Myotonic dystrophy: from linkage with secretor status to mutation detection.
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Adult↗
Biomedical subjects
G R Sutherland
Publications and source records attributed to G R Sutherland.
Intra-operative myocardial ischaemia detected by biplane transoesophageal echocardiography during transurethral prostatectomy.
Recent studies have shown an increased late mortality rate due to cardiovascular causes after transurethral compared with open prostatectomy. This has been linked to the demonstration of haemodynamic changes during transurethral prostatectomy, which may cause ischaemic myocardial injury. We used transoesophageal echocardiography (currently the most sensitive modality for detecting myocardial ischaemia) to study 26 patients during prostatectomy under general anaesthesia. Evidence of myocardial ischaemia (as shown by the development of new regional wall motion abnormalities of the left ventricle) occurred in 4 of 22 patients during transurethral and in 3 of 4 patients during retropubic prostatectomy. An intra-operative fall in systolic as well as diastolic blood pressure occurred in 21 of 22 patients during the transurethral procedure and in all 4 patients during retropubic prostatectomy. The duration of anaesthesia and the operation, and the intra-operative blood loss did not differ significantly between patients with and without evidence of intra-operative myocardial ischaemia. However, the maximum intra-operative fall in systolic and diastolic blood pressure, as well as the mass of the prostatic tissue removed, were significantly greater in patients with than in those without evidence of intra-operative myocardial ischaemia, suggesting that the latter may be related to the extent of surgery and the degree of intraoperative hypotension. In this study, 7 of 26 patients (27%) showed evidence of myocardial ischaemia during prostatectomy. However, it remains difficult to explain why intra-operative myocardial ischaemia should result in an increased cardiovascular mortality rate several years after the operation.
Aged↗
Acute pulmonary artery thromboembolism treated with thrombolysis: diagnostic and monitoring uses of transoesophageal echocardiography.
The central pulmonary arteries and any thrombus within them can be imaged by transoesophageal echocardiography. Its use is reported in the diagnosis and subsequent management of a patient with acute pulmonary embolism, whose response to thrombolytic treatment was monitored by further transoesophageal studies. Transoesophageal echocardiography may be a valuable primary diagnostic procedure in patients who seem to have sustained a significant pulmonary embolus and require urgent intervention.
Echocardiography↗
Thrombolysis as an emergency treatment for a thrombosed prosthetic mitral valve diagnosed by transoesophageal echocardiography.
Intravenous streptokinase was used as an emergency treatment for acute thrombotic obstruction of a Björk-Shiley prosthesis in the mitral position. Transoesophageal echocardiography established the diagnosis and was used to monitor the clinical response to treatment. Because the patient was haemodynamically stable after thrombolysis and because transoesophageal echocardiography showed that the prosthesis was free of thrombus the mitral prosthesis was not replaced.
Aged↗
Additional value of biplane transoesophageal imaging in assessment of mitral valve prostheses.
OBJECTIVES: To determine whether biplane transoesophageal imaging offers advantages in the evaluation of mitral prostheses when compared with standard single transverse plane imaging or the precordial approach in suspected prosthetic dysfunction. DESIGN: Prospective mitral valve prosthesis in situ using precordial and biplane transoesophageal ultrasonography. SETTING: Tertiary cardiac referral centre. SUBJECTS: 67 consecutive patients with suspected dysfunction of a mitral valve prosthesis (16 had bioprostheses and 51 mechanical prostheses) who underwent precordial, transverse plane, and biplane transoesophageal echocardiography. Correlative invasive confirmation from surgery or angiography, or both, was available in 44 patients. MAIN OUTCOME MEASURES: Number, type, and site of leak according to the three means of scanning. RESULTS: Transverse plane transoesophageal imaging alone identified all 31 medial/lateral paravalvar leaks but only 24/30 of the anterior/posterior leaks. Combining the information from both imaging planes confirmed that biplane scanning identified all paravalvar leaks. Five of the six patients with prosthetic valve endocarditis, all three with valvar thrombus or obstruction, and all three with mitral annulus rupture were diagnosed from transverse plane imaging alone. Longitudinal plane imaging alone enabled diagnosis of the remaining case of prosthetic endocarditis and a further case of subvalvar pannus formation. CONCLUSIONS: Transverse plane transoesophageal imaging was superior to the longitudinal imaging in identifying medial and lateral lesions around the sewing ring of a mitral valve prosthesis. Longitudinal plane imaging was superior in identifying anterior and posterior lesions. Biplane imaging is therefore an important development in the study of mitral prosthesis function.
Adult↗
Cerebral metabolic and histological effects of thioacetamide-induced liver failure.
Acute liver failure was induced in rats by successive administrations of thioacetamide over 3 days. At progressing stages of hepatic encephalopathy (HE), brains were fixed with microwave irradiation for analysis of metabolite levels or with formaldehyde for histopathological analysis. Metabolite levels were determined using 1H-nuclear magnetic resonance spectroscopy of perchloric acid extracts of the frontal cortex, parietal or occipital cortex, hippocampus, striatum, brain stem, and cerebellum. After thioacetamide treatment, thioacetamide and its metabolites were detected in the brains at levels that did not correlate with the stage of HE. No changes were observed in the levels of N-acetylaspartate, alanine, gamma-aminobutyric acid, aspartate, or inositol in any brain region after thioacetamide treatment. HE was accompanied by elevated glutamine, glucose, and lactate throughout the brain. At all stages of HE, taurine was decreased in the neocortex and hippocampus, and glutamate and choline compounds were decreased in the frontal cortex. None of the metabolite changes showed progression with the stage of HE. Progressing HE was accompanied by increasing neuronal injury in layer III of the neocortex, in the Purkinje cells of the cerebellum, and in the hippocampus, particularly in the CA4 sector. The similarity of this distribution of injury to that associated with excitotoxic injury suggests that metabolic abnormalities after acute hepatic failure may give rise to adverse effects at excitatory (glutamatergic) neuronal receptors, leading to neuronal injury and clinical symptoms of progressing encephalopathy in this model. However, neuronal injury and the presence of thioacetamide and its metabolites in the brain raise questions about the validity of thioacetamide-induced liver failure as a model for clinical HE.
Animals↗
Localization of the human vitamin D 24-hydroxylase gene (CYP24) to chromosome 20q13.2-->q13.3.
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Chromosome Mapping↗
Integration of the cytogenetic and genetic linkage maps of human chromosome 16 using 50 physical intervals and 50 polymorphic loci.
A comprehensive genetic linkage map constructed from 50 loci represented by 68 markers was anchored to 50 cytogenetically defined intervals on human chromosome 16. The linear order of the loci on the cytogenetic map was compatible with the independently derived linear order on the genetic map. The sex-averaged genetic length is 164.5 cM, with an average distance between loci of 3.3 cM. Sex-specific distances are 132.8 cM in males and 201.8 cM in females. This is the first detailed synthesis of genetic and cytogenetic maps for any human chromosome and is the first step in correlating the genetic and physical maps of this chromosome. The combined map, containing 15 loci with a minimum heterozygosity of 60% and 6 PCR-formatted microsatellite markers, will be useful for assignment and regional localization of disease genes to this chromosome.
Chromosome Mapping↗
A microsatellite marker within the duplicated D16S79 locus has a null allele; significance for linkage mapping.
The dinucleotide repeat 16AC66f3 was characterised from D16S79A within a duplicated section of 16p13.11, which is duplicated on all normal chromosome 16's. This marker has a common null allele caused by polymorphism within one of the primer sites. A redesigned primer overcame this problem; however, this allowed amplification of two dinucleotide repeats, at D16S79A and D16S79B, with an overlapping and uninterpretable distribution of alleles. Thus, the 16AC66F3 marker with a null allele is potentially useful for linkage mapping, as it avoids the ambiguity associated with the genotyping of homologous AC repeats at this duplicated locus. The distribution of additional D16S79 RFLPs flanking FRA16A is clarified.
Alleles↗
Quantification of left-to-right atrial shunting and defect size after balloon mitral commissurotomy using biplane transesophageal echocardiography, color flow Doppler mapping, and the principle of proximal flow convergence.
BACKGROUND: The flow convergence region (FCR), a zone of progressive laminar velocity acceleration, can be imaged by color Doppler proximal to stenotic and regurgitant orifices. Theoretically, FCR proximal to a discrete circular and planar orifice consists of concentric hemispheric shells of equal and accelerating velocities centered at the orifice. According to the continuity principle, flow rate across any of these isovelocity surfaces equals flow rate through the orifice. The aim of this study was to investigate whether these principles could be applied to quantify left-to-right shunting and the size of atrial septal defects after balloon mitral commissurotomy. METHODS AND RESULTS: Biplane transesophageal echocardiography (TEE) with color flow imaging was performed on 36 consecutive patients (mean age, 57 +/- 16 years; range, 14-78 years) immediately before and within 24 hours of balloon (Inoue, n = 33; Mansfield, n = 3) mitral commissurotomy. Left-to-right atrial shunting was detected by TEE in 33 patients (92%) and by oximetry in 11 patients (31%). The radius r of FCR was measured from the first aliasing limit, at a Nyquist velocity reduced to 11 cm/sec by zero-shifting, to the orifice in the atrial septum. FCR was assumed to be hemispherical. Hence, flow rate (Q) was calculated as 2 pi r2 Vr, where Vr is the velocity at a radial distance r. The velocity profile of transatrial flow was assessed by means of high pulse repetition frequency, from which the maximum flow velocity (Vp) and the velocity-time integral (VTI) were obtained. The flow area of the atrial septal defect was calculated as Qm, the maximal flow rate, divided by Vp. Hence, shunt flow was calculated as flow area x VTI x heart rate. FCR was analyzed in two orthogonal planes. Mean Qm (38.1 +/- 26.5 versus 5.3 +/- 2.7 mL/sec), flow area (22.1 +/- 11.2 versus 4.4 +/- 2.0 mm2), and shunt flow (1,590 +/- 1,070 versus 200 +/- 130 mL/min) on transverse plane imaging were all significantly higher in patients with shunts detected by oximetry than in those without. Similar results were obtained from longitudinal plane imaging. Qm correlated well with oximetric shunt flow (r = 0.89-0.94, p < 0.001) and shunt ratio (r = 0.91-0.94, p < 0.001). Flow area correlated closely (r = 0.93-0.94, p < 0.001) with area determined by direct measurement from two-dimensional echocardiography. Shunt flow determined by FCR also correlated closely (r = 0.94-0.98, p < 0.001) with that determined by oximetry and that derived from two-dimensional echocardiography and pulsed Doppler (r = 0.96, p < 0.001). CONCLUSIONS: The flow convergence region imaged by TEE color flow mapping provides new and accurate quantitative information on atrial shunt flow and defect size after balloon mitral valvotomy. It is a quick, reliable, and fairly simple method that can be readily incorporated into routine clinical practice.
Adolescent↗
Dilated cardiomyopathy in haemophiliacs infected with the human immunodeficiency virus.
Infection with the human immunodeficiency virus (HIV) can result in several cardiac abnormalities including dilated cardiomyopathy. These phenomena have been described in people contracting the virus through sexual intercourse, injection drug use and by vertical transmission. We have identified recently two Scottish haemophiliacs who have developed dilated cardiomyopathy in the context of HIV infection acquired through treatment with contaminated factor VIII. The significance of this finding is discussed.
Adolescent↗
The detection of fat embolism by transoesophageal echocardiography during reamed intramedullary nailing. A study of 24 patients with femoral and tibial fractures.
We performed transoesophageal echocardiography on 24 patients during reamed intramedullary nailing of 17 tibial and seven femoral fractures. In 14 patients there was only minimal evidence of emboli passing through the heart, but in six copious showers of small emboli (< 10 mm maximum dimension) were observed. In four other patients, there were also multiple large emboli (> 10 mm maximum dimension). Three of these patients developed fat embolism syndrome postoperatively and one died. Earlier nailing was associated with smaller quantities of emboli.
Adolescent↗
Familial Mediterranean fever (FMF) in Moroccan Jews: demonstration of a founder effect by extended haplotype analysis.
Familial Mediterranean fever (FMF) is an autosomal recessive disease causing attacks of fever and serositis. The FMF gene (designated "MEF") is on 16p, with the gene order 16cen-D16S80-MEF-D16S94-D16S283-D16S291-++ +16pter. Here we report the association of FMF susceptibility with alleles as D16S94, D16S283, and D16S291 among 31 non-Ashkenazi Jewish families (14 Moroccan, 17 non-Moroccan). We observed highly significant associations at D16S283 and D16S291 among the Moroccan families. For the non-Moroccans, only the allelic association at D16S94 approached statistical significance. Haplotype analysis showed that 18/25 Moroccan FMF chromosomes, versus 0/21 noncarrier chromosomes, bore a specific haplotype for D16S94-D16S283-D16S291. Among non-Moroccans this haplotype was present in 6/26 FMF chromosomes versus 1/28 controls. Both groups of families are largely descended from Jews who fled the Spanish Inquisition. The strong haplotype association seen among the Moroccans is most likely a founder effect, given the recent origin and genetic isolation of the Moroccan Jewish community. The lower haplotype frequency among non-Moroccan carriers may reflect differences both in history and in population genetics.
Alleles↗
Unusual behaviour of a human autosome having two rare folate sensitive fragile sites.
A mother and daughter who have two rare folate sensitive fragile sites on the same homolog of chromosome 12 are recorded. This confirms the folate sensitive nature of the fragile site at 12q24.13. The behaviour of the chromosome with the two fragile sites is described, which includes the propensity for the two fragile sites to associate with each other when simultaneously expressed.
Adult↗
Genotype-phenotype relationships in fragile X syndrome: a family study.
Relationships between the measures of intellectual and physical status in the fragile X syndrome and the size of amplification of the fragile X-specific fragment, equivalent to the number of CCG repeats within the FMR1 locus, were studied by a maximum-likelihood scoring technique for analysis of pedigree data. This allows for estimation of random effects (genetic and environmental variance) concurrently with other (fixed) effects in a quantitative trait. FMR1 expression is usually shut down in males penetrant for the fragile X syndrome who have hypermethylated CCG amplifications of > or = 0.6 kb. The assumption of the step versus curvilinear function representing this relationship was tested by the likelihood-ratio criterion. The maximum-likelihood parameters were based on the most appropriate model for each measure. The results were indicative of the presence of a curvilinear relationship between the amplification size and the two intellectual scores, the Peabody Picture Vocabulary Test and Block Design Test, measuring verbal and spatial abilities, respectively. Reasons for the unexpected curvilinear regression between the amplification size and intellectual scores were explained further by methylation analysis of fragile X males with amplifications of 0.6 < delta < or = 1.2 kb who appeared to be responsible for the curvilinearity of the relationship. Four of these showed unmethylated status of the amplified bands in lymphocytes, which were presumably transcriptionally active. Removal of the aberrant individuals led to the anticipated step function between amplification and intellectual scores. For the combined anthropometric score, as well as for several single physical measures, the step function was the most appropriate model regardless of the inclusion or omission of the aberrant individuals in the pedigree sample.
Adolescent↗
Nuclear magnetic resonance study of cerebrospinal fluid from patients with multiple sclerosis.
Proton nuclear magnetic resonance (NMR) spectroscopy was used to examine cerebrospinal fluid (CSF) from patients (n = 30) with actively progressive multiple sclerosis (MS). Metabolite concentrations obtained from the spectra were compared to those determined from the spectra of CSF from control patients (n = 27) with benign spinal disorders. No significant difference was found between the 2 groups for most constituents, including lactate, glutamine, citrate, creatine and creatinine, and glucose. Acetate levels were significantly higher in MS patients, while formate levels were significantly lower, than the controls. There were no significant differences in metabolite concentrations in CSF from early and longstanding MS patients. A peak due to an unidentified compound was found at 2.82 ppm in the spectra of CSF from patients with actively progressive MS, but not in the spectra of CSF from the controls. The peak was not found in spectra of CSF from patients with AIDS dementia complex (n = 9) or Parkinson's disease (n = 5), but it did appear in spectra of CSF from 1 patient with Jakob-Creutzfeldt disease (out of 3 examined) and from 1 patient (out of 7) with Guillain-Barré disease. The unidentified compound is volatile and, from the chemical shift of the observed NMR peak, is probably an N-methyl compound. As such, it may be an intermediate in the cholinoglycine cycle, in which an abnormality has been proposed to exist in MS patients.
Adult↗
Refined mapping of the gene causing familial Mediterranean fever, by linkage and homozygosity studies.
Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by attacks of fever and serosal inflammation; the biochemical basis is unknown. We recently reported linkage of the gene causing FMF (designated "MEF") to two markers on chromosome 16p. To map MEF more precisely, we have now tested nine 16p markers. Two-point and multipoint linkage analysis, as well as a study of recombinant haplotypes, placed MEF between D16S94 and D16S80, a genetic interval of about 9 cM. We also examined rates of homozygosity for markers in this region, among offspring of consanguineous marriages. For eight of nine markers, the rate of homozygosity among 26 affected inbred individuals was higher than that among their 20 unaffected sibs. Localizing MEF more precisely on the basis of homozygosity rates alone would be difficult, for two reasons: First, the high FMF carrier frequency increases the chance that inbred offspring could have the disease without being homozygous by descent at MEF. Second, several of the markers in this region are relatively nonpolymorphic, with a high rate of homozygosity, regardless of their chromosomal location.
Base Sequence↗