Clinical Exome Sequencing as a Novel Tool for Diagnosing Loeys-Dietz Syndrome Type 3.

OBJECTIVE/BACKGROUND: In rare genetic vascular syndromes the diagnosis may not be apparent from the phenotype, but might be important for proper management. METHODS: A previously healthy woman without dysmorphic features presented with pregnancy associated vascular dissections and aneurysms. Next generation clinical exome sequencing was performed. RESULTS: The differential diagnosis of spontaneous arterial dissection is outlined. The patient's diagnosis became evident after clinical exome sequencing detected a novel missense mutation in the evolutionary conserved region of SMAD3, confirming the diagnosis of Loeys-Dietz syndrome (LDS) type 3. A brief overview of the various types of LDS and their management is presented. CONCLUSION: Clinical exome sequencing proved useful in diagnosing LDS type 3 where detailed vascular surveillance and timely intervention with a low threshold is recommended.

Infrapopliteal run-off and the outcome of femoropopliteal percutaneous transluminal angioplasty.

BACKGROUND: The outcome of percutaneous transluminal angioplasty (PTA) of peripheral arterial lesions is influenced by several factors, including the haemodynamic conditions. Our study tested: (a) whether infrapopliteal run-off after completed PTA influenced the time course of restenosis/reocclusion of the femoropopliteal arterial segment, and (b) whether worsening of infrapopliteal run-off influenced the long-term femoropopliteal patency after PTA. PATIENTS AND METHODS: Among 245 patients treated by femoropopliteal PTA we enrolled 176 patients who consented to regular follow-up. Concomitant infrapopliteal PTA was performed whenever feasible. The technical success of PTA and the patency of calf arteries were assessed by angiography. Infrapopliteal run-off was scored by a modification of the Society for Vascular Surgery criteria. The treated patients' limbs were divided into a group with good infrapopliteal run-off and a group with compromised run-off. Follow-up examination of the femoropopliteal arterial segment was performed by vascular ultrasonography (US) 1, 6 and 12 months after PTA, and an adverse outcome was defined by a > or = 50 % stenosis, i.e., at least doubling of the maximal systolic velocity, or occlusion - evidenced by the absence of flow. The patency of calf arteries was re-assessed by US 12 months after PTA. RESULTS: One month after femoropopliteal PTA 19 / 83 (23 %) of patients with compromised run-off developed the combined end-point of restenosis or reocclusion in comparison to 10 / 93 (11 %) with good run-off (p = 0.03). After 6 months the incidence of restenosis/reocclusion had increased in both groups at an approximately equal rate, but the differences were no longer significant: 39 / 80 (49 %) in the compromised run-off group vs. 36 / 83 (43 %) in the good run-off group after 6 months, p = 0.49, and 42 / 73 (57 %) vs. 38 / 73 (52 %) after 12 months, p = 0.51. However, in patients' limbs with good periprocedural run-off that deteriorated into compromised run-off in the year after PTA, femoropopliteal restenosis/reocclusion occurred more often than in limbs which retained good run-off: 10 / 14 (71 %) vs. 18 / 51 (35 %), p = 0.02. CONCLUSIONS: Compromised postprocedural infrapopliteal run-off predisposes to early restenosis/reocclusion after femoropopliteal PTA. Deterioration of infrapopliteal run-off in the year after femoropopliteal PTA is accompanied by worsening of long-term femoropopliteal patency.

Repetitive paroxysms of supraventricular tachyarrhythmias triggered during pediatric cardiac interventions: suppression after short infusion of amiodarone.

Arrhythmias are the most common major complications encountered during pediatric cardiac catheterizations. This report describes the management of repetitive paroxysms of supraventricular tachyarrhythmias triggered by catheter manipulation during interventional procedures in two children. After 15 minutes, amiodarone infusion (25 microg/kg/min) eliminated further paroxysms in both patients, allowing both interventions to be completed safely and effectively.

Treatment options in Western hepatocellular carcinoma: a prospective study of 224 patients.

BACKGROUND/AIMS: Though hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world, the optimal therapeutic strategy is still poorly defined. This is mainly due to geographic differences in HCC which may affect the validity of treatment regimens in differents areas of the world. The aim of the present study was to analyze the natural course of the disease as well as to assess the efficacy of different therapeutical schemes in HCC observed in Ljubljana (Slovenia) and Trieste (Italy), two cities in Western Europe situated close to each other. METHODS: During the period from January 1988 to December 1993, 224 consecutive patients (132 in Trieste and 92 in Ljubljana) with HCC were enrolled in the study. Patients were treated with the following 3 schemes: surgery 39 (17.4%), transcatheter chemoembolization (TACE) 116 (51.8%), and no treatment 69 (30.8%). The tumor was classified by Okuda staging and the liver disease by Child-Pugh score. Patients were followed up for 12-60 months, with an average of 40 months. The response rate to TACE and recurrence following surgery were evaluated. Comparative analysis of survival between different treatment groups was performed. RESULTS: The natural course of the disease, and other characteristics of the HCC, showed a typical Western type of tumor. Liver disease was scored as Child A in 58%, Child B in 30% and Child C in 12%, and the tumor was staged as Okuda I in 52%, Okuda II in 37% and Okuda III in 11%, respectively. Treatment with TACE was followed by an objective response in 27%, with a median survival of 31 months. Surgery was followed by a recurrence rate of 77% within 19.5 months and median survival of 49 months. The overall median survival of nontreated patients was 8 months. Survival in each group of patients differed significantly between all three consecutive stages of Okuda (p<0.001). In contrast, the differences in survival were significant only between Child A and B (p<0.02). The differences between Child B and C were not significant. CONCLUSIONS: This study emphasizes the importance of staging in the choice of treatment modality and diffusion of HCC in affecting an overall response to treatment and survival. Surgery is highly effective in monofocal HCC of Okuda I and II without cirrhosis. TACE is effective in Okuda I and II and Child A cirrhosis only. The treatment of HCC in Child B cirrhosis needs further studies. In Child C and/or Okuda stage III of HCC, any treatment except pure symptomatic relief is detrimental and should not be used.

Flow-injection binding assays: a way to increase the speed in binding analyses.

A flow-injection analysis system was equipped with a small column containing immobilized concanavalin A. Pulses containing glucosides or glycoproteins were passed over the column, the lectin bound the carbohydrates. By using horseradish peroxidase as a labeled carbohydrate and letting it compete with other glucosides or mannosides a competitive binding assay for the latter was set up. When the enzyme activity had been evaluated, the column was rinsed and reconditioned, allowing a new assay to be run. To speed up the assay, substrates for the enzyme marker, peroxidase, were present in the perfusing buffer. A computerized evaluation of the absorbance peak allowed the time of the assay cycle to be reduced to 70 s. The sensitivity of this binding assay was fully comparable with those reported for other systems using the same reactants.