Subcortical vascular disease in elderly patients with treatment resistant depression.
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Biomedical subjects
Publications and source records attributed to S Simpson.
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The effect of diet on the number of gustatory and olfactory sensilla was investigated in locusts. Insects fed for the final two stadia on nutritionally adequate synthetic foods have fewer sensilla on the maxillary palps and antennae than insects fed on the usual rearing diet of seedling wheat. This effect was seen irrespective of the nutritional balance of the foods and was independent of the concentration of nutrients present or the size of the insect. Supplying wheat odour to locusts fed synthetic foods had no effect on the number of sensilla present on the palps, but completely reversed the decrease in the number of olfactory sensilla of the antennae and partially reversed the decrease in the number of antennal uniporous trichoid sensilla. Locusts that were allowed to select between two nutritionally unbalanced but complementary synthetic foods had a higher number of sensilla on the maxillary palps than those fed individual synthetic foods, providing the two foods differed substantially in their protein:carbohydrate ratios. Insects also developed more sensilla if they were fed on two foods of identical nutritional composition but with different added flavours (1% tannic acid or amygdalin). Exposing locusts to synthetic foods for a single stadium did not cause any significant decrease in sensilla number. The results suggest that the number of sensilla that develop in a given sensory field is influenced by the variety of chemical stimuli experienced and the chemical complexity of the environment as provided by the presence of distinct individual sources of stimulation.
Maintenance of carbohydrate balance via changes in CO2 output volume was investigated in locusts using a flow-through respirometer. The effect of an imbalance in the dietary protein to digestible carbohydrate ratio on expired CO2 levels was measured in locusts fed one of two synthetic diets [7% protein, 21% digestible carbohydrate (7:21) and 21% protein, 7% digestible carbohydrate (21:7)]. Additionally, the effect of dietary dilution was investigated by feeding locusts one of two diets with a close-to-optimal ratio of protein to carbohydrate, one containing 7% protein and 7% digestible carbohydrate (7:7) and the other containing 21% protein and 21% digestible carbohydrate (21:21). For insects fed unbalanced diets, a higher CO2 output volume was measured during feeding on diet 7:21 when compared with insects fed on diet 21:7. Locusts also expired a greater volume of CO2 during the entire 2h observation period. This response is consistent with specific metabolic control of carbohydrate balance via enhanced respiration. For insects fed balanced diets, the total volume of CO2 expired over the duration of a meal was greater for insects fed diet 7:7 than for those fed diet 21:21, although this was due entirely to meals lasting longer on the more dilute diet. However, the basal level of respiration rate was greater for insects fed diet 21:21 and, as a result, over the entire 2h period, CO2 output volume did not differ between locusts fed diet 7:7 or 21:21. A possible mechanism for enhanced CO2 output volume on the nutritionally unbalanced diet was investigated, namely triglyceride/fatty-acid substrate cycling. There was no evidence for the presence of the thermogenic effect of this particular cycle on locusts as a means for dealing with excess ingested carbohydrate.
This article reviews our current understanding of the outcome of depression in older people and factors predictive of outcome. Research into neurobiological factors that may be of relevance to outcome is touched on, with suggestions for improving outcome.
This article describes the construction of population estimates for mid-1991 for electoral wards in England and Wales and postal sectors in Scotland. It shows how earlier work adjusting 1991 census figures at national and local authority level for undercount and other factors has been extended to smaller areas in a way that produces estimates which are consistent with the estimates for larger areas. Estimates for smaller areas are needed to calculate employment, health and other indices, and as a starting point for population estimates between census years.
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Prenatal alcohol exposure (FAE) has been associated with multiple anomalies, including a selective developmental delay of sympathetic innervation in lymphoid organs. Sympathetic neurons require nerve growth factor (NGF) for their development and maintenance, and recent evidence has suggested that alcohol impairs the synthesis and/or biological activity of NGF in selected central and peripheral neurons. Thus, the present study examined the hypothesis that NGF administration to FAE rats during early postnatal development would reverse some of the peripheral sympathetic deficits. Neonate rats, FAE and the corresponding control cohorts, received daily treatments of NGF or cytochrome C (0.3 mg/kg; s.c.) for various time intervals, and were killed 24 hr or 10 days after the last treatment. The measured parameters included norepinephrine (NE) concentrations in the spleen and heart, which receive nor-adrenergic innervation from the coeliac ganglion and the superior cervical ganglion (SCG), respectively. In addition, we measured the activity of pineal N-acetyltransferase (NAT), the rate-limiting enzyme of melatonin biosynthesis, which depends on sympathetic innervation from the SCG. The data show that chronic, but not acute, NGF treatments reversed the FAE-related deficits in splenic NE concentrations as well as in pineal NAT activity in a time- and age-dependent manner. Sympathetic neurons play an important role in immune modulation. Thus, the altered splenic NE levels and pineal NAT activity may play a role in immune deficits associated with exposure to alcohol in utero.
Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35-75 years of age with low-density lipoprotein (LDL) cholesterol of 115-190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30-75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.
The loss of adipose tissue during energy restriction may be accompanied by a loss of lean body mass, including bone mass. Because most of the body lead burden is in the skeleton, we studied the effects of weight loss on the concentrations of lead in bone, blood and several organs in rats with prior but not current lead exposure. Concentrations of the essential divalent metals calcium, copper, iron, magnesium and zinc were also determined for comparison with lead. Lead-exposed rats (n = 25) were randomly assigned to one of three treatment groups: weight maintenance (WM), moderate weight loss (MWL) or substantial weight loss (SWL). For the two last-named groups, food intake was restricted for 4 wk to 70 and 40% of that of the WM group. Lead concentrations did not differ significantly (ANOVA, P > 0.05) among the three groups for blood, brain and bone. Significantly higher liver lead concentrations were observed in the SWL rats than in the WM and MWL groups. In general, organ concentrations of calcium, copper, magnesium and zinc were either lower or did not differ in the groups losing weight compared with the WM group. In contrast, organ Iron concentrations of the SWL group were higher than those of the other groups except in brain where there were no significant differences. The total liver content of lead was highest in the SWL group, but the lead content of other organs did not differ among the treatment groups. The contents of calcium, copper, magnesium and zinc generally were lower in the MWL and SWL groups than in the WM group in the liver and some of the other organs. The results demonstrate that weight loss can increase the quantity and concentration of lead in the liver, even in the absence of continued lead exposure. The data also demonstrate considerable differences among organ divalent metals in response to weight loss.
Scores on the Profile of Mood States Inventory of 15 volleyball players at a small southwestern university were compared by means of regression analysis to the players' final season statistics. The analysis showed that Vigor as measured was related to several volleyball statistics.
Transforming growth factor beta (TGF-beta) inhibits proliferation of keratinocytes cultured from normal anogenital epithelia; however, human papillomavirus (HPV)-immortalized cell lines often exhibit increased resistance. Present results demonstrate that TGF-beta 1 (1-10 pM) stimulates growth of multiple HPV-immortalized cell lines when cultures are maintained under conditions promoting squamous differentiation (MCDB153-LB medium with 1.0 mM calcium and without epidermal growth factor and bovine pituitary extract). Growth stimulation by TGF-beta 1 was not due to altered expression of type I or II receptors, but was increased after extended passage of cells in culture. Differentiation of immortal keratinocytes resulted in induction of RNAs encoding two markers of squamous differentiation, involucrin and keratin 1, and decreased expression of RNAs for the epidermal growth factor (EGF) receptor and two ligands, amphiregulin and TGF-alpha. Growth stimulation by TGF-beta 1 occurred indirectly via establishment of an autocrine loop. TGF-beta 1 increased expression of RNAs encoding the EGF-R and amphiregulin, and also increased numbers of cell-surface EGF-Rs without altering their affinity. In contrast, TGF-beta 1 inhibited autonomous growth and transcription of amphiregulin RNA in normal keratinocytes. Growth stimulation by TGF-beta 1 could be blocked by a monoclonal antibody that competes for binding to the EGF-R or by a mixture of monoclonal antibodies that neutralize amphiregulin activity, confirming the importance of this autocrine pathway. Thus, partial abrogation of the growth inhibitory response to TGF-beta 1 sensitizes HPV-immortalized keratinocytes to a growth stimulatory signal mediated by an EGF-R-dependent pathway involving autocrine stimulation by amphiregulin.
Cervical cancer is a malignancy closely associated with human papillomavirus (HPV). However, some cervical carcinomas occur in the absence of the virus. Two HPV-negative cervical carcinoma cell lines, C-33A and HT-3, were examined by G-banding and fluorescence in situ hybridization (FISH) using several whole chromosome and satellite probes. Combined conventional banding and FISH analysis significantly enhanced identification of complex and cryptic chromosome rearrangements. Common to both cell lines were translocations of chromosome 1, involving a specific site on the short arm and partial or complete loss of the short arm of chromosome 9, as well as loss of chromosome 13. The C-33A line had a relatively simple chromosomal constitution, with chromosome 1 being involved in translocations with chromosomes 9, 18, and 21. Karyotype reconstruction of G-banded and painted chromosomes indicate a net loss of DNA as a result of unbalanced translocations, which occurred only at site 9p24 and loss of one copy of chromosomes 13 and 14. In contrast, HT-3 cells had complex rearrangements and deletions of chromosomes 1p, 3p, 9p, 10q/p, 11p/q, and 17p, all regions with known tumor suppressor genes. The deletions observed in these HPV-negative cervical carcinomas will be important in delineating regions of tumor suppressor genes.
The results of two recently completed studies, one in the Trent Region and the other in the Anglia and Oxford Region, of the information-related behaviour of general medical practitioners (GPs) and of information activities within the general practices illustrating the information seeking behaviour of GPs, their generation of information, and communication within, to and from the practice. GPs stated that there is a need for more information to enable practices to function within the changing NHS environment. The increasing emphasis on evidence-based medicine also creates the need for appropriate information sources. The Trent study resulted in guidelines for best information practice, especially the need for each practice to have an information strategy. The Anglia and Oxford Study examined the role which the library and information services could play in supporting primary health care.
The CD3 zeta chain of the TCR plays a pivotal role in the activation of T cell responses toward foreign antigen and in the selection of the T cell repertoire. T lymphocytes from mice deficient in CD3 zeta (CD3 zeta/eta-/- mice) express very few cell surface TCR-CD3 complexes, and these animals have poorly developed thymuses which lack single-positive CD8 and CD4 thymocytes. Nevertheless, a substantial number of single-positive CD4+ and CD8+ T lymphocytes are found in peripheral lymphoid organs of CD3 zeta/eta-/- animals. Using double-mutant mice, generated by breeding CD3 zeta/eta-/- mice with others deficient in the expression of either class I or class II MHC molecules, we demonstrate here that positive selection of peripheral CD4+ and CD8+ T lymphocytes can occur in the absence of CD3 zeta/eta molecules. Analysis of the intestinal intra-epithelial lymphocytes from CD3 zeta/eta-/- mice revealed a novel T cell population expressing high levels of an alternative TCR alpha beta, due to the replacement of CD3 zeta by Fc epsilon RI gamma. Developmentally, these cells also depend on class I MHC expression. In contrast, TCR gamma delta/Fc epsilon RI gamma+ T cells develop independently of MHC class I or class II molecules. These experiments demonstrate that the unique subset of intestinal TCR alpha beta/Fc epsilon RI gamma+ lymphocytes is developmentally dependent on MHC expression. The restricted expression of TCR alpha beta/Fc epsilon RI gamma+ cells in the intestinal mucosa (rather than the thymus or lymph nodes) supports the hypothesis that selection of these T cells occurs extrathymically.
Twenty-two chronic psychiatric patients enrolled in a psychoeducational rehabilitation program were assessed before and after the program to determine whether participation decreased severity of psychopathology and improved community functioning and quality of life. The program consisted of five 14-week modules that provided training in five skill areas: medication and symptom self-management, coping with anxiety and depression, social skills, living skills, and leisure skills. Most patients experienced significantly reduced psychopathology and negative symptoms and improved quality of life and community functioning. The program appears helpful to clients, and a controlled trial to further evaluate its effects is underway.
BACKGROUND: A 71-year-old man with no previous psychiatric history presented with an acute onset of obsessive-compulsive disorder (OCD) symptoms associated with a right inferior parietal infarct. There were no abnormal neurological signs. There were no noteworthy abnormalities on neuropsychological testing. METHOD: Whereas a computerised tomography scan showed only a right inferior parietal infarct, a single photon emission computerised tomography (SPECT) scan revealed that in addition to the infarct there was decreased regional cerebral blood flow in the right basal ganglia and temporal areas. There was higher activity in the right orbitofrontal area than in the left. RESULTS: The patient improved with standard drug therapy and psychotherapy. CONCLUSIONS: SPECT is effective in the diagnosis of neuropsychiatric disorders such as OCD, and the pathological changes in brain metabolism detected by SPECT may be reversed by both drug therapy and psychotherapy.
The aims of the study reported here were to describe the information-related behavior of general medical practitioners, to study information communication in general practices, and to establish guidelines for good practice. General practitioners (GPs) were interviewed, and information and communication audits also involving other staff at the practices were undertaken. The main reasons why GPs needed information were for patient care, managing the practice, legal and ethical matters, and teaching trainee GPs. Most practices had problems with internal and external communication and the storage and retrieval of information. The main conclusion is that practices need to have an information strategy that considers human, manual, and computer aspects of information handling.