Morphometric analyses of hominoid crania, probabilities of conspecificity and an approximation of a biological species constant.

Thackeray has previously explored the possibility of using a morphometric approach to quantify the "amount" of variation within species and to assess probabilities of conspecificity when two fossil specimens are compared, instead of "pigeon-holing" them into discrete species. In an attempt to obtain a statistical (probabilistic) definition of a species, Thackeray has recognized an approximation of a biological species constant (T=-1.61) based on the log-transformed standard error of the coefficient m (log sem) in regression analysis of cranial and other data from pairs of specimens of conspecific extant species, associated with regression equations of the form y=mx+c where m is the slope and c is the intercept, using measurements of any specimen A (x axis), and any specimen B of the same species (y axis). The log-transformed standard error of the co-efficient m (log sem) is a measure of the degree of similarity between pairs of specimens, and in this study shows central tendency around a mean value of -1.61 and standard deviation 0.10 for modern conspecific specimens. In this paper we focus attention on the need to take into account the range of difference in log sem values (Δlog sem or "delta log sem") obtained from comparisons when specimen A (x axis) is compared to B (y axis), and secondly when specimen A (y axis) is compared to B (x axis). Thackeray's approach can be refined to focus on high probabilities of conspecificity for pairs of specimens for which log sem is less than -1.61 and for which Δlog sem is less than 0.03. We appeal for the adoption of a concept here called "sigma taxonomy" (as opposed to "alpha taxonomy"), recognizing that boundaries between species are not always well defined.

The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration.

Rac1-GTPases serve as intermediary cellular switches, which conduct transient and constitutive signals from upstream cues, including those from Ras oncoproteins. Although the sirtuin1 (SIRT1) deacetylase is overexpressed in several human cancers and has recently been linked to cancer cell motility as a context-dependent regulator of multiple pathways, its role in Rac1 activation has not been reported. Similarly, SIRT2 has been demonstrated to be upregulated in some cancers; however, studies have also reported its role in tumor suppression. Here, we demonstrate that SIRT1 and SIRT2 positively regulate the levels of Rac1-GTP and the activity of T-cell lymphoma invasion and metastasis 1 (TIAM1), a Rac guanine nucleotide exchange factor (GEF). Transient inhibition of SIRT1 and SIRT2 resulted in increased acetylation of TIAM1, whereas chronic SIRT2 knockdown resulted in enhanced acetylation of TIAM1. SIRT1 regulates Dishevelled (DVL) protein levels in cancer cells, and DVL along with TIAM1 are known to augment Rac activation; however, SIRT1 or 2 has not been previously linked with TIAM1. We found that diminished sirtuin activity led to the disruption of the DVL1-TIAM1 interaction. We hence propose a model for Rac activation where SIRT1/2 positively modulates the DVL/TIAM1/Rac axis and promotes sustained pathway activation.

Chronic idiopathic constipation: a psychological enquiry.

BACKGROUND: Intractable idiopathic constipation in women is often associated with psychosocial problems. AIMS: To determine the past and current psychological factors associated with slow and normal transit constipation. PATIENTS: Twenty-eight consecutive patients referred for biofeedback treatment were interviewed before the procedure. All were women. Transit studies revealed that 12 had slow transit constipation (STC) and 16 had normal transit constipation (NTC). METHODS: Patients were assessed for evidence of previous and current psychiatric diagnoses using a standardized diagnostic interview schedule. A full family and social history was noted. Self-rating scales were used to measure psychological distress, abnormal attitudes to eating and current psychosocial functioning. RESULTS: The mean age of the 28 patients was 38.2 years (SD = 10.8) with a mean duration of symptoms of 17.5 years (SD = 16.9). Seventeen (61%) had a current psychiatric disorder and 18 (64%) a previous episode of psychiatric illness. The mean age of the 16 NTC patients was 38.4 years (SD = 10.1) with a mean duration of symptoms of 12.4 years (SD = 15.9). By contrast, the 12 STC patients had a much longer mean duration of constipation (24.3 years; SD = 16.4), a mean age of 37.9 years (SD = 12.1), with half having an onset in childhood. The STC patients reported more psychosocial distress on the rating scales than those with NTC, and only one did not experience some form of adverse life event or gynaecological procedure in the 6 months before the onset of constipation. Eleven (39%) of the 28 women had had a hysterectomy at a mean age of 36 years, but only four (14%) reported a history of sexual abuse. Of the nine (32%) patients who reported markedly distorted attitudes to food, six had NTC and three had STC. CONCLUSIONS: Of consecutive patients undergoing psychological assessment for intractable constipation, three fifths had evidence of current, and two thirds a previous, affective disorder. One third reported distorted attitudes to food. Although STC is a chronic disorder accompanied by high rates of psychological distress, it does not appear to be associated with gross functional impairment. We suggest that patients who present to surgical departments with chronic intractable constipation should routinely have a psychological assessment.

Comparison of the effects of sibutramine and other weight-modifying drugs on extracellular dopamine in the nucleus accumbens of freely moving rats.

The acute effects of systemic administration of the anti-obesity agent sibutramine on extracellular dopamine (DA) in the nucleus accumbens of freely moving rats were studied using in vivo microdialysis and compared with the actions of phentermine and d-amphetamine at doses 1x and 3x their respective 2 h ED(50) values to reduce food intake in rats. At the lower dose, sibutramine did not elevate extracellular DA concentrations; however, at the higher dose (6.0 mg kg(-1), i.p.) it caused a modest and prolonged increase in extraneuronal DA. A maximal rise was observed at 60 min post-sibutramine treatment (+231% compared to controls) with DA levels remaining elevated for up to 160 min post treatment. In contrast, phentermine and d-amphetamine significantly enhanced DA efflux at both the lower and higher doses. These elevations of DA levels were significantly greater than that seen with the corresponding dose of sibutramine over 0-80 min post treatment. Maximal rises in DA levels resulting from the higher dose of each drug were +733% (phentermine, 3.9 mg kg(-1), i.p.) and +603% (d-amphetamine, 1.5 mg kg(-1), i.p.) compared to controls 40 min post treatment. The highest doses of phentermine and d-amphetamine increased rat locomotor activity up to 100 min and 160 min post treatment, respectively, whereas the equivalent sibutramine dose had no effect. These findings therefore suggest that dopaminergic reward mechanisms are not involved in the reduction of food intake by sibutramine. Furthermore, they are consistent with the view that sibutramine lacks abuse potential.

Initial seizure threshold in the clinical practice of bilateral electroconvulsive therapy in Edinburgh, Scotland.

Initial seizure threshold was measured by empirical titration in 137 patients referred for bilateral electroconvulsive therapy (ECT) for the treatment of depressive illness. Treatment was given by an Ectron Series 5A ECT machine. The median and modal thresholds were 75 mC and the range was 50-200 mC. The only statistically significant relationship among initial threshold and age or gender was the correlation of age with threshold in men (rho = 0.46, p < 0.01). All patients (n = 22) younger than 30 years had an initial threshold < 100 mC, but age and gender did not predict threshold accurately for older men or women.

Molecular dynamics of the H-ras gene-encoded p21 protein; identification of flexible regions and possible effector domains.

We previously reported a complete computer-based three-dimensional structure for residues 1-171 of the Gly 12-containing ras-gene-encoded p21 protein complexed with GDP. This structure was subsequently shown to closely agree with a high-resolution x-ray crystallographic structure of p21. In this communication, we report a molecular dynamics stimulation of the modelled structure in an explicit shell of water molecules to identify domains within the protein that are unusually flexible. These domains represent regions which are most likely to undergo important conformational changes when the protein is activated by binding to GTP or by oncogenic amino acid substitutions such as Val for Gly 12. The starting structure was surrounded with water molecules, temperature-equilibrated and then followed over a 100 ps trajectory during which time the energy converged after about 50 ps. Regions of the protein that were found to have the largest coordinate fluctuations involved residues 12-16, 30-35, 40-52, 60-73, 85-89, 101-109, 119-123, and 127-131. Many of these sequences with high flexibility have been implicated in the functioning of this protein. Since the overall largest fluctuations were observed for residues 101-106 and 119-123, p21 peptides containing these residues (96-110 and 115-126) were synthesized and were found to inhibit strongly the effects of oncogenic p21 protein in an oocyte maturation assay. These results indicate that the flexible p21 sequences may constitute critical functional domains of the activated protein and that this general approach may be useful for identification of important functional domains in proteins.

The use of continuous peritoneal dialysis in Europe for the treatment of children with end-stage renal failure: data from the EDTA Registry.

The demographic data on the use of continuous peritoneal dialysis in Europe for children starting renal replacement therapy under the age of 15 years was obtained from data collected by the Registry of the European Dialysis and Transplant Association--European Renal Association (EDTA Registry) on individual patient questionnaires 1980-1986. Continuous ambulatory peritoneal dialysis (CAPD) and its variants appeared to be increasingly utilised as treatment for children with end-stage renal failure (ESRF) and accounted for approximately 25% of all renal replacement therapy (RRT). Important differences in its use in various European countries are demonstrated. The proportional contribution of CAPD to treatment was higher during the first year of RRT and gradually decreased thereafter. No significant sex differences existed in the use of this treatment. Approximately 70% of all patients on CAPD were older than 6 years of age, but it is in those under 6 years that the highest proportion are put on CAPD as first method of treatment for end-stage renal failure. The most common cause of abandonment of this treatment was peritonitis, which contributed 50% of the drop-out rate.

Kidney transplantation in primary oxalosis: data from the EDTA Registry.

This paper reports the results of 98 first kidney transplantations in patients with oxalosis as the primary renal disease as recorded by the EDTA Registry. There were 79 patients who received a cadaveric (CAD) graft and 15 patients with a living related donor (LRD) graft; the type of donor was not recorded for four patients. Initial graft survival appeared to be better after LRD as compared to CAD grafts but at 3 years the poor survival was similar with 23% for LRD and 17% for CAD grafts. CAD graft survival did not differ between children and adults and was not affected by the waiting time on dialysis. A slight improvement was observed in grafts performed in the years 1983-1986 as compared to grafts performed in earlier years. The causes of failure reported were mainly rejection (33%) and recurrence of primary renal disease (31%). In view of the poor results related to recurrence of oxalosis in the graft, the potential of combined kidney and liver transplantation is discussed.

Would monitoring by electroencephalogram improve the practice of electroconvulsive therapy?

Estimates of seizure length made by the treating psychiatrist were compared with estimates made by six-channel EEG in 100 electroconvulsive treatments in 22 depressed patients. In 70 treatments the doctor observed a fit which was shorter than 25 seconds. No doctor restimulated a patient in such a case and on only three occasions was the electrical stimulus increased at the next treatment. EEG monitoring revealed that only 30 of the treatments resulted in a seizure of less than 25 seconds, and this was detected in almost all cases by the treating doctor. The potential value of EEG monitoring was to identify patients whose visible seizure was short but where cerebral seizure length was satisfactory. Trainee psychiatrists often mismanage patients who have short seizures.

EDTA Registry centre survey, 1986. Report from the European Dialysis and Transplant Association Registry.

This paper summarises the information given on the 1986 EDTA Registry centre questionnaire which was returned by 82% of the 2,065 known dialysis and transplant centres in 33 European countries. Information is given on the number of patients alive on haemodialysis according to the type of dialysis facilities available where the patient was receiving dialysis and the number of patients receiving special types of dialysis. The centre questionnaire also included questions on testing for HIV infection, serological evidence or symptoms of AIDS and the diagnosis of hepatitis B in patients and staff. The data given in response to these questions are presented together with data on the involvement of dietitians and social workers in the treatment of patients with end stage renal failure. Finally, information on transplant activity in Europe and the treatment policies of transplanting centres is provided.

Survival on renal replacement therapy: data from the EDTA Registry.

Extensive survival data are presented from the EDTA Registry's files for patients who started renal replacement therapy in 1970-1974 compared to 1980-1984. The contribution of the different treatment modalities (haemodialysis, continuous peritoneal dialysis, and transplantation) to the survival of patients according to geographical region is also shown. Survival on renal replacement therapy, irrespective of treatment modality and of primary renal disease, was best in the 10-14-year-old patients, with 58% at 10 years and 52% at 15 years, and decreased with rising age to 28% at 10 years and 16% at 15 years in patients aged 45-54 when they commenced therapy in 1970-1974. When comparing the 0-4-year-old with the 10-14-year-old cohort of the paediatric patients, 5-year survival rates for patients starting renal replacement therapy in the early eighties declined from 85% to 70% with decreasing age. Treatment policy, as reflected by the proportion of patients on different modes of therapy, varied markedly between European regions but affected survival to a small extent only. The large population with diabetic nephropathy incurred annual mortality rates 2-3 times greater than those observed in patients with 'standard' primary renal diseases. Haemodialysis and continuous peritoneal dialysis, although not comparable because of important differences in selection policy, yielded similar survival rates. Patients and graft survival rates have improved markedly when comparing patients starting renal replacement therapy in the early seventies with the eighties; particularly for cadaveric transplantation. Patient survival after second grafting was similar to that after first grafting, with 83% at 5 years after second cadaveric grafting in the 15-44-year-old cohort, vs 85% after first cadaver transplantation in 1980-1984. Second cadaveric graft survival was superior to average first-graft survival for those recipients whose first graft had been functioning for more than 1 year. However, second-graft survival in rapid rejectors of a first graft as well as third cadaveric graft survival were curtailed by the large number of early losses, with only 52% of third grafts functioning at 1 year. For living related donor transplantation, parents were mostly used in children whilst identical siblings predominated in adults older than 45. In the early eighties, patient survival was 92% at 5 years for recipients younger than 15, 87% for the 15-45 year old cohort and 72% for those aged 45 or older.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of seizure duration on serum TSH concentration after ECT.

Serum thyroid stimulating hormone (TSH) concentrations were measured by a sensitive immunoradiometric assay in 14 patients immediately before and after the first treatment of a course of electroconvulsive therapy (ECT). There was a close correlation (r = +0.70, p less than 0.01) between the increase in TSH concentration 15 min after ECT and the duration of seizure activity as measured by EEG. This observation may help clarify previous contradictory findings on the effects of ECT on TSH concentrations. There was no correlation between the increase in serum TSH concentration and the extent of recovery from depressive illness.

Electron probe microanalysis of elemental composition of mouse cardiac myocytes during post-natal maturation.

Elemental concentrations in the cytoplasm and nucleus of t tests post-natal mouse myocytes were measured at 2, 4, 8, 16, 32 days and in adults using electron probe X-ray microanalysis. Using an analysis of variance test, significant age dependent changes were found in intracellular potassium, sulfur, phosphorus, and chlorine concentrations (mg/kg dry weight), while sodium and magnesium concentrations did not show significant changes. The application of t tests following linear regression analyses (age versus concentration for each element) did, however, give a significant slope for cytoplasmic sodium, potassium, sulfur, and phosphorus values. The findings correspond closely with an emission spectroscopy-titrimetric study of whole heart ventricle of the same developmental period (Hazelwood and Nichols, '70).

Home treatment in haemophilia: clinical, social and economic advantages.

Twenty-eight severely affected haemophiliacs were observed for 3 months under treatment as hospital out-patients and for the subsequent 9 months while treating themselves at home. Delay in receiving treatment and financial costs were both clearly reduced by home treatment, the patients recovered from individual bleeds more quickly and reported a greater sense of personal freedom and independence. The amount of treatment required did not materially change and no untoward effects were noted; the use of analgesics tended to be less.