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Biomedical subjects

M Grace

Publications and source records attributed to M Grace.

At least 163 records · Page 9Linked to original sources
PubMed1993

Comparative pharmacokinetics and pharmacodynamics of two marketed bid formulations of diltiazem in healthy volunteers.

Cardizem SR and Bi-Tildiem were both approved in their respective countries on the basis of clinical trials demonstrating efficacy and safety in the treatment of angina pectoris. In this cross-over randomized study, we assessed whether these two sustained-release formulations of diltiazem have equivalent pharmacokinetic and pharmacodynamic profiles. Twenty-four young healthy male volunteers were hooked to Holters and ambulatory blood pressure monitors for 24 h to establish baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), sinus rate and PR intervals. They then received a single dose of 120 mg of diltiazem from one formulation. The pharmacodynamic measurements were recorded for a further 24 h and blood samples were collected over 36 h for evaluation of diltiazem in plasma by a high-performance liquid chromatogrpahic (HPLC) method. The procedures were repeated with the alternate formulation after a 7 d wash-out. Pharmacokinetics showed statistically significant (p < 0.01) differences in AUC0-12 with means (+/- SD) of 519.2(+/- 172.8) and 429.6(+/- 147.2) ng h ml-1, AUC0-36 of 835.6(+/- 281.6) and 730.9 (+/- 271.5) ng h ml-1 and Cmax of 89.1(+/- 30.3) and 61.1(+/- 21.2) ng ml-1 for Cardizem SR and Bi-Tildiem, respectively. The only pharmacodynamic parameter showing a statistically significant difference in change from baseline between the two formulations was DBP with mean (+/- SD) change in AUC0-12 of -13.6(+/- 20.8) and +8.4(+/- 31.7) mm Hg h (p = 0.0135) and in AUC0-24 of -33.0(+/- 43.7) and -0.3(+/- 59.2) mm Hg h (p = 0.0463) for Cardizem SR and Bi-Tildiem, respectively. These findings suggest that assessment of efficacy of sustained-release formulations of diltiazem by bioequivalence could be misleading. They also confirm that a single dose of diltiazem does not elicit a significant pharmacodynamic response in healthy volunteers. Equivalence for such formulations should therefore be demonstrated by pharmacodynamic evaluation or clinical studies in a patient population.

Adult↗
PubMed1993

Effects of neuropeptide Y on ingestion of flavored solutions in nondeprived rats.

Recent evidence suggests that in addition to altering energy balance, neuropeptide Y (NPY) may stimulate ingestive behavior by modifying the orosensory quality of ingested substances. The present experiments investigated the effect of intracerebroventricular administration of NPY (5 micrograms/5 microliters) on ingestion of various flavored solutions in nondeprived rats. Experiment 1 examined the effects of NPY on ingestion of a range of concentrations of saline, sucrose, and saccharin solutions in single-bottle tests. Results indicated that NPY stimulates ingestion of both sucrose and saccharin solutions that are normally palatable. In Experiment 2, palatable sucrose solutions flavored with either orange or black cherry Kool-Aid for separate training groups were selectively associated with NPY injection during single-bottle training sessions. Subsequent two-bottle preference tests showed a significant shift in preference toward the flavor paired with NPY during training. The results of these experiments extend previous findings by showing that NPY can stimulate ingestion of sweet solutions regardless of caloric value and may potentiate sweet taste preference via an associative mechanism.

Animals↗
PubMed1993

One-year outcome of elderly and young patients admitted to intensive care units.

OBJECTIVE: To compare the outcome of patients over and under age 65 admitted to two intensive care units (ICUs). DESIGN: Prospective, two-center study. Convenience sample of all admissions to two adult ICUs for a 1-yr period, with a 1-yr follow-up. SETTING: Adult multidisciplinary closed ICUs. PATIENTS: All patients (n = 1,040) admitted to two ICUs during a 1-yr period were entered into the study, except patients with self-induced poisoning. Of these patients, 145 patients were lost to follow-up. INTERVENTIONS: Admission statistics on all patients included demographic, case mix, and severity data. Variables associated with intensive care unit outcomes at discharge (length of stay, mortality) and at 1 yr from admission (mortality, functional capacity, health attitudes) were analyzed. Vital status was confirmed from both Alberta Vital Statistics and Alberta Health. Follow-up interviews were conducted with all available survivors. RESULTS: The elderly group (> 65 yrs) comprised 46% of patients studied. Both age groups (> 65 yrs and < 65 yrs) had comparable demographics and illness severity measures. Although ICU and 1-yr mortality rates differed between groups (16% of > 65 yrs vs. 12.9% of < 65 yrs ICU mortality and 49% of > 65 yrs vs. 31% of < 65 yrs 1-yr mortality), age was not a major contributor to the variance in outcome. At 1 yr, 65% of patients admitted to the study were alive. Follow-up interviews were conducted with 75% of survivors. Assessment of activities of daily living showed that the elderly patients were similar to younger patients. The elderly demonstrated more positive health attitudes than younger survivors. Functional capacity was significantly associated with health attitudes of younger patients, but not for older survivors. CONCLUSIONS: Age does not have an important impact on outcome from critical illness, which is most strongly predicted by severity of illness, length of stay, prior ICU admission and respiratory failure. Satisfaction with personal health should not be inferred from the functional status of elderly survivors of intensive care.

Activities of Daily Living↗
PubMed1993

Attempted experimental modification of the postlaminectomy membrane by local instillation of recombinant tissue-plasminogen activator gel.

A prospective, randomized, blinded trial involving 25 adult mongrel dogs was performed to evaluate whether placement of a fat graft or local instillation of recombinant tissue-plasminogen activator gel (rt-PA) could modify the development of a postlaminectomy membrane. One component of the study involved the performance of a lumbar laminectomy and placement of gel rt-PA, free fat, or no tissue placement over the exposed dura mater. Three months later the animals were killed and sections of spine were removed en bloc, decalcified, and examined histologically. No significant differences were found in the degree of cellular fibrosis or heavy collagen production. A similar laminectomy at another lumbar level was also followed by gel rt-PA, free fat, or no tissue placement. Three months after surgery, surgery was performed again at this level immediately before death. There were no differences in the adhesiveness of the laminectomy membrane to dura mater or roots. It was concluded that the local instillation of gel rt-PA after laminectomy did not inhibit scar formation or scar adherence to the dura mater.

Adipose Tissue↗
PubMed1993

No relaxation on drug safety and efficacy.

The background and current status of legislation and practice relating to drug certification in Canada are examined. An outline is given of procedures introduced to handle the growing workload faced by the regulatory authority.

Canada↗
PubMed1992

Quality development.

The problem with improving quality in dental practice is not so much a difficulty with understanding exactly what quality means, but more a lack of clear guidance as to how to take the simple, practical steps to achieving that improvement in the daily pressures of practice life. This article describes Quality Development, a simple and practical method that can be used in general practice to help the dental team achieve the objectives in quality care that are appropriate to them.

Dental Care↗
PubMed1992

Somatic reenactment in the treatment of posttraumatic stress disorder.

Somatic reenactments, like other intrusive symptoms in post-traumatic stress disorder, such as flashbacks and nightmares, reproduce the mental content of traumatic events. Four cases are presented from survivors of military trauma and civilian catastrophes. The patients were part of larger research projects carried out by the University of Cincinnati Traumatic Stress Study Center. Understanding such symptoms as repetitions of the trauma itself proved useful therapeutically, especially in consolidating the working alliance.

Adaptation, Psychological↗
PubMed1992

Effective periodontal control.

One of the major difficulties in periodontal care is that knowing the principles is of very little practical help when it comes to treating individual patients. This article discusses the identification of susceptible patients, the measurements of sites of disease and identification of active bursts of disease when the patient is on a maintenance programme that can be easily performed by the dental practitioner.

Dental Plaque↗
PubMed1992

Comparison of PT and aPTT values drawn by venipuncture and arterial line using three discard volumes.

BACKGROUND: Blood samples obtained through heparinized arterial catheters are used routinely for a variety of laboratory tests. Accuracy of coagulation studies performed from samples obtained in this fashion continues to be questioned, particularly in regard to the minimum discard volume necessary to clear the catheter of heparinized solution. OBJECTIVE: To examine differences between prothrombin time and activated partial thromboplastin time values obtained from blood drawn by venipuncture and from an indwelling intra-arterial line using three discard volumes. METHODS: Prothrombin time and activated partial thromboplastin time samples were drawn by venipuncture from 41 critically ill adult patients. Simultaneously, three consecutive blood samples of 2.3 mL were drawn from the arterial line after an initial discard volume of 3 mL (discard volumes of 3.0, 5.3 and 7.6 mL). RESULTS: Significant differences were found between arterial and venous prothrombin time values for the 3-mL discard volume group, as well as between arterial and venous activated partial thromboplastin time values for all three discard volume groups (paired t-test, Bonferroni correction). CONCLUSION: We recommend that when drawing prothrombin time and activated partial thromboplastin time samples from an arterial line, a 5.3-mL discard volume be used.

Adult↗
PubMed1991

Central administration of the opioid antagonist, LY255582, decreases short- and long-term food intake in rats.

A variety of opioid antagonists have been reported to decrease short-term food intake, but few appear to reduce long-term intake. In the present study we evaluated the effect of a relatively new class of opioid antagonists, 3,4-dimethyl-4-phenylpiperidines, on short-term and long-term food intake after central administration. We also evaluated their affinities for the mu and kappa opioid receptor sites in synaptosomal membranes derived from rat whole brain tissue (minus cerebellum) and guinea-pig cortex, respectively. The affinities for the mu receptor sites were LY255582 greater than LY217273 greater than LY256897 greater than naloxone greater than LY227444. The affinities for the kappa receptor sites were LY255582 greater than LY256897 = LY217273 greater than LY227444. LY255582 reduced food intake for up to 24 h after a single intraventricular injection. Doses as low as 1 microgram of LY255582 decreased food intake for up to 4 h. All other drugs were much less powerful. Naloxone and LY256897 only decreased food intake after injection of the 100 microgram dose. LY227444 and LY217273 failed to decrease intake at all doses tested. LY255582 (100 micrograms) decreased food intake over a 7 day period when injected intraventricularly once per day. The body weight of the rats also decreased during the 7 day period. Upon cessation of drug administration body weights and food intake approached control levels. Thus, LY255582 appears to be a very potent and long-acting anorectic agent which may be useful in the treatment of obesity. The mu and kappa binding profile of the phenylpiperidines does not seem to clearly correlate with their anorectic activity.

Animals↗
PubMed1991

Beta-funaltrexamine (beta-FNA) decreases deprivation and opioid-induced feeding.

We studied the effect of the mu antagonist, beta-funaltrexamine (beta-FNA) on deprivation and opioid-induced feeding. Intracerebroventricular pre-treatment of 20 h deprived rats with 0.1, 1, 10 and 20 nmol of beta-FNA decreased feeding by 24%, 50%, 50% and 38% during the first hour. Central administration of beta-FNA (0.1, 1 and 10 nmol) also decreased feeding induced by the mu opioid agonist, DAMGO by 57%, 60% and 71%. Feeding induced by the delta agonist, DSLET, was decreased by pre-treatment with beta-FNA; but only during the 1-2 h time points, a time when relatively little food was ingested. Intraventricular injection of beta-FNA failed to alter feeding stimulated by the kappa opioid agonist, U-50,488H. These data further substantiate a role for the opioid receptor in deprivation and opioid-induced feeding.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Adverse reactions to the preschool (fifth) dose of adsorbed diphtheria-pertussis-tetanus vaccine in Canadian children.

OBJECTIVE: To quantify accurately the rate of adverse reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid-pertussis vaccine-tetanus toxoid (DPT) vaccine and to test the hypothesis that large local reactions are attributable to the diphtheria toxoid. DESIGN: Double-blind randomized controlled trial. SETTING: Suburban community public health unit. PARTICIPANTS: Healthy children 4 to 5 years of age with a history of having received four doses of adsorbed DPT vaccine. INTERVENTIONS: Subjects were given either the standard DPT vaccine (with 25 Lf units of diphtheria toxoid) or a modified DPT vaccine (with 10 Lf units of diphtheria toxoid). They were assessed 24 hours later by a nurse. Serum samples obtained before vaccination were tested for diphtheria and tetanus antitoxin levels by means of neutralization assay and enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of large local reactions (an area of redness or swelling or both of 5 cm or greater) 24 hours after vaccination in the two groups. Relation between serum antitoxin levels before vaccination and the rate of large local reactions in each group. RESULTS: Of the 250 subjects enrolled 124 received the standard vaccine and 126 the modified one. Large local reactions occurred in 71% of the subjects receiving the standard vaccine and 52% of those receiving the modified one (p less than 0.01). In the former group large erythematous reactions occurred significantly more often in those with an elevated prevaccination diphtheria antitoxin level than in those without an elevated level; no relation was found between such reactions and the prevaccination tetanus antitoxin level. Reduced arm movement was evident in 45% of the children in the two groups. Few had systemic adverse reactions. CONCLUSIONS: Large local reactions occur frequently after the preschool administration of the DPT vaccine. These reactions are uncomfortable but not serious. They result in part from the large amount of diphtheria toxoid in the standard DPT vaccine.

Child, Preschool↗
PubMed1991

The flexible boundaried group: format, techniques, and patients' perceptions.

The model of a flexible boundaried group was developed to manage the problem of irregular group attendance of chronic mentally ill patients. The central element in the model enables patients to determine, within limits, the frequency with which they will attend sessions. Review of attendance records and patient interviews from one flexible group suggest that members adhere to their contractual agreement and are accepting of irregular attenders. This finding has been supported by experiences in three additional groups composed of chronically ill individuals. These groups, comprised of regular, core attenders and peripheral members, become cohesive and form a viable therapeutic treatment structure.

Chronic Disease↗
PubMed1991

The carboxyl-terminal region of human interferon gamma is important for biological activity: mutagenic and NMR analysis.

Deletion of nine amino acids from the carboxyl terminus of human IFN gamma (residues 138--146; LFRGRRASQ) resulted in a 7-fold increase in specific antiviral activity. Similar increases in receptor binding affinity were seen. Deletion of residues 136 and 137 (QM) had little additional effect, but removal of Ser135 resulted in a sharp drop in antiviral activity. Further removal of residues 133 and 134 (KR) lowered antiviral activity to 1% of the peak value. Comparison of the proton NMR spectra of selected deletions down to residue 132 showed that there was no significant change in the core protein structure. Deletions down to residue 125 had the same antiviral activity as those to 132, but changes could now be seen in the aromatic proton NMR spectrum of this shorter derivative. Substitution of the homologous murine sequence between residues 124 and 130 (human SPAAKTG; murine LPESSLR) resulted in only a small decrease in antiviral activity, further suggesting that the precise sequence in this region was not critical for activity. Ser135 was substituted with a number of other amino acids with little or no change in activity. The importance of the residues between 131 and 134 for biological activity was corroborated by mutagenesis, although some substitutions in this region were tolerated.

Animals↗