Biomedical subjects
Publications and source records attributed to S L Stern.
We measured serum and RBC folate levels in 17 outpatients taking lithium for the prophylaxis of recurrent major affective disorder. In contrast to a previous report, we found no evidence for low folate concentrations or for any significant correlation between folate levels and affective morbidity.
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The extent to which some of the more prevalent and potent carcinogens in cigarette smoke could be transferred from circulating blood into the milk of lactating rats was determined. One hour after i.v. administration of benzo[a]pyrene (BaP), N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to the dams, the levels of these carcinogens were determined in both blood and milk specimens. The average amount of radioactivity detected 1 h after administration of 14C-labeled BaP was 0.21% of the administered dose per ml of milk as compared with 0.17% per ml of blood. The amount of NNN in milk ranged from 0.20 to 0.36% of the administered dose per ml which closely paralleled the levels detected in blood. NNK is readily converted in vivo to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). The sum of NNK and NNAL was similar in the blood and milk of treated dams. There was, however, a major difference in the ratio of NNAL/NNK as detected in milk and blood. The ratio of NNAL/NNK in blood ranged from 1.3:1 to 1.9:1 while the ratio in milk ranged from 2.4:1 to 3.3:1. In a comparative study of the levels of NNN in the blood and milk of lactating rats at less than 1.0, 20, 60, 120 and 240 min after administration, it was confirmed that similar concentrations of NNN are present in blood and milk 1 h after administration. These data indicate that these carcinogens, which are present in both cigarette smoke and tobacco, can be transferred into the milk of lactating rats.
Both the dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test have been reported to be useful in subtyping some depression diagnoses. Whether the DST discriminates delusional from nondelusional depression remains controversial, but this possibility has not been studied for the TRH test. The authors evaluated DST and TRH test results in 29 depressed hospitalized patients; both tests significantly discriminated patients with nonendogenous depression from those with endogenous depression. Furthermore, postdexamethasone cortisol levels but not the change in thyroid-stimulating hormone discriminated the patients with endogenous delusional depression from those with endogenous nondelusional depression.
Sixty-three blood samples were obtained from 48 subjects taking tricyclic antidepressants. Samples were simultaneously collected in Becton-Dickinson Vacutainer tubes for measurement of serum and plasma tricyclic antidepressant concentrations. Serum was drawn into red stopper tubes (without gel separator) and into speckled stopper serum separator tubes (with gel separator), while plasma was collected in green stopper tubes (heparinized). Imipramine, desipramine, amitriptyline, and nortriptyline concentrations were all significantly lower in serum separator samples than in either plasma or red stopper serum collection tubes. Serum and plasma concentrations were similar.
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Premenstrual syndrome is of interest to health care professionals today because of media attention and large numbers of women who are concerned about their premenstrual symptoms. At the same time, there is a lack of consensus as to diagnostic criteria and specific treatment. There appears to be a relationship between mood disorders such as major depression and luteal phase symptoms. An approach to the diagnosis and treatment of the patient with premenstrual syndrome is described.
The authors determined the lifetime prevalence of affective disorder in the first- and second-degree relatives, excluding children, of 27 bulimic women who had never had anorexia nervosa and 27 women with no history of an eating disorder. Family diagnoses were made blind to the proband's diagnosis. The prevalence of affective disorder was 9% in the relatives of the bulimic probands and 10% in the relatives of the control probands, a nonsignificant difference. These findings are in contrast to reports of an increased prevalence of affective disorder in the relatives of patients with anorexia nervosa.
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The authors critically review several drug combinations that may be of promise in the management of depressions that do not respond to treatment with a single drug. These include the use of tricyclic antidepressants with monoamine oxidase inhibitors (MAOI's), L-triiodothyronine (T3), methylphenidate, lithium carbonate, L-tryptophan, reserpine, and neuroleptics; MAOI's with lithium and L-tryptophan; and L-tryptophan with allopurinol. The authors stress the need for further double-blind, controlled studies to evaluate the safety and efficacy of these combinations.
The authors review several approaches that show promise for predicting which antidepressant medication will be best for a particular patient and for achieving maximum benefit from each drug. These include delineation of clinical and historical characteristics associated with response to various drugs, use of psychological tests, assessment of biochemical and electroencephalographic parameters, evaluation of mood response to amphetamine, determination of acetylator status, and measurement of plasma tricyclic levels and degree of inhibition of platelet monoamine oxidase. The authors believe that the use of these approaches may improve our ability to help depressed patients.
The authors describe 2 cases in which withdrawal symptoms occurred during the course of imipramine therapy, after the patients had failed to take a single daily dose of medication. They note that similar withdrawal symptoms have been noted upon discontinuation of imipramine and its derivatives desipramine and chlorimipramine, but have not--with one exception--been reported in association with other tricyclics.
Tricyclic antidepressant plasma levels were measured in patients and healthy subjects after a single dise of desmethylimipramine (DMI) or imipramine (IMI) and after chronic dosing to steady states. Tricyclic plasma levels measured 24 hr after the single oral dose correlated with steady-state plasma levels. In patients receiving DMI there was a correlation (r = 0.97, n = 10) between 24-hr and steady-state DMI levels, while in normal subjects receiving IMI the correlation was r = 0.92 (n = 20) between 24-hr and steady-state total tricyclic levels (IMI plus its metabolite, DMI). These results suggest the possibility that after a test dose of tricyclic antidepressant, a patient may be put on a "therapeutic" dosage regimen without delay.
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