Densitometry for assessment of effect of lung volume reduction surgery for emphysema.

To explore if change in the extent of emphysema correlated with change in lung function, the effect of resection of emphysematous tissue was studied by computed tomography (CT) densitometry. In addition, the current authors studied how surgery-induced change in emphysema related to lung density in control subjects. In total, 30 patients (14 females; mean+/-sd age 59+/-10 yrs) with severe emphysema before and 3 months after lung volume reduction surgery (LVRS), 48 patients with moderate emphysema and 76 control subjects were investigated. Lung density (15th percentile point) of both lungs and heterogeneity of lung density between 12 isovolumetric partitions in each lung were calculated from chest CT images. The 15th percentile point and its heterogeneity could distinguish controls from subjects with moderate emphysema with a sensitivity and specificity of >95%. LVRS significantly increased lung density by 5.0+/-10.9 g.L(-1) (n=30). Improvement in the diffusing capacity of the lung for carbon monoxide and in residual volume significantly correlated with an increase in lung density (n=20 and 28, respectively). Change in forced expiratory volume in one second did not correlate with change in lung density. In conclusion, lung density 15th percentile point is a valuable surrogate marker for detection of both the extent of and reduction in emphysema.     

Lung Transplant Recipients Holding Companion Animals: Impact on Physical Health and Quality of Life

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.     

Quantitative study of blood-brain barrier permeability changes after experimental whole-brain radiation.

Basic mechanisms underlying the tolerance and reaction of the central nervous system to ionizing radiation are not known precisely. We investigated the possibility of a change in blood-brain barrier (BBB) function as a causative factor for early delayed whole-brain radiation-induced cerebral dysfunction. Rats were exposed to conventional fractionation (200 cGy/d, 5 d/wk; total dose, 4000 cGy). BBB changes were assessed by means of the quantitative 14C-alpha-aminoisobutyric acid technique and electron microscopy. Studies of the passage of horseradish peroxidase across the BBB permitted comparative quantitative isotopical and qualitative morphological data. Experiments were carried out 2 to 3 weeks after the completion of the radiation exposure. The transport of 14C-alpha-aminoisobutyric acid across the BBB increased significantly in cerebral cortex and cerebellar gray matter, averaging 1.3 to 1.5 times over the normal values. Electron microscopy disclosed an intense vesicular response of the cortical microvascular endothelium that occurred without the opening of the tight junctions and resulted in an intense transport of HRP across the intact endothelium. The present data indicate that moderate doses of whole-brain radiation induce well-defined changes in BBB function, which possibly are involved in the pathogenesis of radiation-induced cerebral dysfunction in humans.     

Contribution of computerized tomography to the diagnosis of patients with non-calcified solitary pulmonary nodule, without known neoplasm]

We define a solitary pulmonary noncalcified nodule (NPS) as a single focal rounded or ovoid lesion in the lung parenchyma, less than 4 cm in diameter, without associated adenopathy, atelectasis or pneumonia. An NPS, in the absence of a known primary malignancy, can be lung cancer (NPSM), a metastasis of unknown origin (NPSMT), or a benign lesion (NPSB). The best approach to the management of NPS and the value of CT are still controversial and uncertain. The finding on cross-section CT of a bronchus leading directly to, or contained within, the nodule is called "positive CT bronchus sign" (CT-BS). Our study was aimed at investigating the usefulness of CT bronchus sign, as studied on thin-slice (2 mm thick) CT sections, in order to establish the most appropriate diagnostic sequence in patients with solitary noncalcified pulmonary nodules (NPS). We evaluated 47 NPS (9 NPSB, 34 NPSM and 4 NPSMT) with thin-slice CT to detect the presence of CT bronchus sign. Seventeen cases had CT-BS (15 NPSM; 1 NPSB; 1 NPSMT); of them, 13 were diagnosed by means of transbronchial biopsy and brushing (TBB). Only one case (NPSM) of the 30 (19 NPSM; 3 NPSMT; 8 NPSB) without CT-BS, was diagnosed by TBB. TBB was negative in the 9 NPSB. The CT-BS is not pathognomonic of malignancy; in fact, the sign was observed in NPSB (one tuberculoma) too. Our results suggest that the CT bronchus sign is valuable in predicting the success of TBB in malignant solitary pulmonary nodules. On the other hand, it seems to be useless for NPSB. Therefore, to establish the most appropriate diagnostic sequence, thin-section CT should be performed in each patient with peripheral noncalcified lung lesions to plan whether TBB or transthoracic needle aspiration should come next. If biopsy results are poor, either surgery or the "wait and watch for growth" approaches can be suggested. The choice can be guided by the presence of predisposing factors for cancer or infection.     

Effects of lung volume reduction surgery for emphysema on diaphragm dimensions and configuration

Part of the functional benefit provided by lung volume reduction surgery (LVRS) may be related to improvement in respiratory muscle function resulting from changes in diaphragm dimension and configuration. To study these changes, we obtained 3D reconstructions of the muscle using spiral computed tomography in 11 patients with severe emphysema before and 3 mo after surgery, and in 11 normal subjects matched for sex, age, height, and weight. Bilateral LVRS was performed by thoracoscopy in eight patients and by sternotomy in three patients. Acquisitions were made in the supine posture at relaxed FRC, midinspiratory capacity, and TLC. On average, LVRS produced a 51 +/- 11% increase in FEV(1) and a 30 +/- 4% decrease in FRC. The total surface area of the diaphragm (A(di)) and of the zone of apposition (A(ap)) at FRC increased by 17 +/- 4% and 43 +/- 8%, respectively, but the surface area of the dome did not change. Compared with the values recorded in the normal subjects, postoperative values of A(di) and A(ap) at FRC were reduced by 11% (p < 0.05) and 24% (p < 0.005), respectively. The curvature of the dome increased at TLC in the left sagittal plane, but was otherwise unaffected by the procedure. We conclude that LVRS substantially increases A(di) and A(ap), but does not significantly improve diaphragm configuration at FRC.     

Prevalence and prediction of exercise-induced oxygen desaturation in patients with chronic obstructive pulmonary disease

Background: Previous studies with small sample sizes reported contradicting findings as to whether pulmonary function tests can predict exercise-induced oxygen desaturation (EID). Objective: To evaluate whether forced expiratory volume in one second (FEV(1)), resting oxygen saturation (SpO(2)) and diffusion capacity for carbon monoxide (DLCO) are predictors of EID in chronic obstructive pulmonary disease (COPD). Methods: We measured FEV(1), DLCO, SpO(2) at rest and during a 6-min walking test as well as physical activity by an accelerometer. A drop in SpO(2) of >4 to <90% was defined as EID. To evaluate associations between measures of lung function and EID univariate and multivariate analyses were used and positive/negative predictive values were calculated. Receiver operating characteristic curve analysis was performed to determine the most useful threshold in order to predict/exclude EID. Results: We included 154 patients with COPD (87 females). The mean FEV(1) was 43.0% (19.2) predicted and the prevalence of EID was 61.7%. The only independent predictor of EID was FEV(1) and the optimal cutoff value of FEV(1) was at 50% predicted (area under ROC curve, 0.85; p < 0.001). The positive predictive value of a threshold of FEV(1) <50% was 0.83 with a likelihood ratio of 3.03 and the negative predicting value of a threshold of FEV(1) ≥80% was 1.0. The severity of EID was correlated with daily physical activity (r = -0.31, p = 0.008). Conclusions: EID is highly prevalent among patients with COPD and can be predicted by FEV(1). EID seems to be associated with impaired daily physical activity which supports its clinical importance.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Time trend and age-period-cohort effect on incidence of thyroid cancer in Connecticut, 1935–1992

Recent studies from Europe suggest a continuing increase in thyroid cancer, but it is unclear whether this trend also applies to the United States. The current study examined the long-term trend of thyroid cancer in Connecticut. Our results show that the overall age-adjusted incidence rate of thyroid cancer has been increasing in Connecticut, from 1.30/100,000 in 1935–1939 to 5.78/100,000 in 1990–1992 in females, and from 0.30/100,000 in 1935–1939 to 2.77/100,000 in 1990–1992 in males. The increase mainly comes from papillary carcinoma of the thyroid. The birth cohort analyses indicate that the increase in thyroid cancer occurred among cohorts born between 1915 and 1945, which experienced an increase of 31.4% every 5 years in males and 17.3% in females over the period 1960–1979. For those born since the 1945 cohort, the incidence has been decreasing, at rates of 9.3% and 8.3% every 5 years over the period 1975–1992 in males and females, respectively. Age-period-cohort modeling results also suggest a strong birth cohort effect on the observed time trend in both sexes, which closely follows the introduction of radiation treatment of benign childhood conditions in the head and neck between 1920 and the 1950s in the United States. Our results are consistent with the suggested radiation hypothesis, indicating that radiation treatment of benign childhood conditions in the head and neck is largely responsible for the observed increase of thyroid cancer in Connecticut. © 1996 Wiley-Liss, Inc.     

Tubers from patients with tuberous sclerosis complex are characterized by changes in microtubule biology through ROCK2 signalling

Most patients with tuberous sclerosis complex (TSC) develop cortical tubers that cause severe neurological disabilities. It has been suggested that defects in neuronal differentiation and/or migration underlie the appearance of tubers. However, the precise molecular alterations remain largely unknown. Here, by combining cytological and immunohistochemical analyses of tubers from nine TSC patients (four of them diagnosed with TSC2 germline mutations), we show that alteration of microtubule biology through ROCK2 signalling contributes to TSC neuropathology. All tubers showed a larger number of binucleated neurons than expected relative to control cortex. An excess of normal and altered cytokinetic figures was also commonly observed. Analysis of centrosomal markers suggested increased microtubule nucleation capacity, which was supported by the analysis of an expression dataset from cortical tubers and control cortex, and subsequently linked to under‐expression of Rho‐associated coiled‐coil containing kinase 2 (ROCK2). Thus, augmented microtubule nucleation capacity was observed in mouse embryonic fibroblasts and human fibroblasts deficient in the Tsc2/TSC2 gene product, tuberin. Consistent with ROCK2 under‐expression, microtubule acetylation was found to be increased with tuberin deficiency; this alteration was abrogated by rapamycin treatment and mimicked by HDAC6 inhibition. Together, the results of this study support the hypothesis that loss of TSC2 expression can alter microtubule organization and dynamics, which, in turn, deregulate cell division and potentially impair neuronal differentiation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd