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Biomedical subjects

J D Allen

Publications and source records attributed to J D Allen.

At least 19 recordsLinked to original sources

Failure of countershock-type pulses in vitro to adversely alter mitochondrial oxidative phosphorylation.

STUDY OBJECTIVE: The aim of the study was to investigate a potential mechanism of myocardial injury after DC countershock. The effect of countershock-type electrical discharges on rabbit heart mitochondrial oxygen consumption was measured in vitro using a novel respiration cell. MEASUREMENTS AND MAIN RESULTS: Mitochondria were isolated from the hearts of adult Dutch and New Zealand White rabbits. Single rectangular shocks (voltage gradients 20 to 80 V/cm; 5 ms duration) caused no significant changes in state 3 oxygen consumption in standard incubation medium. Single and multiple defibrillator shocks (critically damped sine waveform; 5 ms duration) with peak voltage gradients of 242 to 659 V/cm similarly had no significant effect on state 3 oxygen consumption. CONCLUSION: At voltage gradients similar to and greater than those causing myocardial cell injury and necrosis, electrical discharges do not directly depress mitochondrial function. Therefore, the reduction in mitochondrial oxygen consumption observed following transthoracic shocks in vivo may invoke other mechanisms (eg, intracellular calcium influx, high circulating noradrenaline, or free radical formation in the intact heart).

Animals

Oxidative metabolism and myocardial blood flow changes after transthoracic DC countershocks in dogs.

Changes in oxidative metabolism and myocardial blood flow were investigated in adult greyhounds following transthoracic shocks from a DC cardiac defibrillator (400 Joules stored energy, damped sine wave, 0.5 min intervals). Myocardial lactate extraction became negative maximally at 1 min, following both two (mean -24% +/- SEM24) or five (-193% +/- 148) shocks and returned to baseline by 6-15 min. Transient reductions were also observed in myocardial extraction of pyruvate and free fatty acids but not glucose. Myocardial necrosis assessed at 4 h following the shocks was 0.05 g (+/- 0.03) after two shocks, 6.5 g (+/- 1.5) after five shocks and zero in controls. Mean peak noradrenaline levels in arterial (785 +/- 319 pg.ml-1) and coronary sinus (916 +/- 313 pg.ml-1) blood at 1 min after five shocks were higher than after 0 shocks (82 +/- 33 pg.ml-1 and 201 +/- 63 pg.ml-1 respectively), P < 0.05. Great cardiac venous blood flow was measured by a thermodilution technique, with continuous infusion of 0.9% saline, before, during and after five shocks. Mean blood flow fell from 47 +/- 13 ml.min-1 to a minimum of 36 +/- 7 ml.min-1 during shocks, and then rose to 83 +/- 17 ml.min-1 at 2 min after the fifth shock (P < 0.05). Following damaging countershocks, oxidative metabolism is depressed, in keeping with a primary disturbance of mitochondrial function. These metabolic changes are not secondary to ischaemia, since an increase in blood flow in the great cardiac vein (GCV) is observed. Vasodilatation of the coronary vascular bed must occur to account for this.

Analysis of Variance

Failure of a single postpartum prostaglandin treatment to improve the reproductive performance of dairy cows.

A study was conducted to evaluate the effects of postpartum prostaglandin treatment on reproduction in 3 seasonal calving dairy herds. Recently calved lactating dairy cows were paired on herd, age, calving date and previous production index. One cow in each of the 196 pairs received a single intramuscular injection of 25 mg of the prostaglandin analogue, dinoprost, between 14 and 28 days after calving. Subsequent reproduction was monitored. Within each herd and overall, there was no significant effect of treatment on the intervals from calving to first service, mating start date to first service, calving to conception, mating start date to conception and first service to conception. Treatment also had no significant effect on 21-day submission and pregnancy rates, on the proportion of each group not pregnant at the end of mating, and on first service pregnancy rates. Responses to treatment did not vary between cows calving within 50 days of mating start date and earlier calving cows or between cows aged less than 5 years and older cows.

Animals

Frequency analysis of ventricular fibrillation and resuscitation success.

In 56 patients, frequency analysis of the electrocardiogram of ventricular fibrillation exhibited power spectra with a distinct dominant frequency. The greatest success for resuscitation from ventricular fibrillation is recorded when ventricular fibrillation develops after the patient comes under coronary care. Of the 41 patients in whom the onset and first 8 s of ventricular fibrillation were artefact-free the mean dominant frequency of primary ventricular fibrillation (no cardiogenic shock or cardiac failure) in 21 patients was 6.2 +/- 0.2 Hz, significantly higher than the mean dominant frequency of the first 8 s of secondary ventricular fibrillation (cardiogenic shock or heart failure) (4.0 +/- 0.2 Hz, 20 patients, p = 0.0001). In these patients the peak-to-trough amplitude (ECG) of the first 8 s of ventricular fibrillation was similar in both primary and secondary ventricular fibrillation as was the mean duration of ventricular fibrillation prior to the first DC shock. There was a significantly lower success rate for resuscitation from secondary ventricular fibrillation (6 of 20 patients) compared with resuscitation from primary ventricular fibrillation (18 of 21 patients, chi 2 17.8, p = 0.001). Of the remaining 15 patients who were collapsed between 3 and 20 min before the arrival of the mobile coronary care unit, the dominant frequency of the first 8 s of ventricular fibrillation fell with increased duration of collapse (from 5.5 Hz at 3 min to a mean of 2.1 Hz at 20 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Effect of warm air on the shear bond strength of composite resins.

This investigation evaluated the operating characteristics of a recently introduced tooth dryer and its effect on the bond strength of three composite resins to etched enamel. The effect of varying air pressure, distance from the tip of the tooth dryer, and distance laterally from mid-air stream on temperature were measured using a rapid-response thermocouple. Specimens were subjected to shear forces either immediately after bonding or after 5 days of water storage. The air stream required from 32 to 41 seconds to reach maximal temperature; however, more than 90% of the maximal temperature was obtained in 20 seconds. There was an increase in temperature with increased air pressure and a decrease in temperature with increasing distance from the tip. The temperature dropped rapidly laterally from the center of the air stream. The shear bond strength measurements were significantly higher for the specimens prepared using the tooth dryer for one composite resin tested immediately after bonding; there was no statistically significant difference for the other resins. The effect of warm air on the shear bond strength of composite resins to etched enamel may be dependent on the resin used and the time between bonding and testing.

Air

CD4 immunoadhesins in anti-HIV therapy: new developments.

CD4, the cell-surface receptor for the human immunodeficiency virus (HIV), is a member of the immunoglobulin (Ig) gene superfamily. It contains 4 extracellular sequences homologous to Ig variable domains, the first of which (V1) is sufficient for binding to HIV. To develop CD4 as an anti-HIV therapeutic, we engineered a CD4 immunoadhesin (CD4-IgG)--a fusion protein containing the V1 and V2 domains of CD4 with the hinge and Fc regions of human Ig heavy chain. A chimeric protein of this type has several advantages compared to the soluble receptor, including a greatly extended in vivo half-life and greater avidity for HIV; moreover, like an antibody, it performs effector functions via its Fc domains, such as complement activation and antibody-dependent cell-mediated cytotoxicity. In vivo experiments show that CD4-IgG protects against HIV-I IIIB infection of chimpanzees when administered prior to viral challenge. In addition, CD4-IgG is transferred efficiently across the placenta from mother to fetus in rhesus monkeys. To evaluate its safety in humans, we conducted a phase-I clinical trial in adult patients with AIDS and AIDS-related complex. We found that, in a total of 16 patients, administration of CD4-IgG was well tolerated at doses up to 1000 micrograms/kg of body weight, with no important clinical or immunological toxicities noted. Given its unique properties, particularly the ability of CD4-IgG to cross the placenta, we plan to focus future clinical efforts on preventing infection of newborns via maternal-fetal transfer of HIV.

Acquired Immunodeficiency Syndrome

Overdentures and the periodontium.

Several periodontal factors are critical to the prognosis of overdenture abutment teeth. This literature review outlines these factors and discusses the documented effects of long-term overdenture use on periodontal health. The efficacy of a professional periodontal maintenance program, which is coordinated with a home oral hygiene program, is related to the success of overdenture therapy.

Dental Abutments

Time-dependence of inducible ventricular tachycardia in a chronic canine model.

The natural history of inducible ventricular tachycardia in post-infarction dogs was followed with serial programmed electrical stimulation (PES: 1-3 extrastimuli, 4 msec duration, 2 x diastolic threshold). Arrhythmia inducibility was defined as a minimum of four unstimulated ventricular ectopic beats. Of 119 dogs prepared for chronic electrophysiological study, 87 (73.1%) were ambulant 24 hours after surgery. Mean infarct size was 11.1 +/- 1.5% of left ventricular (LV) mass for animals dying in the first week, before stimulation. 92.4% of 66 animals were inducible when stimulated at one week, 66.7% at two weeks and 64.3% and 55.6% at the third and fourth weeks respectively (p less than 0.01, Chi-square analysis). Infarct sizes fell from 7.0 +/- 0.5% LV mass at first stimulation to 4.6 +/- 0.8% at third stimulation and could not be visualized thereafter (p less than 0.01,ANOVA). There was no statistical difference between infarct sizes for inducible and non-inducible animals, but in both cases infarcts were smaller (p less than 0.01) than for those animals which died suddenly during the first week. This time-dependent decrease in arrhythmia inducibility, which may be related to infarct size, should be considered when similar models are employed for chronic electrophysiological studies.

Animals

Film thickness of die coating agents.

Die coating agents are often used during the fabrication of porcelain margins for crowns and fixed partial dentures. These agents seal microscopic irregularities within the stone die and resist abrasion. This investigation measured the film thickness of several die coating agents. A specific reference point was used during the measurement process. The results indicate that there is no significant difference between the die coating agents examined under the conditions of the study. The film thickness measurements ranged between 0.367 microns for Duro Super Glue Material and 2.3 microns for Zap CA material.

Acrylic Resins

Novel murine homeo box gene on chromosome 1 expressed in specific hematopoietic lineages and during embryogenesis.

We describe here a new murine homeo box gene, denoted Hlx, which is expressed within specific hematopoietic lineages. The cDNA sequence indicates that Hlx differs markedly from known vertebrate homeo box genes, and linkage analysis of an interspecific murine backcross showed that it resides at a novel homeo box locus on the distal portion of mouse chromosome 1. The Hlx homeo domain is most similar to that of the Drosophila H2.0 gene, but outside this region the two polypeptides are related only within a few short segments, the most notable being a motif (denoted Hep) also partially conserved in the engrailed and invected homeo proteins and possibly related to an octapeptide in certain paired box proteins. The presence of an intron within the Hlx homeo box at the same position as in several divergent Drosophila genes (H2.0, labial, Distal-less, proboscipedia, Abdominal-B, NK-1) suggests an ancient evolutionary relationship between these genes. RNA analysis of 67 murine hematopoietic cell lines and normal hematopoietic cells revealed Hlx expression throughout the myeloid/macrophage lineage and at early stages of B lymphocyte development but not in T lymphocytes, erythroid cells, or mast cells. Hence, Hlx is a candidate regulator of hematopoietic lineage commitment and maturation. It probably also functions outside the hematopoietic system, however, because Hlx mRNA could be detected in diverse adult tissues and in embryos from as early as day 8 of development.

Amino Acid Sequence

Predictability of repeated challenge: effects on cardiovascular activity in the type A (coronary prone) behavior pattern.

Fifty-two healthy young adults classified either as Type A (coronary prone) or Type B were randomly assigned to a vigilance task during which observing responses produced targets according to either a predictable (i.e., fixed-interval 90-sec) or a nonpredictable (i.e., random-interval 90-sec) reinforcement schedule. During the task, blood volume pulse, interbeat interval, masseter (EMG) activity, and blood pressure were monitored. Transient peripheral vasomotor constriction and heart rate increases were initiated within an 8- to 12-sec period following target detection with the predictable schedule, with subjects evincing greater responsivity than their nonpredictable schedule counterparts. Type A subjects assigned to the random-schedule evinced significantly shorter heart rate and blood volume pulse response durations than did Type B subjects. Longer postevent EMG elevations were evidenced by subjects assigned to the predictable schedule. No significant blood pressure differences were found among the groups. The impact of challenge-contingent behavior on cardiovascular responsivity and the relevance of attentional processes to this relationship and to cardiovascular risk are discussed.

Adult

Occurrence of temporomandibular disorder symptoms in healthy young adults with and without evidence of bruxism.

Few studies have specifically examined the association between bruxism and symptoms of temporomandibular disorders in adults. In this study 569 freshmen dental students entering the Medical College of Georgia over a 10-year period completed an 18-item "yes/no" questionnaire relating to awareness of tooth clamping/clenching/grinding and signs and symptoms of oral, facial, and craniomandibular discomfort, pain, and disorders. A higher proportion of females than males reported that they were aware of clamping and clenching their teeth, as well as symptoms of stiff jaw, sore jaw or teeth, cracking or locking jaw joint, and headaches in the morning. Reported awareness of tooth clamping and clenching and of someone having heard tooth grinding was significantly associated with reported pain, discomfort, or other sensations in, in front of, or behind the ear in the overall subject group.

Adult

Fourier analysis of ventricular fibrillation of varied aetiology.

Fast Fourier Transform analysis was used to study ventricular fibrillation induced by several different methods in 43 greyhounds anaesthetized with sodium pentobarbitone. The dominant frequency at the body surface of ventricular fibrillation induced electrically in non-ischaemic hearts was initially 9.9 +/- 0.7 Hz, remained above 9 Hz for 70 s and then rapidly fell to 5 Hz. The dominant frequency of ventricular fibrillation induced by acute occlusion (initially 12.3 +/- 0.2 Hz), or by reperfusion (12.2 +/- 0.4 Hz) of the anterior descending branch of the left coronary artery, showed a similar time-course. However, ventricular fibrillation induced by administration of potassium (4.8 +/- 0.8 Hz) or ouabain (7.1 +/- 1.1 Hz) was significantly slower. Fibrillation recorded from the endocardium of the heart initially showed a similar dominant frequency to that recorded at the body surface, but there was no significant fall in frequency over 3.3 mins. There was little difference in the time-course of fibrillation in the non-ischaemic heart recorded directly from the epicardium or from a surface lead. These findings may be of relevance to the poor response to DC countershock after prolonged ventricular fibrillation, hyperkalaemia or cardiac glycosides.

Animals

UK-52,046 (a novel alpha 1-adrenoceptor antagonist) and the role of alpha-adrenoceptor stimulation and blockade on atrioventricular conduction.

The effects of increasing intravenous (i.v.) doses of prazosin, phenylephrine, flecainide, and UK-52,046 on blood pressure (BP), heart rate (HR) and the specialized conduction system (AH and HV intervals) were investigated in anaesthetized dogs. Results indicated that UK-52,046 (1-8 micrograms/kg) had no effect on BP or HR, but reduced (p less than 0.05) BP at doses of 16 and 32 micrograms/kg; no change occurred in HR. During sinus rhythm (SR) the AH or HV intervals did not change as compared with placebo; on pacing (PA) UK-52,046 (4-16 micrograms/kg) decreased the AH interval. After prazosin BP decreased (p less than 0.05) after 20-40 micrograms/kg; HR increased after all doses (5-40 micrograms/kg). The HV interval was unaltered, but the AH interval decreased after 40 micrograms/kg during SR and PA. After phenylephrine (continuous infusion, 50 micrograms/ml/min) BP increased at 33 min and HR was decreased at 23 and 33 min. The AH interval lengthened during PA (p less than 0.05), but there was no effect on the HV interval. Administration of flecainide (0.5-2.0 mg/kg) had no effect on BP or HR but increased the HV interval during SR and PA (1 and 2 mg/kg, p less than 0.05). The results indicate that the alpha 1-adrenoceptor agonist phenylephrine and the alpha 1-adrenoceptor antagonist prazosin, on PA altered the AH (but not the HV) intervals in opposite directions in association with changes in HR and BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists

Pharmacological analysis of established ventricular fibrillation.

1. The effects of anti-arrhythmic drugs on the power spectrum of established ventricular fibrillation induced by endocardial electrical stimulation, have been studied in greyhounds anaesthetized with sodium pentobarbitone (35 mg kg-1, i.v.). 2. In dogs receiving no drug, initial recording of ventricular fibrillation showed a dominant frequency of 9.9 +/- 0.7 Hz (lead II) and 10.0 +/- 0.6 Hz (endocardium). After 3.3 min the frequency had fallen to 4.0 +/- 0.4 Hz in lead II, but remained high in the endocardium (10.7 +/- 0.5 Hz). 3. Lignocaine significantly reduced the dominant frequency for fibrillation recorded from lead II at (0-80 s), and for endocardial fibrillation at (0-200 s). 4. Pretreatment with propranolol or bretylium had little effect on the time course of the dominant frequency of fibrillation in lead II or the endocardium. 5. Verapamil prevented the fall in frequency seen in lead II after 80 s in the no drug group. A significantly higher frequency was maintained in both lead II (14.7 +/- 0.9 Hz) and the endocardium (14.8 +/- 0.9 Hz) for 3.3 min, compared with the no drug group (P less than 0.01). 6. Activation of fast sodium channels may determine the rapid frequency of the initial stages of ventricular fibrillation. The rapid fall in dominant frequency in lead II after fibrillation for 80 s can be prevented by calcium channel blockade and may be due to intracellular accumulation of calcium.

Animals