Neuroprotective properties of valproate

Neuropsychiatric disturbances are extremely common in Alzheimer’s disease (AD), and represent integral features of the illness, as well as appropriate targets for therapy. We are interested in designing trials aimed at preventing or delaying the emergence of psychopathology in AD. For symptomatic treatment of agitation, mood stabilizers, particularly sodium valproate, have proved to be beneficial in some patients. Since these effects take several weeks to emerge, we considered that they might be dependent on potentially neuroprotective actions of valproate, such as inhibition of apoptosis and slowing of neurofibrillary tangle formation. In this article we present the rationale for testing the neuroprotective potential of valproate experimentally in mouse models of tauopathy and in a clinical trial of patients with AD who lack psychopathology at baseline. Together, these studies will provide important tests of the hypothesis that valproate, either through inhibition of tau phosphorylation or some other mechanism, is a useful therapeutic agent to modify disease progression in AD.     

Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.

Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.     

绝经前后T1期乳腺癌患者临床特征的分析

目的:分析T1期(肿瘤直径<2cm)原发性乳腺癌女性患者绝经前后在肿瘤大小、病理分类、淋巴结转移率和数目。方法:常规病理检验以及应用免疫组化、HE法分别测定绝经前乳腺癌患者和绝经后乳腺癌患者者的ER、PR。结果:两组患者在肿瘤大小上无明显差异,但绝经前乳腺癌患者浸润导管癌的百分比为 84. 7%,绝经后乳腺癌患者的浸润导管癌百分比为 62. 2%,经χ2 检验,P<0. 01。两组淋巴结转移率分别为 39. 3%和 25. 5%,经χ2 检验,P<0. 01。两组ER和PR阳性伴淋巴结转移的比例经χ2 检验,P<0. 05。结论:绝经前乳腺癌患者和绝经后乳腺癌患者在病理分类、淋巴结转移率及数目、ER、PR阳性伴淋巴结转移上有显著性差异。对于T1原发性乳腺癌患者不论有无淋巴结转移,均应行癌肿切除伴Ⅰ、Ⅱ级淋巴结清扫。     

Impact of type 2 diabetes mellitus on diffuse inflammatory activation of de novo atheromatous lesions: Implications for systemic inflammation

AimsLocal coronary and systemic inflammation is pronounced in patients with diabetes mellitus (DM). Intracoronary thermography detects local inflammation and C-reactive protein (CRP) is a marker of systemic inflammation. We investigated whether or not, in patients with DM, thermal heterogeneity of culprit lesions (CLs) correlates with that of non-culprit lesions (NCLs) and with systemic inflammation.MethodsWe included DM patients who had two angiographically significant lesions and were undergoing percutaneous coronary intervention. We measured the temperature difference (ΔT) between the lesion and proximal vessel wall.ResultsWe included 104 (n = 208 lesions) patients: 32 (n = 64 lesions) had DM and 72 (n = 144 lesions) were non-DM (control group). ΔT was increased in DM in both CLs and NCLs (CLs: DM = 0.12 ± 0.06 °C; no DM = 0.06 ± 0.04 °C; P < 0.01 versus NCLs: DM = 0.13 ± 0.08 °C versus no DM = 0.06 ± 0.05 °C; P < 0.01). Patients with DM had similar ΔT in CLs and NCLs (P = 0.49). A linear correlation was detected between heat production in all lesions and CRP (R = 0.45; P < 0.01), which was attributed to the correlation of ΔT in lesions of patients with DM and CRP (R = 0.32; P < 0.01). In lesions of patients with low CRP, a greater rate of discrepancy was found, as 100% of lesions in patients with DM versus 66.1% of lesions of patients without DM had a high ΔT in one or both lesions (P < 0.01).ConclusionIn patients with DM, local inflammatory activation is diffuse and correlates with systemic inflammation. However, low systemic inflammatory activation does not always predict an increase in local thermal heterogeneity.     

How far do patients with sensory ataxia benefit from so-called “proprioceptive rehabilitation”?

A rehabilitation program including foot sensory stimulation, balance and gait training with limited vision was performed in 24 patients with clinically defined sensory ataxia. There were 15 patients with bilateral somatosensory loss related to chronic neuropathy and nine patients with unilateral loss-related to multiple sclerosis. After training, balance control assessed using the Berg Balance Test improved similarly in both groups, and Romberg's sign disappeared in some patients, suggesting an improvement in dynamic balance and in the proprioceptive contribution. Conversely, balance assessed on a static force platform remained similar in the open-eyes condition and improved in the closed-eyes condition only in patients with unilateral sensory loss. These results show that ataxic patients can improve their balance with better results in dynamic conditions and that the relative contribution of proprioceptive and visual inputs may depend on the extent of somatosensory loss.     

Exploration simplifiée des atteintes plexiques par réduction aux atteintes nerveuses et radiculaires connues

The anatomic complexity of the brachial plexus makes its electrophysiological exploration difficult. Electrodiagnosis nevertheless plays a crucial role in assessing brachial plexopathies, particularly in the perspective of post-traumatic surgical reconstructions. The evaluation aims to locate as precisely as possible injuries within the plexus, as well as to determine their severity and capacity for recovery. This requires various sensory nerve conduction studies and needle EMG recordings of “marker” muscles. Plexopathies differ from radiculopathies by altered sensory nerve responses and unaltered functional innervation of paracervical muscles. We propose to simplify the exploration of brachial plexopathies by following some practical rules derived from a reanalysis of the brachial plexus anatomic sketch. Two main simplification rules can be deduced from an analysis of the anatomic sketch. First it would be judicious to associate the plexopathies involving a single element of the brachial plexus with distinct etiological and symptomatic patterns according to the altered element, as one does for peripheral nerve and root pathologies. The second proposal relies on the observation that each supraclavicular “truncal” element (upper, middle, or lower) of the brachial plexus results from reunion of cervical root nerves and behaves like a “super-root” for the upper limb, while each infraclavicular “cord” element (posterior, lateral, or medial) is the sum of two or more peripheral nerves and behaves like a “super-nerve”. Accordingly, the motor and sensory abnormalities associated with the lesion of a single plexus branch may occupy a clinical and electrophysiological territory that recovers those of its constituants. Except the unaltered paracervical muscles, it is useful to reduce the topographical semiology of truncal lesions to well-known cervical radiculopathies (upper trunk neuropathy to C5 and C6 associated radiculopathies, middle trunk neuropathy to C7 radiculopathy, lower trunk neuropathy to C8 and T1 associated radiculopathies); and that of cord lesions to well-known mononeuropathies of the upper limb (for example, a posterior cord neuropathy may be considered as a full radial mononeuropathy associated with an axillary one). This method of simplification allows to demystify the brachial plexopathies and to facilitate their comprehension and exploration.     

Necrotizing soft tissue infections

Necrotizing soft tissue infections (NSTI) represent a spectrum of diseases characterized by extensive rapidly progressive necrosis that may involve the skin, subcutaneous tissues, fascia or muscle. Their progress is extremely fast, leading often to sepsis and septic shock that ends up in multiple organ failure with abrupt and high mortality. A variety of classification systems have been developed based on parameters such as anatomic location of the disease or microbiology. There are a number of factors that predispose to the spread of these soft tissue infections, such as delays in recognition, immune suppression, diabetes mellitus and advanced age. The use of broad‐spectrum antibiotics tends to mask the severity of the underlying infection, modulates the clinical presentation, and even delays hospital admission. The most important factor affecting outcome in NSTI is early diagnosis and aggressive radical surgical treatment. The medical records of 13 patients who had been treated for NSTI from 1996 to 2005 were reviewed, retrospectively. There were eight men (61.5%) and five (38.5%) women. Mean age was 56 years (range 27–73). Seven cases of infection involved the perineal region (54%), two the lower limb, one the upper limb and three the abdominal wall/trunk. The most common associated comorbidity was diabetes mellitus in five patients (38.5%). A single organism was identified in two (15%) and multiple organisms in 11 (85%) patients. Necrotizing aponeurositis Type I was the most common of the polymicrobial necrotizing infections. Overall survival was 85%, and the mean hospital stay for survivors was 35 days (range 17–92).     

Ipsilateral Aymand’s and Richter’s hernia, complicated by necrosing fascitis

This study presents the case of a patient with necrobiosis or necrosing fascitis of the inguinal region, secondary to a complicated Amyand’s hernia with a concomitant ipsilateral Richter’s hernia. The patient was treated with open trans-abdominal surgery and hernia repair through the pre-peritoneal approach, plus anti-microbians, and thrice-daily wound cleansing and dressings to the inguinal region. Evolution was satisfactory. There are no reports in the literature of a case such as this.     

Entrapment of pacemaker lead by a large netlike Eustachian valve within the right atrium

Summary During pacemaker implantation in a patient with permanent atrial fibrillation, it remained impossible to advance a passive fixation lead with fins through the right atrium. However, a lead with a retractable screw easily passed the right atrium and was positioned in the right ventricle. Transesophageal echocardiography revealed an extensive net–like perforated Eustachian valve within the right atrium that had caused entrapment of the anchor fins during lead implantation. Remnants of embryonal structures within the right atrium should be considered a rare possible barrier during pacemaker implantation.     

Psychosocial Effects of Physical and Verbal Abuse in Postmenopausal Women

PURPOSE The purpose of this study was to examine the psychological effects of physical and verbal abuse in a cohort of older women.METHODS This observational cohort study was conducted at 40 clinical sites nationwide that are part of the Women’s Health Initiative (WHI) Observational Study. We surveyed 93,676 women aged 50 to 79 years using the mental health subscales and the combined mental component summary (MCS) score of the RAND Medical Outcomes Study 36-item instrument.RESULTS At baseline, women reporting exposure to physical abuse only, verbal abuse only, or both physical and verbal abuse had a greater number of depressive symptoms (1.6,1.6, and 3 more symptoms, respectively) and lower MCS scores (4.6, 5.4, and 8.1 lower scores, respectively) than women not reporting abuse. Compared with women who had no exposure to abuse, women had a greater increase in the number of depressive symptoms when they reported a 3-year incident exposure to physical abuse only (0.2; 95% confidence interval [CI], −0.21 to 0.60), verbal abuse only (0.18; 95% CI, 0.11 to 0.24), or both physical and verbal abuse (0.15; 95% CI, −0.05 to 0.36); and they had a decrease in MCS scores when they reported a 3-year incident exposure to physical abuse only (−1.12; 95% CI, −2.45 to 0.12), verbal abuse only (−0.55; 95% CI, −0.75 to −0.34), and both physical and verbal abuse (−0.44; 95% CI, −1.11 to −0.22) even after adjustment for sociodemographic characteristics.CONCLUSION Exposure to abuse in older, functionally independent women is associated with poorer mental health. The persistence of these findings suggests that clinicians need to consider abuse exposure in their older female patients who have depressive symptoms. Clinicians caring for older women should identify women at risk for physical and verbal abuse and intervene appropriately.