Relapse of tardive dyskinesia due to reduction in clozapine dose

Clozapine is a second-generation (atypical) antipsychotic agent, which has been proven efficient against the positive and negative symptoms of schizophrenia, with a low propensity to induce tardive dyskinesia (TD). Compared with typical antipsychotics, it has a greater affinity for dopamine D4 than D2 receptors and additional action on serotonin 5-HT_2A receptors. Due to its weak D₂ blocking action, it produces few extra pyramidal side effects and TD is rare. TD is one of the muscular side effects of antipsychotic drugs, especially the older generation like haloperidol. TD does not occur until after many months or years of taking antipsychotic drugs. TD is primarily characterized by abnormal involuntary movements of the tongue, lips or jaw, as well as facial grimacing or extremities that develop in association with the use of antipsychotic medications. TD can be embarrassing to the affected patient in public. The movements disappear during sleep and women are at greater risk than men for developing TD.     

Severe acute pancreatitis with pseudocyst bleeding due to hepatitis E virus infection

Coincidence of acute pancreatitis caused by hepatitis E virus (HEV) infection is rare. We report a case of severe acute pancreatitis in the course of acute hepatitis E in a 35-year-old man who presented with jaundice for 1 week. Serum was positive for IgM anti-HEV and negative for hepatitis A, B and C viruses. There was upper abdominal tenderness and fullness with absent bowel sounds. A diagnosis of acute pancreatitis was made and confirmed with elevated serum lipase 2,032 U/L and amylase 1,287 U/L. Two weeks after admission he had an increase in abdominal pain associated with oliguria and hemodynamic instability. Serum creatinine had increased and hemoglobin had dropped along with metabolic acidosis. Ultrasound showed hemorrhage into the pseudocyst, which was confirmed by contrast-enhanced computed tomography scan (which also ruled any pseudoaneurysm as the cause of bleed). He was hemodialysed and transfused blood. However, he developed refractory hypotension and did not respond to inotropes. After a rapid downhill course, he did not survive. Hepatitis E virus infection was complicated with the development of acute pancreatitis, which was severe with multiorgan failure and had a fatal outcome.     

Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis

Synergistic interactions were observed between CIs and antifungal agents against 53 (90%) of 59 Cryptococcus neoformans isolates from solid organ transplant recipients with cryptococcosis and may account for better outcomes in patients with cryptococcosis receiving these immunosuppressive agents.     

Understanding the impact of grain structure in austenitic stainless steel from a nanograined regime to a coarse-grained regime on osteoblast functions using a novel metal deformation–annealing sequence

Metallic biomedical devices with nanometer-sized grains (NGs) provide surfaces that are different from their coarse-grained (CG) (tens of micrometer) counterparts in terms of increased fraction of grain boundaries (NG > 50%; CG < 2–3%). The novel concept of ‘phase-reversion’ involving a controlled deformation–annealing sequence is used to obtain a wide range of grain structures, starting from the NG regime to the CG regime, to demonstrate that the grain structure significantly impacts cellular interactions and osteoblast functions. The uniqueness of this concept is the ability to address the critical aspect of cellular activity in nanostructured materials, because a range of grain sizes from NG to CG are obtained in a single material using an identical set of parameters. This is in addition to a high strength/weight ratio and superior wear and corrosion resistance. These multiple attributes are important for the long-term stability of biomedical devices. Experiments on the interplay between grain structure from the NG regime to CG in austenitic stainless steel on osteoblast functions indicated that cell attachment, proliferation, viability, morphology and spread varied with grain size and were favorably modulated on the NG and ultrafine-grain structure. Furthermore, immunofluorescence studies demonstrated stronger vinculin signals associated with actin stress fibers in the outer regions of the cells and cellular extensions on the NG surface. The differences in the cellular response with change in grain structure are attributed to grain structure and degree of hydrophilicity. The study lays the foundation for a new branch of nanostructured materials for biomedical applications.     

Antigen receptor-induced activation and cytoskeletal rearrangement are impaired in Wiskott-Aldrich syndrome protein-deficient lymphocytes.

The Wiskott-Aldrich syndrome protein (WASp) has been implicated in modulation of lymphocyte activation and cytoskeletal reorganization. To address the mechanisms whereby WASp subserves such functions, we have examined WASp roles in lymphocyte development and activation using mice carrying a WAS null allele (WAS(-)(/)(-)). Enumeration of hemopoietic cells in these animals revealed total numbers of thymocytes, peripheral B and T lymphocytes, and platelets to be significantly diminished relative to wild-type mice. In the thymus, this abnormality was associated with impaired progression from the CD44(-)CD25(+) to the CD44(-)CD25(-) stage of differentiation. WASp-deficient thymocytes and T cells also exhibited impaired proliferation and interleukin (IL)-2 production in response to T cell antigen receptor (TCR) stimulation, but proliferated normally in response to phorbol ester/ionomycin. This defect in TCR signaling was associated with a reduction in TCR-evoked upregulation of the early activation marker CD69 and in TCR-triggered apoptosis. While induction of TCR-zeta, ZAP70, and total protein tyrosine phosphorylation as well as mitogen-activated protein kinase (MAPK) and stress-activated protein/c-Jun NH(2)-terminal kinase (SAPK/JNK) activation appeared normal in TCR-stimulated WAS(-)(/)(-) cells, TCR-evoked increases in intracellular calcium concentration were decreased in WASp-deficient relative to wild-type cells. WAS(-)(/)(-) lymphocytes also manifested a marked reduction in actin polymerization and both antigen receptor capping and endocytosis after TCR stimulation, whereas WAS(-)(/)(-) neutrophils exhibited reduced phagocytic activity. Together, these results provide evidence of roles for WASp in driving lymphocyte development, as well as in the translation of antigen receptor stimulation to proliferative or apoptotic responses, cytokine production, and cytoskeletal rearrangement. The data also reveal a role for WASp in modulating endocytosis and phagocytosis and, accordingly, suggest that the immune deficit conferred by WASp deficiency reflects the disruption of a broad range of cellular behaviors.     

Changes in wavefront aberration with pharmaceutical dilating agents

PURPOSE: Finding the best way to capture the wavefronts of small pupils for refractive surgery has become a more pressing issue as the general population ages. This study explores whether pharmaceutical dilation impacts wavefront measurement and pupil centroid. METHODS: Baseline measurements were performed on 32 eyes using the VISX WaveScan Wavefront system. Pupils were dark adapted. One drop of 0.05% tropicamide was placed in each eye, and wavefront measurements were conducted at 10, 20, and 30 minutes. One drop each of 0.5% tropicamide and 2.5% phenylephrine were administered after the measurements. Wavefronts were captured again 30 minutes after the last eye drop. All patients returned for repeated procedures. Wavefront analysis was performed using the same pupillary area as the smallest capture from the same visit. Pupil center shift was taken into account. RESULTS: Mean patient age was 40 +/- 12 years (range: 20 to 59 years). Mean dark-adapted pupil was 6.40 +/- 1.17 mm. Pupil centers shifted randomly after pharmacological dilation compared to the dark-adapted condition. Pupil centers of 45% of the population shifted by > or = 0.2 mm. Repeatability coefficients were established for the wavefront measurements. After controlling for pupil diameter and pupil center, total high order aberrations root-mean-square (RMS) had changed significantly in 18% of the population. The diluted tropicamide formula, which caused less dilation effect, also induced less high order aberration RMS change. CONCLUSIONS: Pharmaceutical dilation agents cause random shifts of the pupil centroid from the dark-adapted pupil condition and could induce changes in wavefront measurements. Caution is required when resorting to dilation to obtain a wavefront measurement of smaller pupils.     

Chronic actinic dermatitis--a study of clinical features

BACKGROUND: Chronic actinic dermatitis (CAD), one of the immune mediated photo-dermatoses, comprises a spectrum of conditions including persistent light reactivity, photosensitive eczema and actinic reticuloid. Diagnostic criteria were laid down about 20 years back, but clinical features are the mainstay in diagnosis. In addition to extreme sensitivity to UVB, UVA and/or visible light, about three quarters of patients exhibit contact sensitivity to several allergens, which may contribute to the etiopathogenesis of CAD. This study was undertaken to examine the clinical features of CAD in India and to evaluate the relevance of patch testing and photo-aggravation testing in the diagnosis of CAD. METHODS: The clinical data of nine patients with CAD were analyzed. Histopathology, patch testing and photo-aggravation testing were also performed. RESULTS: All the patients were males. The average age of onset was 57 years. The first episode was usually noticed in the beginning of summer. Later the disease gradually tended to be perennial, without any seasonal variations. The areas affected were mainly the photo-exposed areas in all patients, and the back in three patients. Erythroderma was the presenting feature in two patients. The palms and soles were involved in five patients. Patch testing was positive in seven of nine patients. CONCLUSIONS: The diagnosis of CAD mainly depended upon the history and clinical features. The incidence of erythroderma and palmoplantar eczema was high in our series. Occupation seems to play a role in the etiopathogenesis of CAD.     

Imiquimod 5% cream for the treatment of actinic keratoses

Actinic keratoses (AKs) are premalignant inflammatory skin lesions with the potential to transform into squamous cell carcinoma (SCC). There are several treatment options available for patients presenting with multiple AKs. Imiquimod is believed to stimulate and enhance host immune responses locally against skin tumors and viral infections. Five clinical studies to date have demonstrated its safety and efficacy in the treatment of actinic keratoses. Long-term follow-up studies examining recurrence rates are limited.     

Clitoria ternatea and the CNS

The present investigation was aimed at determining the spectrum of activity of the methanolic extract of Clitoria ternatea (CT) on the CNS. The CT was studied for its effect on cognitive behavior, anxiety, depression, stress and convulsions induced by pentylenetetrazol (PTZ) and maximum electroshock (MES). To explain these effects, the effect of CT was also studied on behavior mediated by dopamine (DA), noradrenaline, serotonin and acetylcholine. The extract decreased time required to occupy the central platform (transfer latency, TL) in the elevated plus maze (EPM) and increased discrimination index in the object recognition test, indicating nootropic activity. The extract was more active in the object recognition test than in the EPM. The extract increased occupancy in the open arm of EPM by 160% and in the lit box of the light/dark exploration test by 157%, indicating its anxiolytic activity. It decreased the duration of immobility in tail suspension test (suggesting its antidepressant activity), reduced stress-induced ulcers and reduced the convulsing action of PTZ and MES. The extract exhibited tendency to reduce the intensity of behavior mediated via serotonin and acetylcholine. The effect on DA- and noradrenaline-mediated behavior was not significant. In conclusion, the extract was found to possess nootropic, anxiolytic, antidepressant, anticonvulsant and antistress activity. Further studies are necessary to isolate the active principle responsible for the activities and to understand its mode of action.