No association between the deficit syndrome in psychosis and summer birth in the Southern Hemisphere

Recent studies have shown that individuals with schizophrenia who are born in summer have an increased odds of have deficit syndrome versus nondeficit syndrome. This study extends this work to examiningthis issue in patients from the Southern Hemisphere. Data which included OPCRITrSCAN items and demographic information was obtained for Australian-born cases from the Australian National Mental Health Survey. Followingpreviously published methods, cases were assigned to the deficit group Žns153.or non-deficit groupŽns228.. A logistic regression analysis was used to ascertain whether beingborn in summer ŽDecember, January, February.in the Southern Hemisphere altered the odds of havingdeficit syndrome. There was no association between summer birth and odds of havingdeficit versus non-deficit schizophrenia ŽOdds Ratios0.75, 95% CI 0.49–1.16.. Based on our previous work showingthat the size of the winterrspringbirth excess in schizophrenia is reduced in the Southern Hemisphere, we speculate that factors that influence the association between summer birth and non-deficit syndrome may also vary across geography andror latitude. The Stanley Foundation supported this project.

Association between HIV-1 infection, the etiology of genital ulcer disease, and response to syndromic management

Background: Reports on the effect of HIV-1 infection on healing rates of ulcers are conflicting. Goal: The goal was to determine the etiology and response to treatment of genital ulcer disease (GUD) in relation to HIV-1 infection. Study Design: This was a cohort study of patients with GUD treated with local syndromic management protocols. Results: Among the 587 recruited, the prevalences of infections due to HSV, Treponema pallidum, Chlamydia trachomatis (lymphogranuloma venereum [LGV]), Haemophilus ducreyi, Calymmatobacterium granulomatis, and HIV-1 were 48%, 14%, 11%, 10%, 1%, and 75%, respectively. The prevalence of T pallidum was higher among men (P = 0.03), and an association was seen among HIV-1-seronegatives on univariate and multivariate analyses (P < 0.001; P = 0.01). The prevalence of C trachomatis (LGV) was higher among females (P = 0.004), and an association was seen among HIV-1-seropositives on univariate analysis (P = 0.04). At follow-up, 40/407 (10%) showed a decreased healing tendency, not associated with ulcer etiology or HIV-1 seropositivity. Conclusion: Response to syndromic management of GUD was acceptable and not associated with HIV-1 coinfection.

Association of increased levels of heavy-chain ferritin with increased CD4(+) CD25(+) regulatory T-Cell levels in patients with melanoma

We have shown previously that melanoma cells in culture release heavy-chain ferritin (H-Ferritin) into supernatants and that this is responsible for the suppression of responses of peripheral blood lymphocytes stimulated by anti-CD3. These effects were mediated by activation of regulatory T cells to produce interleukin (IL)-10. In the present study, we examined whether a similar relation might exist between levels of H-Ferritin and activation of regulatory T cells in patients with melanoma. Ferritin levels were evaluated by ELISA and regulatory T-cell numbers were assessed by three-color flow cytometry to identify CD4(+) CD25(+) CD69(-) T cells. CD69 positive cells were excluded to avoid inclusion of normal activated CD4, CD25 expressing T cells. Measurements of H- and light-chain (L)-Ferritin by ELISA revealed that H- but not L-Ferritin was elevated in the circulation of melanoma patients. In addition, these studies revealed a marked increase in the number of CD4+ CD25+ CD69- T cells in such patients, compared with age-matched controls. The ratio of H-Ferritin:L-Ferritin correlated with the levels of regulatory T cells consistent with a causal relation between unbound H-Ferritin levels and the activation of regulatory T cells. H-Ferritin or regulatory T cells did not, however, correlate with the stage of the melanoma. These results provide evidence for the importance of H-Ferritin in the induction of regulatory T cells in patients with melanoma and provide additional insight into the suppression of immune responses in such patients.

Is there an association between chronic lung disease and abdominal aortic aneurysm expansion?

Background: Although there is evidence demonstrating an association between chronic obstructive pulmonary disease (COPD) and abdominal aortic aneurysm (AAA), it is not clear whether COPD predicts greater rates of expansion of established aneurysms. We sought such an association in a cohort of men with aneurysms detected in a population-based study of screening for aneurysms. Methods: In addition to regular aortic ultrasound scans, 179 men with AAA underwent full lung function testing in order to identify the presence of COPD and its subgroups, emphysema and other obstructive ventilatory defects (OVD). The rate of expansion of each aneurysm was calculated and the men were divided into 'rapid expanders' (3 mm or more per year) and 'slow expanders' (less than 3 mm per year). Any association with the presence of COPD or smoking was tested using a multivariate model. Results: Over a median follow-up period of 36 months the mean rate of aortic expansion for the cohort of 179 men was 2.1 mm/year. There was no significant difference in prevalence of COPD (68% overall) or having ever been a smoker (87% overall) between the rapid expanders and the slow expanders. Conclusions: Although there was a high prevalence of COPD among men with an AAA, there was no association between the rate of expansion of AAA and the presence of any form of this disease.

Association of tumor necrosis factor-alpha polymorphisms and ozone-induced change in lung function

Ozone is a major air pollutant with adverse health effects which exhibit marked inter-individual variability. In mice, regions of genetic linkage with ozone-induced lung injury include the tumor necrosis factor-alpha (TNF), lymphotoxin-alpha (LTA), Toll-like receptor 4 (TLR4), superoxide dismutase (SOD2), and glutathione peroxidase (GPX1) genes. We genotyped polymorphisms in these genes in 51 individuals who had undergone ozone challenge. Mean change in FEV1 with ozone challenge, as a percentage of baseline, was -3% in TNF -308G/A or A/A individuals, compared with -9% in G/G individuals (p = 0.024). When considering TNF haplotypes, the smallest change in FEV1 with ozone exposure was associated with the TNF haplotype comprising LTA +252G/TNF -1031T/TNF -308A/TNF -238G. This association remained statistically significant after correction for age, sex, disease, and ozone concentration (p = 0.047). SOD2 or GPX1 genotypes were not associated with lung function, and the TLR4 polymorphism was too infrequent to analyze. The results of this study support TNF as a genetic factor for susceptibility to ozone-induced changes in lung function in humans, and has potential implications for stratifying health risks of air pollution.

Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.

Can a N-2-fixing Gluconacetobacter diazotrophicus association with sugarcane be achieved?

Several published studies claim that high rates of N-2 fixation occur in sugarcane and sorghum, and have ascribed this result to infection by the bacterium Gluconacetobacter diazotrophicus, abetted by arbuscular mycorrhizal infection ( Glomus clarum). These results have not been confirmed within Australia. In this study, G. diazotrophicus was detected in stalks of field-grown sugarcane in Australia ( based on phenotypic tests, and a PCR test using species-specific primers developed to amplify a fragment of the G. diazotrophicus 16S rRNA gene). Isolates were nitrogenase positive ( acetylene reduction assay) in vitro. However, in glasshouse trials involving inoculation of sugarcane setts with G. diazotrophicus, co-inoculation with mycorrhizae, and plant growth under low N status, recovery of bacteria from maturing plants was variable. At 165 days from planting, no appreciable N-2-fixation, as assessed by dry weight increment, N budget, or N-15 ratio, of either an Australian or a Brazilian cultivar of sugarcane, or a sorghum cultivar, was achieved. We conclude that a N-2-fixing sugarcane - G. diazotrophicus association is not easily achievable, being primarily limited by a lack of infection.

Hyperplastic polyposis - Association with colorectal cancer

Hyperplastic polyposis is a loosely defined syndrome initially thought not to confer a clinically important predisposition to colorectal cancer. The aim of the current study was to examine the clinical, histologic, and molecular features of a prospective series of cases meeting a strict definition of the condition. Twelve patients were identified, seven of whom had developed colorectal cancer. Most polyps were hyperplastic, but 11 patients also had polyps containing dysplasia as either serrated adenomas. mixed polyps, or traditional adenomas. The mean percentage of dysplastic polyps in patients with cancer was 35%, and in patients without cancer, 11%(p < 0.05). Microsatellite instability (MSI) was present in 3 of 47 hyperplastic polyps and two of right serrated adenomas. Kras was mutated in 8 of 47 hyperplastic polyps and two of eight serrated adenomas. No polyps showed loss of heterozygosity of chromosomes 5q, 1p, or 18q. Two of seven cancers showed a high level of MSI. It is concluded that hyperplastic polyposis is associated with a high risk of colorectal cancer. Hyperplastic polyps are the dominant type of polyp, but most cases have some dysplastic epithelium. A higher proportion of dysplastic polyps is associated with increased cancer risk. Clonal generic changes are observed in some hyperplastic polyps and serrated adenomas.

Yarrol terrane of the northern New England Fold Belt: forearc or backarc?

The Upper Devonian to Lower Carboniferous volcanosedimentary rocks of the Yarrol terrane of the northern New England Fold Belt have previously been ascribed to a forearc basin setting. New data presented here, however, suggest that the Yarrol terrane developed as a backarc basin during the Middle to early Late Devonian. Based on field studies, we recognise four regionally applicable strati graphic units: (i) a basal, ?Middle to Upper Devonian submarine mafic volcanic suite (Monal volcanic facies association); (ii) the lower Frasnian Lochenbar beds that locally unconformably overlie the Monal volcanic facies association: (iii) the Three Moon Conglomerate (Upper Devonian - Lower Carboniferous): and (iv) the Lower Carboniferous Rockhampton Group characterised by the presence of oolitic limestone. Stratigraphic and compositional differences suggest the Monal volcanic facies association post-dates Middle Devonian silicic-dominated magmatism that was coeval with gold-copper mineralisation at Mt Morgan. The Lochenbar beds, Three Moon Conglomerate and Rockhampton Group represent a near-continuous sedimentary record of volcanism that changed in composition and style from mafic effusive (Late Devonian) to silicic explosive volcanism (Early Carboniferous). Palaeocurrent data from the Three Moon Conglomerate and Rockhampton Group indicate dispersal of sediment to the west and northwest, and are inconsistent with derivation from a volcanic-are source situated to the west (Connors-Auburn Arch). Geochemical data show that the Monal volcanic facies association ranges from tholeiitic subalkaline basalts to calc-alkaline basaltic andesite. Trace and rare-earth element abundances are distinctly MORE-like (e.g, light rare earth element depletion), with only moderate enrichment of the large-ion lithophile elements in some units, and negative Nb anomalies, suggesting a subduction-related signature. Basalts of the Monal volcanic facies association are best described as transitional between calc-alkali basalts and N-MORB. The elevated high field strength element contents (e.g. Zr, Y, Ti) are higher than modern island-are basalts, but comparable to basalts that floor modern backarc basins. This geochemical study, coupled with stratigraphic relationships, suggest that the eruption of backarc basin basalts followed widespread Middle Devonian, extension-related silicic magmatism (e.g. Retreat Batholith, Mt Morgan), and floored the Yarrol terrane. The Monal volcanic facies association thus shows similarities in its tectonic environment to the Lower Permian successions (e.g. Rookwood Volcanics) of the northern New England Fold Belt. These mafic volcanic sequences are interpreted to record two backarc basin-forming periods (Middle - Late Devonian and Late Carboniferous - Early Permian) during the Late Palaeozoic history of the New England Orogen. Silicic-dominated explosive volcanism, occurring extensively across the northern New England Fold Belt in the Early Carboniferous (Varrol terrane, Campwyn Volcanics, Drummond and Burdekin Basins), reflects another period of crustal melting and extension, most likely related to the opening of the Drummond Basin.

Back, chest and abdominal pain: How good are spinal signs at identifying musculoskeletal causes of back, chest or abdominal pain?

Background: Spinal signs found in association with atypical chest and abdominal pain may suggest the pain is referred from the thoracic spine. However, the prevalence of such signs in these conditions has rarely been compared with that in those without pain. In this study, the prevalence of spinal signs and dysfunction in patients with back, chest and abdominal pain is compared with that in pain free controls. The aim of the study is to determine the significance of spinal findings in patients with such pain. Methods: A general practitioner blinded to the patients' histories performed a cervical and thoracic spinal examination on general practice patients with back, chest and/or abdominal pain and on controls without pain. Thoracic intervertebral dysfunction was diagnosed on the basis of movement and palpation findings. Results: Seventy three study patients plus 24 controls, were examined. For cervical spinal signs, pain in the back, chest and/or abdomen was associated with pain with active movements and overpressure at end range and with loss of movement range. For thoracic spinal signs, this association held for pain with active movements and overpressure, but not with loss of movement range. The prevalence of thoracic intervertebral dysfunction was 25.0% in controls, 65.5% with chest/abdominal pain, 72.0% with back pain and 79.0% with back pain with chest/abdominal pain. This prevalence was higher with chest pain than with abdominal pain. Conclusions: The results show an association, but not a causal link between thoracic intervertebral dysfunction and atypical chest/abdominal pain. A spinal examination should be performed routinely assessing these conditions. The minimum examination for the detection of intervertebral dysfunction is testing for pain with spinal movements and palpation for tenderness. The interpretation of positive signs requires knowledge of their prevalence in pain free controls and in patients with visceral disease

Association of bowel movement frequency and use of laxatives with the occurrence of symptomatic gallstone disease in a prospective study of women

OBJECTIVES: The authors prospectively examined the association between bowel movement frequency (used as a proxy for intestinal transit), laxative use, and the risk of symptomatic gallstone disease. METHODS: A total of 79,829 women, aged 36–61 yr, without a history of symptomatic gallstone disease and free of cancer, responded to a mailed questionnaire in 1982 that assessed bowel movement frequency and use of laxatives. Between 1984 and 1996, 4,443 incident cases of symptomatic gallstone disease were documented. Relative risks (RRs) of symptomatic gallstone disease and 95% confidence intervals (CIs) were calculated using logistic regression. RESULTS: After controlling for age and established risk factors, the multivariate RRs were, compared to women with daily bowel movements, 0.97 (95% CI 0.86–1.08) for women with bowel movements every third day or less, and 1.00 (95% CI 0.91–1.11) for women with bowel movement more than once daily. No trend was evident. As compared to women who never used laxatives in 1982, a significant modest inverse association was seen for monthly laxative use, with a multivariate RR of 0.84 (95% CI 0.72–0.98), and weekly to daily laxative use was associated with a RR of 0.88 (95% CI 0.78–1.02). CONCLUSIONS: These findings do not support an association between infrequent bowel movements and risk of symptomatic gallstone disease in women, and indicate that simple questions directed at bowel movement frequency are unlikely to enhance our ability to predict risk of symptomatic gallstone disease. The slightly inverse association between use of laxatives and risk of symptomatic gallstone disease may be due to a mechanism that is not related to bowel movement frequency.

Tolerance or immunity to a tumor antigen expressed in somatic cells can be determined by systemic proinflammatory signals at the time of first antigen exposure

Mice transgenic for the E7 tumor Ag of human papillomavirus type 16, driven from a keratin 14 promoter, express E7 in keratinocytes but not dendritic cells. Grafted E7-transgenic skin is not rejected by E7-immunized mice that reject E7-transduced transplantable tumors. Rejection of recently transplanted E7-transgenic skin grafts, but not of control nontransgenic grafts or of established E7-transgenic grafts, is induced by systemic administration of live or killed Listeria monocytogenes or of endotoxin. Graft recipients that reject an E7 graft reject a subsequent E7 graft more rapidly and without further L. monocytogenes exposure, whereas recipients of an E7 graft given without L. monocytogenes do not reject a second graft, even if given with L. monocytogenes. Thus, cross-presentation of E7 from keratinocytes to the adaptive immune system occurs with or without a proinflammatory stimulus, but proinflammatory stimuli at the time of first cross-presentation of Ag can determine the nature of the immune response to the Ag. Furthermore, immune effector mechanisms responsible for rejection of epithelium expressing a tumor Ag in keratinocytes are different from those that reject an E7-expressing transplantable tumor. These observations have implications for immunotherapy for epithelial cancers.

The microsomal epoxide hydrolase Tyr113His polymorphism: Association with risk of ovarian cancer

Functional significance has been demonstrated in vitro for the exon 3 T-->C Tyr113His amino acid substitution polymorphism of the microsomal epoxide hydrolase (EPHX) gene. The higher activity or fast TT genotype was previously reported to be associated with an increased risk of ovarian cancer, and this association may reflect enhanced activation of endogenous or exogenous substrates to more reactive and mutagenic derivatives. Components of cigarette smoke are examples of exogenous substrates subject to such bioactivation, and smoking exposure may thus modify the risk associated with the EPHX polymorphism. We examined 545 cases of epithelial ovarian cancer and 287 unaffected controls for this EPHXT-C genetic variant to investigate whether, in the Australian population, the TT genotype was associated with (i) specific ovarian tumor characteristics; (ii) risk of ovarian cancer, overall or for specific subgroups; and (iii) risk of ovarian cancer in smokers specifically. Genotyping was carried out using the Perkin-Elmer ABI Prism 7700 Sequence Detection System for fluorogenic polymerase chain reaction allelic discrimination. Stratification of the ovarian cancer cases according to tumor behavior (low malignant potential or invasive), grade, stage, and p53 immunohistochemical status failed to show any heterogeneity with respect to the genotype defined by the EPHX polymorphism. There was a suggestion of heterogeneity with respect to histologic subtype (P= 0.03), largely due to a decreased frequency of the TT genotype in endometrioid tumors. EPHX genotype distribution did not differ significantly between unaffected controls and ovarian cancer cases (overall, low malignant potential, or invasive) either overall or after stratification by smoking status. However, the TT genotype was associated with a decreased risk of invasive ovarian cancer of the endometrioid subtype specifically (age-adjusted odds ratio = 0.38, 95% confidence interval=0.17-0.87). The results suggest that the proposed EPHX-mediated bioactivation of components of cigarette smoke to mutagenic forms is unlikely to be involved in the etiology of ovarian cancer in general but that a greater rate of EPHX-mediated detoxification may decrease the risk of endometrioid ovarian cancer. (C) 2001 Wiley-Liss, Inc.

No significant association between progesterone receptor exon 4 Val660Leu G/T polymorphism and risk of ovarian cancer

Epidemiological studies suggest that ovarian cancer is an endocrine-related tumour, and progesterone exposure specifically may decrease the risk of ovarian cancer. To assess whether the progesterone receptor (PR) exon 4 valine to leucine amino acid variant is associated with specific tumour characteristics or with overall risk of ovarian cancer, we examined 551 cases of epithelial ovarian cancer and 298 unaffected controls for the underlying G-->T nucleotide substitution polymorphism. Stratification of the ovarian cancer cases according to tumour behaviour (low malignant potential or invasive), histology, grade or stage failed to reveal any heterogeneity with respect to the genotype defined by the PR exon 4 polymorphism. Furthermore, the genotype distribution did not differ significantly between ovarian cancer cases and unaffected controls. Compared with the GG genotype, the age-adjusted odds ratio (95% confidence interval) for risk of ovarian cancer was 0.78 (0.57-1.08) for the GT genotype, and 1.39 (0.47-4.14) for the TT genotype. In conclusion, the PR exon 4 codon 660 leucine variant encoded by the T allele does not appear to be associated with ovarian tumour behaviour, histology, stage or grade. This variant is also not associated with an increased risk of ovarian cancer, and is unlikely to be associated with a large decrease in ovarian cancer risk, although we cannot rule out a moderate inverse association between the GT genotype and ovarian cancer.