Prevalence of genetic haemochromatosis and iron overload in patients attending rheumatology and joint replacement clinics.

BACKGROUND & AIMS: Genetic Haemochromatosis (GH) is common in North European and Celtic populations and is associated with arthropathy. We aimed to measure the frequency of the common GH mutations (C282Y and H63D), the carrier frequency of C282Y and markers of iron overload in patients who were referred to our rheumatology and joint replacement clinics. METHODS: Unselected patients attending these clinics were anonymously tested for the described mutations. Transferrin saturation and serum ferritin were also measured and if elevated, the patients had predictive counselling then named GH mutation testing. The carrier and mutation frequencies were also determined in 340 local controls. RESULTS: One hundred and sixty-one unselected patients attending these clinics were studied. The C282Y mutation carrier frequency was 1 in 5.2 in patients compared with 1 in 8.1 in controls (p < 0.005). The overall mutation frequencies were similar in patients and controls. One patient was found to be a homozygous for the C282Y mutation and eight were compound heterozygotes. Seven other patients had a raised ferritin, one of whom was a C282Y heterozygote. CONCLUSION: The C282Y carrier frequency is significantly higher in patients attending rheumatology and joint replacement clinics than in controls. Screening of these patients for GH should be considered.

The changing face of hepatitis B in greater Glasgow: epidemiological trends 1993-2007.

BACKGROUND AND AIMS: Whilst hepatitis B (HBV) is historically uncommon in Scotland, anecdotal experience suggests an increasing prevalence of chronic infection. We sought to establish whether the incidence of chronic HBV is increasing in Greater Glasgow, and whether patients are assessed in secondary care. METHODS: The regional virus centre database identified HBV surface antigen (HBsAg) positive samples. For adult patients tested in Glasgow between 1993-2007 the first positive test was identified and classified as acute or chronic infection serologically. Clinic referral and attendance data was then obtained. RESULTS: 1,672 patients tested HBsAg positive; 1051 with chronic infection, 421 acute and 200 indeterminate. New diagnoses of HBV remained stable over time, however falling numbers of acute cases were mirrored by a rise in chronic cases from 40 to 119 per annum between 2000 and 2007. Of 193 patients diagnosed in 2006 and 2007, 51% were not seen in secondary care due to non referral (43%) or non attendance (8%). CONCLUSION: Chronic HBV trebled in Glasgow between 2000 and 2007. Most patients were not assessed in secondary care. Improved levels of clinic referral and attendance are required to ensure best care for HBV patients in Glasgow.

Understanding Cannabis-Based Therapeutics in Sports Medicine.

CONTEXT: With increased use of cannabis-based products by the public for both recreational and medical use, sports medicine clinicians should be informed of historical context, current legal considerations, and existing evidence with regard to efficacy, safety, and risks in the athletic community. EVIDENCE ACQUISITION: A review of ClinicalTrials.gov, MEDLINE, and CINAHL from 2015 to present was conducted with emphasis on the most recent literature using search terms, cannabis, nabiximols, cannabinoids, pain management, THC, CBD, and marijuana. Bibliographies based on original search were utilized to pursue further literature search. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 3. RESULTS: At present, limited high-quality studies exist for use of cannabinoids for acute pain, chronic pain, or concussion. None of the trials involving cannabinoids included the athletic population. Thus, results from this clinical review are extrapolated to conditions of the sports medicine population. For acute pain, 2 small-randomized double-blinded crossover trials concluded no immediate effect of cannabinoid therapy. More robust evidence exists for treatment of chronic pain conditions through meta-analysis and systemic reviews. Cannabinoid therapy exhibits moderate efficacy as a treatment for some chronic pain conditions. Investigations included a broad spectrum of chronic pain conditions, including neuropathic, musculoskeletal, inflammatory, and central pain conditions, and reveal reduction in pain and improvement of quality of life with limited adverse effects. For concussion, evidence is based on preclinical in vitro and animal models revealing possible neuroprotective effects as well as 2 clinical studies involving the presence of cannabinoids for concussion (some sports-related), but there are no high-quality trials evaluating efficacy for treatment with cannabinoids at this time. CONCLUSION: Although various biochemical explanations exist on the use of cannabinoid therapy through modulation of the endocannabinoid system for several medical issues affecting athletes, recommendations from clinicians must be extrapolated from a majority of research done in the nonathletic population. Lack of strong-quality clinical evidence, coupled with inconsistent federal and state law as well as purity issues with cannabis-based products, make it difficult for the sports medicine clinician to widely recommend cannabinoid therapeutics at present. Future larger, higher quality clinical research studies with standardized pure extracts will better guide appropriate medical use going forward. At present, evidence for a multitude of therapeutic applications is emerging for cannabinoid treatment approaches. With emphasis placed on patient-centered clinical decisions, cannabinoids hold promise of treatment for athletes with chronic pain conditions. Clinicians who treat the athletic community must consider legal and ethical issues when discussing and recommending the use of cannabinoids, with acknowledgment of inconsistencies in purity of various formulations and concerns of drug testing.

Prohibited Contaminants in Dietary Supplements.

CONTEXT: With the increasing use of unregulated dietary supplements, athletes are at continued risk from adverse medical events and inadvertent doping. EVIDENCE ACQUISITION: A review of Clinical Key, MEDLINE, and PubMed databases from 2012 to 2017 was performed using search terms, including dietary supplement, contamination, doping in athletes, inadvertent doping, and prohibited substances. The references of pertinent articles were reviewed for other relevant sources. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 3. RESULTS: Poor manufacturing processes and intentional contamination with many banned substances continue to occur in dietary supplements sold in the United States. Certain sectors, such as weight loss and muscle-building supplements, pose a greater threat because they are more likely to be contaminated. CONCLUSION: Athletes will continue to be at risk for adverse events and failed doping tests due to contaminated dietary supplements until legislation changes how they are regulated. In the interim, there are several steps that can be taken to mitigate this risk, including improved education of medical staff and athletes and use of third party-certified products.

A cardiovascular disease policy model: part 2-preparing for economic evaluation and to assess health inequalities.

OBJECTIVES: This is the second of the two papers introducing a cardiovascular disease (CVD) policy model. The first paper described the structure and statistical underpinning of the state-transition model, demonstrating how life expectancy estimates are generated for individuals defined by ASSIGN risk factors. This second paper describes how the model is prepared to undertake economic evaluation. DESIGN: To generate quality-adjusted life expectancy (QALE), the Scottish Health Survey was used to estimate background morbidity (health utilities) and the impact of CVD events (utility decrements). The SF-6D algorithm generated utilities and decrements were modelled using ordinary least squares (OLS). To generate lifetime hospital costs, the Scottish Heart Health Extended Cohort (SHHEC) was linked to the Scottish morbidity and death records (SMR) to cost each continuous inpatient stay (CIS). OLS and restricted cubic splines estimated annual costs before and after each of the first four events. A Kaplan-Meier sample average (KMSA) estimator was then used to weight expected health-related quality of life and costs by the probability of survival. RESULTS: The policy model predicts the change in QALE and lifetime hospital costs as a result of an intervention(s) modifying risk factors. Cost-effectiveness analysis and a full uncertainty analysis can be undertaken, including probabilistic sensitivity analysis. Notably, the impacts according to socioeconomic deprivation status can be made. CONCLUSIONS: The policy model can conduct cost-effectiveness analysis and decision analysis to inform approaches to primary prevention, including individually targeted and population interventions, and to assess impacts on health inequalities.

Sending your teenagers away. Controlled stress decreases neurotic vulnerability.

OBJECTIVE: To study the effect of a controlled stressor on the rate of personality maturity. DESIGN: Eighteen-month prospective controlled study. SETTING: General community. EXPERIMENTAL: Exposed to the stress of 12 months' intercultural experience. CONTROL: Remained in usual environment. MAIN OUTCOME MEASURE: A measure of personality vulnerability/maturity derived from a canonical correlational combination of trait anxiety, locus of control, and defense style. RESULTS: Exchange students exposed to the stressor made significantly greater gains in personality maturity (0.28 vs 0.03 SD: P < or = .01) than did the control students matched on this measure at baseline. CONCLUSION: Exchange students exposed to the stress of living abroad showed a substantial decrease in vulnerability, which should decrease the risk of future neurotic disorders in this group.

A cardiovascular disease policy model that predicts life expectancy taking into account socioeconomic deprivation.

OBJECTIVES: A policy model is a model that can evaluate the effectiveness and cost-effectiveness of interventions and inform policy decisions. In this study, we introduce a cardiovascular disease (CVD) policy model which can be used to model remaining life expectancy including a measure of socioeconomic deprivation as an independent risk factor for CVD. DESIGN: A state transition model was developed using the Scottish Heart Health Extended Cohort (SHHEC) linked to Scottish morbidity and death records. Individuals start in a CVD-free state and can transit to three CVD event states plus a non-CVD death state. Individuals who have a non-fatal first event are then followed up until death. Taking a competing risk approach, the cause-specific hazards of a first event are modelled using parametric survival analysis. Survival following a first non-fatal event is also modelled parametrically. We assessed discrimination, validation and calibration of our model. RESULTS: Our model achieved a good level of discrimination in each component (c-statistics for men (women)-non-fatal coronary heart disease (CHD): 0.70 (0.74), non-fatal cerebrovascular disease (CBVD): 0.73 (0.76), fatal CVD: 0.77 (0.80), fatal non-CVD: 0.74 (0.72), survival after non-fatal CHD: 0.68 (0.67) and survival after non-fatal CBVD: 0.65 (0.66)). In general, our model predictions were comparable with observed event rates for a Scottish randomised statin trial population which has an overlapping follow-up period with SHHEC. After applying a calibration factor, our predictions of life expectancy closely match those published in recent national life tables. CONCLUSIONS: Our model can be used to estimate the impact of primary prevention interventions on life expectancy and can assess the impact of interventions on inequalities.

A confocal microscopic survey of serotoninergic axons in the lumbar spinal cord of the rat: co-localization with glutamate decarboxylase and neuropeptides.

Patterns of co-localization of serotonin with glutamate decarboxylase (the synthetic enzyme for GABA) or each one of eight neuropeptides (calcitonin gene-related peptide, dynorphin, enkephalin, galanin, neuropeptide Y, neurotensin, substance P and somatostatin) were investigated with dual-colour confocal laser scanning microscopy in the lumbar spinal cords of three adult rats. Four regions of the gray matter were studied (laminae I-II, V, IX and X). The extent of co-localization was estimated by direct assessment of merged pairs of optical sections and by automated image analysis. Co-localization of serotonin and glutamate decarboxylase was found only in a few axons of laminae I-II but was not detected in other laminae. Peptides were not co-localized with serotonin in the superficial dorsal horn but considerable co-localization was found in motor nuclei and sparse co-localization was found in laminae V and X. Galanin and substance P frequently co-existed with serotonin in lamina IX but some co-localization with dynorphin, somatostatin, [Met]enkephalin and neuropeptide Y was also detected. Galanin, substance P and dynorphin were also co-localized with serotonin in a few axons of the deep dorsal horn and in the gray matter around the central canal. Neurotensin and calcitonin gene-related compound did not co-exist with serotonin in any of the laminae investigated. This evidence suggests that different populations of serotoninergic axons project to different regions of the spinal gray matter. Those containing glutamate decarboxylase terminate in the superficial dorsal horn and are likely to be involved in antinociception, whereas those containing peptides terminate principally in motor nuclei and are likely to modulate motor activity.

The role of action reflexes in the damping of mechanical oscillations.

Reflex responses measured during voluntary contraction of the muscle being stretched are known to differ markedly from reflex responses elicited from passive muscle. The term 'action tonic stretch reflex' or 'action TSR' has been used previously to describe a reflex response to continuous stretch, separated from voluntary activity by means of a cross-correlational and spectrographic analysis. In this paper it is proposed that the action TSR play a functional role during voluntary movement by damping the transient oscillations associated with the natural resonant frequencies of the limbs. It is suggested that oscillations excite an action TSR force response with phase lead ahead of muscle stretch. This force response can be resolved into two force components, one of which has a 90 degree phase lead ahead of muscle stretch and behaves like a viscous friction reaction force causing damping of oscillations. Three experiments which support this proposition are described. (1) Analog computer model stimulation studies of a muscle supporting a mass-spring load reveal that damping only occurs when the force response has a phase lead ahead of muscle stretch. When the force response has a phage lag behind muscle stretch, the system is unstable and the amplitude of oscillation increases with time. (2) It is demonstrated that when a mass-spring load is supported as rigidly as possible by the human arm, reaction forces from the arm damp and mass-spring oscillations more rapidly than when the mass-spring is rigidly supported. Electromyogram (EMG) recordings reveal that mass-spring oscillations excite action TSR responses with phase lead ahead of muscle stretch. (3) Recordings of elbow angle and biceps EMG during rapid forearm flexion or extension movements followed by sudden stops reveal critically damped oscillations in the elbow angle signal (i.e. no more than one or two small overshoots), which are accompanied by EMG action TSR responses with phase lead ahead of muscle stretch.

Complement depletion suppresses Lewis rat experimental allergic neuritis.

Lewis rats immunized with myelin and complete Freund's adjuvant were treated with cobra venom factor (CVF) which depletes the C3 component of complement. CVF given at day 9 delayed the onset of experimental allergic neuritis (EAN) by 2-3 days and when given at days 9 and 12 delayed the onset of EAN by 4-5 days. Lumbar nerve roots of CVF-treated rats had significantly less demyelination than those from control EAN rats.

The effects of nerve growth factor on neurite outgrowth from cultured adult and aged mouse sensory neurons.

The present study demonstrated, by detailed computer image analysis, that cultured aged (2 years) as well as adult (6 months) mouse sensory neurons retained a capacity for neurite extension throughout the 9-day period investigated. Neurites arose predominantly from intermediate- and large-sized neurons. The numbers of neurites, the neurite with the major or longest length, the number of branches and the total extent of neuritogenesis were measured blindly from a total of 440 adult and 451 aged neurons, in five independent experiments for each, and data were statistically tested by ANOVA. The results demonstrated that NGF significantly enhanced neurite outgrowth from aged neurons in a low density enriched culture system as well as from adult neurons, and thereby extends the previous findings from other laboratories [7,25], which only monitored the response of young adult neurons. For total neurite lengths of adult and aged neurons differences were evident by the end of the 9-day culture period: major neurite length enhancement was predominantly responsible for the effect on adult neurons, whereas increased branch lengths contributed more in the case of aged neurons.

Mental disorder and season of birth--a southern hemisphere study.

Studies on the relationship between season of birth and mental disorder have been substantially confined to northern hemisphere regions. Such studies have generally found an excess of winter births of schizophrenics, and variably an excess of winter births of manic-depressive and mentally retarded patients. In the present study information on sex, diagnosis and date of birth was obtained on all 20,358 patients first admitted to psychiatric facilities in New South Wales between July 1970 and June 1974 and born in New South Wales. The collective 1962-71 monthly live-births for New South Wales were used as a control. A significant winter excess was found for the female schizophrenic group, while a significant spring excess was found for neurotic patients, most marked in those with anxiety neurosis. It is hypothesized that the relationship between schizophrenia and winter birth is consequent upon a greater sensitivity of schizophrenics to those physiological factors which determine conception in the general population.

Depressive illness: the role of aggression further considered.

Measures of depression and undischarged drive were obtained for 292 psychiatric in-patients. In 200 of these cases inhibition of aggression was also assessed. All patients were classified as being endogenously depressed, reactively depressed, or as suffering from non-depressive primary disorders. The latter group was subdivided into secondarily depressed and non-depressed groups. The 3 depressed groups were then compared with the non-depressed subjects in respect of drive level and inhibition of aggressionmall 3 depressed groups showed significantly higher driver level than did the non-depressed subjects. The endogenous depressives also inhibited significantly more of their aggression than did the non-depressed subjects. The results are consistent with a drive inhibition theory of depression. However, while endogenous depression seems to be associated more specifically with the inhibition of aggression, reactive depression may be associated rather with the inhibition of drive generally.

Sexually transmitted diseases in Edinburgh: patients under 18 years of age.

PIP: Sexually transmitted diseases in Edinburgh have been appearing in increasingly younger populations in the past 15 years. In 1976, 70% of female patients to the Edinburgh clinic were under age 24, compared to 56% in 1967. All patients under 18 on the date of their first attendance at the clinic in 1967 and 1977 were studied. In 1977, 93 males and 160 females under 18 attended. 14% of the boys and 15% of the girls were under 16. Gonorrhea was diagnosed in 21 boys and 35 girls. 75% of boys were heterosexual, but 15 (18%) had homosexual experience. 61% of girls and 53% boys had only 1 sexual partner, but 14% of boys claimed 4 or more, compared to 1.5% of girls. Almost 60% girls were involved in a regular sexual relationship, though in 10% other partners were also involved. Only 35% boys had a regular partner. 144 girls had a sexual relationship when they visited the clinic. Of these, 38 used no contraception; 83 used oral contraceptives; 13 relied on a condom. Increased knowledge of contraceptive practice appeared to be having an effect, with 3/160 girls in 1977 being pregnant when they visited the clinic, compared to 14/137 in 1967. The number of illegitimate births to mothers under 20 has not dropped, but the number in older age groups has. IN 1967 there were no figures relating to homosexuality. The proportion of clinic patients under 18 almost doubled between 1967 and 1977.^ieng

Chemical composition of degrading mangrove leaf litter and changes produced after consumption by mangrove crabNeosarmatium smithi (Crustacea: Decapoda: Sesarmidae).

The leaves of the mangroveCeriops tagal contained 3.2-4.1% (all percentages relate to dry weight) ofD-1-O-methyl-muco-inositol previously unreported in mangroves. They consisted of 37% aqueous acetone-water-soluble material, 18% water-insoluble polysaccharides, and ca. 50% polyphenols, which include soluble and insoluble tannins and lignin. The polysaccharide component sugars were glucose, arabinose, uronic acids, mannose, xylose, galactose, and rhamnose in the proportions 28∶26∶22∶10∶7∶5∶2, respectively. The leaves were pectate rich, and the low level of glucan was presumed to consist mainly of cellulose. After four weeks of biodegradation, ca. 60% of the acetone-water-soluble material was lost from the leaves. Degradation processes greatly altered the polysaccharide components in the leaves. Pectates were rapidly degraded, while other polysaccharides, although reduced proportionately, resisted degradation at about the same level, and all component sugars were found in the 8-week-old leaves. "Apparent lignin" contents increased from 15 to >30% during biodegradation up to eight weeks. The yields of the major fractions in corresponding fecal material fromNeosarmatium smithi showed a similar trend to the diets. An enrichment of the insoluble residue was noticeable due to the digestion of dialyzable material. The fecal carbohydrate content was greatly reduced (7-11%) and the "apparent lignin" increased (27-39%) due to its resistance to degradation. All dietary polysaccharide component sugars were found in the fecal residues, including some uronic acids. The leaves also contained a readily water-soluble fraction (15%) which consisted of pectates strongly complexed with proanthocyanidins.