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Biomedical subjects

A A Stokhof

Publications and source records attributed to A A Stokhof.

At least 19 recordsLinked to original sources

The canine sarcoglycan delta gene: BAC clone contig assembly, chromosome assignment and interrogation as a candidate gene for dilated cardiomyopathy in Dobermann dogs.

Dilated cardiomyopathy (DCM) is a common disease of the myocardium recognized in human, dog and experimental animals. Genetic factors are responsible for a large proportion of cases in humans, and 17 genes with DCM causing mutations have been identified. The genetic origin of DCM in the Dobermann dogs has been suggested, but no disease genes have been identified to date. In this paper, we describe the characterization and evaluation of the canine sarcoglycan delta (SGCD), a gene implicated in DCM in human and hamster. Bacterial artificial chromosomes (BACs) containing the canine SGCD gene were isolated with probes for exon 3 and exons 4-8 and were characterized by Southern blot analysis. BAC end sequences were obtained for four BACs. Three of the BACs overlapped and could be ordered relative to each other and the end sequences of all four BACs could be anchored on the preliminary assembly of the dog genome sequence (www. ensembl.org). One of the BACs of the partial contig was localized by fluorescent in situ hybridization to canine chromosome 4q22, in agreement with the dog genome sequence. Two highly informative polymorphic microsatellite markers in intron 7 of the SGCD gene were identified. In 25 DCM-affected and 13 non DCM-affected dogs seven different haplotypes could be distinguished. However, no association between any of the SGCD variants and the disease locus was apparent.

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[En bloc ligation of the thoracic duct in twelve dogs with idiopathic chylothorax].

Twelve dogs with idiopathic chylothorax were treated by en bloc ligation of the thoracic duct. Six dogs recovered completely. Minimal follow-up in this group was 12 months. Five dogs were euthanized within 5 months of surgery because of persisting liquothorax: two with chylous and three with non-chylous effusions. One dog was euthanized 2 months after surgery because of a recurrence of dyspnoea. It is concluded that the results are comparable with those of a previously described surgical treatment; however, the technique described here is less complicated because it does not require mesenteric lymphangiography.

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[Arterial hypertension in the cat. A pathobiologic and clinical review with emphasis on the ophthalmologic aspects].

Arterial hypertension in cats appears to be an often underdiagnosed problem. Sudden disturbances of vision caused by intraocular haemorrhage and/or detached retina are often related to hypertension. The ability to measure blood pressure routinely in cats, by using an indirect method, has increased knowledge of feline hypertension in recent years. In cats mainly secondary hypertension is described, caused by as a consequence of renal disease, hyperthyroidism, chronic anaemia, primary aldosteronism, and a high-salt diet. This article describes the (patho) physiology of blood pressure control, the different methods of blood pressure measurements and the causes, clinical manifestations, and possibilities of antihypertensive therapy. Given our current knowledge, blood pressure should be measured regularly in older cats (> 10 years), especially in those with renal insufficiency, hyperthyroidism, or visual disturbances of unknown origin. Blood pressure measurements using the Doppler method is a relatively cheaply, quick and simple, method with enough reliability. Hence this method should be incorporated in veterinary practice.

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[Thoracic surgery in companion animals. The role of Professor Dr. G.H.B. Teunissen (1907-1998)].

By this review we commemorate professor dr. dr. h.c. G.H.B. Teunissen, who died on August 20, 1998. We report his important role in the development of human and small animal thoracic surgery in the Netherlands following his appointment as professor in the Small Animal Clinic of the State University of Utrecht in January 1947. Comparing Teunissen's publications on thoracic surgery with other literature on this subject in the same period shows that he was aware of and made use of the possibilities of the developments at that time. Thanks to his contributions, the small animal thoracic surgery in Utrecht is internationally recognized.

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ECG of the "newborn" mouse (Mus domesticus) with specific reference to comparative AV transmission.

INTRODUCTION: The objective of this study was to record the ECG of the smallest living mammal to extend the domain of data for comparative AV nodal electrophysiologic purposes. These data are needed to establish the relationship between the PR interval and heart size in mammalian species of all sizes. METHODS AND RESULTS: In recently born mice (age 1.5 to 8 weeks) weighing between 2.5 and 10 g and with estimated heart weights between 15 and 60 mg, ECGs, using bipolar limb leads, were recorded during general anesthesia. The PR interval, representing AV transmission time was about 40 msec, which is quite long for hearts of this size. On the basis of detailed analysis of the data, we postulate the presence of a fixed delay or discontinuous propagation in the AV node not only in newborn mice, but in mammals of all sizes. CONCLUSION: AV transmission times obtained in mammals (including humans) cannot be explained on the basis of generally accepted, classic AV conduction theories. The acceptance of the presence of a fixed delay in the AV node may ultimately be of value to better understand AV node function during sinus rhythm and supraventricular arrhythmias.

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[Recent insights into the possibilities of resuscitation of dogs and cats].

This article reviews the present state of the art of resuscitation of dogs and cats. The purpose of resuscitation is to revive animals so that the vital functions resume together with a normal brain function. Resuscitation must be started as soon as the cardiopulmonary arrest has been confirmed. Adequate ventilation and effective circulation to the most vital body organs, the heart and the brain, have the highest priority. They can be achieved by endotracheal intubation, artificial ventilation with 100% oxygen and rhythmic compression of the closed chest or direct cardiac massage following thoracotomy. Medical therapy is an important part of resuscitation. In the absence of a central venous route, deep endotracheal administration is the preferred method of administration. Most medications can be administered through the endotracheal tube in this fashion.

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Age variance of left ventricular diameters in dogs with cardiac disease.

Ventricular size increases during growth, but often due to cardiac disease. This study aims to describe left ventricular dimension interrelations using a representation that is applicable to patients with cardiac disease, and subsequently to statistically study possible age and gender influences in a large population. In retrospect we analyzed echocardiographically obtained diameters of the left ventricle in 442 dogs of various breeds with congenital or acquired heart disease. Also, we compared our findings with published data on humans and other animals. Multivariate regression analysis was applied to assess possible influences of age and gender. A high correlation was found for end-systolic diameter (ESD) versus end-diastolic diameter (EDD): ESD (cm) = -1.01 cm + 0.93 x EDD (cm) with r = 0.94, p < .00001. Next, these patients were categorized into three age groups (divisions at 3 and 7 years). We detected a slight age dependent effect: the regression coefficients for the younger group differed from the two older groups. No significant gender-related influence was detected. The observation of a high correlation for the ESD versus EDD relationship could be confirmed by reanalysis of published data on normal individuals and human patients. The newly described relationship between ESD and EDD applies in particular to cardiac patients. This is a relevant finding, because clinically important indices of ventricular performance generally depend on ESD, EDD or both. Thus, ESD versus EDD offers a convenient framework for studies on cardiac volume regulation and performance in the cardiopathological spectrum, while permitting incorporation of modulating effects related to age.

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[Possibilities and status of heart surgery in dogs].

Before use of cardiovascular surgical techniques and procedures in humans, many experiments, e.g., hypothermic circulatory arrest and cardiopulmonary bypass using the heart-lung machine, have been performed in the dog. As a consequence experimental canine cardiovascular surgery is highly developed. This has not resulted in the routine performance of open heart surgery in veterinary medicine, probably because of the high costs. Cardiovascular surgery in the dog is generally limited to interventions not depending on hypothermic circulatory arrest or cardiopulmonary bypass. The clinical cardiovascular surgery in dogs can be divided into routine and more specialized interventions. The first category includes correction of peritoneopericardial diaphragmatic hernia, pericardial fenestration in dogs with pericardial effusion, treatment of persistent right aortic arch, and patent ductus closure. The specialized interventions include dilation of pulmonic and aortic stenoses and pacemaker implantation. The diagnosis and surgical treatment of such diseases is described. New developments in cardiovascular surgical treatment that can be expected include catheter techniques for occlusion of shunts and dilations using balloons, because the financial costs of these procedures are not prohibitive.

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Relationship between atrial fibrillation and primary hypothyroidism in the dog.

Atrial fibrillation (AF) and primary hypothyroidism are most often diagnosed in middle-aged and older dogs of large and giant breeds. We hypothesized that the frequency of primary hypothyroidism may be higher in dogs with AF than in those without AF. Two groups were investigated. Group 1 (March 1987-June 1990) consisted of 128 dogs with AF. A thyroid-stimulating hormone (TSH) stimulation test was performed in dogs with a low voltage on the ECG and low uptake of pertechnetate on a thyroid scan. Group 2 (July 1990-July 1991) consisted of both dogs with AF (n = 38) and control dogs (n = 235) in which plasma thyroxine (T4) was measured. If T4 was below 15 nmol/l, a TSH stimulation test was performed. The frequencies of primary hypothyroidism in group 1 (8/128) and in the group 2 AF dogs (3/38) were not different, but were higher than in the control animals (3/235) (P < 0.05). The group 1 and the group 2 AF dogs were found to be comparable, and pooling of the data of the two groups enhanced the significance of the frequency of primary hypothyroidism in dogs with AF versus the control animals (11/166 versus 3/235) (P < 0.01). We concluded that the frequency of primary hypothyroidism in dogs with AF is higher than in the group of control dogs without AF. This may be due to the additional cardiovascular changes accompanying primary hypothyroidism in dogs that already have heart disease.

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Seven cases of heartworm disease (dirofilariosis) in dogs in The Netherlands.

We present here the clinical history, diagnosis, and treatment of seven dogs with dirofilariosis. All dogs were imported into the Netherlands after residing in an area in which dirofilariosis is endemic. In three of these dogs the infection was occult, for the serological test was positive but there was no microfilaraemia. Weight loss, coughing, dyspnoea, and decreased exercise tolerance were the most prominent clinical signs. Two of the dogs had the characteristic electrocardiographic and radiographic signs of enlargement of the right heart. Treatment with thiacetarsamide and ivermectin resulted in complete remission in six dogs. One dog died, presumably as a result of acute renal failure. In the past year (1992-1993) seven cases of canine dirofilariosis were diagnosed, nearly equal to the number in the preceding 10 years (n = 9). This most probably reflects the greater sensitivity of the serological diagnosis of dirofilariosis in comparison with identification of microfilariae in the circulation, but a real increase in the number of dogs with dirofilariosis as a result of growing international traffic of tourists accompanied by pets cannot be excluded.

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Effect of pericardiocentesis on circulating concentrations of atrial natriuretic hormone and arginine vasopressin in dogs with spontaneous pericardial effusion.

Factors regulating the secretion of atrial natriuretic hormone (ANH) and arginine vasopressin (AVP) have not been elucidated fully. In several studies the release of these peptides has been studied by inducing both increased atrial pressure and atrial distension. A few studies employ cardiac tamponade, allowing the effect of atrial pressure and atrial stretch to be studied separately. In eleven dogs with spontaneous cardiac tamponade the effect of pericardiocentesis on circulating concentrations of ANP and AVP was studied. Pericardiocentesis was followed by a prompt rise in (non-elevated) plasma ANH concentrations from 21.6 +/- 7.3 to 65.4 +/- 17.1 pmol/l (mean +/- SEM). The initially slightly elevated AVP concentration of 5.5 +/- 1.5 pmol/l declined following pericardiocentesis to 2.1 +/- 0.5 pmol/l. In three dogs the systolic arterial pressure was measured indirectly and the central venous pressure was measured with a fluid-filled catheter. Before and after pericardiocentesis arterial pressure readings did not change significantly. Central venous pressure values showed an immediate very steep significant decrease after centesis. It is concluded that ANH release is primarily regulated by stretch and not by atrial pressure, that plasma AVP concentrations are moderately elevated in cardiac tamponade and that in cardiac tamponade pericardiocentesis causes a rapid decline in plasma AVP concentration.

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Survival time in dogs with spontaneous atrial fibrillation related to scintigraphically measured cardiac performance.

In 40 canine patients with spontaneous atrial fibrillation (AF) cardiac performance was measured scintigraphically and correlated with the survival time (ST) following the diagnosis of AF. The parameters used for cardiac performance were heart rate (HR), end-diastolic left ventricular volume (EDV), ejection fraction of the left ventricle (EF), left ventricular regurgitation fraction (RF) and cardiac output (CO). ST varied from 3 days to 780 days. Two groups of animals were distinguished as previously described: group A (EF less than 0.3, n = 26) and group B (EF greater than or equal to 0.3, n = 14). The median ST (90 days) in group A was only weakly significant (p = 0.1) shorter than in group B (150 days). RF was significantly lower in group A than in group B (p less than 0.001). A weak correlation was found between ST and EF (r = 0.28; p = 0.04). It was concluded that the prognosis in the described AF patients is slightly favourable if EF is normal or only moderately reduced.

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Pulmonary scintigraphy in canine lobar and sublobar airway obstruction.

The intrapulmonary distribution of the inhalation-to-perfusion ratio (I/P) was studied after placement of an obstruction in a sublobar bronchus (SLO) or in a lobar bronchus (LO) in 17 anesthetized prone (sternal recumbent) dogs. Placement of an SLO or LO did not induce any significant changes in the standard ventilatory and hemodynamic parameters measured. With the use of 99mTc aerosol inhalation combined with 99mTc perfusion lung scintigraphy, parameters quantifying the inhalation (I) to perfusion (P) mismatching at regional as well as at intraregional levels were calculated. The SLO increased the relative ventilation to the lung containing the obstruction, induced a shift of blood from the obstructed segment to the rest of the same lung, and increased the ratio between the mean I and the mean P (regional mismatching factor) in both the obstructed segment and the lung containing the obstruction. The LO diverted air and blood away from the obstructed lobe to the contralateral lung, but blood to a lesser extent. The LO decreased the regional mismatching factor in the obstructed lobe but also in the lung containing the obstruction. It also increased significantly the intraregional I to P mismatching in the obstructed lobe as well as in the rest of the same lung. After withdrawal of LO and reinsufflation of the collapsed lobe, blood continued to leave this lobe, while the withdrawal of SLO allowed recovery of the initial perfusion. This suggests that both hypoxic vasoconstriction and mechanical factors such as vascular distortion are involved in the blood shifts observed, and require some delay to be relieved. It is concluded that in dogs compensating mechanisms such as collateral ventilation are very effective. In case of SLO, I to the lung involved is increased. In case of LO, vasoconstriction in response to alveolar hypoxia could not fully compensate for the decreased I to the obstructed lobe.

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Effect of timing of transient diastolic changes in ventricular filling on LV performance in dogs.

The influence of acute volume changes during diastole on the contractile state of the left ventricle has been studied in the closed-chest dog. Volume changes were introduced by means of a servo-controlled pump system connected to the left ventricular cavity by an apical cannula. Pressure measurements were made in the left ventricle and aorta. Flow sensors in the mitral valve and around the ascending aorta monitored ventricular inflow and outflow patterns. The ventricular performance was evaluated in terms of the ratio between end-systolic pressure and end-systolic volume (P/Ves). By changing the time of occurrence of the volume interventions from the rapid filling phase of diastole to the atrial contraction phase, the relative contributions of rapid filling and atrial contraction to the mitral flow were changed. When the rapid filling was changed by the volume intervention, the effect on the contractile status of the heart, expressed as the P/Ves value, was small. In contrast, when the volume intervention took place during the atrial contraction phase, the effect on the P/Ves value was much larger. Comparison with muscle fiber experiments suggests that length-dependent calcium sensitivity of troponin and length-dependent conductivity of the sarcolemma are the underlying fundamental mechanisms. Therefore, we conclude that the influence of an intervention in ventricular filling on the inotropic state of the left ventricle is dependent on the timing of the intervention.

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Radionuclide angiocardiography in the normal dog: first-pass studies.

The first pass of a bolus of radioactivity (99mTc) through the heart and lungs was studied in 27 anaesthetised healthy adult mongrel dogs, using a gamma camera with a computer on-line. Bodyweights ranged from 9 to 60 kg, heart rate from 108 to 150 beats min-1. Quantitative analysis revealed that the distribution volume (DV) of the labelled blood, the cardiac output (CO), the stroke volume (SV) and pulmonary blood volume (PBV) were almost proportional to the bodyweight. Specific results were: DV 120 ml kg-1, CO 136 ml kg-1, SV 1.11 ml kg-1, PBV 6.9 ml kg-1. The pulmonary transit time varied between 1.0 and 3.6 seconds. Clinical applicability of the method, including visual inspection of camera images and quantitative analysis of a time-activity curve of the lung, was demonstrated for one dog with an aortic stenosis and another with a left-to-right shunt.

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