Performance of rapid prescreening and 100% rapid review as internal quality control methods for cervical cytopathology.

BACKGROUND: An objective of quality control for cervical cytopathology is reducing high rates of false-negative results of laboratory tests. Therefore, methods to review smears such as rapid prescreening and 100% rapid review, which have shown better performance detecting false-negative results, have been widely used. The performance of rapid prescreening and the performance of 100% rapid review as internal quality control methods for cervical cytology examinations were evaluated. METHODS: For 24 months, 9318 conventional cervical cytology smears underwent rapid prescreening and routine screening. The 100% rapid review method was performed for 8244 smears classified as negative during routine screening. Any discordant results underwent detailed review to define the final diagnosis. This was considered the gold standard for evaluating the performance of rapid prescreening and 100% rapid review. RESULTS: Routine screening showed increases of 13.3% and 11.5% in the detection of abnormal smears with rapid prescreening and 100% rapid review, respectively. The relative percentage variation showed a 38.1% increase in the diagnosis of atypical squamous cells of undetermined significance with routine screening and rapid prescreening and a 12.5% increase in the diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion with both rapid prescreening and 100% rapid review. Sensitivity rates of rapid prescreening and routine screening were 48.2% and 83.2%, respectively. Sensitivity rates of rapid prescreening and 100% rapid review were 65.7% and 57.8%, respectively, for detecting false-negative results. CONCLUSIONS: Inclusion of rapid prescreening and/or 100% rapid review improved the diagnostic sensitivity of the cervical cytology examination and reduced false-negative results of routine screening and can provide good quality control.

Influence of beta blockers on survival in dogs with severe subaortic stenosis.

BACKGROUND: Subaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical. OBJECTIVE: To determine the influence of beta blocker treatment on survival time in dogs with severe SAS. METHODS: Retrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011. RESULTS: Fifty dogs met the inclusion criteria. Twenty-seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all-cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all-cause (P = .93) or cardiac-cause (P = .97) mortality analyses. CONCLUSIONS: Beta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death.

Minimally invasive per-catheter patent ductus arteriosus occlusion in dogs using a prototype duct occluder.

BACKGROUND: Per-catheter patent ductus arteriosus (PDA) occlusion in dogs with devices intended for humans is associated with technical difficulties, high rates of procedure abandonment, device migration, and residual ductal flow. HYPOTHESIS: Use of a custom-made canine duct occluder (Amplatz Canine Duct Occluder, ACDO) would be feasible in dogs of varying weights and somatotypes and effective in occluding a wide range of PDA shapes and sizes. ANIMALS: Eighteen client-owned dogs of various breeds with PDA. Weights ranged from 3.8 to 32.3 kg (median, 17.8 kg), and angiographic minimal ductal diameters ranged from 1.1 to 6.9 mm (median, 3.7 mm). Ductal morphologies included types IIA, IIB, and III. METHODS: Per-catheter PDA occlusion with the ACDO was performed in all dogs. Persistent or recurrent ductal flow was assessed at the end of the procedure by angiography and at 1 day, 3 months, and >or=12 months after the procedure by echocardiography. RESULTS: Successful ACDO placement was achieved in all 18 dogs. One dog required a 2nd procedure with a larger ACDO after the 1st device migrated to the pulmonary vasculature. Complete occlusion was confirmed in 17 of 18 dogs during the procedure, as well as at 1 day and 3 months after the procedure, and in 12 of 13 dogs evaluated at >or=12 months after the procedure. CONCLUSIONS AND CLINICAL IMPORTANCE: Per-catheter PDA occlusion in dogs with the ACDO is feasible and effective in dogs of a wide range of weights and somatotypes and with PDAs of varying shapes and sizes.

Primary cardiac fibrosarcoma with pulmonary metastasis in a Labrador Retriever.

A 6-year-old, neutered male Labrador Retriever was diagnosed with congestive heart failure, and an echocardiogram revealed a large mass inside the pericardial sac associated with the left ventricle. At necropsy, the dog had marked ascites, mild hydrothorax, marked hydropericardium, and an 11.0 x 7.0 x 6.0 cm, tan and red, firm, well-demarcated mass attached to the left ventricular free wall. The mass was diagnosed as a fibrosarcoma based on the morphologic appearance and supportive immunohistochemical staining. To our knowledge, this is the first case report of a primary fibrosarcoma involving the left ventricular free wall myocardium, epicardium, and pericardium with a pulmonary metastasis in a dog.

Previous-beat contraction history is not influenced by mechanosensitive ion channel blockade.

OBJECTIVES: Prior studies have shown that the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, a phenomenon called "previous-beat contraction history". This previous-beat contraction history, which appears to be an interplay between the mechanical events of one contraction and the activation state of the next contraction, could depend, at least in part, on mechanosensitive ion channels. The purpose of this study, therefore, was to test the hypothesis that mechanosensitive ion channels contribute to previous-beat contraction history: If previous-beat contraction history depends on mechanosensitive ion channels, the magnitude of its effect should be decreased by blocking mechanosensitive ion channels. METHODS: We performed experiments in buffer-perfused isolated rabbit hearts in which left ventricular pressure and volume were controlled with a servo-motor system. We evaluated the pulse interval-dependent expression of previous-beat contraction history under control conditions (no drug) and in the presence of 100 and 500 microM streptomycin, a blocker of mechanosensitive ion channels. RESULTS: Under control conditions, previous-beat contraction history nor its dependence on pulse interval was influenced significantly by either concentration of streptomycin. CONCLUSION: Mechanosensitive ion channels do not play a role in the expression of previous-beat contraction history in the left ventricle of the isolated rabbit heart.

Functional effects of EMD-57033 in isovolumically beating isolated rabbit hearts.

The results of isolated myocyte and cardiac muscle experiments indicate that inotropic agents that increase responsiveness of myofilaments to Ca2+ (so-called Ca2+ sensitizers) may prolong myocardial contraction and increase diastolic tone, but the importance of these effects in the whole heart is unclear. Therefore, we studied the effects of the Ca2+ sensitizer EMD-57033 (EMD) on left ventricular (LV) contractile events and passive properties in isovolumically beating isolated rabbit hearts that were buffer perfused at 30 degrees C. Several LV pressure and timing variables were evaluated, including the passive pressure-volume relationship, the Frank-Starling relationship, and the wall stress dependence of the duration of relaxation during perfusion with 0, 2, and 4 microM EMD. EMD (2 microM) increased average peak developed pressure of the Frank-Starling relationship by approximately 18%. In contrast, the peak developed pressure of the Frank-Starling relationship decreased toward control with 4 microM EMD, and therefore all the results presented pertain to 2 microM EMD. The maximum developed pressure at baseline volume was increased by approximately 19% by 2 microM EMD, and this was accompanied by an increase in contraction duration of approximately 13%, due exclusively to slowed relaxation. The relative contributions of maximal wall stress (sigma max) versus an independent negative lusitropic effect of EMD were determined at three LV volumes. At baseline volume, just less than one-half of the effect to slow relaxation was ascribable to an increase in sigma max, whereas the remainder was due to an independent EMD effect. LV passive properties were unchanged by perfusion with 2 microM EMD. We conclude that EMD is a potent inotrope in our isolated rabbit heart preparation, which has no effect on diastolic tone and causes a modest prolongation of contraction duration due to slowed relaxation. At baseline volume, approximately 50% of the slowed relaxation was ascribable to positive inotropy leading to increased sigma max, whereas the remaining approximately 50% was ascribable to a direct negative lusitropic effect of EMD. We discuss our results in terms of the current hypotheses regarding the mechanism of action of the Ca2+ sensitizers.

Characterization of chronotropic and dysrhythmogenic effects of atropine in dogs with bradycardia.

OBJECTIVE: To characterize the magnitude, character, and time course of chronotropic and dysrhythmogenic responses of dogs with vagally mediated bradycardia to atropine sulfate. DESIGN: Latin square design. ANIMALS: Seven clinically normal adult mixed-breed dogs. PROCEDURE: Vagally mediated bradycardia was induced with morphine and fentanyl citrate. Atropine (0.02 mg/kg of body weight) was administered i.v., s.c., or i.m.. Electrocardiograms were recorded continuously for 5 minutes before and for 35 minutes after atropine administration or until a sustained parasympatholytic response was observed. Data were digitized, analyzed independently for changes in atrial and ventricular rate, and compared between different routes of administration. RESULTS: All dogs developed second-degree atrioventricular (AV) block after i.v. administration of atropine, and 71% of dogs developed AV block after s.c. or i.m. administration. The AV block arose and resolved more rapidly with i.v. administration than with s.c. or i.m. administration. The AV block was principally attributable to an increase in the atrial rate prior to increases in the ventricular rate. Atropine, regardless of route of administration, potentiated baseline ventricular bradycardia in 62% of the experiments (mean heart rate decrease of 16 beats/min; decreased to < 20 beats/min in 2 dogs for < or = 10 seconds). Duration of the bradycardic potentiation was longer with s.c. administration (9.1 minutes, s.c., vs 1.4 minutes, i.v., and 4.6 minutes, i.m.). Parasympatholytic rate was higher for i.v. than s.c. or i.m. administration (128 beats/min vs 92 beats/min and 101 beats/min). Two dogs given atropine s.c. failed to resolve the AV block and attain sinus rhythm. CONCLUSIONS: Administration of 0.02 mg of atropine/kg by i.v., i.m., and s.c. routes for vagally mediated bradycardia in dogs consistently induces AV block and occasional brief potentiation of ventricular bradycardia. CLINICAL RELEVANCE: Parasympathomimetic effects occur and resolve most rapidly and consistently, and the stable parasympatholytic effect is of greatest magnitude after i.v. administration. Thus, vagally mediated bradycardia in clinically normal dogs appears to be best abolished by i.v. administration of atropine.

Mechanical determinants of left ventricular relaxation in isovolumically beating hearts.

Both pressure and volume have been proposed to determine the speed of left ventricular (LV) relaxation, but their relative importance is not known. Accordingly, we used isolated, buffer-perfused, isovolumically beating ferret hearts to study the effects of maximal developed pressure (Pdmax) and LV volume (V) on the speed of LV relaxation. Experiments were performed at 30 degrees C, and the hearts were paced at a baseline interbeat interval (BI) of 800 ms. Pdmax was varied independently of V by use of seven BI (75 to 133% of baseline BI), which resulted in test beats that developed a range of Pdmax due to varying degrees of restitution. Pdmax was also varied by setting V at five levels (80 to 120% of baseline V) during the test beats. Speed of relaxation was quantified as the time period of pressure decay from 75 to 25% Pdmax (T75-25). Data were analyzed by multiple linear regression. Increases in both Pdmax and V independently prolonged T75-25, and T75-25 was 1.45 times more sensitive to Pdmax than to V. However, when Pdmax and V were combined to estimate maximal wall stress (sigma max), the effects of Pdmax and V, as well as relative circumferential muscle length (estimated by V1/3), were not important determinants, and T75-25 depended on sigma max alone. Thus we conclude that 1) Pdmax and V are both determinants of the speed of LV relaxation and that Pdmax is approximately 1.5 times more important than V, and 2) the effects of Pdmax and V on relaxation act via the common mechanism of sigma max.

Series coupled non-contractile elements are functionally unimportant in the isolated heart.

OBJECTIVE: In order to evaluate possible artefact in interpretations of contractile behaviour in isolated heart experiments, the relative elastances of series coupled non-contractile and contractile components of the left ventricle of the isolated heart were evaluated. METHODS: Hearts were isolated from ferrets and rabbits and mounted on a servo-controlled volume regulation device. These hearts were made to beat isovolumetrically until a selected volume perturbation was introduced. Constant flow volume withdrawals at two flow values were performed over a period of < 20 ms centred around the time of peak isovolumetric pressure. Three levels of isovolumetric pressure were produced using basal, extrasystolic, and potentiated beats. Pressure responses to volume withdrawals at two flows and three isovolumetric pressures were then analysed using a mathematical model to evaluate relative values of series coupled contractile and non-contractile elastances. To validate the analysis procedure, a non-contractile series artefact with known elastance was coupled to the left ventricle; volume perturbations were then applied to the coupled left ventricle-artefact system; responses were analysed and the estimate of series coupled non-contractile elastance was compared to the known elastance of the added artefact. RESULTS: A wide range of isovolumetric pressures [208(SD 40) mmHg] was produced in the ferret with basal, extrasystolic, and potentiated beats. A lesser range of isovolumetric pressures [50(15) mmHg] was produced in the rabbit. The mathematical model fitted the data very well in both the ferret and rabbit. The elastance of the series coupled non-contractile component could be estimated only in some ferrets. When estimated in the ferret, the elastance of the series coupled non-contractile component was never less than 4x that of the contractile component. When a series artefact of sufficiently low value was coupled with the native left ventricle, the elastance of the non-contractile component could be reliably estimated in both ferrets and rabbits and the estimated value approximated that of the added artefact. This indicated that the elastance of the series coupled non-contractile component of the native left ventricle was much higher than that of the added artefact. CONCLUSIONS: The series coupled non-contractile component of the isolated heart possesses a very much higher elastance than the contractile component. In fact, the elastance of the non-contractile component is so great that it contributes very little to the dynamic behaviour of the left ventricle. Virtually all of the elastance of the left ventricle of the isolated heart is due to the contractile component.

Resection of subvalvular aortic stenosis. Surgical and perioperative management in seven dogs.

Open heart surgery was performed during cardiopulmonary bypass (CPB) to surgically correct subvalvular aortic stenosis in seven dogs. After initiation of total CPB, cardiac arrest was induced by antegrade and retrograde administration of blood cardioplegia. The subvalvular fibrous stenosis was resected through a transverse aortotomy. Intraoperatively and postoperatively, dobutamine, nitroprusside, lidocaine, blood(-products), and crystalloid solutions were used to manage hypotension and optimize cardiac index. Aortic cross-clamp time varied from 73 to 166 minutes, and duration of CPB varied from 130 to 210 minutes. Iatrogenic incision into the mitral valve in two dogs was the most significant intraoperative complication. Postoperative complications included: hypoproteinemia (n = 7), premature ventricular depolarization (n = 6), increased systemic vascular resistance index (n = 5), increased O2 extraction (n = 3), pulmonary edema (n = 2), and decreased cardiac index (n = 1). All seven dogs were discharged alive and in stable condition. Six dogs are alive and in stable condition after a mean follow up of 15.8 months. This is the first detailed report of CPB in a series of clinical veterinary patients. Using the techniques described in this paper, open heart surgery of considerable duration can be performed successfully in dogs with significant myocardial hypertrophy and endomyocardial fibrosis secondary to subvalvular aortic stenosis.

Cor triatriatum dexter in two dogs.

Cor triatriatum dexter is a congenital heart defect in which the embryologic right sinus venosus valve persists as a septum within the right atrium. Cor triatriatum dexter was diagnosed in 2 dogs on the basis of clinical signs, two-dimensional echocardiography, and cardiac catheterization. In 1 of the dogs, the condition was successfully treated by surgical resection of the intra-atrial septum. In the second dog, the defect was associated with an incomplete persistent cranial left vena cava and Ebstein's anomaly; surgery was declined.

Serum digoxin concentrations in canine congestive heart failure.

Digoxin was administered to dogs (n = 10) in congestive heart failure, at an oral dosage rate of 0.01 mg kg-1 lean body mass twice daily. Lean body mass was determined by reducing gross mass by the estimated degree of ascites and body fat. The dose was further adjusted for factors such as renal and hepatic function, the bioavailability of different formulations, and the size of the patient. Trough and peak serum digoxin concentrations were determined after 10 days of digitalisation, or when signs of toxicity became apparent. Serum digoxin concentrations in 6 of the 10 dogs were found to be partially or completely in the toxic or subtherapeutic range. This indicates that an oral digoxin dosage rate of 0.01 mg kg-1 lean body mass administered twice daily, even when adjusted appropriately for factors that affect digoxin pharmacokinetics, provides no more than a rough approximation of the precise dose required to provide serum digoxin concentrations within the therapeutic range. The observations also lend support to a recent recommendation that the digoxin dosage rate should be based on body surface area, although even when administered on this basis, serum digoxin concentrations outside of the therapeutic range could be anticipated.