The development and validation of the Leiden Bother and Needs Questionnaire for patients with pituitary disease: the LBNQ-Pituitary

Background

Patients report persisting impairment in quality of life (QoL) after treatment for pituitary disease. At present, there is no questionnaire to assess (a) whether patients with pituitary disease are bothered by these consequences, and (b) their needs for support.

Objective

To develop and validate a disease-specific questionnaire for patients with pituitary disease which incorporates patient perceived bother related to the consequences of the disease, and their needs for support.

Methods

Items for the Leiden Bother and Needs Questionnaire for patients with pituitary disease (LBNQ-Pituitary) were formulated based on results of a recent focus group study (n = 49 items). 337 patients completed the LBNQ-Pituitary and six validated QoL questionnaires (EuroQoL-5D, SF-36, MFI-20, HADS, AcroQol, CushingQoL). Construct validity was examined by exploratory factor analysis. Reliabilities of the subscales were calculated with Cronbach’s alphas, and concurrent validity was assessed by calculating Spearman’s correlations between the LBNQ-Pituitary and the other measures.

Results

Factor analyses produced five subscales (i.e., mood problems, negative illness perceptions, issues in sexual functioning, physical and cognitive complaints, issues in social functioning) containing a total of 26 items. All factors were found to be reliable (Cronbach’s alphas all ≥.765), and the correlations between the dimensions of the LBNQ-Pituitary and other questionnaires (all P ≤ .0001) demonstrated convergent validity.

Conclusions

The LBNQ-Pituitary can be used to assess the degree to which patients are bothered by the consequences of the pituitary disease, as well as their needs for support. It could also facilitate an efficient assessment of patients’ needs for support in clinical practice. We postulate that paying attention to needs for support will lead to optimal patient care (e.g., improvement in psychosocial care), and positively affect QoL.

     

A comparison of the genetic and clinical risk factors for arterial hypertension between indigenous and non-indigenous people of the Shoria Mountain Region

Background: This study investigated the non-genetic and genetic risk factors for arterial hypertension (AH) in two ethnic groups living in the Mountain Shoria region: Shors and non-indigenous people.

Methods: Clinical and epidemiological study of compactly living population in the remote areas of the Mountain Shoria (Orton, Ust-Kabyrza, Sheregesh settlements, Kemerovo region). 1178 residents of these settlements were surveyed with the help of continuous sampling method; the sample consisted of adults (18 years and older).

Results: The prevalence of AH was lower in Shors (39.9% vs. 46.1%), mainly due to differences between men from the different groups: 33.2% vs. 45.8%. The percentage of people with AH, overweight, and obesity (including transabdominal obesity) in the different age groups did not differ between ethnicities. We identified statistically significant differences in the prevalence of hypertension according the two ethic groups according to age, body weight, and abdominal obesity. I/D ACE and ADRA2B polymorphisms were associated with AH. In DD ACE and DD ADRA2B carriers, there were fewer hypertensive patients in Shors than in non-indigenous people: 40.6% vs. 58.6% and 38.3% vs. 64.0%, respectively. In DD ACE carriers, more Shors had AH (60.0% vs. 37.1%).

Conclusion: Among Shors, the following factors increased AH risk: female sex, age, hypercholesterolemia, hyperbetacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), glucose intolerance, and the DD ACE, CT MTHFR, and AA ADRB1 genotypes; among the non-indigenous population, the main factors were age, hypercholesterolemia, hyperbetacholesterinemia, hypoalfacholesterinemia, hypertriglyceridemia, obesity (including transabdominal obesity), and ID ACE genotype.     

Lipoprotein particle distribution and size, insulin resistance, and metabolic syndrome in Alaska Eskimos: the GOCADAN study

Background

Metabolic syndrome (MS) is associated with dyslipidemia, and insulin resistance (IR) may be a main determinant of this dyslipidemia.

Objective

To determine how lipoprotein particle concentration and size are related to MS and IR in a population-based sample of Alaska Eskimos.

Design

Participants underwent a physical exam, personal interview, collection of biological specimens, and diagnostic tests.

Setting

This study was conducted in the Norton Sound region of Alaska.

Participants

One thousand one hundred fifty-eight Inupiat Eskimo adults (women = 653, men = 505).

Main outcome measures

Lipoprotein particle profile was evaluated by nuclear magnetic resonance (NMR) and related to presence of MS and level of IR.

Results

Participants with MS had (a) significantly higher concentrations of all VLDLs and a larger VLDL size (women, p = 0.007; men, p = 0.0001); (b) higher concentrations of small LDL (women, p < 0.0001; men, p = 0.09) and lower concentrations of large LDL (women, p < 0.0001), leading to a smaller overall LDL size (women, p < 0.0001; men, p < 0.05); (c) significantly lower concentrations of large HDL (both genders, p < 0.0001) and an increase in intermediate (women, p < 0.05) and small HDL (women, p < 0.0001; men, p < 0.004). Lipoprotein profile with increasing HOMA-IR resembled that of individuals with MS.

Conclusions

In this population MS is characterized by lipoprotein distribution and size abnormalities independent of obesity, age, and other cardiovascular risk factors, including lipid concentration. IR seems the major determinant.     

Exaggerated adrenomedullary response to immobilization in mice with targeted disruption of the serotonin transporter gene

This study examined whether serotonin transporter (5-HTT) gene knockout influences adrenomedullary, sympathoneural, or hypothalamo-pituitary-adrenal responses to acute immobilization. In conscious, cannulated mice, arterial plasma concentrations of catecholamines, ACTH, and corticosterone were measured at baseline and after 15 min of immobilization. Tissue levels of serotonin (5-HT), catecholamines, and hormones were also measured in pituitary and adrenal glands. At baseline, adrenal and pituitary 5-HT concentrations in knockout (5-HTT(-/-)) mice were markedly lower than those in littermate control (5-HTT(+/+)) mice, whereas the groups did not differ in levels of catecholamines or hormones in plasma or tissue. Immobilization increased plasma levels of catecholamines, ACTH, and corticosterone in all genotypes. 5-HTT(-/-) mice had exaggerated responses of plasma epinephrine to immobilization and significant reductions in adrenal epinephrine, norepinephrine, and 5-HT contents compared with values in littermate controls. Pituitary ACTH was significantly reduced after immobilization in 5-HTT(-/-) mice only, but increases in plasma ACTH and corticosterone levels did not differ between genotypes. The results suggest that one 5-HTT function is to restrain adrenomedullary activation in response to immobilization. Exaggerated adrenomedullary responses seem to be an autonomic correlate of the anxiety-like behaviors in 5-HTT knockout mice.     

FDG PET/CT imaging in the diagnosis of osteomyelitis in the diabetic foot

Purpose

Osteomyelitis, the most serious complication of the diabetic foot, occurs in about 20?% of patients. Early diagnosis is crucial. Appropriate treatment will avoid or decrease the likelihood of amputation. The objective of this study was to assess the value of FDG PET/CT in diabetic patients with clinically suspected osteomyelitis.

Methods

Enrolled in this prospective study were 39 consecutive diabetic patients (29 men and 10 women, mean age 57?years, range 28–71?years) with 46 suspected sites of foot infection. Of these 39 patients, 38 had type 2 and 1 type 1 diabetes for 4–25?years, and 28 were receiving treatment with insulin. FDG PET/CT was interpreted for the presence, intensity (SUVmax) and localization of increased FDG foci. Final diagnosis was based on histopathology and bacteriology of surgical samples, or clinical and imaging follow-up.

Results

Osteomyelitis was correctly diagnosed in 18 and excluded in 21 sites. Of 20 lesions with focal bone FDG uptake, 2 were false-positive with no further evidence of osteomyelitis. Five sites of diffuse FDG uptake involving more than one bone on CT were correctly diagnosed as diabetic osteoarthropathy. FDG PET/CT had a sensitivity, specificity and accuracy of 100?%, 92?% and 95?% in a patient-based analysis and 100?%, 93?% and 96?% in a lesion-based analysis, respectively, for the diagnosis of osteomyelitis in the diabetic foot.

Conclusion

FDG PET/CT was found to have high performance indices for evaluation of the diabetic foot. The PET component identified FDG-avid foci in sites of acute infection which were precisely localized on fused PET/CT images allowing correct differentiation between osteomyelitis and soft-tissue infection.     

Lysophosphatidic acid pretreatment prevents micromolar atorvastatin-induced endothelial cell death and ensures the beneficial effects of high-concentration statin therapy on endothelial gene expression

Because of the pleiotropic effects of statins, it may potentially be used as a locoregional adjuvant in vascular revascularization, tissue engineering, and regenerative procedures. Electron probe X-ray microanalyses and oligonucleotide microarrays were used to identify the global effects of micromolar concentrations of atorvastatin on the gene expression and cell viability of endothelial cells in different states of lysophosphatidic acid (LPA)-induced activation. Treatment with 1-μM atorvastatin for 24 hours significantly reduced the viability of human vascular endothelial cells (HUVECs). However, the same treatment of LPA-preactivated HUVECs produced elevated cell viability levels and an optimal vascular gene expression profile, including endothelial nitric oxide synthase overexpression, endothelin-1 repression, an anti-inflammatory genetic pattern, and upregulation of molecules involved in maintaining the endothelial barrier (vascular endothelial cadherin, claudin 5, tight junction protein 1, integrin β4). The atorvastatin treatment also produced a repression of microRNA 21 and genes involved in cell proliferation and neointimal formation (vascular endothelial growth factor [VEGF] A, VEGF receptor 1, VEGFC). Results obtained suggest that micromolar atorvastatin therapy can enhance global endothelial function, but its effects on cell viability vary according to the baseline state of cell activation (preactivated, postactivated, or not activated). Preactivation with LPA protects HUVECs against atorvastatin-induced apoptosis and delivers optimal levels of cell viability and functionality.     

New 2-Thiopyridines as Potential Candidates for Killing both Actively Growing and Dormant Mycobacterium tuberculosis Cells

From in vivo observations, a majority of M. tuberculosis cells in latently infected individuals are in a dormant and probably nonculturable state, display little metabolic activity, and are phenotypically resistant to antibiotics. Despite many attempts, no specific antimicrobials effective against latent tuberculosis have yet been found, partly because of a lack of reliable and adequate in vitro models for screening of drug candidates. We propose here a novel in vitro model of M. tuberculosis dormancy that meets the important criteria of latency, namely, nonculturability of cells, considerable reduction of metabolic activity, and significant phenotypic resistance to the first-line antibiotics rifampin and isoniazid. Using this model, we found a new group of 2-thiopyridine derivatives that had potent antibacterial activity against both actively growing and dormant M. tuberculosis cells. By means of the model of M. tuberculosis nonculturability, several new 2-thiopyridine derivatives were found to have potent antitubercular activity. The compounds are effective against both active and dormant M. tuberculosis cells. The bactericidal effects of compounds against dormant M. tuberculosis was confirmed by using three different in vitro models of tuberculosis dormancy. The model of nonculturability could be used as a reliable tool for screening drug candidates, and 2-thiopyridine derivatives may be regarded as prominent compounds for further development of new drugs for curing latent M. tuberculosis infection.