Selective Augmentation of Striatal Functional Connectivity Following NMDA Receptor Antagonism: Implications for Psychosis

The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain''s fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral ‘limbic'' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal ‘associative'' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness.     

Involvement of central nervous system disclosing Waldenstrom's disease: demonstration of intrathecal secretion of immunoglobulin M]

We report the case of a 68-year old woman complaining of disorders of memory and persistent headaches in whom the diagnosis of Waldenstr?m's macroglobulinaemia (WM) was made. Computerized tomography of the brain showed a butterfly-shaped hyperdensity in the splenium of the corpus callosum, with ventricular dilatation. Magnetic resonance imaging displayed high-intensity signals on T2-weighted sequences. Protein immunoelectrophoresis elicited an IgM kappa peak. The CSF was found to contain proteins and lymphocytes in excess, and immunohistochemical staining confirmed the predominance of anti-kappa and the presence of intrathecal IgM secretion. Chemotherapy was temporarily effective on the memory disorders, but the patient died 26 months after the beginning of treatment. Central nervous system manifestations are seldom observed in WM, and they are now grouped under the name of Bing-Neel syndrome. Psychic disorders are rarely reported. It is suggested that IgM secretion plays a predominant role in the pathogenesis of leucoencephalitis, and this is supported by the finding of intrathecal IgM synthesis.     

Muscle function and muscle balance in lower limbs are not impaired in individuals with general joint hypermobility

Sport Sciences for Health - The generalized joint hypermobility (GJH) syndrome is a condition characterized by a connective tissue disorder that may negatively affect the muscle function and muscle...     

Thoracoscopic surgery in elderly lung cancer patients

Age is a recognized risk factor for death after thoracotomy in elderly patients with lung cancer. Among other factors, the genesis of this risk is the physiologic debilitation that occurs after division of the intrathoracic respiratory muscles during thoracotomy, as well as the loss of lung tissue after lung resection. Recent advances in video-assisted thoracic surgery (VATS) techniques provide an alternative to standard thoracotomy in elderly lung cancer patients, resulting in decreased recovery times and fewer perioperative complications. Likewise, smaller lung resections (VATS-guided limited wedge resection versus lobectomy with thoracotomy) can be adequate oncologic procedures in patients with a limited life expectancy but resectable disease. We studied these alternative procedures in a cohort of thoracic surgical patients at the Brigham and Women's Hospital in Boston, MA. Proposed investigations of the psychosocial implications of thoracic surgery in the elderly, irrespective of the safety of these maneuvers, are addressed.     

Pathophysiology of rhinitis. 1. Assessment of the sources of protein in methacholine-induced nasal secretions

Nasal provocation tests with normal saline and methacholine (MC) were performed in 25 atopic and 27 nonatopic subjects in an effort to assess the sources of protein in induced airway secretions. Nasal lavages obtained at baseline and after provocation were analyzed for albumin, total protein, secretory IgA (sIgA), and total IgA. Compared with baseline levels or saline provocation, MC provocation increased the secretion of albumin (p less than 0.025), total protein (p less than 0.001), sIgA (p less than 0.025), and total IgA (p less than 0.025), but did not significantly affect the relative proportions of albumin-to-total protein (albumin percent) or sIgA-to-total IgA (sIgA/total IgA ratio). Nasal pretreatment with atropine significantly inhibited MC-induced secretion of all 4 proteins, again without affecting the albumin percent or the sIgA/total IgA ratio. Because MC is known to stimulate atropine-inhibitable secretion of glandular products, these data suggest that sIgA and albumin may accompany glandular secretions. Immunohistochemical analyses of nasal turbinates confirmed that secretory component was found only on serous cells within submucous glands. Thus, it appears that cholinergic stimulation may regulate sIgA secretion and thereby participate in local nasal (and possibly respiratory tract) immunity.     

Neonatal hyperglycaemia and abnormal development of the pancreas

Transient and permanent neonatal diabetes mellitus (TNDM and PNDM) are rare conditions occurring in around 1 per 300,000 live births. In TNDM, growth-retarded infants develop diabetes in the first few weeks of life, only to go into remission after a few months with possible relapse to permanent diabetes usually around adolescence or in adulthood. In PNDM, insulin secretory failure occurs in the late fetal or early postnatal period. The very recently elucidated mutations in KCNJ11 and ABCC8 genes, encoding the Kir6.2 and SUR1 subunits of the pancreatic K(ATP) channel involved in regulation of insulin secretion, account for a third to a half of the PNDM cases. Molecular analysis of chromosome 6 anomalies and the KCNJ11 and ABCC8 genes encoding Kir6.2 and SUR1 provides a tool for distinguishing transient from permanent neonatal diabetes mellitus in the neonatal period. Some patients (those with mutations in KCNJ11 and ABCC8) may be transferred from insulin therapy to sulphonylureas.     

Buccal lymphomatoid granulomatosis

A 57 year old man was referred to us with multiple long-standing, recurring and refractory mouth ulcers involving the palate, the intermaxillary folds, the inner side of the cheeks, the frenum of the tongue, a tonsil, the pharynx, the gums and a lower lip. Multiple biopsies had excluded a lymphoma, a carcinoma and infection. A new biopsy showed a polymorphous granuloma with up to 40% of atypical lymphoid cells. No angiitis was present, but an angiocentric pattern was present in the granuloma. The atypical cells stained positively with OKT3 and OKT4 antisera. The patient also had cardiac rhythm disturbances with defects on the myocardial scan and a proteinuria. Thus, we suspected the diagnosis of lymphomatoid granulomatosis, although there were no pulmonary nodules. Cyclophosphamide and prednisone were given with immediate success. As the doses were gradually decreased, a small relapse occurred. It was controlled by increasing the cyclophosphamide dosage for six months. The patient is now in complete remission more than four years after having discontinued the treatment. Thus, lymphomatoid granulomatosis can be diagnosed on the basis of a biopsy of buccal ulcers and in the absence of the classical pulmonary nodules. We found no evidence that the atypical cells were lymphomatous; rather, the very good response to the treatment points to a curable granulomatosis.     

Type 2 Diabetes and COVID-19–Related Mortality in the Critical Care Setting: A National Cohort Study in England,March–July 2020

OBJECTIVETo describe the relationship between type 2 diabetes and all-cause mortality among adults with coronavirus disease 2019 (COVID-19) in the critical care setting.RESEARCH DESIGN AND METHODSThis was a nationwide retrospective cohort study in people admitted to hospital in England with COVID-19 requiring admission to a high dependency unit (HDU) or intensive care unit (ICU) between 1 March 2020 and 27 July 2020. Cox proportional hazards models were used to estimate 30-day in-hospital all-cause mortality associated with type 2 diabetes, with adjustment for age, sex, ethnicity, obesity, and other major comorbidities (chronic respiratory disease, asthma, chronic heart disease, hypertension, immunosuppression, chronic neurological disease, chronic renal disease, and chronic liver disease).RESULTSA total of 19,256 COVID-19–related HDU and ICU admissions were included in the primary analysis, including 13,809 HDU (mean age 70 years) and 5,447 ICU (mean age 58 years) admissions. Of those admitted, 3,524 (18.3%) had type 2 diabetes and 5,077 (26.4%) died during the study period. Patients with type 2 diabetes were at increased risk of death (adjusted hazard ratio [aHR] 1.23 [95% CI 1.14, 1.32]), and this result was consistent in HDU and ICU subsets. The relative mortality risk associated with type 2 diabetes decreased with higher age (age 18–49 years aHR 1.50 [95% CI 1.05, 2.15], age 50–64 years 1.29 [1.10, 1.51], and age ≥65 years 1.18 [1.09, 1.29]; P value for age–type 2 diabetes interaction = 0.002).CONCLUSIONSType 2 diabetes may be an independent prognostic factor for survival in people with severe COVID-19 requiring critical care treatment, and in this setting the risk increase associated with type 2 diabetes is greatest in younger people.