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Biomedical subjects

M Hinds

Publications and source records attributed to M Hinds.

At least 19 recordsLinked to original sources

Motivational forces affecting participation in post-registration degree courses and effects on home and work life: a qualitative study.

Over the past decade, pre- and post-registration education for nurses and midwives in the United Kingdom has undergone major change, creating an atmosphere where continuing professional development is a matter of priority for individual health care staff. Against this context of change, and as part of a larger study of continuing education and training in the National Health Service, a cohort of participants in a part-time health studies degree course were interviewed using a semi-structured schedule. Twenty-nine nurses, midwives and allied professional staff described their motives for participation in the course and its effects on their professional and personal lives. Data collected in interviews were analysed using qualitative methods and revealed that participation was encouraged by both professional and personal factors. For many staff participation was prompted by negative feelings about themselves and their professional status. Participation in the course was associated with (largely negative) changes in home and family life and most participants faced additional financial burdens. The findings of the study have implications for policy relating to the funding of continual professional education for nurses and other health care staff. Health care staff are receiving mixed messages about continuing education from policy makers and employers. Dependence on willingness and ability to pay for post-registration degree-level studies is unlikely to be an efficient or equitable means of ensuring lifelong learning for healthcare staff.

Adult

Maintenance of atrial fibrillation in anesthetized and unanesthetized sheep using cholinergic drive.

Atrial fibrillation (AF) was induced electrically and the duration of AF was measured in six isoflurane-anesthetized sheep (weight range 54.5-72.7 kg), and in five unanesthetized sheep (weight range 60-75 kg). In the anesthetized sheep, AF was induced by direct electrical stimulation of the right atrium with a catheter electrode and the duration of AF was determined. Intravenous neostigmine (10 micrograms/kg IV) was administered and the duration of AF was again measured. Then cholinergic drive was increased by bilateral electrical vagal stimulation; AF was induced and the duration of AF was measured. In the anesthetized animals with no neostigmine or vagal stimulation, 34% of the episodes of AF lasted 10 seconds, 11% lasted 20 seconds, and only 1% lasted 200 seconds. However, in one anesthetized animal AF was sustained for 4,800 seconds with no drug or vagal support. The administration of neostigmine alone in 3 anesthetized animals more than doubled the average duration of AF. In the animals with vagal stimulation (after neostigmine), AF persisted throughout stimulation, but ceased shortly after vagal stimulation was terminated at 2,220, 4,500, and 3,840 seconds. The AF frequency ranged from 325-750/min. The unanesthetized sheep were lightly sedated with a small dose (200 micrograms/kg IM) of xylazine to make them less sensitive to environmental noise; then AF was induced and its duration was timed. After these measurements, neostigmine was administered (30 micrograms/kg IM) and cholinergic drive was produced reflexly by intravenous injection of 60-2,000 micrograms of phenylephrine. AF was electrically induced at the time of maximum reflex slowing in heart rate. For the control (no drug) studies, 64% of the AF episodes lasted 10 seconds, 20% lasted 20 seconds, and only 2% of the episodes lasted as long as 140 seconds. When phenylephrine was injected after neostigmine to provide increased cholinergic drive, the duration of fibrillation depended on the dose of phenylephrine. In a 60-kg sheep, the duration of AF increased from 1 second with an intravenous dose of 60 micrograms to 700 seconds with an intravenous dose of 2,000 micrograms. However, there was a considerable range in responsiveness to the reflex cholinergic drive provided by the intravenous phenylephrine; for example a single intravenous 500-micrograms dose produced AF ranging from 190-540 seconds among the sheep. The duration of AF was most controllable in the anesthetized sheep, following neostigmine administration and with bilateral vagal stimulation. In the unanesthetized sheep, AF could generally be sustained for more than the duration of the half-life (about 4 minutes) of phenylephrine following neostigmine. However, there was a large variation in the duration of AF among the animals for the same dose of phenylephrine. This study identifies two methods (direct vagal stimulation and reflex vagal stimulation) for providing the cholinergic drive needed to sustain AF in the adult sheep. The duration of AF is sufficiently long to enable the measurement of electrical atrial defibrillation threshold.

Anesthesia, General

Effects of oral creatine supplementation on multiple sprint cycle performance.

This study examined the influence of oral creatine monohydrate supplementation on repeated 10 s cycle ergometer sprint performance. Seventeen recreationally active males (mean +/- SD age, body mass, height, and peak oxygen uptake = 20.5 +/- 1.2 yr, 72.1 +/- 10.3 kg, 176.8 +/- 6.6 cm and 3.87 +/- 0.91 l.min-1, respectively) participated in the 16 day experiment. All subjects initially completed a VO2peak test and were then administered glucose (4 x 10 g per day) in a single blind fashion for four days, after which they completed the first series of multiple sprints (7 x 10 s). Following the sprints, subjects were matched on sprint performance and divided into two groups (n = 8, placebo (Pl); and n = 9, creatine (Cr)). For the following four days, diets were supplemented with either Cr (4 x 70 mg.kg-1 body mass per day mixed with 5 g glucose) or glucose (4 x 10 g per day); supplementation during this phase was double-blind. Subjects then repeated the multiple sprint and VO2peak tests. Measures of peak power output (PPO), mean power output (MPO), end-power output (EPO), and percent power decline were recorded during the sprints. Each 10 s sprint was separated by 30 s of passive recovery except for sprints five and six which were separated by five minutes. Venous blood was sampled at rest, immediately after sprint five, before sprint six, and following sprint seven for the analysis of plasma lactate and blood pH. Expired air was sampled for five minutes following sprint seven for the calculation of post-exercise VO2. Analysis of variance revealed that four days of Cr supplementation did not influence multiple sprint performance, plasma lactate, blood pH and excess post-sprint oxygen consumption. Furthermore, VO2peak was unchanged following Cr supplementation. The data suggest that either the four day period of Cr supplementation failed to significantly raise resting muscle [Cr], or that multiple sprint performance was not enhanced by increases in resting muscle [Cr].

Adult

The pumping and left ventricular unloading capabilities of the ventricular synchronous skeletal-muscle ventricle.

The pumping and left ventricular unloading capabilities of the left ventricular, ventricular synchronous skeletal-muscle ventricle were determined in nine anesthetized dogs ranging in weight from 20.7 to 31.8 kg. The ventricular synchronous skeletal-muscle ventricle consists of the left rectus abdominis muscle wrapped around a 4-mil-thick polyethylene pouch (wrapped volume 80 to 100 ml) connected to the left ventricular apex with no valve and to the aorta via a prosthetic heart valve. The rectus muscle is timed to contract tetanically and relax during left ventricular ejection. This arrangement provides a high precontraction pressure for the rectus muscle and a high muscle capillary blood flow during skeletal muscle relaxation. The timing signal for initiation of the train of stimulating pulses (40/sec) was derived from the ventricular electrogram. The delay for the stimulus train determines the preload for the rectus muscle and along with the stimulus train duration determines ventricular synchronous skeletal-muscle ventricle stroke volume, which was measured by electric impedance. With unconditioned rectus muscles (70 to 120 gm) and with a pumping ratio of 1:3, ventricular synchronous skeletal-muscle ventricle stroke volume average 26.1 ml, which provided an average output of 876 ml/min. The normalized ventricular synchronous skeletal-muscle ventricle output was 35.6 ml/min per kilogram of body weight. In a typical resting dog (and man), the normalized cardiac output is 70 ml/min per kilogram. Therefore the ventricular synchronous skeletal-muscle ventricle is capable of pumping 52% of the cardiac output (with a pumping ratio of 1:3). The optimum train delay from the apex of the ventricular electrogram ranged from 10 to 100 msec. The left ventricular ejection period averaged 309 msec, and this determines the time available for the rectus muscle to contract and relax. Evidence for unloading the left ventricle is shown by the reduced left ventricular diastolic pressure and stroke volume for the postassisted beats.

Animals

Phorbol regulation of topoisomerases I and II in human leukemia cells. Studies in an additional cell pair sensitive or resistant to phorbol-induced differentiation.

We previously reported (Zwelling et al., Cancer Res 50: 7116-7122, 1990) that etoposide-induced DNA cleavage and mRNA coding for topoisomerase II are reduced in HL-60 cells induced to differentiate by phorbol ester. Reduction of etoposide-induced cleavage and topoisomerase II message did not occur in the derived cell line 1E3 (which is resistant to phorbol-induced differentiation), implying that topoisomerase II activity may be related to the state of cell differentiation. We have extended these studies using a new phorbol sensitive/resistant cell pair, S (sensitive) and PET (phorbol ester tolerant). Phorbol ester exposure not only reduced etoposide-induced DNA cleavage and topoisomerase II mRNA in S cells but also decreased the amount of immunoreactive topoisomerase II enzyme in whole S cells. However, immunoreactive topoisomerase II extracted from the nuclei of phorbol-treated S cells was not reduced compared with that from the nuclei of untreated S cells. This suggests that topoisomerase II contained in nuclear extracts is not always representative of the total cellular enzyme. Dramatic decreases in the amount, activity, or gene expression of topoisomerase II were not observed after phorbol treatment of the resistant PET cells; this is consistent with the potential involvement of topoisomerase II in monocytoid differentiation. Levels of topoisomerase I enzyme and mRNA fell in both S and PET cells after phorbol treatment; therefore, the genes for topoisomerases I and II did not appear to be regulated coordinately.

Cell Differentiation

Etiology and outcome of diarrhea after marrow transplantation: a prospective study.

BACKGROUND/AIMS: Acute diarrhea after marrow transplant is usually ascribed to acute graft-vs.-host disease (GVHD) or infection, with a reported 40%-50% incidence of infection. The aim of this study was to determine the incidence of acute diarrhea after transplantation, its causes, and its outcome. METHODS: Two hundred ninety-six patients were followed up; patients with diarrhea were studied using standard evaluation of stool plus immunoelectron microscopy; assays for astrovirus, picobirnavirus, and Norwalk virus; and gene-probe methods for toxin-producing Escherichia coli. In 38 patients with diarrhea, intestinal biopsy specimens and duodenal fluid were also analyzed. RESULTS: One hundred fifty acute diarrheal episodes developed in 126 patients (an incidence of 43%). Intestinal infection was found in 20 of 150 episodes: viruses (astrovirus, adenovirus, cytomegalovirus, and rotavirus) in 12 patients, nosocomially acquired bacteria (Clostridium difficile and Aeromonas) in 7 patients, and mixed infection in 1 patient. Acute GVHD was responsible for 72 of 150 episodes (48%). Clinical signs and symptoms of infection and GVHD were similar. In 58 of 150 episodes (39%), no clear etiology could be found for self-limited diarrhea. CONCLUSIONS: Intestinal infection accounted for 13% and acute GVHD for 48% of diarrheal episodes. The most common infecting organisms were astrovirus, C. difficile, and adenovirus. Most cases of diarrhea after marrow transplant are not caused by infection.

Acute Disease

Stroke volume with dynamic cardiomyoplasty during ventricular fibrillation in the acute dog.

The objective of this study was to determine the pumping capability of dynamic cardiomyoplasty during induced ventricular fibrillation. In this acute study of 6 dogs, the pumping capability of the unconditioned left latissimus dorsi (LD) muscle (141 to 292 gm), wrapped around both ventricles, was investigated during induced ventricular fibrillation. Left-ventricular and femoral artery pressure, the ECG and aortic root flow velocity were monitored. Prior to inducing ventricular fibrillation, the ability of the unconditioned LD muscle to augment stroke volume (SV), was quantified as the area under the aortic flow-velocity record. The ventricles were then fibrillated and, after 10 sec, rhythmic 250 msec trains (1/sec) of stimuli (40/sec) were delivered to the thoracodorsal nerve to contract the LD muscle tetanically. In no case could dynamic cardiomyoplasty produce the same SV as when the ventricles were beating normally. In one animal, the SV attained two percent of the normal SV by 5 contractions; in another, the SV reached one percent by 25 contractions. In the remaining animals, the SV varied around 20% of the prefibrillation SV. By 90 contractions, the stroke volume was 10% of the prefibrillation value. The progressive decrease in SV was likely a consequence of LD muscle ischemia and fatigue, since the latissimus dorsi muscle provided low blood flow during the period of fibrillation.

Animals

Further characterization of an amsacrine-resistant line of HL-60 human leukemia cells and its topoisomerase II. Effects of ATP concentration, anion concentration, and the three-dimensional structure of the DNA target.

The characterization of type II topoisomerases from amsacrine-sensitive (HL-60) and amsacrine-resistant (HL-60/AMSA) human leukemia cells was extended. The intercalator resistance and etoposide sensitivity of the HL-60/AMSA cells themselves were confirmed, and the stability of this pharmacologic phenotype over many hundreds of cell generations was demonstrated. Prolonging exposure of HL-60/AMSA cells to amsacrine did not alter their sensitivity relative to that of HL-60 cells. Improved methods of immunoblotting allowed clear demonstration that the topoisomerase II within these cells exhibited sensitivity and resistance characteristics that mirrored those of the cells and the isolated enzymes themselves. Additional biochemical characterization of the type II topoisomerases indicated that both enzymes relaxed supercoiled DNA in a distributive fashion and that the ATP concentrations at which optimal catalytic activity of the two enzymes was exhibited were identical. The enzymes differed, however, in their activity optima in buffers of various type and ionic strength. Furthermore, the inability of the HL-60/AMSA enzyme to exhibit enhanced DNA cleavage in the presence of amsacrine could be overcome if the DNA target molecule contained a bend cloned into its polylinker region. By contrast, a bend in a DNA plasmid containing no polylinker was resistant to amsacrine-enhanced cleavage in the presence of HL-60/AMSA topoisomerase II, as was a plasmid containing a polylinker with no bend. This suggests that an unusual DNA conformation (a bend) in a specific DNA context (a polylinker) may be a favored site for topoisomerase II action. It also suggests a mechanism by which the sites and extent of topoisomerase II activity can be controlled in cells.

Adenosine Triphosphate

The ventricular-synchronous, skeletal-muscle ventricle: preliminary feasibility studies.

The two requirements for the optimal use of skeletal muscle wrapped around a pouch used to pump blood are:(1) a low pouch diastolic pressure (to assure a high muscle capillary blood flow; and (2) a high pouch precontraction pressure (PCP) (to assure a forceful muscle contraction). Both requirements are satisfied with the pumping method described herein. This new type of skeletal-muscle ventricle (SMV) consists of a rectus abdominis muscle wrapped around a pouch connected to the left ventricular apex (with no valve) and to the aorta via a one-way valve. Consequently, the pressure in the SMV pouch is always equal to left ventricular pressure. The high PCP is obtained by stimulating the rectus muscle to contract at the desired left ventricular pressure. The R (or P) wave of the cardiac electrogram initiates a delayed train of stimuli to cause the rectus muscle to contract tetanically and expel blood from the pouch. We have designated this pumping configuration the ventricular-synchronous SMV (VS-SMV). In this study, eight acute anesthetized dogs were used. The muscles were unconditioned and among the items investigated were the importance of the delay (d) between the R (or P) wave and the onset of the stimulus train, the optimal stimulus frequency and train duration, the VS-SMV output with different ratios of VS-SMV to left ventricular contractions, unloading of the left ventricle, Frank-Starling curves for the VS-SMV, pressure-volume loops for the VS-SMV with and without contraction of the rectus muscle, and washout characteristics of the VS-SMV. It was found that a stimulus frequency of 40/sec, and a train duration of 250 msec is optimal. It was also found that choice of the proper delay from the R or P wave provided maximal augmentation in stroke volume, typically 20 to 40 mL. Pumping with a ratio of 1:2 provided VS-SMV outputs ranging from 20 to 140 mL/min per kg of body weight. With this same pumping ratio, cardiac output increased by 28% and the post-VS-SMV contraction, left ventricular stroke volume was reduced. The Frank-Starling curves showed that PCPs on the order of aortic pressure are needed for the most forceful muscle contraction. With this new pumping configuration, the left ventricle resembles an atrium which delivers blood to the VS-SMV that is stimulated to contract when the desired PCP is reached. Studies were also conducted in which the VS-SMV outlet (valve end) was closed and filling and emptying occurred through the left ventricle.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdominal Muscles

The importance of timing muscle contraction in dynamic cardiomyoplasty.

This acute dynamic cardiomyoplasty (CMP) study used ten dogs (weight range 21-32 kg) and was designed to determine the importance of the train of stimuli initiation time when applied to the thoracodorsal nerve, which innervates the latissimus dorsi (LD) muscle that is wrapped around the ventricles. Using the P wave of the cardiac electrogram to trigger a special delay circuit, the stimulus train could be initiated from the apex of the R wave to any time throughout and at the end of the isovolumic period, signaled by opening of the aortic valve. The cardiac electrogram (which contained the R wave), left ventricular pressure (LVP), aortic flow velocity (AFV), beat-by-beat stroke volume (SV), femoral artery pressure, and the envelope of the stimulus train were recorded as the onset of the stimulus train was varied from the R wave to the end of the isovolumic period with a pumping ratio of one LD contraction for every seven ventricular contractions. In four dogs there was a pronounced increase in the augmentation in LVP, AFV, and SV when the stimulus train was initiated later than 40 msec after the first peak of the R wave. In five dogs the augmentation in LVP, AFV, and SV was not as clearly apparent, although all of these dogs exhibited an optimal train delay. Data were not obtained on one dog due to an anomalous LD muscle blood supply. For all of the dogs, the optimum train delay from the R wave averaged 58 msec (range 40-80 msec). The average augmentation in SV was 26% (range 13%-45%). The same muscle-wrap tightness was used in all dogs. In one dog, the muscle-wrap tightness was varied, and by tightening the wrap the SV augmentation increased from 17% to 27%. For all dogs the range of augmentation in SV (13%-45%) perhaps represents variations in muscle-wrap tightness, which may be a major uncontrolled factor in dynamic CMP.

Animals

Observations on in situ degradation of forage cell components in alfalfa and Italian ryegrass.

The rate and extent of degradation of forage feed fractions contained in alfalfa and Italian ryegrass hays were determined. Nylon bags filled with 4 g of each forage were suspended in the rumen of two cannulated cows immediately before feeding and incubated for 10 different times (0, 2, 4, 8, 12, 24, 48, 72, 120, and 168 h). The alfalfa hay, which had lower NDF, showed a lower extent, but a higher rate, of NDF degradation than the Italian ryegrass (41.1 vs. 59.8% and 4.64 vs. 2.91%/h, respectively). Alfalfa cell walls were degraded more rapidly than Italian ryegrass even though their lignin content was higher. The hemicellulose fermentation of alfalfa showed a longer lag time (13 h) and an undegradable fraction nearly twice that for Italian ryegrass (63.3 vs. 37.1%). Cellulose from alfalfa was degraded at a higher rate than NDF or ADF, indicating that cellulose may be the primary site of hydrolysis of the cell wall in the rumen. Calculations based on in situ degradability indicate that alfalfa can have a higher inclusion than Italian ryegrass in diets for dairy cows because of lower NDF and greater availability of cell contents.

Animal Feed

Components of intrinsic drug resistance in the rat hepatoma.

A carcinogen-transformed rat hepatoma cell line (Reuber H-35) was utilized as a model system for investigation of the biochemical factors which may limit the effectiveness of chemotherapy in intrinsically resistant tumors such as hepatocellular carcinoma. Northern blotting demonstrated expression of mRNA coding for the P-170 membrane-glycoprotein associated with the multi-drug resistance phenotype, while Western blotting identified the P-170 glycoprotein in the hepatoma cell membrane. Consistent with these observations, tumor cell sensitivity to the vinca alkaloids, vincristine and vinblastine, to the anthracycline antibiotics, Adriamycin and daunorubicin, and to the demethylepipodophyllotoxin derivative, VM-26, was enhanced by continuous incubation in the presence of the calcium channel antagonist, verapamil. Verapamil produced a minimal change in cell sensitivity to the demethylepipodophyllotoxin derivative, VP-16, and to the aminoacridine, m-AMSA. Relatively high detoxification potential via the glutathione metabolic pathway was also observed in the hepatoma cell. The capacity of topoisomerase II in nuclear extracts from the hepatoma cell to mediate cleavable complex formation stimulated by VM-26, VP-16 and m-AMSA appeared to be at least comparable to, if not greater than that from drug-sensitive HL-60 cells, suggesting that drug resistance may not occur at the level of this enzyme. Consistent with findings in a number of tumor cell lines resistant to antineoplastic drugs, the antiproliferative activity of the topoisomerase II inhibitors VM-26, VP-16 and m-AMSA appeared to be dissociable from the induction of DNA strand breaks, suggesting that such lesions in DNA may fail to fully account for the antiproliferative activity of these agents in the hepatoma cell.

Animals