Non-invasive magnetic resonance myelography in spontaneous intracranial hypotension.
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Adult↗
Biomedical subjects
S C Patel
Publications and source records attributed to S C Patel.
MRI-guided, open trial of abciximab for ischemic stroke within a 3- to 24-hour window.
The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) > or = 4 (11.1 +/- 5.9), treated within 3 to 24 (13.6 +/- 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 +/- 3.2 and the 24-hour lesion growth on DWI was +23% (-50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.
Abciximab↗
Neuronal localization and association of Niemann Pick C2 protein (HE1/NPC2) with the postsynaptic density.
Niemann-Pick disease type C (NP-C) is an inherited disorder that is characterized biochemically by cellular cholesterol and glycolipid storage, and clinically by progressive neurodegeneration. Most cases of NP-C are caused by inactivating mutations of the npc1 gene, but about 5% are linked to npc2, which encodes a soluble cholesterol binding protein, previously identified as epididymal secretory glycoprotein 1 (HE1). The present study was carried out to investigate the immunocytochemical localization of HE1/NPC2 protein in the mouse brain. Using an antibody against recombinant HE1/NPC2, we found HE1/NPC2 to be localized predominantly in neurons in the brain. Immunoreactivity for HE1/NPC2 was observed in pyramidal or projection neurons in the cerebral cortex and amygdala, and Purkinje neurons in the cerebellum. Neurons in the thalamus, hypothalamus, and globus pallidus were lightly labeled, or unlabeled. This regional pattern of expression of HE1/NPC2 is similar to our previous findings with NPC1, with a low level of expression of both NPC1 and HE1/NPC2 proteins in regions derived from the diencephalon, such as the thalamus and hypothalamus. In contrast to NPC1, however, which is predominantly in astrocytes, HE1/NPC2 was observed mainly in neurons. Electron microscopic immunocytochemistry showed that HE1/NPC2 is present in the cytosol of dendrites and on post-synaptic densities (PSD). The occurrence of HE1/NPC2 in the PSD was confirmed by Western blots of PSD-enriched brain subcellular fractions that showed the presence of HE1/NPC2 together with the PSD-associated protein, PSD-95. These results suggest that NPC1 and HE1/NPC2 are differentially enriched in astrocytes and neurons, respectively, and that HE1/NPC2 may function in supporting the integrity of the PSD of neurons.
Animals↗
Differential trafficking of the Niemann-Pick C1 and 2 proteins highlights distinct roles in late endocytic lipid trafficking.
UNLABELLED: The cellular location of Niemann-Pick C2 protein (NPC2) in cultured human fibroblasts and Chinese hamster ovary cells was examined immunocytochemically and in living cells by expression of a functional red fluorescent protein chimeric analogue. RESULTS: NPC2 is present in the lysosomes of both cholesterol-depleted and -replenished cells, unlike Niemann-Pick C1 protein (NPC1) which is recruited to late endosomes only upon uptake of low-density lipoprotein. With mobilization of cholesterol from lysosomes, immunocytochemical detection of NPC2 in lysosomes is greatly diminished, whereas NPC1 remains in the late endosomal compartment. We found a partial overlap in the trafficking and organellar sites of accumulation of NPC2 and NPC1. In living cells, NPC2 traffics with NPC1 in late endosomal tubules. However, in contrast to NPC1, which remains either in late endosomal vesicles and tubules or at the peripheries of cholesterol-laden lysosomes, NPC2 moves into the central core of lysosomes. Glycolipid analysis reveals that, in contrast to null mutant NPC1 cells, which accumulate GM2 ganglioside only at the plasma membrane, with no endocytic storage, absence of NPC2 protein in null mutant NPC2 cells does not block internalization of GM2 into endocytic vesicles. This difference in the cellular distribution of GM2 in NPC1 and NPC2 null mutants is the first report of a variation in the phenotypic expression of these genotypically distinct lesions. CONCLUSION: We speculate that while NPC1 may play a major role in the sorting of glycolipids as well as cholesterol within the late endosomes, NPC2 primarily plays a role in the egress of cholesterol and, potentially, glycolipids from lysosomes. These proteins appear not to be integrated into a tightly bound biological complex, but rather represent separate functional entities that complement each other.
Animals↗
Laparoscopic appendicectomy at the Aga Khan Hospital, Nairobi.
OBJECTIVE: To evaluate our experience of laparoscopic appendicectomy at the Aga Khan Hospital, Nairobi over a six year period from the inception of the technique and to assess its advantages and disadvantages. DESIGN: Case series study. SETTING: The Aga Khan Hospital, Nairobi. PATIENTS: One hundred and six cases operated on from May 1996 to June 2002. MAIN OUTCOME MEASURES: Clinical presentation, age and sex demographics, average hospital stay, operating time, intra-operative and post-operative complications and outcome. RESULTS: There was a female preponderance with a female to male ratio of 2:3:1. Mean age was 30.6 years. There was a slightly more number of patients with recurrent appendicitis as opposed to the acute form. Totally laparoscopic procedure was in 39.6% of the cases, laparoscopic assisted in 45.3%. The conversion rate to an open procedure was 15.1%. Post operative port-site infection was 8.5%. No mortality was reported in these series. However there was one case which required re-operation following significant port site haemorrhage. Mean post-operative hospital stay was 2.2 days. CONCLUSION: Laparoscopic appendicectomy is a safe procedure in well trained hands. The major advantages are less morbidity and excellent cosmesis. Discovery of other intraabdominal pathologies is possible through laparoscopy as opposed to classical appendicectomy.
Adolescent↗
Functional MRI-BOLD of brainstem structures during visually triggered migraine.
BACKGROUND: Previously, hyperoxia and blood volume increase were reported in the red nucleus and substantia nigra during spontaneous migraine with aura. OBJECTIVE: To further understand the pathophysiologic role of these centers, activation of brainstem structures was investigated in patients with visually triggered migraine. METHODS: Twenty-six patients with migraine (23 with aura and 3 without aura), and 10 normal control subjects were studied with blood oxygen level-dependent (BOLD) fMRI during repeated checkerboard visual stimulation. Three axial image sections, which covered the occipital cortex and brainstem, were acquired 224 times with a temporal resolution of 3.5 seconds. RESULTS: Repetitive visual stimulation triggered symptoms in 12 patients; four who had migraine with aura developed both visual symptoms and headaches, and six who had migraine with aura and two who had migraine without aura had headaches only. Four patients who had migraine with aura experienced the onset of their usual aura or onset of their typical headache either during the experiment or immediately after. In the remaining 10 patients with migraine, and all control subjects, visual stimulation failed to trigger symptoms at any time. In 75% of the patients who developed symptoms during stimulation, baseline T2*-weighted MR signal intensities increased in the red nucleus and substantia nigra before occipital cortex signal elevation or the onset of visually triggered symptoms. CONCLUSION: Activation (hyperoxia and blood volume increase) of the red nucleus and substantia nigra in association with visually triggered symptoms of migraine suggest that these brainstem structures are a part of a neuronal network activated during an attack.
Adult↗
Lack of clinical significance of early ischemic changes on computed tomography in acute stroke.
CONTEXT: The prevalence and clinical significance of early ischemic changes (EICs) on baseline computed tomography (CT) scan of the head obtained within 3 hours of ischemic stroke are not established. OBJECTIVE: To determine the frequency and significance of EIC on baseline head CT scans in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA (recombinant tissue plasminogen activator) Stroke Trial. DESIGN AND SETTING: The original study, a randomized controlled trial, took place from January 1991 through October 1994 at 43 sites, during which CT images were obtained within 3 hours of symptom onset and prior to the initiation of rt-PA or placebo. For the current analysis, detailed reevaluation was undertaken after October 1994 of all baseline head CT scans with clinical data available pretreatment (blinded to treatment arm). PATIENTS: Of 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%). MAIN OUTCOME MEASURES: Frequency of EICs on baseline CT scans; association of EIC with other baseline variables; effect of EICs on deterioration at 24 hours (>/=4 points increase from the baseline National Institutes of Health Stroke Scale [NIHSS] score); clinical outcome (measured by 4 clinical scales) at 3 months, CT lesion volume at 3 months, death at 90 days; and symptomatic intracranial hemorrhage (ICH) within 36 hours of treatment. RESULTS: The prevalence of EIC on baseline CT in the combined rt-PA and placebo groups was 31% (n = 194). The EIC was significantly associated with baseline NIHSS score (rho = 0.23; P<.001) and time from stroke onset to baseline CT scan (rho = 0.11; P =.007). After adjusting for baseline variables, there was no EIC x treatment interaction detected for any clinical outcome, including deterioration at 24 hours, 4 clinical scales, lesion volume, and death at 90 days (P>/=.25), implying that EIC is unlikely to affect response to rt-PA treatment. After adjusting for NIHSS score (an independent predictor of ICH), no EIC association with symptomatic ICH at 36 hours was detected in the group treated with rt-PA (P>/=.22). CONCLUSIONS: Our analysis suggests that EICs are prevalent within 3 hours of stroke onset and correlate with stroke severity. However, EICs are not independently associated with increased risk of adverse outcome after rt-PA treatment. Patients treated with rt-PA did better whether or not they had EICs, suggesting that EICs on CT scan are not critical to the decision to treat otherwise eligible patients with rt-PA within 3 hours of stroke onset.
Aged↗
Neurodegeneration in Niemann-Pick type C disease mice.
Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disorder associated with intracellular cholesterol and glycolipid trafficking defects. Two separate genes, NPC1 and NPC2, have been linked to NP-C. NPC1 encodes a polytopic membrane-bound protein with a putative sterol-sensing domain. NPC2 has been recently identified as epididymal secretory glycoprotein 1. The NPC1 protein functions in the vesicular redistribution of endocytosed lysosomal cargo, but how its inactivation leads to neurodegeneration is not known. The neurological symptoms of NP-C typically appear after a period of normal early development and reflect progressive degeneration of widespread brain regions. Here we have delineated the pattern of neurodegeneration in NP-C mice, whose genetic defect has been shown to be an inactivating mutation of the mouse NPC1 gene. The results reveal a spatially and temporally specific pattern of degeneration of nerve fibers followed by degeneration of neuronal cell bodies beginning as early as day 9 and continuing throughout life. We have recently showed that in the primate brain, the NPC1 protein is localized predominantly within perisynaptic astrocytic processes. The present observations suggest that a functional disturbance in NPC1 could disrupt vesicular transport of cholesterol, glycolipids and possibly other endocytic cargo in glia, which is critical for maintaining the integrity of neurons.
Aging↗
Macular hole surgery in high myopia.
PURPOSE: To evaluate the anatomic and functional outcomes of macular hole surgery in high myopia and to determine whether surgery is beneficial in myopic eyes with macular holes. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Twenty eyes of 18 highly myopic subjects who underwent pars plana vitrectomy for macular holes. METHODS: We analyzed demographics, preoperative, and postoperative characteristics in 20 eyes with macular holes with a mean of 10.4 months duration and myopia of 6 diopters or greater. MAIN OUTCOME MEASURES: Macular hole closure rate and mean visual acuity preoperatively and postoperatively. RESULTS: Mean subject age was 56.4 years and preoperative visual acuity was 20/100+2. The macular hole was closed with one surgery in 60.0% of eyes and in 85.0% of eyes with one or more surgeries. The mean final acuity in all eyes was 20/63, and 40.0% improved greater than three Snellen lines at the final visit. The use of adjunctive agents seemed to have no effect on macular hole closure or visual acuity. A subgroup of three myopic eyes with retinal detachments surrounding the macular hole had successful closure with visual acuity improvement in two of three eyes. CONCLUSIONS: Macular hole surgery can give substantial visual improvement in myopic eyes with macular holes, but the anatomic closure rates are lower than in eyes with idiopathic macular holes, and thus a higher reoperation rate is required.
Female↗
Necrotizing fasciitis of abdominal wall in AIDS.
Necrotizing fasciitis (NF) is an uncommon but potentially lethal soft-tissue infection. Mortality rate is high and has not changed since it was first described by Meleny. Although immunodeficiency is a risk factor for NF, there is only one reported case of NF in AIDS involving the cervical region. We report the first case of necrotizing fasciitis of the abdominal wall in an AIDS patient.
Abdominal Muscles↗
Immunocytochemical localization of apolipoprotein D in oligodendrocyte precursor-like cells, perivascular cells, and pericytes in the human cerebral cortex.
Apolipoprotein D, a lipocalin transporter of small hydrophobic molecules including sterols, steroid hormones and arachidonic acid, is a widely expressed protein in peripheral and neural tissues. It has been shown to be upregulated in the context of neural injury, and with neuronal degeneration and regeneration. Here we have used light and electron microscopic immunocytochemistry with immunogold labeling to delineate the pattern of expression of apoD in the human brain. Our results confirm previous observations that apoD is a predominantly glial protein in the nervous system. In addition we have found that apoD is present in the cytosol and outer membrane of the nuclear envelope of glial cells in the neuropil. The labeled glial cells were putatively identified as a population of oligodendrocyte precursor cells. Immunoreactivity was also associated with the cytosol of perivascular cells, and lysosomes of pericytes, in the walls of blood vessels. These observations suggest a potential role for glial cells and apoD, in the transport of sterols and small hydrophobic molecules to, or from, blood vessels in the cortex.
Adult↗
Cytokine modulation of costimulatory molecules on human fetal retinal pigment epithelial cells.
PURPOSE: Experiments were performed to evaluate the effect of various pro- and anti-inflammatory cytokines on the human fetal retinal pigment epithelium's (HFRPE) expression of major histocompatibility complex (MHC) and costimulatory molecules. METHODS: Pure cultures of HFRPE cells were isolated. HFRPE cells were incubated in the presence of Interferon-gamma (IFN-gamma), IFN-beta, Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-1beta (IL-1beta), Tumor Growth Factor-beta (TGF-beta), and a combination of IFN-gamma and TGF-beta (pre-incubation and simultaneously incubated). The expression of MHC class I and class II, Intercellular cell adhesion molecule (ICAM-1), B7-1 (CD80), and B7-2 (CD86) molecules was quantitatively analyzed by flow cytometry. RESULTS: The cultured HFRPE cells expressed high levels of MHC class I and low levels of MHC class II and ICAM-1 molecules. After culture with the above mentioned cytokines, IFN-gamma up-regulated the HFRPE's expression of MHC class II and ICAM-1. IFN-beta and IL-beta1 only up-regulated the expression of ICAM-1. TGF-beta was unable to suppress the up-regulatory effect of IFN-gamma in HFRPE cells (pre-incubated and simultaneously incubated). The other cytokines did not have any significant effect on HFRPE's expression of MHC I and II or the selected costimulatory molecules. CONCLUSIONS: Our findings indicate that TGF-beta cannot suppress up-regulating effects of IFNgamma- on HFRPE's expression of MHC and costimulatory molecules. Overall, the weak or lack of expression of costimulatory molecules after stimulation with various cytokines further confirms that HFRPE cells are weak antigen presenting cells.
Antigen-Presenting Cells↗
Insulin-like growth factor 1 regulates developing brain glucose metabolism.
The brain has enormous anabolic needs during early postnatal development. This study presents multiple lines of evidence showing that endogenous brain insulin-like growth factor 1 (Igf1) serves an essential, insulin-like role in promoting neuronal glucose utilization and growth during this period. Brain 2-deoxy-d- [1-(14)C]glucose uptake parallels Igf1 expression in wild-type mice and is profoundly reduced in Igf1-/- mice, particularly in those structures where Igf1 is normally most highly expressed. 2-Deoxy-d- [1-(14)C]glucose is significantly reduced in synaptosomes prepared from Igf1-/- brains, and the deficit is corrected by inclusion of Igf1 in the incubation medium. The serine/threonine kinase Akt/PKB is a major target of insulin-signaling in the regulation of glucose transport via the facilitative glucose transporter (GLUT4) and glycogen synthesis in peripheral tissues. Phosphorylation of Akt and GLUT4 expression are reduced in Igf1-/- neurons. Phosphorylation of glycogen synthase kinase 3beta and glycogen accumulation also are reduced in Igf1-/- neurons. These data support the hypothesis that endogenous brain Igf1 serves an anabolic, insulin-like role in developing brain metabolism.
Animals↗
Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity.
Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.
Animals↗
A model for xenogenic immune response.
PURPOSE: To develop a model for analyzing the immune response after xenogenic human fetal retinal pigment epithelium (HFRPE) transplantation. MATERIALS AND METHODS: Pure sheets of HFRPE cells were isolated and attached to poly (DL-lactide-co-glycolide) polymer films and HFRPE spheroids were formed. The spheroids were transplanted into the subretinal space of New Zealand albino rabbits and were observed for 5 months. Bare polymer films were transplanted into the subretinal space of Dutch Belted pigmented rabbits, serving as control. RESULTS: The polymer film was biodegraded within 3 weeks in the subretinal space. No signs of inflammation in the retina or choroid were observed. The HFRPE spheroids were easily transplanted into the subretinal space. The immune response was followed with ophthalmoscopy. Light microscopy indicated a localized immune response in the transplanted area in which the retina and the choroid were infiltrated with immune cells. This infiltration was denser in the choroid. CONCLUSIONS: HFRPE spheroid transplantation may be utilized as a model for studying the xenogenic immune response after HFRPE transplantation. This model may also have applications in evaluating the role of immune suppressive agents in preventing rejection after HFRPE transplantation.
Absorbable Implants↗
A meta-analysis of the Papanicolaou smear and wet mount for the diagnosis of vaginal trichomoniasis.
PURPOSE: To obtain reliable estimates of the sensitivity and specificity of the cervical Papanicolaou (Pap) smear and wet mount to diagnose vaginal trichomoniasis. METHODS: Articles indexed in MEDLINE (1976-1998) about diagnostic tests for trichomoniasis and their listed references were retrieved. Thirty studies (9,501 patients) that used trichomonas culture as a gold standard were selected. Studies were defined as level I if they fulfilled at least two of the following three criteria: consecutive patients were evaluated prospectively, the decision to culture was not influenced by test results, and there was independent and blind comparison with culture. Studies were classified as level II if one criterion was fulfilled, and as level III otherwise. RESULTS: The pooled sensitivity of the Pap smear for the diagnosis of trichomoniasis among level I studies was 57% (95% confidence interval [CI]: 51% to 63%) and the pooled specificity was 97% (95% CI: 93% to 100%). The likelihood ratio for a positive Pap smear was 19 among level I studies (range: 8 to 62). The pooled sensitivity of the wet mount among level I studies was 58% (95% CI: 51% to 66%); among level II studies, the sensitivity was 72% (95% CI: 62% to 81%), and among level III studies, the sensitivity was 82% (95% CI: 67% to 97%). The overall specificity of the wet mount was 99.8%. CONCLUSIONS: A positive Pap smear for trichomonads in settings in which trichomoniasis is common (prevalence > or =20%) requires treatment. A positive Pap smear is indeterminate when the prevalence of trichomoniasis is about 10%; thus, clinicians should either confirm the diagnosis by culture or treat all such patients, recognizing that some patients will be treated unnecessarily. A culture should be obtained in women with a positive Pap smear who are unlikely to have trichomoniasis (prevalence < or =1%). While a positive wet mount is diagnostic, a negative wet mount does not exclude trichomoniasis.
Chi-Square Distribution↗
Algorithm for interpreting the results of frequency doubling perimetry.
PURPOSE: To evaluate an algorithm for the identification of glaucomatous visual field defects with the screening mode of frequency doubling technology. METHODS: Screening-mode frequency doubling technology and Swedish interactive threshold algorithm perimetry were performed on 137 of 150 consecutive patients referred to a glaucoma specialist. We created an algorithm for the frequency doubling technology that gave increased importance to both more severe defects and defects closer to fixation. These values were then compared with the results of the Swedish interactive threshold algorithm visual fields evaluated by the glaucoma hemifield test, two masked glaucoma specialists, and a published definition of glaucomatous damage to determine sensitivity and specificity of the frequency doubling technology screening mode for detecting glaucoma.
Adult↗
Neuronal localization of sterol regulatory element binding protein-1 in the rodent and primate brain: a light and electron microscopic immunocytochemical study.
Sterol regulatory element binding proteins are membrane-bound transcription factors that activate expression of several genes controlling cellular cholesterol and fatty acid homeostasis. The present study aimed to investigate the in vivo expression of sterol regulatory element binding protein-1 in the normal rodent and primate brain, and in the brain in Niemann-Pick type C disease mice. These mutant animals have lysosomal cholesterol accumulation and progressive neurodegeneration caused by an inactivating mutation of the NPC1 gene whose protein product functions in vesicular lipid trafficking. Western blot analysis of rat hippocampal homogenates with an affinity purified rabbit polyclonal antibody directed against an internal epitope of sterol regulatory element binding protein-1 identified a major 68,000 mol. wt protein consistent with the amino-terminal, transcriptionally active fragment of sterol regulatory element binding proteins-1. Immunocytochemically, this antibody revealed dense sterol regulatory element binding protein-1 staining of nuclei and light staining of the cytoplasm of cells in the neocortex and hippocampus in the rat, mouse and monkey brain. By electron microscopy of immunogold-labeled brain sections, these densely labeled cells were found to be neurons. In contrast, normal glial cells had little or no sterol regulatory element binding protein-1 immunoreactivity even at a developmental stage (postnatal day 9) which coincides with active myelination in the rat brain. Also, in contrast to the normal mouse brain, Niemann-Pick type C mice showed reduced staining of cortical and hippocampal neuronal nuclei. Since sterol regulatory element binding protein-1 has been shown to be a transcriptional regulator of fatty acid synthesis in vivo, the current findings of a predominantly neuronal nuclear expression of the 68,000 mol. wt transcriptionally active fragment of sterol regulatory element binding protein-1 highlights the established role of phospholipid metabolites and other fatty-acid containing lipids in neuronal signal transduction and other neuronal functions. Reduced sterol regulatory element binding protein-1 expression in neurons in Niemann-Pick type C may reflect a deficiency in fatty acid synthesis that could contribute to the neuronal dysfunction in this disorder.
Animals↗