Submergence of a previously restored maxillary first molar associated with mesial tilting of an adjacent tooth.
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Biomedical subjects
Publications and source records attributed to J T Biggs.
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In areas lacking public water supplies and where fluoride is not naturally present in the well water, school fluoridation programs have been shown to be effective and safe. Reductions of up to 38.9% in the rate of dental decay have been reported. Higher levels of fluoride are used in the school water than in public water because of the limited time the children are in school. The relatively low cost of the necessary equipment and chemicals can easily be justified by taking into account the amount of dental decay that can be prevented. Interested parents, teachers, or administrators should contact their state health department for technical assistance.
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The kinetics of doxepin (DOX) hydrochloride were studied in 7 volunteers after the oral administration of 75 mg. Peak plasma concentrations of DOX ranged from 8.8 to 45.8 ng/ml and were reached within 4 hr. The disappearance of DOX was biphasic and followed first-order kinetics. The mean DOX half life (t1/2) was 16.8 hr and in individuals ranged from 8.2 to 24.5 hr. The mean apparent volume of distribution was 20.2 L/kg and ranged from 9.1 to 33.3 L/kg. The estimated first-pass metabolism of DOX ranged from 55% to 87% of the oral dose assuming complete absorption. Significant quantities of the metabolite desmethyldoxepin (DMD) were produced. Peak levels of DMD ranged from 4.8 to 14.5 ng/ml and were reached between 2 and 10 hr after administration. The mean t1/2 of DMD was 51.3 hr and in individuals ranged from 33.2 to 80.7 hr. There was no correlation between the DOX and DMD t1/2s. The amount of DMD produced correlated with the plasma concentration of DOX and appears to explain the correlation between the steady-state concentrations of DOX and DMD in patients given DOX.
The kinetics of protriptyline were examined in 8 subjects after a single oral dose of 30 mg protriptyline hydrochloride. Peak protriptyline levels ranged from 10.4 to 22.3 ng/ml and were reached 6 to 12 hr after the oral dose. The mean protriptyline half-life (t1/2) was 74.3 hr and ranged from 53.6 to 91.7 hr in individual subjects, confirming the long t1/2 of protriptyline reported by Moody and associates. The estimated first-pass metabolism of protriptyline was relatively small, ranging from 10% to 25% of the oral dose, assuming complete absorption. The mean volume of distribution was 22.5 L/kg and ranged from 15.0 to 31.2 L/kg. No relationship was found between the kinetics of protriptyline and those of doxepin studied previously in 7 of the 8 subjects.
The clinical pharmacokinetics of amitriptyline were studied in four volunteers after the oral administration of 75 mg. Peak amitriptyline plasma concentrations ranged from 10.8 to 43.7 ng/ml. The disappearance was biphasic and followed first-order kinetics. The mean elimination half-life was 36.1 hours. The mean estimated first-pass metabolism of amitriptyline was 60 per cent. Significant quantities of the metabolite, nortriptyline, were produced although peak concentrations ranged from only 5.9 to 12.3 ng/ml. The relationship between these findings to clinical practice and earlier reports is discussed.
Nine or 10 serial steady-state plasma measurements of amitryptyline, desipramine, desmethyldoxepin, doxepin, imipramine, nortriptyline, or protriptyline were made in 23 depressed patients. Each patient was monitored for compliance by pill counts, and sampling time was controlled carefully to determine intrapatient variability of steady-state tricyclic levels on a day-to-day basis. The coefficients of variation during serial sampling of the various ingested drugs were: amitriptyline, 21%; desipramine, 26%; doxepin, 21%; imipramine, 14%; nortriptyline, 13%; and protriptyline, 17%. The therapeutic ranges for the tricyclic antidepressants are relatively wide, so coefficients of variation of these magnitudes indicate that the position of an individual patient in relation to the optimal therapeutic range can be reliably determined on a clinical basis.
Described as the drugs of choice in treating acute depression, the tricyclics are unusual in that too high a dosage may be as ineffective as one that is too low, and plasma levels may vary as much as 30-fold among patients given the same dosage. After the recommended approach to determining appropriate dosage has been tried, the 15% or so of patients who do not respond are not likely to benefit from a switch of drugs.
The Zung Self-rating Depression Scale (ZSDS) correlated well (0.69) with the treating physician's global rating in 26 depressed out-patients during the six weeks of treatment with a tricyclic anti-depressant. In a larger sample of 41 patients, a high correlation was found between the ZSDS and the Hamilton Rating Scale. The sensitivity of the ZSDS was found to be adequate. The scale was able to differentiate, at the 0.05 level, four severity groups classified on the basis of the global rating. The importance of the direct relationship between the range of severity studied and the value of the correlation coefficient was discussed. Previous investigations and the results of this study indicate that the ZSDS is a valid and sensitive measure of clinical severity in depressed patients and support its continued use as a research instrument.
An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.
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