Reduction in post-operative nausea and vomiting (PONV) by preoperative risk stratification and adherence to a standardized anti emetic prophylaxis protocol in the day-care surgical population.

CONTEXT: Postoperative nausea (PON) and postoperative vomiting (POV) are the most undesirable morbidity after anaesthesia. There is paucity of data on PONV from the Indian subcontinent. AIMS: We aim to study the prevalence of PON and POV, associated risk factors and the effect of following standardized risk stratification and prophylaxis protocols in the day care patient population. SETTINGS AND DESIGN: This was a prospective cohort study at a tertiary care teaching institute. METHODS AND MATERIAL: Data from 500 patients undergoing day care surgery over a period of 12 months were analysed. We used the Apfel scoring system for evaluation of risk of post-operative nausea and vomiting (PONV) for each participant. A standard PONV prophylaxis protocol was used intra-operatively. STATISTICAL ANALYSIS USED: Data analysis was done using the Mann-Whitney U test, the Chi-square and Fisher's exact test. RESULTS: The period prevalence of post-operative nausea (PON) and post-operative vomiting (POV) was 2.04% and 2.45%, respectively, in this study. The prevalence of PONV in each risk category was lower than that predicted by the Apfel score due to utilization of a standard anti-emetic prophylactic protocol. We found younger age, previous history of nausea, previous history of vomiting, urological surgeries and alcohol consumption as significant risk factors for postoperative nausea. Longer duration of surgery, previous history of nausea, alcohol consumption and higher BMI were the significant risk factors for postoperative vomiting. CONCLUSIONS: Adherence to preoperative risk stratification and a standard anti-emetic prophylactic protocol can significantly reduce the prevalence of postoperative nausea and vomiting.

Lumbar Erector Spinae Plane Block for Posterior-Superior Iliac Spine Bone Graft Site Pain in Patients Undergoing Occipitocervical and C1-C2 Fusion for Atlantoaxial Dislocation/Odontoid Fracture-A Case Series.

Pain at the autologous bone graft site from the posterior-superior iliac spine (PSIS) is severe enough to affect the postoperative ambulation. It adds to the morbidity of the surgical procedure. Inadequate pain management at the graft site not only affects the postoperative recovery but also can lead to chronic pain. We report the use of ultrasound (US)-guided lumbar erector spinae plane block (ESPB), to deliver effective analgesia for this pain. Patients who underwent occipitocervical fusion (OCF) and C1-C2 fusion using PSIS for atlantoaxial dislocation (AAD)/odontoid fracture from January to March 2020 and who received US-guided lumbar ESPB were retrospectively studied. All the necessary data were collected from the inpatient hospital, anesthesia, and the acute pain service records. A total of six patients received lumbar ESPB, of which one received a single shot injection, and the rest five had a catheter placement for postoperative analgesia. The average volume of intraoperative and postoperative bolus was 27(range: 15-30) and 21 (range: 15-30) mL of 0.2% ropivacaine, respectively. All patients achieved a unilateral sensory blockade ranging from L1 to L3 dermatomes. None of our patients had a numerical rating scale of > 4 on movement at any time point during the first 48 hours except in one, in whom only a single shot bolus was given. No complications related to ESPB were noted. All were ambulated on the second postoperative day except one. The average length of hospital stay was 6 (range: 4-10) days. US-guided lumbar ESPB provides excellent analgesia for PSIS bone graft site pain and promotes early ambulation.

[Sterilisation of patient specific surgical guide for dental implantology made in a hospital: Validation of a sterility test and structural deformation study]. / Stérilisation de guides d'implantologie imprimés sur mesure à l'hôpital : validation d'un essai de stérilité et étude de déformation.

Medical device made to measure by 3D printing are now emerging in hospital. In order to improve the precision of surgery and facilitate the treatment of complicated cases, patient specific surgical guides for dental implantology are made by stereolithography in our facial surgical unit. This new activity requires to ensure the safety of patients and health personnel by validating the various step of the manufacturing circuit. In this context, the goal of this work was to study the quality of autoclave sterilisation of the patient specific surgical guide made to measure in our hospital. A protocol of sterility test was designed and validated. Sterility of implantology guides 0, 7, 14 and 28 days after sterilisation was checked. The impact of the autoclave sterilisation on the medical device structure was evaluated by visual check and during surgeries. The sterility of the implantology guides up to 28 days after sterilisation was also validated. The protocol of sterility test executed can be extended to other hospitals interested in validating a sterility test. No deformation was observed by surgeons during the dental implant process. Future studies may be necessary to check the accurate impact of sterilisation on surgical guide structure.

[Medication reconciliation in a department of internal medicine and infectious and tropical diseases: Feedback after one year practice]. / Conciliation médicamenteuse d'entrée en service de médecine interne : retour d'expérience après un an de pratique.

Since April 2015, medication reconciliation is performed in our Department. The objective of this study is to assess the impact of this activity on patients' care after one year of practice. METHODS: All patients who received medication reconciliation between April-October 2015 and June-December 2016 were included in this retrospective study. Undocumented unintentional discrepancies (DNIND) which result from the comparison between the patient's usual treatments and the medication prescribed at admission were collected. Then, a multidisciplinary discussion was initiated to correct them. The gravity of each DNIND was determined a posteriori. RESULTS: A statistical comparison between the two studies (2015 vs. 2016) showed the following significant results: decrease in DNIND (0.9 vs. 0.43), in percentage of patients with at least one DNIND (43% vs 31% P <5.10-6), in reconciliation time (43min vs. 23min) and no significant difference in the distribution of DNIND typology. The main therapeutic classes are: metabolism-diabetes-nutrition (21%), cardiology (18%), pneumology (17%) and neurology-psychiatry (15%). Drugs mainly concerned with DNIND are inhaled anti-asthmatics (13% of the medicines with DNIND), vitamins (8% of DNIND) and the levetiracetam antiepileptic drug (5% of DNIND). CONCLUSION: The implementation of the reconciliation medication allowed a significant reduction of the DNIND that permits to improve the patient healthcare pathway.

A hippocampus to prefrontal cortex neural pathway inhibits food motivation through glucagon-like peptide-1 signaling.

The hippocampus and the medial prefrontal cortex (mPFC) are traditionally associated with regulating memory and executive function, respectively. The contribution of these brain regions to food intake control, however, is poorly understood. The present study identifies a novel neural pathway through which monosynaptic glutamatergic ventral hippocampal field CA1 (vCA1) to mPFC connectivity inhibits food-motivated behaviors through vCA1 glucagon-like peptide-1 receptor (GLP-1R). Results demonstrate that vCA1-targeted RNA interference-mediated GLP-1R knockdown increases motivated operant responding for palatable food. Chemogenetic disconnection of monosynaptic glutamatergic vCA1 to mPFC projections using designer receptors exclusively activated by designer drugs (DREADDs)-mediated synaptic silencing ablates the food intake and body weight reduction following vCA1 GLP-1R activation. Neuropharmacological experiments further reveal that vCA1 GLP-1R activation reduces food intake and inhibits impulsive operant responding for palatable food via downstream communication to mPFC NMDA receptors. Overall these findings identify a novel neural pathway regulating higher-order cognitive aspects of feeding behavior.

Can the combination of laparoscopy and enhanced recovery improve long-term survival after elective colorectal cancer surgery?

AIM: Enhanced recovery after surgery (ERAS) programmes and laparoscopic techniques both provide short-term benefits to patients undergoing colorectal cancer surgery. ERAS protocol compliance may improve long-term survival in those undergoing open colorectal resection but as laparoscopic data has not been reported. Therefore, we aimed to investigate the impact of the combination of laparoscopy and ERAS management on 5-year overall survival. METHODS: A dedicated prospectively populated colorectal cancer surgery database was reviewed. Patient inclusion criteria were biopsy-proven colorectal adenocarcinoma, undergoing elective surgery undertaken with curative intent. All patients were managed within an established ERAS programme and routinely followed up for 5 years. Overall survival was measured using the log-rank Kaplan-Meier method at 5 years. RESULTS: Eight hundred fifty-four patients met the inclusion criteria. Four hundred eighty-one (56%) cases were laparoscopic with 98 patients (20%) requiring conversion. There were no differences in patient or tumour demographics between the surgical groups. Median ERAS protocol compliance was 93% (range 53-100%). Five-year overall survival was superior in laparoscopic cases compared with that of converted and open surgery (78 vs 68 vs 70%, respectively, p < 0.007). An open approach (HR 1.55, 95%CI 1.16-2.06, p = 0.002) and delayed hospital discharge (> 7 days, HR 1.5, 95%CI 1.13-1.9, p = 0.003) were the only modifiable risk factors associated with poor survival. CONCLUSIONS: The use of a laparoscopic approach with enhanced recovery after surgery management appears to have long-term survival benefits following colorectal cancer resection.

Lateral hypothalamic GLP-1 receptors are critical for the control of food reinforcement, ingestive behavior and body weight.

Increased motivation for highly rewarding food is a major contributing factor to obesity. Most of the literature focuses on the mesolimbic nuclei as the core of reward behavior regulation. However, the lateral hypothalamus (LH) is also a key reward-control locus in the brain. Here we hypothesize that manipulating glucagon-like peptide-1 receptor (GLP-1R) activity selectively in the LH can profoundly affect food reward behavior, ultimately leading to obesity. Progressive ratio operant responding for sucrose was examined in male and female rats, following GLP-1R activation and pharmacological or genetic GLP-1R blockade in the LH. Ingestive behavior and metabolic parameters, as well as molecular and efferent targets, of the LH GLP-1R activation were also evaluated. Food motivation was reduced by activation of LH GLP-1R. Conversely, acute pharmacological blockade of LH GLP-1R increased food motivation but only in male rats. GLP-1R activation also induced a robust reduction in food intake and body weight. Chronic knockdown of LH GLP-1R induced by intraparenchymal delivery of an adeno-associated virus-short hairpin RNA construct was sufficient to markedly and persistently elevate ingestive behavior and body weight and ultimately resulted in a doubling of fat mass in males and females. Interestingly, increased food reinforcement was again found only in males. Our data identify the LH GLP-1R as an indispensable element of normal food reinforcement, food intake and body weight regulation. These findings also show, for we believe the first time, that brain GLP-1R manipulation can result in a robust and chronic body weight gain. The broader implications of these findings are that the LH differs between females and males in its ability to control motivated and ingestive behaviors.

Endemic goitre and hypothyroidism in an adult female patient dependent on total parenteral nutrition.

We present the case of a thirty-year-old female patient who was referred to the endocrinology team with an enlarging goitre and biochemical hypothyroidism. She had been dependent on total parenteral nutrition for the previous six years as a result of intestinal failure thought to be caused by possible underlying mitochondrial disease. The patient also suffers from a Desmin myopathy, and at present, the exact aetiology behind her intestinal failure is not certain. The goitre was smooth and had been enlarging slowly over the previous few months. Thyroid peroxidase antibodies were found to be within normal range. Further analysis of the case showed that twelve months earlier the patients total parenteral nutrition (TPN) feed had been altered as a result of manganese toxicity. The current feeding regimen did not contain a trace element additive which had previously supplied iodine supplementation. A little detective work established that iodine content to the TPN had been reduced, the trace element additive (Additrace) was recommenced providing 1 µmol of iodine per day, equating to 130 µg of iodine. Following this change, thyroid-stimulating hormone levels returned to normal and the goitre quickly reduced in size. We present a rare case of endemic goitre and hypothyroidism in a patient receiving inadequate iodine supplementation through total parenteral nutrition. LEARNING POINTS: Endemic goitre and hypothyroidism secondary to iodine deficiency are rare in the developed world. However, the diagnosis should be considered in the setting of a diffuse goitre and negative thyroid antibodies.Although rare, endemic goitre should be considered in patients who present with hypothyroidism and who are dependent on total parenteral nutrition.Treatment with levothyroxine is not required in endemic goitre as thyroid function tests generally normalise with the addition of iodine to the diet/total parenteral nutrition regimen.Iodine supplementation at a level recommended by the European Society for Clinical Nutrition and Metabolism (ESPEN) was observed to quickly normalise this patient's thyroid function tests.

Does hospital readmission following colorectal cancer resection and enhanced recovery after surgery affect long term survival?

AIM: Hospital readmission is undesirable for patients and care providers as this can affect short-term recovery and carries financial consequences. It is unknown if readmission has long-term implications. We aimed to investigate the impact of 30-day readmission on long-term overall survival (OS) following colorectal cancer resection within enhanced recovery after surgery (ERAS) care and explore the reasons for and the severity and details of readmission episodes. METHOD: A dedicated, prospectively populated database was reviewed. All patients were managed within an established ERAS programme. Five-year OS was calculated using the Kaplan-Meier method. The number, reason for and severity of 30-day readmissions were classified according to the Clavien-Dindo (CD) system, along with total (initial and readmission) length of stay (LoS). Multivariate analysis was used to identify factors predicting readmission. RESULTS: A total of 1023 consecutive patients underwent colorectal cancer resection between 2002 and 2015. Of these, 166 (16%) were readmitted. Readmission alone did not have a significant impact on 5-year OS (59% vs 70%, P = 0.092), but OS was worse in patients with longer total LoS (20 vs 14 days, P = 0.04). Of the readmissions, 121 (73%) were minor (CD I-II) and 27 (16%) required an intervention of which 16 (10%) were returned to theatre. Gut dysfunction 32 (19%) and wound complications 23 (14%) were the most frequent reasons for readmission. Prolonged initial LoS, rectal cancer and younger age predicted for hospital readmission. CONCLUSION: Readmission does not have a significant impact on 5-year OS. A broad range of conditions led to readmission, with the majority representing minor complications.

Is Month of Birth a Risk Factor for Colorectal Cancer?

Introduction. The developmental origins of health and disease hypothesis and season of birth have been linked to a wide variety of later life conditions including cancer. Whether any relationship between month and season of birth and colorectal cancer exists is unknown. Methods. A case-control study was performed with month of birth extracted from a dedicated colorectal cancer database. Age and gender matched patients were used as a control group. Generalised linear models were fitted with Poisson and negative binomial responses and logarithmic links. A forward stepwise approach was followed adding seasonal components with 6- and 12-month periods. Results. 1019 colorectal cancer patients and 1277 randomly selected age and gender matched controls were included. For both men and women there is an excess of colorectal cancer in those born in autumn and a corresponding reduction of risk among those born in spring (p = 0.026). For the identified September peak, the excess risk for colorectal cancer was 14.8% (95% CI 5.6-32.3%) larger than the spring trough. Conclusion. There is a seasonal effect in the monthly birth rates of people who are operated for colorectal cancer with a disproportionate excess of cancer in those born in September. Further large studies are required to validate these findings.

Quantification of multiple waterborne pathogens in drinking water, drainage channels, and surface water in Kampala, Uganda, during seasonal variation.

Longitudinal water quality monitoring is important for understanding seasonal variations in water quality, waterborne disease transmission, and future implications for climate change and public health. In this study, microfluidic quantitative polymerase chain reaction (MFQPCR) was used to quantify genes from pathogens commonly associated with human intestinal infections in water collected from protected springs, a public tap, drainage channels, and surface water in Kampala, Uganda, from November 2014 to May 2015. The differences in relative abundance of genes during the wet and dry seasons were also assessed. All water sources tested contained multiple genes from pathogenic microorganisms, with drainage channels and surface waters containing a higher abundance of genes as compared to protected spring and the public tap water. Genes detected represented the presence of enterohemorrhagic Escherichia coli, Shigella spp., Salmonella spp., Vibrio cholerae, and enterovirus. There was an increased presence of pathogenic genes in drainage channels during the wet season when compared to the dry season. In contrast, surface water and drinking water sources contained little seasonal variation in the quantity of microbes assayed. These results suggest that individual water source types respond uniquely to seasonal variability and that human interaction with contaminated drainage waters, rather than direct ingestion of contaminated water, may be a more important contributor to waterborne disease transmission. Furthermore, future work in monitoring seasonal variations in water quality should focus on understanding the baseline influences of any one particular water source given their unique complexities.

Heat shock protein concentration and clarity of porcine lenses incubated at elevated temperatures.

PURPOSE: To quantify the concentration of heat shock proteins in lenses in lens organ culture at elevated temperatures, and to examine the relation between elevated temperature and lens clarity. METHODS: Pig lenses obtained from a local abattoir were dissected aseptically and incubated in medium M199 without serum for 4 days to stabilize, and lenses with protein leakage of less than 10 mg/l were obtained for heat shock exposure. Heat shock was performed by incubation for 1 h in M199 without serum at various temperatures ranging from 37 °C to 55 °C. After incubation for 24 h, cataract blurring of the images was assessed using Scantox™ and Scion Image analysis of the lens photographs. Lens homogenates were subsequently analyzed for Hsp70 and Hsp27 with western blotting. RESULTS: The degree of cataract blurring of the images increased with increasing temperature, but the two functional measures provided different results. Focal length inconsistency, as assessed with the back vertex distance standard error of the mean (BVD SEM; the variability in focal lengths measured at 20 equally spaced locations across the lens, Scantox™), increased nearly linearly with the heat treatment temperature. In contrast, decreased clarity, evident by a fuzzy image with lower contrast, was not markedly altered as the temperature rose until a threshold of approximately 47.5 °C. The inducible isoform of the Hsp70 family (Hsp70) of heat shock proteins was increased at all temperatures above the control except those above 50 °C. Changes in Hsp27 were less clear as the protein content increased only at the incubation temperatures of 39 °C and 48.5 °C. CONCLUSIONS: The porcine lens demonstrates subtle changes in the variability of the focal length, and the variability increases as the incubation temperature rises. In contrast, lens clarity is relatively stable at temperatures up to 47.5 °C, above which dramatic changes, indicative of the formation of cataracts, occur. The lens content of Hsp70 was elevated in lenses exposed to heat shock only up to 50 °C. These data suggest that in a stressful environment, Hsp70 may be associated with protection against loss of clarity. In addition, the functional measures BVD SEM and clarity assess different qualities of the lens, with the former likely more sensitive to subtle changes in the protein structure.

Brain-specific epigenetic markers of schizophrenia.

Epigenetics plays a crucial role in schizophrenia susceptibility. In a previous study, we identified over 4500 differentially methylated sites in prefrontal cortex (PFC) samples from schizophrenia patients. We believe this was the first genome-wide methylation study performed on human brain tissue using the Illumina Infinium HumanMethylation450 Bead Chip. To understand the biological significance of these results, we sought to identify a smaller number of differentially methylated regions (DMRs) of more functional relevance compared with individual differentially methylated sites. Since our schizophrenia whole genome methylation study was performed, another study analysing two separate data sets of post-mortem tissue in the PFC from schizophrenia patients has been published. We analysed all three data sets using the bumphunter function found in the Bioconductor package minfi to identify regions that are consistently differentially methylated across distinct cohorts. We identified seven regions that are consistently differentially methylated in schizophrenia, despite considerable heterogeneity in the methylation profiles of patients with schizophrenia. The regions were near CERS3, DPPA5, PRDM9, DDX43, REC8, LY6G5C and a region on chromosome 10. Of particular interest is PRDM9 which encodes a histone methyltransferase that is essential for meiotic recombination and is known to tag genes for epigenetic transcriptional activation. These seven DMRs are likely to be key epigenetic factors in the aetiology of schizophrenia and normal brain neurodevelopment.

Characterization of municipal waste in Kampala, Uganda.

UNLABELLED: In Kampala, Uganda, about 28,000 tons of waste is collected and delivered to a landfill every month. Kampala Capital City Authority (KCCA) records show that this represents approximately 40% of the waste generated in the city. The remaining uncollected waste is normally dumped in unauthorized sites, causing health and environmental problems. However, the organic fraction of domestic waste can provide an opportunity to improve livelihoods and incomes through fertilizer and energy production. This study characterized the municipal waste generated in Kampala and delivered to Kiteezi landfill between July 2011 and June 2012, that is, covering the dry and wet months. On each sampling day, waste was randomly selected from five trucks, sorted and weighed into different physical fractions. Samples of the organic waste from each truck were analyzed for total solids, major nutrients, and energy content. During the wet months, the waste consisted of 88.5% organics, 3.8% soft plastics, 2.8% hard plastics, 2.2% paper, 0.9% glass, 0.7% textiles and leather 0.2% metals, and 1.0% others. During the dry months, the waste consisted of 94.8% organics, 2.4% soft plastics, 1.0% hard plastics, 0.7% papers, 0.3% glass, 0.3% textile and leather, 0.1% metals, and 0.3% others. The organic waste on average had a moisture content of 71.1% and contained 1.89% nitrogen, 0.27% phosphorus, and 1.95% potassium. The waste had an average gross energy content of 17.3 MJ/kg. It was concluded that the organic waste generated can be a suitable source of some plant nutrients that are useful especially in urban agriculture. IMPLICATIONS: The result of the waste characterization in Kampala was found to be significantly different from that obtained for other Sub-Saharan African (SSA) cities, showing that studies assuming average values for the waste fractions are likely to result in erroneous results. Furthermore, no reduction in organic fraction of the waste was noticed when compared with a study done two decades ago in spite of greatly improved economic status of Kampala city, a finding that is not in agreement with several other similar studies done for other SSA cities.

Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients.

Recent studies suggest that genetic and environmental factors do not account for all the schizophrenia risk, and epigenetics also has a role in disease susceptibility. DNA methylation is a heritable epigenetic modification that can regulate gene expression. Genome-wide DNA methylation analysis was performed on post-mortem human brain tissue from 24 patients with schizophrenia and 24 unaffected controls. DNA methylation was assessed at over 485,000 CpG sites using the Illumina Infinium HumanMethylation450 Bead Chip. After adjusting for age and post-mortem interval, 4641 probes corresponding to 2929 unique genes were found to be differentially methylated. Of those genes, 1291 were located in a CpG island and 817 were in a promoter region. These include NOS1, AKT1, DTNBP1, DNMT1, PPP3CC and SOX10, which have previously been associated with schizophrenia. More than 100 of these genes overlap with a previous DNA methylation study of peripheral blood from schizophrenia patients in which 27,000 CpG sites were analysed. Unsupervised clustering analysis of the top 3000 most variable probes revealed two distinct groups with significantly more people with schizophrenia in cluster one compared with controls (P=1.74 × 10(-4)). The first cluster composed of 88% of patients with schizophrenia and only 12% controls, whereas the second cluster composed of 27% of patients with schizophrenia and 73% controls. These results strongly suggest that differential DNA methylation is important in schizophrenia etiology and add support for the use of DNA methylation profiles as a future prognostic indicator of schizophrenia.

A model of poorly controlled type 1 Diabetes Mellitus and its treatment with aerobic exercise training.

BACKGROUND: Modern exogenous insulin therapy can improve the quality of life of Type 1 Diabetic Mellitus (T1DM) patients, although maintenance of normal glycaemic levels is often a challenge given the variety of factors that alter it. A number of studies have examined the effect of exercise in T1DM; however, the majority of experimental studies have utilized diabetic rodents with severe hyperglycaemia. Given that T1DM patients are likely to refrain from hyperglycaemia, studies examining the effects of regular exercise in which blood glucose is poorly controlled would better represent the T1DM population. METHODS: The current study examined the ability of a ten-week aerobic exercise training program to modify markers of cardiovascular function and bone health in STZ-induced diabetic rodents maintained in the 9-15 mM glycaemic range through insulin therapy. RESULTS: Moderate hyperglycaemia, when prolonged, leads to significant changes in cardiac structure, bone health, and glucose handling capacity. Ten weeks of exercise was able to alleviate many of these deleterious events as no significant cardiovascular functional alterations were evident except a reduction in resting heart rate and an increase in stroke volume index. Further, despite changes in cardiac dimensions, exercise was able to elevate cardiac output index and increase the E/A ratio of exercising diabetic animals which would be indicative of improvements of cardiac function. CONCLUSIONS: Together, this study demonstrates that despite moderate hyperglycaemia, the combined role of a ten-week exercise training program coupled with insulin therapy is able to alleviate many of the well-known complications associated with diabetes progression.

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia.

Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. It is known that extrapyramidal adverse effects are associated with increased drug occupancy of the dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1, rs1800497, is associated with decreased striatal DRD2 density. The aim of this study was to identify whether the A1(T) allele of DRD2/ANKK1 was associated with akathisia (as measured by Barnes Akathisia Rating Scale) in a clinical sample of 234 patients who were treated with antipsychotic drugs. Definite akathisia (a score ≥ 2 in the global clinical assessment of akathisia) was significantly less common in subjects who were prescribed SGAs (16.8%) than those prescribed FGAs (47.6%), p < 0.0001. Overall, 24.1% of A1+ patients (A1A2/A1A1) who were treated with SGAs had akathisia, compared to 10.8% of A1- (thus, A2A2) patients. A1+ patients who were administered SGAs also had higher global clinical assessment of akathisia scores than the A1- subjects (p = 0.01). SGAs maintained their advantage over FGAs regarding akathisia, even in A1+ patients who were treated with SGAs. These results strongly suggested that A1+ variants of the DRD2/ANKK1 Taq1A allele do confer an associated risk for akathisia in patients who were treated with SGAs, and these variants may explain inconsistencies found across prior studies, when comparing FGAs and SGAs.

Myocardial accumulation and localization of the inducible 70-kDa heat shock protein, Hsp70, following exercise.

Exercise increases the 70-kDa heat shock protein (Hsp70) in the myocardium, and this exercise-induced increase is associated with significantly improved cardiac recovery following insult. However, while heat shock has been shown to elevate Hsp70 primarily in the cardiac vasculature of the myocardium, the localization following exercise is unknown. Male Sprague-Dawley rats performed continuous treadmill running at 30 m/min for 60 min (2% incline) on either 1 or 5 consecutive days. At 30 min and 24 h following exercise, hearts were extirpated, and the left ventricle was isolated, OCT-cork mounted, and sectioned for immunofluorescent analysis. Whereas immunofluorescent analysis revealed little to no Hsp70 in control hearts and 30 min postexercise, the accumulation of Hsp70 24 h after a single exercise bout or 5 days of training was predominantly located in large blood vessels and, in particular, colocalized with a marker of smooth muscle. Furthermore, higher core temperatures attained during exercise led to more abundant accumulation in smaller vessels and the endothelium. It is concluded that the accumulation of myocardial Hsp70 following acute exercise predominantly occurs in a cell type-specific manner, such that changes in the cardiac vasculature account for much of the increase. This accumulation appears first in the smooth muscle of larger vessels and then increases in smaller vessels and the endothelium, as core temperature attained during exercise increases. This finding supports the observations after heat shock and further suggests that the vasculature is a primary target in exercise-induced cardioprotection.