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Biomedical subjects

M J Feldman

Publications and source records attributed to M J Feldman.

At least 37 records · Page 2Linked to original sources

Oxypurinol protects normothermic ischemic hearts.

Rabbit hearts were mounted on a Langendorff apparatus and after measurement of baseline hemodynamic function exposed to 30 minutes normothermic arrest. Hearts were reperfused at 37 degrees C with buffer solution containing oxypurinol in different concentration: group II (0.01 mM), group III (0.1 mM), group IV (1 mM). Group I did not receive active drug and served as control. Each group consisted of eight hearts. After reperfusion, hemodynamic function was again measured and compared to baseline. Groups III and IV showed significantly less deterioration (p less than 0.05) than the control, while group II was better than the control, but in general differences were nonsignificant. We conclude that oxypurinol ameliorates ischemic cardiac damage following normothermic cardiac arrest. The beneficial effect of oxypurinol is most likely due to the drug's scavenging effect of oxygen-free radicals.

Animals↗

Prevention of reperfusion injury in ischemic-reperfused hearts by oxypurinol and allopurinol.

We investigated the effects of the xanthine oxidase inhibitor allopurinol and its metabolite oxypurinol on isolated rabbit hearts. To assess the potential role of these drugs in preventing reperfusion injury, hearts were perfused using Langendorff techniques, held globally ischemic for 3 h at 15 degrees C, and then reperfused. During perfusion, hearts received Krebs-Henseleit solution maintained at 37 degrees C. Aortic perfusion pressure was held constant at 80 cm H2O. Prior to ischemia, hearts were arrested with a constant volume of KCl cardioplegia. Using a left ventricular (LV) balloon, developed pressures were measured prior to and following global ischemia. In addition, coronary circulation (CC) was measured before and after ischemia. All hearts were paced at 260 beats/min. We studied four groups: group 1 received 1 mM allopurinol, group 2 received 1 mM oxypurinol, group 3 received 90 IU/ml superoxide dismutase (SOD) plus 8085 IU/ml catalase (CAT), and group 4 received no treatment and served as a control. Each group consisted of 8 animals. Hearts receiving drug treatment did so during the first 5 min of reperfusion. Displaying all data as a function of LV volume, postischemic values were compared to preischemic values. Multivariate analysis and Tukey tests were used to detect significant differences between groups. When compared to the control group, all drug-treated groups significantly recovered end-diastolic function. Peak systolic pressure decreased significantly in the SOD/CAT group as compared to all other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗

Sulfinpyrazone prolongs survival and decreases platelet uptake of heart allografts.

The purpose of this study was to evaluate the potential benefit of the platelet active drug sulfinpyrazone (SPZ) on uptake of indium-III-oxine (111In)-labeled platelets and survival of rat heart allografts. Lewis rats bearing ACI heterotopic heart transplants were treated with SPZ in high, intermediate, or low doses. In 111-labeled platelet uptake was measured 5 days postoperatively and calculated as a ratio between the transplanted and native hearts. Left and right ventricles were measured separately. SPZ given in doses of 400 and 200 mg/kg daily significantly decreased platelet uptake in the graft and reduced the ratio of uptake between transplanted and native hearts (P less than 0.05). In animals treated with SPZ 100 mg/kg/day platelet uptake was not significantly less than that of the nontreated control animals. Survival of allografts was determined by daily palpation and compared to vehicle-treated controls. Mean graft survival was prolonged for animals treated with 100 mg/kg and 200 mg/kg daily, i.e., 19.0 +/- 3.02 and 11.42 +/- 1.97 days, respectively. Animals administered 400 mg/kg did not have longer graft survival than controls (6.63 +/- 0.66 versus 6.31 +/- 0.18 days). Most animals in the 400 mg/kg group died as a result of adverse side effects of the drug. We conclude that SPZ in low to intermediate doses prolongs allografted heart survival. The enhanced survival in the lower dose group may in part be due to mechanisms other than platelet adhesiveness.

Animals↗

Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats.

There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection.

Animals↗

Leukotrienes in experimental spinal cord injury.

Leukotrienes are a group of noncyclized fatty acid eicosanoids which are formed from the breakdown of arachidonic acid. They are potent mediators of inflammation and may contribute to secondary injury in the central nervous system. All mammalian tissue including cerebral cortex is capable of synthesizing these; however, clear documentation of leukotriene formation in the spinal cord is lacking. We subjected 55 rabbits to weight drops of 200, 300, and 400 gm/cm, respectively, on an exposed spinal cord. The traumatized spinal cord was removed after periods of 15, 30, and 45 minutes and 1, 2, 4, 8, and 24 hours. Radioimmunoassay for leukotriene B-4 was then performed on the specimens. Significant (p less than 0.05) elevation was noted in the 200 and 300 gm/cm groups with peak levels occurring in the first 4 hours. The 400 gm/cm group showed significant depression of values below control levels from 2 to 24 hours. We conclude that in sublethal central nervous system injury leukotrienes are produced in significant amounts and may contribute to secondary spinal cord injury.

Animals↗

Normal catch-up growth in rats severely food-restricted prior to lesions of the dorsomedial hypothalamic nucleus: the first 48 hours.

Following a brief period of ad lib (AL) feeding, 45-day-old male Sprague-Dawley rats were either fed AL or food-restricted (REST) for 21 days to 50% of the intake of the AL rats. At this time, some AL and some REST rats received electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL), whereas other AL and REST rats were sham-operated (CON). Following this, all rats were refed (REF) AL and killed two days later. At this time, DMNL-REST + REF and DMNL-AL weighed as much as CON-REST + REF and CON-AL, whereas the body weight of the DMNL-AL group began to separate from the CON-AL group; carcass lipid and protein were normal among the groups. DMNL-AL laid down more % lipid and % protein/g food eaten than CON-AL; this was not the case in the REST + REF groups. DMNL-AL were hypophagic vs. CON-AL, but DMNL-REST + REF ate as much as CON-REST + REF. Compared to DMNL-AL, DMNL-REST + REF increased their food intake more than four-fold and also utilized food energy more efficiently than DMNL-AL rats. Epididymal fat pads and kidneys were smaller in REST + REF vs. AL groups, irrespective of brain manipulation. Plasma glucose and growth hormone were normal among the groups, but plasma insulin concentrations were higher in REST + REF DMNL and CON groups vs. DMNL-AL and CON-AL, respectively. Glucose incorporation into epididymal fat pad lipid and CO2 and liver lipid was elevated in REST-REF groups vs. respective AL groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The relationship between knowledge about acquired immunodeficiency syndrome and the implementation of universal precautions by registered nurses.

The relationship between the level of knowledge of registered nurses (RNs) concerning acquired immunodeficiency syndrome (AIDS)-related issues and the practical observance of universal precautions was studied. It was hypothesized that the more knowledge a nurse has concerning AIDS the more likely he or she is to implement universal precautions. All registered nurses who have direct patient contact (N = 400) and are employed at a Northeastern teaching medical center, were provided a packet of three questionnaires and encouraged to participate. Two hundred thirteen (53%) RNs returned completed questionnaires. Subgroups were examined for trends relating such parameters as age and the amount of AIDS knowledge, using analysis of variance. The major hypothesis was tested by correlating the overall scores for AIDS knowledge and the implementation score. Results indicated no relationship between knowledge and the implementation of universal precautions (r = -0.12). When evaluating scores according to work areas, those subjects with higher knowledge scores had lower practice scores. Other demographic variables showed no influence on either knowledge or implementation scores as measured by this study. Further study is needed to understand what factors will motivate RNs to implement universal precautions.

Acquired Immunodeficiency Syndrome↗

Dietary protein restriction and renal injury in the spontaneously hypertensive rat.

We examined the influence of a low-protein diet on the course of the renal injury in spontaneously hypertensive rats (SHR) and SHR given antihypertensive drug therapy (SHRD). Antihypertensive drug treatment was hydralazine, reserpine, and chlorothiazide. Wistar-Kyoto (WKY) rats served as normotensive controls. SHR, SHRD, and WKY were each placed on a 24, 14, and 10% protein diet at 5 wk and followed to 80-90 wk of age. Untreated SHR showed a steady rise in protein excretion from 5 to 70 wk regardless of dietary protein content. Protein excretion in SHRD on a 24% protein diet was similar to untreated SHR. However, SHRD on a 14 or 10% diet had a more moderate increase in protein excretion. Glomerular, tubular, and vascular pathology in untreated SHR was not influenced by dietary protein intake. Despite successful antihypertensive therapy, kidney pathology in SHRD on a 24% diet was not significantly different from untreated SHR. In contrast, SHRD on 14 or 10% protein diets had less segmental glomerulosclerosis and vascular pathology than untreated SHR. The results indicate that dietary protein restriction does not influence the course of renal injury in untreated SHR. However, the combination of antihypertensive drug therapy with protein restriction in SHR delays and may arrest progression of glomerulosclerosis and proteinuria.

Animals↗

Nurse practitioner perceptions of facilitators and constraints to practice.

The purpose of this study was to identify and explain conditions that served to constrain and/or facilitate the practice of Veterans Administration (VA) nurse practitioners (NPs). A 60% stratified random sample of all full-time VA NPs was surveyed. The sample represented NPs from the four hospital complexity levels and six geographic regions. A 92% response rate was obtained for a sample of 257 NPs. On the whole, VA NPs appeared to experience more facilitation than constraint. Areas that seemed to be especially positive for VA NPs were related to the direct delivery of care, and areas that interfered with their practice were related to administrative issues. NP practice is facilitated if there is a feeling of status, opportunity for professional growth, and NP personal satisfaction. Status can be influenced by independence in practice, support from top nurse administrators, and enough clerical support. Professional growth can be enhanced by providing opportunities for continuing education, research, physician back-up, and medical center committee membership. Personal satisfaction may be promoted through job security, independence in practice, fringe benefits, continuity of caseload, and opportunity for promotion. Throughout the analyses, independence repeatedly surfaced as an important criterion in the facilitation of NP practice.

Delivery of Health Care↗

Further evidence for the existence of an "organismic" set point in rats with dorsomedial hypothalamic nucleus lesions (DMNL rats): normal catch-up growth.

The present study was performed to assess the capacity of rats with dorsomedial hypothalamic nucleus lesions (DMNL rats) and sham-operated controls (CON) for catch-up growth following body weight (b.wt.) reduction prior to DMNL (and sham-lesion) production. Male SD rats (45 days, 157 +/- 1.3 g) were maintained for 11 days ad lib (ADLIB) after arrival and then divided into two groups. One group continued to feed ADLIB, the other group was fed half of the ration eaten by ADLIB rats for 32 days. At this point each group was divided into two subgroups. One subgroup received DMNL, the other subgroup consisted of CON. From then on all rats were fed ADLIB [except for one group of CON that was pair-fed to the ADLIB DMNL rats (PF-CON)] for 37 days (69th day of experiment) and then killed. DMNL rats lesioned at normal b.wt. (ADLIB DMNL) showed a precipitous drop in food intake, b.wt. and efficiency of food utilization (EFU). In striking contrast, rats that had received DMNL after b.wt. restriction (REST DMNL) and were then refed ADLIB showed a dramatic rise in food intake, b.wt., change in b.wt. and EFU, the latter being almost twice that of the ADLIB DMNL. Notably, the PF-CON weighed less than the ADLIB CON and utilized food poorer than ADLIB CON, REST CON and ADLIB DMNL. Liver weight (both absolute and relative (per kg 3/4 b.wt.) was reduced in DMNL irrespective of dietary treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recovery of rats with dorsomedial hypothalamic nucleus lesions (DMNL rats) from body weight restriction: effect of duration of postoperative prerestriction period.

The present study was performed to see whether somatic and underlying metabolic-adaptive responses of DMNL rats and sham-operated controls (CON) to body weight restriction and subsequent refeeding could be influenced by the duration of ad lib feeding between lesion production and start of restriction. In contrast to previous studies (42 and 55 days, respectively) this time was reduced to 25 days. Restriction was similar, i.e., 27 days. DMNL rats show the same adaptive capacity in most parameters as do restricted CON. However, this response was at a lower level of absolute body weight, appropriate, so it appears, for their DMNL-induced lower body weight. In some parameters different responses were noted, however, suggesting that the time of ad lib feeding following the DMNL does indeed affect adaptive responses. Notably, this is the case in both DMNL and CON commensurately. Linear growth was reduced by restriction in the present but not in the two previous studies. Food intake showed a pronounced "overshoot" on refeeding but did not previously. Efficiency of food utilization was normal in the present study but depressed previously. A rise in plasma free fatty acids was not evident but was so in previous experiments. We concluded that, although DMNL rats respond to food restriction and recovery like similarly-treated CON, the duration of the ad lib feeding before restriction and/or the absolute age of the animals at that time, do indeed affect some parameters. This may be related to the fact that different aspects of the DMNL syndrome declare themselves in a sequential rather than a simultaneous manner.

Adipose Tissue↗

Future research recommendations for establishing NP effectiveness.

An information synthesis was conducted to examine nurse practitioner effectiveness as substantiated in existing literature. After an extensive computerized and manual search of the literature, 248 documents judged by staff to be relevant to the topic were reviewed by a content-area expert (N = 11 members), and a methodology expert (N = 8 members). Experts had been chosen on the basis of multiple nominations from an extensive national survey of professional nurses in leadership positions. Upon completing the respective reviews, experts identified key areas in support of NP effectiveness that had not been established or clarified in existing literature. A summary and discussion of the experts' recommendations for future studies in support of nurse practitioner effectiveness are presented.

Costs and Cost Analysis↗

Cost analysis of antibiotics in the management of perforated or gangrenous appendicitis.

Costs associated with treating patients for gangrenous or perforated appendicitis were compared. Patients received single agent therapy with cefoperazone or cefamandole or combination antibiotics consisting of clindamycin and serum level-adjusted gentamicin. Forty-eight patients received cefamandole, 47 received cefoperazone, and 52 received combination clindamycin and gentamicin. Costs to the pharmacy for drugs were greater for the combination therapy; however, the higher failure rate associated with the cephalosporins created greater expenses for the single agent therapy than for combination therapy.

Adolescent↗

Fibrin seal--an alternative to suture repair in experimental pulmonary surgery.

Fibrin seal (FS) a biological tissue adhesive was evaluated as a sealant of lung parenchyma. New Zealand White (NZW) rabbits underwent a right upper lobe wedge resection. The defect was repaired with FS, suture (S), or a combination of S and FS (SFS). Five rabbits from each treatment group were sacrificed on postoperative Days 1, 3, and 14. The ventilatory pressure required to produce air leak was measured and the wet weight of normal vs hemorrhagic lung tissue determined. Although leak pressure was lowest in FS on Day 1 (P less than 0.05), leak pressure was equal to S and SFS of Day 3 and highest on Day 14 (P less than 0.01). FS-treated lungs had less hemorrhagic tissue than S and SFS (P less than 0.0001). Microscopically S and SFS repairs had large areas of hemorrhagic necrosis while FS showed minimal changes. We conclude that FS is an effective sealant of lung parenchyma.

Animals↗

Somatic, metabolic and endocrine correlates of set point recovery in food-restricted and ad lib-fed weanling rats with dorsomedial hypothalamic lesions.

Male Sprague-Dawley rats received either electrolytic lesions in the dorsomedial hypothalamic nuclei (DMNL rats) or sham-operations (CON), and were fed lab chow ad lib for 41 post-operative (POP) days. Subsequently one lesioned (DNML-AL) and one control group (CON-AL) continued to receive lab chow ad lib until the end of the experiment (POP day 78). A second lesioned (DMNL-RE) and control group (CON-RE) were given 80% of the amount of food eaten by their ad lib-fed counterparts for 28 days. At this time several rats from each group were killed. The remaining animals were then given lab chow ad lib for nine days and then also killed. Both DMNL-RE and CON-RE recovered their lowered body weight, food intake and feeding efficiency and showed the same pattern and relative magnitude as their ad lib-fed counterparts. Similarly, carcass lipid, epididymal fat pad lipid, incorporation of glucose-U-C14 into fat pad saponifiable lipid, total lipid, total glycogen (DPM/protein), liver protein, incorporation of glucose into liver CO2 and concentrations of plasma glucose, glycerol, triglycerides and free fatty acids normalized on refeeding to the same extent and in the same pattern in DMNL-RE as in CON-RE. In contrast to previous studies, plasma insulin was lower in DMNL-AL than in CON-AL but DMNL-RE and CON-RE had similar levels on refeeding. Also on refeeding, both DMNL-RE and CON-RE showed the same enhanced glucose incorporation into liver total lipid. The data show that DMNL rats, although smaller in size and hypophagic in absolute terms, recovered lost body weight--at least under our relative mild reduction of 80% of their ad lib-fed controls--with the same competence and in the same time interval as sham-operated controls. It is quite possible that a more severe restriction of body weight would have uncovered some deficits in DMNL rats, however. Under the constraints of the present experimental arrangement, the data strengthen previous evidence for the existence in DMNL rats of an "organismic" set point that makes for a "scaled-down" but homeostatically normal animal.

Animals↗

The effect of in vivo glucose administration on human erythrocyte Ca2+-ATPase activity and on enzyme responsiveness in vitro to thyroid hormone and calmodulin.

To characterize endogenous control mechanisms for human erythrocyte membrane Ca2+-ATPase ("calcium pump") activity, we studied the effect of changes in blood glucose concentration in vivo within the physiologic range on Ca2+-ATPase activity in red cells. Red cells obtained in the course of induced hyperglycemia were also studied to determine susceptibility of membrane Ca2+-ATPase to stimulation in vitro by thyroid hormone and calmodulin, both of which have been shown previously to enhance Ca2+-ATPase activity. Oral glucose administration (75 g) to eight healthy, adult subjects induced predictable increases in concentrations of blood glucose and immunoreactive insulin. Basal levels of activity of Ca2+-ATPase in red cells obtained after glucose ingestion fell 55% (P less than 0.025) by 30 min after glucose with recovery of enzyme activity to levels not significantly different from basal by 60 min. Activity of red cell Ca2+-ATPase at time zero was significantly stimulated in vitro by thyroxine (T4, 10(-10) M), triiodo-L-thyronine (T3, 10(-10) M), and calmodulin (100 ng/mg membrane protein). In vivo glucose administration led to depression of red cell enzyme responsiveness in vitro to T4 and T3; recovery from this effect did not occur by 120 min after oral administration of glucose. Calmodulin responsiveness of the enzyme in vitro was less significantly reduced in red cells obtained after glucose ingestion. Intravenous (i.v.) glucose administration (20 g) to five subjects also led to decreased basal enzyme activity (61% of fasting level at 20 min). A significant decrease in response of enzyme to T4 was achieved by 8 min after glucose administration (P less than 0.02), with recovery by 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A comparison of the practices used for distribution of controlled substances in Massachusetts hospitals with those reported nationally.

A survey questionnaire concerning the procedures used to distribute controlled substances was mailed to 100 randomly selected Massachusetts hospital pharmacies. The tabulated results were compared to a similar study surveying 285 short-term medical and surgical hospitals nationwide. Of the 58 responding hospitals, 47 (81%) reported controlling either all or some Schedule III Controlled Substances in a manner similar to that used for the distribution and accountability of Schedule II drugs. A total of 42 (72%) reported maintaining the same systems for Schedule IV agents. In contrast, only 24 (42%) of those respondents reported controlling Schedule V drugs in a manner similar to Schedule II Controlled Substances. Similar to the findings of a nationwide study, many of the responding Massachusetts hospitals reported selective inclusion of those Schedule III, IV, and V drugs possessing an increased risk of illicit diversion into a more controlled distribution system. In conclusion, many Massachusetts hospitals distribute and account for controlled substances in a manner similar to that used nationwide.

Drug and Narcotic Control↗