Double-masked, placebo-controlled study of intravenous levetiracetam for the treatment of status epilepticus and acute repetitive seizures in dogs.

BACKGROUND: Status epilepticus (SE) and acute repetitive seizures (ARS) are common canine neurologic emergencies. No evidence-based studies are available to guide treatment in veterinary patients. Parenteral levetiracetam (LEV) has many favorable properties for the emergency treatment of seizures, but its safety and efficacy in dogs for SE and ARS are unknown. HYPOTHESIS: Intravenous LEV is superior to placebo in controlling seizures in dogs with SE or ARS after treatment with IV diazepam. ANIMALS: Nineteen client-owned dogs admitted for SE or ARS. METHODS: Randomized, placebo-controlled, double-masked study. Dogs with SE or ARS were randomized to receive IV LEV (30 or 60 mg/kg using an adaptive dose-escalation approach) or placebo, in addition to standard of care treatment. They were monitored for at least 24 hours after admission for additional seizures. RESULTS: The responder rate (defined as dogs with no additional seizures after administration of the study medication) after LEV was 56% compared with 10% for placebo (P = .06). Dogs in the placebo group required significantly more boluses of diazepam compared with the LEV group (P < .03). Seizure etiologies identified were idiopathic epilepsy (n = 10), inflammatory central nervous system disease (n = 4), intracranial neoplasia (n = 2), hepatic encephalopathy (n = 1), and 2 dogs had no cause determined. No serious adverse effects were attributable to LEV administration. CONCLUSIONS AND CLINICAL IMPORTANCE: LEV was safe and potentially effective for the treatment of SE and ARS in these client-owned dogs. Larger, controlled clinical trials are needed to confirm this preliminary observation.

Awareness of memory functioning in early Alzheimer's disease: lessons from a comparison with healthy older people and young adults.

To compare awareness of memory in people with early Alzheimer's disease (AD) with older and younger control groups in order to clarify the contributions of disease and ageing. Twenty-one individuals with early AD, 32 older people (OP) and 32 younger people (YP) estimated their performance before and following each of four tests of memory. Those with AD significantly overestimated performance prior to testing, confirming the presence of unawareness for prediction. Their estimates were adjusted for age in a similar way to those of OP, who predicted their performance accurately. Younger people significantly underestimated their performance. Following memory tests, YP and those with AD significantly adjusted their ratings towards greater accuracy but on average those with AD still overestimated. There were variations in post-test ratings from over to under prediction in all three groups. Heightened awareness post-performance may open possibilities of cognitive rehabilitation to consolidate momentary into more long-term awareness, whilst the operation of possible psychosocial influences suggests that emotion oriented interventions to increase acceptance and decrease shame might be helpful.

An in vitro model of early islet amyloid polypeptide (IAPP) fibrillogenesis using human IAPP-transgenic mouse islets.

The mechanisms underlying insufficient insulin secretion and loss of beta-cell mass in feline and human type 2 diabetes mellitus are incompletely understood. However, islet amyloid polypeptide (IAPP)-derived islet amyloidosis (IA) has been linked to increased rates of beta-cell apoptosis and, therefore, our goal was to develop an in vitro model of IAPP fibrillogenesis using isolated pancreatic islets from mice transgenic for human IAPP (hIAPP Tg mice). Islets from hIAPP Tg mice, from mice transgenic for non-amyloidogenic murine IAPP (mIAPP Tg mice), and from the FVB background strain were exposed to normal (5.5 mM) or high (28 mM) glucose conditions in cell culture for 8 days. On days 0 and 8, islets were collected for electron microscopy (EM). EM showed no abnormalities in the mIAPP Tg or FVB islets at either time point. On day 8, hIAPP Tg islets cultured at high glucose concentration formed extracellular IAPP-derived flocculent deposits. No significant differences in rates of apoptosis were found between groups. Our findings, therefore, show that in vitro culture of hIAPP Tg mouse islets under high glucose conditions produces a readily available and rapidly inducible model of IAPP-derived fibrillogenesis and enables the study of early phases of the molecular pathogenesis of IA.

Acalculous cholecystitis in four canine cases: ultrasonographic findings and use of ultrasonographic-guided, percutaneous cholecystocentesis in diagnosis.

Canine cholecystitis is diagnosed infrequently. Clinical signs, physical examination findings, and clinicopathological abnormalities are nonspecific. Few reports exist of associated ultrasonographic findings which also are nonspecific for the disorder. Ultrasonographic-guided, percutaneous cholecystocentesis has been suggested for diagnostic confirmation. The present report further documents ultrasonographic findings associated with canine acalculous cholecystitis and demonstrates the utility of ultrasonographic-guided, percutaneous cholecystocentesis in confirmation of the diagnosis in a prospectively acquired clinical case series.

Canine gastric neoplasia: utility of ultrasonography in diagnosis.

The utility of ultrasonography in the diagnosis of canine gastric neoplasia was evaluated prospectively in a series of six cases subsequently confirmed as having adenocarcinoma by cytological or histological examination or both. Gastric neoplasia was associated with mural thickening with loss of normal wall sonographic layers and decreased or absent local motility. Sonographic findings were consistent with tumor localization obtained by other diagnostic methods employed. Ultrasonographic-guided, percutaneous, fine-needle aspirations biopsies were successful in two of the three cases in which they were performed. Ultrasonography appears useful in the diagnostic of canine gastric neoplasia.

The use of a synthetic prostaglandin E1 analog as a gastric protectant against aspirin-induced hemorrhage in the dog.

Misoprostol prevented gastric hemorrhage in dogs, each of which received aspirin (35 mg/kg body weight, orally q 8 hrs for 10 days). All dogs receiving aspirin alone had gastroscopic and histopathological lesions. No lesions were noted in four of five dogs given aspirin plus misoprostol (15 micrograms/kg body weight, q 8 hrs for five days; then 7.5 micrograms/kg body weight, q 8 hrs for five days). Four of 10 dogs receiving 15 micrograms/kg body weight of misoprostol developed diarrhea. The misoprostol dose was reduced to 7.5 micrograms/kg body weight, and the diarrhea subsided.

Hypophosphatemia and hemolytic anemia associated with diabetes mellitus and hepatic lipidosis in cats.

Hypophosphatemia associated with hemolytic anemia was diagnosed in five cats with diabetes mellitus and in one cat with idiopathic hepatic lipidosis. The hematocrit began decreasing within 24 to 48 hours after documented hypophosphatemia in each case. The anemia resolved in all five surviving cats. Because of the temporal relationship and lack of other detectable causes, hemolytic anemia was presumed to be caused by hypophosphatemia. There were increased Heinz bodies in three of six hypophosphatemic cats during episodes of hemolysis. Intravenous potassium phosphate administration corrected the hypophosphatemia in four of five cats. The effective dosages of intravenous phosphate ranged from 0.011 to 0.017 mmol of phosphate/kg/h for 6 to 12 hours. Hypocalcemia (5.4 to 8.7 mg/dL) occurred in four of five cats treated with intravenous phosphate; however, only one cat developed clinical signs attributable to hypocalcemia. Based on this retrospective study, we recommend monitoring serum phosphorus concentration every 6 to 12 hours in cats likely to become hypophosphatemic. Treatment of hypophosphatemia in cats is warranted because of the apparent increased susceptibility of cats to hypophosphatemia-induced hemolysis. Cats with severe hypophosphatemia (< or = 1.5 mg/dL) should be given oral or parenteral phosphate if contraindications do not exist.

Ultrasonographic appearance of primary and metastatic canine hepatic tumors. A review of 48 cases.

Forty-eight cases of dogs with primary and metastatic hepatic neoplasia were reviewed to determine if a predictable relationship between sonographic appearance and neoplastic cell type could be found. A focal mass was almost always a hepatocellular carcinoma (14 of 15) and 71% of these were hyperechoic. Focal or multifocal hyperechoic masses were most likely to be carcinomas (14 of 15). Focal or multifocal mixed neoplasms were most likely to be carcinomas (6 of 7). Two distinct patterns of lymphosarcoma were found: diffuse, mildly hyperechoic (6/11) and multifocal, hypoechoic (5/11). No neoplastic cell-type predictions could be made for focal or multifocal hypoechoic lesions. Diffuse fine or coarse patterns with minimal architectural distortions could be mistaken for normal or degenerative processes. However, in the presence of increased serum liver enzyme values, these subtle sonographic changes would warrant a liver biopsy to differentiate neoplastic infiltrate from non-neoplastic infiltrative and degenerative processes.

Hypernatremia.

Hypernatremia is a potentially life-threatening electrolyte abnormality. This problem develops most often because of loss of water from the animal, but in rare cases hypernatremia results from gain of sodium chloride. Important conditions predisposing to hypernatremia include diarrhea, vomiting, heat stroke, fever, limited access to water, excessive diuretic use, renal diseases, and pituitary diabetes insipidus. This condition rarely develops if animals have adequate access to water. Clinical signs relate to central nervous system derangements and can progress to seizures and coma. Diagnosis is based on the serum sodium concentration; treatment should be instituted if it is greater than 170 mEq per L. Treatment is based on knowledge of the volume status of the patient and the probable cause for the hypernatremia. In general, 5 per cent dextrose in water or other hypotonic fluids are given slowly intravenously. The rate of administration should be adjusted so the water deficit is replaced over 48 to 72 h. Too rapid correction of hypernatremia can lead to cerebral edema and worsening of the animal. In cases of salt intoxication, diuretics must be given in addition to slow water replacement to avoid the development of pulmonary edema.

Reassessment of cytologic values in canine cerebrospinal fluid by use of cytocentrifugation.

Using cytocentrifugation, nearly one fourth of canine cerebrospinal fluid (CSF) samples with cell counts in the normal range had abnormalities in cell type or morphologic features. Cerebrospinal fluid samples from 145 dogs with neurologic disorders were evaluated by use of this method. These results indicate that low hemacytometer counts in canine CSF should not be interpreted as normal. By increasing the detection of abnormalities in CSF, cytocentrifugation might improve diagnosis and treatment of canine neurologic disease.

Clinical signs, diagnosis, and treatment of alkalemia in dogs: 20 cases (1982-1984).

Alkalemia (pH greater than 7.50) was measured in 20 dogs admitted over a 3-year period for various clinical disorders. Alkalemia was detected in only 2.08% of all dogs in which blood pH and blood-gas estimations were made. Thirteen dogs had metabolic alkalosis (HCO3- greater than 24 mEq/L, PCO2 greater than 30 mm of Hg), of which 8 had uncompensated metabolic alkalosis, and of which 5 had partially compensated metabolic alkalosis. Seven dogs had respiratory alkalosis (PCO2 less than 30 mm of Hg, HCO3- less than 24 mEq/L); 4 of these had uncompensated respiratory alkalosis and 3 had partially compensated respiratory alkalosis. Ten dogs had double or triple acid-base abnormalities. Dogs with metabolic alkalosis had a preponderance of clinical signs associated with gastrointestinal disorders (10 dogs). Overzealous administration of sodium bicarbonate or diuretics, in addition to anorexia, polyuria, or hyperbilirubinemia may have contributed to metabolic alkalosis in 8 of the dogs. Most of the dogs in this group had low serum K+ and Cl- values. Two dogs with metabolic alkalosis had PCO2 values greater than 60 mm of Hg, and 1 of these had arterial hypoxemia (PaO2 less than 80 mm of Hg). Treatments included replacement of fluid and electrolytes (Na+, K+, and Cl-), and surgery as indicated (8 dogs). Six dogs with respiratory alkalosis had a variety of airway, pulmonary, or cardiac disorders, and 3 of these had arterial hypoxemia. Two other dogs were excessively ventilated during surgery, and 1 dog had apparent postoperative pain that may have contributed to the respiratory alkalosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Thoracic vertebral osteochondroma in a cat.

A thoracic vertebral (T5) osteochondroma was discovered in a 1 1/2-year-old male blue Persian cat with a history of acute hind limb paresis. Myelography revealed a mass on the dorsal surface of the vertebral body, which resulted in dorsal compression of the spinal cord. A dorsal laminectomy was performed, and the mass was rongeured entirely from the vertebral body. Although the cat's progress was initially slow after surgery, its neurologic status was assessed to be near normal, 15 months later.

Medical Research Council leukaemia trial--UKALL V: an attempt to reduce the immunosuppressive effects of therapy in childhood acute lymphoblastic leukemia. Report to the Council by the Working Party on Leukaemia in Childhood.

The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival, intermittent continuing chemotherapy, although less immunosuppressive, is less effective than conventional continuous therapy in the treatment of ALL. In this study, 3 years of chemotherapy appeared superior to 2 years.

Inherited, chronic, progressive hepatic degeneration in Bedlington terriers with increased liver copper concentrations: clinical and pathologic observations and comparison with other copper-associated liver diseases.

One hundred nineteen hepatic tissue samples from 117 Bedlington Terriers were divided into 6 groups depending on the severity of histopathologic hepatic changes. Group 0 comprised dogs with microscopically normal livers. Group I dogs had copper-positive, lipofuscin-containing lysosomes present in centrilobular hepatocytes. Microfoci of hepatic necrosis, in addition to the increased numbers of the copper-positive, lipofuscin-containing lysosomes in centrilobular and periportal hepatocytes, were present in group II dogs. Group III dogs had more copper-positive, lipofuscin-containing lysosomes present translobularly and morphologic changes consistent with chronic active hepatitis. Mixed micro- or macronodular cirrhosis and translobular presence of copper-positive, lipofuscin-containing lysosomes characterized group IV dogs. Dogs in group V had massive hepatic necrosis and morphologic changes that were consistent with the changes in group III and IV dogs. Histochemical staining for copper was useful in making the microscopic diagnosis of this disease and was shown to be necessary in early diagnosis (group I) when other clinical and pathologic values associated with this syndrome were not consistently abnormal. Copper histochemical stains varied in sensitivity. Timm's silver sulfide was more sensitive for copper than was rubeanic acid, which was more sensitive than rhodanine staining. The brown pigment associated with the copper in the lysosomes was shown to be lipofuscin pigment with the aid of histochemical staining with orcein, Prussian blue, periodic acid-Schiff, and acid-fast stains together with fluorescent microscopy (excitation maxima: 365 nm; emissions: 420 + nm). Since these were positive only in later stages of the hepatic disease, they were not especially useful in its early diagnosis. The severity of the histopathologic hepatic changes was shown to increase with age and was associated with increasing hepatic copper concentration. These observations illustrate that this inherited, chronic hepatic degeneration in the Bedlington Terrier is progressive. Clinical chemical tests were diagnostically useful only in later stages of the disease. Alanine transaminase activity was of most value, but was not always abnormal, even when severe hepatic damage was present. Clinical signs of hepatic disease were seen in dogs in groups III, IV, and V. Death due to hepatic failure occurred only in dogs in groups III, IV, and V. Hemosiderin was present in increased amounts in the liver, bone marrow, spleen, and lymph nodes of affected Bedlington Terriers, indicating that a possible defect in iron metabolism and/or an increase in RBC turnover existed.(ABSTRACT TRUNCATED AT 400 WORDS)

Hepatic cirrhosis associated with long-term primidone therapy in a dog.

The anticonvulsant drug, primidone, was believed to be responsible for the development of hepatic cirrhosis in a 9-year-old German Shepherd Dog with idiopathic epilepsy. Marked increases in serum alanine aminotransferase, serum alkaline phosphatase, total bilirubin, and sulfobromophthalein retention, as well as decreases in albumin and BUN supported the diagnosis of hepatic failure. Biochemical abnormalities improved after primidone was discontinued. Previous reports indicated a poor prognosis for anticonvulsant-induced hepatic failure; however, this dog has remained stable for over a year after diagnosis and proper therapy.

Chronic hepatitis. An emerging syndrome in dogs.

Chronic active hepatitis has been recognized in humans since the 1950s but has been recognized only recently as a disease syndrome in dogs. The author describes this diverse group of chronic inflammatory liver diseases and discusses the factors related to its etiology, pathogenesis, diagnosis, and therapy.

Immunofluorescence studies of renal basement membranes in dogs with spontaneous diabetes.

Renal tissue from 12 dogs with spontaneous diabetes and 16 control dogs were studied by light, immunofluorescence, and electron microscopies. Significant linear staining for immunoglobulin G and albumin were observed in the glomerular and tubular basement membranes of dogs with spontaneous diabetes--similar to that observed in human diabetes. On immunohistochemical grounds, it would appear that the dog with spontaneous diabetes is an appropriate model of diabetes in persons.