Patients Enrolled in Large Randomized Clinical Trials of Antiplatelet Treatment for Prevention After Transient Ischemic Attack or Ischemic Stroke Are Not Representative of Patients in Clinical Practice: the Netherlands Stroke Survey

Background and Purpose—Many randomized clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of new vascular events in patients with a recent transient ischemic attack or ischemic stroke. Evidence from these trials forms the basis for national and international guidelines for the management of nearly all such patients in clinical practice. However, abundant and strict enrollment criteria may limit the validity and the applicability of results of randomized clinical trials to clinical practice. We estimated the eligibility for participation in landmark trials of antiplatelet drugs of an unselected group of patients with stroke or transient ischemic attack from a national stroke survey. Methods—Nine hundred seventy-two patients with transient ischemic at

Endocrinology of physiological and progestin-induced canine anoestrus

The oestrous cycle of the domestic bitch is unique with regard to its considerable length compared with that of most other domestic animals. A non-seasonal anoestrus, with a duration that may last from 2 to 10 months, follows each oestrous cycle. The anoestrus can be prolonged by oestrus-preventing drugs such as progestins. The general aim of the studies in this thesis was to get further insight into the endocrinology of the physiological and the progestin-induced canine anoestrus. Studies performed throughout recent years have made clear that during the course of canine anoestrus many endocrinological changes take place at the hypothalamic, pituitary, and ovarian level. Apart from these changes, there are indications of involvement of dopaminergic influences. The results of the study described in Chapter 3 provide forceful evidence that the bromocriptine-induced shortening of the interoestrous interval is not triggered by a decline in plasma prolactin concentration. The results of the study described in Chapter 4 provides additional evidence that the premature onset of oestrus brought about by a dopamine agonist must be due to some other dopamine-agonistic effect, probably increased FSH secretion. The study in Chapter 5 is a report on the effects of GnRH administration on the plasma concentrations of reproductive hormones in intact and OVX bitches. The data presented in this study demonstrate that provocative testing of the pituitary-ovarian axis using GnRH may be helpful in differentiating between bitches in anoestrus and neutered bitches. The study reported in Chapter 6 describes the basal and GnRH-induced plasma concentrations of FSH and LH in four anoestrous and four OVX bitches. In this report indications were found that measurement of the plasma FSH concentration in a single plasma sample may prove reliable for determination of neuter status. Taken together, the results of the studies described in Chapters 5 and 6 provide a basis for the diagnosis of remnant ovarian tissue and verification of neuter status in the bitch. Chapters 7 and 8 are reports on the effect of MPA on canine adenohypophyseal function. The results of both studies demonstrate that treatment with MPA affects the hypothalamic-pituitary-ovarian axis. Oestrus, ovulation, and a subsequent luteal phase did not occur in any of the bitches during treatment with MPA. The prevention of oestrus by MPA cannot be ascribed to a significant reduction in circulating levels of either FSH or LH. On the contrary, during the first months of MPA treatment there was an increase in basal plasma FSH and LH, which may be due to a direct oestrus-preventing effect of MPA at the ovarian level. With continuing MPA treatment, basal plasma gonadotrophin concentrations returned to pretreatment levels and the pituitary FSH response to GnRH stimulation decreased, while several LH pulses were not accompanied by a significant FSH pulse, suggesting that MPA treatment attenuated pituitary FSH sensitivity to endogenous GnRH. The study in Chapter 7 also provides an integral picture of the effects of MPA treatment on adenohypophyseal function

Endocrinology of physiological and progestin-induced canine anoestrus

The oestrous cycle of the domestic bitch is unique with regard to its considerable length compared with that of most other domestic animals. A non-seasonal anoestrus, with a duration that may last from 2 to 10 months, follows each oestrous cycle. The anoestrus can be prolonged by oestrus-preventing drugs such as progestins. The general aim of the studies in this thesis was to get further insight into the endocrinology of the physiological and the progestin-induced canine anoestrus. Studies performed throughout recent years have made clear that during the course of canine anoestrus many endocrinological changes take place at the hypothalamic, pituitary, and ovarian level. Apart from these changes, there are indications of involvement of dopaminergic influences. The results of the study described in Chapter 3 provide forceful evidence that the bromocriptine-induced shortening of the interoestrous interval is not triggered by a decline in plasma prolactin concentration. The results of the study described in Chapter 4 provides additional evidence that the premature onset of oestrus brought about by a dopamine agonist must be due to some other dopamine-agonistic effect, probably increased FSH secretion. The study in Chapter 5 is a report on the effects of GnRH administration on the plasma concentrations of reproductive hormones in intact and OVX bitches. The data presented in this study demonstrate that provocative testing of the pituitary-ovarian axis using GnRH may be helpful in differentiating between bitches in anoestrus and neutered bitches. The study reported in Chapter 6 describes the basal and GnRH-induced plasma concentrations of FSH and LH in four anoestrous and four OVX bitches. In this report indications were found that measurement of the plasma FSH concentration in a single plasma sample may prove reliable for determination of neuter status. Taken together, the results of the studies described in Chapters 5 and 6 provide a basis for the diagnosis of remnant ovarian tissue and verification of neuter status in the bitch. Chapters 7 and 8 are reports on the effect of MPA on canine adenohypophyseal function. The results of both studies demonstrate that treatment with MPA affects the hypothalamic-pituitary-ovarian axis. Oestrus, ovulation, and a subsequent luteal phase did not occur in any of the bitches during treatment with MPA. The prevention of oestrus by MPA cannot be ascribed to a significant reduction in circulating levels of either FSH or LH. On the contrary, during the first months of MPA treatment there was an increase in basal plasma FSH and LH, which may be due to a direct oestrus-preventing effect of MPA at the ovarian level. With continuing MPA treatment, basal plasma gonadotrophin concentrations returned to pretreatment levels and the pituitary FSH response to GnRH stimulation decreased, while several LH pulses were not accompanied by a significant FSH pulse, suggesting that MPA treatment attenuated pituitary FSH sensitivity to endogenous GnRH. The study in Chapter 7 also provides an integral picture of the effects of MPA treatment on adenohypophyseal function

Incomplete endothelialization of an intravascular implant and fatal late-onset bacterial ductal arteritis in a dog with occluded patent ductus arteriosus

An 18‐month‐old male Akita Inu dog developed fever and lameness 8 months after successful transcatheter closure of a patent ductus arteriosus with an Amplatz Canine Duct Occluder (ACDO). Corynebacterium species were cultured from 3 blood samples. Echocardiography showed a vegetative process on the aortic valves. The dog died spontaneously 3 days after development of the initial signs. Necropsy confirmed the presence of bacterial ductal arteritis and myocarditis, and revealed an incomplete endothelialization of the intraductal metal implant. The reason for the lack of (neo)endothelialization of the ACDO remains unknown. We conclude that late‐onset bacterial device‐related ductal arteritis can develop in dogs where the implant is incompletely covered by a protective endothelial layer

Incomplete endothelialization of an intravascular implant and fatal late-onset bacterial ductal arteritis in a dog with occluded patent ductus arteriosus

An 18‐month‐old male Akita Inu dog developed fever and lameness 8 months after successful transcatheter closure of a patent ductus arteriosus with an Amplatz Canine Duct Occluder (ACDO). Corynebacterium species were cultured from 3 blood samples. Echocardiography showed a vegetative process on the aortic valves. The dog died spontaneously 3 days after development of the initial signs. Necropsy confirmed the presence of bacterial ductal arteritis and myocarditis, and revealed an incomplete endothelialization of the intraductal metal implant. The reason for the lack of (neo)endothelialization of the ACDO remains unknown. We conclude that late‐onset bacterial device‐related ductal arteritis can develop in dogs where the implant is incompletely covered by a protective endothelial layer

Cardiorenal and endocrine effects of synthetic canine BNP1-32 in dogs with compensated congestive heart failure caused by myxomatous mitral valve disease

Background: The effects of synthetic brain natriuretic peptide (BNP1-32) on cardiorenal and renin angiotensin aldosterone system in dogs with naturally occurring congestive heart failure (CHF) are unknown. Objectives: To evaluate the cardiorenal and endocrine effects of SC administered synthetic canine BNP1-32, with or without furosemide, in dogs with CHF caused by myxomatous mitral valve disease (MMVD). Animals: Seven client-owned male dogs with compensated American College of Veterinary Internal Medicine stage C CHF caused by MMVD on chronic treatment with furosemide, benazepril, and pimobendan. Methods: A single-dose, crossover, pilot study. Each dog received a dose of BNP1-32 (5 μg/kg), furosemide (2 mg/kg), and both BNP1-32/furosemide (5 μg/kg and 2 mg/kg, respectively) SC with a 2-week washout period among each treatment. Between- and within-treatment effects were evaluated using linear mixed modeling with restricted maximum likelihood estimation and evaluation of least square differences. Results: Rapid absorption of BNP1-32 and a corresponding rise in urinary cyclic guanosine monophosphate excretion was observed at 1-2 hours after any treatment containing BNP1-32 (P <.05). However, BNP1-32 did not influence measured cardiorenal variables. Plasma aldosterone concentrations were below quantifiable levels in majority of the samples. Conclusions and Clinical Importance: No beneficial cardiorenal effects were detected. It is possible that dogs with chronic CHF have a reduction in natriuretic peptide responsiveness

Cardiorenal and endocrine effects of synthetic canine BNP1-32 in dogs with compensated congestive heart failure caused by myxomatous mitral valve disease

Background: The effects of synthetic brain natriuretic peptide (BNP1-32) on cardiorenal and renin angiotensin aldosterone system in dogs with naturally occurring congestive heart failure (CHF) are unknown. Objectives: To evaluate the cardiorenal and endocrine effects of SC administered synthetic canine BNP1-32, with or without furosemide, in dogs with CHF caused by myxomatous mitral valve disease (MMVD). Animals: Seven client-owned male dogs with compensated American College of Veterinary Internal Medicine stage C CHF caused by MMVD on chronic treatment with furosemide, benazepril, and pimobendan. Methods: A single-dose, crossover, pilot study. Each dog received a dose of BNP1-32 (5 μg/kg), furosemide (2 mg/kg), and both BNP1-32/furosemide (5 μg/kg and 2 mg/kg, respectively) SC with a 2-week washout period among each treatment. Between- and within-treatment effects were evaluated using linear mixed modeling with restricted maximum likelihood estimation and evaluation of least square differences. Results: Rapid absorption of BNP1-32 and a corresponding rise in urinary cyclic guanosine monophosphate excretion was observed at 1-2 hours after any treatment containing BNP1-32 (P <.05). However, BNP1-32 did not influence measured cardiorenal variables. Plasma aldosterone concentrations were below quantifiable levels in majority of the samples. Conclusions and Clinical Importance: No beneficial cardiorenal effects were detected. It is possible that dogs with chronic CHF have a reduction in natriuretic peptide responsiveness

Single-dose pharmacokinetics and cardiovascular effects of oral pimobendan in healthy cats

Abstract not availableM. Yata, A.J. McLachlan, D.J.R. Foster, A.S. Hanzlicek, N.J. Beijerin

Atrial septal defect in a ferret

Abstract A 2-year-old, male castrated ferret (Mustela putorius furo) was presented with progressive abdominal distention and loss of muscle mass despite normal appetite. Physical examination findings included pale mucous membranes, a prolonged capillary refill time, a pulse rate greater than 300 beats/min, and severe abdominal distention. Abdominal ultrasound showed free abdominal fluid and an enlarged liver with distended hepatic veins and caudal vena cava. During the echocardiographic examination, abnormalities observed included a 2-mm-diameter left-to-right shunting atrial septal defect (ASD) with concurrent severe dilatation of the right atrium and eccentric hypertrophy of the right ventricle with mild pulmonary hypertension. All other echocardiographic measurements were within normal limits. The owner declined treatment, and the ferret was euthanized. Postmortem examination confirmed the ultrasonographic findings. The free abdominal fluid (200 mL) was a non-septic fibropurulent exudate. Decompensated right-sided heart failure due to ASD and exudative peritonitis of undetermined origin were the final diagnoses. To our knowledge, this is the first report of an ASD in a ferret