The development of the PAR Index (Peer Assessment Rating): reliability and validity.

The PAR Index has been developed to provide a single summary score for all the occlusal anomalies which may be found in a malocclusion. The score provides an estimate of how far a case deviates from normal alignment and occlusion. The difference in scores between the pre- and post-treatment cases reflects the degree of improvement and, therefore, the success of treatment. Excellent reliability was exhibited within and between examiners (Intraclass Correlation Coefficient, R greater than 0.91). The components of the PAR Index have been weighted to reflect current British orthodontic opinion and is flexible in that the weightings could be changed to reflect future standards and standards currently being achieved in other countries. The PAR Index offers uniformity and standardization in assessing the outcome of orthodontic treatment.     

A short review of the relationship between intestinal permeability and inflammatory joint disease

The potential aetiological relationship between increased intestinal permeability and inflammatory joint disease is reviewed. The known physiology of intestinal permeability is outlined and the alterations which occur in different disease states are described. A rationale is given for the hypothesis that the gut is the likely source of the antigens causing inflammatory arthritis, and the studies of this hypothesis to date are reviewed.     

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

Endocrine and exocrine pancreatic function in treated coeliac disease

Pancreatic function was assessed prospectively in a group of 18 treated adult coeliac patients, most of whom were asymptomatic. The para-aminobenzoic acid (PABA) test indicated exocrine pancreatic insufficiency in three patients, all of whom had persisting gastrointestinal symptoms. Arginine, 5 g intravenously, was used to stimulate pancreatic islet cells; basal and stimulated concentrations of plasma insulin, C-terminal glucagon, N-terminal glucagon, and blood glucose did not differ from asymptomatic nondiabetic control subjects. After gluten withdrawal, coeliac patients who responded clinically had no evidence of significant pancreatic impairment, but consideration of exocrine pancreatic insufficiency is worthwhile in those patients with persisting symptoms.     

Insulin sensitivity and B-cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes

We used the minimal model technique to obtain concurrent measurements of whole-body insulin sensitivity and pancreatic B-cell responsiveness to glucose during the third trimester of pregnancy. Insulin sensitivity in normal pregnant women (n = 8) was reduced to only one third that of a group of nonpregnant women (n = 7) of similar age and relative weight. This marked insulin resistance was compensated by reciprocal enhancement of the first and second-phase insulin responses to intravenous glucose, which were increased threefold as compared with the nonpregnant women. Women with gestational diabetes mellitus (n = 16) had mean insulin sensitivity that was similar to that of the normal pregnant group, which indicates that insulin action was appropriate for the late phase of pregnancy in the gestational diabetic group. By contrast, the mean first-phase insulin response was significantly reduced in women with gestational diabetes mellitus, as compared with that of normal pregnant women (p less than 0.001). However, approximately one fifth of the group with gestational diabetes mellitus had first-phase responses that did not fall below the 95% confidence interval for the mean in normal pregnant women. The mean second-phase response was also lower in the group with gestational diabetes, although the difference was of borderline statistical significance (p less than 0.09). Our findings reveal the quantitative nature of the reciprocal changes in insulin sensitivity and B-cell function that normally accompany late pregnancy. They further indicate that during the third trimester, mild gestational diabetes is characterized by an impairment of pancreatic B-cell function rather than an exaggeration of the normal insulin resistance of late pregnancy.     

A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D?' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.     

Sex differences in physiological and affective responses to stress in remitted depression

Major depressive disorder (MDD) is associated with alterations in stress physiology. Severe melancholic depression is characterized by hypercortisolism, but community dwelling mildly depressed individuals and those with remitted MDD have shown reduced or normal reactivity to stress. There are also pronounced sex differences both in the incidence of MDD and in stress reactivity. To explore the relationships among depression history, sex differences, and stress, we examined stress reactivity in people with and without a history of MDD. Twenty-two participants with remitted MDD (12 men and 10 women) and 36 never depressed comparison participants (22 men and 14 women) participated in the study. Cortisol and alpha-amylase (sAA) were sampled from saliva before, 10 min after, and 30 min after the Trier Social Stress Test (TSST). Participants filled out the Positive Affect Negative Affect Schedule (PANAS) before and after they underwent the TSST. Women with remitted MDD showed reduced cortisol response to the TSST compared with the never MDD women, while men with remitted MDD showed comparable cortisol reactivity to the never depressed men. The groups did not differ on sAA reactivity to stress. The remitted MDD group (overall and men and women separately) reported greater negative affect both before and after stress compared to the never depressed group. Women from both groups reported greater post-stress negative affect than men. In contrast, men from both groups reported higher positive affect before and after stress than women. Given that the sex difference findings were not dependent on depression history, self-reported affective differences in response to stress may predate depressive symptoms and contribute to sex differences in depression incidence.     

The relationship of clozapine and haloperidol treatment response to prefrontal,hippocampal, and caudate brain volumes

OBJECTIVE: The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol. METHOD: Partially responsive outpatients with schizophrenia who participated in a 10-week, parallel-group, double-blind comparison of clozapine and haloperidol and who had an available magnetic resonance imaging scan were included in the current study. Prefrontal gray and white matter, hippocampal, and caudate volumes were manually measured. The Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) were used to assess symptom changes. The Simpson-Angus Rating Scale was used to assess extrapyramidal symptoms. RESULTS: Twenty-two patients randomly assigned to clozapine and 23 patients assigned to haloperidol met study entry criteria. There were significant interactions between treatment and right prefrontal gray matter volume for BPRS total score and SANS total score. There were no significant treatment-by-brain structure interactions for BPRS positive symptom items. Right prefrontal gray matter volume was also related to differential treatment effects for the BPRS subscales of anxiety/depression and hostility and the Simpson-Angus Rating Scale akathisia item. CONCLUSIONS: These results suggest that there is a differential interaction among clozapine and haloperidol, brain structure, and treatment response. Partially responsive patients with larger brain volumes may be more likely to experience the benefits of clozapine treatment, but they may be more vulnerable to side effects and experience a subsequent worsening of their symptoms when treated with haloperidol.     

Tensions between the conduct of randomised controlled trials in health promotion research and the role of autonomy in human health and well being

The goal of developing increasingly effective interventions to change health‐related behaviours, which is an inevitable result of the use of the scientific method, conflicts with respect for the autonomy and dignity of the individual. This paper recommends a new direction for the field of health promotion based on building people's capacity to exercise autonomy, in the ethically relevant meaning of the term, and thereby promote a more comprehensive understanding of the goals of the field, a state of health that includes the irreducible ethical dimension signified by human dignity.