Increased salt retention and hypertension from non-steroidal agents in the elderly

We studied blood pressure and natriuretic responses to acute salt loading, and the effect of non-steroidal anti-inflammatory agents on these responses, in five healthy normotensive women aged 65 to 71 years. Five women aged 25 to 31 years acted as controls. Intravenous saline loading, with and without prior ingestion of ibuprofen, was 15 ml/kg/h for 3 h. Baseline blood pressures were higher in the elderly. Saline infusion without ibuprofen raised systolic blood pressure (SBP) by about 25 mmHg in the older group only. Ibuprofen increased baseline SBP in the elderly (129 +/- 6 vs. 116 +/- 5 mmHg, p < 0.05). Saline loading after ibuprofen again raised blood pressure by about 25 mmHg in the elderly only. The elderly group showed markedly increased sodium excretion during saline loading, but this was reduced by ibuprofen. Ibuprofen had no effect on SBP or sodium excretion in controls. Ageing appears to increase susceptibility to salt retention and hypertension from non-steroidal anti-inflammatory agents.      

Imaging of thoracic aortic dissection

Acute thoracic aortic dissection has a high mortality if untreated, so the diagnosis must be rapidly made if mortality is to be lowered significantly. Multiple imaging techniques are often used. This retrospective study from 1988 to 1993 assesses the usefulness in diagnosis of chest X-rays, computed tomography (CT) scanning, aortography, magnetic resonance imaging (MRI), trans-thoracic (TTE) and trans-oesophageal (TOE) echocardiography. Forty-two patients with a final clinical diagnosis of dissection were studied. The diagnosis was confirmed in 16 (13 at surgery and three at autopsy). Three died with dissection given as the only cause for death. Chest X-ray abnormalities were seen in all 19 patients with surgery or death from dissection, with a widened mediastinum and/or dilated aorta being present in 17. In the group of 16 patients with surgery or autopsy proof, CT scans found dissections in 9 of 12 patients studied and correctly classified the type in only five. Aortography was performed in five, with accurate depiction of dissection and type in all. TTE found dissections in three of eight patients imaged by this method. MRI and TOE were performed each on two patients, with accurate depiction of dissection and type in each. Because of the relatively low sensitivity of CT scanning in defining aortic dissections Westmead Hospital is currently assessing the use of TOE as the prime imaging modality prior to surgical intervention.     

Assessment of self-poisoning patients by psychiatrists and junior medical staff.

Case notes of patients admitted to hospital or seen in the casualty department following an overdose were assessed in a standardized way. The medical records were deficient in several important areas, especially for those patients seen in casualty and not referred to a psychiatrist. If only selected patients were to be assessed by psychiatrists, closer monitoring of the psychiatric assessments and management initiated by junior medical staff would be required. Although the poor records may reflect lack of motivation as much as lack of education, there was no significant relationship between the doctors' attitudes towards self-poisoning patients in general and the standard of their assessments.     

A double mutant [N543H+2393del9] allele in the LDL receptor gene in familial hypercholesterolemia: effect on plasma cholesterol levels and cardiovascular disease

Familial hypercholesterolemia is a genetic disorder caused by mutations in the LDL receptor gene. During a survey of mutations of LDL receptor gene in Spanish FH patients we found two mutations in the same allele: a missense N543H mutation in exon 11 and a 9bp inframe deletion (2393del9) located in exon 17. This double mutant allele was founded in 10 out of 458 unrelated patients: one homozygous FH [N543H+2393del9] + [N543H+2393del9], one compound heterozygote [N543H+2393del9] + [W-18X+E256K] and 8 heterozygotes. Flow cytometric analysis showed a defective LDL binding (20% of normal value) and internalization (23%) in lymphocytes from the homozygous patient; furthermore, studies of mitogen-stimulated lymphocytes demonstrated that the ability of LDL to support cell proliferation was impaired. Unexpectedly, not all carriers of the double mutant allele develop hypercholesterolemia and, furthermore, cholesterol-lowering treatment of the homozygous patient resulted in a 58% LDL cholesterol reduction. In conclusion, the phenotypic expression in the homozygous and heterozygous patients presented here, as well as the LDL-receptor residual activity, allowed the classification of this mutation as mild extending the group of mild mutations found at homozygosity.     

Psychiatrists' models of mental illness and their personal backgrounds.

Seventy-nine junior psychiatrists at the Maudsley Hospital answered 16 biographical questions and a 68-item questionnaire measuring attitudes to the psychoanalytical, biological, social, behavioural, and anti-medical models of mental illness. The psychoanalytical model was the most clearly defined and its adherents the most dogmatic, while those supporting the social model were the most eclectic. Sex, social class, education and political sympathy proved a poor guide to the orientation of the respondent. Individuals who had decided on a career in psychiatry before entering medical school were the most critical of the biological model. Biologically minded psychiatrists were older and, in contrast to Kreitman's findings, there was a shift from a psychoanalytical to a biological preference with increasing psychiatric experience. The importance of scientific attitudes in psychiatry was endorsed by biologically and behaviourally inclined psychiatrists but denigrated by supporters of the analytical approach. Adherents of the psychoanalytical model had as many academic qualifications as the biologically inclined, but had fewer publications and were less active in research. It appears that interest in psychoanalysis is antipathetic to the development of scientific attitudes conducive to research.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Psychological correlates of pain behavior in patients with chronic low back pain

Pain behaviors that are excessive for the degree of known physical disease are common in patients with chronic low back pain and are frequently assumed to arise from a comorbid depressive illness. Although some studies have confirmed an association between depression and excessive pain behavior, methodologic problems (such as the use of depression ratings that also recorded symptoms attributable to physical disease) make interpretation of this finding difficult. We recruited 54 consecutive patients with chronic (>6 months) low back pain from a hospital clinic. Subjects completed self-rated assessments of anxiety and depression (Hospital Anxiety and Depression Scale) designed to be minimally affected by physical symptoms, along with assessments of disability (ODQ), pain (visual analogue scale), pain behavior (Waddell checklist), and physical impairment. Seventeen subjects (31%) exhibited excessive pain behavior. Overall, they were no more depressed or anxious than the remainder, although men with excessive pain behavior showed a trend toward being more depressed. Patients with excessive pain behavior were more disabled (self-rated and observer-rated), reported greater pain, and were more likely to be female and to have pain of shorter duration. Pain behavior did not correlate with anxiety or depression, but correlated with measures of disability and pain intensity. Factor analysis revealed that physical disability, pain intensity, and pain behavior loaded heavily on the first factor. Anxiety and depression loaded together on a separate factor. We conclude that pain behaviors were not related to anxiety or depression in our group, although gender differences between groups could have contributed to our negative findings. Pain behaviors may influence other physical measures. Further studies are required to investigate the relation between depression and pain behavior while controlling for gender differences.     

Depression and social stress in Pakistan

BACKGROUND: The high prevalence of depression in developing countries is not well understood. This study aimed to replicate the previous finding of a high prevalence of depression in Pakistan and assess in detail the associated social difficulties. METHOD: A two-phase survey of a general population sample in a Pakistani village was performed. The first-phase screen used the Personal Health Questionnaire (PHQ) and the self-rating questionnaire (SRQ). A one in two sample of high scorers and a one in three sample of the low scorers were interviewed using the Psychiatric Assessment Schedule (PAS) and Life Events and Difficulties Schedule (LEDS). RESULTS: A total of 259 people were screened (96% response rate). The second stage yielded 55 cases, of whom 54 had depressive disorder, and 48 non-cases. The adjusted prevalence of depressive disorders was 44-4% (95% CI 35.3 to 53.6): 25.5% in males and 57.5% in females. Nearly all cases had lasted longer than 1 year. Comparison of the cases and non-cases indicated that cases were less well educated, had more children and experienced more marked, independent chronic difficulties. Multivariate analysis indicated that severe financial and housing difficulties, large number of children and low educational level were particularly closely associated with depression. CONCLUSION: This study confirms the high prevalence of depressive disorders in Pakistan and suggests that this may be higher than other developing countries because of the high proportion of the population who experience social adversity.     

Depression, illness perception and coping in rheumatoid arthritis

This study aimed to establish the relationship between depression, illness perception, coping strategies, and adverse childhood events in rheumatoid arthritis patients. Sixty-two out-patients with rheumatoid arthritis (RA) completed the Hospital Anxiety and Depression Scale, Illness Perception Questionnaire, London Coping with Rheumatoid Arthritis Questionnaire, and Childhood Development Questionnaire, and underwent a clinical assessment of their physical state. Depressed patients were more disabled than the nondepressed, had a more negative view of their illness, and used more negative coping strategies. There was no association between depression and childhood adversity. Once disability was controlled for, there continued to be a significant correlation between depression and: (i) viewing the consequences of the illness negatively (Spearman's correlation coefficient [r]=0.37, p=0.003); and (ii) the perceived ability to control the illness (r= -0.26, p=0.04). The relationship between depression and negative coping strategies became insignificant. This study indicates the close relationship between depression and a negative view of the illness.     

Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice

The present studies report erythropoietin (Ep) production in primary cultures of a human renal carcinoma from a patient with erythrocytosis that has been serially transplanted to BALB/c nude mice. The levels of erythropoietin in the culture media were estimated using the exhypoxic polycythemic mouse assay (EHPCMA), fetal mouse liver erythroid colony- forming technique (FMLC), and a radioimmunoassay (RIA). The spent culture media of the exponentially growing cells contained less than 10 mU/ml of Ep measured by RIA. However, after the cells became confluent, Ep levels (RIA) in the spent media showed a marked increase to approximately 300 mU/ml. Ep levels estimated using the FMLC and EHPCMA were approximately 2/3 and 1/10, respectively, of those measured by RIA. Rabbit antiserum to highly purified human urinary Ep (70,400 U/mg protein) was utilized for immunocytochemical (peroxidase-antiperoxidase method) localization of Ep in the cultured cells. Very few of the cells in exponential growth exhibited Ep-like immunoreactivity, whereas intense Ep-like immunoreactivity was observed in the cytoplasm of the cells maintained in culture for a prolonged period after reaching confluency. The most intense staining was observed in some of the cells forming domes. The domes developed after the cells reached confluency, and their numbers increased with increasing time in confluent culture, in parallel with the increase in Ep levels in the spent media. This primary cell culture system of a renal cell carcinoma maintained in nude mice, which produces immunologically and biologically active Ep, may provide a useful model for studies of the mechanism of Ep production.