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Biomedical subjects

N Khan

Publications and source records attributed to N Khan.

At least 91 records · Page 5Linked to original sources
PubMed2001

Corticotropin (ACTH) acts directly on amygdala neurons to down-regulate corticotropin-releasing hormone gene expression.

The hormone corticotropin (ACTH) is employed as therapy for diverse neurological disorders, but the mechanisms for its efficacy remain unknown. ACTH promotes the release of adrenal steroids (glucocorticoids), and most ACTH effects on the central nervous system (CNS) have been attributed to activation of glucocorticoid receptors. However, in several human disorders, ACTH has therapeutic actions that differ qualitatively or quantitatively from those of steroids. This study tested the hypothesis that ACTH directly influences limbic neurons via the recently characterized melanocortin receptors and focused on the effects of ACTH on the expression of corticotropin-releasing hormone (CRH), a neuropeptide involved in neuroimmune functions and in certain developmental seizures. The results demonstrated that ACTH potently reduced CRH expression in amygdala neurons. This down-regulation was not abolished by experimental elimination of steroids or by blocking their receptors and was reproduced by a centrally administered ACTH fragment that does not promote steroid release. Importantly, selective blocking of melanocortin receptors prevented ACTH-induced down-regulation of CRH expression. Taken together, these data indicate that ACTH activates central melanocortin receptors to modulate CRH gene expression in amygdala, supporting the notion that direct, steroid-independent actions of ACTH may account for some of its established clinical effects on the CNS.

Adrenocorticotropic Hormone↗
PubMed2001

Parkinson's disease is not associated with the combined alpha-synuclein/apolipoprotein E susceptibility genotype.

A recent study showed significant association of sporadic Parkinson's disease with a polymorphism within the alpha-synuclein gene and closely linked DNA markers on chromosome 4q and the APOE epsilon4 allele. A combined alpha-synuclein/APOE-epsilon4 genotype increased the relative risk of developing Parkinson's disease 12-fold. We failed to confirm this association in a much larger sample of histopathologically proven cases of Parkinson's disease and controls.

Alleles↗
PubMed2001

Tephrosia purpurea ameliorates N-diethylnitrosamine and potassium bromate-mediated renal oxidative stress and toxicity in Wistar rats.

In an earlier communication, we have shown that Tephrosia purpurea ameliorates benzoyl peroxide-induced oxidative stress in murine skin (Saleem et al. 1999). The present study was designed to investigate a chemopreventive efficacy of T purpurea against N-diethylnitrosamine-initiated and potassium bromate-mediated oxidative stress and toxicity in rat kidney. A single intraperitoneal dose of N-diethylnitrosamine (200 mg/kg body weight) one hr prior to the dose of KBrO3 (125 mg/kg body weight) increases microsomal lipid peroxidation and the activity of xanthine oxidase and decreases the activities of renal antioxidant enzymes viz., catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, phase II metabolizing enzymes such as glutathione-S-transferase and quinone reductase and causes depletion in the level of renal glutathione content. A sharp increase in blood urea nitrogen and serum creatinine has also been observed. Prophylactic treatment of rats with T. purpurea at doses of 5 mg/kg body weight and 10 mg/kg body weight prevented N-diethylnitrosamine-initiated and KBrO3 promoted renal oxidative stress and toxicity. The susceptibility of renal microsomal membrane for iron ascorbate-induced lipid peroxidation and xanthine oxidase activities were significantly reduced (P<0.01). The depleted levels of glutathione, the inhibited activities of antioxidant enzymes, phase II metabolizing enzymes and the enhanced levels of serum creatinine and blood urea nitrogen were recovered to a significant level (P<0.01). All the antioxidant enzymes were recovered dose-dependently. Our data indicate that T purpurea besides a skin antioxidant can be a potent chemopreventive agent against renal oxidative stress and carcinogenesis induced by N-diethylnitrosamine and KBrO3.

Animals↗
PubMed2001

Diagnosis and management of febrile children using the WHO/UNICEF guidelines for IMCI in Dhaka, Bangladesh.

OBJECTIVE: To determine whether the fever module in the WHO/UNICEF guidelines for the integrated management of childhood illness (IMCI) identifies children with bacterial infections in an area of low malaria prevalence. METHODS: Physicians assessed a systematic sample of 669 sick children aged 2-59 months who presented to the outpatient department of Dhaka Shishu Hospital, Bangladesh. FINDINGS: Had IMCI guidelines been used to evaluate the children, 78% of those with bacterial infections would have received antibiotics: the majority of children with meningitis (100%), pneumonia (95%), otitis media (95%) and urinary tract infection (83%); and 50% or less of children with bacteraemia (50%), dysentery (48%), and skin infections (30%). The current fever module identified only one additional case of meningitis. Children with bacteraemia were more likely to be febrile, feel hot, and have a history of fever than those with dysentery and skin infections. Fever combined with parental perception of fast breathing provided a more sensitive fever module for the detection of bacteraemia than the current IMCI module. CONCLUSIONS: In an area of low malaria prevalence, the IMCI guidelines provide antibiotics to the majority of children with bacterial infections, but improvements in the fever module are possible.

Bacterial Infections↗
PubMed2000

A woman with leg cramps and rash.

A 68-year-old woman presented with generalized weakness and a rash on her lower extremities. The weakness began one week earlier, shortly after treatment for leg cramps and two days before the rash appeared. She had also had blood-streaked sputum a few days before admission. There was no history of bleeding diathesis, nose bleeding, hematuria, vasculitis, muscle or joint aches, cinchonism, or exposure to tuberculosis. She denied fever, chills, night sweats, leg pain or swelling, chest pain, or abdominal pain.

Aged↗
PubMed2000

Synthesis of the C-glycoside analogue of a novel sialyl Lewis X mimetic.

Sialyl Lewis X (sLex) mimetics that can function as selectin antagonists have received considerable attention in connection with the development of novel antiinflammatory therapies. An interesting structure that emerged from the studies of the Wong group is the 1,1-Gal-Man disaccharide 2, reported to bind E-selectin 5 times more strongly than sLex. The C-glycoside derivative 3 is of interest both as a conformational probe for selectin binding and as a hydrolytically stable analogue. Herein we illustrate a novel methodology for beta-C-galacto-disaccharides in the synthesis of 3. The protocol has as a key step a novel oxocarbenium ion-enol ether cyclization to give a C1-substituted galactal.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Conformational differences between O- and C-glycosides: the alpha-O-man-(1-->1)-beta-Gal/alpha-C-Man-(1-->1)-beta-Gal case--a decisive demonstration of the importance of the exo-anomeric effect on the conformation of glycosides.

The conformational behavior of alpha-O-Man-(1-->1)-beta-Gal (1) and its C-analogue (2) has been studied using J/NOE NMR data, molecular mechanics, molecular dynamics, and ab initio calculations. The population distribution around the glycosidic linkages of 1 and 2 is rather different, especially for the alpha-Man linkage. A lower limit for the exo-anomeric effect in water has been experimentally determined.

Carbohydrate Conformation↗
PubMed2000

A novel tau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies.

Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies is a neurodegenerative disease that resembles corticobasal degeneration. It is characterized by the presence of abundant neuronal and glial tau protein deposits. Here we describe a novel silent mutation in exon 10 of tau (N296N) in this familial dementia. By exon trapping, the mutation produced an increase in the splicing in of exon 10, indicating that it probably causes disease through an overproduction of four-repeat tau.

Base Sequence↗
PubMed2000

Simplified quantitative determination of cerebral perfusion reserve with H2(15)O PET and acetazolamide.

The measurement of regional cerebral blood flow (rCBF) and perfusion reserve (PR) with H2(15)O positron emission tomography (PET) and acetazolamide challenge is of importance in evaluating patients with cerebrovascular disease and is thought to be useful in selecting patients for possible vascular surgery. Full quantitative assessment of rCBF with PET requires arterial blood sampling, which is inconvenient in a clinical setting. In this work, we present a simple non-invasive method with which to quantitatively evaluate PR in one PET session lasting no more than 30 min. In ten patients with cerebrovascular disease, rCBF was measured with H2(15)O PET under the baseline condition and after administration of 1 g acetazolamide using a standard technique involving arterial blood sampling. The activity accumulated over 60 s was normalized to injected activity per kilogram body weight (nAA) and compared with rCBF in eight different brain regions. A high linear correlation was found for PR based on nAA (PRnAA) and rCBF (PRrCBF) (PRnAA=0.843 PRrCBF + 0.092, r=-0.83, Pearson's correlation coefficient). Bland-Altman analyses further confirmed that PRnAA reflects PR in a quantitative manner. These results demonstrate that the method based on normalized counts allows the quantitative assessment of PR without blood sampling.

Acetazolamide↗
PubMed2000

Transverse clivus fracture: case presentation and significance of clinico-anatomic correlations.

BACKGROUND: Bilateral transverse basal skull fractures resulting from lateral crushing injuries involve fractures of the clivus that present clinically with multiple cranial nerve injuries and possible delayed vascular injuries due to the tight neural and vascular entry and exit routes present in this region. A case of a young patient with an extensive basal skull fracture is presented with description of the clinical signs and symptoms in relation to the neuroradiological findings. Clinico-anatomic correlations have been reiterated. CASE DESCRIPTION: A case of a young patient suffering a bilateral crush injury resulting in a basal transverse clivus and petrous bone fracture is presented. Multiple cranial nerve injuries, unilateral and bilateral, were present (CN III, VI, VII). This clinical presentation correlated well with the anatomical location and extension of the respective cranial nerves at the level of the skull base and along the fracture line extending bilaterally through the clivus and petrous bone. CONCLUSIONS: Initial neurological and neuroradiological investigations should be aimed at promptly detecting cranial nerve injuries and their correlating fracture injuries at the skull base. The possible development and progression of delayed neurological deficits should also be kept in mind and investigated.

Adult↗
PubMed2000

Identification of the Hind III polymorphic site in the PAI-1 gene: analysis of the PAI-1 Hind III polymorphism by PCR.

The identification of the Hind III polymorphic site in the 3' end of the plasminogen activator inhibitor 1 (PAI-1) gene and a simple method to identify the Hind III polymorphism rapidly in the PAI-1 gene using PCR is described. The Hind III restriction site was identified by restriction site mapping and sequence analysis from a cosmid DNA clone. Genomic DNA was isolated from individual human umbilical cords and a 754-bp fragment of the human PAI-1 gene was amplified by PCR. Aliquots of the PCR products were digested with Hind III and analyzed by agarose gel electrophoresis. The presence of two fragments, 754 and 567 bp, was identified, and they were designated as 1/1 (750-bp band), 1/2 (754- and 567-bp bands), and 2/2 (567-bp band). The PCR method is considerably less time consuming than the conventional DNA genotyping using Southern blot analysis. To ensure that this new method identified the same PAI-1 genotypes as previously identified by Hind III restriction fragment length polymorphism (RFLP), samples were simultaneously genotyped by PCR and Southern blot analysis. Both methods identified the same Hind III genotypes in all the samples, confirming the reliability of this new PCR method for the rapid identification of the Hind III polymorphism in the human PAI-1 gene.

3' Untranslated Regions↗
PubMed2000

Validation of predictors of extubation success and failure in mechanically ventilated infants and children.

OBJECTIVE: To validate predictors of extubation success and failure in mechanically ventilated infants and children by using bedside measures of respiratory function. DESIGN: Prospective, descriptive study. SETTING: A university-affiliated children's hospital with a 51-bed critical care area. PATIENTS: All infants and children who were mechanically ventilated for > or =24 hrs except neonates < or =37 wks gestation and patients with neuromuscular disease. INTERVENTIONS: None. MEASUREMENTS AND METHODS: Extubation failure was defined as reintubation within 48 hrs of extubation in the absence of upper airway obstruction. Failure rates were calculated for different ranges (selected a priori of preextubation measures of breathing effort, ventilator support, respiratory mechanics, central inspiratory drive, and integrated indices useful in adults. Effort of spontaneous breathing was assessed by the respiratory rate standardized to age, the presence of retractions and paradoxic breathing, inspiratory pressure, maximal negative inspiratory pressure, ratio of inspiratory pressure to maximal negative inspiratory pressure, and tidal volume indexed to body weight of a spontaneous breath. Ventilator support was measured by F(IO2), mean airway pressure, oxygenation index, and the fraction of total minute ventilation provided by the ventilator. Respiratory mechanics was assessed by peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and the CROP (compliance, rate, oxygenation, and pressure) indexed to body weight, the integrated indices useful in predicting extubation failure in adults, were also calculated. A regression test for a linear trend in proportions was performed with preselected ranges and the corresponding failure rates. The failure rates from this study (validation group) were compared to those published previously (prediction group) by the chi-square test for proportions. The distribution of categorical variables between groups was analyzed by using the chi-square test or the Fisher's exact test, and p < .05 was considered significant. MAIN RESULTS: The study involved 312 patients. There were no differences in any of the clinical characteristics between the prediction and validation groups. The reasons for reintubation were similar in both groups. Preextubation data were also similar between the two groups. There were no differences between the prediction and the validation groups in failure rates with different ranges. There were no differences in the failure rates for any of the cutoff values for peak ventilatory inspiratory pressure, mean airway pressure, F(IO2), oxygenation index, dynamic compliance, tidal volume indexed to body weight of a spontaneous breath, fraction of total minute ventilation provided by the ventilator, and mean inspiratory flow. CONCLUSIONS: Bedside measures of respiratory function can predict extubation success and failure in infants and children. Both a low risk and a high risk of failure can be determined by using these measures. Integrated indices useful in adults do not reliably predict extubation success or failure in infants and children. Our study validates our previously published study.

Child, Preschool↗
PubMed2000

Use of phage antibodies to distinguish closely related species of protozoan parasites.

Acanthamoeba are typically identified in the laboratory using culture and microscopic observation. In this paper we describe the isolation and specificity of antibody fragments that can be used for the identification of Acanthamoeba. A phage library expressing a large repertoire (approx. 5 x 10(9)) of antibody fragments was used to generate two libraries one enriched for bacteriophage that exhibit genus specific binding and the other containing bacteriophage that bind specifically to pathogenic Acanthamoeba. Individual clones were isolated on the basis of binding by ELISA, and then flow cytometry and immunofluorescence were used for further characterisation. Four monoclonal antibodies were isolated, specific for Acanthamoeba at the generic level with clone HPPG6 exhibiting the highest level of binding. Furthermore clone HPPG55 was specific for pathogenic species of Acanthamoeba.

Animals↗
PubMed2000

Epley's manoeuvre: treatment of choice for benign paroxysmal positional vertigo.

Benign paroxysmal positional vertigo (BPPV) is one of the commonest causes of peripheral vestibular disorders. In this prospective study 21 patients with BPPV were treated by Epley's manoeuvre. All patients had an immediate improvement in their symptoms. Recurrence was noted in three patients who required further treatment sessions with resultant improvement in all. However, one patient who originally had suffered from Ménière's disease involving the same ear for more than 14 years developed another recurrence which was treated successfully by further application of Epley's manoeuvre. This study supports the usefulness of Epley's manoeuvre for the treatment of BPPV.

Adolescent↗
PubMed2000

A new artifact-free device for frameless, magnetic resonance imaging-guided stereotactic procedures.

OBJECTIVE: A new, artifact-free, nonobstructive device was required for planning, guiding, and performing stereotactic procedures in an open magnetic resonance imaging (MRI) system (Signa SP; General Electric, Milwaukee, WI). DESCRIPTION OF INSTRUMENTATION: We devised an MRI-compatible instrument set that was adapted to an optical triangulation system (FlashPoint System; Image Guided Technologies, Boulder, CO) and consisted of a Pathfinder for planning burr holes and trajectories and a Snapper-Stereoguide for guiding minimally invasive instruments such as biopsy cannulae, endoscopes, and laser fibers. The instruments were composed of biocompatible plastic (polyacetal). During evaluation, special attention was paid to safety, accuracy, operation times, and susceptibility artifacts of the system. RESULTS: The first 20 stereotactic procedures performed in the open MRI scanner included 15 biopsies, 1 cyst and 3 abscess evacuations, and 1 endoscopic procedure for treatment of multiseptate hydrocephalus. There were no adverse outcomes, and all biopsies were diagnostic. The frameless stereotactic system in combination with the FlashPoint System proved to be accurate, with a mean error of 1.5 mm. The biopsy devices did not cause any susceptibility artifacts. Highly vascularized structures were clearly visible and were included in the trajectory planning. With experience, the procedure time was reduced to less than 1 hour. CONCLUSION: This device was found to be quite helpful for planning and guiding stereotactic procedures in the open MRI scanner. Nearly real-time planning and monitoring of stereotactic procedures and the positional accuracy of the system make the open MRI system a definite improvement, compared with conventional stereotactic systems.

Adolescent↗