number and cost of new technologies grow, it is increasingly important that we develop sound policies for payment for those technologies while their clinical impacts are being defined. Such policies need to balance social interests in promotion of innovation, early access to promising technology, patient safety, control of health care costs, and return on investment. We present a rationale, policy options, and a proposal for insurance coverage of experimental technology.

Decision Making, Organizational↗
PubMed1994

Requirement for transcription factor IRF-1 in NO synthase induction in macrophages.

Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents. Interferon (IFN)-gamma and lipopolysaccharide stimulate NO production by transcriptionally up-regulating the inducible NO synthase (iNOS). Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1-/- mice) produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation. Two adjacent IRF-1 response elements were identified in the iNOS promoter. Infection with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type mice. Thus, IRF-1 is essential for iNOS activation in murine macrophages.

Amino Acid Oxidoreductases↗
PubMed1994

Autogenic-feedback training: a potential treatment for orthostatic intolerance in aerospace crews.

Postflight orthostatic intolerance has been identified as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder that are both effective and practical. A considerable body of clinical research has demonstrated that people can be taught to increase their own blood pressure voluntarily, and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The current pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, autogenic-feedback training (AFT), three men and two women participated in four to nine training (15-30-minute) sessions. At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures, that the subjects made ranged between 20 and 50 mm Hg under both supine and 45 degrees head-up tilt conditions. These findings indicate that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Furthermore, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.

Adult↗
PubMed1994

Effects of carbohydrate and protein meals on cardiovascular levels and reactivity.

This study examined the effects of standard laboratory stressors on cardiovascular measures before and after the consumption of a modest meal. A mental arithmetic task and a reaction time task were administered before and 2 h after a carbohydrate or a protein meal. A noncaloric placebo meal and a fasting condition were included as control treatments. The caloric meals, in particular the carbohydrate meal, induced an increase in cardiac output, ventricular contractility, and systolic blood pressure. Total peripheral resistance and diastolic blood pressure dropped. Although postprandial adjustments were substantial, stress reactivity patterns generally were not perturbed by the meals. Only heart rate reactivity was stronger after eating the carbohydrate meal. It is concluded that subjects' meal consumption prior to their participation in a psychophysiological experiment needs to be taken into account.

Adolescent↗
PubMed1994

Hostility and the response to diuretic in mild-to-moderate hypertension.

Forty-two patients with mild-to-moderate hypertension between the ages of 35 and 65 (23 men, 19 women) were studied to determine whether psychological characteristics can help differentiate between responders and nonresponders to diuretic (hydrochlorothiazide 25 mg and triamterene 50 mg). To qualify for inclusion in the study, the subjects were required to have a mean unmedicated clinic diastolic blood pressure (DBP) between 95 and 110 mm Hg. Positive response to diuretic was defined as a reduction in clinic DBP < or = 90 mm Hg. Of the 42 subjects, 22 were responders to diuretic, achieving a BP level of 129/86 mm Hg, a reduction of 16/11 mm Hg from their unmedicated level. Nonresponders achieved a reduction of 8/4 mm Hg. Compared with nonresponders, responders were characterized by slightly lower initial BP levels and significantly lower scores on the Buss-Durkee Hostility Inventory and several subscales of this test. The pattern of results indicated higher levels of suppressed hostility in the nonresponders. Ambulatory BP data paralleled the clinic BP changes.

Adult↗
PubMed1994

Inhaled furosemide is not effective in acute asthma.

As previous studies have suggested that inhaled furosemide may have a protective effect against certain types of provocative challenges in asthmatic subjects, we investigated the role of furosemide in treating acute asthma exacerbations. Twenty-four patients (n = 24) with acute asthma were entered into the study on presenting to the emergency department. They were blindly randomized to receive one of three drug regimens: (1) inhaled furosemide (40 mg) (n = 8); (2) inhaled metaproterenol (15 mg) (n = 7); or (3) the combination of furosemide (40 mg) and metaproterenol (15 mg) (n = 9). We measured FEV1 at entry (time 0) and 15, 30, 45, and 60 min after inhalation of the individual drugs or the combination from a face mask nebulizer. At entry, the three groups did not differ significantly in age (mean +/- SEM = 37.6 +/- 3.6, 38.5 +/- 3.6, and 41.0 years, respectively; p = 0.770), baseline FEV1 (1.01 +/- 0.27, 1.04 +/- 0.27, and 1.25 +/- 0.14 L, respectively; p = 0.620), or theophylline levels (2.87 +/- 1.8, 7.39 +/- 2.8, and 5.29 +/- 2.6 micrograms/ml, respectively; p = 0.498). Pretreatment and posttreatment potassium levels were similar among the three groups. Inhalation of furosemide alone resulted in a 14.9 +/- 10.5 percent change in FEV1 percent from baseline, which was not statistically significant. In contrast, metaproterenol alone resulted in a 42.9 +/- 15.2 percent increase in FEV1 percent (F ratio = 6.226; p = 0.0028). The combination of furosemide and metaproterenol resulted in a change in FEV1 percent that was not statistically different compared with metaproterenol alone (FEV1 percent = 41.9 +/- 12 percent). No significant adverse effects occurred in any of the groups.

Acute Disease↗
PubMed1994

Biological functions of IFN-gamma and IFN-alpha/beta: lessons from studies in gene knockout mice.

Mice with a targeted disruption in the IFN-gamma receptor gene (IFN-gamma R0/0) provided a useful model to ask to what extent other cytokines could replace IFN-gamma in macrophage activation. In thioglycollate-elicited peritoneal macrophages from wild-typy (WT) mice, TNF enhanced nitric oxide (NO) release in the presence of IFN-gamma, though TNF alone was not effective. In macrophages from IFN-gamma R0/0 mice, which are not responsive to IFN-gamma, TNF completely failed to stimulate NO release. The NO inducing effects of IFN-alpha/beta were indistinguishable in IFN-gamma R0/0 and WT macrophages. The important role of IFN-gamma in the regulation of the induced expression of MHC class II antigen (Ia) was confirmed by showing that after systemic infection with the BCG strain of Mycobacterium bovis, peritoneal macrophages from IFN-gamma R0/0 mice had a lower level of Ia expression than macrophages from WT mice. BCG infection was not lethal for WT mice whereas all IFN-gamma R0/0 mice died 7-9 weeks after infection. It is well known that BCG infection greatly sensitizes mice to lethal action of LPS. Injection of LPS 2 weeks after BCG inoculation was significantly less lethal for IFN-gamma R0/0 mice than for WT mice. Reduced lethality of LPS correlated with a drastically reduced TNF-alpha production in the IFN-gamma R0/0 mice after BCG infection and LPS challenge. The greatly reduced ability of BCG-infected IFN-gamma R0/0 mice to produce TNF-alpha may be an important factor in their inability to resist BCG infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mice that lack the interferon-gamma receptor have profoundly altered responses to infection with Bacillus Calmette-Guérin and subsequent challenge with lipopolysaccharide.

Mice with a targeted disruption of the interferon gamma receptor gene (IFN-gamma R0/0 mice) and control wild-type mice were inoculated with the Bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis. BCG infection was not lethal for wild-type mice whereas all IFN-gamma R0/0 mice died approximately 7-9 wk after inoculation. Histological examination at 2 and 6 wk after BCG inoculation showed that livers of IFN-gamma R0/0 mice had higher numbers of acid-fast bacteria than wild-type mice, especially at 6 wk. In parallel, the livers of IFN-gamma R0/0 mice showed a reduction in the formation of characteristic granulomas at 2 wk after inoculation. Injection of lipopolysaccharide (LPS) 2 wk after BCG inoculation was significantly less lethal for IFN-gamma R0/0 mice than for wild-type mice. Reduced lethality of LPS correlated with a drastically reduced production of tumor necrosis factor alpha (TNF-alpha) in the IFN-gamma R0/0 mice. Interleukin 1 alpha (IL-1 alpha) and IL-6 levels in the serum were also significantly reduced in the IFN-gamma R0/0 mice after BCG infection and LPS challenge. The greatly reduced capacity of BCG-infected IFN-gamma R0/0 mice to produce TNF-alpha may be an important factor in their inability to resist BCG infection. These results show that the presence of a functional IFN-gamma receptor is essential for the recovery of mice from BCG infection, and that IFN-gamma is a key element in the complex process whereby BCG infection leads to the sensitization to endotoxin.

Animals↗
PubMed1993

Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.

We consider how to combine several independent studies of the same diagnostic test, where each study reports an estimated false positive rate (FPR) and an estimated true positive rate (TPR). We propose constructing a summary receiver operating characteristic (ROC) curve by the following steps. (i) Convert each FPR to its logistic transform U and each TPR to its logistic transform V after increasing each observed frequency by adding 1/2. (ii) For each study calculate D = V - U, which is the log odds ratio of TPR and FPR, and S = V + U, an implied function of test threshold; then plot each study's point (Si, Di). (iii) Fit a robust-resistant regression line to these points (or an equally weighted least-squares regression line), with V - U as the dependent variable. (iv) Back-transform the line to ROC space. To avoid model-dependent extrapolation from irrelevant regions of ROC space we propose defining a priori a value of FPR so large that the test simply would not be used at that FPR, and a value of TPR so low that the test would not be used at that TPR. Then (a) only data points lying in the thus defined north-west rectangle of the unit square are used in the data analysis, and (b) the estimated summary ROC is depicted only within that subregion of the unit square. We illustrate the methods using simulated and real data sets, and we point to ways of comparing different tests and of taking into account the effects of covariates.

Carcinoma, Non-Small-Cell Lung↗
PubMed1993

Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon gamma receptor.

Availability of mice with a targeted disruption of the interferon gamma (IFN-gamma) receptor gene (IFN-gamma R0/0 mice) made it possible to examine parameters of macrophage activation in the absence of a functional IFN-gamma receptor. We asked to what extent other cytokines could replace IFN-gamma in the induction of nitric oxide or major histocompatibility complex class II antigen (Ia) expression in peritoneal macrophages. In thioglycollate-elicited macrophages from wild-type mice, tumor necrosis factor (TNF) alone was virtually ineffective in inducing release of NO2- (the endproduct of nitric oxide generation), but TNF enhanced NO2- release in the presence of IFN-gamma. In macrophages from IFN-gamma R0/0 mice, which were unresponsive to IFN-gamma, TNF completely failed to stimulate NO2- release. The stimulatory actions of IFN-alpha/beta on NO2- release were indistinguishable in wild-type and IFN-gamma R0/0 macrophages: IFN-alpha/beta was ineffective on its own, showed marginal stimulation of NO2- release in combination with TNF, and was moderately effective in the presence of lipopolysaccharide. The level of constitutive Ia antigen expression was not significantly different in peritoneal macrophages from wild-type and IFN-gamma R0/0 mice. An increased Ia expression was induced by IL-4 and granulocyte-macrophage colony-stimulating factor in both wild-type and IFN-gamma R0/0 macrophages, but the magnitude of this induction was less than with optimal concentrations of IFN-gamma in macrophages from wild-type mice. IFN-alpha/beta showed only a minor stimulatory effect on Ia expression in both wild-type and IFN-gamma R0/0 macrophages. Simultaneous treatment of wild-type macrophages with IFN-alpha/beta and IFN-gamma reduced the IFN-gamma-induced Ia expression in wild-type macrophages, but IFN-alpha/beta did not show an inhibitory effect on IL-4- or granulocyte-macrophage-colony-stimulating factor-induced Ia expression in either wild-type or IFN-gamma R0/0 macrophages. The important role of IFN-gamma in the regulation of the induced expression of major histocompatibility complex class II antigen was confirmed by showing that after systemic infection with the BCG strain of Mycobacterium bovis resident peritoneal macrophages from IFN-gamma R0/0 mice had a lower level of Ia expression than macrophages from wild-type mice. The inability of other cytokines to substitute fully for IFN-gamma in macrophage activation helps to explain the earlier observed decreased resistance of IFN-gamma R0/0 mice to some infections.

Animals↗
PubMed1993

Labeling of fractured human skin with antibodies to BM 600/nicein, epiligrin, kalinin and other matrix components.

A variety of methods were used to fracture the dermal-epidermal junction (DEJ) of human skin. These included warm and hot phosphate buffered saline, trypsin, cold 1 M salt, potassium bromide and proteolytic digestion with dispase. The localization and sensitivity of basement membrane components (bullous pemphigoid antigen, BM 600/nicein, epiligrin, kalinin, laminin, collagens IV and VII (EBA antigen) and linkin) were determined after the DEJ was fractured by each method. We found that the basement membrane zone proteins, BM 600/nicein, epiligrin and kalinin remained with the dermal side of the DEJ fractured through the lamina lucida by cold salt, phosphate buffered saline and potassium bromide. BM 600/nicein, epiligrin and kalinin were not detected after treatment with trypsin. In contrast, laminin, another glycoprotein in the lamina lucida, was insensitive to all of the procedures, but co-localized to the dermal side of DEJ-fractured skin. We also found that separation of the DEJ with brief exposure of skin to 56 degrees C provided a useful substrate for testing the autoantibodies in the sera of patients with epidermolysis bullosa acquisita (EBA). Heat-separated skin can be prepared in a significantly shorter period of time than salt-separated skin.

Antibodies↗
PubMed1993

Factors affecting the development of skin cancer after scalp irradiation.

A nested case control study of persons who developed skin cancer after scalp irradiation in childhood revealed two risk factors for the appearance of radiation-induced skin cancer: (a) an apparently higher radiation dose delivered inadvertently, manifested by a higher prevalence of alopecia and radiation dermatitis (RR = 3.4; CI 1.3-8.8); (b) a more frequent exposure to the sun, manifested by summer sunbathing (RR = 2.6; CI 1.1-6.1). These findings may have certain implications with regard to the understanding of radiation-induced cancer, after low-dose radiation exposure, in general.

Adolescent↗
PubMed1992

Continuous physiological changes and subjective reports in panic patients: a preliminary methodological report.

Six panic disorder patients and six matched control subjects were studied using a new technique allowing continuous and simultaneous monitoring of physiological responses (blood pressure, heart rate, respiration) and subjective reports of anxiety and panic. This was done before, during, and after CO2 inhalation. Panic patients had significantly higher variability in their heart rate, blood pressure, and breathing rate than the control subjects. They also had irregular breathing patterns with frequent pauses. We identified three different patterns of response to CO2 inhalation in the panic patients. Some patients who panicked on CO2 showed a definite association between changes in physiological responses that preceded their subjective ratings of anxiety; however, others did not show this pattern. The possibility of different physiological mechanisms of panic in different patients is discussed.

Adolescent↗
PubMed1992

Sarcomas of the flexor fossae in children: is amputation necessary?

Successful management of sarcomas of the extremities in children implies not only achievement of local control but also satisfactory function and maintenance of the growth potential. The popliteal and antecubital fossae, because of their complex neurovascular anatomy, all of which is essential, make resection with satisfactory margins difficult. We reviewed our experience with 14 patients (3 to 20 years old; median, 13 years) with soft tissue sarcomas arising in the popliteal (11 patients) or antecubital (3 patients) fossae. There were four rhabdomyosarcomas (3 alveolar, 1 embryonal) and 10 other sarcomas, the most frequent being synovial sarcoma (5 patients). Chemotherapy was given to all patients with rhabdomyosarcomas. The one patient presenting with metastatic disease was treated, after biopsy of the primary, by chemotherapy and radiation and survived 21 months. In three patients, the primary management was an above-the-knee amputation and two of three survived (3 and 43 months). In 10 patients a wide local excision of the primary tumor was performed. Radiation therapy was administered to five, either as external beam (3 patients) or as brachytherapy (2 patients). In this group, there were no local recurrences. Four patients remain free of disease (4 months to 18 years) and one developed pulmonary metastasis. Among the five non-irradiated patients, three developed local recurrences, requiring above-the-knee amputation for disease. The fourth patient relapsed in the lung and only one of the five is free of disease at 36 months. Of the 8 patients not treated with amputation, one acquired a leg length discrepancy, which required correction, and one has a minimal extension deficit of the knee.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗