The role of epsilon phenotype in brain glucose consumption in Alzheimer’s disease

The aim of our study was to investigate the impact of the epsilon phenotype in brain glucose consumption in a population with Alzheimer’s disease. Statistical Parametric Mapping (SPM8) was used to investigate differences in brain glucose consumption (as detectable by means of 18F FDG-PET/CT) in the population examined. A total of 129 patients (72 females and 57 males) with a diagnosis of probable AD according to the NINCDS-ADRDA criteria underwent the PET/CT examination. The mean (SD) age of the patients was 70 (± 7) years; the mean Mini-Mental State Examination was 19(± 5.6). 59 expressed epsilon 4 phenotype (E4) and 70 expressed the epsilon 3 phenotype (E3). Cerebral spinal fluid amyloid, tau, and t-tau have been measured resulting equal to 367.4 (± 149.1), 584.7 (± 312.1), and 79.2(± 45.9) pg/ml, respectively. Patients with confirmed amyloid and Tau changes were classified as AD. Patients with amyloid changes but negative Tau, considered as high risk of AD, were classified as IAD. Age, sex, MMSE, scholarship, and CSF parameters were used as a covariate in the SPM analyses. We did not find significant differences in age, gender, and MMSE and CSF parameters among groups. In the analysis of the AD group as compared to AD-E3, AD-E4 subjects show a significant reduction of brain glucose consumption in inferior frontal gyrus bilaterally (BA 45, BA 47). In the analysis of the IAD group as compared to IAD-E3, IAD-E4 subjects show a significant reduction of brain glucose consumption in right in medial, middle, and superior frontal gyrus (BA10, BA11), and in left medial and middle frontal gyrus (BA10, BA11). The differences between IAD-E3 and AD-E3 and between IAD-E4 and AD-E4 (and vice versa analysis) resulted not significant. APO-e4 is related to a major involvement of the frontal cortex confirming its role of risk factor in AD, while APO-3 seems not related to a specific pattern, supporting the hypothesis of neutral/protective role in AD.     

Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [¹⁸F]FDG and [¹¹C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).     

Uniportal vs standard three-port VATS technique for spontaneous pneumothorax: comparison of post-operative pain and residual paraesthesia.

OBJECTIVE: VATS using the conventional three ports is currently the technique of choice for blebectomy/bullectomy for spontaneous pneumothorax. However, the procedure has recently been shown to have neurological complications related to the port sites. Uniportal VATS has recently been proposed as an alternative to conventional three-port VATS. It is anticipated that the single incision will predispose to a lower incidence of neurological complications. METHODS: We report our initial single surgeon experience of uniportal VATS (n = 16) and provide a comparison of post-operative pain and residual paraesthesia to conventional three-port procedures (n = 19) for the same pathology. RESULTS: In both groups, the pneumothorax pathology was principally primary. There was no difference between the groups in terms of age, spirometry, tissue resected, drainage time and inpatient stay. A difference was, however, noted in inpatient pain scores. The uniportal group had a lower median score of 0.4 (visual analogue range 0-4) while the three-port technique reported 0.8 (P = 0.06, Mann-Whitney test). The maximum score trend was similar (1.4 vs. 2.6, respectively, P < 0.001, Mann-Whitney test). Follow-up for uniportal and three-port VATS averaged 9.4+/-6.6 and 32.1+/-9.9 months, respectively. One patient in the three-port group had a pneumothorax recurrence. Three-port VATS also had a higher residual pain score (0.5) compared to uniportal VATS (0.3). Of clinical significance was the incidence of neurological complications. Eighty-six percent of uniportal patients reported no symptoms. The remaining experienced only mild 'numbness' or 'swelling'. However, in the three-port group, only 42% reported no symptoms. A similar number experienced 'numbness'. Two females described sexual dysfunction due to altered breast sensitivity. Seventeen percent (2/12) reported 'pins and needles'. CONCLUSIONS: Uniportal VATS appears to be tolerable, safe and efficient in treating spontaneous pneumothorax in our series. Moreover, post-operative pain and paraesthesia incidence was lower than three-port VATS. Prospective randomised trials are important to evaluate this technique.     

Elective transplant pneumonectomy in a 38-year-old man.

Transplant pneumonectomy is a rarely performed procedure. It is occasionally carried out in the course of retransplantation. To our knowledge, resection of a transplanted lung without its replacement and with successful outcome in the adult has not been previously reported. We present a case of elective left transplant pneumonectomy in a 38-year-old man 6 years after left single-lung transplant. At 12 months after resection, the patient remains well, with good exercise tolerance.     

Contribution of Blockade of the Noradrenaline Carrier to the Increase of Extracellular Dopamine in the Rat Prefrontal Cortex by Amphetamine and Cocaine

This study was performed to investigate the relative role of noradrenaline (NA) and dopamine (DA) carrier blockade in the effects of psychostimulants on DA transmission in the rat prefrontal cortex (PFCX). To this end, changes of extracellular DA and NA in the PFCX and of extracellular DA in the nucleus accumbens (NAc) were measured following the administration of amphetamine and cocaine, which are known to bind to both DA and NA carriers, or GBR 12909, a selective DA carrier blocker. After non-intravenous injection, amphetamine (0.25 and 0.5 mg/kg, s.c.) and cocaine (5 and 10 mg/kg, i.p.) increased extracellular DA in the PFCX to a larger extent than in the NAc, while the reverse applied to GBR 12909 (2.5 and 5 mg/kg, i.p.). These differences were obtained in spite of the fact that the three drugs elicited at each dose level a similar peak increase of extracellular DA in the NAc. Amphetamine and cocaine also increased extracellular NA in the PFCX and this effect was quantitatively similar to that on extracellular DA in the same area. Intravenous doses of cocaine and GBR 12909, corresponding to those which maintain self-administration in the rat, while equieffective in raising extracellular DA in the NAG, had different effects on extracellular DA in the PFCX. In fact, in contrast to cocaine, GBR 12909 increased extracellular DA in the PFCX to a lesser extent than in the NAc or did not modify it at all. The peak increase of extracellular DA in the PFCX was highly correlated to that of NA in the same area but was poorly correlated to the increase of extracellular DA in the NAc. These results suggest that amphetamine and cocaine increase extracellular DA in the PFCX largely through the blockade of the NA carrier. Direct evidence for this hypothesis was provided by the observation that, when the NA carrier was blocked by reverse dialysis of the PFCX with desipramine (1 μM), cocaine and GBR 12909 lost their differences in the ability to increase extracellular DA in the PFCX.     

Predicted versus observed FEV1 in the immediate postoperative period after pulmonary lobectomy.

OBJECTIVE: Scanty information can be found regarding ppoFEV1% correlation with true FEV1% in the immediate days after surgery, when most cardio-respiratory complications are developed. This prospective multicentric investigation aims to describe the evolution of FEV1 in a series of uneventful lobectomy cases before hospital discharge, and to identify factors associated with the variation of postoperative residual FEV1, with the ratio between the actual and the predicted postoperative FEV1 measured during the first 6 postoperative days. METHODS: One hundred and sixty-one patients submitted to lobectomy were prospectively enrolled in the study. Patients with chest wall resections and postoperative complications were excluded. Data from a total of 125 patients were thus used for the analysis. The following clinical variables were recorded: age, preoperative FEV1, ppoFEV1, presence of chronic obstructive pulmonary disease (COPD), surgical approach (VATS or muscle-sparing thoracotomy), side (right or left) and site (upper or lower) of resection, type of analgesia (epidural or intravenous), and daily visual analogue pain score (VAS). FEV1 was measured in every patient at hospital admission and daily until discharge or up to postoperative day 6. Random effects time-series cross-sectional regression analyses were performed to identify factors associated with variation of postoperative residual function (100-(preoperative FEV1-postoperative FEV1/preoperative FEV1 x 100)), and of FEV1 ratio ((actual postoperative FEV1 x 100)/ppoFEV1). For these analyses, the dependent variables (postoperative residual function and FEV1 ratio) and the pain score were analysed as panel longitudinal data. The regression analyses were subsequently validated by bootstrap procedure. RESULTS: FEV1% was lower at first postoperative day and increased gradually up to day 6 but mean values never reached ppoFEV1%. Pain scores decreased from day 1 to day 6. Preoperative FEV1 (p<0.0001) and postoperative pain score (p<0.0001) resulted independently and reliably inversely associated with postoperative residual FEV1 (model R2, 0.16). Preoperative FEV1 (p=0.001), postoperative pain score (p<0.0001), and epidural analgesia (p=0.04) resulted independently and reliably associated with postoperative FEV1 ratio (model R2, 0.13). CONCLUSION: Current methods of prediction of postoperative FEV1 greatly underestimated the real functional loss in the immediate postoperative period. Therefore, for the purpose of a more accurate risk stratification we need to correct the traditional prediction of postoperative FEV1.