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1.
Clin Neurophysiol ; 159: 41-55, 2024 03.
Article in English | MEDLINE | ID: mdl-38246117

ABSTRACT

OBJECTIVE: This scoping review provides an overview of artificial intelligence (AI), including machine and deep learning techniques, in the interpretation of clinical needle electromyography (nEMG) signals. METHODS: A comprehensive search of Medline, Embase and Web of Science was conducted to find peer-reviewed journal articles. All papers published after 2010 were included. The methodological quality of the included studies was assessed with CLAIM (checklist for artificial intelligence in medical imaging). RESULTS: 51 studies were identified that fulfilled the inclusion criteria. 61% used open-source EMGlab data set to develop models to classify nEMG signal in healthy, amyotrophic lateral sclerosis (ALS) and myopathy (25 subjects). Only two articles developed models to classify signals recorded at rest. Most articles reported high performance accuracies, but many were subject to bias and overtraining. CONCLUSIONS: Current AI-models of nEMG signals are not sufficient for clinical implementation. Suggestions for future research include emphasizing the need for an optimal training and validation approach using large datasets of clinical nEMG data from a diverse patient population. SIGNIFICANCE: The outcomes of this study and the suggestions made aim to contribute to developing AI-models that can effectively handle signal quality variability and are suitable for daily clinical practice in interpreting nEMG signals.


Subject(s)
Amyotrophic Lateral Sclerosis , Artificial Intelligence , Humans , Electromyography , Needles
2.
Trials ; 22(1): 297, 2021 Apr 21.
Article in English | MEDLINE | ID: mdl-33883024

ABSTRACT

BACKGROUND: Surgical site infections (SSI) are frequent complications after elective abdominal surgery. We designed the Enhanced PeriOperative Care and Health Protection programme (EPO2CH) care bundle, comprising of intraoperative high fractional inspired oxygen; intraoperative goal-directed fluid therapy; active preoperative, intraoperative and postoperative warming; glucose control and treatment of hyperglycaemia (> 10 mmol L- 1) in diabetics as well as non-diabetics; and wound irrigation before closure using an aqueous antiseptic. We hypothesise that EPO2CH added to standard care reduces the incidence of SSI compared to standard care alone for elective abdominal surgery. METHODS: This trial is designed as an open label, pragmatic randomised controlled parallel-group multicentre superiority trial. The primary endpoint is the incidence of SSI, defined by the Centers for Disease Control and prevention, within 30 days after surgery. The incidence of SSI is assessed using the Dutch national complication register and medical chart review. Secondary endpoints include the SSI incidence within 90 days, incidence of anastomotic leakage at 30 and 90 days, the incidence of incisional hernia within 1 year, mortality within 1 year and 5 years, quality of life, health and disability, and cost-effectiveness. Primarily, an intention-to-treat analysis will be performed to estimate the relative risk using a log binomial model. If not feasible, a logistic regression will be used to estimate the odds ratio. A per-protocol analysis will also be performed. Furthermore, the attributive effect of the distinct interventions will be explored. DISCUSSION: The results of the EPO2CH trial will determine if the EPO2CH bundle is effective to prevent SSI incidence for patients undergoing elective abdominal surgery. Details of the statistical analysis are described in this Statistical Analysis Plan (SAP). TRIAL REGISTRATION: Registration number: Dutch Trial Register Trial NL5572 . Registered on March 3, 2016. SAP version: V1.0, January 8, 2020. This SAP has been written based on study protocol V10.


Subject(s)
Quality of Life , Surgical Wound Infection , Abdomen/surgery , Elective Surgical Procedures , Humans , Perioperative Care , Surgical Wound Infection/diagnosis , Surgical Wound Infection/prevention & control
4.
Am J Surg ; 215(5): 973-979, 2018 05.
Article in English | MEDLINE | ID: mdl-29397894

ABSTRACT

BACKGROUND: Alpha-1 adrenergic blockers used to treat postoperative urinary retention (POUR) may also have a preventative role. Here we assess the evidence behind their prophylactic use on POUR prevention. STUDY DESIGN: PRISMA guidelines were followed. All studies reviewed for eligibility, data extraction, and risk of bias assessment. Pooled risk ratios with 95% confidence intervals calculated using a random effects model. Heterogeneity assessed using Forest plots, I2 statistic and Chi-squared Cochran's Q-statistic. RESULTS: Fifteen RCTs (1732 patients) included. Prophylactic alpha-1 adrenergic blockers significantly reduced risk of POUR, 13.16% vs 30.24%, RR = 0.48 (95%CI: 0.33; 0.70, p-value = .001), without a statistically significant increase in adverse events. Substantial heterogeneity found between included studies (I2 = 65.49% [95%CI:48.49; 95.01] & Q-statistic 43.46 (p-value<.001)). Subgroup analysis revealed strong risk reduction and little heterogeneity in males (RR:0.33, 95%CI:0.23; 0.47, p-value<.001, I2:10.58) and patients receiving spinal anesthesia (RR:0.26, 95%CI:0.14; 0.46, p-value<.0001, I2 = 0%). CONCLUSION: Prophylactic alpha-1 adrenergic blockers reduce risk of POUR in males and after spinal anesthesia.


Subject(s)
Adrenergic alpha-1 Receptor Antagonists/therapeutic use , Postoperative Complications/prevention & control , Urinary Retention/prevention & control , Humans , Randomized Controlled Trials as Topic
5.
Br J Surg ; 104(2): e118-e133, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28093723

ABSTRACT

BACKGROUND: Triclosan-coated sutures (TCS) were developed to reduce the risk of surgical-site infection (SSI). Level 1A evidence of effectiveness has been presented in various recent meta-analyses, yet well designed RCTs have not been able to reproduce these favourable results. The aim of this study was to evaluate all available evidence critically with comprehensive analysis to seek a more reliable answer regarding the effectiveness of TCS in the prevention of SSI. METHODS: PubMed, MEDLINE, Embase and Cochrane Library databases were searched from 1990 to November 2015 for RCTs that compared TCS with sutures that were exactly the same, but uncoated, in the prevention of SSI. Pooled relative risks (RRs) with corresponding 95 per cent confidence intervals were estimated using a random-effects model. Metaregression was used to substantiate subgroup effects, trial sequential analysis was employed to assess the risk of random error, and quality of evidence was determined using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-one RCTs including 6462 patients were included. Risk of bias was serious. Pooled effects showed a RR of 0·72 (95 per cent c.i. 0·60 to 0·86; P < 0·001) for all publications. At a risk of 138 SSIs per 1000 procedures, the use of TCS reduced this by 39 (95 per cent c.i. 19, 55). Trial sequential analysis confirmed a RR reduction of 15 per cent for the use of TCS. CONCLUSION: GRADE assessment shows moderate-quality evidence that TCS are effective in reducing SSI. Trial sequential analysis indicates that the effect was robust, and additional data are unlikely to alter the summary effect.


Subject(s)
Anti-Infective Agents, Local/administration & dosage , Coated Materials, Biocompatible/administration & dosage , Surgical Wound Infection/prevention & control , Sutures , Triclosan/administration & dosage , Humans , Randomized Controlled Trials as Topic , Surgical Procedures, Operative/statistics & numerical data
6.
Scand J Med Sci Sports ; 24(5): 773-8, 2014 Oct.
Article in English | MEDLINE | ID: mdl-23600756

ABSTRACT

Neovascularization is frequently observed in tendinopathy. Previous studies have focused on the role of neovascularization in Achilles tendinopathy, but have been conducted in small series. It is still unclear whether the degree of neovascularization is related to severity of symptoms. The purpose was to study the relationship between ultrasonographic neovascularization and clinical severity in patients with Achilles tendinopathy. In this prospective cohort study, data on 127 patients (141 tendons) were assembled from databases of three clinical trials. All patients followed an eccentric exercise program. The Öhberg neovascularization score (0-4+) and Victorian Institute of Sports Assessment-Achilles (VISA-A) score (split into domains: pain, function and activity) were collected during baseline and follow-up. The relationship between neovascularization and VISA-A score was calculated. At baseline, 107 tendons (76%) showed some degree of neovascularization. In 556 coupled measurements, neovascularization was weakly related to the VISA-A score [Exp (B) 1.017, 95% confidence interval (CI), 1.007-1.026]. No significant relationship was found between neovascularization and the pain domain (P = 0.277) and the activity domain (P = 0.283), but there was between neovascularization and the function domain of the VISA-A score [Exp (B) = 1.067, 95% CI 1.018-1.119]. In conclusion, neovascularization in Achilles tendinopathy is weakly related to clinical severity, mainly based on the function domain of the VISA-A score.


Subject(s)
Achilles Tendon/blood supply , Achilles Tendon/injuries , Neovascularization, Physiologic , Tendinopathy/physiopathology , Achilles Tendon/diagnostic imaging , Adult , Cross-Sectional Studies , Databases, Factual , Female , Humans , Male , Middle Aged , Musculoskeletal Pain/etiology , Musculoskeletal Pain/physiopathology , Prospective Studies , Randomized Controlled Trials as Topic , Tendinopathy/complications , Tendinopathy/diagnostic imaging , Trauma Severity Indices , Ultrasonography
7.
Br J Sports Med ; 46(3): 214-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22075719

ABSTRACT

BACKGROUND: Eccentric exercises have the most evidence in conservative treatment of midportion Achilles tendinopathy. Although short-term studies show significant improvement, little is known of the long-term (>3 years) results. AIM: To evaluate the 5-year outcome of patients with chronic midportion Achilles tendinopathy treated with the classical Alfredson's heel-drop exercise programme. STUDY DESIGN: Part of a 5-year follow-up of a previously conducted randomised controlled trial. Methods 58 patients (70 tendons) were approached 5 years after the start of the heel-drop exercise programme according to Alfredson. At baseline and at 5-year follow-up, the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire score, pain status, alternative treatments received and ultrasonographic neovascularisation score were recorded. RESULTS: In 46 patients (58 tendons), the VISA-A score significantly increased from 49.2 at baseline to 83.6 after 5 years (p<0.001) and from the 1-year to 5-year follow-up from 75.0 to 83.4 (p<0.01). 39.7% of the patients were completely pain-free at follow-up and 48.3% had received one or more alternative treatments. The sagittal tendon thickness decreased from 8.05 mm (SD 2.1) at baseline to 7.50 mm (SD 1.6) at the 5-year follow-up (p=0.051). CONCLUSION: At 5-year follow-up, a significant increase of VISA-A score can be expected. After the 3-month Alfredson's heel-drop exercise programme, almost half of the patients had received other therapies. Although improvement of symptoms can be expected at long term, mild pain may remain.


Subject(s)
Achilles Tendon/injuries , Exercise Therapy/methods , Tendinopathy/therapy , Adult , Follow-Up Studies , Heel , Humans , Injury Severity Score , Middle Aged , Musculoskeletal Pain/etiology , Patient Satisfaction , Tendinopathy/diagnostic imaging , Treatment Outcome , Ultrasonography
8.
Br J Sports Med ; 45(13): 1026-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21926076

ABSTRACT

BACKGROUND: Achilles tendon disorders, like Achilles tendinopathy, are very common among athletes. In the general population, however, knowledge about the incidence of Achilles tendinopathy is lacking. Design Cross-sectional study. METHODS: In a cohort of 57.725 persons registered in primary care, the number of patients visiting the general practitioner (GP) with diagnosis of mid-portion Achilles tendon problems was counted using computerised registration networks of GPs in 2009. Subsequently, the authors assessed associations of these rates with demographic characteristics. RESULTS: The incidence rate of Achilles tendinopathy is 1.85 per 1,000 Dutch GP registered patients. In the adult population (21-60 years), the incidence rate is 2.35 per 1,000. In 35% of the cases, a relationship with sports activity was recorded. CONCLUSION: This is the first report on incidence rates of mid-portion Achilles tendinopathy in general practice. With an incidence of 1.85 per 1,000 registered persons, Achilles tendinopathy is frequently seen by GPs. The actual incidence might even be higher due to study limitations. More research on the frequency of this injury is required.


Subject(s)
Achilles Tendon , Tendinopathy/epidemiology , Adult , Age Distribution , Cross-Sectional Studies , Female , Humans , Incidence , Male , Middle Aged , Netherlands/epidemiology , Sex Distribution , Young Adult
9.
Br J Sports Med ; 44(16): 1153-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-19666626

ABSTRACT

OBJECTIVE: To assess whether three-dimensional imaging of the Achilles tendon by ultrasonographic tissue characterisation (UTC) can differentiate between symptomatic and asymptomatic tendons. DESIGN: Case-control study. SETTING: Sports Medical Department of the Hague Medical Centre. PATIENTS: Twenty-six tendons from patients with chronic midportion Achilles tendinopathy were included. The "matched" control group consisted of 26 asymptomatic tendons. INTERVENTIONS: Symptomatic and asymptomatic tendons were scanned using the UTC procedure. One researcher performed the ultrasonographic data collection. These blinded data were randomised, and outcome measures were determined by two independent observers. MAIN OUTCOME MEASUREMENTS: The raw ultrasonographic images were analysed with a custom-designed algorithm that quantifies the three-dimensional stability of echo patterns, qua intensity and distribution over contiguous transverse images. This three-dimensional stability was related to tendon structure in previous studies. UTC categorises four different echotypes that represent (I) highly stable; (II) medium stable; (III) highly variable and (IV) constantly low intensity and variable distribution. The percentages of echo-types were calculated, and the maximum tendon thickness was measured. Finally, the inter-observer reliability of UTC was determined. RESULTS: Symptomatic tendons showed less pixels in echo-types I and II than asymptomatic tendons (51.5% vs 76.6%, p<0.001), thus less three-dimensional stability of the echo pattern. The mean maximum tendon thickness was 9.2 mm in the symptomatic group and 6.8 mm in the asymptomatic group (p<0.001). The Intraclass Correlation Coefficient (ICC) for the interobserver reliability of determining the echo-types I+II was 0.95. The ICC for tendon thickness was 0.84. CONCLUSION: UTC can quantitatively evaluate tendon structure and thereby discriminate symptomatic and asymptomatic tendons. As such, UTC might be useful to monitor treatment protocols.


Subject(s)
Achilles Tendon/diagnostic imaging , Imaging, Three-Dimensional/methods , Tendinopathy/diagnostic imaging , Adolescent , Adult , Case-Control Studies , Female , Humans , Male , Middle Aged , Observer Variation , Ultrasonography , Young Adult
10.
Br J Sports Med ; 44(9): 673-7, 2010 Jul.
Article in English | MEDLINE | ID: mdl-18838406

ABSTRACT

OBJECTIVE: The study examined whether the addition of a night splint to eccentric exercises is beneficial for functional outcome in chronic midportion Achilles tendinopathy. DESIGN: One-year follow-up of a randomised controlled single blinded clinical trial. SETTING: Sports medicine department in a general hospital. PATIENTS: 58 patients (70 tendons) were included. INTERVENTIONS: All patients completed a 12-week heavy load eccentric training programme. One group received a night splint in addition to eccentric exercises. MAIN OUTCOME MEASUREMENTS: Outcome scores were: Victorian Institute of Sport Assessment-Achilles (VISAA) score, subjective patient satisfaction and neovascularisation score measured with power Doppler ultrasonography (PDU). RESULTS: For both groups the VISA-A score increased significantly (from 50 to 76 (p<0.01) in the eccentric group and from 49 to 78 (p<0.01) in the night splint group). No significant differences in the VISA-A score were found between the groups from baseline to one year (p = 0.32). The presence of neovessels at baseline did not predict a change in the VISA-A score after one year in the whole group (p = 0.71). CONCLUSION: Eccentric exercises with or without a night splint improved functional outcome at one year follow-up. At follow-up there was no significant difference in clinical outcome when a night splint was used in addition to an eccentric exercise programme. Between 3 months and one year follow-up, a continuing increase in the VISA-A score was found. Assessment of the neovascularisation score with PDU at baseline has no prognostic value on long-term clinical outcome.


Subject(s)
Achilles Tendon , Exercise Therapy/methods , Splints , Tendinopathy/therapy , Adult , Aged , Chronic Disease , Follow-Up Studies , Humans , Middle Aged , Patient Satisfaction , Prospective Studies , Single-Blind Method , Young Adult
11.
Scand J Med Sci Sports ; 19(5): 616-20, 2009 Oct.
Article in English | MEDLINE | ID: mdl-18694435

ABSTRACT

The objective was to retrospectively examine whether a manual therapy technique is effective in the treatment of chronic adductor-related groin pain in athletes. Thirty-three athletes with chronic adductor-related groin pain were approached. Thirty patients gave their consent to participate in the study. Patient satisfaction, return to activity and numeric pain score were recorded. Patients were treated after prewarming of the muscles; one hand is used to control the tension in the adductor muscles and the other hand is used to move the hip into abduction and external rotation. This flowing, circular motion stretches the adductor muscle group. The movement is repeated three times in one treatment session. Twenty-five out of 30 (83%) athletes reported a good or excellent satisfaction. Twenty-seven out of 30 (90%) athletes had resumed sport at (15/30) or below (12/30) their previous level of activity. The pain score for during or after activity decreased significantly from 8.7 to 2.2 after the treatment (P<0.01). This study shows that the manual therapy treatment might be a promising treatment for chronic adductor-related groin pain in athletes.


Subject(s)
Groin/physiopathology , Musculoskeletal Manipulations/standards , Pain Management , Adolescent , Adult , Athletic Injuries/physiopathology , Chronic Disease , Female , Hip Joint/physiopathology , Humans , Male , Muscle, Skeletal/physiopathology , Outcome Assessment, Health Care/methods , Retrospective Studies , Rupture, Spontaneous/physiopathology , Young Adult
13.
Ecotoxicology ; 10(1): 35-50, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11227816

ABSTRACT

In lowland areas of the Netherlands, any peat sediments will gradually become enriched with anthropogenically derived Polycyclic Aromatic Hydrocarbons. Due to Dutch policy standards these (anaerobic) sediments are not allowed to be dredged and placed onto land. Under aerobic conditions, however, biodegradation of PAH is greatly enhanced. This degradation is further stimulated by colonisation of the sediments by earthworms. Laboratory experiments show that although earthworms do not avoid PAH-contaminated sediment, their burrowing-activity is reduced. Furthermore, these sediments have no significant ecotoxicological impacts on earthworms. Experimental introduction of earthworms into PAH-contaminated OECD-soil will result in a decrease in overall PAH content. In field surveys no significant differences in earthworm numbers between locations with fresh and old sediment could be found. It is concluded that dredging of PAH-contaminated sediment poses a very limited environmental threat, and that putting these sediments on land will improve PAH-biodegradation, partly through the colonisation by and activities of earthworms.


Subject(s)
Geologic Sediments/chemistry , Oligochaeta/physiology , Perylene/analogs & derivatives , Polycyclic Aromatic Hydrocarbons/chemistry , Soil Pollutants , Animals , Anthracenes/analysis , Benzo(a)pyrene/analysis , Biodegradation, Environmental , Chromatography, High Pressure Liquid , Chrysenes/analysis , Fluorenes/analysis , Hydrogen-Ion Concentration , Netherlands , Oligochaeta/growth & development , Perylene/analysis , Phenanthrenes/analysis , Soil , Statistics, Nonparametric
14.
Am J Med Genet ; 96(6): 831-5, 2000 Dec 04.
Article in English | MEDLINE | ID: mdl-11121191

ABSTRACT

Serotonergic dysfunction has been implicated in the pathophysiology of affective disorders and suicidality. Especially the density of the 5-HT2A receptor was claimed as being increased in suicidality, proposed as an adaptive upregulation due to reduced serotonergic transmission. Recent studies have shown an association of allele C of the 5-HT2A-T102C polymorphism with suicidal ideation in patients with major depression. The purpose of this study was to test whether this proposed marker indicates susceptibility not only to suicidal ideation in depressed patients but also to suicidality as a syndrome. We investigated the 5-HT2A-T102C polymorphism in 131 suicide victims with unknown underlying psychiatric diagnoses, 84 patients with major depression with or without suicidal ideation, and 125 healthy controls. We were unable to find any association of genotype or allele frequencies to major depression, suicidal ideation, or suicide as a syndrome. Thus, our results suggest that this polymorphism may not commonly be involved in the susceptibility to suicidality. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:831-835, 2000.


Subject(s)
Receptors, Serotonin/genetics , Suicide , Adult , Aged , Aged, 80 and over , Alleles , Amino Acid Substitution , DNA/genetics , Depressive Disorder/genetics , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic , Receptor, Serotonin, 5-HT2A , Suicide/psychology
15.
Psychiatry Res ; 96(1): 51-61, 2000 Sep 25.
Article in English | MEDLINE | ID: mdl-10980326

ABSTRACT

The aim of this study was to investigate [3H]paroxetine binding and impulsivity in alcohol-dependent and age-matched control subjects in relation to a 5'-promoter region serotonin transporter (5-HTT) polymorphism (5-HTTLPR). Alcohol-dependent subjects were hypothesized to show a decreased number of bindings sites and a lower dissociation constant. 5-HTTLPR S-genotype carriers in both alcohol-dependent and control subjects were expected to show significantly fewer binding sites and a lower dissociation constant. Influences of impulsive traits, chronic daily alcohol intake, duration of alcohol dependence, age of onset and age on [3H]paroxetine binding were also investigated. Inpatients meeting DSM IV alcohol dependence criteria and of German descent were recruited to avoid ethnic stratification effects. One hundred and seventeen control subjects of similar social status were recruited from a town community. Blood samples were taken from both alcohol-dependent and control subjects to determine 5-HTTLPR genotypes using PCR of lymphocyte DNA, and to perform platelet [3H]paroxetine binding (binding capacity: B(max); and dissociation constant: K(D)). Impulsivity was assessed using the Barratt impulsiveness scale version 5 (BIS-5) in alcohol-dependent subjects only. Alcohol-dependent subjects were subdivided into low or high impulsivity groups using a median-split of the BIS-5 scale. The control group was slightly older than the alcohol-dependent group (not statistically significant). [3H]paroxetine binding was investigated in 72 control subjects and 72 patients, of which five patients met type 2 alcohol dependence criteria. Genotyping was carried out in all patients and control subjects. A significant influence of duration of alcohol dependence was found on the [3H]paroxetine binding K(D) but not B(max.) Neither alcohol-dependent nor control subjects showed any differences in B(max) or K(D). S-allele carriers did not show a decreased binding or lower dissociation constant. Furthermore, no significant interaction between B(max) and K(D) with either 5-HTTLPR genotype or impulsivity was revealed. This was the first study to investigate platelet [3H]paroxetine binding in alcohol-dependent and age-matched control subjects in relation to the 5-HTTLPR genotype. No differences concerning 5-HTTLPR-alleles were found in these groups Furthermore, no significant interaction between these parameters and impulsivity was shown in alcohol-dependent subjects. These results do not support previous results of altered [3H]paroxetine binding sites in alcohol-dependent subjects or 5-HTTLPR S-allele carriers. K(D) might be influenced by duration of alcohol dependence, but not sufficiently to yield differences between alcohol-dependent and control subjects.


Subject(s)
Alcoholism/genetics , Impulsive Behavior/genetics , Paroxetine/metabolism , Polymorphism, Genetic , Selective Serotonin Reuptake Inhibitors/metabolism , Serotonin/genetics , Adult , Aged , Alcoholism/metabolism , Blood Platelets/drug effects , Case-Control Studies , Female , Gene Expression Regulation/genetics , Genes, Reporter/genetics , Genotype , Humans , Male , Middle Aged , Paroxetine/pharmacology , Phenotype , Promoter Regions, Genetic , Serotonin/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology
16.
Mol Psychiatry ; 5(2): 193-5, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10822348

ABSTRACT

There is abundant evidence that the serotonin (5-HT) system is modulating mood and several behavioural traits and that disturbances in the regulation of this system can be associated with severe behavioural malfunctions, as aggressive implusive and suicidal behaviour.1 Recently a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was identified2 and the presence of one or two short alleles was associated with anxiety-related personality traits3 and several psychiatric disturbances, such as affective disorder4 or severe alcohol dependence.5 With respect to the importance of the 5-HT transporter in serotonergic transmission, we have genotyped the DNA of 58 Caucasian suicide victims (with unknown psychiatric diagnoses) and 110 healthy controls for the biallelic functional polymorphism in the 5-HTTLPR. We found a highly significant increased frequency of suicide victims being carriers of one or two short alleles (Fisher's Exact Test, two sided, P = 0.0003), which suggests that a genetically altered protein function within the serotonergic pathway might be involved in suicidality, independently from the clinical diagnosis.


Subject(s)
Carrier Proteins/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Polymorphism, Genetic , Suicide , Alleles , Female , Genetic Carrier Screening , Genotype , Germany , Humans , Male , Middle Aged , Nerve Tissue Proteins/genetics , Reference Values , Serotonin Plasma Membrane Transport Proteins , Violence , White People
17.
Neurosci Lett ; 284(1-2): 113-5, 2000 Apr 21.
Article in English | MEDLINE | ID: mdl-10771175

ABSTRACT

Several studies have attempted to confirm an association between a deletion/insertion polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and Alzheimer's disease independent from the apolipoprotein E (APOE) varepsilon4 status. We examined this deletion/insertion polymorphism of the serotonin transporter gene in a sample of 222 consecutively recruited gerontopsychiatric patients which was divided into four different diagnostic groups: Alzheimer's disease (N=84), mild cognitive impairment (N=29), subjective cognitive complaints (N=49), depression/other psychiatric disorders (N=56) and 118 healthy, non-demented controls. The aim of this approach was to test whether the investigated polymorphism has a high enough selectivity and specificity to distinguish between the different gerontopsychiatric disorders or to differentiate genetically AD from other forms of dementia, respectively. We could not detect any significant differences in the allelic distribution of the deletion/insertion polymorphism of the 5-HTT gene between the four patient subgroups and the control group. This finding indicates that the serotonin transporter does not appear to be a major susceptibility factor in the pathophysiology of Alzheimer's disease and other psychogeriatric disorders.


Subject(s)
Aging/genetics , Carrier Proteins/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Mental Disorders/genetics , Mental Disorders/physiopathology , Nerve Tissue Proteins , Polymorphism, Genetic/genetics , Aged , Alleles , Alzheimer Disease/genetics , Alzheimer Disease/physiopathology , Female , Gene Deletion , Humans , Male , Middle Aged , Mutagenesis, Insertional/genetics , Phenotype , Serotonin/genetics , Serotonin Plasma Membrane Transport Proteins
18.
Arthritis Rheum ; 42(11): 2482-8, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10555044

ABSTRACT

OBJECTIVE: To analyze the genotypes of the promoter region of the serotonin transporter gene (5-HTT) in patients with fibromyalgia (FM). METHODS: Genomic DNA from 62 patients meeting the American College of Rheumatology 1990 criteria for FM and 110 healthy controls was analyzed by polymerase chain reaction. Additionally, the psychopathologic state of 52 of the FM patients was evaluated using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R). RESULTS: The 5-HTTLPR genotypes in FM patients versus controls were distributed as follows: L/L 27% versus 34%, L/S 42% versus 50%, and S/S 31% versus 16%. FM patients with the S/S genotype had higher mean scores on the BDI and the SCL-90-R compared with those in the L/L and L/S groups. CONCLUSION: A higher frequency of the S/S genotype of 5-HTT was found in FM patients compared with healthy controls. The S/S subgroup exhibited higher mean levels of depression and psychological distress. These results support the notion of altered serotonin metabolism in at least a subgroup of patients with FM.


Subject(s)
Carrier Proteins/genetics , Fibromyalgia/genetics , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Nerve Tissue Proteins , Polymorphism, Genetic , Regulatory Sequences, Nucleic Acid/genetics , Adult , Aged , Female , Gene Frequency , Genetic Markers , Genotype , Humans , Male , Middle Aged , Serotonin Plasma Membrane Transport Proteins
19.
Neurobiol Dis ; 6(5): 433-9, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10527809

ABSTRACT

Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.


Subject(s)
Fibromyalgia/genetics , Polymorphism, Genetic , Receptors, Serotonin/genetics , Adult , Age of Onset , Aged , Alleles , Female , Fibromyalgia/physiopathology , Fibromyalgia/psychology , Gene Frequency , Genotype , Germany , Humans , Male , Middle Aged , Pain Measurement , Receptor, Serotonin, 5-HT2A , Sex Characteristics
20.
Psychiatry Res ; 81(2): 157-62, 1998 Nov 16.
Article in English | MEDLINE | ID: mdl-9858033

ABSTRACT

Acute and chronic exposure to ethanol influences intracellular calcium homeostasis via NMDA receptors, direct regulation of calcium channels or the phosphoinositide pathway. To explore the influence of alcohol withdrawal on calcium metabolism, we have investigated the resting and phytohemagglutinin (PHA) stimulated [Ca2+]i in lymphocytes of 10 alcoholics before, during and after withdrawal. Our findings suggest that both compartments of the PHA-stimulated signal are affected in alcoholics, with flattening of the initial peak and sustained calcium influx, as long as severe vegetative signs are present. MANOVA results showed significant interaction effects for both measurement points, for the initial peak, 40 s after stimulation (P = 0.05), and especially for the sustained influx at the end of the observation period (P = 0.001). The detailed mechanisms of this disturbed calcium homeostasis need further investigation.


Subject(s)
Alcohol Withdrawal Delirium/immunology , Alcoholism/immunology , Calcium Signaling/immunology , Lymphocyte Activation/immunology , Phytohemagglutinins/immunology , Adult , Alcoholism/rehabilitation , Calcium/blood , Female , Homeostasis , Humans , Male , Middle Aged
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