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Biomedical subjects

J Hare

Publications and source records attributed to J Hare.

At least 37 records · Page 2Linked to original sources
PubMed1993

Cardioversion, defibrillation, and overdrive pacing of ventricular arrhythmias: the effect of moricizine in dogs with sustained monomorphic ventricular tachycardia.

The purpose of this investigation is to define whether the antiarrhythmic drug moricizine has beneficial or adverse effects on currently used antitachycardia and antifibrillatory devices. These studies were performed in a dog model of sustained monomorphic ventricular tachycardia (VT). In 11 dogs, the left anterior descending artery and all surrounding epicardial collateral feeder vessels were ligated. Defibrillator patches were implanted and the dogs were allowed to recover. After a 7-day recovery period, effective refractory period (ERP), end diastolic threshold (EDT), VT induction, and VT and ventricular fibrillation (VF) termination data were collected before and after moricizine infusion (2 mg/kg). In this experimental model, moricizine caused the following electrophysiological changes: a prolongation of the ERP from 173 +/- 14 to 182 +/- 15 (P < 0.02) with no significant effect on the EDT for pacing; a prolongation of the VT cycle length from 175 +/- 18 to 201 +/- 23 msec (P < 0.003); an increased cycle length required for overdrive pacing from 136 +/- 20 to 157 +/- 22 msec (P < 0.01); no effect on the energy required to cardiovert VT; an increase in the defibrillation threshold from 7.5 +/- 4 to 9.4 +/- 4 joules (P < 0.006) and; in 5 of the 8 dogs with VT, the VT could be initiated with somewhat less aggressive stimulation. Significant beneficial electrophysiological physiological effects were noted on the VT cycle length, including a proportionately prolonged overdrive pacing cycle length for VT termination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Characterization and functional analysis of the expression of intercellular adhesion molecule-1 in human papillomavirus-related disease of cervical keratinocytes.

We have investigated the expression of intercellular adhesion molecule-1 (ICAM-1) in squamous neoplasia of the cervix and have noted a significant induction of the molecule in high-grade intra-epithelial lesions. Using monolayer and organotypic in vitro tissue culture systems, we have shown that there is no constitutive ICAM-1 expression on cervical keratinocytes immortalized but not transformed by human papillomavirus type 16, whereas two human papillomaviruses type 16 containing and fully transformed cervical keratinocyte lines do constitutively express the molecule. All cell types, including human papillomavirus-negative normal cervical keratinocytes, can be induced to up-regulate their expression of ICAM-1 by pro-inflammatory cytokines such as interferon-gamma. In addition, we have used an in vitro adhesion assay to show that ICAM-1:lymphocyte function antigen-1 interaction is functionally important in lymphocyte binding to cervical keratinocytes, suggesting a role for ICAM-1 in retaining and enabling functional activity of lymphocytes in the cervix in intraepithelial neoplasia.

Carcinoma in Situ↗
PubMed1992

The S-oxidative degradation of a novel corticosteroid tipredane (INN). Part I: Preliminary investigations into the hydrogen peroxide S-oxidation of tipredane.

The C-17 dithioketal moiety of the corticosteroid tipredane (INN, I) has been shown to undergo peroxide oxidation yielding an array of sulphoxide epimers. All epimers have been isolated and characterized by spectroscopic techniques. Oxidation of the C-17 beta methylthio-substituent appeared to occur exclusively giving a 4:1 ratio of the S:R configuration at the sulphoxide moiety. Both methylthiosulphoxide epimers (V) have been shown to be susceptible to thermolysis yielding the monoethylthio- derivative (VI) via elimination of methylsulphenic acid. As expected from stereochemical considerations at the C-17 position the S epimer has been found to be more susceptible than its corresponding R epimer towards thermolysis. The monomethylthiosulphoxide epimers (III) were produced in a 1:1 ratio, indicating that they were formed from the oxidation of the corresponding monomethylthio- derivative (VII). This probably arose from the elimination of ethylsulphenic acid from the alpha-ethylthiosulphoxide (VIII).

Administration, Topical↗
PubMed1992

Iontophoretic transmyocardial drug delivery. A novel approach to antiarrhythmic drug therapy.

BACKGROUND: Antiarrhythmic drugs often fail to achieve therapeutic effects without toxic systemic levels. Direct transport of drugs into the myocardium may circumvent this problem and may also provide new insights into antiarrhythmic drug effect on arrhythmogenic tissues. In a canine model, procainamide (PA) was delivered iontophoretically using pulsed current synchronized with the ventricular depolarization via an implantable defibrillator patch electrode that was modified to contain a 3.6-ml chamber. Myocardial tissue concentrations of PA were evaluated in 7-day myocardial infarcts (n = 16) that were exposed to 10 minutes of iontophoretic PA delivery and compared with passive diffusion (n = 5) and intravenous (n = 16) PA. These dogs were followed for 3 hours. The infarcted tissue PA levels were compared with normal myocardium. Coronary and systemic blood levels of PA, effective refractory period (ERP), diastolic threshold, and efficacy of ventricular tachycardia (VT) suppression were evaluated throughout the follow-up period. METHODS AND RESULTS: Three hours after 10 minutes of iontophoretic, passive, and intravenous PA, the epicardial layer concentration in the center of the infarcted zone was 840 +/- 853 micrograms/g, 93 +/- 90 micrograms/g, and 15 +/- 8 micrograms/g of tissue, respectively. In the endocardial layer, the PA concentrations with iontophoresis were 38 +/- 57 micrograms/g and were significantly higher than those achieved with either passive diffusion 38 +/- (4 +/- 2 micrograms/g) or with intravenous delivery (11 +/- 5 micrograms/g) (p less than 0.05). Epicardial tissue PA concentrations 3 hours after iontophoresis, passive diffusion, and intravenous PA in the normally perfused tissues were 14 +/- 13 micrograms/g, 3 +/- 2 micrograms/g, and 16 +/- 8 micrograms/g of PA, respectively. Venous blood levels were 2 +/- 3 micrograms/ml 3 hours after iontophoresis, 1 +/- 1 microgram/ml 3 hours after passive PA delivery, and 11 +/- 7 micrograms/ml with intravenous administration (p less than 0.05 intravenous versus passive and iontophoresis). Iontophoretic delivery of PA resulted in 22 +/- 29 msec ERP prolongation intramurally in the infarcted zone with no significant normal tissue ERP prolongation. Passive delivery of PA produced no significant changes in ERP. After intravenous infusion, the ERP in the infarcted zone increased by 35 +/- 29 msec and 13 +/- 12 msec in the normal tissue. Sustained monomorphic VT was induced in 20 animals. In one of these animals, only nonsustained VT could be induced at baseline; however, after intravenous PA, VT could be induced and remained inducible throughout the 3-hour follow-up period. In the iontophoretic delivery group, PA suppressed VT in all of the animals, with termination time ranging from 20 seconds to 7 minutes. In three cases, sustained monomorphic VT could be reinduced, two after 60 minutes and one after 120 minutes. However, in seven dogs, VT could not be induced during the 3-hour follow-up period. None of the dogs in which PA was delivered iontophoretically into the infarcted myocardium developed VT that was not induced before delivery of the drug. Intravenous PA administration resulted in VT suppression in one of 10 dogs. In two dogs, VT could not be induced before intravenous infusion of PA. However, after intravenous PA, VT could be induced. Immunohistochemical mapping of the PA within the infarcted tissue revealed transmural PA distribution. CONCLUSIONS: These data show that 1) the delivery of high transmural concentrations of PA directly into infarcted myocardium is both feasible and effective...

Animals↗
PubMed1992

Agreement between patients and their self-selected surrogates on difficult medical decisions.

BACKGROUND: Several studies have demonstrated that surrogate decision makers often are unable to use substituted judgment when asked to make decisions for incompetent patients. This study further explored this question, using a relatively young, healthy sample of 50 patient/surrogate pairs. METHODS: Patients were randomly recruited from a community family practice clinic and asked to select a surrogate. Five case vignettes were presented to patients and surrogates during separate interviews. Vignettes asked for decisions related to ventilation, resuscitation, and tube feeding for a patient in permanent coma, amputation as life-extending treatment for a mentally confused patient, and chemotherapy for a decisionally incapacitated patient with advanced cancer. Factors considered important to decision making were also investigated. RESULTS: As groups, patients and surrogates were similar as they chose to withdraw or continue treatment in the same proportions. However, within individual pairs, agreement on treatment occurred only 70% of the time even though surrogates were asked to base their treatment decisions on substituted judgment. The kappa coefficients indicated that the rate of agreement in individual vignettes was low. Patients considered "burden on the family" and "time left to live" as the most important factors in choosing among difficult treatment options, while surrogates identified the patients' pain as the most important factor. CONCLUSIONS: The high rate of discrepant decisions underscores the importance of effective patient-surrogate communication before medical decision-making incompetence occurs. The potential of increasing patient-surrogate agreement on difficult medical decisions by educational interventions should be explored.

Adult↗
PubMed1991

Immunocytochemical characterization of large granular lymphocytes in normal cervix and HPV associated disease.

A quantitative immunocytochemical study of large granular lymphocytes (LGLs) in the normal cervix and in human papillomavirus (HPV) associated disease was performed using a panel of monoclonal antibodies which included those for LGL surface markers CD56, CD16, and CD57. Only CD56-positive cells were found within the ectocervical epithelium and these cells increased in number in cervical intraepithelial neoplasia (CIN) in comparison with normal cervix. Examination of serial sections and double labelling suggests that these cells are CD3+, CD8+, CD56+, CD16+. The observed increase in number of this subset was not associated specifically with HPV infection but was related to CIN. Lymphocytes expressing all three LGL markers were found in the stroma and CD16(+)-positive cells clustered around endocervical glands with occasional cells extending into the endocervical epithelium. These results indicate that a small subset of LGLs which express T-cell markers is increased in number in CIN. Cells expressing classical NK markers are restricted to the stroma and are not found within the ectocervical epithelium.

Adult↗
PubMed1989

Nurses' fear of death and comfort level with dying patients.

This study examined differences in nurses' fear of death and level of comfort with patients having a poor prognosis for survival, as a function of the nurses' occupational level, work setting, and level of exposure to such patients. In addition, the relationship among the multidimensional aspects of fear of death and level of comfort with patients' poor prognosis was assessed. The sample included 312 professional and paraprofessional nurses who worked in hospitals and nursing homes. Level of comfort with working with dying patients was found to differ significantly by exposure to such patients and by occupational role. Fear of death for significant others was found to differ significantly by work setting. Finally, a significant inverse relationship was found between comfort working with dying patients and overall fear of death. Suggestions for future research are presented.

Attitude of Health Personnel↗
PubMed1988

Characterization of a new subfamily of class I genes in the H-2 complex of the mouse.

A previously undescribed subfamily of mouse class I MHC genes, consisting of two to three members, has been identified. The structure and organization of one of these, Mb1, has been determined. Mb1 consists of five exons with open reading frames and potentially encodes a class I-like transmembrane protein. In the genome, Mb1 is linked to the H-2 complex, mapping telomeric to Qa. However, this gene has low (ca. 60%) nucleotide identity with other class I sequences and is no more related to mouse class I genes than to class I genes from other species. Mb1 transcripts have not been found in a variety of adult tissues or cell lines, suggesting that, if Mb1 is expressed, its expression is highly regulated. From DNA sequence identity and intron-exon organization, Mb1 appears to be a primordial gene which antedates mouse speciation and which has evolved independently of the rest of the class I gene family. Examination of various species of wild mice demonstrates the presence of a discrete Mb1 subfamily over long evolutionary periods of time.

Amino Acid Sequence↗
PubMed1988

Predictors of burnout in professional and paraprofessional nurses working in hospitals and nursing homes.

Burnout is a phenomenon in which the cumulative effects of a stressful work environment gradually overwhelm the defenses of staff members, forcing them to psychologically withdraw. To understand the experience of professional and paraprofessional nurses suffering from burnout requires a close examination of the environments in which they function. This study examined interpersonal, intrapersonal and situational factors expected to contribute to the six dimensions of burnout among nursing staff who worked in acute care and long-term care health facilities. The sample included 312 professional and paraprofessional nurses. The following research question was explored using a series of stepwise multiple regression analyses: of the following variables interpersonal (professional exposure to patients with poor prognosis for survival, work relationships, informal support), intrapersonal (coping strategies, fear of death, comfort working with patients with poor prognosis for survival) and situational (personal and work demographics), which are the significant predictors of the six dimensions of burnout in professional and paraprofessional nurses? Findings revealed that work relationships and tension-releasing and instrumental problem-focused coping were the most powerful predictors of burnout. Based upon this, it was concluded that nursing burnout is both an organizational and a personal problem. Recommendations for practice are presented.

Acute Disease↗
PubMed1986

Functional translation of exercise responses from graded exercise testing to exercise training.

This study attempts to develop a quantitative approach to the prescription of absolute exercise intensity during level ground ambulation (min/mile) or cycle ergometry (kpm) from responses observed during GXT. A total of 345 subjects performed GXT and exercise training sessions with either the Bruce treadmill protocol and level ground ambulation (N = 154) or cycle ergometry (N = 191). Responses from 90% of each group were used to generate equations for predicting training pace (or power output) from the time (or power output) during the GXT when target HR was achieved. FAI was also included in the prediction of training pace (or power output). The remaining 10% of subjects in each group were used to cross-validate the prediction equations. The correlation between the time (or power output) during GXT when the training HR was observed and the pace of ambulation (or power output) was 0.70 for treadmill walking and 0.88 for cycle-cycle. Correlations were increased by the addition of FAI to the prediction equation. The results of this investigation suggest that the absolute intensity of exercise for training can be predicted accurately from GXT results.

Cardiac Rehabilitation↗