Three-Dimensional Dosimetry of a Beta-Emitting Radionuclide Using PRESAGE Dosimeters.

Three-dimensional dose distributions from liquid brachytherapy were measured using PRESAGE(®) dosimeters. The dosimeters were exposed to Y-90 for 5.75 days and read by optical tomography. The distributions are consistent with estimates from beta dose kernels.

Autonomous Hedgehog signalling is undetectable in PC-3 prostate cancer cells.

The Hedgehog signalling pathway has been implicated in the development of prostate cancer, although this area remains controversial. Some but not all studies have noted relatively high Hedgehog pathway activity in commonly used prostate cancer cell lines. We aimed to evaluate the widely used PC-3 cell line as a model to investigate Hedgehog signalling in a prostate cancer setting. Using a sensitive Hedgehog inducible luciferase reporter assay, we found no evidence of autonomous Hedgehog signalling in PC-3 cells, irrespective of passage number. In addition, manipulations that should either increase (an oxysterol) or decrease (cyclopamine) Hedgehog pathway activity had no effect on reporter activity, and cyclopamine treatment did not affect PC-3 cell viability. Therefore, our findings contradict some earlier reports and caution against the use of PC-3 cells to investigate the Hedgehog pathway in a prostate cancer setting.

Tumor therapy with targeted atomic nanogenerators.

A single, high linear energy transfer alpha particle can kill a target cell. We have developed methods to target molecular-sized generators of alpha-emitting isotope cascades to the inside of cancer cells using actinium-225 coupled to internalizing monoclonal antibodies. In vitro, these constructs specifically killed leukemia, lymphoma, breast, ovarian, neuroblastoma, and prostate cancer cells at becquerel (picocurie) levels. Injection of single doses of the constructs at kilobecquerel (nanocurie) levels into mice bearing solid prostate carcinoma or disseminated human lymphoma induced tumor regression and prolonged survival, without toxicity, in a substantial fraction of animals. Nanogenerators targeting a wide variety of cancers may be possible.

An outbreak of toxoplasmosis in farmed mink (Mustela vison S.).

A large Wisconsin mink (Mustela vison) farm experienced an outbreak of toxoplasmosis in the spring of 1999 following an outbreak of canine distemper during the previous fall. Major clinical signs for pregnant females included reduced feed consumption, abortions, and stillborn kits; kits < or =3 weeks old experienced ataxia and mortality. Of 7,800 females, 1,976 (26%) lost their entire litter either from abortion or neonatal mortality. Kit mortality from 7 days to 3 weeks of age was 3,300, and overall kit mortality attributed to the toxoplasmosis outbreak was 10,408. Six neonatal mink kits, 12 3-week-old kits, and 2 adult female mink were submitted to the University of Minnesota Veterinary Diagnostic Laboratory for diagnostic workup. Gross postmortem lesions were limited to empty stomachs (12 of 12 kits) and pale livers (4 of 12 kits) for the 3-week-old kits. Major microscopic lesions included interstitial pneumonia, encephalitis, encephalomalacia, and myocarditis. Toxoplasmosis was diagnosed by microscopic lesions, microscopic lesion distribution, and the detection of Toxoplasma gondii tachyzoites by immunohistochemistry. This is the first detailed report of an outbreak of toxoplasmosis in mink in the United States.

Efficacy of neomycin sulfate water medication on the control of mortality associated with colibacillosis in growing turkeys.

The objective of this investigation was to evaluate the efficacy, safety, and toxicity of neomycin sulfate (Neomix 325) water medication to control mortality associated with colibacillosis (Escherichia coli) in growing turkeys. One efficacy trial was conducted at five locations; each location included 2,880 sexed 21-d-old turkey poults that were naturally challenged with litter from turkey flocks that had colibacillosis. Between 5 and 7 d after challenge, and when mortality had reached 0.5%, poults were randomized within sex into three treatment groups of 0, 11, or 22 mg neomycin sulfate/kg body weight. In each location, each treatment was replicated 12 times with 40 poults per sex per replicate. All treatments were administered in the drinking water for 5 d. The pivotal decision criterion was mortality. Mortality was defined as 1) supported mortality (SM): positive microbial culture for E. coli and gross lesions, 2) diagnosed mortality (DM): diagnosed as associated with E. coli but not supported by lesions or positive microbiological cultures, 3) overall mortality (OM): mortality associated with E. coli or other microorganisms and miscellaneous reasons such as accidents (trampling or suffocations). Performance data (growth and feed utilization) also were measured and are reported without statistical analysis. Results from this efficacy study clearly demonstrated the effectiveness of neomycin sulfate against E. coli as measured by a reduction in mortality. In the target animal safety and toxicity study (done in conjunction with the efficacy study), neomycin sulfate in the drinking water at 66, 110, or 220 mg/kg per d for 15 d had no observable adverse effects on poult performance, as measured by feed or water consumption, body weight, gross pathology, or mortality.

Biodistribution and dosimetry of an aqueous solution containing sodium 3-(125I)iodo-4-hydroxybenzenesulfonate (Iotrex) for brachytherapy of resected malignant brain tumors.

UNLABELLED: Iotrex is an aqueous radiotherapy solution containing sodium 3-(125I)iodo-4-hydroxybenzenesulfonate (125I-HBS), which is used as the radiation source for the brachytherapy of resected of brain tumor cavity margins with the GliaSite catheter. During routine clinical use of this brachytherapy applicator and radiation source, approximately 0.1% of the afterloaded Iotrex will diffuse through the GliaSite balloon. Our purpose was to assess the radiation doses to normal organs under routine clinical use of the GliaSite. METHODS: Five groups of rats received intracerebral injections of an 131I-HBS solution (131I used as a surrogate for 125I in the synthesis of 125I-HBS) with one group sacrificed at 15 minutes, 30 minutes, 1 hour, 2 hours and 4 hours post-administration. Urine was collected and activity retention in numerous organs was measured. The biodistribution data were used to estimate radiation doses to normal organs of the Reference Adult Male and Female phantoms. RESULTS: Radioactivity was rapidly and completely cleared from the brain (98% cleared by 2 hours) and total body (urinary clearance; 93%@2 hours). No organ retained > 0.7% of the radioactivity at 4 hours. For 100% loss of the radiotherapy solution from the balloon catheter (device failure), all organs would receive less than 100 mGy (10 rad), except the bladder wall (2800 mGy, 280 rad), uterus (130 mGy, 13 rad) and distal colon (270 mGy, 27 rad). Under normal conditions, all organ doses are 1000-fold lower (< 3 mGy or 0.3 rad). CONCLUSIONS: Under routine clinical conditions, the radiation doses to normal organs are inconsequential. Should the maximum clinical load of Iotrex (16.7 GBq of 125I) be released intracerebrally, the radiation doses to all organs would be below the thresholds for deterministic effects.

Description of osteomyelitis lesions associated with Actinomyces pyogenes infection in the proximal tibia of adult male turkeys.

Actinomyces pyogenes was isolated from osteomyelitis lesions from the proximal tibia of mature tom turkeys. Gram-stained impression smears of the lesions resulted in bacteria that appeared as club-shaped, gram-positive pleomorphic rods. The bacteria grew better in a reduced-oxygen environment. The lesions were well demarcated and cavernous, ranging from purulent to caseous in consistency.

Tubular duplication of the cervical portion of the esophagus in a foal.

Tubular duplication of the cervical portion of the esophagus was diagnosed in a 10-day-old female Quarter Horse. The foal was examined because of the development of a 12- to 15-cm diameter mass at the caudal aspect of the mandible after suckling. The foal was dyspneic when in lateral recumbency. Radiography and ultrasonography revealed a fluid- and gas-filled mass. Endoscopy revealed a normal-appearing upper airway and esophagus. Complete surgical resection of the mass was successful. The mass had a 3-mm diameter communication with the esophageal lumen at the pharyngoesophageal oriface. Histologic examination revealed stratified squamous epithelium lining the cyst-like cavity. The wall of the mass had circumferential and longitudinal layers of smooth muscle with few submucosal glands. The clinical, gross pathologic, and histopathologic findings were consistent with tubular duplication of the cervical portion of the esophagus.

Pleuropneumonia caused by Actinobacillus pleuropneumoniae biotype 2 in growing and finishing pigs.

Actinobacillus pleuropneumoniae biotype 2 was isolated in pure culture or as the predominant isolate from the lungs of 9 growing and finishing pigs with pleuropneumonia. Gross and microscopic lesions resembled those caused by A. pleuropneumoniae biotype 1 serotypes (Nos. 1, 5, and 7) traditionally seen in the United States. The overall mortality rate for growing and finishing pigs on this 1,200-sow farrow-to-finish farm ranged from 0.37% to 0.84% per month from July 1990 to February 1991, and mortality due to respiratory disease ranged from 0.17% to 0.52% per month for the same period. This Actinobacillus species did not require V factor (no satellitism on blood agar with a Staphylococcus streak), was strongly beta-hemolytic, and demonstrated restriction fragment length polymorphisms in hybridization studies with A. suis, A. lignieresii, and A. equuli. Biochemically, the isolate most closely resembled A. pleuropneumoniae, and a DNA fragment considered specific for A. pleuropneumoniae biotypes 1 and 2 was demonstrated using polymerase chain reaction. Necrohemorrhagic pleuropneumonia similar to that caused by A. pleuropneumoniae biotype 1 was reproduced experimentally in 2 4-week-old pigs inoculated intratracheally with broth cultures of the A. pleuropneumoniae biotype 2. This study demonstrated the presence of A. pleuropneumoniae biotype 2 in the United States.

Lesions of perirenal hemorrhage syndrome in growing turkeys.

Turkeys from six market flocks were examined at 8 to 19 weeks of age to assess morphologic lesions of perirenal hemorrhage syndrome (PHS). PHS was diagnosed in 165 of 715 turkeys necropsied, and 82 turkeys served as age- and weight-matched controls. The most consistent gross findings were rounded pectoral muscles of normal color, ingesta-filled crops and gizzards, variable retroperitoneal perirenal hemorrhage, a swollen dark red and light purple spleen, congested intestinal blood vessels, and pulmonary edema and/or hemorrhage. The main histologic lesions of PHS were perivascular edema in lungs and kidneys, vascular congestion of various organs, renal perivenous hemorrhage, and proliferative arterial and arteriolar lesions in the spleen and kidneys that were more severe than those in controls. Heart weights, including mean relative weights of the right and combined left ventricles and interventricular septa, were significantly greater in turkeys that died with PHS than in controls. Scores for tibial dyschondroplasia and "breast blisters" were more severe in turkeys that died with PHS than in controls. The cardiovascular system appeared to be the PHS target system.

Squamous cell carcinoma as a cause of dyspnea and blindness in a horse.

An 8-year-old Quarter Horse mare was examined for chronic nasal discharge and obstruction of both nasal passages. A solid mass lesion was identified in the maxillary sinuses, soft palate, nasal and pharyngeal cavities. Palliative surgery was used to debulk the lesion and facilitate nasal airflow. Squamous cell carcinoma was diagnosed from surgical biopsies. Approximately 7-8 weeks after surgery, the mare was observed to be acutely blind. Ophthalmologic examination revealed central origin blindness and active retinitis. The squamous cell carcinoma had reobstructed the nasal passages. Pressure by the expanding tumor deformed the ethmoid and sphenoid bones resulting in compression of the optic tracts. No bony invasion by the tumor was present.

The incidence of perirenal hemorrhage syndrome in six flocks of market turkey toms.

Four flocks of the Nicholas strain and two of the British United turkey (BUT) strain of large white market turkey toms were monitored from 8 to 19 weeks of age to identify the presence, incidence, age distribution, and possible cause(s) of perirenal hemorrhage syndrome (PHS), or acute hypertensive angiopathy. Mortality rates varied among the flocks from 0.81% to 1.78% of total poults started. Nicholas flocks has a distinct peak in mortality between 9 and 14 weeks of age. PHS was the main cause of mortality from 8 to 14 weeks of age in all flocks except one, and the incidence diminished after 15 weeks of age. No significant bacterial pathogens were detected in any of the PHS cases. Distinct peaks in overall weekly mortality between 10 and 13 weeks of age similar to those in the four Nicholas flocks were also observed in six of 10 Minnesota flocks surveyed separately.

Perirenal hemorrhage syndrome in market turkey toms: effect of management factors.

Differences in the overall mortality rates and mortality due to perirenal hemorrhage syndrome (PHS) were compared in large white Nicholas tom turkeys. The study evaluated the effects of 1) four different light and temperature treatments; 2) three feed additives proposed to have anti-stress effects (reserpine, acetylsalicylic acid, and increased calcium); 3) toe-clipping on mortality, various disease conditions, and production parameters. Mortality varied from 0.60% to 3.57% among groups. Increased room temperature (21 C), toe-clipping, step-up/step-down lighting, and dietary reserpine reduced the incidence of PHS as compared with lower room temperature (13 C), no toe-clipping, intermittent lighting (2 hours light, 4 hours dark), and no dietary reserpine. Dietary aspirin or elevated calcium levels had no effect on PHS incidence. Overall mortality was greatest in the warmer rooms.

Poliomyelomalacia, pancreatic necrosis, and cerebellar malacia in turkey poults.

Two-to-5-week-old turkey poults from three large Minnesota flocks exhibited ataxia, flaccid paralysis, and up to 5% mortality as unexpected death. The major post-mortem finding was cerebellar hemorrhage and softening detected in 22 of 89 clinically affected poults. Histologic findings were severe focal or multifocal poliomyelomalacia in the lumbosacral intumescentia of the spinal cord, cerebellar malacia, and single-cell or multifocal coagulative necrosis of pancreatic acinar cells. Thirty of 32 clinically affected poults examined had microscopic spinal cord lesions, 12 of 48 had cerebellar lesions, and 26 of 47 had pancreatic lesions. Gross and microscopic cerebellar lesions resembled those of vitamin E deficiency in chicks. Hepatic selenium levels were approximately twice normal expected levels for poults.