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Biomedical subjects

T C Smith

Publications and source records attributed to T C Smith.

At least 55 records · Page 3Linked to original sources
PubMed1993

Regulatory volume decrease in Ehrlich ascites tumor cells is not mediated by a rise in intracellular calcium.

Ehrlich ascites tumor cells suspended in hyposmotic solution initially swell and then shrink back towards normal volume, a process known as regulatory volume decrease (RVD). RVD is characterized by a specific loss of KCl, although the mechanism for this is currently unknown. The hypothesis that a rise in intracellular calcium ([Ca2+]i) activates calcium-sensitive ion conductances to initiate RVD was investigated. The results indicate that in the Ehrlich cell no rise in [Ca2+]i occurs when the extracellular osmolality is reduced from 300 mosM to 180 mosM. These findings were substantiated by the lack of sensitivity of RVD to the Ca(2+)-sensitive K+ channel blockers charybdotoxin (CTX) and nifedipine. In contrast, the ionophore ionomycin induced a cell shrinkage that was sensitive to CTX and nifedipine indicating that a rise in [Ca2+]i could play a role in cell volume reduction but that this occurred by a mechanism different from that observed in RVD. The conclusion from these experiments is that Ca2+ does not act as a second messenger for RVD in the Ehrlich cell.

Animals↗
PubMed1993

Management skills for directors of nursing.

What skills, tasks, and behaviors lead to effective management performance? The author reports a study in which directors of nursing were asked to assess their own skill performance and identify conflicts between management skills required of directors of nursing versus professional role expectations. Results provide a broader understanding of the director of nursing's role requirements and provide a validated base from which schools of nursing can plan curricula to prepare future nurse administrators.

Adult↗
PubMed1993

Nasal capnography in children: automated analysis provides a measure of obstruction during sleep.

A detailed analysis was made of nasal capnograms obtained from sleeping children with differing degrees of sleep-induced respiratory obstruction, the severe form being known as obstructive sleep apnoea. Clinical observations of these children were compared with analyses of nasal capnography data. During periods when the degree of obstruction was consistent throughout the first hour of sleep, the means and coefficients of variation of several parameters, derived from the capnograms were calculated. The coefficients of variation showed a close relationship to the degree of obstruction. In comparison, measures of end-tidal carbon dioxide concentration proved to be a very insensitive index of the degree of obstruction. The conclusion is that the usefulness of nasal capnography in predicting and grading obstruction can easily be extended by the use of statistical measures of dispersion and that this concept warrants further work.

Airway Obstruction↗
PubMed1993

Squamous cell carcinoma in plantar ulcers in leprosy. A case control study.

The objective of this case-control study was to identify factors associated with the development of squamous cell carcinoma (SCC) in plantar ulcers of leprosy patients. We examined 2 matched groups consisting of leprosy patients with and without SCC in a plantar ulcer. No correlations were found between the development of SCC and race, profession, place of origin, duration of leprosy, the type and duration of leprosy chemotherapy, presence of bone involvement and type of ulcer care treatment given. The only statistically valid finding was that the duration of the ulcer was significantly lower in the group with malignant change. In this group there was an apparently higher use of pesticides, the difference being not of statistical significance. It is concluded that factors other than ulcer duration need to be looked for, in order to identify factors influencing malignant change in plantar ulcers of leprosy patients.

Carcinoma, Squamous Cell↗
PubMed1993

Leprosy trends in northern Thailand: 1951-1990.

Data of new, previously untreated leprosy patients from 6 northern provinces of Thailand, diagnosed at McKean Rehabilitation Center, Chiang Mai and associated clinics between 1951 and 1990 were analysed. The following trends were found: 1) Decreasing numbers of new, previously untreated patients. 2) Increasing average age of patients at onset and presentation of disease. 3) Decreasing duration between onset and presentation. 4) Increasing percentage of patients presenting within the first year of symptoms. 5) Increasing percentage of paucibacillary cases. 6) Decreasing percentage of patients presenting with deformity. These trends are a reflection of those seen for the whole of Thailand and indicate that leprosy control is being effective. Patients are presenting at an earlier stage than before, with consequent reduction in disability and infectivity. Better usage of chemotherapy since 1976 has helped to reduce the transmission of bacilli from person to person, combined with effective health education activities which have dispelled some wrong ideas about leprosy and encouraged patients to seek help early in the course of the disease. Additional factors related to public health and living standards have also contributed.

Adolescent↗
PubMed1992

Clinical pharmacology of adinazolam and N-desmethyladinazolam mesylate following single intravenous infusions of each compound in health volunteers.

The tolerability, pharmacokinetics and pharmacodynamics of adinazolam and N-desmethyladinazolam (NDMAD) were assessed following intravenous infusions of 5, 10, 15, and 20 mg adinazolam mesylate, 10, 20, 30 and 40 mg NDMAD mesylate, and placebo. Six subjects per dose level received treatments in a double-blind crossover design. No clinically significant changes were seen in blood pressure, pulse, respiration, or clinical laboratory parameters. Untoward effects typical of benzodiazepines were observed almost exclusively after NDMAD administration. Adinazolam and NDMAD pharmacokinetics were dose-independent. NDMAD clearance was 50% of the value for adinazolam. Adinazolam and NDMAD administrations increased uric acid clearance and decreased plasma uric acid. Adinazolam administration had no significant effect on psychomotor performance. NDMAD administration produced dose related decreases in performance; 286 ng/ml NDMAD produced a 50% decrease in DSST. These results confirm that adinazolam and NDMAD both produce uricosuria and definitively show that adinazolam is devoid of benzodiazepine-like effects at therapeutic concentrations; NDMAD mediates these effects. Uricosuric activity is present for both compounds, but the relative potencies are still unknown.

Adolescent↗
PubMed1992

Hypoxia in sleeping children: overnight studies can be reduced to 4 hours without loss of clinical significance.

Twelve recordings of overnight pulse oximetry representing a range of severity of obstructive sleep disturbance were evaluated by 7 experienced clinicians. Each recording was then scored by counting the number of minutes in each hour affected at any time by a fall in saturation to below 90%. Comparison of the clinical evaluation and the overall scores gave a clear level of 5 minutes per hour at and above which all the assessors agreed that the charts had clinically important desaturation. Overnight pulse oximetry was then performed on 25 children aged between 12 months and 10 years about to undergo adenotonsillectomy. The charts were scored by the method above with a score of 5 or more indicating a positive result for hypoxic episodes. The scores for shortened analysis periods of 1, 2, 3 and 4 hours duration were compared with the overall score and no cases which were negative, up to and including 4 hours, became positive in the overall result. Thus recording pulse oximetry for 4 hours provides sufficiently accurate information for clinical purposes.

Child↗
PubMed1991

N-desmethyladinazolam pharmacokinetics and behavioral effects following administration of 10-50 mg oral doses in healthy volunteers.

Results of previous studies suggest that N-desmethyladinazolam, the major metabolite of adinazolam in man, contributes substantially to psychomotor effects and sedation observed following adinazolam administration. Therefore, the pharmacokinetics and pharmacodynamics of N-desmethyladinazolam were explored following administration of single oral doses of placebo and solutions containing 10, 30, and 50 mg N-desmethyladinazolam mesylate in a double-blind, randomized, four-way crossover design to 15 healthy male volunteers. Plasma concentrations of N-desmethyladinazolam were determined by HPLC. Psychomotor performance tests (digit symbol substitution and card sorting by fours and suits), memory tests and sedation scoring were also performed following drug administration. N-Desmethyladinazolam pharmacokinetics were dose independent over this range. Dose-related performance effects were observed at 1, 2, and 6 h after dosing. Memory was likewise affected at 2 h. Psychomotor performance decrements correlated with log N-desmethyladinazolam plasma concentrations. Analysis of the relationship between percentage decrements in digit-symbol substitution and plasma N-desmethyladinazolam using the Hill equation revealed a EC50 of 325 ng/ml. These results establish the relationship between N-desmethyladinazolam plasma concentrations and performance effects; these data will be helpful in assessing the contribution of N-desmethyladinazolam to clinical effects observed after adinazolam administration.

Adult↗
PubMed1991

Squamous cell carcinoma in chronic ulcers in leprosy: a review of 38 consecutive cases.

The histories of 38 consecutive cases of squamous cell carcinoma (SCC) arising in chronic ulcers of leprosy patients treated between 1981 and 1990 at the McKean Rehabilitation Centre, Northern Thailand were analysed retrospectively. The study included 37 individual patients; 29 males and 8 females. The average age was 60 years, the average duration of leprosy was 34 years and the average duration of ulcers was 12 years. Most patients (76%) came from leprosy settlements. Patients with borderline-tuberculoid (BT) leprosy were most commonly affected (63%), followed by lepromatous (LL) leprosy (21%) and borderline-lepromatous (BL) leprosy (16%). Four patients (11%) had histories of SCC on other extremities. Metastatic spread was observed in 2 cases (5%), both instances leading to death. The commonest site of involvement of SCC was the foot, but it was seen on the knee in 1 patient and on the hand in 2 others. The incidence rate of SCC in the group at risk (leprosy patients with disability grading 1 and 2) is calculated as being 0.79:1000 per year. SCC was seen in 1.8% of all cases admitted for ulcer care at the Centre. Treatment is by radical amputation. SCC in chronic ulcers in leprosy patients cannot be considered rare and emphasizes the need for an active policy of disability prevention in leprosy programmes.

Adult↗
PubMed1990

Clinical pharmacology of adinazolam and N-desmethyladinazolam mesylate after single oral doses of each compound in healthy volunteers.

The tolerance, pharmacokinetics, and pharmacodynamics of adinazolam and N-desmethyladinazolam (NDMAD) were assessed after single oral doses of 10, 30, and 50 mg adinazolam mesylate, NDMAD mesylate, and placebo. Within doses, six healthy male volunteers received these treatments in a double-blind crossover design. No clinically significant changes were observed in blood pressure, pulse, respiration, or clinical laboratory test results. Untoward effects were typical of benzodiazepines. Adinazolam and NDMAD kinetics were dose independent. Greater than 95% of the adinazolam dose was metabolized to NDMAD. Adinazolam and NDMAD mesylate produced dose-related increases in uric acid clearance and decreases in plasma uric acid. Both adinazolam and NDMAD mesylate administration resulted in dose-related sedation and decrements in psychomotor performance. Within doses, decrements produced by adinazolam and NDMAD were quantitatively similar. These results suggest that both adinazolam and NDMAD possess uricosuric activity and support the hypothesis that NDMAD primarily mediates benzodiazepine-like effects of adinazolam mesylate.

Administration, Oral↗
PubMed1990

Pharmacokinetics and dose proportionality of cefmetazole in healthy young and elderly volunteers.

The pharmacokinetics and dose proportionality of cefmetazole were studied in 24 healthy volunteers (12 young and 12 elderly). Each volunteer received single 0.5-, 1-, and 2-g doses of cefmetazole administered intravenously over 5 min according to a three-way crossover design. Serial plasma and urine samples were collected over a 24-h period following dosing and assayed for cefmetazole by a high-performance liquid chromatography method. Results of the dose proportionality portion of the study indicated that cefmetazole pharmacokinetics are linear and proportional with dose in both age groups. Comparisons of pharmacokinetic parameters between the young and elderly groups indicated that the systemic clearance was significantly lower in elderly than in young volunteers (92.4 versus 112 ml/min). Additionally, creatinine clearance was significantly lower in elderly (74.1 ml/min) than in young (92.9 ml/min) subjects. No significant differences between age groups were observed for volume of distribution, urinary recovery, terminal half-life, nonrenal clearance, or renal clearance, although half-life was slightly prolonged in elderly volunteers relative to that in young volunteers (1.54 versus 1.34 h), and renal clearance was slightly lower in elderly than in young volunteers (83.7 versus 96.1 ml/min). Both systemic and renal clearance were significantly correlated with creatinine clearance. These results indicate that the observed age-related differences in the pharmacokinetics of cefmetazole are most likely due to differences in renal function between the two age groups. The small reduction in cefmetazole elimination in the elderly would not warrant dose adjustment in this population.

Adult↗