A two-decade experience of head and neck paragangliomas in a whole population-based single centre cohort.

Paragangliomas are rare neuroendocrine tumours arising from neural crest-derived tissue. In the head and neck region typical locations are the carotid bifurcation, vagal nerve or jugulotympanic region. Paragangliomas are normally benign, and malignant transformation is rare. During the past decade the understanding of the genetic and molecular aetiology has had an important clinical impact on the management of PGs. This is a retrospective review of all histologically verified paragangliomas diagnosed and managed at an academic tertiary care referral centre between 1990 and 2010. Data on age, sex, symptoms, tumour location, management and follow-up were recorded. There were 64 patients with 74 tumours. Thirty-six per cent of the tumours were located in the carotid body region, 48 % in the jugulotympanic region and 15 % in the vagal nerve. One tumour was located in the dorsal neck. Most (95 %) of the patients were treated primarily with surgery and with curative intent. Definitive radiation therapy was primarily given to two patients. Recurrent or residual tumours were treated with surgery in three patients and with radiation therapy in nine patients. The typical long-term post-operative sequel was vocal cord paralysis. Local recurrence was found in 6 % of patients. Symptoms and findings related to paragangliomas are variable and management should be individualized. Surgery remains the primary choice of the current treatment options, but often is challenging and warrants a multidisciplinary approach. We present an algorithm on the management of head and neck paragangliomas based on current knowledge.

Past chlamydial infection is not associated with primary fallopian tube carcinoma.

We conducted a retrospective seroepidemiological study to evaluate the relationship between past chlamydial infection and primary fallopian tube carcinoma (PFTC). Postoperative serum samples were drawn from 79 consecutive patients treated for PFTC in 1985-2000. For each case two controls were selected. Serum samples were analysed for IgG antibodies to different C. trachomatis serotype pools and to C. pneumoniae. Seropositivity in general or serum antibody levels to different C. trachomatis serovars or C. pneumoniae did not differ between PFTC patients and controls. The lack of association between anti-chlamydial antibodies and PFTC suggests that past chlamydial infection does not play a role in the etiopathogenesis of PFTC. However, because chlamydial infection is common at young age and PFTC develops decades later, we cannot definitively exclude the possibility that C.trachomatis contributes to the development of PFTC.

Midlife income, occupation, APOE status, and dementia: a population-based study.

OBJECTIVE: To examine the relationship between socioeconomic factors and APOE carrier status on the development of dementia. METHODS: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1449 (73%) subjects aged 65 to 79 years were re-examined in 1998. The diagnosis of dementia among the nonparticipants was derived from patient records of the local hospitals and primary health care clinics. RESULTS: Low income level at old age was related to dementia, but low income level at midlife was not a risk factor for dementia. Dementia was also associated with decreasing income level, from midlife to old age 21 years later, when dementia was diagnosed. A sedentary occupation (office, service, or intellectual work) was associated with a decreased risk for dementia among participants; however, when the nonparticipants were included in the analysis, the associations were no longer significant. Low educational level and the APOE epsilon4 allele independently increased the risk for dementia. CONCLUSIONS: Reduction in income level during follow-up and low income level at old age might be the consequence of a dementing process rather than being associated with risk evolution of dementia.

Lack of association between serum antibodies to Chlamydia trachomatis and a history of recurrent pregnancy loss.

OBJECTIVE: To study the relation between recurrent pregnancy loss (RPL) and infection with Chlamydia trachomatis, and to compare the prevalence of antibodies to C. trachomatis in women with primary and secondary RPL. DESIGN: Prospective comparative study. SETTING: University hospital and university student health center. PATIENT(S): Seventy patients with RPL were selected from women attending an RPL outpatient clinic; 40 normal parous women and 94 asymptomatic sexually active women served as controls. INTERVENTION(S): Blood samples were collected during the clinical examinations for RPL. MAIN OUTCOME MEASURE(S): Serum immunoglobulin (Ig) G and IgA antibodies were detected by two independent methods, a recombinant ELISA specific to the genus Chlamydia and microimmunofluorescence testing specific to the species C. trachomatis. RESULT(S): There was no statistically significant difference in the frequencies of IgG or IgA between the women with RPL and the controls. The antibody frequencies were similar in the women with primary and secondary RPL. CONCLUSION(S): The presence of serum antibodies to C. trachomatis is not associated with RPL. Women with primary and secondary RPL do not differ with respect to the prevalence of antichlamydial antibodies. Thus, women with RPL do not benefit from screening for chlamydial IgG or IgA antibodies.

Correlates of initiation to cannabis use: a 5-year follow-up of 15-19-year-old adolescents.

Initiation to cannabis is often the first step in the use of illicit drugs. We studied the correlates of initiation in a 5-year follow-up study. A total of 21.4% of the subjects reported using cannabis at some time. Of the 139 users, 89.2% had tried cannabis not more than once or a few times. This initiation to cannabis was related to male gender, absence of mother, frequent lack of interest and early age at first sexual intercourse in logistic regression analysis. These factors seem to be useful in predicting initiation to cannabis.

Detection of Chlamydia trachomatis antibodies by 2 novel tests: rELISA and peptide EIA.

The performance of 2 newly developed enzyme immunoassays (EIAs) intended for the routine serological diagnosis of chlamydial infections was evaluated. rELISA is based on a recombinant lipopolysaccharide antigen which detects chlamydia genus-specific antibodies, and Chlamydia trachomatis EIA is based on a peptide derived from major outer membrane protein and is therefore species-specific. Both tests distinguished patients with tubal factor infertility (TFI) or pelvic inflammatory disease (PID) from the controls. The prevalence of IgA antibodies was higher for the PID patients than for the TFI patients; the finding indicates a more active state of infections for the PID patients. Furthermore, C. trachomatis EIA detected more IgG antibodies in the TFI patients than in patients with non-tubal factor infertility. In conclusion, rELISA detected chlamydial antibodies in general, and C. trachomatis EIA detected species-specific antibodies. These EIA tests may be useful in the serodiagnosis of chlamydial infection.

Prospective seroepidemiological study of role of human papillomavirus in non-cervical anogenital cancers.

OBJECTIVE: To evaluate the association between infection with the major oncogenic types of human papillomavirus and the risk of developing non-cervical anogenital cancers in a cohort followed up prospectively. DESIGN: Data from two large serum banks to which about 700,000 people had donated serum samples were followed up for a mean of 8 years. People who developed non-cervical anogenital cancers during follow up were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Within this cohort a nested case-control study was conducted based on the serological diagnosis of infection with human papillomavirus types 16, 18, and 33. SUBJECTS: 81 cases and 240 controls matched for sex, age, and storage time of serum samples. MAIN OUTCOME MEASURES: Odds ratios of developing non-cervical anogenital cancers in presence of IgG antibodies to specific micro-organisms. RESULTS: Subjects seropositive for human papillomavirus type 16 had an increased risk of developing non-cervical anogenital cancers (odds ratio 3.1 (95% confidence interval 1.4 to 6.9)). Subjects seropositive for type 33 also had an increased risk (odds ratio 2.8 (1.0 to 8.3)) but not significantly after adjustment for infection with type 16. Seropositivity for human papillomavirus type 16 was associated with an increased risk of developing vulvar and vaginal cancers (odds ratio 4.5 (1.1 to 22)) and a strongly increased risk of developing preinvasive vulvar and vaginal lesions (odds ratio infinity (3.8 to infinity)). Seropositivity for human papillomavirus type 18 increased the risk of developing preinvasive lesions (odds ratio 12 (1.2 to 590)). High, but non-significant odds ratios for types 16 and 33 were seen for penile cancers. CONCLUSIONS: This study provides prospective seroepidemiological evidence that infection with human papillomavirus type 16 confers an increased risk of developing non-cervical genital cancers, particularly vulvar and vaginal cancers.

CCN activity and hygroscopic growth of organic aerosols following reactive uptake of ammonia.

Recent field observations suggest that ammonium salts of organic acids may be very important in accounting for aerosols' properties in many environments. In this study we present laboratory experiments and calculations on the influence of ammonia reaction with organic aerosol components and its effect upon their (1) subsaturation hygroscopic growth (HG) and (2) supersaturation cloud condensation nuclei (CCN) activity. By using adipic acid (slightly soluble), citric acid (soluble), and di(ethylene glycol) monovinyl ether (DEGMVE, nonacidic compound) aerosols we show the feasibility and importance of atmospherically relevant acid-base neutralization by ammonia for different organic species. It is suggested that the formation of ammonium salts due to reaction of ammonia with slightly soluble organic acids (such as adipic acid) can affect the CCN activity and hygroscopic growth of aerosols with a significant organic component. It is further confined that the reaction involves carboxylic groups, it requires presence of water in the aerosol, and that the effects are stronger for less soluble organic acids.

Effect of body fatness and glucogenic supplement on lipid and protein mobilization and plasma leptin in dairy cows.

Twenty-four multiparous Ayrshire cows were used in an experiment to test the effect of body fatness and glucogenic supplement, fed during the transition period, on lipid and protein mobilization and plasma hormone concentrations. Eight weeks before their expected calving date, the cows were divided into blocks of 4. Two cows with the highest body condition score within each block were then allocated to a test (T) group and the other 2 cows to a control (C) group. To scale up the differences between fatter and thinner cows, the estimated energy allowance was 40% higher in group T than in group C between d 56 and 21 prepartum. For the final 3 wk before calving, all the cows were fed according to energy recommendations for pregnant cows. Within C and T groups and blocks, cows were randomly assigned into groups with (G1) or without (G0) glucogenic supplement. Division to G0 and G1 groups was made 2 wk before the expected calving and continued for 56 d postpartum. After calving, all the cows received grass silage ad libitum and a common daily concentrate allowance. No significant differences were detected in feed intake and milk yield between C and T. The T groups showed an earlier rise of nonesterified fatty acids as calving approached and had higher plasma nonesterified fatty acids during the final week of pregnancy and lactation wk 1 to 3. At the same time, adipose tissue samples from fatter cows tended to show higher in vitro lipolytic responses to added norepinephrine, as monitored by glycerol release. Protein mobilization was elevated during the final week of pregnancy and tended to be more increased in fatter cows. Glucogenic supplement did not decrease lipid or protein mobilization. Fatter cows had higher plasma leptin concentration prepartum, showed a more pronounced decrease in leptin concentration near calving, and had higher plasma leptin concentration after calving. In conclusion, fatter cows initiated more extensive mobilization of body fat before calving and this continued during the first lactation weeks. Plasma leptin concentration in early-lactation cows was associated with body fatness and not with estimated energy balance.

Purification of major lignin peroxidase isoenzymes from Phanerochaete chrysosporium by chromatofocusing.

The basidiomycete Phanerochaete chrysosporium produces several isoforms of lignin peroxidase, which catalyzes the oxidative depolymerization of lignin To date, ion-exchange chromatography and preparative isoelectric focusing (IEF) have been commonly used for isolation of lignin peroxidase isoenzymes. In this work we have purified major lignin peroxidases to high purity by a one-step chromatographic method, chromatofocusing. The purified isoenzymes were identified by analytical IEF using isoenzymes purified by preparative IEF as standards. The specific activities and spectral properties of the isoenzymes were comparable with the previously published data. The predominant isoenzyme under the growth conditions used was LiP 4.65. Almost 50% of the lignin peroxidase activity applied into the column was recovered in the LiP 4.65 fraction. The total recovery of the lignin peroxidase activity was over 80%.

Association of Chlamydia pneumoniae IgA antibodies with recently symptomatic asthma.

To determine whether recently diagnosed adult-onset asthma is associated with serologic evidence of chronic Chlamydia pneumoniae infection, we performed a case-control study in a primary care clinic of cases with asthma (25 adults reporting first symptoms of asthma within 2 years of enrollment) and 45 concurrently enrolled sex and age (+/- 10 years) matched non-asthmatic controls with normal pulmonary function. C. pneumoniae-specific IgA, IgG and IgG4 antibodies, and circulating immune complexes (CIC) were measured by microimmunofluorescence testing. Results showed that frequencies of IgG titres > or = 16 (92%), IgG4 titres > or = 16 (20%) and CIC > or = 4 (60%) in asthma patients were not significantly different from those of controls. However, asthmatics had a significantly higher prevalence of C. pneumoniae-specific IgA titres > or = 10 (72% of cases vs 44% of controls, P < 0.05). After adjustment for the effects of age, sex and smoking, the odds ratio for an association of IgA and asthma was 3.7 (95% confidence interval 1.2-11.5). We conclude that recently symptomatic reversible airway obstruction in adults is associated with the presence of C. pneumoniae-specific IgA antibodies, a proposed indicator of chronic respiratory C. pneumoniae infection.

Host immune response to Chlamydia pneumoniae heat shock protein 60 is associated with asthma.

Chlamydia pneumoniae infection has been associated with asthma. It has also been suggested that heat shock protein 60 (Hsp60) belonging to a class of highly conserved proteins may play a role in the pathogenesis of chlamydial infections. The purpose was to study whether the host immune response to C. pneumoniae Hsp60 is associated with asthma and decreased pulmonary function. An enzyme immunoassay was used to measure immunoglobulin-(Ig)A and IgG antibodies against recombinant C. pneumoniae Hsp60 and human Hsp60 in a study group consisting of 24 cases of recently symptomatic asthma and 62 nonasthmatic controls. A strong (r=0.50) and significant (p<0.001) correlation was observed between C. pneumoniae and human Hsp60 IgA antibodies, but only C. pneumoniae Hsp60 IgA antibodies were significantly associated with asthma (p = 0.02). Pulmonary function, as measured by forced expiratory volume in one second, also inversely correlated (r = -0.23, p = 0.04) with the quantity of C. pneumoniae Hsp60 IgA antibodies, suggesting an association with the severity of pulmonary obstruction. By showing an association of Chlamydia pneumoniae heat shock protein 60 immunoglobulin A antibodies with asthma, the results support the hypothesis of an association between Chlamydia pneumoniae infection and asthma and support the need for further investigations on the role of heat shock protein 60 in the pathogenesis of asthma.

Impact of hand-rearing on morphology and physiology of the capercaillie (Tetrao urogallus).

Morphological and physiological disparities between 20 captive and 11 wild capercaillies were determined. Birds, their pectoral and leg muscles, hearts, livers and gizzards were weighed. The length of small intestines and caeca were measured. Haemoglobin, haematocrit, glucose, triglycerides, total protein, uric acid and thyroid hormones as well as the cytochrome c-oxidase activity of the pectoral muscle and heart were determined. The glycogen and protein contents of pectoral and leg muscles and liver were analysed. Chemical composition (water, fat, protein, ash) of muscles and liver was determined. Captive males had heavier pectoral muscles than wild ones. The result was opposite in females. Wild birds had heavier hearts, livers, and gizzards, and also longer small intestines and caeca than captive birds. The cytochrome c-oxidase activity of pectoral muscle and heart was higher in wild than in hand-reared birds. The chemical composition of livers of wild birds differed significantly from that of hand-reared capercaillies. Plasma uric acid and T(4) concentrations were higher in captive than in wild birds. The observed differences in digestive system and liver can result in diminished ability of captive birds to utilise natural food nutrients. Decreased cytochrome c-oxidase activity of hand-reared birds can affect their takeoff and flying capacity and increase their vulnerability to predation. These facts may contribute to the low survival of hand-reared birds after release.

Tannins--a dietary problem for hand-reared grey partridge Perdix perdix after release?

A 4-week feeding trial on 22 grey partridges Perdix perdix was conducted in this study. Seven birds were fed commercial poultry food, seven natural food and eight commercial poultry food containing 6% of quebracho-tannin. Our results suggest that 6% dietary tannin, when added to a commercial food with high protein content, effects the grey partridge only slightly. No difference was seen in food consumption and body mass remained stable. However, birds fed tannin had longer small intestines, which most probably indicate gastrointestinal detoxication. They also excreted a high amount of tannin in their faeces. In addition, no between-group variation was seen in cytochrome P450 enzymes. Birds fed natural food had high concentration of nitrogen in intestinal excreta and high plasma alanine concentrations. They also suffered a rapid decrease in body mass after the change in diet and their body mass remained low. This may indicate increased protein excretion and/or catabolism of endogenous nutrient reserves. Potential short-term effects of the change in diet were seen in plasma. These findings coincide with the high mortality period of birds released into the wild.

Serological evidence of an association between Chlamydia pneumoniae infection and lung cancer.

Epidemiological evidence suggests that airway obstruction is an independent risk factor for lung cancer and that this cannot be explained by active or passive smoking alone. Chlamydia pneumoniae infection has been associated with chronic bronchitis and its exacerbates. Our aim was to evaluate the association between chronic C. pneumoniae infection and risk of lung cancer among male smokers. Smoking males with lung cancer (n = 230) and their age- and locality-matched controls were selected among participants of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The presence of C. pneumoniae infection was assessed by analyzing specific antibodies and immune complexes in 2 serum samples collected with a 3-year interval before the lung cancer diagnosis. The diagnosis of chronic infection was based on stable levels of positive specific IgA antibody (titer > or = 16) and immune complex (titer > or = 4). Relative risks were estimated by odds ratios (OR) adjusted for age, locality and smoking history by a conditional logistic regression model. Markers suggesting chronic C. pneumoniae infection were present in 52% of cases and 45% of controls and hence were positively associated with the incidence of lung cancer (OR 1.6; 95% confidence interval [CI] 1.0-2.3). The incidence was especially increased in men younger than 60 years (OR 2.9; 95% CI 1.5-5.4) but not in the older age group (OR 0.9; 95% CI 0.5-1.6). Before concluding that C. pneumoniae infection is a new independent risk factor for lung cancer, corroboration from other studies with larger number of cases and longer follow-up is needed.

IgG subclass-specific antibodies in Chlamydia pneumoniae infections.

IgG subclass-specific antibodies to Chlamydia pneumoniae and chlamydial lipopolysaccharide (LPS) were analysed in paired sera obtained from 15 patients with primary C. pneumoniae pneumonia and from 16 pneumonia patients with reinfection, as well as in single sera of 40 subjects with possible chronic C. pneumoniae infection and 40 healthy controls. The microimmunofluorescence (MIF) method was used to measure total IgG, IgM and IgG subclass-specific antibodies to C. pneumoniae protein antigens and enzyme immunoassay (EIA) to measure antibodies against the LPS antigen. By MIF, IgG1 antibodies to C. pneumoniae were demonstrated in all individuals of the 3 patient groups and also in all healthy controls. IgG2 subclass antibodies were not found by MIF. IgG3 antibodies were detected in 40% of patients with primary infection, in 31% of patients with reinfection, in 25% of those with chronic infection and in 8% of the controls. IgG4 antibodies were associated with acute C. pneumoniae infection and were found in 13% of primary infections and 31% of reinfections. The subclass pattern of LPS antibodies resembled that of protein antibodies measured by MIF: IgG1 was the most common subclass among the antibodies to LPS.

Serological evidence of an association between chlamydial infections and malignant lymphomas.

Chronic infections may predispose to malignant growth. Recently, serological markers of chronic Chlamydia pneumoniae infection have been associated with lung cancer. Our aim was to study the possible association between chronic chlamydial infections and malignant lymphomas. The present case-control study involved 72 patients with lymphoma (31 females and 41 males) and matched controls. 53 patients had non-Hodgkin's lymphoma (NHL) and 19 had Hodgkin's disease. The sera, collected at the time of diagnosis, were tested for IgG antibodies and immune complexes to C. pneumoniae and C. trachomatis by a microimmunofluorescence method and ELISA and for IgG antibodies and immune complexes to Helicobacter pylori by ELISA. The serological markers suggesting chronic chlamydial infection were associated with malignant lymphoma. The association was most evident for the presence of C. pneumoniae-specific immune complexes in NHL (OR = 7.3, 95% CI 2.2-25) and appeared to be limited to men. No association between H. pylori antibodies or immune complexes and malignant lymphomas could be demonstrated. Our study provides seroepidemiological evidence of an association between chronic chlamydial infections and lymphomas.

Low levels of serum vitamins A and E in blood and subsequent risk for cervical cancer: interaction with HPV seropositivity.

Nutritional factors have been associated with risk of cervical cancer, but it is unclear whether the associations are of etiological significance or secondary to human papillomavirus (HPV) exposure. A delineation of this question requires a prospective study with invasive cancer as the end point. We conducted a nested case-control study in Finland and Sweden within a joint cohort of 405,000 women followed up for, on average, 4 years. Blood samples from 38 prospective cases of invasive cervical cancer diagnosed between 1985 and 1994 and 116 controls matched for age, country, and sample storage time were available for the study. Levels of retinol or unoxidized alpha-tocopherol in the blood were not risk factors for cervical cancer. However, joint-effect analysis of low levels of retinol disclosed statistically significant (p = 0.023) synergistic (more than multiplicative) interaction with HPV (HPV16, HPV18, or HPV33) seropositivity (observed relative risk = 2.6, 95% confidence interval = 0.7-8.8, expected relative risk = 0.3). Retinol might act as an effect modifier of the HPV-associated risk for cervical cancer; exposed women may require adequate levels for immunologic surveillance of HPV.

Chlamydia trachomatis infection as a risk factor for invasive cervical cancer.

Cervical carcinoma is a sexually transmitted disease most strongly linked with human-papillomavirus (HPV) infection. We conducted a prospective sero-epidemiologic study to evaluate the role of Chlamydia trachomatis infection in the development of cervical carcinoma, with invasive cancer as an end point. A nested case-control study within a cohort of 530000 Nordic women was performed. Linking data files of 3 Nordic serum banks and the cancer registries of Finland, Norway and Sweden identified 182 women with invasive cervical carcinoma diagnosed during a mean follow-up of 5 years after serum sampling. The serum samples of the cases and matched cancer-free controls were analyzed for IgG antibodies to C. trachomatis, C. pneumoniae (a control microbe) and HPV types 16, 18 and 33, as well as for serum cotinine (an indicator of tobacco smoking). Serum antibodies to C. trachomatis were associated with an increased risk for cervical squamous-cell carcinoma (HPV- and smoking-adjusted OR, 2.2; 95% CI, 1.3-3.5). The association remained also after adjustment for smoking both in HPV16-seronegative and -seropositive cases (OR, 3.0; 95% CI, 1.8-5.1; OR, 2.3, 95% CI, 0. 8-7.0 respectively). No such association was found for C. pneumoniae. Our prospective study provides sero-epidemiologic evidence that infection with C. trachomatis confers an increased risk for subsequent development of invasive squamous-cell carcinoma of the uterine cervix.

Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma.

CONTEXT: Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown. OBJECTIVE: To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC. DESIGN AND SETTING: Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries. SUBJECTS: One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls. MAIN OUTCOME MEASURE: Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels. RESULTS: Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1. 6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend). CONCLUSIONS: Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.