Doppler sonographic parameters for detection of carotid stenosis: is there an optimum method for their selection?

OBJECTIVE: A wide range of Doppler threshold values for carotid stenosis is found in the literature. We undertook this study to compare methods of derivation and to determine if an optimum strategy of threshold selection exists for a high-risk population. MATERIALS AND METHODS: From the sonograms of all patent internal carotid arteries, peak systolic velocity in the internal carotid artery (ICA(PSV)) and the ratio of peak systolic velocity in the internal carotid artery to that of the common carotid artery (ICA(PSV)/ CCA(PSV)) were compared with the percentage of angiographically determined stenosis. Receiver operating characteristic curves were generated for levels of stenosis > or =60% and > or =70%. Doppler thresholds were chosen on the basis of maximum accuracy and on the basis of > or =90% sensitivity and specificity. Patients were then segregated into symptomatic and asymptomatic cohorts, and the above process was repeated. An effectiveness analysis was also conducted using various Doppler thresholds. Thresholds derived using these three methods were compared and optimal values chosen. RESULTS. Of 333 carotid arteries that fit inclusion criteria, 132 were found in asymptomatic patients and 201 in symptomatic patients. Maximum accuracy, > or =90% sensitivity and specificity, and effectiveness analysis each produced different ranges of thresholds. We chose final thresholds that maintained patient outcome profiles. For asymptomatic patients at the > or =60% stenosis level, thresholds were ICA(PSV) = 200 cm/sec and ICA(PSV)/CCA(PSV) = 3.0. For symptomatic patients with stenosis > or =70%, thresholds were ICA(PSV) = 175 cm/sec and ICA(PSV)/CCA(PSV) = 2.5. CONCLUSION: Considerable latitude exists in the choice of carotid Doppler thresholds. We propose a rational strategy for threshold selection based on a combination of three commonly used methods. Our observations indicate that it appears advisable to consider symptomatic and asymptomatic patients separately and to apply appropriately derived thresholds.     

The effects of the new antiarrhythmic E 047/1 on postoperative ischemia-induced arrhythmias in dogs

Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. IMPLICATIONS: Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.     

Robot training enhanced motor outcome in patients with stroke maintained over 3 years

In an attempt to improve motor recovery of the upper limb after stroke, we added a robot (MIT-Manus) experience that provided additional goal-directed sensorimotor activity to standard rehabilitation treatments. The first trial produced a significant decrease in motor impairment in the upper limb for the treated group. In re-evaluating 12 of those 20 patients, nearly 3 years later, robot-trained patients showed further significant decreases in impairment measures of the affected limb. The groups were comparable at the start of the study.     

Prevalence of three common polymorphisms in the A-subunit gene of factor XIII in patients with coronary artery disease

Activated blood coagulation factor XIII has an important role in the final stage of the clotting cascade by the covalent crosslinking of alpha- and gamma-fibrin chains. We have recently shown that a functional polymorphism in exon 2. codon 34 of the FXIII A-subunit gene is protective against myocardial infarction. To investigate the prevalence of three other common point mutations in the A-subunit gene (codon 564, C to T, 650 G to A and 651 G to C) and their association with FXIII activity and antigen levels, 275 patients with coronary artery disease and 196 controls were studied. There was no difference in the prevalence of the polymorphisms between patients and controls or between patients with or without MI. Only genotype at codon 564 was associated with FXIII activity with lower activities in subjects possessing the T allele. There was evidence of linkage disequilibrium between codon 34 and codon 564. These results suggest that FXIIIVal34Leu is the only common polymorphism in the coding region of the A-subunit gene of FXIII associated with coronary artery disease.     

Association of the platelet glycoprotein IIb HPA-3 polymorphism with survival after acute ischemic stroke

BACKGROUND AND PURPOSE: The role of polymorphisms of the platelet glycoprotein (GP) IIb/IIIa receptor in the development of cardiovascular disease has been the subject of intensive research. The aim of this study was to determine the association of the HPA-3 polymorphism of platelet GPIIb with ischemic stroke and subsequent survival and to identify possible interactions of HPA-3 with classic risk factors. METHODS: HPA-3 genotype was determined by restriction fragment length polymorphism in 515 patients with ischemic stroke and 423 healthy, age-matched control subjects. RESULTS: There was no significant difference in the genotype distribution of patients and controls, nor was there any difference when patients were subclassified into small- and large-vessel disease. The genotype distribution of the 231 patients subsequently dying during 2.8 years of follow-up (aa=45.0%, ab=46.8%, bb=8.2%) was significantly different from that of those still alive (aa=37.0%, ab=48.2%, bb=14. 8%) (P=0.03). In a Cox regression model, the relative risks for poststroke mortality in patients of aa and ab genotype compared with those of bb genotype were 2.42 (95% CI, 1.24 to 4.71) and 2.13 (95% CI, 1.09 to 4.17), respectively, after we accounted for confounding factors. In addition, significant interactions of HPA-3 with the Pl(A) polymorphism of GPIIIa (P=0.002) and with fibrinogen (P=0.01) were identified in relation to mortality. CONCLUSIONS: HPA-3 is related to poststroke mortality, and the significant interaction of HPA-3 with Pl(A) and fibrinogen suggests that it may in some way influence the interaction of GPIIb/IIIa with fibrinogen, particularly in the presence of high fibrinogen.     

Angiotropic large B-cell lymphoma with clinical features resembling subacute combined degeneration of the cord

Angiotropic large cell lymphoma is a rare neoplastic disorder associated with a high mortality. The hallmark of the disease is lymphoid proliferation confined to the intravascular compartment without local tissue or vessel wall infiltration [1]. This feature is so striking that the disease was originally thought to arise from endothelial tissue and early cases were described as malignant angioendotheliomatosis. However, application of immunohistochemical methods for detection of lymphoid markers such as the CD45 and CD20 cell surface markers has confirmed its lymphoid origin, usually of B-cell lineage [2]. Clinical manifestations of the disease are protean and are due to multifocal medium and small vessel occlusion by tumour cells [3]. Characteristic sites of involvement are skin and central nervous system and although an ante-mortem diagnosis can be made from a biopsy specimen, it is often unsuspected [4]. We present a case of angiotropic large B-cell lymphoma in a 74-year-old man who presented with urinary symptoms and had a neurological picture resembling subacute combined degeneration of the cord.     

The validity of DSM-IV alcohol abuse: drunk drivers versus all others

OBJECTIVE: Prior research in a community sample indicated that almost half the individuals receiving a diagnosis of DSM-IV alcohol abuse did so on the basis of only one symptom, driving after drinking too much. While this is certainly unwise behavior, it may not be a psychiatric disorder. Therefore, we investigated the differential validity of this subgroup of abuse cases by testing the association of a set of external validating criterion variables with three groups: those who met criteria for abuse just for drinking-driving, those who met criteria by other means and those with no alcohol diagnosis. Present status of past cases of abuse was also investigated. METHOD: Subjects were 22,204 U.S. household residents (a subset of a national probability sample) interviewed in 1992 with the Alcohol Use Disorders and Associated Disabilities Interview Schedule. The generalized logit model was the principal means of analysis. RESULTS: Subjects who met criteria for DSM-IV alcohol abuse just for drinking-driving differed from subjects with no diagnosis on about half the variables tested, while those who met criteria for abuse in other ways differed from subjects with no diagnosis on all variables tested. The two abuse groups differed from each other on some but not all variables. Past cases of abuse for drinking-driving and past cases of other abuse were equally likely to have remitted in the last 12 months, and slightly less likely to meet criteria for current dependence. CONCLUSIONS: Further conceptual and empirical work is needed to resolve the difficulties with the DSM-IV alcohol abuse category.     

Leucovorin, 5-fluorouracil,and gemcitabine: A phase I study

Gemcitabine is a chemotherapy agent with efficacy in the treatment of lung, pancreas, bladder and breast cancer. It inhibits DNA synthesis by interfering with cytidine triphosphate production and also inhibits the activity of ribonucleotide reductase. Gemcitabine may potentiate fluorouracil's inhibition of thymidylate synthase. This inhibition would be expected to be sequence dependent, occurring only if gemcitabine were administered following fluorouracil (5FU).The combination of leucovorin, 5-FU, and gemcitabine was assessed in this phase I trial. Eligibility requirements included refractory solid tumor malignancy; adequate hematologic, renal and hepatic reserve; no prior therapy with the combination of leucovorin and 5FU, or with gemcitabine; ECOG performance status 0–2, and signed informed consent.Eleven men and nine women were eligible. The median age was 52.5 years and the median performance status was 1. All but three patients had prior chemotherapy. The starting doses were leucovorin 20 mg/m², 5FU 255 mg/m² and gemcitabine 600 mg/m². 5FU and gemcitabine were escalated in tandem to 340 mg/m² and 800 mg/m² and thereafter to 425 mg/m² and 1000 mg/m², respectively. Gemcitabine administration always followed that of 5FU by 30 minutes. The median number of cycles was 2 (range 1–32). Two patients at the starting dose had disease progression within the first cycle with one death on day 28. One patient with cholangiocarcinoma had a partial response and remained on study for 40 months. There were no other responses.The maximum tolerated dose is leucovorin 20 mg/m², 5FU 340 mg/m², and gemcitabine 800 mg/m². The impact of drug sequence remains undetermined.