Double-guidewire-assisted cannulation in ERCP: novel applications

Even in experienced hands, a common problem at endoscopic retrograde cholangiopancreatography (ERCP) is difficulty in reaching a selective cannulation of the common bile duct or pancreatic duct. The success rate of biliary cannulation has improved markedly in many centers after the adoption of double-guidewire-assisted cannulation technique in cases in which the guidewire repeatedly passes into the pancreatic duct although the common bile duct is intended. Here, we describe 2 novel applications of the double-guidewire technique for difficult cannulation in ERCP. In particular, we emphasize that in addition to difficult biliary cannulation, double-guidewire technique may prove useful in difficult pancreatic cannulation. The double-guidewire technique is feasible also in cases in which the guidewire repeatedly passes into the cystic duct instead of the intended common hepatic duct and intrahepatic radicals. ERCP endoscopists should be aware of all modifications of double-guidewire technique to further increase the success rates of selective cannulations in ERCP.     

Dynamical Casimir effect in a Josephson metamaterial

The zero-point energy stored in the modes of an electromagnetic cavity has experimentally detectable effects, giving rise to an attractive interaction between the opposite walls, the static Casimir effect. A dynamical version of this effect was predicted to occur when the vacuum energy is changed either by moving the walls of the cavity or by changing the index of refraction, resulting in the conversion of vacuum fluctuations into real photons. Here, we demonstrate the dynamical Casimir effect using a Josephson metamaterial embedded in a microwave cavity at 5.4 GHz. We modulate the effective length of the cavity by flux-biasing the metamaterial based on superconducting quantum interference devices (SQUIDs), which results in variation of a few percentage points in the speed of light. We extract the full 4 × 4 covariance matrix of the emitted microwave radiation, demonstrating that photons at frequencies symmetrical with respect to half of the modulation frequency are generated in pairs. At large detunings of the cavity from half of the modulation frequency, we find power spectra that clearly show the theoretically predicted hallmark of the Casimir effect: a bimodal, “sparrow-tail” structure. The observed substantial photon flux cannot be assigned to parametric amplification of thermal fluctuations; its creation is a direct consequence of the noncommutativity structure of quantum field theory.     

Serum macrophage inhibitory cytokine-1 concentrations correlate with the presence of prostate cancer bone metastases.

Macrophage-inhibitory cytokine-1 (MIC-1) is a divergent member of the transforming growth factor beta superfamily. It is up-regulated by nonsteroidal anti-inflammatory drugs and is highly expressed in human prostate cancer leading to high serum MIC-1 concentrations with advanced disease. A role for MIC-1 has been implicated in the process of early bone formation, suggesting that it may also mediate sclerosis at the site of prostate cancer bone metastases. Consequently, the aim of this study was to retrospectively determine the relationship of serum MIC-1 concentration and other markers related to current and future prostate cancer bone metastasis in a cohort of 159 patients with prostate cancer. Serum markers included cross-linked carboxy-terminal telopeptide of type I collagen, prostate-specific antigen, and amino-terminal propeptide of type I procollagen (PINP). The mean values of all the biomarkers studied were significantly higher in patients with baseline bone metastases (BM+, n = 35), when compared with those without bone metastases (BM-, n = 124). In a multivariate logistic model, both MIC-1 and PINP independently predicted the presence of baseline bone metastasis. Based on receiver operator curve analysis, the best predictor for the presence of baseline bone metastasis was MIC-1, which was significantly better than carboxy-terminal telopeptide of type I collagen, prostate-specific antigen, and PINP. Patients who experienced bone relapse had significantly higher levels of baseline MIC-1 compared with patients who did not (1476.7 versus 988.4; P = 0.03). Current use of acetylsalicylic acid did not influence serum MIC-1 levels in this cohort. Although requiring validation prospectively, these results suggest that serum MIC-1 determination may be a valuable tool for the diagnosis of current and future bone metastases in patients with prostate cancer.     

Hemiarthroplasty or osteosynthesis in cervical hip fractures: matched-pair analysis in 892 patients

Our aim was to compare hemiarthroplasty (HA) and osteosynthesis (OS) in the treatment of cervical hip fractures using matched-pair analysis, especially with regard to different age groups. Data concerning all hip fractures (excluding pathological fractures) at the University Hospitals of Lund in Sweden, where osteosynthesis with LIH hook-pins was used exclusively, and of Oulu in Finland, using mainly cementless Austin-Moore hemiarthroplasty, were registered during 1989-1996 using the same standardized hip fracture forms filled in preoperatively and at 4 months follow-up. Altogether 446 pairs matched for age, sex, place of residence and walking ability at the time of fracture were found. Patients aged 55-80 years seemed to benefit more, with regard to function, from OS than older patients. At 4 months follow-up, 38% of HA and 48% of OS patients lived in their own homes, 16% and 27% were able to walk alone outdoors, and 11% versus 16% were able to walk without any aids, respectively. At 1 year follow-up, mortality was significantly lower among the OS patients, but the reoperation rate was significantly higher. In conclusion, OS is associated with a better function and lower mortality than HA, especially in younger patients, and it is recommended as the primary treatment for cervical hip fractures in patients younger than 80 years and with good ambulatory capacity, whereas the oldest patients can also be safely treated by HA.     

Regional effects of donepezil and rivastigmine on cortical acetylcholinesterase activity in Alzheimer's disease

Donepezil and rivastigmine are acetylcholinesterase (AChE) inhibitors used to improve cholinergic neurotransmission and cognitive function in Alzheimer's disease (AD). This study examined direct effects of these drugs on AChE activity in the frontal, temporal, and parietal cortices in AD. Six AD patients were scanned with positron emission tomography before and after 3 months of treatment with donepezil (10 mg/day), and five AD patients were scanned before and after 3 to 5 months of treatment with rivastigmine (9 mg/day). Healthy unmedicated controls were imaged twice to evaluate the reproducibility of the method. A specific AChE tracer, [methyl-11C]N-methyl-piperidyl-4-acetate, and a 3D positron emission tomography system with MRI coregistration were used for imaging. Treatment with donepezil reduced the AChE activity (k3 values) in the AD brain by 39% in the frontal (p < 0.001, Bonferroni corrected), 29% in the temporal (p = 0.02, corrected) and 28% in the parietal cortex (p = 0.05, corrected). The corresponding levels of inhibition for rivastigmine were 37% (p = 0.003, corrected), 28% (p = 0.03, uncorrected) and 28% (p = 0.05, corrected). When the treatment groups were combined, the level of AChE inhibition was significantly greater in the frontal cortex compared to the temporal cortex (p = 0.03, corrected). The test-retest analysis with healthy subjects indicated good reproducibility for the method, with a nonsignificant 0% to 7% intrasubject variability between scans. The present study provides first evidence for the effect of rivastigmine on cortical AChE activity. Our results indicate that the pooled effects of donepezil and rivastigmine on brain AChE are greater in the frontal cortex compared to the temporal cortex in AD. This regional difference is probably related to the prominent temporoparietal reduction of AChE in AD. We hypothesize that the clinical improvement in behavioral and attentional symptoms of AD due to AChE inhibitors is associated with the frontal AChE inhibition.     

Body build from birth to adulthood and risk of asthma

BACKGROUND: Few reports aimed at the study of adulthood obesity and asthma have taken into account the effects of size at birth and obesity in adolescence. This paper examines the combined effect of size at birth and obesity in both adolescence and adulthood on the risk of asthma at age 31 years. METHODS: The study was derived from a prospectively population-based Finnish birth cohort born in 1966, for which data were collected in pregnancy and at various ages. Adulthood doctor-diagnosed asthma with current symptoms and results of skin prick tests were obtained in 1997. The analysis was limited to 4719 subjects with complete information on asthma and atopy and anthropometric measures at various ages. RESULTS: Ponderal index at birth had a U-shaped association with adult atopy, OR 1.30 (95% CI: 1.11-1.52) for the lowest tertile and OR 1.33 (95% CI: 1.13-1.55) for the highest tertile, as compared to the middle tertile. The association was independent of obesity later in life. Those obese (BMI > or = 95th percentile) in adolescence (OR 2.09, 95% CI: 1.23-3.57) and in adulthood (OR 1.99, 95% CI: 1.14-3.47) had a higher occurrence of adult asthma than those with BMI < 85th percentile. Both estimates were reduced after mutual adjustment. CONCLUSIONS: Size at birth has a long-lasting effect on atopy in adulthood, which is independent of weight in adolescence and adulthood. Those who were obese in adolescence and adulthood tended to have a higher risk of asthma in adulthood. These findings underline the importance of considering the life course of obesity in the analyses of asthma and atopy.     

Spontaneous epileptiform activity mediated by GABA(A) receptors and gap junctions in the rat hippocampal slice following long-term exposure to GABA(B) antagonists

Recent evidence suggests that excessive GABA(A) receptor-mediated transmission can lead to neuronal hyperexcitability and hypersynchrony. We show now that exposure of a rat hippocampal slice to GABA(B) receptor antagonists (CGP 55845A and CGP 35348) in the absence of ionotropic glutamatergic transmission leads to a progressive synchronization of spontaneous interneuronal activity. In about 30% of over 200 slices examined, the GABA(A)-mediated spontaneous activity produced field responses in the CA1 soma region with a positive-going phase of up to 5 mV, followed by a long-lasting negative deflection with a simultaneous extracellular K(+) transient. These bicarbonate-dependent GABAergic ictal-like events (GIEs) were associated with biphasic (hyperpolarizing/depolarizing) intracellular responses and with synchronous bursting of the pyramidal neurons. The GIEs could not be reversed by wash-out of the GABA(B) receptor antagonists or by baclofen, but they were inhibited by agonists acting on presynaptic mu-opioid and cannabinoid (CB1) receptors pointing to a down-regulation of presynaptic GABA(B) receptors. GIEs were dependent on intracellular carbonic anhydrase, and potentiated by maneuvers that increase intracellular pH. They were blocked by the Cx36-specific gap-junction (gj) blocker, quinine/quinidine, as well as by the broad-spectrum gj blocker, octanol. These data suggest that enhanced GABAergic activity with functional interneuronal connectivity via gjs is sufficient to trigger epileptiform activity in the absence of ionotropic glutamatergic transmission.     

Genetic boundaries of the schizophrenia spectrum: evidence from the Finnish Adoptive Family Study of Schizophrenia

OBJECTIVE: Identification of the genetically related disorders in the putative schizophrenia spectrum is an unresolved problem. Data from the Finnish Adoptive Family Study of Schizophrenia, which was designed to disentangle genetic and environmental factors influencing risk for schizophrenia, were used to examine clinical phenotypes of schizophrenia spectrum disorders in adopted-away offspring of mothers with schizophrenia spectrum disorders. METHOD: Subjects were 190 adoptees at broadly defined genetic high risk who had biological mothers with schizophrenia spectrum disorders, including a subgroup of 137 adoptees at narrowly defined high risk whose mothers had DSM-III-R schizophrenia. These high-risk groups, followed to a median age of 44 years, were compared diagnostically with 192 low-risk adoptees whose biological mothers had either a non-schizophrenia-spectrum diagnosis or no lifetime psychiatric diagnosis. RESULTS: In adoptees whose mothers had schizophrenia, the mean lifetime, age-corrected morbid risk for narrowly defined schizophrenia was 5.34% (SE=1.97%), compared to 1.74% (SE=1.00%) for low-risk adoptees, a marginally nonsignificant difference. In adoptees whose mothers had schizophrenia spectrum disorders, the mean age-corrected morbid risk for a schizophrenia spectrum disorder was 22.46% (SE=3.56%), compared with 4.36% (SE=1.51%) for low-risk adoptees, a significant difference. Within the comprehensive array of schizophrenia spectrum disorders, schizotypal personality disorder was found significantly more often in high-risk than in low-risk adoptees. The frequency of the group of nonschizophrenic nonaffective psychoses collectively differentiated high-risk and low-risk adoptees, but the frequencies of the separate disorders within this category did not. The two groups were not differentiated by the prevalence of paranoid personality disorder and of affective disorders with psychotic features. CONCLUSIONS: In adopted-away offspring of mothers with schizophrenia spectrum disorders, the genetic liability for schizophrenia-related illness (with the rearing contributions of the biological mothers disentangled) is broadly dispersed. Genetically oriented studies of schizophrenia-related disorders and studies of genotype-environment interaction should consider not only narrowly defined, typical schizophrenia but also schizotypal and schizoid personality disorders and nonschizophrenic nonaffective psychoses.     

Neuroimaging supports the clinical diagnosis of methanol poisoning

In addition to visual loss, methanol intoxication can cause brain damage that is revealed by neuroimaging. We report on a 34-year-old man whose visual acuity deteriorated dramatically during his journey round the world, shortly after an evening with excessive alcohol consumption. Two months after the start of visual disturbances he returned to Finland. At examination, poor visual acuity and glaucomatously cupped pale optic discs were detected. The history and clinical findings indicated possible methanol intoxication, which was supported by both CT and MRI. The MRI findings are discussed in the light of the MRI appearance of the pallidum nuclei among patients of different age groups.