The PiCT® test is a reliable alternative to the activated partial thromboplastin time in unfractionated heparin therapy management: results from a multicenter study.

Essentials Activated partial thromboplastin time (APTT) or anti-Xa tests are used to monitor heparin. Prothrombinase-induced Clotting Time (PiCT) was compared to APTT in a clinical study. PiCT shows higher correlation to anti-Xa than APTT does and is more comparable between centers. PiCT demonstrates significantly higher accuracy and reliability than APTT in heparin monitoring. SUMMARY: Background Unfractionated heparin (UFH) is still a commonly used anticoagulant for prevention and treatment of thromboembolism in a variety of situations. Increasingly, chromogenic anti-Xa assays are used for UFH monitoring given the high variability of the activated partial thromboplastin time (APTT) in this setting. On the other hand, and despite the known variability, the APTT test remains the most frequently used monitoring tool in UFH therapy because of its broad availability, lower costs and wide acceptance. Various guidelines continue to recommend the use of the APTT as an anti-Xa surrogate, but this approach remains controversial. Objective To assess the prothrombinase-induced clotting time (PiCT® ) test, reported in seconds, as an alternative to the APTT in the management of UFH-mediated anticoagulation. Methods Plasma samples from patients receiving UFH were obtained in three different centers in the USA and Europe. Samples were analyzed for PiCT, APTT and anti-Xa activities with conditions set to allow comparability. Target-ranges in seconds for PiCT and APTT were established for a UFH concentration of 0.3-0.7 IU mL-1 , derived from anti-Xa results as suggested by the ACCP guidelines. Results PiCT demonstrated better correlation with anti-Xa IU mL-1 than APTT, higher ability to identify samples within target range and, importantly, comparable target-ranges between different centers. Conclusion Accuracy and reliability of PiCT are significantly better than those of APTT in monitoring UFH for anticoagulant therapy.

Prospective evaluation of protein C and factor VIII in prediction of cancer-associated thrombosis.

Venous thromboembolism (VTE) is a preventable disease, yet it is one of the leading causes of death among patients with cancer. Improving risk stratification mechanisms will allow us to personalize thrombo-prophylaxis strategies. We sought to evaluate Collagen and Thrombin Activated Platelets (COAT-platelets) as well as protein C and factor VIII as biomarkers predictive of cancer-associated thrombosis in a prospective cohort of patients with cancer. Protein C was selected as a candidate based on bioinformatics prediction. Blood samples were collected before chemotherapy. All specimen processing was blinded to clinical data. Surveillance and adjudication of the main outcome of VTE was performed for up to 1 year. We used Cox proportional hazard regression to measure the association of biomarkers and incident events using SAS 9.2 for all statistical analysis. Death was modeled as a competing event. Among 241 patients followed for an average of 10.4 months, 15% died and 13% developed a VTE. COAT-platelets were not predictive of VTE. Low levels of pre-chemotherapy protein C (<118%) (HR 2.5; 95% CI 1.1-5.5) and high baseline factor VIII (>261% I) (HR 3.0; 95% CI 1.1-8.0) were predictive of VTE after adjusting for age, Khorana prediction risk, metastatic disease and D dimer. In addition, low protein C was predictive of overall mortality independent of age, metastatic disease and functional status (HR 2.8; 95% CI 1.3-6.0). Addition of these biomarkers to cancer-VTE risk prediction models may add to risk stratification and patient selection to optimize thrombo-prophylaxis.

Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome.

BACKGROUND: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep vein thrombosis (DVT). OBJECTIVE: In the BioSOX study, we investigated whether inflammation markers predict the risk of PTS after DVT. METHODS: We measured C-reactive protein (CRP), ICAM-1, interleukin (IL)-6, and IL-10, at baseline, and 1 month and 6 months after a first proximal DVT, among 803 participants in the SOX trial. Participants were prospectively followed for 24 months for development of PTS. RESULTS: Median CRP levels at 1 month, ICAM-1 levels at baseline, 1 month and 6 months, IL-6 levels at 1 month and 6 months and IL-10 levels at 6 months were higher in patients who developed PTS than in those who did not. Multivariable regression with the median as a cutoff showed risk ratios (RRs) for PTS of 1.23 (95% confidence interval [CI] 1.05-1.45) and 1.25 (95% CI 1.05-1.48) for ICAM-1 at 1 month and 6 months, respectively, and 1.27 (95% CI 1.07-1.51) for IL-10 at 6 months. Quartile-based analysis demonstrated a dose-response association between ICAM-1 and PTS. ICAM-1 and IL-10 were also associated with PTS severity. Analysis of biomarker trajectories after DVT demonstrated an association between the highest-trajectory group of ICAM-1 and PTS. CONCLUSIONS: In this prospective study, ICAM-1 over time was most consistently associated with the risk of PTS. Further study is required to confirm these findings and assess their potential clinical relevance.

Graduated compression stockings to treat acute leg pain associated with proximal DVT. A randomised controlled trial.

Acute deep venous thrombosis (DVT) causes leg pain. Elastic compression stockings (ECS) have potential to relieve DVT-related leg pain by diminishing the diameter of distended veins and increasing venous blood flow. It was our objective to determine whether ECS reduce leg pain in patients with acute DVT. We performed a secondary analysis of the SOX Trial, a multicentre randomised placebo controlled trial of active ECS versus placebo ECS to prevent the post-thrombotic syndrome.The study was performed in 24 hospital centres in Canada and the U.S. and included 803 patients with a first episode of acute proximal DVT. Patients were randomised to receive active ECS (knee length, 30-40 mm Hg graduated pressure) or placebo ECS (manufactured to look identical to active ECS, but lacking therapeutic compression). Study outcome was leg pain severity assessed on an 11-point numerical pain rating scale (0, no pain; 10, worst possible pain) at baseline, 14, 30 and 60 days after randomisation. Mean age was 55 years and 60% were male. In active ECS patients (n=409), mean (SD) pain severity at baseline and at 60 days were 5.18 (3.29) and 1.39 (2.19), respectively, and in placebo ECS patients (n=394) were 5.38 (3.29) and 1.13 (1.86), respectively. There were no significant differences in pain scores between groups at any assessment point, and no evidence for subgroup interaction by age, sex or anatomical extent of DVT. Results were similar in an analysis restricted to patients who reported wearing stockings every day. In conclusion, ECS do not reduce leg pain in patients with acute proximal DVT.

Performance of endovenous foam sclerotherapy in the USA for the treatment of venous disorders: ACP/SVM/AVF/SIR quality improvement guidelines.

OBJECTIVE: This report summarizes the findings of the consensus panel based on the results of the comprehensive questionnaire of US American College of Phlebology annual congress attendees and results of the systematic meta-analysis of the literature and provides quality improvement guidelines for the use of endovenous foam sclerotherapy (EFS) for the treatment of venous disorders, as well as identifies areas of needed research. METHODS: Based on the above data, quality improvement guidelines were developed and reviewed by the ten US consensus panel members and approved by their respective societies. RESULTS: EFS is effective for the treatment of truncal and tributary varicose veins, both as primary treatment and for treatment of recurrence. It may improve the signs and symptoms associated with varicose veins including pain and swelling. EFS is contraindicated in patients who have experienced an allergic reaction to previous treatment with foam or liquid sclerosant, and in patients with acute venous thrombosis events secondary to EFS. CONCLUSION: These guidelines for the use of EFS in the treatment of venous disorders provide an initial framework for the safe and efficacious use of this therapy, and the impetus to promote the evaluation of the questions remaining regarding the use of EFS through well-designed randomized and cohort studies.

Obesity affects short-term folate pharmacokinetics in women of childbearing age.

Maternal folate status and body mass index (BMI) are independent risk factors for neural tube defects (NTD). Population-based studies have identified an inverse association between serum folate and BMI, after adjusting for intake. The objective of this intervention study was to compare the relationship between BMI and the short-term pharmacokinetic response to an oral dose of folic acid. Healthy obese (BMI 30.0 kg m(-2); n=16) and normal-weight (BMI 18.5-24.9 kg m(-2); n=16) women of childbearing age (18-35 years) were administered a single oral dose of folic acid (400 µg). Blood samples were collected over a 10-h period to evaluate the serum folate response. Fasting baseline serum folate was lower in the obese group (P=0.005); in contrast, red blood cell folate was higher (P=0.05). Area-under-the-curve for the absorption phase (0-3 h) and peak serum folate concentrations were lower in obese versus normal-weight women (P<0.005). Overall serum folate response (0-10 h) was lower in obese versus normal-weight women (repeated-measures ANOVA, P=0.001). Data suggest body distribution of folate is significantly affected by obesity, and, should pregnancy occur, may reduce the amount of folate available to the developing embryo. These findings provide additional support for a BMI-adjusted folic acid intake recommendation for NTD risk reduction.

Efficacy and safety of endovenous foam sclerotherapy: meta-analysis for treatment of venous disorders.

AIM: Endovenous foam sclerotherapy (EFS) is used widely throughout the USA for the treatment of venous disorders. The purpose of the quantitative meta-analysis was to systematically and comprehensively evaluate the literature to provide accurate estimates of safety and efficacy outcomes for this procedure. METHODS: A comprehensive electronic search of published literature in several databases was performed using a wide variety of MESH headings. In addition, meeting abstracts and bibliographies of selected references were reviewed for eligible papers. Two reviewers abstracted selected treatment-related data. RESULTS: Of 684 identified manuscripts and abstracts reviewed, 104 papers were abstracted and analysed. More than 50% were published between 2004 and 2008. EFS was found to be effective with similar vein occlusion rates to laser therapy, but less effective than surgery. In addition, major adverse effects were rare. CONCLUSIONS: EFS is a safe and effective therapy for the treatment of venous disorders.

A randomized trial of dalteparin compared with ibuprofen for the treatment of superficial thrombophlebitis.

BACKGROUND: Superficial thrombophlebitis can produce pain and result in a deep vein thrombosis (DVT) if not treated. Conservative therapies including prescription of non-steroidal anti-inflammatory drugs (NSAID) and heat have been standard care. Recently, studies have been published reporting efficacy and safety of low-molecular-weight heparin for the treatment of superficial thrombophlebitis. However, there are few comparative trials to conservative therapy. We studied the effectiveness and safety of treatment with dalteparin compared with ibuprofen in patients with confirmed superficial thrombophlebitis. METHODS: Consecutive patients were randomized to receive daily dalteparin vs. ibuprofen three times daily for up to 14 days. The primary outcome measure was the incidence of extension of thrombus or new symptomatic venous thromboembolism during the 14-day and 3-month follow-up period. The secondary outcome was a reduction in pain. The outcome measure of safety was the incidence of major and minor bleeding. RESULTS: Of 302 consecutive patients screened, 72 were enrolled. Four patients receiving ibuprofen compared with no patients receiving dalteparin had thrombus extension at 14 days (P = 0.05), however, there was no difference in thrombus extension at 3 months. Both treatments significantly reduced pain. There were no episodes of major or minor bleeding during the treatment period. CONCLUSIONS: Dalteparin is superior to the NSAID ibuprofen in preventing extension of superficial thrombophlebitis during the 14-day treatment period with similar relief of pain and no increase in bleeding. However, questions concerning the optimal treatment duration should be explored in future trials.

Performance of endovenous foam sclerotherapy in the USA.

PURPOSE: To assess practice patterns of endovenous foam sclerotherapy (EFS) use in the USA. METHODS: A multidisciplinary panel of US experts was convened and developed a questionnaire to assess use of EFS. US attendees at the American College of Phlebology 2009 Annual Congress were asked to complete the questionnaire. RESULTS: Of 776 questionnaires distributed, 239 were completed (31%). The majority of respondents (87%) reported using EFS for the treatment of venous disorders. Foam sclerotherapy was used by a wide variety of specialists in every region of the USA. The most common indication was sclerosis of recurrent truncal or tributary veins of the leg. There was variation among practitioners in the indications for use, pre- and postprocedural evaluation and procedure methodology. CONCLUSIONS: The results of this questionnaire show widespread usage of EFS and are important in the development of national quality improvement guidelines for the performance of EFS.

Treatment of upper-extremity deep vein thrombosis.

BACKGROUND: Upper extremity deep vein thrombosis (DVT) can result in fatal pulmonary embolism if not treated. Patients with malignancy may be at particularly high risk. Heparin or low-molecular-weight heparin followed by warfarin has been used as standard treatment for lower extremity DVT. However, a paucity of studies exist reporting the efficacy and safety of these regimens in patients with upper extremity DVT. We studied the effectiveness and safety of treatment with dalteparin sodium followed by warfarin and also dalteparin sodium monotherapy for 3 months in patients with confirmed upper extremity DVT. METHODS: Consecutive patients with confirmed upper extremity DVT received daily dalteparin sodium for 5-7 days followed by warfarin therapy for 3 months (phase I) or dalteparin sodium monotherapy for 3 months (phase II). The primary outcome measure was the incidence of new symptomatic venous thromboembolism during the 3-month follow-up period. The outcome measure of safety was the incidence of major and minor bleeding. RESULTS: Of 631 consecutive patients screened, 74 were eligible and 67 enrolled. No patients receiving either phase I (0%; 95% CI, 0-12%) or phase II (0%; 95% CI, 0-9%) therapy had venous thromboembolism on 3-month follow-up. One patient (4%; 95% CI, 0-18%) receiving phase I therapy experienced major bleeding. Five patients died during the follow-up period; none were attributed to pulmonary embolism. CONCLUSIONS: Patients with upper extremity DVT may be treated safely with either dalteparin sodium followed by warfarin or dalteparin sodium monotherapy for 3 months with a good prognosis.

Development of late, symptomatic abdominopelvic lymphoceles more than 10 years following pediatric reconstructive urologic procedures.

PURPOSE: Rare reports of symptomatic abdominopelvic lymphoceles following pediatric genitourinary reconstruction do exist; however there are no data regarding the development or management of late symptomatic lymphoceles. We report on the clinical presentation of these lymphoceles 10 or more years following initial urologic surgery. MATERIALS AND METHODS: We reviewed 480 patients following major intra-abdominal urologic reconstructive procedures from 1986 to 2009 for development of late, symptomatic abdominopelvic lymphoceles. A minimum of 10 years post-surgical follow up was required for inclusion. RESULTS: Late symptomatic lymphoceles developed in 4/480 (0.8%) patients. Median length of follow up post reconstruction was 13.5 years (range 10-17). Median time to lymphocele development was 12 years (range 8-16). Symptoms at presentation included abdominal distension (4/4, 100%), nausea and vomiting (3/4, 75%), flank pain/progressive hydroureteronephrosis (3/4, 75%), and obstructive pyelonephritis (1/4, 25%). Additional surgical procedures that may have contributed to lymphocele development were present in 100%. 75% (3/4) of the patients underwent open surgical drainage, with one electing observation for intermittent symptoms. Exploration revealed loculated fluid collections between bowel loops and dense adhesions; symptoms resolved although small asymptomatic recurrences developed in all patients. CONCLUSIONS: Late, symptomatic abdominopelvic lymphoceles following major pediatric urinary tract reconstruction or diversion develop in <1% patients. Many undergo subsequent abdominopelvic surgery, which may contribute to development of these late, pathologic lymphoceles. Open surgical drainage is usually required with excellent outcome.

Long-term follow up of enteric bladder augmentations: the risk for malignancy.

OBJECTIVE: To determine the risk of bladder cancer following enteric bladder augmentation. MATERIALS AND METHODS: Patients followed for care after an enteric bladder augmentation have been entered into a registry; individuals followed for a minimum of 10 years were evaluated. RESULTS: The study criteria were met by 153 patients. Indications for bladder augmentation were neurogenic bladder in 97, exstrophy in 38 and posterior urethral valves in 18. There was a median follow-up interval of 27 years (range 10-53). A total of seven cases of malignancy developed. Median time to tumor development following augmentation was 32 years (range 22-52). Two patients with neurogenic bladder developed transitional cell carcinoma; both were heavy smokers (>50 pack per year history). Two patients with a history of posterior urethral valves and renal transplantation developed adenocarcinoma of the enteric augment. Three patients with bladder exstrophy developed multifocal adenocarcinoma of the augmented bladder. Two patients remain alive, 5 and 6 years following radical cystoprostatectomy; five died of cancer-specific causes. CONCLUSIONS: Malignancy following enteric bladder augmentation arose in 4.5% (7/153) of our patients and was associated with coexisting carcinogenic stimuli (prolonged tobacco/chronic immunosuppressive exposure), or alternatively with the inherent risk of malignancy existing with bladder exstrophy.

Long-term followup of visual internal urethrotomy for management of short (less than 1 cm) penile urethral strictures following hypospadias repair.

PURPOSE: We reviewed the results of direct vision urethrotomy for short (less than 1 cm) penile urethral strictures following hypospadias surgery. MATERIALS AND METHODS: Patients with less than 1 cm anterior penile urethral strictures located proximal to the meatus underwent direct vision urethrotomy. Based on the type of initial urethroplasty patients were randomly divided into treatment with direct vision urethrotomy vs direct vision urethrotomy plus clean intermittent catheterization for 3 months. Success was defined as absent obstructive voiding symptoms and a normal urine flow 2 years following the last patient instrumentation. RESULTS: Of patients with urethral strictures following hypospadias repair 44% (32) had previously undergone tubularized graft urethroplasty and 56% (40) had previously undergone flap urethroplasty, including a tubularized island flap in 18, an onlay flap in 11 and urethral plate urethroplasty in 11. Direct vision urethrotomy alone was performed in 51% of patients (37), and direct vision urethrotomy and clean intermittent catheterization were performed in 49% (35). Success with the 2 methods was similar, that is 24% (9 of 37 patients) vs 22% (8 of 35). Following direct vision urethrotomy all patients with tubularized graft urethroplasty showed failure (0 of 32). Success was noted in 11% of patients (2 of 18) with tubularized island flap urethroplasty compared to 72% (8 of 11) with onlay urethroplasty and 63% (7 of 11) with urethral plate urethroplasty (each p <0.05). CONCLUSIONS: The addition of clean intermittent catheterization to direct vision urethrotomy does not improve the likelihood of success. Direct vision urethrotomy for short (less than 1 cm) urethral stricture usually fails following any type of tubularized graft or flap urethroplasty but it had moderate success following onlay flap and urethral plate urethroplasties.

Double-blind placebo controlled study of alpha-adrenergic receptor antagonists (doxazosin) for treatment of voiding dysfunction in the pediatric population.

PURPOSE: We sought to determine whether the alpha-adrenergic antagonist doxazosin could be used as primary therapy in children with voiding dysfunction. MATERIALS AND METHODS: Children were assigned to maintain a voiding diary and then randomly divided into a double-blind placebo controlled protocol (0.5 mg doxazosin or placebo). Duplicate uroflow studies with post-void residual evaluations and assessment of dysfunctional voiding scores were performed on initiation and completion of the study. At the conclusion parents were asked to rank the perceived improvement of the urinary incontinence (ie parental subjective perception of improvement). RESULTS: No significant differences between doxazosin (18) and placebo (20) treated patients were found in the number of incontinent days per week, severity of incontinent episodes or alterations in uroflow patterns. Although not significant, 2 findings suggested a beneficial effect of doxazosin over placebo. Specifically, doxazosin decreased the number of incontinent episodes weekly from a median of 18 to 4, while the number of incontinent episodes weekly in the placebo group remained essentially unchanged, decreasing from 15 to 14 (p = 0.13). Doxazosin also improved the dysfunctional voiding scores over placebo, for an improvement of -3 vs 0 points. Further substantiating a doxazosin effect over placebo was the subjective perception of the parents that doxazosin significantly improved urinary continence (p <0.02). CONCLUSIONS: Compared to placebo, doxazosin did not demonstrate a significant objective benefit, but produced a significant subjective benefit in the treatment of urinary incontinence secondary to voiding dysfunction.

Management of urinary incontinence and nocturnal enuresis in attention-deficit hyperactivity disorder.

PURPOSE: We sought to determine whether attention-deficit hyperactivity disorder (ADHD) influences the resolution of urinary incontinence (UI, or diurnal and nocturnal wetness) and monosymptomatic nocturnal enuresis (NE). MATERIALS AND METHODS: We performed a retrospective review of patients with ADHD, UI and NE. Individuals with UI were treated with timed voiding, and anticholinergics were added only after timed voiding failed. Patients with NE were treated with either an enuretic alarm, desmopressin or imipramine. Statistical comparisons used a control population matched for age, sex, IQ, and urinary and gastrointestinal symptoms. RESULTS: The presence of ADHD had a negative effect on the resolution of incontinence, with 68% of the patients with ADHD becoming continent compared to 91% of controls (p <0.01). Two factors impact the resolution of wetness in patients with ADHD-treatment noncompliance and IQ. Treatment noncompliance was found in 48% of the patients with ADHD compared to 14% of controls (p <0.01). The IQ of patients with ADHD affected success, with 32% of children with an IQ of less than 84 achieving continence compared to 80% of those with an IQ of 84 or greater (p <0.01). Patients with ADHD and NE responded similarly to controls when using desmopressin and imipramine. However, they were less likely to exhibit a durable response following management with an enuretic alarm (19% vs 66%, p <0.01). CONCLUSIONS: Treatment of urinary incontinence in children with ADHD is impaired compared to those without ADHD, and is directly affected by compliance and IQ.

p53 immunopositivity in histologically favorable Wilms tumor is not related to stage at presentation or to biological aggression.

PURPOSE: Previous studies have suggested that increased p53 expression is associated with advanced stage and biologically aggressive (chemotherapy resistant) Wilms tumors. We decided to test the hypothesis that increased immunopositivity of p53 is associated with biological aggressiveness in patients with histologically favorable Wilms tumors. MATERIALS AND METHODS: We reviewed the charts of all patients with unilateral Wilms tumor treated at our institution between 1976 and 2001. Histological characteristics, tumor stage, clinical course and p53 expression as determined by immunohistochemical analysis were determined. All immunohistological evaluations were performed on tissue obtained before administration of chemotherapy. RESULTS: A total of 63 cases of unilateral histologically favorable Wilms tumor were assessed. Five cases (8%) were p53 positive. No significant relationship to p53 expression or stage at presentation was noted in 1 of 21 (5%) stage 1, 3 of 21 (14%) stage 2, 1 of 11 (9%) stage 3 and 0 of 10 stage 4 tumors positive for up-regulation of p53. Of the 5 patients with up-regulated p53 expression 1 (20%) had documented disease progression or relapse while on standard National Wilms Tumor Study chemotherapy. Of the 58 patients who were p53 negative 10 (17%) had disease progression or relapse while on standard National Wilms Tumor Study chemotherapy (p >0.3). CONCLUSION: In contrast to previously published studies, we found no correlation of p53 expression to either tumor stage at presentation (p >0.3) or prognosis (p >0.3) in individuals with histologically favorable Wilms tumor assessed for immunopositivity before administration of chemotherapy.

Penoscrotal transposition: review of 53 patients.

PURPOSE: Penoscrotal transposition is a rare congenital abnormality of the external genitalia. We determine whether there is a genetic basis for this disorder, define the incidence of coexisting organ system anomalies, and compare the results of surgical techniques to correct transposition and hypospadias. MATERIALS AND METHODS: We report the largest, single institution series of 53 patients 1 day to 30 years old with penoscrotal transposition. RESULTS: Of the patients 13% had a family history of penoscrotal transposition. Interestingly, we identified 1 family in which inheritance occurred in an X-linked recessive manner. There were 17 (32%) patients who had abnormalities in other organ systems, with the genitourinary system in 9 affected most. A total of 79% of patients had hypospadias and 81% chordee. These anomalies were corrected with a single stage Thiersch-Duplay urethroplasty in 6 patients and complex repair with bladder or buccal mucosa, or a staged procedure in 34. Complication rates for urethroplasty were similar. Correction of the transposition included a Glenn-Anderson technique in 37 patients, Singapore rotational flaps in 7 and V-Y procedure in 6. The Glenn-Anderson repair produced the best cosmetic results and was associated with a significantly lower incidence of complications (p = 0.001). CONCLUSIONS: We identified a subgroup of patients with a family history of penoscrotal transposition. Treatment requires an awareness of the association with other organ system anomalies. The Glenn-Anderson technique was the most successful method to correct transposition. Most patients required release of chordee and complex urethroplasty for hypospadias.

Quantitative comparisons of 16S rRNA gene sequence libraries from environmental samples.

To determine the significance of differences between clonal libraries of environmental rRNA gene sequences, differences between homologous coverage curves, CX(D), and heterologous coverage curves, CXY(D), were calculated by a Cramér-von Mises-type statistic and compared by a Monte Carlo test procedure. This method successfully distinguished rRNA gene sequence libraries from soil and bioreactors and correctly failed to find differences between libraries of the same composition.

A case report of warfarin resistance due to azathioprine and review of the literature.

A 32-year-old woman with a history of deep vein thrombosis (DVT), steroid-dependent ulcerative colitis, and osteoporosis was prescribed azathioprine for a steroid-sparing effect. Stable, therapeutic international normalized ratios (INRs) were obtained with warfarin 35 mg/week during a 6-week postpartum course to treat an initial DVT. Ten days after completing warfarin therapy, azathioprine was begun. A recurrent DVT occurred 9 days later, and an increase in warfarin dosage to 120 mg/week was necessary to achieve an INR of 2.0-3.0. The patient denied changes in warfarin adherence, dietary vitamin K intake, or medical conditions. The addition of azathioprine was the only change in her regimen. Review of the literature found only limited reports of an interaction between warfarin and azathioprine, with increases in warfarin requirements of 3-4 times. Careful monitoring and caution are recommended when administering these two drugs concomitantly.

Association between results of ambulatory electrocardiography and development of cardiomyopathy during long-term follow-up of Doberman pinschers.

OBJECTIVE: To characterize ambulatory electrocardiographic results of overtly healthy Doberman Pinschers and determine associations between those results and development of dilated cardiomyopathy. DESIGN: Cohort study. ANIMALS: 114 (58 male, 56 female) overtly healthy Doberman Pinschers without echocardiographic evidence of cardiac disease on initial examination. PROCEDURE: Echocardiograms and 24-hour ambulatory electrocardiograms (Holter recordings) were obtained initially and at variable intervals. The status (live vs dead) of all dogs was known at least 2 years and as long as 10 years after initial examination (mean [+/- SD] follow-up time, 4.33 +/- 1.84 years). Associations between development of dilated cardiomyopathy and number of ventricular premature contractions (VPC), age, and sex were determined. RESULTS: 55 dogs (48%) did not have VPC on initial Holter recordings, and only 8 dogs had > 50 VPC/24 hours. The likelihood that a dog would have VPC was associated with increasing age and being male. At least 1 VPC/24 hours, and in particular, > 50 VPC/24 hours or > or = 1 couplet or triplet of VPC/24 hours, were predictive of subsequent development of dilated cardiomyopathy. Fifty-four dogs (47%) developed dilated cardiomyopathy; 12 were still alive at the end of the study, and 42 had died. Twenty-five of these 42 dogs died after the onset of congestive heart failure (CHF), 15 died suddenly before the onset of overt CHF, and 2 died of noncardiac causes. More males developed dilated cardiomyopathy than females, and dogs that died suddenly were approximately 1 year younger than those that developed CHF. CONCLUSIONS AND CLINICAL RELEVANCE: Results of high-quality Holter recordings may be used to identify overtly healthy Doberman Pinschers that are at a high risk for dilated cardiomyopathy.