Nocardia farcinica pericarditis after kidney transplantation despite prophylaxis.

A deceased-donor kidney transplant recipient developed purulent pericarditis caused by Nocardia despite trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis for Pneumocystis jirovecii. She was treated empirically with ceftriaxone and amikacin and subsequently underwent sternotomy with drainage of an intrapericardial abscess. Culture and susceptibility data demonstrated Nocardia farcinica, which was susceptible to SMX and amikacin, although resistant to ceftriaxone. Nocardia asteroides, the more common human pathogen, is generally susceptible to third-generation cephalosporins and TMP-SMX. N. farcinica is rare in the United States, more virulent and resistant than N. asteroides, and is more likely to cause disseminated disease. Successful therapy of disseminated Nocardia infections is dependent upon choice of appropriate empiric antibiotics in addition to surgical drainage of purulent fluid collections. TMP-SMX prophylaxis may not be sufficient to prevent infections due to Nocardia species in all immunosuppressed transplant recipients. Here, a rare complication of this unusual pathogen is discussed.

Antibiotic optimization. An evaluation of patient safety and economic outcomes.

BACKGROUND: Although numerous reports have described interventions designed to influence antibiotic utilization, to our knowledge none have been evaluated in a randomized study. METHODS: Adult inpatients receiving 1 or more of 10 designated parenteral antibiotics for 3 or more days during a 3-month period were randomized to an intervention (n = 141) and a control (n = 111) group using an unblocked, computer-generated random number table. Obstetric patients and those seen in infectious disease consultation were excluded. The intervention group received antibiotic-related suggestions from a team consisting of an infectious disease fellow and a clinical pharmacist. Both groups were evaluated for clinical and microbiological outcomes as well as antibiotic utilization via prospective chart reviews and analysis of the hospital's administrative database. RESULTS: Sixty-two (49%) of the intervention group patients received a total of 74 suggestions. Sixty-three (84%) of these suggestions were implemented; the majority involved changes in antibiotic choice, dosing regimen, or route of administration. Per patient antibiotic charges were nearly $400 less in the intervention group vs controls (P = .05). Almost all the savings were related to lower intravenous antibiotic charges. Clinical and microbiological response, antibiotic-associated toxic effects, in-hospital mortality, and readmission rates were similar for both groups. Multiple linear regression analysis identified randomization to the intervention group and female sex as the sole predictors of lower antibiotic charges. There was a trend toward a shorter length of stay for the intervention group (20 vs 24.7 days, P = .11). CONCLUSIONS: This is the first randomized study to evaluate whether antibiotic choices can be influenced in a cost-effective fashion without sacrificing patient safety. We demonstrate that 50% of patients initially treated with expensive parenteral antibiotics can have their regimens refined after 3 days of therapy and that these modifications result in good clinical outcomes with a substantial reduction in antibiotic expense.

Parvovirus-like enteropathy in Missouri turkeys.

A viral enteric disease of young turkeys characterized by stunting of affected birds, diarrhea, and increased mortality is described. Eosinophilic intranuclear inclusion bodies were found in the absorptive epithelial cells of the ileum. Electron microscopy of formalin-fixed tissue revealed that the intestinal inclusions contained numerous loosely packed 15-to 20-nm hexagonal particles. The size, shape, and intranuclear location have been used to tentatively identify these particles as parvoviruses.

Heritability and biochemistry of gangliosidosis in emus (Dromaius novaehollandiae).

The progeny of two emu breeder pairs, which had a history of producing offspring with gangliosidosis, were monitored for 15 mo. DNA fingerprinting revealed that individuals in each breeder pair were not related to each other. One breeder pair had 13 progeny that reached or exceeded the age of 1 mo, and six of these progeny developed gangliosidosis. The mean age at which these affected emus were euthanatized, with distinct neurologic disease, or died was 5.7 mo. The second emu pair had 13 progeny, seven of which developed gangliosidosis, with a mean age of euthanasia/death of 4.6 mo. Affected emus died or were euthanatized from 2 to 8 mo of age. The primary clinical sign in the affected emus was mild to severe ataxia. Severe hemorrhage into the body cavity or the muscles of the thigh was noted in 8 of 13 of the affected emus. Brain ganglioside levels were evaluated in six of the affected emus and six controls. Significant increases (P < 0.05) in gangliosides GM1 and GM3 were noted, with 2.3- and 4.9-fold increases in these two gangliosides, respectively, in affected emus. Furthermore, the diseased emu brains contained ganglioside GM2, whereas this monosialoganglioside was undetectable in the brains of normal controls. Total mean brain ganglioside sialic acid in affected emus was increased 3.3-fold in comparison with controls. Serum chemistries revealed elevated cholesterol and decreased uric acid levels in affected emus. Gangliosidosis in emus is an inherited disease process that, in the current study, caused 50% mortality in the progeny of two emu breeder pairs. The elimination of this lethal gene from emu breeder stock is essential for the long-term economic viability of the United States emu industry.

Gangliosidosis in emus (Dromaius novaehollandiae).

A 6-month-old female emu (Dromaius novaehollandiae) died following acute central nervous system signs. Hematoxylin-and-eosin-stained sections revealed that neurons of the brain were distended with nonstaining 1-to-2-microns vacuoles. Ultrastructural examination of the affected neurons revealed numerous membranous cytoplasmic bodies (MCBs) similar in appearance to the MCBs seen in mammalian gangliosidoses. A full sibling of this emu was donated for study. This 7-month-old female emu was stunted compared with hatchmates. Neurologic examination revealed hypermetric gait, persistent head tremor, and mild ataxia. No gross lesions were evident at postmortem. Histopathologic and electron microscopic findings were similar to those in the index case in that swollen, pale neurons were present in the cerebrum, pons, medulla, cerebellum, spinal cord, spinal ganglia, autonomic ganglia, myenteric plexus, and ganglion cell layer of the retina. Analysis of brain gangliosides of the affected 7-month-old emu revealed 14- and 25-fold increases of GM1 and GM3 gangliosides, respectively, compared with control emus. The total brain ganglioside sialic acids were, on a wet weight basis, 519 micrograms/g (control A), 658 micrograms/g (control B), and 1800 micrograms/g (affected emu). The familial association seen with this condition suggests that emus are affected by an inherited disorder similar to mammalian gangliosidoses.

Naturally acquired enteric adenovirus infection in Syrian hamsters (Mesocricetus auratus).

Intranuclear inclusions indicative of adenovirus infection were detected microscopically in formalin-fixed intestinal tissues from preweanling Syrian hamsters. The amphophilic intranuclear inclusion bodies were observed in ileal enterocytes from 16-to 24-day-old hamsters. Electron microscopy revealed large numbers of 72 +/- 3-nm viral particles typical of adenoviridae in enterocytic nuclei. Serum antibodies reacted with mouse adenovirus strains K87 and, to a lesser extent, FL, by indirect fluorescent antibody testing. Clinical disease was not associated with the adenoviral infections. Hamsters from 10 production colonies, including all major commercial Syrian hamster suppliers in the United States, were surveyed and all had serologic or histopathologic evidence of adenovirus infection.

Parthenogenic activation of pig oocytes by protein kinase inhibition.

Previous studies have shown that protein kinase stimulators can induce the release of the metaphase II arrest in mouse ova. The present report is about the role of protein kinase in parthenogenic activation of pig oocytes, which was studied using a broad-spectrum protein kinase inhibitor. Metaphase II oocytes were obtained via in vitro maturation. Two sources of H7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine, HCl] were tested--Sigma (H7s) and Calbiochem (H7c). Both were found to be equally effective in promoting release of the metaphase II block. Activation, release of the metaphase II arrest, and progression to the first interphase could be induced at the highest percentage with an exposure to 2.0 mM H7s for 80 min (68.1%). In another experiment, H7c resulted in 69.5% activation, while iso-H7 [1-(5-isoquinolinesulfonyl)-3-methylpiperazine, HCl] at a similar concentration and exposure duration resulted in 25.7% activation. H7s and H7c were more effective than iso-H7 in inducing the appearance of a 22-kDa protein that is associated with normal fertilization in the pig. In contrast, although pronuclei could form and the protein profiles were indicative of activation, cortical granule exocytosis did not occur, and oocytes failed to develop to the blastocyst stage after H7 treatment. In contrast to the H7-treated oocytes, electrostimulation resulted in pronuclear formation, the appearance of the 22-kDa protein, release of cortical granules, and development to the blastocyst stage. These data demonstrate that broad-spectrum inhibitors of protein kinase are unable to induce all the events associated with normal fertilization.

In vitro model of adhesion and invasion by Bacillus piliformis.

An in vitro model of Bacillus piliformis infection was developed to investigate the mechanisms of adhesion and internalization of this obligate intracellular bacterium. Adhesion and internalization events were examined by electron microscopic evaluation of infected Caco-2 cell monolayers. A few bacteria were identified in apical surface invaginations and in vacuoles subjacent to the apical surface, whereas the majority of bacteria were observed free within the cytoplasm, suggesting that B. piliformis entered epithelial cells via a phagocytic process and rapidly escaped the phagosome. To confirm that host cell phagocytosis was involved in entry of B. piliformis into mammalian cells, Intestine 407 cells were treated with the phagocytic inhibitor cytochalasin D, infected with B. piliformis, and evaluated for bacterial internalization by double-fluorescence labeling. The results showed decreased intracellular bacteria, suggesting that internalization was dependent on host cell microfilament function. To examine the role of B. piliformis in internalization, growth of live and Formalin-killed bacteria was compared. Dead bacteria were not internalized, suggesting that B. piliformis actively participates in internalization. B. piliformis appears to enter host cells by a bacterially directed phagocytic process. The in vitro system described should prove invaluable in further investigations of B. piliformis pathogenic mechanisms.

Fine-morphology of chief cells in human gastric mucosa after secretin.

Quantitative ultrastructural studies of human gastric mucosal chief cells during secretory stimulation have not been reported previously. In five healthy subjects we studied the effect of intravenous administration of 2 CU/kg of GIH secretin on gastric chief-cell ultrastructure. Gastric biopsies for quantitative ultrastructural analysis were obtained before and 15 and 30 min after secretin administration. Electron micrographs of 150 chief cells were analyzed by the Loud quantitative method. After secretin administration the percentage area occupied by zymogen granules decreased significantly at 15 and 30 min. At corresponding times membrane profile concentration (rough endoplasmic reticulum) increased significantly over basal values. This study provides morphological evidence of increased activity of chief cells after secretin administration.

Intestinal capillary filtration in acute and chronic portal hypertension.

The impact of acute and chronic portal hypertension on the dynamics of intestinal microvascular fluid exchange was examined in anesthetized, fasted, sham-operated control rats with normal portal pressures (CON), during acute elevations in portal pressure (APH) in control rats, and in rats in which chronic portal hypertension (CPH) was produced by calibrated stenosis of the portal vein 10 days prior to the experiments. Although intestinal blood flow and vascular resistance were not altered by APH in control rats, CPH was associated with an increased intestinal blood flow and reduced intestinal vascular resistance when compared with CON and APH. Intestinal capillary pressure and lymph flow were elevated in APH and CPH relative to control values. However, the increase in both variables was greater in CPH. The capillary filtration coefficient was elevated only in CPH. The transcapillary oncotic pressure gradient was not altered by APH or CPH. Interstitial fluid pressure was increased from -1.1 mmHg in CON to 3.9 mmHg during APH and to 5.0 mmHg in CPH. The results of this study indicate that chronic elevations in portal venous pressure produce larger increments in intestinal capillary pressure and filtration rate than do acute elevations in portal venous pressure of the same magnitude. However, the potential edemagenic effects of elevated capillary pressure in both acute and chronic portal hypertension are opposed by increases in lymph flow and interstitial fluid pressure.

Erythrocytes and erythrocyte morphologies of healthy and colony-born owl monkeys (Aotus lemurinus griseimembra).

Inadequate availability of hematological reference data seriously restricts optimal utilization of the owl monkey (Aotus lemurinus griseimembra) as an experimental model. The current study investigated erythrocytic morphology in peripheral blood of healthy, colony-born owl monkeys. The blood of the subjects contained discoid erythrocytes, poikilocytes, and showed considerable anisocytosis. Also observed were nucleated erythrocytes, erythrocytes with Howell-Jolly bodies, and reticulocyte types I, II, and III. Heinz bodies were not detected.

Effects of feeding Fusarium fujikuroi culture material containing known levels of moniliformin in turkey poults.

An experiment was conducted with 180 female turkey poults to evaluate the effects of Fusarium fujikuroi M-1214 culture material, containing moniliformin (M), on turkey poults. Day-old female poults were allotted randomly to dietary treatments containing 0, 0.24, 0.48, 0.72, 0.96, 1.44, 1.92, 2.40 and 2.88% M culture material (MCM). These levels of MCM supplied 0, 25, 50, 75, 100, 150, 200, 250 or 300 mg M/kg of feed. Significant mortality occurred in poults fed 200 (six out of 20), 250 (nine out of 20) and 300 (nine out of 20) mg M/kg feed. Poults fed 100 mg M/kg or greater had lower (P<0.05) feed intakes than controls. Decreased body weight gains were observed in poults fed diets containing 100 mg M/kg or higher. In contrast, feed conversion was only affected (P<0.05) at dietary levels of 200 mg M/kg feed or higher. Increased heart weights (P<0.05) were observed in poults fed greater than or equal to 50 mg M/kg. Gross lesions of M toxicity were a generalized cardiomegaly. Histopathology revealed focally extensive to generalized loss of car-diomyocyte cross striations (granular change) and numerous large cardiomyocyte nuclei in poults fed greater than or equal to 50 and 100 mg M/kg, respectively. Results indicated that Fusarium fujikuroi culture material containing moniliformin at greater than or equal to 50 mg M/kg is toxic to turkey poults.

Cutaneous melanocytomas in 10 young cattle.

Ten melanocytomas from 10 cattle were diagnosed by histopathologic examination of biopsy specimens submitted to the Veterinary Medical Diagnostic Laboratory, University of Missouri, between 1 January 1986 and 31 December 1993. One tumor was congenital; the others were first noticed between 2 months and 2 years of age (means = 9.9 months). Six tumors occurred in purebred (3) or crossbred (3) Angus cattle; one tumor each occurred in a Holstein, a Shorthorn, a Simmental, and a beef calf of unrecorded breed or coat color. Five calves were female, and five were male. Five tumors occurred in truncal dermis or subcutis (three in abdominal skin), four occurred on a limb, and one occurred on the jaw. Tumors varied in histologic appearance, but all were pigmented and all had few mitotic figures. Outcome was known for 8/10 cattle. In four cattle followed for at least 1 year, the tumor did not recur after surgical excision. Another heifer had residual gray tissue at the tumor site after surgery but remained in the herd without regrowth of the tumor 30 months after excision. Three other calves were slaughtered within 6 months of excision without apparent recurrence of the tumor.