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Biomedical subjects

A Benson

Publications and source records attributed to A Benson.

At least 19 recordsLinked to original sources
PubMed1999

A phase II study of 5-fluorouracil, leucovorin, and interferon-alpha in the treatment of patients with metastatic or recurrent gastric carcinoma: an Eastern Cooperative Oncology Group study (E5292).

BACKGROUND: Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-alpha (IFN-alpha) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS: Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-alpha (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-alpha on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS: The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3-4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS: Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.

Adult↗
PubMed1998

Corneal light scattering with stromal reformation after laser in situ keratomileusis and photorefractive keratectomy.

OBJECTIVE: To correlate corneal light scattering with keratocyte and extracellular matrix reformation after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). SETTING: Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, USA. METHODS: Sixteen pigmented rabbit eyes were randomly divided into 2 groups. Group 1 (n = 8) had a 5.0 mm, -10.0 diopter (D) LASIK treatment and Group 2 (n = 8), a 5.0 mm, -10.0 D surface PRK treatment after mechanical epithelial debridement. The stromal surface exposed at surgery was stained with dichlorotriazinylaminofluorescein (DTAF) solution. Slitlamp biomicroscopic and objective measurement of corneal light scattering using a scatterometer were performed 1 and 2 days and 1, 2, 3, 4, 8, and 12 weeks after surgery. In each group, 2 corneas were harvested at 1 week and 1 month and 4 corneas were harvested at 12 weeks. Tissue sections were examined by light and fluorescence microscopy. The percentage of newly formed stromal tissue was calculated and correlated with the scatterometry index. RESULTS: In Group 1, corneas remained clear and healed without significant scarring throughout the study. In Group 2, subepithelial scarring was noted. Extracellular matrix reformation peaked at 1 month and showed a slight regression thereafter. The percentage of extracellular matrix reformation was strongly correlated with the scatterometry index (r = .86, P < .001). CONCLUSIONS: In this study, significant subepithelial stromal tissue reformation followed PRK. The percentage of extracellular matrix reformation correlated well with the objective corneal light scattering measurements.

Animals↗
PubMed1998

Implementing health promoting nursing: the integration of interpersonal skills and health promotion.

Health promoting nursing practice is seen as the way forward for the nursing profession. This paper outlines the meaning of health promotion and distinguishes between a traditional and new paradigm approach. The research examining the extent to which a new paradigm approach is practised demonstrates that, to date, nurses predominantly adopt the traditional approach to health promotion. It is argued that the integration of interpersonal skills and health promotion within nursing curricula is crucial in enabling the transfer of theoretical concepts into practice. The ways in which this integration has been approached within one college of nursing are described. The difficulties encountered in attempting this integration and accomplishing a philosophical shift from a traditional to a new paradigm approach to health promotion are discussed and critiqued. Specifically conflicts that occur at an interpersonal, organizational and societal level are identified and proposed as explanations for the slow implementation of health promoting nursing.

Clinical Competence↗
PubMed1997

Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: a frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial.

Human colonic cancer is associated with multiple genetic deletions, mutations, and alterations in gene expression; in contrast, gene amplification has not been recognized as a prominent characteristic of human colonic tumors. Although the c-myc gene is overexpressed in approximately 70% of human colonic cancers, previous studies have not detected frequent gene amplification or rearrangement of c-myc in these tumors, although such amplification has been reported in chemically induced rodent colon cancer and quantitative analysis of gene copy number has shown the gene to be amplified at a low level in mucinous and poorly differentiated human colon carcinomas. Using rigorously controlled blot methodology, we have established that the c-myc gene, located at 8q21, exhibited amplification of 87% to 35-fold in 7 of 10 human colonic carcinoma cell lines. This was highly significant even at a low level of amplification in HT29 cells (P < 0.0001). Cytogenetic analysis by G-banding did not detect aneuploidy involving chromsome 8q, suggesting that the amplification for the c-myc gene on 8q was relatively specific, and this was consistent with a lack of amplification detected for the c-mos gene on 8q24, which was assayed similarly. The same methodology then revealed amplification of c-myc from 1.5-fold to 5-fold in 32% of tumors from 149 patients entered into a multi-institutional Phase III study of adjuvant therapy for colon cancer. c-myc status was not related to time to recurrence or death, but low levels of c-myc amplification identified a subset of patients who showed a statistically significant increase in disease-free survival, and a corresponding trend to longer overall survival, in response to adjuvant therapy with 5-fluorouracil plus levamisole. Presence of c-myc amplification was not related to incidence of p53 mutations.

Carcinoma↗
PubMed1996

Phase III study of bolus versus infusion fluorouracil with or without cisplatin in advanced colorectal cancer.

BACKGROUND: Phase II studies of fluorouracil (5-FU) administered by protracted intravenous infusion have suggested an improved response rate and decreased toxicity profile when compared with 5-FU given by bolus injection in patients with metastatic colorectal cancer. Additional studies have suggested further enhancement of infusion 5-FU activity when it is combined with low-dose weekly cisplatin administration. PURPOSE: This phase III study in adults with metastatic colorectal cancer was planned as a comparison of objective response rates, toxicity, and survival in patients receiving bolus versus protracted-infusion 5-FU with or without cisplatin. METHODS: Four hundred ninety-seven previously untreated patients with advanced, measurable metastatic colorectal cancer were randomly assigned to receive treatment A (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2), treatment B (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2, plus weekly cisplatin at 20 mg/m2), treatment C (5-FU at 300 mg/m2 per day by continuous infusion), or treatment D (5-FU at 300 mg/m2 per day by continuous infusion plus weekly cisplatin at 20 mg/m2). All drugs were administered intravenously. Enrollment in the trial occurred from August 1987 through December 1990, and follow-up was through September 1995. The Kaplan-Meier method was used to estimate overall and disease-free survival, and Cox regression models were used to assess the effects of patient characteristics on survival. All P values resulted from two-sided tests. RESULTS: Objective tumor response was observed in 28 (18%) of 153 patients receiving treatment A, in 45 (28%) of 159 patients receiving treatment C (C versus A; P = .045), and in 47 (31%) of 153 patients receiving treatment D (D versus A; P = .016). Because of excessive toxicity, treatment B was discontinued after only 12 patients had begun treatment. Median time to disease progression was 5.1 months for patients in arm A compared with 6.2 and 6.5 months for patients in arms C and D, respectively (C versus A, P = .007; D versus A, P = .017). Patterns of toxic effects differed substantially among the treatment arms. Forty-five percent of the patients receiving bolus 5-FU alone (A) experienced grade 3-4 leukopenia, with two sepsis-related deaths. Hand-foot syndrome and mucositis were the major treatment-limiting toxic effects for patients in the two treatment arms involving infusion. Despite the improvement in response rates and time to disease progression with infusion 5-FU with or without cisplatin (C and D, respectively) (P = .003), the overall survival for the three groups (A, C, and D) was similar (P = .307). This may have been due in part to a longer median survival time of 10.4 months for patients in arm A, compared with an anticipated survival of 7 months. CONCLUSION: 5-FU given as a continuous infusion produced a higher objective response rate, a modest prolongation in time to disease progression, and less life-threatening myelosuppression in patients than bolus 5-FU. Concomitant treatment with low-dose cisplatin caused added toxicity and complexity of treatment and did not provide a major clinical benefit. No statistically significant survival differences were observed among the three treatment groups.

Antimetabolites, Antineoplastic↗
PubMed1996

Caring for relatives with serious mental illness: the development of the Experience of Caregiving Inventory.

The aim of this study was to develop a practical, comprehensive, and valid self-report measure of the experience of caring for a relative with a serious mental illness. The notion of caregiver "burden' was rejected; instead caregiving was conceptualised within a 'stress-appraisal-coping' framework. A 66-item version of the Experience of Caregiving Inventory (ECI) was derived from analyses of responses from 626 caregivers, and then tested on an independent sample of 63 relatives of patients with schizophrenia recently in acute care. The extent to which the ECI complied with the stress-coping model was tested, especially the degree to which it, in association with coping, predicted psychological morbidity in carers. Ten sub-scales with good internal consistency resulted from our analyses, eight negative (difficult behaviours; negative symptoms; stigma; problems with services; effects on the family; the need to provide backup; dependency; loss) and two positive (rewarding personal experiences; good aspects of the relationship with the patient). The ECI, in conjunction with coping style, predicted a large proportion of the variance in the General Health Questionnaire (GHQ). We concluded that the ECI taps salient dimensions of caregiving distinct from, although linked with, coping and psychological morbidity. It has potential as a useful outcome measure for interventions aimed at promoting caregiver well-being.

Adaptation, Psychological↗
PubMed1996

A controlled trial of a counselling intervention for caregivers of relatives with schizophrenia.

The effectiveness of short-term interventions to reduce caregiver 'burden' has not been clearly demonstrated. This study assessed the value of six weekly sessions of counselling for key relatives of patients with schizophrenia. The counselling had educational and problem-solving components and was conducted in the family home in the absence of the patient. A randomised controlled design was used. The subjects were the principal caregivers of patients consecutively admitted to acute psychiatric care. Assessments were made pre-treatment and at 3 and 6 months. Of 63 relatives recruited, 47 completed all phases of the study. Relatives in the intervention group reported that they were better able to understand the patient and had a more positive relationship. There were no differences between the intervention and control groups on negative aspects of caregiving or in coping style. Relatives who received the counselling reported slightly greater psychological morbidity at follow-up. However, they all said they would recommend it to others. We concluded that a brief, intensive counselling intervention was of modest benefit to caregivers. Some modifications are suggested.

Adult↗
PubMed1996

The lidgap-Gates (lgGa) mutation for open eyelids at birth maps to mouse chromosome 13.

Complex nonadditive interactions between specific alleles at multiple loci may underlie many so-called multifactorial threshold birth defects. The open-eyelids-at-birth defect in mice is a good model for these defects, and an understanding of its genetic complexity begins with mapping the participating loci. The open-eyelids defect can be part of a syndrome or can occur with no other obvious phenotypic effects. Of the latter nonsyndromic forms, the lidgap series includes four extant mutations that are considered to be alleles based on complementation tests. All show genetic complexity in segregation ratios. None has been mapped previously. On the basis of a strategy of mapping the mutation with the simplest inheritance pattern first, we generated an extensive exclusion map for lidgap-Gates, lgGa, using morphological and protein polymorphisms. We then screened the non-excluded regions in a congenic strain, AEJ.LGG-lgGa, for SSLP markers and located the differential chromosome segment containing the lgGa locus in a region near the distal end of mouse Chromosome (Chr) 13. This linkage was confirmed and refined by typing SSLPs in 64 F2 and 74 BC1 progeny of a cross of LGG/Bc (lgGa/lgGa) to SWV/Bc. The lgGa mutation maps to a 1- to 2-cM region between D13Mit76 and D13Mit53. Integrin alpha 1 and integrin alpha 2, which map to the same general region, are possible candidate loci, based on their embryonic expression and cellular function. Evidence is also presented for a common unlinked recessive suppressor of the open eyelids trait caused by lgGa.

Animals↗
PubMed1996

Neoadjuvant chemotherapy plus concurrent chemotherapy and high-dose radiation for squamous cell carcinoma of the esophagus: a preliminary analysis of the phase II intergroup trial 0122.

PURPOSE: To determine the preliminary acute toxicity and survival results of neoadjuvant chemotherapy followed by concurrent chemotherapy plus high-dose radiation therapy in patients with local/regional squamous cell carcinoma of the esophagus. MATERIALS AND METHODS: Forty-five patients with clinical stage T1-4N0-1M0 squamous cell carcinoma were entered onto the trial. Eight patients were declared ineligible after registration. Patients received three monthly cycles of fluorouracil (5-FU; 1,000 mg/m2/24hr for 5 days) and cisplatin (100 mg/m2 on day 1) (neoadjuvant segment) followed by two additional monthly cycles of 5-FU (1,000 mg/m2/24hr for 5 days) and cisplatin (75 mg/m2 on day 1) plus concurrent 64.8 Gy (combined modality segment). RESULTS: With a median follow-up of 15 months in surviving patients, the incidence of total grade 3+ toxicity during the neoadjuvant chemotherapy segment was 61%, and during the combined modality segment was 72%. Of the 33 patients who started radiation therapy, 91% were able to complete the full course. There were six deaths during treatment, five of which (11%), because of nadir sepsis and/or dehydration, were treatment-related. For the 37 eligible patients, the median disease-free survival duration was 9 months, and the overall median survival was 20 months. CONCLUSION: The preliminary analysis of this trial demonstrated that the incidence of grade 3+ toxicity was similar to that reported in the combined modality arm of the prior Radiation Therapy Oncology Group (RTOG) intergroup esophageal trial RTOG 85-01. However, because of the increased incidence of treatment-related mortality, this treatment program will not be used as an experimental arm of intergroup trial INT 0123 (RTOG 94-05).

Adult↗
PubMed1996

Practising by the seaside.

The doctor in a holiday town must cope not only with his regular patients but also with the tourists that visit the district. Our clinic copes with the influx of tourists by having an efficient casualty room and by recommending that no doctor takes leave during the busiest period.

Adolescent↗
PubMed1995

Developing reflective practice in mental health nursing through critical incident analysis.

Critical incident analysis has been espoused as a valuable method of promoting reflective nursing practice and as a tool for developing curriculum content. Despite an obvious application to mental health nursing, however, there has been little detailed examination of the practicalities and educational value of critical incident analysis within a mental health nursing curriculum. This paper is based on the use of critical incident analysis within the mental health branch of a Project 2000 diploma course. It presents the content of material brought by students, teaching methods used to facilitate learning, and the progressive development of students' reflective processes over the course of a complete branch programme. Using Benner's (1984) From Novice to Expert, the authors explore questions regarding the nature and effects of the critical incident technique in attaining competence in mental health nursing skills. The authors conclude with a theory-based evaluation and analysis of this student-centered experiential approach to learning as a method for developing reflective practice, and suggest areas for educational research.

Clinical Competence↗
PubMed1995

Counseling caregivers of relatives with schizophrenia: themes, interventions, and caveats.

As part of a controlled study of the effectiveness of a counseling program for family caregivers of patients with schizophrenia, we conducted a comprehensive examination of the process. The particular foci were on themes that arose during sessions, principal therapeutic interventions offered, and caveats for counselors working in the field. The most striking finding was the diverse range of themes, covering personal, coping, family, and social aspects of the caregiving experience. This required a correspondingly broad array of interventions. The implications are clear: confining counseling for caregivers to such traditional dimensions as education or attempts to reduce emotional expressiveness denies them the opportunity to deal with other equally relevant concerns.

Adaptation, Psychological↗
PubMed1994

Contrasting patterns of evolutionary divergence within the Acinetobacter calcoaceticus pca operon.

The six enzymes required for catabolism of protocatechuate to succinate and acetylCoA are encoded by the pca genes in the Gram-bacterium, Acinetobacter calcoaceticus. The clustered A. calcoaceticus cat genes encode an analogous set of enzymes associated with the metabolic dissimilation of catechol. The nucleotide (nt) sequences of pcaIJFB and pcaK, reported here, complete evidence showing that all of the pca structural genes are tightly grouped in the order pcaIJFBDKCHG within a single operon. The pcaIJF region is nearly identical in nt sequence to the A. calcoaceticus catIDJF region which exhibits a G+C content and a codon usage pattern exceptional for A. calcoaceticus. In contrast, pcaD, pcaC, pcaH and pcaG have diverged substantially from their evolutionary counterparts in the cat region; all of these divergent genes exhibit G+C contents and codon usage patterns that are typical for A. calcoaceticus. The pcaIJF and catIJF regions are known to exchange DNA sequence information, and this property may have contributed to their nt sequence conservation. The pcaK gene has no counterpart among known cat genes. The deduced amino-acid sequence of PcaK indicates that it may be a transmembrane protein associated with transport.

Acetyl Coenzyme A↗
PubMed1992

An outbreak of respiratory syncytial virus in a bone marrow transplant center.

An outbreak of respiratory syncytial virus (RSV) infection occurred among 31 patients in a marrow transplant center over a 13-week period beginning in January 1990. RSV infection was also documented in 35 family members and employees. Of 18 patients with pneumonia, 14 (78%) died. None of 13 with upper respiratory infection died. Preengraftment patients tended to develop pneumonia more frequently than did engrafted patients. Early administration of ribavirin may have had a beneficial effect in patients with pneumonia. Antigenic and genomic analysis of 14 available isolates suggested that at least four different viral strains were responsible for the outbreak. One group of patients and 1 employee in spatial proximity were infected with the same strain and likely acquired their infections nosocomially. RSV infection in marrow transplant patients is a serious and life-threatening infection with a high mortality rate once pneumonia develops.

Adolescent↗
PubMed1989

Macrophages as targets for inhibition by cyclosporine.

In order to understand the mechanism of immunosuppression by cyclosporine, its effects on macrophage-mediated antigen-specific T cell activation (IL-2 production) were studied in vitro. While cyclosporine (CsA) present during the macrophage-T cell coculture inhibited antigen presentation effectively, pretreatment (2 hr) of macrophages with the drug also caused marked inhibition regardless of the antigen concentration and order of drug/antigen addition. Pretreatment of T cells caused only modest inhibition. With macrophage pretreatment, the structural analog cyclosporine-G had the same inhibitory activity as cyclosporine (cyclosporine-A), whereas dihydro-cyclosporine-D and cyclosporine-H were inactive. Cyclosporine demonstrated saturable binding to macrophages suggesting the existence of CsA-binding sites. A 50% inhibition of IL-2 production was achieved with 10(-6) M CsA and 60-70% of the binding sites were occupied at this concentration. CsA-treated macrophages did not release inhibitory material and the drug did not appear to be transferred from the macrophages to the T cells during the coculture. Although antigen-specific T cells could bind to drug-treated macrophages, they did not produce IL-2. Collectively, these results suggest that CsA has a direct effect on macrophages that subsequently interferes with IL-2 production at a stage following T cell antigen recognition.

Animals↗
PubMed1986

Immunoaffinity chromatography of carcinogen DNA adducts with polyclonal antibodies directed against benzo[a]pyrene diol-epoxide-DNA.

Polyclonal antibodies specific for (+/-)-trans-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(BPDE) CAS: 58917-67-2]-DNA adducts were obtained from the sera of New Zealand White rabbits immunized with BPDE-DNA. These antibodies did not recognize benzo[a]pyrene [(BP) CAS: 50-32-8] or DNA alone or other carcinogen adducts, such as aflatoxin (CAS: 1402-68-2)-DNA or aminopyrene (CAS: 58-15-1)-DNA, up to the concentrations used. In a competitive enzyme-linked immunosorbent assay, 0.18 microgram BPDE-DNA/ml (single stranded), equivalent to 7 pmol BPDE adduct, caused 50% inhibition with this antibody. (When referring to the DNA content of BPDE-DNA, the authors gave the concentration in microgram/ml; when referring to the BPDE content of BPDE-DNA, the authors gave the concentration as pmol/ml.) Chemical and enzymic modifications of the BPDE-DNA substrate suggested that the epitope for the antibody is greater than that represented by a BPDE-nucleoside adduct. The specific BPDE-DNA antibodies were covalently bound to cyanogen bromide-activated Sepharose 4B, and the extent of ligand binding to the immunoaffinity column was measured with the use of [3H]BPDE-DNA as substrate. Maximum binding to the immunoaffinity column was obtained after DNase 1 digestion of [3H]BPDE-DNA: The bound adducts could be readily eluted from the column with 50 mM NaOH. The binding of DNase 1-digested [3H]BPDE-DNA to the immunoaffinity column was dose related and not affected by the addition of unmodified DNA. The columns have proven to be reusable. Samples of [3H]BP-DNA isolated from the skin of mice treated topically with either 0.75 mumol [3H]BP/mouse or 1.5 mumol [3H]BP/mouse were examined by immunoaffinity chromatography. Binding values of 6.0 and 12.2 pmol BP/mg DNA were obtained; these values from immunoaffinity chromatography were slightly lower than those determined by high-pressure liquid chromatography analysis (9 and 17 pmol BP/mg DNA). With chemically reacted BPDE-DNA, around 70% of that applied was retained by immunoaffinity chromatography, whereas with [3H]BP-DNA isolated from the in vivo treatment of mouse skin, only 40% was retained--a possible reflection of the greater heterogeneity of the in vivo BP-DNA adducts. This immunoaffinity chromatography technique should prove useful in the selective examination of levels of BPDE-DNA adducts present in biological samples.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Intravenous etidronate in the management of malignant hypercalcemia.

The treatment of hypercalcemia remains a common problem in the management of many patients with cancer. We have used intravenously administered etidronate disodium as a therapy for hypercalcemia in 26 patients with malignant disease. Patients with persistent hypercalcemia despite adequate hydration and a serum creatinine level less than or equal to 1.5 mg/dL were allowed on study. Treatment consisted of intravenously administered etidronate disodium at 7.5 mg/kg/day in 250 mL of saline infused over two hours on 1, 2, 3, or 4 consecutive days. The serum calcium level in 19 (73%) of 26 patients returned to the normal range with a mean response time of 3 +/- 2 days. Similar response rates were seen in patients with a variety of tumors, including breast cancer, non-small-cell lung cancer, and multiple myeloma. Intravenously administered etidronate appears to be safe and effective therapy for hypercalcemia in patients with malignant disease.

Adult↗