Evaluation of familial influences on the course and severity of schizophrenia among US and Indian cases

Abstract.Background: Prior studies suggest familial (possibly genetic) influences on the course of schizophrenia.Aims: The aim of this study was to compare familial influences on the course and severity of schizophrenia in two independent samples.Method: Thirteen selected measures were compared among affected sibling pairs (ASPs) from Pittsburgh, USA and New Delhi, India (48 US pairs, 53 Indian pairs). For each ASP proband, an unrelated patient was selected randomly from a suitable pool of cases ascertained in the same study (Sibpair proband—comparison case or S-C pairs). Correlations between these pairs were compared.Results: The correlations varied by item and by site. Significant correlations for longitudinal course and pattern of severity were noted among the ASPs from USA, but did not remain significant following corrections for multiple comparisons. Comparisons between the correlations for ASPs and the S-C pairs, used to estimate familial effects, yielded trends for the ASP correlations to be numerically larger than the S-C correlations in both samples. Separate cross-site comparisons revealed several significant differences with regard to several demographic and clinical variables. The possible impact of the cross-site variations on the observed ASP correlations is discussed.Conclusions: Though familial factors did not appear to have a significant impact on course/severity using this novel design, the suggestive trends need to be examined in larger samples.     

Prolonged cannabinoid exposure alters GABA(A) receptor mediated synaptic function in cultured hippocampal neurons

Developing cannabinoid-based medication along with marijuana's recreational use makes it important to investigate molecular adaptations the endocannabinoid system undergoes following prolonged use and withdrawal. Repeated cannabinoid administration results in development of tolerance and produces withdrawal symptoms that may include seizures. Here we employed electrophysiological and immunochemical techniques to investigate the effects of prolonged CB1 receptor agonist exposure on cultured hippocampal neurons. Approximately 60% of CB1 receptors colocalize to GABAergic terminals in hippocampal cultures. Prolonged treatment with the cannabinamimetic WIN 55,212-2 (+ WIN, 1 μM, 24 h) caused profound CB1 receptor downregulation accompanied by neuronal hyperexcitability. Furthermore, prolonged + WIN treatment resulted in increased GABA release as indicated by increased mIPSC frequency, a diminished GABAergic inhibition as indicated by reduction in mIPSC amplitude and a reduction in GABA_A channel number. Additionally, surface staining for the GABA_A β_2/3 receptor subunits was decreased, while no changes in staining for the presynaptic vesicular GABA transporter were observed, indicating that GABAergic terminals remained intact. These findings demonstrate that agonist-induced downregulation of the CB1 receptor in hippocampal cultures results in neuronal hyperexcitability that may be attributed, in part, to alterations in both presynaptic GABA release mechanisms and postsynaptic GABA_A receptor function demonstrating a novel role for cannabinoid-dependent presynaptic control of neuronal transmission.     

Dantrolene inhibits the calcium plateau and prevents the development of spontaneous recurrent epileptiform discharges following in vitro status epilepticus

Status epilepticus is a clinical emergency that can lead to the development of acquired epilepsy following neuronal injury. Understanding the pathophysiological changes that occur between the injury itself and the expression of epilepsy is important in the development of new therapeutics to prevent epileptogenesis. Currently, no anti‐epileptogenic agents exist; thus, the ability to treat an individual immediately after status epilepticus to prevent the ultimate development of epilepsy remains an important clinical challenge. In the Sprague–Dawley rat pilocarpine model of status epilepticus‐induced acquired epilepsy, intracellular calcium has been shown to increase in hippocampal neurons during status epilepticus and remain elevated well past the duration of the injury in those animals that develop epilepsy. This study aimed to determine if such changes in calcium dynamics exist in the hippocampal culture model of status epilepticus‐induced acquired epilepsy and, if so, to study whether manipulating the calcium plateau after status epilepticus would prevent epileptogenesis. The in vitro status epilepticus model resembled the in vivo model in terms of elevations in neuronal calcium concentrations that were maintained well past the duration of the injury. When used following in vitro status epilepticus, dantrolene, a ryanodine receptor inhibitor, but not the N‐methyl‐d ‐aspartic acid channel blocker MK‐801 inhibited the elevations in intracellular calcium, decreased neuronal death and prevented the expression of spontaneous recurrent epileptiform discharges, the in vitro correlate of epilepsy. These findings offer potential for a novel treatment to prevent the development of epileptiform discharges following brain injuries.     

Evaluation of functional impairment in psoriasis

BACKGROUND: Psoriasis is a chronic disease, the course of which is punctuated by exacerbations and remissions. The impact of a chronic, relapsing, and disfiguring disease such as psoriasis on occupational, social, and other areas of functioning is substantial and needs attention. AIM: The purpose of this study was to assess the level and nature of functional impairment in psoriasis. METHODS: Forty-three consecutive patients attending the dermatology clinic of a rural hospital were studied for psychiatric comorbidity and the level of functioning, using a semistructured questionnaire. RESULTS: Psoriasis affected social functioning of 48% patients, led to decreased work efficiency in 51.1% and to subjective distress at work in 62.8% of patients. Stress in home environment and interpersonal relationships was reported by 69.8%. Social and occupational functioning worsened with increasing severity of psoriasis after 1-year duration of illness. Patients complaining of pruritis frequently had anxiety disorders. Psychiatric comorbidity was detected in 67.4% cases. CONCLUSION: Substantial proportion of patients suffered deterioration of functioning, especially with increasing duration of illness. Thus, timely attention by dermatologists is needed in order to limit the disability caused by psoriasis. To achieve this, liaison with psychiatrist would be crucial along with illness education and emotional support.     

Rat Renal Mesenchymal Tumor as an Experimental Model for Human Congenital Mesoblastic Nephroma: II. Comparative Pathology

The morphological features of kidney neoplasms induced by ethylnitrosourea (ENU) with or without prior irradiation were examined with a view to comparing them with human renal tumors of childhood. The rat renal tumors consisted of poorly differentiated, highly mitotic mesenchymal cells frequently attempting to differentiate along fibroblastic and myofibroblastic lineages. Though the host renal tubules were frequently entrapped in these tumors, immature tubules and islands of epithelial cells occasionally were seen to form an integral part of the neoplasms. Rarely, adenomatous areas surrounded by mesenchymal proliferation were observed. None of the tumors had the blastemal component that is the hallmark of nephroblastoma. The rat mesenchymal tumors resembled the human congenital mesoblastic nephroma.     

Neonatal osteomyelitis and septic arthritis

The records of seventeen neonates (13 males and 4 females) with osteomyelitis and septic arthritis, who were admitted over a 3 year period, were reviewed. Neither prematurity nor low birth weight seemed to be a predisposing factor. The majority of the neonates (88.2%) had some antecedent illness or were subjected to certain procedures in the neonatal period. Paucity of movement of limb, fever and local swelling of the joint were the most frequent presenting symptoms. Deep soft tissue swelling was the frequently noted radiographic change (58.8%). Bone scintigraphy was abnormal in 7 out of 11 cases. Of the 21 sites involved, femur and humerus accounted for 76.1% of cases. Four of seventeen neonates had multiple bone involvement. Arthritis was present in fifteen neonates. Of the organisms isolated, Staphylococcus aureus was the commonest.     

Hospitals and union elections

This study examines union certification elections in hospitals from October 1994 to September 1997. Results indicate that union win rates were significantly higher in single-union elections and larger bargaining units. On the other hand, union win rates were significantly lower in church-related hospitals and hospitals that belonged to a health care system or had higher payroll costs. Unions also appeared to win elections at a higher rate in this period than in the past.     

Prediction of timed vital capacity from height and weight in children in the age group of 5 to 12 years

In the present study 350 school boys and 350 school girls in the age group of 5 to 12 yr were studied. It was observed that there is parallel progressive increase in physical growth and pulmonary function in this age group. There was positive significant correlation of FEV₁ with height and weight.     

Oxidant signalling in carcinogenesis: a commentary

It is becoming increasingly evident that reactive oxygen species (ROS) act at different stages of carcinogenesis, and thus play multiple roles in oncogenesis. In addition to being mutagenic and initiating tumors, ROS or carcinogens that result in ROS generation may affect tumor promotion and progression through varied effects on growth promoting, growth inhibitory, or apoptotic signaling pathways.