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Biomedical subjects

L Neumann

Publications and source records attributed to L Neumann.

At least 19 recordsLinked to original sources

The effect of balneotherapy at the Dead Sea on the quality of life of patients with fibromyalgia syndrome.

Fibromyalgia (FS) is an idiopathic chronic pain syndrome defined by widespread non-articular musculoskeletal pain and generalised tender points. As there is no effective treatment, patients with this condition have impaired quality of life (QoL). The aim of this study was to assess the possible effect of balneotherapy at the Dead Sea area on the QoL of patients with FS. Forty-eight subjects participated in the study; half of them received balneotherapy, and half did not. Their QoL (using SF-36), psychological well-being and FS-related symptoms were assessed prior to arrival at the spa hotel in the Dead Sea area, at the end of the 10-day stay, and 1 and 3 months later. A significant improvement was reported on most subscales of the SF-36 and on most symptoms. The improvement in physical aspects of QoL lasted usually 3 months, but on psychological measures the improvement was shorter. Subjects in the balneotherapy group reported higher and longer-lasting improvement than subjects in the control group. In conclusion, staying at the Dead Sea spa, in addition to balneotherapy, can transiently improve the QoL of patients with FS. Other studies with longer follow-up are needed to support our findings.

Balneology↗

Outcomes of a brief alcohol abuse prevention program for Israeli high school students.

PURPOSE: To implement a brief intervention aimed at reducing abuse of alcohol among adolescents, and to assess its effectiveness. METHODS: One thousand 10th-grade students from seven high schools, chosen by random from the roster of all schools in southern Israel, were assigned to intervention and control groups. The intervention, which was based on Botvin's social skills theory, was conducted over 3 days and included dissemination of information, workshops, lectures by guest experts, and activity areas. It was administered by the staff of the high schools and the Psychological Counseling Service in Israel. A self-administered questionnaire was answered anonymously by students in the 10th grade (pretest) and again in the 11th and 12th grades (posttests). It included questions on sociodemographic data, alcohol-related habits, smoking habits, use of illicit drugs, knowledge, and attitudes. Data were collected between 1994 and 1997 with a 76% follow-up rate at 2 years. RESULTS: At baseline there was no statistical difference in alcohol consumption between the intervention and control groups. At 1- and 2-year follow-up the rates of alcohol consumption did not change in the intervention group (p > .05) but rose significantly in the control group (p < .001). In multiple regression analysis the variables male gender, positive attitudes, cigarette smoking, availability of illegal drugs, and intervention group were significant predictors of alcohol consumption. CONCLUSIONS: The results of this study show the effectiveness of this intervention program, based on reduced alcohol consumption in the intervention group at 1- and 2-year follow-up, compared with the control group. Compared with other programs, the present intervention is brief, intensive, and relatively easy to implement.

Adolescent↗

Classic, atypically severe and neonatal Marfan syndrome: twelve mutations and genotype-phenotype correlations in FBN1 exons 24-40.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome, an autosomal dominant disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. There is a remarkable degree of clinical variability both within and between families with Marfan syndrome as well as in individuals with related disorders of connective tissue caused by FBN1 mutations and collectively termed type-1 fibrillinopathies. The so-called neonatal region in FBN1 exons 24-32 comprises one of the few generally accepted genotype-phenotype correlations described to date. In this work, we report 12 FBN1 mutations identified by temperature-gradient gel electrophoresis screening of exons 24-40 in 127 individuals with Marfan syndrome or related disorders. The data reported here, together with other published reports, document a significant clustering of mutations in exons 24-32. Although all reported mutations associated with neonatal Marfan syndrome and the majority of point mutations associated with atypically severe presentations have been found in exons 24-32, mutations associated with classic Marfan syndrome occur in this region as well. It is not possible to predict whether a given mutation in exons 24-32 will be associated with classic, atypically severe, or neonatal Marfan syndrome.

Adolescent↗

Retinal angiomatosis and von Hippel-Lindau disease.

BACKGROUND: To evaluate the significance of angioma number (single or multiple) for the presence of von Hippel-Lindau (VHL) disease in patients presenting with capillary retinal angioma. METHODS: Forty-one nonrelated patients presenting with capillary retinal angioma were evaluated. An ophthalmic workup, screening for other organ lesions, and molecular genetic screening for a mutation of the VHL gene was performed. The diagnosis of VHL was made on the basis of the personal and family history, the presence of other VHL-associated organ lesions, or the presence of a mutation of the VHL gene. RESULTS: Thirteen patients (32%) presented with a single angioma and 28 patients (68%) presented with multiple angiomas. In 81% of all patients, VHL could be diagnosed. Diagnosis of VHL could be readily made by the personal or family history in 51% of all patients. In another 27% of all patients, VHL disease was evidenced by screening for other VHL-associated lesions. In two patients (3%) VHL could be diagnosed by molecular genetics only. All patients with multiple retinal angiomas had VHL disease and, in 38% of patients with a single angioma, VHL was present. Reasons for a missing family history in patients with VHL disease were the presence of a de novo mutation (15% of VHL patients) or clinical anticipation of VHL disease (18% of VHL patients). CONCLUSION: The presence of multiple retinal angiomas strongly suggests VHL disease, which, however, can be obscured by presence of a de novo mutation or by clinical anticipation of VHL disease in affected families. A single retinal angioma may be sporadic as well as the presenting sign of VHL. Diagnosis and screening for this multitumor syndrome is substantially supported by molecular genetics.

Adolescent↗

CLINHAQ scale--validation of a Hebrew version in patients with fibromyalgia. Clinical Health Assessment Questionnaire.

Assessment of health status in patients with rheumatic disease, including fibromyalgia (FM), using structured questionnaires has become an important approach to evaluate treatment and outcome. The objectives of this study were to validate a translated version of the Clinical Health Assessment Questionnaire (CLINHAQ) to be used by Hebrew-speaking populations, and specifically to evaluate its usefulness in fibromyalgia syndrome (FM). The CLINHAQ was translated into Hebrew and administered to 90 women with FM along with the Hebrew versions of the Fibromyalgia Impact Questionnaire (FIQ) and the Quality of Life (QOL) Scale. The CLINHAQ includes scales of functional disability, helplessness, anxiety and depression, as well as assessment of current health status and satisfaction with this. All subjects were asked about the presence and severity (assessed by visual analogue scale) of current FM symptoms (pain, fatigue, anxiety etc.); a count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were measured by dolorimetry. Test-retest reliability was assessed by Pearson correlation coefficients, and internal consistency was evaluated with Cronbach's alpha coefficient of reliability. Construct validity was tested by correlating the CLINHAQ items with measures of symptom severity, count of tender point, tenderness thresholds, physical functioning measured by FIQ, and with a score of QOL. Test-retest reliability coefficients ranged from 0.82 to 0.99, and Cronbach's alpha coefficients from 0.725 to 0.929. Significant moderate to high correlations were obtained between most subscales of CLINHAQ and measures of physical functioning, quality of life and severity of FM symptoms. In conclusion, the CLINHAQ is a reliable and valid instrument for measuring health status and physical functioning in Israeli women with FM.

Adult↗

Musculoskeletal injury as a trigger for fibromyalgia/posttraumatic fibromyalgia.

The issue of musculoskeletal injury as a trigger for fibromyalgia (FM) is controversial. The present review critically evaluates the evidence that trauma can initiate FM, specifically addressing the scope of the problem, the issue of causality, possible pathophysiologic mechanisms, and medicolegal aspects. One major problem is the fact that most of the data come from anecdotal reports and small case series and not from controlled prospective studies. Overall data from the current literature are insufficient to indicate whether causal relationships exist between trauma and FM. However, recent reports suggest that soft tissue trauma to the neck can result in an increased incidence of FM compared with other injuries. Future studies should prospectively document the chronology of symptoms from the onset of trauma and repeatedly evaluate the patients for disability, quality of life, change in occupation, and litigation status.

Female↗

Dietary treatment of hypercholesterolemia: do dietitians do it better? A randomized, controlled trial.

PURPOSE: Current guidelines of the National Cholesterol Education Program (NCEP) recommend initial dietary counseling by physicians for most patients with hypercholesterolemia; referral to a registered dietitian and lipid-lowering drugs are recommended only for patients who remain hypercholesterolemic. We evaluated the incremental value of detailed nutritional counseling by dietitians when added to general nutritional advice provided by physicians. SUBJECTS AND METHODS: Hypercholesterolemic patients detected during a cholesterol screening project were randomly assigned to receive dietary counseling by a physician only (70 patients) or by a physician and a registered dietitian (66 patients). Patients were observed for 1 year to determine compliance with NCEP guidelines. RESULTS: At 3 months, the mean (+/- SD) decrease in the serum low-density lipoprotein (LDL) cholesterol level was 7% +/- 11% in the physician group and 12% +/- 10% in the dietitian group (P <0.004). A decrease of 10% or more in the LDL cholesterol level was seen in 25 patients (36%) in the physician group and 43 patients (65%) in the dietitian group (P <0.001). Only 40 (29%) of the patients in both groups achieved their NCEP target goals at 3 months. The majority of these were low-risk patients with an LDL cholesterol target goal of 160 mg/dL. At 12 months, both groups lost about half of the beneficial effects on LDL cholesterol levels, and the difference between the two groups diminished. CONCLUSIONS: The short-term reduction in LDL cholesterol level achieved after counseling by dietitians is superior to that achieved by physicians. However, long-term compliance remains inadequate. For patients at high risk, consideration should be given to a more aggressive dietary approach and possibly earlier introduction of lipid-lowering medications.

Adult↗

Autonomic dysfunction in patients with fibromyalgia: application of power spectral analysis of heart rate variability.

OBJECTIVES: To assess the interaction between the sympathetic and parasympathetic systems in patients with fibromyalgia syndrome (FM), using power spectrum analysis (PSA) of heart rate variability (HRV). In addition, we explored the association between HRV, measures of tenderness, FM symptoms, physical function, psychological well being and quality of life. METHODS: We studied 22 women with FM and 22 age-matched healthy women. Twenty-minute electrocardiogram recordings were obtained in a supine position during complete rest. Spectral analysis of R-R intervals was done by the fast-Fourier transform algorithm. RESULTS: Heart rate was significantly higher in FM patients compared with controls (P < .006). FM patients had significantly lower HRV compared with controls (P= .001), and higher low-frequency (LF) and lower high-frequency (HF) components of PSA than controls (P < .001). Quality of life, physical function, anxiety, depression, and perceived stress were moderately to highly correlated with LF, HF (in normalized units), and LF/HF. No association was observed between HRV parameters and measures of tenderness and FM symptoms. CONCLUSIONS: The basal autonomic state of patients with FM is characterized by increased sympathetic and decreased parasympathetic tones. Autonomic dysregulation may have implications regarding the symptomatology, physical and psychological aspects of health status.

Algorithms↗

Hereditary spastic paraplegia caused by mutations in the SPG4 gene.

Autosomal dominant hereditary spastic paraplegia (AD-HSP) is a genetically heterogeneous neurodegenerative disorder characterised by progressive spasticity of the lower limbs. The SPG4 locus at 2p21-p22 accounts for 40-50% of all AD-HSP families. The SPG4 gene was recently identified. It is ubiquitously expressed in adult and foetal tissues and encodes spastin, an ATPase of the AAA family. We have now identified four novel SPG4 mutations in German AD-HSP families, including one large family for which anticipation had been proposed. Mutations include one frame-shift and one missense mutation, both affecting the Walker motif B. Two further mutations affect two donor splice sites in introns 12 and 16, respectively. RT-PCR analysis of both donor splice site mutations revealed exon skipping and reduced stability of aberrantly spliced SPG4 mRNA. All mutations are predicted to cause loss of functional protein. In conclusion, we confirm in German families that SPG4 mutations cause AD-HSP. Our data suggest that SPG4 mutations exert their dominant effect not by gain of function but by haploinsufficiency. If a threshold level of spastin were critical for axonal preservation, such threshold dosage effects might explain the variable expressivity and incomplete penetrance of SPG4-linked AD-HSP.

Adenosine Triphosphatases↗

Measuring health status in Israeli patients with fibromyalgia syndrome and widespread pain and healthy individuals: utility of the short form 36-item health survey (SF-36).

OBJECTIVES: To examine the usefulness of the Medical Outcomes Study Short Form-36 (MOS SF-36) in measuring health-related quality of life (QOL) in fibromyalgia syndrome (FMS) patients, and to determine whether subscale scores of SF-36 could distinguish patients with FMS from patients with widespread pain alone, and from healthy individuals. METHODS: The study population included three groups of women: 90 patients with FMS, 96 patients with widespread pain, and 50 healthy controls. In all subjects, health-related QOL was assessed by SF-36. The Health Assessment Questionnaire was used to evaluate functional disability, helplessness and psychological status. FMS-related symptoms and tenderness also were assessed. RESULTS: The 8 subscales of SF-36 showed a consistent pattern for physical function, physical role functioning, body pain, general health, vitality, and social function, with the lowest scores in patients with FMS, intermediate scores in patients with widespread pain alone, and the highest scores in healthy subjects. Emotional role functioning and mental health scores were significantly higher among healthy controls than among patients. The SF-36 subscales of physical functioning, bodily pain, and social functioning were highly correlated with another measure of functional disability (from the Health Assessment Questionnaire) in all patient groups. Most of the subscales were associated with psychological variables (helplessness, depression, and anxiety). All eight subscales of SF-36 were strongly correlated with the mean score of another measure of quality of life, QOL-16. CONCLUSIONS: Most of the SF-36 subscales represent health dimensions relevant to patients with FMS and widespread pain alone. The severity of functional impairment as assessed by the SF-36, distinguishes patients with FMS and widespread pain alone from healthy individuals, and also discriminates between patients with widespread pain alone and FMS patients.

Activities of Daily Living↗

Fibromyalgia syndrome in men.

OBJECTIVE: Fibromyalgia syndrome (FMS) is uncommon in men and data on its characteristics and severity are limited. The current study was undertaken to determine whether the clinical characteristics and the spectrum of this disorder are similar in men and women. METHODS: Forty men with FMS were matched with 40 women by age and educational level. All subjects were asked about the presence and severity (assessed by visual analog scale) of FMS symptoms; a count of 18 tender points was conducted by thumb palpation, and tenderness thresholds were measured by dolorimetry. Psychological status was assessed by the anxiety and depression subscales of the revised Arthritis Impact Measurement Scales. Quality of life was evaluated by two scales, QOL-16 and SF-36, and physical function was measured by the Fibromyalgia Impact Questionnaire. RESULTS: Men with FMS reported more severe symptoms than women, decreased physical function, and lower quality of life. Women had lower tender thresholds than men; however their mean point counts were similar. CONCLUSION: Although FMS is uncommon in men, its health outcome in our study population was worse than in women. Further studies in larger samples and in diverse ethnocultural populations are needed to confirm this observation.

Adult↗

Use of the Functional Bowel Disorder Severity Index (FBDSI) in a study of patients with the irritable bowel syndrome and fibromyalgia.

OBJECTIVE: The purpose of this study was to evaluate the utility of the Functional Bowel Disorder Severity Index (FBDSI) as a measure of severity of disease among patients with the irritable bowel syndrome (IBS) and matched controls. METHODS: A total of 75 IBS patients and 69 matched controls completed questionnaires on bowel symptoms, health status, quality of life, psychological distress, concerns, anxiety, and sense of coherence. All participants also were tested for fibromyalgia (FS), a functional disorder of the musculoskeletal system. All participants were administered a questionnaire that included the FBDSI. On the basis of their responses to the questionnaire, the controls were subdivided as healthy controls (n = 48) or IBS nonpatients (n = 21). On the basis of the FS classification, 75 IBS patients were subdivided as IBS only (n = 50) or IBS and FS combined (n = 25). RESULTS: The mean FBDSI score was higher for the IBS patients than the controls (100.5+/-12.7 and 23.5+/-3.9, respectively; p < 0.001). IBS nonpatients had an intermediate score of 42.3+/-18.0. Patients with both IBS and fibromyalgia had the highest mean FBDSI score: 138.8+/-31.5. There was no association between FBDSI and age or gender, but FBDSI was significantly associated with other measures of health status. CONCLUSIONS: An association was found between the FBDSI and IBS patient status: IBS nonpatients, patients with IBS only, and patients with both IBS and fibromyalgia had increasingly severe scores. The results provide support for the validity of FBDSI as a measure of illness severity in functional gastrointestinal disorders.

Adult↗

The prevalence of pain complaints in a general population in Israel and its implications for utilization of health services.

OBJECTIVE: To determine the prevalence of pain complaints, specifically of chronic widespread pain, in the general population; and to explore the utilization of health services by various pain groups. METHODS: Cross sectional population survey of 2210 adults in the southern part of Israel, who were classified into 5 pain groups: no pain, transient pain, chronic regional pain, chronic widespread pain, and other. Participants were interviewed about pain patterns and utilization of health services. RESULTS: Forty-four percent reported pain on the day of the interview. The prevalence of chronic widespread pain in the study population was 9.9%, 14% in women and 3% in men (p<0.01). The prevalence in the Israeli adult population was estimated after adjusting for sex and age as 10.2%. The prevalence of any chronic pain (regional or widespread) increased with age. The prevalence of chronic widespread pain was significantly higher in women than in men across all age groups (p<0.01). Persons with chronic widespread pain reported most frequent visits to their physicians (10.8 visits/year) and most frequent use of antiinflammatory and analgesic drugs. They were more frequently referred to specialists and tended to be hospitalized slightly more often. CONCLUSION: In the general population in Israel, widespread pain is common, and its prevalence is comparable with reports from USA, UK, and Canada.

Absenteeism↗

Influenza virus vaccination of patients with systemic lupus erythematosus: effects on disease activity.

OBJECTIVE: To determine whether vaccination of patients with systemic lupus erythematosus (SLE) with influenza virus vaccine is associated with exacerbation of SLE. METHODS: The study population comprised 24 patients with SLE who received influenza vaccine (cases group) and 24 other SLE patients who did not receive the vaccine (controls group). The primary outcome measure was the SLE Disease Activity Index (SLEDAI) scores 6 weeks and 12 weeks after vaccination. Secondary outcome measures included: number of SLE flares, defined as any increase in the SLEDAI > or = 3 points, and activity of renal disease. Repeated measurements MANOVA was used to compare the SLEDAI scores of the cases and controls. RESULTS: All patients were women. The mean age at enrollment into the study was 46.1 and 40.6 years for the cases and controls, respectively. The mean disease duration was 9.1 for the cases and 9.3 years for the controls. SLEDAI scores for the cases and controls were 6.6 and 8.9 at vaccination, 4.9 and 6.8 at Week 6, and 5.1 and 6.7 at Week 12, respectively. The SLEDAI scores of the cases and controls at the 3 different assessments were not statistically different (p = 0.28). However, within each group the decrease in the SLEDAI over time was statistically significant (p = 0.02). Three and 6 flares were observed in the cases and controls, respectively, (p = 0.27) during the 12 weeks of followup. Improvement in the renal disease was observed in the cases and controls. CONCLUSION: Influenza virus vaccine is safe for patients with SLE. Patients with SLE should be encouraged to receive the vaccine according to the recommendation given by the Immunization Practices Advisory Committee.

Adult↗

The assessment of functional impairment in fibromyalgia (FM): Rasch analyses of 5 functional scales and the development of the FM Health Assessment Questionnaire.

OBJECTIVE: Functional assessment by self-report questionnaire plays an important role in most rheumatic conditions, but psychometric properties of questionnaires have not been studied in fibromyalgia (FM), particularly by Rasch analysis, which allows for examining adequacy of the questionnaire scale. To assess currently used instruments, we examined the Fibromyalgia Impact Scale (FIQ), 4 versions of the Health Assessment Questionnaire (HAQ), and the Medical Outcome Survey Short Form (SF-36). METHODS: More than 2,500 patients from 4 sites (3 US, 1 Israel) completed the FIQ. The HAQ questionnaires were completed by 1438 patients participating in the US National Data Bank for Rheumatic Diseases. Seven hundred sixty patients from Wichita, Kansas, completed the SF-36. Rasch analysis was applied separately to each of these data sets. RESULTS: The FIQ systematically underestimated functional impairment by its handling of activities not usually performed. All questionnaires had problems with non-unidimensionality and ambiguous items when applied to patients with FM. In addition, scales were found to be non-linear. Because of these findings we used the 20 item HAQ questionnaire as an item bank to develop a new questionnaire more suitable for use in FM, the fibromyalgia HAQ (FHAQ). This questionnaire fits the Rasch model well, is relevant, is linear, and has a long, well spaced scale. CONCLUSION: No available functional assessment questionnaire works well in FM. A new questionnaire, the FHAQ, was developed. It has appropriate metric properties and should function well in this condition. Since the FHAQ is a subset of the larger HAQ questionnaire, a new questionnaire is not required; only a different method of scoring is needed. Additional studies regarding sensitivity to change are required to fully validate the FHAQ.

Disability Evaluation↗

Kinetic analysis of peptide binding to the TAP transport complex: evidence for structural rearrangements induced by substrate binding.

The transporter associated with antigen processing (TAP) plays a key role in the class I major histocompatibility complex (MHC) mediated immune surveillance. It translocates peptides generated by the proteasome complex into the endoplasmic reticulum (ER) for loading onto MHC class I molecules. At the cell surface these MHC complexes are monitored for their antigenic cargo by cytotoxic T-lymphocytes. Peptide binding to TAP is the essential step for peptide selection and for subsequent ATP-dependent translocation into the ER lumen. To examine the pathway of substrate recognition by TAP, we employed peptide epitopes, which were labeled with an environmentally sensitive fluorophore. Upon binding to TAP, a drastic fluorescence quenching of the fluorescent substrate was detected. This allowed us to analyze TAP function in real-time by using a homogeneous assay. Formation of the peptide-TAP complex is composed of a fast association step followed by a slow isomerization of the transport complex. Proton donor groups moving in proximity to the fluorescence label cause fluorescence quenching. Taken together, this peptide-induced structural reorganization may reflect the crosstalk of structural information between the peptide binding site and both nucleotide-binding domains within the TAP complex.

ATP Binding Cassette Transporter, Subfamily B, Mem↗