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Biomedical subjects

N Khan

Publications and source records attributed to N Khan.

At least 145 records · Page 8Linked to original sources
PubMed1997

High-affinity agonist binding is not sufficient for agonist efficacy at 5-hydroxytryptamine2A receptors: evidence in favor of a modified ternary complex model.

In this study, the relationship between high-affinity agonist binding and second messenger production was examined at native and mutant 5-hydroxytryptamine2A receptors. At native 5-hydroxytryptamine2A receptors all agonists, with the exception of quipazine, discriminated between high- and low-affinity states of the receptor, as determined by analysis of competition binding assays. There was no correlation between the ability of selected agonists to label the high-affinity agonist state and to augment phosphoinositide hydrolysis. Quipazine, which did not discriminate between the affinity states of the receptor, behaved as a full agonist. Similar results were obtained when a point mutation (F340L) of a highly conserved phenylalanine located in transmembrane domain VI was examined. With the F340L mutant, most of the agonists tested labeled significantly fewer high-affinity sites, compared with the native receptor. There was no significant relationship between high-affinity agonist binding and second messenger production. Bufotenine and 4-iodo-3,5-dimethoxyphenylisopropylamine labeled similar percentages of high-affinity agonist binding sites (22% vs. 26%), but 4-iodo-3,5-dimethoxyphenylisopropylamine behaved as a full agonist, whereas bufotenine was devoid of detectable agonist activity. The inability of selected agonists to activate phosphoinositide hydrolysis was not due solely to lower agonist affinity for the mutant receptor, because the binding affinity of quipazine was unchanged by the F340L mutation but quipazine had no detectable agonist activity at the mutant receptor. Our results demonstrate that the ability of an agonist to promote the high-affinity state of the 5-hydroxytryptamine2A receptor is not correlated with its ability to augment second messenger production. These results are consistent with recent models of G protein-receptor functioning (e.g., modified ternary complex model) that predict that additional transition states of the receptor-ligand complex are essential for agonist efficacy.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1997

Comparative evaluation of breast lesions with the help of impression smears, histopathology and mammography.

A total of 148 surgically removed benign and malignant breast lesions were studied to correlate cytomorphologial features in impression smears and histopathological sections. Mammograms were taken prior to surgery. Role of mammography in detection of non-palpable breast lesions was enlightened. Impression smears helped in quick diagnosis (intraoperative) and overall accuracy obtained was 97.4%. Cluster predominant and Grade II nuclear grading on smear pattern was seen in 58.8% and 57.4% cases respectively amongst the 68 malignant cases. 45% cases revealed non-palpable breast lesions on mammography which was later confirmed on histopathology.

Breast Diseases↗
PubMed1997

Congenital hematometrocolpos in a circumcised girl. An anomaly superimposed by cultural mutilating practices.

A rare case associated with congenital hematometrocolpos in a circumcised 13 years old Somalian girl is presented. Emphasis on proper history is highlighted. Mutilation caused by bad cultural practice of female circumcision which is although not a problem in Pakistan, is brought into notice for those who may be unaware of perineal appearance of a circumcised female and stitched over vagina.

Adolescent↗
PubMed1996

Diurnal variation of blood pressure in adolescents with type 1 diabetes: dippers and non-dippers.

The study aimed to determine the prevalence of impaired nocturnal BP fall in adolescents with Type 1 diabetes. Thirty-six normoalbuminuric normotensive adolescents with Type 1 diabetes (19 males, 17 females) aged 14.4 +/- 2.1 years (mean +/- SD) with duration of 4.0 (2.6-7.5) years (median (25-75th percentile)) and 23 controls (11 males, 12 females) aged 15.0 +/- 1.6 years were studied. Day/night BP variation was examined using Ambulatory Accutracker II Monitor (Raleigh, NC). Recordings were made at 30 min intervals during the day and 60 min intervals during the night. Time records were set according to individual diaries. There was no significant difference in day and night systolic or diastolic BP or in mean day/night BP variability between patients with Type 1 diabetes and control subjects. 15/36 patients compared to 3/23 controls (chi squared = 5.43, p < 0.02) were non-dippers defined as a nocturnal fall in either systolic (13/36) or diastolic (6/36) BP or both (4/36) of less than 10%. These non-dippers had normal day-night ratio of heart rate when compared with the remainder of the patients or controls. In conclusion a significant number of young normotensive normoalbuminuric patients with Type 1 diabetes show an impaired fall in blood pressure at night, predominantly in systolic BP. These changes may be relevant to the long-term development of macrovascular or microvascular disease.

Adolescent↗
PubMed1996

Looking for the artery of Adamkiewicz: a quest to minimize paraplegia after operations for aneurysms of the descending thoracic and thoracoabdominal aorta.

All patients undergoing resection of thoracic or thoracoabdominal aneurysms at Mount Sinai Hospital since November 1993 had spinal cord function monitored with somatosensory-evoked potentials as part of a multimodality approach to reducing spinal cord injury. In the segment to be resected, each pair of intersegmental vessels was sequentially clamped, and they were subsequently sacrificed only if no change in somatosensory evoked potentials occurred within 8 to 10 minutes after occlusion. Adjunctive protective measures included mild hypothermia (31 degrees to 33 degrees C), distal perfusion, corticosteroids, maintenance of high normal blood pressures, avoidance of nitroprusside, and cerebrospinal fluid drainage. Ninety-five consecutive patients operated on since 1993 (group II) were compared with 138 earlier patients (group I). Preoperative characteristics such as age, sex, etiology of aneurysm, emergency operation, and reoperation did not differ between groups, nor did operative variables such as incidence of rupture and extent of resection. Group I had slightly more smokers and slightly fewer hypertensive individuals. Group II patients had a significantly better outcome with respect to in-hospital mortality (10.5% vs 18%, p = 0.045) and paraplegia (2% vs 8%, p = 0.008). By multivariate analysis, rupture and diabetes were associated with significantly higher in-hospital mortality, and smoking greatly increased the incidence of paraplegia. The extent of the aneurysm was a major determinant of mortality and paraplegia. The low paraplegia rate in group II was achieved without reattachment of a single intercostal or lumbar artery. No patient with fewer than 10 intersegmental arteries severed had paraplegia, and spinal cord ischemia was reversible in three patients after adjunctive maneuvers were performed to improve perfusion, suggesting that spinal cord blood supply is unlikely to depend on a single "artery of Adamkiewicz."

Aged↗
PubMed1996

A cross-sectional study of canine dimorphism in establishing sex identity: comparison of two statistical methods.

The occurrence of canine tooth dimorphism in Indian subjects has been investigated and the use of two statistical methods of evaluation compared. These were the methods of N.G. Rao and co-workers published in 1988 and quadratic discriminant analysis for correct classification of sex. Parameters considered were (i) the mesiodistal width of maxillary and mandibular canines, (ii) the maxillary canine arch width (intercanine distance) and (iii) the mandibular canine arch width. The results indicated significant dimorphism of the maxillary and mandibular canine teeth. When the results of the arch widths were subjected to the two statistical methods, differing results were obtained in the accuracy of sex classification. The percentage of correct classifications of sex was higher when using quadratic discriminant analysis.

Adolescent↗
PubMed1996

Stomatognathic dysfunctional symptoms in Saudi Arabian adolescents.

Secondary school Saudi students participated in a questionnaire about stomatognathic dysfunction symptoms. The adolescents were interviewed about general health, peripheral joint disease, chewing function, oral parafunctions, and symptoms of dysfunction. Thirty-two per cent of participants had at least one dysfunction symptom. Pain on opening was the most common (35.7%), followed by headache (33.6%), and joint sounds (32.2%). Symptoms increased with decline in general health, particularly the health of peripheral joints. Chewing functions were not impaired. Tooth loss did not affect dysfunction symptoms in adolescents, whilst a weak relation was evident between oral parafunctions and symptoms of mandibular dysfunction.

Adolescent↗
PubMed1996

Cloning, characterization, and chromosomal localization of a human 5-HT6 serotonin receptor.

We describe the cloning and characterization of a human 5-HT6 serotonin receptor. The open reading frame is interrupted by two introns in positions corresponding to the third cytoplasmic loop and the third extracellular loop. The human 5-HT6 cDNA encodes a 440-amino-acid polypeptide whose sequence diverges significantly from that published for the rat 5-HT6 receptor. Resequencing of the rat cDNA revealed a sequencing error producing a frame shift within the open reading frame. The human 5-HT6 amino acid sequence is 89% similar to the corrected rat sequence. The recombinant human 5-HT6 receptor is positively coupled to adenylyl cyclase and has pharmacological properties similar to the rat receptor with high affinity for several typical and atypical antipsychotics, including clozapine. The receptor is expressed in several human brain regions, most prominently in the caudate nucleus. The gene for the receptor maps to the human chromosome region 1p35-p36. This localization overlaps that established for the serotonin 5-HT1D alpha receptor, suggesting that these may be closely linked. Comparison of genomic and cDNA clones for the human 5-HT6 receptor also reveals an Rsal restriction fragment length polymorphism within the coding region.

Adenylyl Cyclases↗
PubMed1996

Predictors of extubation success and failure in mechanically ventilated infants and children.

OBJECTIVE: To predict extubation success and failure in mechanically ventilated infants and children using bedside measures of respiratory function. DESIGN: Prospective collection of data. SETTING: A university-affiliated children's hospital with a 51-bed critical care unit. PATIENTS: All infants and children who were mechanically ventilated for at least 24 hrs, except neonates < or = 37 wks gestation and patients with neuromuscular disease. INTERVENTIONS: Bedside measurements of cardiorespiratory function were obtained immediately before extubation. MEASUREMENTS AND MAIN RESULTS: 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, ventilatory 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 paradoxical breathing, inspiratory pressure, maximal negative inspiratory pressure (maximal negative inspiratory pressure), inspiratory pressure/maximal negative inspiratory pressure ratio, and tidal volume indexed to body weight of a spontaneous breath. Ventilatory support was measured by the fraction of inspired oxygen (F10(2)), mean airway pressure, oxygenation index, and the fraction of total minute ventilation provided by the ventilator. Respiratory mechanics were assessed by determination of peak ventilatory inspiratory pressure and dynamic compliance. Central inspiratory drive was assessed by mean inspiratory flow. Frequency to tidal volume ratio and the compliance, rate, oxygenation, and pressure indexed to body weight, the integrated indices useful in predicting extubation failure in adults, were also calculated. Thirty-four of the 208 patients who were studied were reintubated for an overall failure rate of 16.3% (95% confidence interval 11.3% to 21.4%). The reasons for reintubation were poor effort (n = 8), excessive effort (n = 14), altered mental status or absent airway reflexes (n = 2), cardiovascular instability (n = 3), inadequate oxygenation (n = 3), respiratory acidosis (n = 3), and undocumented (n = 1). Extubation failure increased significantly with decreasing tidal volume indexed to body weight of a spontaneous breath, increasing F10(2), increasing mean airway pressure, increasing oxygenation index, increasing fraction of total minute ventilation provided by the ventilator, increasing peak ventilatory inspiratory pressure, or decreasing mean inspiratory flow (p < .05). Dynamic compliance showed a trend of increasing failure rate with decreasing dynamic compliance but did not reach statistical significance (p = .116). Respiratory rate standardized to age, inspiratory pressure, maximal negative inspiratory pressure, inspiratory pressure/maximal negative inspiratory pressure ratio, frequency to tidal volume ratio, and compliance, rate, oxygenation, and pressure did not show any trend in failure rate with increasing or decreasing values. Threshold values that defined a low risk (< or = 10%) and a high risk (> or = 25%) of extubation failure could be determined for tidal volume indexed to body weight of a spontaneous breath, F10(2), mean airway pressure, oxygenation index, fraction of total minute ventilation provided by the ventilator, peak ventilatory inspiratory pressure, dynamic compliance, and mean inspiratory flow. Neither a low nor a high risk of failure could be defined for frequency to tidal volume ratio or the compliance, rate, oxygenation, and pressure (CROP) index. CONCLUSIONS: Bedside measurements 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 using these measures. Integrated indices useful in adults do not reliably predict extubation success or failure in

Child↗
PubMed1996

Evaluation of an infectivity standard for real-time quality control of human immunodeficiency virus type 1 quantitative micrococulture assays. Participating Laboratories of The AIDS Clinical Trials Group.

Quantitative microculture assays of cryopreserved human immunodeficiency virus type 1-infected cell suspensions and culture supernatants were compared among seven assays sites. There was no significant change in titer during 1 year of storage. The overall standard deviation for infected cell suspensions was approximately 0.8 log10 virus titer. A method for detecting deviant assay results was developed and was used to identify two donor cell preparations (n = 54) that gave consistently low titers.

Cell Culture Techniques↗
PubMed1996

Relationship of hepatocyte growth factor in human umbilical vein serum to gestational age in normal pregnancies.

Hepatocyte growth factor (HGF) is expressed in placental syncitium and fetal organs and acts as a mitogen, motogen, and morphogen in vitro, suggesting a role in fetal growth and development. We aimed to examine the correlates of serum HGF in human cord blood. HGF was measured by ELISA using recombinant human HGF and mouse MAb to recombinant human HGF (Immunology Institute, Tokyo). Umbilical vein blood was collected prospectively at 148 deliveries including 94 normal pregnancies and 54 pregnancies complicated by medical conditions, primarily diabetes mellitus and pregnancy-induced hypertension. Growth parameters, gestation, pregnancy history, and perinatal events were recorded. Sera from 54 adolescents and 32 adult controls were also analyzed. Cord HGF [0.97 (0.66-1.33) ng/mL] [median (25-75 percentile)] was higher than HGF levels in adolescent sera [0.28 (0.21-0.35) ng/mL, p < 0.0001] and adult control sera [0.23 (0.14-0.31) ng/mL, p < 0.0001]. Cord HGF correlated with gestational age (r = 0.42, p = 0.0001) in normal pregnancies, with term babies (n = 69) having higher cord HGF than babies less than 37 wk of gestation (n = 25) [1.11 (0.78-1.45), 0.78 (0.46-1.03) ng/mL, p = 0.0007]. However, there was no relationship between gestation and cord HGF in complicated pregnancies. Cord HGF did not differ at term between appropriate for gestational age babies and small for gestational age babies. There were no independent correlations between cord HGF and birth weight, birth length and placental weight. We provide evidence for the first time that cord HGF levels are high and relate to gestation in normal pregnancies. HGF may have a significant role in fetal development during pregnancy.

Adolescent↗
PubMed1996

Levels of autistic behaviour among the mentally handicapped children in Zimbabwe.

The manifestation of autistic behaviours in relation to the Diagnostic and Statistical Manual of Mental Disorders (1987) Revised Criteria for Autism was investigated among 18 mentally handicapped children. The Autistic Behaviour Checklist and the Behaviour Rating Instrument for Autistic (and other Atypical) Children were used to collect data. All the three major categories of the DSM III-R were observed in varying frequencies in the subjects. In addition other behaviours not described in the DSM III-R such as disturbances in perception and labile mood were also observed. Generally the DSM III-R categories are supported by empirical evidence as found in this and other studies. Consideration should be given to the inclusion of characteristics such as abnormal responses to sensory stimuli and disturbances in developmental rate in Category C of DSM III-R to make it more flexible to cater for non classical autism.

Adolescent↗
PubMed1996

Rapid agonist-induced internalization of the 5-hydroxytryptamine2A receptor occurs via the endosome pathway in vitro.

The mechanism by which agonists induce 5-hydroxytryptamine2A (5-HT2A) receptor internalization was investigated in a clonal cell line stably transfected with the 5-HT2A receptor cDNA. Confocal laser microscopy of immunolabeled 5-HT2A receptors in control (untreated) cells demonstrated that most of the immunoreactivity was associated with the cell surface. After quipazine administration, a significant increase in intracellular immunofluorescence was measured. Time course studies demonstrated rapid agonist-dependent internalization of 5-HT2A receptors, with significant internalization occurring as early as 5 min after agonist administration at 37 degrees. In GF-62 cells, agonist-induced internalization was blocked by preincubation with the 5-HT2A receptor antagonist ketanserin. Internalization was also temperature sensitive because agonist-induced internalization did not occur at 4 degrees. Dual-label experiments disclosed that 5-HT2A and transferrin receptors were internalized via the same endocytotic vesicles. These results suggest that 5-HT2A receptors and transferrin receptors are internalized via the endosomal pathway in GF-62 cells. Although 5-HT2A receptors were internalized, down-regulation, or loss of radioligand binding sites, did not occur. Our results demonstrate that agonists rapidly induce 5-HT2A receptor internalization via the endosomal pathway and that internalization can be dissociated from down-regulation.

3T3 Cells↗
PubMed1996

Substance use among rural secondary schools in Zimbabwe: patterns and prevalence.

OBJECTIVE: To survey drug use among rural secondary school students. DESIGN: Self reported questionnaires developed by the World Health Organisation and translated into Shona were distributed to randomly selected students from 36 schools. SETTING: Nyanga District secondary schools, Zimbabwe. SUBJECTS: 1,000 secondary school students, males and females, forms one to six. MAIN OUTCOME MEASURES: Demographic variables, prevalence rates, frequency of drug use, first time usage, breakdown by age, sex and school type. RESULTS: Alcohol was the commonest "ever taken" substance (34.9pc), followed by tobacco (18.5pc), solvents (6.9pc) and cannabis (34.9pc). Frequency of use was low and use of other categories of drugs was negligible. CONCLUSIONS: Appropriate educational programmes need to be formulated and tailored to meet the needs of rural adolescents.

Adolescent↗
PubMed1996

Hepatitis C antibodies in haemodialysis and pattern of end-stage renal failure in Gassim, Saudi Arabia.

As by the end of 1992, 96 (47 females; 49 females) patients were on regular dialysis treatment for end stage renal failure (ESRF) in 5 haemodialysis HD units, the Gassim region of Saudi Arabia. Because of lack of facilities, paediatric patients were under-represented, age range being 11 to 80 years. Systemic hypertension (47%), followed by hereditary/congenital conditions (23%) and non-insulin dependent diabetes mellitus NIDDM (19%) were the most common causes of ESRF in the region. One patients developed ESRF 14 years after donor nephrectomy. Overall prevalence of HCAb was 50% with a range of 17.24% to 83%. Based, especially, on the findings in two of the units which between them handle 57% (55/96) of the patients, we believe that the practice of machine isolation policy (MIP) rather than blood transfusion is largely responsible for this wide variation in prevalence between the centres. Considering the very high overall prevalence of the Kingdom, we suggest the MIP should no longer be optional and should be part of the universal infection precautions for HD patients. Comparing Gassim with findings from Taif, there may be some variation in the pattern of ESRF between different parts of the Kingdom. More reports will be needed to document this. Donor nephrectomy as a cause of ESRF is being recorded for the first time in the Kingdom. Vigilance is important. Similarly, we believe that sexual intercourse as a probable route of hepatitis C virus HCV transmission is being recorded for the first time in the Kingdom.

Adolescent↗
PubMed1996

The results of ab interno laser thermal sclerostomy combined with cataract surgery versus trabeculectomy combined with cataract surgery 6 to 12 months postoperatively.

BACKGROUND AND OBJECTIVE: When cataract surgery and glaucoma surgery are combined, the theoretical advantages of pressure control, removal of the visual impairment, and protection against an increase in intraocular pressure (IOP) in the immediate postoperative period are gained. The authors' objective was to determine whether ab interno laser thermal sclerostomy (LTS) combined with cataract surgery would be as effective as trabeculectomy combined with cataract surgery. PATIENTS AND METHODS: Ab interno LTS was compared with trabeculectomy, retrospectively, for patients who had undergone combined cataract and glaucoma surgery. RESULTS: There was no significant difference in the numbers of patients using no medications or fewer medications at 6 and 12 months. There was a greater reduction in IOP in the LTS group. CONCLUSIONS: LTS may be better than trabeculectomy in combined cataract and glaucoma surgery because it reduces the IOP more. Compared with trabeculectomy, LTS is simpler to perform and adds less operating time to cataract surgery. Continued follow-up is recommended.

Adult↗
PubMed1995

A simple method for isolating human endothelin converting enzyme free from contamination by neutral endopeptidase 24.11.

Subcellular fractionation of the phosphoramidon sensitive membrane-bound endothelin converting enzyme (ECE-1) activity from homogenates of bovine aortic endothelial cells and the human endothelial cell line EA.hy 926, combined with studies of intact cells, shows ECE-1 to be localised primarily to the plasma membrane with the topology of an ectoenzyme. To overcome the problem of neutral endopeptidase 24.11 contaminating the human ECE-1 activity solubilised from the plasma membrane fractions of EA.hy 926, we have used isoelectric focusing to simultaneously solubilise and separate these activities. The metallopeptidase ECE-1 obtained displayed a neutral pH optimum, a molecular weight of 250 kDa on gel filtration chromatography and was inhibited by phosphoramidon with an IC50 of 0.8 microM.

Animals↗