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.     

Radiation dose reduction during hysterosalpingography: an application of scanning-beam digital radiography

Hysterosalpingography was performed in 31 patients by means of a low-dose scanning-beam digital radiographic system. The technique permits adequate evaluation of gynecologic abnormalities while allowing significant reduction in radiation: 2.4-mR (6.1 X 10(-7) C/kg) exposure to the skin and 0.7-mrad (7 X 10(-6) Gy) mean dose to the ovaries per image obtained. Sixteen patients demonstrated readily recognizable and documented abnormalities, corroborated by laparoscopy, laparotomy, or other supportive evidence.     

Influence of complement on sperm motility

Isolated sperm from normo-, oligo- and astheno-spermic men were incubated for 20 h in medium supplemented with 8% heat-inactivated or untreated human serum, and in medium with heated or untreated serum deficient in complement factor C3. Before and after incubation, sperm motility was assessed by means of a computer-assisted semen analyser. The results did not show significant differences between the motility of sperm incubated in heated or untreated serum. It is concluded that heating of homologous serum is not necessary for preserving sperm motility and in some cases may even be disadvantageous.     

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.     

Image-directed percutaneous biopsies with a biopsy gun

Core tissue for histologic study is believed by many pathologists to be more diagnostic than material from needle aspiration. Recently, a biopsy "gun" has been introduced, which simplifies core biopsies. With this device, 182 biopsies of multiple anatomic sites were performed with ultrasonic, computed tomographic, and fluoroscopic guidance and 18-gauge needles. High-quality histopathologic specimens were obtained in 177 of the biopsies, and diagnostic target tissue was obtained in 167. Only three significant complications occurred: one bleeding complication that required transfusion and two cases of pneumothorax that necessitated placement of chest tubes. The biopsy gun eliminated the disjointed movements of conventional "skinny" needle biopsies, and none of the samples demonstrated significant "crush" artifact or obscuring blood, problems that are commonly associated with manual biopsy techniques. Patient discomfort was decreased with this system compared with that of manual biopsies, and the total procedure time was reduced. Because of these distinct advantages, the authors now use the biopsy gun exclusively for all percutaneous biopsies and recommend that other institutions consider the use of this biopsy method.     

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.