Etiological heterogeneity in Hodgkin's disease: HLA linked and unlinked determinants of susceptibility independent of histological concordance

Forty-one multiplex families, from published sources and new data from the National Cancer Institute, segregating for Hodgkin's disease and HLA, have been studied. A reanalysis of these data strongly suggests a recessive mode of inheritance for susceptibility to Hodgkin's disease. The HLA haplotype sharing data between affected relatives demonstrate that approximately 60% of cases in multiplex families are due to an HLA-linked susceptibility gene, the remaining 40% being due to other familial factors. The data clearly support the hypothesis of etiological heterogeneity for Hodgkin's disease, with both HLA-linked and HLA-unlinked factors being responsible. Finally, there is an increased concordance of histological types between affected relatives, but this concordance seems independent of HLA sharing.     

Loss of basal forebrain P75(NTR) immunoreactivity in subjects with mild cognitive impairment and Alzheimer's disease.

The long-held belief that degeneration of the cholinergic basal forebrain was central to Alzheimer's disease (AD) pathogenesis and occurred early in the disease process has been questioned recently. In this regard, changes in some cholinergic basal forebrain (CBF) markers (e.g. the high affinity trkA receptor) but not others (e.g., cortical choline acetyltransferase [ChAT] activity, the number of ChAT and vesicular acetylcholine transporter-immunoreactive neurons) suggest specific phenotypic changes, but not frank neuronal degeneration, early in the disease process. The present study examined the expression of the low affinity p75 neurotrophin receptor (p75(NTR)), an excellent marker of CBF neurons, in postmortem tissue derived from clinically well-characterized individuals who have been classified as having no cognitive impairment (NCI), mild cognitive impairment (MCI), and mild AD. Relative to NCI individuals, a significant and similar reduction in the number of nucleus basalis p75(NTR)-immunoreactive neurons was seen in individuals with MCI (38%) and mild AD (43%). The number of p75(NTR)-immunoreactive nucleus basalis neurons was significantly correlated with performance on the Mini-Mental State Exam, a Global Cognitive Test score, as well as some individual tests of working memory and attention. These data, together with previous reports, support the concept that phenotypic changes, but not frank neuronal degeneration, occur early in cognitive decline. Although there was no difference in p75(NTR) CBF cell reduction between MCI and AD, it remains to be determined whether these findings lend support to the hypothesis that MCI is a prodromal stage of AD.     

Le dilemme du réfugié

The experiences of trauma, displacement, and forced migration faced by refugees raise profound questions about the relationship of self and community. This article explores some ways in which the intrapsychic dynamics of refugees' suffering and remembering interact with the larger social dynamics of refugee communities and host societies. The narrative construction of the self constitutes the pivot between the realms of the social and the psychological and rests on cultural meta-narratives. In Euro-American folk psychology two of the meta-narratives or concepts of the self can be compared in terms of their root metaphors: the adamantine self, characterized by its integrity, coherence, autonomy, self-definition, self-determination and self-control; and the transactional self, characterized by its fluidity, sensitivity to context, deference to authority, multivocality, deference and yielding to or accommodating others. These two accounts of the self shape how we view people who have suffered wrenching transformations of their worlds through violence, dislocation and loss. The changes produced through the therapeutic process can be understood as the development of a form of dialogue that is at once, within and without, personal and transcendental, rooted in communal tradition and in the open confrontation of the face of the other. The ethics of storytelling has its necessary counterpart in the ethics of listening, of witnessing and taking part in the creation of community through copresence.     

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).