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.

Comparison of four-day and seven-day pantoprazole-based quadruple therapy as a routine treatment for Helicobacter pylori infection.

BACKGROUND: H. pylori eradication is usually performed with three or four drugs for at least seven days. Recently four reports have shown a cure rate of approximately 90% using a four-day quadruple therapy. The objectives of this prospective study were: 1) to evaluate the efficacy of pantoprazole-based quadruple therapy, and 2) to compare the efficacy and tolerability of four-day with seven-day quadruple therapy. METHODS: The study was performed in a single centre. The first 56 consecutive patients with nonulcer dyspepsia or peptic ulcer disease and proven H. pylori infection received seven days of quadruple therapy (pantoprazole, bismuth, tetracycline and metronidazole). At least six weeks after treatment, endoscopy was repeated with six biopsies of the antrum and corpus for histology, urease test and culture. The next 59 consecutive patients followed the same protocol but received four-day quadruple therapy. RESULTS: Using an intention-to-treat analysis, the cure rate in the seven-day treatment group was 54/56 (96.4%, 95% confidence interval (CI) 87.7-99.6%). In the per protocol analysis the cure rate was 53/55 (96.3%, 95% CI 87.5-99.6%). Primary metronidazole resistance was observed in seven patients. All were cured. Using an intention-to-treat analysis, the cure rate in the four-day treatment group was 51/59 (86.4%, 95% CI 75.0-94.0%). In the per protocol analysis the cure rate was 50/58 (86.2%, 95% CI 74.6-93.8%). Primary metronidazole resistance was observed in seven patients, four of whom were cured. In three out of eight patients in whom four-day treatment failed, secondary metronidazole resistance was induced. Both treatment regimens were well tolerated. The difference between cure rates of both regimens did not reach statistical significance (p=0.0585). CONCLUSION: Routine use of both four-day and seven-day pantoprazole-based quadruple anti-H. pylori treatment is effective and well tolerated. The results of both regimens reach the required eradication standard, but results with the seven-day regimen were slightly but not significantly better. Seven-day treatment may be superior, especially in case of metronidazole resistance, and should be preferred.

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 1 year most likely because of reduced neorectal capacity and RAIR recovery in the presence of a low basal anal sphincter pressure.

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 beholder.

Artemisinin or chloroquine for blood stage Plasmodium vivax malaria in Vietnam.

Chloroquine-resistant Plasmodium vivax has not yet occurred in Vietnam. The efficacy of artemisinin for P. vivax was not established. We conducted a double-blind randomized study involving 240 inpatients with P. vivax malaria who received artemisinin (40 mg/kg over 3 days) plus placebo chloroquine (Art) or chloroquine (25 mg/kg over 3 days) plus placebo artemisinin (Chl). Patients were followed up with weekly blood smears for 28 days. In each group 113 cases were analysed. All patients recovered rapidly. The median (range) parasite clearance time of regimen Art was 24 h (8-72) and of Chl 24 h (8-64; P = 0.3). Parasites reappeared in two cases in each group on day 14, in eight cases in each group (7%) on day 16 and in 25 (23%) and 18 (16%) cases, respectively, at the end of 4-week follow-up (P = 0.3). The population parasite clearance curve followed a mono-exponential decline. The parasite reduction ratio per 48 h reproduction cycle was 2.3 x 104 for both regimens. We conclude that artemisinin and chloroquine are equally effective in the treatment of P. vivax infections in Vietnam. Reappearance of parasites before day 16 (7%) suggests the emergence of chloroquine resistance. Three days of artemisinin monotherapy does not prevent recrudescence.

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.

Is compulsory overseas medical screening of migrants justifiable?

For more than four decades the international Organization for Migration (IOM) has been providing medical screening of prospective migrants according to the admission requirements of resettlement countries. The main reason resettlement countries impose mandatory medical screening is to prevent the entrance of migrants with certain health problems in the belief that they pose a potential public health risk or financial burden to the nation. High rates of communicable diseases among foreign-born residents of industrial countries have raised concern about the impact of international migration on transmission of such diseases and the role and efficacy of medical screening. IOM's experience provides insight into the complex and sensitive problems related to mandatory screening of migrant populations, including: conflicting objectives, epidemiological concerns, uncertain economic benefit, and ethical dilemmas. Medically sound screening mechanisms must be formulated that meet the needs of receiving countries while responding to the epidemiology of disease, the rights of individuals, and the public health concerns of the community.

Migration and health-the international perspective.

Mass movement of people is not a new phenomenon. There are significant differences, however, between contemporary migration and that of yesterday. Modern communication and transportation makes it possible for people and their health problems to travel further and more quickly than ever before. The Plan of Action produced by the 1994 International Conference on Population in Cairo estimates that there are 125 million migrants world-wide. The cause of concern is not only linked to the numbers, but also to the new patterns and categories of migrants that give the strong feeling that the problem is getting out of control. This presents a challenge which urgently asks for response and action on various levels including health and social services. European states started to develop policies that would link immigration to health care policies. "Health for All" strategies, only towards the end of the 1980s, if at all. There are six areas, where health policies and programmes explicitly should take the needs of the immigrants into consideration: (1) communication and understanding, (2) control of infectious diseases, (3) mother and child care, (4) occupational health, (5) violence and (6) health indicators among migrants. To improve the health status of migrant families immigrant receiving countries need to put ethnic policies high on the public health agenda, they need to provide adequate health services to immigrants and there is a crucial need for training and preparing health professionals to understanding perspectives that differ from their own ethnic orientation, and to provide adequate and effective responses.

Prevalence of tuberculosis in Vietnamese migrants: the experience of the Orderly Departure Program.

This study aimed to describe the Internal Organization for Migration (IOM) tuberculosis screening and treatment program in Ho-Chi-Minh City (Vietnam); and to review the prevalence of tuberculosis and treatment outcome in a cohort of Vietnamese migrants and refugees prior to their departure. From 1 November 1992 to 1 June 1993, prospective migrants and refugees bound to the United States, Australia, and Canada underwent medical examination by IOM in Ho-Chi-Minh City. Screening for tuberculosis was based on chest x-rays, and the diagnosis was confirmed by smear examination. Smear-positive patients received short-course chemotherapy, directly supervised, with isoniazid, rifampicin, ethambutol, and pyrazinamide. Out of 39,581 persons screened, 322 were smear-positive (641 per 100,000), and started treatment. Follow-up varied from a minimum of 12 months to a maximum of 18 months. At that time, 265 (82%) were cured, while the remaining either continued treatment with first-line drugs (24), started second-line treatment (17), or failed to be cured for various reasons (16). This report confirms the efficacy of short course chemotherapy and directly observed treatment for tuberculosis, in the context of one of the largest screening programs for prospective migrants. Follow-up in receiving countries would help clarify risk factors for both new infection and relapse of tuberculosis.

No real progress towards equity: health of migrants and ethnic minorities on the eve of the year 2000.

The paper reviews the available evidence on access to health care and two health outcomes, perinatal mortality and accident/disability, for migrant and ethnic minorities in selected receiving industrialized countries. The health of these communities is analyzed using the entitlement approach, which considers health as the product of both the individual's private endowments and the social environment he or she faces. Migrants, especially first and second generations, and ethnic minorities often have reduced entitlements in receiving societies. Not only are they exposed to poor working and living conditions, which are per se determinants of poor health, but they also have reduced access to health care for a number of political, administrative and cultural reasons which are not necessarily present for the native population. The paper argues that the higher rates of perinatal mortality and accidents/disability observed in many migrant groups compared to the native population are linked to their lower entitlements in the receiving societies. Policies aimed at reducing such health gaps need to be accompanied by a more general effort to reduce inequalities and to promote full participation of these groups in the mainstream of society.

[Refugees and migrants]. / Flyktninger og folkeflyttinger.

Today, there are about 14 million refugees worldwide. The United Nations' High Commissioner for Refugees supports them with legal aid, food supplies, housing and preventive health measures, and also tries to find a permanent residence for the refugees. In recent years, there has been increasing awareness about the great number of internally displaced persons in many countries, and of the extent of economic migration. The fear that immigrants may be a threat to the public health, especially as regards import of infectious diseases such as HIV, hepatitis B and tuberculosis, is diminishing. The cultural aspects of health care among immigrants require increased attention, both from the immigrants themselves, and the countries to which they immigrate.

Factors affecting primary health care utilization.

Using a one-stage random probability sample of households, 5806 people in an area of Norway were interviewed about illness, use of medicines, self-treatment and visits to the doctor in the previous two weeks. Several social and demographic variables that might influence primary health care utilization were divided into five categories: need of medical care; self-care; availability of the doctor; sociodemographic factors; social network factors. Multiple classification analysis was used for the statistical analysis. The greatest influence on the percentage of people seeing the doctor was the need for medical care, the second largest influence was self-care. The availability of the doctor had a different effect according to whether the illness was chronic or non-chronic. Difficulties in reaching the doctor reduced the number of consultations for non-chronic diseases while the opposite was the case for chronic diseases. Among the sociodemographic variables neither level of education nor income had any influence on utilization when other variables were taken into account. Increasing age, however, caused a large increase in the percentage seeing the doctor, except after the age of 85 years when there was a large drop in consultation rate despite increasing illness. Social network factors had little effect on health care utilization.