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Biomedical subjects

S Kimmel

Publications and source records attributed to S Kimmel.

At least 19 recordsLinked to original sources
PubMed2001

Dual neurokinin NK(1)/NK(2) antagonists: N-[(R,R)-(E)-1-arylmethyl-3-(2-oxo-azepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamides and 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-arylmethyl-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamides.

Based on the structure of N-[(R,R)-(E)-1-(4-chlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (1), attempts to improve the NK(2) affinity have resulted in the discovery of N-[(R,R)-(E)-1-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3,5-bis(trifluoromethyl)benzamide (9, DNK333) exhibiting a 5-fold improved affinity to the NK(2) receptor in comparison to 1. Simplification of the structure via elimination of a chiral centre led to 3-[N'-3,5-bis(trifluoromethyl)benzoyl-N-(3,4-dichlorobenzyl)-N'-methylhydrazino]-N-[(R)-2-oxo-azepan-3-yl]propionamide (22), a potent and fairly balanced NK(1)/NK(2) antagonist.

Animals↗
PubMed2001

Modeling emotion and behavior in animated personas to facilitate human behavior change: the case of the HEART-SENSE game.

The goal of this research is to determine whether a computer based training game (HEART-SENSE) can improve recognition of heart attack symptoms and shift behavioral issues so as to reduce pre-hospitalization delay in seeking treatment. Since treatment delay correlates with adverse outcomes, this research could reduce myocardial infarction mortality and morbidity. In Phase I we created and evaluated a prototype virtual village in which users encounter and help convince synthetic personas to deal appropriately with a variety of heart attack scenarios and delay issues. Innovations made here are: (1) a design for a generic simulator package for promoting health behavior shifts, and (2) algorithms for animated pedagogical agents to reason about how their emotional state ties to patient condition and user progress. Initial results show that users of the game exhibit a significant shift in intention to call 9-1-1 and avoid delay, that multi-media versions of the game foster vividness and memory retention as well as a better understanding of both symptoms and of the need to manage time during a heart attack event. Also, results provide insight into areas where emotive pedagogical agents help and hinder user performance. Finally, we conclude with next steps that will help improve the game and the field of pedagogical agents and tools for simulated worlds for healthcare education and promotion.

Algorithms↗
PubMed2001

Predicting post-coronary bypass surgery atrial arrhythmias from the preoperative electrocardiogram.

BACKGROUND: Atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is a common occurrence and adds to the morbidity and cost associated with the procedure. Various therapies have been demonstrated to reduce the risk of post-CABG AF, but their use should be targeted to high-risk patients. The purpose of this study was to develop a prediction rule for post-CABG AF on the basis of patient age and the preoperative electrocardiogram (ECG). METHODS: The charts of 152 consecutive patients undergoing isolated CABG at one institution were reviewed and the preoperative ECG was analyzed with use of commercially available software. Logistic regression was performed and age-adjusted predictors of the primary end point, any post-CABG AF, were derived. The discriminatory values of the various models were compared by receiver-operating characteristic curves. RESULTS: Sixty-four patients (42.1%) had AF. Multivariable predictors were dichotomized on the basis of variable distribution, and a high-risk patient population was identified by age >65 years, PR interval >/=180 milliseconds (age-adjusted odds ratio [OR] 2.12, P =.05), and a P-wave duration in lead V1 >/=110 milliseconds (age-adjusted OR 2.30, P =.02). CONCLUSIONS: This study demonstrates that post-CABG AF can be predicted preoperatively from patient age and evidence of intra-atrial conduction delay on ECG. Such information can be used to guide prophylactic therapy.

Atrial Fibrillation↗
PubMed2000

Contemporary trends in coronary intervention: a report from the Registry of the Society for Cardiac Angiography and Interventions.

This report of the Registry for the Society for Cardiac Angiography and Interventions provides data on the trends in coronary interventional procedures from the time period June 1966 through December 1998. A total of 19,510 consecutive coronary interventional procedures were recorded. Over this time period, significant trends in coronary stent implantation were recorded along with a decreasing reliance on balloon angioplasty as sole therapy. Patients with acute myocardial infarction comprised an increased fraction of all procedures. Almost half of all interventions were performed in patients with multivessel disease. Finally, decreasing rates of in-hospital death and emergent bypass surgery compared to prior reports from the registry characterize the current practice of interventional cardiology. Cathet. Cardiovasc. Intervent. 49:19-22, 2000.

Aged↗
PubMed1999

T cells are necessary and critical for xenograft rejection in new concordant cardiac xenotransplant model.

BACKGROUND: A new vascularized concordant xenotransplant model using the Chinese hamster as donor and mouse as recipient species is reported. This model takes advantage of the wealth of informative immune reagents and knockout and transgenic backgrounds available for the mouse. METHODS: Heterotopic auxillary cardiac transplantation was performed. The mean survival time was assessed by daily palpation. Xenoreactive antibody production was measured by flow cytometry, and cardiac xenografts were examined by light microscopy. RESULTS: The tempo of xenograft rejection in this model is consistent with concordant species combination. IgM and IgG3 responses were not critical for the concordant xenograft rejection. Long-term survival (>100 days) of the concordant cardiac xenografts was observed without any immunosuppression in nude mice. Reconstitution of nude mice with CD3+ T cells induced the xenograft rejection in 5.7 days (P<0.01). CONCLUSION: This new concordant cardiac xenotransplant model demonstrates that T-dependent xenogeneic immune response is necessary and critical for the xenograft rejection.

Animals↗
PubMed1999

Prognostic significance of atrial fibrillation in patients at a tertiary medical center referred for heart transplantation because of severe heart failure.

Atrial fibrillation (AF) occurs frequently in advanced heart failure. The prognostic significance of AF remains controversial. To determine the relation of AF to survival in patients with advanced heart failure, 234 consecutive patients referred for heart transplantation evaluation from January 1993 to June 1996 were studied to determine the effect of AF on event-free survival (freedom from death, heart transplantation, or placement of a left ventricular assist device). Clinical characteristics of the study population included: age, 51 +/- 17 years; maximum exercise oxygen consumption, 14.2 +/- 5.3 ml/kg/min; left ventricular ejection fraction, 24 +/- 11%; pulmonary capillary wedge pressure, 23 +/- 9 mm Hg; and ischemic etiology, 52%. Medical therapy included: diuretics (86%), angiotensin-converting enzyme inhibitors (80%), digoxin (80%), and anticoagulation therapy (72%). Mean duration of follow-up was 1.1 +/- 1.0 years. Sixty-two patients (27.4%) had AF. One-year event-free survival of the study population was 48%. No difference in event-free survival between patients with and without AF was observed. Univariate predictors of decreased event-free survival included: (1) advanced New York Heart Association class; (2) higher pulmonary capillary wedge pressure; (3) lower cardiac index; (4) lower maximum exercise oxygen consumption; (5) use of inotropic therapy; and (6) greater pulmonary artery systolic pressure. By multivariate analysis, independent predictors of decreased event-free survival included advanced New York Heart Association class (p <0.002) and higher pulmonary capillary wedge pressure (p = 0.02). Thus, AF in patients with advanced heart failure is not associated with decreased event-free survival.

Adult↗
PubMed1998

Head-upright tilt table testing. A safe and easy way to assess neurocardiogenic syncope.

Head-upright tilt table testing has emerged as an exciting technique for evaluating episodes of autonomically mediated syncope. It may be performed using gravity alone as the provocative stimulus or with the addition of isoproterenol. The classic neurocardiogenic response to the test is a sudden drop in blood pressure followed by a decrease in heart rate, but other abnormal response patterns have also been reported. Continuing investigations will improve understanding of autonomic disturbances that cause orthostatic intolerance and will help elaborate the role of tilt table testing in their evaluation and management.

Humans↗
PubMed1998

Growth in children following liver transplantation.

Although liver transplantation (OLT) has become standard therapy for end-stage liver disease in children, growth after OLT remains an area of concern. We reviewed our experience with growth after OLT at the Hospital for Sick Children in 83 patients who survived at least 1 yr post-transplant. Our aims were to describe the success rate in steroid cessation in patients after transplantation, to examine the effect of transplantation on subsequent growth, to see if steroid reduction had a beneficial effect on growth, and to quantify the risk of stopping steroids on rejection. Patients below age 5 yr were weaned off steroids more easily than those over age 5: 19.2% vs. 0% (p<0.05), 65.9% vs. 50%, and 79.5% vs. 37.5% (p<0.05) at post-transplant years 1, 2, and 3, respectively. Pre-transplant, 30% of patients were below the third percentiles for height and weight. Post-transplant, there was a steady improvement in the distribution of patients above the 3rd percentile, so that by post-transplant year 6, only 5% were below the 3rd percentile. Height and height velocity percentiles were found to correlate inversely with total yearly steroid dose (mg/kg) at post-transplant years 2, 3 and 6 (p<0.05). In 60% of patients, steroids were successfully discontinued. In these patients, height and height velocity percentiles have achieved a near normal distribution with 40% and 46% of patients above the 50th percentile for height and height velocity percentiles, respectively. No grafts were lost to rejection in those off steroids, and all rejection episodes were easily reversed. We conclude that the majority of children can be weaned off steroids successfully after OLT and that growth in those children in the presence of good graft function is near normal.

Body Height↗
PubMed1996

Parenteral ketorolac and risk of gastrointestinal and operative site bleeding. A postmarketing surveillance study.

OBJECTIVE: To evaluate the risk of gastrointestinal and operative site bleeding associated with the use of parenteral ketorolac tromethamine. DESIGN: Postmarketing surveillance inception cohort study. SETTING: A total of 35 hospitals throughout the Philadelphia, Pa, region, 1991 to 1993. PATIENTS: Patients administered 10,272 courses of parenteral ketorolac therapy were compared with patients administered 10,247 courses of a parenteral opiate who were matched to the ketorolac patients by hospital, admitting service, and date of initiation of study drug. MAIN OUTCOME MEASURES: Medical records were reviewed for demographics, medical history, doses and duration of study drug, various aspects of the hospital course including surgery and concomitant medications, and adverse events. RESULTS: The multivariate adjusted odds ratio (OR) comparing ketorolac with opiates for gastrointestinal bleeding was 1.30 (95% confidence interval [CI], 1.11 to 1.52); for operative site bleeding, the OR was 1.02 (95% CI, 0.95 to 1.10). The OR was elevated further in subjects 75 years of age or older for both gastrointestinal bleeding (OR = 1.66; 95% CI, 1.23 to 2.25) and operative site bleeding (OR = 1.12; 95% CI, 0.94 to 1.35). A dose-response relationship was evident between average daily ketorolac dose and both gastrointestinal bleeding and operative site bleeding (trend test P < .001 for both). When analgesic therapy lasted 5 or fewer days, ketorolac was associated with only a small increased risk of gastrointestinal bleeding (OR = 1.17; 95% CI, 0.99 to 1.30); when therapy was prolonged beyond 5 days, the OR was 2.20 (95% CI, 1.36 to 3.57). The association of ketorolac with operative site bleeding was not affected by duration of therapy. CONCLUSIONS: The overall associations between ketorolac use and both gastrointestinal bleeding and operative site bleeding are small. However, the risk associated with the drug is larger and clinically important when ketorolac is used in higher doses, in older subjects, and for more than 5 days. Improving physicians' prescribing practices by limiting the dose and duration of ketorolac use, especially in the elderly, should enhance its overall risk-benefit balance.

Adolescent↗
PubMed1992

Inaccuracies in certification of nonmelanoma skin cancer deaths.

Nonmelanoma skin cancer is the most common cancer site in the United States, yet mortality from this cause is poorly understood. We sought medical records of the 16 reported deaths during 1979 through 1987 from this cause (International Classification of Diseases, 9th version [ICD-9], code 173) among Rhode Island residents to evaluate the accuracy of the reported cause of death. Of the 110 cases for which the cause of death could be classified as correct or incorrect, 59 (54%) were misclassified, 49 (83%) of which were mucous-membrane, squamous-cell carcinomas of the head and neck. For most of these, the written death certificate diagnosis was squamous-cell carcinoma of the head and neck, which was coded 173.4. Other problematic diagnoses were cancer of the head and neck and malignant fibrous histiocytoma. In response to a mailed survey, most health departments replied that squamous-cell carcinoma of the head and neck was coded under rubric 173 and malignant fibrous histiocytoma was coded under rubric 171, but there was no unanimity. The misclassification of other causes of death to ICD-9 rubric 173 is substantial. The vast majority were coded to rubric 173.4 and were due to a small number of diagnoses that are recognizable on examination of the death certificate.

Abstracting and Indexing↗
PubMed1991

Nonmelanoma skin cancer mortality. A population-based study.

To estimate the magnitude of nonmelanoma skin cancer mortality and describe its parameters, we reviewed the medical records of all deaths certified as due to this cause among Rhode Island residents from 1979 through 1987. After excluding acquired immunodeficiency syndrome-associated Kaposi's sarcoma, we confirmed that nonmelanoma skin cancer was the cause of death for 51 individuals, a quarter of the number of melanoma deaths reported. The age-adjusted nonmelanoma skin cancer mortality rate was 0.44/10(5) per year. Fifty-nine percent were due to squamous cell carcinoma, and 20% were due to basal cell carcinoma. Most appeared actinically induced. Among deaths from squamous cell carcinoma, the mean age was 73 years. At least 80% of the squamous cell carcinomas metastasized, and 47% arose on the ear. None appeared due to refusal of treatment. Among deaths from basal cell carcinoma, the mean age was 85 years, and refusal of surgical intervention was documented in 40%. Study of nonmelanoma skin cancer mortality provides for estimation of the magnitude of this problem, complements other studies of prognosis, and helps guide prevention, early detection, and treatment.

Adult↗
PubMed1988

Integrating and evaluating online bibliographic searching with clinical experiences of third year medical students.

In this paper, we describe the Clinical Health Information Retrieval Project (CHIRP), a trial program which provided online access to MEDLINE for third year students on medicine and pediatrics clerkships at The University of North Carolina School of Medicine. We present the project evaluation plan, report data from student questionnaires and interviews with the chief residents, clerkship directors, and clerkship coordinators, identify problems encountered, and address considerations for extension of the project.

Attitude of Health Personnel↗
PubMed1987

Non-steroidal anti-inflammatory drugs: how do they work?

Current dogma holds that non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (for example, indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli such as C5-derived peptides and leukotriene B4 even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and Quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the post-stimulation rise in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil enhance intracellular levels of cyclic AMP.

Adult↗
PubMed1985

Modes of action of aspirin-like drugs.

Current dogma holds that nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (e.g., indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli, such as C5-derived peptides and leukotriene B4, even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3 mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the poststimulation increase in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil activation as reflected by their capacity to inhibit movements of Ca and to enhance intracellular levels of cyclic AMP.

Anti-Inflammatory Agents↗
PubMedDate not supplied

Factors associated with emergency department utilization for nonurgent pediatric problems.

OBJECTIVE: To identify specific caretaker and utilization characteristics predictive of the use of the emergency departments (EDs) for nonurgent reasons. Each year more than 20 million children in the United States seek medical care in EDs. Between one third and one half of these visits are for nonurgent reasons. DESIGN: A descriptive study conducted during a 6-month period. SETTING: Two urban hospital EDs. MEASURE: A questionnaire was designed to elicit information about specific caretaker characteristics and their reasons for using the ED for their child's nonurgent medical care. SUBJECTS: Two hundred caretakers and children brought to the ED for nonacute medical care. Caretakers in this study included mothers (82%) with a mean age of 30 years, single caretakers (70%), and unemployed caretakers (60%). The average age of the children was 6.2 years. RESULTS: Most caretakers (92%) reported having a continuity physician for their children. Caretakers who reported being taken to the ED when they were children (P<.002) and those with Medicaid insurance (P<.001) were more likely to view the ED as the usual site of care. Being a single parent was a predictor for nonurgent visits (P<.05). CONCLUSIONS: Predicting which caretakers are at risk for using the ED for nonurgent care when their children are sick provides the primary care physician a means of identifying specific patients who may benefit from interventions designed to promote a more cost-effective approach to using medical resources. Arch Fam Med. 2000;9:1086-1092

Child↗