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Biomedical subjects

K Khan

Publications and source records attributed to K Khan.

At least 73 records · Page 4Linked to original sources
PubMed1998

A sensitive and robust method for measles RNA detection.

The aim of this study was to compare measles RNA amplification methods and to develop and select the most rapid, sensitive and robust procedure. The use of hybrid capture for measles RNA isolation was evaluated, and three RNA amplification detection techniques were compared. These were: (a) reverse transcription followed by nested polymerase chain reaction (RT-PCR) with MMLV reverse transcriptase and Taq polymerase; (b) a combined RT-PCR reaction using rTth polymerase; and (c) NASBA. An internal positive control was also developed. The sensitivities of the detection methods were quantified by using a dilution series of a known amount of total RNA from measles-infected Vero cells or by calculation of the number of transcript molecules (produced from a recombinant plasmid containing an insert measles nucleoprotein DNA) present in each amplification reaction, respectively. The results indicated that hybrid capture followed by combined RT-PCR with rTth polymerase was the most reproducibly robust and sensitive protocol and could detect as few as 10(4) synthetic measles RNA transcripts added to tissue homogenates. However, NASBA proved to be the most sensitive method for measles RNA detection in water.

Animals↗
PubMed1998

Measles IgM immunoreactivity in patients with inflammatory bowel disease.

AIM: The purpose of our study was to examine measles IgM immunoreactivity in patients with inflammatory bowel disease. PATIENTS AND METHODS: In an International collaborative study, serum measles IgM immunoreactivity was assayed in consecutive outpatients with Crohn's disease (n = 95), ulcerative colitis (n = 79), viral hepatitis (n = 63) and blood donors (n = 30). Two commercial measles assays--enzyme linked immunosorbent assay and indirect fluorescence assay--and a Public Health Laboratory Service (PHLS) "in house" antibody capture radioimmunoassay were used. Results were compared with serum rubella and Epstein-Barr virus-specific IgM immunoreactivity, total serum IgM, and measles IgG immunoreactivity. Twenty patients with inflammatory bowel disease were studied serially over a 4-month period. RESULTS: By enzyme linked immunosorbent assay, the prevalence of raised serum measles IgM immunoreactivity was significantly greater in patients with Crohn's disease 23/95 (24%) and ulcerative colitis 20/79 (27%) compared with hepatitis patients 2/63 (3%) and normal controls 0/30 (0%) (p < 0.001). Indirect fluorescence assay produced significantly more positive results than enzyme linked immunosorbent assay in both Crohn's disease (50/87; 57%) and ulcerative colitis (35/68; 51%) but not in controls (0%) (p < 0.001). In contrast, no sera were positive using MCRIA. In the enzyme linked immunosorbent assay, measles IgM immunoreactivity did not correlate with either total IgM, rubella or Epstein-Barr virus IgM immunoreactivities-which were not raised-measles IgM immunoreactivity, or disease activity. Patients not receiving steroids were more likely to have raised measles IgM immunoreactivity (p < 0.5). All sera tested for Rheumatoid factor were negative. Of 20 patients with inflammatory bowel disease studied by ELISA over a 4-month period, 50% showed raised measles IgM immunoreactivity at some stage. CONCLUSION: The data suggest a specific and fluctuating immune response to measles virus in patients with Crohn's disease and ulcerative colitis, that may be modified by corticosteroid therapy.

Adult↗
PubMed1998

Neurodegenerative Alzheimer-like pathology in PDAPP 717V-->F transgenic mice.

In summary, PDAPP mice overexpressing a mutation associated with some cases of familial early-onset AD express several of the major pathological hallmarks associated with AD. Amyloid plaques in PDAPP mice appear quite similar to A beta deposits in AD as shown by a variety of different antibodies and stains, and are of both the diffuse and compacted varieties. Additionally, a subset of these amyloid plaques appear to be neuritic plaques. Neurodegenerative changes, including the loss of synaptic and dendritic proteins, abnormal phosphorylation of cytoskeletal elements, subcellular degenerative changes, and the deposition of lysosomal and acute phase proteins has also been seen in PDAPP mouse brains. Reactive astrocytosis and microgliosis have also been observed in association with the amyloid plaques in the PDAPP mice. No neurofibrillary tangles or paired helical filaments have been found in the mice to date. It remains unknown whether mice are capable of generating these in a manner comparable to AD in less than two years. Extensive behavioral analyses are currently being performed in these mice, and preliminary results indicate that the PDAPP mice are significantly impaired on a variety of different learning and memory tests. In conclusion, the PDAPP mouse model doesn't display all the pathological hallmarks of AD, but it does display most of them in a robust manner that increases with age and gene dosage. Therefore, this transgenic model provides evidence that alterations in APP processing and A beta production can result in AD-like neuropathology, can contribute to a mechanistic understanding of AD (since examination of AD brains yields a static view, and we are unable to view the development of various pathological changes), as well as providing an useful animal model for the testing of various therapeutic interventions directed towards specific aspects of the neurodegenerative process.

Alzheimer Disease↗
PubMed1997

Stability measurement of oligonucleotides in serum samples using capillary electrophoresis.

An in vitro stability study of unmodified and modified antisense oligonucleotides in human serum was performed with a previously developed capillary electrophoretic method using either micellar solution or entangled polymer solution depending on the oligonucleotide length to be separated. A method has been devised and validated for the extraction of oligonucleotides from serum using anion-exchange centrifugal filter units. The extracted samples were desalted by a drop dialysis method. The serum half-lives and the degradation patterns of unmodified and modified oligonucleotides are compared. The modified oligonucleotide used in this study is protected from exonuclease activity present in human serum by terminal 1,3-propanediol modification.

Base Sequence↗
PubMed1997

Amyloid precursor protein processing and A beta42 deposition in a transgenic mouse model of Alzheimer disease.

The PDAPP transgenic mouse, which overexpresses human amyloid precursor protein (APP717V-->F), has been shown to develop much of the pathology associated with Alzheimer disease. In this report, levels of APP and its amyloidogenic metabolites were measured in brain regions of transgenic mice between 4 and 18 months of age. While absolute levels of APP expression likely contribute to the rate of amyloid beta-peptide (Abeta) deposition, regionally specific factors also seem important, as homozygotic mice express APP levels in pathologically unaffected regions in excess of that measured in certain amyloid plaque-prone regions of heterozygotic mice. Regional levels of APP and APP-beta were nearly constant at all ages, while A beta levels dramatically and predictably increased in brain regions undergoing histochemically confirmed amyloidosis, most notably in the cortex and hippocampus. In hippocampus, A beta concentrations increase 17-fold between the ages of 4 and 8 months, and by 18 months of age are over 500-fold that at 4 months, reaching an average level in excess of 20 nmol of A beta per g of tissue. A beta1-42 constitutes the vast majority of the depositing A beta species. The similarities observed between the PDAPP mouse and human Alzheimer disease with regard to A beta42 deposition occurring in a temporally and regionally specific fashion further validate the use of the model in understanding processes related to the disease.

Age Factors↗
PubMed1997

Early active mobilization after second stage flexor tendon grafts.

We assessed the results of nine two-stage tendon reconstructions. The tendon graft was the ipsilateral palmaris longus tendon inserted into a tunnel which had been previously created by a silicone spacer. Early active mobilization was commenced 48 hours after surgery according to a previously described protocol (Small et al, 1989). Using the grading system of Kleinert and Verdan (1983) the results were: one excellent, two good, five fair and one poor. Using the Buck-Gramcko et al (1976) grading system there were three excellent, two good, two satisfactory and two poor results. There were no cases of tendon graft rupture or dehiscence of the junction between tendon and graft.

Adult↗
PubMed1997

Hip and ankle range of motion in elite classical ballet dancers and controls.

OBJECTIVE: To report range of motion at the hip and ankle in male and female ballet dancers compared with controls. DESIGN: Cross-sectional cohort study with convenience control sample. SETTING: National classical ballet school in Australia. PARTICIPANTS: Thirty-three female and 30 male full-time ballet students of mean (SD) age 16.9 (0.8) and 18.0 (1.4) years, respectively. Controls were 31 female and 16 male nondancing, normally active university students of average ages 18.8 +/- 0.6 and 18.8 +/- 0.9 years, respectively. MAIN OUTCOME MEASURES: Degrees of range of motion of left and right sides for the following four movements: standing plié in parallel-passive ankle dorsiflexion (DF), standing turnout in the balletic first position-lower limb external rotation (LLER), supine hip external rotation (ER), supine hip internal rotation (IR). Two additional ranges of motion were calculated. External rotation below the hip joint (BHER) was derived by subtracting hip ER from LLER, and total supine hip rotation (Hip IR + ER) was derived by summing hip ER and hip IR. MAIN RESULTS: On both left and right sides, dancers had greater LLER (p < 0.0001) and hip ER (p < 0.0001) but lesser hip IR than the controls (p < 0.0001). Female but not male dancers had greater total supine hip rotation (hip ER+IR) than controls (p < 0.05). There was no difference in either BHER or ankle DF between dancers and controls. Within dancers, females had greater range in both left and right hip IR, LLER, and hip IR + ER. There was no difference in hip ER. Regression analysis revealed that LLER related to hip ER in both males and females. CONCLUSIONS: Elite classical dance students had greater hip external rotation (both ER and LLER) and less hip internal rotation than controls but similar BHER and ankle DF. Since ER below the hip joint and ankle DF do not differ between dancers and controls, despite repeated training of these movements in ballet, there may be anatomical (bony/ligamentous) limitations to these movements.

Ankle Joint↗
PubMed1997

Neonatal abstinence syndrome due to codeine.

The neonatal abstinence syndrome (NAS) is a potentially life threatening illness associated with significant morbidity especially in the neonatal period. A case of NAS due to codeine prescribed for pain relief during pregnancy is reported. Clinicians should be aware that narcotic derivatives prescribed in late pregnancy can give rise to this type of problem.

Acetaminophen↗
PubMed1996

Manganese toxicity in children receiving long-term parenteral nutrition.

BACKGROUND: In patients receiving long-term parenteral nutrition (PN), cholestatic disease and nervous system disorders have been associated with high blood concentrations of manganese. In such patients, the normal homoeostatic mechanisms of the liver and gut are bypassed and the requirement for this trace element is not known; nor has it been certain whether hypermanganesaemia causes the cholestasis or vice versa. We explored the direction of effect by serial tests of liver function after withdrawal of manganese supplements from children receiving long-term PN. We also examined the relation between blood manganese concentrations and brain lesions, as indicated by clinical examination and magnetic resonance imaging (MRI). METHODS: From a combined group of 57 children receiving PN we identified 11 with the combination of hypermanganesaemia and cholestasis; one also had a movement disorder. Manganese supplements were reduced in the first three and withdrawn in the remainder. MRI was done in two of these children. We also looked at manganese concentrations and MRI scans in six children who had received PN for more than 2 years without developing liver disease. FINDINGS: In the hypermanganesaemia/cholestasis group, four of the 11 patients died. In the seven survivors baseline whole-blood manganese was 615-1840 nmol/L, and after 4 months it had declined by a median of 643 nmol/L (p < 0.01). Over the same interval total bilirubin declined by a median of 70 mumol/L (p < 0.05). Two of these children had movement disorders, one of whom survived to have an MRI scan; this showed, with T1 weighted images, bilateral symmetrically increased signal intensity in the globus pallidus and subthalamic nuclei. Such changes were also seen in five other children--one from the hypermanganesaemia/cholestasis group and four of six in the long-term PN group without liver disease (in all of whom blood manganese was above normal). INTERPRETATION: The cholestasis complicating PN is multifactorial, but these results add to the evidence that manganese contributes. In view of the additional hazard of basal ganglia damage from high manganese levels in children receiving long-term PN, we recommend a low dose regimen of not more than 0.018 mumol/kg per 24 h together with regular examination of the nervous system.

Bilirubin↗
PubMed1996

Capillary electrophoresis of oligonucleotides: micellar system or entangled polymers.

The capillary electrophoretic separation of oligonucleotides (12-24 bases in length) using a micellar system or an entangled polymer solution was compared. Micellar electrokinetic capillary chromatography was performed using a fused-silica capillary whereas a J&W DB-17-coated capillary was used for capillary electrophoresis in entangled polymer solution. In both cases, a number of parameters were evaluated to improve separation. For example, the influence of concentration of copper(II) ions and sodium dodecyl sulfate, variation in applied voltage and temperature were investigated in the micellar system. The influence of variation in pH was also studied. The two methods were also compared with respect to their efficiencies. The results of quantitation showed better within-day and day-to-day repeatability for the entangled polymer solution. Both methods gave a comparable limit of detection of about 30 pg at a signal-to-noise ratio of 3.

Cations, Divalent↗
PubMed1996

Yellowfever mosquito (Diptera:Culicidae) introduced into Landi Kotal, Pakistan, by tire importation.

Although the recent distribution of yellowfever mosquito, Aedes aegypti (L.), in Pakistan has been restricted to the port city of Karachi, adult and immature mosquitoes breeding in imported tires in warehouses at Landi Kotal (North-West Frontier Province) were identified as Ae. aegypti. The patterns of tire trade and the current disjunct distribution of Ae. aegypti indicated that the introduction into Landi Kotal may have been either from Karachi or India. Thermal fog application of pirimiphos-methyl and residual spray of malathion during 1993 reduced abundance in October-November. Living larvae or adults were not found during January 1994, apparently because of cold weather. However, Ae. aegypti reappeared during May-June 1994, most probably from eggs that overwintered. Population increased during late August when another round of spray using the same insecticides and fenthion as an additional larvicide again reduced abundance. Although this mosquito apparently has not spread into neighboring areas, its survival at Landi Kotal through all seasons despite control measures indicates its potential of becoming established in other areas of Pakistan.

Aedes↗
PubMed1996

Stress fracture of the body of the talus in athletes demonstrated with computer tomography.

PURPOSE: This article describes a series of four previously unreported stress fractures of the body of the talus. CASE SUMMARY: The four patients presented with ankle pain of gradual onset for periods of three weeks to 12 months. Radioisotope scans in all four patients showed identical pictures of markedly increased uptake in the region of the body of the talus. Computed tomographic scan images were also similar showing a distinct fracture line through the posterolateral aspect of the body of the talus extending into the subtalar joint. All four patients were treated differently ranging from rest to surgery, but no treatment appears totally successful. DISCUSSION: A single case of stress fracture of the neck of talus has previously been reported in a runner, but no previous cases of stress fracture of the body of the talus have been reported. The mechanism may be that in the presence of excessive subtalar pronation and plantar-flexion, the lateral process of the calcaneus impinges on the concave posterolateral corner of the talus. No treatment appeared totally successful but the authors would recommend a six week period of non-weight-bearing rest. RELEVANCE: The diagnosis of stress fracture of the body of the talus should be considered in the athlete who presents with gradual onset of ankle pain.

Adult↗
PubMed1996

Stress fracture of the neck of the seventh and eighth ribs: a case report.

PURPOSE: This article describes a previously unreported site of stress fracture. CASE SUMMARY: A 20-year-old female sculler presented with a 10-day history of posterolateral thoracic pain and marked tenderness maximally over the seventh and eighth costovertebral joints. A radioisotope bone scan showed foci of increased uptake posteriorly in the region of the seventh and eighth ribs. Computed tomographic scan confirmed and diagnosis of stress fracture of the neck of the seventh and eighth ribs. DISCUSSION: Stress fractures of the ribs have previously been reported in rowers. All previous reports have involved fractures in the posterolateral aspect of the ribs. The mechanics of this fracture at the neck of the ribs is uncertain. RELEVANCE: This case is the first reported of a stress fracture of the neck of the ribs. It should be considered in the differential diagnosis of a rower with thoracic spine pain.

Adult↗
PubMed1996

Direct in situ nucleic acid amplification: control of artefact and use of labelled primers.

Aims-To evaluate factors which ameliorate false positive artefacts with direct in situ PCR using labelled dNTPs; to investigate the use of labelled primers to overcome this artefact whilst maintaining sensitivity.Methods-Sections of measles (RNA virus) infected Vero cells with cytoplasmic signal or cytomegalovirus (DNA virus) infected fibroblasts with nuclear signal were collected. In situ PCR (or in situ RT-PCR) was carried out by methods permitting evaporation. Reagents or conditions which may control false positive artefacts using labelled dNTPs were investigated systematically. Labelled primers were tested to overcome artefacts, with adjuncts which improve sensitivity.Results-No reagent nor condition investigated was able to control the artefact with labelled dNTPs. Excessive digestion and incomplete DNAse treatments exacerbated the artefact, whereas novobiocin decreased both specific signal and artefact. However, the artefact was controlled by labelled primers, albeit with relatively low sensitivity. Sensitivity using labelled primers could be increased using alcohol fixation, albumin or Perfectmatch.Conclusions-A repair process is implicated for the artefact using labelled dNTPs. Excessive digestion or DNAse treatment may exacerbate DNA damage by disrupting histones or the DNA, respectively. Labelled primers control this artefact, albeit with reduced sensitivity, which may be improved by precipitation fixatives (alcohol) and reagents which enhance specific reaction.

Journal Article↗