Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE: Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS: We conducted a prospective cohort study involving 991 patients ≥ 65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION: In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial.

BACKGROUND: Cervical screening identifies many women with low-grade abnormalities. In vitro and in vivo studies have shown that diindolylmethane (DIM) could potentially halt (cervical) carcinogenesis. We report on a randomised controlled trial of the effect of DIM in women with low-grade cervical cytological abnormalities. METHODS: We conducted a pragmatic double-blind, randomised controlled trial of 150 mg DIM (from BioResponse DIM) or placebo daily for 6 months in women with newly diagnosed, low-grade cytological abnormalities. Randomisation was in the ratio 2 (DIM) to 1 (placebo). All women were invited for colposcopy at 6 months with biopsy of any abnormality. RESULTS: Of the 551 randomised women available for analysis, 9% on DIM and 12% on placebo had cervical intraepithelial neoplasia-2 (CIN2) or worse after 6-month supplementation (risk ratio (RR) 0.7 (95% confidence interval (CI): 0.4-1.2)), whereas 4.6% and 5.1%, respectively, had CIN3 or worse (RR 0.9 (95% CI: 0.4-2.0)). A total of 27.3% of women on DIM and 34.3% on placebo had no sign of disease (negative cytology, colposcopy and human papilloma virus (HPV) tests) at 6 months (RR 0.8 (95% CI: 0.6-1.0)). Of those HPV-positive at baseline, 69% (114 out of 166) of the DIM group were positive at 6 months compared with 61% (43 out of 71) of the placebo group: RR 1.1 (95% CI: 0.9-1.4). Diindolylmethane supplementation was well tolerated. CONCLUSION: The results suggest that short-term DIM supplementation (150 mg day(-1)) is well tolerated, but is unlikely to have an effect on cytology or HPV infection. Uncertainty remains regarding its effect on CIN2+.

Cervical cancer incidence in young women: a historical and geographic controlled UK regional population study.

BACKGROUND: The commencing age of cervical screening in England was raised from 20 to 25 years in 2004. Cervical cancer incidence in young women of England is increasing. It is not clear if this is due to either greater exposure to population risk factors or reduced cervical screening. METHODS: We measured if the relative risk of cervical cancer in younger women (20-29 years) of the north-east of England (NE) differed to that of women aged 30yrs and above since 2004. We also measured average annual percentage change (AAPC) in the 3 yr moving average incidence for all age-groups. Regional screening coverage rate and population risk factors were reviewed. Comparisons were made with Wales where screening continues to commence from the age of 20yrs. RESULTS: Cervical cancer incidence in women aged 20-29 increased annually by an average of 10.3% between 2000 and 2009. The rise in women aged 30-39 was less steep (3.5%/year) but no significant rise was observed in women aged 40-49. Socioeconomic factors remained stable or improved during the time period except for the incidence of chlamydia, herpes simplex and in particular, genital warts, which increased significantly in young women. Data from Wales show similar results. CONCLUSION: The incidence of cervical cancers in young women of the NE is increasing. The rise in incidence is unrelated to the change in screening policy in 2004. Close monitoring of incidence in young women and a greater attempt to reverse the current decline in screening coverage of women aged 25-29 years are recommended.

Birth outcomes following treatment for precancerous changes to the cervix: a population-based record linkage study.

OBJECTIVE: To examine whether treatments for precancerous changes to the cervix are associated with adverse birth outcomes in subsequent pregnancies. DESIGN: Population-based retrospective cohort study using electronic linkage of data from the Welsh cervical screening programme and a national routine child health database. SETTING: Wales. POPULATION: A total of 174,325 women aged 20-39 years who received cervical screening between April 2001 and March 2004. METHODS: Logistic regression was used to compare the odds of each birth outcome between women who had negative cervical smears and women who received either colposcopy ± punch biopsy only or colposcopy and excisional or ablative treatments, adjusted for confounding factors (e.g. age, social deprivation and smoking). MAIN OUTCOME MEASURES: Preterm birth (before 37, 32 and 28 weeks of gestation), and low birthweight (<2500 g). RESULTS: Compared with women who had negative cervical smears, the odds ratio for preterm birth (<37 weeks) was significantly increased in women who had colposcopy only (adjusted odds ratio 1.54, 95% CI 1.32-1.80) and single excisional treatment (adjusted odds ratio 1.77, 95% CI 1.47-2.13). Similar results were observed for preterm birth at <32 weeks of gestation. There was no increased risk of preterm birth or low birthweight for women who had treatment compared with women who had colposcopy only. CONCLUSION: Women who were referred for colposcopy had an increased risk of preterm births regardless of whether or not they received treatment to the cervix. This increased risk could be the result of common risk factors for abnormal smears and preterm birth.

Recognition of child maltreatment in emergency departments in Europe: Should we do better?

OBJECTIVES: To evaluate the different policies to recognize child maltreatment in emergency departments (EDs) in Europe in order to define areas of improvement. METHODS: A survey was conducted on the recognition of child maltreatment in EDs in European countries with a focus on screening methods, parental risk factors, training and hospital policies. The survey was distributed through different key members from the EUSEM, REPEM and the EuSEN. A summary score based on the NICE guideline (4 questions on child characteristics, 4 questions on parental characteristics and 5 questions on hospital policy) was calculated. RESULTS: We analysed 185 completed surveys, representing 148 hospitals from 29 European countries. Of the respondents, 28.6% used a screening tool, and 31.8% had guidelines on parental risk factors. A total of 42.2% did not follow training based on child characteristics, and 57.6% did not follow training on parental characteristics. A total of 71.9% indicated that there was a need for training. 50.8% of the respondents reported a standardized policy for the detection of child maltreatment. Translating the survey results to NICE summary scores of the EDs in Europe, we found that 25.6% (34/133) met most, 22.6% (30/133) met some and 51.9% (69/133) met few of the NICE guideline recommendations. More specifically, with respect to hospital policies, 33.8% (45/133) met most, 15.0% (20/133) met some and 51.1% (68/133) met few of the NICE guideline recommendations. CONCLUSION: There is high variability regarding policies for child maltreatment detection and only a quarter of the EDs met most of the NICE guideline recommendations for child maltreatment. There is a need for the use of screening tools, training of ED staff and implementation of local hospital policies.

The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1beta processing.

The autoinflammatory disorders Muckle-Wells syndrome, familial cold urtecaria and chronic infantile neurological cutaneous and articular syndrome are associated with mutations in the NALP3 (Cryopyrin) gene, which is the central platform of the proinflammatory caspase-1 activating complex, named the inflammasome. In patients with another autoinflammatory disorder, familial Mediterranean fever (FMF), mutations in the SPRY domain of the Pyrin protein are frequently found. Recent evidence suggests that Pyrin associates with ASC, an inflammasome component, via its Pyrin domain, thereby halting the inflammatory response. This interaction, however, does not explain the effects of mutations of the SPRY domain found in FMF patients. Here we show that the Pyrin SPRY domain not only interacts with NALP3, but also with caspase-1 and its substrate pro-interleukin(IL)-1beta. Whereas a Pyrin knockdown results in increased caspase-1 activation and IL-1beta secretion, overexpression of the SPRY domain alone blocks these processes. Thus Pyrin binds to several inflammasome components thereby modulating their activity.

Human papillomavirus prevalence in women attending routine cervical screening in South Wales, UK: a cross-sectional study.

In this cross-sectional population-based study we determine human papillomavirus (HPV) prevalence in South Wales to provide comprehensive baseline data for future assessment of the impact of prophylactic HPV vaccination and to help inform future screening strategies. Liquid-based cytology samples from women attending routine cervical screening were collected (n=10 000: mean age 38 years, 93% cytology negative, and 64.8% from the 50% least deprived LSOA according to social deprivation score (SDS)). High-Risk (HR) and Low-Risk HPV screening was performed using HPV PCR-EIA with genotyping of HR positives and data correlated with age, SDS and cytology. Overall HPV prevalence was 13.5% (9.3% age standardised) and the most frequent HR types were HPV 16, 31, 18 and 58. In HR HPV-positive cases 42.4% had a single HR type and they were predominant in women with severe cytological abnormalities. Here, 66% of all HR HPV cases were in women aged 30 years of age or less and SDS had no significant effect on HPV status. HPV prevalence increased significantly with degree of dyskaryosis from 7% in cytology negative samples to 80% in samples with severe cytological abnormalities (P-value <0.0001). Overall, 46% of HR HPV cases were positive for the two HR types targeted by the prophylactic vaccines (HPV 16 and HPV 18). The data presented represents the largest type-specific investigation of HPV prevalence in an unselected UK population.

Radioisotope contaminations from releases of the Tomsk-Seversk nuclear facility (Siberia, Russia).

Soils have been sampled in the vicinity of the Tomsk-Seversk facility (Siberia, Russia) that allows us to measure radioactive contaminations due to atmospheric and aquatic releases. Indeed soils exhibit large inventories of man-made fission products including 137Cs (ranging from 33,000 to 68,500 Bq m(-2)) and actinides such as plutonium (i.e. 239+240Pu from 420 to 5900 Bq m(-2)) or 241Am (160-1220 Bq m(-2)). Among all sampling sites, the bank of the Romashka channel exhibits the highest radioisotope concentrations. At this site, some short half-life gamma emitters were detected as well indicating recent aquatic discharge in the channel. In comparison, soils that underwent atmospheric depositions like peat and forest soils exhibit lower activities of actinides and 137Cs. Soil activities are too high to be related solely to global fallout and thus the source of plutonium must be discharges from the Siberian Chemical Combine (SCC) plant. This is confirmed by plutonium isotopic ratios measured by ICP-MS; the low 241Pu/239Pu and 240Pu/239Pu atomic ratios with respect to global fallout ratio or civil nuclear fuel are consistent with weapons grade signatures. Up to now, the influence of Tomsk-Seversk plutonium discharges was speculated in the Ob River and its estuary. Isotopic data from the present study show that plutonium measured in SCC probably constitutes a significant source of plutonium in the aquatic environment, together with plutonium from global fallout and other contaminated sites including Tomsk, Mayak (Russia) and Semipalatinsk (Republic of Kazakhstan). It is estimated that the proportion of plutonium from SCC source can reach 45% for 239Pu and 60% for 241Pu in the sediments.

The estrogen-responsive B box protein: a novel enhancer of interleukin-1beta secretion.

The estrogen-responsive B box protein (EBBP) and Pyrin belong to a family of structurally related proteins. While mutations in the pyrin gene cause an autoinflammatory disease, the biological function of EBBP is unknown. In this study, we identified the proinflammatory cytokine interleukin-1beta (IL-1beta) as an EBBP-binding partner. Furthermore, caspase-1 and NACHT, LRR and Pyrin domain containing protein (NALP) 1, two components of the recently identified inflammasome, a platform for the activation of caspase-1, also interact with EBBP. These proteins bind to the RFP domain of EBBP, suggesting that this domain of so far unknown function is an important protein-binding domain. EBBP was secreted in a caspase-1-dependent manner from cultured cells, and its secretion was enhanced by IL-1beta. Vice versa, endogenous and overerexpressed EBBP increased IL-1beta secretion. These results provide evidence for a role of EBBP in innate immunity by enhancing the alternative secretion pathway of IL-1beta.

A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA.

T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens.

The Mad1 transcription factor is a novel target of activin and TGF-beta action in keratinocytes: possible role of Mad1 in wound repair and psoriasis.

Activin A, a member of the transforming growth factor beta (TGF-beta) superfamily, affects keratinocyte proliferation and differentiation in vitro and in vivo. However, little is known about the mechanisms of activin action in keratinocytes, and its target genes have not been identified. In this study, we demonstrate that activin A and TGF-beta1 directly induce the expression and activity of Mad1, an antagonist of the c-Myc transcription factor, in the human HaCaT keratinocyte cell line. Expression and activity of Mad1 was strongly induced by both factors in keratinocytes, although the intensity of induction was different for activin A and TGF-beta1. To determine a possible role of activin and TGF-beta in the regulation of mad1 expression in vivo, we analysed its expression during cutaneous wound repair when high levels of these factors are present. Expression of mad1 mRNA and protein, but not of other mad genes, increased significantly after skin injury, particularly in polymorphonuclear leukocytes and in suprabasal keratinocytes of the hyperproliferative epithelium. Elevated levels of mad1 mRNA were also detected in the hyperthickened epidermis of psoriatic patients. Since Mad1 regulates proliferation and/or differentiation of various cell types, our results suggest that this transcription factor mediates at least in the part the anti-mitotic and/or differentiation-inducing activities of TGF-beta and activin in keratinocytes.

Mouse fibroblast growth factor 10: cDNA cloning, protein characterization, and regulation of mRNA expression.

Fibroblast growth factor 7 (FGF-7) or keratinocyte growth factor (KGF), is a potent and specific mitogen for epithelial cells. We have recently identified a novel human FGF-7 homologue, named FGF-10. To study the expression of this new FGF family member and its regulation in wound repair, we cloned the mouse FGF-10 (mFGF-10) cDNA. The encoded protein is 92% identical to human FGF-10 and 91% identical to rat FGF-10. When expressed in mammalian 293 cells, the mFGF-10 protein was glycosylated but remained cell- or extracellular matrix-associated. Upon addition of heparin, mFGF-10 protein was released into the media. mRNA encoding mFGF-10 was relatively abundant in lung, skin, brain and heart. In the skin, both FGF-7 and mFGF-10 were expressed in the dermal, but not the epidermal compartment. In contrast to FGF-7, mFGF-10 expression was not induced during cutaneous wound repair. In cultured fibroblasts, expression of mFGF-10 was strongly repressed by transforming growth factor beta and tumor necrosis factor alpha, whereas epidermal growth factor and interleukin-1beta had no effect. These results demonstrate a differential regulation of mFGF-10 and FGF-7 expression in vitro and during the wound healing process.

Cloning, expression, characterization and role of the leader sequence of a lipase from Rhizopus oryzae.

A lipase from Rhizopus oryzae DSM 853 (ROL) was cloned from a chromosomal gene bank, sequenced and overexpressed in Escherichia coli. ROL and its precursors ProROL and PreProROL were purified and their pH and temperature profile was determined. In contrast to ROL, ProROL and PreProROL had considerably higher thermostability and a slightly higher pH optimum. Moreover, it could be demonstrated by in vitro experiments that the natural leader sequence of ROL is able to inhibit the folding supporting properties of the prosequence, resulting in a retardation of folding. In addition, there is strong evidence that all different lipase forms derived from Rhizopus sp. described in the literature are a result of different proteolytic processing and originate from the same gene.

Blood loss estimation in epistaxis scenarios.

Thirty-two members of staff from the Ear, Nose and Throat Department at Warrington General Hospital were asked to estimate blood loss in commonly encountered epistaxis scenarios. Results showed that once the measured volume was above 100 ml, visual estimation became grossly inaccurate. Comparison of medical and non-medical staff showed under-estimation was more marked in the non-medical group. Comparison of doctors versus nurses showed no difference in estimation, and no difference was found between grades of staff.

Physical activity and risk of bleeding in elderly patients taking anticoagulants.

BACKGROUND: Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. OBJECTIVES: To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. PATIENTS/METHODS: In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. CONCLUSIONS: A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

Reduced expression of PDGF and PDGF receptors during impaired wound healing.

A series of studies has shown that application of platelet-derived growth factor (PDGF) to a wound enhances the process of wound repair, especially in animals with wound-healing defects. In the current study, we investigated the regulation of PDGF A and PDGF B and their receptors during wound repair in mice. Both ligands and both types of receptor were expressed in normal and wounded skin, whereby PDGF A and PDGF B proteins were found at different sites in the healing wound. Surprisingly, no significant induction of these genes was observed after skin injury in normal mice, and expression levels were similar at all stages of the repair process. To determine a possible role of endogenous PDGF in normal wound healing, we subsequently analyzed the regulation of PDGF and PDGF receptors during wound healing in healing-impaired animals. Genetically diabetic db/db mice showed a significant reduction in PDGF A and A-type receptor expression in nonwounded and wounded back skin. Furthermore, expression of the B-type receptor was also reduced during the repair process. Systemic glucocorticoid treatment caused a severe defect in wound repair that was accompanied by reduced expression of PDGF A and B and of the B-type receptor in the early phase of wound healing. These results provide an explanation for the beneficial effect of exogenous PDGF in the treatment of wound-healing disorders. Furthermore, our data suggest that a certain expression level of PDGF and its receptors is essential for normal repair.

Effect of age on D2 dopamine receptors in normal human brain measured by positron emission tomography and 11C-raclopride.

Human postmortem and animal experimental results suggest a decline of the cerebral dopaminergic neuronal system with age. In this study, the radiotracer carbon 11-labeled-raclopride and positron emission tomography were applied to determine the effect of age on striatal D2 dopamine receptors in 32 healthy volunteer subjects (age range, 21 to 68 years; median, 31 years). An index of specific 11C-raclopride binding was calculated for putamen, caudate nucleus, and other brain regions in each subject. A significant decrease with age of the index for specific tracer uptake was found in putamen and caudate nucleus. The decrease was steep until 30 years, but slower afterward. After approximately 30 years of age, the decline of specific 11C-raclopride binding in putamen was found to be 0.6% per year. Our results suggest that D2 dopamine receptor binding sites (mainly postsynaptically located) decrease as a consequence of normal aging in parallel with the decline of the presynaptic nigrostriatal dopaminergic neuronal system.

[11C]raclopride and positron emission tomography in previously untreated patients with Parkinson's disease: Influence of L-dopa and lisuride therapy on striatal dopamine D2-receptors.

We studied cerebral dopamine D2-receptor binding using [11C]raclopride and PET in 18 previously untreated patients with Parkinson's disease (PD) and 14 healthy volunteer subjects. Sixteen patients were scanned before and after 3 to 4 months of stable oral therapy with either L-dopa (300 mg/d) (n = 7) or lisuride (0.8 to 1.2 mg/d) (n = 9). Two additional patients were investigated before and after a continuous IV infusion of L-dopa. In addition, we studied the effect of acute IV L-dopa and lisuride administration on [11C]raclopride binding in a healthy rhesus monkey. At baseline, PD patients showed higher uptake values in the putamen than did healthy subjects (p < 0.0001). Oral lisuride treatment lowered [11C]raclopride uptake in the putamen (-19%) and in the caudate nucleus (-15%) compared with baseline, but the difference did not reach significance upon Bonferroni correction for multiple comparisons. However, putamen tracer uptake returned to baseline in two patients when we repeated [11C]raclopride scans 4 days after lisuride withdrawal. Oral L-dopa treatment did not induce changes in the putamen or caudate nucleus indices. Acute lisuride (25 micrograms) administration in a healthy monkey reduced striatal uptake values, but acute injection of L-dopa (300 mg) did not. The results suggest that lisuride blocks [11C]raclopride binding at dopamine D2-receptor sites and demonstrate that 3 to 4 months' oral therapy with L-dopa or lisuride does not change striatal dopamine D2-receptor density in PD patients.

Preoperative and postoperative glucose consumption in mesiobasal and lateral temporal lobe epilepsy.

We have studied 25 patients with interictal 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) before and after selective surgery for temporal lobe epilepsy (TLE). Based on the findings of the presurgical evaluation, including ictal intracranial EEGs, histopathologic findings, and the postoperative outcome, we classified the patients in three subgroups: (1) patients with TLE of lateral temporal origin (n = 5), (2) patients with mesiobasal limbic TLE associated with mesial gliosis (n = 14), and (3) patients with mesiobasal limbic TLE and small mesial tumors (n = 6). Postoperatively, patients with mesiobasal limbic TLE and mesial gliosis and five of six patients with mesiobasal limbic TLE and mesial tumors were seizure-free; the remaining sixth patient had one generalized seizure. Patients with TLE of lateral temporal origin had more than 90% reduction of seizure frequency. The main postoperative metabolic findings were as follows: (1) marked increase of regional cerebral metabolic rate of glucose (rCMRglu), both in the ipsilateral and, significantly, in the contralateral hemisphere in patients with mesiobasal limbic TLE and mesial gliosis-the changes of brain metabolism were characteristic for patients with the syndrome of "mesial temporal lobe epilepsy" (MTLE); (2) decrease of rCMRglu values in the contralateral mesiobasal temporal lobe (TL) cortex in all patient groups--the reduction of rCMRglu in homologous brain structures contralateral to the operated side provides evidence for stronger interhemispheric connections between both mesial TL structures than were hitherto supposed; and (3) a trend toward a normalization of rCMRglu values in the ipsilateral temporal neocortex 12 months after surgery in patients with MTLE syndrome.