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Biomedical subjects

N A Syed

Publications and source records attributed to N A Syed.

At least 19 recordsLinked to original sources
PubMed2006

Stroke-associated pneumonia: microbiological data and outcome.

INTRODUCTION: Pneumonia is a common complication after acute stroke. It affects the outcome adversely. However, data regarding microbiology of stroke-associated pneumonia and its effect on outcome is scarce. METHODS: Stroke-associated pneumonia was identified through chart review of all ICD-9 identified adult stroke patients admitted to our hospital over a period of four years (1998-2001). The demographical, laboratory, radiological, microbiological data and outcome of patients with stroke-associated pneumonia were recorded and analysed. RESULTS: 443 patients with stroke were admitted over the four-year period and 102 (23 percent) had stroke-associated pneumonia. Their ages range from 28 to 100 (mean 64+/-14) years. 69 (68 percent) were men. Median length of stay was nine days compared to four days for all stroke patients. 68 (67 percent) patients manifested pneumonia within 48 hours and 34 (33 percent) after 48 hours of admission. Yield of tracheal aspirate cultures was 38 percent and that of chest radiographs was 25 percent. Pseudomonas aeruginosa and Staphylococcus aureus were the most common organisms (12 percent each) followed by Streptococcus pneumoniae and Klebsiella pneumoniae (4 percent each). Patients with infiltrates on chest radiographs were more likely to have positive tracheal aspirate cultures (p-value is 0.003). 35 patients (34 percent) expired during hospital stay. Positive chest radiographs and tracheal aspirates were independent predictors of prolonged hospital stay (p-value is less than 0.005). CONCLUSION: Pneumonia is a common medical complication of stroke. It is associated with a high mortality and prolongs the hospital stay. The yield of chest radiographs and tracheal aspirates is low. However, these are independent predictors of prolonged hospital stay. Pseudomonas aeruginosa and Staphylococcus aureus are most common organisms in stroke-associated pneumonia.

Adult↗
PubMed2004

Effects of dietary protein source and level on intestinal populations of Clostridium perfringens in broiler chickens.

Two experiments were conducted to examine the effect of the level of dietary crude protein and protein source on intestinal populations of Clostridium perfringens in broilers. In experiment 1, 6 groups of 12 birds were fed diets containing 230,315 or 400 g/kg crude protein with soy protein concentrate (SPC) or low-temperature-dried fishmeal as the major protein sources in a 2 x 3 factorial arrangement of treatments. A significant interaction between protein source and level was observed where the number of C. perfringens present in the ileum and cecum increased as the level of crude protein in the diets increased from 230 to 400 g/kg in the birds fed fishmeal-based diets (P < 0.05) but not in the birds fed SPC-based diets. In experiment 2, the dietary treatments used were arranged in a 2 x 2 factorial arrangement with 2 levels of crude protein (230 and 400 g/kg) and 2 protein sources (SPC or fishmeal). The main effects of protein source and protein level significantly (P < 0.05) affected numbers of C. perfringens without interaction. Amino acid analysis of the diets showed that the glycine and methionine contents of the fishmeal diets were elevated compared with the SPC diets. This suggests that the level of crude protein, protein source, and amino acid content of diets affect the growth of C. perfringens in the lower intestinal tract of the broiler chicken and might be predisposing factors to outbreaks of clinical necrotic enteritis.

Amino Acids↗
PubMed2003

Moyamoya disease: an elusive diagnosis.

OBJECTIVE AND BACKGROUND: Moyamoya disease is an idiopathic vasculopathy of circle of Willis. Stroke is a common presentation. We describe clinical and radiological features of moyamoya disease in four patients. SETTING: Tertiary care center in a metropolitan city. MATERIALS AND METHODS: Patients with moyamoya disease were identified by ICD-9 coding system of the hospital medical records. Demographic characteristics, clinical features/presentation, laboratory investigations and radiological investigations were recorded and analyzed. RESULTS: Four patients (three children and one adult) presented with hemiparesis. One patient expired during hospital stay. Two patients underwent surgery (synangiosis). EEGs of three patients showed focal abnormalities. Neuroimaging showed ischemic infarctions in all patients. Findings on four vessel digital substraction angiography and/or magnetic resonance angiography were compatible with moyamoya disease. CONCLUSION: Moyamoya disease should be considered in all young patients, especially children, presenting with stroke.

Adolescent↗
PubMed2003

Cost of acute stroke care at a tertiary care hospital in Karachi, Pakistan.

OBJECTIVE: To evaluate cost of acute stroke care and its determinants at a tertiary care hospital in Karachi and to find out predictors of high cost care. Acute stroke is a leading cause of morbidity and mortality. Cost of care is the single most important determinant in availability of acute stroke care at a tertiary care hospital in Pakistan. It is also an important factor in development of public health policies and medical insurance plans. Average annual income in Pakistan is 4881 rupees (85 U dollars). METHODS: Medical and billing records of 443 patients with acute stroke were retrospectively reviewed from 1998-2001 at The Aga Khan University Hospital (AKUH), Karachi. Acute stroke care at AKUH usually includes routine laboratory investigation including Lipid profile, Magnetic resonance imaging/angiography (MRI/MRA), Echocardiogram, Carotid Doppler's ultrasound and medical management in the Stroke care unit. RESULTS: 443 patients were included in study. Age range was 25-98 years (Mean 58 years). 269 (61%) were male. Length of hospital stay was 1 day; 67 patients, 2 days; 83 patients, 3 days; 70 patients, 4-5 days; 87 patients, 6-10 days; 75 patients, 11-30 days; 49 patients and more than 30 days; 12 patients. Average length of stay was five days and median length was three days. Average total cost was 70,714 rupees (1179 U dollars) which included average radiology cost; 12,507 rupees (208 U dollars), average laboratory cost; 8365 rupees (139 U dollars), average pharmacy cost; 13,320 rupees (222 U dollars) and average bed/room charges; 27,552 rupees (459 U dollars). Length of hospital stay is the most important determinant of cost. Average total cost for patients who stayed for 1 day was 19,597 rupees (326 U dollars), 2-3 days; 25,568 rupees (426 U dollars), 4-7 days; 49,705 rupees (828 U dollars), 8-30 days; 153,586 rupees (2559 U dollars), more than 30 days; 588,239 rupees (9804 U dollars). Average cost for general ward was 60,574 rupees (1010 U dollars), private ward was 74,880 rupees (1248 U dollars) and intensive care unit was 155,010 rupees (2583 U dollars). CONCLUSION: Cost of acute stroke care is extremely high as compared to average national income at our hospital. Most important determinant of cost is length of hospital stay. Cost cutting measures and increased funding from state are necessary to increase the availability of acute stroke care.

Acute Disease↗
PubMed2003

Ischemic stroke subtypes in Pakistan: the Aga Khan University Stroke Data Bank.

OBJECTIVE: Frequency of ischemic stroke subtypes is influenced by ethnic and geographic variables. Our objective was to identify various stroke subtypes and its determinants at a tertiary care hospital. METHODS: We prospectively collected data on ischemic stroke subtypes admitted to The Aga Khan University Hospital in Karachi. RESULTS: A total of 596 patients were enrolled in 22 months in the Aga Khan Universtiy Stroke Registry. These included 393 patients with Ischemic stroke, 126 patients with intracerebral hemorrhage, 50 patients with subarachnoid hemorrhage and others. The ischemic stroke group was classified according to the TOAST criteria and comprised of lacunar 168/393 (42.7%); large artery atherosclerosis 106/393 (26.9%); cardioembolic 24/393 (6.1%); undetermined 80/393 (20.3%); and other determined types 15/393 (3.8%). The high proportion of lacunar strokes in our population may be due to high burden of inadequately treated hypertension and diabetes. Clear cut cardioembolic stroke was relatively infrequent in our population. CONCLUSION: Lacunar stroke is the most common subtype of stroke in our patient population. This is most likely secondary to uncontrolled hypertension.

Adult↗
PubMed2003

Should carotid endarterectomy be performed for symptomatic carotid stenosis in Pakistan?

OBJECTIVE: The risk of stroke and death associated with carotid endarterctomy is operator dependant. Data regarding risks of this procedure are not available in Pakistan and therefore it is difficult to make accurate risk benefit analysis for individual patients. Our objective was to determine safety of carotid endarterectomy at an academic tertiary care center in Pakistan. METHODS: Patients who underwent carotid endarterectomy (CEA) at our hospital during a ten-year period were identified through ICD-9 coding system of the hospital medical records. Demographic features, associated medical problems and immediate postoperative complications were recorded and analyzed. RESULTS: Sixty-three carotid endarterectomies were performed on 59 patients. Ages range from 43 to 80 (mean 61 +/- 8) years; 53 were male and 10 were female. Common associated diseases among these patients were hypertension; 38 (64.4%), ischemic heart disease; 26 (44%), diabetes mellitus; 24 (40.7%), dyslipidemia; 19 (32.2%) and renal insufficiency; 13 (22%). Most common complication was neuropraxia (transient neuropathy); 5 (7.9%), followed by pneumonia and stroke; each in 3 (4.8%) patients. None of the strokes related to the surgical procedure were disabling. Two of the patients who had stroke, recovered fully within 17 weeks and one recovered partly but was independent in all daily activities of living (ADLs). One patient died following simultaneous coronary artery bypass graft (CABG) and CEA. The risk of stroke or death for patients undergoing CEA was high with simultaneous CABG (3/11, 27%) and low for patients undergoing CEA alone (1/52, 2%). CONCLUSION: Carotid endarterectomy is a safe procedure in patients with symptomatic carotid stenosis at our hospital and should be performed, when indicated.

Adult↗
PubMed2001

Thalidomide neuropathy in patients treated for metastatic prostate cancer.

We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection.

Action Potentials↗
PubMed2000

Cutaneous silent periods in patients with Fabry disease.

We assessed the cutaneous silent period (CSP) in 24 patients with Fabry disease with small-fiber sensory neuropathy and 12 normal subjects to test the hypothesis that small-diameter afferents are responsible for producing the CSP. Sensory nerve conduction studies and quantitative sensory testing for cold and vibration detection thresholds were also measured. Overall, Fabry patients had impaired thermal, but not vibration, detection thresholds, with greatest impairment in the feet. In the upper extremity, CSP latencies, duration, and suppression of electromyographic activity (EMG) did not differ. In the lower extremity, patients had reduced suppression of EMG during the CSP compared to normal controls. CSP durations exhibited a bimodal distribution in patients, including a subset of seven patients with durations shorter than all controls. This subset had profound loss of thermal sensation in the feet, but this was also true of some patients who had normal CSPs. Patients with shortened CSPs had modestly elevated vibration thresholds and reduced sensory potentials in comparison to patients with normal CSPs. Reduced CSPs in Fabry patients are associated with, but not entirely explained by, the severity of small-fiber neuropathy as measured by quantitative sensory testing. The possibility that large-diameter fibers provide a minor contribution to producing the CSP should be considered.

Action Potentials↗
PubMed2000

Reciprocal regulation of glycogen phosphorylase and glycogen synthase by insulin involving phosphatidylinositol-3 kinase and protein phosphatase-1 in HepG2 cells.

The effect of insulin on glycogen synthesis and key enzymes of glycogen metabolism, glycogen phosphorylase and glycogen synthase, was studied in HepG2 cells. Insulin stimulated glycogen synthesis 1.83-3.30 fold depending on insulin concentration in the medium. Insulin caused a maximum of 65% decrease in glycogen phosphorylase 'a' and 110% increase in glycogen synthase activities in 5 min. Although significant changes in enzyme activities were observed with as low as 0.5 nM insulin level, the maximum effects were observed with 100 nM insulin. There was a significant inverse correlation between activities of glycogen phosphorylase 'a' and glycogen synthase 'a' (R2= 0.66, p < 0.001). Addition of 30 mM glucose caused a decrease in phosphorylase 'a' activity in the absence of insulin and this effect was additive with insulin up to 10 nM concentration. The inactivation of phosphorylase 'a' by insulin was prevented by wortmannin and rapamycin but not by PD98059. The activation of glycogen synthase by insulin was prevented by wortmannin but not by PD98059 or rapamycin. In fact, PD98059 slightly stimulated glycogen synthase activation by insulin. Under these experimental conditions, insulin decreased glycogen synthase kinase-3beta activity by 30-50% and activated more than 4-fold particulate protein phosphatase- activity and 1.9-fold protein kinase B activity; changes in all of these enzyme activities were abolished by wortmannin. The inactivation of GSK-3beta and activation of PKB by insulin were associated with their phosphorylation and this was also reversed by wortmannin. The addition of protein phosphatase-1 inhibitors, okadaic acid and calyculin A, completely abolished the effects of insulin on both enzymes. These data suggest that stimulation of glycogen synthase by insulin in HepG2 cells is mediated through the PI-3 kinase pathway by activating PKB and PP-1G and inactivating GSK-3beta. On the other hand, inactivation of phosphorylase by insulin is mediated through the PI-3 kinase pathway involving a rapamycin-sensitive p70(s6k) and PP-1G. These experiments demonstrate that insulin regulates glycogen phosphorylase and glycogen synthase through (i) a common signaling pathway at least up to PI-3 kinase and bifurcates downstream and (ii) that PP-1 activity is essential for the effect of insulin.

Androstadienes↗
PubMed2000

Motor cortex excitability in stiff-person syndrome.

Muscle stiffness in stiff-person syndrome (SPS) is produced by continuous, involuntary firing of motor units that is thought to be caused by an autoimmune mediated dysfunction of GABA-ergic inhibitory neurones. We have postulated that the loss of GABA-ergic inputs from spinal interneurones alone is insufficient to produce tonic firing of motor neurones and that excessive supraspinal excitation could also play a role. To determine whether SPS is associated with dysfunction in supraspinal GABA-ergic neurones, we assessed the excitability of the motor cortex with transcranial magnetic stimulation (TMS) in seven SPS patients and seven age-matched healthy volunteers. SPS patients had normal central motor conduction times, normal thresholds for motor evoked potentials (MEPs) in leg muscles, and a normal MEP stimulus versus response recruitment curve with increasing TMS intensities in resting hand and leg muscles. Cortical silent periods were shortened in leg muscles. Intracortical inhibition and excitation were assessed while recording from the abductor pollicis brevis, using a paired pulse TMS paradigm with subthreshold conditioning stimuli. Patients had decreased inhibition and markedly increased facilitation at short intervals. Using paired suprathreshold TMS, patients exhibited increased facilitation at 20- and 40-ms intervals. These results point to a hyperexcitability of the motor cortex in SPS, which could be explained by impairment of supraspinal GABA-ergic neurones, leading to an impaired balance between inhibitory and excitatory intracortical circuitry.

Action Potentials↗
PubMed1999

Blink reflex recovery in facial weakness: an electrophysiologic study of adaptive changes.

OBJECTIVE: To study the electrophysiologic effects of unilateral facial weakness on the excitability of the neuronal circuitry underlying blink reflex, and to localize the site of changes in blink reflex excitability that occur after facial weakness. BACKGROUND: Eyelid kinematic studies suggest that adaptive modification of the blink reflex occurs after facial weakness. Such adaptations generally optimize eye closure. A report of blepharospasm following Bell's palsy suggests that dysfunctional adaptive changes can also occur. METHODS: Blink reflex recovery was evaluated with paired stimulation of the supraorbital nerve at different interstimulus intervals. Comparisons were made between normal control subjects and patients with Bell's palsy who either recovered facial strength or who had persistent weakness. RESULTS: Blink reflex recovery was enhanced in patients with residual weakness but not in patients who recovered facial strength. Facial muscles on weak and unaffected sides showed enhancement. In patients with residual weakness, earlier blink reflex recovery occurred when stimulating the supraorbital nerve on the weak side. Sensory thresholds were symmetric. CONCLUSION: Enhancement of blink reflex recovery is dependent on ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve on the paretic side suggests that sensitization may be lateralized, and suggests a role for abnormal afferent input in maintaining sensitization. Interneurons in the blink reflex pathway are the best candidates for the locus of this plasticity.

Adaptation, Physiological↗
PubMed1999

Cancer-associated retinopathy.

Patients with systemic cancer may have a variety of ocular complaints. Most commonly these are metastases or adverse effects of therapy. Paraneoplastic syndromes, like cancer-associated retinopathy, rarely cause ophthalmic symptoms. We describe a patient with a malignant mixed mullerian tumor and cancer-associated retinopathy who had circulating serum antibodies to recoverin and cells positive for recoverin in the tumor. We discuss the typical clinical symptoms as well as the pathophysiology of this uncommon disorder.

Antigens, Neoplasm↗
PubMed1998

Mechanisms underlying spinal motor neuron excitability during the cutaneous silent period in humans.

The transient suppression of muscle contraction during the cutaneous silent period (CSP) could be produced either through postsynaptic inhibition of motoneurons or through presynaptic inhibition of the excitatory inputs to motoneurons that sustain voluntary contraction. We sought to delineate the mechanisms underlying the CSP in hand muscles by measuring changes in H-reflexes and motor-evoked potentials (MEPs) produced by transcranial magnetic stimulation (TMS) during the CSP in 10 healthy volunteers. H-reflexes and MEPs both measure the excitability of the motoneuron pool and activate similar subpopulations of motoneurons through different pathways. Inhibition of H-reflexes and MEPs of similar size was maximal at the midpoint of the CSP and gradually returned to baseline. The similar time course of recovery suggests that the H-reflex and MEP are affected by inhibition at a common site, most likely postsynaptic inhibition of the motoneurons.

Adult↗
PubMed1998

SPARC deficiency leads to early-onset cataractogenesis.

PURPOSE: To determine the role of SPARC (secreted protein, acidic, and rich in cysteine) in cataractogenesis by examining mice deficient in a matricellular protein SPARC. METHODS: Mice were rendered SPARC-deficient by a targeted disruption of the gene. Slit-lamp microscopy and histology were used to examine the eyes of SPARC-null and wild-type mice from birth to 14 months of age. RESULTS: SPARC-null mice developed opacities in the posterior cortex of the eye as early as 1.5 months after birth. The diffuse cataracts appeared to progress toward the anterior cortex and reached maturity in many animals by 3.5 months of age. Early stages of cataractogenesis in SPARC-null mice included inhibition of normal lens fiber cell differentiation, degeneration of fiber cells, vacuole formation at the equator, and liquefaction of the cortex. No cataracts were detected in wild-type mice up to the age of 8 months. CONCLUSIONS: The early onset of cataracts in SPARC-null mice establishes that the gene is essential to the maintenance of lens transparency.

Animals↗
PubMed1998

Transgenic mice with pigmented intraocular tumors: tissue of origin and treatment.

PURPOSE: To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS: Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS: Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS: Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

Animals↗
PubMed1997

Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant.

The use of viruses to treat tumors has received renewed interest with the availability of genetically defined attenuated mutants. Herpes simplex virus (HSV) type 1 in particular has been shown to be effective for tumors of neuronal origin. However, the model systems used for these studies rely on the use of explanted tumor cells in immunodeficient animals. We have used a recently developed transgenic mouse model, wherein mice spontaneously develop retinoblastomas, to determine if a mutant HSV has a therapeutic effect against an endogenously arising tumor in an immunocompetent host. The injection of 1 x 10(6) PFU of the neuroattenuated HSV-1/HSV-2 recombinant RE6 into the vitreous of transgenic mice resulted in a significant inhibition of tumor growth compared to injection of medium alone (P = 0.0063). Immunohistochemical analysis of viral antigen showed that viral replication was restricted to focal areas of the tumors and the retinal pigment epithelium. Viral growth was not significantly different in the eyes of transgene-positive and transgene-negative mice, suggesting that enhanced replication in tumor cells may not explain the effects. Tumor cells in the treated eyes were significantly less differentiated than those in the untreated eyes (P = 0.04), suggesting that the virus may replicate better in certain cell types in the tumors. Although the injection of RE6 resulted in a difference in tumor size, the treatment did not result in the elimination of tumors in any of the mice improvements in the efficacy of tumor control are needed if this therapy is to be of use.

Animals↗