The association between physical health and delusional-like experiences: a general population study

Objective

Delusional-like experiences (DLE) are prevalent in the community. Recent community based studies have found that DLE are more common in those with depression and anxiety disorders, and in those with subclinical symptoms of depression and anxiety. Chronic physical disorders are associated with comorbid depression and anxiety; however, there is a lack of evidence about the association of DLE with common physical conditions. The aim of this study was to explore associations between the common physical disorders and DLE using a large population sample.

Methods

Subjects were drawn from the Australian National Survey of Mental Health and Wellbeing 2007, a national household survey of 8841 residents aged between 16 and 85 years. The presence of DLE, selected common physical disorders and symptoms were assessed using a modified World Mental Health Composite International Diagnostic Interview (CIDI) schedule. We examined the relationship between DLE, and physical health-related variables using logistic regression, with adjustments for potential confounding factors.

Results

Of the 8771, 776 (8.4%) subjects positively endorsed one or more DLE. Of the six physical disorders examined, only diabetes and arthritis were significantly associated with the endorsement of DLE. Of the seven broad physical symptoms explored, only hearing problems were consistently associated with DLE.

Conclusion

Delusional-like experiences are common in the Australian community, and are associated with selected chronic physical disorders and with impaired hearing. The direction of causality between these variables warrants closer research scrutiny.     

The association between systemic inflammatory cellular levels and lung function: a population-based study

Background

Lower lung function is associated with an elevated systemic white cell count in men. However, these observations have not been demonstrated in a representative population that includes females and may be susceptible to confounding by recent airway infections or recent cigarette smoking. We tested the hypothesis that lung function is inversely associated with systemic white cell count in a population-based study.

Methods

The study population consisted adults aged 17−90+ years who participated in the Third National Health and Nutrition Examination Survey who did not report a recent cough, cold or acute illness in a non-smoking and smoking population.

Results

In non-smoking adults with the highest quintile of the total white cell count had a FEV₁ 125.3 ml lower than those in the lowest quintile (95% confidence interval CI: −163.1 to –87.5). Adults with the highest quintile of the total white cell count had a FVC 151.1 ml lower than those in the lowest quintile (95% confidence interval CI: −195.0 to −107.2). Similar associations were observed for granulocytes, mononuclear cells and lymphocytes. In current smokers, similar smaller associations observed for total white cell count, granulocytes and mononuclear cells.

Conclusions

Systemic cellular inflammation levels are inversely associated with lung function in a population of both non-smokers and smokers without acute illnesses. This may contribute to the increased mortality observed in individuals with a higher baseline white cell count.     

Kidney stones and hypertension: population based study of an independent clinical association.

OBJECTIVE--To test the hypothesis that kidney stone disease is more frequent among hypertensive men when the effect of possible confounders is allowed for. DESIGN--Cross sectional study of a sample of the male working population conducted as part of the 10 year follow up of a nationwide survey of the prevalence of cardiovascular risk factors. SETTING--The Olivetti factory in Pozzuoli, a suburban area of Naples. POPULATION--688 Male workers (87.9% of the male workforce) aged 21-68. INTERVENTIONS--Anthropometric and blood pressure measurements, blood tests, and administration of a detailed questionnaire aimed at detecting a history of urolithiasis. MAIN OUTCOME MEASURES--Prevalence of a history of urolithiasis among normotensive and untreated and treated hypertensive men adjusted for the possible confounding effects of age, body mass index, renal function, and serum urate and total calcium concentrations. RESULTS--Of the 688 participants 509 were normotensive. Of the remainder, 118 had untreated and 61 treated hypertension. The overall prevalence of a history of urolithiasis was 16.3% (112/688). The relative risk of hypertensive subjects having a history of kidney stones was twice that of the normotensive group (odds ratio 2.11; 95% confidence interval 1.17 to 3.81), the risk being higher when only treated hypertensives were considered (odds ratio 3.16; 95% confidence interval 1.75 to 5.71). The prevalence of a history of urolithiasis was 13.4% (68/509) in the normotensive subjects, 20.3% (24/118) in the untreated hypertensives, and 32.8% (20/61) in the treated hypertensives (p less than 0.001). The age adjusted relative risk in treated hypertensive men was higher than that in the normotensive group (Mantel-Haenszel pooled estimate of odds ratio 2.63; 95% confidence interval 2.23 to 3.10). CONCLUSION--An independent clinical association exists between the occurrence of urolithiasis and hypertension. The increased urinary calcium excretion commonly detected in hypertension may be the pathogenetic link.     

Effect of parathyroid hormone and antagonist on aortic cAMP levels

Experiments were designed to further investigate the vasoactive mechanisms of parathyroid hormone (PTH) on vascular smooth muscle cells. Time courses of the cAMP responses to the fragment (1-34) of bovine PTH (bPTH(1-34)) on cAMP levels have been studied in rat isolated aorta and in aortic myocytes in primary culture. In both aorta and myocytes bPTH (1-34) induced an increase in cAMP levels that was maximal and reached, respectively, 1.6- and 1.9-fold the basal level after 2 min of contact with bPTH (1-34). The effect of bPTH (1-34) on aortic cAMP content was concentration dependent in the range of 30-300 nM. (Nle8,18, Tyr34)-bPTH (3-34)amide, an antagonist of bPTH (1-34) with a stimulant effect on renal and vascular adenylate cyclase activity, inhibited the cAMP-increasing effect of bPTH (1-34). These results are in favour of a role for cAMP in the vasodilating effect of PTH.     

Evidence of association between methylenetetrahydrofolate reductase gene and susceptibility to breast cancer: a candidate-gene association study in a South-eastern European population

The methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a candidate gene for breast cancer (BC). However, the specific role of MTHFR polymorphisms and haplotypes has not been fully clarified and replicated. We examined the association of two common MTHFR polymorphisms (C677T and A1298C) and their haplotypes in a candidate-gene association study, involving 300 female patients with BC and 283 healthy women. The single locus analysis for the two polymorphisms revealed an association only for the C677T polymorphism [odds ratio (95% confidence interval), OR=2.05 (1.21-3.48)], but adjustment for age diminished this association [OR=1.76 (0.92-3.42)]. The menopausal status showed no significant effect in the association between the MTHFR polymorphisms and BC. The analysis of haplotypes showed an association for the C677-A1298 haplotypes (p=0.04). The available evidence from our study may support a contributory role of MTHFR polymorphisms in BC development. Future larger studies may help in elucidating the genetics of BC further.     

Vitamin d, parathyroid hormone and their associations with hypertension in a chinese population

Background

Conflicting reports support or refute an association between vitamin D deficiency with high levels of parathyroid hormone (PTH) and raised blood pressure or hypertension.

Objective

To explore the associations of serum vitamin D and PTH levels with blood pressure and risk of hypertension in a Chinese population.

Methods

A population-based cross-sectional study was conducted among 1,420 Chinese participants, aged 20–83 years, in 2010. Anthropometric phenotypes and blood pressure were evaluated. Serum lipids, 25-hydroxyvitamin D [25(OH)D] and PTH were measured.

Results

One thousand four hundred and twenty participants, including 566 women (39.9%), were evaluated in 2010. Four hundred and eighty seven were hypertensive (34.3%), of whom 214 (43.9%) received antihypertensive treatment. The median concentrations of serum 25(OH)D and PTH were 22.0 ng/ml and 2.83 pmol/l, respectively. Serum 25(OH)D and natural log of PTH levels were not independently associated with blood pressure in a multivariable adjusted linear regression analysis of 1,206 participants not receiving antihypertensive treatment (P>0.05). In logistic regression analyses, serum 25(OH)D levels were not associated with risk of hypertension in single and multiple regression models. One unit increments of natural log of PTH levels were significantly associated with risk of hypertension in the crude model (OR = 1.78, 95% confidence interval 1.38–2.28, P<0.0001) and model adjusted for age and sex (OR = 1.41, 95% confidence interval 1.08–1.83, P = 0.01). However, these associations were attenuated and became nonsignificant (OR = 1.29, 95% confidence interval 0.98–1.70, P = 0.07) after further adjustment for body mass index, current alcohol intake, current smoking, glomerular filtration rate and family history of hypertension.

Conclusions

Serum vitamin D and PTH levels are not independently associated with blood pressure or risk of hypertension in a Chinese population.     

The association between blood coagulation activity and lung function: a population-based study

Background

Increased in susceptibility to thrombotic disease may be associated with lower lung function. If causal, this association may suggest an area for development of new interventions for lung disease. The aim of this study was to investigate the association between blood coagulation activation as measured by plasma d-dimers and lung function.

Methodology/Principal Findings

We conducted a cross-sectional study on 2463 randomly selected adults in 1991 and followed up 1252 of these individuals in 2000. Plasma D-dimer levels, a marker of activity of blood coagulation pathways, were analysed in the baseline 1991 samples. There was an inverse cross-sectional association between plasma D-dimer and Forced Expiratory Volume in one second, with a decrease of 71 ml per µg FEU/ml increment in plasma D-dimer (95% confidence intervals CI: −135 to −6), and a decrease in Forced Vital Capacity (97 ml per µg FEU/ml increase in D-dimer, 95%CI: −170 to −24). These associations were attenuated after adjustment for serum highly sensitive CRP. No association was observed between plasma D-dimer and the decline in lung function between 1991 and 2000.

Conclusions/Significance

The cross-sectional findings are consistent with the hypothesis that activation of blood coagulation pathways is associated with decreased lung function, and that systemic inflammation may contribute to this relation. However, the lack of an association with decline in lung function suggests that clotting pathways that involve d-dimers may not be a promising therapeutic target for new interventions for respiratory disease.     

Dopamine-stimulated parathyroid hormone release in vitro: further evidence for a two-pool model of parathyroid hormone secretion

Bovine parathyroid tissue was placed in an in vitro perifusion system for the study of parathyroid hormone secretion stimulated by low calcium and dopamine. Dopamine caused a transient increase in parathyroid hormone release, while low calcium caused a sustained increase in parathyroid hormone secretion. The dopamine response was similar to that caused by isoproterenol. After parathyroid hormone release had been stimulated by dopamine there was no response to isoproterenol, suggesting they cause the release of the same cellular pool of hormone. Inhibition of protein synthesis with cycloheximide eliminated the response to low calcium, with no effect on dopamine-stimulated parathyroid hormone release. These studies suggest dopamine stimulates the release of a limited quantity storage pool of parathyroid hormone, while low calcium causes a sustained release of hormone by stimulating secretion of newly synthesized hormone. Low calcium has little or no effect on release of the storage granule pool of parathyroid hormone.     

The pathophysiology of hyperuricemia in essential hypertension: a pilot study

We have examined whether hyperuricemia in essential hypertension may be related to an increased insulin secretion thereby enhancing the tubular reabsorption of sodium and thus uric acid. Insulin hypersecretion, as elicited by the oral glucose tolerance test (OGTT), increased a mean of 5-fold in 12 essential hypertensive patients. Urinary uric acid to creatinine ratio significantly diminished by a mean of 62% after the OGTT. Simultaneously, urinary sodium to creatinine ratio decreased by a mean of 54%. These results suggest that insulin may mediate uric acid underexcretion due to its tubular sodium retaining effect in essential hypertensive patients.     

The association between adherence to the Mediterranean diet and adiponectin levels among healthy adults: the ATTICA study

Adiponectin is thought to exert anti-inflammatory actions. The aim of the present work was to evaluate the association of long-term adherence to the Mediterranean diet with adiponectin levels, in a sample of cardiovascular disease-free adults. In a random sub-sample of “ATTICA” study, 532 men and women, serum adiponectin was measured. Among several sociodemographic, clinical and biological factors, adherence to the Mediterranean diet was assessed by a special diet score (MedDietSCore) that incorporated the inherent characteristics of this traditional diet. Unadjusted analysis revealed that participants who were in the highest tertile of the diet score had an average 41% higher adiponectin levels, as compared to those who were in the lowest tertile (P<.001). Multiadjusted data analysis showed that compared to the highest tertile of diet score, participants in the middle or the lowest one had an average 0.99±0.22 (P=.001) and 1.05±0.27 μg/ml (P=.001) lower adiponectin levels after adjusting for age, sex and various bioclinical factors. Adherence to the Mediterranean diet was associated with an increase on adiponectin levels. This finding may partially explain beneficial effects of this traditional healthy diet on the cardiovascular system.     

Serum parathyroid hormone: a double antibody radioimmunoassay.

A radioimmunoassay for parathyroid hormone (PTH) using a double antibody system is described. Because of the immunolgoical heterogeneity of the hormone in human serum, the standard used has been serum from a patient with parathyroid carcinoma. With the use of the synthetic 34 amino acid N-terminal fragment of PTH, the anti-PTH antiserum was determined to react primarily with the N-terminal end of the molecule. PTH was detectable in the sera of 25% of normal subjects and elevated in 18 of 19 patients with parathyroid adenoma and carcinoma. Serum PTH levels were elevated in 3 of 5 patients with parathyroid hyperplasia.     

The canine renal parathyroid hormone receptor is a glycoprotein: characterization and partial purification

Covalent labeling of the canine renal parathyroid hormone receptor with [125I]bPTH(1-34) reveals several major binding components that display characteristics consistent with a physiologically relevant adenylate cyclase linked receptor. Through the use of the specific glycosidases neuraminidase and endoglycosidase F and affinity chromatography on lectin-agarose gels, we show here that the receptor is a glycoprotein that contains several complex N-linked carbohydrate chains consisting of terminal sialic acid and penultimate galactose in a beta 1,4 linkage to N-acetyl-D-glucosamine. No high mannose chains or O-linked glycans appear to be present. The peptide molecular weight of the deglycosylated labeled receptor is 62,000 [or 58,000 if the mass of bPTH(1-34) is excluded]. The binding of [125I]bPTH(1-34) to the receptor is inhibited in a dose-dependent fashion by wheat-germ agglutinin, but not by either succinylated wheat-germ agglutinin or Ricinus communis lectin, suggesting that terminal sialic acid may be involved in agonist binding. A combination of lectin affinity chromatography and immunoaffinity chromatography affords a 200-fold purification of the covalently labeled receptor.     

Immunoreactive parathyroid hormone levels in platyrrhini and catarrhini: A comparative analysis with three different assays

Serum concentrations of the hormonal form of vitamin D₃—1,25-dihydroxy-vitamin D₃ [1,25-(OH)₂-D₃]—are elevated in many genera of platyrrhines when compared to catarrhines; this elevation is presumed to result from a decrease in the ability of the target cell receptor effectively to recognize 1,25-(OH)₂-D₃. The activity of the renal 25-hydroxyvitumin D₃-1α-hydroxylase, the mammalian enzyme which synthesizes the majority of the circulating 1,25-(OH)₂-D₃, is accelerated by parathyroid hormone (PTH). In order to determine whether the elevated serum concentrations of 1,25-(OH)₂-D₃ in platyrrhines were the result of relative hyperparathyroidism, we measured serum levels of immunoreactive parathyroid hormone (iPTH) in normocalcemic platyrrhines, catarrhines, and human subjects with assays that recognize different domains of the human PTH molecule. Antisera directed against the biologically active, aminoterminus of PTH yielded comparable mean values for iPTH among three test groups. The mean concentration of iPTH as assessed by a “proximal” midregion assay was significantly reduced in platyrrhine serum when compared to either human or catarrhine serum. A “distal” midregion assay yielded a reduced mean value for iPTH in both platyrrhine and catarrhine serum when compared to human serum. These data suggest that 1) high circulating levels of 1,25-(OH)₂-D₃ in New World primates are not the result of hyperparathyroidism; and 2) structural homology between human and primate PTH diminishes progressively as one moves toward the carboxyterminus of the molecule and is lost more rapidly in the platyrrhine than in the catarrhine hormone.     

Interactions between parathyroid hormone and prostaglandins on renal cortical cyclic AMP

Effects of parathyroid hormone (PTH) and several prostaglandins (PGs) on cyclic AMP (cAMP) metabolism were studied and compared in isolated renal cortical tubules from male hamsters. Both production and intracellular degradation of cAMP were increased by PTH and each of the PGs tested (PGE₂, PGE₁, PGI₂). Production of cAMP was increased to similar levels by maximal concentrations of PTH and each PG, however, degradation of cAMP was significantly higher in response to PTH than with any of the PGs. This difference in intracellular degradation of cAMP was responsible for the much higher concentrations of cAMP in renal cortical tubules exposed to PGs (PGE₁, PGE₂, PGI₂) than to PTH. Submaximal amounts of each PG produced additive increases in cAMP concentrations in the presence of maximal amounts of PTH. Additivity of the combined responses was lost, however, as the PGs concentrations reached their maximas. The results suggest that renal PGs (PGE₂ and PGI₂) may modulate the effects of PTH on cAMP concentrations in renal cortical tubules.     

The association between household socioeconomic position and prevalent tuberculosis in Zambia: a case-control study

Background

Although historically tuberculosis (TB) has been associated with poverty, few analytical studies from developing countries have tried to: 1. assess the relative impact of poverty on TB after the emergence of HIV; 2. explore the causal mechanism underlying this association; and 3. estimate how many cases of TB could be prevented by improving household socioeconomic position (SEP).

Methods and Findings

We undertook a case-control study nested within a population-based TB and HIV prevalence survey conducted in 2005–2006 in two Zambian communities. Cases were defined as persons (15+ years of age) culture positive for M. tuberculosis. Controls were randomly drawn from the TB-free participants enrolled in the prevalence survey. We developed a composite index of household SEP combining variables accounting for four different domains of household SEP. The analysis of the mediation pathway between household SEP and TB was driven by a pre-defined conceptual framework. Adjusted Population Attributable Fractions (aPAF) were estimated.Prevalent TB was significantly associated with lower household SEP [aOR = 6.2, 95%CI: 2.0–19.2 and aOR = 3.4, 95%CI: 1.8–7.6 respectively for low and medium household SEP compared to high]. Other risk factors for prevalent TB included having a diet poor in proteins [aOR = 3.1, 95%CI: 1.1–8.7], being HIV positive [aOR = 3.1, 95%CI: 1.7–5.8], not BCG vaccinated [aOR = 7.7, 95%CI: 2.8–20.8], and having a history of migration [aOR = 5.2, 95%CI: 2.7–10.2]. These associations were not confounded by household SEP. The association between household SEP and TB appeared to be mediated by inadequate consumption of protein food. Approximately the same proportion of cases could be attributed to this variable and HIV infection (aPAF = 42% and 36%, respectively).

Conclusions

While the fight against HIV remains central for TB control, interventions addressing low household SEP and, especially food availability, may contribute to strengthen our control efforts.     

Purification and characterization of a receptor for human parathyroid hormone and parathyroid hormone-related peptide

The human parathyroid hormone (PTH) receptor (hPTH1R), containing a 9-amino acid sequence of rhodopsin at its C terminus, was transiently expressed in COS-7 cells and solubilized with 0.25% n-dodecyl maltoside. Approximately 18 microg of hPTH1R were purified to homogeneity per mg of crude membranes by single-step affinity chromatography using 1D4, a monoclonal antibody to a rhodopsin epitope. The N terminus of the hPTH1R is Tyr(23), consistent with removal of the 22-amino acid signal peptide. Comparisons of hPTH1R by quantitative immunoblotting and Scatchard analysis revealed that 75% of the receptors in membrane preparations were functional; there was little, if any, loss of functional receptors during purification. The binding affinity of the purified hPTH1R was slightly lower than membrane-embedded hPTH1R (K(d) = 16.5 +/- 1.3 versus 11.9 +/- 1.9 nm), and the purified receptors bound rat [Nle(8,21),Tyr(34)]PTH-(1-34)-NH(2) (PTH-(1-34)), and rat [Ile(5),Trp(23),Tyr(36)]PTHrP-(5-36)-NH(2) with indistinguishable affinity. Maximal displacement of (125)I-PTH-(1-34) binding by rat [alpha-aminoisobutyric acid (Aib)(1,3),Nle(8),Gln(10),Har(11),Ala(12),Trp(14),Arg(19),Tyr(21)]PTH-(1-21)-NH(2) and rat [Aib(1,3),Gln(10),Har(11),Ala(12),Trp(14)]PTH-(1-14)-NH(2) of 80 and 10%, respectively, indicates that both N-terminal and juxtamembrane ligand binding determinants are functional in the purified hPTH1R. Finally, PTH stimulated [(35)S]GTP gamma S incorporation into G alpha(s) in a time- and dose-dependent manner, when recombinant hPTH1R, G alpha(s)-, and beta gamma-subunits were reconstituted in phospholipid vesicles. The methods described will enable structural studies of the hPTH1R, and they provide an efficient and general technique to purify proteins, particularly those of the class II G protein-coupled receptor family.     

Decrease in calcitonin and parathyroid hormone mRNA levels and hormone secretion under long-term hypervitaminosis D3 in rats

In calcium homeostasis, vitamin D3 is a potent serum calcium-raising agent which in vivo regulates both calcitonin (CT) and parathyroid hormone (PTH) gene expression. Serum calcium is the major secretagogue for CT, a hormone product whose biosynthesis is the main biological activity of thyroid C-cells. Taking advantage of this regulatory mechanism, long-term vitamin D3-induced hypercalcemia has been extensively used as a model to produce hyperactivation, hyperplasia and even proliferative lesions of C-cells, supposedly to reduce the sustained high calcium serum concentrations. We have recently demonstrated that CT serum levels did not rise after long-term hypervitaminosis D3. Moreover, C-cells did not have a proliferative response, rather a decrease in CT-producing C-cell number was observed. In order to confirm the inhibitory effect of vitamin D3 on C-cells, Wistar rats were administered vitamin D3 chronically (25,000 IU/d) with or without calcium chloride (CaCl2). Under these long-term vitamin D3-hypercalcemic conditions, calcium, active metabolites of vitamin D3, CT and PTH serum concentrations were determined by RIA; CT and PTH mRNA levels were analysed by Northern blot and in situ hybridization; and, finally, the ultrastructure of calciotrophic hormone-producing cells was analysed by electron microscopy. Our results show, that, in rats, long term administration of vitamin D3 results in a decrease in hormone biosynthetic activities of both PTH and CT-producing cells, albeit at different magnitudes. Based upon these results, we conclude that hypervitaminosis D3-based methods do not stimulate C-cell activity and can not be used to induce proliferative lesions of calcitonin-producing cells.