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Biomedical subjects

E P Lester

Publications and source records attributed to E P Lester.

At least 19 recordsLinked to original sources
PubMed1992

Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting.

PURPOSE: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis. PATIENTS AND METHODS: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose > or = 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration. RESULTS: A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P < .001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (> 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (aspartate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%). CONCLUSION: A 32-mg single dose of ondansetron is more effective than a single 8-mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis.

Adult↗
PubMed1991

Concomitant cisplatin and hyperfractionated external beam irradiation for advanced malignancy of the head and neck.

The combination of cisplatin and hyperfractionated external beam irradiation (HEBI), followed by salvage surgery when indicated, was evaluated in patients with advanced stage squamous cell carcinoma of the head and neck. Thirty patients with stage III (n = 5) or IV (n = 25) disease received intravenous cisplatin 100 mg/m2 by 6-hour continuous infusion on days 1, 21, and 42 of HEBI. Radiation fractions of 110 cGy were given twice daily, separated by 4 to 6 hours, beginning within 12 hours after cisplatin delivery. Doses to the primary site ranged from 60 to 76.35 Gy (median: 72.3 Gy), with 60 to 74 Gy to nodal sites. Follow-up ranged from 4 to 28 months (median: 19 months). Clinical complete response of the primary site was seen in 27 of 29 patients (93%), and complete clinical clearance of adenopathy in 20 of 26 (76%). A second biopsy 6 to 8 weeks after completion of treatment showed residual disease in both the primary and nodal sites in three patients, and in only the primary site in one patient. Four patients with persistent adenopathy had pathologic confirmation at surgery. Four patients had recurrence after negative biopsy results 6 to 9 months after treatment biopsy. At present, with median follow-up of 19 months, eight patients (26%) have died secondary to uncontrolled primary or nodal disease. Two patients have died of nonrelated causes. Overall, 10 of 30 patients (66%) remain alive with no evidence of disease. Mucositis and weight loss were the most common side effects of treatment. Seven patients developed significant xerostomia, and four have cisplatin-related hearing loss requiring amplification. The early evidence of excellent response (89% pathologic complete response of primary sites; 78% complete response of nodal sites), coupled with acceptable treatment morbidity, warrants further study of this approach.

Adult↗
PubMed1991

Cisplatin and fluorouracil chemotherapy does not yield long-term benefit in locally advanced head and neck cancer: results from a single institution.

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.

Adolescent↗
PubMed1990

Gender and identity issues in the analytic process.

The influence of gender--of analyst and analysand--in the unfolding of the analytic process is being addressed. A brief discussion of the reasons why such influence was either dismissed or denied in the analytic literature until recently, is followed by an overview of possible analyst-analysand interactions in the four gender-related dyads. Finally two specific developments, not uncommon in the transference of female patients in analysis with female analysts (and their countertransference implications) are presented. The first refers to the issues around closeness and distance with the maternal object (usually expressed as issues over control and as a sado-masochistic struggle with the analyst in the transference), while the second to the erotization of the transference.

Acting Out↗
PubMed1989

Database and search techniques for two-dimensional gel protein data: a comparison of paradigms for exploratory data analysis and prospects for biological modeling.

Two-dimensional (2-D) polyacrylamide gel electrophoresis can detect thousands of polypeptides, separating them by apparent molecular weight (Mr) and isoelectric point (pI). Thus it provides a more realistic and global view of cellular genetic expression than any other technique. This technique has been useful for finding sets of key proteins of biological significance. However, a typical experiment with more than a few gels often results in an unwiedly data management problem. In this paper, the GELLAB-II system is discussed with respect to how data reduction and exploratory data analysis can be aided by computer data management and statistical search techniques. By encoding the gel patterns in a "three-dimensional" (3-D) database, an exploratory data analysis can be carried out in an environment that might be called a "spread sheet for 2-D gel protein data". From such databases, complex parametric network models of protein expression during events such as differentiation might be constructed. For this, 2-D gel databases must be able to include data from other domains external to the gel itself. Because of the increasing complexity of such databases, new tools are required to help manage this complexity. Two such tools, object-oriented databases and expert-system rule-based analysis, are discussed in this context. Comparisons are made between GELLAB and other 2-D gel database analysis systems to illustrate some of the analysis paradigms common to these systems and where this technology may be heading.

Algorithms↗
PubMed1989

Studies of the affective state in bereaved children.

The process of bereavement in children ranges from the absence of grief to symptoms of anxiety and conduct disturbances. Some psychoanalytic opinion holds that the absence of grief, associated with lack of cognitive maturity, leads to the development of psychopathology later in life. Other writers describe a mourning response, taking the form of ambivalence, anxiety, and care giving, which may protect against subsequent depression. This paper describes the affective response in 16 children ages four to 17 years, two to three years following the death of a parent, in order to further characterize developmental aspects of the emotional repertoire of bereavement. Only children aged 12 and over were depressed according to the Poznansky Children's Depression Rating Scale and criteria in the DSM-III. Conduct disturbances were observed in the younger children and some of the older children and were correlated with depression in the group as a whole. This suggests that the expression of depressive affect depends on maturation and that the young child may register grief only through anxiety and negativism. Examples of this spectrum of responses are offered in two case vignettes.

Adaptation, Psychological↗
PubMed1989

GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.

We evaluated, in a multi-center trial, the safety and efficacy of GR 38032F (GR-C507/75), a novel and selective serotonin antagonist, in preventing acute emesis in chemotherapy-naive patients receiving treatment with regimens containing high-dose cisplatin (greater than or equal to 100 mg/m2). Eighty-five patients were randomized to receive GR 38032F, 0.18 mg/kg, either every six or every eight hours for three doses, beginning 30 minutes before cisplatin. Patients were evaluated for emetic episodes (vomiting or retching) over a 24-hour period following cisplatin. All patients were evaluable for toxicity and 83 were evaluable for efficacy. The overall antiemetic response rate was 75% (55% complete response [CR], 20% major response). No difference in antiemetic control between the two administration schedules was noted. Patients with histories of heavy ethanol use had significantly better antiemetic control (74% CR) than modest or non-drinkers (33% CR). Toxicity of GR 38032F was modest and independent of administration schedule. The most common adverse events included mild hepatic transaminase elevations, self-limited diarrhea, dry mouth, headache, and mild sedation. Our data indicate that GR 38032F is a safe and effective agent in the control of acute cisplatin-induced nausea and vomiting. Additional trials exploring dosing, schedule, and comparison to standard antiemetic agents are indicated.

Acute Disease↗
PubMed1989

Diffuse large-cell lymphoma of B-cell origin and deficient T-cell function in a patient with rheumatoid arthritis.

An increased incidence of non-Hodgkin's lymphoma has been described in patients with rheumatoid arthritis. Mechanisms related to abnormal immune regulation have been postulated, but no patients with rheumatoid arthritis and lymphoma have been previously well characterized immunologically. We describe here a patient with long-standing rheumatoid arthritis in whom a B-cell diffuse large-cell lymphoma developed. He was found to have a severe T-cell immunodeficiency and evidence of persistent Epstein-Barr virus infection. Epstein-Barr nuclear antigen was not found to be present within lymphoma cells. The combination of defective T-cell function and persistent Epstein-Barr virus infection may have predisposed this patient with rheumatoid arthritis to the development of a malignant clone of B lymphocytes.

Arthritis, Rheumatoid↗
PubMed1986

On transference: developmental and clinical considerations.

Following a short historical overview of the evolution of the concept of transference, the factors involved in this process are examined. The developmental or dynamic aspects of transference, that is, its illusory character defined by the "potential space" within which transference develops, and the importance of the holding environment at the early stages of therapy for an optimal development of transference are discussed. To understand resistances, Merton Gill's distinction of resistances to the awareness of the transference, and resistances to the resolution of the transference are particularly relevant. Finally, the concept of transference neurosis is focused upon. Detailed clinical vignettes are given to illustrate the points made. Although the clinical material is taken from sessions of patients in analysis the theoretical implications pertaining to the transference are equally applicable to the practice of psychoanalytic psychotherapy. It is in this spirit that throughout the paper the terms "therapeutic" and "analytic" are used interchangeably.

Defense Mechanisms↗
PubMed1986

Pregnancy, developmental crisis and object relations: psychoanalytic considerations.

The psychoanalytic literature until recently was focused on the task of understanding and conceptualizing motherhood as 'not secondary' (to the girl's wish for the penis) but the central organizer of the woman's sexual drive. Pregnancy was viewed as a developmental crisis but little had been written on the internal shifts and realignments in the mental organization of the woman during pregnancy. Material from the analyses of three women during their first pregnancy is discussed and some theoretical conclusions are offered.

Adult↗
PubMed1986

Narcissism and the personal myth.

Kris (1956) described the concept of the personal myth as an autobiographical story built around a family romance fantasy seen specifically in obsessive characters and serving a defensive function. In this paper the concept of the personal myth was expanded to include similar defensive constellations originating from within the grandiose self, built around omnipotent and omniscient fantasies and occurring in character formations with pregenital, narcissistic pathology. The case of a known author and poet, Nikos Kazantzakis, was used to illustrate the thesis of the paper. The available biographical material and the work of the author offer evidence to support the claim that the author's personal myth was a protective shield against anxiety originating in early narcissistic traumata.

Creativity↗
PubMed1985

Lymphocyte blastogenesis. Post-transcriptional controls of protein synthesis.

To better understand the regulation of macromolecular synthesis in the response of lymphocytes to a mitogen, we have used two-dimensional electrophoresis to search for specificity in the early increase seen in protein synthesis in human lymphocytes treated with phytohemagglutinin and examined the role of new RNA synthesis in this response. Our results confirm a major increase in overall protein synthesis after 4 h of phytohemagglutinin treatment. A further disproportionate increase in the synthetic rates of certain polypeptides was observed using two-dimensional polyacrylamide gel electrophoresis. While actinomycin-D reduced protein synthesis to a level below that of untreated cells, phytohemagglutinin nonetheless enhanced total protein synthesis even in the presence of actinomycin. Some, but not all, of the disproportionate increases in synthesis seen for certain polypeptides are blocked by actinomycin. These results imply the existence of multiple mechanisms controlling protein synthesis early in the course of lymphocyte stimulation. At least some of these do not require new RNA synthesis and thus operate at a post-transcriptional level.

Blood Proteins↗
PubMed1985

Psychopathology in the offspring of parents with bipolar affective disorders.

Thirty-nine children from intact families with a manic-depressive parent were evaluated by a semi-structured clinical interview and a number of rating scales for the presence or absence of psychopathology. This sample represents a larger one than in an earlier study, which showed minimal offspring psychopathology compared with reports of other investigators. The current study also examines the inter-relationships between the presence or absence of offspring psychopathology with both genetic loading and a number of psychosocial variables including measures of parental marital adjustment, severity and chronicity of proband parent illness and early exposure of children to parental illness. Nine of the thirty-nine children, (23%) received a positive DSM-III diagnosis, with depression of the dysthymic type being the most common. There was no significant correlation between genetic loading and offspring psychopathology. However, there were significant associations between children with psychopathology and paternal marital dissatisfaction and the age and chronicity of illness of the proband parent as compared with the children with no psychopathology.

Adolescent↗
PubMed1985

The female analyst and the erotized transference.

The concept of erotized transference is discussed from Freud's original writings on the subject to those of recent contributors. It is noted that there exists an almost complete absence of reports in the literature of male patients developing an erotized transference to their female analysts. The question of how significant the gender of the analyst is in the unfolding of the transference and its vicissitudes is raised. It is maintained that the four possible analyst/analysand dyads differ qualitatively in that resistance and identification in the transference may be enhanced or inhibited by the gender of the analyst and/or the homosexual or heterosexual nature of the dyad. The erotized transference to the female analyst is focused upon as a vehicle to the study of such qualitative differences. It is hypothesized that the expression of strong erotic urges to the female analyst by the male patient is somewhat inhibited by the fantasy of the overwhelming pre-oedipal mother. In contrast, such erotic feelings are freely expressed by the female patient. Two cases, a male and a female, are described to support the above hypothesis.

Adult↗
PubMed1982

Effect of interferons on protein synthesis in human lymphocytes: enhanced synthesis of eight specific peptides in T cells and activation-dependent inhibition of overall protein synthesis.

Lymphoblastoid and fibroblast IFN inhibited PHA stimulation of overall protein synthesis in human lymphocytes by ca. 30%. Inhibition occurred within the first 6 hr of PHA treatment and was not progressive. DNA synthesis at 48 hr was inhibited to the same extent. Overall protein synthesis in resting lymphocytes was not detectably inhibited by IFN concentrations up to 1000 U/ml. Thus, inhibition of protein synthesis and subsequent reduction of cell proliferation by IFN require certain early events in mitogen activation. Resting lymphocytes were not unresponsive to IFN treatment, however. Two-dimensional electrophoretic analysis of newly synthesized proteins after IFN treatment showed enhanced synthesis of a specific set of eight peptides (I-peptides), which were shown to be synthesized in T lymphocytes. This enhancement was produced by both IFN-alpha and IFN-beta after 4 to 6 hr of exposure and was identical for all lymphocyte donors studied. After growth stimulation, IFN treatment produced no enhancements of additional peptides, although the original eight I-peptides were enhanced as usual. It is concluded that the biochemical activities of the I-peptides, which remain to be determined, cannot inhibit protein synthesis in resting lymphocytes, but may do so after mitogen activation, when the major physiologic restriction of lymphocyte protein synthesis is released. Alternatively, the I-peptides may be unrelated to regulation of protein synthesis but may be involved in viral protection or enhancement of NK activity.

Blood Proteins↗
PubMed1980

Polyamines as physiological substrates for transglutaminases.

When normal human blood lymphocytes are treated with mitogen in the presence of [3H]putrescine, label is incorporated into a few cellular proteins. Labeled N-(gamma-glutamyl) putrescine, N1-(gamma-glutamyl)spermidine, and N8-(gamma-glutamyl)spermidine were identified in exhaustive proteolytic digests of the cellular protein fraction. The enzyme-mediated clotting of rat seminal plasma to which 14C-labeled spermidine and spermine are added is accompanied by incorporation of the polyamines into a number of seminal plasma proteins. Proteolytic digests of the protein fraction from this clotted seminal plasma contain labeled N1-(gamma-glutamyl)spermidine, N8-(gamma-glutamyl)spermidine, N1,N8-bis(gamma-glutamyl)spermidine, N1-(gamma-glutamyl)spermine, and N1,N12-bis(gamma-glutamyl)spermine. These findings support a proposal that polyamines serve as substrates for transglutaminases both in cells and in an extracellular fluid. They show differences in cellular and extracellular substrate properties of the polyamines and indicate cross-linking through these amines in the extracellular system, but provide no evidence for such cross-linking in the cells.

Humans↗