Gender Patterns of Socioeconomic Differences in Premature Mortality: Follow-up of the Hungarian Epidemiological Panel

Background

Gender differences in premature mortality rates and in the size of socioeconomic inequalities in mortality vary across countries.

Purpose

We aimed to quantify the gender differences in the association between socioeconomic status (SES) and premature all-cause mortality and to analyse whether psychosocial factors might associate between SES and mortality among men and women separately in the middle-aged Hungarian population.

Method

Men (n?=?1130) and women (n?=?1529), aged 40–69 years, participants in the Hungarian Epidemiological Panel (2002) were followed up for 3.5 years for total mortality. Cox proportional hazard models were used to evaluate the association between several socioeconomic measures and total death.

Results

During the follow-up, 99 men (8.8%) and 53 women (3.5%) died. The age-adjusted hazard ratios and the Rothman’s synergy indexes showed that each measure of socioeconomic position was more deleterious in men compared with women. When investigating potential explanatory factors for the SES–mortality association, we found that adjustment for severe depression resulted in the most pronounced reduction in the regression coefficients for the association between most socioeconomic factors and male premature death. There was no indication that depression would mediate between SES and mortality in women. Work stress factors, poor lifestyle and low social support also contributed to the explanation of the link between socioeconomic disadvantage and premature death in men.

Conclusion

Middle-aged Hungarian men seem to be considerably more vulnerable to the chronic stress of material disadvantage than women. This effect modification by gender might partly be explained by a stronger connection between low SES and depressive symptoms in men.     

The assessment of neural injury following open heart surgery by physiological tremor analysis

Introduction

The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor.

Material and methods

We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3^rd to 5^th post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test.

Results

We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p < 0.01). The magnitude of the shift was not significantly higher for females than for males (p < 0.157). We found no significant difference between the shift and the cross-clamp or perfusion time (p < 0.6450).

Conclusions

The assessment of physiological tremor by means of our novel, feasible method may provide a deeper insight into the mechanism of central nervous system damage associated with open heart surgery.     

Genetic profile of bone metastases in renal cell carcinoma

OBJECTIVE: The aim of this study was to define specific genetic alterations which are common in bone metastases in renal cancer patients. METHODS: Tumor DNA from 31 metastases and 13 related primary tumors was extracted from paraffin embedded tissue sections. DOP-PCR was performed to amplify the whole DNA. After labelling by PCR, CGH was performed according to standard protocols. RESULTS: The mean number of aberrations per metastasis was 6.3 (1-13). Losses of chromosomes 3p (76%), 6 (20%), 8p (20%), 9 (34%), 14q (27%) and 18 (20%) as well as gains of chromosomes 5 (45%), 8q (34%) and 17 (27%) were detected frequently. Thirteen related primary tumors were also investigated. In 7 cases, at least one identical alteration was found in both primary tumor and metastases. In these cases, the number of alterations was mostly higher in primary tumors than in metastases without statistical significance. However, in general, the frequency of alterations was higher in metastases. CONCLUSIONS: Bone metastases from renal cell carcinoma are characterized by typical genetic alterations. Changes leading to metastasizing happen early in tumor pathogenesis. However, further accumulation of genetic changes occurs in metastases leading to a more complex genetic pattern which might be necessary for progression to clinically relevant metastases.     

Efficacy and safety of gadodiamide (Gd-DTPA-BMA) in renal 3D-magnetic resonance angiography (MRA): a phase II study

PURPOSE: To determine the most efficacious dose of gadodiamide for three-dimensional (3D) contrast-enhanced (CE) magnetic resonance angiography (MRA) of the renal arteries on a patient level based on the sensitivity in detecting the main hemodynamically relevant (> or =50% or occlusion) renal artery stenosis (RAS) using intra-arterial digital subtraction angiography (IA DSA) as the gold standard. MATERIALS AND METHODS: This prospective, randomized, double-blind, parallel-group, multicenter study included 273 patients referred to IA DSA for suspected RAS. Patients underwent 3D CE MRA after injection of 0.01, 0.05, 0.1, or 0.2mmol/kg of body weight gadodiamide (0.5mmol/ml). The images were assessed for location and degree of RAS by independent blinded readers (MRA: three readers, IA DSA: one reader). Hypothesis testing for a significant trend in sensitivity across dose groups was based on the one-sided Cochran-Armitage style trend test for each independent MRA reader. RESULTS: The lowest dose group (0.01mmol/kg) proved non-efficacious in detecting hemodynamically relevant (i.e., > or =50% or occlusion) RAS. A statistically significant dose trend (p<0.001) was shown for each of the three independent readers. Depending on reader, the sensitivity obtained with 0.05, 0.1, and 0.2mmol/kg was 63.9-86.1%, 75.8-91.4% and 80.6-90.6%, the specificity was 66.7-73.9%, 59.3-75.0%, and 59.3-75.0% and accuracy was 67.8-78.9%, 75.4-77.4%, and 76.3-81.0%, for the three dose groups, respectively. There were eight non-severe adverse events (AEs). Three serious AEs occurring in one patient were judged not related to gadodiamide by the on-site investigator. CONCLUSION: A significant dose trend between the four doses examined was observed. The lowest dose (0.01mmol/kg) differed significantly from those of the other three doses. Based on the analysis of the primary and secondary endpoints, 0.1mmol/kg gadodiamide appears to be the most suitable dose in diagnosing hemodynamically relevant RAS. The present study also demonstrated gadodiamide to be safe and well tolerated.     

Iodine-125 Brachytherapy of Brain Stem Tumors

PURPOSE: To report on iodine-125 ((125)I) interstitial irradiation in the treatment of brain stem tumors. PATIENTS AND METHODS: Two patients with brain stem tumors were treated with CT- and image fusion-guided (125)I stereotactic brachytherapy. RESULTS: By March 2003, the patients had been followed up for 47 and 13 months, respectively. In case 1, the tumor volume was 1.98 cm(3) on the control CT, indicating a 65.5% shrinkage as compared to a target volume of 5.73 cm3 at the time of brachytherapy. In case 2, shrinkage was more distinct. After irradiation, the cyst volume was 0.16 cm(3) on the control MRI, indicating a 97.4% shrinkage as compared to a target volume of 6.05 cm(3) at the time of brachytherapy, i. e., the metastasis had virtually disappeared. CONCLUSION: CT- and image fusion-guided (125)I stereotactic brachytherapy can be performed during the biopsy session. The procedure can be well planned dosimetrically and is surgically precise.     

Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial

Raloxifene reduces vertebral fracture risk in postmenopausal women with osteoporosis and established osteoporosis, but its efficacy in women with osteopenia has not been studied. The objective of this study was to evaluate the effect of raloxifene hydrochloride on the risk of vertebral fractures in postmenopausal women with osteopenia and to compare this effect with that in women with osteoporosis as defined by the bone mineral density (BMD) T-score at the hip. We studied the 3204 postmenopausal women with osteopenia or osteoporosis without vertebral fractures at baseline in the Multiple Outcomes of Raloxifene Evaluation trial. Compared with placebo, 60 mg/day raloxifene reduced the risk of new vertebral fractures at 3 years independent of baseline total hip BMD. The relative risk for new vertebral fractures for the raloxifene group compared with placebo was 0.53 (95% CI, 0.32-0.88) for those with osteopenia and 0.31 (0.06-0.71) for those with osteoporosis. In raloxifene-treated women the rate of vertebral fracture was similar in women with osteoporosis (2%) to that in women with osteopenia (1.9%). For clinically apparent vertebral fractures, the relative risk of fracture in the osteopenia group for raloxifene was 0.25 (0.04-0.63) compared with placebo. There were no new clinical vertebral fractures in women with osteoporosis receiving raloxifene, whereas four occurred in the placebo group. We conclude that treatment with 60 mg/day raloxifene significantly decreases the risk of new vertebral fractures and new clinical vertebral fractures in postmenopausal women without baseline vertebral fracture who have osteopenia or osteoporosis.     

Placental gene expression patterns of epidermal growth factor in intrauterine growth restriction

Objective

In this study, we compared human placental gene expression patterns of epidermal growth factor (EGF) in pregnancies with intrauterine growth restriction (IUGR) vs. normal pregnancies as control.

Study design

Gene expression of EGF was determined from human placental samples collected from all pregnancies presenting with IUGR at our institution during the study period January 1, 2010–January 1, 2011. Multiple clinical variables were also assessed including maternal age, gestational weight gain, increase of BMI during pregnancy and fetal gender.

Results

A total of 241 samples were obtained (101 in the IUGR pregnancy group, 140 in the normal pregnancy group). EGF was found to be underexpressed in the IUGR group compared to normal pregnancy (Ln2^α: −1.54; p < 0.04). Within the IUGR group no fetal gender-dependent difference was seen in EGF gene expression (Ln2^α: 0.44; p < 0.06). Similarly, no significant difference in EGF expression was noted in cases with more vs. less severe forms of IUGR (Ln2^α: −0.08; p = 0.05). IUGR pregnancies were significantly more common in the maternal age group 35–44 years compared to other age groups. Gestational weight gain and gestational BMI increase were significantly lower in IUGR pregnancies compared to controls.

Conclusions

Placental expression of EGF was found to be reduced in IUGR pregnancies vs. normal pregnancies. This may partly explain the smaller placental size and placental dysfunction commonly seen with IUGR. An increased incidence of IUGR was observed with maternal age exceeding 35 years. The probability of IUGR correlated with lower gestational weight gain and lower BMI increase during pregnancy.     

β‐catenin expression and claudin expression pattern as prognostic factors of prostatic cancer progression

OBJECTIVE

To investigate the patterns of expression of the junctional proteins β‐catenin and claudins in different prognostic groups of patients with prostatic cancer, to determine their value as prognostic markers.

PATIENTS AND METHODS

We evaluated the samples of 30 patients who had a radical prostatectomy for organ‐confined cancer (pT2N0M0), men with clinically advanced cancer, and a control group with benign prostatic hyperplasia. Using immunohistochemistry applied to tissue microarrays, each group was evaluated for claudin‐1, ‐2, ‐3, ‐4, ‐5, ‐7, ‐8 and ‐10, and β‐catenin expression.

RESULTS

There were differences among the three groups in the expression of claudin‐1 (P = 0.001), ‐2 (P = 0.014), ‐3 (P = 0.027), ‐4 (P = 0.001), ‐8 (P = 0.001) and β‐catenin (P = 0.002), regardless of Gleason score. By contrast, claudin‐5, ‐7 and ‐10 patterns were not significantly different among the groups. Furthermore, claudin‐1 (P = 0.014) and ‐4 (P = 0.004) could be used to distinguish between those patients who had metastases and those who did not.

CONCLUSIONS

The pattern of claudin expression could be a novel diagnostic marker in re‐classifying adenocarcinomas, and an additional sensitive predictive factor for a clinically poor prognosis. Our results suggest that patients with organ‐confined and advanced cancer are subsets with distinct claudin expression profiles, and that claudin‐4 is related to cellular differentiation in prostate cancer, which is not only the receptor molecule for the Clostridium perfringens enterotoxin, and thus a theoretical future therapeutic target for prostate cancer, but also a marker of progression.