Common variants of catechol-O-methyltransferase influence patient-controlled analgesia usage and postoperative pain in patients undergoing total hysterectomy.

Catechol-O-methyltransferase (COMT) gene polymorphisms and haplotypes have been associated with both experimental and clinical pain phenotypes. In this prospective study, we investigated the association of three common polymorphisms with experimentally induced pressure pain, postoperative pain and amount of self-administered morphine in 973 patients who underwent scheduled total hysterectomy. DNA extracted from peripheral blood was genotyped for three COMT polymorphisms by Taqman assay or a PCR-based method. In the overall sample, rs4633 and rs4680 were significantly associated with morphine use, whereas rs4818 was associated with time-averaged pain scores. Statistically significant associations were found between COMT rs4633 and rs4680 genotypes and the amount of morphine self-administered through a patient-controlled analgesia pump. For rs4818, the only statistically significant association was with time-averaged pain scores. Haplotype analysis showed statistically significant association of the low pain sensitivity haplotype with time-averaged pain scores; and average pain sensitivity haplotype with total morphine and weight-adjusted morphine.

Cockayne Syndrome due to a maternally-inherited whole gene deletion of ERCC8 and a paternally-inherited ERCC8 exon 4 deletion.

Cockayne Syndrome (CS) is an autosomal recessive disorder that causes neurological regression, growth failure and dysmorphic features. We describe a Chinese female child with CS caused by deletions of exon 4 of ERCC8 on one chromosome and exons 1-12 on the other chromosome. By using chromosomal microarray, multiplex ligation-dependant probe analysis and long range PCR, we showed that she inherited a 277 kb deletion affecting the whole ERCC8 gene from the mother and a complex rearrangement resulting in deletion of exon 4 together with a 1,656 bp inversion of intron 4 from the father. A similar complex rearrangement has been reported in four unrelated Japanese CS patients. Analysis of the deletion involving exon 4 identified LINE and other repeat elements that may predispose the region to deletions, insertions and inversions. The patient also had insulin-dependent diabetes mellitus, a rare co-existing feature in patients with CS. More research will be needed to further understand the endocrine manifestations in CS patients.

Sensory and motor deficits exist on the non-injured side of patients with unilateral tendon pain and disability--implications for central nervous system involvement: a systematic review with meta-analysis.

INTRODUCTION: Tendinopathy manifests as activity-related tendon pain with associated motor and sensory impairments. Tendon tissue changes in animals present in injured as well as contralateral non-injured tendon. This review investigated evidence for bilateral sensory and motor system involvement in unilateral tendinopathy in humans. METHODS: A comprehensive search of electronic databases, and reference lists using keywords relating to bilateral outcomes in unilateral tendinopathy was undertaken. Study quality was rated with the Epidemiological Appraisal Instrument and meta-analyses carried out where appropriate. Analysis focused on comparison of measures in the non-symptomatic side of patients against pain-free controls. RESULTS: The search revealed 5791 studies, of which 20 were included (117 detailed reviews, 25 met criteria). There were 17 studies of lateral epicondylalgia (LE) and one each for patellar, Achilles and rotator cuff tendinopathy. Studies of LE were available for meta-analysis revealing the following weighted pooled mean deficits: pressure pain thresholds (-144.3 kPa; 95% CI -169.2 to -119.2 p<0.001), heat pain thresholds (-1.2°C; 95% CI -2.1 to -0.2, p<0.001), cold pain thresholds (3.1°C; 95% CI 1.8 to 4.4, p<0.001) and reaction time (37.8 ms; 95% CI 24.8 to 50.7, p<0.001). DISCUSSION: Deficits in sensory and motor systems present bilaterally in unilateral tendinopathy. This implies potential central nervous system involvement. This indicates that rehabilitation should consider the contralateral side of patients. Research of unilateral tendinopathy needs to consider comparison against pain-free controls in addition to the contralateral side to gain a complete understanding of sensory and motor features.

Ministry of Health clinical practice guidelines: depression.

The Ministry of Health (MOH) have updated the clinical practice guidelines on Depression to provide doctors and patients in Singapore with evidence-based treatment for depression. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Depression, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/home/Publications/guidelines/cpg/2012/depression.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

The influence of ATP-binding cassette sub-family B member -1 (ABCB1) genetic polymorphisms on acute and chronic pain after intrathecal morphine for caesarean section: a prospective cohort study.

BACKGROUND: Polymorphisms of the ATP-binding cassette sub-family B member -1 (ABCB1) gene that codes for P-glycoprotein could influence the efflux of morphine from the central nervous system affecting its analgesic action. We investigated the effect of ABCB1 gene polymorphisms on analgesia and the development of persistent pain in post caesarean patients. METHODS: Women of Chinese descent who received spinal anaesthesia with intrathecal morphine for elective caesarean section were recruited. They were given intravenous morphine via a patient-controlled analgesia pump for postoperative analgesia. Blood samples were collected and analysed for the presence of C1236T, G2677T/A and C3435T single nucleotide polymorphisms of the ABCB1 gene. We primarily investigated the association between ABCB1 polymorphisms and the effect of morphine. In a postpartum phone survey of the subjects six months after surgery, the occurrence of persistent abdominal wound scar pain was established. RESULTS: We found no significant statistical difference in total morphine consumption, pain scores and side effects among the various genotypes. For C3435T polymorphism, there was a trend towards the association of the T allele and persistent pain for three months after surgery but this did not reach statistical significance (P=0.07). The TT genotype had the longest mean survival time of wound pain in comparison with CT and CC genotypes (P=0.004 and P=0.014, respectively). CONCLUSION: Polymorphisms of ABCB1 were not associated with differences in morphine use in the first 24h after surgery. Women with the T allele of C3435T polymorphism showed a trend towards a higher risk of developing persistent postoperative pain.

Readiness exercise to combat avian influenza.

AIM: To examine the readiness of our hospital for the potential pandemic threat of avian influenza, we developed and implemented simulation case scenarios in our hospital. METHODS: Two volunteers, who assumed the identity of 'actual' patients, were trained to simulate acute respiratory symptoms following a visit to an avian influenza-affected area, and their identities and locations were kept confidential prior to the readiness exercise. A team of auditors was stationed at high-risk areas to assess adherence to the use of personal protective equipment (PPE) and infection control procedures. RESULTS: A total of 324 healthcare workers and 84 administrators participated in this hospital-wide exercise. Following disclosure of their symptoms, the 'patients' were masked and isolated in negative-pressure rooms. A quarantine order was enforced on 38 inpatients and 45 healthcare workers who were present in the affected wards at the time of the exercise, which mandated the use of PPE. Although all affected healthcare workers were competent in the use of PPE, we observed breaches in PPE and isolation procedures in eight medical and nursing students, and 10 healthcare attendants. The exercise concluded after H5N1 tests returned negative. CONCLUSION: We recommend the use of case simulation as an effective means of assessing potential breaches in infection control procedures.

Overcoming preconceptions and perceived barriers to medical communication using a 'dual role-play' training course.

BACKGROUND: Communication is a core component of clinical competence. We introduced a dual role-play (DRP) course, in which participants role-played both the doctor-candidate and the standardized patient. The aim of the study was to assess the usefulness of a DRP communication course for physicians and to identify factors that inhibit effective medical communication. METHODS: We conducted four medical communication skills courses from 2004 to 2006. A questionnaire was administered before and after completion of each course. We assessed respondents' confidence levels before and after the course and sought to identify perceived barriers to effective communication among medical trainees in Singapore. Finally, we asked if they found participation in the course and its DRP nature to be useful. RESULTS: Twenty-six participants, 20 men, 6 women, of mean age 30.2 years (standard deviation (SD) 2.01) completed the survey. The pre-course confidence levels (rated on a scale of 1-10) of 6.23 (SD 1.18) rose significantly to 7.58 (SD 0.95) on completion of the course (P = 0.001, Wilcoxon signed rank test). All respondents felt that they had benefited from participation in the medical communication skills course. 24 (92.3%) respondents deemed it useful to have role-played both the doctor and standardized patient in the exercise. We identified respondents with language difficulties to have benefited the most from the course (P = 0.031, odds ratio 2.906 (95%CI 0.292-5.519), linear regression analysis). CONCLUSION: DRP is an effective way to train doctors in medical communication.

Botulinum toxin: description of injection techniques and examination of controversies surrounding toxin diffusion.

The benefits derived from botulinum toxin (BTX) injections may be negated by unintentional weakness of adjacent uninjected muscles. Such weakness may be the result of inaccurate targeting, or diffusion of BTX to surrounding muscles. Several techniques, using electromyographic, endoscopic or imaging guidance are purported to increase the accuracy of targeting. Diffusion of BTX is thought to be influenced by factors such as dose, concentration, injectate volume, number of injections, site and rate of injection, needle gauge, muscle size, muscular fascia, distance of needle tip from the neuromuscular junction, and protein content of the BTX formulation. This article describes techniques that aim to increase the accuracy of BTX injections and examines the controversies surrounding diffusion of BTX following injection.

Trend in metals variation in Tasik Chini, Pahang, Peninsular Malaysia.

Water from 15 sampling stations in Tasik Chini (Chini Lake), Peninsular Malaysia were sampled for 12 months from September 2004 until August 2005 and analyzed for 11 metals including iron (Fe), aluminum (Al), manganese (Mn), barium (Ba), zinc (Zn), lead (Pb), copper (Cu), cadmium (Cd), nickel (Ni), chromium (Cr) and cobalt (Co). Results showed that the mean (min-max) metal concentrations (in micrograms per liter) in Tasik Chini waters for the 12 months sampling based on 15 sampling stations (in descending order) for Fe, Al, Mn, Ba, Zn, Pb, Cu and Cd were 794.84 (309.33-1609.07), 194.53 (62.37-665.93), 29.16 (16.68-79.85), 22.07 (15.64-29.71), 5.12 (2.224-6.553), 2.36 (1.165-4.240), 0.832 (0.362-1.443) and 0.421 (0.254-0.696) respectively. Concentration for three metals i.e. Ni, Cr and Co were too low and not detected by the graphite furnace Atomic Absorption Spectrophotometry (AAS). Comparison with various water quality standards showed that the mean metals concentration in surface water of Tasik Chini were low and within the range of natural background except for Fe and Al. In general, metal concentrations in Tasik Chini water varied temporally and spatially. The main factors influencing these metal concentrations in the water were the raining season and mining activities. Stations located at Tanjung Jerangking and Melai areas were the most effected due to those factors.

Segmental dystonia following electrocution in childhood.

Electrical injuries to the extremities may result in a range of neurologic manifestations, which include movement disorders such as parkinsonism, segmental myoclonus, choreoathetosis, tremors and dystonia. A 66-year-old man developed segmental dystonia of the right upper extremity at the age of nine, three years after he accidentally held a live 240-V electrical wire in his right hand. MRI brain and cervical cord were normal. We discuss this unusual cause of secondary dystonia and review the literature.

Attitudes of medical students to placebo therapy.

BACKGROUND: Studies have described opposing perceptions of placebo use, with laypersons for and health-care workers against it. Opinions of medical students have not previously been elicited. This study was based on online electronic survey on beliefs, knowledge and attitudes about placebo therapy, that is, use of placebo in clinical practice, rather than in randomized controlled clinical trials. METHODS: The participants were preclinical (years 1, 2) and clinical (years 3-5) medical students. Descriptive analyses and chi2 tests were used to compare the opinions of preclinical and clinical students with statistical significance set at P < 0.05. RESULTS: Four hundred and two (35.6%) out of 1153 students responded, of which 181 were preclinical and 221 were clinical students. Two hundred and eighty-five (70.9%) students felt that placebo therapy was acceptable and 134 (33.3%) believed that it was beneficial in organic disease. Fifty-two (12.9%) students felt that it was ethical to prescribe placebo for organic disease with known definitive treatment, 259 (64.4%) for organic disease with no known treatment and 328 (81.6%) for psychogenic disease. More preclinical than clinical students approved of placebo therapy (odds ratio 2.140 (95% confidence interval 1.161-3.944), P = 0.015) and opined that it was ethical to prescribe placebo therapy to organic diseases for which there was appropriate treatment (odds ratio 1.800 (95% confidence interval 0.992-3.266), P = 0.053). A greater number of clinical when compared with preclinical students said that there is evidence that placebo therapy has a beneficial effect on organic disease (odds ratio 2.299 (95% confidence interval 1.468-4.405), P < 0.001). CONCLUSION: Our medical students felt that placebo therapy is acceptable in certain situations. We identified their erroneous acceptance of placebo therapy in organic diseases, for which there is established treatment, as an area to be addressed in our undergraduate curriculum.

Symptoms associated with electrophysiologically verified carpal tunnel syndrome in Asian patients.

Sensory symptoms are crucial for the diagnosis of carpal tunnel syndrome (CTS). We have studied the spectrum of sensory symptoms in 67 cases of neurophysiologically confirmed CTS in Singapore and investigated the correlation of semi-quantitative clinical ('Historical-Objective') and neurophysiological ('Bland') scales. The range of sensory symptoms was large. The more frequent use of the terms 'woodenness' and 'aching' rather than 'pins and needles' suggests racial and cultural differences in symptom expression, or recognition of previously ignored descriptors. 'Numbness' (97%) was the most common descriptive symptom, followed by 'tingling' (81%), 'tightness' (60%), 'aching' (45%), 'woodenness' (39%) and 'pins and needles' (33%). Less common were 'deadness' (27%), prickling (24%), and cramp-like pain (18%). Uncommon sensations included 'jabbing' (10%), 'shooting pain' (10%), 'stabbing' (9%), 'tight-band like pressure' (9%), 'cold' (8%), 'crushing' (6%) and 'burning' (6%). The semi-quantitative clinical and neurophysiological scales correlated well (Pearson 0.645, P<0.001).

Headaches and the N95 face-mask amongst healthcare providers.

BACKGROUND: During the 2003 severe acute respiratory distress syndrome epidemic, healthcare workers mandatorily wore the protective N95 face-mask. METHODS: We administered a survey to healthcare workers to determine risk factors associated with development of headaches (frequency, headache subtypes and duration of face-mask wear) and the impact of headaches (sick days, headache frequency and use of abortive/preventive headache medications). RESULTS: In the survey, 212 (47 male, 165 female) healthcare workers of mean age 31 years (range, 21-58) participated. Of the 79 (37.3%) respondents who reported face-mask-associated headaches, 26 (32.9%) reported headache frequency exceeding six times per month. Six (7.6%) had taken sick leave from March 2003 to June 2004 (mean 2 days; range 1-4 days) and 47 (59.5%) required use of abortive analgesics because of headache. Four (2.1%) took preventive medications for headaches during this period. Multivariate logistic regression showed that pre-existing headaches [P = 0.041, OR = 1.97 (95% CI 1.03-3.77)] and continuous use of the N95 face-mask exceeding 4 h [P = 0.053, OR = 1.85 (95% CI 0.99-3.43)] were associated with development of headaches. CONCLUSIONS: Healthcare providers may develop headaches following the use of the N95 face-mask. Shorter duration of face-mask wear may reduce the frequency and severity of these headaches.

Botulinum toxin-A injections via electrical motor point stimulation to treat writer's cramp: pilot study.

PURPOSE: Writer's cramp describes a task-specific dystonia, in which the act of writing initiates dystonic posturing of the hands. Previous studies have described the efficacy of injections of botulinum toxin type-A (BTX-A) under electromyographic guidance, in which the injected muscle is either voluntarily, or less often, electrically (electrical motor point stimulation, EMPS) activated to ensure that the needle is in the target muscle. We performed an open label, prospective study to assess the efficacy of BTX-A injections, performed with EMPS under electromyographic guidance. METHODS: Eight patients (seven male and one female) of mean age 44 (range 25-66) were recruited. All had idiopathic writer's cramp. Outcome measures, which included timed writing, objective assessment of dystonia (modified Ashworth scale and a visual analog scale rating) and patient assessment of functional disability, were assessed before injections and at six weeks follow-up. RESULTS: The total dose of BTX-A injected for writer's cramp ranged from 50 to 130 units, which was less than that reported in previous studies using muscle activation techniques (up to 300 units). Improvements were observed in all outcome measures. Patients reported mild (non-disabling) weakness of injected, but not of uninjected muscles. CONCLUSION: Lower dosages of BTX-A, administered using EMPS, offers the advantages of decreased cost and increased accuracy of targeting, while achieving good outcomes.

Adult-onset re-emergent stuttering as a presentation of Parkinson's disease.

INTRODUCTION: The basal ganglia-thalamocortical motor circuits are postulated to play a key role in the aetiopathogenesis of stuttering. The main dysfunction is thought to be an impairment in the ability of the basal ganglia to produce timing cues for the initiation of the next motor segment of speech, explaining the association of acquired and re-emergent stuttering with diseases such as dystonia and Parkinson's disease. CLINICAL PICTURE: We describe a 61-year-old man presenting with re-emergent stuttering and mild hypomimia, only to develop unilateral rest tremors, hypo- and bradykinesia, rigidity and gait difficulties one year later. TREATMENT AND OUTCOME: His parkinsonism responded well to treatment with bromocriptine, but he continued to stutter. DISCUSSION: This case illustrates the association between acquired or re-emergent stuttering and basal ganglia disorders, and highlights the need to assess such patients for an underlying aetiology.