Significant differences in the effects of magnetic field exposure on 7,12-dimethylbenz(a)anthracene-induced mammary carcinogenesis in two substrains of Sprague-Dawley rats

We have shown previously (S. Thun-Battersby et al., Cancer Res., 59: 3627-3633, 1999) that power-line frequency (50-Hz) magnetic fields (MFs) at micro T-flux densities enhance mammary gland tumor development and growth in the 7,12-dimethylbenz(a)anthracene (DMBA) model of breast cancer in female Sprague-Dawley (SD) rats. We also demonstrated that MF exposure results in an enhanced proliferative activity of the mammary epithelium of SD rats (M. Fedrowitz et al., Cancer Res., 62: 1356-1363, 2002), which is a likely explanation for the cocarcinogenic or tumor-promoting effects of MF exposure in the DMBA model. However, in contrast with our data, in a similar study conducted by Battelle in the United States, no evidence for a cocarcinogenic or tumor-promoting effect of MF exposure was found in the DMBA model in SD rats (L. E. Anderson et al., Carcinogenesis, 20: 1615-1620, 1999). Probably the most important difference between our and the Battelle studies was the use of different substrains of SD rats; the United States rats were much more susceptible to DMBA than the rats used in our studies. This prompted us to compare different substrains of SD outbred rats in our laboratory in respect to MF effects on cell proliferation in the mammary gland, susceptibility to DMBA-induced mammary cancer, and MF effects on mammary tumor development and growth in the DMBA model. The SD substrain (termed "SD1") used in all of our previous studies was considered MF-sensitive and used for comparison with another substrain ("SD2") obtained from the same breeder. In contrast with SD1 rats, no enhanced cell proliferation was determined after MF exposure in SD2 rats. MF exposure significantly increased mammary tumor development and growth in SD1 but not SD2 rats. These data indicate that the genetic background plays a pivotal role in effects of MF exposure. Different strains or substrains of rats may serve to evaluate the genetic factors underlying sensitivity to cocarcinogenic or tumor-promoting effects of MF exposure.     

Graded reoxygenation with chemical inhibition of oxidative phosphorylation improves posthypoxic recovery in murine hippocampal slices

Rapid and complete tissue reoxygenation is a prime goal of present stroke therapy. However, reoxygenation may trigger detrimental cascades that partially antagonize beneficial effects. It was our goal to investigate selective grading of reoxygenation with targeting of single mitochondrial complexes in murine hippocampal slices. Population spike amplitude (PSAP) and NADH were measured during hypoxic hypoxia (15 min) and recovery (45 min). With onset of reoxygenation, slices were treated for different times with amobarbital (1 mM), malonate (2 mM), or cyanide (1 mM), inhibitors of mitochondrial complex I, II, or IV, respectively. Other slices were treated with nicotinamide (1 mM). Posthypoxic recovery of PSAP increased from 32% +/- 43% of onset in control slices to 52% +/- 59% (P <.05) upon treatment with amobarbital for 1 min and to 62% +/- 37% (P <.05) upon treatment with malonate. With nicotinamide, posthypoxic recovery improved to 73% +/- 25% (P <.05). Oxidation of NADH was prolonged upon treatment with amobarbital, whereas no change in NADH oxidation was observed with malonate and nicotinamide. Thus, grading of reoxygenation with selective targeting of mitochondrial complex I or II but not of complex IV improves outcome upon reoxygenation in murine hippocampal slices.     

Microstructural white matter changes in carriers of the DYT1 gene mutation

We tested the hypothesis that the DYT1 genotype is associated with a disorder of anatomical connectivity involving primarily the sensorimotor cortex. We used diffusion tensor magnetic resonance imaging (DTI) to assess the microstructure of white matter pathways in mutation carriers and control subjects. Fractional anisotropy (FA), a measure of axonal integrity and coherence, was reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of DYT1 carriers. Abnormal anatomical connectivity of the supplementary motor area may contribute to the susceptibility of DYT1 carriers to develop clinical manifestations of dystonia.     

Evaluation of the German Type D Scale (DS14) and prevalence of the Type D personality pattern in cardiological and psychosomatic patients and healthy subjects

The Type D personality pattern, consisting of negative affectivity and social inhibition, has been shown by Denollet et al. to predict adverse prognosis in patients with coronary heart disease. For measuring the Type D characteristics, Denollet has devised the 14 item Type D scale (DS14). In the present study, this instrument was translated into German. The validity, reliability and adequacy of the German DS14 were then tested in 2421 persons, including cardiological and psychosomatic patients as well as healthy factory workers. The results document sound psychometric properties of the scale. Cronbach's alpha was 0.87 for the negative affectivity subscale and 0.86 for social inhibition. The two-factor structure of the original instrument could be clearly replicated. The prevalence rates of the Type D pattern were lowest in cardiological patients (25 %) and highest in psychosomatic patients (62 %). The prevalence in this German sample of cardiology patients was also lower than the one observed in healthy factory workers (32.5 %) and in CHD samples reported in the literature. These group differences could not be accounted for by differences in age and sex distribution. In conclusion, the DS14 is a valid and reliable instrument that can be used for an economic evaluation of the Type D characteristics in patients and healthy persons. The possible meaningfulness of the low Type D prevalence in cardiac patients and the prognostic relevance of this pattern require further study.     

Longitudinal study of energy expenditure in preterm neonates <30 weeks' gestation during the first three postnatal weeks

OBJECTIVES: The objective of this study was to measure energy expenditure (EE) in a contemporary population of preterm neonates <30 weeks' gestation. STUDY DESIGN: Prospective longitudinal cohort study in 26 consecutive preterm neonates (gestational age, 27 weeks [23-29] [median, range]; birth weight, 980 g [554-1592]). EE was measured by indirect calorimetry on postnatal days 1, 3, 5, 10, and 21. Data on body weight, energy intake, and medical therapy were prospectively collected. RESULTS: EE increased from 121 +/- 25 kJ/kg per day (29 +/- 6 kcal/kg per day) (mean +/- SD) on day 1 to 222 +/- 25 kJ/kg per day (53 +/- 6 kcal/kg per day) on day 21. An energy deficit occurred only on day 1. EE was closely related to energy intake: For each additional kJ given, EE increased by 0.3 kJ (r = 0.789, P <.0001). Neonates with a birth weight <1000 g did not have a more pronounced energy deficit than the heavier neonates. EE during nasal continuous positive airway pressure in the first postnatal week was 25% lower than during spontaneous respiration. CONCLUSIONS: EE could be predicted from energy intake with acceptable accuracy in preterm neonates <30 weeks' gestation during the first 3 postnatal weeks. There was no prolonged energy deficit.     

Impact of diabetes screening on quality of life

OBJECTIVE: Diagnosis of a chronic illness can have a negative impact on patients' perception of their well-being ("labeling" effect). We sought to determine the effects of a new diagnosis of diabetes, discovered by systematic screening, on patients' health-related quality of life (HRQoL) 1 year after diagnosis. RESEARCH DESIGN AND METHODS: We performed diabetes screening at the Durham Veterans Affairs Medical Center of 1,253 outpatients, aged 45-64 years, who did not report having diabetes. Our initial screen was a serum HbA(1c) measurement. All subjects with HbA(1c) > or = 6.0% were invited for follow-up measurement of blood pressure and fasting plasma glucose. A case of unrecognized diabetes was defined as HbA(1c) > or = 7.0% or fasting plasma glucose > or = 7 mmol/dl. HRQoL was measured by Medical Outcomes Study Short Form 36 (SF-36) for all patients at baseline and 1 year after enrollment. Linear multivariable models were used to determine the independent effect of the new diagnosis of diabetes on HRQoL. RESULTS: Mean SF-36 Physical Component Score (PCS) for all patients was 36.2, and mean Mental Component Score (MCS) was 49.6. A total of 56 patients (4.5%) were found to have diabetes at screening. Patients found to have diabetes at screening had mean PCS of 35.6, which was not different from a mean PCS of 36.3 for those patients found not to have diabetes (P = 0.67). After adjusting for baseline PCS values, PCS 1 year after screening was similar for patients with and without diabetes found at screening (P = 0.95). Similarly, patients found to have diabetes at screening had mean MCS of 48.8; those found not to have diabetes had MCS of 49.6 (P = 0.70). After adjusting for baseline MCS values, MCS 1 year after screening was also similar between the two groups (P = 0.77). CONCLUSIONS: For patients with a new diagnosis of diabetes discovered through systematic screening, HRQoL is similar to patients found not to have diabetes. Furthermore, HRQoL scores remain stable over the year after screening. This suggests that screening for diabetes has minimal, if any, "labeling" effect with respect to HRQoL.     

Estimation of ocular perfusion: a practical oriented comparison of different methods

BACKGROUND: Ocular haemodynamics play a prominent part in many ocular diseases. This leads to the need to determine ocular perfusion. Several studies reveal advantages of colour Doppler imaging (CDI) in ophthalmologic diagnostics. Little is known about correlation of CDI results with other methods. PATIENTS AND METHODS: N = 56 eyes were examined with CDI, laser Doppler flowmetry (LDF) and Langham-OBF (LOBF). Correlations between the methods were identified by the Spearman correlation coefficient (R). RESULTS: LDF correlated with time average maximum (TAMx) and mean (TAMn) velocity assessed by CDI in the long posterior ciliary artery (TAMx: R = 0.466, p = 0.038, n = 20; TAMn: R = 0.462; p = 0.040, n = 20), but not in the short posterior ciliary artery. LOBF correlated with pulsatility index (PI) and resistive index (RI) of CDI in short (PI: R = 0.514, p = 0.002, n = 35; RI: R = 0.438, p = 0.008, n = 35) and long posterior ciliary arteries (PI: R = 0.436, p = 0.009, n = 35; RI: R = 0.506, p = 0.002, n = 35). DISCUSSION: Methods strengthen each other by partial correlation. CDI allows a more detailed insight into ocular perfusion than the other methods.     

Functional imaging of cognition in Parkinson's disease

PURPOSE OF REVIEW: Cognitive deficits that occur even early in the course of Parkinson's disease have received increasing attention in current imaging research. The exact physio-pathological processes mediating the deficits and the complex relationship of cognitive signs and antiparkinsonian treatment are not well understood. A clearer understanding of these mechanisms could potentially influence treatment choices, drug development and, ultimately, patient care. RECENT FINDINGS: Abnormal networks identified in studies of resting state metabolism in Parkinson's disease represent metabolic markers for remote effects of striato-nigral degeneration. These metabolic changes include subcortico-cortical networks, in particular cognitive cortico-striato-pallidal-thalamocortical loops. Recent brain studies focus on intervention-related brain changes. They illustrate different task-specific changes in brain activation with deep brain stimulation and with levodopa. Variable results of stimulation can be attributed to different effects on segregated cortico-striato-pallidal-thalamocortical loops during stimulation. By contrast, the heterogeneity observed in studies with levodopa possibly reflects the disease-stage and task-specific effects of levodopa. A decline in caudate dopamine modulated basal ganglia outflow appears to contribute to executive dysfunction and to brain activation changes in these loops at early Parkisnon's disease stages, while mesocortical degeneration mediated increases of inefficient dorsolateral prefrontal cortex activation may display a feature of more advanced disease stages only. SUMMARY: Despite evidence for the role of dopamine and cortico-striato-pallidal-thalamocortical loops in cognition, the specific contributions of mesocortical dopamine depletion and striatal dysfunction with downstream consequences on the loops remain to be separated. Additionally, more research is needed into the role of non-dopaminergic pathology in cognitive decline in Parkinson's disease.