Phase I evaluation of low-dose suramin as chemosensitizer of doxorubicin in dogs with naturally occurring cancers

BACKGROUND: Low and nontoxic concentrations (10-50 microM) of suramin, which is a nonspecific inhibitor of multiple growth factors, including fibroblast growth factors, enhances the activities of cytotoxic chemotherapeutic agents, such as doxorubicin and paclitaxel, both in vitro and in vivo. Suramin has not been evaluated as a chemosensitizing agent in dogs with cancer. HYPOTHESIS: Nontoxic suramin can be used safely as a chemosensitizer in dogs. ANIMALS: Sixteen dogs of various breeds with measurable tumors were treated; 1 dog that had undergone amputation for osteosarcoma received adjuvant therapy. METHODS: The dogs received 53 courses of treatment with suramin in combination with doxorubicin. The suramin dosage was 6.75 mg/kg IV 3 h before standard doxorubicin administration every 2 weeks. The pharmacokinetics and clinical efficacy were determined. RESULTS: The pharmacokinetics of low-dose suramin followed a 2-compartment model with half-lives of 2 h and 6 days. The distribution volume was a 0.34 +/- 0.12 L/kg, and clearance was 1.86 +/- 0.76 mL/kg/h. During the time interval that doxorubicin was present at therapeutically active concentrations (ie, from the start of infusion to 24 hours), the plasma concentrations were maintained within 20% of the target range (8-60 microM) in 72% of the treatments. The toxicity of the suramin/doxorubicin combination was mild and comparable to the toxicity expected for doxorubicin monotherapy. Objective partial responses were observed in 2 out of 16 evaluable dogs (13%). All 5 dogs that previously received doxorubicin showed improved responses to the suramin/doxorubicin combination. CONCLUSIONS AND CLINICAL IMPORTANCE: A fixed, low-dose suramin regimen yields the desired target plasma concentrations in most dogs, and appears to enhance the activity of doxorubicin without enhancing toxicity.     

Factors associated with preweaning mortality on commercial pig farms in England and Wales

Data from 67 pig farms with a variety of farrowing systems were used to identify factors associated with preweaning mortality in British pig herds. The median mortality reported by the farmers was 10.7 per cent (interquartile range 8.5 to 14 per cent). There was a significantly higher mortality when the pigs were weaned when they were older. A multivariable Poisson model was developed into which the types of farrowing system on each farm and the age at weaning were forced. Factors associated with a lower preweaning mortality rate were insulating the farrowing building, providing extra heat at farrowing, giving the piglets iron injections, dipping their navels, using fan ventilation and using artificial lighting systems. Factors associated with a higher mortality rate were a later weaning age, the use of infra-red lamps rather than other forms of supplementary heat, and the use of a creep without any bedding.     

Serratospiculosis in a New Zealand Falcon (Falco novaeseelandiae)

CASE HISTORY: An adult New Zealand falcon was presented with metacarpal fractures in the left wing. CLINICAL FINDINGS: In addition to the fractures, radiographs revealed an area of opacity in the air sacs. A few days after hospitalisation and initiation of treatment of the fractures, the bird developed signs of respiratory disease; the area of opacity was found to have increased in size and density. Treatment with antibiotics and nebulisation was commenced; the bird initially responded but respiratory signs subsequently worsened and the bird died. At necropsy, air sacculitis and bronchopneumonia were associated with numerous nematodes in the air sacs, which were morphologically consistent with Serratospiculum guttatum. DIAGNOSIS: Serratospiculosis CLINICAL RELEVANCE: The discovery of this parasite and the associated disease for the first time in New Zealand indicates that it should be considered in the differential diagnosis of respiratory disease in falcons and possibly other raptors in New Zealand.     

Laparoscopic intestinal exploration and full-thickness intestinal biopsy in standing horses: a pilot study

OBJECTIVE: To assess a laparoscopic technique for equine intestinal biopsy. STUDY DESIGN: Experimental study. ANIMALS: Seven adult horses. METHODS: Food but not water was withheld for 36 hours before laparoscopy. In 3 horses (group A) standing, right laparoscopic access to different small intestinal segments was compared with ventral median celiotomy access. Inaccessible segments were identified at necropsy. In 4 horses (group B), the feasibility of obtaining full-thickness duodenal and cecal biopsies and any associated morbidity were evaluated. Biopsy specimens were collected during standing right laparoscopy using a 2-step procedure and intracorporeal suturing technique, and abdominal lavage was performed. Horses were monitored clinically and by abdominal fluid cytology and microbial culture, and repeat laparoscopy was performed on day 6. RESULTS: Standing right flank laparoscopy provided good observation of small intestinal segments and enabled manipulation of all but 15-20 cm of the duodenum and approximately 40 cm more ileum compared with ventral median celiotomy. Group B horses had no complications, no adhesions, and no bacterial growth from peritoneal fluid samples. None of the horses had signs of abdominal pain. CONCLUSION: A 2-stage intestinal biopsy technique performed during standing, right flank laparoscopy may be a safe alternative to exploratory celiotomy and biopsy in normal horses. CLINICAL RELEVANCE: Right flank laparoscopy allows biopsy of intestinal segments including duodenum and 50% more of the ileum than is accessible by ventral median celiotomy. This technique should be evaluated in clinical patients.     

Elemental compositions of comet 81P/Wild 2 samples collected by Stardust

We measured the elemental compositions of material from 23 particles in aerogel and from residue in seven craters in aluminum foil that was collected during passage of the Stardust spacecraft through the coma of comet 81P/Wild 2. These particles are chemically heterogeneous at the largest size scale analyzed ( approximately 180 ng). The mean elemental composition of this Wild 2 material is consistent with the CI meteorite composition, which is thought to represent the bulk composition of the solar system, for the elements Mg, Si, Mn, Fe, and Ni to 35%, and for Ca and Ti to 60%. The elements Cu, Zn, and Ga appear enriched in this Wild 2 material, which suggests that the CI meteorites may not represent the solar system composition for these moderately volatile minor elements.     

Integrating socio‐economic and biophysical models: revision of a land‐use allocation model

Integration of large‐area, economically driven macro‐models and small‐area, biophysically based models in the Canadian agricultural sector was described recently in the development of a land‐use allocation model (LUAM). We have since developed and integrated an improved methodology for allocating crop area changes generated for large areas by the Canadian Regional Agricultural Model (CRAM) to much smaller Soil Landscapes of Canada (SLC) polygons. Validation of outputs showed considerable improvement. The new coefficients of determination (R²) between simulated and actual data, with previous values in brackets, were 0.69 for fodder corn (0.54), 0.88 for wheat (0.62), 0.77 for hay (0.26), 0.54 for alfalfa (not previously reported), 0.88 for soya bean (0.26) and 0.86 for grain corn (0.22). The best result was obtained for soya bean, with a normalized root mean square error (NRMSE) of 0.31%, and the poorest for alfalfa, with NRMSE = 17.34%.     

Assay for fluorescein diacetate hydrolytic activity: Optimization for soil samples

With the increased interest in integrated soil bioecosystem studies, there is a need to have a method of measuring overall microbial activity potential. Hydrolysis of fluorescein diacetate [3′,6′-diacetylfluorescein (FDA)] has been suggested as a possible method because the ubiquitous lipase, protease, and esterase enzymes are involved in the hydrolysis of FDA. Following hydrolysis of FDA, fluorescein is released and can be measured spectrophotometrically. Our objective was to optimize the assay for FDA hydrolytic activity in soil samples and determine the kinetic parameters involved in this reaction. The optimized method involves extraction and quantitative measurement of the fluorescein released when 1.0 g of soil is incubated with 50 ml of 60 mM Na-phosphate solution (buffered at pH 7.6) at 37 °C for 3 h. Results showed that FDA hydrolysis was optimum at buffer pH 7.6 and the soil enzymes were denatured at temperatures above 60 °C. Three soils were used to optimize this method: Heiden clay, Raub silt loam, and Cecil sandy loam. This procedure is simple, precise, and can be used in commercial soil testing laboratories to determine general microbial activity and as a soil quality indicator.     

Determination of Mirex in human blood serum containing polychlorinated biphenyls by using packed column gas chromatography.

An analytical method has been developed that uses electron capture/gas-liquid chromatography to determine Mirex in serum containing polychlorinated biphenyls (PCBs) (Aroclor 1260). With this method, 0.2 ppb Mirex can be determined in 4 mL serum that also contains 10 ppb PCBs. The method provides approximately 70% recovery of Mirex at 1.0 and 3.5 ppb. The coefficients of variation are 4.5 and 4.6% at 1.0 and 3.5 ppb, respectively. In a cooperative study with the Ohio Department of Health, the Centers for Disease Control used this method to determine the extent of exposure of Salem, OH, residents to Mirex. Confirmation of Mirex was obtained by using high resolution gas chromatography and high resolution mass spectrometry.     

Nonfatal occupational injury among California farm operators

We conducted a population-based telephone survey addressing farm-work-related (FWR) injuries among California farm operators. Of 1947 participants (80.4% response), 135 farm operators reported 160 FWR injuries in the preceding year, yielding a one-year cumulative incidence for any FWR injury of 6.9% (95% CI 5.8%-8.2%), or a mean 8.2 FWR injuries per 100 farmers in the preceding year (95% CI 6.8-9.7). Multiple injury events in the same individual occurred more frequently than predicted by chance. Sprains and strains (29.4%) were the most frequently reported injury and predominantly involved the back. Overexertion represented the most frequent external cause (24.2%), followed by machinery (14.3%), falls (13.0%), and animals (12.4%). Factors associated with FWR injury included white ethnicity (OR 3.19; 95% CI 1.38-7.36), increased annual hours worked on the farm, low levels of administrative work, and increased percentage of time working with livestock. FWR injury experience of California farm operators is comparable with that reported for other agricultural populations. Above-expected frequency of multiple injuries supports involvement of personal or environmental risk factors. Preventive efforts should focus on higher-risk groups and preventing overexertion and muscle strain and injury related to machinery, falls, and animals, especially livestock.