Importance of serum phosphate in elderly patients with diabetes mellitus

BACKGROUND Metabolic disturbances including changes in serum calcium,magnesium or phosphate(P) influence the prevalence of type 2 diabetes mellitus(DM).We assessed the importance of serum P in elderly patients with type 2 DM vs nondiabetes mellitus(non-DM) in relation to renal function.AIM To determine the association between serum P and serum glucose or insulin resistance in diabetic and non-diabetic patients.METHODS One hundred-ten subjects with a mean age of 69.02±14.3 years were enrolled.Twenty-nine of the participants had type 2 DM(26.4%).The incidence of hypertension,smoking and receiving vitamin D(vitD) derivates were recorded.The participants were classified by both estimated glomerular filtration rate(eGFR) and albuminuria categories according to the Kidney Disease Improving Global Outcomes 2012 criteria.RESULTS We divided the patients in two groups according to the P cut-off point related to DM value.A comparison between high and low P showed that body mass index30.2±6.3 vs 28.1±4.6(P=0.04),mean glucose 63.6 vs 50.2(P=0.03),uric acid 6.7±1.6 vs 6.09±1.7(P=0.05),mean intact-parathyroid hormone 68.06 vs 47.4(P=0.001),systolic blood pressure 147.4±16.7 vs 140..2±16.1(P=0.02),mean albuminuria 63.2 vs 50.6(P=0.04) and eGFR 45.6±22.1 vs 55.4±21.5(P=0.02)were significantly different.χ~2 tests showed a significant association between high P and DM,hypertension,receiving vitD,smoking and eGFR stage(χ~2=6.3,P=0.01,χ~2=3.9,P=0.03,χ~2=6.9,P=0.009,χ~2=7.04,P=0.01 and χ~2=7.36,P=0.04,respectively).The adjusted model showed that older age,female gender and increased body mass index were significant predictors of type 2 DM when entering the covariates.CONCLUSION High serum P contributes to vascular and metabolic disturbances in elderly patients with type 2 DM and renal impairment.     

Effects of acute and chronic desipramine treatment on somatostatin receptors in brain

The effects of acute (5 mg/kg, IP twice daily for 2 days) and chronic (5 mg/kg IP twice daily for 21 days) administration of desipramine (DMI) on [¹²⁵I]-Tyr¹¹-somatostatin binding sites in brain were examined. There was no change in [¹²⁵I]Tyr¹¹-somatostatin binding in membranes prepared from the frontal cortex, striatum, and hippocampus of rats acutely or chronically treated with DMI as compared to non treated animals. [¹²⁵I]Tyr¹¹-Somatostatin binding was increased in membranes prepared from the rat nucleus accumbens only after chronic DMI administration. Scatchard analysis of the binding data from the nucleus accumbens showed that [¹²⁵I]Tyr¹¹-somatostatin labels a single population of somatostatin binding sites with an affinity constant, K_d, of 1.8±0.60 nM and a B_max of 330±90 fmol/mg protein. Chronic treatment with DMI increased the B_max (500±140 fmol/mg protein) but had no effect on the K_d. This finding shows a regional effect of DMI on [¹²⁵I]Tyr¹¹-somatostatin binding sites in rat brain and suggests that somatostatin may play a role in the pathophysiology of depression.     

Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.     

B7.2-Ig fusion proteins enhance IL-4-dependent differentiation of tumor-sensitized CD8+ cytotoxic T lymphocyte precursors

The B7/CD28 co-stimulatory pathway plays a critical role in T cell activation and differentiation. Our previous study demonstrated that administration of B7.2-Ig fusion proteins to tumor-bearing mice elicits IL-4-dependent, CD8+ T cell-mediated tumor regression. Here, we investigated whether B7.2-Ig stimulation of tumor-sensitized CD8+ CTL precursors during in vitro antigen re-sensitization actually results in their differentiation into mature CTLs and if so, whether such a process depends on IL-4 signals. Splenocytes from tumor-sensitized (tumor-bearing or tumor-immunized) mice exhibited low levels of anti-tumor CTL responses upon culturing alone, but induced strikingly enhanced CTL responses when stimulated in vitro with B7.2-Ig fusion proteins. Because CTLs were not generated from normal splenocytes even by B7.2-Ig stimulation, the expression of the B7.2-Ig effect required the in vivo tumor sensitization of CD8+ CTL precursors. Administration of anti-CD4 or anti-CD40 ligand (CD40L) to mice before tumor sensitization resulted in almost complete inhibition of CTL responses generated in the subsequent culture containing B7.2-Ig. In contrast, anti-IL-4 did not influence in vivo tumor sensitization required for CTL induction. However, B7.2-Ig stimulation of tumor-sensitized splenocytes enhanced IL-4 production and neutralization of this IL-4 with anti-IL-4 potently down-regulated CTL responses. These results indicate that B7.2-Ig enhances IL-4-dependent differentiation of anti-tumor CD8+ CTL precursors that can be sensitized in vivo depending on collaboration with CD4+ T cells involving CD40L function.     

Prediction of AVM obliteration after stereotactic radiotherapy using radiobiological modelling

This study was carried out in order to derive the radiobiological parameters of the dose-response relation for the obliteration of arteriovenous malformation (AVM) following single fraction stereotactic radiotherapy. Furthermore, the accuracy by which the linear Poisson model predicts the probability of obliteration and how the haemorrhage history, location and volume of the AVM influence its radiosensitivity are investigated. The study patient material consists of 85 patients who received radiation for AVM therapy. Radiation-induced AVM obliterations were assessed on the basis of post-irradiation angiographies and other radiological findings. For each patient the dose delivered to the clinical target volume and the clinical treatment outcome were available. These data were used in a maximum likelihood analysis to calculate the best estimates of the parameters of the linear Poisson model. The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was studied. AVM radiosensitivity was assumed to be the same for all the patients. The radiobiological model used was proved suitable for predicting the treatment outcome pattern of the studied patient material. The radiobiological parameters of the model were calculated for different AVM locations, bleeding histories and AVM sizes. The range of parameter variability had considerable effect on the dose-response curve of AVM. The correlation between the dosimetric data and their corresponding clinical effect could be accurately modelled using the linear Poisson model. The derived response parameters can be introduced into the clinical routine with the calculated accuracy assuming the same methodology in target definition and delineation. The known volume dependence of AVM radiosensitivity was confirmed. Moreover, a trend relating AVM location with its radiosensitivity was observed.     

Regulation of dopaminergic transmission and cocaine reward by the Clock gene

Although there are clear interactions between circadian rhythms and drug addiction, mechanisms for such interactions remain unknown. Here we establish a role for the Clock gene in regulating the brain's reward circuit. Mice lacking a functional Clock gene display an increase in cocaine reward and in the excitability of dopamine neurons in the midbrain ventral tegmental area, a key brain reward region. These phenotypes are associated with increased expression and phosphorylation of tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis), as well as changes in several genes known to regulate dopamine activity in the ventral tegmental area. These findings demonstrate the involvement of a circadian-associated gene, Clock, in regulating dopamine function and cocaine reward.     

Association of malignancy with diseases causing interstitial pulmonary changes

A number of studies have shown a high incidence of lung cancer in patients with idiopathic pulmonary fibrosis (9.8 to 38%) compared to control subjects (2 to 6.4%). A similar trend occurs in other entities that affect the interstitial lung compartment, such as systemic sclerosis and sarcoidosis, as well as occupational diseases. The pathogenesis of lung cancer in patients with diffuse pulmonary fibrosis is still unclear. Recent progress in molecular and cellular biology has shed some light on the possible interactions of several types of inflammatory cells, following the deleterious effects of toxic factors leading to alveolitis, and destruction and disorganization of lung parenchyma, which results in fibrosis. Further research in the field would enhance our understanding of the pathogenic mechanisms of cancer development in these patients, and to explain the reason for the different incidence of lung cancer in patients with various interstitial lung diseases.     

Systemic sclerosis associated with generalized vasculitis and hypopituitarism

Systemic sclerosis (SSc) is a progressively evolving multisystemic disorder of unknown etiology. Beyond skin, several other organs can also be affected with a severity of involvement that is often heterogeneous. We describe a 53-year-old female patient who was admitted urgently to the hospital almost collapsed, because of numerous bleeding deep skin ulcers, located all over the body. Clinical findings and autoantibody screening were typical of SSc. Moreover, both histopathology and immunofluorescence findings were compatible with scleroderma and vasculitis as well. In addition, pituitary hormone investigation revealed severely damaged function of the gland. We assume that severe skin ulceration and serious hypopituitarism were both implications of underlying SSc-associated vasculitis. To the best of our knowledge, these peculiar clinical manifestations have not been described in the international literature to date.     

West Nile virus in mosquitoes in Greece

Epidemics of West Nile virus (WNV) occurred for two consecutive years in Greece (in 2010 and 2011). A total of 16,116 adult Culex pipiens mosquitoes collected in two peripheries, Central Macedonia and Thessaly, were tested for WNV infection. WNV lineage 2 was detected in 6/296 mosquito pools, three in each year. The H₂₄₉P substitution in the NS3 protein, previously associated with increased pathogenicity and thermotolerance, was detected in all six WNV-positive mosquito pools. When 21 individual C. pipiens mosquitoes were tested for the locus CQ11 to distinguish between the two C. pipiens forms, pipiens and molestus, 71.4 % were identified as pipiens, 4.7 % as molestus, and 19 % as hybrid pipiens/molestus, giving the first evidence that both C. pipiens biotypes are present in Greece, with a significant proportion being hybrids. The exact role of the C. pipiens forms and hybrids in the WNV epidemiology, in combination or not with the H₂₄₉P substitution in the virus genome, remains to be elucidated.     

Balantidium coli pneumonia in an immunocompromised patient

A fatal case is reported of Balantidium coli pneumonia in a 71-y-old woman suffering from anal cancer. The diagnosis was made by the discovery of motile trophozoites in a wet mount from bronchial secretions. The usual habitat of the parasite is the colon; lung balantidiasis is very rare.