Population pharmacokinetics of a single intramuscular administration of tulathromycin in adult desert tortoises (Gopherus agassizii).

Tulathromycin, a long acting macrolide antibiotic, has demonstrated efficacy against respiratory pathogens including Mycoplasma bovis and M. hyopneumoniae. A pharmacokinetic study was performed to evaluate the clinical applicability of tulathromycin in desert tortoises following a single intramuscular dose of 5 mg/kg. A single blood sample was collected from 110 different desert tortoises at 0.25, 0.5, 1, 4, 8, 24, 48, 72, 120, and 240 h following drug administration. Plasma concentrations of the parent form of tulathromycin were measured using liquid chromatography/mass spectrometry. As each tortoise was only bled once, pharmacokinetic parameters were initially estimated using a naïve pooled data approach. Given the variability in the data, population-based compartmental modeling was also performed. Using nonparametric population compartmental modeling, a two-compartment model with first-order absorption and elimination best fit the data. An observed Cmax of 36.2 ± 29.7 µg/mL was detected at 0.25 h (observed Tmax ). The elimination half-life (T½el ) was long (77.1 h) resulting in detectable plasma concentrations 240 h postadministration. This study represents a preliminary step in evaluating the utility of tulathromycin in chelonian species and demonstrates that population data modeling offers advantages for estimating pharmacokinetic parameters where sparse data sampling occurs and there is substantial variability in the data.

Quinpirole hydrochloride, a potential anti-parkinsonism drug.

Quinpirole hydrochloride, a putative dopamine agonist, was investigated in animal models of central dopaminergic activity, to evaluate its possible role in the treatment of Parkinson's disease. The drug induced stereotyped sniffing in rats but, unlike apomorphine, did not produce a maximal behavioural response (stereotyped gnawing). Pretreatment with neuroleptics blocked the stereotypy induced by quinpirole. Quinpirole reversed the effects of reserpine and alpha-methyl-paratyrosine, caused dose-dependent contralateral rotations in rats with unilateral lesions of the substantia nigra induced by 6-hydroxydopamine and induced vomiting in dogs. Small doses of quinpirole decreased locomotor activity, an effect presumably mediated by pre-synaptic autoreceptors. Quinpirole bound to D2 dopamine receptors in the striatum of the rat. The chronic injection of both subthreshold and suprathreshold doses, failed to induce behavioral supersensitivity. These data indicate that quinpirole can stimulate central dopaminergic receptors, and that it is a partial agonist with direct-acting properties. Quinpirole differs from other dopaminergic drugs and may be useful for the therapy of Parkinson's disease.

Eradication of Helicobacter pylori with pantoprazole and two antibiotics: a comparison of two short-term regimens.

BACKGROUND: High rates of Helicobacter pylori eradication can be achieved by combining proton pump inhibitors with two antibiotics. However, in the search for an optimal therapy a direct comparison of different regimens is necessary. METHODS: For this open study, 331 patients with duodenal ulcer were screened and randomly allocated to either pantoprazole 40 mg b.d., clarithromycin 500 mg b.d., and metronidazole 500 mg b.d. (PCM) or pantoprazole 40 mg b.d., amoxycillin 1000 mg b.d., and clarithromycin 500 mg b.d. (PAC) for 7 days. Both combinations were followed by a 7-day therapy with pantoprazole 40 mg o.d. alone. Eradication of H. pylori was assessed by use of a 13C-urea breath test 4 weeks after the intake of the last medication. RESULTS: Eradication rates were 90% in intention-to-treat patients from the PCM (132 out of 147; 95% CI: 84-94%) and the PAC group (135 out of 150; 95% CI: 84-94%). H. pylori was eradicated in 112 out of 117 per protocol patients of the PCM group (96%; 95% CI: 90-99%) and in 119 out of 126 patients of the PAC group (94%; 95% CI: 89-98%). Rapid relief from ulcer pain and a decrease in the mean intensity of other gastrointestinal symptoms was observed. Sixty-nine patients reported adverse events, none of which were related to the intake of pantoprazole. Four serious adverse events, none related to the trial medication, were observed. CONCLUSIONS: Both pantoprazole-based short-term triple therapies are highly effective and well-tolerated treatment regimens in the eradication of H. pylori.

Electrolyte composition of human breast milk beyond the early postpartum period.

The electrolyte composition of breast milk beyond 6 months postpartum has not been extensively examined, particularly chloride concentrations. A total of 140 samples of breast milk from 30 breast-feeding mothers were collected and analyzed. Mean mother's values +/- standard error of sodium (141 +/- 17 mg/L), potassium (480 +/- 11 mg/L), and chloride (452 +/- 32 mg/L) were found to be stable after 4 months postpartum until weaning commenced. Considerable variability was found for each constituent, equally divided between intra-individual and inter-individual for chloride and potassium, and predominantly intra-individual for sodium and lactose. In light of reported nutritional deficiency states involving electrolytes in exclusively breast-fed infants, it is possible that the variability of breast milk electrolyte concentrations may adversely affect infant nutrition in selected cases of older exclusively breast-fed infants.

Clinical prediction of assaultive behavior among male psychiatric patients at a maximum-security forensic facility.

OBJECTIVE: Patient characteristics associated with the clinical prediction of assaultive behavior in a forensic psychiatric hospital were compared with characteristics associated with actual assaultive behavior. METHODS: Treating psychiatrists at a New York forensic psychiatric hospital were asked to predict which of a sample of 183 recently admitted male patients were likely to show assaultive behavior during a three-month period. The predictions were compared with incident reports of actual assaultive behavior. Several patient characteristics, including race, legal status, age, education, criminal history, psychiatric symptoms rated independently by raters other than the treating psychiatrists, and ward behavior, were examined for their association with predicted and actual assaultive behavior. RESULTS: Clinicians' rate of correct prediction of assaultive behavior was 71 percent, with a diagnostic sensitivity of 54 percent and a diagnostic specificity of 79 percent. Characteristics associated with the prediction of assaultive behavior were race, transfer from a civil facility because of violence or dangerousness, age, education, arrests for violent offenses, childhood physical abuse, hostility, temper (or nurses' assessment of the patient's irritability), and inability to follow ward routine. Characteristics associated with actual assaultive behavior were transfer from a civil hospital, dual diagnosis of schizophrenia and substance abuse or dependence, childhood physical abuse, age, thought disorder, and temper. CONCLUSIONS: Clinicians were significantly more accurate than chance in prospectively predicting which male forensic patients would show assaultive behavior. However, some of the factors associated with clinical prediction, such as race, ability to follow ward routine, and arrest history, were not associated with actual assaultive behavior. In addition, clinicians failed to use dual diagnosis of schizophrenia and substance use disorder as a predictor.

Fecal shedding and antimicrobial susceptibility of selected bacterial pathogens and a survey of intestinal parasites in free-living waterfowl.

Free-living waterfowl residing in metropolitan parks in central Ohio were surveyed for the fecal shedding and antimicrobial susceptibility patterns of Campylobacter jejuni, Escherichia coli, Salmonella spp., and Pasteurella multocida. In addition, a survey for intestinal parasites was also conducted in these same waterfowl to determine parasite burdens in free-living waterfowl. Prevalences of 67%, 50%, and 0.2% of E. coli, C. jejuni, and Salmonella spp., respectively, were observed for all waterfowl species. Pasteurella multocida was not isolated from the sampled population. Salmonella java was isolated from one mallard duck. Statistically, there was a significantly higher E. coli isolation rate for mallard ducks than for Canada geese, but no difference was observed for C. jejuni isolation rates between waterfowl species. Antimicrobial susceptibility testing was conducted via the disk diffusion method and multidrug resistance was exhibited for penicillin G, lincomycin, vancomycin, erythromycin, and bacitracin. In addition, the prevalence of endoparasites in these sampled waterfowl ranged from 5% to 66%. Protozoan oocysts were most prevalent followed by nematode ova. No trematode or cestode ovum was recovered from this sampled population.

Necrotizing typhlocolitis associated with a spirochete in rheas (Rhea americana).

Necrotizing typhlocolitis was diagnosed in 13 juvenile common rheas (Rhea americana) from three separate of geographically isolated Ohio flocks, with mortality ranging from 25% to 80%. At postmortem examination, a diphtheritic membrane covered ulcerated cecal mucosa. Histologically, cecal sections showed necrosis and granulomatous-to-suppurative inflammation that extended into the submucosa and often surrounded large eosinophilic colonies of bacteria. Warthin-Starry staining showed these colonies to be composed of entangled spirochetes that invaded the submucosa and frequently were present transmurally. Similar organisms were identified by Warthin-Starry staining in the cecum of a juvenile rhea from a fourth flock that histologically had mild lymphocytic typhlitis. Scanning and transmission electron microscopy demonstrated the presence of a spirochete in the ceca. Anaerobic culture yielded a gram-negative, beta-hemolytic spirochete. Coccidia, histomonads, and Salmonella spp. were consistently absent.

Suspected neonatal isoerythrolysis in two Baird's tapirs (Tapirus bairdii).

Two Baird's tapir (Tapirus bairdii) calves born at the Columbus Zoo from the same sire and dam developed hemolytic anemia that was consistent in history and clinical signs with neonatal isoerythrolysis (NI). One calf developed severe, fatal hemolytic anemia after being fed maternal colostrum, and the other developed moderate hemolytic anemia after being fed equine colostrum. No cross-reactivity was demonstrated between sire and dam blood samples, and both tapirs possessed serum antibodies reactive against equine blood group Ca and antigens reactive with several equine blood group D antibodies. Electrophoresis demonstrated significant genetic diversity between tapir and equine blood proteins. Agglutination testing demonstrated strong reactivity between a far greater percentage of equine colostrum samples when tested against sire and dam tapir blood (61% and 65%, respectively) than would be expected for equine blood (2%). These data are suggestive of a diagnosis of NI but are not definitive. Further study is required to determine whether NI occurs in tapirs and whether equine colostrum is harmful to tapir calves.

Hematology and clinical chemistry reference ranges for clinically normal, captive New Guinea snapping turtle (Elseya novaeguineae) and the effects of temperature, sex, and sample type.

Median values and confidence intervals for hematology and serum and plasma chemistry parameters were established for 29 male and female healthy New Guinea snapping turtles (Elseya novaeguineae) held at 24.5 degrees C and 30.0 degrees C. Creatine kinase, albumin, potassium, and phosphorus values were significantly higher at 24.5 degrees C than at 30.0 degrees C. Glucose, alkaline phosphatase, aspartate transaminase, alanine aminotransferase, total carbon dioxide, and chloride values were significantly higher at 30.0 degrees C than at 24.5 degrees C. Cholesterol and calcium values were significantly higher in females than in males. Hemoglobin, packed cell volume, and bilirubin were significantly higher in males than in females, and bile acid values were significantly higher in serum than in plasma.

Treatment of gastritis in cheetahs (Acinonyx jubatus).

Three cheetahs (Acinonyx jubatus) had a clinical history of chronic spiral bacteria-associated gastritis and three cheetahs had no clinical history of gastritis. Gastric biopsies were obtained from all six cheetahs prior to treatment for gastritis and 3 wk and 1 yr posttreatment. The cheetahs were treated with tetracycline hydrochloride 500 mg p.o. q.i.d., metronidazole 250 mg p.o. q.i.d., and bismuth subsalicylate 300 mg p.o. q.i.d. Each drug was administered concurrently for 7 days. Following this treatment, each cheetah was maintained on 300 mg bismuth subsalicylate p.o. s.i.d. for 1 yr. The three cheetahs with a history of gastritis were culture positive for Helicobacter acinonyx and remained positive during the entire study. The three cheetahs with no clinical history of gastritis were culture negative for H. acinonyx, but gastric biopsies revealed Gastrospirillum-like bacteria (tentatively named Helicobacter heilmannii) pretreatment. Gastric biopsies were negative for H. heilmannii on subsequent examinations. Although the treatment did not eradicate H. acinonyx, it did provide symptomatic relief from the vomiting, anorexia, and weight loss associated with clinical gastritis. The use of endoscopically guided gastric mucosal biopsies for urease testing and histopathologic examination of Warthin-Starry-stained sections is a sensitive and specific method of diagnosing spiral bacteria-associated gastritis. Treatment of spiral bacteria-associated gastritis in cheetahs should include the rational use of antibiotics (tetracycline or amoxicillin and metronidazole), bismuth compounds, and omeprazole and evaluation of husbandry methods to reduce stress.

Systemic candidiasis in a cheetah (Acinonyx jubatus).

Systemic candidiasis, with involvement of the spleen, liver, kidneys, and lymph nodes, was diagnosed in a geriatric captive cheetah (Acinonyx jubatus). The animal had a long clinical history of intermittent chronic gastritis associated with Helicobacter acinonyx and chronic renal failure, both of which were repeatedly treated with broad-spectrum antimicrobial therapy. Following euthanasia, a postmortem examination showed numerous microabscesses and granulomas composed of degenerate eosinophils and containing asteroids or Splendore-Hoeppli material throughout the body. Yeast, pseudohyphae, and infrequently branching septate hyphae, demonstrated with special stains, were identified as a Candida sp. by fluorescent antibody testing. Low genetic variation in cheetahs may increase their susceptibility to infectious agents. Additional factors contributing to the overgrowth and dissemination of Candida sp. in this case may have included changes in the bacterial flora of the alimentary tract as a result of repeated antimicrobial therapy and alterations in the topography of the alimentary mucosa caused by chronic gastritis.

Serum biochemistry of captive and free-ranging gray wolves (Canis lupus).

Normal serum biochemistry values are frequently obtained from studies of captive sedentary (zoo) or free-ranging (wild) animals. It is frequently assumed that values obtained from these two populations are directly referable to each other. We tested this assumption using 20 captive gray wolves (Canis lupus) in Minnesota, USA, and 11 free-ranging gray wolves in Alaska, USA. Free-ranging wolves had significantly (P < 0.05) lower sodium, chloride, and creatinine concentrations and significantly higher potassium and blood urea nitrogen (BUN) concentrations; BUN to creatinine ratios; and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities relative to captive wolves. Corticosteroid-induced alkaline phosphatase activity (a marker of stress in domestic dogs) was detected in 3 of 11 free-ranging wolves and in 0 of 20 captive wolves (P = 0.037). This study provides clear evidence that serum biochemical differences can exist between captive and free-ranging populations of one species. Accordingly, evaluation of the health status of an animal should incorporate an understanding of the potential confounding effect that nutrition, activity level, and environmental stress could have on the factor(s) being measured.

Gastric spiral bacilli in captive cheetahs.

Two kinds of gastric spiral bacilli were identified in the stomachs of captive cheetahs with naturally occurring gastritis. One type was morphologically similar to 'Gastrospirillum hominis'. This organism could not be cultured in vitro. Some of these bacteria had superficial helical filaments, and others did not. The other type was morphologically, biochemically, and bacteriologically similar to Helicobacter pylori. This organism is most likely a new species of Helicobacter. One or both of these bacteria may have been responsible for the gastritis seen in these cheetahs.

The ongoing risk assessment in the treatment of forensic patients on conditional release status.

In New York State, patients who have been found not criminally responsible by reason of mental disease or defect, eventually become outpatients while still under the supervision of the courts. The treatment of these patients on outpatient orders of condition poses special problems. Treatment needs to center on the issues related to patient's potential for harmful/violent behavior. Therefore, outpatient clinicians need to conduct periodic risk assessments and must continuously monitor identified risk indicators. The author outlines steps for information gathering and evaluation necessary for risk assessment. Treatment of these patients is conceptualized as ongoing clinical risk identification and management. It is framed by a treatment contract that integrates mandates of the Orders of Conditions with information gathered through ongoing risk assessments and spells out legal and other consequences that may arise from non-compliance.

[Changes in esophageal function caused by sclerotherapy of esophageal varices in children and adolescents with portal hypertension--a manometric study]. / Veränderungen der Osophagusfunktion durch Sklerotherapie von Osophagusvarizen bei Kindern und Jugendlichen mit portaler Hypertension--eine manometrische Studie.

Morphological changes of the oesophageal wall, induced by injection sclerotherapy of oesophageal varices, may produce functional disturbances which are difficult to evaluate especially in children. Therefore manometric studies in 33 consecutive patients with portal hypertension (age: 2-18 years) were performed and functional parameters as of the oesophagus and oesophageal sphincter were recorded in different stages of treatment. The results were compared to findings in healthy children. From our studies we could conclude that functional disturbances seen in sclerolised patients must be set in relation to functional changes which we could see in patients without treatment of oesophageal varices. Endosclerosis affects essential parameters of oesophageal function; however, a large reversibility after termination of the treatment could be documented. The clinical relevance of the recorded findings and the diagnostic value of oesophageal manometry are discussed.