Cost-effectiveness of training rural providers to identify and treat patients at risk for fragility fractures.

UNLABELLED: This is a cost-effectiveness analysis of training rural providers to identify and treat osteoporosis. Results showed a slight cost savings, increase in life years, increase in treatment rates, and decrease in fracture incidence. However, the results were sensitive to small differences in effectiveness, being cost-effective in 70 % of simulations during probabilistic sensitivity analysis. INTRODUCTION: We evaluated the cost-effectiveness of training rural providers to identify and treat veterans at risk for fragility fractures relative to referring these patients to an urban medical center for specialist care. The model evaluated the impact of training on patient life years, quality-adjusted life years (QALYs), treatment rates, fracture incidence, and costs from the perspective of the Department of Veterans Affairs. METHODS: We constructed a Markov microsimulation model to compare costs and outcomes of a hypothetical cohort of veterans seen by rural providers. Parameter estimates were derived from previously published studies, and we conducted one-way and probabilistic sensitivity analyses on the parameter inputs. RESULTS: Base-case analysis showed that training resulted in no additional costs and an extra 0.083 life years (0.054 QALYs). Our model projected that as a result of training, more patients with osteoporosis would receive treatment (81.3 vs. 12.2 %), and all patients would have a lower incidence of fractures per 1,000 patient years (hip, 1.628 vs. 1.913; clinical vertebral, 0.566 vs. 1.037) when seen by a trained provider compared to an untrained provider. Results remained consistent in one-way sensitivity analysis and in probabilistic sensitivity analyses, training rural providers was cost-effective (less than $50,000/QALY) in 70 % of the simulations. CONCLUSIONS: Training rural providers to identify and treat veterans at risk for fragility fractures has a potential to be cost-effective, but the results are sensitive to small differences in effectiveness. It appears that provider education alone is not enough to make a significant difference in fragility fracture rates among veterans.

Comparison of equilibrium and non-equilibrium distribution coefficients for the human drug carbamazepine in soil.

The distribution coefficient (KD) for the human drug carbamazepine was measured using a non-equilibrium technique. Repacked soil columns were prepared using an Airport silt loam (Typic Natrustalf) with an average organic matter content of 2.45%. Carbamazepine solutions were then leached through the columns at 0.5, 1.0 and 1.5 mL min(-1) representing average linear velocities of 1.8, 3.5 and 5.3 cm h(-1) respectively. Each flow rate was replicated three times and three carbamazepine pulses were applied to each column resulting in a total of 9 columns with 27 total carbamazepine pulses. Breakthrough curves were used to determine KD using the parameter fitting software CXTFIT. Results indicate that as flow rate decreased from 5.3 to 1.8 cm h(-1), KD increased an average of 21%. Additionally, KD determined by column leaching (14.7-22.7 L kg(-1)) was greater than KD determined by a 2h batch equilibrium adsorption (12.6 L kg(-1)). Based on these KD's carbamazepine would be generally characterized as non-mobile in the soil investigated. However, repeated carbamazepine applications resulted in an average 22% decrease in KD between the first and third applications. Decreasing KD is attributed to differences in sorption site kinetics and carbamazepine residence time in contact with the soil. This would indicate that the repeated use of reclaimed wastewater at high application rates for long-term irrigation or groundwater recharge has the potential to lead to greater transport of carbamazepine than KD determined by batch equilibrium would predict.

Sorption/Desorption of lincomycin from three arid-region soils.

The antibiotic lincomycin is commonly found in treated municipal waste water and in waste from swine and poultry production. Environmental disposal of these wastes has the potential to introduce a significant mass of lincomycin into the ecosystem. In the present study, a series of sorption and desorption experiments were conducted to determine the potential mobility of lincomycin in soils from arid environments. Sorption and desorption isotherms were obtained for lincomycin using three different soils. Isotherms were fit to the Freundlich equation. Adsorption of lincomycin was found to have a of 11.98 for a biosolid-treated soil (1.58% OC) and a of 210.15 for a similar unamended soil (1.42% OC). It was also found that for a low-organic-content soil the was 5.09. The differences in adsorption can be related to the soil pH and the pKa of lincomycin (7.5-7.8). When the soil solution pH is below the pKa, the cationic species of lincomycin dominates, resulting in increased water solubility. Interaction with the cation exchange complex is minimal due to a high solution cation concentration (Ca and Na). Desorption isotherms also indicate that when the solution pH is lower than the pKa, retention of lincomycin is reduced. Our results indicate that the mobility of lincomycin in these arid region soils is dependent on soil pH.

Efficacy and uptake of soil-applied imidacloprid in the control of Asian citrus psyllid and a citrus leafminer, two foliar-feeding citrus pests.

The systemic neonicotinoid insecticide imidacloprid, Admire Pro, was applied to 3- and 4-yr-old nonbearing 'Rio Red' grapefruit, Citrus x paradisi Macfad., trees in 2006 and 2007, respectively, to determine its effects in the control of two major citrus pests, the Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), and a citrus leafminer Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae). Young flush shoots were randomly collected weekly for 13 and 11 wk in 2006 and 2007, respectively, to determine the infestation levels and densities of immature stages of both Asian citrus psyllid and P. citrella. Additional flush shoot samples were collected in 2007 and titers of imidacloprid in leaf tissue were determined using an enzyme-linked immunosorbent assay. Soil application of imidacloprid significantly reduced the infestation levels and densities of both pests on flush shoots, starting from the second week post application. The effects of the neonicotinoid insecticide were similar in both years. Analysis of imidacloprid concentration in leaf tissue showed a gradual increase during the first 3 wk, and titers remained well above 200 ppb for 11 wk postapplication. Significant positive correlations were obtained between imidacloprid titers in leaf tissue and the percentage of control levels achieved for both pests. A high level of suppression of both P. citrella and Asian citrus psyllid populations on citrus trees was associated with imidacloprid titer in leaf tissue >200 ppb, which was reached 2 wk after soil treatment. Although soil application of imidacloprid did not provide rapid knockdown of Asian citrus psyllid and P. citrella populations, it resulted in chronic residues in leaf tissue and long-term suppression of both pests.

Application of alternative fumigants through drip irrigation systems.

ABSTRACT Strawberry fields in California (9,500 ha annually) are pre-plant fumigated with methyl bromide and chloropicrin to prevent serious soil pest and disease problems. Although soil fumigation with methyl bromide has ensured stability of strawberry production, its use is being discontinued because of its effect on stratospheric ozone. The likely short-term alternatives such as 1,3-dichloropropene, chloropicrin, and metham sodium, although not ozone depleters, are potentially hazardous to the environment and humans if applied improperly. Water-soluble formulations of alternative fumigants can be applied through drip irrigation systems established to irrigate crops. In comparison to conventional shank methods of injection, application of soluble formulations through drip irrigation systems would be economical and environmentally friendly, reduce worker exposure, and allow for simultaneous or sequential application of a combination of fumigants. This paper discusses techniques developed to apply alternative fumigants through drip irrigation systems, and reviews ongoing studies to determine optimum application rates, soil conditions, plastic mulches, and amount of irrigation water used to apply these alternative fumigants.

Tophaceous pseudogout: a pitfall in the diagnosis of chondrosarcoma.

Tumoral calcium pyrophosphate dihydrate deposition disease (TCPPD, tumoral or tophaceous pseudogout) is a rare nonneoplastic entity which mimics soft-tissue or skeletal malignancy. We present here the fine-needle aspiration cytology findings of a unique case of TCPPD in a 76-yr-old woman, with a large paraischial soft-tissue mass diagnosed as a malignant neoplasm. The difficulty in diagnosing such lesions by fine-needle aspirates is discussed and reviewed in the context of known cases from the literature.

Enhanced acetaminophen hepatotoxicity in transgenic mice overexpressing BCL-2.

Mitochondria play an important role in the cell death induced by many drugs, including hepatotoxicity from overdose of the popular analgesic, acetaminophen (APAP). To investigate mitochondrial alterations associated with APAP-induced hepatotoxicity, the subcellular distribution of proapoptotic BAX was determined. Based on the antiapoptotic characteristics of BCL-2, we further hypothesized that if a BAX component was evident then BCL-2 overexpression may be hepatoprotective. Mice, either with a human bcl-2 transgene (-/+) or wild-type mice (WT; -/-), were dosed with 500 or 600 mg/kg (i.p.) APAP or a nonhepatotoxic isomer, N-acetyl-m-aminophenol (AMAP). Immunoblot analyses indicated increased mitochondrial BAX-beta content very early after APAP or AMAP treatment. This was paralleled by disappearance of BAX-alpha from the cytosol of APAP treated animals and, to a lesser extent, with AMAP treatment. Early pathological evidence of APAP-induced zone 3 necrosis was seen in bcl-2 (-/+) mice, which progressed to massive panlobular necrosis with hemorrhage by 24 h. In contrast, WT mice dosed with APAP showed a more typical, and less severe, centrilobular necrosis. AMAP-treated bcl-2 (-/+) mice displayed only early microvesicular steatosis without progression to extensive necrosis. Decreased complex III activity, evident as early as 6 h after treatment, correlated well with plasma enzyme activities at 24 h (AST r(2) = 0.89, ALT r(2) = 0.87) thereby confirming a role for mitochondria in APAP-mediated hepatotoxicity. In conclusion, these data suggest for the first time that BAX may be an early determinant of APAP-mediated hepatotoxicity and that BCL-2 overexpression unexpectedly enhances APAP hepatotoxicity.

Patellar metastasis from a squamous carcinoma of the lung: a case report.

Bone is a common site of metastasis from lung cancer. Metastasis to the patella, however, is rare. A 76-year-old man presented with knee pain caused by an isolated patellar metastasis from squamous cell carcinoma of the lung. Treatment was delayed secondary to delay in diagnosis. In cases of bone pain that are unexplained or out of proportion to a traumatic event, more extensive diagnostic studies should be done.

Human aromatase in high yield and purity by perfusion chromatography and its characterization by difference spectroscopy and mass spectrometry.

Expression of human cytochrome P450 aromatase (CYP19A1, aromatase) was accomplished at a high level using a baculovirus expression system in an insect cell suspension culture. Using the relatively new chromatographic technique of perfusion chromatography, a very rapid procedure for purification of the protein from solubilized cells was developed. At extraordinary flow rates of between 3 and 9 column volumes per minute, all chromatographic procedures could be performed, including setup, equilibration, and column regeneration steps, in less than 2 h, not including brief dialysis periods. Total yields were 40-52% and resulted in preparations with specific content values of 17.1 nmol aromatase/mg protein. Final purified preparations showed virtually no typical P450 spectra under standard conditions, but displayed full activity with typical enzyme kinetic parameters. These unusual results suggest that standard methods of P450 measurement are inappropriate when applied to aromatase. The findings are fully consistent with those encountered previously for purified preparations from a human placental source and led us to a new aromatase quantification method based on ligand-induced difference spectroscopy. A new HPLC assay is described which rapidly separates heme and apoprotein while measuring total heme content. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was employed with both glycosylated and deglycosylated forms of the final purified product to confirm its identity as a glycosylated cytochrome P450.

Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas.

PURPOSE: To determine whether treatment-induced pathologic necrosis correlates with local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. PATIENTS AND METHODS: Four hundred ninety-six patients with intermediate- to high-grade extremity soft tissue sarcomas received protocol neoadjuvant therapy. All patients underwent surgical resection after neoadjuvant therapy and had pathologic assessment of tumor necrosis in the resected specimens. RESULTS: The 5- and 10-year local recurrence rates for patients with > or = 95% pathologic necrosis were significantly lower (6% and 11%, respectively) than the local recurrence rates for patients with less than 95% pathologic necrosis (17% and 23%, respectively). The 5- and 10-year survival rates for the patients with > or = 95% pathologic necrosis were significantly higher (80% and 71%, respectively) than the survival rates for the patients with less than 95% pathologic necrosis (62% and 55%, respectively). Patients with less than 95% pathologic necrosis were 2.51 times more likely to develop a local recurrence and 1.86 times more likely to die of their disease as compared with patients with > or = 95% pathologic necrosis. The percentage of patients who achieved > or /= 95% pathologic necrosis increased to 48% with the addition of ifosfamide as compared with 13% of the patients in all the other protocols combined. CONCLUSION: Treatment-induced pathologic necrosis is an independent predictor of both local recurrence and overall survival in patients who receive neoadjuvant therapy for high-grade extremity soft tissue sarcomas. A complete pathologic response (> or = 95% pathologic necrosis) correlated with a significantly lower rate of local recurrence and improved overall survival.

Soft tissue echinococcosis: a report of two cases and review of the literature.

Echinococcosis (hydatid cyst disease) is a zoonotic infection caused by the parasitic tapeworm Echinococcus. The larval stage of this parasite can implant in many organs of the body, most commonly the liver, and create internal budding cystic masses. Echinococcal cysts also can implant in soft tissues; however, a review of the literature revealed no published case with the patient initially presenting with a soft tissue mass. Two such cases are reported in the current study. Physicians who evaluate soft tissue masses, particularly in patients from Echinococcus-endemic areas, need to include echinococcosis in their differential diagnoses. The current treatment of choice for soft tissue echinococcosis is wide resection combined with perioperative medical therapy.

The innervation of the triangular fibrocartilage complex: nitric acid maceration rediscovered.

Injury to the triangular fibrocartilage complex (TFCC) is frequently implicated in the etiology of ulnar-sided wrist pain. This study examines the nervous anatomy of the TFCC using a nitric acid maceration technique and attempts to correlate this information with known tear patterns. Ten fresh frozen cadaveric specimens were studied in detail. Gross dissection of each upper-extremity specimen included removal of all flexor and extensor tendons. After identification and labeling with permanent color of the ulnar nerve, dorsal sensory branch of the ulnar nerve, posterior interosseous nerve, anterior interosseous nerve, and median nerve, an en bloc excision of the distal radioulnar region was performed. Digestion of the soft tissue was performed with nitric acid at sequential concentrations of 50% and 33% for 9 of 10 specimens. The digestion was halted by immersing the specimen in a mixture of 10% formaldehyde and 1% glycerine. After removal of bone, the specimens were fixed in paraffin, sectioned, and stained with hematoxylin and eosin. Nine of the 10 specimens were studied microscopically to determine the contribution of the grossly identified nerves to each zone of the triangular fibrocartilage complex as defined by Palmer's classification of acute TFCC tears. The anterior interosseous, median, and superficial radial nerves did not contribute to the innervation of the TFCC. The intraarticular course of the peripheral nerves could not be defined in the one specimen that was not digested with nitric acid. Nitric acid maceration is a rediscovered technique for identifying the nervous anatomy of soft tissues. The study showed that the triangular fibrocartilage complex is innervated by branches of the posterior interosseous, ulnar, and dorsal sensory ulnar nerves in a fairly consistent manner. Improved treatment of TFCC tears may result from an enhanced understanding of the supporting structures' innervation and mechanical function.

Efficacy of 1,3-dichloropropene in soil amended with compost and unamended soil.

1,3-Dichloropropene (1,3-D) is a likely alternative soil fumigant for methyl bromide. The objective was to determine root-knot nematode, Meloidogyne incognita, survival in microplots after exposure to 1,3-D for various periods of time in soil that have previously been amended with compost. The treatments were 1,3-D applied broadcast at 112 liters/ha and untreated controls in both compost-amended and unamended soil. Soil samples were collected from each microplot at 6, 24, 48, 72, and 96 hours after fumigation at three depths (0-15, 15-30, and 30-45 cm). One week after fumigation, six tomato seedlings were transplanted into each microplot and root galling was recorded 6 weeks later. Plants grown in fumigated compost-amended soil had more galls than plants from fumigated unamended soil at P

Structure toxicity relationships--how useful are they in predicting toxicities of new drugs?

This chapter provides just a few newer examples of structural moieties found in drugs that have been associated with reactive metabolite formation and toxicities. For a discussion of several other structures in drugs that undergo metabolic activation to reactive intermediates, the reader is directed to previous volumes in this series and other chapters in this book, as well as a previous condensed review (Nelson, 1982). Since that review, some new knowledge allows us to better predict that some structural moieties are more likely than others to form drug reactive metabolites that may be involved in causing toxic effects in humans. For example, most aniline-, thiophene-, and nitroaromatic-containing drugs have had a relatively high incidence of adverse effects, and it would be prudent in the drug discovery process to avoid these substructures if possible. However, as illustrated by the case of olanzapine, these structures may be important for potent activity, and could therefore be beneficial in some cases. The glitazones represent a new class of drugs with a unique thiazolidinedione structure. This raises two important points. First, it demonstrates how limited our knowledge base is in regard to structure toxicity relationships when new structures are introduced. Our approaches must be very empirical and are far from quantitative for the reasons outlined in the introduction. Secondly, the glitazones point out the importance of benefit/risk considerations. This was a new structural class of drugs with a unique spectrum of action that is very beneficial in the treatment of a major disease. Despite some suspected risk of toxicity, based on early trials, troglitazone was approved for use with careful monitoring. This author believes that was the right decision, as was the decision to withdraw the drug when the risk became unacceptable, especially with the introduction of safer alternatives. If this were just another NSAID (e.g., bromfenac), there would be little reason for approval. In summary, as I pointed out previously (Nelson, 1982), with our limited knowledge of structure toxicity relationships, we can only make reasonable judgments as to risk assessment of a new drug in humans, and hope that we neither release a dangerous chemical entity nor, as importantly, abort an effective one.

A real-time ST-segment monitoring algorithm for implantable devices.

Continuous ST-segment monitoring by implantable devices may lead to clarification of the substrate of arrhythmias, clarification of the origin of nonspecific chest pain, and titration or preventative application of established anti-ischemic therapies. Although ST-segment monitoring algorithms are available for surface electrocardiogram, the computational demand of algorithms for implantable devices must be minimized for considerations of device longevity. The new algorithm first locates a fiducial point (FPT) at the dominant peak of each QRS complex. The ST-segment deviation (measured at 2 rate-adaptive delays after FPT, eg, FPT + 96 ms and FPT + 152 ms at 60 BPM) with respect to the isoelectric level (measured at the minimum slope preceding the QRS) is then measured. The following features are also quantified by simple operations: R-R interval, R-wave slope, R-wave amplitude, ST-segment slope, and noise content during the isoelectric segment. Inconsistencies in these features relative to their adaptive normal ranges are used to reject noisy or ectopic beats and sudden morphology changes. Finally, the ST-segment deviation over time is filtered to reject rates of change that are not likely attributable to human ischemia. Performance of the algorithm was evaluated on the European Society of Cardiology ST-T Database, which contains 180 hours of ambulatory electrocardiogram with 250 expert-annotated ischemic episodes. The sensitivity was 79% [74% 84%] (mean [95% CI]) and positive predictivity was 81% [76% 86%]. This performance is statistically equivalent to that of published electrocardiogram algorithms that were validated on the same dataset. Estimates of computational burden suggest that the algorithm could process two channels of electrogram continuously for more than 5 years with current implanted device technology. In conclusion, we have developed an algorithm for ST-segment monitoring that can be implemented in current implantable devices with sensitivity and positive predictivity that are comparable with the state-of-the-art.

Molecular structure-property relationships for alkenes.

Structure-property relationships were obtained for 11 physical and chemical properties (boiling points (bp), melting points (mp), molar refractions (MR), molar volumes (MV), heats of combustion (HCKJ), molar heats of vaporization (HVMOL), flashpoints (FLASHK), second virial coefficients (VIRC2), critical temperatures (Tc), critical pressures (Pc), and viscosities (VISC)) for a data set consisting of 162 C4-C9 monoalkenes. Both molecular connectivity indices and ad hoc descriptors were tested as structural descriptors, and both produced high-quality regression equations for most of the properties. As was observed in an earlier study of alkanes [J. Am. Chem. Soc. 110 (1988) 4186], mp were not well described by either descriptor set. For most properties, the mass/bulk of the molecule was found to be the most important structural feature determining the property, suggesting that dispersion forces play a dominant role in determining those properties influenced by intermolecular interactions. The amount of branching in the molecule and the nature of the double bond environment were also found to be influential features.

Adenovirus-interleukin-12-mediated tumor regression in a murine hepatocellular carcinoma model is not dependent on CD1-restricted natural killer T cells.

The cytokine interleukin-12 (IL-12) has shown potent antitumor activity in several tumor models. Recently, natural killer (NK) T cells have been proposed to mediate the antitumor effects of IL-12. In this study, the antitumor response of IL-12 was investigated in a gene therapeutic model against s.c. growing mouse hepatocellular carcinomas using an adenoviral vector expressing murine IL-12 (AdVmIL-12). An adenoviral-based system was chosen because of the ability of adenoviruses to transduce dividing and nondividing cells and because of their high transduction efficiencies. Our goals were to examine the efficacy of AdVmIL-12 in a hepatocellular carcinoma model and to investigate the mechanism of the AdVmIL-12-mediated antitumor response with specific interest in the role of NK T cells. Our studies demonstrate that intratumoral AdVmIL-12-mediated regression of s.c. hepatocellular tumors is associated with rapid antitumor responses. AdVmIL-12 treatment was associated with an immune cellular infiltrate consisting of CD4 and CD8 T lymphocytes, macrophages, NK cells, and NK T cells. Antibody ablation of CD4 and CD8 T cells and use of NK cell-defective beige mice failed to abrogate the response to AdVmIL-12. Studies in T-cell- and B-cell-deficient severe combined immunodeficient and recombinase activating gene-2-deficient mice and T-cell-, B-cell-, and NK cell-defective severe combined immunodeficient/beige mice also failed to abrogate this response. AdVmIL-12 retained potent antitumor activity in mice with specific genetic defects in immune cellular cytotoxicity (perforin knockout mice) and costimulation (CD28 knockout mice). Use of mice with specific NK T cell deficiencies, Valpha14 T-cell receptor and CD1 knockout mice, also failed to abrogate the response to AdVmIL-12. Histological and immunohistochemical studies of AdVmIL-12-treated tumors showed extensive inhibition of neovascularization and a marked decrease in factor VIII-stained endothelial cells. Our studies indicate that the antitumor response of AdVmIL-12 is independent of direct cytotoxic cellular immunity (specifically, the function of NK T cells) and suggest that the initial mechanisms of AdVmIL-12-mediated tumor regression involve inhibition of angiogenesis.

Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen.

Acetaminophen (APAP), a widely used analgesic and antipyretic agent, can cause acute hepatic necrosis in both humans and experimental animals when consumed in large doses. It is generally accepted that N-acetyl-p-benzoquinone imine (NAPQI) is the toxic, reactive intermediate whose formation from APAP is mediated by cytochrome P450. Several forms of P450 in humans, including 2E1, 1A2, 2A6, 3A4, have been shown to catalyze the oxidation of APAP to NAPQI. We now present evidence which demonstrates that human cytochrome P450 2D6 (CYP2D6) is also involved in the bioactivation of APAP. The formation of NAPQI from APAP by cDNA-expressed CYP2D6 was examined. K(m) and V(max) values were 1.76 mM and 3.02 nmol/min/nmol of P450, respectively, such that the efficiency of CYP2D6 in the conversion of APAP to NAPQI is approximately one-third of that of CYP2E1. The contribution of CYP2D6 to the total formation of NAPQI from APAP (1 mM) in human liver was investigated using quinidine (1 microm) as a CYP2D6-specific inhibitor, and varied from 4.5 to 22.4% among 10 livers, with an average at 12.6%. The correlation between the contribution of CYP2D6 to NAPQI formation in human liver microsomes and the CYP2D6 activity probed by the O-demethylation of dextromethorphan was studied, and found to be strong (r(2) = 0.85), and significant (P <.0001). Our findings indicate that CYP2D6, one of the major P450 isoforms in humans and also one of the pharmacogenetically important isoforms, may contribute significantly to the formation of the cytotoxic metabolite NAPQI, especially in CYP2D6 ultra-rapid and extensive metabolizers and at toxic doses of APAP when plasma APAP concentrations reach 2 mM or more.

Recurrent gastrointestinal stromal sarcomas.

Gastrointestinal stromal sarcomas, formerly categorized as leiomyosarcomas of gastrointestinal origin, have a common pattern of intraperitoneal dissemination. Despite surgical resection with or without adjuvant systemic chemotherapy the vast majority of these patients succumb to intraperitoneal sarcomatosis and/or hepatic metastases. In an attempt to improve upon the morbidity and mortality associated with this disease we and several other centers have begun treating these patients with intraperitoneal chemotherapy. We have found that aggressive surgical resection with postoperative intraperitoneal chemotherapy has significantly lowered the peritoneal recurrence rate in patients with recurrent gastrointestinal stromal sarcomas as compared to those who have undergone surgical resection alone. However, this treatment approach has proven to be ineffective in preventing hepatic metastases, and thus has had little effect upon overall survival. With the treatment of primary rather than recurrent disease we hope to interrupt the disease process at an earlier stage further decreasing peritoneal recurrences and potentially improving survival.

Primary osteosarcoma of a metatarsal bone.

Although osteosarcoma is the most common primary bone malignancy of childhood and adolescence that is not related to marrow cells, involvement of the short tubular bones is uncommon. In contrast to more conventional sites, where the tumor is usually high grade and found in adolescents, osteosarcoma of the small bones is more likely to be low grade, and is often seen in older individuals. We present a case of low-grade primary osteosarcoma of a metatarsal bone in a 25-year-old woman.