Baccalaureate-M.D. programs.
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Education, Medical, Undergraduate↗
Biomedical subjects
J Allen
Publications and source records attributed to J Allen.
Acute effects of nitrendipine in pregnancy-induced hypertension.
The acute effects of a single, 20 mg oral dose of nitrendipine were studied in 10 women at between 32 and 42 weeks gestation with stable pregnancy-induced hypertension (PIH). Blood pressure (BP), maternal heart rate and fetal heart rate (FHR) were assessed for 8 h after nitrendipine intake together with the plasma levels of nitrendipine, noradrenaline, adrenaline, plasma renin activity (PRA) and vasopressin. The mean initial systolic/diastolic BP was 158 (SEM 3.7)/108 (SEM 2.7) mmHg. Within 1 h stable, reduced mean BP-levels of 141-145/90-95 mmHg were reached and maintained for 4 h after medication. This antihypertensive effect was closely related to the maternal plasma concentration of nitrendipine, which reached a maximum of 9.1 (SEM 2.6) ng/ml 3 h after tablet intake. After 4 h, systolic and diastolic BPs slowly increased in parallel to a successive decrease in plasma concentrations of nitrendipine. Maternal heart rate increased by less than 10%, while FHR remained unchanged. No hypotensive incidents occurred. The initial mean plasma concentrations of noradrenaline, adrenaline, vasopressin and PRA did not change during the treatment. No major maternal and no fetal side-effects were observed. Three of 10 patients experienced mild, transient facial flushing.
Adult↗
Whole-cell and single-channel calcium currents of isolated smooth muscle cells from saphenous vein.
Whole-cell and single-channel calcium currents in enzymatically isolated dog saphenous vein cells were recorded by the patch-clamp method. Test pulses to negative potentials from holding potentials of -90 to -40 mV elicited currents that inactivated quickly and in a voltage-dependent manner (called I low for low threshold). A second calcium current persisted even at relatively positive holding potentials of -30 to -10 mV, required stronger depolarizations for maximum current, and inactivated slowly (I high for high threshold). I high transported barium more than calcium, whereas I low transported the two ions equally. Single-channel current records (90 mM barium) showed a larger conductance that activated at relatively positive potentials and a smaller (about one-third) conductance that activated at weak depolarizations. Nitrendipine suppressed I high, and the effect was voltage dependent as observed in cardiac cells, although block of resting channels was much greater in vein cells (KR approximately 10(-8) M). Exposure to the stereoisomer (-)Bay K 8644 increased I high but not I low. The (-)Bay K 8644 also increased the channel activity and prolonged the open time of the larger conductance current. Thus, two types of calcium channels, differing in potential-dependence of activation and inactivation, calcium/barium selectivity, single-channel conductance, and sensitivities to dihydropyridines were identified in smooth muscle cells isolated from a large cutaneous vein.
Animals↗
Combined intracervical PGE2 and intra-amniotic PGF2 alpha for induction of 2nd trimester abortion.
Fourteen consecutive patients (mean gestational age 18.1 weeks, range 15-23 weeks) referred for therapeutic termination of pregnancy were induced into abortion by intra-amniotic PGF2 alpha 40 mg followed by oxytocin stimulation. 14 other patients (mean gestational age 17.9 weeks, range 15-23 weeks) were pretreated with intracervical PGE2 1.0 mg in gel for 4 h prior to induction of abortion with intra-amniotic PGF2 alpha 40 mg without further stimulation. The induction-abortion interval for patients treated with intra-amniotic PGF2 alpha and oxytocin, was 19.1 +/- 2.94 h (+/- SE, n = 14) with a success rate of 80% after 24 h. After pretreatment with intracervical PGE2 1.0 mg in viscous gel, intra-amniotic PGF2 alpha 40 mg induced abortion after 11.2 +/- 1.12 h (+/- SE, n = 14) with a 100% success rate after 24 h. No systemic side effects of the PGE2 pretreatment were noted. No cervical laceration was observed. The results need further confirmation, but still suggest cervical priming with intracervical PGE2 1.0 mg in gel and subsequent induction of abortion by intra-amniotic PGF2 alpha 40 mg as an attractive principle for 2nd trimester abortion.
Abortion, Induced↗
A sense of community, a shared vision and a positive culture: core enabling factors in successful culture based health promotion.
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Community-Institutional Relations↗
Neurohumoral mechanisms and left ventricular hypertrophy: effects of hygienic therapy.
To determine the effects of hygienic (non-drug) therapy on blood pressure (BP) control and its relationship to sympathetic tone and left ventricular mass (LVM) in primary hypertension, plasma norepinephrine (NE) and renin activity (PRA), LVM, and nutritional and behavioral status were assessed in 76 borderline to mild hypertensives. Pretherapy plasma NE was related to diastolic blood pressure (DBP) and PRA (r = 0.24, P less than .05 and r = 0.37, P less than .01, respectively). Plasma NE of high renin patients (221 +/- 52) (mean +/- SD) was greater than that of normal renin patients (159 +/- 61, ng/l, P less than .01). LVM was related to systolic blood pressure (SBP) (P less than .001), DBP (P less than .01) and urinary sodium (P less than .05), and inversely related to PRA (P less than .01). Septal wall thickness was related to hostility (r = 0.42, P less than .05). After seven weeks of hygienic therapy, DBP was reduced by 6 mmHg (P less than .01). The change in SBP was related to baseline plasma NE (P less than .05) and inversely related to LVM (P less than .05). These results suggest that raised sympathetic tone may be a pathogenic factor in primary hypertension and that hygienic therapy lowers BP more effectively in patients with raised sympathetic tone and low LVM.
Adult↗
Epithelial cell proliferation in the rat urinary system induced by parenteral injection of lead salts.
In Wistar rats a single intravascular injection of lead nitrate causes substantial cellular proliferation in the proximal tubules of the kidneys and in the epithelium of the renal pelvis, ureters and urinary bladder. The tritiated thymidine labelling index (LI) reaches a peak 18 to 24 h after injection and the mitotic index (MI) increases to a comparable extent 6 to 10 h later. The proliferation is most prominent in the bladder and proximal tubules and is virtually complete at 48 h. After a single intraperitoneal injection the proliferative changes are confined to the ureteric and bladder epithelium. In all affected tissues the proliferation develops without preceding necrosis and appears to be a hyperplastic phenomenon. After intravascular administration the volume of urine and its total protein content are significantly increased and certain proteins were detected which were not present in the urine of saline controls.
Animals↗
High affinity [3H]zolpidem binding in the rat brain: an imidazopyridine with agonist properties at central benzodiazepine receptors.
[3H]Zolpidem, a novel hypnotic drug possessing a chemical structure unrelated to that of benzodiazepine (BZD) was employed as a new ligand to determine its binding characteristics to membrane preparations of rat cerebral cortex and cerebellum. In both structures, the imidazopyridine [3H]zolpidem bound with high affinity to a single population of recognition sites. The cerebellum possessed a similar number of [3H]zolpidem and [3H]diazepam binding sites, while the cerebral cortex possessed a lower density of [3H]zolpidem than [3H]diazepam binding sites. In contrast to [3H]diazepam binding, [3H]zolpidem binding was not detectable in the spinal cord. In the cortex, BZDs had a similar potency to displace [3H]zolpidem and [3H]diazepam binding while non-BZDs were more potent to inhibit [3H] zolpidem binding than [3H]diazepam binding. The binding of [3H]zolpidem was enhanced by GABA to the same extent as [3H]diazepam binding. The increase in [3H] zolpidem binding caused by chloride ions was less pronounced than that in [3H]diazepam binding. It is concluded that [3H]zolpidem possesses selectivity for BZD receptors with the pharmacological characteristics and regional distribution of the BZD1 receptor subtype. [3H]Zolpidem as a radioligand offers a useful additional tool to study the mechanism of action of hypnotics acting through BZD receptor subtypes.
Animals↗
Conjunctivitis, tracheitis, and pneumonia associated with herpesvirus infection in green sea turtles.
Fourteen juvenile (15- to 20-month-old) green sea turtles (Chelonia mydas), representative of a group of sea turtles with clinical signs of respiratory tract disease, were euthanatized and submitted for necropsy. Macroscopically, lesions included periglottal necrosis, tracheitis with intraluminal caseous and laminated necrotic debris, and severe pneumonia. Several turtles had caseous conjunctival exudate covering the eyes. Microscopically, the turtles had fibrinonecrotic inflammation around the glottal opening, tracheitis, and severe bronchopneumonia and interstitial pneumonia. In multifocal areas, periglottal and tracheal epithelial cells adjacent to areas of necrosis had hypertrophic nuclei with amphophilic intranuclear inclusions. A mixed population of primarily gram-negative microorganisms was isolated from the tracheal and glottal lesions. Attempts at viral isolation in cultures of green sea turtle kidney cells resulted in the development of cytopathic effects characterized by giant cell formation and development of intranuclear inclusions. Using electron microscopy, intranuclear viral particles (88 to 99 nm in diameter) were seen in inclusion-containing tracheal and glottal epithelial cells and infected green sea turtle kidney cells; particles were consistently seen enveloping from nuclear membranes, and mature particles (132 to 147 nm) were found in the cytoplasm. On the basis of size, conformation, location, and presence of an envelope, the particles most closely resembled those of herpes-viruses.
Animals↗
Electrical stimulation releases 3H-betaxolol from rat atrial slices: possible role of noradrenergic nerves.
Under in vitro conditions, 3H-betaxolol was accumulated in rat atrial slices, reaching a tissue-medium ratio of 12.3 +/- 1.8 ml/g. This process was temperature-dependent, but ouabain-resistant. 3H-Betaxolol accumulated in atrial slices was subsequently released by electrical stimulation. The electrically-evoked release of 3H-betaxolol was abolished in the absence of calcium, and reduced in the presence of bretylium 10 microM. After surgical sympathetic denervation by stellate ganglionectomy there was a marked reduction in the endogenous content of noradrenaline and in the retention of 3H-noradrenaline in atrial slices. The concomitant decrease in the amount of 3H-noradrenaline released by electrical stimulation following denervation was modest, although statistically significant. Following sympathetic denervation, the tissue retention of 3H-betaxolol was not significantly affected, but the release of 3H-betaxolol by electrical stimulation was considerably reduced. After pretreatment with reserpine the amount of radioactivity released by electrical stimulation from slices labelled with 3H-betaxolol or 3H-noradrenaline was markedly reduced. The tissue retention of 3H-noradrenaline was reduced to a larger extent than that of 3H-betaxolol following the administration of reserpine. The simultaneous release of noradrenaline and betaxolol by nerve stimulation observed under our experimental conditions may represent a mechanism through which betaxolol can reach selectively the postsynaptic beta 1-adrenoceptors and reinforce beta-adrenoceptor blockade in the heart.
Adrenergic beta-Antagonists↗
Polymorphonuclear leukocyte, T-lymphocyte, and natural killer cell activities in elderly nursing home residents.
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Adult↗
Objective responses to ketoconazole therapy in patients with relapsed progressive prostatic cancer.
The contribution of adrenal androgens to the maintenance and progression of so-called hormone-unresponsive prostatic carcinoma was studied in 20 patients with advanced relapsed disease. The role played by testicular androgens had been negated by prior orchiectomy or concurrent LHRH analogue therapy. Ketoconazole, an antifungal agent which inhibits adrenal and testicular androgenesis, administered in a dose of 400 mg 8-hourly, resulted in optimal suppression of adrenal androgens. The mean serum androstenedione concentration fell from 8.01 +/- 0.84 nMol/l to 1.55 +/- 0.25 nMol/l, P less than 0.001, and serum testosterone from 1.25 +/- 0.14 nMol/l to 0.36 +/- 0.06 nMol/l, P less than 0.01, after 6 months treatment. There was, however, no significant difference between patients receiving 400 and those receiving 200 mg. Androgen suppression resulted in six objective and ten subjective clinical responses. Ablation of both testicular and adrenal androgens can now be achieved using ketoconazole in combination with orchiectomy or LHRH analogues, but the high incidence of side effects may preclude its use in all patients with prostatic cancer. The results of this study support the concept of "total androgen ablation" as primary therapy in advanced prostatic cancer as a possible means of improving survival in this common malignancy.
Acid Phosphatase↗
Diabetes mellitus and pregnancy. A seven-year material of pregnant diabetics, where control during pregnancy was based on a centralized ambulant regime.
A 7-year survey of the outcome of pregnancy complicated by diabetes mellitus, carried out at the Aarhus center, is presented. The material comprised 344 diabetic pregnant women where the control was based mainly on a centralized ambulant regime. The latter half-period was moreover based on self-monitoring of the blood glucose level. This achieved a significantly better blood glucose regulation, with a reduction of the mean blood glucose level from 7.9 to 6.4 mmol/l. Furthermore, the introduction of self-monitoring halved the number of hospitalizations necessary for blood glucose regulation. Pregnancy was complicated in about 35%. The importance of screening for urinary tract infection is emphasized, since this, which was present in 20% of cases, might be a possible factor in ketoacidosis and/or intra-uterine growth retardation. In 19% of the vaginal births it was deemed necessary to give instrumental assistance; 5% had shoulder dystocia. The cesarean section frequency was 31%. The antenatal mortality rate was 1.2% and the uncorrected perinatal mortality was 3.5%, half of the neonatal mortality was due to fatal congenital malformations. About half of the newborn babies required immediate intensive neonatal treatment. Because of the high frequency of complications in pregnant diabetics, during childbirth and in the neonatal period, centralized monitoring by a highly specialized team is necessary in order to maintain the present relatively low perinatal mortality and morbidity rates and the low number of cesarean sections, together with the most convenient control regimen for this highly pathological group. Furthermore, centralization will facilitate research which, together with prepregnancy consultation, may reduce the frequency of major fetal malformations.
Ambulatory Care↗
A preliminary investigation of the parallelogram concept in genetic monitoring and risk estimation.
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Animals↗
Effects of yohimbine on combined xylazine-ketamine-induced sedation and immobilization in juvenile African elephants.
Twenty-two juvenile African elephants were given a combination of xylazine (mean +/- SD = 0.14 +/- 0.03 mg/kg of body weight) and ketamine (1.14 +/- 0.21 mg/kg) as a single IM injection; one elephant was immobilized twice, 77 days apart. After injection, 14 elephants were immobilized, 4 were sedated deeply, 2 were sedated moderately, and 2 were sedated minimally. Immobilized elephants had a mean immobilization time of 11.6 +/- 6.9 minutes. At the conclusion of a variety of clinical procedures, 12 of the 14 elephants immobilized with a single dose combination of xylazine and ketamine were given yohimbine (0.13 +/- 0.03 mg/kg) IV, and the remaining 2 elephants were allowed to recover spontaneously; the elephants given yohimbine had a mean standing time of 2.4 +/- 1.1 minutes. Of the 8 sedated elephants, 5 were given an additional dose of combined xylazine (0.08 +/- 0.03 mg/kg), and ketamine (0.61 +/- 0.19 mg/kg) IM, and 1 elephant was given ketamine (0.47 mg/kg) IV. After injection, 4 of the 8 elephants were recumbent laterally within 17 minutes and 2 remained standing, under deep sedation. Seven of the 8 elephants were given yohimbine (0.13 +/- 0.03 mg/kg) IV; all were ambulatory in 2 minutes. Results indicated that yohimbine may be useful in controlling duration of xylazine-ketamine sedation and immobilization in juvenile African elephants.
Anesthesia, General↗
Effects of exercise on blood pressure, plasma catecholamines, potassium and the electrocardiogram after diuretic and neural-blocking therapy for moderate hypertension.
Blood pressure control in mild and moderate hypertension may reduce morbidity and mortality. On the other hand, antihypertensive drugs may cause adverse metabolic, electrolyte, neural and hemodynamic alterations that detract from their effectiveness. The effect of hydrochlorothiazide (HCTZ) on some of these factors was compared with that of HCTZ and a sympatholytic drug in 20 hypertensive patients with left ventricular hypertrophy and retinopathy. HCTZ controlled blood pressure at rest and during maximum treadmill exercise (-12 mm Hg systolic and diastolic pressure (p less than 0.05), reduced left ventricular mass by 7% (p less than 0.05) and lessened aerobic impairment at maximum treadmill exercise by 45% (p less than 0.05). These effects were further improved after "neural blockade." A potential adverse effect of HCTZ--hypokalemia (-0.6 mEq/liter, p less than 0.01)--and the associated incidence of ectopy during effort (50%) were lessened after neutralizing neural tone. Combination therapy with low-dose diuretic and sympatholytic drugs was effective and well tolerated in patients with cardiac and vascular sequelae of moderately severe hypertension.
Blood Pressure↗
Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: a multicenter double-blind clinical trial.
The efficacy and safety of intravenous esmolol infusion was compared to that of intravenous propranolol injection in patients with supraventricular tachyarrhythmias (SVT) in a multicenter double-blind parallel study. A total of 127 patients were randomized to either the esmolol (n = 64) or propranolol (n = 63) group. Therapeutic response was achieved in 72% of esmolol and 69% of propranolol patients (p = NS). The average dose of esmolol in responders was 115 +/- 11 micrograms/kg/min. Therapeutic response was sustained in the 4-hour maintenance period in 67% of esmolol and 58% of propranolol patients (p = NS). Rate of conversion to normal sinus rhythm was similar in the two treatment groups. After discontinuation, rapid recovery from beta blockade (decrease in heart rate reduction) was observed in esmolol patients (within 10 minutes) compared to propranolol patients (no change in heart rate up to 4.3 hours). The principal adverse effect was hypotension, reported in 23 esmolol (asymptomatic in 19) and four propranolol (asymptomatic in three) patients. In the majority of esmolol patients, hypotension resolved quickly (within 30 minutes) after esmolol was discontinued. It was concluded that esmolol was comparable in efficacy and safety to propranolol in the treatment of patients with SVT. Unlike propranolol, because of the short half-life of esmolol, rapid control of beta blockade is possible with esmolol in clinical conditions when required.
Acute Disease↗