Biomedical subjects
R Ramsay
Publications and source records attributed to R Ramsay.
Depression and physical illness in the elderly.
The authors' study confirmed the high prevalence of depressive symptoms in elderly medical inpatients but found no relationship between the diagnosis of or symptoms of depression and mortality or hospital use. Other studies examining the impact of depression on outcome for elderly patients may not have adequately controlled for the severity of the accompanying physical illness, which may perhaps have been responsible for the reported adverse effects of depression on outcome. An alternative explanation is that the authors' study involved a 1-year follow-up and a longer period of time may be necessary. The study demonstrated that routine screening for depression in acute elderly medical inpatients may be a useful way of detecting coexisting psychiatric morbidity. The routine screening measures were acceptable to patients and may be of considerable potential value in alerting staff to accompanying psychological distress. This study also illustrated the high prevalence of depression in patient samples and the importance and usefulness of screening geriatric inpatients. There are, however, several questions that remain unanswered both in studies reviewed in this article and in the authors' own work. The etiology and mechanism of the association between physical illness and depression are unknown, and there has been a dearth of studies assessing the feasibility and utility of specific treatments for depression in the elderly physically ill.
Two isoforms of murine hck, generated by utilization of alternative translational initiation codons, exhibit different patterns of subcellular localization.
Mammalian hck, a member of the src family of tyrosine kinases, is expressed predominantly in cells of the myeloid and B-lymphoid lineages. Using mutational analysis, we have investigated the molecular basis of two immunoreactive forms of murine hck of 56 and 59 kDa found in numerous hemopoietic cell types. Our results indicate that translation of murine p59hck initiates from a CTG codon located 21 codons 5' of an ATG that is utilized to generate p56hck. We provide evidence that two human hck isoforms are generated by the same mechanism. Subcellular fractionation studies reveal that while p59hck and p56hck are associated with membranes of various murine B-lymphoid and myeloid cell lines, p59hck alone is also located in the cytosol. In contrast to membrane-associated p59hck, which is metabolically labeled with [3H]myristic acid and exhibits amphiphilic properties in Triton X-114 detergent, cytosolic p59hck is hydrophilic, suggesting that it is not acylated. Possible mechanisms are proposed to account for these observations.
Cognitive impairment and death in the elderly.
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Invited review: post-traumatic stress disorder; a new clinical entity?
Recently a spate of large scale disasters has caught public attention. Survivors of unexpected catastrophes find their lives radically changed. They may develop a characteristic pattern of symptoms in response to their exposure to overwhelming stress. Ten years ago, American psychiatrists introduced a new diagnostic category, post-traumatic stress disorder (PTSD), referring to the range of psychological symptoms survivors demonstrate after extreme trauma (Diagnostic and Statistical Manual of Mental Disorders, APA, Washington D.C.). Although the validity of this syndrome remains debatable, the term PTSD is increasingly in use, a practice likely to continue given its inclusion in the draft edition of ICD 10 (WHO, Geneva). This review looks at the evidence that PTSD describes a specific clinical entity. The historical background to the belief that individuals respond to stress is summarized. The criteria that must be fulfilled and methods of establishing a diagnosis are described. A discussion of aetiological factors and the natural history of the psychological response to stress follows, with reference to clinical management, including the provision of effective intervention for survivors to prevent a full blown stress reaction emerging.
Diagnosing and treating dementia.
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Physical exercise and mental health.
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Induction of transformed cells to terminal differentiation.
HMBA induces MEL cells to terminal erythroid differentiation. HMBA causes a decrease in diacylglycerol concentration, a decrease in Ca+2 and phospholipid-dependent protein kinase C activity (within 2 hr). There is an early (within 1-2 hrs) suppression of c-myb and c-myc gene transcription and an increase in c-fos mRNA (within 4 hrs). During the early or "latent" period there is no detectable commitment of MELC to terminal cell division or expression of differentiated genes such as alpha 1 or beta maj globin genes. HMBA-induced commitment to terminal differentiation is detected by 12 hrs and over 95% become committed cells by 48-60 hrs. Commitment is associated with persistent suppression of c-myb gene transcription and elevated levels of c-fos mRNA, whereas the level of c-myc mRNA returns to that of uninduced cells. By 36-48 hrs, transcription of the alpha 1 and beta maj globin genes increases 10-30 fold, and that of rRNA genes is suppressed. Changes in expression of c-myb, c-myc, c-fos and p53 genes that occur early during HMBA-induced differentiation may be important in the multistep process involved in commitment of MEL cells to terminal differentiation. Continued suppression of c-myb gene expression may be required for terminal differentiation of these cells.
Changes in gene expression during hexamethylene bisacetamide induced erythroleukemia differentiation.
HMBA induces MELC to terminal erythroid differentiation. The mechanism of HMBA action is not known. Culture with HMBA causes changes in gene expression which occur during the early "latent period", that is, prior to commitment to terminal differentiation. The inducer causes a decrease in diacylglycerol concentration, a decrease in Ca+2 and a decrease in phospholipid-dependent protein kinase C activity (within 2 hr) (Figure 2). There is an early suppression (within 1-2 hrs) of c-myb and c-myc gene transcription and an increase in c-fos mRNA (within 4 hrs). HMBA-induced commitment to terminal differentiation is detected by 12 hrs and over 95% become committed cells by 48 to 60 hrs. Commitment is associated with persistent suppression of c-myb gene transcription and elevated levels of c-fos mRNA whereas the level of c-myc mRNA returns to that of uninduced cells. By 36 to 48 hrs, transcription of alpha 1 and beta maj globin genes is increased 10 to 30 fold, while that of rRNA genes is suppressed. It is not yet clear how the protein products of proto-oncogenes elicit or modify cellular responses. Changes in expression of c-myb, c-myc, c-fos and p53 genes which occur during HMBA-induced differentiation, as well as in several other systems, suggest that products of these genes may have a role in regulating expression of multiple genes. One possible application of the established pattern of HMBA-induced modulation of gene expression during MELC differentiation may be in following the effects of cyto-differentiation agents during treatment of cancers. Phase I and Phase II chemical trials have been initiated to evaluate HMBA as a cytodifferentiation agent in human neoplasms (65). For most human tumors, assay for cytologic evidence of induced differentiation is difficult at best. Following the effects of a differentiation inducing agent by determining c-myc, or c-myb, mRNA levels may provide useful indicators of biological activity of HMBA and be a basis for evaluating whether continued administration of the agent is of interest in terms of potential clinical efficacy.(ABSTRACT TRUNCATED AT 400 WORDS)
The prevalence of suicidal behaviors, attitudes and associated social experiences in an urban population.
The development of an epidemiological study of mental health, social background factors, suicidal behaviors (suicidal ideas, deliberate self-harm, and attempted suicide), values concerning suicide, and experience of suicide in others is described. 679 adult respondents in a stratified random sample of residents of a large Canadian city were interviewed. Results indicate a more accepting attitude to suicide than reported in previous studies; considerable experience of suicide in others; and a much higher rate of suicidal ideas and action than has been reported in previous work. Thirteen percent of the sample had made plans for suicide in their lifetime, 6% had deliberately harmed themselves, and a further 4% had attempted suicide in their lifetime. In the past year, 4% had made plans for suicide, and 2% had deliberately harmed themselves or had attempted suicide.
Psychosocial correlates of suicidal behaviors in an urban population.
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Visual loss caused by corneal crystals in myeloma: rapid improvement and plasma exchange and chemotherapy.
Recognition of needle-like crystals in the cornea of a patient with deteriorating visual acuity initiated laboratory studies which demonstrated underlying multiple myeloma. Crystal deposition in the cornea occurs only rarely in multiple myeloma, and evidently reflects an unusual tendency for certain paraproteins to form numerous small aggregates which are deposited particularly within, and between, corneal epithelial cells. Treatment with chemotherapy, plus repeated plasma exchange with a normal plasma protein product resulted in significant depletion of crystals, and improvement in visual acuity over a period of three weeks. Accelerated clearance of paraprotein by plasmapheresis appeared to contribute materially to the rapidity of recovery, since recovery was considerably faster than in reported cases where treatment was with chemotherapy alone.
Plasma glucose, insulin, glucagon, and growth hormone in kindreds with maturity-onset type of hyperglycemia in young people.
Two kindreds affected by maturity-onset type of hyperglycemia in young people were studied. The postglucose-load hyperglycemia segregated as an autosomal dominant trait; it was always mild, never requiring insulin, and generally seemed to start in the first two decades of life. Glucose, insulin, glucagon, and growth hormone were measured during glucose-tolerance tests in patients, relatives, and control subjects. Most hyperglycemic patients were found to have insulin deficiency. There was no correlation between the age of the patients and insulin secretion. Plasma glucagon and growth hormone were normal. Maturity-onset type of hyperglycemia in young people may be a frequent type of hyperglycemia, and its identification will generally depend on the presence of a strong family history. The recognition of maturity-onset type of hyperglycemia in young people as a specific disease different from juvenile, insulin-dependent diabetes is important, especially to prevent unnecessary use of insulin in hyperglycemic children.
Kidney transplantation for the uremic diabetic patient.
Although the diabetic patient is at high risk for transplantation and the progression of cardiovascular disease continues, results of our experience indicate that kidney transplantation can be performed with only slightly less favorable results than in the nondiabetic patients. We have found that the survival rate achieved by diabetics who receive a kidney graft is superior to that achieved by diabetic patients who receive dialysis. We also believe that some of the secondary complications of diabetes, which are aggravated by uremia, will be improved and that successful vocational rehabilitation is possible in the majority of diabetic patients.