Cortical inhibition and excitation in abstinent cocaine-dependent patients: a transcranial magnetic stimulation study

Prior transcranial magnetic stimulation studies showed that resting motor threshold is elevated in abstinent cocaine-dependent patients, suggesting a decrease in axonal excitability. In contrast, the increased incidence of seizures and psychosis in this group suggests increased excitability or decreased inhibition. Here, we studied long-interval intracortical facilitation and long-interval intracortical inhibition, paired-pulse transcranial magnetic stimulation measures that are more directly linked to glutamatergic cortical facilitation and GABAergic inhibition, respectively. Ten cocaine-dependent and 10 healthy controls were examined. Resting motor threshold, long-interval intracortical facilitation and long-interval intracortical inhibition were tested from the left motor cortex. The cocaine group showed an elevated resting motor threshold and an increased long-interval intracortical facilitation, whereas long-interval intracortical inhibition was normal. Although the increase in long-interval intracortical facilitation suggests exaggerated cortical glutamatergic excitability, the increase in resting motor threshold may signify a protective mechanism against seizures and psychosis.     

Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder that can progress to cirrhosis, shortening life expectancy. PBC patients are often asymptomatic, present with biochemical cholestasis, and test positive (>or=90%) for antimitochondrial antibodies (AMAs) in serum. Although AMA positivity without biochemical cholestasis may indicate increased risk of future PBC development, the contribution of these antibodies to pathogenesis remains enigmatic. Environmental risks and genetic determinants are likely implicated in PBC etiology. Given the familial aggregation of PBC, we hypothesized that AMAs also aggregate among relatives of PBC probands. We investigated the prevalence of AMAs in first-degree relatives (FDRs) of PBC probands to examine whether AMAs aggregate in such pedigrees. Using a PBC family registry, we prospectively screened for AMAs in the serum of 306 FDRs in 145 pedigrees, 350 PBC probands, and 196 controls who were age-matched, sex-matched, race-matched, and residence-matched to probands. The prevalence of AMA in FDRs and controls was 13.1% and 1%, respectively. Greater prevalence of AMA was found in female FDRs of PBC probands [sisters (20.7%), mothers (15.1%), and daughters (9.8%)] than in male FDRs [brothers (7.8%), fathers (3.7%), and sons (0%)]. CONCLUSIONS: AMAs aggregate among FDRs of PBC probands. Our data have clinical implications for FDRs of PBC probands because AMA positivity may suggest susceptibility to PBC. Thus, the identification and follow-up of these relatives may lead to earlier disease diagnosis and treatment. Furthermore, if AMA development is heritable, this trait will provide a basis to dissect the genetic predisposition to PBC.     

A novel emergency medical services-based program to identify and assist older adults in a rural community

Rural-dwelling older adults experience unique challenges related to accessing medical and social services. This article describes the development, implementation, and experience of a novel, community-based program to identify rural-dwelling older adults with unmet medical and social needs that leveraged the existing emergency medical services (EMS) system. The program specifically included geriatrics training for EMS providers; screening of older adult EMS patients for falls, depression, and medication management strategies by EMS providers; communication of EMS findings to community-based case managers; in-home evaluation by case managers; and referral to community resources for medical and social interventions. Measures used to evaluate the program included patient needs identified by EMS or the in-home assessment, referrals provided to patients, and patient satisfaction. EMS screened 1,231 of 1,444 visits to older patients (85%). Of those receiving specific screens, 45% had fall-related, 69% medication management-related, and 20% depression-related needs identified. One hundred and seventy-one eligible EMS patients who could be contacted accepted the in-home assessment. Of the 153 individuals completing the assessment, 91% had identified needs and received referrals or interventions. This project demonstrated that screening by EMS during emergency care for common geriatric syndromes and linkage to case managers is feasible in this rural community, although many will refuse the services. Further patient evaluations by case managers, with subsequent interventions by existing service providers as required, can facilitate the needed linkages between vulnerable rural-dwelling older adults and needed community-based social and medical services.     

Mechanisms of CNS myelin inhibition: evidence for distinct and neuronal cell type specific receptor systems

Following injury to the adult mammalian central nervous system, regenerative growth of severed axons is very limited. The lack of neuronal repair is often associated with significant functional deficits, and depending on the severity of injury, may result in permanent paralysis distal to the site of injury. A detailed understanding of the molecular mechanisms that limit neuronal growth in the injured spinal cord is an important step toward the development of specific strategies aimed at restoring functional connectivity lost as a consequence of injury. While rapid progress is being made in defining the molecular identity of CNS growth inhibitory constituents, comparatively little is known about their receptors and downstream signaling mechanisms. Emerging new evidence suggests that the mechanisms for myelin inhibition are likely to be complex, involving multiple and distinct receptor systems that may operate in a redundant manner. Furthermore, the relative contribution of a specific ligand-receptor system to bring about growth inhibition may greatly vary among different neuronal cell types. Myelin-associated glycoprotein (MAG), for example, employs different mechanisms to inhibit neurite outgrowth of cerebellar, sensory, and retinal ganglion neurons in vitro. Nogo-A harbors distinct growth inhibitory regions, which employ different signaling mechanisms. The Nogo-66 receptor 1 (NgR1), a shared ligand binding component in a receptor complex for Nogo-66, MAG, and OMgp, participates in neuronal growth cone collapse to acutely presented myelin inhibitors, but is dispensable for longitudinal neurite outgrowth inhibition on substrate-bound Nogo-66, MAG, OMgp, or crude CNS myelin in vitro. Consistent with the idea of cell-type specific mechanisms for myelin inhibition, different types of CNS neurons possess very different regenerative capacities and respond differently to experimental treatment strategies in vivo. We speculate that differences in regenerative axonal growth among different fiber systems are a reflection of their intrinsic ability to elongate axons and their distinct cell surface receptor profiles to respond to the growth inhibitory extracellular milieu. The existence of cell type specific mechanisms to impair regenerative axonal growth in the CNS may have important implications for the development of treatment strategies. Depending on the fiber tract injured, different ligand-receptor systems may need to be targeted in order to elicit robust and long-distance regenerative axonal growth.     

Endomyocardial fibrosis in an adult mimicking left ventricular mass

Endomyocardial fibrosis is a rare condition that occurs primarily in tropical countries. It can often mimick a variety of other common cardiac conditions such as apical hypertrophic cardiomyopathy and Ebstein anomaly. We report a case of a left ventricular mass that at histologic examination was found to be endomyocardial fibrosis.     

Acute myeloid leukaemia presenting with mediastinal myeloid sarcoma: report of three cases and review of literature

Although myeloid sarcomas (MS) are frequently associated with acute myeloid leukaemia (AML), the occurrence of mediastinal MS is a much rarer event. The authors describe a distinct group of three AML patients with mediastinal MS and complex cytogenetics presenting at their centre over a 7-year period. Clinical features consistent with superior vena caval obstruction were noted at presentation in two of the three patients. Mediastinal mass was detected on routine chest radiography, and biopsies confirmed the diagnosis of MS. One patient relapsed after consolidation chemotherapy and died from progressive disease. Two patients underwent allogeneic haemopoietic stem cell transplant, but succumbed to transplant related complications. Review of mediastinal MS over the last 20 years shows that a significant proportion of patients have complex cytogenetic abnormalities and a poor long-term prognosis. Early and accurate diagnosis is essential and patients should be managed along the lines of high risk AML.