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T Ahmad

Publications and source records attributed to T Ahmad.

At least 37 records · Page 2Linked to original sources
PubMed2003

Genotype-phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31.

BACKGROUND AND AIMS: Recent molecular data suggest that genetic factors may underlie the disease heterogeneity observed in both ulcerative colitis (UC) and Crohn's disease (CD). A locus on chromosome 5q has been implicated in susceptibility to CD, and recently refined by linkage disequilibrium mapping to a conserved 250 kb haplotype (5q31). No data regarding the contribution of this locus to clinical phenotype exist. In this case control study, we investigated the contribution of this haplotype to both susceptibility and phenotype of CD and UC. PATIENTS AND METHODS: We studied 330 Caucasian CD and 457 UC patients recruited from a single UK centre. Association with disease susceptibility and phenotype was analysed with haplotypes reconstructed from three single nucleotide polymorphisms chosen to span this susceptibility region. Evidence for possible genetic epistasis between IBD5 and NOD2/CARD15 was sought. RESULTS: Linkage disequilibrium across this region was confirmed, with two haplotypes comprising 88% of all chromosomes. Susceptibility to CD, but not to UC, was associated with homozygosity for a common haplotype, H2 (p(c)=0.002; relative risk (RR) 2.0). Genotype-phenotype analyses demonstrated that this association was particularly strong in patients with perianal disease (p(c)=0.0005; RR 1.7), especially in individuals homozygous for this haplotype (p(c)=0.0005; RR 3.0). Importantly, no association with H2 was found in 186 patients without perianal disease. No evidence of epistasis between IBD5 and NOD2/CARD15 was demonstrated. CONCLUSIONS: The IBD5 risk haplotype is associated with CD only. Genotype-phenotype analysis reveals that the strongest association is observed in patients with perianal CD. While the precise gene involved is unclear, these data provide further molecular evidence for a genetic basis of the clinical heterogeneity of CD.

Adolescent↗
PubMed2003

Skeletal changes in type-2 diabetic Goto-Kakizaki rats.

We characterized appendicular and axial bones in rats with type-2 diabetes in five female Goto-Kakizaki (GK) rats, a strain developed from the Wistar rat showing spontaneous type-2 diabetes, and five age- and sex-matched non-diabetic Wistar rats. The humerus, tibia, metatarsals and vertebral bodies were analysed by peripheral quantitative computerized tomography (pQCT). In diabetic rats, the height of the vertebral bodies and length of the humerus were decreased while the length of the metatarsals was increased. A decreased cross-sectional area was found in the vertebral end-plate region and the tibial metaphysis. Notably, the diaphysis in all long bones showed expansion of periosteal and endosteal circumference. In tibia this resulted in increased cortical thickness, whereas in humerus and metatarsal it was unchanged. Areal moment of inertia was increased in all diaphyses suggesting greater bending strength. The most conspicuous finding in diabetic rats pertained to trabecular osteopenia. Thus, trabecular bone mineral density was significantly reduced in all bones examined, by 33-53%. Our pQCT study of axial and appendicular bones suggests that the typical feature of diabetic osteopathy in the GK rat is loss of trabecular bone and expansion of the diaphysis. The loss of metaphyseal trabecular bone if also present in diabetic patients may prove to underlie the susceptibility to periarticular fracture and Charcot arthropathy. The findings suggest that the risk of fracture in diabetes varies according to the specific sub-regions of a bone. The approach described may prove to be useful in the early detection of osteopathy in diabetic patients who may be amenable to preventive treatment.

Animals↗
PubMed2003

Septic arthritis of the hip in children--Aga Khan University Hospital experience in Pakistan.

OBJECTIVE: To present clinical, radiological and bacteriological features and short term outcome of septic arthritis of the hip in children. METHODS: There were 23 male and 16 female children, including 6 neonates and 10 infants with a mean age of 3.9 years. Diagnosis of septic hip was made on clinical grounds, supplemented by X-rays, leukocyte count and the erythrocyte sedimentation rate (ESR). Thirty nine patients with 40 hips were followed for a mean time period of 76 weeks. All patients had a positive joint aspirate (pus) and underwent surgical decompression along with intravenous antibiotic therapy. RESULTS: Symptoms of pain, fever and restricted range of hip motion were common to all patients. The mean leukocyte count was 14,000 and the mean ESR was 63 mm. Cultures of blood and joint aspirate were positive in 9 and 28 patients respectively. Staphylococus Aureus was the commonest organism (14 patients) identified, and only one patient had Hemophilus influenzae. Seven patients had a mixed osteoarticular infection. Positive clinical response was noted in the mean time period of 8.6 days. In follow-up, four cases developed myositis ossificans and 2 cases showed signs of partial growth plate destruction. CONCLUSION: Our findings of the absence of H. influenzae and the presence of a number of gut organisms are different from the previous studies. Duration of symptoms was an important prognostic factor and correlated well with the final outcome. Early surgical decompression was found to be the treatment of choice. A combined osteoarticular infection should be kept in mind in cases which show a poor response after the initial joint debridement.

Arthritis, Infectious↗
PubMed2003

Relapsing polychondritis in an elderly male.

A 65 years patient presented with left ear swelling, swelling of the nasal bridge with congestion of the eyes. Clinically there was evidence of left auricular chondritis, nasal chondritis and conjunctivitis with a history of multiple similar episodes in the past, features suggestive of relapsing polychondritis. The patient improved with oral prednisolone.

Age Factors↗
PubMed2002

High resolution MIC genotyping: design and application to the investigation of inflammatory bowel disease susceptibility.

The highly polymorphic nonclassical MHC class I chain-related (MIC) genes MICA and MICB encode stress inducible glycoproteins expressed on a variety of epithelial cells including intestinal cells. Interaction with the receptor NKG2D is likely to provide an important costimulatory signal for activation and proliferation of NK cells, activated macrophages and CD8 alphabeta and gammadelta T cells. Fifty-four MICA and 17 MICB alleles have been described to date. Although the functional significance of this polymorphism is not known, the high degree of nonconservative substitution, concentration to the putative ligand-binding site and recent observation that different MICA alleles bind to NKG2D with varying affinity has generated much interest. The MIC genes are attractive functional and positional candidate genes for inflammatory bowel disease susceptibility as a consequence of their position in the HLA region and expression on the gastrointestinal epithelium. We developed a robust, high-resolution PCR-SSP genotyping method that can be incorporated into the standard 'Phototyping' system and which effectively identifies 46 of 54 MICA alleles, and all 17 MICB alleles. We applied this system in combination with microsatellite genotyping of the exon 5 variable number of tandem repeats (VNTR) to the investigation of genetic susceptibility to the inflammatory bowel diseases, ulcerative colitis and Crohn's disease. We studied 248 patients with Crohn's disease, 329 with ulcerative colitis and 354 ethnically matched controls. Linkage disequilibrium patterns between HLA-B, MICA and MICB are presented. Analysis by individual allele or by multilocus haplotype failed to identify any significant disease associations.

Alleles↗
PubMed2002

Altered speech following adenoidectomy: a 20 year experience.

Altered speech related to velopharyngeal insufficiency is a rare but well-recognised complication of adenoidectomy. Over a 20 year period, 42 patients were referred to the Edinburgh cleft team for investigation of altered speech persisting for more than 12 months after adenoidectomy. We studied the cases to ascertain the incidence, clinical features and causes of altered speech in these patients and to assess the efficacy of a selective treatment policy. All data were prospectively collected when the patients were assessed in a multidisciplinary clinic and investigated by videofluoroscopy. Nasopharyngoscopy was also possible in half of the patients. Overall, 27 patients were male and 15 were female, and their mean age was 6.5 years. The incidence was one in 1200 adenoidectomies. Diagnoses included five submucous cleft palates, six occult submucous cleft palates, 22 cases of velopharyngeal disproportion, seven developmental or neurological causes, one iatrogenic palatal injury and one case that defied diagnosis. In six patients treatment was not required, 13 responded to speech therapy and 23 required surgical intervention. The choice of operation was based on the findings at investigation. Ten patients were treated by a superiorly based pharyngeal flap, 10 underwent a sphincteric pharyngoplasty and three had an intravelar veloplasty. Speech outcome was assessed in 36 cases. Treatment resulted in significantly improved speech in all but one patient and normal speech in 16 patients. Persistently altered speech is a rare complication of adenoidectomy. Preoperative screening by clinical examination will prevent some but not all of such problems. When patients present they should undergo multidisciplinary assessment and multi-modality investigation. A good outcome can be anticipated in most patients.

Adenoidectomy↗
PubMed2002

A randomised, controlled trial comparing a tissue adhesive (2-octylcyanoacrylate) with adhesive strips (Steristrips) for paediatric laceration repair.

OBJECTIVE: To compare the tissue adhesive 2-octylcyanoacrylate (Dermabond) with adhesive strips, Steristrips in paediatric laceration repair. METHOD: Children with suitable lacerations were randomly allocated for wound closure with either a tissue adhesive or adhesive strips. Thirty children were treated in each group. Linear Visual Analogue Scores were used to judge parents' and nurses' opinions of the application of each treatment. A similar scoring system was used to judge the cosmetic outcome as viewed by parents and a plastic surgeon. Complications and trial failures were noted. RESULTS: Complete data were available for 44 of the children. Parents viewed the treatments as equally acceptable. In contrast those performing the procedure judged the tissue adhesive more difficult to apply. Scores of cosmetic outcome by both parents and the plastic surgeon showed no significant difference in the treatment method used. There were four children in the tissue adhesive group and one from the adhesive strip group in whom the wounds were unable to be closed. CONCLUSION: Both tissue adhesives and adhesive strips are excellent "no needle" alternatives for the closure of suitable paediatric lacerations. This study suggests that the techniques are similar in efficacy, parental acceptability, and cosmetic outcome. The choice as to which is used may come down to economics and operator preference.

Child↗
PubMed2001

ZD1839 (Iressa), a novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, potently inhibits the growth of EGFR-positive cancer cell lines with or without erbB2 overexpression.

Overexpression of the growth factor receptors EGFR and erbB2 occurs frequently in several human cancers and is associated with aggressive tumour behaviour and poor patient prognosis. We have investigated the effects of ZD1839 (Iressa), a novel EGFR tyrosine kinase inhibitor, on the growth, in vitro and in vivo, of human cancer cell lines expressing various levels of EGFR and erbB2. Proliferation of EGFR-overexpressing A431 and MDA-MB-231 cells in vitro was potently inhibited (50%-70%) by ZD1839 with half-maximally effective doses in the low nanomolar range. In parallel, ZD1839 blocked autophosphorylation of EGFR and prevented activation of PLC-gamma 1, ERK MAP kinases and PKB/Akt by EGF. It also inhibited proliferation in EGFR(+) cancer cell lines overexpressing erbB2 (SKBr3, SKOV3, BT474) by between 20% and 80%, effects which correlated with inhibition of EGF-dependent erbB2 phosphorylation and activation of ERK MAP kinase and PKB/Akt in SKOV3 cells. Oral administration of ZD1839 inhibited the growth of MDA-MB-231 and SKOV3 tumours, established as xenografts in athymic mice, by 71% and 32%, respectively. Growth inhibition coincided with reduced proliferation but no change in apoptotic index. Collectively, these results show that ZD1839, at the doses studied, is a potent inhibitor of proliferation not only in cells overexpressing EGFR but also in EGFR(+) cells that overexpress erbB2.

Cell Division↗
PubMed2001

CD1 genotyping of patients with Mycobacterium malmoense pulmonary disease.

Mycobacterium malmoense is an opportunistic mycobacterium that occasionally causes disease in non-immunosuppressed individuals. As only a few individuals exposed to these organisms actually develop clinical disease, it is possible there is a genetic component to susceptibility. CD1 molecules are capable of presenting antigens from more virulent mycobacteria to T cells; therefore, we were interested in discovering whether recently described polymorphisms in CD1 molecules modulated susceptibility to M. malmoense pulmonary disease. The CD1 system comprises five genes (CD1A, -B, -C, -D, and -E) located on chromosome 1 (1q22-23). CD1 molecules are structurally and functionally related to major histocompatibility complex (MHC) class I molecules and are expressed on dedicated antigen-presenting cells. The primary function of CD1 molecules is to present lipid and glycolipid antigens to T cells. We have developed an allele-specific polymerase chain reaction-sequence-specific primer (PCR-SSP) method of CD1 genotyping. Using this method, we compared the allele and haplotype frequencies of CD1 in 49 HIV-negative patients with M. malmoense pulmonary disease with those in 342 normal controls. The CD1A and CD1E alleles were nominally identified as CD1A*01, CD1A*02, CD1E*01 and CD1E*02, and the control gene frequencies were found to be 5%, 95%, 67% and 33%, respectively. No significant difference was observed between the patient and control cohorts. Positive linkage disequilibrium values of 0.73 were observed between CD1A*02 and CD1E*01 (P<0.0001; chi2 test), and 0.94 between CD1A*01 and CD1E*02 (P<0.0001; chi2 test). Typing was also performed for two previously described CD1D alleles (CD1D*01 and CD1D*02), although only CD1D*01 was detected.

Antigens, CD1↗
PubMed2001

Review article: the genetics of inflammatory bowel disease.

Recent epidemiological, clinical and molecular studies have provided strong evidence that inherited predisposition is important in the pathogenesis of chronic inflammatory bowel diseases. The model most consistent with the epidemiological data suggests that Crohn's disease and ulcerative colitis are related polygenic diseases, sharing some but not all susceptibility genes. Investigators throughout the world have applied the complementary techniques of genome-wide scanning and candidate gene analysis. Four areas of linkage have been widely replicated on chromosomes 16 (IBD1), 12 (IBD2), 6 (IBD3-the HLA region), and most recently on chromosome 14. Fine mapping of these regions is underway. Of the 'positional' candidate genes, most attention has centred on the genes of the major histocompatibility complex. Genes within this region may determine disease susceptibility, behaviour, complications and response to therapy. Hope continues that studies of inflammatory bowel disease genetics will provide fresh insight into disease pathogenesis and soon deliver clinical applications.

Chromosomes, Human, Pair 12↗
PubMed2001

Early discharge after coronary artery bypass graft surgery: are patients really going home earlier?

OBJECTIVE: This study was undertaken to determine whether early discharge after coronary artery bypass grafting allows patients to return home earlier or merely increases the use of outpatient nursing and inpatient rehabilitation services. METHODS: Patterns of discharge were analyzed in 407 patients undergoing bypass grafting in 1990, when there were no early extubations or fast track protocols, and compared with 379 patients in 1998, when these protocols were used. RESULTS: Patients in 1998 had a higher prevalence of class IV angina (35.3% vs 22.8%; P =.006), urgent/emergency surgery (58.3% vs 44.9%; P =.015), and lower ejection fractions (48.9% +/- 16.4% vs 52.9% +/- 13.5%; P =.0002). Despite these increased risk factors, 1998 patients spent less time receiving ventilatory support (10.2 +/- 9.2 vs 26.7 +/- 15.7 hours; P <.001) and had a shorter length of stay (5.4 +/- 2.5 vs 9.2 +/- 4.3 days; P <.001). However, fewer 1998 patients were discharged home (56.7% vs 97.0%; P <.0001). A higher percentage of 1998 patients (43.3% vs 2.9%; P <.00001) were discharged to extended care facilities where their average length of stay was 10.6 +/- 15.1 days. Readmission to the Boston Medical Center was also more common in 1998 patients (5.3% vs 0.5%; P <.0001). CONCLUSIONS: Early extubation and fast track protocols have resulted in earlier discharge from acute care facilities. However, the anticipated earlier return to home has been offset by the increased use of outpatient nursing services, discharges to extended care facilities, and hospital readmissions.

Coronary Artery Bypass↗
PubMed2001

Bone reinnervation after fracture: a study in the rat.

Reinnervation after tibial fracture in the rat was studied by analyzing the occurrence of growth-associated protein 43 (GAP-43), a marker for regenerating nerve fibers, and protein gene product 9.5 (PGP-9.5), a marker for mature nerve fibers, by immunohistochemistry. At 3 days postfracture, GAP-43--immunoreactive nerve fibers were first observed in the fracture hematoma and periosteum. At 7 days postfracture, abundant sprouting of GAP-43--positive fibers was seen in the callus, hyperplastic periosteum, and edge of fibrocartilage. In the latter region, the nerve fibers were nonvascular, showing dense ramifications and terminal sprouting close to chondroid cells. At 14 days and 21 days postfracture, many GAP-43--positive fibers were still sprouting into the fibrocartilage and new woven bone. Fine varicose GAP-43--positive fibers also were present in the bone marrow. In contrast to GAP-43, PGP-9.5-positive nerve fibers were observed only occasionally at 3 days postfracture but gradually increased in number from day 14 to 21. Our study shows that intense nerve regeneration occurs in early fracture healing partly unrelated to neovascularization. Considering that neuronal mediators have been shown to participate in local bone formation and resorption, the nerve regeneration observed may prove to be essential for delivery of neuronal mediators required for normal callus formation and/or neovascularization.

Animals↗
PubMed2000

Attention to bodily sensations: a test of the cognitive-attentional model of panic.

This paper describes a study designed to test the cognitive-attentional model of panic. This model suggests that attention to internal sensations is likely to increase misinterpretation of them as representing a serious threat to health, which in turn might increase anxiety. In the present study, instructions for internal attentional focus were predicted to increase symptom reporting, anxiety, and catastrophic symptom attributions. Two groups, patients diagnosed with panic disorder with agoraphobia (PDA) and normal controls, watched a stressful film; half of each group was asked to attend to their internal sensations while watching, and the other half to focus on the film. In the normal controls, the manipulation was effective in modifying attentional focus, and the self-focused attention group became more anxious, reported more symptoms, and made more negative symptom attributions. However, in the PDA group, attentional focus was high in both conditions, and perhaps for this reason the intervention had no effect on mood, symptoms, catastrophic cognitions, or symptom attribution.

Adaptation, Psychological↗
PubMed1999

Anticipation and execution of a simple reading task enhance corticospinal excitability.

OBJECTIVE: Electromyographic responses (EMG) evoked in the right hand by transcranial magnetic stimulation (TMS) of the left motor cortex are enhanced during continuous reading. This enhancement is the result of increased excitability of the motor cortex. We proposed that anticipation and reading of single words would also enhance corticospinal excitability. We studied the temporal course of corticospinal excitability changes following left and right hemisphere TMS. METHODS: Ten normal volunteers were studied. A warning stimulus (S1) was followed by an imperative stimulus (S2) whereupon a word was presented. Subjects responded by reading the word aloud or reading it silently. In other conditions, no word was displayed and the subjects responded to S2 by saying the word 'Cat', pursing their lips, or doing nothing. EMG was recorded over the contralateral hand following a TMS pulse over the motor cortex during and after the S1-S2 period. RESULTS: Enhancement of EMG amplitudes was significantly greater following left hemisphere TMS. The enhancement in the S1-S2 period and that following S2 had a time course similar to several event-related brain potentials. CONCLUSIONS: There may be a common mechanism underlying both corticospinal excitability and the contingent negative variation, readiness potential and N400.

Adult↗