The overall response rates of malignant melanoma (MM) to ionizing radiation are similar to those of other malignant neoplasms. This is based on recent radiobiological data on MM cell lines and radiobiological analyses of large clinical experiences, using a spectrum of fractionation schedules on diverse MM lesions. In contrast to other carcinomas, MM exhibits an unusual spectrum of radiobiological responses characteristic for early- and late-response tissues implying that there is a wide range of sensitivities to radiation fraction sizes. This is confirmed by clinical response and tumor control data from prospective trials in which different fractionation schedules produced control rates between 40 and > 90%. These experiences suggest that primary MM lesions as well as skin and lymph node metastases may be more responsive to larger fraction sizes than parenchymal metastases. The same holds true when irradiation is used as an adjuvant for locoregional treatment of the primary MM and draining lymphatics. Total doses for maximum tumor control rates remain to be established for the different fractionation schemes of proven effectiveness. Hyperthermia in combination with regionally applied cytotoxic agents or irradiation has produced encouraging enhancements in MM cytotoxicity. However, due to contradicting results, these data need to be validated by additional clinical investigation.

Antineoplastic Agents↗

PubMedDate not supplied

Affective disorders in hospitalized children and adolescents with mental retardation: a retrospective study.

We contrasted a sample of children and adolescents with affective disorders and mental retardation with a comparison group on behavioral symptoms, associated diagnoses, and psychopharmacologic treatment. Fifty consecutive patients with both impaired intellectual functioning and at least one affective disorder admitted to a psychiatric inpatient unit for children and adolescents with developmental disabilities and psychiatric disorders were matched to a group of 50 inpatients without depression. Behavioral symptoms such as suicidal ideation or gestures, crying, irritability, sleep problems, agitation, mood lability, and social withdrawal/isolation occurred significantly more often in the affective group than in the comparison group. Aggression, however, was the most frequent behavior concern for both groups, whereas disruption/destruction was identified significantly more often in the comparison group. Regarding Axis I diagnoses, the comparison group was more often identified with externalizing disorders (ADHD, ODD), though there was a high rate of comorbidity in the affective disorder group. The behavioral symptoms used to diagnosis normally developing children and adolescents appear to be applied in making affective disorders diagnoses in this sample of children and adolescents with mental retardation.

Adolescent↗

PubMedDate not supplied

Colloid mobilization in the field using citrate to remediate chromium.

We investigated the feasibility of cleaning aquifer sediments, long contaminated with chromium (Cr) from a metal plating facility, by detaching colloid-sized sorbents from the immobile aquifer solids and then pumping those colloids to the surface for treatment. In laboratory experiments using aquifer solids from the site, several solutions (water at various pHs, phosphate, oxalate, ascorbate, citrate) were examined for their ability to disperse colloids and Cr. Based on these tests, a 5 mM citrate solution at pH 7 was selected. Subsequently, such a citrate solution was used in the field in two single-well injection-withdrawal experiments. Large quantities of colloids were released immediately after injection. The colloidal particles mobilized by citrate in the field had more than 20 times higher Cr concentrations than did the average aquifer sediments, implying success in mobilizing Cr-associated phases. Further, laboratory and field tests showed that anion exchange of citrate for chromate caused some additional release of Cr from these aquifer solids.

Chelating Agents↗

PubMedDate not supplied

Research benefits of generalized toxicological data retrieval.

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Computers↗

PubMedDate not supplied

Modulation of rat lung Na+,K(+)-ATPase gene expression by hyperoxia.

Rats exposed to 85% O2 for 5-7 days develop tolerance to otherwise lethal hyperoxia (100% O2). The rate of alveolar fluid clearance increases during adaptation to hyperoxia, due in part to increased alveolar epithelial sodium channel activity. In these studies, we have investigated molecular mechanisms leading to increased lung Na+,K(+)-ATPase activity in hyperoxia. We exposed adult rats to 85% O2 (sublethal hyperoxia) for 7 days, followed by 2, 3, or 4 days in 100% O2. Steady-state levels of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNAs increased in whole lung tissue during hyperoxia exposures. Stability of the Na+,K(+)-ATPase alpha 1 and beta 1 subunit mRNA messages in whole lung RNA did not change significantly. Thus, lung Na+,K(+)-ATPase gene expression in sublethal hyperoxia appears to be regulated in part at the transcriptional level. Alveolar epithelial type II (ATII) cell Na+,K(+)-ATPase alpha 1 and beta 1 subunit proteins, measured by quantitative immunofluorescence, increased significantly after sublethal hyperoxia and 100% O2 exposures. Increases in lung fluid clearance after sublethal hyperoxia are associated with increased ATII cell Na+,K(+)-ATPase protein and whole lung Na+,K(+)-ATPase mRNA expression, which correspond to previously described increases in epithelial sodium channel expression under these conditions.

Animals↗

PubMedDate not supplied

A novel hydroxamic acid compound, BMD188, demonstrates anti-prostate cancer effects by inducing apoptosis. II: In vivo efficacy and pharmacokinetic studies.

BACKGROUND: In the preceding paper, we demonstrated that, BMD188 [cis-1-hydroxy-4-(1-naphthyl)-6-octylpiperidine-2-one], a newly synthesized cyclic hydroxamic acid compound, induces potent apoptotic death of prostate cancer cells in vitro. In this project, we studied the in vivo pharmacokinetic behavior and anti-tumor efficacy of this novel compound. MATERIALS AND METHODS: A bioavailability/elimination study was first performed using radiolabeled BMD188 administered to rats through intraperitoneal (i.p.), intravenous (i.v). or oral (p.o.) routes. Based on these pharmacokinetic data as well as pilot experiments on in vivo toxicity, two sets of efficacy studies, with i.p. administered BMD188, were performed in SCID mice or athymic nude mice which had been orthotopically transplanted with Du145 human prostate cancer cells. Tumor growth rate was measured and the final tumor weights and sizes determined. Subsequently, histopathological data were obtained and tumor tissue sections were used for apoptosis (i.e., TUNEL) staining. RESULTS: The pharmacokinetic studies revealed low (approximately 8%) absorption through the p.o. route and high (approximately 70%) absorption through the i.p. route. The average plasma half life (T1/2) of BMD188 was approximately 50 h. Post-absorption, plasma elimination of radioactivity was similar to that in animals given [3H]-188 intravenously. The in vivo efficacy results indicate that i.p. administered BMD188 significantly inhibited the primary growth and local invasion of Du145 prostate cancer cells orthotopically implanted into SCID or athymic nude mice. The tumor-inhibitory effect of BMD188 was due to apoptosis induction in vivo, as revealed by histological analysis as well as TUNEL staining of the tumor tissue sections. CONCLUSION: Collectively, the preceding in vitro and the current in vivo studies suggest that BMD188 and its analogs may find clinical applications in the treatment of prostate cancer patients by inducing apoptotic death of prostate cancer cells.

Animals↗

PubMedDate not supplied

NCTR computer systems designed for toxicologic experimentation. IV. Experiment information system.

The Experiment Information System (EIS) is a computerized data collection, maintenance, and reporting system for specified information values collected during the lifespan of animals assigned to toxicologic investigations at NCTR. The system records and/or controls experimental variables, which might ultimately affect the results, through the operation and integration of the Diet Preparation Subsystem (DPS), the Environmental Monitoring Subsystem (EMS), the Microbiology Subsystem (MBS), and the Chemistry Data Subsystem (CDS). The fifth component of the EIS, the Experimental Data Collection Subsystem (EDCS), is responsible for handling all data generated by, or attributed to, the animals from assignment until death or removal. Through integration of these five subsystems, the history of an animal while on study is recorded and stored for later recall. In addition, "routine" and "special" reports are made available through the system software which enables stringent control of the experiment by the Principal Investigator, Animal Husbandry, and NCTR Management.

Animals↗

PubMedDate not supplied

Vaginal cytology as an aid in predicting normal pregnancy.

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Abortion, Spontaneous↗