Effect of age on the relative efficacy of clozapine in schizophrenia.

OBJECTIVE: Early treatment of schizophrenia improves outcomes. Clozapine appears to have unique benefit when other antipsychotic medication has failed. This systematic review and meta-analysis aims to assess clozapine's superiority over alternative antipsychotic medication and examine whether earlier use is associated with additional benefit. METHOD: Systematic retrieval of blinded, randomized controlled trials comparing clozapine with alternative antipsychotics in adults with schizophrenia. The effect of mean age on relative clozapine response was examined using random effects meta-regression, and multiple linear regression on available patient data. RESULTS: A total of 276 studies were retrieved. Thirty-four studies were included in the meta-analysis. Clozapine was significantly more effective than alternative antipsychotics in reducing psychotic symptoms and increasing response. However, meta-regression failed to show a more significant effect in younger patients (age on effect size (total psychotic symptoms) 0.00, P = 0.79 CI -0.03 to 0.03). Individual patient data were available for two studies, the larger of which showed a significant interaction between younger age and superiority of clozapine. CONCLUSION: The results support clozapine's superiority over other antipsychotics. A convincing effect of age on this effect was not demonstrated, although this was suggested in one study. In view of the age of many of the included studies, and changes in reporting practice over time, new clozapine RCTs, which include age of illness onset as well as age at trial time, would be welcome in order to provide meta-analysable data for future use.

Impact of glycaemic control on fracture risk in 5368 people with newly diagnosed Type 1 diabetes: a time-dependent analysis.

AIMS: To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes. METHODS: People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow-up were collected. A Cox proportional hazards model with HbA1c included as a time-dependent variable was fitted to these data. RESULTS: Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002-1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03-1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c . CONCLUSIONS: In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures.

Proportion of Tubal Factor Infertility due to Chlamydia: Finite Mixture Modeling of Serum Antibody Titers.

In this study, we examined whether the proportion of tubal factor infertility (TFI) that is attributable to Chlamydia trachomatis, the population excess fraction (PEF), can be estimated from serological data using finite mixture modeling. Whole-cell inclusion immunofluorescence serum antibody titers were recorded among infertile women seen at St. Michael's Hospital in Bristol, United Kingdom, during the period 1985-1995. Women were classified as TFI cases or controls based on laparoscopic examination. Finite mixture models were used to identify the number of component titer distributions and the proportion of serum samples in each, from which estimates of PEF were derived. Four titer distributions were identified. The component at the highest titer was found only in samples from women with TFI, but there was also an excess of the second-highest titer component in TFI cases. Minimum and maximum estimates of the PEF were 28.0% (95% credible interval: 6.9, 50.0) and 46.8% (95% credible interval: 23.2, 64.1). Equivalent estimates based on the standard PEF formula from case-control studies were 0% and over 65%. Finite mixture modeling can be applied to serological data to obtain estimates of the proportion of reproductive damage attributable to C. trachomatis Further studies using modern assays in contemporary, representative populations should be undertaken.

Pelvic inflammatory disease and salpingitis: incidence of primary and repeat episodes in England.

Pelvic inflammatory disease (PID) and more specifically salpingitis (visually confirmed inflammation) is the primary cause of tubal factor infertility and is an important risk factor for ectopic pregnancy. The risk of these outcomes increases following repeated episodes of PID. We developed a homogenous discrete-time Markov model for the distribution of PID history in the UK. We used a Bayesian framework to fully propagate parameter uncertainty into the model outputs. We estimated the model parameters from routine data, prospective studies, and other sources. We estimated that for women aged 35-44 years, 33·6% and 16·1% have experienced at least one episode of PID and salpingitis, respectively (diagnosed or not) and 10·7% have experienced one salpingitis and no further PID episodes, 3·7% one salpingitis and one further PID episode, and 1·7% one salpingitis and ⩾2 further PID episodes. Results are consistent with numerous external data sources, but not all. Studies of the proportion of PID that is diagnosed, and the proportion of PIDs that are salpingitis together with the severity distribution in different diagnostic settings and of overlap between routine data sources of PID would be valuable.

Incidence of Chlamydia trachomatis infection in women in England: two methods of estimation.

Information on the incidence of Chlamydia trachomatis (CT) is essential for models of the effectiveness and cost-effectiveness of screening programmes. We developed two independent estimates of CT incidence in women in England: one based on an incidence study, with estimates 'recalibrated' to the general population using data on setting-specific relative risks, and allowing for clearance and re-infection during follow-up; the second based on UK prevalence data, and information on the duration of CT infection. The consistency of independent sources of data on incidence, prevalence and duration, validates estimates of these parameters. Pooled estimates of the annual incidence rate in women aged 16-24 and 16-44 years for 2001-2005 using all these data were 0·05 [95% credible interval (CrI) 0·035-0·071] and 0·021 (95% CrI 0·015-0·028), respectively. Although, the estimates apply to England, similar methods could be used in other countries. The methods could be extended to dynamic models to synthesize, and assess the consistency of data on contact and transmission rates.

Familiarisation to and reproducibility of cycling at 110% peak power output.

AIM: This study investigated the familiarisation to and test re-test reproducibility of constant load cycling at 110% peak power output (WPEAK). METHODS: Eleven healthy, but not cycle trained, males performed a graded incremental exercise test to ascertain WPEAK followed by three trials (T1, T2 and T3) at 110% WPEAK to exhaustion. Trials were separated by ~7 days. RESULTS: Although there was no difference in time to exhaustion (TLIM) between T1 and T2 (P=0.100) and T2 and T3 (P=0.095) respectively, a difference was observed between T1 and T3 (P=0.046). Correlation coefficients, coefficients of determination, limits of agreement (LoA) and within-subject coefficient of variation (CV) improved across trials demonstrating T2 and T3 had the strongest relationship (T1 vs. T3: r=0.73; r2=0.53; Bias=40 s; CV=14%; T1 vs. T2: r=0.66; r2=0.43; Bias=24 s; CV=10%; T2 vs. T3: r=0.97; r2=0.95; Bias=16 s; CV=7%). There was no difference across trials for HR (P=0.12), BLa (P=0.76), RER (P=0.52), VE, (P=0.32), VO2, (P=0.33), local RPE (RPEL; P=1) and overall RPE (RPEO; P=0.91) at exhaustion or BLa (P=0.76) and pH (P=0.47) 5-minutes post-exercise. CONCLUSION: Constant load cycling at 110% WPEAK is a reliable protocol when assessing supramaximal exercise performance after completion of two familiarisation trials.

The effect of age and sex on peak oxygen uptake during upper and lower body exercise: A systematic review.

BACKGROUND: Large scale population norms for peak oxygen uptake (VO2peak) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper body functional capacity has an important role in activities of daily living far less is known regarding the effect of age and sex on upper body functional capacity (i.e. arm crank ergometry; ACE). The aim of this review was to determine the effect of age and sex on VO2peak obtained during ACE and CE in the same participants. METHOD: The review was pre-registered with PROSEPERO (Ref: CRD42022349566). A database search using Academic Search Complete including CINAHL complete, CINHAL Ultimate, Medline, PubMed, SPORTDiscus was undertaken. RESULTS: The initial search yielded 460 articles which was reduced to 243 articles following removal of duplicates. Twenty-five articles were subsequently excluded based on title resulting in 218 articles considered for retrieval. Following review of the abstracts, 78 further articles were excluded leaving 140 to be assessed for eligibility. Eighty-five articles were subsequently excluded, resulting in 55 articles being included. The decrease in VO2peak with age during CE was consistent with previous studies. Decreases in VO2peak during ACE with age, although paralleling those of CE, appeared to be of greater functional importance. When changes in VO2peak were considered below the age of 50 years little change was observed for absolute VO2peak during ACE and CE. In contrast, relative VO2peak demonstrated decreases in VO2peak for both ACE and CE likely reflecting increases in body mass and body fat percentage with age. After 50 years of age absolute and relative VO2peak demonstrated more similar and subtle responses. Heterogeneity across studies for both absolute and relative VO2peak between ACE and CE was large. Although strict inclusion criteria were applied, the inter-individual variation in sample populations was likely the main source of heterogeneity. There was a considerable lack data sets available for ages above 40 years of age. CONCLUSIONS: These responses suggest that upper body VO2peak decreases in line with that of the lower body but, due to the lower peak values achieved during ACE, decreases in VO2peak may have more profound functional impact compared to that for the lower body. Using absolute and relative measures of VO2peak results in different age-related profiles when considered below 50 years of age. To further our understanding of whole body ageing more data is required for participants in mid and later life. The association between VO2peak and underlying physiological factors with age needs to be studied further, particularly in conjunction with activities of daily living and independent living.

The effects of elevated levels of sodium bicarbonate (NaHCO3) on the acute power output and time to fatigue of maximally stimulated mouse soleus and EDL muscles.

This study examined the effects of elevated buffer capacity [~32 mM HCO3(-)] through administration of sodium bicarbonate (NaHCO3) on maximally stimulated isolated mouse soleus (SOL) and extensor digitorum longus (EDL) muscles undergoing cyclical length changes at 37 °C. The elevated buffering capacity was of an equivalent level to that achieved in humans with acute oral supplementation. We evaluated the acute effects of elevated [HCO3(-)] on (1) maximal acute power output (PO) and (2) time to fatigue to 60 % of maximum control PO (TLIM60), the level of decline in muscle PO observed in humans undertaking similar exercise, using the work loop technique. Acute PO was on average 7.0 ± 4.8 % greater for NaHCO3-treated EDL muscles (P < 0.001; ES = 2.0) and 3.6 ± 1.8 % greater for NaHCO3-treated SOL muscles (P < 0.001; ES = 2.3) compared to CON. Increases in PO were likely due to greater force production throughout shortening. The acute effects of NaHCO3 on EDL were significantly greater (P < 0.001; ES = 0.9) than on SOL. Treatment of EDL (P = 0.22; ES = 0.6) and SOL (P = 0.19; ES = 0.9) with NaHCO3 did not alter the pattern of fatigue. Although significant differences were not observed in whole group data, the fatigability of muscle performance was variable, suggesting that there might be inter-individual differences in response to NaHCO3 supplementation. These results present the best indication to date that NaHCO3 has direct peripheral effects on mammalian skeletal muscle resulting in increased acute power output.

Cooling strategies improve intermittent sprint performance in the heat of athletes with tetraplegia.

BACKGROUND: Precooling has been shown to enhance performance in repeated sprint exercise in able-bodied subjects in a hot environment. Spinal cord injury causes thermoregulatory impairment with a detrimental effect on performance. This study assessed whether cooling strategies before and during exercise in the heat enhances sprint performance in athletes with tetraplegia. METHODS: Eight male athletes with tetraplegia performed intermittent arm crank exercise in the heat (32.0 degrees C (0.1 degrees C); humidity, 50% (0.1%)) for a maximum of 60 min or until exhaustion. Trials involved a no-cooling control (CON), precooling (PRE) or cooling during exercise (DUR). Each intermittent sprint protocol consisted of varied periods of passive rest, maximal sprinting and active recovery. RESULTS: Both PRE and DUR cooling strategies improved the ability of the athletes to repeatedly perform high-intensity sprints, with times to exhaustion (TTE), whereas during the CON trial, athletes demonstrated a reduction in the total number of sprints and TTE (47.2 (10.8), 52.8 (5.8) and 36.2 (9.6) min for CON, PRE and DUR, respectively). Core temperature was significantly higher for CON (37.3 degrees C (0.3 degrees C)) when compared with both PRE and DUR (36.5 degrees C (0.6 degrees C) and 37.0 degrees C (0.5 degrees C), respectively, p<0.01). Ratings of perceived exertion and thermal sensation upon exhaustion or completion were not different. CONCLUSIONS: Athletes with tetraplegia should use a precooling or during-exercise cooling strategy specific to the characteristics of their sport when exercising in hot conditions.

Evaluation of clopidogrel responsiveness after drug-eluting stent implantation.

Clopidogrel is a cornerstone of medical therapy in patients with cardiovascular disease, reducing the rate of ischemic events in patients with acute coronary syndrome, ST elevation myocardial infarction, and those undergoing percutaneous coronary intervention (PCI). Prolonged dual antiplatelet therapy with aspirin and a thienopyridine is mandated after drug-eluting stent implantation. However, there is substantial variability in the pharmacokinetics and pharmacodynamics of clopidogrel among individuals, and a lack of effect has been associated with adverse outcome after PCI, including drug-eluting stent thrombosis. The development of platelet function assays that can be performed in the clinical laboratory or at the point-of-care has made it possible to integrate the evaluation of clopidogrel response into clinical practice. Clinical utilization of platelet function testing requires an understanding of the types of methodologies that are available, the interpretation of the results that are provided, and the different potential treatment options in patients who are identified to be at risk. Several ongoing randomized clinical trials are testing the safety and efficacy of individualized antiplatelet therapy based on platelet function testing to reduce ischemic events after PCI with drug-eluting stents.

Evaporative heat loss insufficient to attain heat balance at rest in individuals with a spinal cord injury at high ambient temperature.

The aim of the study was to determine whether climatic limits for achieving heat balance at rest are affected by spinal cord injury (SCI). Twenty-three men [8 able-bodied (AB), 8 with paraplegia (PP), and 7 with tetraplegia (TP)] rested in 37°C and 20% relative humidity (RH) for 20 min. With the ambient temperature held constant, RH was increased by 5% every 7 min, until gastrointestinal temperature (Tgi) showed a clear inflection or increased by >1°C. Tgi, skin temperatures, perceptual responses, and metabolic energy expenditure were measured throughout. Metabolic heat production [AB: 123 (21) W, PP: 111 (15) W, TP: 103 (29) W; means (SD)] and required rate of evaporative cooling for heat balance [Ereq; AB: 113 (20) W, PP: 107 (17) W, TP: 106 (29) W] were similar between groups (P = 0.22 and P = 0.79). Compared with AB, greater increases in Tgi were observed in TP (P = 0.01), with notable increases in mean skin temperature (Tsk) for TP and PP (P = 0.01). A Tgi inflection point was demonstrated by seven AB, only three of eight PP, and no TP. Despite metabolic heat production (and Ereq) being similar between groups, evaporative heat loss was not large enough to obtain heat balance in TP, linked to a shortfall in evaporative cooling potential. Although PP possess a greater sweating capacity, the continual increase in Tgi and Tsk in most PP, although lower than for TP, implies that latent heat loss for PP is also insufficient to attain heat balance.NEW & NOTEWORTHY In the absence of convective heat loss, at temperatures around 37°C evaporative heat loss is insufficient to attain heat balance at rest in individuals with paraplegia and tetraplegia. This finding was directly linked to a shortfall in evaporative cooling potential compared with required evaporative cooling. In this environment, individuals with both paraplegia and tetraplegia cannot subjectively determine the magnitude of their thermal strain; thus perceptual responses should not be relied upon for this population group.

Effects of external loads on postural sway during quiet stance in adults aged 20-80 years.

The purpose of this study was to investigate the effects of holding external loads on postural sway during upright stance across age decades. Sixty-five healthy adults (females, n = 35), aged 18-80 years were assessed in four conditions; (1) standing without holding a load, holding a load corresponding to 5% body mass in the (2) left hand, (3) right hand and (4) both hands. The centre of pressure (COP) path length and anteroposterior and mediolateral COP displacement were used to indirectly assess postural sway. External loading elicited reductions in COP measures of postural sway in older age groups only (P < 0.05). No changes were observed in younger or intermediate aged adults (P > 0.05). Holding external loads during standing is relevant to many activities of daily living (i.e. holding groceries). The reduction in postural sway may suggest this type of loading has a stabilising effect during quiet standing among older adults.

Gestational dyslipidaemia and adverse birthweight outcomes: a systematic review and meta-analysis.

BACKGROUND: Low and high birthweight is known to increase the risk of acute and longer-term adverse outcomes, such as stillbirth, infant mortality, obesity, type 2 diabetes and cardiovascular diseases. Gestational dyslipidaemia is associated with a numbers of adverse birth outcomes, but evidence regarding birthweight is still inconsistent to reliably inform clinical practice and treatment recommendations. OBJECTIVE: The aim of this study was to explore the relationship between maternal gestational dyslipidaemia and neonatal health outcomes, namely, birthweight, metabolic factors and inflammatory parameters. METHODS: We searched systematically Embase, MEDLINE, PubMed, CINAHL Plus and Cochrane Library up to 1 August 2016 (with an updated search in MEDLINE at the end of July 2017) for longitudinal studies that assessed the association of maternal lipid levels during pregnancy with neonatal birthweight, or metabolic and inflammatory parameters up to 3 years old. RESULTS: Data from 46 publications including 31,402 pregnancies suggest that maternal high triglycerides and low high-density-lipoprotein cholesterol levels throughout pregnancy are associated with increased birthweight, higher risk of large for gestational age and macrosomia and lower risk of small-for-gestational age. The findings were consistent across the studied populations, but stronger associations were observed in women who were overweight or obese prior to pregnancy. CONCLUSIONS: This meta-analysis suggested that the potential under-recognized adverse effects of intrauterine exposure to maternal dyslipidaemia may warrant further investigation into the relationship between maternal dyslipidaemia and birthweight in large prospective cohorts or in randomized trials.

Effects of two cooling strategies on thermoregulatory responses of tetraplegic athletes during repeated intermittent exercise in the heat.

Athletes with spinal cord injury (SCI), and in particular tetraplegia, have an increased risk of heat strain and consequently heat illness relative to able-bodied individuals. Strategies that reduce the heat strain during exercise in a hot environment may reduce the risk of heat illness. To test the hypotheses that precooling or cooling during intermittent sprint exercise in a heated environment would attenuate the rise in core temperature in tetraplegic athletes, eight male subjects with SCI (lesions C(5)-C(7); 2 incomplete lesions) undertook four heat stress trials (32.0 +/- 0.1 degrees C, 50 +/- 0.1% relative humidity). After assessment of baseline thermoregulatory responses at rest for 80 min, subjects performed three intermittent sprint protocols for 28 min. All trials were undertaken on an arm crank ergometer and involved a no-cooling control (Con), 20 min of precooling (Pre), or cooling during exercise (Dur). Trials were administered in a randomized order. After the intermittent sprint protocols, mean core temperature was higher during Con (37.3 +/- 0.3 degrees C) compared with Pre and Dur (36.5 +/- 0.6 degrees C and 37.0 +/- 0.5 degrees C, respectively; P < 0.01). Moreover, perceived exertion was lower during Pre (13 +/- 2; P < 0.01) and Dur (12 +/- 1; P < 0.01) compared with Con (14 +/- 2). These results suggest that both precooling and cooling during intermittent sprint exercise in the heat reduces thermal strain in tetraplegic athletes. The cooling strategies also appear to show reduced perceived exertion at equivalent time points, which may translate into improved functional capacity.

The effects of arm crank ergometry, cycle ergometry and treadmill walking on postural sway in healthy older females.

Older adults are increasingly being encouraged to exercise but this may lead to muscle fatigue, which can adversely affect postural stability. Few studies have investigated the effects of upper body exercise on postural sway in groups at risk of falling, such as the elderly. The purpose of this study was to compare the effects arm crank ergometry (ACE), cycle ergometry (CE) and treadmill walking (TM) on postural sway in healthy older females. In addition, this study sought to determine the time necessary to recover postural control after exercise. A total of nine healthy older females participated in this study. Participants stood on a force platform to assess postural sway which was measured by displacement of the centre of pressure before and after six separate exercise trials. Each participant completed three incremental exercise tests to 85% of individual's theoretical maximal heart rate (HRMAX) for ACE, CE and TM. Subsequent tests involved 20-min of ACE, CE and TM exercise at a relative workload corresponding to 50% of each individual's predetermined heart rate reserve (HRE). Post fatigue effects and postural control recovery were measured at different times after exercise (1, 3, 5, 10, 15 and 30-min). None of the participants exhibited impaired postural stability after ACE. In contrast, CE and TM elicited significant post exercise balance impairments, which lasted for ∼ 10 min post exercise. We provide evidence of an exercise mode which does not elicit post exercise balance impairments. Older adults should exercise caution immediately following exercise engaging the lower limbs to avoid fall risk.

Multivariate meta-analysis using individual participant data.

When combining results across related studies, a multivariate meta-analysis allows the joint synthesis of correlated effect estimates from multiple outcomes. Joint synthesis can improve efficiency over separate univariate syntheses, may reduce selective outcome reporting biases, and enables joint inferences across the outcomes. A common issue is that within-study correlations needed to fit the multivariate model are unknown from published reports. However, provision of individual participant data (IPD) allows them to be calculated directly. Here, we illustrate how to use IPD to estimate within-study correlations, using a joint linear regression for multiple continuous outcomes and bootstrapping methods for binary, survival and mixed outcomes. In a meta-analysis of 10 hypertension trials, we then show how these methods enable multivariate meta-analysis to address novel clinical questions about continuous, survival and binary outcomes; treatment-covariate interactions; adjusted risk/prognostic factor effects; longitudinal data; prognostic and multiparameter models; and multiple treatment comparisons. Both frequentist and Bayesian approaches are applied, with example software code provided to derive within-study correlations and to fit the models.

Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

Secretion of human epidermal growth factor from Saccharomyces cerevisiae using synthetic leader sequences.

We have investigated different leader sequences for their ability to direct the efficient secretion of human epidermal growth factor (hEGF) from Saccharomyces cerevisiae. We designed a consensus signal sequence which directs secretion of hEGF from yeast as efficiently as the yeast invertase signal sequence. However, secretion is increased over fivefold by the introduction, after the signal sequence, of a synthetic 19-amino acid (aa) pro-sequence containing a cleavage recognition site for the KEX2 protease. Even in the absence of an Asn-linked glycosylation site, secretion of hEGF using the synthetic prepro-leader was as efficient as that directed by the alpha-factor leader. The role of the KEX2 protease cleavage site was investigated by mutation of the yeast alpha-factor KEX2 site (cleavage after Lys-Arg). Cleavage was obtained with the following order of efficiency, Lys-Arg greater than Pro-Arg greater than Asp-Arg, although the sequence context was also found to affect efficiency.

Abnormalities in color vision and contrast sensitivity in Parkinson's disease.

Dopamine is a neurotransmitter found in the retina. Delays in the visual evoked responses and abnormalities in contrast sensitivity occur in patients with Parkinson's disease. Improvement in the P100 has followed L-dopa therapy. Suspected abnormalities at the retinal level in Parkinson's disease are observed in reductions in photopic, scotopic, and pattern-derived electroretinograms. We studied 35 patients with Parkinson's disease and 26 controls of comparable age and visual acuities using visual evoked responses, color vision, and contrast sensitivity testing. Contrast sensitivity thresholds were significantly different at most frequencies tested, using both stationary and temporally modulated sinusoidal gratings. The total error score of the Farnsworth-Munsell 100 Hue Test revealed significant differences between the patients and controls. The contrast thresholds derived from certain spatial frequencies and the total error in color score were significantly related to the duration of disease. A stepwise discriminant analysis correctly identified 94% of the patients and 94% of the controls. The significant error in chromatic discrimination observed in Parkinson's disease patients may be due to altered intraretinal dopaminergic synaptic activity in these patients.