Symptomatic improvement after mesh removal: a prospective longitudinal study of women with urogynaecological mesh complications.

OBJECTIVE: To compare clinical characteristics and outcomes in patients undergoing excision of polypropylene urogynaecological mesh for pain, mesh exposure or both. DESIGN: Prospective, longitudinal cohort. SETTING: Academic tertiary referral centre. POPULATION: Women undergoing complete vaginal mesh excision for mesh exposure and/or pain. METHODS: Clinical and patient-reported outcomes assessing pain (visual analog scale, VAS), bother (Pelvic Floor Distress Inventory, PFDI) and functional impact (Pelvic Functional Impact Questionnaire, PFIQ) were collected at baseline, 6, 12 and 24 months after complete mesh excision. Outcomes were compared by mesh type (sling, prolapse [transvaginal or sacrocolpopexy mesh], both) and complication (pain, exposure, both). MAIN OUTCOME MEASURES: 'Much better' or 'Very much better' on Patient Global Impression of Improvement (PGI-I) up to 2 years after removal. RESULTS: Of 173 women, 48 underwent removal for pain, 27 for exposure and 98 for exposure plus pain. 'Moderate to severe' baseline symptoms were reported by 75%; the most prevalent and severe symptom was dyspareunia. Patients with pain alone were most bothered (PFDI median 234.2, interquartile range 83, P = 0.02) and had the highest functional impact (PFIQ median 181, interquartile range 138, P < 0.001). After excision, only 33.3% of women with pain alone reported 'improved' symptoms (PGI-I), versus 73.9% with exposure, 58.3% with exposure plus pain (P = 0.03) with no differences in PGI-I by mesh type. VAS scores decreased in all groups, but PFDI and PFIQ did not improve in pain patients. CONCLUSIONS: In women experiencing a pain complication after urogynaecological mesh insertion, mesh removal often does not improve symptoms. TWEETABLE ABSTRACT: Only 33% of women with pain complications have improved symptoms after urogynaecological mesh removal.

Signalling processes involved in C-peptide-induced chemotaxis of CD4-positive lymphocytes.

Previous data from our group demonstrated that C-peptide induces chemotaxis of CD4-positive lymphocytes in-vitro, mediated by activation of G-protein and PI 3-kinase gamma, but additional signalling pathways involved in this process remained unexplored. In the present study we further analyze intracellular signalling pathways which lead to C-peptide-induced CD4-positive lymphocyte migration. We provide evidence that C-peptide-induced chemotaxis of CD4-positive lymphocytes is critically dependent on activation of Src-kinase and RhoA, Rac-1 and Cdc42 GTPases. Furthermore, C-peptide stimulates phosphorylation of PAK, LIMK and cofilin downstream of Rac-1 and Cdc42, leading to cofilin inactivation and actin filament stabilization. In addition, C-peptide induces ROCK kinase activity and MLC phosphorylation downstream of RhoA, thereby stimulating myosin mediated cell contraction. In contrast, C-peptide does not activate ERK1/2, p38 or Akt in CD4-positive lymphocytes. Our data support an active role of C-peptide in CD4-positive lymphocyte chemotaxis and elucidate molecular mechanisms in C-peptide-induced cell migration.

The characteristics of patients with possible familial hypercholesterolemia-screening a large payer/provider healthcare delivery system.

BACKGROUND: Familial hypercholesterolemia (FH) is an under-diagnosed condition. AIM: We applied standard laboratory criteria across a large longitudinal electronic medical record database to describe cross-sectional population with possible FH. METHODS: A cross-sectional study of Clalit Health Services members. Subjects who met the General Population MED-PED laboratory criteria, excluding: age <10 years, documentation of thyroid, liver, biliary or autoimmune diseases, a history of chronic kidney disease stage 3 or greater, the presence of urine protein >300 mg/l, HDL-C>80 mg/dl, active malignancy or pregnancy at the time of testing were considered possible FH. Demographic and clinical characteristics are described at time of diagnosis and at a single index date following diagnosis to estimate the burden on the healthcare system. The patient population is also compared to the general population. RESULTS: The study cohort included 12 494 subjects with out of over 4.5 million members of Clalit Health Services. The estimated prevalence of FH in Israel was found to be 1:285. These patients are notably positive for, and have a family history of, cardiovascular disease and risk factors. For most of them the LDL-C levels are not controlled, and only a quarter of them are medically treated. CONCLUSIONS: By using the modified MED-PED criteria in a large electronic database, patients with possible FH can be identified enabling early intervention and treatment.

Wavelet analysis of the frontal auditory evoked potentials obtained in the passive oddball paradigm in healthy subjects and schizophrenics.

The goal of the present study was to apply the oscillatory brain dynamics model to the structural and quantitative analysis of neurocognitive functions considered as a potential marker of schizophrenia. This was achieved in tests of the detection of auditory events deviating in the regular auditory stream (oddball paradigm, MMN effect). It was hypothesized that the post-stimulus peaks of the oscillation power localized in post-stimulus time in the definite EEG oscillators represented neuro-electrical 'events' evoked in the specific neuronal nets characterized by this oscillation frequency band. We suggest that the time-frequency destination of these events related to the activation of the functional neuronal nets could be used for the determination of specific neurocognitive functions. Thus it was an attempt to distinguish the different neuro-functional parts of auditory processing and to compare these results between healthy subjects and patients with schizophrenia. The present results demonstrate the significant difference between the frontal averaged EEG oscillatory dynamics in healthy subjects and patients with schizophrenia related to neurocognitive function marked by the MMN and orienting response N200/P300a.

Coronary stent restenosis and the association with allergy to metal content of 316L stainless steel.

BACKGROUND: Most intra-coronary stents in use are made of 316 L stainless steel, which contains nickel, chromate and molybdenum. Whether inflammatory and allergic reactions to metals contribute to in-stent restenosis is still a matter of debate. AIM: The aim of this study was to ascertain the relationship between metal allergy and the occurrence of in-stent restenosis. METHODS: Ninety-nine adult patients who underwent two cardiac catheterisations, up to two years apart, were included in the study. Seventy patients had patent stents at the second angiogram (patent stent group) and 29 were found to have in-stent restenosis (restenosis group). All patients underwent patch testing with the relevant metals and the 316L stainless steel plate. RESULTS: Twenty-eight (28.3%) patients were found to have an allergy to at least one metal. There was no significant difference in the prevalence of metal allergy between the patent stent group and the restenosis group (28.6 and 27.6%, respectively; p = 0.921). CONCLUSIONS: Our data do not support the theory that contact allergy plays a role in the pathogenesis of in-stent restenosis.

The discrete and combined effect of SREBP-2 and SCAP isoforms in the control of plasma lipids among familial hypercholesterolaemia patients.

BACKGROUND AND AIM: Hypercholesterolaemia is a major risk factor for atherosclerosis. Cholesterol is modulated by genetic and environmental factors. An important regulatory pathway is controlled by the sterol-regulatory element-binding proteins (SREBPs) and the SREBP cleavage-activating protein (SCAP). Both SREBP-2 and SCAP are candidates to contribute to the development of atherosclerosis. We investigated the possible effects of the variability of proteins involved in this regulatory pathway on plasma lipids among familial hypercholesterolaemia patients. METHODS AND RESULTS: Single nucleotide polymorphisms (SNPs) in the genes encoding SREBP-2 and SCAP causing amino acid changes at positions 595 (595G/A) and 796 (796I/V), respectively, were genotyped in 801 FH individuals originating from Israel, The Netherlands, and Switzerland. A linear regression model to examine the associations between SREBP-2 and SCAP isoforms and lipid and lipoprotein levels was used. In females, homozygosity either for the SREBP-2-595A or for the SCAP-796I isoform was associated with higher LDL-cholesterol plasma concentrations (14.7 mg/dl and 20.3 mg/dl, respectively). Surprisingly, heterozygosity for the combination SREBP-2-595A/SCAP-796I was associated with a decrease of 30.28 mg/dl in LDL-C (p-value for gene-gene interaction=0.09). No such effect was observed among FH males. Subgroup analysis considering the most frequent (N>/=24) LDL receptor mutations (del191-2, ins313+1-2, C660X, E207K, S285L) revealed further gene-dosage- and gender-dependent effects of the SCAP mutations on LDL-cholesterol concentrations (p=0.0345). These effects were, however, not present when less frequent LDL receptor mutations were investigated. CONCLUSIONS: These results suggest a possible gene-gene interaction between the genes encoding SREBP-2 and SCAP that modulate plasma lipids in a strictly gender-specific fashion. Further investigation is needed to confirm this effect. A study in a larger FH group or in non-FH hypercholesterolaemic subjects may further define the role of this regulatory mechanism in determining plasma lipid concentration.

Kleptomania: diagnosis and treatment options.

Kleptomania--the inability to resist the impulse to steal objects, not for personal use or monetary gain--is currently classified in psychiatric nomenclature as an impulse control disorder. However, some of the principle features of the disorder, which include repetitive intrusion thoughts, inability to resist the compulsion to perform the thievery and the relief of tension following the act, suggest that kleptomania may constitute an obsessive-compulsive spectrum disorder. Kleptomania is commonly under-diagnosed and is often accompanied by other psychiatric conditions, most notably affective, anxiety and eating disorders, and alcohol and substance abuse. Individuals with the disorder are usually referred for treatment due to the comorbid psychiatric complaints rather than kleptomanic behaviour per se. Over the past century there has been a shift from psychotherapeutic to psychopharmacological interventions for kleptomania. Pharmacological management using selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) and other antidepressants, mood stabilisers and opioid receptor antagonists, as adjuvants to cognitive-behavioural therapy, has produced promising results.

Effects of haloperidol on human plasma magnesium.

The effect of haloperidol treatment on human plasma levels of magnesium (Mg), calcium (Ca) and phosphorus (P) was assessed. Haloperidol treatment significantly reduced plasma Mg but not plasma Ca or P levels. This finding contrasts with studies using other neuroleptics where reductions in both Mg and Ca concentrations were observed. The addition of lithium to haloperidol treatment resulted in an elevation of plasma Mg, but not Ca or P, to levels significantly greater than those at baseline. The reduction of Mg levels by haloperidol may reflect the ion's involvement in the pathology of psychosis and/or in the mechanism of generating extrapyramidal side effects.

Electrochemical biosensors: recommended definitions and classification.

Two Divisions of the International Union of Pure and Applied Chemistry (IUPAC), namely Physical Chemistry (Commission 1.7 on Biophysical Chemistry formerly Steering Committee on Biophysical Chemistry) and Analytical Chemistry (Commission V.5 on Electroanalytical Chemistry) have prepared recommendations on the definition, classification and nomenclature related to electrochemical biosensors: these recommendations could, in the future, be extended to other types of biosensors. An electrochemical biosensor is a self-contained integrated device, which is capable of providing specific quantitative or semi-quantitative analytical information using a biological recognition element (biochemical receptor) which is retained in direct spatial contact with an electrochemical transduction element. Because of their ability to be repeatedly calibrated, we recommend that a biosensor should be clearly distinguished from a bioanalytical system, which requires additional processing steps, such as reagent addition. A device that is both disposable after one measurement, i.e. single use, and unable to monitor the analyte concentration continuously or after rapid and reproducible regeneration, should be designated a single use biosensor. Biosensors may be classified according to the biological specificity-conferring mechanism or, alternatively, to the mode of physico-chemical signal transduction. The biological recognition element may be based on a chemical reaction catalysed by, or on an equilibrium reaction with macromolecules that have been isolated, engineered or present in their original biological environment. In the latter cases. equilibrium is generally reached and there is no further, if any, net consumption of analyte(s) by the immobilized biocomplexing agent incorporated into the sensor. Biosensors may be further classified according to the analytes or reactions that they monitor: direct monitoring of analyte concentration or of reactions producing or consuming such analytes; alternatively, an indirect monitoring of inhibitor or activator of the biological recognition element (biochemical receptor) may be achieved. A rapid proliferation of biosensors and their diversity has led to a lack of rigour in defining their performance criteria. Although each biosensor can only truly be evaluated for a particular application, it is still useful to examine how standard protocols for performance criteria may be defined in accordance with standard IUPAC protocols or definitions. These criteria are recommended for authors. referees and educators and include calibration characteristics (sensitivity, operational and linear concentration range, detection and quantitative determination limits), selectivity, steady-state and transient response times, sample throughput, reproducibility, stability and lifetime.

Immunosensor for extra-lab measurements based on liposome amplification and capillary migration.

A novel prototype immunosensing device has been developed which incorporates the simplicity of competitive immunochromatography with the rapid signal amplification capabilities of marker-loaded liposomes. An avidin capture zone provides direct readout of the analyte concentration.

Differential effect of acute and chronic haloperidol administration on dopamine turnover in rat nigrostriatal and retinal dopaminergic neurons.

Haloperidol-induced increases in DOPAC and HVA declined in the striatum but remained unchanged in the retina after chronic pretreatment with haloperidol (1-4 weeks). DA concentrations were unaffected in the striatum but decreased in the retina after acute or chronic haloperidol administration. Light stimulation increased both retinal DA and DOPAC. The findings indicate that acute and chronic haloperidol affect nigrostriatal and retinal DA neurons differentially. In addition, DA neurons in retina respond differently to activations by haloperidol and light.

Ehlers-Danlos syndrome simulating child abuse.

We report an unusual insight into the impact of an inherited skin disorder on persons and their families through a child abuse evaluation that was concluded by the diagnosis of Ehlers-Danlos syndrome (EDS) in a 6-year-old girl. To our knowledge, no similar case has been reported in the literature, although other such cases of confusion in diagnosis have been confirmed.

IFCC document stage 3, draft 1, dated 1989 02 01. An approved IFCC recommendation. IFCC method (1988) for tonometry of blood: reference materials for pCO2 and pO2. International Federation of Clinical Chemistry Scientific Division. Committee on pH, Blood Gases and Electrolytes.

A reference method for tonometry of blood is described. The document covers the theory of tonometry, the materials and equipment needed, and essential aspects of the tonometry procedure for blood. The partial pressures of oxygen and carbon dioxide in tonometered blood are accurately known and therefore this blood is recommended for assessing the accuracy of blood gas analyzers. Tonometry of blood samples from patients may also be used in the determination of acid-base quantities and hemoglobin-oxygen affinity, e.g. p50.

Determination of potato glycoalkaloids using a liposome immunomigration, liquid-phase competition immunoassay.

Polyclonal anti-solanine antibodies were raised and used in the assembly of a liposome immunomigration, liquid-phase competition strip immunoassay. In this format, a similar cross-reactivity was observed between the glycoalkaloids alpha-solanine and alpha-chaconine. The strip assay was implemented to quantitate total glycoalkaloids (TGA) from potatoes. Recoveries in spiked potato samples using the strip assay and water:acetic acid:sodium bisulfite extracting solvent were in the range of 84-111%. The values of the TGA quantitations by the strip assay as compared with those obtained by HPLC, in nonspiked tubers coming from cloned potato samples donated by potato breeders, were equivalent and highly correlated (r(2) = 0.91). The strip assay proved advantageous over HPLC for extra-laboratory measurements such as the rapid identification of samples that should be rejected due to an elevated TGA content.

Polyphenolic composition of raisins.

The polyphenolics of raisins were extracted, separated by HPLC, and characterized by their UV-vis spectra, and their concentrations measured. Color measurements and browning indices were also determined. Samples (n = 20) included sun-dried, dipped, and golden raisins. Comparisons were also made with fresh and frozen Thompson Seedless grapes. Golden raisins (which are treated with SO(2)) had the highest amount of hydroxycinnamic acids and the highest lightness values. In comparison with fresh grapes, percent losses of the two major hydroxycinnamics (caftaric and coutaric acids) in sun-dried, dipped, and golden raisins were on the order of 90%. Flavonols were not influenced by processing as much as hydroxycinnamics, while procyanidins and flavan-3-ols were completely degraded in all raisin samples. Formation of hydroxymethylfurfural and loss of amino acids in sun-dried and dipped raisins are ascribed to Maillard browning reactions.

Investigation of two multichannel image detectors for use in spectroelectrochemistry.

Two multichannel image detectors, a vidicon and a silicon photodiode array, were investigated for their performance as detectors in ultraviolet-visible absorption spectroelectrochemical experiments. Their spectral band-pass, dispersion, dynamic range, and precision of absorbance measurements were compared. o-Tolidine was used as a model compound to study their performance in a spectro-potentiostatic experiment using an optically transparent thin-layer electrode. Both detectors performed well, but the silicon photodiode array had twice the spectral resolution and dynamic absorbance range of the vidicon detector.

Development of flow-injection liposome immunoanalysis (FILIA) for imazethapyr.

Imazethapyr is the herbicide developed for use in leguminous crops. In this study, flow-injection liposome immunoanalysis (FILIA) has been shown to be capable of measuring imazethapyr in a buffered solution with a detection limit of 0.1 ppb through the optimization process. Protein A coated glass beads covalently conjugated with antibody were contained in a glass column, and this column was used as an immunoreactor. Liposomes which encapsulated a fluorescent dye, sulforhodamine B (SRB) or carboxyfluorescein (CF), generated the analytical signal. By loading larger volumes of sample onto the column, it was shown that the detection limit could be lowered. Liposomes containing carboxyfluorescein gave more sensitive response and a lower detection limit than those with sulforhodamine B. Also, improved response was obtained by using a smaller flow cell in the fluorescence detector due to the reduced dilution effect.

Flow-injection liposome immunoanalysis (FILIA) for alachlor.

An automated Flow-Injection Liposome ImmunoAnalysis (FILIA) system has been modified from a previous design, using a specific environmental contaminant, the herbicide alachlor, as a model analyte. Signal amplification by means of fluorescent marker-loaded, analyte-tagged liposomes provides high sensitivity. The computer controlled system is composed of commercially available components, with the exception of the column packing material, which has to be prepared for each specific analyte to be determined. The use of such components means that the system is easily modified. The relationships between antibody concentration and assay speed and sensitivity are explored, and the possibilities of using the system for determination of multiple analytes is discussed.

Evaluation of compulsory ambulatory treatment in Israel.

The effectiveness of Israel's compulsory ambulatory treatment order was evaluated based on a one-year follow-up of the 326 orders served during the first four years of implementation. Demographic, epidemiological, clinical, and legal data were obtained from patient records. Success was defined as continuous treatment for the entire six-month period of compulsory ambulatory treatment, or as voluntary hospitalization during or after the compulsory treatment period. The compulsory ambulatory treatment order was found to be efficacious in 43.3 percent of the cases; in 32.5 percent it did not succeed in preventing compulsory hospitalization, and in the remaining cases (22.1 percent), success was partial.

The generation of psychosis: a pragmatic approach.

The paper discusses the role of speech in the generation of psychosis. The traditional phenomenological approach describes schizophrenic speech as desocialized, autistic and destructive. Based on 'Speech Act Theory', we argue that patients in an acute psychotic state assign maximal illocutionary force to their utterances and mark these speech acts as felicitous. We hypothesize that the pragmatic approach can serve a special role in bilingual patients, the mother tongue being more pronounced in the generation of the psychosis. This view gains support from clinical experience and case studies and can be used as a treatment strategy for bilingual patients.