Heart rate variability in childhood obesity

Obesity is characterized by hemodynamic and metabolic alterations. Autonomic control on cardiac function involvement is controversial. The aim of the study was to assess early sign of cardiac autonomic dysfunction in obesity, using time- and frequency-domain heart rate variability (HRV) analysis in a pediatric population. Methods: 32 obese children (OB) (17 M, 15 F; 13.9±1.7 y) were compared with 13 healthy lean subjects (7M, 6F; 12.9±1.6y). For each participant, the authors performed a clinical examination, laboratory testing, blood pressure (BP) measurements, and 24-hour electrocardiograph/ambulatory BP monitoring. The spectral power was quantified in total power, low-frequency (HF) power, index of sympathetic tone, high-frequency (HF) power, index of vagal tone, and LF/HF ratio. Low frequency and HF were averaged to obtain 3 measures: 24-hour, daytime, and nighttime levels. Total, long-term, and short-term time-domain HRV values were calculated. Results: The obese children had higher casual and ambulatory BP, and higher fasting glucose, insulin, and triglyceride levels. Overall HRV values were not significantly lower in OB. The obese children had significantly lower 24-hour and nighttime high-frequency normalized units, and time-domain measures of vagal activity. Low-frequency power showed an inverse but not significant pattern. The OB group had significantly greater 24-hour and nighttime LF/HF ratios. Conclusions: The authors found an increase in heart rate and in BP associated with parasympathetic heart rate control decrease in stabilized obese normotensive children.     

Genomic microdeletions associated with epilepsy: not a contraindication to resective surgery

Purpose: Several recent reports of genomic microdeletions in epilepsy will generate further research; discovery of more microdeletions and other important classes of variants may follow. Detection of such genetic abnormalities in patients being evaluated for surgical treatment might raise concern that a genetic defect, possibly widely expressed in the brain, will affect surgical outcome. Methods: A reevaluation was undertaken of clinical presurgical data, histopathology of surgical specimen, and postsurgical outcome in patients with mesial temporal lobe epilepsy (MTLE) who have had surgical treatment for their drug‐resistant seizures, and who have been found to have particular genomic microdeletions. Key Findings: Three thousand eight hundred twelve patients with epilepsy were genotyped and had a genome‐wide screen to identify copy number variation. Ten patients with MTLE, who had resective epilepsy surgery, were found to have 16p13.11 microdeletions or other microdeletions >1 Mb. On histopathology, eight had classical hippocampal sclerosis (HS), one had nonspecific findings, and one had a hamartoma. Median postsurgical follow‐up time was 48 months (range 10–156 months). All patients with HS were seizure‐free after surgery, International League Against Epilepsy (ILAE) outcome class 1, at last follow‐up; the patient with nonspecific pathology had recurrence of infrequent seizures after 7 years of seizure freedom. The patient with a hamartoma never became seizure‐free. Significance: Large microdeletions can be found in patients with “typical” MTLE. In this small series, patients with MTLE who meet criteria for resective surgery and harbor large microdeletions, at least those we have detected, can have a good postsurgical outcome. Our findings add to the spectrum of causal heterogeneity of MTLE + HS.     

Relationship between severity of MR perfusion deficit and DWI lesion evolution

OBJECTIVE: To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion. METHODS: Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion. RESULTS: Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size. CONCLUSION: Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.     

A longitudinal Swedish study on screening for squamous cell carcinoma and adenocarcinoma: evidence of effectiveness and overtreatment.

BACKGROUND: Organized Papanicolaou (Pap) screening has markedly reduced the incidence of cervical squamous cell carcinoma (SCC). However, the potential for overtreatment of precursor lesions is quite high for SCC, and the effectiveness of Pap screening for prevention of cervical adenocarcinoma is questionable. METHODS: Using the nationwide, virtually complete Swedish Cancer Register, we analyzed standardized incidence rates for SCC in situ (CIS), SCC, adenocarcinoma in situ (AIS) and adenocarcinoma, between 1968 and 2002. For each county, we calculated Spearman correlations between incidence of in situ lesions and incidence of invasive cancer, 5, 10, and 15 years later. We also used generalized estimating equation (GEE) models to compare adjusted estimates for associations between in situ incidences and invasive carcinomas over counties. RESULTS: The overall decrease in SCC incidence in Sweden following the introduction of cervical screening confirms the beneficial nature of cervical screening on SCC incidence over the last 30 years. A similar benefit was not apparent for adenocarcinoma. GEE estimates for the relative change in SCC for an increase of 100 CIS cases per 100,000 women-years were 1.05 for the 5-year and 1.02 for the 10-year lag periods. For adenocarcinoma and AIS, similar analyses gave corresponding estimates of 1.17 for the 5-year and 1.08 for the 10-year lag periods. The lack of an inverse correlation suggests that increased reported incidence of CIS in certain counties did not forecast a reduction in SCC for those counties. CONCLUSION: Our data confirm the effectiveness of Pap smear screening in reducing the incidence of SCC, but suggest no clear benefit on adenocarcinoma. Our data also suggest that relaxed histopathologic criteria for diagnosis of cervical CIS may increase its recorded incidence with no measurable benefit in the reduction of invasive cancer.     

Ultraviolet Light and Non-Hodgkin's Lymphoma

In the beginning of this century, a Danish dermatologist, Professor Niels Finsen, received the Nobel Prize for his showing of the beneficial effects of UV-light on certain skin diseases. We have subsequently learned that UV-light is far from being only beneficial to our health. UV-light is an important risk factor for malignant melanoma and squamous cell carcinoma of the skin (1). Furthermore, UV-light appears to have immunosuppressive effects, not only on the local skin, but on the immune system in general (2-4). Recently, it was suggested that UV-light may also increase the risk of non-Hodgkin's lymphoma (NHL) (5, 6).     

Relationships of serum leptin to clinical and anthropometric findings in obese patients

Background: The authors evaluated the relationship between leptin and the clinical, anthropometric and metabolic variables connected to the metabolic syndrome in obese individuals. Methods: A large group of patients with different degrees of obesity was investigated: body mass index (BMI) values, serum leptin, fasting glucose and insulin, triglycerides and HDL-cholesterol concentrations, insulin resistance index and blood pressure were measured. Results: On multiple regression analysis, serum leptin levels appeared to be positively correlated to the BMI and to the serum HDL-cholesterol concentration. Principal component factor analysis revealed three factors, explaining 61.3% of the total variance of the sample. General features of these factors were: factor 1 - BMI values and serum leptin and fasting glucose concentration; factor 2 - systolic and diastolic blood pressure and serum triglycerides and HDL-cholesterol concentration; factor 3 - fasting serum insulin concentration and insulin resistance index. Conclusions: In obese subjects multiple factors underlie the metabolic syndrome and therefore more than one mechanism may account for the clustering characteristics. In obese patients leptin loads only one factor, and therefore leptin does not appear to be a key feature in the metabolic syndrome. On the contrary, multiple correlation and factor analysis data give rise to the hypothesis that in obese patients, leptin may play a protective role against cardiovascular risk.     

Tetrasomy 15q11-q13 identified by fluorescence in situ hybridization in a patient with autistic disorder

We report a female child with tetrasomy of the 15q11-q13 chromosomal region, and autistic disorder associated with mental retardation, developmental problems and behavioral disorders. Combining classical and molecular cytogenetic approaches by fluorescence in situ hybridization technique, the karyotype was demonstrated as 47,XX,+mar.ish der(15)(D15Z1++,D15S11++,GABRB3++,PML-). Duplication of the 15q proximal segment represents the most consistent chromosomal abnormality reported in association with autism. The contribution of the GABA receptor subunit genes, and other genes mapped to this region, to the clinical symptoms of the disease is discussed.     

Use of diffusion weighted MRI to predict the occurrence and severity of hemorrhagic transformation in a rabbit model of embolic stroke

Alpha-synuclein is a brain presynaptic protein that is linked to familiar early onset Parkinson's disease and it is also a major component of Lewy bodies in sporadic Parkinson's disease and other neurodegenerative disorders. Alpha-synuclein expression increases in substantia nigra of both MPTP-treated rodents and non-human primates, used as animal models of parkinsonism. Here we describe an increase in alpha-synuclein expression in a human neuroblastoma cell line, SH-SY5Y, caused by 5-100 microM MPP+, the active metabolite of MPTP, which induces apoptosis in SH-SY5Y cells after a 4-day treatment. We also analysed the activation of the MAPK family, which is involved in several cellular responses to toxins and stressing conditions. Parallel to the increase in alpha-synuclein expression we observed activation of MEK1,2 and ERK/MAPK but not of SAPK/JNK or p38 kinase. The inhibition of the ERK/MAPK pathway with U0126, however, did not affect the increase in alpha-synuclein. The highest increase in alpha-synuclein (more than threefold) in 4-day cultures was found in adherent cells treated with low concentrations of MPP+ (5 microM). Inhibition of ERK/MAPK reduced the damage caused by MPP+. We suggest that alpha-synuclein increase and ERK/MAPK activation have a prominent role in the cell mechanisms of rescue and damage, respectively, after MPP+ -treatment.