Invasive bacterial infections following influenza: a time-series analysis in Montréal, Canada, 1996-2008.

BACKGROUND: Shared seasonal patterns, such as between influenza and some respiratory bacterial infections, can create associations between phenomena not causally related. OBJECTIVES: To estimate the association of influenza with subsequent bacterial infections after full adjustment for confounding by seasonal and long-term trends. METHODS: Time series of weekly counts of notified cases of invasive infections with Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae and Streptococcus pyogenes, in Montréal, Canada, 1996-2008, were modelled by negative binomial regression, with terms representing seasonal and long-term trends and terms for numbers of positive laboratory tests for influenza A and B. RESULTS: The associations of S. pneumoniae, H. influenzae and N. meningitidis with influenza disappeared after seasonal terms were added to the model. However, the influenza B count remained associated with the S. pyogenes counts for the same week and the following week: S. pyogenes incidence rate ratios were 1.0376 (95% CI: 1.0009-1.0757) and 1.0354 (0.9958-1.0766), respectively, for each increase of 1 in the influenza count. CONCLUSIONS: Influenza B accounts for about 8 percnt; of the incidence of invasive S. pyogenes infections, over and above any effect associated with modellable seasonal and long-term trends. This association of influenza B with S. pyogenes infections can be attributed largely to the years 1997, 2001, 2007 and 2008, when late peaks in influenza B counts were followed by peaks in S. pyogenes notifications. This finding reinforces the case for universal immunization against influenza, as partial protection against the 'flesh eating disease'.

Glucocorticoid-induced TNFR family-related receptor (GITR)-expression in tumor infiltrating leucocytes (TILs) is associated with the pathogenesis of esophageal adenocarcinomas with and without Barrett's mucosa.

BACKGROUND: Esophageal adenocarcinomas (EACs) arise due to gastroesophageal reflux, with Barrett's esophagus (BE) regarded as precancerous lesion. Glucocorticoid-induced TNFR family-related Receptor (GITR)-mediated inflammation of tumor infiltrating leucocytes (TILs) in the tumor microenvironment might play a role during the multistep carcinogenetic process as either tumor promoting factor according to an inflammatory microenvironment or as a feature of anti-tumor activity. METHODS: Immunohistochemical analysis of GITR expression was analyzed in esophageal cancer (n=70: 41 EAC with BE, 19 EAC without BE, and n=10 esophageal squamous-cell carcinomas, ESCC), the adenocarcinoma cell line OE-33, and peripheral blood leucocytes (PBLs) of EAC patients, furthermore in biopsies of BE without intraepithelial neoplasia (IN) (n=18). Results were correlated with clinicopathological parameters and five-year survival rates. Immunohistochemical GITR expression results were confirmed on mRNA level (RT-PCR). RESULTS: Quantification showed a significant increase of 25% GITR positive TILs in EAC with BE (p< 0.05) compared to 13% in adjacent BE, 24% in EAC without BE, 14% in ESCC, and 1% in BE without IN. High GITR levels were not significantly associated with clinicopathologic features which may predict worse clinical outcome and had no impact on survival (p= 0.7878). Increased GITR expression of peripheral blood leucocytes (PBLs) in EAC patients was shown on protein level (32%) and confirmed by RT-PCR (3.7-fold difference compared to normal tissue). CONCLUSIONS: This study provides for the first time evidence that GITR expression of TILs is associated in the pathogenesis of Barrett's esophagus. Our findings suggest that GITR-expression of TILs is associated with cancer progression. Its role as either tumor promoting factor %according to an in the inflammatory microenvironment or as a feature of anti-tumor activity and promising target for molecular therapies needs to be substantiated in further investigations.

Psychostimulant augmentation during treatment with selective serotonin reuptake inhibitors in men with paraphilias and paraphilia-related disorders: a case series.

BACKGROUND: We describe an open trial of psychostimulants (primarily methylphenidate sustained release [SR]) added to selective serotonin reuptake inhibitors (SSRIs; primarily fluoxetine) during the course of pharmacologic treatment of men with paraphilias and paraphilia-related disorders (PRDs). METHOD: Twenty-six men with paraphilias (N = 14) or PRDs (N = 12) were assessed for life-time mood disorders and attention-deficit/hyperactivity disorder (ADHD) as defined by DSM-IV. All men were assessed at baseline for total sexual outlet and average time per day associated with paraphilia/PRD sexual behaviors. The indications for the addition of a psychostimulant to a stable dose of SSRI included the retrospective diagnosis of ADHD with persistent adult symptoms despite pharmacotherapy with an SSRI (N = 17); residual paraphilia/PRD fantasies, urges, and activities despite SSRI pharmacotherapy (N = 16); the persistence or presence of residual depressive symptoms despite SSRI pharmacotherapy (N = 6); relapse or loss of SSRI efficacy during the treatment of sexual impulsivity disorders (N = 4); and treatment of SSRI-induced side effects (N = 4). RESULTS: SSRI pharmacotherapy (mean +/- SD duration = 8.8+/-11.1 months) had statistically significant effects in diminishing paraphilia/PRD-related total sexual outlet (p < .001) and average time/day spent in paraphilia/PRD sexual behavior (p < .001). Addition of methylphenidate SR (mean dose = 40 mg/day; mean +/- SD duration = 9.6+/-8.2 months) was associated with additional statistically significant effects on paraphilia/PRD-related total sexual outlet (p = .003) and average time per day (p = .04) in addition to improvement of putative residual ADHD and depressive symptoms. CONCLUSION: Methylphenidate SR can be cautiously and effectively combined with SSRI antidepressants to ameliorate paraphilias and paraphilia-related disorders for the indications listed above.

Psychopharmacologic treatments for nonparaphilic compulsive sexual behaviors.

This article reviews the use of pharmacologic agents to treat nonparaphilic compulsive sexual behaviors (paraphilia-related disorders). Recent data suggest that serotonergic antidepressants, especially serotonin reuptake inhibitors (SRIs), may be effective in treating nonparaphilic sexual behaviors characterized by hypersexuality. The rationale, prescriptive use, and limitations of SRIs are reviewed, as are the proposed mechanisms of action, prescriptive use, and side effects of medications that lower serum testosterone (including triptorelin and the antiandrogens medroxyprogesterone acetate and cyproterone acetate).The potential use of psychostimulants, mood stabilizers, and atypical antipsychotics for paraphilia-related disorders in specific clinical situations is discussed. Practical guidelines, augmentation strategies with adjunctive psychopharmacologic agents, and indications regarding pharmacologic combinations of the above medications are suggested.

The paraphilia-related disorders: an empirical investigation of nonparaphilic hypersexuality disorders in outpatient males.

The frequency distribution of nonparaphilic hypersexual behaviors was investigated in an outpatient sample of 206 consecutively evaluated males seeking help for sexual impulsivity disorders (SIDs), either paraphilia-related disorders (PRD; n = 63) or paraphilias (PA; n = 143). Paraphilia-related disorders associated with help-seeking behaviors included compulsive masturbation (sample prevalence, 69%), protracted heterosexual or homosexual promiscuity (51%), pornography dependence (50%), telephone-sex dependence (24%), and severe sexual desire incompatibility (12%). Eighty-six percent of the PA sample reported at least one lifetime PRD. The subgroup of males with both PAs and lifetime PRDs (n = 123) self-reported the greatest number of lifetime SIDs, the highest incidence of physical and sexual abuse, the fewest years of completed education, and the highest likelihood of current unemployment or disability. As well, the subgroup of males with PAs but no lifetime PRDs (n = 20) self-reported the fewest lifetime SIDs; this subgroup was not statistically different from the PRD group on these aforementioned variables. These data suggest that social disadvantage, as assessed in this sample, is associated with the cumulative incidence of SIDs but not necessarily with the diathesis to develop paraphilic disorders.

The effect of EDTA as an anticoagulant on the osmotic fragility of erythrocytes.

The osmotic fragility test is used to determine the extent of red blood cell haemolysis produced by osmotic stress. Since the quality of this test may easily be influenced by environmental and technical factors we have determined osmotic fragility reference values in our own conditions. The results show significantly increased osmotic resistance of erythrocytes in our conditions vs the published values for blood samples anticoagulated with heparin. Furthermore, the use of EDTA as an anticoagulant increased the osmotic fragility of red blood cells as compared with heparin. We conclude that EDTA can be used as an anticoagulant for the osmotic fragility test in order to simplify routine procedures. However, every laboratory should determine its own reference values which would reflect the local environmental and technical factors.

Attention-deficit/hyperactivity disorder in males with paraphilias and paraphilia-related disorders: a comorbidity study.

BACKGROUND: We describe a study of DSM-III-R Axis I diagnoses of lifetime comorbid nonsexual disorders in 60 males with paraphilias (PAs; N = 42) and nonparaphilic forms of sexual impulsivity-designated paraphilia-related disorders (PRD; N = 18). METHOD: Subjects completed a semistructured intake questionnaire and sexual inventories, the Inventory to Diagnose Depression, and the Wender Utah Retrospective Scale for the diagnosis of childhood attention-deficit/hyperactivity disorder (ADHD). The lifetime prevalence of Axis I diagnoses of both sexual and nonsexual disorders was ascertained from the aforementioned data and follow-up psychiatric interviews. RESULTS: Subjects in both PA and PRD groups were diagnosed as having a lifetime prevalence of any mood disorder (71.7%), especially dysthymic disorder (66.7%); any anxiety disorder (43.3%), especially social phobia (28.3%); any psychoactive substance abuse disorders (45.0%), especially alcohol abuse (30.0%); and any impulse disorders NOS (25.0%), especially speeding/reckless driving (16.7%). The only diagnosis that statistically significantly distinguished the PA from the PRD sample (p = .01) was retrospectively diagnosed childhood ADHD, identified in 40.0% of the total sample (50.0% PA vs.16.7% PRD). Childhood ADHD was associated with the presence of educational and behavioral problems, lower current mean income, social/legal consequences associated with antisocial impulsivity, cocaine abuse, increased prevalence of comorbid lifetime mood and impulse disorder NOS, and more diagnoses of lifetime Axis I nonsexual and sexual disorders. CONCLUSION: Although depressive disorders were the most common Axis I diagnoses across groups, childhood ADHD was the only Axis I disorder statistically significantly associated with paraphilias, socially deviant and aggressive forms of sexual impulsivity.

Hypersexual desire in males: an operational definition and clinical implications for males with paraphilias and paraphilia-related disorders.

The longitudinal history and temporal stability of total sexual outlet (TSO) in a group of outpatient males with paraphilias (PA) and paraphilia-related disorders (PRD) was assessed. Based on extant normative data from contemporary population-based surveys of sexual behavior, it was hypothesized that a persistent TSO of 7 or more orgasms/week for a minimum duration of 6 months be considered as the lower boundary for hypersexual desire in males. In almost all statistical analyses, the PA (n = 65) and PRD (n = 35) groups were not statistically different. The mean current TSO (PA, 7.4 +/- 5.7; PRD, 8.0 +/- 4.2) as well as the current average time consumed in all unconventional sexual behaviors (1-2 hr/day) were not statistically different. Unconventional sexual behaviors (i.e., related to PAs or PRDs) leading to orgasm constituted 77% of current TSO. In the combined group (n = 100), 72% (n = 72) reported a hypersexual TSO of 7 or greater. Age of onset of hypersexual TSO in the PAs (19.2 +/- 6.8 years; range 10-43) and the PRDs (21.0 +/- 8.6; range 10-46) and the duration of hypersexual TSO (PA, 11.1 +/- 11.2 years; PRD, 10.5 +/- 9.1) were not significantly different. Fifty-seven males (57%) reported a TSO of 7 or more for a minimum duration of 5 years. Clinical implications of reconceptualizing PAs and PRD as sexual desire disorders are discussed.

Distamycin-A derivatives potentiate tumor-necrosis-factor activity via the modulation of tyrosine phosphorylation.

The cytotoxic activities of 2 novel distamycin-A derivatives, FCE 24517 and FCE 25450A, alone and in combination with tumor-necrosis factor-alpha (TNF), were studied. Both drugs, especially FCE 25450A, analyzed extensively here, inhibited the growth of HL60 promyelocytic cells, and human SV80 and murine L929 transformed fibroblasts in a dose-dependent manner. The growth-inhibitory potential of sequential exposure to the distamycin-A analogs and TNF was determined. A 4-hr treatment of L929 fibroblasts with 100-1,000 ng/ml FCE 25450A, followed by 2 ng/ml TNF, resulted in a synergistic anti-proliferative effect. The synergism of FCE 24517 with TNF was less profound. Experiments to elucidate the mechanism underlying the cooperation revealed that FCE 25450A pre-treatment almost completely abolished the elevated tyrosine phosphorylation of a 137-kDa and other membranal proteins and prevented the de-phosphorylation of another protein band observed in L929 cells in the presence of TNF. FCE 25450A alone induced no changes in the phosphotyrosine profile of the cells. The effect of FCE 25450A was counteracted by the tyrosine-phosphatase inhibitor orthovanadate. In parallel, the inhibitor also diminished the antiproliferative action of the FCE 25450A/TNF combination. These findings suggest that, beyond their cytotoxic effects as single agents, the distamycin derivatives increase the sensitivity of cells to TNF. This effect is governed via the inhibition of TNF-induced tyrosine phosphorylation of specific proteins which are probably involved in the development of TNF resistance. Thus, protein de-phosphorylation might provide an additional mechanism of action of these novel distamycin-A-derived drugs.

A monoamine hypothesis for the pathophysiology of paraphilic disorders.

A monoamine pathophysiological hypothesis for paraphilias in males is based on the following data: (i) the monoamines norepinephrine, dopamine, and serotonin are involved in the appetitive dimension of male sexual behavior in laboratory animals; (ii) data gathered from studying the side effect profiles of antidepressant psychostimulant, and neuroleptic drugs in humans suggest that alteration of central monoamine neurotransmission can have substantial effects on human sexual functioning, including sexual appetite; (iii) monoamine neurotransmitters appear to modulate dimensions of human and animal psychopathology including impulsivity, anxiety, depression, compulsivity, and pro/antisocial behavior, dimensions disturbed in many paraphiliacs; (iv) pharmacological agents that ameliorate psychiatric disorders characterized by the aforementioned characteristics, especially central serotonin enhancing drugs, can ameliorate paraphilic sexual arousal and behavior.

The roles of protein phosphorylation/dephosphorylation in tumor necrosis factor antitumor effects.

The roles of protein phosphorylation and dephosphorylation in the tumor necrosis factor (TNF) cytotoxic and antiproliferative effects on L-929-transformed fibroblasts were explored. Genistein and erbstatin, specific inhibitors of tyrosine kinase, had antiproliferative but not cytotoxic effects on the cells by themselves and synergistically enhanced the cytotoxic and antiproliferative effects of TNF-alpha. Immunoblot analysis with a monoclonal antiphosphotyrosine antibody revealed that TNF, administered for 5-180 min, induced tyrosine dephosphorylation of two pairs of membranal proteins, 34-36 kDa and 50-52 kDa, and potentiated tyrosine phosphorylation of a 115-kDa protein in both the cytosolic and membranal fractions of the cells. A very brief exposure (30 sec) to TNF induced rapid phosphorylation of several proteins, whereas genistein, but not inhibitors of other protein kinases, enhanced this effect of TNF. The results suggest that TNF activity could be potentiated by the inhibition of tyrosine phosphorylation and point to specific proteins that are dephosphorylated on tyrosine in response to TNF.

Preliminary observations of DSM-III-R axis I comorbidity in men with paraphilias and paraphilia-related disorders.

BACKGROUND: We describe a comorbidity study of DSM-III-R-defined Axis I diagnoses comparing male outpatient paraphiliacs to men with nonparaphilic forms of sexual impulsivity designated as paraphilia-related disorders. METHOD: Data were prospectively collected from 60 consecutively evaluated outpatient males, aged 21-53 years, seeking treatment for the principal disorders of paraphilias (N = 34) and/or paraphilia-related disorders (N = 26). Subjects completed a semistructured psychiatric Intake Questionnaire and Sexual Inventory. The lifetime prevalence of DSM-III-R Axis I diagnoses, including disorders of sexual impulsivity, was assigned by follow-up psychiatric interviews. RESULTS: Both groups of men were diagnosed with an elevated lifetime prevalence of mood disorders (76.7%), especially early-onset dysthymia (53.3%); psychoactive substance abuse (46.7%), especially alcohol abuse (40.0%); and anxiety disorders (46.7%), especially social phobia (31.6%). The predominant forms of sexual impulsivity reported by both groups were "nonparaphilic" paraphilia-related disorders: compulsive masturbation (73.3%), protracted promiscuity (70.0%), and dependence on pornography (53.3%). CONCLUSION: There were no major differences in lifetime Axis I diagnoses to differentiate men with paraphilic disorders from those with paraphilia-related disorders. Both groups were likely to acknowledge multiple paraphilias and/or multiple paraphilia-related disorders suggesting that sexual impulsivity has diverse manifestations, which can include culturally "deviant" as well as "normative" behaviors. Several hypotheses regarding the possible etiologic relationship between depressive disorders and sexual impulsivity are suggested.

[The birthing stool--an obstetrical risk?]. / Gebärhocker--ein geburtshilfliches Risiko?

During 1992, 140 women out of a total of 1122 used the delivery chair at the department for obstetrics and gynaecology at the LKH Mödling. We compared them to a control group in the supine position. In order to evaluate the safety of deliveries on the delivery chair, we studied the duration of the stages of labour, rate and degree of soft tissue injuries, maternal blood loss, fetal outcome and complications in the puerperium. The use of the delivery chair showed no increased risk to either the mother or the fetus and therefore represents an appropriate alternative to the traditional supine position for delivery.

Sertraline pharmacotherapy for paraphilias and paraphilia-related disorders: an open trial.

Twenty-four men with paraphilias (PA; n = 13) and paraphilia-related disorders (PRD; n = 11) were consecutively treated with sertraline (mean dose, 100 mg/day; mean duration, 17.4 +/- 18.6 weeks). Baseline depression severity, total sexual outlet (TSO), and average time per day (ATD) spent in unconventional sexual behavior were obtained. At outcome, sertraline produced a statistically significant reduction in unconventional TSO and ATD in both PAs and PRDs without adversely affecting conventional TSO. This therapeutic effect was independent of baseline depression severity score. Clinically significant improvement was reported by approximately one-half of the men who complied with at least 4 weeks of sertraline pharmacotherapy. Nine men who failed to respond to sertraline were subsequently given fluoxetine. Fluoxetine (mean dose, 50 mg/day; mean duration, 30 weeks) produced a clinically significant effect in 6 additional men. Overall, 17 of the 24 men (70.8%) who received pharmacological treatment with sertraline and/or fluoxetine for at least 4 weeks sustained a clinically significant response, at times lasting more than 1 year. The evolving role of selective serotonin reuptake inhibitors for the amelioration of sexual impulse disorders is discussed.

Rapid interferon-gamma-stimulated tyrosine phosphorylation of cytosolic and membranal proteins in HL-60 promyelocytic cells.

The involvement of tyrosine phosphorylation in the early stages of interferon-gamma (IFN gamma)-induced monocytic differentiation of HL-60 cells was studied. Immunoblotting analysis demonstrated that IFN gamma induced rapid changes in the tyrosine phosphorylation of several endogenous cytosolic and membranal proteins. The most prominent of these polypeptides was a 84 kDa protein. In membranes, the IFN gamma-induced phosphorylation of this protein was detectable in 5 min, remained elevated for 3 h and declined thereafter, while a gradual decrease in the phosphotyrosine content was observed in cytosols. In parallel, a 40% increase in the phosphotyrosine phosphatase activity was detected in the later stages of IFN gamma treatment. Rapid changes in tyrosine phosphorylation were detected also in a 64 kDa protein. In contrast, 2-day exposure to IFN gamma was needed to potentiate significantly the tyrosine phosphorylation of a 36 kDa membranal polypeptide. These data support the involvement of tyrosine phosphorylation in the early stages of IFN gamma-induced monocytic differentiation of HL-60 cells.

A comparative study of nonparaphilic sexual addictions and paraphilias in men.

BACKGROUND: A definition of nonparaphilic sexual addiction (NPSA) is offered and the literature suggesting comorbidity between NPSA and paraphilias (PAs) is reviewed. We describe a study to clarify the relationship between NPSA and PA. METHOD: Thirty consecutive male respondents to an advertisement (PA: N = 15; NPSA: N = 15) were evaluated. The frequency of sexual behaviors, total sexual outlet, intensity of sexual desire, time spent in unconventional sexual behaviors, and a total sexual interest ratio were measured. Group differences were statistically examined using the Fisher's exact probability test (one-tailed). Concomitant psychological, social, work, financial, legal, and medical sequelae were ascertained. RESULTS: The most prevalent lifetime sexual behaviors in both groups were NPSAs, especially compulsive masturbation, ego-dystonic promiscuity, and dependence on pornography. Mean total sexual outlet in both groups was approximately three times that of a comparable "normal" male sample. Components of total sexual outlet were reported in a nonnormative distribution pattern, and NPSA/PA sexual behaviors eclipsed conventional sexual activities in all measures. Group differences in measures of sexual behavior frequency, intensity, and time consumed by these behaviors were not statistically significant. CONCLUSION: The cormorbid presence of multiple NPSAs in 93% of the paraphilic men accompanied by comparable sexual and psychosocial sequelae suggests that NPSAs may represent a culturally adapted form of psychopathology that can also be manifested as PAs. A definition of hypersexual desire is offered, and a relationship between hypersexual desire and unconventional sexual outlet is suggested.