Epidemiological investigation of risk factors for campylobacter colonization in Norwegian broiler flocks.

An epidemiological investigation was conducted to identify risk factors related to hygiene and husbandry practices which determine the introduction of Campylobacter spp. into broiler chicken flocks. All 176 broiler farms in an area in southeastern Norway participated in the study. Each farm was represented by one flock selected at random during a one-year period. The flocks were examined for campylobacter colonization at slaughter, and the flock managers were subsequently interviewed about hygiene and husbandry practices. Campylobacter spp. were recovered from 32 (18%) of the flocks. The proportion of colonized flocks varied geographically and seasonally with a peak in the autumn. The following variables were found to be independently associated with an increased risk of campylobacter colonization using logistic regression analysis: (i) feeding the broilers undisinfected water (odds ratio (OR) = 3.42, P = 0.045), (ii) tending other poultry prior to entering the broiler house (OR = 6.43, P = 0.007), (iii) tending pigs before entering the house (OR = 4.86, P = 0.037), (iv) geographic region (Hedmark versus Ostfold county) (OR = 2.91, P = 0.023, (v) season (autumn versus other seasons) (OR = 3.43; P = 0.008). Presence of rats on the farm was associated with an increased risk, but this factor did not reach statistical significance (OR = 3.96, P = 0.083). Preventive measures should include disinfection of drinking water and strict hygienic routines when the farm workers enter the rearing room. The results indicate that disinfection of drinking water is the preventive measure most likely to have the greatest impact on the prevalence of campylobacter among broiler chicken flocks in the study area (population attributable fraction = 0.53).     

TP53 gene mutations predict the response to neoadjuvant treatment with 5-fluorouracil and mitomycin in locally advanced breast cancer.

PURPOSE: Recent studies have found an association between certain TP53 mutations and resistance to anthracycline-based primary medical therapy in breast cancer. The purpose of this study was to investigate whether TP53 mutational status also might influence the response to a non-anthracycline-containing regimen in primary breast cancer. EXPERIMENTAL DESIGN: Thirty-five patients with locally advanced breast cancer were investigated for TP53 mutations before receiving combination chemotherapy with 5-fluorouracil (1000 mg/m(2) on days 1 and 2) and mitomycin (6 mg/m(2) on day 2), administered every 3 weeks for 2-10 cycles in the neoadjuvant setting. RESULTS: Mutations in the TP53 gene, in particular those affecting loop domains L2 or L3 of the p53 protein, were associated with lack of response to chemotherapy (i.e., increase in the diameter product of tumor lesion by >/=25%; P = 0.177 for all mutations and P = 0.006 for those affecting L2/L3 domains, respectively). No statistically significant correlation between TP53 LOH and response to therapy was seen. CONCLUSION: This study revealed a significant association between lack of response to 5-fluorouracil and mitomycin and mutations affecting the L2/L3 domains of the p53 protein. Together with our previous finding that such mutations predict resistance to weekly doxorubicin, our data suggest that mutations affecting this particular domain of the p53 protein may cause resistance to several different cytotoxic compounds applied in breast cancer treatment.     

Squamous cell carcinomas of the head and neck in Norway, 1953-92: an epidemiologic study of a low-risk population

Trends in incidence, five-year relative survival, and mortality among patients in Norway with squamous cell carcinoma of the oral sites, oro-/hypopharynx, and larynx were studied for the period 1953-92. Throughout the first part of the study period, age-adjusted incidence rates (AAIR) of oral cancer remained stable in both genders. Since the end of the 1960s, AAIRs increased by 13 percent per five-year period in males and 12 percent in females. The figures suggest increased male incidence rates of oral cancer in younger age groups. During the same period, AAIRs of cancers of the oro-/hypopharynx in males increased by 19 percent per five-year period. The AAIRs of laryngeal cancer increased steadily from 1953-92 among both males and females by 17 percent and 21 percent per five-year period, respectively. For all sites, changes in AAIRs for males were greater in rural than in urban areas. No improvement in detection of disease at a localized stage was observed for either gender. There are indications of improvements in the five-year relative survival rates for oral and pharyngeal cancer in both genders. For all sites, relative survival was better in younger than in older patients. Only in the case of pharyngeal cancer in males was an increase in disease-specific mortality rates positive for a time trend.     

Autoantibodies against 21-hydroxylase and side-chain cleavage enzyme in autoimmune Addison's disease are mainly immunoglobulin G1

OBJECTIVE: Immunoglobulin G (IgG) antibodies to the steroidogenic enzymes 21-hydroxylase (21OH) and side-chain cleavage enzyme (SCC) are important diagnostic markers for autoimmune Addison's disease and autoimmune polyendocrine syndromes (APS) types I and II. The characterization of autoantibody (IgG) subclasses may reveal information on how tIssue destruction takes place; therefore, IgG subtypes of anti-21OH and anti-SCC antibodies from sera of patients with Addison's disease, APS I and APS II were determined using recombinant 21OH and SCC. METHODS: SCC(51-521) and his-SCC(51-521) were expressed by pET-scc in the Escherichia coli strain BL21 Star (DE3) and inclusion bodies were purified. Full-length, human 21OH fused to an N-terminal 6x histidine affinity tag was expressed in insect cells by using the baculovirus expression system bac-to-bac. Western blots were used to investigate the IgG subtype(s) of the autoantibodies against 21OH and SCC in patients and healthy blood donors. RESULTS: All anti-SCC positive sera (n=10) contained autoantibodies of the IgG1 subclass, while four out of ten also contained IgG3. All anti-21OH positive sera (n=16) had autoantibodies exclusively against IgG1. Sera from 20 healthy subjects did not show any reactivity against 21OH or SCC. CONCLUSIONS: The finding of a predominating IgG1 response against 21OH and SCC may suggest that T helper (Th) cells of the Th1 subclass are involved in destruction of the adrenal cortex in patients with autoimmune Addison's disease.     

Autoimmune adrenocortical failure in Norway autoantibodies and human leukocyte antigen class II associations related to clinical features

Autoimmune destruction of the adrenal cortex is the most common cause of primary adrenocortical insufficiency (Addison's disease) in industrialized countries. We have investigated a large Norwegian cohort of patients with Addison's disease in terms of clinical manifestations, autoantibodies, and human leukocyte antigen (HLA) class II haplotypes. The study comprised 94 patients (54 females) of ages 6-85 yr (mean 45 yr) with, either isolated Addison's disease or part of autoimmune polyendocrine syndrome type II. Among those diagnosed before the age of thirty, 53% were men, while among those diagnosed at 30 or above, 30% were men. Altogether 77 (82%) of the 94 patients had autoantibodies against 21-hydroxylase (21OH). Thirty-eight of the 40 patients with disease duration 5 yr or less had such autoantibodies. This frequency fell to 60% among patients with a disease duration greater than 35 yr. Five women had gonadal failure. This failure correlated with antibodies against side-chain cleavage enzyme (P = 0.03). Antibodies against glutamic acid decarboxylase and IA2 correlated with the presence of type 1 diabetes (P < 0.005 and P = 0.003, respectively). The frequency of the HLA DRB1*03-DQA1*05-DQB1*02 (DR3-DQ2) and DRB1*04-DQA1*03-DQB1*0302 (DR4-DQ8) haplotypes were positively correlated to Addison's disease, whereas the DRB1*01-DQA1*0101-DQB1*0501 (DR1-DQ5) haplotype was negatively correlated. In addition, the DRB1*04 subtype DRB1*0404 was increased among Addison patients relative to controls. We verify that autoimmunity is the main cause of Addison's disease in our cohort. In younger patients, the disease is equally common in men and women. Measurement of autoantibodies against 21OH is a valuable tool in establishing the etiological diagnosis, especially in patients with a short disease duration. Addison's disease is associated with the DR3-DQ2 and DR4 (0404)-DQ8 haplotypes. A particularly high risk for disease development is observed when these occur in a heterozygous combination (DR3-DQ2/DR4-DQ8).     

Cancer risk after renal transplantation in the nordic countries, 1964–1986

The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow-up. Information on 5,692 Nordic recipients of renal transplants in 1964–1982 was linked with the national cancer registries (1964-1986) and population registries. Person-years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age- and calender-specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10-fold to 30-fold above expectation, were associated with cancers of the lip, skin (non-melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva-vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer. © 1995 Wiley-Liss. Inc.     

Prevalence of antibodies to Brucella spp. and risk factors related to high-risk occupational groups in Eritrea

In a study of three high-risk occupational groups using Rose Bengal and complement fixation tests, the highest prevalence (7.1%) was found among dairy farm workers and owners in randomly selected dairy-cattle farms, followed by veterinary personnel (4.5%) and inhabitants in pastoralist areas (3.0%). There was no evidence for significant differences between the three populations. Among dairy farm workers, a higher risk was associated with the presence of sheep in the farm (OR = 13.2, CI = 2.2-76.7). In the pastoral area, a high risk was linked to having close contact with animals (OR = 6.32, CI = 0.88-infinity), while a reduced risk was seen for contact with cattle (OR = 0.18, CI = 0-1.30). Symptoms suggestive of brucellosis were more commonly observed among the dairy farm workers, mainly found in the highlands, than among the pastoralist area inhabitants, where malaria is prevalent. The study documents not only the presence of serological and clinical evidence of human brucellosis, but also risk factors related to it in Eritrea, for the first time.