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Biomedical subjects

R Berkowitz

Publications and source records attributed to R Berkowitz.

At least 37 records · Page 2Linked to original sources

Differential production of human chorionic gonadotropin and free subunits in gestational trophoblastic disease.

Serum levels of human chorionic gonadotropin (hCG) and its free subunits (alpha hCG and beta hCG) were determined by means of highly sensitive and specific monoclonal and antipeptide-based monoclonal immunoradiometric assays. During normal pregnancy, the beta hCG to hCG ratio appears constant at approximately 0.5% after 5 weeks of gestation. In contrast, gestational choriocarcinoma was characterized by absolute serum beta hCG levels varying from three to 280 times greater than the maximum values observed during pregnancy and by exceedingly high beta hCG to hCG ratios. In complete hydatidiform mole, this ratio was intermediate between normal pregnancy and choriocarcinoma. The ratios of free beta hCG to hCG will distinguish normal from complete molar pregnancy (p less than 10(-8)), hydatidiform mole from choriocarcinoma (p less than 10(-4)), and choriocarcinoma from normal pregnancy (p less than 10(-8)) with high probability. Finally, it was found by means of the high sensitivity hCG immunoradiometric assays (less than 0.02 ng/ml) that this assay predicted very early tumor recurrence in patients with gestational choriocarcinoma.

Adult

Need for theophylline in severe steroid-requiring asthmatics.

Concern about side-effects of theophylline prompted us to investigate whether this drug could be eliminated from the multi-medication regimen of severe asthmatics. We studied patients with a demonstrated requirement for systemic steroids who were taking most other available anti-asthma medications in an attempt to reduce systemic steroids while maintaining clinical stability. Five in-patients, 12-15 years old, completed a double-blind, cross-over trial of theophylline vs placebo. All were stable for 4 weeks prior to the study with normal spirometry and mildly elevated lung volumes. Regular medications consisted of long-acting theophylline with levels between 12 mcg/ml and 16 mcg/ml, and prednisone 10-30 mg on alternate days. In addition, they were all taking inhaled metaproterenol, cromolyn sodium, atropine sulphate, and beclomethasone dipropionate four times daily (qid). Patients received either theophylline or placebo during two drug periods. All other medications were unchanged. Parameters measured were symptom score, number of extra respiratory treatments (prn RTs), increase in steroid dosage, and daily spirometry. During the placebo period, all five patients required increased steroids, daily spirometry decreased and three patients developed severe exacerbations unrelated to viral infection. A marked increase in symptom score occurred within 48 hr of discontinuing theophylline in all. These findings emphasize that theophylline is beneficial in a subset of severe asthmatics who cannot be controlled with all other available bronchodilators, cromolyn, and inhaled and systemic steroids.

Adolescent

Expressed emotion in individual and family settings: a comparative study.

Expressed emotion ratings were performed, in two separate settings, on the parents of 20 children suffering from anorexia nervosa. Ratings were made on conventional individual interviews and on videotapes of a family interview. Comparison of ratings in the two settings showed a very high correlation for 'critical comments'. Findings on the other scales were harder to interpret, but significant correlations as well as differences were noted. Expressed emotion rated in family interviews provides new possibilities for the study of families.

Adolescent

Correlation between outer-membrane lysis and susceptibility of mitochondria to inhibition by adriamycin and polyamines.

Pretreatment of rat liver mitochondria with digitonin or osmotic shock increases their susceptibility to respiratory inhibition by adriamycin and polyamines. Since enhanced inhibitor sensitivity coincides in each case with lysis of the mitochondrial outer membranes, the possibility is raised that this membrane represents a permeability barrier to certain polar, organic cations.

Animals

Albuterol protects against exercise-induced asthma longer than metaproterenol sulfate.

Both metaproterenol sulfate and albuterol are inhaled medications commonly used to prevent exercise-induced bronchospasm. Their efficacy and duration of action in controlling exercise-induced bronchospasm were compared with placebo in 18 asthmatic children (age range: 12 to 17 years) in a single-blind randomized crossover study. Standardized treadmill exercise challenges were repeated every two hours for up to six hours following the initial exercise test. With the initial exercise challenge, both active medications blocked exercise-induced bronchospasm with equal efficacy. On the other hand, when the duration of action of the medications was compared: albuterol blocked exercise-induced bronchospasm longer than metaproterenol sulfate in eight subjects, the reverse was true in only one patient, and the medications blocked for equal duration in nine subjects. Thus, although both active agents were equally efficacious in blocking exercise-induced bronchospasm initially, the duration of action of albuterol was significantly (P less than .05) longer on serial testing than that of metaproterenol sulfate. Both medications were significantly better than placebo in efficacy and duration of action.

Adolescent

A controlled trial of social intervention in the families of schizophrenic patients: two year follow-up.

The two-year follow-up results are reported of a trial of social intervention in families of schizophrenic patients in high social contact with high-expressed emotion (EE) relatives. For those patients who remained on antipsychotic medication throughout the two years, the social intervention significantly reduced the relapse rate. In those experimental families where relatives' EE and/or face-to-face contact was lowered, the relapse rate was 14% compared with 78% for control patients on regular medication (P = 0.02).

Adult

Sonographically monitored amniocentesis to decrease intraoperative complications.

The rates of intraoperative complications (dry and bloody taps) of two amniocentesis techniques were compared in 1300 patients undergoing second trimester procedures for genetic indications. The sonographically guided technique consisted of the selection of a site for needle insertion with ultrasound, removal of the transducer, and immediate amniocentesis. The sonographically monitored technique consisted of the continuous visualization of the needle during the entire procedure. Six hundred twelve amniocenteses were performed with the sonographically guided technique and 688 with the sonographically monitored technique. There was a statistically significant decrease in the incidence of bloody and dry taps of the first needle insertion (relative risk = 38%, P less than .0001) and also in the number of patients that required multiple needle insertions (relative risk = 42%, P less than .0001) with the sonographically monitored technique.

Amniocentesis

Characterization of antigenic components from circulating immune complexes in patients with gestational trophoblastic neoplasia.

The authors have studied serial circulating immune complex (CIC) levels in 15 patients with gestational trophoblastic neoplasia (GTN) for several reasons. Gestational trophoblastic neoplasia can easily be followed from presentation to remission, and CIC changes can be compared with changes in human chorionic gonadotropin (HCG) which is a specific and quantitative marker of trophoblastic tumor load. Twelve patients with hydatidiform molar pregnancy presented with normal CIC levels (255 delta OD450 +/- 97, mean SE [standard error]) as measured by our antigen nonspecific polyethylene glycol (PEG) turbidity assay. Only after reduction in tumor load as monitored by a fall in HCG did CIC rise. In contrast, three patients with choriocarcinoma presented with significantly elevated CIC levels (513 delta OD450 +/- 147, P less than 0.05 compared to normals) which slowly declined in parallel with HCG levels following evacuation and chemotherapy. Sera at peak PEG-CIC from three patients with molar pregnancy or choriocarcinoma were precipitated with 3.75% polyethylene glycol to concentrate circulating immune complexes. Circulating immune complex levels were fractionated on Sephadex G-200 in an acid buffer (pH = 2.8). An identifiable antigenic component of the CIC in both diseases was found to be paternal HLA antigen. This was demonstrated by the ability of the latest eluting CIC fraction to inhibit paternal lymphocyte lysis using anti-HLA antisera against the husband's HLA tissue type. In each case, this fraction contained no immunoglobulin or beta-2 microglobulin and was antigenically crossreactive with only one of the husband's HLA haplotypes. The authors believe the PEG-CIC assay has allowed them to define the kinetics of host humoral response in GTN, and has provided a method for recovering immunogenic tumor-associated antigens from these complexes which may apply to other solid tumors.

Antigen-Antibody Complex

Educating relatives about schizophrenia.

An education program, which was part of a controlled trial of intervention with families of schizophrenic patients, is described and evaluated. The evidence suggests that this kind of education has a role to play in psychosocial intervention. Assessment of its impact should include not only changes in information acquired but also in attitudes.

Adult

The management of schizophrenic patients: the nurses' view.

A small study is described in which nurses were asked how they deal with specific management problems in schizophrenia. Their responses suggest that their approach may provide valuable information for both professionals and relatives.

Adaptation, Psychological

Psychophysiological responses of schizophrenic patients to high and low expressed emotion relatives: a follow-up study.

Measurements of skin conductance response frequencies (SCRf) were obtained from 30 acutely ill schizophrenic patients during a standardised videotaped interview, conducted with the patient's key relative present. Significant differences in SCRf's were demonstrated between patients whose relatives had high and low Expressed Emotion (EE) respectively. Patients at high risk of relapse were allocated either to a control or an experimental group, the latter being offered a number of social interventions in order to reduce the relative's EE and/or contact with the patient. Follow-up measurements were obtained on 19 patients nine months after discharge. Although social intervention was highly successful in reducing relapse rates, its effects did not appear to be directly mediated via SCRf, which was found to be independently related to relapse.

Adult

Psychosocial relevance and benefit of neuroleptic maintenance: experience in the United Kingdom.

The benefits of psychosocial intervention were studied in patients on maintenance neuroleptics who live in high face-to-face contact with relatives who have high levels of expressed emotion. This group is at high risk of relapse when maintained on neuroleptics without social intervention. Relatives of patients in the experimental group received three types of intervention: an educational program, a relatives' group, and family therapy. The goal of intervention was to reduce face-to-face contact and/or relatives' levels of expressed emotion. The results at 9-month and 2-year follow up indicate the benefits of psychosocial intervention, while pointing out the danger in discontinuing maintenance neuroleptics for patients who live in stressful family environments.

Adolescent

Identification of material with paternal HLA antigen immunoreactivity from purported circulating immune complexes in patients with gestational trophoblastic neoplasia.

Circulating immune complex(es) (CIC) have been shown to rise progressively only when patients with hydatidiform molar pregnancy enter gonadotropin-documented remission. The CIC in 3 patients with gestational trophoblastic neoplasia (GTN)--1 with hydatidiform mole and 2 with choriocarcinoma--were characterized. Their clinical course was monitored by serial antigen-nonspecific polyethylene glycol (PEG) 6000-CIC assay and simultaneous human chorionic gonadotropin (HCG) assay from presentation until sustained gonadotropin-documented remission. As serial HCG progressively decreased to normal following surgical or chemotherapeutic reduction in tumor burden, PEG-CIC concurrently rose. Serum obtained at or near peak PEG-CIC levels was precipitated by 3.75% PEG 6000 and fractionated by column chromatography on Sephadex G-200 (exclusion limit, greater than 600,000 mol wt) in glycine-HCl and 1 M NaCl buffer at pH 2.8. None of the 5 elution fractions obtained from the 3 patients contained HCG or anti-HCG activity. However, in the hydatidiform molar patient, fractions 1 through 3 (mol wt greater than 67,000--and containing immunoglobulin) were shown to competitively inhibit complement-dependent antibody lysis on 1 of 4 paternal HLA haplotype (AW32) targets. In 2 of the 3 patients studied, low-molecular-weight fractions (not containing immunoglobulin) significantly inhibited reference anti-HLA binding of antisera directed against only 1 of 4 paternal HLA haplotypes. The immunospecificity of this inhibition was confirmed by criss-cross control assays in which elution fractions obtained from both of these patients were tested for inhibition of lymphocytolysis of both sets of paternal lymphocytes. None of these fractions were immunoreactive to maternal HLA haplotypes. Further analysis of serum from the hydatidiform molar patient revealed that no free complement-fixing antibody against paternal antigens could be found by conventional screening assays in unfractionated patient sera. Three of 4 paternal HLA antigens or non-complement-fixing anti-HLA immunoglobulin was detected in unfractionated pretreatment, treatment, and remission sera of the hydatidiform molar patient. Only in this patient's remission sera was unbound AW32 antigen or non-complement-fixing anti-AW32 antibody detected. These data demonstrate the successful characterization of at least 1 specific antigen fractionated from a tumor-associated immune complex. The implication that some patients with GTN may recognize and react to immunogenic paternal HLA antigens as part of their successful response to therapy for trophoblastic tumor is discussed.

Antigen-Antibody Complex

Comparison of a rabbit heteroantiserum and a murine monoclonal antibody raised against a human epithelial ovarian carcinoma cell line.

An ovarian carcinoma cell line (OVCA 432) and a B-lymphocyte line (LAZ 446) were established from the same donor. A heteroantiserum (D-100) was prepared in rabbits against OVCA 432 and absorbed with LAZ 446, human AB erythrocytes, and the CX-1 colorectal cell line. After absorption, D-100 reacted by indirect immunofluorescence with six of six epithelial ovarian carcinoma cell lines and cryostat sections of 18 of 18 epithelial ovarian tumors but bound to zero of 12 nonovarian tumor cell lines. Despite a lack of reactivity with nonovarian tumor cell lines, D-100 reacted with epithelial components of normal ovary, fallopian tube, endometrium, endocervix, breast, colon, and epididymis. A murine monoclonal antibody (OC 133) was also raised against OVCA 432 and selected for lack of reactivity with the autologous B-lymphocyte line LAZ 446. OC 133 reacted with six of six ovarian carcinoma cell lines and cryostat sections of seven of 19 ovarian tumors, but it also reacted with five of five nonovarian tumor cell lines. Of 12 normal tissues examined, OC 133 reacted with endometrium and endocervix only. Whereas D-100 bound to serous, mucinous, endometrioid, and clear cell ovarian neoplasms, OC 133 bound only to serous tumors. In developing monoclonal reagents, cell lines may provide a useful source of antigen, but promising antibodies should be screened for reactivity with sections of normal and malignant human tissues.

Animals

Life events, relatives' expressed emotion and maintenance neuroleptics in schizophrenic relapse.

Data from two studies, one naturalistic and the other a controlled trial, were analysed to clarify the relationships between independent life events. Expressed Emotion of a key relative, maintenance neuroleptics and the relapse of schizophrenia. It was found that patients in the community who are unprotected by medication are vulnerable either to acute stress in the form of life events or to chronic stress in the form of living with a high Expressed Emotion relative. Patients on regular medication are protected against one or other stress, but are very likely to relapse if the two forms of stress occur together. A model of schizophrenic susceptibility to environmental stress is constructed to incorporate these observations.

Adult

Characteristics of expressed emotion: its relationship to speech and looking in schizophrenic patients and their relatives.

The measure expressed emotion (EE) is an established indicator of characteristics in the relatives of schizophrenic patients which predict relapse. Despite this, little is known of its construct validity except that schizophrenic patients are less calm in the presence of high EE than low EE relatives. There is also tentative evidence that schizophrenic patients show heightened avoidance responses to aversive social stimuli. It was therefore hypothesized that acutely ill schizophrenic patients would show social behaviours characteristic of avoidance in interaction with high but not low EE relatives. This hypothesis was not confirmed as no patient difference was found, but there were differences in the behaviour of high and low EE relatives. High EE relatives spend more interview time talking and less in looking at the patients. Low EE relatives were more prepared to be silent. This is consistent with the general tendency of high EE relatives to be socially intrusive and low EE relatives to be supportive to schizophrenic patients.

Adult