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Biomedical subjects

W Black

Publications and source records attributed to W Black.

At least 19 recordsLinked to original sources

A pharmacokinetic study of ethanol inhibition of micronuclei induction by urethane in mouse bone marrow erythrocytes.

Urethane (ethyl carbamate) is a genotoxic carcinogen in fermented products and alcoholic beverages. The genotoxicity of urethane requires metabolic activation. Metabolism of urethane is mediated by multiple pathways, and ethanol is known to inhibit the esterase hydrolysis pathway of urethane, which accounts for over 95% of urethane metabolism. This report shows that ethanol also inhibits the induction of micronuclei by urethane in mouse bone marrow erythrocytes, presumably by inhibiting the minor pathway that generates genotoxic metabolite(s). In this study, male CD-1 mice were administered urethane, ethanol, or urethane co-administered with increasing amounts of ethanol in single intraperitoneal injections. Bone marrow polychromatic erythrocytes (PCE) obtained 24 h after injection were scored for micronuclei. The dose of urethane was 1000 mg/kg, and the doses of ethanol were 0, 625, 1250, 2000, 2250, 2500, 3000 and 3500 mg/kg. The blood ethanol level at each dose was determined. Two pharmacokinetic parameters, Cmax and AUC, were estimated for each dose. The observed Cmax of ethanol at doses of 1250, 2000, 2250, 2500, 3000 and 3500 mg/kg were 1.39, 2.84, 3.15, 3.69, 4.13 and 4.76 mg/ml, with AUCs of 1.37, 4.84, 5.88, 7.28, 10.76 and 13.51 mg.h/ml, respectively. Urethane treatment alone markedly increased the micronucleus frequency from 0.1% in the vehicle control to 2.47%. This magnitude of increase was suppressed when urethane was co-administered with ethanol at ethanol doses of 2500 mg/kg and above. At 2500, 3000 and 3500 mg/kg, the micronucleus frequencies reduced from 2.47% to 0.9, 0.44 and 0.28%, respectively. This study shows that ethanol inhibits the induction of micronuclei by urethane.

Animals

Paediatric hospital services: are we satisfying our adolescent patients?

This study evaluated the satisfaction of adolescents with general inpatient services in a paediatric hospital. The results suggest that the adolescents were generally satisfied with the services provided. However, a number of concerns were expressed about the physical characteristics of the wards, the day to day organization of the wards, and the lack of opportunity to participate in treatment planning. The results also suggest that adolescents' satisfaction with inpatient services will be improved if more attention is given to the physical surroundings in hospital wards and the level of privacy afforded to adolescent inpatients. Finally, the results draw attention to the importance adolescents place on being involved in decisions about their treatment planning. There is a great need for studies which focus on adolescents' perceptions of health services. This will help to ensure that adolescents receive services they perceive to be relevant and effective.

Adolescent

Tuberculosis in young adults and the elderly. A prospective comparison study.

OBJECTIVES: To compare the clinical, bacteriologic, and radiologic features of pulmonary and pleural tuberculosis in young adults and the elderly and determine if any differences exist between both groups. DESIGN: Prospective recruitment of all patients diagnosed as having pulmonary and pleural tuberculosis in British Columbia, Canada. SETTING: A population-based sample from a provincial control program TB registry. PATIENTS: A total of 218 consecutive patients whose conditions were diagnosed between January 1990 and May 1991. We excluded 15 HIV-positive patients whose conditions were diagnosed during this study. INTERVENTION: Standardized data collection of symptoms, bacteriology, and review of radiology by two readers blind to the clinical and epidemiologic data. MAIN RESULTS: There were 142 young adult patients and 76 elderly patients. The young adults had a mean age of 41.2 years and the elderly group had a mean age of 75 years of age. Fever (p = 0.002) and night sweats (p = 0.02) were more common in young adults. In culture-proven disease, hemoptysis, fever, and cough were more common in young adult (p = 0.03, 0.02, and 0.01, respectively). There was no difference in the duration of symptoms between the two groups. The odds ratio for cancers other than lung cancer, 3.98 (confidence interval, 1.49, 10.65) in the elderly group was the only significant risk factor to differ between the two groups. Skin test responses to 5TU PPD were positive in 86.2 percent of young adults and 67.6 percent of elderly patients tested (p = 0.03). A total of 79.6 percent of young adults and 88.15 percent of the elderly patients (not significant) were culture positive. Comparison of radiologic findings in young adults vs elderly patients showed no significant differences apart from those with miliary TB 0.7 percent vs 6.7 percent (p = 0.04). CONCLUSIONS: In this population-based study, young adults were more likely to have hemoptysis, fever, and cough and to have a positive PPD response. Cancer was significantly associated as a risk factor in the older age group. There was no difference in bacteriologically proven disease or radiologic findings between the two groups, apart from the more common occurrence of miliary TB in the elderly.

Adult

Report of the International Workshop on Screening for Breast Cancer.

BACKGROUND: Over the past 30 years, eight major randomized controlled trials of breast cancer screening--with mammography and/or clinical breast examination--have been conducted. Results from several trials have been updated during the past year, and initial results of three other trials have been reported. PURPOSE: The National Cancer Institute held an International Workshop on Screening for Breast Cancer in February 1993 to conduct a thorough and objective critical review of the world's most recent clinical trial data on breast cancer screening, consider the new evidence, assess the current state of knowledge, and identify issues needing further research. METHODS: Investigators representing the eight randomized controlled trials of breast cancer screening in women aged 40-74 presented published and unpublished data. Evidence relating to the effectiveness of breast cancer screening in different age groups, especially women aged 40-49, was presented. RESULTS: For women aged 40-49, randomized controlled trials consistently demonstrated no benefit from screening in the first 5-7 years after study entry. A meta-analysis of six trials found a relative risk of 1.08 (95% confidence interval = 0.85-1.39) after 7 years' follow-up. After 10-12 years of follow-up, none of four trials have found a statistically significant benefit in mortality; a combined analysis of Swedish studies showed a statistically insignificant 13% decrease in mortality at 12 years. Only one trial (Health Insurance Plan) has data beyond 12 years of follow-up, and results show a 25% decrease in mortality at 10-18 years. Statistical significance of this result is disputed, however. In women aged 50-69, all studies show mortality reductions; three of four studies show reductions of about 30% at 10-12 years after study entry. Results from two of these trials were statistically significant. Too few women over age 70 have been included in studies for adequate analysis. CONCLUSIONS: For women aged 40-49, randomized controlled trials of breast cancer screening show no benefit 5-7 years after entry. At 10-12 years, benefit is uncertain and, if present, marginal; thereafter, it is unknown. For women aged 50-69, screening reduces breast cancer mortality by about a third. Currently available data for women age 70 or older are inadequate to judge the effectiveness of screening. IMPLICATIONS: Randomized trials have provided stronger scientific evidence regarding the effectiveness of screening for breast cancer than for any other cancer. However, much still needs to be learned. Periodic gatherings of scientists in the field should speed the process.

Adult

Spectrum of tuberculosis in patients with HIV infection in British Columbia: report of 40 cases.

OBJECTIVE: To review the clinical features, treatment and outcome of all known cases of tuberculosis in patients with human immunodeficiency virus (HIV) infection in British Columbia between 1984 and 1990. DESIGN: Retrospective case review. SETTING: Provincial tuberculosis registry and university-affiliated HIV clinic. PATIENTS: All people with HIV infection in whom active tuberculosis was diagnosed during the study period. RESULTS: All 40 patients identified were men; their mean age was 38 years. Of the subjects 30 (75%) were homosexual, 6 (15%) were homosexual and used intravenous drugs, 2 (5%) just used intravenous drugs, and 1 (2%) had had heterosexual contact with prostitutes; for the remaining subject the risk factor for HIV infection was not established. In all cases cultures of specimens from 15 body sources yielded Mycobacterium tuberculosis. Thirty-five of the patients had acquired immunodeficiency syndrome (AIDS), and five had HIV infection uncomplicated except for tuberculosis. In 28 (70%) of the cases no AIDS-defining disease had previously been diagnosed, and in 23 (58%) extrapulmonary tuberculosis represented the AIDS-defining disease. Symptoms at presentation included weight loss (in 80% of the cases), fever (in 75%), cough (in 70%) and night sweats (in 55%). The mean CD4 lymphocyte count was 0.2 x 10(9)/L (in 15 cases). Tuberculin skin test results were positive in 8 of 16 cases. The most striking radiologic finding was intrathoracic adenopathy. All except one of the 36 patients who received appropriate treatment responded favourably at first. Adverse reactions necessitating changes in treatment occurred in 12 (33%) of the cases. Relapse occurred after completion of therapy in two cases (one at 3 weeks and the other at 9 months after treatment was stopped). Tuberculosis was the cause of death in five cases. CONCLUSIONS: Tuberculosis in people with HIV infection commonly presents as extrapulmonary disease and precedes or coincides with other AIDS-defining opportunistic infections. In most cases tuberculosis is the AIDS-defining disease. Even though radiologic findings are often unusual physicians should suspect tuberculosis. A careful examination for evidence of disease at multiple sites should be done. The duration and choice of therapy must be adequate to avoid relapse.

Acquired Immunodeficiency Syndrome

Diastolic potentials recorded by surface electrocardiographic signal averaging during sustained ventricular tachycardia: possible origin from the reentrant circuit.

ECG signal averaging can detect low amplitude diastolic potentials in sinus rhythm. We, therefore, recorded signal-averaged ECGs during eight episodes of inducible uniform sustained VT with coincident atrial pacing to look for continuous diastolic electrical activity. Simultaneous AV pacing in seven patients served as controls. The number of QRS complexes averaged (187 +/- 47 vs 183 +/- 63), the noise level (1.26 +/- 0.88 vs 1.39 +/- 0.47) and cycle length (385 +/- 52 vs 404 +/- 40) did not differ between VT and paced recordings. In each lead the difference in onset between the unfiltered surface recording and the filtered data (40 Hz bidirectional) was significantly greater in VT than the paced recordings (25 +/- 16 vs 11 +/- 8 msec, P = 0.0012). These late diastolic (pre-QRS) potentials were greater than 15 msec duration in 65% of the leads in VT versus 20% of paced recording (P = 0.021). The maximum value was greater than 20 msec in six VT (75%) versus one (14%) paced recording (P = 0.019). The earliest filtered onset in any lead preceeded the earliest surface activity by greater than 12 msec, in 6 VT versus one paced recording (P = 0.019). Early diastolic (post-QRS) potentials were also longer in VT than pacing (49 +/- 40 versus 5 +/- 20, P = 0.001) and exceeded 38 msec in seven of the VTs but none of the paced recordings (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Atrioventricular Node

Inflammatory pseudotumor (pseudosarcoma) of the bladder.

Inflammatory pseudotumor (pseudosarcoma) of the bladder is a benign proliferative lesion of the submucosal stroma easily mistaken for a malignant neoplasm clinically and histologically. The lesion was first described as a separate entity in a report of 2 patients. Three additional cases have been reported since then. We describe pseudosarcomatous bladder tumors arising in 2 adolescents. Both patients presented with sudden onset of gross painless hematuria related to large polypoid and ulcerated bladder masses found on endoscopy. Initial pathological analysis was interpreted as poorly differentiated sarcoma in both patients but subsequent reviews were consistent with a benign process resembling nodular fasciitis. Simple excision in both patients has been successful in eradicating the lesion. The findings in these 2 patients are described with a discussion of the pathophysiology and review of the literature.

Adolescent

Megestrol acetate as primary hormonal therapy for advanced breast cancer.

The records of 133 patients treated with megestrol acetate as primary hormonal therapy for advanced breast cancer were reviewed retrospectively, using International Union Against Cancer (UICC) criteria for response. The median age was 65 years, 121 patients were over age 50, and the age range was 39 to 94 years. Response rates (complete response [CR] + partial response [PR]/total) by qualitative receptor level, with levels of 10 fmol/mg of protein considered positive, were as follows (ER = estrogen receptor, PgR = progesterone receptor): For ER + PgR+, 13 + 15/56 (50%); for those with one positive receptor, 0 + 12/47 (26%); for ER - PgR-, 0 + 0/12 (0%); and for receptor-unknown cases, 2 + 3/18 (14%). Response for ER less than 30 fmol/mg was 2 + 6/39 (21%); for ER 30 to 50, 1 + 5/16 (40%); and for ER greater than 50 fmol/mg, 11 + 15/56 (46%). For PgR less than 30, response was 0 + 6/37 (16%); for PgR 30 to 50 fmol/mg, 1 + 4/14 (36%); and for PgR greater than 50 fmol/mg, 12 + 13/54 (46%). For the 75 patients with a disease-free interval (DFI) of 2 years or less, the response rate was 5 + 1/75 (8%), and for the 58 patients with DFI greater than 2 years, 10 + 12/60 (37%). For patients with prior chemotherapy, 3 + 8/49 (22%) had an objective response. For those with no prior chemotherapy, 12 + 19/84 (37%) responded. Response by dominant site of disease was as follows: soft tissue 12 + 9/43 (49%), bone 2 + 13/49 (31%), viscera 2 + 5/41 (17%). Of these seven patients with visceral dominant disease who responded, all had PgR levels greater than 50 fmol/mg, all but one had an ER level over 100 fmol/mg, all but one were over age 65, and all but two received no prior chemotherapy. We conclude that megestrol acetate is effective initial hormonal therapy for patients with advanced breast cancer. It may have some role to play in the treatment of carefully selected cases with visceral disease.

Adult

The construction of a cloning vector designed for gene replacement in Bordetella pertussis.

We report here the construction of a plasmid cloning vector, pRTP1, designed to facilitate exchange of cloned and chromosomal alleles of the human bacterial pathogen Bordetella pertussis. pRTP1 provides the ability to successively select two homologous recombination events within the cloned sequences. The first is by selection for maintenance of the ampicillin-resistance gene on the plasmid which is unable to replicate autonomously after transfer via conjugation. The second selection, via streptomycin (Sm) selection, is against the maintenance of vector sequences which contain a gene encoding the Sm-sensitive allele of the gene for ribosomal protein S12 thus rendering an otherwise Sm-resistant strain Sm-sensitive. We demonstrate the use of this vector to introduce an unmarked mutation, constructed in vitro, into the chromosomal locus encoding pertussis toxin.

Bordetella pertussis

Sepsis from sinusitis in nasotracheally intubated patients. A diagnostic dilemma.

The cause of sepsis in the intensive care unit patient can be a perplexing diagnostic problem. We have recently encountered seven patients who had sepsis associated with sinusitis of the paranasal sinuses. They represented 26 percent of all patients who had nasotracheal intubation for 5 days or more. Sinusitis as a complication of nasotracheal intubation has been previously reported, but its frequency has not been appreciated. Three case reports are presented to emphasize the importance of making this diagnosis. Standard x-ray studies will not adequately demonstrate all the paranasal sinuses. We have utilized computerized tomography to study these patients and found it to clearly demonstrate all the paranasal sinuses. We suggest a plan to help prevent sinusitis from nasotracheal intubation. Should this complication occur, however, the nasotracheal tube should be removed and the sinuses surgically drained or treated aggressively with topical agents.

Aged

Osseous destruction by neurofibroma diagnosed in infancy as "desmoplastic fibroma".

A 2-month-old male infant presented with a lytic lesion of the distal radius which was diagnosed as desmoplastic fibroma. Tumor recurred following en bloc resection of the distal radius and forearm, necessitating an elbow disarticulation. Subsequently, the child developed multiple café-au-lait spots, and histologic sections have been reinterpreted as neurofibromatosis. This case illustrates the potential difficulty in diagnosing neurofibromatosis when few or no classic stigmata of the disease are present.

Adult

Coronary myointimal hyperplasia in freshwater Lake Michigan salmon (genus Oncorhynchus). Evidence for lipoprotein-related atherosclerosis.

The relationship between plasma lipoprotein concentration and histologic myointimal proliferative lesions in the coronary vessels was examined in 37 freshwater Chinook salmon (Oncorhynchus tshawytscha). The fish were obtained during the migrating, schooling, and spawning periods of the fourth year of life. Plasma apoB polypeptides were maximally elevated in the migrating fish in correlation with a high degree of coronary vascular disease. Both the relative incidence and the severity of lesions were greater in migrating salmon as compared with spawning fish. In contrast, plasma apoA polypeptides were maximally elevated in association with reduced levels of plasma apoB in spawning fish in which coronary lesions were reduced in severity and incidence. Simultaneous observations confirmed the relative decrease in circulating thyroid hormone and increase in adrenal cortical hormones characteristic of the maturation process. These data in the mature freshwater Lake Michigan Chinook salmon provide direct support for the hypothesis that coronary proliferative atherogenesis proceeds in parallel with excessive exposure to apoB-containing lipoproteins and that reversal is associated with excessive exposure to apoA-containing lipoproteins. The temporal relationship to altered hormone status is described, but the pathophysiologic significance for atherogenesis cannot be determined from these data.

Adrenal Cortex Hormones

Development of a hand sensitivity test for the hypersensitive hand.

An instrument was developed to measure the effects of a desensitization program on hand hypersensitivity. It was standardized with 40 "normal" subjects ages 20 to 40 of both sexes and two ethnic groups. Results showed reliability coefficients ranging from .74 to .82 for the three modalities employed in the test. Analyses of variance of agreement between test and retest scores revealed no significant differences in reliability due to hand used, sex, or ethnicity. It was concluded that the instrument could be used as both a clinical and research tool for the measurement of hand sensitivity.

Adult