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Biomedical subjects

A J Block

Publications and source records attributed to A J Block.

At least 91 records · Page 5Linked to original sources
PubMed1984

Does flurazepam ingestion affect breathing and oxygenation during sleep in patients with chronic obstructive lung disease?

For two consecutive nights, 20 patients with chronic obstructive pulmonary disease (COPD) without significant carbon dioxide retention were monitored by polysomnography in a sleep laboratory study of the effects of flurazepam ingestion. In a double-blind, controlled, randomized fashion, they ingested 30 mg of flurazepam or placebo on one night and the alternate compound on the other night. Flurazepam increased the frequency of sleep-disordered breathing events (p less than 0.01), the frequency of episodes of desaturation (p less than 0.01), the duration of desaturation (p less than 0.01), and the severity of desaturation (p less than 0.05). Although the findings were significant, the magnitude of the changes was small. In 17 of the 20 patients, the ingestion of a single 30-mg flurazepam tablet did not cause clinically significant oxygen desaturation or breathing disturbance. The active drug did increase total sleep time (p less than 0.001) and thus was an effective hypnotic in patients with COPD.

Aged↗
PubMed1983

Increased ventricular ectopy and sleep apnea following ethanol ingestion in COPD patients.

The effects were assessed of ingestion of 1 ml/kg of 100 proof vodka on sleep-disordered breathing, nocturnal oxygen desaturation, and ventricular ectopy in patients with chronic obstructive pulmonary disease (COPD). Ethanol ingestion (mean blood alcohol concentration of 40 mg/dl) was associated with a significant increase in the number of premature ventricular contractions (PVCs) per night and the number of PVCs per hour of sleep-period time, but was not associated with other ventricular dysrhythmias. Ethanol also increased the number of episodes of apnea, total duration of apnea, and the number of episodes of apnea per hour of total sleep time, but there was no significant change in hypopnea or oxygen desaturation. Ethanol decreased total sleep time but did not significantly alter sleep stage distribution. This study demonstrates that moderate ethanol consumption increased ventricular ectopy and sleep apnea in patients with COPD.

Adult↗
PubMed1983

Medroxyprogesterone acetate and COPD. Effect on breathing and oxygenation in sleeping and awake patients.

The effects of oral medroxyprogesterone acetate (MPA) (20 mg three times daily) were assessed on sleep-disordered breathing and on arterial blood gas levels in awake patients with chronic obstructive pulmonary disease (COPD). Seventeen men and two women (mean baseline PaO2, 65 mm Hg; PaCO2, 41 mm Hg; and FEV1/FVC ratio, 48 percent) participated in a double-blind, placebo-controlled, randomized study. After an initial night of polysomnography and daytime arterial blood gas analysis, the patients were randomized to receive either MPA or an identical placebo for one month; the studies were then repeated. The alternate compound was given for an additional month, and the studies were performed a third time. MPA in awake patients was associated with an increased mean PaO2 value, reduced PaCO2, and increased pH. Although there was no significant change in the number of episodes of sleep apnea, hypopnea, desaturation, or the minimal saturation, MPA marginally decreased the number of minutes of total sleep time when oxygen saturation was less than 90 percent (p = .06). In conclusion, MPA improves oxygenation and CO2 elimination and increases the pH in awake patients with COPD, but during sleep, does not significantly affect disordered breathing and only marginally improves desaturation.

Acid-Base Equilibrium↗
PubMed1982

Effect of flurazepam on sleep-disordered breathing and nocturnal oxygen desaturation in asymptomatic subjects.

We assessed the effect of 30 mg of oral flurazepam on sleep-disordered breathing and nocturnal oxygen desaturation by performing a double-blind, placebo-controlled, randomized study. Asymptomatic subjects, 17 men and three women (mean age 49 years, mean weight 79 kg), were monitored for two consecutive nights. Flurazepam was given to 10 subjects on night 1 and to 10 subjects on night 2. Placebo was ingested on the other nights. Polysomnographic determinations included chest wall movement by impedance pneumography, nasal and oral airflow by thermistor probes, and continuous oxygen saturation by ear oximetry. Flurazepam was associated with significant increases in the number of sleep events (p = 0.01), episodes of apnea (p less than 0.01), and total duration of apnea (p less than 0.01). The number of episodes of hypopnea of desaturation did not significantly increase, although the degree of desaturation increased after flurazepam ingestion (p = 0.04). Total sleep time significantly increased (p = 0.04), but could not account for the increased number of events. Sleep stage distribution was minimally altered by ingestion of flurazepam.

Adult↗
PubMed1982

On the kinetics and dynamics of tocainide and its metabolites.

The kinetics of tocainide, a new antiarrhythmic, and two of its metabolites, lactoxylidide (LX) and tocainide carbamoyl glucuronide (TG), were examined in patients given tocainide for 7 days following an acute myocardial infarction. In these patients kinetics were much the same as those reported for volunteers and for patients treated with tocainide for chronic extra ventricular beats. Mean half-life for tocainide, LX, and TG were 13.6, 29.1 and 13 hr. At steady state mean metabolite to tocainide ratios in serum were 0.48 for LX and 0.28 for TG. Using animal models, we examined the relative antiarrhythmic, direct cardiac, and central nervous system (CNS) effects of tocainide and LX. LX, the deaminated alcohol metabolite, had no antiarrhythmic, direct cardiac, or CNS toxic effects. These data suggest that tocainide, unlike many antiarrhythmic drugs, has no active metabolites.

Aged↗
PubMed1982

The effect of weight loss on sleep-disordered breathing and oxygen desaturation in morbidly obese men.

Four morbidly obese men who had been found to have significant sleep-disordered breathing and oxygen desaturation were restudied after an average weight loss of 108 kg (range 53-155 kg). In all subjects, weight loss was accompanied by a significant reduction in the number of episodes per hour of sleep-disordered breathing events. In three of the four subjects, there was improvment in the severity of desaturation accompanying abnormal breathing. The two subjects with daytime somnolence and hypercapnia prior to weight loss showed the most dramatic improvement in desaturation. This suggests that obesity is a cause, rather than an effect, of the sleep apnea syndrome.

Adult↗
PubMed1981

Synthesis of alkylaminoalkylamides of substituted 2-aminopyrroles as potential local anesthetic and antiarrhythmic agents I: alpha-Amines.

The synthesis, local anesthetic and antiarrhythmic properties, and CNS toxicity of 19 2-(2-alkylaminoalkylamido)pyrroles are described. Most of the compounds exhibited local anesthetic activity by the guinea pig wheal test, and four showed activity comparable to or greater than that of lidocaine. Most compounds also exhibited antiarrhythmic activity; five compounds had activity comparable to that of lidocaine, and one was more potent. All compounds exhibiting antiarrhythmic activity also were toxic to the central nervous system.

Amides↗
PubMed1981

Synthesis of alkylaminoalkylamides of substituted 2-aminopyrroles as potential local anesthetic and antiarrhythmic agents. II: beta-Amines.

The synthesis, local anesthetic and antiarrhythmic properties, and CNS toxicity of 14 2-(3-alkylaminoalkylamido)-pyrroles are described. Most of the compounds exhibited local anesthetic activity by the guinea pig wheal test, with seven showing comparable or greater activity than lidocaine. Most compounds also exhibited antiarrhythmic activity; three compounds had more potent activity than lidocaine. All compounds exhibiting antiarrhythmic activity also were toxic to the CNS. However, two of the three compounds having greater activity than lidocaine possessed more desirable therapeutic indexes.

Amines↗
PubMed1981

Alcohol increases sleep apnea and oxygen desaturation in asymptomatic men.

Using standard sleep techniques, we performed a placebo-controlled and randomized study to assess the effect of alcohol ingestion (2 ml/kg of body weight) on breathing and oxygen saturation during sleep. Twenty asymptomatic men volunteered for the two-night study: 11 were given a placebo on night 1, and alcohol on night 2 (group A); nine were given alcohol on night 1 and a placebo on night 2 (group B). We compared the incidence of sleep events (apnea, hypopnea and arterial oxygen disaturation) during the nights the subjects received alcohol and during the nights they received the placebo. Alcohol was associated with significant increases in the occurrence of the following: the number of sleep events (207 to 383,p less than 0.01), the events of arterial oxygen disaturation (118 to 226, p less than 0.01) and the number of apneic events (20 to 110, p less than 0.01). Alcohol had no significant effects on the number of times hypopnea occurred. Values obtained during sleep on the control night after alcohol ingestion also showed that the episodes of arterial oxygen desaturation remained statistically increased over control values before the ingestion of any alcohol (p = 0.01). These results show that in asymptomatic men alcohol ingestion increases the incidence of arterial oxygen desaturation and disordered breathing during sleep and that the increase in arterial oxygen desaturation persists for an additional night, even when no alcohol is consumed.

Adult↗
PubMed1981

Menopause, medroxyprogesterone and breathing during sleep.

Twenty-one postmenopausal women were monitored for sleep-disordered breathing and nocturnal oxygen desaturation to evaluate the contribution of progestational hormones to the occurrence of these sleep events. For approximately one month 11 subjects received 30 mg of medroxyprogesterone (MPG) daily, and 10 received placebo tablets in a randomized, double-blind controlled study. Respiration, saturation and electroencephalography were monitored during one night of sleep before and one night after therapy. Contrasted with the low incidence of disordered breathing and desaturation in premenopausal women, 71 percent of the postmenopausal women had such events. In the placebo-treated group, all measured variables of sleep and breathing were identical on the two nights, which suggested that the findings of a single night of sleep monitoring may be representative of other nights of sleep. Although several subjects appeared to show improvement with MPG, only the maximum duration of apnea was significantly reduced the second night (p less than 0.03).

Adult↗
PubMed1981

New antiarrhythmic agents. 5. alpha-Aminoaceto-2,6-xylidides with functionalized amide alkyl substituents.

The synthesis of aminoaceto-2',6'-xylidides substituted on the amide nitrogen with 2-(diethylamino)ethyl, 2-aminoethyl, 2-hydroxyethyl, and 2-ethoxyethyl groups is described. The 2-aminoethyl derivatives were prepared by treatment of N-(2-phthalimidoethyl)-2',6'-xylidine with chloroacetyl chloride, followed by treatment with either potassium phthalmide or diethylamine. Hydrazinolysis of the phthalimides liberated the free amines. The remaining target compounds were produced by alkylation of lidocaine or of 2-phthalimidoaceto-2',6'-xylidide with the appropriate halide and sodium hydride, followed by hydrazinolysis where necessary. All target compounds were evaluated for antiarrhythmic efficacy against chloroform-induced ventricular tachycardia, as well as for acute CNS toxicity in mice. Most of the target compounds were more potent than the corresponding secondary amides and had improved therapeutic margins toward CNS toxicity. The diamines N-(2-aminoethyl)-2-aminoaceto-2',6'-xylidide (13) and N-(2-aminoethyl)--2-(diethylamino)aceto-2',6'-xylidide (29) are especially promising in this respect. Several compounds were tested as spinal anesthetics.

Acetanilides↗
PubMed1981

New antiarrhythmic agents. 6. Quantitative structure-activity relationships of aminoxylidides.

The synthesis and pharmacological evaluation of primary and tertiary aminoxylidides with the amino group in the 2-7 position of the acyl chain are described. 2,6-Xylidine was acylated with haloacyl halides and converted to the target compounds by direct amination or by the Gabriel procedure. Alternatively, 2,6-xylidine was coupled with keto acids, and the ketoxylidides were converted to the amines by reductive amination. The target compounds were evaluated in mice both for antiarrhythmic efficacy against chloroform-induced tachycardia and for central nervous system toxicity. Experimentally determined values of partition coefficients and pKa values were used for quantitative structure-activity analyses. While the antiarrhythmic activity could be described as a function of log P alone, the CNS toxicity was best described as a function of both log P and pKa. The results suggest that antiarrhythmic potency can be increased by increasing lipophilicity, while the therapeutic index can be improved by increasing the pKa.

Animals↗
PubMed1981

Respiratory insufficiency associated with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a disease that may present with gastrointestinal, psychiatric, or neurologic symptoms. We describe two patients in whom AIP was first diagnosed during episodes of acute respiratory insufficiency. The biochemical defects, clinical presentations, pathophysiology, diagnostic criteria, and treatment of AIP are reviewed. We emphasize that AIP should be considered in the differential diagnosis of every patient with unexplained respiratory failure. Once considered, AIP is relatively simple to diagnose and specific therapeutic measures can be instituted.

Acute Disease↗
PubMed1981

A radiographic method for measuring steady-state functional residual capacity in the supine patient. A method suitable for sleep studies.

We have devised a method to measure functional residual capacity (FRC) in the recumbent, spontaneously breathing patient. Simultaneous anteroposterior and lateral chest radiographs were exposed at the end of an exhalation, as determined by tracings of flow sensed by a nasal thermistor. The volume of the lungs was then planimetrically measured. Functional residual capacity was sequentially measured in 20 supine subjects, both by a helium dilution technique and by the radiographic technique. Planimetric measurement of FRC correlated well with the helium dilution technique, with a range of FRC measurements from 1.53 to 6.41 L (r = 0.94). This method of measuring lung volume should be useful in evaluating changes in FRC associated with different sleep stages and in explaining the mechanisms causing nocturnal oxygen desaturation in patients with chronic obstructive lung disease.

Functional Residual Capacity↗