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Biomedical subjects

G F Russell

Publications and source records attributed to G F Russell.

At least 55 records · Page 3Linked to original sources

Mutagenic activity of a nitrosated early Maillard product: DNA synthesis (DNA repair) induced in HeLa S3 carcinoma cells by nitrosated 1-(N-L-tryptophan)-1-deoxy-D-fructose.

HeLa S3 cells in suspension were incubated at 37 degrees C with various concentrations of the Amadori compound 1-(N-L-tryptophan)-1-deoxy-D-fructose (Trp-Fru), of its nitrosated analogue NO-Trp-Fru and of sodium nitrite, for varying periods of time, and were assayed for viability (trypan blue exclusion test) and for intracellular DNA, RNA and protein synthesis. None of the compounds tested had any effect on cell viability, or on RNA and protein synthesis apart perhaps from a slightly inhibitory action. While Trp-Fru remained ineffective also as far as intracellular DNA synthesis was concerned, both NO-Trp-Fru and NaNO2 had a major effect on DNA synthesis. With NaNO2, stimulation of DNA synthesis occurred at concentrations above 1 mM in the growth medium, but with NO-Trp-Fru synthesis increased at concentrations below 1 microM. The excess DNA synthesis (i.e. synthesis above control activity) observed with NO-Trp-Fru and also with NaNO2 was due to DNA repair. This was verified by keeping the cells under conditions that prevented normal semi-conservative replication but permitted DNA repair ('unscheduled DNA synthesis'). Two major routes are suggested by which NO-Trp-Fru could damage DNA.

Cell Survival↗

Observations on the relationship between anxiety and depressive symptoms during the course of depressive illnesses.

1 Roth et al. (1972) have proposed that within the affective disorders there are two distinct syndromes--anxiety and depression--differentiated by the relative predominance of these symptoms, the presence or absence of premorbid maladaptive traits, and the natural outcome of the disorder. 2 Goldberg (1982) on the other hand has suggested that there is a substantial overlap between the two syndromes, and the symptoms of anxiety and depression correlate highly with each other. 3 Patients tend to be treated with an anxiolytic or an antidepressant drug according to the predominance of anxiety or depressive symptoms. 4 There is conflicting evidence regarding the relative effectiveness of tricyclic antidepressants in psychotic (or endogenous) and neurotic (or reactive) depressive illness. Paykel (1972), however, found that the psychotic-neurotic dichotomy was not helpful in predicting outcome, whereas anxious depressives tended to respond poorly. 5 In three patients with affective illness, tested at regular intervals over the course of several weeks, anxiety and depressive symptoms fluctuated in a way which suggested that they were yoked to each other. A worsening indicated simultaneous deterioration of these symptoms. When they improved, this may have been due to the beneficial effects of the antidepressant drug administered. These findings suggest that antidepressants act, or fail to act, in a fundamental manner on the illness itself rather than on individual symptoms.

Anxiety↗

Suppression of bulimic symptoms with methylamphetamine.

Eight patients with bulimia nervosa were given methylamphetamine or placebo intravenously under double blind controlled conditions. In every patient, methylamphetamine reduced self-ratings of hunger and amount of food eaten as measured under laboratory conditions. This shows that the food intake of patients with bulimia nervosa can be modified by experimental drugs. The symptom of bulimia (rapid, excessive and distressing eating) which may be followed by self-induced vomiting or purgation was seen in four patients after receiving placebo but in none after receiving methylamphetamine. These findings suggest that the severe symptom of bulimia may be amenable to drug treatment. Further studies are needed to explore the mechanism by which methylamphetamine appears to prevent bulimia.

Adult↗

Comparative double-blind trial of mianserin hydrochloride (Organon GB94) and diazepam in patients with depressive illness.

1. The antidepressant action of mianserin was tested in a double-blind clinical trial lasting 6 weeks. Forty-six patients with moderate to severe degrees of depression were treated at random with mianserin or diazepam. Patients who failed to improve by week 3 were taken out of the trial. 2. Mianserin was more effective than diazepam in reducing scores on the Hamilton Rating Scale for depression. Fewer patients allocated to mianserin had to be withdrawn from the trial on account of failure to improve. Mianserin was more effective than diazepam in reducing symptoms of 'retarded depression' and as effective as diazepam in reducing symptoms of 'anxious depression'. 3. Mianserin did not cause any more side-effects than diazepam, very few side-effects being encountered with either drug. 4. The design of this trial on antidepressant drugs is commended on ethical grounds.

Adjustment Disorders↗

The effects of clomiphene citrate on the hypothalamic-pituitary-gonadal axis in anorexia nervosa.

Serum luteinizing hormone (LH) responses to a course of clomiphene citrate were studied in eleven patients with anorexia nervosa at different stages of the illness. In malnourished patients basal levels of LH were invariably low. With the resumption of a normal weight a small but definite rise in LH levels was observed but this spontaneous response to weight gain was variable in that many patients continued to exhibit abnormally low LH levels. The response to clomiphene in terms of a rise in basal LH levels after administration of the drug, followed by a second peak of LH and subsequent menstrual bleeding, was clearly dependent in part on the patient's nutritional state. In the malnourished state the response to clomiphene was usually either absent or incomplete. After the resumption of a more normal weight, the patients invariably showed an initial rise in LH after the clomiphene, but the second LH peak and subsequent menstruation were frequently not demonstrated. Six patients maintained a normal body weight for at least six months after a course of clomiphene, but only three of them resumed cyclical menstrual bleeding. It was concluded that factors additional to the nutritional state contribute to the prolonged amenorrhoea in anorexia nervosa and that clomiphene appears to have only a limited role in the treatment and management of patients with the disorder. Some aspects of current knowledge of the endocrine mechanisms that regulate normal menstruation and of the mode of action of clomiphene are outlined. The results of the present study are discussed against this background in an attempt to elucidate further the hypothalamic disorder underlying the amenorrhoea in anorexia nervosa.

Adolescent↗

The effects of administering lithium carbonate on the balance of Na, K and water in manic-depressive patients.

Eleven patients in remission from manic-depressive illness were studied by means of metabolic balances before and after the administration of lithium carbonate. Lithium caused a sharp diuresis of isotonic saline and a smaller excretion of potassium over the course of two days. During the subsequent two days there occurred a compensatory retention of Na, K and water. These short-term changes were not associated with any significant alteration in the patients' mood. There was no significant and systematic retention of Na, K or water over the 14 days of Li administration. The recovery of Li was measured simultaneously. During the first week only a proportion of the administered Li was recovered in the urine and faeces, suggesting that a gradual distribution of Li throughout its body space was occurring. After the first week, nearly all the administered Li was recovered, indicating an equilibrium with an even distribution of the ion throughout its body space. This equilibrium was more complete at this early stage in those patients who had been given a smaller dose of lithium carbonate.

Adolescent↗

Gas-liquid chromatography and mass spectrometric ion selective detection of sterigmatocystin in grains.

A method was developed for direct gas-liquid chromatographic-mass spectrometric (GLC-MS) analysis of nonderivatized sterigmatocystin in wheat, rice, barley, and corn. Sterigmatocystin was extracted from spiked grain samples by 2 methods, both of which yielded high recoveries of 14C-labeled sterigmatocystin (greater than 90%). Extracts were cleaned up by gel permeation chromatography on polystyrene with tetrahydrofuran as the eluant. Chromatography of 14C-labeled compound indicated good recoveries (greater than 90%). The GLC-MS system was modified to give an all-glass chromatographic pathway to the ion source. Short glass or quartz columns packed with silicone liquid phase on inert supports gave the best results. Trace levels of sterigmatocystin were very labile in all gas chromatographic systems and levels below 5 ppb in grains were detected only with great difficulty. The GLC-MS system was utilized in the mass fragmentography mode, with selective ion monitoring of the m/e 295, 306, and 324 peaks. These ions were present in only trace levels in all control grain samples, indicating minimal interference from other compounds. The limit of accurate detectability (20 ng) on spiked grain samples was lower than previously reported. Lower levels of sterigmatocystin (1 ppb or 4 ng on column) could be detected in grains by using the mass fragmentography mode, but these levels could not be measured accurately.

Chromatography, Gas↗

Value of family background and clinical features as predictors of long-term outcome in anorexia nervosa: four-year follow-up study of 41 patients.

This is a prognostic study on 41 patients with anorexia nervosa (including three males) who satisfied defined diagnostic criteria. The patients had all been admitted to a metabolic unit where the mainstay of treatment was nursing care aimed at rapid restoration of body weight. A follow-up was conducted after a minimum lapse of four years after each patient's discharge from hospital. The outcome of the patient's illness was expressed in terms of an 'average outcome score' and a 'general outcome'. The series included a relatively high proportion of patients with a long illness who had received previous psychiatric treatment. Their families tended to come from higher social classes; a disturbed relationship with the patient was frequent. Premorbid disturbances in personality development were also common. The immediate response to treatment was excellent, with the majority of the patients returning to a normal weight, but relapses after discharge were common and readmissions were necessary in half the patients. At follow-up, the patients fell into the following defined categories: 'good' (39%), 'intermediate' (27%), 'poor' (29%), died (5%). Most of the patients who failed to recover continued to display the clinical features characteristic of anorexia nervosa. Among predictors of an unfavourable outcome were found a relatively late age of onset, a longer duration of illness, previous admissions to psychiatric hospitals, a disturbed relationship between the patient and other members of the family, and premorbid personality difficulties. It is suggested according to the severity of their illness, rather than on the method of treatment itself. The illness may last several years before eventual improvement or recovery, and a follow-up study must be extended over at least four years to be meaningful. An accurate prediction of eventual outcome is almost impossible, but late recoveries justify an optimistic outlook and continued therapeutic endeavour.

Adolescent↗