Lesion-Specific and Vessel-Related Determinants of Fractional Flow Reserve Beyond Coronary Artery Stenosis

Objectives

The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR.

Proliferation of non-Hodgkin-lymphoma lymphocytes in vitro is dependent upon follicular dendritic cell interactions

Follicular dendritic cells (FDC) are located within the B-cell follicles of non-malignant lymphatic tissues and within non-Hodgkin-lymphomas (NHL) derived from the germinal centre or the mantlezone. The interactions between FDC and non-neoplastic B-cells have been extensively investigated but so far no data on functional studies with FDC isolated from lymphoma tissue are available. Using an enzyme cocktail to digest lymph nodes from patients with NHL followed by density centrifugation, single cell suspensions enriched in FDC and B-lymphocytes were obtained. In these preparations FDC formed small cellular clusters with an average of five neoplastic lymphocytes for every FDC. Immunocytochemistry with Ki67 revealed that after 24 h of culture 23.7% of the cells within the clusters were in late G1 to M phase. In contrast, only 10.2% of the lymphoma cells scattered outside the clusters were in these activated stages. As visualized by autoradiography, after 72 h of incubation the rate of proliferation was 16.8 times higher for the lymphoma cells involved in cluster formation as compared to those lymphocytes not associated with FDC. The data indicate that in vitro FDC from NHL lymph nodes form a microenvironment favourable for the activation and proliferation of lymphoma cells. The search for cytokines secreted by FDC in lymphoma tissue is under way.     

The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women

OBJECTIVE To investigate the basal levels of gonadotrophins and sex steroids, with special reference to the effects of obesity and body fat distribution, In premenopausal women, both those with polycystic ovary syndrome (PCOS) and those with normal ovaries and regular menstrual cycles. DESIGN Cross-sectional study. The separate effects of obesity (and body fat distribution and fasting Insulin levels) and PCOS on endocrine variables were evaluated by means of analysis of covariance. PATIENTS Sixty-seven women with anovulatory menstrual cycles and polycystic ovaries according to ultrasonography and 59 women with normal ovaries and regular cycles, both groups covering a wide range of body mass index (BMI, PCOS, 17·6-37·4, mean 25·7 kg/m²; controls, 18·8-40·9, mean 25·1 kg/m²). MEASUREMENTS Serum levels of gonadotrophins, sex steroid hormones, prolactin and GH obtained in the early follicular phase in the controls, fasting insulin levels, anthropometric measures (BMI, skinfolds, waist hip ratio). RESULTS Mean serum concentrations of LH, andro-stenedione, testosterone, the free androgen index (FAI; all P < 0·0001) and DHEAS (P < 0·01) were higher, and serum FSH (P < 0·01) and serum SHBG levels lower (P < 0·0001), in the PCOS group than in the controls. Women with PCOS had a more pronounced upper body fat distribution and higher fasting insulin levels than the controls. Independent of PCOS, BMI was positlvely associated with serum levels of FSH (P < 0·001) and negatively with levels of LH (P < 0·05), LH/FSH ratio (P < 0·0001), SHBG (P < 0·0001) and androstenedione (P < 0·01), whereas for levels of testosterone, FAI and DHEAS the impact of obesity differed significantly between the groups. Thus, in the PCOS group, testosterone levels (P < 0·05) and the FAI (P < 0·001) were positively associated with BMI, whereas they were constant throughout the entire range of BMI in the controls. DHEAS levels were positively associated with BMI in the PCOS group (P < 0·05) and negatively in the controls (P < 0·01). Measures of upper body fat were related to testosterone and FAI levels, independent of BMI. CONCLUSIONS Lower FSH levels were found in women with PCOS than during the early follicular phase of normally ovulating women, suggesting a role in anovulation in PCOS. Obesity itself exerted effects on endocrine variables, with the net result of a reduced LHIFSH ratio and lower serum levels of androstenedione and SHBG in both groups; obesity was associated with increased levels of DHEAS, testosterone and FAI exclusively in the women with PCOS. The results underline the endocrine impact of obesity and body fat distribution and the necessity of applying reference values of BMI matched subjects when establishing the endocrine profile of women with PCOS.     

Tender point scores and their relations to signs of mobility, symptoms, and disability in female home care personnel and the prevalence of fibromyalgia syndrome

OBJECTIVE: In this study of female home care personnel employed in a municipality (n = 643; participation rate 94%) we investigated (1) the prevalence of tender points and fibromyalgia (FM); (2) the relationships between tender point score and other signs and symptoms; (3) if subgroups based on the tender point score differed with respect to signs, symptoms, disability, and health related quality of life; and (4) signs that showed the strongest intercorrelations with disability and health. METHODS: The following variables were registered: (1) Signs: joint mobility, spinal posture and mobility, tender points, and segmental mobility and pain provocation at L4-S1 levels of the low back. (2) Symptoms: pain and pain intensity and other symptoms. (3) Disability (i.e., self-rated reduced capacity for everyday activities and employment) and health: 3 indices and sick leave. RESULTS: The tender point score correlated with the number of pain regions and the pain intensities, and the amount of other symptoms, sick leave, and disability. Tender point score was the strongest regressor of the investigated signs in regression of the 2 disability indices. Segmental pain showed the strongest correlation with tender point score. Three subgroups identified by tender point score showed significant differences in segmental pain, prevalence and intensity of different symptoms, disability, and health related quality of life. The prevalence of FM was 2.0%. CONCLUSION: Tender point score together with different symptoms showed relatively strong correlations with disability. A relatively high prevalence of FM was found in occupationally active female home care personnel.     

Ethanol-induced malfunction of neutrophils respiratory burst on patients suffering from alcohol dependence

Background: Polymorphonuclear, neutrophil granulocytes (PMN) play a major role in the control of infections, and people who abuse alcohol are susceptible to infections. Resistance against infections ensues intracellularly following initial phagocytosis of microorganisms with the oxygen‐dependent respiratory burst, the key enzyme of which is the respiratory burst oxidase, whereby oxygen radicals are produced for microbial destruction. To date there is insufficient information available in connection with the process of impaired defence against infection in patients suffering from alcohol dependence. Therefore, our investigation was carried out to determine the influence of alcohol exposition on the formation of oxygen radicals and the respiratory burst. Methods: 4.5 ml of whole blood was taken from 10 healthy adults and 10 patients suffering from alcohol dependence. An additional 3.5 ml of whole blood was taken from the alcoholic patients for determination of the blood alcohol concentration. The respiratory burst of PMN was tested using the Four‐Colour‐Continuous Flow Cytometer. Each experimental procedure consisted of 4 test samples [negative controls, Escherichia coli, FMLP‐supplement (N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanin), PMA‐supplement (phorbol‐12‐myristate‐13‐acetate)]. Differing concentrations of ethanol were also introduced to each of the tests performed (0.20 to 4.00 g/l). Results: Ethanol revealed a marked decrease of burst activity in those patients suffering from alcoholism with increased alcohol concentration. A dependence between the burst activity and the ethanol concentration was seen to be statistically significant. This effect was only evident after stimulation with E. coli and FMLP in those patients with alcohol dependence. Conclusion: The results presented in this study show an impairment in the function of PMN in those patients addicted to alcohol due to the decrease in burst activity. In view of the results of the different stimuli, the second‐messenger effects were not evident. A clarification of this phenomenon could well be assumed as an allosteric receptor effect on the burst oxidase, namely, a direct effect on the phagocytosis interaction between circulating granulocytes and causative organisms.     

The effect of hepatectomy on glucose homeostasis in pig and in man.

BACKGROUND/AIMS: The liver is regarded the most important source of glucose production and it is common practice to administer glucose during human liver transplantations to avoid hypoglycaemia. The purpose of this study was to evaluate the importance of extra-hepatic contribution (kidney, gut and muscle) to the glucose homeostasis in the anhepatic pig and in man during the anhepatic phase of human liver transplantations. METHODS: Blood glucose and lactate were monitored in the anhepatic phase in 46 patients undergoing liver transplantation. Arterial-venous differences of lactate, glucose, glycerol, alanine and free fatty acids were measured over kidney, gut and hind leg in 18 pigs made anhepatic. RESULTS: Blood glucose did not change significantly and blood lactate increased only marginally during the anhepatic phase of human orthotopic liver transplantation. In the anhepatic pig, however, blood glucose decreased with a halflife of about 26 min and blood lactate increased. Kidney gluconeogenesis was 0.116+/-0.016 mmol min(-1). Fifty percent of kidney glucose output could be accounted for by lactate- and glycerol uptake. CONCLUSIONS: The results show that in humans extra hepatic gluconeogenesis is sufficient to maintain normal blood glucose in the anhepatic phase of orthotopic liver transplantation, while in the pig this was not the case.     

Anti-VEGF agents confer survival advantages to tumor-bearing mice by improving cancer-associated systemic syndrome

The underlying mechanism by which anti-VEGF agents prolong cancer patient survival is poorly understood. We show that in a mouse tumor model, VEGF systemically impairs functions of multiple organs including those in the hematopoietic and endocrine systems, leading to early death. Anti-VEGF antibody, bevacizumab, and anti-VEGF receptor 2 (VEGFR-2), but not anti-VEGFR-1, reversed VEGF-induced cancer-associated systemic syndrome (CASS) and prevented death in tumor-bearing mice. Surprisingly, VEGFR2 blockage improved survival by rescuing mice from CASS without significantly compromising tumor growth, suggesting that “off-tumor” VEGF targets are more sensitive than the tumor vasculature to anti-VEGF drugs. Similarly, VEGF-induced CASS occurred in a spontaneous breast cancer mouse model overexpressing neu. Clinically, VEGF expression and CASS severity positively correlated in various human cancers. These findings define novel therapeutic targets of anti-VEGF agents and provide mechanistic insights into the action of this new class of clinically available anti-VEGF cancer drugs.     

18F‐Fluorodeoxyglucose (FDG)‐PET features of focal nodular hyperplasia (FNH) of the liver

Abstract: Aim: The aim of this paper is to describe the imaging pattern of focal nodular hyperplasia (FNH) by ¹⁸F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET). Methods: Eight consecutive asymptomatic patients with histologic proof of FNH underwent 18F‐FDG PET imaging. The lesions were found incidentally. The 18F‐FDG PET imaging was performed with a dedicated PET tomograph after intravenous injection of 300–370 MBq 18F‐FDG. The 18F‐FDG accumulation in the lesions was (semi)quantified by calculating the standardized uptake value (SUV) and SUV has been corrected for the lean body mass (LBM). Eight patients with liver metastases spread from melanoma (n=2) and colorectal carcinoma (n=6) served as controls. The size of the FNH lesions and of the control group ranged from 2.0 to 8.5 cm (mean 4.83 cm±2.37) and from 1.5 to 6 cm (mean 3.28±1.52), respectively. Results: While in malignant liver lesions the accumulation of 18F‐FDG was significantly increased, all FNH lesions showed normal or even decreased accumulation of 18F‐FDG. In FNH lesions, SUV ranged between 1.5 and 2.6 (mean 2.12±0.38), whereas all liver metastases showed an increased SUV ranging between 6.20 and 16.00 (mean 10.07±3.79). The SUV corrected for LMB (SUV_LBM) was similar to the SUV and ranged between 0.9 and 2.2 (mean 1.81±0.41) for FNH and between 5.9 and 16.3 (mean 9.15±4.03), respectively. Conclusion: In contrast to liver metastases, there is no increased glucose metabolism in FNH in vivo. The imaging feature of FNH by 18F‐FDG‐PET imaging is not specific for FNH; however, it may be helpful to differentiate FNH from liver metastases in cancer patients if radiological methods are not diagnostic.