Anterior cervical hypertrichosis (hairy throat): is it a sign to worry about?
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Child↗
Biomedical subjects
A Nanda
Publications and source records attributed to A Nanda.
Stroke in the young: relationship of active cocaine use with stroke mechanism and outcome.
BACKGROUND: Cocaine and other vasoactive substances are known causes of cerebrovascular disease. Ictus during drug intake adversely affects outcome. MATERIALS AND METHODS: A retrospective review revealed 42 patients with cocaine abuse and stroke. Aneurysmal bleed occurred in 15 patients; the rest had stroke. The outcome of stroke because of cocaine intoxication was analyzed. RESULTS: Mean age for stroke was 38 (+/- 8.5 SD) years; males out-numbered females (20 : 7) similar to the pattern seen in subarachnoid hemorrhage (SAH) following aneurysm rupture. Nine had intracerebral hematomas, 6 had SAH with intracerebral hemorrhage (ICH)/ infarct, I had transverse myelopathy. Transient ischemic attack was identified in 4. Carotid occlusion was found in 2, and slow-flow in the vertebrobasilar system in 1. Fifteen were known hypertensives. Cocaine was the principal substance in all patients; 7 used other substances including marijuana and heroin. Three patients had HIV, 3 had hepatitis, 2 had syphilis, and 1 had tuberculosis. Urinalysis was positive for cocaine metabolites in 15; 2 had late analysis. Nine had ICH or SAH with poor neurological status at admission and died. Cocaine intoxication correlated with fatal cerebrovascular accident (CVA) (p < 0.001) and poor Glasgow Outcome Score (GOS) (p < 0.001). CONCLUSION: Stroke and cocaine use correlated with fatal CVA and poor outcome. Prompt diagnostic intervention may reveal the incidence of CNS injury with cocaine abuse.
Adult↗
Clinicoepidemiological features and course of 43 cases of bullous pemphigoid in Kuwait.
BACKGROUND: The clinicoepidemiological characteristics and course of bullous pemphigoid (BP) have not been described in populations from the Arabian Gulf. Hypothesis. Ethnic and regional variations can influence the clinical behaviour and course of autoimmune diseases. METHODS: In this study, 43 patients with BP, registered in our autoimmune bullous diseases (ABD) clinic over a span of 14 years, were studied to determine the clinicoepidemiological features and course of the disease in our region. RESULTS: BP was observed to be the second commonest ABD in our clinic (27%), with a minimum estimated incidence of 2.6 cases/million/year among the referral population. The largest proportion (93%) of the patients was of Arab ethnicity and the female to male ratio was 5.1 :1. Mean +/- SD age at diagnosis was 65.20 +/- 18.80 years. Most of the patients (96%) had moderate to severe disease, and mucosal involvement was seen in 37% of the patients. Systemic steroids (prednisolone 20-60 mg daily) alone or in combination with azathioprine, intravenous immunoglobulins, tetracyclines, mycophenolate mofetil or dapsone were used to treat theses cases. At the last follow-up, 32% of patients were in complete remission and off treatment. The first-year mortality was 30%. Old age and poor general medical condition were the significant risk factors (P < 0.05) contributing to the mortality. CONCLUSION: The study highlights the regional variations of BP and thus a need to uncover the ethnic, genetic and geographical influences, if any, responsible for these variations.
Adult↗
Primary intravitreal hydatid cyst: diagnosis on cytological examination.
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Adult↗
Current developments using emerging transdermal technologies in physical enhancement methods.
Transdermal drug delivery using patches offers many advantages, but is limited primarily by the stratum corneum barrier. Amongst the various methods to overcome this barrier, physical methods are gaining in popularity and commercial devices development. Macroflux, MTS and Silex are based on microporation, involving use of microneedles that pierce thereby bypassing the stratum corneum. Intraject , Powderject and Helios are based on needleless jet injectors wherein very fine, solid particulate drug, is fired directly into the skin, using high-pressure gas. Med- Tats incorporate use of modified drug-containing tattoos, which bind to the skin, wherein the drug is absorbed. CHADD is based on use of heat, which increases skin - permeation of drugs. High-power, pulsed lasers transmit positive mechanical forces to the skin and create intercellular channels into the skin transiently. Sonophoresis involves use of ultrasound, which transiently disrupts the stratum corneum barrier. This technique offers a non-invasive transdermal extraction of interstitial fluids of sampling body fluids. Modified Liposomes include Ethosomes (containing alcohol) and Transferosomes (containing surfactants), which have enhanced skin permeability. Pulsed magnetic fields may create transient pores in cell membranes, including skin, resulting in increased permeation. Iontophoresis is based on application of electric potential for enhancing the movement of substances to and from the body. Dupel, Ionzyme, Liposite, ETrans, Phoresor and Drionic are based on iontophoresis. GlucoWatch offers non-invasive blood glucose monitoring, based on reverse iontophoresis. This review outlines recent commercial developments in physical transdermal drug delivery technology and the specific devices and applications being targeted by the pharmaceutical industry.
Adjuvants, Pharmaceutic↗
Intraspinal synovial cysts: a retrospective study.
BACKGROUND: We report the clinical presentation, radiographic studies, intraoperative findings, histopathological analysis, and post-treatment outcome in 26 patients diagnosed with spinal synovial cysts (SSCs). AIMS: To describe the clinical presentation, radiographic studies, operative findings, and postoperative follow-up in 26 patients with SSCs. SETTINGS AND DESIGN: The study was retrospective in design, involving chart review. Individual patient data was tabulated and patterns were recognized. MATERIALS AND METHODS: The charts for 26 patients who underwent surgical extirpation of SSC between April 1993 and October 2002 were retrospectively reviewed. Specifically, initial clinical presentation, pertinent radiographs (X-rays, magnetic resonance imaging, computed tomography), intraoperative findings, histopathology, and postoperative follow-up were noted. STATISTICAL ANALYSIS USED: Patient data was tabulated and analyzed for patterns in demographics, symptoms and histopathology. RESULTS: SSCs were more common in females than males (17:9 ratio). Presenting symptoms were back pain with radiculopathy in 13 (50%), radicular pain in the absence of back pain in 10 (38%), and back pain without radicular pain in three (11%). In addition, 17 patients (65%) had sensory deficit, and 9 (35%) had motor deficit. Most SSCs occurred at the lumbar (19/26) or lumbosacral (5/26) regions, with only 2 (2/26) in the thoracic region. One patient had bilateral SSC at the L4-5 level. Intraoperatively, each cyst was located adjacent to a degenerated facet joint. These lesions could grossly be identified intraoperatively and histopathological confirmation was achieved in all the cases. CONCLUSIONS: SSCs are important lesions to consider in the differential diagnosis of lumbar epidural masses and surgical resection leads to significant improvement in the majority of cases.
Humans↗
Complexation of celecoxib with beta-cyclodextrin: characterization of the interaction in solution and in solid state.
Inclusion complexation between celecoxib, a specific cyclooxygenase II inhibitor, and beta-cyclodextrin (beta-CD) was studied in solution and solid state. Drug cyclodextrin complexes were prepared by spray drying while physical mixtures were obtained by simple blending. Inclusion complexes were characterized by nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), and polarimetry. Phase solubility analysis was carried out to determine the stability constant. Solubility studies revealed the existence of a 1:1 complex between celecoxib and beta-CD. NMR studies suggested a strong interaction between celecoxib and beta-CD prepared by spray drying. XRD and SEM analysis illustrated that celecoxib existed as an amorphous complexed form in spray-dried complexes. Dissolution studies showed that the celecoxib entrapped in spray-dried complexes dissolved much faster than the uncomplexed drug and physical mixtures. The data obtained suggest that celecoxib forms an inclusion complex with beta-CD in solution and solid state, which was confirmed by various analytical techniques. A shorter t50% of dissolution is found for the formulation prepared by spray drying when compared on a weight basis in a USP II apparatus.
Calorimetry, Differential Scanning↗
A case of retroperitoneal fibrosis in a patient following HSCT.
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Adult↗
Sweet's syndrome (acute febrile neutrophilic dermatosis) associated with adenocarcinoma of prostate and transitional cell carcinoma of urinary bladder.
Association of Sweet's syndrome (SS) with solid tumours is found in about 15% of all malignancy-associated cases, but an association with two malignancies occurring in the same patient has been rarely reported. In the present report, we describe an 82-year-old male with SS in association with adenocarcinoma of the prostate and transitional cell carcinoma of the urinary bladder.
Adenocarcinoma↗
N-methyl-D-aspartate receptor activation in human cerebral endothelium promotes intracellular oxidant stress.
Cerebral endothelial cells in the rat, pig, and, most recently, human have been shown to express several types of receptors specific for glutamate. High levels of glutamate disrupt the cerebral endothelial barrier via activation of N-methyl-d-aspartate (NMDA) receptors. We have previously suggested that this glutamate-induced barrier dysfunction was oxidant dependent. Here, we provide evidence that human cerebral endothelial cells respond to glutamate by generating an intracellular oxidant stress via NMDA receptor activation. Cerebral endothelial cells loaded with the oxidant-sensitive probe dihydrorhodamine were used to measure intracellular reactive oxygen species (ROS) formation in response to glutamate receptor agonists, antagonists, and second message blockers. Glutamate (1 mM) significantly increased ROS formation compared with sham controls (30 min). This ROS response was significantly reduced by 1) MK-801, a noncompetitive NMDA receptor antagonist; 2) 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate, an intracellular Ca(2+) antagonist; 3) LaCl(3), an extracellular Ca(2+) channel blocker; 4) diphenyleiodonium, a heme-ferryl-containing protein inhibitor; 5) itraconazole, a cytochrome P-450 3A4 inhibitor; and 6) cyclosporine A, which prevents mitochondrial membrane pore transition required for mitochondrial-dependent ROS generation. Our results suggest that the cerebral endothelial barrier dysfunction seen in response to glutamate is Ca(2+) dependent and may require several intracellular signaling events mediated by oxidants derived from reduced nicotinamide adenine dinucleotide oxidase, cytochrome P-450, and the mitochondria.
Brain↗
Human neuroepithelial cells express NMDA receptors.
L-glutamate, an excitatory neurotransmitter, binds to both ionotropic and metabotropic glutamate receptors. In certain parts of the brain the BBB contains two normally impermeable barriers: 1) cerebral endothelial barrier and 2) cerebral epithelial barrier. Human cerebral endothelial cells express NMDA receptors; however, to date, human cerebral epithelial cells (neuroepithelial cells) have not been shown to express NMDA receptor message or protein. In this study, human hypothalamic sections were examined for NMDA receptors (NMDAR) expression via immunohistochemistry and murine neuroepithelial cell line (V1) were examined for NMDAR via RT-PCR and Western analysis. We found that human cerebral epithelium express protein and cultured mouse neuroepithelial cells express both mRNA and protein for the NMDA receptor. These findings may have important consequences for neuroepithelial responses during excitotoxicity and in disease.
Animals↗
Glutamate causes a loss in human cerebral endothelial barrier integrity through activation of NMDA receptor.
l-Glutamate is a major excitatory neurotransmitter that binds ionotropic and metabotropic glutamate receptors. Cerebral endothelial cells from many species have been shown to express several forms of glutamate receptors; however, human cerebral endothelial cells have not been shown to express either the N-methyl-D-aspartate (NMDA) receptor message or protein. This study provides evidence that human cerebral endothelial cells express the message and protein for NMDA receptors. Human cerebral endothelial cell monolayer electrical resistance changes in response to glutamate receptor agonists, antagonists, and second message blockers were tested. RT-PCR and Western blot analysis were used to demonstrate the presence of the NMDA receptor. Glutamate and NMDA (1 mM) caused a significant decrease in electrical resistance compared with sham control at 2 h postexposure; this response could be blocked significantly by MK-801 (an NMDA antagonist), 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethyoxybenzoate (an intracellular Ca2+ antagonist), and N-acetyl-L-cystein (an antioxidant). Trans(+/-)-1-amino-1,3-cyclopentanedicarboxylic acid, a metabotropic receptor agonist (1 mM), did not significantly decrease electrical resistance. Our results are consistent with a model where glutamate, at excitotoxic levels, may lead to a breakdown in the blood brain barrier via activation of NMDA receptors.
Biological Transport↗
Multiple hyperbaric oxygenation (HBO) expands the therapeutic window in acute spinal cord injury in rats.
Hyperbaric oxygenation (HBO) therapy has been reported to improve neurological recovery following spinal cord injury (SCI). In the present study, we examined whether multiple HBO expands the therapeutic window for acute SCI. Single HBO (2.8 ATA, 1 hour) treatment was used at 30 minutes, 3 hours, and 6 hours following SCI, and serial HBO treatment (once daily for 1 week) at 6 hours and 24 hours post-injury. Mild SCI was induced by adjusting the height for a weight drop insult (10 g) to 6.25 mm above the exposed spinal cord. The group of animals receiving a single HBO intervention beginning at 30 minutes and 3 hours, or serial HBO treatment starting at 6 hours following the injury had a significantly better neurological recovery than animals with SCI only. The results of this study demonstrate that multiple HBO expands the therapeutic window for acute SCI to 6 hours after injury, further that serial HBO administration is superior to single HBO therapy.
Acute Disease↗
Heat shock proteins expression in brain stem after subarachnoid hemorrhage in rats.
The pathogenesis of brain damage after subarachnoid hemorrhage (SAH) especially at molecular or gene level remains unclear. We used complimentary deoxyribonucleic acid (cDNA) macroarray technique and compared gene expression in brain stem after experimental SAH in rats. The upregulation of several heat shock proteins (HSPs) demonstrated by cDNA array was further confirmed by Western blotting. The expressions of 9 genes were upregulated 30 minutes or 2 days after SAH. They included four upregulated HSPs: HSP90alpha, HSP60, HSP27, and HSP10. Western blotting demonstrated increases in the HSP27 and HSP10 proteins on Day 2. SAH enhanced the induction of several HSP mRNAs in the brainstems, even though the functions of these HSPs after SAH remain unclear.
Animals↗
Apoptosis, blood-brain barrier, and subarachnoid hemorrhage.
This study was undertaken to investigate the role of apoptosis in the integrity of blood-brain barrier (BBB) in subarachnoid hemorrhage (SAH). BBB permeability changes were examined and found increased on day 7 in a double hemorrhage rat model using Evans blue dye. The BBB permeability increase is coincidental to brain microvascular endothelial cell apoptosis (expression of caspase-8 and -9) occurring on Day 7. However, caspase-8 and caspase-9 inhibitors failed to protect the BBB. Considering that treatment did not completely inhibit apoptosis in brain microvascular endothelial cells, higher doses, earlier and/or multiple applications, and, possibly, more potent caspase inhibitors may be needed.
Animals↗
Clinicopathological features and HLA tissue typing in pemphigoid gestationis patients in Kuwait.
Pemphigoid gestationis (PG) is a rare autoimmune disease of pregnancy. We report a series of 22 cases of PG in Kuwait. They constituted 18% of all the autoimmune bullous diseases registered in our centre over a span of 11 years. PG was observed to be the third most common bullous disease in our region. Ninety-five per cent of the patients were of Arab ethnicity. The clinical features observed in our patients were comparable to those reported elsewhere. Systemic steroids (prednisolone 20-60 mg daily) remained the mainstay of treatment to control the active disease and an optimal dose of 20 mg of prednisolone was maintained throughout the pregnancy and immediate postpartum period. We observed a favourable outcome of pregnancies complicated by PG without any associated maternal or foetal morbidity. Kuwaiti patients with PG were observed to have a predominance of HLA-DR3 and DQ2 antigens. No predominance of HLA-DR4 antigen was observed.
Adolescent↗
Cell surface tumor endothelial markers are conserved in mice and humans.
We recently identified genes encoding tumor endothelial markers (TEMs) that displayed elevated expression during tumor angiogenesis. From both biological and clinical points of view, TEMs associated with the cell surface membrane are of particular interest. Accordingly, we have further characterized four such genes, TEM1, TEM5, TEM7, and TEM8, all of which contain putative transmembrane domains. TEM5 appears to be a seven-pass transmembrane receptor, whereas TEM1, TEM7, and TEM8 span the membrane once. We identified mouse counterparts of each of these genes, designated mTEM1, mTEM5, mTEM7, and mTEM8. Examination of these mTEMs in mouse tumors, embryos, and adult tissues demonstrated that three of them (mTEM1, mTEM5, and mTEM8) were abundantly expressed in tumor vessels as well as in the vasculature of the developing embryo. Importantly, expression of these mTEMs in normal adult mouse tissues was either undetectable or detected only in a small fraction of the vessels. These results demonstrate conservation of human and mouse tumor angiogenesis at the molecular level and support the idea that tumor angiogenesis largely reflects normal physiological neovasculaturization. The coordinate expression of TEM1, TEM5, and TEM8 on tumor endothelium in humans and mice makes these genes attractive targets for the development of antiangiogenic therapies.
Animals↗
Differential responses of human neuroblastoma and glioblastoma to apoptosis.
Staurosporine, a protein kinase and etoposide, a topoisomerase II inhibitor, are known to enhance apoptosis. The differential effects of these agents on T98G glioblastoma and SK-N-SH neuroblastoma, cell lines both derived from human tumors, have not been determined. We assessed cellular viability, DNA fragmentation and laddering, chromatin condensation, and Poly(ADP-ribose) polymerase (PARP) cleavage induced by these agents at a series of concentrations and times. In addition, to gain an understanding of the mechanism by which these agents work, we measured Protein Kinase C (PKC) activity. Staurosporine induced significant alterations in all apoptotic parameters tested in both cell lines. Etoposide induced apoptotic alterations similar to those caused by staurosporine in neuroblastoma but produced no detectable apoptotic changes in glioblastoma cells. Etoposide induced membrane but not cytosolic PKC activity in neuroblastoma but had no effect on PKC activity in glioblastoma. Our results show that the induction of apoptosis is cell type dependent. PKC activity appears to be crucial in the initiation of apoptosis.
Antineoplastic Agents, Phytogenic↗