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Biomedical subjects

M Child

Publications and source records attributed to M Child.

13 recordsLinked to original sources
PubMed2006

Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir in healthy volunteers.

Mycobacterium tuberculosis is a concern in patients with human immunodeficiency virus (HIV) infection. Rifampin (RIF), an agent used against M. tuberculosis, is contraindicated with most HIV protease inhibitors. Atazanavir (ATV) has clinical efficacy comparable to a standard of care regimen in naive patients and, when dosed with low-dose ritonavir (RTV), also in treatment-experienced patients. We evaluated here the safety and pharmacokinetics of ATV, resulting from three regimens of ATV, RTV, and RIF in 71 healthy subjects. The pharmacokinetics for ATV and RTV were assessed after 6 and 10 days of dosing with ATV 400 mg (n = 53) and with ATV-RTV at 300 and 100 mg (ATV/RTV 300/100; n = 52), respectively. Steady-state pharmacokinetics for ATV, RTV, RIF, and desacetyl-rifampin (des-RIF) were measured after 10 days of dosing of ATV/RTV/RIF 300/100/600 (n = 17), ATV/RTV/RIF 300/200/600 (n = 17), or ATV/RTV/RIF 400/200/600 (n = 14). An RIF 600-alone arm was enrolled as a control group (n = 18). With ATV/RTV/RIF 400/200/600, ATV area under the concentration-time curve values were comparable, but the C(min) values were lower relative to ATV 400 alone. ATV exposures were substantially reduced for the other RIF-containing regimens relative to ATV 400 alone and for all regimens relative to ATV/RTV 300/100 alone. RIF and des-RIF exposures were 1.6- to 2.5-fold higher than with RIF 600 alone. The incidence of grade 3/4 alanine aminotransferase/aspartate aminotransferase values was limited to 1 subject each in both the ATV/RTV/RIF 300/200/600 and the ATV/RTV/RIF 400/200/600 treatments. Coadministration of ATV with RIF was safe and generally well tolerated. Since ATV exposures were reduced in all regimens, ATV and RIF should not be coadministered at the dosing regimens studied.

Anti-HIV Agents↗
PubMed2003

Cell-cell interactions influence resistance and survival of Salmonella serotype Typhimurium to environmental stress.

AIMS: The aim of this work was to study the effects of prolonged nutrient stress on survival, cell interactions and resistance to inimical processes in Salmonella serotype Typhimurium. METHODS AND RESULTS: Salmonella Typhimurium cells were subjected to prolonged incubation in the stationary phase of growth and the properties of starved cells (old) were investigated with reference to those of exponentially-growing cells (young). Competition experiments between old and young cells revealed cell-cell interactions that influenced stationary phase survival and response of the bacterium to heat stress. During prolonged incubation of cells, cycles of resistance and sensitivity to heat stress were identified. Competition experiments between old and young cells revealed that the resistance of young cells to heat increased to levels more like those of stationary phase cells than growing cells. The presence of old cells influenced the phenotype of young cells, possibly by means of cell-cell interactions. There was no evidence for the involvement of any extracellularly-produced factors in this phenomenon, but a requirement that the old competitor cells be viable could be demonstrated. CONCLUSIONS: It is proposed that the complex interactions within stationary phase cultures of Salm. Typhimurium may be due to cycles of mutation in concert with an as yet undefined interaction between old cells and growing ones. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides evidence for active and diverse responses to nutrient stress within populations of Salm. Typhimurium that promote survival and that may be important for the success of this bacterium as a pathogen.

Cell Communication↗
PubMed1999

[The early angiographic follow-up of myocardial revascularization in a minithoracotomy: the results of the first 100 consecutive cases].

The use of the left internal thoracic artery anastomized to the left anterior descending coronary artery via a small left thoracotomy to revascularize the anterior wall of the left ventricle has gained wide acceptance since its introduction into clinical practice a few years ago. A mandatory, postoperative angiographic control was suggested in order to check the surgical results of this new method of revascularization. We herein analyze the results of the in-hospital angiographic control of a series of 100 consecutive patients who underwent minimally invasive coronary artery bypass. In all 100 patients the thoracic graft, the anastomosis and the target vessel were patent, with no anomalies in 90 subjects. In 4 patients, a sharp angulation of the thoracic artery in the last third before the anastomosis to the native vessel was observed; in 3 subjects, the arterial graft had been anastomized to a diseased tract of the target vessel and in 3 cases a significant stenosis of the target vessel beyond the anastomosis was documented; in 2 cases the persistence of a thoracic artery branch was discovered. Since 1) neither in-hospital total occlusion of the thoracic graft to the left anterior descending coronary artery via a small thoracotomy was documented nor a significant incidence of major anomalies was observed; 2) the anomalies documented seem to be clinically negligible and may regress in the midterm postoperative period; 3) Doppler flow analysis is able to detect not only the patency but also the presence of significant stenosis in the arterial graft; the in-hospital angiographic control of this surgical technique should be limited to patients with abnormal ultrasonic data or with reappearance of myocardial ischemia in the anterior wall of the left ventricle, thus not reducing the advantages in terms of speed and cost-control of this type of myocardial revascularization.

Aged↗
PubMed1999

Refractory coronary artery spasm with superimposed thrombosis: successful treatment with Palmaz-Schatz stent.

Prinzmetal variant angina due to epicardial coronary artery spasm is a disease usually treated with drug therapy with successful results. A case of variant angina, refractory to conventional pharmacological treatment, and complicated by coronary artery thrombosis, was treated with percutaneous transluminal coronary angioplasty and stenting with good immediate and late clinical results.

Aged↗
PubMed1998

Neonatal sex hormones have 'organizational' effects on the hypothalamic-pituitary-adrenal axis of male rats.

Sex hormones have activational effects on the hypothalamic-pituitary-adrenal (HPA) axis in adulthood: For example, corticosterone release is influenced by gonadal status. These experiments investigated whether sex hormones have organizational effects on the HPA axis of male rats: Do sex hormones have relatively permanent effects on its development? In adults, both neonatal (neoGDX) and adult gonadectomy (adult GDX) resulted in elevated corticosterone (CORT) levels in response to stress compared to intact rats. Five days of testosterone propionate (TP) replacement was not as effective at attenuating CORT levels in neoGDX rats as in adult GDX rats. Neonatal GDX elevated corticosterone binding globulin (CBG) levels, whereas adult GDX was without effect. In Experiment 2 the effects of neonatal gonadectomy and neonatal treatment with either TP, estradiol benzoate (EB), or oil vehicle was examined. Despite 14 days of hormone replacement, neoGDX showed elevated CORT levels in response to stress compared to all other groups. A single neonatal dose of TP or EB in neoGDX rats eliminated the increased responsiveness. Neonatal TP and EB were without effect in sham-operated rats. Plasma CBG levels were elevated in neoGDX groups regardless of neonatal hormone treatment. Corticosteroid receptor binding levels were examined in various brain areas and the pituitary in two groups most different in their androgen experience: NeoGDX and shams that did not receive treatments as adults. NeoGDX had lower levels of glucocorticoid receptor, and higher levels of mineralocorticoid receptor binding in the pituitary. No other receptor differences were found. These experiments suggest that neonatal sex hormones influence the sensitivity of the HPA axis to sex hormones in adulthood and, thus, that they have organizational effects in addition to activational effects on HPA function.

Animals↗
PubMed1997

Assessment of left internal mammary artery grafts using dipyridamole Doppler echocardiography.

Color Doppler echocardiography of the left mammary artery was combined with dipyridamole testing in order to assess the presence of significant (>70%) graft stenosis in 87 patients with a mammary artery graft to the left anterior descending coronary artery presenting with chest pain. Occluded grafts are detected by absent diastolic flow velocities at baseline, whereas the response of the diastolic flow velocity to dipyridamole distinguishes patients with critical versus noncritical stenosis of a patent graft.

Blood Flow Velocity↗
PubMed1995

Prompt and safe femoral hemostasis with a collagen device after intracoronary implantation of Palmaz-Schatz stents.

We report the safety and efficacy of sealing the femoral puncture site with percutaneously applied collagen after Palmaz-Schatz stent implantation in 100 consecutive patients. Patients were anticoagulated with continuous heparin infusion, overlapping oral anticoagulants, and antiplatelet therapy by dextran, aspirin, and dipyridamole. At the time of sheath removal and collagen application, the mean activated partial thromboplastin time and prothrombin time values expressed as international normalized ratio were 3.2 +/- 2.1 and 1.6 +/- 0.7, respectively. The hemostasis time ranged from 1 to 8 minutes (mean 2.18 +/- 2.08 minutes). Only two (2%) patients had major puncture-site bleeding (not seal related in one case) that required surgery and blood transfusions. Small (< 6 cm) and medium (6 to 10 cm) hematomas observed in 12 (12%) and 2 (2%) patients, respectively, resolved spontaneously without sequelae. Local infection developed in 2 (2%) patients, who were successfully treated with antibiotics without clinical consequences. Subacute stent thrombosis was observed in only 1 (1%) patient. Repeat catheterization through the same femoral artery was performed at 6-month follow-up in 55 patients without difficulty or vascular complications. These findings suggest that percutaneous collagen application after coronary stenting is a secure method of achieving prompt and effective femoral hemostasis with a low incidence of major vascular bleeding complications despite intense anticoagulation. Stable hemostasis may allow continued full-dose anticoagulation, reducing the risk of stent subacute thrombosis.

Administration, Cutaneous↗
PubMed1987

Antigenic stimulation and the occurrence of multiple myeloma.

To evaluate whether potent or prolonged stimulation of the immune system increases the risk of multiple myeloma, the authors compared 698 myeloma cases which occurred between July 1, 1977 and June 30, 1981 in four geographic areas of the United States with 1,683 demographically similar controls from the same areas. Cases and controls were interviewed about past exposures which may have involved antigenic challenge. Although few positive associations emerged, those most consistent with the immune stimulation hypothesis were modest associations between myeloma and a history of rheumatic fever (relative risk (RR) = 1.74, 95% confidence interval (CI) = 1.09-2.77) and between myeloma and urinary tract infection (RR = 1.30, 95% CI = 1.00-1.69, when self-respondent cases were compared with controls). Little association was found between the risk of myeloma and the number of past viral illnesses, number of bacterial illnesses, or number of allergy desensitization injections. Myeloma risk was found to be inversely related to the number of diseases against which a subject reported having been immunized, perhaps because of differences in socioeconomic status between cases and controls. These findings provide little support for the immune system stimulation hypothesis of myeloma etiology, but because of the limitations of interview techniques for assessing antigen exposure, further studies using laboratory methods may be warranted.

Aged↗
PubMed1987

Changing cigarette habits and bladder cancer risk: a case-control study.

With the use of data from the 8,764 subjects in the National Bladder Cancer Study, the separate contribution of various aspects of a person's cigarette smoking history to his increased risk of bladder cancer was estimated. These estimates have not been previously available, owing to the smaller sizes of earlier studies. Our data indicated that people who have only smoked unfiltered cigarettes have higher risks than those who have only smoked filtered cigarettes but that people who have switched from unfiltered to filtered have experienced no reduction in risk. Our data also indicated that smoking cessation substantially reduced the risk. The former smoker appeared to benefit both because he stopped adding to the burden of irreversible damage and because he ceased being exposed to some reversible hazard. Thus the former smoker had a lower risk than the current smoker even though they had smoked the same number of cigarettes daily for the same number of years, but the former smoker's risk remained higher than the risk of a person who never smoked. Our data suggest that one-half of the bladder cancer occurring among men in the United States and one-third of that among women is caused by cigarette smoking.

Adult↗
PubMed1986

Toxic substance exposure and multiple myeloma: a case-control study.

By means of a population-based, multicenter case-control investigation, certain toxic substances were evaluated as risk factors for multiple myeloma. Interviews were completed on 698 subjects with newly diagnosed multiple myeloma, and 1,683 controls were selected from the same geographic areas as those of the cases. Respondents were asked if they had ever been "highly" exposed" to one or more of a list of toxic substances or to other substances not on the list. With the aid of a toxicologist, responses were then categorized into 20 exposure groups. Those who reported past exposure to pesticides had an estimated relative risk of 2.6 for multiple myeloma [95% confidence interval (CI) = 1.5-4.6]. Subjects exposed to a variety of compounds commonly used by painters had an estimated relative risk of 1.6 (95% CI = 1.1-2.4). An increased risk also was found for those who were exposed to sources of carbon monoxide (relative risk = 1.8, 95% CI = 1.0-3.2). Associations of borderline statistical significance were found for metals and organically high polymers (plastics and elastomers). No statistically significant associations were seen for exposure to fertilizers; dyes and inks; alkalies; acids; other caustic substances; chemical asphyxiants; aliphatic, chlorinated, or aromatic hydrocarbons; aldehydes and ketones; ethers; esters; oils; dusts; or asbestos.

Adult↗
PubMed1977

Familial cancer in the general population.

In the course of collecting samples of human milk for the National Cancer Institute, family histories have been assembled since 1971. Ages, causes of death, reproductive histories, and the history and age of occurrence of cancer were obtained for all first degree relatives of the proband's parents. Two thousand and ninety cancers were identified in 31,945 persons. Cancers were confirmed by pathology reports, hospitals' and doctors' records, or death certificates. Of the family lineages, 65.9% had no cancers and 8.0% had two or more. For all cancers taken together, clustering was not significant but there was significantly more observed than expected cancers in lineages with cancer of breast, ovary, skin, corpus uteri, stomach, rectum, lung and bronchus, or colon. Little or no excess was observed in lineages with leukemia, lymphoma, and cancer of the cervix or prostate. The relative risk of breast cancer was increased 1.5 times for daughters and 3.8 times for sisters of women with the disease.

Breast Neoplasms↗