[Validation of a clinical prediction rule for the diagnosis of deep vein thrombosis of the lower limbs in primary care]. / Validation d'un score de prédiction clinique de la thrombose veineuse profonde des membres inférieurs spécifique à la médecine générale.

PURPOSE: Patients with suspected deep vein thrombosis (DVT) are often managed on an outpatient basis. The aim of the study was to validate a clinical prediction rule specifically for use in primary care to help physicians in their decision to start anticoagulant therapy while awaiting ultrasound examination. PATIENTS AND METHODS: Between September 2007 and October 2008, 194 general practitioners prospectively included patients with clinically suspected DVT without clinically suspected pulmonary embolism. All patients underwent a standardized clinical assessment in order to collect items included in the clinical prediction rule (personal history of venous thromboembolism +1, immobilization in previous month+1, estrogen contraceptive+2, active malignancy+3, swelling of the calf+1, the presence of an alternative diagnosis more likely than that of DVT-3. DVT unlikely if score<2, likely if score≥2). RESULTS: Among the 164 included patients, 56 (34%) had DVT of them 28 (17%) had a proximal DVT. Proportions of confirmed DVT were 29% in the unlikely group and 43% in the likely group against 26% and 63% respectively in the derivation study. CONCLUSIONS: This clinical prediction rule might not fulfill the required conditions to be considered as a usable help in the ambulatory management of DVT. Variations of the cut-off value could enhance its performance.

[Validation of a deep vein thrombosis prediction rule in primary care]. / Validation d'un score de probabilité clinique de thrombose veineuse profonde des membres inférieurs spécifique à la médecine générale.

OBJECTIVE: Suspected deep vein thrombosis (DVT) of lower limbs (LL) may require different tools to rule out or confirm the diagnosis. Clinical probability provides help to select useful tests, interpret their results, and decide to treat the patient meanwhile. Clinical prediction rules that risk stratify patients with suspected DVT can be established from inpatients, but no prediction rule not requiring laboratory tests has been established from primary care patients. We previously derived and internally validated such a prediction rule. The aim of this study is to externally validate this score. PATIENTS AND METHODS: The score was applied to Optimev outpatients with suspected LL-DVT, and without suspected pulmonary embolism. Sensitivity and specificity were calculated for proximal and distal DVT, according to each score. The area under the ROC curve was calculated for each kind of DVT, in order to assess the validity of the score on predicting the presence or absence of DVT. RESULTS: Among 3523 outpatients prospectively included in the Optimev study for suspected LL DVT, overall prevalence of DVT was 29.7% (n=1046), ranging from 21.7% in the non-high score probability, to 61.4% in the high score probability. The area under the ROC curve was 0.79 [CI 95%, 0.77-0.80]. With subgroup analysis, the area under curve was 0.83 [CI 95%, 0.82-0.85] for proximal DVT, and 0.75 [CI 95%, 0.73-0.77] for distal DVT. CONCLUSION: This score reliably identifies primary care patients with LL DVT, whether proximal or distal.

PARP-3 associates with polycomb group bodies and with components of the DNA damage repair machinery.

Poly(ADP-ribose) polymerase 3 (PARP-3) is a novel member of the PARP family of enzymes that synthesize poly(ADP-ribose) on themselves and other acceptor proteins. Very little is known about this PARP, which is closely related to PARP-1 and PARP-2. By sequence analysis, we find that PARP-3 may be expressed in two isoforms which we studied in more detail to gain insight into their possible functions. We find that both PARP-3 isoforms, transiently expressed as GFP or FLAG fusions, are nuclear. Detection of endogenous PARP-3 with a specific antibody also shows a widespread nuclear distribution, appearing in numerous small foci and a small number of larger foci. Through co-localization experiments and immunoprecipitations, the larger nuclear foci were identified as Polycomb group bodies (PcG bodies) and we found that PARP-3 is part of Polycomb group protein complexes. Furthermore, using a proteomics approach, we determined that both PARP-3 isoforms are part of complexes comprising DNA-PKcs, PARP-1, DNA ligase III, DNA ligase IV, Ku70, and Ku80. Our findings suggest that PARP-3 is a nuclear protein involved in transcriptional silencing and in the cellular response to DNA damage.

Amiodarone reduces procedures and costs related to atrial fibrillation in a controlled clinical trial.

BACKGROUND: Atrial fibrillation is the most common sustained cardiac arrhythmia, and engenders significant health care costs. The impact of various treatment options for atrial fibrillation on hospital costs has not been evaluated in a randomized trial. METHODS: We analysed 1-year follow-up data on 392 patients randomized to low dose amiodarone (200 mg. day(-1)) or alternative first-line therapy (sotalol or propafenone) in a multicentre trial (Canadian Trial of Atrial Fibrillation, CTAF). RESULTS: Patients in the amiodarone group had fewer electrical cardioversions (65 vs 109 for patients in the sotalol/propafenone group, P<0.0001), and pacemaker insertions (4 vs 11, P=0.07). The average amiodarone patient spent fewer days in hospital (0.47 vs 0.97, P=0.01), and incurred lower costs ($532 vs $898, P=0.03), for admissions where atrial fibrillation was the admitting diagnosis. Average total hospital costs per patient for all admissions, as well as average combined hospital and physician costs per patient, showed wide variations within the treatment arms and were not significantly different between groups. CONCLUSION: For patients in whom antiarrhythmic drug therapy is indicated, low dose amiodarone significantly reduces atrial fibrillation-related costs by reducing the number of atrial fibrillation-related procedures.

Endovascular abdominal aortic aneurysm (AAA) repair since the FDA approval. Are we going too far?

BACKGROUND: Since the FDA approval of endovascular devices for abdominal aortic aneurysm (AAA) repair, clinicians have been relaxing the strict inclusion criteria of the clinical trials. We have reviewed our experience during and after the clinical trials to examine changes in patient selection, technical aspects of the procedure, and outcome. METHODS: A review of a prospectively compiled database of all endovascular AAA repairs performed at our institution was performed. RESULTS: Endovascular AAA repair was attempted in 130 patients: 46 (35.4%) as a part of clinical trials (Group I), and 84 (64.6%) since the FDA approval of the devices (Group II). Significant differences in patient selection included: a higher proportion of short (<15 mm) proximal necks in Group II (28.6 vs 0.0%, p<0.001), and a higher proportion of iliac occlusive disease in Group II (48.8 vs 15.4%, p=0.001). Additional trends suggested that Group II AAA's were more complex, including increased proximal neck angulation, increased proximal calcification, increased presence of proximal thrombus, and increased iliac tortuosity. Significant differences in technical aspects of the procedure included increased usage of iliac angioplasty (46.4 vs 13.3%, p<0.001), iliac stenting (31 vs 8.9%, p<0.01), and conduit access to the external iliac artery (10.7 vs 0%, p=0.03) in Group II. Analysis of outcome revealed a decreased incidence of the following in Group II cases: conversions to open repair (2.4 vs 10.9%), lower extremity ischemia (3.6 vs 13.0%), and graft limb occlusion (2.4 vs 8.7%). Other major perioperative complications did not differ significantly between the 2 groups. However, although the overall rate of any endoleak noted in the postoperative course was decreased in Group II cases (26.2 vs 32.6%), the incidence of proximal or distal attachment site leaks has increased (11.9 vs 4.3%, p=0.14). Although this comparison did not reach statistical significance, the magnitude of the increase is concerning. CONCLUSIONS: Although we have been able to offer endovascular AAA repair to a larger number of patients since FDA approval, endovascular management of increasingly complex proximal necks and increased iliac artery disease appears to have increased the incidence of attachment site endoleaks. Although many of these leaks have been successfully managed with adjunctive endovascular procedures, their increasing incidence is worrisome and suggests that we may need to re-evaluate current inclusion criteria for using this technology. Although difficult access issues have been handled with adjunctive procedures, the presence of a short, angulated proximal neck may be difficult to overcome, and may not be well suited for endovascular repair with the currently available devices.

Carotid endarterectomy in patients 55 years of age and younger.

Prior studies have suggested that young patients may be more prone to recurrent disease after carotid endarterectomy (CEA). The goal of this study was to review a series of CEAs performed on younger patients (< or = 55 years) and to determine if these patients are more likely to develop recurrent stenosis. A review was conducted of CEAs performed from 1985 through 1994. Analysis was performed on a study group of 94 young patients who underwent 109 CEAs during this time. A control group of 222 patients older than 55 years who underwent 256 CEAs during the years 1991 through 1993 was selected for comparison. During a mean of nearly 4 years of follow-up, younger patients were significantly more likely to experience a late failure of CEA, including total occlusion of the operated artery, or recurrent stenosis requiring redo surgery. Careful patient evaluation is important in choosing younger patients who require CEA. Implications of these data include mandating careful noninvasive follow-up examinations for younger patients undergoing CEA.

Carotid endarterectomy in female patients: are the concerns of the Asymptomatic Carotid Atherosclerosis Study valid?

OBJECTIVES: Although the results of the Asymptomatic Carotid Atherosclerosis Study clearly demonstrated the benefit of surgical over medical management of severe carotid artery stenosis, the results for women in particular were less certain. This was to some extent because of the higher perioperative complication rate observed in the 281 women (3.6% vs 1.7% in men). The objective of this study was to review a large experience with carotid endarterectomy in female patients and to determine whether the perioperative results differed from those of male patients. METHODS: A review was conducted of a prospectively compiled database on all carotid endarterectomies performed between 1982 and 1997. Operations performed in 991 female patients were compared with those performed in 1485 male patients. RESULTS: Female patients had a significantly lower incidence of diabetes, coronary artery disease, and contralateral carotid artery occlusion than did male patients. Female patients had a significantly higher incidence of hypertension. There were no significant differences in the age, smoking history, anesthetic route, shunt use, or clamp tolerance between the two groups. Of 991 female patients, 659 (66.5%) had preoperative symptoms, whereas 332 (33.5%) cases were performed for asymptomatic stenosis. Among 1485 male patients, 1041 (70.1%) had symptoms, and 444 (29.9%) were symptom free before surgery. There were no significant differences noted in the perioperative stroke rates between men and women overall (2.3% vs 2.4%, P =.92), or when divided into symptomatic (2.5% vs 3.0%, P =.52) and asymptomatic (2.0% vs 1.2%, P =.55) cases. CONCLUSIONS: Carotid endarterectomy can be performed with equally low perioperative stroke rates in men and women in both symptomatic and asymptomatic cases. In this series, symptom-free female patients had the lowest overall stroke rate. The concerns of the Asymptomatic Carotid Atherosclerosis Study regarding the benefit of carotid endarterectomy in female patients should therefore not prevent clinicians from recommending and performing carotid endarterectomy in appropriately selected symptom-free female patients.

Causes of perioperative stroke after carotid endarterectomy: special considerations in symptomatic patients.

In order to maximize the efficacy of carotid endarterectomy (CEA), the rate of perioperative stroke must be kept to a minimum. A recent analysis of carotid surgery at our institution found that most perioperative strokes were due to technical errors resulting in thrombosis or embolization. From 1992 through 1997 we have performed nearly 1200 additional CEAs; the purpose of this study was to examine recent trends in the causes of perioperative stroke, with specific attention to differences in symptomatic and asymptomatic patients. The records of 1041 patients undergoing 1165 CEAs were reviewed from a prospectively compiled database. Analysis of these data showed that a history of preoperative stroke appears to increase the risk of perioperative stroke after CEA. Surgical factors associated with perioperative stroke include an inability to tolerate clamping, use of an intraarterial shunt, and having surgery performed under general anesthesia; these factors are clearly interrelated and only the use of intraarterial shunting remains a risk factor by multivariate analysis. Over half of all perioperative strokes (54%) appear to be caused by intraoperative or postoperative thrombosis and embolization. The patient requiring use of intraarterial shunting and/or with a preoperative stroke most likely has a significant watershed area of brain at increased risk of infarction. However, technical errors are still the most common cause of perioperative stroke in these high-risk patients. Such high-risk patients may manifest clinical stroke from small emboli that may be tolerated by asymptomatic clamp-tolerant patients. Technical precision and appropriate cerebral protection are particularly critical for successful outcomes in high-risk patients.

Transcatheter embolization of complex pelvic vascular malformations: results and long-term follow-up.

OBJECTIVES: Vascular malformations of the pelvis are rare and present a difficult therapeutic challenge. Surgical treatment is notoriously difficult and carries a high likelihood of recurrence. Surgical proximal ligation of a feeding vessel may in fact be contraindicated, because it can make subsequent transcatheter therapy impossible. The purpose of this study was to review our results with transcatheter embolization therapy in symptomatic complex pelvic vascular malformations in 35 patients. METHODS: A retrospective review was conducted of a prospectively compiled database of all patients undergoing transcatheter therapy of a pelvic vascular malformation at our institution. RESULTS: The mean age of the patients was 34 years (range, 16 months-66 years), and 51% were male. The most common presenting symptoms included pain (59%), a visible or palpable lesion (62%), associated palpable pulsation or thrill (44%), hemorrhage (27%), congestive heart failure (18%), and symptoms due to mass effect (35%). A significant number of patients had undergone previous, unsuccessful attempted surgical treatment of the lesion (32%). The most common type of lesion noted on arteriography was arteriovenous shunting (89%). Patients required a mean of 2.4 embolization procedures (range, 1-11 procedures) over a mean period of 23.3 months (range, 1-144 months). The most common agents used were rapidly polymerizing acrylic adhesives. The most common vessels involved and treated were branches of the hypogastric artery (82%). More than one procedure were performed in 20 patients (53%). Seven were planned as staged embolizations, whereas 13 were due to residual or recurrent symptoms. Adjunctive surgical procedures were performed subsequent to embolization therapy in five patients (15%). Eighty-three percent of patients were asymptomatic or significantly improved at a mean follow-up of 84 months (range, 1-204 months). CONCLUSIONS: Pelvic vascular malformations are difficult to eradicate completely, and recurrences are common. Many patients require multiple therapeutic interventions. However, most of these difficult cases have good results in the long term. Transcatheter embolization plays a significant role in, and may be the treatment of choice for, symptomatic pelvic vascular malformations.

Genetic Variability of Canadian Populations of the Sapstain Fungus Ophiostoma piceae.

ABSTRACT Genetic diversity was studied in seven Canadian populations of Ophiostoma piceae, the most prevalent sapstain fungus in Canadian softwoods. A total of 239 single-spore isolates were recovered following a systematic survey of sapstain fungi in logs and lumber at seven selected sawmills in six Canadian provinces (British Columbia, Alberta, Saskatchewan, Ontario, Québec, and New Brunswick). Sampling was carried out on five commercially important softwood species: balsam fir (Abies balsamea), white spruce (Picea glauca), black spruce (Picea mariana), jack pine (Pinus banksiana), and lodgepole pine (Pinus con-torta var. latifolia). The A and B mating types occurred at equal frequency (MAT A/ MAT B = 1.00:1.13) over all populations. Pseudo-allelic frequencies were estimated at each of 24 putative genetic loci by scoring for presence or absence of random amplified polymorphic DNA fragments generated by five primers. A total of 237 haplotypes were found among the 239 isolates, revealing a high level of genotypic diversity among isolates. Total gene diversity (H(T) = 0.414) was mostly attributable to diversity within populations (H(S) = 0.369). Thus, only 11.2% of the total variability was attributable to frequency differences among populations. An analysis of molecular variance revealed that most genetic variability occurred within subpopulations within mills (84.3%; P < 0.001), whereas low but statistically significant levels of genetic differentiation were also observed among subpopulations within populations (5.4%; P < 0.001) and among populations (10.3%; P < 0.001). Estimates of Nei' genetic distances were not correlated with geographic distances among sampling locations (r = -0.092; P = 0.310), although principal component analysis indicated that subpopulations located east of Saskatchewan were grouped on the same side of the second principal component axis. Overall, results suggest moderate genetic differentiation of O. piceae in Canada, which is consistent with the observation that sexual reproduction is frequently observed in this fungus.

Immediate reexploration for the perioperative neurologic event after carotid endarterectomy: is it worthwhile?

PURPOSE: When managing a new neurologic deficit after carotid endarterectomy (CEA), the surgeon is often preoccupied with determining the cause of the problem, requesting diagnostics tests, and deciding whether the patient should be surgically reexplored. The goal of this study was to analyze a series of perioperative neurologic events and to determine if careful analysis of their timing and mechanisms can predict which cases are likely to improve with reoperation. METHODS: A review of 2024 CEAs performed from 1985 to 1997 revealed 38 patients who manifested a neurologic deficit in the perioperative period (1.9%). These cases form the focus of this analysis. RESULTS: The causes of the events included intraoperative clamping ischemia in 5 patients (13.2%); thromboembolic events in 24 (63.2%); intracerebral hemorrhage in 5 (13.2%); and deficits unrelated to the operated artery in 4 (10.5%). Neurologic events manifesting in the first 24 hours after surgery were significantly more likely to be caused by thromboembolic events than by other causes of stroke (88.0% vs. 12.0%, P<.002); deficits manifesting after the first 24 hours were significantly more likely to be related to other causes. Of 25 deficits manifesting in the first 24 hours after surgery, 18 underwent immediate surgical reexploration. Intraluminal thrombus was noted in 15 of the 18 reexplorations (83. 3%); any technical defects were corrected. After the 18 reexplorations, in 12 cases there was either complete resolution of or significant improvement in the neurologic deficit that had been present (66.7%). CONCLUSIONS: Careful analysis of the timing and presentation of perioperative neurologic events after CEA can predict which cases are likely to improve with reoperation. Neurologic deficits that present during the first 24 hours after CEA are likely to be related to intraluminal thrombus formation and embolization. Unless another etiology for stroke has clearly been established, we think immediate reexploration of the artery without other confirmatory tests is mandatory to remove the embolic source and correct any technical problems. This will likely improve the neurologic outcome in these patients, because an uncorrected situation would lead to continued embolization and compromise.

The effect of a venous anastomosis Tyrell vein collar on the primary patency of arteriovenous grafts in patients undergoing hemodialysis.

PURPOSE: Vein collars and patches are used at the distal anastomoses of infrainguinal prosthetic grafts to improve graft patency. We initiated a randomized, prospective study to determine whether a Tyrell vein collar at the venous anastomosis of forearm loop arteriovenous grafts (AVGs) would improve patency. METHODS: Patients who required new forearm AVGs were randomized to (1) a standard end-to-side graft-vein anastomosis (control group) or (2) a Tyrell vein collar between the graft and the vein (study group). End points were (1) graft thrombosis, (2) graft removal and ligation, or (3) inadequate graft function. Randomization of 75 subjects was planned. The study was terminated early for ethical reasons. RESULTS: Seventeen patients (eight men, nine women) with a mean age of 52.8 years (range, 31-79 years) had 17 grafts placed (control group, n = 10; study group, n = 7). Comorbidities were not different between the groups (P>.05). Six (86%) of seven study grafts failed by 9 months (mean, 4.6 months). Four (66%) failed study grafts had venous outflow tract stenosis from intimal hyperplasia. This was confirmed at surgery in three and by angiography in one. The 9-month primary patency was 80% for the control group versus 17% for the study group (P =.015). Smaller outflow vein diameter in the study group (P =. 048) did not account for this inferior graft patency. CONCLUSION: A Tyrell vein collar at the venous anastomosis of a forearm AVG resulted in premature graft failure. The use of a Tyrell vein collar may accelerate venous anastomosis intimal hyperplasia.

Voluntary class absences and other behaviors in college students: an exploratory analysis.

In a survey of 120 sophomore and junior undergraduate college students, we found that those who admitted to cutting class for no reason during the previous month had a lower mean GPA than those who reported no voluntary absences. Cutting class was related to reports of getting drunk, speeding, breaking the law, and visiting home, although reports of speeding, getting drunk, and breaking the law were not related to GPA. The 11 students who reported feeling depressed had a lower GPA than those without depression, while the 18 students who had not visited their families in the previous month had higher GPAs than those who had visited their families. Implications for scale development are discussed.

Spousal homicide and suicide in Quebec.

Domestic violence is a cause for major concern in psychiatry today, yet little is known about the amplitude and dynamics of spousal homicide and extended suicide. Within the jurisdiction of the Quebec Coroner's Office, the investigation files on all consecutive cases of deceased victims of intrafamilial violence occurring between 1991 and 1998 were reviewed. Using a validated checklist, a variety of variables were systematically collected and reviewed for descriptive analysis. Three hundred eighty-eight cases of death were studied. Of this sample, 145 cases (37.4%) concerned victims of conjugal homicide. Fifty-eight cases (40.01%) concerned victims whose homicidal spouses subsequently killed themselves. Suicidal offenders were more likely to be men, to be estranged from their spouse through separation, and, most often, to have used a firearm in the commission of the extended homicide-suicide. The majority of offenders suffered from clinical symptoms of depression. This study emphasizes the need to develop a detailed tool to assist coroners in the field and police investigators with the gathering of specific information that will be of use to clinical researchers.

Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators.

BACKGROUND: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. RESULTS: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.

Isolation of the left innominate artery in an elderly patient without congenital heart disease.

We report a rare anomaly consisting of a right aortic arch with an isolated left innominate artery in an elderly man without congenital heart disease.

Expression of human interleukin-17 in Pichia pastoris: purification and characterization.

A Pichia pastoris expression clone has been developed to produce the human cytokine interleukin-17 (hIL-17). Characterization of purified recombinant hIL-17 made with this clone demonstrated that it shared many characteristics with hIL-17 produced in mammalian cells. The hIL-17 produced in Pichia had the correct N-terminus of natural mature hIL-17 and a glycosylation pattern similar to hIL-17 produced in mammalian cells; both Pichia and human cells add approximately 5 kDa of sugars via N-linked glycosylation and both express a mixture of the glycosylated and nonglycosylated forms. Gel filtration provides evidence that the Pichia produced hIL-17 exists as a dimer in solution. A combination of cation-exchange and gel-filtration chromatography yielded 3.5 mg of highly purified and biologically active hIL-17 from a 10-liter fermentation. These results show that P. pastoris is a useful system to produce recombinant hIL-17 in structure/function studies of this molecule.

Symptomatic venous hypertension because of occult iliofemoral deep vein thrombosis: a report of two cases.

Two 25-year-old males with symptomatic venous hypertension (venous claudication, n = 1; swollen leg, n = 1) were evaluated for iliofemoral venous occlusive disease. One patient had a common femoral vein/external iliac vein occlusion with no history of deep vein thrombosis or trauma. The second patient had an acute deep vein thrombosis superimposed on a chronic external iliac vein stenosis. No source of extrinsic venous compression was identified in either patient. Venous reconstruction with vein bypass (patient no. 1) and vein patch angioplasty (patient no. 2) led to resolution of their hypertensive symptoms. Intraoperative examination of the involved vein segments revealed chronic changes consistent with a prior occult deep vein thrombosis in both patients. Occult iliofemoral deep vein thrombosis in young healthy males is rarely seen. The acute deep vein thrombosis may manifest minimal or no symptoms but it can lead to chronic venous occlusive disease and serious post-phlebitic morbidity. In this context, these two cases are discussed with a review of the pertinent literature.