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Biomedical subjects

R Strand

Publications and source records attributed to R Strand.

At least 19 recordsLinked to original sources
PubMed2001

The role of risk assessments in the governance of genetically modified organisms in agriculture.

Controversy abounds in the governance of genetically modified organisms (GMOs) for use in agriculture, partly due to ideological differences. Technological optimism and the "shallow" and the "deep" ecology movements are three influential ideologies that are seen to differ both on value commitments and factual beliefs with respect to GMOs. Factual matters are clarified but not resolved by science, since the scientific community faces uncertainty and apparent contradiction between different research perspectives, notably molecular biology, ecology and the social sciences. Scientific advice plays a key role in the governance of GMOs and ought to be construed so as not to exclude legitimate arguments from ideological perspectives present in the process of governance. This paper analyses the role and use of risk assessments and argues that they be replaced by forms of advice that consider a broader spectrum of scientific evidence and insights, e.g. impact assessments and evaluations of inherent sources of uncertainty and ignorance. A few practical measures to that effect are discussed.

Agriculture↗
PubMed2001

[Does knowledge hurt?].

The rate of production of medical knowledge is high and increasing, and medical practitioners find it hard to keep up. Still, production of new knowledge is normally considered to be unambiguously desirable. This paper is a philosophical reflection upon this assumption of desirability. It is noted that the health sector appears to be subject to the law of diminishing returns; this implies that more doctors and more medical technology may at some level do more harm than good. We argue that Bacon's legitimization of knowledge (knowledge is power) is less forceful in the face of biological and psychosomatic complexity. Medical research may lead to unintended harm through at least two mechanisms. First, biomedical knowledge is reified through the introduction of new medical technology whose effects are not fully known, and may lead to uncontrollable adverse effects on a clinical and societal level. Second, exaggerated attention paid to the production and implementation of biomedical factual knowledge may prevent the development and teaching of personal clinical skills, including phronesis, the individual judgemental powers that enable us to judge which goals are worth striving for, and which are not.

Humans↗
PubMed2001

[Risk, uncertainty and ignorance in medicine].

Exploration of healthy patients' risk factors for disease has become a major medical activity. The rationale behind primary prevention through exploration and therapeutic risk reduction is not separated from the theoretical assumption that every form of uncertainty can be expressed as risk. Distinguishing "risk" (as quantitative probabilities in a known sample space), "strict uncertainty" (when the sample space is known, but probabilities of events cannot be quantified) and "ignorance" (when the sample space is not fully known), a typical clinical situation (primary risk of coronary disease) is analysed. It is shown how strict uncertainty and sometimes ignorance can be present, in which case the orthodox decision theoretical rationale for treatment breaks down. For use in such cases, a different ideal model of rationality is proposed, focusing on the patient's considered reasons. This model has profound implications for the current understanding of medical professionalism as well as for the design of clinical guidelines.

Decision Making↗
PubMed1996

In vivo interpretation of in vitro effect studies with a detailed analysis of the method of in vitro transcription in isolated cell nuclei.

In vitro experimental approaches are of central importance to contemporary molecular and cellular biology and toxicology. However, the scientific value or impact of in vitro results depends on their relevance in vivo. In vitro effect studies address inobservable in vivo phenomena through experiments on analogous in vitro phenomena. We present a theoretical basis developed to evaluate the in vivo relevance of in vitro effect studies. As a case study, the procedure for measuring specific gene transcription in isolated cell nuclei (¿nuclear run-off method¿) is analyzed. It is concluded that current evidence fails to justify in vivo interpretations of nuclear run-off experiments within the framework of theoretical models of transcription, implying that quantitative in vivo interpretations are unwarranted. Qualitative interpretations of nuclear run-off experiments may be justified by inferring ¿the best explanation¿, especially when significant in vitro effects follow in vivo perturbations. Elements of a general theory are proposed. It is concluded that quantitative in vivo interpretations are warranted primarily in biochemical quantitation of biomolecules, while studies on biological function should be interpreted qualitatively in terms of causal explanations. Inferences to the best explanations are strengthened through additional evidence and the creation of experimental differences (effects).

Animals↗
PubMed1994

The choice of resuspension medium for isolated rat liver nuclei: effects on nuclear morphology and in vitro transcription.

Standard protocols for in vitro transcription assay (nuclear run-off) include 10-40% (v/v) glycerol (of various ionic strength) in the medium used for resuspension/storage of the isolated nuclei. In the present work the morphological and functional properties of nuclei isolated from rat liver have been studied as a function of the content of glycerol, sucrose and inorganic ions (K+ and Mg2+) in the resuspension medium. In contrast to earlier reports, glycerol was found not to be essential to maintain morphological integrity and RNA polymerase activity in frozen/stored nuclei. Nuclear pellets, resuspended and stored in isoosmotic sucrose media, were found to give morphologically intact and transcriptionally active nuclei. Furthermore, these nuclei displayed a higher specific hybridization signal for the differentially expressed genes encoding peroxisomal beta-oxidation enzymes, relative to the total RNA synthesis, than nuclei resuspended and stored in a hyperosmotic glycerol-containing medium. The concentrations of inorganic ions were also found to affect nuclear morphology. Flow cytometry indicated DNA leakage from nuclei at insufficient concentrations of K+ and Mg2+, and high ionic strength favoured aggregation and disintegration of nuclei. Our findings indicate that quantitative results from nuclear run-off experiments should be interpreted with caution until the process of transcription in isolated nuclei is better understood.

Animals↗
PubMed1994

The changing activities of a regional marrow donor program.

BACKGROUND: A regional marrow donor program was established in 1982. Following the establishment of the National Marrow Donor Program (NMDP) in 1987, the activities of this regional program changed. STUDY DESIGN AND METHODS: To better understand the changes that occurred in the regional marrow donor program, its donor recruitment and marrow collection activities through 1991 were studied retrospectively. Data analyzed included the total number of potential donors, the number and types of potential donors recruited each year, the number of searches performed, the number of samples collected for HLA-DR typing and mixed lymphocyte culture testing, and the number of transplants in both programs from 1987 through 1991. Statistical analysis was performed by using chi-square. RESULTS: Initially, only persons who donated platelets by apheresis were enrolled into the program. In 1986, the regional program's first drive to recruit people who were not apheresis donors occurred. The number of such drives increased each year, and in 1991, 12 drives occurred, which resulted in the recruitment of 1313 potential marrow donors. From 1987 to 1991, the number of potential donors in the regional program grew from 3252 to 9146, but the proportion of apheresis donors in the program decreased. In 1987, 91.9 percent of marrow donors at the regional center had been apheresis donors, but in 1991, 41.7 percent had been apheresis donors. The number of marrows donated at the regional center increased from 11 in 1987 to 29 in 1989, but then fell to 24 per year in 1990 and 1991. The decrease in the number of donations at the regional program was due to the rapid growth in the NMDP file of potential marrow donors and the selection of donors whose HLA antigens were more compatible with those of the transplant recipients. In 1989, the regional program contained 4.6 percent of all HLA-A,B-typed and 11.2 percent of all HLA-A,B,DR-typed potential donors in the NMDP and collected 15.3 percent of all marrows. However, in 1991, the regional program contained 2.0 percent of HLA-A,B-typed donors and 4.1 percent of HLA-A,B,DR-typed donors and collected 5.3 percent of marrows. In 1987, 18 percent of the people who donated marrow at the regional center were phenotypically HLA-A,B,DR identical with the recipient, but in 1991, 92 percent of donor-recipient pairs were phenotypically HLA-A,B,DR identical. CONCLUSION: Recruitment activities became an increasingly larger part of the Regional Marrow Donor Program's activities. Increasing the size of the file of potential donors was necessary to maintain a constant number of donations. Persons who were not regular blood donors were an important part of the marrow donor program.

Blood Donors↗
PubMed1989

Attitudes and physical condition of unrelated bone marrow donors immediately after donation.

Annually, over 3000 bone marrow transplants are performed worldwide involving HLA-identical sibling donors. However, only 30 percent of those patients who need a bone marrow transplant have a matched sibling donor. Programs have been developed to provide volunteer unrelated bone marrow donors for patients without sibling donors. Because bone marrow donation requires a high level of altruism, especially on the part of a donor unrelated to the patient, it is important to determine the effect of donation on the donor. Serious medical complications during the collection of marrow from related donors have been reported only rarely, but there have been no reports on the psychosocial and physical effects of the bone marrow donation process on volunteer unrelated bone marrow donors. The first 20 unrelated volunteers who donated bone marrow through the authors' volunteer bone marrow donor program were surveyed. They suffered no serious emotional or physical aftereffects. Seventeen of 20 donors reported that making the decision to donate was easy, and 16 reported making the decision to donate right away. Nine of 20 donors, however, stated that a friend or family member discouraged them from donating. All 20 donors thought that they were well prepared for the donation process. Four donors thought that the donation process required more time than they expected, but four donors thought the reverse. One person thought the process was more painful than they expected; however, 12 found the process to be less painful than expected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Neurological complications of hemolytic-uremic syndrome.

Of 78 children identified with hemolytic-uremic syndrome at the Children's Hospital, Boston, from 1976 to 1986, 16 patients (20.5%) had neurological manifestations during their hospitalization. The most common manifestations were significant alterations in consciousness (coma, stupor) in 12 patients, and either generalized or partial seizures in ten patients. Others included hemiplegia (4 patients), decerebrate posturing (3), cortical blindness (2), hallucinations (1), and dystonic posturing (1). Cranial computed tomographic scans were abnormal in eight of 11 patients scanned. The abnormalities included diffuse cerebral edema (4 patients), large vessel infarctions (3), diffuse multiple small infarcts (4), and multiple hemorrhages (1). Five patients died as a result of their central nervous system complications, and six had neurological sequelae at discharge. Five patients recovered and at discharge had no evidence of neurological dysfunction.

Brain↗
PubMed1989

Pre-irradiation chemotherapy for infants and children with medulloblastoma: a preliminary report.

From March, 1984, through June, 1987, 21 newly diagnosed children with high-risk medulloblastoma (Chang Stage T3 to T4) were treated on a 9-week postoperative, pre-irradiation chemotherapy regimen consisting of vincristine and cisplatin. The children over 2 years old then received radiation therapy. Six infants (aged 6 to 18 months) were maintained on chemotherapy consisting of MOP (nitrogen mustard, vincristine, and procarbazine) until the age of 2 years, at which time they were referred for irradiation. Of 13 children with measurable disease following surgery, five showed a definite response on computerized tomography scans to vincristine and cisplatin (one complete response and four partial responses) and five others showed clear marginal responses. Four of the six infants were disease-free at 19, 32, 35, and 57 months from diagnosis. One infant developed progressive disease at the completion of the vincristine and cisplatin course, and a second infant had progression during MOP administration. Three of the 21 children developed hearing loss within the speech frequencies during cisplatin treatments, but there were no other major toxicities. Fifteen children remained disease-free with a median follow-up period of 35 months (range 19 to 57 months). Chemotherapy given between surgery and radiotherapy may allow for the direct evaluation of a specific drug regimen and permit the postponement of radiation therapy in infants. Pre-irradiation vincristine and cisplatin was well tolerated and effective in shrinking the tumor in most children with medulloblastoma. Such chemotherapy regimens have the potential for extending long-term survival in high-risk children.

Adolescent↗
PubMed1987

Nonrandom chromosomal aberrations and clonal chromosomal evolution in acute leukemia associated with Down's syndrome.

Nine Down's syndrome (DS) children, four with acute leukemia, one with acute leukemia as well as rhabdomyosarcoma, and four with other hematologic disorders, were analyzed for constitutional and acquired chromosomal aberrations. Acquired clonal chromosomal aberrations were identified only in the acute leukemia cases, and four of the five acute leukemia demonstrated numerical and/or structural aberrations involving chromosomes #8, #19, and #21. Of the 11 aneuploid stem cell lines identified in the five acute leukemia cases, trisomy 21, trisomy 8, trisomy 19, and tetrasomy or pentasomy 21 was found in 11, seven, four, and two lines, respectively. The frequent appearance of multiple stem cell lines with common and/or overlapping chromosomal aberrations in acute leukemia cases demonstrates the existence of genomic instability and heterogeneity of the neoplastic cell population, which results from clonal chromosomal evolution. Furthermore, trisomy 19 was identified only with the concurrent presence of trisomy 8, suggesting that the nondisjunction of chromosome #19 probably occurred after that of #8. Trisomy 21 was observed in every aneuploid stem cell line and, in one case, trisomy 21 was maintained in the bone marrow leukemic cells but not in the orbital rhabdomyosarcoma cells, indicating that this constitutional chromosomal aberration is probably crucial for and predisposed to the development of acute leukemia in DS patients. The association of acquired clonal chromosomal aberrations, especially those involving chromosomes #8, #19, and #21, with DS acute leukemia strongly suggests the clinical implication of cytogenetic analysis in the diagnosis of acute leukemia development in DS patients.

Acute Disease↗
PubMed1986

Traumatic parturitional intracranial hemorrhage.

Twenty-five cases of intracranial hemorrhage due to injury at birth, encountered over a seven-year period, are presented. CT scans showed many different pathways of spread of tentorial hemorrhage; the likelihood of an arterial source is emphasized. Recurrent or delayed bleeding was documented twice. Surgical evacuation of hematomas was necessary in 10 cases, seven involving hemorrhage into the posterior fossa. There were three deaths, one due to pulmonary hemorrhage complicating subtentorial subdural hematoma, another due to severe central parenchymal hemorrhage and a third because of postoperative cerebellar hemorrhage due to disseminated intravascular coagulation. Three survivors are dependent on shunts, two because of the birth injury. The outcome for neurological and intellectual function depends more on associated asphyxia than on the trauma.

Arteries↗
PubMed1986

Nasal airway obstruction: CT assessment.

Twenty-one cases of nasal airway obstruction were analyzed using computed tomography (CT) at the Children's Hospital in Boston between 1980 and 1984. Seven of these patients had stenosis of the entire nasal passage, two had stenosis of the anterior nasal cavity, and 12 had atresia of the posterior choanae. The spectrum of these abnormalities and the optimum technique for CT scanning are discussed.

Child↗
PubMed1986

Immunological heterogeneity in human melanoma: immunogenic alloantigen expression in autologous host.

A patient presented with a primary melanoma, Level IV, 2.5 mm thick; 30 excised lymph nodes were all negative for tumor. Four local recurrences followed in the ensuing 17 months. Tumor cells cultured at this time were epithelioid. Autoimmunization was followed by a disease-free interval of 15 months. Postimmunization, the patient's lymphocytes destroyed his melanoma cells in culture and were stimulated in mixed cell culture by his irradiated tumor cells. Cells grown from the relapsing tumor were spindle/dendritic with bizarre morphology and were not attacked by his lymphocytes in culture. Using a C' fixation technique, DR antigen profiles of the patient's B-cells and both tumor cell types showed that the immunizing tumor was positive for DR antigens 3, 5, and 8, none of which were present on his B-cells which had DR 2 and 4. Both B-cells and immunizing tumor cells were positive for DQ antigens. The relapsing tumor cells were positive for DR2 and negative for all other D region antigens tested. The evidence suggests that given a melanoma of heterogeneous cell population, autoimmunization against the predominant immunogenic cell inhibits tumor growth but allows the ascendance of a nonimmunogenic tumor cell type.

Antigens, Neoplasm↗
PubMed1984

NMR imaging in temporal lobe epilepsy due to gliomas.

Magnetic resonance (MR) imaging has been shown to have greater sensitivity than X-ray CT in a broad range of intracranial pathologic processes. In regions in which CT is likely to suffer degradation of image quality due to a variety of bone artifacts, the advantages of MR are even more striking. Previous reports have emphasized the relative advantages of MR in studies of the posterior fossa. The present report documents the potential for similar advantages of MR in demonstration of middle fossa anatomy and in identification and characterization of temporal lobe lesions. In three patients with anterior temporal lobe gliomas and temporal lobe epilepsy, MR (even with the use of an early prototype, resistive system of 0.15 T) was clearly superior to contrast-enhanced CT in demonstrating the pathology. This considerably assisted preoperative evaluation.

Adolescent↗
PubMed1983

Congenital hydrocephalus due to villous hypertrophy of the telencephalic choroid plexuses. Case report.

A case of villous hypertrophy or bilateral papilloma of the choroid plexus of the lateral ventricles is reported. The child exhibited known features associated with overproduction of cerebrospinal fluid, hydrocephalus that was difficult to control, ascites after ventriculoperitoneal shunting, and relief after surgical removal of the papillomatous tissue. A unique feature is the complexity of the telencephalic choroid plexuses as shown by computerized tomography and ultrasound in the newborn period.

Cerebral Ventricle Neoplasms↗