Search PubMed⌕ Search

Biomedical subjects

M Roper

Publications and source records attributed to M Roper.

At least 19 recordsLinked to original sources

Application notes on the use of softer X-rays for anomalous powder diffraction.

An in-vacuum diffractometer has been modified to collect powder diffraction data from a sample of promazine hydrochloride. Strong anomalous contrast has been observed at, or close to, the sulphur edge. Based on the data collected, a bespoke diffractometer has been designed that, together with minor changes to the geometry of the experiment, will enable the routine collection of powder data at absorption edges below 5.5 keV.

Equipment Design↗

Reliability of the services assessment for children and adolescents.

OBJECTIVE: This study examined the test-retest reliability of a new instrument, the Services Assessment for Children and Adolescents (SACA), for children's use of mental health services. METHODS: A cross-sectional survey was undertaken at two sites. The St. Louis site used a volunteer sample recruited from mental health clinics and local schools. The Ventura County, California, site used a double-blind, community-based sample seeded with cases of service-using children. Participating families completed the SACA and were retested within four to 14 days. The reliability of service use items was calculated with use of the kappa statistic. RESULTS: The SACA- Parent Version had excellent test-retest reliability for both lifetime service use and previous 12-month use. The SACA also had good to excellent reliability when administered to children aged 11 and older for lifetime and 12-month use. Reliability figures for children aged nine and ten years were considerably lower for lifetime and 12-month use. The younger children's responses suggested that they were confused about some questions. CONCLUSIONS: This study demonstrates that parents and older children can reliably report use of mental health services by using the SACA. The SACA can be used to collect currently unavailable information about use of mental health services.

Adolescent↗

Informant-based determinants of symptom attenuation in structured child psychiatric interviews.

Informant-related determinants of item attenuation, that is, the drop-off in symptom endorsement rates at retest, were examined in an enriched community subsample of 245 parent-child pairs drawn from the National Institute of Mental Health Methods for Epidemiology of Child and Adolescent Mental Disorders Study. Youngsters and their parents were interviewed with the Diagnostic Interview Schedule for Children (Version 2.3; DISC-2.3) on two occasions with a mean test-retest interval of 12 days. Item attenuation rates were high for both informants, with adults failing to confirm 42% and children 58% of baseline responses at retest. Stepwise regressions revealed that item attenuation at DISC-P retest was higher for adult informants who were younger, and who reported on older and less impaired children. On the DISC-C, attenuation was higher for children who were less impaired, rated as doing worse in school, and who had a longer test-retest interval. These results are broadly consistent with past studies examining the determinants of attenuation and test-retest reliability and have implications for the design and use of structured diagnostic instruments.

Adolescent↗

Scales, diagnoses, and child psychopathology: II. Comparing the CBCL and the DISC against external validators.

Using a multimethod multistage screening procedure, the authors interviewed 201 parents and their children with the Diagnostic Interview Schedule for Children (DISC 2.1). In addition, parents completed the Child Behavior Checklist (CBCL) and other survey measures, while their children completed self-report scales. Receiver operating characteristic (ROC) analyses were done to determine optimal cutpoints on the CBCL, referenced to DISC diagnostic "caseness." DISC diagnoses, DISC "stem" symptoms, CBCL scores, and CBCL ROC-outpoints were compared against "external validators," in order to determine the comparative advantages of each approach for assessing child psychopathology. Overall findings suggest that the controversies about "best" assessment strategies may be artificial: When both assessment approaches are compared using similar methods, they are reasonably comparable. However, highly specific diagnostic categories may show fewer relationships with external validators and may therefore need more systematic validational studies.

Adolescent↗

Test-retest reliability of the Diagnostic Interview Schedule for Children (DISC 2.1). Parent, child, and combined algorithms.

BACKGROUND: Previous research has not compared the psychometric properties of diagnostic interviews of community samples and clinically referred subjects within a single study. As part of a multisite cooperative agreement study funded by the National Institute of Mental Health, 97 families with clinically referred children and 278 families identified through community sampling procedures participated in a test-retest study of version 2.1 of the Diagnostic Interview Schedule for Children (DISC 2.1). METHODS: The DISC was separately administered to children and parents, and diagnoses were derived from computer algorithms keyed to DSM-III-R criteria. Three sets of diagnoses were obtained, based on parent information only (DISC-P), child information only (DISC-C), and information from either or both (DISC-PC). RESULTS: Test-retest reliabilities of the DISC-PC ranged from moderate to substantial for diagnoses in the clinical sample. Test-retest kappa coefficients were higher for the clinical sample than for the community sample. The DISC-PC algorithm generally had higher reliabilities than the algorithms that relied on single informants. Unreliability was primarily due to diagnostic attenuation at time 2. Attenuation was greatest among child informants and less severe cases and in the community sample. CONCLUSIONS: Test-retest reliability findings were consistent with or superior to those reported in previous studies. Results support the usefulness of the DISC in further clinical and epidemiologic research; however, closely spaced or repeated DISC interviews may result in significant diagnostic attenuation on retest. Further studies of the test-retest attenuation phenomena are needed, including careful examination of the child, family, and illness characteristics of diagnostic stability.

Adolescent↗

Prevalence of mental disorder in military children and adolescents: findings from a two-stage community survey.

OBJECTIVE: Because previous reports have suggested that children of military families are at greater risk for psychopathology, this study examines the levels of psychopathology in an epidemiological community sample of military children all living on a military post. METHOD: Standardized psychopathology rating scales and a structured diagnostic interview (the Diagnostic Interview Schedule for Children [DISC], version 2.1) were used in a multimethod, multistage survey; 294 six- to seventeen-year-old military children and their parents participated in the study. RESULTS: Parent- and child-administered structured DSM-III-R DISC interviews indicated that children's levels of psychopathology were at levels consistent with studies of other normal samples. In addition, parents' and children's symptom checklist ratings of children were at national norms, as were parents' ratings of their own symptoms. CONCLUSIONS: Overall results do not support the notion that levels of psychopathology are greatly increased in military children. Further studies of military families should address the effects of rank and socioeconomic status, housing, and the current impact of life stressors on the parents as well as the children, in order to avoid drawing erroneous conclusions about parts or all of the military community.

Adolescent↗

Chemical analysis, prevention, and low-level dosimetry of heterocyclic amines from cooked food.

Potent mutagenic and carcinogenic heterocyclic amines are produced from heated food derived from muscle. These compounds are present at part-per-billion levels and consist primarily of the amino-imidazoazaarene class of chemicals. Additional mutagens present in the meat are not as clearly characterized. Commercial fried-beef patties (hamburgers) have low levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 0.1-0.68 ng/g meat for MeIQx and slightly lower for 4,8-DiMeIQx. The formation of these heterocyclic amines can be reduced by microwave pretreatment of meat, with the resulting liquid being poured off before frying. The Ames/Salmonella mutagenic activity was reduced to 5-10% of that of non-microwave-treated samples. MeIQx and DiMeIQx concentrations were reduced to 12% and 50% of levels in the non-microwave-treated samples, respectively. MeIQx adducts, as measured by accelerator mass spectrometry, were found to be linear with doses from 5 mg/kg to 500 ng/kg. Linear DNA binding at low doses is important for assuming linear risk estimation from the high animal-feeding doses causing cancer to the low human-dietary exposures. Extrapolating from the rodent TD50 dose to humans gives a maximum credible risk from consumption of heterocyclic amines of approximately 1/1000 exposed individuals.

DNA↗

Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice.

The metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), a heterocyclic amine carcinogen detected in cooked meats, was investigated in mice. In 3-methylcholanthrene-induced mice administered 0.1, 1.0 and 10 mg/kg [14C]PhIP (i.p.), urinary and fecal excretion over 24 h accounted for 16% and 42-56% of the dose respectively. Urinary excretion of unchanged parent compound accounted for only 0.5-0.8% of the administered dose. At all doses, the major urinary metabolite was identified as 4'-(2-amino-1-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulfate and this metabolite comprised approximately 5% of the dose. Uninduced mice excreted greater than 13% of a 10 mg/kg dose as the sulfate conjugate. Urinary excretion of both 2-amino-1-methyl-6-(4'-hydroxy)-phenylimidazo[4,5-b]pyridine (4'-hydroxy-PhIP) and a glucuronide conjugate of 2-hydroxyamino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (N-hydroxy-PhIP) was also higher (4-fold) in uninduced versus induced mice. The decreased urinary excretion of P450-derived metabolites via induction contrasted with increased metabolite formation by hepatic microsomal preparations. 4'-Hydroxy-PhIP and N-hydroxy-PhIP were produced in amounts nearly 7- and 3-fold higher respectively by induced versus uninduced microsomal incubations at 50 microM [3H]PhIP. At concentrations less than 10 microM, PhIP was almost exclusively converted by the induced preparations to an unidentified metabolite that was not retained by the C18 column. This metabolite, which also was formed in incubations with either 4'-hydroxy-PhIP or N-hydroxy-PhIP, was produced by microsomes from uninduced animals at a much slower rate. Covalent binding to microsomal protein in incubations with [3H]PhIP was concentration-dependent and 2- to 4-fold higher in induced than uninduced preparations. Covalent binding in liver and kidney of induced mice administered [14C]PhIP was dose dependent. At 10 mg/kg PhIP, adducts were produced at 1.7-fold higher levels in livers of induced versus uninduced mice, but renal binding was higher in uninduced animals. These studies indicate the importance of cytochrome P450 and other xenobiotic enzymes in the metabolism, disposition and activation of PhIP.

Animals↗

A phase I study of interleukin-2 in children with cancer.

Recombinant interleukin-2 (IL-2) produces clinical responses in approximately 20% of adult patients with renal cell carcinoma and melanoma, with both high-dose bolus and continuous infusion regimens. Because of the lower toxicity of continuous infusion, we elected to investigate in a Phase I trial a 5-day continuous infusion repeated for three weeks in children with malignancies refractory to standard therapy. Nineteen children with solid tumors and eight children with hematologic malignancies were entered into the study. The maximum tolerated dose was 3 x 10(6) U/m2/day, with dose-limiting toxicities occurring in five of seven patients treated at the 5 x 10(6) U/m2/day dose level. Dose-limiting toxicities included hypotension, hyperbilirubinemia, thrombocytopenia, pulmonary/pleural effusion, and nephrotoxicity. Serum IL-2 levels were detectable at the higher dose levels and were comparable to those observed in adult patients. Hematologic changes at the higher dose levels included rebound lymphocytosis occurring within 48 h of discontinuation of IL-2, eosinophilia, and decreased platelet counts. No objective responses to therapy were seen. We have identified a dose and schedule of administration for IL-2 in pediatric patients that can be given without intensive care unit support. Pediatric Phase II trials examining the anti-tumor activity of IL-2 given by this schedule are in progress.

Adolescent↗

Serum CD25 levels during interleukin-2 therapy: dose dependence and correlations with clinical toxicity and lymphocyte surface sCD25 expression.

Using an enzyme-linked immunosorbent assay (ELISA), we have measured serum levels of a soluble form of the p55 subunit of the interleukin-2 receptor complex, soluble CD25 (sCD25), at regular intervals in the sera of 51 pediatric and adult cancer patients receiving recombinant human interleukin-2 (IL-2). The IL-2 was administered in repetitive weekly cycles alone or in combination with lymphokine-activated killer (LAK) cells. Levels of CD25 correlated with clinical toxicities reflected by nadir blood pressures, percentages of weight gained, and minimum Karnofsky performances during IL-2 therapy. Coadministration of autologous in vitro activated LAK cells together with IL-2 did not significantly affect the pattern of sCD25 release relative to administration of IL-2 alone. Examination of sCD25 release in response to different doses of IL-2 revealed a statistically significant dose effect of IL-2 on the sCD25 levels in patient sera. In addition, the level of sCD25 in patient sera also correlated strongly with expression of CD25 on the surface of peripheral blood lymphocytes (PBL) obtained from patients following IL-2 therapy. These studies demonstrate the utility of the sCD25 ELISA as a clinical tool for monitoring patients on treatment regimens that include IL-2.

Antigens, CD↗

Proposed structures for an amino-dimethylimidazofuropyridine mutagen in cooked meats.

New analytical data allow the structure of a potent mutagen previously reported present in cooked meats to be proposed. The mutagen was isolated from a fried mixture of beef, creatine and milk, simulating a meat recipe previously shown to produce this compound. High-resolution mass spectra indicate a mol. wt of 202 and the formula C10H10N4O. Mutagenic activity was 10,000 TA1538 revertants per microgram in the Ames Salmonella test. From the NMR data, peaks showing an amino group at 6.812 p.p.m. and an N-methyl group at 3.520 p.p.m. were found, typical for the amino-imidazo structure commonly found in cooked meats. Additional signals at 2.440 p.p.m. (three protons), 7.653 (one proton) and 6.531 (one proton) were observed. A structure of 2-amino-(1 or 3),6-dimethylfuro[2,3(or 3,2)-e]imidazo- [4,5-b]pyridine was proposed based on the mass and NMR spectral data and comparison to literature compounds. The methylimidazofuropyridine reported here is probably related to another mutagen in cooked meats with a mol. wt of 216 with an additional methyl group on either the furan or pyridine rings.

Animals↗

Oncology.

Explore the source record for details and available documents.

Humans↗

A phase II study of interleukin-2 and lymphokine-activated killer cells in patients with metastatic malignant melanoma.

Thirty-six patients with metastatic melanoma were entered into a study of the therapeutic efficacy of adoptive immunotherapy with high-dose interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells. Thirty-two patients who received all components of the therapy are evaluable for response, and all patients are evaluable for toxicity. Sites of disease included lung, liver, subcutaneous nodules, and intra-abdominal metastases. One complete response (CR) and five partial responses (PRs) resulted from treatment (19% response rate). The median response duration was 5 months, with the durable CR continuing at 31+ months and one durable PR continuing for 13 months. Sites of response included lung, liver, subcutaneous nodules, and lymph nodes. Response, response duration, or site of response did not correlate with the total dose of IL-2 administered, rebound lymphocytosis, or the number of LAK cells infused. Toxicity included hypotension, fluid retention with a "capillary leak syndrome" in most patients, and transient multiorgan dysfunction that resolved promptly after the completion of therapy. Adverse cardiac events occurred in 16% of patients, with one myocardial infarction leading to a death. This study confirms the activity of the initial IL-2/LAK cell regimen in metastatic melanoma reported by Rosenberg et al, supporting the concept of adoptive immunotherapy as an important new treatment approach for this disease.

Adult↗