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Biomedical subjects

J D Russell

Publications and source records attributed to J D Russell.

At least 55 records · Page 3Linked to original sources

Can overuse of psychotropic drugs by the elderly be prevented?

Despite increasing awareness of the problems associated with long term psychotropic use, consumption by the elderly remains high. This study examines some of the reasons for this with a view to prevention. Fifty seven elderly patients using psychotropic medication were interviewed to determine the prevalence of psychiatric illness, patterns of drug use, the reasons for the initial prescription and any relationship to life events. Attitudes to continued use were also assessed. The results suggest that levels of psychotropic use by the elderly could be reduced by improved management of life crises and insomnia.

Aged↗

Psychiatry and the frontal lobes.

The frontal lobes of the brain have long been regarded as enigmatic in their function and perhaps should be considered even more so in states of dysfunction. Observed associations between structural lesions and psychiatric symptoms and the demonstration of disturbed function and morphology in the frontal lobes of individuals suffering from major psychiatric disorders have led to increased interest in this brain area. Psychiatrists have been particularly concerned with seeking the aetiogenesis of common diagnostic entities and this article attempts to synthesize the available facts. A brief overview of relevant biological data precedes a description of methods of neuropsychological testing and the clinical features arising from frontal lobe damage. A discussion of the role of the frontal lobes in some aspects of personality function follows. Neuropsychiatric features associated with known frontal lobe pathology are described, prefacing a discussion of those psychiatric conditions where an aetiological role for frontal lobe dysfunction has been proposed.

Brain Diseases↗

Differential glucocorticoid regulation of collagen mRNAs in human dermal fibroblasts. Keloid-derived and fetal fibroblasts are refractory to down-regulation.

Abnormal regulation of collagen synthesis has been observed in fibroblasts from keloids, benign collagenous tumors that develop as a result of an inherited defect in dermal wound healing. Hydrocortisone reduces the rate of collagen synthesis in fibroblasts from normal adult dermis and scars, but fails to down regulate collagen synthesis in keloid-derived fibroblasts. We show here that loss of glucocorticoid control of collagen synthesis in keloid cells is due to an inability of hydrocortisone to reduce the levels of types I, III, and V collagen mRNA, whereas it coordinately lowers these RNAs in normal adult cells. The defective regulatory mechanism is expressed only in fibroblasts from the lesion. Fibroblasts from uninvolved dermis respond normally to hydrocortisone. Not all glucocorticoid-modulated matrix proteins are abnormally regulated in this disorder; fibronectin mRNA is induced to a similar extent in normal and keloid cells. The failure of hydrocortisone to reduce collagen gene expression is also seen in fibroblasts from fetal dermis. We have reported similarities between keloid and fetal cells with regard to growth factor requirements and growth response to hydrocortisone. Thus, keloids may be due to the inappropriate expression of a pattern of growth and matrix production that is developmentally regulated.

Adult↗

Calcium antagonists and acute renal failure.

PURPOSE: To critically review the question of whether calcium antagonists can prevent or attenuate post-ischemic acute renal failure (ARF). PATIENTS AND METHODS: Using a computer-assisted search, we identified all experimental and clinical studies published in English between 1980 and 1988 in which the main research question addressed the efficacy of verapamil, diltiazem, or nifedipine in the treatment of post-ischemic ARF. Studies were then selected for review based on clearly specified inclusion criteria and evaluated against accepted methodologic guidelines. RESULTS: In experimental studies of warm renal ischemia, calcium antagonists provided significant protection of glomerular filtration rate (GFR) when given before and after ischemic injury; however, isolated pre- or post-ischemic treatment produced equivocal results. In autotransplantation studies on protracted cold ischemia, verapamil produced a modest, although physiologically significant, increase in GFR during warm reperfusion but failed to alter graft survival. Studies of calcium antagonists in humans with ARF have been confined to patients undergoing renal transplantation. Diltiazem given both to donor grafts and to recipients produced a significant reduction in the rate of delayed graft function but failed to improve one-year graft survival. This result may be due to the study of small numbers of low-risk patients. At present, there is no conclusive evidence that one calcium antagonist is more efficacious than another in the treatment of post-ischemic ARF. CONCLUSIONS: Calcium antagonists appear to prevent or reduce the severity of post-ischemic ARF only when given prior to and after the ischemic insult. As a result, these agents will have most utility in the setting of renal transplantation. Although the efficacy of these agents in reducing delayed graft function appears to be established, their failure to improve graft survival is poorly understood and requires further investigation.

Acute Kidney Injury↗

Anorexia tardive: a diagnosis of exclusion?

An elderly female patient is described in whom rapid severe weight loss appeared initially to be of psychogenic origin and self-induced. A diagnosis of late-onset anorexia nervosa or anorexia tardive was made when early investigations revealed no abnormality apart from changes that were consistent with malnutrition, and when typical behavioural and psychological factors together with putative psychodynamic issues were revealed. At first, nasogastric feeding was beneficial, but a stormy hospital course ensued. Further investigations revealed the presence of neoplastic disease which at post-mortem examination proved to be small-cell carcinoma of the lung.

Aged↗

Reduced growth-factor requirement of keloid-derived fibroblasts may account for tumor growth.

Keloids are benign dermal tumors that form during an abnormal wound-healing process in genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloid fibroblasts responded differently than normal adult fibroblasts to transforming growth factor beta. Whereas transforming growth factor beta reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of a growth-control mechanism that is developmentally regulated.

Adult↗

Benzodiazepine use in a rural general practice population.

This study investigates the prevalence and pattern of benzodiazepine use in an isolated Australian rural general practice setting. Some clinical features of psychological dependence were also examined. Data were obtained from 771 patients attending each of two general practices over a five-day period. The results indicated that 11.3% of the sample had used a benzodiazepine in the preceding four weeks and that 82% of these had been regular users for over six months. Prevalence increased with age and 36.5% of patients over the age of 70 were using benzodiazepines. Features suggesting some degree of psychological dependence were found in over 50% of users. The findings illustrate the extensive and prolonged use of benzodiazepines and raise questions about overuse and dependence, particularly in the elderly.

Adolescent↗

Incidence of herpes genitalis in Northern Ireland in 1973-83 and herpes simplex types 1 and 2 isolated in 1982-4.

During 1973 - 83 there was a pronounced rise in the number of new cases of herpes genitalis in Northern Ireland. This study of 127 patients with herpes genitalis shows that 30% had herpes simplex virus type 1 (HSV 1) and 70% had herpes simplex virus type 2 (HSV 2) infections. Of 41 sexual contacts who attended, only seven had herpes genitalis (caused in each case by HSV 2); another patient had a history of genital lesions, and one other of oral lesions, but HSV was not isolated from either patient. None of the other sexual contacts had a history of oral or genital infection. Of 31 women with herpes genitalis who consented to undergoing cervical cytology, five had atypical changes (all had primary herpes genitalis). Of these, four were infected with HSV 1 and one with HSV 2.

Female↗

Sexually transmitted diseases, T cell subsets, and sexual practices in homosexual men attending an STD clinic.

Sixty three homosexually active men and 42 heterosexual men answered questionnaires regarding aspects of their social life and sexual practices. Assessment of past sexually transmitted disease showed the homosexual group to have had a significantly greater incidence of syphilis, gonorrhoea, perianal warts, and cytomegalovirus infections. T cell subset counts were carried out, and results for 60 of the homosexual men and 39 of the heterosexual men showed that the homosexuals had a significantly greater mean T cell suppressor cell count (p = 0.0019). The mean T helper cell count was not significantly different between the two groups, but it was significantly more (p = 0.033) in the more promiscuous homosexuals (who had more than 20 sexual partners a year) than in the heterosexuals. No relation was found between T cell subset counts and evidence of past cytomegalovirus infection. The practice of passive anal intercourse, oroanal sex, and swallowing semen during oral sex did not appear to influence T cell subset counts in the homosexuals.

Adult↗

Echovirus type 7 outbreak in Northern Ireland during 1984.

During 1984, 118 patients with echovirus type 7 infection were diagnosed. The incidence in Northern Ireland was more than three times higher than the rest of the United Kingdom. The outbreak peaked in June and July, with the highest incidence in Belfast and the eastern part of Northern Ireland. All patients were sufficiently unwell to require hospital admission. Aseptic meningitis was the commonest illness (54.2%) followed by gastroenteritis (22.0%), respiratory tract infections (11.9%) and influenza-like illnesses (8.5%). Males (62%) were affected more than females and 50 patients (42%) were less than one year old. The present epidemic had features in common with four previous enterovirus epidemics, except that the under one year age group was predominantly affected and no family or street outbreaks were detected.

Adolescent↗

Glucocorticoid receptors in human fibroblasts derived from normal dermis and keloid tissue.

Hydrocortisone stimulates proliferation and System A amino acid transport in cultured human fibroblasts, while decreasing production of collagen. Fibroblasts isolated from keloid tissue have an unusual glucocorticoid response; they are hyporesponsive with regard to proliferation and collagen production but hyperresponsive with regard to the induction of System A amino acid transport (Russell, J. D., Russell, S. B., and Trupin, K. M. (1978) J. Cell. Physiol. 97, 221-229; Russell, S. B., Russell, J. D., and Trupin, J. S. (1982) J. Biol. Chem. 256, 9525-9531). We show here that despite these differences, the glucocorticoid receptors of keloid cells do not differ from those of normal dermal fibroblasts in steroid specificity, dissociation constant (Kd), total number of binding sites (Bmax), or nuclear binding of glucocorticoid-receptor complexes. A single glucocorticoid binding species of molecular weight 93,000 was found in both cell types. A monolayer assay for glucocorticoid receptor binding is described which facilitates analysis of multiple strains of cultured cells. This assay gives the same specificity and dissociation constants as the conventional cytosol assay, but it is more sensitive. The magnitude of induction of System A amino acid transport was found to be directly proportional to glucocorticoid receptor occupancy in both keloid-derived and normal fibroblasts. This induction requires serum, which can be replaced with 1 nM insulin.

Amino Acids↗

Hydrocortisone induction of system A amino acid transport in human fibroblasts from normal dermis and keloid.

The rate of proline transport increases when human dermal fibroblasts are grown in physiological levels of hydrocortisone. This response to hydrocortisone is significantly greater in fibroblasts derived from keloids, benign dermal tumors caused by an inherited abnormality in wound healing (Russell, S. B., Russell, J. D., and Trupin, J. S. (1982) J. Biol. Chem. 257, 9525-9531). We report here that increased transport activity is largely accounted for by an increase in Vmax of the System A component of proline uptake; this stimulation is 1- to 2-fold in normal fibroblasts and 5- to 10-fold in keloid-derived cells. Similar results are obtained with 2-(methylamino)isobutyric acid, a specific substrate of System A transport, and for the System A components of glycine and alanine uptake. The stimulatory effect of the hormone is blocked by cycloheximide and actinomycin D in both keloid and normal cells. Hydrocortisone did not alter the measured membrane potential in either cell type. These data suggest that hydrocortisone induces a protein specifically involved in System A amino acid transport. Keloid cells may provide a unique opportunity to study this protein.

Amino Acids↗

Variation in prolyl hydroxylase activity of keloid-derived and normal human fibroblasts in response to hydrocortisone and ascorbic acid.

The effects of ascorbic acid and hydrocortisone on activity of prolyl hydroxylase in fibroblasts from keloid and normal human dermis were investigated and compared to the effects of these agents on collagen synthesis. Prolyl hydroxylase activity in normal fibroblasts grown to confluency in 1.5 microM hydrocortisone was approximately half that of cells grown without the steroid. The concentration of hydrocortisone effective in reducing enzyme activity was the same as that for reducing the rate of collagen synthesis; a half-maximal effect on both parameters was achieved at 10(-7) M. Hydrocortisone lowered enzyme activity through most of the culture cycle. Fibroblasts derived from keloids were significantly less subject to hydrocortisone-mediated reduction of prolyl hydroxylase activity and rate of collagen synthesis. This difference between keloid and normal cells was dependent on the simultaneous presence of ascorbic acid and hydrocortisone. These data suggest that the defect in wound healing that results in keloid formation is associated with a change in a regulatory mechanism that controls the rate of collagen synthesis and is sensitive to physiological levels of hydrocortisone. Continuous culture of fibroblasts in medium supplemented with ascorbic acid also lowered prolyl hydroxylase activity. Unlike the effect of hydrocortisone, growth in ascorbate increased the rate of collagen synthesis and affected keloid and normal strains equally.

Ascorbic Acid↗

Alteration of amino acid transport by hydrocortisone. Different effects in human fibroblasts derived from normal skin and keloid.

The rate of proline transport increases significantly when human dermal fibroblasts are grown with 1.5 microM hydrocortisone. Fibroblasts derived from keloid tissue are significantly more stimulated than normal fibroblasts. An average increase of 41% is obtained with 8 normal strains, whereas uptake in 8 keloid-derived strains increases 210%. Similar results are obtained with the system A amino acid analogue 2-(methylamino)isobutyric acid, for which the uptake rate increases 87% and 329% in normal and keloid cells, respectively. The hydrocortisone-mediated increase in proline transport and the difference between keloid and normal fibroblasts are observed throughout the culture cycle and after depletion of amino acid pools. The uptake of nine other amino acids are differentially altered in normal and keloid cells. Competition experiments with 2-(methylamino)isobutyric acid indicate that the greatest differences occur with amino acids that are transported preferentially by the A system. Inhibition of the hydrocortisone-mediated increase by progesterone and a lag period of approximately 3 h indicate that hydrocortisone is regulating proline transport by a cytosolic receptor mechanism.

Amino Acids↗

Fibroblast heterogeneity in glucocorticoid regulation of collagen metabolism: genetic or epigenetic?

Cultured fibroblasts derived from normal human dermis show a consistent 62% inhibition of collagen synthesis by hydrocortisone, whereas cultures derived from keloids average only 30% inhibition and show a much larger strain to strain variation ranging from 75% inhibition to 49% stimulation. Examination of fibroblast clones indicates that this high variation among keloid strains is not due to differences in the proportion of normal and keloid cells in the mass culture populations. Small but significant differences in the effect of hydrocortisone on collagen deposition are also seen among these clonal populations, but are not related to the type of tissue from which cultures were derived. Two to three-fold differences among clones derived from a single individual were observed, possibly suggesting functional heterogeneity of dermal fibroblasts with regard to collagen metabolism under control conditions and in response to hydrocortisone. However, this variation among clones may simply reflect differences in clonal growth, inasmuch as both collagen synthesis and deposition, and the effect of hydrocortisone on these processes, are strongly affected by population density.

Cells, Cultured↗