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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 289 records · Page 16Linked to original sources

Evaluation of a single injection method, using iohexol, for estimating glomerular filtration rate in cats and dogs.

OBJECTIVE: To evaluate the utility of a method for estimating glomerular filtration rate (GFR) after single IV administration of iohexol. DESIGN: The plasma clearance of iodine (PCI), taken as the quotient of the administered dose of iodine (300 to 600 mg of l/kg of body weight) divided by the area under the plasma iodine concentration versus time curve determined by 4 methods (PCI1-PCI4). The results for PCI were compared with simultaneously obtained values for the urinary clearance of exogenously administered creatinine (CCr), a widely accepted method for the measurement of GFR in cats and dogs. ANIMALS: Cats and dogs that were renal intact (n = 5 cats; n = 1 dog) or had renal mass reduced by partial nephrectomy (n = 5 cats; n = 7 dogs). RESULTS: Values for PCI were closely related (R2 values ranged from 0.947 to 0.992; P < 0.0001 in all cases) to CCr. Despite this close correlation between CCr and PCI, the 95% confidence interval for the difference between PCI3 and CCr included values that exceeded 1.4 ml/min/kg, which represents 50% of the mean value for CCr in renal-intact cats. CONCLUSIONS: Determination of PCI provided a reliable estimate of GFR in cats and dogs of this study. However, differences between 1 of the methods (PCI3) and CCr are clinically important, emphasizing the need to use more than simple linear regression analysis and correlation coefficients when attempting to validate new measurement techniques. CLINICAL RELEVANCE: The determination of PCI provided a reliable estimate of GFR in cats and dogs of this study.

Animals↗

A high frequency of distinct ATM gene mutations in ataxia-telangiectasia.

The clinical features of the autosomal recessive disorder ataxia-telangiectasia (AT) include a progressive cerebellar ataxia, hypersensitivity to ionizing radiation, and an increased susceptibility to malignancies. Epidemiological studies have suggested that AT heterozygotes may also be at increased risk for malignancy, possibly as a consequence of radiation exposure. A gene mutated in AT patients (ATM) has recently been isolated, making mutation screening in both patients and the general population possible. Because of the relatively large size of the ATM gene, the design of screening programs will depend on the types and distribution of mutations in the general population. In this report, we describe 30 mutations identified in a panel of unrelated AT patients and controls. Twenty-five of the 30 were distinct, and most patients were compound heterozygotes. The most frequently detected mutation was found in three different families and had previously been reported in five others. This corresponds to a frequency of 8% of all reported ATM mutations. Twenty-two of the alterations observed would be predicted to lead to protein truncation at sites scattered throughout the molecule. Two fibroblast cell lines, which displayed normal responses to ionizing radiation, also proved to be heterozygous for truncation mutations of ATM. These observations suggest that the carrier frequency of ATM mutations may be sufficiently high to make population screening practical. However, such screening may need to be done prospectively, that is, by searching for new mutations rather than by screening for just those already identified in AT families.

Ataxia Telangiectasia↗

The National Women's Tobacco Control Plan.

Although many health organizations have acknowledged women's tobacco control as a public health priority, to date there has not been a national agenda, nor a coordinating mechanism in place, to ensure the reduction of women's tobacco use and exposure. The Women United Against Tobacco Workshop (the Workshop) was held to address these gaps. The consensus of the Workshop is represented by the National Women's Tobacco Control Plan (the Plan) which outlines goals, priorities, recommendations and implementation steps for reducing women's tobacco use and exposure. The development of a national organization dedicated to implementing the Plan is key to preserving the momentum gained at the Workshop.

Consumer Advocacy↗

Phase I study of high-dose etoposide phosphate in man.

Etoposide is a widely used cytotoxic agent with a broad spectrum of activity in human malignancies. This agent has been incorporated into many transplant regimens although toxicity occurs because of its poor water solubility and toxic excipients. Etoposide phosphate, a water soluble prodrug of etoposide, has been studied at conventional dosages in man and shown to have advantages over the parent compound. We have extended our previous experience with this new agent to evaluate the levels needed in transplantation protocols. This phase I study of intravenous high-dose etoposide phosphate over 2 h on days 1 and 2 was designed to determine whether or not dose linearity between the amount of etoposide phosphate administered to patients and generation of etoposide in vivo as seen with conventional dosages of this agent would be present at transplant-dose levels. In addition, the toxicities of these dose levels with the short infusion schedule were defined. A conservative dose escalation scheme was chosen based upon prior knowledge of etoposide. Thirty-one patients (19 male, 12 female) with CALGB performance status 0-1 with a variety of solid tumors entered this study. The patients were treated with dose levels of etoposide phosphate given as the etoposide-equivalent doses of 250, 500, 750, 1000, 1200, 1400, and 1600 mg/m2/day in 250-400 ml of normal saline given as an intravenous infusion over 2 h on days 1 and 2 every 28 days. After the maximal tolerated dose level was determined on this schedule, additional patients received etoposide phosphate as a 4 h infusion on both days in an attempt to reduce toxicities. G-CSF (5 micrograms/kg/day) was administered subcutaneously to all patients from day 3 until the WBC > or = 10000/microliters. Nonhematologic toxicity was considered to be dose limiting. Serial plasma samples for pharmacokinetics were obtained from patients on day 1 of cycle 1. For the 2 h infusion, the maximum tolerated dose of etoposide phosphate was 1000 mg/m2/day x 2 with dose limiting mucositis. In the small number of patients studied, the maximum tolerated dose was reached for the 4 h infusion at 1400 mg/m2/day of drug, again due to mucositis. Other toxicities, despite the rapid infusion schedule, were modest with transient mild headache being most common. At the highest doses etoposide phosphate was efficiently and rapidly dephosphorylated to etoposide. Etoposide generated by dephosphorylation of etoposide phosphate had plasma disposition curves characteristic of etoposide administered parenterally. One partial response occurred in a patient with small cell lung cancer. Etoposide phosphate can be rapidly infused in modest fluid volumes at dosages required for transplantation protocols with minimal acute side-effects. On a 2 h schedule, mucositis becomes the dose limiting nonhematologic toxicity. Mucositis seems to correlate with peak dose levels of the drug rather than total drug administered. On a 4 h infusion schedule given sequentially for 2 days, the maximum tolerated dosage could be increased 40% compared to the 2 h schedule. The relative ease of administration and the rapid conversion of this prodrug into etoposide should make it useful in high-dose therapy settings.

Adult↗

[Is there a social consensus which defines and understands the problems of conjugal violence?].

Why is that some relationships, initially harmonious, tip into violence and abuse? Many studies have examined the phenomenon to attempt to circumscribe the incidence and seize its dynamics. These studies seem to bring out a social phenomenon of quite serious amplitude. Thus, according to a study conducted by MacLeod and Cadieux in 1980, one in ten women is battered on a regular basis. According to Statistics Canada, in 1993, 25% of Canadian women have been victim of violence by their partner since the age of sixteen. Among this group, 15% are still living with the same partner. Moreover, despite programs destined to help victims of conjugal violence, the number of cases declared appears to have diminished. Such alarming results have brought many researchers to study the problem further. In the last ten years, some progress has thus been realized in the understanding of the phenomenon of violence against women. Programs of intervention, government involvement, judiciarization of certain forms of abuse, sensitization of the public regarding conjugal violence as well as denunciation of cases of violence have marked this progress. In spite of a rising conscience regarding conjugal violence, research sometimes runs up against obstacles. In spite of complex modelization of concepts and factors of prediction of the phenomenon, results sometimes appear disappointing. Thus, is there a social consensus on a definition of the problem and its dynamics? The authors will try to answer this question by reviewing different theoretical approaches used to define conjugal violence. They will then attempt to make a critical analysis of these theories by examining different empirical studies realized in this field.

Domestic Violence↗

Use of the Terumo SP catheter system for crossing the pulmonary valve in infants with critical pulmonary valve stenosis.

In short, this method (the Terumo SP hydrophilic-polymer coated microcatheter system) has proved to be safe, effective, and flexible; it has allowed us to cross critically stenotic valves when standard methods have failed, enabling us to accomplish balloon valvuloplasty with good results in patients who might have otherwise required surgical intervention because of inability to cross the pulmonary valve.

Cardiac Catheterization↗

Is New Zealand's recent increase in campylobacteriosis due to changes in laboratory procedures? A survey of 69 medical laboratories.

AIMS: To evaluate the contribution of changing procedures in microbiology laboratories over the previous 5 years to the increase in campylobacteriosis notifications. To assess whether regional differences in notification rates are due to variations in laboratory procedures. METHODS: A questionnaire was sent to 69 New Zealand medical laboratories, requesting data on their identification procedures for enteric pathogens, including campylobacter. RESULTS: Changes over the last 5 years in laboratory techniques were insufficient to account for a marked increase in campylobacter isolations. On the basis of data provided by 12 laboratories, the number of specimens that grew campylobacter increased by 49% between 1992 and 1993. Differences in laboratory methods do not explain regional differences in campylobacter notification rates. CONCLUSION: Changes in laboratory methodologies over the last 5 years do not appear to account for the recent national increase in campylobacteriosis notifications.

Campylobacter↗

Recommended guidelines for uniform reporting of pediatric advanced life support: the pediatric Utstein Style. A statement for healthcare professionals from a task force of the American Academy of Pediatrics, the American Heart Association, and the European Resuscitation Council. Writing Group.

This consensus document is an attempt to provide an organized method of reporting pediatric ALS data in out-of-hospital, emergency department, and in-hospital settings. For this methodology to gain wide acceptance, the task force encourages development of a common data set for both adult and pediatric ALS interventions. In addition, every effort should be made to ensure that consistent definitions are used in all age groups. As health care changes, we will all be challenged to document the effectiveness of what we currently do and show how new interventions or methods of treatment improve outcome and/or reduce cost. Only through collaborative research will we obtain the necessary data. For these reasons, and to improve the quality of care and patient outcomes, it is the hope of the task force that clinical researchers will follow the recommendations in this document. It is recognized that further refinements of this statement will be needed; these recommendations will improve only when researchers, clinicians, and EMS personnel use them, work with them, and modify them. Suggestions, emendations, and other comments aimed at improving the reporting of pediatric resuscitation should be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital of the King's Daughter, Division of Critical Care Medicine, 601 Children's Lane, Norfolk, VA 23507.

Child↗

Dentists' perceptions of orthodontic services.

In this investigation the orthodontic referral patterns of the dentists working within two FHSA areas in the north of England were surveyed. A sub-sample of 149 of the dentists was selected and they were sent a postal questionnaire directed at their perceptions of the service provided and factors influencing their choice of orthodontist. One hundred and twenty one questionnaires (90%) were returned. It was found that 26.4 of the dentists did not refer an orthodontic patient and 51% referred to only one type of treatment provider. The most important factors governing their choice of orthodontic treatment provider were the length of treatment waiting list (62%) and the standard of treatment provided (66.9). In addition, the dentists' perceptions of the roles of the orthodontic services were not in concordance with those of the orthodontic treatment providers. They also expressed a degree of dissatistfaction with the orthodontic services.

Attitude of Health Personnel↗

A fiber-optic cocaine biosensor.

A fiber-optic biosensor was developed for detection of cocaine, its metabolites, and other coca alkaloids, using a monoclonal antibody (mAb) against a derivatized benzoylecgonine (BE). The mAb was immobilized noncovalently on quartz fibers and a flow fluorometer was used to detect changes in evanescent wave fluorescence. A fluorescein (FL) conjugate of BE bound to the mAb specifically in a saturable manner and with high affinity (Kd = 7.6 nM). Cocaine or other test compounds competed with FL-BE for binding to the mAb in a concentration-dependent manner, thereby reducing the initial rate or steady-state fluorescence. Addition of cocaine to the flow buffer after reaching steady-state fluorescence enhanced the dissociation of bound FL-BE, and cocaine removal allowed fiber regeneration for multiple measurements. The detection limits for cocaine, cocaethylene, norcocaine, and BE were 5, 5, 29, and 30 ng/ml, respectively, but for ecgonine it was 4600 ng/ml and for methylecgonine it was 2000 ng/ml. Tropacocaine was detected at 10 ng/ml, but atropine was detected at 2900 ng/ml. The biosensor discriminated by 833-fold between cocaine and its stereoisomer pseudococaine. Structural features necessary for high-affinity recognition by this mAb are benzoate and 3 beta configuration, both of which are found in BE, cocaine, norcocaine, and cocaethylene.

Antibodies, Monoclonal↗

Recommended guidelines for uniform reporting of pediatric advanced life support: the Pediatric Utstein Style. A statement for healthcare professionals from a task force of the American Academy of Pediatrics, the American Heart Association, and the European Resuscitation Council.

This consensus document is an attempt to provide an organized method of reporting pediatric ALS data in out-of-hospital, emergency department, and in-hospital settings. For this methodology to gain wide acceptance, the task force encourages development of a common data set for both adult and pediatric ALS interventions. In addition, every effort should be made to ensure that consistent definitions are used in all age groups. As health care changes, we will all be challenged to document the effectiveness of what we currently do and show how new interventions or methods of treatment improve outcome and/or reduce cost. Only through collaborative research will we obtain the necessary data. For these reasons, and to improve the quality of care and patient outcomes, it is the hope of the task force that clinical researchers will follow the recommendations in this document. It is recognized that further refinements of this statement will be needed; these recommendations will improve only when researchers, clinicians, and EMS personnel use them, work with them, and modify them. Suggestions, recommendations, and other comments aimed at improving the reporting of pediatric resuscitation should be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital of The King's Daughter, Division of Critical Care Medicine, 601 Children's Lane, Norfolk, VA 23507.

Child↗

Caffeine enhances doxorubicin cardiac toxicity in an animal model.

Based on in vitro data suggesting an interaction between methylxanthines and doxorubicin in regulating Ca2+ across muscle sarcoplasmic reticulum, this study was designed to test the hypothesis that a commonly used methylxanthine, caffeine, might influence the cardiac toxicity of doxorubicin. Three days following doxorubicin treatment, in vivo intracardiac pressures, cardiac outputs, in vitro cardiac weights, and cardiac electron microscopy were performed. Guinea pigs were treated with doxorubicin alone, doxorubicin plus caffeine, caffeine alone, and sterile saline as a control measure. Animals treated with doxorubicin had no significant differences in in vivo hemodynamics compared to the control animals. The average histology score was slightly but not statistically greater than the control animals, score (1.19 +/- 0.36 vs 1.60 +/- 0.34, respectively, P = NS). Animals receiving both doxorubicin and caffeine compared to the control animals had important differences in left ventricular systolic pressure (67 +/- 10 vs 92 +/- 7 mmHg; P = .003), cardiac output (154 +/- 35 vs 217 +/- 41 mL/min; P = .0174), stroke volume (.59 +/- 12 vs .79 +/- .07 mL; P = .0045), and histology score (2.36 +/- 0.21 vs 1.19 +/- 0.36; P = .028). There were no differences in left or right heart filling pressures between treatment groups. As an independent confirmation, there was a weak but statistically significant negative correlation between the biopsy score and cardiac output or stroke volume for all four groups of animals (r = .44, P = .031 and r = -.42, P = .040, respectively). These data are consistent with caffeine and doxorubicin having additive or potentiating effects on cardiac toxicity in this animal model.

Animals↗

Recommended guidelines for uniform reporting of pediatric advanced life support: the pediatric Utstein style.

This statement is the product of a task force meeting held June 8, 1994, in Washington DC in conjunction with the First International Conference on Pediatric Resuscitation and a follow-up task force writing group meeting held September 18, 1994, in Chicago. Draft versions of the statement were circulated for comment to all members of the task force, the American Heart Association Subcommittee on Pediatric Resuscitation, and several outside reviewers. This statement and the International Conference on Pediatric Resuscitation were cosponsored by the American Academy of Pediatrics and the American Heart Association. The development of this statement was authorized by the American Academy of Pediatrics; the American Heart Association National Subcommittees on Pediatric Resuscitation, Basic Life Support, and Advanced Cardiac Life Support, the Committee on Emergency Cardiac Care, the Science Advisory Committee; and the European Resuscitation Council. In addition to the writing group, members of the Pediatric Utstein Task Force are Paul Anderson, M Douglas Baker, Jane Ball, Desmond Bohn, Dena Brownstein, J Michael Dean, Niranjan Kissoon, Bruce Klein, Patrick Malone, Karin McCloskey, James McCrory, P Pearl O'Rourke, Mary Patterson, Charles Schleien, James Seidel, Joseph J Tepas III, and Becky Yano.

Child↗

Octreotide exacerbated fasting hypoglycaemia in a patient with a proinsulinoma; the glucostatic importance of pancreatic glucagon.

Octreotide, a long-acting somatostatin analogue, has been used to alleviate hypoglycaemia in patients with insulinomas. Transient worsening of fasting hypoglycaemia following octreotide has also been described (Stehouwer et al., 1989). We describe a patient with a 'proinsulinoma' in whom octreotide caused rapid and prolonged symptomatic worsening of fasting hypoglycaemia. Catecholamine and cortisol counterregulatory hormonal responses were normal but those of glucagon and GH were impaired. Acute neuroglycopaenic symptoms were present during octreotide induced hypoglycaemia, which was accompanied by and attributed to an acute reduction in pancreatic glucagon secretion in the presence of persistent and unsuppressed hyperproinsulinaemia. This suggests that glucagon may be important in maintaining glucose homeostasis in chronic hypoglycaemia due to endogenous hyperinsulinism even though its concentration in the peripheral blood is not raised.

Blood Glucose↗