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Biomedical subjects

K Norton

Publications and source records attributed to K Norton.

At least 37 records · Page 2Linked to original sources
PubMed1994

Outcome of outpatient psychotherapy in a random allocation treatment study of anorexia nervosa.

Ninety subjects with DSM-III-R anorexia nervosa were randomly allocated to four treatment options, one inpatient, two outpatient, and one comprising an assessment interview only. Twenty were thus offered a package of outpatient individual and family psychotherapy. At 2-year follow-up, 12 of the 20 were classed as well, or very nearly well, according to operationally defined criteria. Statistically significant improvements over time were obtained for weight, mean body mass index (BMI), and also for psychological, sexual, and socioeconomic adjustments. Weight and BMI changes were significantly better than for the assessment only group, some of whom had received extensive treatment elsewhere. The style of the outpatient therapy and compliance with it are described in some detail and prognostic indicators for the treated and untreated groups presented. Lower weights at presentation and vomiting were associated with poorer outcome, although age and length of history were not.

Adaptation, Psychological↗
PubMed1993

Synergistic efficacy of O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in a human colon cancer xenograft completely resistant to BCNU alone.

The DNA repair protein O6-alkylguanine-DNA alkyltransferase (alkyltransferase) repairs cytotoxic DNA damage formed by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). High levels of this repair protein cause tumor drug resistance to nitrosoureas. To investigate the ability of a direct alkyltransferase inhibitor, O6-benzylguanine, to reverse the nitrosourea resistance of human colon cancer cells, we studied the VACO 6 cell line which has high alkyltransferase and is completely resistant to BCNU at maximal tolerated doses in the xenograft model. O6-Benzylguanine at 0.5 microgram/mL for 1 hr inactivated VACO 6 alkyltransferase by > 98% and reduced the IC50 of BCNU by 3- to 4-fold. Further analysis indicated that these two agents act in a highly synergistic fashion. In xenograft bearing athymic mice, dose-dependent depletion of hepatic and tumor alkyltransferase was noted. To maintain alkyltransferase depletion in the xenograft for at least 24 hr, two doses of 60 mg/kg O6-benzylguanine were given 1 hr prior and 7 hr after BCNU. Under these conditions, VACO 6 xenografts became responsive to BCNU with significant reductions (P < 0.001) in the tumor growth rate. The combination increased toxicity to the host, reducing the maximum tolerated dose of BCNU by approximately 50%. This study provides definitive evidence that high alkyltransferase activity is responsible for BCNU resistance in human colon cancer xenografts and that with careful drug scheduling, O6-benzylguanine can sensitize a tumor which is completely unresponsive to BCNU alone. Further studies which optimize the therapeutic index of BCNU and O6-benzylguanine in vivo will define the schedule to be used in broader preclinical studies.

Alkyl and Aryl Transferases↗
PubMed1993

The prevention of thymic lymphomas in transgenic mice by human O6-alkylguanine-DNA alkyltransferase.

Nitrosoureas form O6-alkylguanine-DNA adducts that are converted to G to A transitions, the mutation found in the activated ras oncogenes of nitrosourea-induced mouse lymphomas and rat mammary tumors. These adducts are removed by the DNA repair protein O6-alkylguanine-DNA alkyltransferase. Transgenic mice that express the human homolog of this protein in the thymus were found to be protected from developing thymic lymphomas after exposure to N-methyl-N-nitrosourea. Thus, transgenic expression of a single human DNA repair gene is sufficient to block chemical carcinogenesis. The transduction of DNA repair genes in vivo may unravel mechanisms of carcinogenesis and provide therapeutic protection from known carcinogens.

Animals↗
PubMed1993

Expression of CA19-9, DU-PAN-2, and SPan-1 antigens on two types of normal salivary mucins.

Mucins are important in cancer diagnosis and therapy. A better understanding of the characteristics of mucins in normal and malignant tissues could make them more effective clinical targets. Levels of the sialylated carbohydrate mucin antigens CA19-9, DU-PAN-2, SPan-1, and TAG-72 are elevated in sera from patients with pancreatic cancer. In this study we examined normal saliva for the presence of these antigens. TAG-72 reactivity was not detected in the samples examined. SPan-1 expression correlated with the expression of CA19-9 except in Le(a)- individuals. In these individuals CA19-9 was absent; SPan-1 was expressed to varying degrees. Little, if any, reactivity was detected with four monoclonal antibodies directed against the MUC1 mucin peptide. A high-buoyant-density-fraction (1.35 to 1.55 g/mL) of normal saliva, containing most of the sialic acids and O-linked oligosaccharides, was separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Western blots showed that CA19-9, DU-PAN-2, and SPan-1 antigens were found on two forms of mucins. DU-PAN-2 reactivity was detected only in the absence of the sulfhydryl reducing agent beta-mercaptoethanol. The two main forms of antigens differed in molecular size (150 kDa and greater than 400 kDa) and buoyant density (1.38 and 1.49 g/mL) and have been reported to differ in amino-acid composition. In colon or pancreas, the CA19-9, DU-PAN-2, and SPan-1 carbohydrate structures have been reported to be present on the MUC1 mucin peptide. Our present results suggest that in saliva, these carbohydrate antigens may be found on mucin peptides other than MUC1.

Antigens, Neoplasm↗
PubMed1992

New approach to the management of airway obstruction in "high risk" neonates.

Epignathus is a rare tumor of newborns that is associated with a high mortality secondary to airway obstruction in the neonatal period. Due to recent advances in prenatal ultrasound and magnetic resonance imaging techniques, accurate in utero diagnosis of this rare teratoma will enable the health care team to prepare for "emergency" management of a difficult airway. We present a case of a newborn with a large epignathus diagnosed prenatally who underwent tracheotomy with intact maternal-fetal circulation. After airway stabilization, maternal-fetal circulation was interrupted and the epignathus was successfully removed. To our knowledge, this is the first extrauterine surgical procedure successfully performed using this technique. A new approach to airway management in "high risk" neonates involving the cooperative efforts of pediatricians, neonatologists, anesthesiologists, and otolaryngologists is presented.

Airway Obstruction↗
PubMed1992

The Separation-Individuation Inventory. Association with borderline phenomena.

The Separation Individuation Inventory (SII; Christenson and Wilson, J. Nerv. Ment. Dis., 173:561-565, 1985) was designed to assess adult psychopathology construed in terms of the concepts of separation and individuation (Mahler, Pine, and Bergman, The Psychological Birth of the Human Infant: Symbiosis and Individuation, 1975). Its reported use is confined to the original authors' paper, which compared scores of 20 subjects with borderline personality disorder with the scores of staff control subjects. We report the association of the SII with two self-report measures of borderline personality diagnosis and phenomenology. Our British samples, from the staff and residents in a therapeutic community for severely personality-disordered clients, thus complement the original American work. The SII was found to have good internal consistency, respectable screening parameters, and high correlations with indications of trait psychopathology. We suggest a slight modification to the scoring of the inventory and two main areas for additional research.

Adult↗
PubMed1991

Enhanced repair of O6-methylguanine DNA adducts in the liver of transgenic mice expressing the ada gene.

The capacity to repair O6-methylguanine-DNA adducts was measured in the liver of transgenic mice expressing a chimeric gene consisting of the inducible P-enolpyruvate carboxykinase (GTP) promoter linked to the bacterial O6-alkylguanine-DNA alkyltransferase (ada) gene. Under induced conditions, total hepatic alkyltransferase reached 32.8 +/- 4.2 (SE) fmol/micrograms DNA compared to 7.8 +/- 1.1 fmol/micrograms DNA in nontransgenic mice. Administration of methylnitrosourea or nitrosodimethylamine to both groups of mice produced O6-methylguanine-DNA adducts which resulted in repair-mediated depletion of total hepatic alkyltransferase in a dose-dependent fashion. In nontransgenic mice, depletion of hepatic alkyltransferase occurred at lower doses of carcinogen, and recovery of alkyltransferase activity occurred later than in ada+ transgenic mice. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of residual alkyltransferase activity after methylating agent exposure indicated that the bacterial as well as endogenous mammalian alkyltransferases were functioning as DNA repair proteins in hepatocytes in vivo. Analysis of O6-methylguanine- and N7-methylguanine-DNA adducts in the liver of transgenic and nontransgenic mice after treatment with one dose of 50 mg/kg methylnitrosourea i.p. revealed that transgenic mice repaired in situ O6-methylguanine-DNA adducts approximately 3 times faster than nontransgenic mice, commensurate with the increase in alkyltransferase activity. Thus, ada+ transgenic mice treated with methylnitrosourea have lower levels of persistent mutagenic O6-methylguanine adducts than ada- nontransgenic mice. Hepatic expression of bacterial alkyltransferase appears to protect mice from the DNA-damaging effects of N-nitroso compounds in vivo.

Animals↗
PubMed1991

Addressing racism in psychiatry: is the therapeutic community model applicable?

Several reports have documented the failure of statutory psychiatric services in Britain to provide for the needs of clients from minority ethnic groups. Black clients are particularly underrepresented in Psychotherapy for reasons which are complex and varied, but include the institutionalised racism which pervades British society. We argue that the Therapeutic Community (TC) model of treatment (or aspects of it deployed in other mental health situations) provides a potential for a less racist service. Using the Henderson Hospital TC as a case in point, we argue that the TC is an approach which can meet the needs of black peoples. However, it is acknowledged that despite the ideological suitability of the TC model for black clients, in practice the Henderson Hospital is not fulfilling its role in providing therapy to this group. We discuss possible explanations and suggest the practical changes necessary, so that Henderson Hospital can meet the needs of clients in a multi-cultural Britain.

Black or African American↗
PubMed1991

A controlled study of the effect of therapies aimed at adolescent and family psychopathology in anorexia nervosa.

Ninety patients with severe anorexia nervosa fulfilling DSM-III-R criteria were assessed in depth in terms of their family developmental psychopathology and then randomly allocated to either one of three treatment groups or to no treatment. In three treatment regimes, a behavioural approach to diet and weight gain was coupled with individual and family psychotherapy directed at the adolescent maturational problems. All three treatment regimes were highly significantly effective at one year in terms of weight gain, return of menstruation, and aspects of social and sexual adjustment. Body weights above those at pubertal onset were achieved for the group mean maximum and one-year follow-up weights for all three treatment groups but not the control group.

Adolescent↗
PubMed1988

Choroid plexus cysts in the fetus: a benign anatomic variant or pathologic entity? Report of 41 cases and review of the literature.

During a 22-month period, 6288 women undergoing prenatal sonographic studies in the second and third trimesters were evaluated prospectively to determine the incidence of choroid plexus cysts in the fetus, to follow the natural course of these cysts in intrauterine life, and to determine the association of chromosomal and anatomic anomalies in these fetuses. We diagnosed choroid plexus cysts in 41 fetuses, an incidence of 0.65%. Unilateral and bilateral cysts were equally frequent, and in most cases diagnosed by 21 weeks' gestation. On follow-up scans, the cysts had completely disappeared by 23-24 weeks in 80% of the cases, and by 28 weeks in another 10%. Once resolved, the cysts did not recur, and a normal sonogram in the late second trimester predicted normal scans in late pregnancy and in the neonate. One fetus had a chromosomal abnormality (trisomy 18). Associated anatomic anomalies were detected in three fetuses, including the one with trisomy 18. We believe that in the great majority of cases, fetal choroid plexus cysts are benign transient variants of normal intracranial anatomy. It is, however, important to conduct a careful sonographic search for associated anomalies. Chromosomal studies are strongly recommended whenever associated anatomic abnormalities are detected and when the choroid plexus cysts are large, bilateral, and persistent beyond 20-22 weeks' gestation.

Adult↗
PubMed1987

Osteosarcoma: relation between extent of marrow infiltration on CT and frequency of lung metastases.

Thirty-seven patients with osteosarcoma were evaluated by CT of both the involved bone and the lungs. The ratio of the extent (E) of the involved marrow segment to the length (L) of involved bone (E/L) was correlated with the presence and subsequent development of pulmonary metastases. The marrow was evaluated by CT for the presence of tumor by measuring mean attenuation coefficients on serial axial scans. Three patient groups were identified: group 1 consisted of seven patients with lung metastases at presentation (mean E/L = 61%), group 2 consisted of 10 patients who developed lung metastases or recurrent tumor either during or after chemotherapy (mean E/L = 39%), and group 3 consisted of 20 patients who completed therapy and remained disease-free (mean E/L = 28%). All patients received chemotherapy in addition to surgical resection except for two patients in group 1. No patient with an E/L ratio greater than 50% remained disease-free for more than 14 months after the initial diagnosis. Fifty percent or greater involvement of the marrow cavity thus carries a particularly poor prognosis, and its absence or presence can be used as a significant prognostic aid in osteosarcoma.

Adolescent↗
PubMed1983

Anorexia nervosa.

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Adolescent↗