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Biomedical subjects

R Dhillon

Publications and source records attributed to R Dhillon.

At least 19 recordsLinked to original sources
PubMed2006

Screen-detected mucinous breast carcinoma: potential for delayed diagnosis.

AIM: To describe the imaging features of 34 screen-detected mucinous carcinomas lesions. MATERIALS AND METHODS: The BreastScreen Western Australia (WA) database between January 1991 and December 2003 was searched. During this period, 214,507 women were screened and 2745 cases of invasive carcinoma and 45 cases of mucinous carcinoma were recorded. Case notes, radiology films and pathology reports of patients with mucinous carcinoma were reviewed. Thirty-four radiologically detected pure mucinous carcinomas are described. RESULTS: Of the pure mucinous carcinomas, the average age at diagnosis was 65 years (range 48-82 years), which was higher than that of other women with breast cancer (average age 60 years) screened at BreastScreen WA. Characteristic mammographic features of mucinous carcinoma are well-circumscribed masses with lobulated margins (26/34). Only 39% (11/28) of tumours were detected at ultrasound, as the smaller lesions less than 15mm in diameter were often isoechoic with normal fat. Where histological grade was reported at excision, most (25/26) were low to medium-grade tumours (Bloom, Richardson and Elston grade I and II). A significant number of lesions (13/34) were evident on the previous screening examination where they were misinterpreted as benign lesions. However, none of these cases had positive axillary lymph nodes at final diagnosis. CONCLUSION: Although mammographically benign appearances of mucinous carcinoma caused a delay in diagnosis in 38% of the present cases, mucinous breast carcinomas have a favourable prognosis, as they are often low-grade tumours and rarely metastasize. Delay in diagnosis for these tumours in a screening programme may not lead to a significant adverse outcome for most women.

Adenocarcinoma, Mucinous↗
PubMed2005

Staged surgical management of hypoplastic left heart syndrome: a single institution 12 year experience.

OBJECTIVE: To describe a 12 year experience with staged surgical management of the hypoplastic left heart syndrome (HLHS) and to identify the factors that influenced outcome. METHODS: Between December 1992 and June 2004, 333 patients with HLHS underwent a Norwood procedure (median age 4 days, range 0-217 days). Subsequently 203 patients underwent a bidirectional Glenn procedure (stage II) and 81 patients underwent a modified Fontan procedure (stage III). Follow up was complete (median interval 3.7 years, range 32 days to 11.3 years). RESULTS: Early mortality after the Norwood procedure was 29% (n = 95); this decreased from 46% (first year) to 16% (last year; p < 0.05). Between stages, 49 patients died, 27 before stage II and 22 between stages II and III. There were one early and three late deaths after stage III. Actuarial survival (SEM) was 58% (3%) at one year and 50% (3%) at five and 10 years. On multivariable analysis, five factors influenced early mortality after the Norwood procedure (p < 0.05). Pulmonary blood flow supplied by a right ventricle to pulmonary artery (RV-PA) conduit, arch reconstruction with pulmonary homograft patch, and increased operative weight improved early mortality. Increased periods of cardiopulmonary bypass and deep hypothermic circulatory arrest increased early mortality. Similar factors also influenced actuarial survival after the Norwood procedure. CONCLUSION: This study identified an improvement in outcome after staged surgical management of HLHS, which was primarily attributable to changes in surgical technique. The RV-PA conduit, in particular, was associated with a notable and independent improvement in early and actuarial survival.

Cardiopulmonary Bypass↗
PubMed2003

Sildenafil as a treatment for pulmonary hypertension.

Severe, chronic pulmonary hypertension in childhood is uncommon, difficult to treat, and carries a poor prognosis. Sildenafil (Viagra, Pfizer) has been used successfully in adults with pulmonary hypertension as monotherapy or in combination with inhaled prostacyclin. Here we report on its use in three children.

Administration, Oral↗
PubMed2002

Transcatheter closure of atrial septal defect preserves right ventricular function.

OBJECTIVES: To determine the effects of atrial septal defects (ASD) and their closure on systolic and diastolic right and left ventricular function; and by comparing surgical closure with transcatheter device closure, to establish differences attributable to cardiopulmonary bypass. DESIGN: Cross sectionally guided M mode echocardiographic ventricular long axis function was measured prospectively before and within one week after ASD closure by device in 17 patients and by surgery in 12 patients, and compared with 18 normal subjects. RESULTS: All indices of right ventricular function were impaired after surgery: mean total excursion, -1.89 cm (95% confidence interval (CI), -2.18 to -1.59); peak shortening rate, -9.09 cm/s (-10.82 to -7.35); peak lengthening rate, -9.26 cm/s (-11.09 to -7.43). Total excursion and peak lengthening rate were preserved after device closure, at -0.12 cm (-0.28 to 0.05) and 0.01 cm/s (-2.29 to 2.31), respectively. Left ventricular free wall function was unchanged after closure by either method, while all septal measurements were reduced after closure by either method (changes ranging from -3.51 to -0.32; 95% CI ranging from -4.90 to -0.13). CONCLUSIONS: Left ventricular free wall function is unaffected by ASD closure, whereas septal function is impaired, irrespective of the method of closure. Right ventricular function, both systolic and diastolic, is impaired by cardiopulmonary bypass but preserved after device closure. These findings support the transcatheter approach to ASD closure in anatomically suitable defects.

Balloon Occlusion↗
PubMed2001

A genomewide scan for loci predisposing to type 2 diabetes in a U.K. population (the Diabetes UK Warren 2 Repository): analysis of 573 pedigrees provides independent replication of a susceptibility locus on chromosome 1q.

Improved molecular understanding of the pathogenesis of type 2 diabetes is essential if current therapeutic and preventative options are to be extended. To identify diabetes-susceptibility genes, we have completed a primary (418-marker, 9-cM) autosomal-genome scan of 743 sib pairs (573 pedigrees) with type 2 diabetes who are from the Diabetes UK Warren 2 repository. Nonparametric linkage analysis of the entire data set identified seven regions showing evidence for linkage, with allele-sharing LOD scores > or =1.18 (P< or =.01). The strongest evidence was seen on chromosomes 8p21-22 (near D8S258 [LOD score 2.55]) and 10q23.3 (near D10S1765 [LOD score 1.99]), both coinciding with regions identified in previous scans in European subjects. This was also true of two lesser regions identified, on chromosomes 5q13 (D5S647 [LOD score 1.22] and 5q32 (D5S436 [LOD score 1.22]). Loci on 7p15.3 (LOD score 1.31) and 8q24.2 (LOD score 1.41) are novel. The final region showing evidence for linkage, on chromosome 1q24-25 (near D1S218 [LOD score 1.50]), colocalizes with evidence for linkage to diabetes found in Utah, French, and Pima families and in the GK rat. After dense-map genotyping (mean marker spacing 4.4 cM), evidence for linkage to this region increased to a LOD score of 1.98. Conditional analyses revealed nominally significant interactions between this locus and the regions on chromosomes 10q23.3 (P=.01) and 5q32 (P=.02). These data, derived from one of the largest genome scans undertaken in this condition, confirm that individual susceptibility-gene effects for type 2 diabetes are likely to be modest in size. Taken with genome scans in other populations, they provide both replication of previous evidence indicating the presence of a diabetes-susceptibility locus on chromosome 1q24-25 and support for the existence of additional loci on chromosomes 5, 8, and 10. These data should accelerate positional cloning efforts in these regions of interest.

Chromosome Mapping↗
PubMed2001

Studies of association between the gene for calpain-10 and type 2 diabetes mellitus in the United Kingdom.

Variation in CAPN10, the gene encoding the ubiquitously expressed cysteine protease calpain-10, has been associated with type 2 diabetes in Mexican Americans and in two northern-European populations, from Finland and Germany. We have studied CAPN10 in white subjects of British/Irish ancestry, using both family-based and case-control studies. In 743 sib pairs, there was no evidence of linkage at the CAPN10 locus, which thereby excluded it as a diabetes-susceptibility gene, with an overall sib recurrence risk, lambda(S), of 1.25. We examined four single-nucleotide polymorphisms (SNP-44, -43, -19, and -63) previously either associated with type 2 diabetes or implicated in transcriptional regulation of calpain-10 expression. We did not find any association between SNP-43, -19, and -63, either individually or as part of the previously described risk haplotypes. We did, however, observe significantly increased (P=.033) transmission of the less common C allele at SNP-44, to affected offspring in parents-offspring trios (odds ratio 1.6). An independent U.K. case-control study and a small discordant-sib study did not show significant association individually. In a combined analysis of all U.K. studies (P=.015) and in combination with a Mexican American study (P=.004), the C allele at SNP-44 is associated with type 2 diabetes. Sequencing of the coding region of CAPN10 in a group of U.K. subjects revealed four coding polymorphisms-L34V, T504A, R555C, and V666I. The T504A polymorphism was in perfect linkage disequilibrium with the diabetes-associated C allele at SNP-44, suggesting that the synthesis of a mutant protein and/or altered transcriptional regulation could contribute to diabetes risk. In conclusion, we were not able to replicate the association of the specific calpain-10 alleles identified by Horikawa et al. but suggest that other alleles at this locus may increase type 2 diabetes risk in the U.K. population.

Alleles↗
PubMed2001

Chondroid metaplasia in a fibroepithelial polyp of the tongue.

This report describes the development of chondroid metaplasia within a fibroepithelial polyp situated on the tongue. Although fibroepithelial polyps in this location are not unusual, chondroid metaplasia in such a lesion in this position has not, as far as the authors are aware, been described previously. The aetiology and the pathogenesis of the lesion are discussed.

Adult↗
PubMed2000

Alkaline earth complexes of 1,4,7,10-tetrakis(2-hydroxyethyl)- and 1,4,7,10-tetrakis(2-methoxyethyl)-1,4,7,10-tetraazacyclododecane: an equilibrium and kinetic study.

The 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane complexes [M(thec12)]2+, where M2+ = Mg2+, Ca2+, Sr2+, and Ba2+, are characterized by log(K/dm3 mol-1) = 2.86 +/- 0.09, 7.41 +/- 0.04, 6.47 +/- 0.04, and 4.84 +/- 0.03 at 298.2 K in aqueous Et4NClO4 (I = 0.10 mol dm-3), where K is a potentiometrically determined stability constant. The analogous literature values for the 1,4,7,10-tetrakis(2-methoxyethyl)-1,4,7,10-tetraazacyclododecane complexes [M(tmec12)]2+ are 2.47, 5.47, 5.00, and 4.72. The enantiomerization of eight-coordinate delta- and lambda-[M(thec12)]2+ is characterized by k(298.2 K) = 2310 +/- 260, 582 +/- 17, and 445 +/- 5 s-1, delta H++ = 19.1 +/- 0.8, 33.3 +/- 0.5, and 43.9 +/- 0.4 kJ mol-1, and delta S++ = -117 +/- 4, -80.3 +/- 1.8, and -47.0 +/- 1.3 J K-1 mol-1 when M2+ = Mg2+, Ca2+, and Ba2+, respectively, in methanol-12C-d4 as shown by 13C NMR spectroscopy. For the enantiomerization of eight-coordinate delta- and lambda-[M(tmec12)]2+, k(298.2 K) = 310 +/- 1 and 688 +/- 3 s-1, delta H++ = 54.0 +/- 0.2 and 39.6 +/- 0.1 kJ mol-1, and delta S++ = -16.1 +/- 0.5 and -57.9 +/- 0.3 J K-1 mol-1 when M2+ = Ca2+ and Ba2+, respectively. However, [Mg(tmec12)]2+ has a seven-coordinate structure where one of the methoxy groups is not coordinated and exchange of the methoxy groups between the coordinated and free states is characterized by k(298.2 K) = 163,000 +/- 8000 s-1, delta H++ = 35.8 +/- 0.4 kJ mol-1, and delta S++ = -25.1 +/- 1.7 J K-1 mol-1. The intermolecular exchange of thec12 and tmec12 between the coordinated and free states is substantially slower than the enantiomerizations in the first five complexes and the intramolecular exchange process observed in [Mg(tmec12)]2+.

Journal Article↗
PubMed2000

Psychological well-being and coping patterns in infertile men.

OBJECTIVE: To determine whether differences existed in mood and coping styles among fertile men, oligoasthenospermic men, or euspermic men whose wives were undergoing ovulation stimulation with clomiphene and IUI. DESIGN: A cross-sectional research design. SETTING: Hospital-based academic fertility clinic. PATIENT(S): 30 fertile men with currently pregnant wives, 30 euspermic and 30 oligoasthenospermic men in couples undergoing ovulation stimulation with clomiphene and IUI. INTERVENTION(S): Measures of psychological well-being and coping were administered. MAIN OUTCOME MEASURE(S): Biodemographic information, and psychometric measures of mood and coping. RESULT(S): There were no significant differences among the groups on any of the measures except the Family Inventory of Life Events (FILE), in which fertile men reported higher stress levels. FILE scores in all groups were moderate, indicating typical levels of family stress. CONCLUSION(S): Mood and coping in the three groups were similar. This study suggests that men's psychological adjustment to their own infertility and to unexplained infertility is generally healthy.

Adaptation, Psychological↗
PubMed2000

Coarctation of the aorta in dizygotic twins.

The incidence of congenital heart disease is higher in monozygotic than dizygotic twins, with a higher concordance rate. Although coarctation of the aorta has previously been reported in monozygotic twins, to the best of our knowledge it has not been described in dizygotic twins. We report here such a concurrence in dizygotic twins conceived by in-vitro fertilisation. The finding provides support for both genetic and environmental factors in the aetiology of congenital heart disease. Furthermore, it highlights our lack of data regarding the outcome of in-vitro fertilisation.

Aortic Coarctation↗
PubMed2000

Pulmonary vascular-bronchial interactions: acute reduction in pulmonary blood flow alters lung mechanics.

BACKGROUND: Postoperative pulmonary hypertension in children after congenital heart surgery is a risk factor for death and is associated with severe acute changes in both pulmonary vascular resistance and lung mechanics. OBJECTIVE: To examine the impact of changes in pulmonary blood flow on lung mechanics in preoperative children with congenital heart disease, in order to assess the cause-effect relation of pulmonary vascular-bronchial interactions. DESIGN: Prospective, cross sectional study. SETTING: Cardiac catheterisation laboratory, general anaesthesia with mechanical ventilation. INTERVENTIONS: Variation of pulmonary blood flow (Qp) by either balloon occlusion of an atrial septal defect before interventional closure, or by complete occlusion of the pulmonary artery during balloon pulmonary valvuloplasty for pulmonary valve stenosis. MAIN OUTCOME MEASURES: Ventilatory tidal volume (Vt), dynamic respiratory system compliance (Cdyn), respiratory system resistance (Rrs). RESULTS: 28 occlusions were examined in nine patients with atrial septal defect (median age 9.5 years) and 22 in eight patients with pulmonary stenosis (median age 1.2 years). Normalisation of Qp during balloon occlusion of atrial septal defect caused no significant change in airway pressures and Rrs, but there was a small decrease in Vt (mean (SD): 9.61 (0.85) to 9.52 (0.97) ml/kg; p < 0.05) and Cdyn (0.64 (0.11) to 0.59 (0.10) ml/cm H(2)O*kg; p < 0.01). These changes were more pronounced when there was complete cessation of Qp during balloon valvuloplasty in pulmonary stenosis, with a fall in Vt (9.71 (2.95) to 9.32 (2.84) ml/kg; p < 0.05) and Cdyn (0.72 (0.29) to 0.64 (0.26) ml/cm H(2)O*kg; p < 0.001), and there was also an increase in Rrs (25.1 (1. 7) to 28.8 (1.6) cm H(2)O/litre*s; p < 0.01). All these changes exceeded the variability of the baseline measurements more than threefold. CONCLUSIONS: Acute changes in pulmonary blood flow are associated with simultaneous changes in lung mechanics. While these changes are small they may represent a valid model to explain the pathophysiological impact of spontaneous changes in pulmonary blood flow in clinically more critical situations in children with congenital heart disease.

Adolescent↗
PubMed1999

Transcatheter closure of atrial septal defects in adults with the Amplatzer septal occluder.

OBJECTIVE: To assess the efficacy and complications of device occlusion of atrial septal defects in adults, using the Amplatzer septal occluder (ASO). DESIGN: A prospective interventional study. SETTING: Paediatric cardiology departments in two European teaching hospitals. PATIENTS: The first 20 patients accepted for atrial septal defect device occlusion, on the basis of transoesophageal echocardiography. Sixteen patients had larger defects with right heart dilatation, while the primary indication for closure in four was a history of early paradoxical embolism. INTERVENTIONS: Transcatheter atrial septal defect occlusions performed under transoesophageal echocardiography and fluoroscopic guidance between December 1996 and June 1998. OUTCOME MEASURES: Success of deployment of ASO devices, procedure and fluoroscopic times, complications, and symptoms. RESULTS: The ASO device was successfully implanted in all 20 patients (14 female), median age 44.2 years, with no complications. Of the 16 patients with right heart dilatation, the median Qp:Qs was 2.5:1. Defects measured 11-22 mm (median 18) on transoesophageal echocardiography, with balloon sized diameter (and device size) of 13-28 mm (median 20). For all 20 patients, the procedure time ranged from 38-78 minutes (median 61), and fluoroscopy 8.4-24.7 minutes (median 15.2). There were residual shunts in three patients at the end of the procedure, which were trivial (</= 1 mm) as assessed by transoesophageal echocardiography, and persisted for more than six months in only one patient. Follow up ranged from 0.1-1.5 years (median 0.7). There have been no late complications. CONCLUSIONS: The ASO device can be used successfully to close selected oval fossa defects in adults, with minimal procedural morbidity and excellent early results.

Adolescent↗
PubMed1998

Effect of dopamine on renal function after arteriography in patients with pre-existing renal insufficiency.

Contrast media-induced nephropathy is one of the leading causes of hospital-acquired renal failure, occurring most frequently in patients with pre-existing renal insufficiency. We prospectively studied 55 patients with chronic renal insufficiency (serum creatinine concentration 1.4 to 3.5 mg/dl) who underwent abdominal aortography and arteriography of the lower extremities. The patients were randomized into two groups. Group 1, 28 patients, received dopamine 2.5 mcg/kg beginning 1 hour before arteriography and continuing for 12 hours. Group 2 received an equal volume of saline for the same period of time. Serum creatinine and 12-hour creatinine clearance were measured before arteriography and for 4 consecutive days afterward. Acute contrast-induced decrease in renal function was defined as increase in the baseline serum creatinine concentration > or = 0.5 mg/dl. On day 1 postarteriography the serum creatinine increased from baseline .193 mg/dl for controls while the dopamine group decreased slightly from baseline .018 mg/dl (p = 0.002). Excepting day 1 postarteriography, there was no statistical difference between groups, and serum levels for both groups increased linearly from baseline across time (dopamine p = 0.028, control p = 0.025). In patients with pre-arteriography baseline serum levels greater than or equal to 2.0 mg/dl, however, the increase in serum creatinine from baseline levels was consistently and significantly greater in the control group through the fourth day (0.012 < or = p < or = 0.049). Creatinine clearance did not change significantly from baseline after arteriography in the dopamine group (baseline versus days 1 through 4, 0.238 < or = p < or = 0.968); however, the control group showed a significant linear decrease in creatinine clearance from baseline through the fourth day after arteriography (p = 0.016). Dopamine infusion prevented a rise in serum creatinine 24 hours after angiography in patients with pre-existing renal insufficiency, and protected against contrast-induced decrease in renal function in patients whose baseline serum creatinine was > or = 2.0 mg/dl.

Aged↗
PubMed1997

The Neurospora crassa cya-5 nuclear gene encodes a protein with a region of homology to the Saccharomyces cerevisiae PET309 protein and is required in a post-transcriptional step for the expression of the mitochondrially encoded COXI protein.

The cya-5 nuclear mutant of Neurosopora crassa was previously shown to be deficient in cytochrome aa3, cytochrome c oxidase activity, and the immunologically detectable COXI protein. We have now demonstrated that the mitochondria of this mutant contain mRNA for the COXI protein and that COXI cannot be detected during pulse-chase labeling experiments of mitochondrial translation products. Cloning and analysis of the cya-5 gene reveal a long open reading frame capable of encoding a 1136 amino-acid protein. Sequence analysis suggests that the potential CYA-5 protein contains a mitochondrial targeting sequence at its amino-terminus. The long open reading frame also contains a 200 amino-acid region with homology to the PET309 protein, which is required for the production or stability of intron-containing coxI mRNAs, as well as the translation of mature coxI mRNAs, in the yeast Saccharomyces cerevisiae. These data suggest that the CYA-5 protein of N. crassa is required in a post-transcriptional step for COXI expression, most probably for the efficient translation of coxI mRNA.

Amino Acid Sequence↗