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.

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.

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.

Formation risk of toxic and other unwanted compounds in pressure-assisted thermally processed foods.

Consumers demand, in addition to excellent eating quality, high standards of microbial and chemical safety in shelf-stable foods. This requires improving conventional processing technologies and developing new alternatives such as pressure-assisted thermal processing (PATP). Studies in PATP foods on the kinetics of chemical reactions at temperatures (approximately 100 to 120 °C) inactivating bacterial spores in low-acid foods are severely lacking. This review focuses on a specific chemical safety risk in PATP foods: models predicting if the activation volume value (V(a) ) of a chemical reaction is positive or negative, and indicating if the reaction rate constant will decrease or increase with pressure, respectively, are not available. Therefore, the pressure effect on reactions producing toxic compounds must be determined experimentally. A recent model solution study showed that acrylamide formation, a potential risk in PATP foods, is actually inhibited by pressure (that is, its V(a) value must be positive). This favorable finding was not predictable and still needs to be confirmed in food systems. Similar studies are required for other reactions producing toxic compounds including polycyclic aromatic hydrocarbons, heterocyclic amines, N-nitroso compounds, and hormone like-peptides. Studies on PATP inactivation of prions, and screening methods to detect the presence of other toxicity risks of PATP foods, are also reviewed.

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.

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 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.

Post-partum hypocalcemia: idiopatic hypoparathyroidism manifested early in lactation.

Hypocalcemia associated with labor and lactation is a rare condition reported previously in patients with hypovitaminosis D. We here describe a case of a young woman in whom symptomatic severe hypocalcemia appeared after her second delivery, early in lactation. At the end of lactation the condition worsened. We review all previously reported cases and suggest a possible physiologic explanation for the association between pregnancy, lactation and the appearance of symptomatic hypocalcemia.

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.

Time zone change and major psychiatric morbidity: the results of a 6-year study in Jerusalem.

Psychiatric morbidity among foreign tourists is usually connected to external factors such as unfamiliar surroundings, language problems, and special religious experiences, as well as biological factors such as dyschronism of circadian rhythms. Long-range flights through several time zones are typically followed by symptoms of jet lag such as fatigue, severe sleep schedule disturbance, impairment of cognitive functions, and even mild depression. Jet lag is generally attributed to a conflict between external time cues and internal biological rhythms. This study examined the possible association between jet lag and psychiatric morbidity among long-distance travelers hospitalized in the Jerusalem Mental Health Center, Kfar Shaul Hospital between 1993 and 1998. This was a prospective open-label study. Patients (n = 152) were divided into two groups based on the number of time zones crossed in the flight to Israel: group I, seven time zones or more (n = 81); and group II, three time zones or less (n = 71). The direction of flight was mainly eastbound. After controlling the two groups for demographic and religious background, past psychiatric history, and diagnosis on admission (P > 0.1, Fisher's exact test), the possible association between jet lag and psychotic or major affective disorder was evaluated according to the following criteria: (1) absence of major mental problems before the flight or good remission of an existing disorder 1 year or more before flight; and (2) the appearance of psychotic or major affective syndromes during the first 7 days after landing. The number of first psychotic/major affective episodes in both groups presumed as associated with jet lag was found similar (P =.5), whereas the number of relapses conjoint with jet lag in the seven or more time zone group was significantly higher (P =.04). The results suggest that the dyschronism of circadian rhythms and jet lag possibly play a role in the exacerbation of major psychiatric disorders.

Detection of viable Cryptosporidium parvum using DNA-modified liposomes in a microfluidic chip.

This paper describes a microfluidic chip that enables the detection of viable Cryptosporidium parvum by detecting RNA amplified by nucleic-acid-sequence-based amplification (NASBA). The mRNA serving as the template for NASBA is produced by viable C. parvum as a response to heat shock. The chip utilizes sandwich hybridization by hybridizing the NASBA-generated amplicon between capture probes and reporter probes in a microfluidic channel. The reporter probes are tagged with carboxyfluorescein-filled liposomes. These liposomes, which generate fluorescence intensities not obtainable from single fluorophores, allow the detection of very low concentrations of targets. The limit of detection of the chip is 5 fmol of amplicon in 12.5 microL of sample solution. Samples of C. parvum that underwent heat shock, extraction, and amplification by NASBA were successfully detected and clearly distinguishable from controls. This was accomplished without having to separate the amplified RNA from the NASBA mixture. The microfluidic chip can easily be modified to detect other pathogens. We envision its use in mu-total analysis systems (mu-TAS) and in DNA-array chips utilized for environmental monitoring of pathogens.

Detection of Cryptosporidium parvum using oligonucleotide-tagged liposomes in a competitive assay format.

To meet the technical challenge of accurately and rapidly detecting Cryptosporidium parvum oocysts in environmental water, the authors developed a single-use visual-strip assay. The first step in the overall assay procedure involves extracting C. parvum's mRNA coding for heat-shock protein hsp70, followed by amplification using nucleic acid sequence-based amplification (NASBA) methodology as described previously (Baeumner, A. J.; Humiston, M.; Montagna, R. A.; Durst, R. A. Anal. Chem., in press). Subsequently, generated amplicons are hybridized with dye-entrapping liposomes bearing DNA oligonucleotides (reporter probes) and biotin on their surface. The liposome-amplicon complex is then allowed to migrate upward on a nitrocellulose membrane strip. On the nitrocellulose strip, antisense-reporter probes are immobilized in a capture zone and antibiotin antibodies are immobilized in a second zone above the capture zone. Depending on the presence or absence of amplicon in the sample, the liposomes will bind to the capture zone, or they will be caught via their biotin tag in the second zone. Visual detection or gray-scale densitometry allows the quantification of liposomes that are present in either zone. The detection limit of the assay was determined to be 80 fmol amplicon/test. High accuracy and an internal assay control is established using this competitive format, because the presence or absence of liposomes can be quantified in the two capture zones.

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.

Recent origin and spread of a common Lithuanian mutation, G197del LDLR, causing familial hypercholesterolemia: positive selection is not always necessary to account for disease incidence among Ashkenazi Jews.

G197del is the most prevalent LDL receptor (LDLR) mutation causing familial hypercholesterolemia (FH) in Ashkenazi Jew (AJ) individuals. The purpose of this study was to determine the origin, age, and population distribution of G197del, as well as to explore environmental and genetic effects on disease expression. Index cases from Israel (n=46), South Africa (n=24), Russia (n=7), The Netherlands (n=1), and the United States (n=1) were enlisted. All trace their ancestry to Lithuania. A highly conserved haplotype (D19S221:104-D19S865:208-D19S413:74) was identified in G197del chromosomes, suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the deletion was found to be 20 +/- 7 generations (the 95% confidence interval is 15-26 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 14th century. This corresponds with the founding of the Jewish community of Lithuania (1338 a.d.), as well as with the great demographic expansion of AJ individuals in eastern Europe, which followed this settlement. The penetrance of mutation-linked severe hypercholesterolemia is high (94% of heterozygotes have a baseline concentration of LDL cholesterol (LDL-C) that is >160 mg/dl), and no significant differences in the mean baseline lipid level of G197del carriers from different countries were found. Polymorphisms of apolipoprotein E and of scavenger-receptor class B type I were observed to have minor effects on the plasma lipid profile. With respect to determinative genetic influences on the biochemical phenotype, there is no evidence that could support the possibility of a selective evolutionary metabolic advantage. Therefore, the founder effect in a rapidly expanding population from a limited number of families remains a simple, parsimonious hypothesis explaining the spread of G197del-LDLR-linked FH in AJ individuals.

Familial cluster of fulminant hepatitis A infection.

Hepatitis A virus is a common cause of a self-limited liver disease. Fulminant hepatitis is a rare complication of acute hepatitis A infection. We report a small epidemic of three consecutive fulminant hepatitis A infections in three previously healthy siblings. This is the first report of a cluster of fulminant hepatitis A.

Detection of viable oocysts of Cryptosporidium parvum following nucleic acid sequence based amplification.

A reliable method using nucleic acid sequence based amplification (NASBA) with subsequent electrochemiluminescent detection for the specific and sensitive detection of viable oocysts of Cryptosporidium parvum in environmental samples was developed. The target molecule was a 121-nt sequence from the C. parvum heat shock protein hsp70 mRNA. Oocysts of C. parvum were isolated from environmental water via vortex flow filtration and immunomagnetic separation. A brief heat shock was applied to the oocysts and the nucleic acid purified using an optimized very simple but efficient nucleic acid extraction method. The nucleic acid was amplified in a water bath for 60-90 min with NASBA, an isothermal technique that specifically amplifies RNA molecules. Amplified RNA was hybridized with specific DNA probes and quantified with an electrochemiluminescence (ECL) detection system. We optimized the nucleic acid extraction and purification, the NASBA reaction, amplification, and detection probes. We were able to amplify and detect as few as 10 mRNA molecules. The NASBA primers as well as the ECL probes were highly specific for C. parvum in buffer and in environmental samples. Our detection limit was approximately 5 viable oocysts/sample for the assay procedure, including nucleic acid extraction, NASBA, and ECL detection. Nonviable oocysts were not detected.

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.