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Biomedical subjects

S L Beck

Publications and source records attributed to S L Beck.

At least 19 recordsLinked to original sources

Caffeine decreases the occurrence of cadmium-induced forelimb ectrodactyly in C57BL/6J mice.

BACKGROUND: Cadmium is a well-known animal teratogen. Caffeine is an alkaloid widely consumed by humans. Interactions between teratogens and nonteratogenic doses of other agents are becoming widely studied, as they may shed light on understanding mechanisms of teratogenicity or possible prevention of teratogenic effects. METHODS: C57BL/6JBK mice were injected intraperitoneally (ip) with cadmium sulfate (Cd) at 0, 1.00 (LDCd), 2.50 (MDCd), or 5.00 (HDCd) mg/kg, immediately followed by subcutaneous (sc) administration of 0 or 50 mg/kg caffeine (CAFF) on gestation day (GD) 9. Fetuses were examined on GD 18 for ectrodactyly and other gross morphological malformations. RESULTS: Amelioration of cadmium-induced forelimb ectrodactyly by CAFF was seen in both the high-dose cadmium (HDCd = 65.4%, HDCd+CAFF = 39.2%) and medium-dose cadmium (MDCd = 46.2%, MDCd+ CAFF = 20.8%) treatment groups (P < 0.025). Bilateral expression of ectrodactyly was also decreased in the presence of caffeine. A statistically significant reduction in Cd-induced abnormalities, including: eye, abdominal, and other skeletal defects, was not seen with caffeine addition, although they did trend downward in the caffeine-supplemented groups. Litter size, fetal weight, fetal mortality, and dam weight also were not affected by co-treatment with caffeine. CONCLUSIONS: This study provides evidence that a subteratogenic dose of caffeine can ameliorate cadmium-induced forelimb ectrodactyly in the Cd-sensitive C57BL/6J inbred mouse strain.

Abnormalities, Drug-Induced↗

An ethnographic study of factors influencing cancer pain management in South Africa.

Although the knowledge exists to relieve cancer pain, inadequate pain relief persists as an international health problem. The World Health Organization has recommended a threefold strategy to improve cancer pain management: health policy, drug availability, and education. Yet major barriers to effective cancer pain management exist in every country of the world. Effective strategies to improve pain management must be based on an understanding of the issues in individual countries. This report evaluates cultural and other factors influencing cancer pain management in the Republic of South Africa. This ethnographic field study included multiple methods of data collection: analysis of documents, participant observation, focused interviews, and in-depth interviews of informants (n = 33) who represented multiple stakeholders in a variety of settings. Cultural beliefs and practices form the context for understanding cancer pain and how it is managed. Cultural variability exists regarding cancer as a disease, pain expectations, pain tolerance, pain expression, and health care practices. Key factors that influence how pain is managed included standards, knowledge, resources, communication and the patient-provider relationship, and teamwork and professional relationships. The existence of these factors promotes effective pain management, whereas their absence creates a barrier to achieving this aim.

Cultural Characteristics↗

Folinic acid reduces cleft lip [CL(P)] in A/WySn mice.

The A/WySnBk strain of mice displays 25-35% spontaneous CL(P). Pregnant mice were treated with folinic acid continuously delivered via osmotic minipumps at the rate of 7.6 +/- 0.2 microl/ hr (12 mg/ 24 hr) for the period covering gestation day (gd) 8.5-9.5, early in the critical period for formation of the face. Untreated and osmotic minipump-delivered, saline-treated groups served as controls. Individual fetuses were examined for CL(P) and other abnormalities on gd 18. The treatment resulted in a decrease in the frequency of CL(P) from 40.0+/-7.0% among untreated to 10.2+/-3.3% in the folinic acid group (P<.001). The difference between the folinic-exposed group and the saline-filled minipump and surgical control was also significant (P<.029). With respect to mortality, litter size, and fetal weight, the two minipump groups did not differ significantly, nor did they differ from the untreated group. Thus the reduction in CL(P) frequency was due to the presence of folinic acid and not to effects of the surgical procedures. This study provides evidence that administration of folinic acid during pregnancy has an important ameliorating effect on genetically predisposed CL(P).

Animals↗

Health policy, health services, and cancer pain management in the New South Africa.

In 1982, the World Health Organization (WHO) identified inadequate relief from cancer pain as an international health problem. WHO recommended that governments develop and implement national policies and programs for cancer pain relief. This report evaluates national health policy and the systems of health care delivery in relation to cancer pain management in the new South Africa. This field study included multiple methods of data collection: analysis of documents, field trips with participant observation in sites of care delivery, focused interviews, and in-depth interviews of key informants. The purposive sample of key informants (n = 33) represented multiple stakeholders in a variety of settings. Strengths of the developing health policy include specific recommendations related to palliative care; the shift to universal primary care; policies to support drug availability; the inclusion of morphine and codeine as essential drug at the primary health care level; and the development of a national standard related to cancer pain management. Health services are characterized by two parallel systems of care (private and public) with numerous vestiges of the inequities of apartheid. The management of pain varies by provider and setting; major problems with access exist in the rural areas. Health services in South Africa have been plagued by inequity and inadequate resources. New health policies have set a path to ensure universal access to health care including palliative care for cancer. Their successful implementation is the next necessary step toward improving health services and alleviating the suffering of increasing numbers of individuals with cancer.

Health Policy↗

Planning and conducting a multi-institutional project on fatigue.

PURPOSE/OBJECTIVES: To describe the process used in proposal development and study implementation for a complex multisite project on cancer treatment-related fatigue (CRF), identify strategies used to manage the project, and provide recommendations for teams planning multisite research. DATA SOURCES: Information derived from project team meeting records, correspondence, proposals, and personal recollection. DATA SYNTHESIS: The project was built on preexisting relationships among the three site investigators who then built a team including faculty, research coordinators, staff nurses, and students. Study sites had a range of organizational models, and the proposal was designed to capitalize on the organizational and resource strengths of each setting. Three team members drawn from outside oncology nursing provided expertise in measurement and experience with fatigue in other populations. Planning meetings were critical to the success of the project. Conference calls, fax technology, and electronic mail were used for communication. Flexibility was important in managing crises and shifting responsibility for specific components of the work. The team documented and evaluated the process used for multisite research, completed a major instrumentation study, and developed a cognitive-behavioral intervention for CRF. CONCLUSIONS: Accomplishments during the one-year planning grant exceeded initial expectations. The process of conducting multisite research is complex, especially when the starting point is a planning grant with specific research protocols to be developed and implemented over one year. Explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalize upon those differences, and recruiting a strong research team that included a member with planning grant and team-building expertise were essential elements for success. IMPLICATIONS FOR NURSING PRACTICE: Specific recommendations for others planning multisite research are related to team-building, team membership, communication, behavioral norms, role flexibility, resources, feedback, problem management, and shared recognition.

Communication↗

Terminology of developmental abnormalities in common laboratory mammals (version 1).

This paper presents the first version of an internationally-developed glossary of terms for structural developmental abnormalities in common laboratory animals. The glossary is put forward by the International Federation of Teratology Societies (IFTS) Committee on International Harmonization of Nomenclature in Developmental Toxicology, and represents considerable progress toward harmonization of terminology in this area. The purpose of this effort is to provide a common vocabulary that will reduce confusion and ambiguity in the description of developmental effects, particularly in submissions to regulatory agencies worldwide. The glossary contains a primary term or phrase, a definition of the abnormality, and notes, where appropriate. Selected synonyms or related terms, which reflect a similar or closely related concept, are noted. Nonpreferred terms are indicated where their usage may be incorrect. Modifying terms used repeatedly in the glossary (e.g., absent, branched) are listed and defined separately, instead of repeating their definitions for each observation. Syndrome names are generally excluded from the glossary, but are listed separately in an appendix. The glossary is organized into broad sections for external, visceral, and skeletal observations, then subdivided into regions, structures, or organs in a general overall head to tail sequence. Numbering is sequential, and not in any regional or hierarchical order. Uses and misuses of the glossary are discussed. Comments, questions, suggestions, and additions from practitioners in the field of developmental toxicology are welcomed on the organization of the glossary as well as on the specific terms and definitions. Updates of the glossary are planned based on the comments received.

Animals↗

Evaluation of scheduled J-pouch irrigations on decreasing stool frequency after ileoanal pull-through and ileostomy closure.

This study was intended to determine whether J-pouch irrigations through the efferent limb of the protective ileostomy stoma after ileoanal pull-through are effective in decreasing high stool frequency after ileostomy closure. Patients undergoing ileoanal pull-through may have high stool frequency after ileostomy closure. J-pouch irrigations through the efferent ileostomy stoma may decrease stool frequency by increasing J-pouch volume, improving storage capacity. The study used a randomized, prospective design in a university hospital outpatient setting. Participants (N = 58) were randomly assigned to control and experimental groups. Effectiveness of irrigation was determined by stool frequency. Both groups were taught Kegel exercises (anal muscle strengthening exercises). The experimental group was taught how and when to irrigate the J-pouch daily; the control group was not. Forty-seven subjects, 25 men and 22 women ranging in age from 15 to 65 years, completed the study. Results of MANOVA indicated no significant between-group difference in the average number of times that subjects performed Kegel exercises; however, there was a significant decrease during the 4-week study period (p < 0.001). There was no significant difference between groups in stool frequency, which decreased with time. There also was no significant effect on nocturnal leakage or satisfaction with surgical outcome. Additional clinical variables that were measured but had no significant effect included eating late, pouch size, and intake of sugar, fiber, bulk-forming products, and antidiarrheal agents. The study did not support the effectiveness of J-pouch irrigation in decreasing stool frequency after ileostomy closure. The cost, time commitment, and burden of performing daily irrigations are not warranted in this patient group.

Adult↗

Using patient focus groups for new patient services.

BACKGROUND: This article is intended to illustrate the usefulness of patient input in the strategic planning process and to demonstrate in particular the use of focus groups in concept development, concept testing, and program evaluation. INTERACTIVE PLANNING: Three areas of patient services were designed partly on the basis of patient input. "Service Teams with Appropriate Resources" (STARs) were conceived as basic organizational units to deliver interdisciplinary care to meet the needs of specific groups of patients. A patient services "menu" was envisioned to allow the patient or caregiver to decide which service would most appropriately and efficiently meet patient needs. The "Service Expectation Program" was formulated to ease entry into the hospital by providing information on what patients should expect from the hospital experience. CONCEPT TESTING: Focus groups were used again to test and refine the concepts developed during the interactive planning stage. General themes included the need for improved communication, the desire to be treated with respect and dignity (personhood), the need for coordination across the continuum of care, and the desire for more personal choice and control. ONGOING EVALUATION: Sources of patient feedback used in the ongoing evaluation process included a patient satisfaction survey and a telephone survey. Additional focus groups and telephone surveys are planned. MANAGEMENT ISSUES: The focus group discussions with patients introduced useful data into the quality improvement and interactive planning process. Findings were disseminated to all levels of hospital management and program staff through newsletters, reports, and in-service training sessions. Data were useful in interactive planning, program concept testing, and the development and implementation of new services.

Focus Groups↗

Additional endpoints and overview of a mouse skeletal variant assay for detecting exposure to teratogens.

CD-1 mice were exposed in utero to one of 14 treatment regimes, several of them being replicated, with close agreement between series. Prenatal exposure to a teratogenic dose at a sensitive time enabled detection of 10 of 14 teratogen regimes by alterations in frequency or severity of a substantial number of the 88 variants in the Skeletal Variant Assay System (SVAS) screen when examined at 60-65 days post natal (DPN). These included 2,4,5-T (245T), Trifluralin (TFL), Maneb (MNB), Decamethrin (DMT), Acetazolamide (ACZM) either at 8 days post-coitus (DPC) or days 9-11 PC, trypan blue (TB), or 5' Bromodeoxyuridine (BUDR) on either 7 DPC, 8 DPC, or 9 DPC. Most of these observations have been reported elsewhere. All of the treatment regimes mentioned above, and another group of treatments, could be detected in the exposed CD-1 cohorts when additional endpoints were employed. One such endpoint was "frequently responding variants." These were: Interfrontals (IF), Parted Frontals (PF), Preoptic Sutures (PS), Foramina Transversaria Imperfecta of the first cervical (C) vertebra (FTI C1), FTI of the axis (C2), Accessory (Acc) Transverse Foramina (TF) of C3-C6, malformations of C3-C7, Fourteen (14) Ribs, Carpal Fusions (Fus), Lumbar Fus, 27-Presacral Vertebrae (PSV), and Sacral Fus. This endpoint revealed significant differences in the initial group of 10, plus Captan (CAPT) and Phenytoin (DPH). Yet another useful endpoint reported here was the existence of high magnitude effects (i.e., dramatic alterations in frequency of occurrence of a variant). These included IF in TB and ACZM; PF in ACZM; PS in BUDR; FTI-C1 in TB and 245T; FTI-C2 in 245T; 14 Ribs in ACZM, BUDR, and TFL; Carpal Fus in TB; 27-PSV in ACZM; Fewer than (<) 30 Caudal Vertebrae (Vert) in 245T, TFL; Caudal Fus in TB, ACZM-D9. Eight treatment regimes in all could be detected by the existence of 3 or more high magnitude effects (245T, MNB, TB, ACZM8, ACZM9-11, phenytoin, and possibly BUDR on days 7 or 8, each seen in one of two series only). Clusters of related variants were affected in 9 of the 14 groups: Frontal (F) bones and C Vert in 245T; F bones in ACZM-D8; Fus in Posterior Vert Column in ACZM-D9-11; C Vert and Fus in Vert and articular skeleton in TB; Thoracic (Th) Vert and rib-cage effects in BUDR.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗

Acetazolamide with caffeine causes exencephaly in "resistant" SWV mice.

Pregnant SWV mice were treated on day 9 of gestation (PC) with 50 mg/kg of caffeine (CAFF), 200 mg/kg (LD) or 1000 mg/kg (HD) of acetazolamide (ACZM), or a combination of both agents, or on day 8 PC with both agents (ACZM + CAFF). Untreated (UNTD) and vehicle-treated (VEH) groups served as controls. The SWV strain is widely reported to be resistant to ACZM; it was resistant to ACZM or CAFF + ACZM when treated on day 9 of gestation, but a significant frequency of malformations, primarily exencephaly, was produced by ACZM + CAFF on day 8 PC. This study provides evidence that ACZM, coupled with a subteratogenic dose of caffeine can produce abnormalities in the "resistant" SWV mice, using the endpoint of exencephaly on day 8 of gestation. The mean number of ossified caudal vertebrae in day-9 treatments and ossified cervical vertebral centra in day-8 treatments were reduced. The frequency of ossification of the first cervical vertebra (C1) was reduced from 93% in UNTD to 39% in HD-ACZM day 9 PC and 69% in HD-ACZM + CAFF day 9 PC groups, and was also significantly reduced in the HD-ACZM + CAFF day-8 treated group.

Acetazolamide↗

Dependence of acetazolamide teratogenesis on fetal and not maternal genotypes.

This study assesses the relative contributions of dam and conceptus to sensitivity to acetazolamide teratogenesis in an in vivo mouse model. Reciprocal F1 outcrosses were made between mice resistant to the teratogenic effects of acetazolamide (SWV) and the susceptible C57BL/6JBk line. Female F1 progeny were backcrossed either to C57BL or to SWV males. The F1 outcross resulted in identical fetuses developing in genetically different uterine environments. In the backcrosses, genetically identical hybrid dams were gestating genetically different populations of segregating fetuses. In both F1 outcrosses and backcrosses, as well as in pure-line controls, dams were treated on day 9 of gestation by subcutaneous injection of acetazolamide (ACZM) at a dose level of 1500 mg/kg, or identical volume of the vehicle. The principal abnormality seen was right front limb ectrodactyly. Among pure-line matings, SWV produced no ectrodactyly, but 68% of C57BL showed this defect. Only two cases were seen in outcross of C57BL females to SWV males, and one litter produced three ectrodactylous fetuses in the reciprocal cross. A highly significant increase in ectrodactyly was seen in treated backcrosses to C57BL relative to backcrosses to SWV. Thus, a litter in which most of the genes segregating are from a susceptible line will show major increases in susceptibility, despite being in a heterotic and somewhat resistant uterine environment, whereas the susceptible C57BL uterine environment does not result in significant abnormality in heterozygous resistant fetuses. These results unequivocally demonstrate that it is the genotype of the conceptus, and not the genotype of the dam, nor heterosis, that determines sensitivity to acetazolamide teratogenesis. They further suggest that this genetic approach may be useful in determining the relative contribution of dam and conceptus for other teratogens.

Abnormalities, Drug-Induced↗

Bromodeoxyuridine leaves evidence of prenatal exposure in the postnatal skeleton in CD-1 mice.

Mice from two series of experiments (S1, S2) involving intraperitoneal (ip) injection of dams with 300 (High or H), 60 (Low or L), or 0 (VEH) mg 5'-bromodeoxyuridine (BUDR) per kilogram body weight (mg/kg) in water (15 mL/kg) on day seven (D7), day eight (D8), or in S2 only, day nine (D9) of gestation (9DPC), and untreated (UNTD) controls, were examined between 60 and 65 days postnatal (DPN) for 88 variations of the skeleton. In S1, 65 variants occurred, and in S2 there were 58 variants that occurred. Substantial numbers of significant differences (P less than 0.01) in frequency of occurrence (%) were seen in High dose only. The number of variants that differed from UNTD were 13, 13, 12, 15, and 11 in S1-D7H, S2-D7H, S1-D8H, S2-D8H, and S2-D9H, respectively; the average absolute difference in frequency among significantly affected variants was 16% to 20%. In the same order as above, 13, 12, 8, 10, and 9 variants differed significantly from VEH, and 9, 8, 7, 8, and 8 variants differed significantly from both UNTD and VEH. In contrast, 0, 0, 1, 1, and 0 variants differed from both UNTD and VEH in S1-D7L, S2-D7L, S1-D8L, S2-D8L, and S2-D9L, respectively. Agreement between the two series was good; 11 traits were affected in High dose litters in both series in at least 3 or 4 comparisons (compared with UNTD, VEH, in S1, S2).(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

Preventing hypoxemia and hemodynamic compromise related to endotracheal suctioning.

OBJECTIVE: To help the clinician bridge the gap between research and practice in determining ways to minimize side effects of endotracheal suctioning. DATA SOURCES: This article summarizes four previous reviews of research and studies published between 1984 and 1991 related to oxygenation techniques before, during and after endotracheal suctioning, and hemodynamic consequences of the suctioning procedure. STUDY SELECTION: Studies were reviewed by type of subject: animals, human subjects with normal lung function, and human subjects with abnormal lung function. Research of pediatric and head-injured populations was excluded from this review. DATA EXTRACTION: Oxygenation protocol, endotracheal suction characteristics, outcomes and measurement times, sample and setting, and findings were presented. CONCLUSIONS: Conclusions relate to the effectiveness of various endotracheal suction protocols on prevention of hypoxemia and hemodynamic compromise in intubated patients. DATA SYNTHESIS: An algorithm to guide clinical decision making is presented based on the conclusions of this review of the research.

Algorithms↗

Potentiating effect of caffeine on the teratogenicity of acetazolamide in C57BL/6J mice.

Pregnant C57BL/6J mice were treated with 0 or 50 mg of caffeine (CAFF) per kg, and 0, 200 mg/kg (L) or 1,000 mg/kg (H) of acetazolamide (ACZM) during day 9 of gestation (9DPC). Individual fetuses were examined for gross morphological abnormalities and skeletal variations. The increase in fetal malformations seen, especially right forelimb electrodactyly, was augmented at both dose levels of acetazolamide by concomitant exposure to caffeine. Both frequency and severity of ectrodactyly were potentiated by caffeine. Skeletal examination revealed a reduction of the number of ossified cervical and caudal vertebral centra among litters exposed to ACZM at either dose. In either case (ACZM-H, ACZM-L) that effect was augmented by co-administration of CAFF. The first cervical vertebra (C1) appeared to provide the most sensitive index of teratogenic exposure. This study provides evidence that a subteratogenic dose of caffeine can potentiate the teratogenic effect of acetazolamide in C57BL/6J mice when dams are treated on day 9 of gestation. In addition, skeletal examination provided evidence that simultaneous treatment with both agents delayed fetal development. Many litters exposed to ACZM or both agents displayed a reduction in skeletal ossification even in the absence of gross morphological abnormalities, suggesting that ossification can be used as an indicator of prenatal exposure to potentially harmful substances in the C57BL/6 mouse strain.

Abnormalities, Drug-Induced↗

Mitosis and histopathology in rat liver during methylclofenapate-induced hyperplasia.

Liver hyperplasia was induced in rats by daily administration of methylclofenapate (25 mg/kg by gavage). An increase in the incidence of colchicine-arrested metaphases was observed with peaks occurring at 40 h (1.3%), 64 h (6.4%) and 84 h (6.8%) after the start of treatment. This response contrasted with the much larger (21.3%) peak in arrested metaphases at 36 h after partial hepatectomy, but was still unexpectedly large in comparison with the S-phase response to methylclofenapate reported in a previous study. Progressive hypertrophic histopathological changes were apparent during the whole course of treatment.

Animals↗