Peritoneal carcinomatosis from colorectal or appendiceal origin: correlation of preoperative CT with intraoperative findings and evaluation of interobserver agreement

BACKGROUND AND OBJECTIVES: In patients with colorectal cancer, it is important to diagnose peritoneal carcinomatosis as well as to detect location and size of peritoneal tumor dissemination in view of treatment planning. The aim of this study was to investigate the detection accuracy of computed tomography (CT). METHODS: Preoperative CT-scans from 25 consecutive patients with peritoneal carcinomatosis from colorectal or appendiceal origin were independently blindly reviewed by 2 radiologists. The presence and diameter of tumor deposits were noted in seven abdominopelvic areas. Intraoperative findings were regarded as the gold standard. Agreement was assessed using the Kappa index and the chi-square test. RESULTS: The presence of peritoneal carcinomatosis was detected in 60 and 76% of those patients by each of the radiologist. Detection of individual peritoneal implants was poor (kappa = 0.11/0.23) and varied from 9.1%/24.3% for tumor size <1 cm to 59.3%/66.7% for tumor size >5 cm. Overall sensitivity, specificity, accuracy, positive (PPV) and negative predictive value (NPV) for tumor involvement per area were 24.5%/37.3%, 94.5%/90.4%, 53.0%/60.0%, 86.2%/84.4%, and 47.3%/50.8%, respectively. Accuracy of tumor detection varied widely per anatomic site. Statistically significant interobserver differences were noted, specifically for tumor size of 1-5 cm (P = 0.007) and localization on mesentery and small bowel (kappa = 0.30, P = 0.04). CONCLUSIONS: In colorectal cancer, CT detection of peritoneal carcinomatosis is moderate and of individual peritoneal tumor deposits poor. Interobserver differences are statistically significant. Therefore, preoperative CT seems not to be a reliable tool for detection of presence, size, and location of peritoneal tumor implants in view of treatment planning in patients with colorectal cancer.     

Subjective sleep disturbance in patients with partial epilepsy: a questionnaire-based study on prevalence and impact on quality of life

PURPOSE: This study was designed to assess whether sleep disturbance is more frequent among patients with partial seizures and what impact on quality of life (QoL) sleep disturbance may have on patients with partial seizures. METHODS: Questionnaire booklets were mailed to 1,183 patients from four Dutch clinics. Each patient was asked to find two age- and gender-matched controls to complete the same set of questionnaires [Sleep Diagnosis List (SDL), Medical Outcomes Study (MOS)-Sleep Scale, Groningen Sleep Questionnaire, Epworth Sleepiness Scale, and the SF-36 Health Survey]. The prevalence of sleep disturbance, based on the SDL, was compared between those with partial epilepsy and controls. Mean scores on sleep and the SF-36 Physical (PCS) and Mental (MCS) Component Summary scales were compared. RESULTS: Responses from 486 patients and 492 controls were analyzed. Respondents with partial epilepsy had a highly significant, twofold higher prevalence of sleep disturbance compared with controls (38.6 vs. 18.0%; p < 0.0001). Most sleep-disorder subscales showed significant abnormalities in respondents with epilepsy, compared with controls. Mean SF-36 MCS and PCS scores were significantly lower in respondents with epilepsy compared with controls in both the strata with sleep disturbance and without (all p values <0.05). The presence of a sleep disturbance in respondents with epilepsy was associated with the greatest impairment in QoL. CONCLUSIONS: Sleep disturbance is more than twice as prevalent in persons with partial epilepsy compared with controls, and most domains of sleep are significantly disturbed. Persons with partial epilepsy have significant QoL impairment, and sleep disturbance further compounds this.     

Farmers are at risk for anxiety and depression: the Hordaland Health Study

AIMS: To examine whether, and why, farmers and non-farmers differ regarding levels of anxiety and depression. METHODS: The study encompassed 17 295 workers age 40-49 years, including 917 farmers, from the population-based Hordaland Health Study 1997-99 (HUSK). Levels of anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively). Self-reported information on various work-related factors, demographics, lifestyle and somatic health problems was included. The main analytical methods were univariate analysis of variance (ANOVA)/Kruskal-Wallis test, chi(2)/Fisher's exact test and logistic regression. RESULTS: Compared with non-farmers, farmers had higher levels and prevalences of depression, particularly the male farmers, who also had higher anxiety levels. Among men, farmers reported longer work hours, lower income, higher psychological job demands and less decision latitude compared with non-farmers. Farmers had physically heavier work and a lower level of education than non-farmers. Generally, the differences were largest between full-time farmers and non-farmers. Differences in anxiety and depression levels between male full-time farmers and non-farmers could be explained by the farmers' longer work hours, physically harder work and lower income. CONCLUSIONS: Farming is associated with increased levels of anxiety and increased levels and prevalences of depression. As regards depression, preventative measures and screening for cases in need of treatment should be strongly considered.     

In vitro evaluation of a hydroxypropyl cellulose gel system for transdermal delivery of timolol

In this work, the development of a gel reservoir for a timolol (TM) transdermal iontophoretic delivery system is investigated. TM gel is prepared using hydroxypropyl cellulose (HPC) and the permeability of TM from the gel through an artificial membrane (Polyflux) and pig stratum corneum (SC) is studied. For a constant TM donor concentration, the TM transport across the Polyflux membrane alone decreases when the concentration of the gel increases due to increase of the gel viscosity. For constant gel concentration, however, the TM permeation across the membrane increases when the TM donor concentration increases. In addition, no effect of the electrical current (iontophoresis, current density 0.5 mA cm-2) on the TM permeation is found. For the combination of the Polyflux membrane with pig SC, the TM transport is much lower than for the membrane alone and the SC fully controls the TM delivery. In this case, the application of electrical current enhances the TM delivery 13-15 times in comparison to passive (no current) transport. According to our estimation, the daily TM dose (10-60 mg) can be delivered by an iontophoretic patch with Polyflux membrane area of 6-36 cm2 containing 20% (w/w) HPC gel and 15 mg cm-3 of TM.     

1-alkyl-4-acylpiperazines as a new class of imidazole-free histamine H(3) receptor antagonists

With the aim of identifying structurally novel, centrally acting histamine H(3) antagonists, arrays of monoacyldiamines were screened. This led to the discovery of a series of 1-alkyl-4-acylpiperazines which were potent antagonists at the human histamine H(3) receptor. The most potent amides had antagonist potencies in the subnanomolar range.     

Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients

Some breast cancer survivors experience cognitive decline following chemotherapy. We prospectively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTC group; n = 28) or standard-dose chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC group; n = 39); stage-I breast cancer patients who had received no systemic chemotherapy (no-CT group; n = 57); and healthy control subjects (n = 60). All patients underwent neuropsychologic testing before and 6 months after treatment (12-month interval); control subjects underwent repeated testing over a 6-month interval. No differences in cognitive functioning between the four groups were observed at the first assessment. More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time (25% versus 6.7%; odds ratio [OR] = 5.3, 95% confidence interval [CI] = 1.3 to 21.2, P = .02). No such difference was observed for the FEC or the no-CT groups (FEC versus control: OR = 2.2, 95% CI = 0.5 to 9.1, P = .27; no-CT versus Control: OR = 2.2, 95% CI = 0.6 to 8.0; P = .21). Some cytotoxic treatment for breast cancer affects cognition in a subset of women.     

High plasma concentrations of human urotensin II do not alter local or systemic hemodynamics in man

OBJECTIVE: Human urotensin II (hUII) is an endocrine hormone that acts as a potent arterial vasoconstrictor in both in vitro and in vivo studies in animals. We examined, for the first time, the local and systemic hemodynamic response to hUII in man in vivo. METHODS: Four healthy male volunteers took part in pilot studies and 11 in definitive studies. Forearm blood flow (FBF) was measured in response to intra-arterial infusion of authentic, biologically active hUII (incremental rates of 0.001-300 pmol min(-1)) and saline placebo using venous occlusion plethysmography. Blood pressure, heart rate, cardiac output and hUII plasma concentrations were also measured. Forearm studies were repeated in five subjects with inhibition of endothelial mediators using aspirin and a "nitric oxide clamp". Dorsal hand vein diameter was determined by a standard displacement technique in response to local administration of hUII (3-300 pmol min(-1)) with and without nitric oxide synthase inhibition. RESULTS: There was no significant change in FBF during brachial infusion of saline or hUII (dose range, 0.001 to 300 pmol min(-1)). A nitric oxide clamp did not unmask vasoactive effects of hUII. Human UII infusions (100 and 300 pmol min(-1)) significantly increased plasma hUII concentrations from baseline (12 +/- 3 pmol l(-1)) to 106 +/- 15 and 307 +/- 98 pmol l(-1), respectively. Despite high circulating hUII concentrations, no change was seen in systemic hemodynamics and ECGs were unchanged. Human UII had no effect on hand vein diameter (n=6). CONCLUSIONS: In contrast to our hypothesised role of hUII, we found no vasoactive responses to hUII in vivo, consistent with recent in vitro studies in human blood vessels, but in contrast to non-human primate studies in vivo. Our data do not support a key role for hUII in the regulation of vascular tone and resting blood pressure in man. However, studies with hUII receptor antagonists are also needed before firm conclusions can be drawn.     

Addison's disease: the potentially life-threatening tan

Addison's disease is a potentially life-threatening endocrine disorder. The classic dermatologic sign of Addison's disease is diffuse hyperpigmentation of the skin with focal hyperpigmentation of scars, nails, and the oral mucosa. Recognition of these dermatologic manifestations in a patient with otherwise vague constitutional symptoms warrants a consideration of Addison's disease.     

IgE-mediated allergy to phytase -- a new animal feed additive

BACKGROUND: Although fungal phytase is frequently used as an additive to animal feed few investigations of its allergenic property have been conducted. METHODS: Fifty-three subjects occupationally exposed to powdered phytase from Aspergillus niger were studied. Exposure data and symptoms were registered by the company physician. RESULTS: Thirty-eight subjects complained of work-related respiratory symptoms and 14 of them showed phytase-specific IgE antibodies; only one asymptomatic subject revealed such antibodies. IgE antibodies were significantly more frequently found in the high-exposure group (technical centre) when compared with the low-exposure group (laboratories, experimental animal husbandry). Phytase-specific IgG antibodies were present in 19 symptomatic (50%) and five (33%) asymptomatic subjects. CONCLUSIONS: Our results demonstrate that powdered fungal phytase is a highly sensitizing substance whose inhalation exposure should be avoided. Hypersensitivity symptoms could be prevented by means of extensive hygienic measures and ongoing medical surveillance.