Bioaccumulation of lead in different organs of Ctenopharyngodon Idella (grass fish) and Tor putitora (Mahseer) fish.

Bioaccumulation of toxic heavy metals in the human body can give rise to adverse health effects, the severity of which depends upon their dosage and duration of exposure. In this study, yearlings of two different species of edible fish, i.e., Tor putitora (Mahseer) and Ctenopharyngodon Idella (grass carp), were exposed to different concentrations of lead nitrate in a controlled environment of aquarium for three different lengths of duration (14, 28, and 60 days). The bioaccumulation of lead in different organs, including gills, skin, muscles, liver, intestine, and swim bladder of the fish, was assessed using atomic absorption spectrometry. Generally, the highest lead concentration was observed in the gills and lowest in the muscles for both species at each experimental dosage and duration. In 14-days exposure, the relative pattern of bioaccumulation in different organs was observed as gill > liver > skin > intestine > swim bladder > muscle for both fish species. Similarly, the pattern of bioaccumulation observed in 28-days exposure was as: gill > liver > intestine > skin > swim bladder > muscle in both species. Whereas, pattern in 60-days exposure was observed as gill > liver > intestine > swim bladder > muscle > skin. The data shows that grass carp had stored higher concentrations of lead than Mahseer, which may be attributed to the fact that they are omnivorous. Furthermore, the lowest bioaccumulation was recorded in the muscles until the 56th day of the exposure, after which the concentration steadily increased in the muscles. The observed pattern highlights the importance of exposure's duration to lead; chronic exposure could result in its bioaccumulation at toxic concentrations in the muscles, which is particularly of concern because the fish muscles are heavily consumed as food worldwide.

DNA Sensing using Nano-crystalline Surface Enhanced Al(2)O(3) Nanopore Sensors.

A new solid-state, Al(2)O(3) nanopore sensor with enhanced surface properties for the real-time detection and analysis of individual DNA molecules is reported. Nanopore formation using electron beam based decomposition transformed the local nanostructure and morphology of the pore from an amorphous, stoichiometric structure (O to Al ratio of 1.5) to a hetero-phase crystalline network, deficient in O (O to Al ratio of ~0.6). Direct metallization of the pore region was observed during irradiation, thereby permitting the potential fabrication of nano-scale metallic contacts in the pore region with potential application to nanopore-based DNA sequencing. Dose dependent phase transformations to purely γ and/or α-phase nanocrystallites were also observed during pore formation allowing for surface charge engineering at the nanopore/fluid interface. DNA transport studies revealed an order of magnitude reduction in translocation velocities relative to alternate solid-state architectures, accredited to high surface charge density and the nucleation of charged nanocrystalline domains. The unique surface properties of Al(2)O(3) nanopore sensors makes them ideal for the detection and analysis of ssDNA, dsDNA, RNA secondary structures and small proteins. These nano-scale sensors may also serve as a useful tool in studying the mechanisms driving biological processes including DNA-protein interactions and enzyme activity at the single molecule level.

Utilization of oral hypoglycemic agents in a drug-insured U.S. population.

OBJECTIVE: Clinical trials provide information regarding the safety and efficacy of medications used to manage type 2 diabetes but do not elucidate drug effectiveness in a typical managed care environment. The aim of this study was to characterize "real-world" drug utilization patterns from both a prescriber and a patient perspective. RESEARCH DESIGN AND METHODS: We conducted a retrospective analysis of a large administrative pharmacy claims database, using data on continuously pharmacy benefit-eligible members prescribed oral hypoglycemic agents (OHAs). RESULTS: The 12-month persistence rate for the OHA cohort was low, ranging from 31% for alpha-glucosidase inhibitors to 60% for metformin; compliance rates varied between 70 and 80%. During the first 12 months of therapy, 36% of the patients remaining on therapy at 12 months had one or more therapy modifications. The mean number of therapy changes increased with the length of patient follow-up, with more than half of all patients experiencing at least one therapy change over the duration of follow-up. CONCLUSIONS: These findings document the wide variation in utilization patterns associated with pharmacological management of type 2 diabetes, suggesting that opportunity exists to optimize its pharmacological management.

Meningiomas: report of a hospital-based registry.

This is a hospital-based epidemiologic study of meningiomas. Of 1321 central nervous system tumours, meningiomas constituted 21% of the cases, being the second largest category of a single histologic type after astrocytomas. Of the 267 meningiomas studied, 247 were intra-cranial (92.5%). The age of the patients varied between 6 to 84 years. Histological subclassification is presented and treatment schedules discussed. 261 (98%) meningiomas were histologically benign and 5 were malignant meningiomas (1.9%). A 5-year follow-up was available in most cases, with the help of which it was possible to understand the biological behaviour of various sub-types and the influence of other parameters such as location and treatment schedules. Of note was the fact, that out of 261 patients with benign meningiomas, 11 succumbed in the immediate post-operative period and in 8 of these cases, the tumour was located at the base of the skull.

pubmed.mineR: an R package with text-mining algorithms to analyse PubMed abstracts.

The PubMed literature database is a valuable source of information for scientific research. It is rich in biomedical literature with more than 24 million citations. Data-mining of voluminous literature is a challenging task. Although several text-mining algorithms have been developed in recent years with focus on data visualization, they have limitations such as speed, are rigid and are not available in the open source. We have developed an R package, pubmed.mineR, wherein we have combined the advantages of existing algorithms, overcome their limitations, and offer user flexibility and link with other packages in Bioconductor and the Comprehensive R Network (CRAN) in order to expand the user capabilities for executing multifaceted approaches. Three case studies are presented, namely, 'Evolving role of diabetes educators', 'Cancer risk assessment' and 'Dynamic concepts on disease and comorbidity' to illustrate the use of pubmed.mineR. The package generally runs fast with small elapsed times in regular workstations even on large corpus sizes and with compute intensive functions. The pubmed.mineR is available at http://cran.rproject. org/web/packages/pubmed.mineR.

Prostacyclin infusion in acute cerebral infarction.

We gave prostacyclin infusions to seven patients with acute cerebral infarction. Patients without CT evidence of infarction improved, but those who already had hypodensities on CT did not benefit. Increased platelet activity, measured by plasma beta-thromboglobulin, decreased significantly (p less than 0.01) during prostacyclin administration to normal levels, but rose again after the infusion. These results indicate that prostacyclin can be given safely in doses adequate to suppress platelet function. Our findings encouraged us to proceed with a controlled trial of its clinical efficacy.

Patterns of failure following bone marrow transplantation for metastatic breast cancer: the role of consolidative local therapy.

PURPOSE: The purpose of this analysis is to evaluate the patterns of failure and the role of local therapy in conjunction with bone marrow transplantation (BMT) for metastatic or recurrent breast cancer. METHODS AND MATERIALS: Between June 1986 and November 1991, 46 patients with hormone unresponsive metastatic or recurrent breast cancer underwent high dose chemotherapy (HDC) with hematopoietic stem cell support. The most commonly used preparative regimen consisted of thiotepa (750 mg/m2), cisplatin (150 mg/m2), and cyclophosphamide (120 mg/kg) followed by autologous BMT. Consolidative surgery or irradiation was considered in patients whose cancer responded to BMT and had localized sites of disease. RESULTS: Six patients (13%) died of BMT-related complications. Of the remaining 40 patients, 22 were candidates for consolidative therapy, and 18 of those patients received consolidative irradiation (17 patients) or surgery (1 patient) to one or more sites. At median follow-up of 27 months (range, 20-78), 12 of 18 (67%) patients have continuous local control at the 22 consolidated sites (1 of 4 controlled at chest wall sites, 7 of 8 at regional nodal sites, 7 of 7 at localized bone sites, and 1 of 3 at lung/mediastinal sites). Toxicity of consolidative irradiation was mainly limited to myelosuppression in 6 of 17 patients. Two patients did not complete the consolidative local therapy, one because of hematologic toxicity and one because of rapid systemic tumor progression during treatment. CONCLUSION: In patients with localized areas of extravisceral metastases, consolidative irradiation is feasible with acceptable hematologic toxicity. Consolidative irradiation can result in continuous local control, especially in isolated bone metastases and in regional nodal sites; however, the advantage is less clear in patients undergoing consolidative irradiation for chest wall failures. Because distant visceral metastases still remain a major site of failure after this HDC regimen, a more effective systemic therapy is needed. Consolidative local treatment should be considered in future HDC/BMT protocols for metastatic breast cancer, especially in localized nodal and osseous sites.

Cutaneous and subcutaneous Ewing's sarcoma: an indolent disease.

PURPOSE: The occurrence of extraosseous Ewing's sarcoma (ES) in deep soft tissues has been well described, but cases in which this tumor occurs in a primary cutaneous or subcutaneous site have rarely been reported. The superficial variant may be less aggressive than are the more common bony and deep soft tissue counterparts with an apparently favorable outcome. A retrospective review of patients with cutaneous or subcutaneous ES was conducted to analyze outcome and patterns of failure. METHODS AND MATERIALS: Between July 1985 and March 1997, 14 patients with cutaneous or subcutaneous ES were treated at St. Jude Children's Research Hospital. The median age at presentation was 16 years (range 7-21 years). Anatomic locations included trunk and pelvis (7), upper or lower extremity (4), and head and neck (3). The median size of the lesion was 3 cm (range, 1-12 cm). Thirteen had definitive surgical resections, and one had biopsy of the mass at the time of referral. They were enrolled on institutional (12) or cooperative group (2) protocols. All patients received chemotherapy, composed of vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide, and dactinomycin. Patients on institutional protocols received radiation (36 Gy) to the operative bed (150-180 cGy/fraction/day). Postoperative radiotherapy was omitted for 2 patients who had complete resection on the cooperative group study. RESULTS: No patients had metastatic disease at presentation. Thirteen patients had wide local excision of the primary tumors prior to enrollment on chemotherapy; surgical margins were negative (10), microscopically positive (2), and indeterminate (1). Eleven patients received radiotherapy to the tumor bed; 2 with clear surgical margins were treated without irradiation. The patient who had biopsy only received induction chemotherapy followed by definitive surgical resection and postoperative radiotherapy. The median follow-up was 77 months (range 17-111 months). None of the patients has developed local recurrence or distant metastasis. Several of the patients developed treatment-related sequelae, including veno-occlusive disease of the lung and hemorrhagic cystitis (1), myelodysplastic syndrome (1), chemotherapy-induced ovarian failure (1), moist desquamation (1), and dermatofibroma within the radiotherapy volumes (1). CONCLUSIONS: Cutaneous and subcutaneous ES are associated with an indolent course and a favorable prognosis when treated with combined modality therapy. Elimination of radiation therapy following complete resection has been tested in the POG 9354 trial. The high rate of local control, low rate of metastatic disease, and excellent overall outcome may suggest a role for less intensive chemotherapy, as well as tailoring to diminish or avoid radiation therapy in completely resected cases, with a goal to minimize toxicity while maintaining a high cure rate.

Long-term follow-up of patients treated with primary radiotherapy for supradiaphragmatic Hodgkin's disease at St. Jude Children's Research Hospital.

OBJECTIVE: To assess disease control, patterns of relapse, factors predictive of relapse, and late effects of treatment, we reviewed all cases of supradiaphragmatic (SD) Hodgkin's disease (HD) treated with primary radiation therapy (RT) at our institution. METHODS: We retrospectively reviewed the disease characteristics, treatment history, and long-term outcome of the 106 patients with Stage I and II supradiaphragmatic HD who received definitive irradiation at St. Jude Children's Research Hospital between 1970 and 1995. As of the date of analysis, 95 patients are alive, with a median follow-up of 13.3 years (range, 1.9-24.2 years). RESULTS: The median age at diagnosis was 14.7 years (range, 3.7-22.7). Involved-field RT was given to 13 patients (12%), whereas 37 (35%) had mantle RT, 51 patients (48%) had subtotal nodal irradiation, and 5 (5%) had total nodal irradiation. Relapsed disease developed in 26 patients at a median of 1.8 years (range, 0.2-9.3 years). The 5- and 10-year estimated cumulative incidences of relapse were 20.9% +/- 4.0% and 25.1% +/- 4.3%, respectively. With a median dose of 36 Gy (range, 32-40), in-field failure rate was 6.2%, whereas subdiaphragmatic relapse in sites irradiated prophylactically was 1.5%. There was a trend toward an increased incidence of relapse with higher ESR (p = 0.088) and greater number of sites of disease (p = 0.087). Age, stage, histology, nodal disease > or = 6 cm, the presence of bulky mediastinal disease, and the method of staging did not affect the incidence of relapse. The pattern of failure could not be predicted based on the stage of disease, the extent of subdiaphragmatic staging, the extent of radiation therapy, or the sequence of RT fields-"ping pong" vs. sequential. Subset analysis of Stage II patients revealed significantly more relapses in clinically staged patients. Excluding Stage IA patients with high cervical disease or peripheral nodal disease, nodal extension failures were more common for patients undergoing limited-volume RT, whereas extranodal relapses were likely after STNI or TNI. The estimated 10- and 15-year cumulative incidences of second malignancies were 2.9% +/- 1.6% and 7.9% +/- 3.3%, respectively. Our patients are at increased risk of second malignancies (11-fold), and fatal cardiac (68-fold) and infectious (33-fold) complications. Overall survival at 10 years was 90.8% +/- 3.2%; event-free survival was 72.1% +/- 5.0%. CONCLUSIONS: The current analysis confirms the curative potential of RT for HD in children and adolescents. Despite successful salvage therapy, relapsed disease remained the principal cause of death in our cohort. Excess risk of septic death in asplenic patients, fatal heart disease, and second malignancies may further compromise the ultimate cure of HD in long-term survivors.

Pediatric choroid plexus neoplasms.

PURPOSE: Choroid plexus tumors (CPT) are rare childhood neoplasms. The relatively small number of reported cases and the controversies surrounding the clinical and pathological classification of these tumors have made it difficult to define a standard of care for these patients. Our intention is to contribute to the body of knowledge of these tumors and further define the role of adjuvant therapy. METHODS AND MATERIALS: We performed a retrospective review of 14 children with choroid plexus neoplasms referred to St. Jude Children's Research Hospital between October 1985 and December 1987. Ten patients had choroid plexus carcinoma (CPC) based on pathologic criteria and evidence of brain invasion at surgery or leptomeningeal disease (M+); 4 patients had choroid plexus papilloma (CPP). Patients with CPP were initially treated with surgery alone whereas patients with CPC were generally treated with postoperative therapy that included chemotherapy (CT) and/or craniospinal irradiation (CSI) with a focal boost to the primary site. For most patients CT consisted of combinations of cyclophosphamide, etoposide, vincristine, and a platinum agent. The median CSI dose was 35.2 Gy (range 24-46.2 Gy). The median primary site dose was 55.2 Gy (range 49.6-64 Gy). RESULTS: Seven of the 10 CPC cases presented with leptomeningeal dissemination; two of these patients have succumbed to disease. Of the 3 patients with M0 status, all are alive with no evidence of disease (NED). The medial time to relapse from the time of surgery was 5.3 mo (range 3-25 mo). Seven CPC patients were treated with gross total resection (GTR). Three of these patients (2 M0, 1 M+) received CT without CSI and are currently NED (27, 69, and 60 mo respectively). One M+ patient progressed on CT and has stable disease after CSI (6 mo), one (M0) received CT and CSI and is NED (120 mo), one (M+) is currently on CT with objective response (3 mo) and one (M+) died of progressive disease (24.5 mo) despite CT and CSI. Three patients with CPC had subtotal resection (STR). One of these patients (M+) received CT and CSI and is NED (23 mo), one (M0) had an elective second resection GTR alone and is currently NED (153 mo), and one (M+) developed progressive disease (13.5 mo) while on CT and died despite CSI. Among the 4 CPP patients, GTR was performed in two; both were NED at 54 and 81 mo. Two patients with CPP (one with focal atypia) were treated with STR initially; both transformed to CPC at 7 and 27 mo, respectively. Both were currently NED following salvage with (1) GTR and CSI alone (98 mo) or (2) STR, CT, and CSI (62 mo). Six of the 12 survivors in this series had significant neuropsychological sequelae. CONCLUSION: The prognosis of CPP is good for patients treated with GTR. Malignant transformation occurred in 2 CPP patients with less than GTR. Patients with localized CPC who undergo GTR have had a favorable outcome with the addition of chemotherapy or irradiation. CSI may not be routinely indicated in M0 children following GTR. There is evidence that salvage with radiation therapy may be successful following progression on chemotherapy. For patients treated with STR, the use of CT and CSI appears to be necessary.

Magnetic microcapsules as novel biomonitors of cross-linking agents and diet-dependent reactive oxygen species in the human gastrointestinal tract.

Six healthy, scientifically informed human volunteers were given 14C-labeled polyethyleneimine (PEI) microcapsules by mouth. Fecal 14C recovery was inversely related to mean gut transit time (r = -0.66), and the extent of cross-linking between the membrane and core PEI was inversely related to total fecal output (r = -0.81). Cross-linking of PEI microcapsules may be a biomonitor of endogenous cross-linking agents within the human gastrointestinal tract. Extensive loss of [14C]CH3 label occurred from the microcapsules during human transit and in in vitro fermentations with human fecal flora. A mechanism whereby reactive oxygen species could arise in the iron-rich core of these microcapsules, leading to loss of [14C]CH3 label, is proposed.

Squamous cell cancer of female urethra. Successful treatment with chemoradiotherapy.

We report the case of a seventy-four-year-old woman with advanced squamous cell carcinoma of the urethra who achieved complete biopsy-proved regression of the tumor for more than thirty months after therapy with 5-fluorouracil, mitomycin-C, and radiotherapy.

Regional localization of [14C] methylphenidate in rabbit brain.

1. Neuroanatomical distribution of [14C] methylphenidate has been examined in rabbit brain following intracerebroventricular administration. 2. After about a week of implantation of cannula, in lateral ventricle, in albino rabbits, [14C] methylphenidate was injected through the cannula. The distribution of [14C] methylphenidate was examined at 15, 60 and 180 min after the injection in twelve brain regions. 3. The highest levels were observed at the first sampling time (15 min), in medulla and cervical spinal cord. Pons, caudate, tegmentum and hypothalamus also showed significant uptake of [14C] methylphenidate. Cerebral cortex and thalamus showed very low uptake. 4. The uneven distribution suggests a special affinity of methylphenidate for certain brain regions. The implications of this finding for the central actions of methylphenidate are discussed.

The influence of nisoldipine--a "calcium entry blocker" on drug induced stereotyped behavior in rats.

In view of potential ability of calcium entry blockers to affect Ca2+ fluxes in neurons, the effects of nisoldipine on phencyclidine (PCP) and apomorphine (APO) induced stereotyped behavior have been examined in 3 and 4 week old rats. The rats (3 and 4 weeks old) were pretreated with either 0.2 ml of saline + ethanol mixture (10:1 v/v) or nisoldipine (25 mg/kg) i.p., 5 min before the i.p. administration of PCP (5 mg/kg) or APO (10 mg/kg). While nisoldipine pretreatment significantly blocked the PCP induced stereotypy in 3 and 4 week old rats, the APO induced stereotypy was not altered. These preliminary data suggest that nisoldipine specifically blocks PCP induced stereotypy probably by antagonizing it effects at the presynaptic level. The significance of this finding in relation to mechanism of action of PCP and calcium entry blockers is discussed.

Distribution and excretion of 1,8-dinitro[14C]pyrene in the mouse.

The disposition of the environmental pollutant and potent mutagen and carcinogen, 1,8-dinitropyrene (DNP) in female BALB/c mice was investigated. In the first 48 h after oral administration of 1,8-dinitro[4,5,9,10-14C]pyrene ([14C]DNP), 42% of the dose was eliminated in the faeces and 12% in the urine. Faeces was the major pathway of excretion with 45% of the dose being eliminated by this route in 9 days. Distribution of DNP in various tissues (blood, liver, spleen, lungs, kidneys, stomach, small and large intestine) was studied over 9 days. There was a linear increase in the concentration of radioactive material in the blood, liver and kidneys up to 6 h after [14C]DNP administration, representing 0.27, 2.9 and 0.21% of the radioactive dose, respectively. The corresponding figures after 24 h decreased to 0.1, 1.6 and 0.12%, respectively. In comparison, radioactivity present in the spleen and lungs was low and did not significantly change with time. In studies with ligated sections of the gastrointestinal tract, DNP absorption was from the small and large intestine and there was none from the stomach. The rate of absorption of DNP from the small intestine was greater than that from the large intestine, although overall uptake of the compound was poor (more than 80% of the original dose was recovered from the ligated small intestine after 120 min). The data from these studies suggest that although absorption of orally administered DNP is slow, the compound or its metabolites persist in the body for long periods and the liver should be considered as the major target organ.

Interaction with microsomal lipid as a major factor responsible for S9-mediated inhibition of 1,8-dinitropyrene mutagenicity.

1,8-Dinitropyrene (1,8-DNP), present in polluted air, is a rodent carcinogen and a potent, direct-acting mutagen in salmonella typhimurium TA98. This mutagenicity is markedly reduced in the presence of mammalian hepatic S9 or microsomes. We demonstrate that at least a substantial part of this effect is attributable to non-enzymatic processes. The microsomal-dependent inhibition was unaffected by omission of an NADPH-generating system or when the cytochrome P-450 inhibitor, SKF-525A, or the cytochrome P-448 inhibitor, ellipticine, was incorporated in the metabolic activation system, suggesting that mixed function oxidases are not involved. Heat inactivation partially decreased the ability of induced S9 to reduce DNP mutagenicity. Substitution of S9 with a similar concentration of bovine serum albumin did not affect DNP activity. Thus non-specific binding to microsomal protein is not involved. However, when lipids, derived from uninduced microsomes, were added to incubations of DNP and S. typhimurium TA98, mutagenicity was decreased. Furthermore, substitution of microsomal lipids with a suspension of phosphatidylcholine (PC), a major lipid constituent of microsomes, affected DNP mutagenicity similarly. An increase in PC concentration resulted in a greater inhibitory effect. The reduction in DNP mutagenicity observed with microsomal lipids or with PC was less than that detected with uninduced S9, whilst the mutagenicity of 2-nitrofluorene was reduced to an approximately equal extent by lipids and S9. This phenomenon may be responsible for the S9-mediated detoxification of other mutagenic nitroaromatic compounds and may have important implications for mutagenicity testing.

Inhibition of dinitropyrene mutagenicity in vitro and in vivo using Salmonella typhimurium and the intrasanguinous host-mediated assay.

Dinitropyrenes (DNP), present in polluted air, are potent direct-acting mutagens in Salmonella typhimurium TA98. This mutagenicity is markedly reduced in the presence of rat-liver S9 or microsomes. This has now been confirmed using mouse hepatic fractions. Since most in vitro test systems do not adequately simulate conditions encountered in the intact animal, we have investigated dinitropyrene mutagenicity to Salmonella in the host-mediated assay. 1,8-Dinitropyrene (1,8-DNP) given p.o. to BALB/c mice induced a weak mutagenic effect in S. typhimurium TA98 recovered from the liver 1 h after i.v. administration (optimum time). Over the entire dose range tested no toxicity to bacterial cells was detected. Mutation induction in vivo was dose-related with maximum response at 1 mg DNP/kg body weight. This optimum dose, however, was non-mutagenic to strains TA98/1,8-DNP6 (O-transacetylase-deficient) or TA98NR/1,8-DNP6 (nitroreductase- and O-transacetylase-deficient). 1,3-Dinitropyrene and 1,6-dinitropyrene were weakly mutagenic to TA98 at doses similar to 1,8-DNP. Studies with [14C]1,8-DNP showed that 1 h after oral dosing (1 mg/kg), over 100 ng of 1,8-DNP equivalents were present in the liver (= 0.73% dose). However, only about 5.5 ng were present in the bacterial pellet, suggesting that hepatic components in vivo, as in vitro, bind to DNP, thus interfering with its interaction with Salmonella.

Squash preparation and frozen section in intraoperative diagnosis of central nervous system tumors.

OBJECTIVE: To investigate the diagnostic accuracy of squash preparation (smears) and frozen section (FS) in the rapid intraoperative diagnosis of central nervous system (CNS) tumors. STUDY DESIGN: One hundred eighty-three CNS tumors were examined over a period of 18 months (January 1995-June 1996). All these were open biopsies, and the smear interpretation was compared with FS findings and paraffin section diagnosis. RESULTS: In 183 tumors, squash preparation was satisfactory in 156 cases (85.2%), and the diagnostic accuracy was 89.7% (140/156). The accuracy of FS diagnosis was 90.4% (141/156). CONCLUSION: The squash smear preparation is a fairly accurate and reliable tool in the rapid intraoperative diagnosis of CNS tumors. The accuracy of this technique is nearly as good as that of FS (P value = .9877). With the advent of stereotactic biopsies, the pathologist may have to depend entirely upon cytologic features for a definitive diagnosis.

Traumatic diaphragmatic rupture: associated injuries and outcome.

A retrospective case note analysis was performed on all patients treated for traumatic diaphragmatic rupture (TDR) at a major teaching hospital between January 1990 and August 1998. Patients were identified from the prospectively maintained UK Trauma and Research Network Database. Of the 480 cases of torso trauma admitted during the study period, 16 (3.3%) had TDR. Blunt trauma accounted for 13 (81%) of the injuries. A radiological pre-operative diagnosis was made in 10 (62.5%) patients. Seven of these were made on initial chest radiography, two on ultrasound scan and one on computed tomography. All patients underwent a midline laparotomy and TDR was subsequently diagnosed at operation in 6 patients. The left hemidiaphragm was ruptured in 14 (87.5%) patients and there was visceral herniation in 8 (50%). Twelve patients with blunt trauma had associated abdominal and extra-abdominal injuries, but only one of the three patients with penetrating trauma had other injuries. The median Injury Severity Score (range) was 21 (9-50). The median time (range) spent on the intensive care unit was 2 days (0-35 days). Pulmonary complications occurred in 7 (44%) patients. Two (12.5%) patients died from associated head injuries. TDR results from blunt and penetrating torso trauma, is uncommon, rarely occurs in isolation and is associated with a high morbidity and mortality. A high index of suspicion makes early diagnosis more likely as initial physical and radiological signs may be lacking.

RTOG 0518: randomized phase III trial to evaluate zoledronic acid for prevention of osteoporosis and associated fractures in prostate cancer patients.

BACKGROUND: RTOG 0518 evaluated the potential benefit of zoledronic acid therapy in preventing bone fractures for patients with high grade and/or locally advanced, non-metastatic prostate adenocarcinoma receiving luteinizing hormone-releasing hormone (LHRH) agonist and radiotherapy (RT). METHODS: Eligible patients with T-scores of the hip (<-1.0, but >-2.5 vs >-1.0) and negative bone scans were prospectively randomized to either zoledronic acid, 4 mg, concurrently with the start of RT and then every six months for a total of 6 infusions (Arm 1) or observation (Arm 2). Vitamin D and calcium supplements were given to all patients. Secondary objectives included quality of life (QOL) and bone mineral density (BMD) changes over a period of three years. RESULTS: Of 109 patients accrued before early closure, 96 were eligible. Median follow-up was 36.3 months for Arm 1 and 34.8 months for Arm 2. Only two patients experienced a bone fracture (one in each arm) resulting in no difference in freedom from any bone fracture (P=0.95), nor in QOL. BMD percent changes from baseline to 36 months were statistically improved with the use of zoledronic acid compared to observation for the lumbar spine (6% vs -5%, P<0.0001), left total hip (1% vs -8%, P=0.0002), and left femoral neck (3% vs -8%, P=0.0007). CONCLUSIONS: For patients with advanced, non-metastatic prostate cancer receiving LHRH agonist and RT, the use of zoledronic acid was associated with statistically improved BMD percent changes. The small number of accrued patients resulted in decreased statistical power to detect any differences in the incidence of bone fractures or QOL.