Biomedical subjects

Mohammed Khan

Publications and source records attributed to Mohammed Khan.

17 recordsLinked to original sources

PubMed2006

Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance.

AIMS: Recent advances in cardiovascular magnetic resonance (CMR) include improved image quality with steady-state free precession (SSFP) sequences and advanced post-processing of high temporal resolution ventricular function. We used these techniques to establish the reference values for right ventricular (RV) volumes and function. METHODS AND RESULTS: We studied 120 healthy subjects (60 men, 60 women; from 20 to 80 years) after exclusion of cardiovascular abnormality. Data were generated from SSFP cines, with three-dimensional modelling. Gender, body surface area (BSA), and age were independent predictors of several RV parameters. Normalized RV mass (RVM) and absolute and normalized RV volumes decreased significantly with age, whereas ejection fraction increased. For diastolic variables, absolute and normalized early peak filling rate (PFR(E)) decreased and absolute and normalized active peak filling rate (PFR(A)) in males increased, with decreased PFR(E)/PFR(A). Increasing BSA was associated with increased RVM, volumes, and PFR(E). Gender significantly influenced absolute and normalized mass and volumes, and absolute and normalized PFR(A). CONCLUSION: These data using state-of-the-art CMR show that normal values of RV systolic and diastolic parameters vary significantly by gender, BSA, and age. Appropriate reference ranges normalized to all three variables should be used in the determination of normality or severity of abnormality of RV dimensions and function.

Adult↗

PubMed2006

Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy.

OBJECTIVES: We studied the prognostic implications of midwall fibrosis in dilated cardiomyopathy (DCM) in a prospective longitudinal study. BACKGROUND: Risk stratification of patients with nonischemic DCM in the era of device implantation is problematic. Approximately 30% of patients with DCM have midwall fibrosis as detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR), which may increase susceptibility to arrhythmia and progression of heart failure. METHODS: Consecutive DCM patients (n = 101) with the presence or absence of midwall fibrosis were followed up prospectively for 658 +/- 355 days for events. RESULTS: Midwall fibrosis was present in 35% of patients and was associated with a higher rate of the predefined primary combined end point of all-cause death and hospitalization for a cardiovascular event (hazard ratio 3.4, p = 0.01). Multivariate analysis showed midwall fibrosis as the sole significant predictor of death or hospitalization. However, there was no significant difference in all-cause mortality between the 2 groups. Midwall fibrosis also predicted secondary outcome measures of sudden cardiac death (SCD) or ventricular tachycardia (VT) (hazard ratio 5.2, p = 0.03). Midwall fibrosis remained predictive of SCD/VT after correction for baseline differences in left ventricular ejection fraction between the 2 groups. CONCLUSIONS: In DCM, midwall fibrosis determined by CMR is a predictor of the combined end point of all-cause mortality and cardiovascular hospitalization, which is independent of ventricular remodeling. In addition, midwall fibrosis by CMR predicts SCD/VT. This suggests a potential role for CMR in the risk stratification of patients with DCM, which may have value in determining the need for device therapy.

Adult↗

PubMed2006

Hedgehog pathway gene expression during early development of the molar tooth root in the mouse.

Sonic hedgehog is a secreted protein important for many aspects of embryonic development. In the developing tooth, Shh expression is restricted to the epithelial compartment and plays an important role during both initiation and subsequent coronal morphogenesis. We have investigated the expression of Shh and constituent members of the signalling pathway during early development of the molar tooth root in the mouse and find the presence of transcripts in Hertwig's epithelial root sheath. These epithelial cells of the root sheath and the surrounding apical mesenchyme of the dental papilla and follicle also expressed the Shh receptor Ptc1, agonist Smo and Gli downstream transcriptional effectors; however, this response occurred over short range. In contrast, the Shh antagonists Hip1 and Gas1 were both expressed at a distance from these responding cells, in more peripheral regions of the developing root. Transcripts of the Skn acyl transferase lacked specific expression in early root structures.

Animals↗

PubMed2006

Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis.

RATIONALE: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence. OBJECTIVES: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations. METHODS: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age>6.0 yr, FEV1>or=40% predicted, and corticosteroid use>3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo. MEASUREMENTS AND MAIN RESULTS: Fluticasone group: n=84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n=87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23-1.48) fluticasone versus placebo. CONCLUSIONS: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.

Administration, Inhalation↗

PubMed2006

Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of fallot and its relationship to adverse markers of clinical outcome.

BACKGROUND: Late morbidity and mortality remain problematic after repair of tetralogy of Fallot (TOF). We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) would be present in adults with repaired TOF and would be related to adverse markers of outcome. METHOD AND RESULTS: LGE was scored in the right and left ventricles (RV and LV) of 92 adult patients who had undergone TOF repair. RV LGE was seen in all patients at surgical sites located in the outflow tract (99%) or the site of ventricular septal defect patching (98%) and in the inferior RV insertion point (79%) and trabeculated myocardium (24%). LV LGE (53%) was located at the apex consistent with apical vent insertion (49%), in the inferior or lateral wall consistent with infarction (5%), or in other areas (8%). Patients with supramedian RV LGE score were older (38 versus 27 years, P<0.001) and more symptomatic (38% versus 8% in New York Heart Association class II or greater, P=0.001), had increased levels of atrial natriuretic peptide (7.3 versus 4.9 pmol/L, P=0.041), and had a trend to higher brain natriuretic peptide (12.3 versus 7.2 pmol/L, P=0.086), exercise intolerance (maximum VO2 24 versus 28 mL.min(-1).kg(-1), P=0.021), RV dysfunction (RV end-systolic volume 61 versus 55 mL/m2, P=0.018; RV ejection fraction 50% versus 56%, P=0.007), and clinical arrhythmia (26% versus 10%, P=0.039). Non-apical vent LV LGE also correlated with markers of adverse outcome. In a multivariate model, RV LGE remained a predictor of arrhythmia. CONCLUSIONS: RV and LV LGE were common after TOF repair and were related to adverse clinical markers, including ventricular dysfunction, exercise intolerance, and neurohormonal activation. Furthermore, RV LGE was significantly associated with clinical arrhythmia.

Adolescent↗

PubMed2006

Laparoscopic mesh repair of a diaphragmatic hernia of Bochdalek.

The advent of minimally invasive surgery has facilitated the laparoscopic repair of diaphragmatic hernias. One of the difficulties associated with long-standing Bochdalek or Morgagni hernias is that the herniated contents are often quite adherent to the diaphragmatic defect and require considerable dissection before the reduction of herniated organs. Ultrasonic dissection using a harmonic coagulation shears allowed safe, bloodless division of the long-standing adhesions, which is essential for atraumatic reduction of herniated thoracic contents. We herein report the successful laparoscopic mesh repair of a Bochdalek hernia in a 67-year-old man.

Aged↗

PubMed2006

Incidence of atrial fibrillation in heart transplant patients: long-term follow-up.

BACKGROUND: The incidence of atrial fibrillation (AF) in heart transplant patients has not been well documented. METHODS: To determine the incidence of AF in a cohort of patients undergoing cardiac transplantation, clinical data were obtained from a prospectively collected database for all consecutive orthotopic heart transplantation (OHT) patients and for all consecutive coronary artery bypass graft (CABG) surgery patients between January 1984 and March 2004 at our institution. A cohort of 1,714 OHT patients and low-risk CABG (normal ejection fraction [EF] and no left ventricular hypertrophy [LVH]) patients were age- and sex-matched. RESULTS: The average age in the two groups was 56 +/- 7 years with 87% male and 81% white race and body mass index (BMI) of 26 +/- 4. There were 3 cases of AF (0.3%) in the OHT group and 757 cases of AF (21%) in the low-risk CABG group. The strongest independent predictor of freedom from postoperative AF was having had a transplant (odds ratio [OR] 96, 95% confidence interval [CI] 13-720). The incidence of AF, atrial flutter (AFL), and supraventricular tachycardia (SVT) in OHT was 0.33, 2.8%, and 1.3%, respectively. Given that incidence of AF, AFL, and SVT in historical post-CABG population is 25%, 17%, and 4.3%, transplanted patients appear to have lower incidence of AF, AFL, and SVT than the reference population. Consistent with this, transplanted patients underwent few ablation procedures for atrial arrhythmias. Additionally, the three patients with AF had bicaval anastomoses suggesting the possibility of PACs originating in the donor superior vena cava (SVC) or IVC (inferior vena cava) initiating AF in these patients. CONCLUSIONS: In a cohort study of transplant and low-risk CABG patients, the strongest independent predictor of freedom from AF is having undergone transplant surgery. One potential explanation for the markedly lower incidence of AF may be effective isolation of thoracic veins with documented cases retaining the native SVC.

Aged↗

PubMed2005

Randomized comparison of stentless versus stented valves for aortic stenosis: effects on left ventricular mass.

BACKGROUND: Aortic valve replacement (AVR) is the established treatment for severe aortic stenosis. In response to the long-term results of aortic homografts, stentless porcine valves were introduced as an alternative low-resistance valve. We conducted a randomized trial comparing a stentless with a stented porcine valve in adults with severe aortic stenosis. METHODS AND RESULTS: The primary outcome was change in left ventricular mass index (LVMI) measured by transthoracic echocardiography and, in a subset, by cardiovascular MR. Measurements were taken before valve replacement and at 6 and 12 months. Patients undergoing AVR with an aortic annulus < or =25 mm in diameter were randomly allocated to a stentless (n=93) or a stented supra-annular (n=97) valve. There were no significant differences in mean LVMI between the stentless versus stented groups at baseline (176+/-62 and 182+/-63 g/m2, respectively) or at 6 months (142+/-49 and 131+/-45 g/m2, respectively), although within-group changes from baseline to 6 months were highly significant. Changes in LVMI measured by cardiovascular MR (n=38) were consistent with the echo findings. There was a greater reduction in peak aortic velocity (P<0.001) and a greater increase in indexed effective orifice area (P<0.001) in the stentless group than in the stented group. There were no differences in clinical outcomes between the 2 valve groups. CONCLUSIONS: Despite significant differences in indexed effective orifice area and peak flow velocity in favor of the stentless valve, there were similar reductions in left ventricular mass at 6 months with both stented and stentless valves, which persisted at 12 months.

Aged↗

PubMed2005

Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children.

The use of noninvasive methods of monitoring airway inflammation, such as exhaled nitric oxide (eNO) and induced sputum, has been shown to improve asthma monitoring and optimize treatment in adult patients with asthma. There is a lack of comparable data in children. Forty children with stable asthma eligible for inhaled steroid reduction were reviewed every 8 weeks, and their inhaled steroid dose halved if clinically indicated. eNO, sputum induction combined with bronchial hyperreactivity testing, and exhaled breath condensate collection were performed at each visit to predict success or failure of reduction of inhaled steroids. Thirty of 40 (75%) children tolerated at least one dose reduction, 12 of 40 (30%) were successfully weaned off, and in total, 15 of 40 (38%) children experienced loss of asthma control. Treatment reduction was successful in all children who had no eosinophils in induced sputum before the attempted reduction. Using multiple logistic regression, increased eNO (odds ratio, 6.3; confidence interval, 3.75-10.58) and percentage of sputum eosinophils (odds ratio, 1.38; confidence interval, 1.06-1.81) were significant predictors of failed reduction. These findings suggest that monitoring airway inflammation may be useful in optimizing treatment in children with asthma.

Administration, Inhalation↗

PubMed2005

High-frequency color Doppler ultrasonography of the spermatic cord arteries: resistive index variation in a cohort of 51 healthy men.

OBJECTIVE: The purpose of this study was to determine the normal range of Doppler ultrasonographic measurements of spermatic cord arteries in a cohort of healthy men. METHODS: The spermatic cord arteries of 51 men were interrogated with color Doppler ultrasonography. The resistive index (RI) of each artery was measured for the entire cohort; peak systolic and end-diastolic velocity values were obtained in a smaller subgroup (n = 31). The artery with the lowest RI was labeled A; the other 2 arteries were identified as B and C. RESULTS: Three separate arteries were identified within the spermatic cord in all individuals. The median RI values for arteries A, B, and C were 0.70 (range, 0.48-0.82), 0.84 (0.67-0.90), and 0.84 (0.72-0.92), respectively. One-way analysis of variance showed a significant difference between the mean RIs of arteries A and B (P < .0001) and arteries A and artery C (P < .0001) but not between B and C (P = .49). Peak systolic and end-diastolic velocity values differed significantly between arteries A and B (P < .0001) and arteries A and C (P < .0001) but not between B and C (P = .31). No age effect was shown for the RI measurements of the cohort. CONCLUSIONS: Color Doppler ultrasonography enables the objective quantification of Doppler measurements of arteries within the spermatic cord. Knowledge of the normal range of Doppler measurements for spermatic cord arteries that supply the testes may be a useful adjunct to the assessment of the testes.

Adolescent↗

PubMed2004

Role of magnetic resonance angiography in the diagnosis of major aortopulmonary collateral arteries and partial anomalous pulmonary venous drainage.

BACKGROUND: Accurate diagnosis of major aortopulmonary collaterals (MAPCAs) and partial anomalous pulmonary venous drainage (PAPVD) in adult patients with congenital heart disease is important but problematic. Three-dimensional contrast-enhanced magnetic resonance angiography (MRA) provides a minimally invasive technique to allow detailed studies in a single breath-hold. METHODS AND RESULTS: We assessed the role of contrast-enhanced 3D MRA in 29 consecutive adult patients with a diagnosis of MAPCAs (n=16) or PAPVD (n=13) made by echocardiogram, cardiac catheterization, or surgical inspection. MRA was performed with a 3D spoiled gradient-echo technique with intravenous gadolinium-DTPA (0.2 mmol/kg). In both types of pathology, there was excellent correlation between MRA and the cardiac catheterization, echocardiogram, or surgical inspection. Additional information was gained for patients with MAPCAs on confluence and size of pulmonary arteries (n=13 had central arteries), pulmonary artery stenosis (n=3), aneurysmal dilatation of pulmonary artery (n=1), and additional anomalous vascular abnormality (n=3). Shunt assessment, where present (9 of 16), showed patency in all cases (100%). For adults with PAPVD, further information was obtained on drainage origin (n=11). There were no complications. CONCLUSIONS: Contrast-enhanced 3D MRA provides a fast, noninvasive, radiation-free method of accurate and comprehensive diagnosis of MAPCAs and PAPVD in adult patients.

Adolescent↗

PubMed2004

Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects.

AIM: The treatment of patients with pulmonary arterial hypertension remains a challenge. We set out to investigate the use of sildenafil, a selective inhibitor of phosphodiesterase type 5, in patients with this disease. METHODS AND RESULTS: Ten patients (8 females, mean age 34.5+/-3.3 years) with pulmonary hypertension underwent right heart catheterisation with vasodilator testing using incremental doses of intravenous sildenafil without adverse events. All patients were subsequently commenced on oral sildenafil 50 mg t.d.s. Nine patients had repeat right heart catheterisation 3 months after the commencement of oral therapy. There was a significant reduction in mean pulmonary artery pressure (from 55.8+/-5.9 to 50.4+/-6.1 mmHg, p=0.038 ) and pulmonary vascular resistance (from 10.1+/-1.7 to 8.6+/-1.5 Wood units, p=0.009 ), and an increase in cardiac output (from 4.7+/-0.3 to 5.0+/-0.4 l/min, p=0.15 ). Furthermore, there was a significant increase in the 6-minute walk test, a mean of 112 m. In response to a quality-of-life questionnaire, patients indicated marked clinical improvement on sildenafil. Sildenafil was discontinued in 1 patient due to a transient visual disturbance. The only patient previously awaiting transplantation was removed from the active transplantation list. CONCLUSIONS: Sildenafil is well tolerated in its intravenous and oral forms and appears to improve both pulmonary haemodynamics and the clinical status of patients with pulmonary hypertension after 3 months of oral therapy.

Administration, Oral↗

PubMed2004

Prevalence, predictors, and mortality significance of the causative arrhythmia in patients with electrical storm.

INTRODUCTION: Electrical storm (ES) is characterized by either refractory ventricular tachycardia (VT) or ventricular fibrillation (VF). However, little is known about the prevalence, predictors, and mortality implications of the causative arrhythmia in ES. We sought to assess the prevalence, predictors, and survival significance of VT and VF as the causative arrhythmia of ES in implantable cardioverter defibrillator (ICD) patients. METHODS AND RESULTS: Consecutive patients from January 2000 to December 2002 who presented to the ICD clinic with > or = 2 separate ventricular arrhythmic episodes requiring shock within 24 hours were included in the study. ICD interrogation confirmed the number of shocks and provided electrograms for interpretation of the causative arrhythmia. Patients were grouped as VF or VT according to the causative arrhythmia. Their prevalence, predictors, and mortality rates were compared. Of 2,028 patients assessed in the ICD clinic, 208 (10%) presented with ES. VF was the cause of ES in 99 of 208 patients, for an overall prevalence of 48%. Original ICD indication, coronary artery disease, and amiodarone therapy were predictive for the causative arrhythmia. There was no mortality difference between the VT and VF groups; however, both groups had significantly increased mortality compared to a control ICD population without ES. CONCLUSION: VF is the causative arrhythmia for a sizable proportion of patients with ES. The initial ICD indication, coronary artery disease, and amiodarone therapy are predictors of the causative arrhythmias in ES. There does not appear to be any mortality difference between ES patients with VT and VF, but mortality is increased in patients with ES versus control ICD patients without ES.

Aged↗

PubMed2002

The germ cell-specific transcription factor ALF. Structural properties and stabilization of the TATA-binding protein (TBP)-DNA complex.

The assembly and stability of the RNA polymerase II transcription preinitiation complex on a eukaryotic core promoter involves the effects of TFIIA on the interaction between TATA-binding protein (TBP) and DNA. To extend our understanding of these interactions, we characterized properties of ALF, a germ cell-specific TFIIA-like factor. ALF was able to stabilize the binding of TBP to DNA, but it could not stabilize TBP mutants A184E, N189E, E191R, and R205E nor could it facilitate binding of the TBP-like factor TRF2/TLF to a consensus TATA element. However, phosphorylation of ALF with casein kinase II resulted in the partial restoration of complex formation using mutant TBPs. Studies of ALF-TBP complexes formed on the Adenovirus Major Late (AdML) promoter revealed protection of the TATA box and upstream sequences from -38 to -20 (top strand) and -40 to -22 (bottom strand). The half-life and apparent K(D) of this complex was determined to be 650 min and 4.8 +/- 2.7 nm, respectively. The presence of ALF or TFIIA did not significantly alter the ability of TBP to bind TATA elements from several testis-specific genes. Finally, analysis of the distinct, nonhomologous internal regions of ALF and TFIIAalpha/beta using circular dichroism spectroscopy provided the first evidence to suggest that these domains are unordered, a result consistent with other genetic and biochemical properties. Overall, the results show that while the sequence and regulation of the ALF gene are distinct from its somatic cell counterpart TFIIAalpha/beta, the TFIIAgamma-dependent interactions of these factors with TBP are nearly indistinguishable in vitro. Thus, a role for ALF in the assembly and stabilization of initiation complexes in germ cells is likely to be similar or identical to the role of TFIIA in somatic cells.

Animals↗

PubMed2002

Regulation of ALF gene expression in somatic and male germ line tissues involves partial and site-specific patterns of methylation.

ALF (TFIIAalpha/beta-like factor) is a germ cell-specific counterpart of the large (alpha/beta) subunit of general transcription factor TFIIA. Here we isolated homologous GC-rich promoters from the mouse and human ALF genes and used promoter deletion analysis to identify sequences active in COS-7 and 293 cells. Further, bisulfite sequence analysis of the mouse ALF promoter showed that all 21 CpG dinucleotides between -179 and +207 were partially methylated in five somatic tissues, brain, heart, liver, lung, and muscle, and in epididymal spermatozoa from adult mice. In contrast, DNA from prepubertal mouse testis and from purified spermatocytes were unmethylated except at C(+19)G and C(+170)G. We also found that ALF expression correlates with a strong promoter-proximal DNase I-hypersensitive site present in nuclei from testis but not from liver. Finally we show that in vitro methylation of the ALF promoter inhibits activity and that 5-aza-2'-deoxycytidine treatment reactivates the endogenous ALF gene in a panel of seven different mouse and human somatic cell lines. Overall the results show that silencing in somatic cells is methylation-dependent and reversible and that a unique CpG-specific methylation pattern at the ALF promoter precedes expression in pachytene spermatocytes. This pattern is transient as remethylation of the ALF promoter in haploid germ cell DNA has occurred by the time spermatozoa are present in the epididymis.

3T3 Cells↗

PubMed2002

Primary psoas abscess.

Psoas abscess is an uncommon condition with varied etiology. Diagnosis is based on symptoms, signs, and CT scan of the abdomen. Treatment consists of adequate drainage either percutaneously or surgically with antibiotic coverage. Serious complications such as sepsis and mortality may result if there is a delay in treatment.

Adult↗

PubMed2002

N-phenylethyl amitriptyline in rat sciatic nerve blockade.

BACKGROUND: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na(+) channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties. METHODS: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH(3) cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model. RESULTS: In vitro, N-phenylethyl amitriptyline at 10 microm elicits a greater block of Na(+) channels than amitriptyline (resting block of approximately 90% vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm. CONCLUSION: N-phenylethyl amitriptyline appears to have a narrow therapeutic range but is much more potent than lidocaine, providing a block duration several times longer than any clinically used local anesthetic. Further work in animal models of neuropathic pain will assess the potential use of this drug.

Amitriptyline↗