Explanation for exclusive maternal origin for congenital form of myotonic dystrophy.
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Biomedical subjects
Publications and source records attributed to G R Sutherland.
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We determined whether 2'-deoxycoformycin (DCF), a potent highly specific inhibitor of adenosine deaminase (ADA), protected against transient forebrain ischemic neuronal injury in rat. Anesthetized male Sprague-Dawley rats received i.p. injections of either saline, 0.5 mg/kg or 5 mg/kg DCF 2 h before undergoing a 10-min forebrain ischemic insult induced by bilateral carotid artery occlusion with concomitant hypotension. Rat brain sections taken 7 days post-ischemia showed damage mostly in the CA1 region of the hippocampus. Quantification of neuronal injury showed no significant differences between saline- or DCF-treated rats. These results indicate that, contrary to previous reports, DCF does not protect against the neuronal damage that follows forebrain ischemia in rat.
Previous studies have shown that overt intrahepatic tumours are associated with subtle changes in liver perfusion that can be measured directly using duplex colour Doppler sonography (DCDS). This study assessed the predictive value of DCDS in the early detection of occult colorectal hepatic metastases. Hepatic arterial and portal venous blood flow was measured in 50 control subjects and 135 patients with colorectal cancer, 67 with overt liver metastases and 68 with an apparently disease-free liver on the basis of computed tomography and laparotomy findings. The Doppler perfusion index (DPI), defined as the ratio of hepatic arterial to total liver blood flow, was calculated. Clear separation of the DPI values of controls and those of patients with overt metastases was observed (P < 0.0001). Thirty-eight of the 68 patients with a disease-free liver also had an abnormally high DPI value. After 1 year of follow-up, 21 patients with an abnormally high DPI at the time of apparently curative primary resection had developed liver metastases and a further four had died without post-mortem examination. The 30 patients with normal DPI remain disease-free. The data suggest that DPI is of value in the early detection of occult liver metastases.
Image-directed Doppler ultrasonography has been used to measure changes in hepatic arterial and portal venous blood flows in 22 controls and 88 patients with colorectal cancer. Doppler Perfusion Index, (DPI, ratio of hepatic arterial to total liver blood flow) and Doppler Flow Ratio (DFR, ratio of hepatic arterial to portal venous blood flow) of controls and patients with overt liver metastases were clearly separated (p < 0.0001). There was a significant reduction in the Hepatic Arterial Resistive Index (HARI) of patients with overt liver metastases (p < 0.0001). Percentage Hepatic Replacement (PHR) by metastases, measured using a computed tomography scanner, did not correlate with DFR or DPI. The results suggest that the measurement of hepatic perfusion changes using image-directed Doppler ultrasonography may be of value in the detection of small liver metastases.
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Transthoracic (TTE) and transesophageal echocardiography (TEE) were performed prospectively on 53 consecutive patients (mean age 59 +/- 14 years) immediately before and within 24 hours of mitral balloon valvotomy to compare the relative value of the two techniques. Biplane TEE was used in 38 patients and single-plane imaging was done in 11. All patients underwent left and right cardiac catheterization, left ventriculography, and coronary angiography. While TEE provided excellent images of the mitral valve in all patients, imaging planes were more limited than by TTE. Mitral valve morphology could be assessed satisfactorily by either technique. Echo scores derived from each showed good correlation (r = 0.90, p < 0.001). TEE transgastric longitudinal scanning provided superior detail of the subvalvar apparatus but only in 20 (53%) of 38 patients. Patients with good transgastric views had significantly smaller left atrial volumes than those without (58 +/- 22 vs 106 +/- 41 cm3, p < 0.001). Mitral valve orifice and the commissures were better assessed by TTE. Before valvotomy, mitral regurgitation (MR) graded by TEE and TTE color flow mapping was concordant with angiography in 80% and 81%, respectively. After valvotomy, TTE color flow mapping failed to detect MR in two of the three patients who developed severe MR. Two of these patients were examined by TEE, which demonstrated both the MR jets as well as leaflet tears. Thrombus was diagnosed in the left atrium in eight patients by TEE and in only one patient by TTE. Biplane TEE was required for accurate thrombus localization and for assessing its size and extent. Five patients with thrombus underwent balloon valvotomy without complications. Left-to-right atrial shunting was detected by TEE and TTE in 95% and 48% of patients, respectively. Flow convergence regions, from which quantitative flow information can be derived, were imaged by TEE only. TTE and TEE have complementary roles. However, TEE is essential for excluding thrombus in the left atrium before balloon valvotomy. After the procedure, TEE is recommended for the evaluation of patients with severe mitral regurgitation.
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The recently published, detailed cytogenetic-based physical map of chromosome 16 has the highest resolution of any autosomal cytogenetic map thus far constructed. The genetic map has been integrated with the cytogenetic map to facilitate the regional localization of disease genes by linkage. Disease genes for tuberous sclerosis, familial Mediterranean fever, Rubinstein-Taybi syndrome and Morquio A syndrome have now been assigned to chromosome 16. The search for the adult polycystic kidney disease gene has recently been narrowed to the analysis of candidate loci on chromosome 16, and localization of the gene determining juvenile Batten disease has been further refined by disequilibrium mapping.
The incidence of vestibular schwannoma (acoustic neuroma) in Manitoba, Canada was reviewed. From 1987 through 1991, 71 tumors were diagnosed in 69 patients. The overall annual incidence rate for both sexes was 1.27/100,000 with male and female annual incidences of 1.31/100,000 and 1.24/100,000 respectively. For males, there was an early peak in the age group 30-39 years (2.1/100,000). Following the fifth decade, the incidence for males plateaued (2.7-3.6/100,000). For females, the incidence increased with age up to age 60-69 years (4.1/100,000). This was followed by a progressive decline in the incidence. Although the incidence of vestibular schwannoma was relatively high, the clinical features were not unlike those previously reported in the literature.
Angiotensin II (AT-II) has been used to target regionally-administered cytotoxic microspheres in patients with intrahepatic tumours. The optimisation of vasoconstrictor targeting requires a knowledge of the blood flow changes induced by agents such as AT-II. We therefore assessed duplex/colour Doppler sonography (DCDS) as a means of evaluating the effects of AT-II infusion on hepatic arterial blood flow (HABF) and arterial resistance in patients with intrahepatic tumours. HABF was measured continuously in nine patients using DCDS before, during and after an infusion of AT-II (15 micrograms in 3 ml of saline over 90 s) via a hepatic artery catheter. In seven patients with less than 30% hepatic replacement by tumour, the baseline level of HABF was 331 +/- 85 ml min-1 (mean +/- s.d.), and this was reduced by 75-80% within 30 s of the start of AT-II infusion. HABF recovered rapidly from the end of the infusion, and increased by up to 20% above the baseline for approximately 2 min. In two patients with greater than 50% hepatic replacement, HABF showed no reduction but rose continuously from the start of AT-II infusion, increasing by a factor of 2-2.5 after 3-4 min. Arterial resistance showed reciprocal changes in all cases. We conclude that DCDS is effective in assessing the temporal changes in hepatic arterial blood flow caused by AT-II. In order to optimise tumour targeting, the injection of microspheres loaded with cytotoxic drugs should be completed before the end of the AT-II infusion. The targeting advantage of AT-II in patients with a high percentage hepatic replacement by tumour should be re-assessed.
In a retrospective multicentre study, the diagnostic potential of transoesophageal 2D-echocardiography (TEE) as compared to precordial 2D-echocardiography (TTE) was determined in 154 patients with primary or secondary tumours of the heart. Additionally, the value of standard diagnostic parameters, such as symptoms, X-ray of the chest and electrocardiogram were evaluated. In 84 patients (24 male, 60 female; age 20-85, mean 56.6 years) intracardial tumours were present, and 70 patients (37 male, 33 female; age 18-79, mean 44.3 years) presented with peri- or paracardial tumours. The main symptoms of patients with intracardial tumours were dyspnoea (60.7%), vena cava syndrome (22.2%) and chest pain (20.2%). Embolization was found in 11.9%. Left or right atrial enlargement was observed on chest X-ray in 23 patients, and echocardiographic abnormalities in 17 cases. The patients with peri- or paracardial tumours presented with dyspnoea in 51.4% of cases, loss in body weight in 20.0% and with vena cava syndrome and chest pain in 17.1%. The chest X-ray was abnormal in 56 patients. Unspecific ST segment changes in the electrocardiogram were observed in five, and arrhythmias in seven cases. Diagnosis of atrial myxomas was achieved by TTE in 95.2%, by TEE in 100%, by angiography in 78.4%, by computed tomography (CT) or magnetic resonance tomography (NMR) in 70%. Identification of the attachment point was made by angiography in 8.1%, by TTE in 64.5% and by TEE in 95.2%. In 22 patients with intracardial tumours (myxomas excepted) diagnosis was achieved by TTE in 90.9%, by TEE in 100%, by CT or NMR in 88.9% and by angiography in 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
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The trinucleotide repeat sequences which become unstable in fragile X syndrome and myotonic dystrophy are located in the untranslated regions of their respective genes, FMR1 and DM1. This implies that a functional constraint other than coding capacity maintains the presence of the repeats. In the case of fragile X syndrome, sequences adjacent to the repeat are methylated in affected individuals and the FMR1 gene is transcriptionally inactive. We demonstrate that the fragile X p(CCG)n repeat itself is methylated in vivo and that methylation of this repeat is able to inhibit in vitro binding of a novel, specific nuclear p(CCG)n binding protein (CCG-BP1)--one of at least 10 distinct simple tandem repeat sequence binding proteins (STR-BPs). We describe additional, apparently distinct, binding activities both for the methylated form of the p(CCG)n repeat and for each of the single strands of the repeat.
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The development of pediatric transesophageal ultrasound imaging represents an important advance in the diagnosis and treatment of the child with congenital heart disease. Although primary diagnostic transesophageal studies are seldom indicated in infants and unoperated children, they have an important role in the older child especially where there has been prior cardiac surgery. Diagnostic studies are most appropriate for abnormalities of venous return, the atria, atrioventricular valves, and the left ventricular outflow tract. Two other important areas in which transesophageal imaging is playing an increasing role in the treatment of the pediatric patient is in monitoring interventional catheterization and in the intraoperative and immediate postoperative monitoring of surgical repair.