Use of urine cortisol:creatinine ratio versus adrenocorticotropic hormone stimulation testing for monitoring mitotane treatment of pituitary-dependent hyperadrenocorticism in dogs.

OBJECTIVE: To evaluate use of urine cortisol-to-creatinine ratio (UC:C) as a means of monitoring response to long-term mitotane treatment in dogs with pituitary-dependent hyperadrenocorticism. DESIGN: Prospective uncontrolled study. ANIMALS: 101 dogs with pituitary-dependent hyperadrenocorticism. PROCEDURE: Urine samples were obtained from dogs on the morning an ACTH stimulation test was performed, and owners were asked their opinion on the health of their dog to monitor response to mitotane treatment. Urine was assayed for cortisol and creatinine concentrations, and UC:C was calculated. The UC:C was compared with post-ACTH plasma cortisol concentration. RESULTS: Post-ACTH plasma cortisol concentration was used to categorize each dog's response to mitotane treatment. The UC:C did not correlate satisfactorily with results of ACTH stimulation testing. Twenty-seven of 85 (32%) dogs would have been incorrectly considered as having received appropriate doses using UC:C. In addition, 16 dogs that received overdoses could not be distinguished from 29 dogs that received appropriate doses. CLINICAL IMPLICATIONS: UC:C does not provide a consistent, correct assessment of mitotane-induced adrenocortical destruction. The ACTH stimulation test, although more time-consuming and expensive, is recommended for monitoring response to mitotane treatment.

Comparison of results of hormonal analysis of samples obtained from selected venous sites versus cervical ultrasonography for localizing parathyroid masses in dogs.

OBJECTIVE: To compare a technique in which samples obtained from selected venous sites are analyzed for parathyroid hormone (PTH) concentration versus usefulness of cervical ultrasonography for localizing primary hyperparathyroidism (PHP) in dogs. DESIGN: Prospective study. ANIMALS: 12 dogs with PHP. PROCEDURE: For each dog, blood samples were collected from the left and right jugular veins and 1 cephalic vein for determination of serum PTH concentration. Ultrasonography of the neck was performed in each dog. Each dog underwent exploratory surgery of the neck. Abnormal appearing parathyroid tissue was removed. Dogs were included in the study if serum calcium concentration decreased within 12 hours after surgery, hypercalcemia completely resolved within 96 hours after surgery, and serum calcium concentration was maintained within the reference range for at least 6 months after surgery. RESULTS: Serum PTH concentrations from the 3 veins were similar in 11 of 12 dogs with PHP. In 1 dog, the serum PTH concentration from the jugular vein ipsilateral to a parathyroid adenoma was greater than that from the contralateral jugular or cephalic vein. Ultrasonography correctly identified a parathyroid mass and its location in 10 of 11 dogs with a solitary abnormal parathyroid gland and in 1 dog in which both parathyroid glands were enlarged. CLINICAL IMPLICATIONS: Surgeons may benefit from knowing the location of abnormal parathyroid tissue in dogs with PHP before surgical exploration. Ultrasonography has potential value for identifying and localizing abnormal parathyroid tissue, whereas sample collection from selected sites for PTH analysis is not likely to be helpful.

Intensive 50-week evaluation of glipizide administration in 50 cats with previously untreated diabetes mellitus.

OBJECTIVE: To evaluate use of the oral hypoglycemic drug glipizide in diabetic cats. DESIGN: Prospective study. ANIMALS: 50 cats with recently diagnosed but untreated diabetes mellitus. PROCEDURE: Each cat received glipizide (5 mg, q 12 h) for 16 weeks. Medication was not given during the subsequent 16 weeks; then glipizide treatment was repeated. Each cat was evaluated prior to treatment and at 2, 4, 8, 12, and 16 weeks during each of the 3 phases: blood samples for serum glucose and insulin determinations were obtained every 2 hours, from 8 AM to 6 PM. A preprandial blood glycosylated hemoglobin percentage was determined for the first sample obtained at each visit. RESULTS: During the first 22 weeks of the study, diabetes worsened in 28 of the 50 cats, which then were disqualified from the study and treated with insulin. Of the remaining 22 cats that improved clinically, 7 had corresponding metabolic improvement in each diabetes-related parameter assessed and did not become hypoglycemic. Six of the 22 cats became hypoglycemic. Glipizide was discontinued, and diabetes did not recur. Serum glucose concentration did not improve in 6. Three cats had metabolic and clinical improvement during initial glipizide treatment, but had recurrence of the disease during repeated treatment; glipizide was discontinued and insulin was administered. None of the 50 treated cats died, and observed morbidity was mild and transient. Transient anorexia and vomiting were observed in 8 cats, and 4 became transiently icteric with abnormal liver enzyme activities. CLINICAL IMPLICATIONS: Trial use of glipizide is feasible in diabetic cats of owners who are unable or unwilling to administer insulin.

Spectrum of mucus-secreting pancreatic neoplasia.

Mucus-secreting pancreatic lesions, most commonly described by the Japanese, are often malignant (as in cystic or mucin-producing adenocarcinomas), but can be benign (hyperplastic or adenomatous cytology). We report a case of total pancreatic ductal enlargement without a localized lesion in which abdominal pain was relieved by endoscopic sphincterotomy and partial septotomy in which cytology remains benign. In the absence of pancreatic cyst, mass, or localized ductal abnormality, total pancreatectomy is the only treatment that can completely remove the risk of malignant degeneration of apparently benign, mucus-secreting pancreatic ductal enlargement. Disability after total pancreatectomy is severe, but the risk of metastasis from mucinous ductal ectasia is low without pancreatic cyst or mass. Therefore, regular observation of mucus-secreting ductal enlargement with computerized tomography and pancreatography are appropriate, especially in older patients. Endoscopic sphincterotomy may relieve symptoms and allow access for ampullary biopsy and brushings.

Use of low- and high-dose dexamethasone tests for distinguishing pituitary-dependent from adrenal tumor hyperadrenocorticism in dogs.

OBJECTIVE: To evaluate low- and high-dose dexamethasone suppression tests for differentiating pituitary dependent hyperadrenocorticism (PDH) from adrenal tumor hyperadrenocorticism (ATH) in dogs. DESIGN: Prospective study. ANIMALS: 181 dogs with PDH and 35 dogs with ATH. PROCEDURE: Plasma cortisol concentrations from dogs with naturally developing hyperadrenocorticism were evaluated before, and 4 and 8 hours after administration of standard low- and high-doses of dexamethasone (0.01 mg/kg of body weight, i.v., and 0.1 mg/kg, i.v.; respectively). RESULTS: In response to the low-dose test, all but 3 dogs had an 8-hours post-dexamethasone plasma cortisol concentration that was consistent with a diagnosis of hyperadrenocorticism, that is, > or = 1.4 micrograms/dl. Criteria used to distinguish PDH from ATH in response to low-dose dexamethasone included a 4-hour post-dexamethasone plasma cortisol concentration < 50% of the basal value or < 1.4 micrograms/dl, or an 8-hours post-dexamethasone plasma cortisol concentration < 50% of the basal concentration. Criteria used to distinguish PDH from ATH in response to high-dose dexamethasone included 4- or 8-hour post-dexamethasone plasma cortisol concentrations < 50% of the basal concentration or < 1.4 micrograms/dl. In response to the low-dose test, 111 dogs met criteria for suppression (each had PDH). In response to the high-dose test, 137 dogs met criteria for suppression (2 had ATH, 135 had PDH). Twenty-six dogs with PDH (12%) had indications of adrenal suppression in response to high-dose but not low-dose testing. CLINICAL IMPLICATIONS: Low-dose dexamethasone test has value as a discrimination test to distinguish dogs with PDH from those with ATH. The high-dose test need only be considered in dogs with hyperadrenocorticism that do not have adrenal suppression in response to the low-dose test.

One-year follow-up evaluation of magnetic resonance imaging of the brain in dogs with pituitary-dependent hyperadrenocorticism.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) brain scans of dogs with pituitary-dependent hyperadrenocorticism (PDH) and no signs of CNS dysfunction 1 year after diagnosis and initial MRI. DESIGN: Prospective study of surviving dogs from a previous study. ANIMALS: 13 dogs underwent MRI of the brain at the time that PDH was diagnosed and prior to treatment. At that time, none of the dogs had clinical signs suggestive of an intracranial mass. Approximately 1 year after diagnosis and MRI, the brain was again evaluated by MRI. RESULTS: On the initial MRI scan, 5 of the 13 dogs had normal findings, and 8 had evidence of a mass (tumor) in the area of the pituitary gland. Of the 5 dogs that had no visible pituitary mass on the initial MRI scan, 3 had a normal MRI brain scan 1 year later. Of the 5 dogs that had no visible pituitary mass on initial MRI scan, 2 had a visible pituitary mass at 1 year. The 8 dogs that had a visible mass on the initial MRI brain scan had easily identified pituitary masses on the second MRI scan. Of these 8 dogs, 4 had no apparent change in pituitary mass size, and 4 had obvious increase in vertical height of the pituitary mass. Of the 4 dogs, 2 developed signs of neurologic dysfunction within 1 year after diagnosis of PDH, presumably attributable to that mass. Of the 13 dogs, 12 were treated with mitotane soon after completion of the initial MRI scan. Sensitivity to mitotane and initial pituitary mass size or growth were not correlated. Of the 13 dogs evaluated initially and 1 year after diagnosis, 10 had pituitary masses identified on MRI brain scans. CLINICAL IMPLICATIONS: The incidence of visible pituitary masses among dogs with PDH at the time of or within a year of diagnosis was > 75%. In 2 dogs, signs of CNS dysfunction developed within 1 year of PDH diagnosis when pituitary masses were > or = 10 mm.

A comparison of meconium, maternal urine and neonatal urine for detection of maternal drug use during pregnancy.

A large scale drug screening study was done to determine the prevalence of drug use in a large metropolitan, obstetric population. Meconium and first voided urine, as well as maternal urine were collected from 423 consecutive deliveries. Urine samples and methanolic extracts of meconium were initially screened by Enzyme Multiplied Immunoassay Technique (EMIT) and then confirmed by Gas Chromatography/Mass Spectrometry (GC/MS). Analysis of cocaine metabolite as benzoylecogonine, cannabinoid as carboxy-THC, codeine, morphine and methadone were included in the study. The positive rate for benzoylecgonine was virtually identical for meconium, maternal urine and neonatal urine (12%). Analysis of meconium was found to be more reliable than analysis of maternal or neonatal urine for the detection of benzoylecgonine. Meconium did not appear to offer an advantage over maternal or neonatal urine for detection of cannabinoid, codeine, morphine, or methadone.

Comparison of mitotane treatment for adrenal tumor versus pituitary-dependent hyperadrenocorticism in dogs.

The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ATH) vs those with pituitary-dependent hyperadrenocorticism (PDH). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocortical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ATH (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with PDH. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment. Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (+/- SD) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 +/- 9.4 for dogs with ATH vs 45.7 +/- 11.9 for dogs with PDH. The mean plasma cortisol concentrations 1 hour after ACTH administration at the 7-day recheck were significantly higher in dogs with ATH (502 +/- 386 nmol/L) than in dogs with PDH (88 +/- 94 nmol/L).(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging to evaluate patency of aortocoronary bypass grafts.

To assess the efficacy of magnetic resonance (MR) imaging in evaluating graft patency after coronary bypass surgery, 20 patients who had prior surgery (average 5.5 years, range 1.5 to 14) and recent cardiac catheterization because of chest pain were studied. No patient had surgical intervention or change in symptoms in the time interval between catheterization and MR imaging. These 20 patients had a total of 47 grafts, defined as proximal anastomoses: 20 to the left anterior descending or diagonal artery (LAD), 13 to the left circumflex artery marginal branches (LCX), and 14 to the right coronary artery or posterior descending artery (RCA). The patients underwent cardiac and respiratory gated MR scans in a 0.5 tesla magnet with an echo time of 22 msec and two repetitions in a 128 X 256 matrix. In-plane resolution was 2.7 mm. Every patient had a scan in the transaxial plane and some underwent scanning in the sagittal and coronal planes as well. A graft was considered patent by MR when a signal-free lumen was visualized in an anatomic position consistent with that of a bypass graft, had a lumen larger than the native vessels, was seen on more than one slice, and was seen at a level higher than that of the native vessels. If a known graft was not seen it was considered occluded. The scans were interpreted by consensus of two physicians aware of the operative but not the cardiac catheterization data.(ABSTRACT TRUNCATED AT 250 WORDS)

A sequential approach to the diagnosis of coronary artery disease using multivariate analysis.

There has been considerable interest in recent years in enhancing the accuracy of noninvasive tests in diagnosing coronary artery disease. The recognition that no currently available test is a perfect predictor has led to the use of probability analysis as a means of assessing the presence or absence of coronary disease. In this article we present a multivariate approach to the diagnosis of coronary disease. One hundred forty-seven patients undergoing coronary angiography, thallium-201 imaging, and exercise ECG were studied. Patients were classified according to age, sex, and typical vs atypical chest pain. Sequential stepwise logistic regression analysis was performed to develop probability statements prior to testing, after exercise ECG, and after exercise ECG and thallium-201. The results indicate that this sequential approach can be used to develop strategies for the diagnosis of coronary disease in the same way as Bayes' theorem, while permitting integration of multiple characteristics into one model.

Critical analysis of the application of Bayes' theorem to sequential testing in the noninvasive diagnosis of coronary artery disease.

The utility of Bayes' theorem in the noninvasive diagnosis of coronary artery disease (CAD) was analyzed in 147 patients who underwent electrocardiographic stress testing, thallium-201 perfusion imaging and coronary angiography. Eighty-nine patients had typical anginal chest discomfort and 58 had atypical chest pain. Sensitivity and specificity of the tests and prevalence of CAD at each level of testing were tabulated and compared with the results generated from Bayes' theorem. The sensitivity of electrocardiographic stress was higher in patients with multivessel CAD than in patients with 1-vessel CAD. Sensitivity, but not specificity, of each test was dependent, in part, on the result of the other test. However, the probabilities calculated from Bayes' theorem when used for sequential testing are remarkably close to the tabulated data. Thus, Bayes' theorem is useful clinically despite some evidence of test dependence. Sequential test analysis by Bayes' theorem is most useful in establishing or ruling out a diagnosis when the pretest prevalence is approximately 50% and when the 2 tests are concordant.

Antiinflammatory agents protect opossum esophagus during radiotherapy.

Eighteen opossums received 2250 rad 60Co to the entire esophagus and lower esophageal sphincter. Animals received treatment with 600 mg aspirin, 25 mg/kg hydrocortisone, or saline before irradiation and twice daily for 1 week after irradiation. At 10 days postirradiation, animals were evaluated for signs of acute esophagitis by esophagoscopy and barium esophagram. Each animal was then killed and the esophagus removed and evaluated histologically. Animals treated with either aspirin or hydrocortisone had significantly milder esophagitis than control irradiated animals.

Radiation esophagitis in the opossum: radioprotection with indomethacin.

Twenty-five opossums (Didelphis virginiana) were evaluated before irradiation by fiberoptic endoscopy and air-contrast barium esophagram examination. All animals received 2250 rad 60Co-irradiation in a single exposure to the entire esophagus and lower exophageal sphincter. Animals received treatment with indomethacin before and daily for 1 wk postirradiation of 16, 16-dimethylprostaglandin E2 before irradiation and every 4 hr for 24 hr postirradiation. Control animals received only injection vehicle. Acute esophagitis occurred 7--10 days postirradiation in control animals and was characterized by erythema, ulceration, and sloughing of esophageal mucosa as determined by air-contrast barium esophagram, endoscopy, and histology. Prostaglandin-treated animals showed more severe evidence of esophagitis than control animals. Indomethacin-treated animals showed no signs or only mild esophagitis posttreatment. It is concluded that indomethacin treatment may significantly reduce the severity of radiation esophagitis perhaps by blockade of prostaglandin synthesis.

Ventriculographic-echocardiographic correlation in patients with asynergy.

The ability of echocardiography to detect segmental ventricular asynergy was evaluated in 41 patients before cardiac catheterization. Of 24 normal posterior wall segments by echocardiography, 23 were also normal by ventriculography, while one was hypokinetic. Of 17 asynergic posterior wall segments by echocardiography, 15 were asynergic and two were normal by ventriculography. Posterior wall excursion for the normal group was 1.30 +/- 0.18 cm (SD), while those demonstrating hypokinesis on ventriculography showed an excursion of 1.05 +/- 0.19 cm (P less than .005), and akinetic segments showed an excursion of 0.97 +/- 0.13 cm (P less than .005). In 15 patients, septal motion as determined by echocardiography was compared with the left anterior oblique ventriculogram. Of nine normal septal motions by echocardiography, seven were also normal by left anterior ventriculography (septal excursion, 0.84 +/- 0.25 cm). Of six patients with decreased echocardiographic septal motion, four were normal and two were abnormal by ventriculography. Although normal echocardiographic septal motion correlated well with ventriculography, decreased septal excursion by echocardiography did not.

The use of echocardiography in determination of reversible posterior wall asynergy.

Recent studies have indicated that nitroglycerin can be delineate potentially reversible asynergic zones depicted ventriculographically. To assess the ability of the echocardiogram to detect reversible asynergy, posterior wall motion was assessed in 19 patients both echocardiographically and ventriculographically before and after nitroglycerin. Thirteen of the 19 patients demonstrated abnormal posterior wall motion both by echocardiography and ventriculography while six were normal by both techniques. In 4 of the 13 asynergic areas, posterior wall excursion improved following nitroglycerin (from 0.99 +/- .07 to 1.30 +/- .07 cm. by echocarciography (p less than .025) with a corresponding improvement in hemiaxis shortening from 12.0 +/- 6.1 per cent to 29.0 +/- 6.7 per cent (p less than .02). In contrast, in nine patients in whom inferior segment hemiaxis shortening was unchanged following nitroglycerin, posterior wall excursion by echocardiography was similarly not improved (1.01 +/- .03 cm. before and 1.02 +/- .03 cm. after nitroglycerin). The effect of nitroglycerin on posterior wall velocity paralleled changes in posterior excursion. The six patients with initially normal posterior excursion showed no significant change by either echocardiography or ventriculography following nitroglycerin. Thus, the echocardiogram is of considerable value in detecting both the presence and potential for improvement of asynergic posterior wall segments.

Nitroprusside therapy. Treatment of hypertensive patients with recurrent resting chest pain, ST-segment elevation, and ventricular arrhythmias.

Five hypertensive patients with acute myocardial infarction and persistent postinfarction hypertension who experienced severe and recurrent resting chest pain, ST elevations, and severe ventricular arrhythmias refractory to conventional treatment with bed rest, sedation, oxygen inhalation, nitrates, and antiarrhythmic agents received sodium nitroprusside by continuous intravenous infusion, titrated to reduce systolic blood pressure to 100 to 110 mm Hg. Treatment resulted in noticeable improvement in symptoms, reduction in ST elevations, and abolition of ventricular arrhythmias in all five patients. In four patients, cessation of nitroprusside infusion after 48 hours resulted in prompt recurrence of hypertension, chest pain, ST-segment elevations, and ventricular arrhythmias. These were all rapidly reversed following reinstitution of the nitroprusside therapy for seven to eight days, strongly suggesting a cause-and-effect relationship. Nitroprusside infusion in these patients suggests a potentially important use for such therapy in this clinical setting.