Effect of β2-adrenoceptor agonists on plasma potassium and cardiopulmonary responses on exercise in patients with chronic obstructive pulmonary disease

Objective: The effect of ₂-adrenoceptor agonist-induced hypokalaemia on cardiac arrhythmias might be exacerbated during exercise, especially in patients with more compromised airway function. Methods: To evaluate the effect of ₂-adrenoceptor agonists on plasma potassium and cardiopulmonary function during exercise, two identical submaximal treadmill exercise tests were performed, at least 48 h apart, by 13 patients with moderate to severe COPD (11 men and 2 women, mean age 66 y, mean FEV₁/FVC ratio 48.9 (2.8)%) 30 min after they had received nebulised fenoterol or salbutamol (2 mg). The experiment was done as a randomised, double-blind, crossover trial after an initial baseline study with vehicle (0.45% saline). Plasma potassium concentration, spirometry and the degree of breathlessness (Borg scale) were measured before treatment and immediately after exercise; oxygen saturation, QTc interval and cardiac rhythm were monitored continuously before, during and for 30 min after exercise. Results: After the saline control, exercise caused an increase in Borg rating (of 4.9), a premature ventricular contractions (VPC) (2.8 beats/min), and a fall in oxygen saturation (-6.7%), but no significant change in plasma potassium (+0.04 mEq·dl^–1), FEV₁ or QTc interval. Inhalation of fenoterol and salbutamol did not affect QTc interval, Borg scale or VPC frequency at rest, but significantly increased the duration of exercise undertaken to reach the submaximal levels (786 s, versus 783 s) compared to the vehicle control. Following exercise, plasma potassium fell after fenoterol by 0.2 mEq·dl^–1 and it increased after salbutamol by 0.1 mEq·dl^–1 compared to baseline levels. Plasma potassium after exercise was significantly lower after fenoterol (3.2 mEq·dl^–1) compared to the saline control (3.7 mEq · dl^–1) and salbutamol (3.6 mEq · dl^–1). Neither fenoterol nor salbutamol had any significant effect on the change in FEV₁, oxygen saturation, Borg scale, frequency of VPCs or QTc interval during or after exercise compared to the saline control. Conclusion: When compared to salbutamol 2 mg, fenoterol 2 mg caused more marked hypokalaemia but no significant difference in cardiopulmonary response in patients with COPD during exercise.     

Demonstration of a software package for the reconstruction of the dynamically changing structure of the human heart from cone beam X-ray projections

The Dynamic Spatial Reconstructor (DSR) is a device constructed at the Biodynamics Research Unit of the Mayo Clinic for (among other things) the visualization of the beating heart inside the intact thorax. The device consists of 28 rotating X-ray sources arranged on a circular arc at 6° intervals (total span 162°) and a matching set of 28 imaging systems. The whole thorax of the patient is projected onto the two-dimensional screen of the imaging systems by cone beams of X rays from the sources. All of the X-ray sources are switched on and off within a total period of 10 milliseconds. The Medical Image Processing Group at the State University of New York at Buffalo has developed a software package for the design and evaluation of algorithms to be used by the DSR. In this paper we illustrate the operation of the package and a particular algorithm for the reconstruction of the dynamically changing structure of the heart from data collected by the DSR.     

Microbial O-carbamylation of novobiocin

Novobiocin was inactivated by Streptomyces niveus US 2094 in fermentation. The inactivation product was isolated and characterized by NMR and MS as 2"-O-carbamylnovobiocin. The MICs of novobiocin and 2"-O-carbamylnovobiocin were determined for S. niveus strains.     

Doppler velocimetry of intraplacental fetal arteries

Doppler velocimetry of the umbilical and intraplacental fetal arteries was studied by color flow mapping in 39 normal pregnancies. The systolic-diastolic ratio (S/D) and pulsatility index of the intraplacental fetal artery downstream to the umbilical artery decreased significantly with advancing gestational age, and its S/Ds were persistently lower than those of the umbilical artery. The difference in the S/D between the umbilical artery and its intraplacental downstream branches decreased with advancing gestational age and approached zero as the pregnancy progressed to term. We conclude that intraplacental fetal arteries, possibly fetal arteries in main stem villi, can be imaged by color flow mapping and that there is a significant "resistance gradient" between the intraplacental fetal artery and the umbilical artery. Intraplacental fetal artery velocimetry using color flow mapping may give further insights into the umbilical-placental circulation.     

Initial results of laser angioplasty under angioscopic guidance for salvage of an ischemic lower limb: preliminary report

From March to July 1989, nine patients at risk for peripheral artery disease underwent intraoperative Nd:YAG laser angioplasty using angioscopy at the Veterans General Hospital (Taipei, Taiwan, Republic of China). Following the laser angioplasty, balloon dilatation was performed in all cases. Eight men and one woman at an average age of 68 were included in the study (range: 58 to 78 years old). Ischemic symptoms included five patients with disabling claudication, four with pain at rest and one with gangrene on the toes. Eight of the nine patients had complete occlusions ranging from 2 to 19 cm in length. Two patients had high degree multiple segmental stenosis of the superficial femoral artery from 1 to 2 cm in length. Initial clinical success (indicated by relief of symptoms and increase in Doppler ankle pressure and index) and improvement in the angiographic luminal diameter was noted in 9 of 10 occluded vessels (90%) that underwent Nd:YAG laser treatment which was delivered at 10 to 12 watts through laser probes. Prelaser intraluminal diameter increased from 0.05 +/- 0.07 to 0.53 +/- 0.07 mm, Doppler ankle pressure index rose from 0.51 +/- 0.12 to 0.81 +/- 0.12, Doppler ankle pressure increased from 62.44 +/- 16.10 to 104 +/- 21.21 mmHg and the amplitude of pulse volume recorder at ankle level rose from 5.77 +/- 2.80 to 12.11 +/- 2.77 mm as compared with prelaser therapy (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Observation of nervous tissue in a Wilms' tumor: its histogenetic significance.

A case of Wilms' tumor occurring in a horseshoe kidney is reported in which bona fide nervous tissue containing ganglion cells was observed. This finding cannot be reconciled with the currently held "metanephrogenic blastema" theory of the histogenesis of this tumor. Masson's concept of "neuroepithelial origin" of the Wilms' tumor should be re-evaluated.     

The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.     

Disposition and metabolic fate of atomoxetine hydrochloride: pharmacokinetics, metabolism, and excretion in the Fischer 344 rat and beagle dog.

These studies were designed to characterize the disposition and metabolism of atomoxetine hydrochloride [(-)-N-methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride; formerly know as tomoxetine hydrochloride] in Fischer 344 rats and beagle dogs. Atomoxetine was well absorbed from the gastrointestinal tract and cleared primarily by metabolism with the majority of its metabolites being excreted into the urine, 66% of the total dose in the rat and 48% in the dog. Fecal excretion, 32% of the total dose in the rat and 42% in the dog, appears to be due to biliary elimination and not due to unabsorbed dose. Nearly the entire dose was excreted within 24 h in both species. In the rat, low oral bioavailability was observed (F = 4%) compared with the high oral bioavailability in dog (F = 74%). These differences appear to be almost purely mediated by the efficient first-pass hepatic clearance of atomoxetine in rat. The biotransformation of atomoxetine was similar in the rat and dog, undergoing aromatic ring hydroxylation, benzylic oxidation (rat only), and N-demethylation. The primary oxidative metabolite of atomoxetine was 4-hydroxyatomoxetine, which was subsequently conjugated forming O-glucuronide and O-sulfate (dog only) metabolites. Although subtle differences were observed in the excretion and biotransformation of atomoxetine in rats and dogs, the primary difference observed between these species was the extent of first-pass metabolism and the degree of systemic exposure to atomoxetine and its metabolites.     

KTP Laser and Neutral Red Phototherapy of Human Squamous Cell Carcinoma

Neutral red (NR) is a cationic, nontoxic vital dye employed as a histologic stain for proliferating cells; it has been used clinically for photodynamic treatment of herpes simplex virus lesions. NR is selectively taken up and concentrated by mitotic cells, an important characteristic for more effective antineoplastic agents. In the present study, UCLA-SO-P3 human squamous carcinoma cells displayed minimal toxicity when incubated with up to 50 μg/ml NR in the absence of light. However, cells incubated with greater than 0.5μg/ml NR followed by exposure to KTP laser light at 532 nm exhibited nearly 100% tumor cell death. The degree of cell toxicity was proportional to NR dose and laser light fluence. This study demonstrates that NR is an excellent cancer cell photosensitizer in vitro, and, after adding additional in vivo preclinical testing, may prove to be a useful agent in photodynamic destruction of head and neck tumors.