Biomedical subjects

R D Reynolds

Publications and source records attributed to R D Reynolds.

At least 91 records · Page 5Linked to original sources

PubMed1987

A comparison of plasma pyridoxal 5'-phosphate concentrations in capillary (finger prick) and venous blood.

The purpose of our study was to investigate the validity of using capillary blood plasma to estimate the pyridoxal 5'-phosphate (PLP) concentration of venous blood plasma. To accommodate the small volumes of capillary blood usually obtained, we modified the experimental conditions of the L-tyrosine apodecarboxylase (TDC) assay for PLP by increasing both the specific activity of 14C-tyrosine and the reaction incubation time. Plasma PLP concentrations determined by the TDC assay and the micro-modified TDC assay were highly correlated (r = 0.995, p = 4.0 X 10(-6)). Using the micro-modified TDC assay, we observed no significant difference between the plasma PLP concentrations of venous and capillary (finger prick) blood from 10 healthy adults. Thus, capillary blood plasma can be used to estimate the PLP concentration of venous blood plasma. This observation will aid in verifying data concerning the vitamin B-6 status assessment of individuals as determined by capillary blood plasma PLP concentrations.

Adult↗

PubMed1987

Zinc, vitamin B-6, and other nutrients in pregnant women attending prenatal clinics in Mexico.

Biochemical measurements and 24-h dietary recalls were conducted early (18.9 +/- 5.9 wk) and late (35.1 +/- 2.0 wk) in pregnancy in women attending clinics in Montemorelos, Mexico. Mean weight gain per week (0.4 +/- 0.2 kg) and birth weight (3381 +/- 456 g) were normal. Intakes tended to decline during pregnancy and declined significantly for zinc (p less than 0.05) and vitamin B-6 (p less than 0.03). Mean Zn intake late in pregnancy was low (7.8 +/- 3.3 mg/d). Various supplements were taken but none contained Zn. During pregnancy mean plasma Zn levels fell (p less than 0.001) and late in pregnancy 57% of the women had values suggestive of poor Zn status (less than or equal to 8.1 mumol/L). These data indicate that Zn intakes of approximately 8 mg/d will not maintain plasma Zn levels in late pregnancy. Erythrocyte glutamic-pyruvic transaminase (EGPT) index and the index of diamine oxidase (DAO), a vitamin B-6-requiring enzyme of placental origin, were correlated suggesting that DAO index may be useful in evaluating vitamin B-6 status in pregnancy.

Adult↗

PubMed1987

Controlled-release oral morphine sulfate in the treatment of cancer pain with pharmacokinetic correlation.

The bioavailability and clinical effects of an oral controlled-release morphine sulfate tablet, MS-contin (MSC; Purdue-Frederick, Norwalk, CT) in comparison to an immediate-release (IRMS) preparation were evaluated in normal subjects and cancer patients, respectively. The inherent slow-release character of MSC was confirmed by 2 1/2 X T1/2 absorption rate, one-half Cmax, and twice Tmax relative to IRMS. The T1/2 elimination of the two morphine preparations was similar, demonstrating insignificant risk of MSC accumulation. The difference in the mean number of side effects experienced by the control group per subject was significant (.70 for MSC and 1.26 for IRMS, P = .05) and was consistent with peak plasma morphine attenuation. The cancer patients were initially switched from their previous analgesic to four hourly IRMS and then to MSC at double the dose every eight hours. The majority had their MSC dosing interval lengthened to every 12 hours with a decrease in the total daily morphine requirement. While the mean duration on MSC was 20.5 days, many patients were followed poststudy for an extended period with no appreciable development of tolerance. Overall, MSC analgesia and side effects were perceived by the patients as superior compared with prestudy opioids. The advantage of less frequent dosing may lead to improvement of the quality of life of cancer patients.

Adult↗

PubMed1987

Pyridoxal phosphate concentrations determined postmortem as an indication of antemortem vitamin B-6 status.

In anticipation of studies relating vitamin B-6 status determined at autopsy to known pathologic causes of death, the postmortem stability of pyridoxal phosphate (PLP) in the plasma, skeletal muscle, and liver of pigs was assessed. Concentrations of plasma K, Mg, Na, and Ca also were examined for postmortem stability using the pig as an experimental model. At 1 hr after death, the mean plasma PLP concentration was essentially unchanged from that observed prior to death. Thereafter, plasma PLP concentration increased with increasing postmortem time interval and was 2.3 times greater than initial by 6 hr postmortem and 7.6 times greater than initial by 12 hr postmortem (P less than 0.01). Skeletal muscle and liver PLP content were 35% lower than initial by 6 hr postmortem (P less than 0.01). Plasma K and Mg were significantly higher by 1 hr postmortem (P less than 0.01) while plasma Na concentration was significantly lower by 1 hr postmortem (P less than 0.01). Plasma Ca concentration was not significantly different at any measured time point. Knowledge of the postmortem time interval appears to be required in order to evaluate the antemortem vitamin B-6 status using pyridoxal phosphate values derived from autopsy samples.

Animals↗

PubMed1987

Phytate:zinc and phytate X calcium:zinc millimolar ratios in self-selected diets of Americans, Asian Indians, and Nepalese.

The literature indicates that phytate:zinc and phytate X calcium:zinc millimolar ratios of a diet may provide useful indexes of the bioavailability of dietary zinc. However, there is little information on the phytate:zinc and phytate X calcium:zinc millimolar ratios for total human diets. We have therefore determined the phytate:zinc and phytate X calcium:zinc millimolar ratios of self-selected diets of 29 American omnivores, 23 American vegetarians, 30 Asian Indian immigrant vegetarians, and 26 Nepalese lactating vegetarians. Criteria for selection of subjects were: good health, no extreme dietary habits, and no intake of nutrient supplements. According to the limited literature, the suggested critical values for phytate:zinc and phytate X calcium:zinc millimolar ratios in animal diets and retrospective calculations from human diets are greater than 10 and greater than 200, respectively. The mean phytate:zinc and phytate X calcium:zinc millimolar ratios of American omnivorous diets in the present study were less than 10 and 200, respectively. Confirmation of the critical molar ratios as indexes of the bioavailability of zinc in human diets has not been established by experimentation. However, if the data from animal studies are applicable to human diets, the present study suggests that phytate has little influence on zinc bioavailability of most American diets. In contrast, the mean phytate:zinc and phytate X calcium:zinc millimolar ratios of all vegetarian diets were above the proposed critical levels. Those data, therefore, suggest that phytate might increase the risk of impaired zinc bioavailability for vegetarians consuming a relatively high level of calcium.

Biological Availability↗

PubMed1987

Antiarrhythmic, electrophysiologic and hemodynamic effects of ACC-9358.

The antiarrhythmic, electrophysiologic and hemodynamic effects of a new antiarrhythmic agent, ACC-9358, were evaluated. In anesthetized dogs, ACC-9358 converted ouabain-induced ventricular tachycardia to normal sinus rhythm at a cumulative dose equal to encainide or flecainide and less than disopyramide. In 24-hr coronary artery ligated dogs, ACC-9358 suppressed spontaneous ventricular arrhythmias for up to 6 hr after oral or i.v. administration. The antiarrhythmic effect and plasma concentrations of ACC-9358 correlated well for both oral (r = 0.88) and i.v. (r = 0.87) administration. ACC-9358, flecainide and disopyramide were equieffective in converting crush-stimulation-induced atrial flutter in anesthetized dogs to normal sinus rhythm. In alpha-chloralose-anesthetized, closed-chest dogs, ACC-9358 slowed impulse conduction through the atria, atrioventricular node, His-Purkinje system and ventricles and prolonged atrial functional refractory period. In conscious dogs, ACC-9358 increased heart rate, reduced stroke volume and had no effect on mean arterial pressure, systemic vascular resistance or cardiac output. In alpha-chloralose-anesthetized dogs, ACC-9358-induced sinus tachycardia was unaffected by propranolol but was blocked by hexamethonium or vagotomy. In isolated cat ventricular muscle, the IC50 for the negative inotropic effect of ACC-9358 was significantly greater than flecainide or disopyramide. These results indicate that ACC-9358 is a potent, broad-spectrum, long-acting, orally and intravenously active class Ic antiarrhythmic agent that 1) may be devoid of active metabolites, 2) exerts little or no vascular effects and 3) has less direct cardiodepressant activity than flecainide or disopyramide.

Animals↗

PubMed1987

Validation of a semi-quantitative food frequency questionnaire: comparison with a 1-year diet record.

The validity of a self-administered semi-quantitative food frequency questionnaire was evaluated for a group of 27 men and women aged 20 to 54. Intakes of 18 nutrients computed from the questionnaire were compared with those derived from 1-year diet records completed approximately 18 months earlier. The questionnaire estimates of mean nutrient intake were within 10% of the mean diet record measurements for 11 of the 18 nutrients evaluated, and the difference was less than 25% for all but one nutrient (total vitamin A). Correlation coefficients comparing unadjusted nutrient intakes measured by the two methods ranged from 0.38 (vitamin C) to more than 0.65 (total calories, total fat, saturated fat, polyunsaturated fat, oleic acid, and cholesterol). The overall mean of correlation coefficients comparing intakes of the 18 nutrients measured by questionnaire and by diet record was 0.60. Coefficients for macronutrients decreased somewhat after adjustment for age and gender or caloric intake. The data provide further evidence that a simple and relatively inexpensive questionnaire can provide useful information on dietary intake over an extended period.

Adult↗

PubMed1986

Antiarrhythmic activity of flestolol, a novel ultra-short-acting beta-adrenoceptor antagonist, in the dog.

The antiarrhythmic activity of flestolol, an ultra-short acting beta-adrenergic blocker lacking appreciable local anesthetic activity, was examined in several different canine ventricular arrhythmia models. Flestolol, at steady state infusions of 1-1,000 micrograms/kg per min, was generally ineffective in reversing either ouabain-induced or delayed ischemia-induced (24 h Harris dog) ventricular tachycardia. However, flestolol (1, 10 and 100 micrograms/kg per min) produced a dose-dependent decrease in l-norepinephrine (5 micrograms/kg i.v.)-induced ventricular tachycardia in the 5-6 day old Harris dog; the effect of 100 micrograms/kg per min flestolol, 94% suppression of norepinephrine-induced ventricular tachycardia, was completely reversed 60 min after termination of flestolol infusion. In pentobarbital-anesthetized open-chest dogs with pretreatment heart rates greater than or equal to 145 beats/min, flestolol (10 micrograms/kg per min) reduced the incidence of ventricular fibrillation resulting from abrupt coronary artery occlusion compared to placebo-treated controls (15% or 2/13 vs. 70% or 7/10, respectively). These results demonstrate that flestolol has an antiarrhythmic profile consistent with its lack of local anesthetic activity and its ultra-short duration of beta-blockade.

Adrenergic beta-Antagonists↗

PubMed1986

Pharmacology and pharmacokinetics of esmolol.

Esmolol is an ultra-short-acting beta-adrenergic blocking agent that possesses minimal partial agonist activity or direct membrane depressant activity. The short duration of action of esmolol is attributable to rapid enzymatic hydrolysis by red blood cell esterases, forming ASL-8123 and methanol. Experiments in the constant-flow-perfused isolated canine hindlimb indicate that therapeutic (beta blocking) doses of esmolol lack direct vascular effects and alpha-adrenergic blocking activity and that therapeutic doses do not interfere with vascoconstrictor effects of peripheral sympathetic nerve stimulation. Esmolol produces cardiac electrophysiologic and hemodynamic effects consistent with those of beta blockade. Specifically, esmolol decreases heart rate, depresses atrioventricular nodal conduction, and decreases determinants of myocardial oxygen demand. The beneficial antiarrhythmic and infarct-size limiting effects of esmolol have been demonstrated in several experimental models. Whereas beta blockers in general are effective in settings of supraventricular arrhythmias, sinus tachycardia, and myocardial ischemia, esmolol provides the added dimension of "titratability." Thus, the short duration of action of esmolol allows for very rapid titration to a preferred steady-state level of beta blockade; rapid adjustment to different steady-state levels of beta blockade, as may be required by changing status of the patient, and rapid disappearance of beta blockade following discontinuation of esmolol infusion, should this be necessary in the event of deleterious cardiac hemodynamic effects. Thus, esmolol is ideally suited for use in the treatment of patients in whom beta blockade is desirable, but in whom level of beta blockade must be very carefully modulated.

Adrenergic beta-Antagonists↗

PubMed1986

Vitamin B6 deficiency and carcinogenesis.

The literature on the occurrence of carcinogenesis as related to vitamin B6 deficiency is reviewed, and several critical areas, such as altered tryptophan metabolism, impaired immune status, and the metabolism of polyamines are discussed in depth. Preliminary results of vitamin B6-related chemotherapy of malignant melanomas are also presented.

Animals↗

PubMed1986

Effect of oral vitamin B6 supplementation on in vitro platelet aggregation.

A randomized, double-blind study was conducted with 12 healthy adult males to determine the effects of oral pyridoxine supplementation on in vitro platelet aggregation. Following a 4-wk baseline period, half the subjects received 100 mg/day of pyridoxine X HCl while the remaining subjects received a placebo for 6 wk. In vitro platelet responses to ADP and collagen and the plasma pyridoxal 5'-phosphate (PLP) concentrations were measured at biweekly intervals. Plasma PLP concentrations increased significantly (p less than 0.001) for those receiving the vitamin B6 compared to baseline values or compared to those receiving the placebo. However, there was no significant effect of increased levels of plasma PLP on collagen-stimulated platelet aggregation and only a slight effect on ADP-stimulated aggregation. Acute administration of 100 mg pyridoxine X HCl failed to alter the in vitro response of platelets to either ADP or collagen. Reevaluation of conclusions based solely on in vitro studies suggesting the use of pyridoxine as an effective in vivo antithrombotic agent may be warranted.

Adenosine Diphosphate↗

PubMed1986

Malignant lymphoreticular lesions in patients with immune disorders resembling acquired immunodeficiency syndrome (AIDS): review of 80 cases.

Reports of high-grade non-Hodgkin's lymphoma, Hodgkin's disease, and lymphocytic leukemia in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-like immune disorders have been increasing. In some cases, histologic alterations of lymph node architecture may precede the development of malignant lesions. Early in the course of the disease, clinical profiles of these patients are indistinguishable from those of patients with AIDS-associated opportunistic infections, but rapidly evolving extranodal lesions often signify the establishment of a lymphoproliferative neoplastic process. The frequent involvement of the central nervous system is responsible for the dismal outcome of the disease in a significant number of patients. A high death rate and poor response to antineoplastic agents have often characterized the course of non-Hodgkin's lymphoma and leukemia, but some patients with Hodgkin's disease have had a favorable response to treatment and a long survival. Aggressive multidisciplinary treatment may effectively avert the devastating consequences of this array of lymphoreticular neoplasms. Studies of these intriguing disorders may provide a better understanding of the interrelationships of infection, immunity, and oncogenesis in man.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Comparison of the parasympatholytic activity of ACC-9358 and disopyramide.

ACC-9358 (N-[(3,5-di(pyrrolidinylmethyl)-4-hydroxy)benzoyl]aniline) is a newly developed analogue of changrolin, an antiarrhythmic agent used in the Peoples Republic of China. Since changrolin and other antiarrhythmic agents exert parasympatholytic activity which may limit their clinical usefulness, it was of interest to examine the parasympatholytic effects of ACC-9358. For comparative purposes we also studied the parasympatholytic activity of disopyramide. In guinea-pig isolated ileal strips, disopyramide, 3-30 microM, and ACC-9358, 100-300 microM, competitively antagonized carbachol-induced contractions with pA2 values of 5.78 and 4.17, respectively. In guinea-pig isolated right atria, disopyramide 3-30 microM, competitively antagonized methacholine-induced slowing of spontaneous beating with a pA2 value of 5.99 whereas ACC-9358, 3-300 microM, produced no significant muscarinic blockade in this preparation. Disopyramide (1.9-15 mg kg-1, i.v.), but not ACC-9358 (7.5-1.5 mg kg-1, i.v.), significantly increased rat pupil diameter in vivo. Disopyramide and ACC-9358 blocked vagal-induced reductions in heart rate in dogs anaesthetized with pentobarbitone. ED50 values were approximately 0.65 and 11.25 mg kg-1, respectively. We conclude that ACC-9358 possesses significantly less parasympatholytic activity than disopyramide.

Animals↗

PubMed1986

Phase I clinical trial of an MAF-containing lymphoblastoid cell line supernatant.

A preliminary Phase I evaluation of macrophage activating factor (MAF) derived from the partially purified supernatant of human RPMI-1788 lymphoblastoid cell line was performed in 4 parts in 39 patients with advanced cancer. The first two parts used subcutaneous routes of administration and the second two parts used a 4-h intravenous infusion method. Individual doses ranged from 0.1 ml (1.7 mg protein) to 100 ml (1,700 mg protein). Subcutaneous dose was limited by the volume of administered material, and an attempt to use a concentrate of the supernatant resulted in severe local skin reactions. Larger doses given intravenously were well tolerated. Resultant toxicity was mild and consisted of transient fever and chills. One patient with malignant melanoma had a complete response of a 3-cm skin metastasis; one patient with breast cancer had disappearance of a skin nodule while visceral disease progressed; and one patient with histiocytic lymphoma had resolution of a conjunctival lesion. Treatment in many patients was associated with an increase in absolute peripheral lymphocytes. In the high-dose intravenous group, a statistically significant increase in the phagocytic index of peripheral blood leukocytes was noted. Lymphoblastoid MAF appears to be relatively safe to administer and has promise both as an antitumor agent and in the treatment of other altered immune conditions.

Adolescent↗

PubMed1986

Phase I clinical trial of MAF containing preparation of RPMI-1788 B-cell human lymphoblastoid lymphokine in advanced cancer patients.

We report a summary of a Phase I clinical trial of the partially purified MAF-containing supernatant of RPMI-1788 human B-cell lymphoblastoid lymphokine conducted in 39 patients with advanced cancer. The trial was conducted in four parts: two subcutaneous and two intravenous routes and schedules of administration. Dose limiting toxicity in the subcutaneous trials was volume dependent. The intravenous trial was remarkably well tolerated so that the maximum tolerable dose exceeded expectations. The study demonstrated modification of the immune system including an increase in skin test reactivity, an increase in absolute lymphocyte counts, alteration in the monoclonal lymphocyte antibody markers, and an increase in MAF activity. Toxicity in the intravenous trial was limited to transient febrile reactions that were ameliorated by increasing the infusion time. Three objective tumor responses were observed.

B-Lymphocytes↗

PubMed1985

Effect of vitamin B-6 (pyridoxine) deficiency on lung elastin cross-linking in perinatal and weanling rat pups.

Weanling and perinatal rats were rendered vitamin B-6 (pyridoxine)-deficient. The rat pups were nursed from vitamin B-6-deficient or -sufficient dams and were killed at day 15 after parturition. The weanling rats were fed vitamin B-6-deficient or -sufficient diets and were killed after 5 weeks of treatment. Lung elastin from the groups of rats was then studied with respect to its content of lysine-derived cross-linking amino acids. Lung lysyl oxidase activity was also measured. B-6 deficiency decreased the number of lysine residues in elastin that were converted into the cross-linking amino acid precursor allysine. However, a more significant defect in cross-link formation was an apparent block in the condensation steps leading to the formation of desmosine. Desmosine was decreased, with an increase in the amounts of aldol condensation products (aldol CP) in elastin. It is proposed that the elevation in aldol CP results from the formation of thiazines, which are produced from the reaction between aldehyde and homocysteine. The concentration of homocysteine is significantly elevated in vitamin B-6-deficient rats.

Amino Acids↗

PubMed1985

Synthesis and antiarrhythmic and parasympatholytic properties of substituted phenols. 3. Modifications to the linkage region (region 3).

As part of a continuing program of systematically modifying the structure of the class I antiarrhythmic drug changrolin, we synthesized 15 analogues in which the linkage between the two aromatic regions was altered. High antiarrhythmic activity and low parasympatholytic activity was found when the linkage region, designated region 3, contained a carbonyl moiety, including ketones, amides, and ureas. Secondary amides were superior to tertiary amides, while amide reversal resulted in no change in activities. One compound in this series, 7, 2,6-bis(1-pyrrolidinyl-methyl)-4-benzamidophenol (ACC-9358), is undergoing preclinical evaluations.

Animals↗

PubMed1985

Depressed plasma pyridoxal phosphate concentrations in adult asthmatics.

In 15 adult patients with bronchial asthma, plasma and erythrocyte pyridoxal phosphate (PLP) concentrations were significantly lower than in 16 controls (P less than 0.0001 and P less than 0.005, respectively). Oral supplementation of seven asthmatics with 50 mg pyridoxine as pyridoxine X HC1 twice daily failed to produce a sustained elevation of PLP in either the plasma or erythrocytes. However, all subjects reported a dramatic decrease in frequency and severity of wheezing or asthmatic attacks while taking the supplement. The reasons for the failure of a uniform elevation in plasma and erythrocyte PLP concentration and for the apparent beneficial effects of pyridoxine supplementation on the asthmatic symptoms of the patients are unknown at present.

Adult↗