Pneumococcal Induced T-activation with Resultant Thrombotic Microangiopathy.

Thrombotic microangiopathies are disorders resulting from platelet thromboses forming in the microvasculature with resultant schistocyte forms. Hemolytic uremic syndrome (HUS) is a microangiopathic hemolytic anemia often complicated by acute renal failure in children. HUS is typically caused by bacterial infection, most commonly enterohemorrhagic Escherichia coli. Neuraminidase-producing organisms, such as Streptococcus pneumoniae have also been reported as potential etiologies. The pathogenesis in these cases involves cleavage of sialic acid residues from the surfaces of erythrocytes, platelets, and glomerular capillary endothelial cells, exposing the Thomsen-Friedenreich antigen, a process known as T-activation. We describe a 2-year-old girl who presented with pneumococcal pneumonia and sepsis ultimately resulting in a thrombotic microangiopathy with acute renal failure, most consistent with HUS. The patient's direct antiglobulin test was positive. Polyagglutination was observed with human adult serum, but not with umbilical cord serum. Her red blood cells (RBCs) were reactive against peanut and soybean lectins, but not Salvia sclarea or Salvia horminum lectins. These findings are consistent with T-activation. Clinicians should be cognizant of the possibility of T-activation with resultant HUS in patients infected with neuraminidase-producing bacteria. Such patients may be difficult to identify using monoclonal typing antisera, as these typically do not have anti-T antibodies. Whether such patients are at risk for transfusion-associated hemolysis is debatable.

Effect of a single dose of dexamethasone on glucose homeostasis in healthy horses by using the combined intravenous glucose and insulin test.

Sustained dexamethasone administration to horses results in insulin resistance, which may predispose them to laminitis. A single dose of dexamethasone is commonly used as a diagnostic aid, yet the effect of a single dose of dexamethasone on glucose homeostasis in horses is not well defined. The objective of this study was to characterize the change in glucose dynamics over time in response to a single dose of dexamethasone. A combined glucose-insulin tolerance test (CGIT) was performed on 6 adult geldings before and at 2, 24, and 72 h postdexamethasone (40 microg/kg of BW, i.v.); a minimum of 1 wk of rest was allowed between treatments. Before any treatment, the CGIT resulted in a hyperglycemic phase followed by a hypoglycemic phase. Dexamethasone affected glucose dynamics in 3 ways: 1) at 2 h, dexamethasone shortened the ascending branch of the negative phase (P < 0.001) of the test, indicating moderate insulin resistance; 2) at 24 h, dexamethasone impaired glucose clearance by extending the positive phase and eliminating the negative phase while insulin was elevated before the CGIT, indicating a decreased response to insulin; and 3) at 72 h, dexamethasone caused a deeper nadir value (P < 0.001) compared with predexamethasone, indicating an increased response to insulin. It was concluded that dexamethasone decreased the response to insulin as early as 2 h and maximally at 24 h. At 72 h, dexamethasone caused an increased response to insulin, which was unexpected.

Fertility aspects in yearling beef bulls grazing endophyte-infected tall fescue pastures.

During a 2-year study, yearling beef bulls were used to determine the effects of grazing on endophyte-infected tall fescue on endocrine profiles, semen quality and fertilisation potential. Bulls were allotted to graze tall fescue pastures infected with Neotyphodium coenophialum (E+; n = 20 per year) or Jesup/MaxQ (Pennington Seed, Atlanta, GA, USA; NTE; n = 10 per year). Bulls were grouped by scrotal circumference (SC), bodyweight (BW), breed composites and age to graze tall fescue pastures from mid-November until the end of June (within each year). Blood samples, BW, SC and rectal temperatures (RT) were collected every 14 days. Semen was collected from bulls every 60 days by electroejaculation and evaluated for motility and morphology. The developmental competence of oocytes fertilised in vitro with semen from respective treatments was determined. Bulls grazing E+ pastures had decreased BW gain (P < 0.01), increased overall RT (P < 0.01) and decreased prolactin (P < 0.01) compared with animals grazing NTE pastures. Neither percentage of normal sperm morphology nor motility differed between bulls grazed on the two pasture types. Semen from E+ bulls demonstrated decreased cleavage rates (P = 0.02) compared with semen from NTE bulls. However, development of cleaved embryos to the eight-cell and blastocyst stages did not differ between the two groups. In conclusion, semen from bulls grazing E+ tall fescue resulted in decreased cleavage rates in vitro, which may lower reproductive performance owing to reduced fertilisation ability.

Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological study.

Ten Chesapeake Bay retriever (CBRS) dogs with hair loss were recruited in collaboration with the American Chesapeake Club. All dogs had nonpruritic, noninflammatory, regionalized hair loss affecting the same areas of the body in male and female dogs. Hormonal investigations showed increased adrenal and sex steroid concentration in seven cases. Histopathology revealed follicular hyperkeratosis and plugging, follicular atrophy, and occasional melanin clumping with malformed hair shafts. This study suggests that hair loss in CBRS is a breed syndrome in which young adult dogs have hair loss characterized by unusual histological features and abnormal steroid production. A familial predisposition seems likely and selective breeding might reduce the occurrence of this condition.

Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma.

BACKGROUND: The purpose of this study was to assess the efficacy and safety of ISIS 3521, an antisense phosphorothioate oligonucleotide to protein kinase C alpha in patients with relapsed low-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-six patients received ISIS 3521 (2 mg/kg/day) as a continuous infusion over 21 days of each 28-day cycle. RESULTS: The median age of the patients was 53 years (range 37-77). Histological subtypes were low-grade follicular lymphoma (n = 22) and B-cell small lymphocytic lymphoma (n = 4). Twenty-one (81%) had stage III/IV disease. The median number of previous lines of chemotherapy was two (range one to six). A total of 87 cycles of ISIS 3521 were administered. Twenty-three patients were assessable for response. Three patients achieved a partial response. No complete responses were observed. Ten patients had stable disease. Grade 3-4 toxicity was as follows: neutropenia (3.8%) and thrombocytopenia (26.9%). CONCLUSIONS: ISIS 3521 has demonstrated anti-tumour activity in patients with relapsed low-grade NHL. There may be a potential role for this agent in combination with conventional chemotherapy for advanced low-grade lymphoma, and further trials are warranted.

The effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase levels in normal dogs.

OBJECTIVE: To assess the effects of topical ocular application of 0.25% demecarium bromide on serum acetylcholinesterase (AChE) levels in normal dogs. ANIMALS: Nine adult mixed breed dogs weighing between 18 and 27 kg. PROCEDURES: Fifty micro L of 0.25% demecarium bromide were applied to one eye of each dog every 8 h for 6 days. Blood was analyzed for AChE levels prior to commencement of eye drops, and at 45 min, 1 h 45 min, 4 h 45 min, 1 day, 3 days, and 7 days following commencement of eye drops using a 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) reaction. RESULTS: Acetylcholinesterase levels declined over the first 24 h following commencement of demecarium administration in most dogs. This decline was highly variable and was statistically significant by 24 h. In some individuals AChE levels were suppressed to levels approaching clinical toxicity. By day 3 AChE levels had risen to levels above baseline in most dogs. CONCLUSIONS: Topical ocular application of demecarium causes transient suppression of systemic acetylcholinesterase levels in most dogs. Acetylcholinesterase levels generally do not fall to toxic levels, but may do so in certain individuals. Demecarium bromide eye drops generally do not cause AChE toxicity, but dogs receiving such therapy should be monitored for signs of AChE toxicity, and concomitant use of other AChE inhibitors should be avoided.

Steroid hormone concentration profiles in healthy intact and neutered dogs before and after cosyntropin administration.

The purpose of this study was to determine steroid hormone concentration profiles in healthy intact and neutered male and female dogs. Seventeen intact female dogs, 20 intact male dogs, 30 spayed female dogs, and 30 castrated male dogs were used in this study. Serum samples were collected before and 1h after cosyntropin administration, and serum concentrations were determined for cortisol, progesterone, 17-OH progesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, and estradiol. Intact male dogs had greater concentrations of DHEAS, androstenedione, and testosterone. Intact female dogs had greater concentrations of progesterone. There was no significant difference in estradiol concentration among the four groups. Intact male dogs had lower concentrations of cortisol post-stimulation. DHEAS and testosterone did not increase in response to ACTH in intact males, and estradiol concentrations did not increase in response to ACTH in any group. Results from this study will enhance interpretation of suspected adrenal and/or gonadal disorders of dogs. Because estradiol concentrations were similar in all groups of dogs, measuring estradiol may not be a useful diagnostic test. Cortisol concentrations for intact male dogs with hyperadrenocorticism may be lower than those of female or neutered dogs.

Leuprolide acetate treatment of adrenocortical disease in ferrets.

OBJECTIVE: To determine the effects of leuprolide acetate, a long-acting gonadotropin-releasing hormone analog, in ferrets with adrenocortical diseases. DESIGN: Case series. ANIMALS: 20 ferrets with adrenocortical disease diagnosed on the basis of clinical signs and plasma sex hormone concentrations. PROCEDURE: Ferrets were treated with leuprolide (100 microg, IM, once), and plasma hormone concentrations were measured before and 3 to 6 weeks after treatment. RESULTS: Leuprolide treatment resulted in significant reductions in plasma estradiol, 17 alpha-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone concentrations and eliminated or reduced clinical signs associated with adrenocortical disease. Decreases in vulvar swelling, pruritus, and undesirable sexual behaviors and aggression were evident 14 days after treatment; hair regrowth was evident by 4 weeks after treatment. The response to treatment was transitory, and clinical signs recurred in all ferrets. Mean +/- SEM time to recurrence was 3.7 +/- 0.4 months (range, 1.5 to 8 months). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that leuprolide can be safely used to temporarily eliminate clinical signs and reduce sex hormone concentrations in ferrets with adrenocortical diseases. However, the safety of long-term leuprolide use in ferrets has not been investigated, and the long-term effects of leuprolide in ferrets with nodular adrenal gland hyperplasia or adrenal gland tumors are unknown.

Individualized patient education and coaching to improve pain control among cancer outpatients.

PURPOSE: An estimated 42% of cancer patients suffer from poorly controlled pain, in part because of patient-related barriers to pain control. The objective of this study was to evaluate the effect of an individualized education and coaching intervention on pain outcomes and pain-related knowledge among outpatients with cancer-related pain. PATIENTS AND METHODS: English-speaking cancer patients (18 to 75 years old) with moderate pain over the past 2 weeks were randomly assigned to the experimental (n = 34) or control group (n = 33). Experimental patients received a 20-minute individualized education and coaching session to increase knowledge of pain self-management, to redress personal misconceptions about pain treatment, and to rehearse an individually scripted patient-physician dialog about pain control. The control group received standardized instruction on controlling pain. Data on average pain, functional impairment as a result of pain, pain frequency, and pain-related knowledge were collected at enrollment and 2-week follow-up. RESULTS: At baseline, there were no significant differences between experimental and control groups in terms of average pain, functional impairment as a result of pain, pain frequency, or pain-related knowledge. At follow-up, average pain severity improved significantly more among experimental group patients than among control patients (P =.014). The intervention had no statistically significant impact on functional impairment as a result of pain, pain frequency, or pain-related knowledge. CONCLUSION: Compared with provision of standard educational materials and counseling, a brief individualized education and coaching intervention for outpatients with cancer-related pain was associated with improvement in average pain levels. Larger studies are needed to validate these effects and elucidate their mechanisms.

Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia.

OBJECTIVE: To evaluate adrenal sex hormone concentrations in neutered dogs with hypercortisolemia. DESIGN: Case series. ANIMALS: 11 neutered dogs with hypercortisolemia. PROCEDURE: Serum samples obtained before and 1 hour after administration of ACTH were evaluated for concentrations of cortisol, progesterone, testosterone, dehydroepiandrosterone sulfate or androstenedione or both, and 17-hydroxyprogesterone. RESULTS: For all dogs, concentrations of 1 or more adrenal sex hormones were substantially greater than reference range values before or after administration of ACTH. Testosterone concentration was not greater than reference range values in any of the dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results emphasize the importance of ruling out hypercortisolemia before measuring adrenal sex hormone concentrations as a means of diagnosing adrenal hyperplasia syndrome (alopecia X) in dogs.

Hyperadrenocorticism associated with excessive sex hormone production by an adrenocortical tumor in two dogs.

An 11-year-old spayed female Labrador Retriever and a 9-year-old castrated male miniature Poodle were evaluated because of clinical signs of hyperadrenocorticism. Cortisol testing did not support a diagnosis of hypercortisolemia in either dog; however, imaging studies revealed unilateral adrenal tumors in both dogs. Serum concentrations of 17-hydroxyprogesterone, progesterone, and estradiol were high in both dogs, and androstenedione concentrations were also high in 1 dog. It is suspected that sex hormone secretion by the adrenal tumors in these dogs resulted in clinical signs of hyperadrenocorticism. Clinical signs and hormonal abnormalities resolved in the male dog after surgical resection of the tumor. There was no improvement in clinical signs after treatment with mitotane in the female dog, which died 2 months after diagnosis. Histologic evaluation confirmed the presence of adrenocortical carcinoma in both dogs.

Hyperadrenocorticism and hyperprogesteronemia in a cat with an adrenocortical adenocarcinoma.

A seven-year-old, neutered male domestic shorthair cat was evaluated for poorly regulated diabetes mellitus and increased skin fragility. Imaging studies revealed a right adrenal gland tumor, but cortisol testing did not support a diagnosis of hyperadrenocorticism. Serum concentrations of progesterone and testosterone were increased compared with a group of normal cats, and the clinical signs were attributed to hyperprogesteronemia. At necropsy, a diagnosis of adrenocortical adenocarcinoma was confirmed, and immunohistochemical staining confirmed the presence of progesterone within the tumor. Clinical signs of hyperadrenocorticism in cats may occur due to increased serum concentrations of hormones other than cortisol.

Cortisol concentrations following stimulation of healthy and adrenopathic dogs with two doses of tetracosactrin.

A prospective study was undertaken to compare intravenous tetracosactrin at doses of 5 microg/kg and 250 microg for diagnosing hyperadrenocorticism in dogs. Both healthy dogs and dogs with pituitary-dependent hyperadrenocorticism were evaluated with the two doses of the drug, and serum cortisol concentrations were compared at 60 minutes post-stimulation. Some of the dogs had additional samples taken at 90 and 120 minutes. For four dogs with hyperadrenocorticism, timed samples were also obtained at 150, 180 and 240 minutes post-injection. Cortisol concentrations 60 minutes after stimulation with either 5 microg/kg or 250 microg intravenous tetracosactrin were similar for both healthy dogs and dogs with hyperadrenocorticism. The lower dose can therefore be used for diagnosing hyperadrenocorticism in dogs.

Alterations in hemograms and serum biochemical analytes of steers after prolonged consumption of endophyte-infected tall fescue.

The objective of the current study was to delineate changes that occur in serum analytes and blood cellular elements in cattle that graze endophyte-infested (Neotyphodium coenophialum) tall fescue. Tall fescue is grown on more than 35 million acres (14.2 million ha) of pasture in the United States, and three-fourths of the pastures are infected with the endophyte at a 60% or greater level. Tall fescue toxicosis caused by endophyte-produced ergot alkaloids continues to be the most important grass-related disease in the United States, in terms of economic loss to animal producers. However, the agronomic attributes of tall fescue make it an attractive forage species because of its ability to withstand cool temperatures, drought, poor soil conditions, and intensive defoliation from herbivore species, including insects. Tall fescue toxicosis is a complex disease and the need exists to understand the mechanisms of the toxic effects in order to institute effective, prophylactic control measures. Our group previously reported changes that occur in serum biochemical analytes of cattle that graze endophyte-infected tall fescue. An additional year's worth of data have been added, strengthening and corroborating these data. Consistent and significant changes associated with tall fescue toxicosis during the 3-yr study included decreased serum concentrations of cholesterol, globulin (increased albumin/globulin ratio), prolactin, total protein, and copper. The activity of alanine aminotransferase was decreased in serum, whereas an increase in serum concentrations of creatinine and total bilirubin occurred. The present report also documents comparative hemograms of cattle that grazed endophyte-infected or endophyte-free tall fescue over a prolonged period. The mean erythrocyte counts were increased in cattle that grazed endophyte-infected tall fescue, whereas mean corpuscular hemoglobin and mean corpuscular volume were decreased, as were mean eosinophil counts. Thus, repeatable changes have been identified that occur in serum biochemical and blood cellular values of cattle grazing endophyte-infected tall fescue that will aid in understanding the pathogenesis of the disease. In addition, these consistently altered parameters can be used to assess the effectiveness of potential prophylactic treatments.

Effect of oral melatonin administration on sex hormone, prolactin, and thyroid hormone concentrations in adult dogs.

OBJECTIVE: To determine the effect of oral melatonin (MT) administration on serum concentrations of sex hormones, prolactin, and thyroxine in dogs. DESIGN: Prospective study. ANIMALS: 8 male and 8 female adult sexually intact dogs. PROCEDURE: 5 male and 5 female dogs were treated with MT (1.0 to 1.3 mg/kg [0.45 to 0.59 mg/lb] of body weight), PO, every 12 hours for 28 days; the other 6 dogs were used as controls. Blood samples were collected on days 0, 14, and 28, and serum concentrations of estradiol-17 beta, progesterone, testosterone, androstenedione, 17-hydroxyprogesterone (17-HP), dihydroepiandrostenedione sulfate (DHEAS), prolactin, and thyroxine were determined. On day 5, serum MT concentrations were measured before and periodically for up to 8 hours after MT administration in 4 treated dogs. RESULTS: Female dogs treated with MT had significant decreases in serum estradiol, testosterone, and DHEAS concentrations between days 0 and 28. Male dogs treated with MT had significant decreases in serum estradiol and 17-HP concentrations between days 0 and 28. Serum MT concentrations increased significantly after MT administration and remained high for at least 8 hours. Prolactin and thyroxine concentrations were unaffected by treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Melatonin is well absorbed following oral administration and may alter serum sex hormone concentrations.

Alterations in bovine serum biochemistry profiles associated with prolonged consumption of endophyte-infected tall fescue.

Tall fescue (Festuca arundinacea) is a forage grass that is widely used in pastures in the eastern US for cattle, sheep and horses. The endophytic fungus Neotyphodium coenophialum is endemic in tall fescue pastures in the US. The turfgrass industry intentionally infects fescue cultivars with strains of the fungus to impart desirable growth and disease tolerance qualities to the plants. In contrast, ergot and pyrrolizidine alkaloid toxins produced by fungus-infected plants have been incriminated causally in bovine tall fescue toxicosis, a poorly defined syndrome of morbidity that occurs in cattle that consume endophyte-infected tall fescue (E+TF). We compared the serum biochemistry profiles from cattle that grazed E+TF with those from control cattle that grazed on endophyte-free tall fescue (E-TF). Cattle were bled on 7 dates from April 1 to August 30, 1996 and on 5 dates from May 1 to July 30, 1997. Cattle that grazed E+TF retained rough winter haircoats and had lesser weight gains, typical of tall fescue toxicosis, compared to those grazing E-TF. They had decreased activities of alkaline phosphatase and alanine aminotransferase. Compared to controls, they had lower values for serum prolactin and globulin concentrations. The concentration of creatinine and the albumin/globulin ratio were increased in the cattle grazing E+TF. Isozyme determination of alkaline phosphatase indicated that the decrease in serum activity of cattle grazing E+TF was due to decreases in both intestinal and bone isozymes. Serum protein electrophoresis indicated that the decrease in serum globulin concentration was due to decreases in both alpha and gamma globulin fractions of this protein. The data collected in these experiments add to our understanding of the alterations that occur in the serum chemistry profiles when cattle consume E+TF for prolonged periods of time.

Endophytic fungal toxin effect on adrenergic receptors in lateral saphenous veins (cranial branch) of cattle grazing tall fescue.

The objective of this research was to characterize the adrenergic receptor response in veins of cattle that grazed tall fescue (Festuca arundinacea Schreb.), with (E+) and without (E-) fungal endophyte (Neotyphodium coenophialum) infection. Measurement of contractile response of lateral saphenous veins to selective adrenergic receptor agonists (alphal, phenylephrine; alpha2, BHT-920) revealed enhanced reactivity (greater contractile response) only for the alpha2 adrenergic receptor in E+ pastured cattle. This response was consistent over a 3-yr grazing period. Significant contractility differences in response to BHT-920 occurred at concentrations of 3x10(-6) M and greater. Early research has reasoned that the enhanced reactivity is due to endophyte toxin effect on intracellular signaling systems. The enhanced contractile effect would alter blood flow dynamics and contribute to clinical signs and pathologic change in animals. The alpha2-adrenergic receptor is also involved in the control of many metabolic reactions. Thus, for drug therapy to be successful in reversing the adverse effects of E+ tall fescue exposure in cattle, effects on the alpha2-adrenergic tissue receptors must be neutralized.

Chronic eosinophilic leukemia and hypereosinophilic syndromes. Proposal for classification, literature review, and report of a case with a unique chromosomal abnormality.

The idiopathic hypereosinophilic syndromes (HES) are rare hematologic disorders characterized by persistent eosinophilia with organ involvement that encompass a wide spectrum of clinical and hematological disease states. We propose a classification scheme to further delineate these patients, and present a case of a 45-year-old male with persistent eosinophilia, severe tissue and hematologic involvement, and trisomy 15. Although multiple cytogenetic abnormalities have been associated with hypereosinophilic syndromes, this is the first reported case where trisomy 15 is the sole chromosomal abnormality.

Comparison of serum cortisol concentrations in clinically normal dogs after administration of freshly reconstituted versus reconstituted and stored frozen cosyntropin.

OBJECTIVE: To evaluate the biological stability of reconstituted cosyntropin after storage at -20 C for 2, 4, and 6 months. DESIGN: Prospective study. ANIMALS: 10 clinically normal dogs. PROCEDURE: Serum cortisol concentrations in dogs were determined before and 1 hour after administration of freshly reconstituted cosyntropin (synthetic ACTH) or cosyntropin that had been reconstituted and stored frozen at -20 C in plastic syringes for 2, 4, and 6 months. Cosyntropin was administered at 5 micrograms/kg (2.3 micrograms/lb) of body weight, i.v. RESULTS: Baseline serum cortisol concentrations were similar at each sampling time. Compared with the effects of freshly reconstituted cosyntropin, administration of cosyntropin that had been frozen did not have a significantly different effect on serum cortisol concentrations. CLINICAL IMPLICATIONS: Cosyntropin can be reconstituted and stored frozen at -20 C in plastic syringes for 6 months with no adverse effects on bioactivity of the polypeptide.