Impairment of Immune Function in Harbor Seals (Phoca vitulina) Feeding on Fish from Polluted Waters

Disease outbreaks with high mortality rates among seals and dolphins have recently attracted considerable public and scientific interest. Allhouyh in most cases morbillivirus infections were shown to be the primary cause of the disease outbreaks, it was speculated that pollution-induced immunosuppression had playat:! a contributory role. Here we present results of a prospective study under semifield conditions, in which two groups of harbor seals (Phoca vitulina) were fed herring from marine regions with different contamination levels; the hig

Determinants of potential drug–drug interaction associated dispensing in community pharmacies in the Netherlands

OBJECTIVE: There are many drug–drug interactions (D–DI) of which some may cause severe adverse patient outcomes. Dispensing interacting drug combinations should be avoided when the risks are higher than the benefits. The objective of this study was to identify determinants of dispensing undesirable interacting drug combinations by community pharmacies in the Netherlands. METHODS: A total of 256 Dutch community pharmacies were selected, based on the dispensing of 11 undesirable interacting drug combinations between January 1st, 2001 and October 31st, 2002. These pharmacies were sent a questionnaire by the Inspectorate for Health Care (IHC) concerning their process and structure characteristics. MAIN OUTCOME MEASURE: The number of times the 11 undesirable interacting drug combinations were dispensed. RESULTS: Two hundred and forty-six questionnaires (response rate 96.1%) were completed. Dispensing determinants were only found for the D–DI between macrolide antibiotics and digoxin but not for the other 10 D–DIs. Pharmacies using different medication surveillance systems differed in the dispensing of this interacting drug combination, and pharmacies, which were part of a health care centre dispensed this interacting drug combination more often. CONCLUSION: Medication surveillance in Dutch community pharmacies seems to be effective. Although for most D–DIs no determinants were found, process and structure characteristics may have consequences for the dispensing of undesirable interacting drug combinations

Exploring sources of heterogeneity in systematic reviews of diagnostic tests

It is indispensable for any meta-analysis that potential sources of heterogeneity are examined, before one considers pooling the results of primary studies into summary estimates with enhanced precision. In reviews of studies on the diagnostic accuracy of tests, variability beyond chance can be attributed to between-study differences in the selected cutpoint for positivity, in patient selection and clinical setting, in the type of test used, in the type of reference standard, or any combination of these factors. In addition, heterogeneity in Study results can also be caused by flaws in study design. This paper critically examines some of the potential reasons for heterogeneity and the methods to explore them. Empirical support for the existence of different sources of variation is reviewed. Incorporation of sources of variability explicitly into systematic reviews on diagnostic accuracy is demonstrated with data From a recent review. Application of regression techniques in meta-analysis of diagnostic tests can provide relevant additional information. Results of such analyses will help understand problems with the transferability of diagnostic tests and to point out flaws in primary studies. As such, they can guide the design of future studies. Copyright (C) 2002 John Wiley Sons, Lt

A prospective evaluation of anorectal function after total mesorectal excision in patients with a rectal carcinoma

Background. Rectum resection with total mesorectal excision (TME) and neorectal anastomosis often compromises anorectal function. Insight into the underlying mechanisms is lacking. Therefore, a prospective study was designed to investigate the relationship between clinical and functional outcomes preoperatively and postoperatively. Methods. Eleven patients with rectal cancer were examined before and 4 and 12 months after surgery and compared with 11 healthy volunteers (HVs). Anorectal (neorectal) function was examined by clinical outcome questionnaire, anal manometry, rectal compliance, and sensation. Six HVs also underwent barostat measurements in the sigmoid colon. Results. Clinical parameters of soiling and passive incontinence (loss of stool without sensation) increased significantly until 12 months postoperatively, whereas urgency and tenesmus increased temporarily, returning to preoperative values at 12 months. In anorectal measurements, anal sphincter function was grossly preserved; however, rectal-anal inhibitory reflex (RAIR) was decreased at 4 months but recovered after 1 year. Neorectal compliance was similar to that of HV sigmoid, increasing slightly after 12 months but still significantly lower than that of normal rectum. Neorectal sensation to pressure distention was similar to that of normal rectum, however accompanied by smaller volumes. Neorectal distention induced contractions of large amplitude at 4 months, returning to normal after 12 months. Conclusions. Our results suggest that the transient increase in urgency and tenesmus after surgery results from a temporary increase in neorectal "irritability " accompanied by some adaptation of compliance in time. In contrast, episodes of incontinence and soiling are increased after I year most likely because of reduced neorectal capacity and RAIR recovery in the presence of a low basal anal sphincter pressur

Facial disfigurement: is it in the eye of the beholder? A study in patients with Graves' ophthalmopathy

OBJECTIVES The importance of facial disfigurement in many diseases necessitates a reliable and valid measure of disfigurement severity for clinical studies. The hypothesis is that a universal concept of disfigurement exists and can be measured in a reliable way. The objectives of this study were to investigate if persons, in particular patients and physicians, can agree on facial disfigurement severity; and to determine the relative contribution of predefined clinical characteristics of patients with Graves' ophthalmopathy (GO) to the overall rating of facial disfigurement severity. DESIGN A panel study was carried out in four different panels, each consisting of four members. PATIENTS We randomly selected 100 slide pairs of GO patients from four available study populations, involving mild, moderate and severe GO patients (mean age 49 years, 76% female) who were treated with either radiotherapy, sham-irradiation, prednisone or orbital decompression. MEASUREMENTS All panel members individually scored the disfigurement severity of 100 GO patients shown on standardized slides on a Visual Analog Scale. In total, 1600 ratings were collected. We calculated within- and between-panel agreement of disfigurement severity and identified determinants of disfigurement. RESULTS Agreement within a panel varied from 0.65 to 0.79 and was highest within the panel of ophthalmologists. Between-panel agreement was 0.67 and was highest between ophthalmologists and laypersons. Compared with the global average, patients overrated and endocrinologists underrated disfigurement severity. Female panellists rated the patients, on average, more disfigured than male panellists. Important determinants of disfigurement were eyelid retraction, severe eyelid swelling and proptosis. Their relative importance was consistent across panels and in contrast to current measures of GO severity. CONCLUSION Facial disfigurement severity can be measured in a reliable way using panels of panellists. Except for some systematic differences between panellists, facial disfigurement does not seem to be in the eye of the beholde

Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: A randomised placebo-controlled trial

Background: Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection. Methods: In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, ω3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0.4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol. Findings: Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92-128]) than those given the control (69% [58-82]) compared with baseline (100%) (p=0.02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0.90 pg/L [0.69-1.18]) than in the control group (1.94 pg/L [1.45-2.59]) (p=0.032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge. Interpretation: Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery

Human herpesvirus 8 infections in the Amsterdam Cohort Studies (1984–1997): Analysis of seroconversions to ORF65 and ORF73

We have shown previously that human herpesvirus 8 (HHV8) seroconversion for antibodies to the latency-associated nuclear antigen encoded by ORF73 and/or the lytic capsid antigen (vp19) encoded by ORF65 is associated with orogenital contact and is strongly linked to the development of Kaposi's sarcoma among HIV-infected individuals in the Amsterdam Cohort Studies. Here, we investigate the relationship between seroconversion to these antigens and primary HHV8 infection. Between 1984 and 1997, 215 HHV8 seroconversions to ORF73 (106 cases or 49%) and/or to ORF65 (159 cases or 74%) were recorded in the cohort of homosexual men. The HHV8 seroconversion rate among HIV-infected homosexual men (6.2 per 100 person years) was consistently higher than among HIV-uninfected men (2.6 per 100 person years). In HIV-infected but not in uninfected individuals, seroconversion to ORF73/latency-associated nuclear antigen precedes that to ORF65/vp19. Antibody levels to both ORF65- and ORF73-encoded antigens were higher in HIV-infected than in HIV-uninfected men, and among HIV-seropositives, antibody levels to ORF65/vp19 rise even higher with declining CD4 cell counts and peak with Kaposi's sarcoma development, suggesting continuing and increasing viral replication. In 10.3% of HHV8 seroconversions, transient serum viremia could be demonstrated before or at seroconversion. Together with the previously reported link between unprotected orogenital sex and HHV8 seroconversion, our observations suggest that HHV8 seroconversions result from primary infections

Phenacetin acts as a weak genotoxic compound preferentially in the kidney of DNA repair deficient Xpa mice.

Chronic use of phenacetin-containing analgesics has been associated with the development of renal cancer. To establish genotoxicity as a possible cause for the carcinogenic effect of phenacetin, we exposed wild type and DNA repair deficient Xpa-/- and Xpa-/-/Trp53+/- mice (further referred as Xpa and Xpa/p53 mice, respectively), carrying a reporter lacZ gene, to 0.75% (w/w) phenacetin mixed in feed. Xpa mice completely lack the nucleotide excision repair pathway, and as such they are sensitive to some classes of genotoxic compounds. Phenacetin exposure induced a significant increase of lacZ mutations in the kidney of both Xpa and Xpa/p53 mice. A minor response was found in liver, whereas no lacZ mutation induction was observed in the spleen of these animals. Interestingly, the observed phenacetin-induced mutant frequencies were higher in male than those found in female mice. This gender difference is probably due to a difference in metabolic rate. Phenacetin-induced mutations mainly consisted of point mutations rather than deletions. The mutational spectra in the kidney of treated WT and Xpa mice were quite similar. Taken together, these results demonstrate that the human carcinogen phenacetin acts as a weak genotoxic agent in an in vivo mouse model system