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Biomedical subjects

B Allen

Publications and source records attributed to B Allen.

At least 19 recordsLinked to original sources

Continuous in vitro propagation and differentiation of cultures of the intramolluscan stages of the human parasite Schistosoma mansoni.

The metazoan parasitic blood flukes, Schistosoma spp., infect over 200 million people worldwide and cause extensive human morbidity and mortality. Research strategies for development of anti-schistosomal agents are impeded by the organism's complex molluscan-mammalian life cycle, which limits experimental approaches and availability of material. We derived long-term continuously proliferative cultures of Schistosoma mansoni sporocysts capable of generating cercariae in vitro. Cultured organisms retained the ability to parasitize the host, and they exhibited developmental regulation of candidate stage-specific genes in the host-free culture system. Evidence for expression of a reverse transcriptase also was found in the cultured organisms, pointing to this activity as a possible mechanistic contributor to the dynamic relationship between the parasite and its hosts. Continuous in vitro propagation of the asexual sporocyst stage allows isolation of clonally derived parasite populations and provides a means to study schistosomal molecular genetics, metabolism, and evasion of host defenses.

Animals

On the origins of congenic MATalpha and MATa strains of the pathogenic yeast Cryptococcus neoformans.

The basidiomycetous yeast Cryptococcus neoformans infects humans and causes a meningoencephalitis that is uniformly fatal if untreated. The organism has a defined sexual cycle involving mating of haploid MATa and MATalpha strains, gene disruption by transformation and homologous recombination is now readily accomplished, and robust animal models for infection have been well established. In addition, a pair of congenic MATalpha and MATa haploid strains have been constructed that permit detailed studies on physiology and virulence by classical genetic approaches. These strains represent a valuable resource for further studies in this organism, and the genomic sequence of one of these strains, JEC21 (=B-4500), was recently chosen to be sequenced by an international consortium. Because of the importance of these strains for genetic studies in C. neoformans and the fact that the genomic sequence of one of these strains is in progress, we review here how these congenic strains were originally constructed.

Animals

Barriers to early detection of cervical-uterine cancer in Mexico.

In Mexico, a woman dies of cervical-uterine cancer every 2 hours, indicating a low impact by the national program for early detection of this cancer, principally because of problems related to quality and coverage. Through a qualitative study, we identified the principal barriers to use of the detection program from the point of view of actual and potential program users. Four focus groups were organized in standard conditions in Mexico City (urban, developed) and in the southern state of Oaxaca (rural, economically disadvantaged area). Participants were either women with at least one previous Papanicolaou (Pap) test or women who had never had the test. Barriers to Pap test use included (1) lack of knowledge about cervical-uterine cancer etiology, (2) not knowing that the Pap test exists, (3) the conception that cancer is an inevitably fatal disease, (4) problems in doctor/medical institution-patient relationships, (5) giving priority to unmet needs related to extreme poverty, (6) opposition by the male sexual partner, (7) rejection of the pelvic examination, (8) long waits for sample collection and receiving results, and (9) perceived high costs for care. To increase coverage of the early detection program for cervical-uterine cancer in Mexico, the needs, perceptions, and beliefs of women and their partners must be taken into account when developing policy and planning, given the role these factors play in the decision-making process that leads to their participation or nonparticipation in this program.

Adult

Initial clinical experience with a fully automatic in-hospital external cardioverter defibrillator.

Sudden cardiac death due to ventricular tachyarrhythmia remains a significant problem in the in-hospital setting. Although the probability of survival is closely correlated with the rapidity of a response by qualified personnel, response times can be prolonged, even in specialized care units. In an effort to decrease response time, a fully automatic external cardioverter defibrillator was recently devised. This device was evaluated in the in-hospital setting to assess safety and efficacy. A total of 79 patients were studied in a multicenter trial. Patients were monitored with fully functional devices in the electrophysiology laboratory (51 patients) and in the cardiac care unit (28 patients). Performance of the device was assessed by comparing automatic responses to any sustained change in cardiac rhythm, either spontaneous or induced, to a retrospective review of stored ECG data and programmed parameters. During a total duration of 964 hours of monitoring, there were 99 episodes of sustained tachycardia. Therapy was appropriately delivered or advised in all episodes. Therapy was advised in one episode of supraventricular tachycardia. There were no episodes of inappropriate therapy delivery. There were no complications or adverse events. The device performed with a sensitivity of 100% and specificity of 98.8% with an average response time of 22 seconds. In conclusion, this automatic external defibrillator was safe, effective, and functioned as designed. Significant improvement in response time to life-threatening ventricular tachyarrhythmia in the in-hospital setting would be expected if this technology was widely adopted.

Adult

Abated cardiovascular responses to chronic oral lisinopril treatment in conscious elderly rats.

To determine whether the cardiovascular effects of chronic treatment with lisinopril are age related, we compared baroreflex sensitivity and pressor responsiveness in 4-mo- and 21-mo-old male rats that had been given oral lisinopril daily for 4 wk. Reflex bradycardia elicited by elevating blood pressure with phenylephrine was stronger in 4-mo-old rats than it was in 21-mo-old rats and also stronger in lisinopril-treated rats than it was in untreated rats of the same age. Pressor responses to angiotensin or norepinephrine were recorded after combined cholinergic and beta-adrenergic blockade and then analyzed not only as absolute but also as percent increases in mean pressure. Although pressor responses seemed to be slightly reduced by lisinopril when expressed as absolute increases in mean pressure, corresponding percent increases were always larger in 4-mo-old rats than they were in 21-mo-old rats and were clearly enhanced by lisinopril more in younger rats. The stronger overall enhancement of pressor responsiveness and reflex bradycardia in younger rats suggests that the cardiovascular effects of lisinopril diminish with advancing age.

Aging

Performance of silicon microdosimetry detectors in boron neutron capture therapy.

Reverse-biased silicon p-n junction arrays using Silicon-On-Insulator technology have been proposed as microdosimeters. The performance of such detectors in boron neutron capture therapy (BNCT) is discussed. This work provides the first reported measurements using boron-coated silicon diode arrays as microdosimeters in BNCT. Results are in good agreement with measurements with gas proportional counters. Various boron-coating options are investigated along with device orientation effects. Finally, a 235U coating is tested to simulate the behavior of the device in a heavy-ion therapy beam.

Boron

Calculation of benchmark doses for reproductive and developmental toxicity observed after exposure to isopropanol.

Reproductive, including developmental, toxicity risk assessment has typically relied on estimation of toxicity criteria values derived from no-observed-adverse-effect levels (NOAELs). The benchmark dose (BMD) approach has been proposed as an alternative that avoids problems with NOAELs. In this analysis of the reproductive and developmental toxicity observed in a multigeneration study of rats exposed to isopropanol, the BMD approach has been applied to all effects exhibiting significant dose-response relationships. The BMD estimates were very consistent across models and across end points; they were within the range of doses (100 to 500 mg/kg/day) that has been suggested as being the NOAEL. The use of the BMD approach for analysis of isopropanol reproductive toxicity is shown to avoid the experiment-specific argument of whether a particular treatment has induced statistically significant differences, compared to controls, in favor of the estimation of experiment-independent doses corresponding to risk levels of interest. The consistency of the BMD estimates, with values of about 420 mg/kg/day, suggests that, for isopropanol, the available multigeneration study data may provide a suitable basis for considering safe exposure.

2-Propanol

Effectiveness of physicians-in-training counseling for smoking cessation in African Americans.

This study examined the effectiveness of smoking cessation counseling by physicians-in-training (residents) with African-American patients. One hundred fifty-eight family and internal medicine residents at a large urban public general hospital participated in the study; two thirds of the residents underwent a 2-hour smoking cessation training program. Ninety-two of the trained physicians counseled from 1 to 18 patients. The majority of physicians were male, with 8% being current smokers. Over a 26-month period, 1086 patients were randomly assigned to intervention and control (usual care) groups. Mean patient age was 44 years, mean years smoking was 25, and mean number of cigarettes smoked per day was 14. There were no differences in biochemically validated smoking cessation rates between the intervention and control groups at 3 or 12 months postenrollment (2% versus 1.8% and 2.2% versus 2.8%, respectively). Losses to follow-up were high at both 3 and 12 months (38% and 40% respectively). Implications for future trials in minority populations are discussed. A brief physician-based smoking cessation message does not appear to be an effective strategy for use with African-American smokers in a large urban public general hospital.

Black or African American

Are Melnick-Needles syndrome and oto-palato-digital syndrome type II allelic? Observations in a four-generation kindred.

Melnick-Needles syndrome (MNS) is a female-limited skeletal dysplasia inherited in a X-linked dominant pattern. Males born to women with MNS may exhibit lethal multiple congenital anomalies, but recurrence of this phenotype within one family has not been reported. Males with oto-palato-digital syndrome type II (OPD II) also demonstrate a multiple congenital anomalies phenotype that includes skeletal dysplasia but the maternal phenotype includes only mild craniofacial anomalies. These two syndromes have been suggested as being allelic despite differences in the described maternal phenotypes. We present a four-generation kindred in which four males had a consistent multiple congenital anomalies phenotype. The females in this family have skeletal changes characteristic of MNS but have only mild craniofacial anomalies and also deafness attributable to ossicular deformity, traits more commonly found in OPD II. The expression of manifestations of MNS and OPD II in males and females in this kindred further suggest that these syndromes are allelic.

Abnormalities, Multiple

Task performance of black and white children across levels of presentation variability.

This study is an examination of the task performance patterns of Black and White, working and middle-class American children across a nonvaried and a varied presentation format condition: the relation of such patterns to activity levels in the home and to standardized achievement was also examined. Performance was better under the varied than the nonvaried format condition. This pattern held for all ethnic group/class combinations with the exception of Black middle-class children, for whom performance under the two conditions was virtually identical. Moreover, Black children, especially Black working-class children, reported greater home activity levels than did their White counterparts. Neither home activity level nor achievement was functionally related to patterns of performance.

Achievement

Risk factors for coronary heart disease among Navajo Indians: findings from the Navajo Health and Nutrition Survey.

Coronary heart disease was uncommon among the Navajo in the past, but appears to have increased substantially over the last few decades. The 1991-1992 Navajo Health and Nutrition Survey, which included interviews and examinations of 303 men and 485 women between the ages of 20 and 91 y, is the first population-based examination of coronary heart disease risk factors in this tribe. Coronary heart disease risk characteristics were common, particularly overweight (men, 35%; women, 62%), hypertension (men, 23%; women, 14%) and diabetes mellitus (men, 17%; women, 25%). Among 20- to 39-y-olds, a large proportion of men reported that they currently smoked cigarettes (23%); use of chewing tobacco or snuff was also prevalent among these 20- to 39-y-old men (37%) and women (31%). Although serum concentrations of total cholesterol were fairly comparable to those seen in the general U.S. population, fasting serum triglyceride concentrations were high (median: men, 132 mg/dL; women, 137 mg/dL), and concentrations of HDL cholesterol were low, particularly among women (median: men, 42 mg/dL; women, 44 mg/dL). Body mass index was associated with levels of most risk factors, and, independently of the level of overweight, a truncal pattern of body fat was related to adverse lipid levels among men. A large proportion of men (20%) and women (30%) reported not having participated in physical activity during the preceding month. Lessons learned from past intervention activities among the Navajo, particularly those for diabetes, may be useful in managing these risk factors to reduce the future burden of coronary heart disease.

Adolescent

Near doubling of heart rate after intravenous verapamil for treatment of atrial fibrillation without preexcitation.

Initial treatment of atrial fibrillation often involves pharmacological therapy to control ventricular response. While verapamil is usually safe and effective when used for this purpose, we report a proarrhythmic response. In this report a 30-year-old female presented with palpitations associated with atrial fibrillation and a ventricular response of 145 beats/min. Soon after she was given 5 mg of intravenous verapamil her ECG documented a regular wide QRS tachycardia at 290 beats/min. After 7 seconds the rhythm returned to an irregularly irregular narrow QRS tachycardia at 125-150 beats/min. At a later electrophysiology study there was neither evidence of preexcitation nor inducible supraventricular or ventricular tachycardia. These data suggest that verapamil may have been associated with acceleration of the heart rate. The mechanism of proarrhythmia may be related to an alteration in the atrial rhythm from atrial fibrillation to atrial flutter, with additional factors as well.

Adult

Low prevalences of HIV infection and sexually transmitted disease among female commercial sex workers in Mexico City.

OBJECTIVES: This study tried to determine human immunodeficiency virus (HIV)/sexually transmitted disease (STD) prevalences among female commercial sex workers in Mexico City. METHODS: A sampling frame was constructed that included bars, massage parlors, and street corners. RESULTS: Prevalences for Treponema pallidum, herpes simplex virus type 2, HIV, Neisseria gonorrhoeae, and Chlamydia trachomatis were 6.4%, 65%, 0.6%, 3.7%, and 11.1%, respectively. A significant association was found between higher STD frequencies and working at street sites. CONCLUSIONS: Most STD frequencies were lower in comparison with rates found for female sex workers in other countries. However, preventive programs against STD/ HIV are needed in this population.

Female