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Biomedical subjects

A Hartman

Publications and source records attributed to A Hartman.

At least 19 recordsLinked to original sources

No adverse effect of vincristine on handwriting in children after completion of therapy.

BACKGROUND: Long-term writing difficulties in children after treatment with vincristine for acute lymphoblastic leukemia, Wilms tumor, B non-Hodgkin lymphoma, and malignant mesenchymal tumors, were investigated. PROCEDURE: Handwriting of 33 survivors and 33 controls matched for age, sex, and grade, was assessed with the BHK-scale. The examiner was blinded for whether a child was a case or a control. RESULTS: No significant difference in writing speed was found. Mean difference in number of letters produced during 5 min was 6.4 (+/-67.1, range -103 to +169). No significant difference was found in quality of writing scores; mean difference in points was 1.5 (+/-7.7, range -19 to +22). Cumulative vincristine dose, age at diagnosis or time since completion of treatment did not affect writing speed or quality. CONCLUSION: Chemotherapy, including vincristine, does not lead to long-term problems in speed or quality of writing in children treated for cancer.

Antineoplastic Agents, Phytogenic↗

Evaluation of the pharmacokinetic interaction between fluvastatin XL and cyclosporine in renal transplant recipients.

OBJECTIVE: To assess the pharmacokinetic interaction between cyclosporine and extended-release fluvastatin (fluvastatin XL), 80 mg for 7 days, in stable renal transplant recipients. METHODS: This was a single-center, open-label study. 17 renal transplant recipients received their standard cyclosporine therapy (Days 1 - 9) plus a once-daily single oral dose of fluvastatin XL, 80 mg (Days 2 - 8). Blood samples were collected and cyclosporine (whole blood) and fluvastatin (plasma) concentrations determined by radioimmunoassay and HPLC fluorescence detection, respectively. Pharmacokinetic parameters were calculated using non-compartment analysis and fluvastatin results were compared with historical controls. RESULTS: Treatment with fluvastatin XL, 80 mg for 7 days, had no significant effect on either the AUC0-12 (3,644 ng x h/ml in the absence of fluvastatin vs. 3,534 ng x h/ml in the presence of fluvastatin) or the Cmax of cyclosporine (983 ng/ml in the absence of fluvastatin vs. 945 ng/ml in the presence of fluvastatin). Co-administration of fluvastatin XL also had no effect on the tmax, t1/2 or apparent clearance (CL/F) of cyclosporine in renal transplant patients. The AUC and Cmax for fluvastatin XL in the presence of cyclosporine (AUC0-24 1,192 ng. x h/ml, Cmax 271 ng/ml) were approximately 2-fold higher compared with historical data for fluvastatin XL alone in healthy volunteers (AUC0-24 630 ng x h/ml, Cmax 102 ng/ml) but lower than the historical data for fluvastatin IR, 40 mg b.i.d. alone in healthy volunteers (AUC0-24 1,340 ng x h/ml, Cmax 443 ng/ml). Tmax, t1/2 and trough levels of fluvastatin in the presence of cyclosporine were also similar to the historical controls. Concomitant administration of cyclosporine and fluvastatin XL was well tolerated by renal transplant recipients. CONCLUSIONS: Fluvastatin XL, 80 mg, and cyclosporine do not show clinically relevant pharmacokinetic interactions.

Administration, Oral↗

Magnesium sulfate in the treatment of refractory ventricular fibrillation in the prehospital setting.

OBJECTIVE: To determine if magnesium sulfate (MgSO(4)) improves outcome in cardiac arrest patients initially in ventricular fibrillation (VF). METHODS: Randomized, prospective, double blind, placebo-controlled, multicenter prehospital trial using 2 g of MgSO(4). Eligible patients were non-traumatic cardiac arrest patients (> or =18 years of age) presenting in VF. The protocol included those patients refractory to three electroshocks. Epinephrine and either 2 g of MgSO(4) or placebo (normal saline) were then administered. The primary outcome variable was return of spontaneous circulation (ROSC) in the field and a perfusing pulse on arrival at the ED. Secondary endpoints included admission to the hospital (ADMT) and hospital discharge (DISC). IRB approval was obtained at all participating centers. RESULTS: Total 116 patients (58 MgSO(4), 58 placebo) were enrolled during the period from 4/1992 to 10/96 with 109 available. There were no significant differences between the groups in baseline characteristics and times to cardio pulmonary resuscitation (CPR), advanced life support (ALS), and first defibrillation, except for time to study drug administration. There was no significant differences in ROSC (placebo, 18.5%, and MgSO(4), 25.5%, P=0.38), ADMT (placebo rate=16.7%, MgSO(4)=16.4%, P=1.0) or DISC (placebo rate=3.7%, MgSO(4)=3.6%, P=1.0). CONCLUSIONS: We failed to demonstrate that the administration of 2 g of MgSO(4) to prehospital cardiac arrest patients presenting in VF improves short or long term survival.

Adolescent↗

Validation of beighton score and prevalence of connective tissue signs in 773 Dutch children.

OBJECTIVE: Validation of the Beighton Score and the prevalence of connective tissue signs were investigated in Dutch children. METHODS: Hypermobility investigation according to Beighton was undertaken in 773 healthy children aged 4-12 years. An inventory of the signs that fitted with connective tissue disorders was compiled. RESULTS: The percentage of general hypermobility at a cutoff point of > or = 4 was 26.5% (range 11.4-49%) in children aged 4-9 yrs. At the age of 10-12 yrs, this percentage was 5.3% (range 0-7.1%). There was good agreement (kappa = 0.65) between the measurement on the left and the right sides at all ages. Of the investigated connective tissue signs, thin transparent skin was noted in 0.1%, blue sclerae in 0.1%, and an elevated palate in 2.3% of the children. It was observed that 8.2% of the children were able to touch their nose with their tongue (Gorlin's sign) and 23.7% were able to touch their chin. The other signs were not observed in any of the children. CONCLUSION: We validated the criteria for performing the Beighton Score in (Dutch) children. A cutoff point of > or = 5 should be chosen for Dutch children aged between 4 and 9 years. It appeared that one-sided Beighton Score could be determined during screening of healthy populations. Additional diagnostic tests are warranted if one of the following signs, such as a thin transparent skin, hyperelastic skin, large hematomas, prominent scars, molluscoid tumors, striae distensae, blue sclerae, elevated palate, and Gorlin's sign, is encountered in a child. Although it is not possible to extrapolate the data, we expect that the findings are relevant for children of Caucasian race.

Child↗

Adolescents with special health care needs in transition: three life histories.

PURPOSE: This study was part of a large multi-method inquiry designed to examine the service and support needs of adolescents with special health care needs who are transitioning to adulthood. METHODS: A multiple case study methodology relying on life history was used to ascertain perspectives of the parents on the longitudinal events and factors in the lives of adolescents with special health care needs that shaped or currently influence adolescent transition to adulthood. Three informants were purposively selected to depict a range of health and socio-economic conditions. Long interviews were conducted and audiotaped and transcribed data were thematically and taxonomically analyzed. RESULTS: Six major themes emerged in the analysis: (1) Begetting a service system, (2) Pathology or not pathology, (3) Educational stability vs. interruptions, (4) Role blurring of parents and providers, (5) Private life made public, and (6) Independence vs. burden. CONCLUSIONS: The study revealed that, consistent with the literature, adolescents with special health care needs do not follow typical developmental sequences, although their needs and desires are no different than those of typical adolescents. The lives of the adolescents and their families are significantly influenced by the timing and nature of the diagnosis, the family's articulation with service providers, and the degree to which school systems are responsive to atypical adolescents. Implications for health providers and future inquiry are advanced.

Adolescent↗

Potent selective nonpeptidic inhibitors of human lung tryptase.

Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure-activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented.

Asthma↗

The American Stop Smoking Intervention Study. Conceptual framework and evaluation design.

Reducing tobacco use, especially cigarette smoking, is a public health priority. The American Stop Smoking Intervention Study (ASSIST) was initiated in 1991 to prevent and reduce tobacco use primarily through policy-based approaches to alter the social-political environment. This article describes the conceptual design, research framework, evaluation components, and analytic strategies that are guiding the evaluation of this demonstration research endeavor. The ASSIST evaluation is a unique analysis of the complex relationships between the social context, public health activity at the state level, tobacco use, and individual behavior. The measures of tobacco control activity developed for this evaluation may be useful in ongoing national cancer control surveillance efforts, and the lessons learned will enhance the development of tobacco control programs.

Humans↗

Neuroimmunologic implications in coronary artery disease.

In this review, the role of the macrophage in the pathophysiology of coronary artery disease (CAD) is examined. The central interaction of macrophage, endothelial cell and smooth muscle cell in the context of hyperlipidemia is considered. The macrophage appears to be at the beginning of a chain of events that starts with elevated low density lipoprotein (LDL). Stress, particularly in those with a core hostility, may be associated not only with higher catecholamine levels but also with higher serum lipid levels. These lipids will in turn be processed to oxidized LDL by macrophage and endothelial cells. Oxidized LDL molecules will contribute to atherosclerotic plaquing. A side effect of such plaque formation may be a diminished vasodilatory response to the nitric oxide (NO) produced by macrophages and endothelium. Indeed, paradoxical vasoconstriction occurs in atherosclerosis in response to neurotransmitters such as serotonin and acetylcholine, which under normal circumstances cause vasodilation. There also is evidence that both macrophages and endothelial cells can regulate NO production through a specific mu 3 morphine receptor, an effect that can be blocked by naloxone. The clinical effectiveness of morphine and nitroglycerin in CAD patients may relate to these mechanisms. More research will be needed to elucidate the neuroimmunologic basis for atherosclerosis with prospects for better treatment and management in future.

Animals↗

Presence of the mu3 opiate receptor in endothelial cells. Coupling to nitric oxide production and vasodilation.

Initial confinement of opiate receptors to the nervous system has recently been broadened to several other cell types. Based on the well established hypotensive effect of morphine, we hypothesized that endothelial cells may represent a target for this opiate substance. Endothelial cells (human arterial and rat microvascular) contain a high affinity, saturable opiate binding site presumed to mediate the morphine effects that is stereoselectively and characteristically antagonized by naloxone. This opiate alkaloid-specific binding site is insensitive to opioid peptides. It is, therefore, considered to be the same subtype of opiate receptor (designated mu3) used in the mediation of morphine in other cell types exhibiting the same binding profile. Experiments with endothelial cultures and the aortic ring of rats cultured in vitro demonstrate that morphine exerts direct modulatory control over the activities of endothelial cells, which leads to vasodilation. It induces the production of nitric oxide, a process that is sensitive to naloxone antagonism and nitric oxide synthase inhibition. In contrast with that of opiates, the administration of opioid peptides does not induce nitric oxide production by endothelial cells. In conclusion, the data presented above reveal a novel site of morphine action, endothelial cells, where a mu3 receptor is coupled to nitric oxide release and vasodilation.

Animals↗

Improving food frequency questionnaires: a qualitative approach using cognitive interviewing.

In an attempt to improve data quality and ease of administration of standard self-administered food frequency questionnaires, various alternative approaches were tried for inquiring about frequency of consumption, portion size, seasonal intake, and food preparation. Evaluation consisted of a cognitive interviewing method in which respondents verbalize their thought process while completing several variations of a questionnaire. Interviewers observed and asked follow-up probe questions to evaluate problems or inconsistencies verbalized by respondents. Consensus and judgment by interviewers and observers suggested several problematic features of food frequency questionnaires: formatting of questions about frequency and portion size; computing average frequencies for aggregated food items or for foods eaten seasonally; comprehension of many items; and ordering of foods. These findings led to cognitive refinement and innovations, which included detailed questions regarding preparation or use of low-fat varieties or other alternatives to help better describe specifics of intake for some foods; questions on seasonal intake for several foods; inclusion of portion size ranges; and additional response categories for frequency of intake. Cognitive interviewing is an important step in pinpointing cognitive problems in dietary questionnaires.

Aged↗

Initial clinical experience with rectus sheath grafts in congenital heart defects.

This study reports on the initial clinical experience using anterior rectus sheath as potentially growing graft material in congenital heart lesions. The first seven patients with complex congenital lesions requiring a rectus sheath graft because of inadequate available pericardium are reviewed. The initial operations were: TOF (unicusp pulmonary valve) (re-op), two Konno procedures (one VSD and one RV patch), two arterial switch procedures for TGA (neoaortic augmentation), two Fontan (re-op) atrial augmentation patch and pulmonary arterioplasty (re-op). Ages ranged from 1 week to 15 years. Follow-up ranged from 1 to 72 months and included open visual inspection at reoperation in 5 cases, angiography in 3 cases, and echocardiography in 4 cases. One early respiratory death occurred in the fourth postoperative week. So far no early bleeding from rectus sheath patches, infection, aneurysmal dilatation, or scar contraction was observed. No manifestation of peripheral emboli was seen. Hernias of the harvest site were absent. We concluded that in absence of pericardium and in areas where future cicatrization or aneurysmal dilatation is undesirable, anterior rectus sheath appears to be a reasonable alternative.

Adolescent↗

Can energy adjustment separate the effects of energy from those of specific macronutrients?

Energy adjustment is used in nutritional epidemiology in an attempt to separate specific effects of macronutrients (carbohydrate, fat, and protein) from one another and from the generic effect of the total quantity of energy consumed. However, models in which the risk of disease is allowed to depend simultaneously on daily total energy consumption and separate components of energy that sum to the total are not identifiable: the specific effects of individual macronutrients and the generic effect of energy cannot be disentangled by multivariate analysis. The standard, residual, and partition methods exclude one or more macronutrients from consideration, thereby allowing estimation, but the parameters that are estimated no longer represent specific macronutrient or generic energy effects. Therefore, an interpretation of a regression coefficient from these methods as a specific effect of a macronutrient or as the generic effect of energy requires additional, almost always questionable, assumptions. For example, a conclusion based on data alone that there is a specific fat effect upon the development of breast cancer but no specific effects of other macronutrients and no generic energy effect is not possible. Notwithstanding these serious problems, some useful etiologic inference still can be made.

Energy Metabolism↗

Outpatient studies of the safety and immunogenicity of an auxotrophic Escherichia coli K-12-Shigella flexneri 2a hybrid vaccine candidate, EcSf2a-2.

A phase II study was conducted in 244 volunteers at Fort Ord, CA, to determine the safety and immunogenicity of EcSf2a-2, a live, oral Shigella vaccine constructed by transfer of genes from Shigella flexneri to Escherichia coli K-12. In this placebo-controlled study, four doses of vaccine ranging from 2.3 to 9.0 x 10(8) colony-forming units were given on days 0, 3, 14 and 17. Vaccine shedding occurred from 1 to 3 days after each dose. The vaccine was well tolerated at every dose tested. Significant levels of IgA, IgG or IgM antibody-secreting cells (ASC) recognizing S. flexneri 2a lipopolysaccharide (LPS) were found in 94% of a volunteer subset tested 7 days after the first dose of EcSf2a-2. Seven days after the third dose, ASC were detected less often (57%), and were mainly IgA. Significant rises in serum antibody to LPS were detected in 37% of vaccine recipients.

Adult↗