Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 49
Filter
2.
J Postgrad Med ; 2023 08 04.
Article in English | MEDLINE | ID: mdl-37555422

ABSTRACT

Context/Aims: Pheochromocytoma and paraganglioma (PPGL) are rare tumors, and data on ambulatory blood pressure monitoring (ABPM) in these patients and the effect of blocking on ABPM parameters is limited. We aimed to describe ABPM parameters in a cohort of PPGL at our center in western India. Methods: Retrospective study of patients with PPGL whose ABPM data was available. Demographic details, secretory status, and ABPM data were retrieved. Coefficient of variability (CV) was calculated as standard deviation/mean in percentage. Results: In the 39 included patients, mean age at presentation was 39.3 ± 14.2 yr; 20 (51.3%) were males, 25 (64.1%) hypertensive, and mean tumor diameter was 5.3 cm. In 18 patients whose baseline ABPM was done without medications, those with nocturnal blood pressure dipping (6/18, 33%) had higher serum metanephrines (median 313.2 vs. 34.7 pg/ml, P = 0.028). Despite normal office blood pressure (BP), 8.9% of systolic BP readings were >140 mmHg, and 1.2% were >160 mmHg. Among 29 patients with both pre and post-block ABPM, mean BP (systolic 121.6 vs. 132.5 mmHg, P = 0.014; diastolic 68.9 vs. 76.4 mmHg, P = 0.005) and percentage of BP readings above 140 mmHg (median 9.4% vs. 24.4%, P = 0.016) were significantly lowered after the preoperative blockade in hypertensive (n = 19) patients, whereas CV was similar. The post-blockade ABPM characteristics were similar in patients blocked with amlodipine or prazosin. Conclusion: ABPM provides additional information about BP characteristics in PPGL. The preoperative blocking decreases the magnitude of BP excursions but does not affect BP variability.

3.
J Postgrad Med ; 69(2): 65-67, 2023.
Article in English | MEDLINE | ID: mdl-36960525
4.
Kathmandu Univ Med J (KUMJ) ; 20(77): 38-42, 2022.
Article in English | MEDLINE | ID: mdl-36273288

ABSTRACT

Background Obesity is becoming serious global public health issue due to sedentary lifestyle and bad eating habits. Dietary and lifestyle practices are directly related to obesity, which can cause serious health problems like cardiac ailments, diabetes, and hypertension etc. Vast varieties of options are available for weight reduction including physical exercises, various diet plans and also the pharmacological agents. Physical activity improves the fitness of the individual and helps in reducing the ill effects of the obesity. Objective To compare the effects of Yoga and Aerobic Exercise on weight circumference, waisthip ratio (WHR) and body mass index (BMI) in overweight and obese individuals. Method An experimental study was started with purposive sampling. Sixty overweight and obese individuals from the community were divided equally into two groups, one group was given supervised yoga asana and the other group was given supervised aerobic exercise for 6 weeks. Waist circumference, waist hip ratio and body mass index were taken pre and post intervention. Result Statistically significant difference was seen in pre and post intervention value of waist circumference, waist hip ratio and body mass index in both the groups with the p value < 0.05. However there was no statistical significant difference noted in waist hip ratio in individuals performing aerobic exercises as p value was > 0.05. Conclusion Both the interventions showed significant reduction in waist circumference, waist hip ratio and body mass index, while better results were noted in the individuals performing yoga asanas.


Subject(s)
Overweight , Yoga , Adult , Humans , Waist-Hip Ratio , Body Mass Index , Overweight/therapy , Waist Circumference , Obesity/therapy , Exercise
6.
Curr Oncol ; 26(2): 80-84, 2019 04.
Article in English | MEDLINE | ID: mdl-31043805

ABSTRACT

Background: The human papillomavirus (hpv) is a common sexually transmitted infection and a primary cause of cervical cancer. The Government of Canada has set a target of reaching 90% hpv vaccine coverage among adolescents by 2025. Here, we examine hpv vaccine uptake in school-based immunization programs across Canada and explore how achieving the 90% target could affect the future incidence of cervical cancer, mortality, and health system expenditures in a cohort of Canadian women. Methods: Data for hpv vaccine uptake in the most recent reported school year available in each jurisdiction were provided in 2017 by jurisdictional school-based immunization programs and were used to estimate a national weighted average of 67%. The OncoSim microsimulation model (version 2.5) was used to compare 3 different levels of hpv vaccine uptake (0%, 67%, 90%) on health and economic outcomes for a hypothetical cohort of all 5- to 10-year-old girls in Canada in 2015. Results: Vaccine uptake for girls in school-based programs varied from 55.0% to 92.0% in the jurisdictions reviewed. The OncoSim model projects that increasing uptake to 90% from 67% would result in a 23% reduction in cervical cancer incidence rates (to 3.1 cases from 4.0 cases per 100,000, averaged across the lifetime of the cohort) and a 23% decline in the average annual mortality rate (to 1.0 deaths from 1.3 deaths per 100,000). Finally, the model projects that the health system will incur a cost of $9 million (1% increase) during the lifetime of the cohort if uptake is increased to 90% from 67%. Costs are discounted (1.5%) and expressed in 2016 Canadian dollars. Costs reflect the payer perspective. Conclusions: Our model shows that increasing hpv vaccine uptake to 90% from current levels for girls in school-based immunization programs could result in substantial reductions in the future incidence and mortality rates for cervical cancer in Canada.


Subject(s)
Mass Vaccination/economics , Models, Theoretical , Papillomavirus Vaccines/therapeutic use , Uterine Cervical Neoplasms/prevention & control , Adult , Aged , Canada , Cost-Benefit Analysis , Female , Humans , Mass Vaccination/statistics & numerical data , Middle Aged , Papillomavirus Vaccines/economics , Uterine Cervical Neoplasms/economics , Young Adult
7.
Curr Oncol ; 24(6): 401-406, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29270052

ABSTRACT

The Canadian Partnership Against Cancer was created in 2007 by the federal government to accelerate cancer control across Canada. Its OncoSim microsimulation model platform, which consists of a suite of specific cancer models, was conceived as a tool to augment conventional resources for population-level policy- and decision-making. The Canadian Partnership Against Cancer manages the OncoSim program, with funding from Health Canada and model development by Statistics Canada. Microsimulation modelling allows for the detailed capture of population heterogeneity and health and demographic history over time. Extensive data from multiple Canadian sources were used as inputs or to validate the model. OncoSim has been validated through expert consultation; assessments of face validity, internal validity, and external validity; and model fit against observed data. The platform comprises three in-depth cancer models (lung, colorectal, cervical), with another in-depth model (breast) and a generalized model (25 cancers) being in development. Unique among models of its class, OncoSim is available online for public sector use free of charge. Users can customize input values and output display, and extensive user support is provided. OncoSim has been used to support decision-making at the national and jurisdictional levels. Although simulation studies are generally not included in hierarchies of evidence, they are integral to informing cancer control policy when clinical studies are not feasible. OncoSim can evaluate complex intervention scenarios for multiple cancers. Canadian decision-makers thus have a powerful tool to assess the costs, benefits, cost-effectiveness, and budgetary effects of cancer control interventions when faced with difficult choices for improvements in population health and resource allocation.

8.
Sci Total Environ ; 599-600: 2142-2155, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28575929

ABSTRACT

Mitigating for the negative impacts of stormwater runoff is becoming a concern due to increased land development. Understanding how land development influences stormwater runoff is essential for sustainably managing water resources. In recent years, aggregate low impact development-best management practices (LID-BMPs) have been implemented to reduce the negative impacts of stormwater runoff on receiving water bodies. This study used an integrated approach to determine the influence of land development and assess the ecological benefits of four aggregate LID-BMPs in stormwater runoff from a mixed land use and land cover (LULC) catchment with ongoing land development. It used data from 2011 to 2015 that monitored 41 storm events and monthly LULC, and a Personalized Computer Storm Water Management Model (PCSWMM). The four aggregate LID-BMPs are: ecological (S1), utilizing pervious covers (S2), and multi-control (S3) and (S4). These LID-BMPs were designed and distributed in the study area based on catchment characteristics, cost, and effectiveness. PCSWMM was used to simulate the monitored storm events from 2014 (calibration: R2 and NSE>0.5; RMSE <11) and 2015 (validation: R2 and NSE>0.5; RMSE <12). For continuous simulation and analyzing LID-BMPs scenarios, the five-year (2011 to 2015) stormwater runoff data and LULC change patterns (only 2015 for LID-BMPs) were used. Results show that the expansion of bare land and impervious cover, soil alteration, and high amount of precipitation influenced the stormwater runoff variability during different phases of land development. The four aggregate LID-BMPs reduced runoff volume (34%-61%), peak flow (6%-19%), and pollutant concentrations (53%-83%). The results of this study, in addition to supporting local LULC planning and land development activities, also could be applied to input data for empirical modeling, and designing sustainable stormwater management guidelines and monitoring strategies.

9.
Curr Oncol ; 23(3): e179-87, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27330355

ABSTRACT

BACKGROUND: Low-dose computed tomography (ldct) screening has been shown to reduce mortality from lung cancer; however, the optimal screening duration and "at risk" population are not known. METHODS: The Cancer Risk Management Model developed by Statistics Canada for the Canadian Partnership Against Cancer includes a lung screening module based on data from the U.S. National Lung Screening Trial (nlst). The base-case scenario reproduces nlst outcomes with high fidelity. The impact in Canada of annual screening on the number of incident cases and life-years gained, with a wider range of age and smoking history eligibility criteria and varied participation rates, was modelled to show the magnitude of clinical benefit nationally and by province. Life-years gained, costs (discounted and undiscounted), and resource requirements were also estimated. RESULTS: In 2014, 1.4 million Canadians were eligible for screening according to nlst criteria. Over 10 years, screening would detect 12,500 more lung cancers than the expected 268,300 and would gain 9200 life-years. The computed tomography imaging requirement of 24,000-30,000 at program initiation would rise to between 87,000 and 113,000 by the 5th year of an annual nlst-like screening program. Costs would increase from approximately $75 million to $128 million at 10 years, and the cumulative cost nationally over 10 years would approach $1 billion, partially offset by a reduction in the costs of managing advanced lung cancer. CONCLUSIONS: Modelling various ways in which ldct might be implemented provides decision-makers with estimates of the effect on clinical benefit and on resource needs that clinical trial results are unable to provide.

10.
Curr Oncol ; 23(Suppl 1): S56-63, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26985148

ABSTRACT

BACKGROUND: In Canada, discussion about changing from cytology to human papillomavirus (hpv) dna testing for primary screening in cervical cancer is ongoing. However, the Canadian Task Force on Preventive Health Care has not yet made a recommendation, concluding that the evidence is insufficient. METHODS: We used the cervical cancer and hpv transmission models of the Cancer Risk Management Model to study the health and economic outcomes of primary cytology compared with hpv dna testing in 14 screening scenarios with varying screening modalities and intervals. Projected cervical cancer cases, deaths, colposcopies, screens, costs, and incremental cost-effectiveness were evaluated. We performed sensitivity analyses for hpv dna test costs. RESULTS: Compared with triennial cytology from age 25, 5-yearly hpv dna screening alone from age 30 resulted in equivalent incident cases and deaths, but 55% (82,000) fewer colposcopies and 43% (1,195,000) fewer screens. At hpv dna screening intervals of 3 years, whether alone or in an age-based sequence with cytology, screening costs are greater, but at intervals of more than 5 years, they are lower. Scenarios on the cost-effectiveness frontier were hpv dna testing alone every 10, 7.5, 5, or 3 years, and triennial cytology starting at age 21 or 25 when combined with hpv dna testing every 3 years. CONCLUSIONS: Changing from cytology to hpv dna testing as the primary screening test for cervical cancer would be an acceptable strategy in Canada with respect to incidence, mortality, screening and diagnostic test volumes.

11.
Sci Total Environ ; 550: 1171-1181, 2016 Apr 15.
Article in English | MEDLINE | ID: mdl-26895037

ABSTRACT

While the urban runoff are increasingly being studied as a source of fecal indicator bacteria (FIB), less is known about the occurrence of FIB in watershed with mixed land use and ongoing land use and land cover (LULC) change. In this study, Escherichia coli (EC) and fecal streptococcus (FS) were monitored from 2012 to 2013 in agricultural, mixed and urban LULC and analyzed according to the most probable number (MPN). Pearson correlation was used to determine the relationship between FIB and environmental parameters (physicochemical and hydrometeorological). Multiple linear regressions (MLR) were used to identify the significant parameters that affect the FIB concentrations and to predict the response of FIB in LULC change. Overall, the FIB concentrations were higher in urban LULC (EC=3.33-7.39; FS=3.30-7.36log10MPN/100mL) possibly because of runoff from commercial market and 100% impervious cover (IC). Also, during early-summer season; this reflects a greater persistence and growth rate of FIB in a warmer environment. During intra-event, however, the FIB concentrations varied according to site condition. Anthropogenic activities and IC influenced the correlation between the FIB concentrations and environmental parameters. Stormwater temperature (TEMP), turbidity, and TSS positively correlated with the FIB concentrations (p>0.01), since IC increased, implying an accumulation of bacterial sources in urban activities. TEMP, BOD5, turbidity, TSS, and antecedent dry days (ADD) were the most significant explanatory variables for FIB as determined in MLR, possibly because they promoted the FIB growth and survival. The model confirmed the FIB concentrations: EC (R(2)=0.71-0.85; NSE=0.72-0.86) and FS (R(2)=0.65-0.83; NSE=0.66-0.84) are predicted to increase due to urbanization. Therefore, these findings will help in stormwater monitoring strategies, designing the best management practice for FIB removal and as input data for stormwater models.


Subject(s)
Agriculture , Environmental Monitoring , Models, Theoretical , Water Microbiology , Rain , Water Movements
12.
Waste Manag Res ; 34(4): 327-36, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26821599

ABSTRACT

Non-renewable energy sources have remained the choice of the world for centuries. Rapid growth in population and industrialisation have caused their shortage and environmental degradation by using them. Thus, at the present rate of consumption, they will not last very long. In this prospective, this study has been conducted. The estimation of energy in terms of biogas and heat from various organic fractions of municipal solid waste is presented and discussed. The results show that organic fractions of municipal solid waste possess methane potential in the range of 3%-22% and their heat capacity ranges from 3007 to 20,099 kJ kg(-1) Also, theoretical biogas potential of different individual fruit as well as vegetable components and mixed food waste are analysed and estimated in the range of 608-1244 m(3) t(-1) Further, the share of bioenergy from municipal solid waste in the total primary energy supply in Pakistan has been estimated to be 1.82%. About 8.43% of present energy demand of the country could be met from municipal solid waste. The study leads us to the conclusion that the share of imported energy (i.e. 0.1% of total energy supply) and reduction in the amount of energy from fossil fuels can be achieved by adopting a waste-to-energy system in the country.


Subject(s)
Biofuels , Refuse Disposal/methods , Solid Waste , Biodegradation, Environmental , Cities , Energy-Generating Resources , Food , Garbage , Methane/metabolism , Pakistan , Prospective Studies , Solid Waste/analysis
13.
J Assoc Physicians India ; 63(4): 60-3, 2015 Apr.
Article in English | MEDLINE | ID: mdl-26591173

ABSTRACT

Primary Sjögren's syndrome is an autoimmune disease presenting classically as keratoconjunctivitis sicca. Renal involvement in Sjögrens's syndrome is less common, and the initial presentation with renal complications without any sicca symptoms is extremely rare. The renal involvement may present with symptoms arising from interstitial nephritis, mainly distal renal tubular acidosis.


Subject(s)
Acidosis, Renal Tubular/etiology , Cryptogenic Organizing Pneumonia/complications , Hypokalemia/complications , Quadriplegia/etiology , Sjogren's Syndrome/complications , Adult , Female , Humans , Sjogren's Syndrome/diagnosis
15.
Colorectal Dis ; 17(9): 748-61, 2015 Sep.
Article in English | MEDLINE | ID: mdl-25891148

ABSTRACT

AIM: Restaging imaging by MRI or endorectal ultrasound (ERUS) following neoadjuvant chemoradiotherapy is not routinely performed, but the assessment of response is becoming increasingly important to facilitate individualization of management. METHOD: A search of the MEDLINE and Scopus databases was performed for studies that evaluated the accuracy of restaging of rectal cancer following neoadjuvant chemoradiotherapy with MRI or ERUS against the histopathological outcome. A systematic review of selected studies was performed. The methodological quality of studies that qualified for meta-analysis was critically assessed to identify studies suitable for inclusion in the meta-analysis. RESULTS: Sixty-three articles were included in the systematic review. Twelve restaging MRI studies and 18 restaging ERUS studies were eligible for meta-analysis of T-stage restaging accuracy. Overall, ERUS T-stage restaging accuracy (mean [95% CI]: 65% [56-72%]) was nonsignificantly higher than MRI T-stage accuracy (52% [44-59%]). Restaging MRI is accurate at excluding circumferential resection margin involvement. Restaging MRI and ERUS were equivalent for prediction of nodal status: the accuracy of both investigations was 72% with over-staging and under-staging occurring in 10-15%. CONCLUSION: The heterogeneity amongst restaging studies is high, limiting conclusive findings regarding their accuracies. The accuracy of restaging imaging is different for different pathological T stages and highest for T3 tumours. Morphological assessment of T- or N-stage by MRI or ERUS is currently not accurate or consistent enough for clinical application. Restaging MRI appears to have a role in excluding circumferential resection margin involvement.


Subject(s)
Endosonography , Magnetic Resonance Imaging , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Chemoradiotherapy, Adjuvant , Humans , Neoadjuvant Therapy , Neoplasm Staging , Rectal Neoplasms/diagnostic imaging
16.
AJNR Am J Neuroradiol ; 36(5): 943-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25767184

ABSTRACT

BACKGROUND AND PURPOSE: MR imaging findings of aneurysm enlargement, aneurysm wall enhancement, perianeurysmal edema, and embolic phenomena following deployment of flow-diverting stents may be relevant to those patients who subsequently experience procedure-related intracranial hemorrhage. We sought to document the routine early postoperative MR imaging findings following flow-diverting stent insertion. MATERIALS AND METHODS: Patients requiring flow-diverting stent placement for treatment or retreatment of cerebral aneurysms were prospectively included in the study during a 26-month period. Early postprocedural MR imaging studies were obtained and compared with preoperative imaging. Patient clinical outcome data were also collected. RESULTS: There were 34 stent-placement procedures during the study period. Aneurysm mural enhancement and mild new perianeurysmal edema were present in 50% and 14%, respectively. Any DWI lesion was present in 57% of cases. New or possibly new foci of susceptibility effect were found ipsilateral to the stent and not associated with diffusion restriction in 66% of cases. There were 2 cases (6%) of parenchymal hemorrhage and 2 major clinical complications (6%) causing permanent morbidity. CONCLUSIONS: Asymptomatic aneurysm mural enhancement is frequently seen following flow-diverting stent placement and should not necessarily be interpreted as a sign of impending aneurysm rupture. This finding often persists despite complete aneurysm occlusion. New small brain parenchymal susceptibility foci following stent placement have not previously been reported, to our knowledge, but were common in our series.


Subject(s)
Intracranial Aneurysm/pathology , Intracranial Aneurysm/surgery , Magnetic Resonance Imaging , Stents , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Postoperative Period , Prospective Studies , Retreatment , Treatment Outcome
17.
J Oral Rehabil ; 42(1): 18-26, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25146890

ABSTRACT

The aims were to determine whether individuals with a past history of pain exhibit (i) altered jaw movement (e.g. reduced amplitude, increased jaw movement variability) in comparison with matched asymptomatic controls, and (ii) correlations between psychological measures (e.g. catastrophising) and altered jaw movement variables. Sixteen participants with a history of trigeminal neuropathic pain (TNP) and 15 age- and gender-matched healthy controls had jaw movements recorded during open/close, free gum chewing and chewing at standardised rates. All completed the Pain Catastrophising Scale (PCS), the Pain Self-Efficacy Questionnaire (PSEQ), and the Depression, Anxiety and Stress Scales (DASS). Velocity and amplitude for open/close and chewing, as well as variability, bias and mean square error for open/close jaw movements were compared between groups. Spearman's rank correlation coefficient was used to relate kinematic variables with psychological variables. Statistical significance: P < 0·05. There were no significant differences in mean jaw velocity and amplitude between the TNP and control groups during the open/close jaw movements or free or standardised chewing. In comparison with control, the TNP participants exhibited significantly greater variability, bias and/or mean square error during slow and/or fast opening, and significantly greater variance in velocity and/or amplitude during free and standardised chewing. There were significant negative correlations between PCS scores and velocity and/or amplitude of free and/or standardised chewing. This exploratory study suggests that individuals with a history of pain have altered patterns of jaw movements in comparison with asymptomatic control participants and that catastrophising may play a role in the manifestation of these altered jaw movements.


Subject(s)
Catastrophization/psychology , Facial Pain , Mastication/physiology , Movement/physiology , Trigeminal Neuralgia , Aged , Case-Control Studies , Facial Pain/physiopathology , Facial Pain/psychology , Female , Humans , Male , Middle Aged , Pain Measurement , Surveys and Questionnaires , Trigeminal Neuralgia/physiopathology , Trigeminal Neuralgia/psychology
18.
Reprod Toxicol ; 50: 49-59, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25461905

ABSTRACT

The use of carbamazepine (CBZ) during pregnancy increases cardiovascular anomalies. In this study CBZ developmental cardiotoxic effects were evaluated using chick cardiomyocyte micromass (MM) culture and mouse embryonic stem cells derived cardiomyocyte (ESDC) systems. In MM culture, CBZ only inhibited the cardiomyocyte contractile activity, while in ESDC it completely ceased the contractile activity at 200 µM with decreased cell viability and protein content. The antioxidant superoxide dismutase (SOD) supplement in MM and ascorbic acid (AA) in ESDC showed protective effects on CBZ toxicity, but elevated levels of reactive oxygen species (ROS) production were recorded with CBZ treatment only in ESDC. CBZ has also affected cardiac connexin 43 expression in both in vitro systems. Our results indicated CBZ induced ROS stress as mechanism of developmental cardiotoxicity at early stage of cardiogenesis in ESDC system compared to MM system's differentiated cells. These toxic effects can be negated by using antioxidant agent.


Subject(s)
Carbamazepine/toxicity , Myocytes, Cardiac/drug effects , Animals , Antioxidants/pharmacology , Chickens , Connexin 43/analysis , Embryonic Stem Cells/cytology , Mice , Reactive Oxygen Species/metabolism , Superoxide Dismutase/pharmacology
19.
Water Sci Technol ; 70(2): 218-25, 2014.
Article in English | MEDLINE | ID: mdl-25051467

ABSTRACT

Stormwater runoff quality is sensitive to land use and land cover (LULC) change. It is difficult to understand their relationship in predicting the pollution potential and developing watershed management practices to eliminate or reduce the pollution risk. In this study, the relationship between LULC change and stormwater runoff quality in two separate monitoring sites comprising a construction area (Site 1) and mixed land use (Site 2) was analyzed using geographic information system (GIS), event mean concentration (EMC), and correlation analysis. It was detected that bare land area increased, while other land use areas such as agriculture, commercial, forest, grassland, parking lot, residential, and road reduced. Based on the analyses performed, high maximum range and average EMCs were found in Site 2 for most of the water pollutants. Also, urban areas and increased conversion of LULC into bare land corresponded to degradation of stormwater quality. Correlation analysis between LULC and stormwater quality showed the influence of different factors such as farming practices, geographical location, and amount of precipitation, vegetation loss, and anthropogenic activities in monitoring sites. This research found that GIS application was an efficient tool for monthly monitoring, validation and statistical analysis of LULC change in the study area.


Subject(s)
Agriculture , Environmental Monitoring/methods , Rain , Water Movements , Water Pollutants, Chemical/chemistry , Geographic Information Systems , Republic of Korea
20.
Mol Psychiatry ; 19(8): 890-4, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23979604

ABSTRACT

Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells. The major clinical feature of this syndrome is a long QT interval that results in cardiac arrhythmias. However, TS also includes cognitive impairment, autism and major developmental delays in many of the patients. We observed the appearance of bipolar disorder (BD) in a patient with a previously reported case of TS, who is one of the very few patients to survive childhood. This is most interesting because the common single-nucleotide polymorphism (SNP) most highly associated with BD is rs1006737, which we show here is a cis-expression quantitative trait locus for CACNA1C in human cerebellum, and the risk allele (A) is associated with decreased expression. To combine the CACNA1C perturbations in the presence of BD in this patient and in patients with the common CACNA1C SNP risk allele, we would propose that either increase or decrease in calcium influx in excitable cells can be associated with BD. In treatment of BD with calcium channel blocking drugs, we would predict better response in patients without the risk allele, because they have increased CACNA1C expression.


Subject(s)
Bipolar Disorder/genetics , Brain/metabolism , Calcium Channels, L-Type/genetics , Down-Regulation/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Autistic Disorder , Bipolar Disorder/complications , Calcium Channels, L-Type/biosynthesis , Cerebellum/metabolism , Gene Expression Profiling , Humans , Long QT Syndrome/complications , Long QT Syndrome/genetics , Male , Parietal Lobe/metabolism , Quantitative Trait Loci/genetics , Syndactyly/complications , Syndactyly/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...