Bile acid stimulation of colonic adenylate cyclase and secretion in the rabbit

In vitro studies have suggested that the cyclic AMP system may be the mediator of bile acid-induced colonic secretion. The aims of our experiments were to quantify thein vivo effect of various doses of deoxycholic acid (DCA) on adenylate cyclase activity (AC) and net secretion in the rabbit colon. AC increased significantly (P<0.01) with each increasing concentration of DCA; at 8 mM the activity was 126±6 pmoles cAMP/mg protein/min, or 4 times the control. Phosphodiesterase activity (PDE) was affected and significantly decreased (P<0.01) only by 8 mM DCA. The volume of luminal fluid increased significantly (P<0.01) as a bicarbonate-rich solution with 4, 6, and 8 mM DCA in graded fashion. In conclusion, stimulation of a colonic mucosal cAMP system is strongly implicated as mediating DCA-induced colonic secretion.Supported in part by NIH grant AM 15631.     

Semen quality and exposure to persistent organochlorine pollutants

BACKGROUND: Inconsistent results have been found in previous human studies on male reproductive toxicity of persistent organochlorine pollutants. The majority of studies have been conducted among selected populations of infertility clients or among occupational cohorts including a limited number of participants. METHODS: We conducted a cross-sectional study of semen quality and serum concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) among 763 men. We included men from all regions in Greenland (n = 194), fishermen from Sweden (n = 185), inhabitants of the city of Kharkiv, Ukraine (n = 195), and inhabitants of the city of Warsaw, Poland (n = 189). Blood samples were analyzed for CB-153 and p,p'-DDE using gas chromatography-mass spectrometry and adjusted for serum lipids. RESULTS: Sperm concentration was not impaired with increasing serum CB-153 or p,p'-DDE levels in any of the separate groups or overall. Similarly, the proportion of morphologically normal sperm was not associated with either CB-153 or p,p'-DDE blood concentration. However, sperm motility was inversely related to CB-153 concentration in Greenland and the Swedish fishermen population. Across all 4 regions, the sperm motility decreased on average by 3.6% (95% confidence interval = 1.7% to 5.6%) per one-unit increase in the log of blood CB-153 (ng/g lipid). The concentration of p,p'-DDE was negatively associated with sperm motility in the Greenlandic population and in the compiled dataset. CONCLUSION: Adult exposure to persistent organochlorine pollutants within the ranges observed in the present study is not likely to cause reduction in sperm concentration or morphology. However, higher exposure may be associated with impaired sperm motility.     

A new molecular approach for cidal vs static antimalarial determination by quantifying mRNA levels

In order to maximise compliance, the future antimalarial treatment should ideally require just a single-dose administration. This, in turn, demands new fast-acting effective drugs. Currently, methods to measure the in vitro killing rate of antimalarials are based on parasite growth. We have developed and validated a method to determine and classify antimalarial agents based on their cidal or static activity following quantitative Real Time PCR (RT-PCR) analysis. The method described here is a fast, reliable and user-friendly technique with a medium throughput. Metabolic activity of the parasite is followed by measuring mRNA expression levels of several genes during 5 parasite life cycles. mRNA from the parasite culture is then retrotranscribed to cDNA and quantified by RT-PCR. This new method provides a rapid and reproducible way to accurately measure the antimalarial activity of new compounds in vitro against Plasmodium falciparum.     

Characteristics and quality of adverse drug reaction reports by pharmacists in Norway

PURPOSE: To evaluate the characteristics and quality of adverse drug reaction (ADR) reports submitted by pharmacists, and thereby assess the possible contribution of pharmacists to the spontaneous reporting system for ADRs in Norway. METHODS: An open, prospective study was conducted where dispensing pharmacists from 39 pharmacies were encouraged to report ADRs over a 3-month period. The submitted ADR reports were compared to reports by physicians from the same time period. All reports were evaluated for selected characteristics, that is distribution of Anatomical Therapeutic Chemical (ATC) classification codes of suspected drugs, distribution of ADRs according to system-organ classes and the quality of the reports. RESULTS: A total of 118 reports covering 274 ADRs received from the pharmacists were compared to 109 ADR reports with 304 ADRs submitted by physicians. Pharmacists more often reported ADRs related to cardiovascular drugs, alimentary tract and metabolism drugs and respiratory drugs, whereas physicians more frequently reported ADRs related to musculoskeletal drugs and antineoplastic and immunomodulating agents. ADRs reported by pharmacists more frequently described gastrointestinal reactions while physicians reported more ADRs in relation to the cardiovascular and blood system. Whereas 68% of the physicians' reports were classified as serious, only 5% of the pharmacists' reports were serious. More than 50% of the reports submitted by pharmacists concerned ADRs following a generic substitution, in contrast to only 2% of the physicians' reports. The pharmacists' reports were found to be of a lower documentation grade. However, there was no substantial difference in a subjective assessment of the quality of information in the reports submitted by the two categories of health professionals. CONCLUSIONS: Pharmacists submit valuable ADR reports which provide information complimentary to physicians' reports. This emphasises that pharmacist ADR reporting might constitute an important addition to the spontaneous reporting system.     

Aspects of healthcare utilisation in self‐reported obstructive lung disease

Introduction: Utilisation of healthcare resources because of pulmonary diseases have previously been presented according to lung function or symptom severity. We aimed to compare the associations of symptoms and lung function to healthcare and social service utilisation in subjects with self‐reported obstructive lung diseases (OLDs) (asthma, chronic obstructive pulmonary disease, chronic bronchitis, emphysema). Materials and Methods: Of 2819 participants aged 27–82 years in the Hordaland County Respiratory Health Survey, 200 subjects (7.1%) self‐reported OLD. They answered 13 questions on respiratory symptoms and 5 questions on use of healthcare and social services. Altogether, 161 participants (81%) completed post‐bronchodilation spirometry. Results: Use of anti‐asthmatic drugs, regular physician's appointment, sick leave payment for the last 12 months, hospital admission for the last 12 months and disability pension were reported by 68%, 63%, 18%, 8% and 7% of those with self‐reported OLD, respectively. Twenty per cent of subjects with self‐reported OLD had not received any healthcare or social services. In adjusted multivariate logistic regression analyses, increase in the respiratory symptom score was significantly associated with more healthcare and social services. Lower forced expiratory volume in 1 s in % predicted, however, was not significantly associated with more use of healthcare and social services. Conclusion: The majority (80%) of subjects in a general population with self‐reported OLD received healthcare services. The utilisation of healthcare and social services was strongly associated to the burden of respiratory symptoms, and, to a lesser degree, to the level and pattern of lung function. Please cite this paper as: Nielsen R, Johannessen A, Bakke PS, Askildsen JE, Omenaas ER and Gulsvik A. Aspects of healthcare utilisation in self‐reported obstructive lung disease. The Clinical Respiratory Journal 2009; 3: 34–41.     

Survival after colorectal cancer in patients with ulcerative colitis: a nationwide population-based Danish study

OBJECTIVES: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). Little is known about how UC impacts CRC prognosis. In a nationwide population-based study we examined the CRC prognosis in UC patients compared to CRC patients without UC. METHODS: From the Danish Cancer Registry and the Danish Hospital Discharge Registry, we identified all CRC patients and all patients with UC in Denmark from 1977 to 1999. We compared survival in 279 UC patients with CRC to all other 71,259 CRC patients and computed mortality rate ratios (MRR). We also compared stage distribution at time of cancer diagnosis. RESULTS: The mean age at time of CRC diagnosis was 62.6 yr in UC patients and 71.2 yr in patients without UC. Cancer stage distribution for localized cancer, regional spread, and distant metastasis were 46.6%, 30.1%, and 16.5% in UC patients compared to 44.0%, 28.3%, and 19.4% in CRC patients without UC. The overall MRR for UC patients with CRC compared with all other CRC patients were 1.24 (95% CI 1.02-1.51) in the first year and 1.17 (95% CI 1.01-1.36) after 5 yr of follow-up. CONCLUSION: UC patients with CRC have a stage distribution similar to patients with CRC without UC. The prognosis of CRC is poorer for UC patients than for patients without UC.