The effect of adalimumab on the vasculature in psoriatic skin lesions.

BACKGROUND: Vascular proliferation is considered an important feature in psoriasis. Early psoriatic changes are characterized by vascular network expansion; healing of the lesions ultimately results in a decreasing size of the vascular network. Currently, the response of the vasculature in psoriatic lesions during treatment of adalimumab is still obscure. OBJECTIVE: To investigate the response of the vasculature in psoriatic lesions during adalimumab treatment, using parameters such as endothelial cell proliferation, vascular network size and alternations in vessel diameter. METHODS: The endothelial cell response (endothelial cell proliferation rate, vascular network size and vessel diameter) was studied, using an immunohistochemical double-staining of Ki67/CD31, in subsequent biopsies of psoriatic lesions from 10 patients treated with adalimumab at baseline, 10 days and 16 weeks after initiation of treatment. RESULTS: In active psoriatic skin the endothelial cell proliferation ratio is high and an increased vascular network size and vessel diameter is found. An evident decrease in all these parameters is found during 16 weeks treatment with adalimumab. Keratinocyte proliferation already decreased significantly and substantially after 10 days treatment. DISCUSSION: Adalimumab treatment of psoriasis causes an evident reduction in endothelial cell proliferation, vascular network size and vessel diameter, parallel to the clinical improvement. Vascular parameters do not capture early improvement to adalimumab treatment, however (non-)invasive measurement of vascular function parallels, the clinical improvement and may be a valuable marker for disease activity.

[Practice assistant sometimes misses urgent request for help: telephone triage in general practice]. / Doktersassistent mist soms hoogurgente hulpvraag.

OBJECTIVE: To assess the organisation and appropriateness of telephone triage in general practices in the Netherlands. DESIGN: Cross-sectional observational study. METHODS: Via e-mail we invited all members of the Dutch Association of practice assistants to complete an online survey. The questionnaire included questions about practice assistants' background characteristics and the practices' triage organisation. Furthermore, they were asked to assess the indicated type of care for a number of fictive case scenarios involving a variety of health problems and levels of urgency. To determine the appropriateness of the respondents' assessments, each was compared to a reference standard agreed by experts. In addition, the association between practice assistants' background characteristics and organizational setup of the triage organisation with the appropriateness of triage was examined. RESULTS: The response rate was 41.1% (N=973). The required care was assessed appropriately in 63.6% of the cases, over-estimated in 19.3% and under-estimated in 17.1% of cases. The sensitivity of identifying patients with a highly urgent problem was 76.7%, whereas the specificity was 94.0%. The appropriateness of the assessments of the required care was higher for more experienced assistants and assistants with regular daily work meetings with the GP. Triage training, use of a triage tool and authorization of advice provision were not associated with appropriateness of triage. CONCLUSION: Triage by practice assistants in general practices is efficient, but potentially unsafe in highly urgent cases. It is therefore important to train practice assistants in the identification of highly urgent cases.

Polychlorinated biphenyl exposure and corticosterone levels in seven polar seabird species.

The role of polychlorinated biphenyls (PCBs) on exposure-related endocrine effects has been poorly investigated in wild birds. This is the case for stress hormones including corticosterone (CORT). Some studies have suggested that environmental exposure to PCBs and altered CORT secretion might be associated. Here we investigated the relationships between blood PCB concentrations and circulating CORT levels in seven free-ranging polar seabird species occupying different trophic positions, and hence covering a wide range of PCB exposure. Blood ∑7PCB concentrations (range: 61-115,632 ng/g lw) were positively associated to baseline or stress-induced CORT levels in three species and negatively associated to stress-induced CORT levels in one species. Global analysis suggests that in males, baseline CORT levels generally increase with increasing blood ∑7PCB concentrations, whereas stress-induced CORT levels decrease when reaching high blood ∑7PCB concentrations. This study suggests that the nature of the PCB-CORT relationships may depend on the level of PCB exposure.

[Immunological analogies between ovarian cancer and pregnancy]. / Analogies immunologiques du cancer de l'ovaire et de la grossesse.

During pregnancy an environment allowing installation of tolerance toward the fetus is set up locally at the materno-fetal interface. Numerous effectors of immunity are involved in this tolerance (NK cell, T cell, Macrophages, dendritic cell). Specific mechanisms during pregnancy attract locally these immunological cells. In the decidua, they are educated toward tolerance. These mechanisms evolve during the pregnancy because at the end of the pregnancy, tolerance is broken to prepare and activate the labor. Ovarian tumors, after having surmounted the immunosurveillance, like trophoblast, chair the installation of a tolerance of their host facilitating the development of the disease. The blocking of these mechanisms of tolerance coupled with activation of mechanisms of defenses offer new perspectives in the treatment of the ovarian cancer. The authors suggest showing the analogies of the tolerance observed during ovarian cancer and pregnancy. The knowledge of the orchestration of the physiological mechanisms observed during pregnancy will offer new therapeutic targets.

Reproducibility of a cough and jump stress test for the evaluation of urinary incontinence.

INTRODUCTION AND HYPOTHESIS: The study seeks to determine whether a urinary cough and jump stress test is reproducible and whether there is a relationship between a stress test and a 24-h pad test and our subjective Stress Incontinence Index. METHODS: Multicenter prospective cohort study of women with subjective stress incontinence. Each patient completed a validated Stress and Urge Incontinence Questionnaire and a 24-h pad test and performed two standardized cough and jump stress tests. RESULTS: All 108 women were incontinent during both the first and second stress tests. There was a large variation in leakage and the leakage was significantly larger during stress test 2 than during stress test 1 (P < 0.02). Correlations found between the stress test and the 24 hour pad test and between the stress test and the Stress Incontinence Index were poor. CONCLUSION: The cough and jump stress test is reproducible and able to document stress leakage.

Immune function and organochlorine pollutants in Arctic breeding glaucous gulls.

Organochlorine contaminants (OCs) are known to affect the immune systems of wildlife, and in this study we assessed the relationship between blood concentration of different OCs and measurements relevant to immune status and function in arctic breeding glaucous gulls (Larus hyperboreus). In 1997 and 2001, we counted white blood cells (heterophils and lymphocytes) from blood smears, and in 2000 and 2001 we injected two novel nonpathogenic antigens (diphtheria and tetanus toxoids) into the pectoral muscle of gulls and measured the primary antibody responses. We then related these measurements to the blood concentrations of three pesticides (hexachlorobenzene [HCB], oxychlordane, and p,p'-dichlorodiphenyldichloroethylene) and seven different polychlorinated biphenyl congeners (PCB 101, 99, 118, 153, 138, 180, and 170). There were significant or near significant positive relationships (0.1 > p > 0.001) between most persistent OCs and the levels of heterophils in the blood for both sexes in 1997 and for male gulls in 2001. Similarly, levels of all persistent OCs and lymphocytes were positively related (0.1 > p > 0.001) in both sexes in 1997. This suggests that OCs are causing alterations to immune systems, which may decrease their efficiency and make the birds more susceptible to parasites and diseases. In female gulls, the antibody response to the diphtheria toxoid was significant and negative for HCB (p < 0.01) and weaker, but significant, for oxychlordane (p < 0.05), suggesting that OCs were causing an impairment of the humoral immunity. Various OCs have been linked to negative effects in our study population, including decreased survival and reproduction, and this study suggests that such compounds also affect immune status and function.

HVAC--the importance of clean intake section and dry air filter in cold climate.

UNLABELLED: HVAC systems, if properly designed, installed, operated and maintained, will improve thermal conditions and air quality indoors. However, the success strongly depends on the design of the system and the quality of the components we use in our HVAC installations. Regrettably, several investigations have revealed that many HVAC installations have a lot of operational and maintenance problems, especially related to moisture, rain and snow entrainment. In short, it seems that too little attention is placed on the design of the intake section, despite the fact that there exists a large number of national and international guidelines and recommendations. This is a serious problem because the air intake is the initial component of the ventilation plant and as such the first line of defense against debris and other outdoor air pollutants. Unfortunately, the design is often an argued compromise between the architect, the civil engineer and the HVAC engineer. In the future, the technical, hygienic and microbiological feature of air intakes must be better ensured in order to avoid the air intake becoming a risk component as regards contamination and indoor air quality. Further, it seems that the magnitude of the problem is not well known, or recognized, by the building designers, engineers and professionals involved in the construction and operation of buildings. This fact needs to be addressed more seriously, because obviously there is a big difference between the idealistic architectonic design, engineering intentions and the real life situation. PRACTICAL IMPLICATIONS: Several practical recommendations for design and operation of HVAC systems are presented. Following the recommendations will result in less pollution from the HVAC-system and increased indoor environmental quality.

Ventilation and health in non-industrial indoor environments: report from a European multidisciplinary scientific consensus meeting (EUROVEN).

Scientific literature on the effects of ventilation on health, comfort, and productivity in non-industrial indoor environments (offices, schools, homes, etc.) has been reviewed by a multidisciplinary group of European scientists, called EUROVEN, with expertise in medicine, epidemiology, toxicology, and engineering. The group reviewed 105 papers published in peer-reviewed scientific journals and judged 30 as conclusive, providing sufficient information on ventilation, health effects, data processing, and reporting, 14 as providing relevant background information on the issue, 43 as relevant but non-informative or inconclusive, and 18 as irrelevant for the issue discussed. Based on the data in papers judged conclusive, the group agreed that ventilation is strongly associated with comfort (perceived air quality) and health [Sick Building Syndrome (SBS) symptoms, inflammation, infections, asthma, allergy, short-term sick leave], and that an association between ventilation and productivity (performance of office work) is indicated. The group also concluded that increasing outdoor air supply rates in non-industrial environments improves perceived air quality; that outdoor air supply rates below 25 l/s per person increase the risk of SBS symptoms, increase short-term sick leave, and decrease productivity among occupants of office buildings; and that ventilation rates above 0.5 air changes per hour (h-1) in homes reduce infestation of house dust mites in Nordic countries. The group concluded additionally that the literature indicates that in buildings with air-conditioning systems there may be an increased risk of SBS symptoms compared with naturally or mechanically ventilated buildings, and that improper maintenance, design, and functioning of air-conditioning systems contributes to increased prevalence of SBS symptoms.

The clinical value of ambulatory urethral pressure recording in women.

The value of ambulatory urethral pressure recording (AUPR) was evaluated by reviewing both data from 116 patients investigated and Ambulatory Urodynamic Monitoring (AUM) tracings. Typical tracings are shown from conditions where we find that AUPR is of value. (i) Stress incontinence where a patient who complains of stress incontinence does not leak during the stress test, but leaks while jumping on a trampoline. (ii) Mixed incontinence--in only 43% of patients complaining of both urge ands stress incontinence mixed incontinence was documented by AUM. Thirty-six per cent of patients complaining of both urge and stress incontinence were found to be stress incontinent and 21% were leaking due to an unstable detrusor. (iii) Urethral closure pressure of 20 cmH2O or less (low urethral closure pressure; LUCP). LUCP was found in 13% of the patients. Patients with LUCP may leak due to stress, unstable detrusor or unstable urethra. We conclude that ambulatory recording of both urethral and bladder pressures in addition to leakage may contribute to a more complete diagnosis and treatment in these conditions.

Evaluation of the subjective and objective effect of maximal electrical stimulation in patients complaining of urge incontinence.

BACKGROUND: Favorable results have been reported following Maximal Electrical Stimulation (MES) of patients with urgency and urge incontinence. However, patient groups have often been mixed and outcome measures poorly defined. We therefore wanted to treat a homogeneous patient population with MES and evaluate the effect by defined subjective and objective outcome measures. METHODS: Eighteen female patients complaining of urge incontinence had MES performed. Before and 3 months after MES, the patients performed a 24 hour micturition chart and pad test. They indicated on a visual analogue scale their subjective degree of urgency and leakage and had an ambulatory urodynamic monitoring performed. Nine months after MES the patients were asked whether their urge incontinence was less, equal or more troublesome than before MES. RESULTS: After MES the patients indicated significantly less urgency and leakage. A significant difference was not found in any of the objective outcome measures after MES. Six out of 18 patients (33%) found their urge incontinence less troublesome 9 months after MES, while 12 (66%) found it unchanged or more troublesome than before. CONCLUSIONS: Significantly subjective effect was found following MES. However, none of the objective outcome measures were significantly improved. We were disappointed by the results and have stopped using the method.

Long-term effects ten years after maximal electrostimulation of the pelvic floor in women with unstable detrusor and urge incontinence.

OBJECTIVE: The purpose was to study any long-term therapeutic effects of maximal electrical stimulation in female urge incontinence. METHODS: A postal questionnaire containing six questions about urinary incontinence was distributed to 30 women who had been treated with maximal stimulation because of unstable detrusor and urge incontinence 9-13 years earlier. The response rate was 90% (27 women). The mean age at follow-up was 62 years. RESULTS: Twenty-one (78%) women reported symptoms of urge incontinence. Among them, 13 had this problem daily, whereas eight only had problems weekly or even more seldom. Nineteen (70%) women reported symptoms of stress incontinence. Twenty-one women would have recommended maximal stimulation to a friend today. CONCLUSION: After approximately ten years most of the women had symptoms of urge incontinence. This was, however, a minor problem among a third of them. A majority of the women were satisfied with maximal stimulation as a treatment modality. The treatment had not prevented a later occurrence of stress incontinence.

Aspects on the actual practice of surgical management of urinary incontinence in Norway and Finland.

OBJECTIVE: To elucidate aspects of the actual practice of surgical management of urinary incontinence in Norway and Finland. METHOD: A questionnaire about preoperative diagnostic procedures, type of surgery, follow-up procedure and number of operations per center and per surgeon per year (1995) was sent to all departments of Gynecology and Obstetrics in Norway and Finland. RESULT: Thirty-one (86%) of the Norwegian and 26 (90%) of the Finnish departments returned the questionnaire. More than 90% of the departments performed preoperative urodynamic evaluation. Burch colposuspension was used by more than 90% of the departments in the two countries. Generally the number of procedures per center and per department was low. Twenty-nine and 12% of the departments respectively did not perform any follow-up after surgery. Only 16% of the Norwegian and 23% of the Finnish centers had controlled results of surgery. CONCLUSION: There seems to be a need for criteria of good clinical practice or a reference program for all steps of surgical management of stress incontinence in order to stimulate the process of quality development of this treatment.

Reliability and validity of stationary cystometry, stationary cysto-urethrometry and ambulatory cysto-urethro-vaginometry.

OBJECTIVE: The purpose of this article is to evaluate the reliability and validity of stationary cystometry, stationary cysto-urethrometry and ambulatory cysto-urethro-vaginometry for the diagnosis of urinary incontinence. MATERIAL AND METHODS: Literature search on reproducibility of cystometry is based on articles written in the English language found in Medline from 1987 to 1993. Five articles were found. These articles had references for another 6 older articles about the same topic. One recently published article is evaluated as well. Data about reproducibility of cystometry performed in these studies are given. Knowledge of reproducibility of cystometry combined with urethrometry, urethro-vagino or rectometry with leak detection during stationary or ambulatory recording is given. An evaluation of validity of the different methods is presented. RESULTS AND CONCLUSION: Conflicting data has been found for sensory parameters of stationary cystometry such as volume or pressure at first desire to void, strong desire to void and maximum cystometric capacity. No data were found concerning the reliability of cystometry for the recording of urinary incontinence. The main problem of urge-incontinent patients is leakage with a strong feeling of urgency. The recording of sensory parameters by cystometry is not valid when the main problem is urge incontinence. Cystometry will be valid for the diagnosis of urge incontinence when a leak detector is used or a mark is made at the tracings when leakage is observed. The reliability of cystometry concerning urge incontinence should be documented. The reliability of a urethral pressure recording when the urethral catheter is extracorporally fixed is low. The reliability and validity of ambulatory cysto-urethro-vaginometry in diagnosing urge incontinence, unstable urethra and genuine stress incontinence seems to be good, but needs better documentation.

Ambulatory urodynamic monitoring of women.

A review of articles concerning ambulatory urodynamic monitoring (AUM) is given AUM, as we practice it, is described. Typical findings in normal continent women, in patients with genuine stress incontinence, unstable detrusor, mixed incontinence, low closure pressure, unstable urethra and during sitting, jumping, and running are given. AUM is indicated and is superior to conventional cystometry in urge incontinent patients and in patients with a supine closure pressure lower than 20 cm H2O. AUM is also indicated in stress incontinent patients not leaking during stress test. AUM may be valuable in drug effect studies and in the study of normal physiology. Abnormalities which are not disclosed with conventional techniques may better be detected by AUM when patients are at their case alone, free from medical observers or are physically or mentally stressed in the situation they usually leak. AUM may, because of the recording of both urethral and bladder pressures, contribute to a more complete understanding of the leak mechanisms.

Clinical and urodynamic assessment of nulliparous young women with and without stress incontinence symptoms: a case-control study.

OBJECTIVE: To assess the prevalence of stress urinary incontinence symptoms in young, nulliparous, physically fit women, evaluate their clinical and urodynamic characteristic, and compare them to a matched asymptomatic control group. METHODS: All first-year physical education students (N = 37) were asked to participate in a four-step study on urinary incontinence. The study included an interview, a clinical examination (incorporating an assessment of pelvic floor muscle strength), ambulatory urodynamics during exercise, and a needle electromyographic assessment of pelvic floor muscles and the striated urethral wall muscle with simultaneous urethral and bladder-pressure measurements. RESULTS: Thirteen (38%) subjects reported stress urinary incontinence symptoms. Eight of the 13 reported the condition to be a social or hygienic problem; six experienced leakage more than once a week. The mean quantity of leakage of the symptomatic women during ambulatory urodynamics was 12 g (range 0-43). No uninhibited detrusor contractions were detected during leakage episodes. Six of seven subjects with symptoms were found to have urodynamic evidence of urethral sphincteric incompetence. There were no differences between the symptomatic and the control group in body mass index, percent body fat, pelvic floor muscle strength, menstrual cycle, and electromyographic patterns. Four of seven women in the symptomatic group had benign hypermobility joint syndrome, whereas there were none in the control group. CONCLUSION: Physically fit nulliparous women have a high prevalence of stress incontinence symptoms and evidence of urethral sphincteric incompetence.