PubMed HealthSearch

Biomedical subjects

J Weitz

Publications and source records attributed to J Weitz.

At least 19 recordsLinked to original sources

A simple clinical model for the diagnosis of deep-vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process.

OBJECTIVES: We recently demonstrated the utility of a clinical model combined with ultrasonography to assist the diagnostic approach in patients with suspected deep-vein thrombosis (DVT). In this study we also sought to demonstrate that the model is useful with impedance plethysmography, a less accurate and less utilized diagnostic test. The original clinical model is slightly cumbersome to use; thus at the completion of the study we attempted to develop a simpler scoring system with a goal of maintaining accuracy. DESIGN: An open, nonrandomized, multicentre trial. SETTING: Three centres, two in Canada, and one in Italy. SUBJECTS: Ambulatory patients with suspected deep-vein thrombosis. INTERVENTIONS: All patients were assessed clinically to determine the probability for deep-vein thrombosis prior to performing impedance plethysmography and venography. We compared the accuracy of impedance plethysmography between the three pretest probability categories of high, moderate and low. All of the above were performed and interpreted by independent observers. When the study was completed, we revised the clinical model by first performing a simple regression analysis then a multiple logistic regression analysis; a scoring system was devised using the latter. RESULTS: Impedance plethysmography is significantly more sensitive and less specific for all DVT in patients with high pretest probability for deep-vein thrombosis (P = 0.001). The post- test probability (positive predictive value) for deep-vein thrombosis with an abnormal impedance plethysmography result was significantly different (P = 0.0001) between the three pretest probability categories. Multiple regression analysis has provided a new model with only nine variables and a simple scoring system. The retrospective application of the revised clinical model, which is simpler to use, suggests it will provide similar results as the original clinical model when combined with impedance plethysmography. The combination of impedance plethysmography and the clinical model suggests patients are likely to have false positive results if they have a low or moderate pretest probability for deep-vein thrombosis and false negative results if the pretest probability is high. The combination of a low pretest probability and a normal impedance plethysmography result may exclude the need for serial testing, and represented more than 50% of our patient population. CONCLUSIONS: The use of the clinical model in conjunction with impedance plethysmography would decrease the number of false positive and negative diagnoses and could markedly decrease the need for serial impedance plethysmography. Combining the clinical model with impedance plethysmography could overcome the fact that impedance plethysmography is clearly less accurate than venous ultrasound imaging. The use of the revised clinical model may increase acceptability and utility, but prospective testing is required before widespread use.

Diagnosis, Differential

Dissemination of tumor cells in patients undergoing surgery for colorectal cancer.

The majority of patients with colorectal cancer present at a stage when the primary cancer can be resected with curative intent. However, despite the high resectability rate, about 30-50% of these patients subsequently develop metastatic disease. In these patients, neoplastic cells were disseminated either before or during surgery of the primary cancer. Due to the lack of appropriate detection systems, the extent of pre- and intraoperative hematogenic tumor cell dissemination has not yet been determined. Using a reverse transcription-PCR assay to amplify cytokeratin 20 transcripts, we were able to detect 10 colorectal cancer cells in 10 ml of blood. Blood samples were taken from 65 patients undergoing resection of primary colorectal cancer or liver metastasis of colorectal cancer pre-, intra-, and postoperatively. Circulating tumor cells were detected in 24 of 58 patients with colorectal resections in correlation to the tumor stage and in 6 of 7 patients who underwent hemihepatectomy for liver metastasis. In 8 of 58 patients with colorectal resection and in 5 of 7 patients with hemihepatectomy, tumor cells could only be detected during or during and after surgery. These results demonstrate that hematogenic tumor cell dissemination is a frequent and early event in colorectal cancer. Surgery enhances the release of tumor cells into the circulation. The long-term follow-up of our patient cohort will provide data on the prognostic relevance of circulating tumor cells and might lead to new therapeutic concepts for perioperative prophylaxis of tumor cell implantation or postoperative adjuvant therapy regimens.

Adult

Analysis of FUS-CHOP fusion transcripts in different types of soft tissue liposarcoma and their diagnostic implications.

In myxoid and round cell liposarcomas, a specific chromosomal translocation [(12;16)(q13;p11)] results in the expression of chimeric fusion transcripts encompassing parts of the FUS gene (16p11) at their 5' ends and the CHOP gene (12q13) at their 3' ends. Using a reverse transcription-PCR protocol, we determined the prevalence of FUS-CHOP fusion transcripts in a series of liposarcoma samples. Fusion transcripts were detected in 13 of 30 biopsy samples from soft tissue liposarcomas. Expression of fusion transcripts was not restricted to myxoid and round cell liposarcomas, as suggested previously; it was also detected in 1 of 3 well-differentiated and 4 of 14 pleomorphic liposarcomas. Sequence analysis revealed four different FUS-CHOP fusion transcript variants, two of which have not been described before. Furthermore, using FUS-CHOP fusion transcripts as targets in reverse transcription-PCR assays, we detected disseminated tumor cells in peripheral blood or bone marrow in 3 of 5 patients undergoing surgery for soft tissue liposarcoma.

CCAAT-Enhancer-Binding Proteins

Fatal hepatic necrosis after isoflurane anaesthesia.

Several halogenated anaesthetic agents have been associated with hepatotoxicity. We report a case of fulminant, fatal hepatic necrosis after uneventful isoflurane anaesthesia in a patient without previous liver disease, who may have been sensitised by previous exposure to enflurane. Although no anti-trifluoroacetyl antibodies could be detected in the patient's serum, isoflurane hepatotoxicity seems very likely to be the reason for fulminant hepatic failure in this patient.

Adult

Ardeparin (low-molecular-weight heparin) vs graduated compression stockings for the prevention of venous thromboembolism. A randomized trial in patients undergoing knee surgery.

BACKGROUND: Deep vein thrombosis is common in patients undergoing major knee surgery. Static graduated compression stockings effectively prevent venous thrombosis in general surgery. Because of the demonstrated prophylactic efficacy of pneumatic compression in knee surgery, the similar efficacy of static graduated compression and pneumatic compression in neurosurgery, and the easier use of static graduated compression in knee surgery, graduated static compression stockings were used as the control arm in our clinical trial. Although low-molecular-weight heparin had been shown to be effective in general surgery and hip replacement, its efficacy was unproved in knee surgery. METHODS: A double-blind, randomized trial compared the combination of low-molecular-weight heparin and graduated compression stockings with graduated compression stockings alone in patients undergoing major knee surgery. Patients received either ardeparin (Normiflo) (low-molecular-weight heparin), 0.005 mL/kg (50 anti-Xa U/Kg), or placebo. Both were administered subcutaneously twice daily commencing 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. Both study groups wore graduated compression stockings. Bilateral venography was performed on day 14, or sooner if the patient was ready for discharge. RESULTS: One hundred twenty-two patients were allocated to receive ardeparin and 124 received placebo. Ninety-six patients in the ardeparin group and 103 in the placebo group had evaluable venograms. Deep vein thrombosis was detected in 28 patients in the ardeparin group and in 60 in the placebo group. Proximal deep vein thrombosis was detected in two patients who received ardeparin and 16 who received placebo. One patient in each group, both of whom did not have venography, experienced pulmonary embolism. Thus, deep vein thrombosis or pulmonary embolism was detected in 29 (29.9%) of the 97 patients in the ardeparin group and in 61 (58.7%) of the 104 patients in the placebo group, a relative risk reduction of 49% (P < 00.1). The rate of major bleeding in the ardeparin group was 2.5%, compared with 2.4% in the placebo group. CONCLUSION: Ardeparin administered postoperatively twice daily is effective and safe for the prevention of venous thrombosis in patients undergoing major knee surgery. Whereas graduated compression stockings have been shown to be effective prophylactic agents in general surgery and neurosurgery, they have little effect in knee surgery.

Aged

A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.

BACKGROUND: Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous standard (unfractionated) heparin. However, the longer plasma half-life, better bioavailability after subcutaneous administration, and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use. We compared these two approaches. METHODS: Patients with acute proximal deep-vein thrombosis were randomly assigned to receive either intravenous standard heparin in the hospital (253 patients) or low-molecular-weight heparin (1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily) administered primarily at home (247 patients). The study design allowed outpatients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early. All the patients received warfarin starting on the second day. RESULTS: Thirteen of the 247 patients receiving low-molecular-weight heparin (5.3 percent) had recurrent thromboembolism, as compared with 17 of the 253 patients receiving standard heparin (6.7 percent; P=0.57; absolute difference, 1.4 percentage points; 95 percent confidence interval, -3.0 to 5.7). Five patients receiving low-molecular-weight heparin had major bleeding, as compared with three patients receiving standard heparin. After randomization, the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital, as compared with 6.5 days for the standard-heparin group; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all. CONCLUSIONS: Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home.

Aged

Aspergillus endocarditis, myocarditis and pericarditis complicating necrotizing fasciitis. Case report and subject review.

A patient with Aspergillus endocarditis, myocarditis and pericarditis is described. A 55-year-old man developed necrotizing fasciitis of the lower abdominal wall, pelvis and right thigh. Despite aggressive surgical débridement and antibiotic coverage, the patient died of multisystem organ failure. Autopsy revealed Aspergillus thromboulcerative endocarditis, myocarditis and pericarditis, acute necrotizing fungal bronchopneumonia and mycotic dissemination to brain, kidney and thyroid gland. A review of the literature showed that in the absence of open-heart surgery Aspergillus endocarditis and myocarditis are very uncommon.

Aspergillosis

Interaction of low molecular weight heparin with ketorolac.

Postoperative patients may receive ketorolac, a nonsteroidal antiinflammatory drug that inhibits platelet function, for analgesia and may receive low-molecular-weight heparin (LMWH) for thrombosis prevention. We investigated whether the combination of these two agents increases blood loss in a rabbit model of hemostasis. In a randomized, blinded study, animals received either intramuscular ketorolac (0.5 mg/kg or 1.0 mg/kg) and subcutaneous saline solution, subcutaneous LMWH (100 U/kg) and intramuscular saline solution, ketorolac (0.5 mg/kg or 1.0 mg/kg) and subcutaneous LMWH (100 U/kg), or intramuscular and subcutaneous saline solution given 30 minutes before ear incision and measurement of blood loss. Collagen-induced platelet aggregation was examined and anti-Xa levels were determined by using a chromogenic substrate method. As compared with results in saline-treated controls, blood loss was significantly increased in animals receiving ketorolac in a dose of 1.0 mg/kg but not in those treated with 0.5 mg/kg. The addition of LMWH did not further increase blood loss above that observed with either dose of ketorolac alone. Platelet aggregation was inhibited by both doses of ketorolac. The anti-Xa levels in the LMWH-treated animals were comparable to those measured in patients receiving these agents for prophylaxis (0.09 to 0.13 U/ml). We conclude that in the rabbit model, LMWH does not augment ketorolac-associated bleeding when both agents are used in doses comparable to those given to human patients.

Animals

Decreased thrombin activity of fibrin clots prepared in cord plasma compared with adult plasma.

We hypothesized that the immaturity of the newborn coagulation system may influence the procoagulant activity of clotbound thrombin. 125I-Labeled fibrin clots were prepared from adult and cord plasma, incubated in their respective plasmas, and fibrinopeptide A (FPA) production was measured. Cord plasma clots generated significantly less FPA compared with adult plasma clots (p < 0.001). Cord plasma clots incubated in adult plasma generated similar amounts of FPA as cord plasma clots in cord plasma. Adult plasma clots incubated in cord plasma clots generated more FPA than adult plasma clots in adult plasma. Adult and cord plasma clots were then incubated with purified human adult fibrinogen, and the discrepancy between adult and newborn plasma clots remained (p < 0.01). To compare the amount of clot bound thrombin, adult and cord plasma clots were sonicated and incubated with fibrinogen. Again, significantly less thrombin was seen in cord clots compared with adult clots (p < 0.01). Because cord plasma has lower prothrombin concentrations (0.5 U/mL) we increased cord plasma prothrombin concentration by the addition of purified prothrombin. Prothrombin supplemented cord plasma clots generated more thrombin than unsupplemented clots (p < 0.01) and in amounts similar to the adult system. In conclusion, decreased amounts of thrombin present in cord plasma clots compared with adult plasma clots results in less FPA production. The low plasma concentration of prothrombin in cord plasma is responsible for this phenomenon.

Adult

Free protein S deficiency may be found in patients with antiphospholipid antibodies who do not have systemic lupus erythematosus.

In order to determine if there is a relationship between antiphospholipid antibodies and reduced free protein S levels, we evaluated 21 patients who had an antiphospholipid antibody but had neither a history of venous thromboembolism nor systemic lupus erythematosus (cases) and 55 matched controls, who did not have an antiphospholipid antibody, a history of thrombosis or systemic lupus erythematosus. Cases and controls had similar protein C and antithrombin levels. Six of 21 cases had reduced free protein S antigen levels, compared to 5 of 55 controls (chi 2 = 5.823 p < 0.025). In addition, the mean free protein S level was significantly lower in cases than in controls (0.30 +/- 0.09 units vs 0.39 +/- 0.13 units, p < 0.01, two-tailed Student's t-test). We conclude that antiphospholipid antibodies are associated with a significant decrease in free protein S levels, and that this acquired free protein S deficiency may contribute to the thrombotic diathesis seen in patients with antiphospholipid antibodies.

Adult

[pHi value as a prognostic parameter in septic and polytrauma patients].

In 17 patients in septic shock and in 12 trauma patients (ISS > or = 20) the gastric pHi and systemic oxygen delivery and consumption were measured every 6 h to evaluate the prognostic significance of the pHi and to determine the relationship between the gastric mucosal oxygenation and the systemic oxygen transport parameters. In the trauma patient the initial pHi has a high prognostic significance (mean survivors = 7.38; non-survivors = 7.15; p < 0.05), while in the septic group no patient with a pathologic pHi (< 7, 35) > or = 12 h survived. Since we found no correlation between pHi and systemic oxygen transport parameters, other factors have to be of greater importance for gut mucosal oxygenation.

Critical Care

Accuracy of clinical assessment of deep-vein thrombosis.

The clinical diagnosis of deep-vein thrombosis is generally thought to be unreliable. From experience, we hypothesised that this widely held view might be incorrect. We developed a clinical model and prospectively tested its ability in three tertiary care centres to stratify symptomatic outpatients with suspected deep-vein thrombosis into groups with high, moderate, or low probability groups of deep-vein thrombosis. We evaluated our clinical model in combination with venous ultrasonography to determine the potential for an improved and simplified diagnostic approach in patients with suspected deep-vein thrombosis. All patients were clinically assessed to determine the probability for deep-vein thrombosis before they had ultrasonography and venography. All tests were performed and interpreted by independent observers. In 529 patients, the clinical model predicted prevalence of deep-vein thrombosis in the three categories: 85% in the high pretest probability category, 33% in the moderate, and 5% in the low category. There was no statistical difference in the performance of the model in the three centres. The model demonstrated excellent interobserver reliability (Kappa = 0.85). There were important differences with ultrasonography between the high and low pretest probability groups for both positive predictive values (100% (95% CI, 94-100%) vs (63% [35-85%], respectively). Thus, use of the clinical model combined with ultrasonography would decrease the number of false positive and negative diagnosis if venography were done when the ultrasound result and pretest probability were discordant. The diagnostic process could be simplified by excluding those patients with low pretest probability and normal ultrasound results from serial testing.

Decision Trees

Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis.

The optimal duration of oral anticoagulant therapy for patients with acute proximal deep vein thrombosis (DVT) is uncertain. Based on the hypothesis that a normal impedance plethysmogram (IPG) following DVT defines a group of patients at low risk of recurrent venous thromboembolism (VTE), a trial was conducted to evaluate the efficacy of only four weeks of warfarin. Patients with venographically confirmed acute proximal DVT who had received four weeks of warfarin after initial heparin and whose four week IPG was normal were allocated to either continue warfarin (targeted International Normalized Ratio 2.0 to 3.0) for a further eight weeks or receive placebo. Patients with an abnormal four week IPG received warfarin for a further eight weeks. Based on clinical characteristics at the time of the qualifying thrombosis, all patients were classified as having either continuing or transient risk factors for recurrent VTE. During the eight weeks following randomization, nine (8.6%) of the 105 placebo patients developed recurrent VTE compared to one (0.9%) of the 109 warfarin patients, P = 0.009. Over the entire 11 months of follow-up, 12 placebo patients developed recurrence compared to seven warfarin patients, P = 0.3. Nineteen of the 192 patients with an abnormal four week IPG experienced recurrence during the nine months after discontinuing warfarin. In the 301 patients who received three months of warfarin in the randomized trial or in the cohort study, all 26 recurrent events were in the 212 patients with continuing risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Comparison of the accuracy of impedance plethysmography and compression ultrasonography in outpatients with clinically suspected deep vein thrombosis. A two centre paired-design prospective trial.

Impedance plethysmography (IPG) and compression ultrasonography (CUS) have been reported to be highly accurate for the diagnosis of deep vein thrombosis (DVT) in symptomatic patients. In many centres CUS has become the method of choice. However, direct comparisons of the accuracy of IPG to CUS have not been performed. To determine the test of choice we performed a two centre prospective comparison of IPG and CUS, with venography, and determined how the size and distribution of thrombi influenced the accuracy of each test. 495 symptomatic outpatients with suspected DVT had evaluable venograms. The prevalence of DVT was 27% (130/495), 84% (109) of which were proximal. The sensitivity of IPG and CUS for proximal vein thrombosis was 77% and 90% respectively (p = .002). The specificity of IPG was 93% whereas the specificity of CUS was 98% (p = 0.04). There were significant differences in accuracy between the two centres as a consequence of differences in the size and location of thrombi The majority of proximal thrombi not detected by IPG and CUS involved less than 5 cm of the distal half of the popliteal vein and most of these thrombi occurred in one centre. Exclusion of these thrombi from the analysis increases the sensitivity of CUS to 99% (86/87) and IPG to 91% (72/79), for proximal thrombi (P = .019). The positive predictive value of CUS was strongly influenced by the number of abnormal venous segments (three sites were examined); 100% (80/80) if two or three sites were abnormal, but only 68% if a single site was involved. We conclude that: 1) CUS is more accurate than the IPG for the diagnosis of DVT in symptomatic outpatients, and this relationship holds true regardless of the size or location of the DVT, 2) the sensitivities of IPG and CUS are much lower for small proximal DVT, and 3) confirmatory venography is warranted if the abnormality with CUS is limited to one venous segment.

Ambulatory Care

A randomized trial comparing activated thromboplastin time with heparin assay in patients with acute venous thromboembolism requiring large daily doses of heparin.

BACKGROUND: The management of heparin therapy in patients who have a subtherapeutic activated partial thromboplastin time (APTT) despite high doses of heparin is problematic because the risk of heparin-associated bleeding increases with dose. Results of experimental studies in animals indicate that when the APTT response to heparin is blunted by infusion of procoagulants, dose escalation can be avoided without compromising efficacy, by monitoring treatment with a heparin assay. METHODS: A randomized, controlled trial was conducted in which patients with acute deep vein thrombosis, pulmonary embolism, or axillary vein thrombosis who required 35,000 U or more of intravenous heparin by continuous infusion during the previous 24 hours were allocated to have their heparin therapy monitored either by anti-factor Xa levels (targeted range, 0.35 to 0.67 U/mL) or by the APTT (targeted range, 60 to 85 seconds). Both ranges were equivalent to a heparin level of 0.2 to 0.4 U/mL by protamine titration. RESULTS: Three (4.6%) of 65 patients in the anti-factor Xa group experienced recurrent venous thromboembolism compared with four (6.1%) of 66 patients in the APTT group (difference, 1.5%; confidence interval, -6.7% to 8.4%) (P = .7). There were four bleeding events (6.1%) in the APTT group compared with one (1.5%) in the anti-factor Xa group (difference, 4.6%; confidence interval, -3.3% to 7.5%) (P = .4). During the period of heparin therapy before warfarin treatment was begun, the patients in the APTT group required a statistically significantly greater amount of heparin compared with the patients in the anti-factor Xa group. The daily mean APTT was subtherapeutic in patients in the anti-factor Xa group, and it was within the therapeutic range in the APTT group. The daily mean anti-factor Xa levels for both groups were within the therapeutic range. CONCLUSION: The heparin assay is a safe and effective method for monitoring heparin treatment in patients with acute venous thromboembolism whose APTT remains subtherapeutic despite large daily doses of heparin. In such patients, dosage escalation can be avoided if the heparin level is therapeutic.

Acute Disease