Electrocardiographic abnormalities are frequently detected in healthy adult Borzoi with a normal echocardiogram.

OBJECTIVE: Borzoi reportedly experience sudden death. The objective of this study was to report ECG intervals, amplitudes, and frequency of ECG abnormalities in clinically healthy Borzoi. METHODS: 98 clinically healthy Borzoi were prospectively recruited and underwent echocardiogram, ECG, and cardiac troponin I testing between October 2020 and December 2022. Standard ECG measurements were obtained. Early repolarization notches and slurs were recorded. RESULTS: Of 82 Borzoi with a structurally normal echocardiogram, ventricular arrhythmias were documented in 8 (10%) dogs, all of which had normal cardiac troponin I concentrations. Median P wave duration was 55 milliseconds (range, 45 to 70 milliseconds). Median PR interval was 125 milliseconds (range, 80 to 175 milliseconds). Thirty-one (38%) Borzoi had first-degree atrioventricular block (PR interval > 130 milliseconds). Median QRS duration was 65 milliseconds (range, 48 to 90 milliseconds). Median QT interval was 235 milliseconds (range, 185 to 275 milliseconds). Twenty-nine (35%) and 15 (18%) of 82 Borzoi had QT intervals > 240 or > 250 milliseconds, respectively. Sixty-seven of 82 (82%) Borzoi had early repolarization notches or slurs. Seventeen of 82 (21%) Borzoi had an abnormality of the ST segment, most commonly convexity/doming. Convexity of the ST segment was intermittent (n = 9) or persistent (4). CONCLUSIONS: Ventricular arrhythmias, early repolarization, prolonged QT intervals, and ST segment abnormalities are not infrequent in clinically healthy Borzoi. P, PR, and QRS durations are commonly prolonged compared to general canine reference intervals. CLINICAL RELEVANCE: Future study into heritable channelopathies in Borzoi is warranted given the frequency of ventricular arrhythmias, repolarization abnormalities, and sudden death in the breed. Breed-specific ECG reference intervals are needed.

Echocardiographic values and prevalence of cardiac abnormalities in clinically healthy adult Borzoi dogs.

OBJECTIVE: To develop breed-specific echocardiographic values for normal Borzoi and to report the prevalence of structural cardiac abnormalities. ANIMALS: 146 clinically healthy, adult Borzoi dogs. METHODS: Cardiac auscultation and standard echocardiograms were performed. Longitudinal follow-up was described in a subset of dogs (n = 25). RESULTS: Most Borzoi were structurally normal (119/146, 81.5%), with breed-specific echocardiographic values generated independently for each sex, as females weighed significantly less than males (30.4 ± 3.8 kg vs 38.3 ± 4.1 kg, respectively; P < .001), and a significant impact of sex was found on most measurements. Physiologic heart murmurs were identified in 64/119 (53.8%) normal dogs. Thirty-six (30.2%) structurally normal dogs had trace or mild mitral regurgitation, and 43 (36.1%) had trace or mild tricuspid regurgitation. Structural cardiac disease was identified in 21 dogs (14.4%), including 9 dogs (6.2%) with dilated cardiomyopathy (DCM), 9 dogs (6.2%) with stage B1 myxomatous mitral valve disease (MMVD), and 3 (2.1%) dogs with congenital abnormalities. Seven dogs (4.8%) had equivocal abnormalities. During follow-up, new dogs were diagnosed with occult DCM (n = 3), equivocal DCM (1), and stage B1 MMVD (2). Two dogs originally diagnosed with DCM (1 occult and 1 equivocal) normalized after diet change. CLINICAL RELEVANCE: Borzoi dogs commonly have physiologic heart murmurs and mild atrioventricular valve regurgitation. Both DCM and MMVD were identified at similar frequencies in healthy Borzoi, although dogs with MMVD all had normal heart sizes. Echocardiographic screening for DCM in Borzoi should be considered, with breed-specific echocardiographic values now available for improved diagnostic confidence.

Use of physical examination, electrocardiography, radiography, and biomarkers to predict echocardiographic stage B2 myxomatous mitral valve disease in preclinical Cavalier King Charles Spaniels.

INTRODUCTION: Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD). Dogs with stage B2 MMVD benefit from medication. OBJECTIVES: To develop (1) breed-specific cut-offs for individual screening tests and (2) predictive models utilizing physical examination (PE), ECG, radiograph, and blood-based biomarker variables in combination for identification of echocardiographic stage B2 MMVD in preclinical CKCS. ANIMALS: Adult, preclinical CKCS not receiving cardiac medications (N = 226). MATERIALS AND METHODS: Prospective, cross-sectional study. Enrolled CKCS underwent PE, ECG, radiography, Doppler blood pressure measurement, echocardiography, and biomarker testing. Dogs were grouped by MMVD stage using echocardiography only. The discriminatory ability of individual tests to identify stage B2 was assessed, and prediction models were developed using variables derived from four 'tests' (PE, ECG, radiography, and biomarkers). RESULTS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and radiographic vertebral heart size (VHS) had the best discriminatory ability of individual diagnostic tests to differentiate stage A/B1 CKCS from stage B2, with an area under the curve (AUC) of 0.855 and 0.843, respectively. An NT-proBNP ≥1138 pmol/L or a VHS ≥11.5 had high specificity for predicting stage B2 (90.1% and 90.6%, respectively). Prediction models incorporating variables from multiple tests had better discriminatory ability than single tests. The four-test prediction model had an AUC of 0.971. Three and two-test models had AUCs ranging between 0.925-0.959 and 0.895-0.949, respectively. CONCLUSIONS: Both NT-proBNP and VHS have good utility for predicting echocardiographic stage B2 MMVD in CKCS as individual tests. Prediction models incorporating multiple test variables have superior discriminatory ability.

Pacemaker-lead-associated thrombosis in dogs: a multicenter retrospective study.

INTRODUCTION: Pacemaker implantation is the treatment of choice for clinically relevant bradyarrhythmias. Pacemaker-lead-associated thrombosis (PLAT) occurs in 23.0-45.0% of people with permanent transvenous pacemakers. Serious thromboembolic complications are reported in 0.6-3.5%. The incidence of PLAT in dogs is unknown. ANIMALS, MATERIALS AND METHODS: multicenter retrospective study of seven centers with 606 client-owned dogs undergoing permanent pacemaker implantation between 2012 and 2019. 260 dogs with a transvenous pacemaker with echocardiographic follow-up, 268 dogs with a transvenous pacemaker without echocardiographic follow-up and 78 dogs with an epicardial pacemaker. RESULTS: 10.4% (27/260) of dogs with transvenous pacemakers and echocardiographic follow-up had PLAT identified. The median time to diagnosis was 175 days (6-1853 days). Pacemaker-lead-associated thrombosis was an incidental finding in 15/27 (55.6%) dogs. Of dogs with a urine protein:creatinine ratio measured at pacemaker implantation, dogs with PLAT were more likely to have proteinuria at pacemaker implantation vs. dogs without PLAT (6/6 (100.0%) vs. 21/52 (40.4%), P=0.007). Urine protein:creatinine ratio was measured in 12/27 (44.4%) dogs at PLAT diagnosis, with proteinuria identified in 10/12 (83.3%) dogs. Anti-thrombotic drugs were used following the identification of PLAT in 22/27 (81.5%) dogs. The thrombus resolved in 9/15 (60.0%) dogs in which follow-up echocardiography was performed. Dogs with PLAT had shorter survival times from implantation compared to those without PLAT (677 days [9-1988 days] vs. 1105 days [1-2661 days], P=0.003). CONCLUSIONS: Pacemaker-lead-associated thrombosis is identified in 10.4% (27/260) of dogs following transvenous pacing, is associated with proteinuria, can cause significant morbidity, and is associated with reduced survival times.

A multicenter, retrospective study of cardiac disease in Borzoi dogs.

Borzoi are large, relatively uncommon sighthounds anecdotally reported to suffer from sudden death. This multicenter retrospective cohort study aimed to describe the sample of Borzoi presenting to veterinary cardiologists for evaluation, with records searched from 14 centers across a study period of up to 20 years. The study sample was comprised of 152 client-owned Borzoi, with dogs most commonly presenting for pre-breed screening in 87/152 (52%), followed by evaluation of an arrhythmia in 28/152 (18%). Of the 131/152 (86%) dogs that had an echocardiogram performed, 85/131 (65%) were structurally normal, with 40/85 (47%) structurally normal dogs having trace or mild atrioventricular valve regurgitation. Tricuspid valve dysplasia was the most commonly diagnosed congenital cardiac disease (n = 6). Myxomatous mitral valve disease (n = 12) and dilated cardiomyopathy (n = 13) were diagnosed at similar frequencies, though 92% of valve disease cases were mild. Only 48/152 (32%) Borzoi had a diagnostic electrocardiogram (ECG) and/or a Holter monitor for arrhythmia screening. Despite this, ventricular arrhythmias were identified during the entirety of the available cardiac evaluation including diagnostic ECG, contemporaneous ECG monitoring during the echocardiogram, and/or Holter monitor in 25/131 (19%) dogs in which an echocardiographic diagnosis was available. Of these 25 Borzoi, 76% had minimal or no structural cardiac disease identified, and five had a family history of sudden death. A sudden death outcome was reported in 3/55 (5%) Borzoi with long-term outcome data available. In conclusion, Borzoi commonly have trace or mild atrioventricular valve insufficiencies, and may develop ventricular arrhythmias and dilated cardiomyopathy.

Non-cardiogenic pulmonary oedema complicating balloon valvuloplasty and stent angioplasty of severe pulmonary valve stenosis in four dogs.

In dogs, balloon valvuloplasty is considered the treatment of choice for severe pulmonary valve stenosis, and this technique is currently performed routinely in specialist referral practices with low morbidity and mortality. Stent angioplasty has also been recently proposed as a viable treatment option. The present case series describes the clinical course of four dogs with severe pulmonary valve stenosis, treated with balloon valvuloplasty or stent angioplasty at four different institutions, which developed non-cardiogenic pulmonary oedema perioperatively after apparently successful dilation of the pulmonary valve. In three cases, there was evidence of some degree of pulmonary hypertension before ballooning. Despite intensive care, the complication proved fatal in three cases. Clinicians should therefore be aware of this life-threatening complication, previously undescribed in dogs.

Thematic synthesis of the experiences of people with hidradenitis suppurativa: a systematic review.

BACKGROUND: Although hidradenitis suppurativa (HS) is known to affect quality of life, little summative knowledge exists on how HS impacts people living with the condition. OBJECTIVES: To synthesize experiences of people with HS within published qualitative research. METHODS: Searches on databases MEDLINE, PsycINFO, Embase and CINAHL were conducted on 17 April 2020. Two independent reviewers screened 5512 publications. Study quality was assessed using the National Institute for Health and Care Excellence quality appraisal checklist for qualitative studies. Thematic synthesis generated descriptive and analytic themes. RESULTS: Fourteen studies were included: four studies fulfilled most quality criteria, eight fulfilled some quality criteria, and two fulfilled few quality criteria. There were three final themes. (i) Putting the brakes on life. The physical, psychological and social consequences of HS resulted in people missing out on multiple life events. This could have a cumulative effect that influences the trajectory of someone's life. (ii) A stigmatized identity: concealed and revealed. People try to conceal their HS, visually and verbally, but this results in anticipation and fear of exposure. Social support and psychological acceptance helped people cope. Connecting to others with HS may have a specific role in preserving a positive self-identity. (iii) Falling through the cracks. Delayed diagnosis, misdiagnosis and lack of access to care were reported. People felt unheard and misunderstood by healthcare professionals, and healthcare interactions could enhance feelings of shame. CONCLUSIONS: There need to be improvements to clinical care to allow people with HS to live their life more fully.

Histologic comparison in two Doberman pinschers with a dilated cardiomyopathy phenotype.

Idiopathic dilated cardiomyopathy (DCM) is a common acquired cardiac disease in large breed dogs with a high prevalence in Doberman pinschers. It is characterized histologically by attenuated wavy fibers and fatty infiltration with degeneration. The phenotypic appearance of DCM includes ventricular dilation with systolic dysfunction and ventricular arrhythmias. These changes can be caused by other etiologies, including infectious, toxic, metabolic, and nutritional deficiencies. Chagas disease is the result of an infection with the protozoal parasite, Trypanosoma cruzi, transmitted by an insect vector. Histopathology of the myocardium is characterized by inflammation, fibrosis, and pseudocysts containing T. cruzi amastigotes. Differentiating idiopathic DCM from infectious myocarditis can be challenging when the clinical presentation and diagnostic test results are similar in affected dogs. We present thoracic radiographs, echocardiography, and post-mortem histopathology images obtained from two Doberman pinschers with similar signalment, clinical presentation, and electrocardiographic and echocardiographic appearance but with different appearing radiographs and different etiologies for their heart disease, one with idiopathic DCM and one with myocarditis attributed to Chagas disease, to highlight the value of considering alternative etiologies for DCM to guide additional clinical evaluation and owner counseling.

Palliative combined cutting and high-pressure balloon valvuloplasty in six dogs with severe, symptomatic subaortic stenosis.

INTRODUCTION/OBJECTIVES: Severe subaortic stenosis (SAS) is a congenital heart defect in dogs that often results in clinical signs and reduced survival. The objective of this study was to describe characteristics of dogs with severe, symptomatic SAS who underwent combined cutting and high-pressure balloon valvuloplasty (CB/HPBV). ANIMALS, MATERIALS, AND METHODS: Retrospective description of the clinical characteristics, CB/HPBV procedural deviations from reported methodology and outcomes in a series of six client-owned dogs with severe, symptomatic SAS. RESULTS: Breeds included two each of Newfoundland, Golden retriever, and German shepherd. Median age was 10.1 months (range: 5-72.3 months), and median weight was 25.5 kg (range: 21.8-36.4 kg). Before CB/HPBV, clinical signs were present in all dogs; four were managed for congestive heart failure (CHF). Three dogs had concurrent congenital heart disease. Median Doppler-estimated left ventricular outflow tract pressure gradient was pre-operatively 149.7 mmHg (range: 89.9-254.7 mmHg) and post-operatively 134.1 mmHg (range: 83.9-181.2 mmHg). Median aortoseptal angle was steep at 136° (range: 109-143°). Clinical improvement was documented in all dogs, based on temporary discontinuation of diuretics and/or owner-perceived reduction in clinical signs. At the time of writing, three dogs had died suddenly, one was euthanized because of recurrence of clinical signs, and one died in CHF. Median survival time was 26.4 months after procedure (range: 6.3-45.8 months). One dog remained alive at 44 months after procedure. CONCLUSIONS: Palliative CB/HPBV is a potential therapeutic option for dogs with severe, symptomatic SAS complicated by concurrent congenital heart disease, arrhythmias, or CHF.

Chester treadmill police tests as alternatives to 15-m shuttle running.

BACKGROUND: Police officers require a specific level of aerobic fitness to allow them to complete personal safety training and specialist roles. Officers' aerobic fitness is assessed using the 15-m multi-stage fitness test (MSFT); however, due to the agility required and risk of injury, two alternative treadmill tests have been designed to predict four of the key minimum VO2 criteria of 35, 41, 46 and 51 ml·kg-1·min-1. AIMS: To investigate the validity and reliability of Chester Treadmill Police Walk Test (CTPWT) and Chester Treadmill Police Run Test (CTPRT). METHODS: Seventy-eight UK police officers (18 females) completed the CTPWT (n = 53) or CTPRT (n = 35), or both, generating a total of 88 data sets. To assess reliability, 43 participants returned for a second visit (T2), to repeat the treadmill test. RESULTS: Mean differences between predicted and actual VO2 at 35, 41, 46 and 51 ml·kg-1·min-1 were as follows -1.1, -2.1, -0.1 and -1.2 ml·kg-1·min-1. Despite a significant under prediction (p = 0.001), a minimum of 92% of participants were within 10% of target VO2 at all levels. There was no significant difference between actual and predicted VO2 in the CTPRT, at 46 ml·kg-1·min-1 (T1 46.0 ± 1.4 or T2 45.1 ± 1.3 ml·kg-1·min-1). Similarly, there was no significant difference at 51 ml·kg-1·min-1 (T2 50.5 ± 1.4 ml·kg-1·min-1). We observed no differences for gender or trial. Ninety-five per cent limits of agreement were at worst -0.25 ± 4.0 ml.kg-1.min-1 between trial 1 and 2. CONCLUSIONS: The CTPWT and the CTPRT provide a valid and reliable alternative to the 15-m MSFT.

Bioimpedance spectroscopy measurements of phase angle and height for age are predictive of outcome in children following surgery for congenital heart disease.

OBJECTIVE: Children with congenital heart disease (CHD) are often growth restricted (low weight- and/or height-for-age) which may increase risk of poor post operative resilience. Bioelectrical impedance spectroscopy (BIS) has been used to determine body composition in different clinical settings and has been shown to mark differences in nutritional state and clinical outcome. In disease conditions were fluid is not normally distributed it is proposed that raw impedance values and BIS derived phase-angle may serve as prognostic indicators of clinical outcome. We sought to describe the relationship between nutritional status, phase-angle and post-operative outcomes in children with congenital heart disease. DESIGN: Single centre prospective cohort study. SETTING: Paediatric Intensive Care Unit (PICU), Southampton Children's Hospital. PATIENTS: 122 children with CHD following cardiac surgery (March 2015-April 2016). Outcome variables included growth, mechanical-ventilation, PICU length of stay (PICU-LOS) and phase-angle at 50 Hz. MEASUREMENTS AND MAIN RESULTS: BIS measurements were taken before and on the day of surgery (day 0), day 2 post-operatively and on discharge from hospital. Pre-operative moderate malnutrition defined as height-for-age-z-score (HAZ) ≤-2 was observed in 28.5% of infants and 20.6% of children. Regression analysis was used to investigate the relationship between phase-angle, HAZ and clinical outcomes. Moderate-malnutrition (HAZ ≤-2) was associated with an increased PICU-LOS (odds ratios (OR) with 95% confidence interval: 1.8; 1.1-2.7, p = 0.008) whilst a low phase-angle (≤2.7° on day 2 was associated with longer PICU-LOS (OR 7.8; 2.7-22.45, p < 0.001)); When the model was adjusted for age, known risk factors and length of surgery, HAZ ≤-2 and phase-angle ≤2.7° on day 2 were associated with longer PICU-LOS (p = 0.001 and p = 0.04 respectively) and together explained 81.7% of the variability in PICU-LOS. CONCLUSIONS: Moderate malnutrition (HAZ ≤-2) in infants and children undergoing cardiac surgery is associated with longer PICU-LOS. Post-operative measures of BIS phase angle may further improve our ability to identifying hose children with an increased risk of prolonged PICU-LOS compared to using pre-operative anthropometry alone.

A comparison of three doses of omeprazole in the treatment of equine gastric ulcer syndrome: A blinded, randomised, dose-response clinical trial.

REASONS FOR PERFORMING THE STUDY: A previous study demonstrated that a dose effect between 1.6 and 4.0 mg/kg bwt of omeprazole per os s.i.d. is present in the treatment of equine gastric ulceration. In the same study, healing of glandular ulceration appeared inferior to healing of squamous ulceration. However, several limitations were recognised in that study and further investigation is warranted. OBJECTIVES: To further investigate the presence of a dose relationship in the treatment of gastric ulceration under conditions that may favour omeprazole efficacy such as administration prior to exercise and after a brief fast, and potential differences between the response of squamous and glandular ulceration to omeprazole therapy. STUDY DESIGN: A blinded, randomised, dose-response clinical trial. METHODS: Sixty Thoroughbred racehorses with grade ≥2/4 squamous and/or glandular ulceration were identified by gastroscopy. Horses were randomly assigned to receive either 1.0, 2.0 or 4.0 mg/kg bwt of enteric coated omeprazole per os s.i.d. 1-4 h prior to exercise. Gastroscopy was repeated at approximately 28 days. RESULTS: The lower doses studied (1.0 and 2.0 mg/kg bwt) were noninferior to the reference dose (4.0 mg/kg bwt) in the treatment of squamous ulceration. Healing was greater in squamous ulceration than glandular ulceration (86% vs. 14%; P<0.0001). Improvement in ulcer grade was more likely in squamous lesions than glandular lesions (96% vs. 34%; P<0.0001). Worsening of the glandular ulcer grade was observed in 36% of horses. CONCLUSIONS: The results of this study suggest that, under the conditions studied, where omeprazole is administered before exercise and following a brief fast, doses of omeprazole as low as 1 mg/kg bwt per os s.i.d. may be as effective as higher doses. The proportion of glandular ulceration that heals with 28 days of omeprazole therapy is less than that of squamous ulceration.

A comparison of two doses of omeprazole in the treatment of equine gastric ulcer syndrome: a blinded, randomised, clinical trial.

REASONS FOR PERFORMING THE STUDY: Studies on omeprazole have reported that doses as low as 0.7 mg/kg bwt per os are potent suppressors of acid production. Yet, to date, no studies have compared treatment efficacy of different doses in clinical cases of equine gastric ulceration. Furthermore, no studies have been performed to compare the healing response of the squamous and glandular mucosa to acid suppression therapy. OBJECTIVES: To compare: 1) the efficacy of 2 doses of omeprazole in the treatment of primary squamous and glandular gastric ulceration; and 2) the healing response of primary squamous and glandular gastric ulceration to acid suppression therapy. STUDY DESIGN: A blinded, randomised, dose-response clinical trial. METHODS: Twenty Thoroughbred racehorses with grade ≥2/4 glandular ulceration were identified on gastroscopy. Seventeen horses also had grade ≥2/4 squamous ulceration. Horses were randomly assigned to one of 2 groups. Horses received either 2.0 g (high dose: 4.0 mg/kg bwt) or 0.8 g (low dose: 1.6 mg/kg bwt) of oral omeprazole per os once daily. Gastroscopy was repeated at 28-35 days. RESULTS: Time and dose significantly affected grades of squamous (P<0.0001, P = 0.02) and glandular (P = 0.006 and 0.005) ulceration. Data analysis did not support our hypothesis that the lower dose would have similar effects (i.e. be noninferior) to the higher dose when considering ulcer healing and ulcer improvement. Improvement was more likely with the high dose for the squamous (P = 0.05) but not glandular (P = 0.4) mucosa. The percentage of glandular ulcers that improved was less than squamous ulcers (P = 0.02). CONCLUSIONS: The results suggest that a dose-response exists for the treatment of both squamous and glandular ulcers. Improvement of glandular ulcers was not as complete as observed with squamous ulcers and current equine gastric ulcer syndrome treatment recommendations may not be appropriate for glandular disease.

Negative prognostic factors for head and neck cancer in the young.

PURPOSE: To evaluate the prognosis of head and neck (HN) squamous cell carcinoma (SCC) diagnosed in young people (≤40 years), and to compare it with the typical older patients. METHODS: The study population comprised 69 HN cancer patients below the age of 40 years. An equal-sized control group of older patients was pair-matched with the young cases. Cases and controls were compared for type and frequency of recurrence, in addition to survival. Tongue tumor specimens from 12 women of the study group (6 young and 6 old) were included in a pilot immunohistochemical analysis of estrogen receptors (ER) expression. RESULTS: Young patients with early (T1,T2) tongue cancer had shorter overall survival (OS) than their matched controls, but the finding was marginally non-significant (p=0.056). In the young population, late neck metastasis was a particularly aggravating factor for survival (p=0.004). In the case of tongue SCCs, young women were at the greatest risk of recurrence than any other gender-age combination (p=0.006). However, only 8.3% of tumors expressed ER. CONCLUSION: Early-stage tongue cancer, regional recurrence, and tongue SCCs in women are negative prognostic factors for young HN cancer patients. Treatment modifications targeting these subgroups might be beneficial.

An outbreak of Pontiac fever due to Legionella longbeachae serogroup 2 found in potting mix in a horticultural nursery in New Zealand.

Previous outbreaks of Pontiac fever have invariably been associated with water droplet spread of Legionella spp. In January 2007 three workers from a horticultural nursery were admitted to hospital with non-pneumonic legionellosis. Investigations showed that a working party of ten people had been exposed to aerosolized potting mix; nine of these workers met the case definition for Pontiac fever. The presence of genetically indistinguishable Legionella longbeachae serogroup 2 was demonstrated in clinical specimens from two hospitalized workers and in the potting mix to which they had been exposed. A further seven cases were diagnosed by serological tests. This is the first documented outbreak of Pontiac fever from L. longbeachae serogroup 2 confirmed from inhalation of potting mix. Pontiac fever is likely to be under-diagnosed. We advocate the introduction of an industry standard that ensures the use of face masks when handling potting mix and attaching masks and warning labels to potting mix bags sold to the public.

Physiological and functional impact of an unsupervised but supported exercise programme for claudicants.

OBJECTIVES: To evaluate an unsupervised home-based exercise programme for physiological, functional, and quality of life impact in patients with symptomatic peripheral arterial disease. DESIGN: Prospective cohort with exercise intervention. MATERIALS: Human performance laboratory with non-invasive haemodynamic assessment facilities. METHODS: Forty-seven patients with symptomatic peripheral arterial disease (mean age 67.6+/-7 years, 33 males) participated in an unsupervised home-based exercise programme. Heart rate (HR), ankle brachial blood pressure index (ABPI), leg blood flow (BF), and blood lactate were measured before and after a graded treadmill walk at baseline and after the 12-week exercise programme. Maximum walking distance (MWD) during the treadmill walk was measured at baseline and 12 weeks. Exercise compliance, functional parameters, and quality of life (VascuQoL) were assessed by questionnaire. RESULTS: MWD, leg BF, and VascuQoL scores increased significantly, while resting HR, exercise HR, and end of walk rate-pressure-product (RPP) decreased significantly after 12 weeks. Exercise compliance was significantly correlated with increase in MWD (r=0.89, p<0.001) and QOL score improvement (r=0.61, p<0.001). CONCLUSIONS: This supported but unsupervised exercise programme generated improvements in walking distance and leg blood flow without detectable increases in cardiorespiratory work. Exercise compliance is related to MWD and VascuQoL score in a dose-response manner.

Experience of the use of trabectedin (ET-743, Yondelis) in 21 patients with pre-treated advanced sarcoma from a single centre.

AIMS: Trabectedin (ET-743, Yondelis) is a marine-derived alkaloid that has two actions. It binds in the minor groove of DNA resulting in a conformational change; thus potentially altering interactions with transcription factors and other DNA binding proteins and it also interacts with the transcription-coupled nucleotide excision repair machinery to induce lethal double-stranded DNA breaks. In recent phase II trials it has shown considerable activity in the treatment of sarcomas. Here the use of trabectedin in patients with advanced refractory sarcoma from a single institution is presented. MATERIALS AND METHODS: Twenty-one patients with advanced refractory sarcoma from a single UK centre were treated with trabectedin on a named patient compassionate basis programme. All patients had received prior treatment with an anthracycline, and 95% had received ifosfamide. RESULTS: The patients received a median of four cycles of treatment. Objective partial responses were seen in three patients (14%) and a further eight patients (38%) achieved durable stable disease for a median duration of 4.5 months. The estimated 3- and 6-month progression-free survival was 58.8 and 17.6%, respectively. Six patients experienced early disease progression, and four patients died while on treatment. One death was due to treatment-related toxicity. Overall the drug was relatively well tolerated, with hepatic and haematological toxicities most commonly encountered. Both necessitated delays and/or dose reductions in a proportion of patients. Other significant toxicities were nausea, vomiting and asthenia. CONCLUSION: The disease responses and durable nature of disease stabilisation seen in a proportion of our patients support the continued investigational use of this drug in the treatment of advanced soft tissue sarcomas.

Automated PCR setup for forensic casework samples using the Normalization Wizard and PCR Setup robotic methods.

Human genome, pharmaceutical and research laboratories have long enjoyed the application of robotics to performing repetitive laboratory tasks. However, the utilization of robotics in forensic laboratories for processing casework samples is relatively new and poses particular challenges. Since the quantity and quality (a mixture versus a single source sample, the level of degradation, the presence of PCR inhibitors) of the DNA contained within a casework sample is unknown, particular attention must be paid to procedural susceptibility to contamination, as well as DNA yield, especially as it pertains to samples with little biological material. The Virginia Department of Forensic Science (VDFS) has successfully automated forensic casework DNA extraction utilizing the DNA IQ(trade mark) System in conjunction with the Biomek 2000 Automation Workstation. Human DNA quantitation is also performed in a near complete automated fashion utilizing the AluQuant Human DNA Quantitation System and the Biomek 2000 Automation Workstation. Recently, the PCR setup for casework samples has been automated, employing the Biomek 2000 Automation Workstation and Normalization Wizard, Genetic Identity version, which utilizes the quantitation data, imported into the software, to create a customized automated method for DNA dilution, unique to that plate of DNA samples. The PCR Setup software method, used in conjunction with the Normalization Wizard method and written for the Biomek 2000, functions to mix the diluted DNA samples, transfer the PCR master mix, and transfer the diluted DNA samples to PCR amplification tubes. Once the process is complete, the DNA extracts, still on the deck of the robot in PCR amplification strip tubes, are transferred to pre-labeled 1.5 mL tubes for long-term storage using an automated method. The automation of these steps in the process of forensic DNA casework analysis has been accomplished by performing extensive optimization, validation and testing of the software methods.