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S Anderson

Publications and source records attributed to S Anderson.

At least 289 records · Page 16Linked to original sources
PubMed1995

Down-regulation of the intrarenal renin-angiotensin system in the aging rat.

Progressive deterioration of renal function occurs during normal aging. Previous studies on the aging kidney have demonstrated glomerular hemodynamic changes, specifically, glomerular capillary hypertension, as maladaptations that lead to proteinuria and glomerular sclerosis over time. Aging rats treated with angiotensin-converting enzyme inhibition have relatively less proteinuria and sclerosis, suggesting that age-related changes in renal function may be associated with alterations in the intrarenal renin-angiotensin system, which thus may play a major role in the pathogenesis of these maladaptations. To investigate this possibility, renal and systemic renin-angiotensin systems were examined at an early phase of the aging process (3 months) and at a later phase (12 months) in male Sprague-Dawley rats. Although plasma renin and serum angiotensin-converting enzyme concentrations did not differ significantly, the intrarenal system showed down-regulation of renin mRNA and angiotensin-converting enzyme levels with aging, whereas angiotensinogen levels remained stable. The decrease in renin mRNA appeared to precede the fall in plasma renin concentration in the aging process. Additional studies in 15-month-old rats confirmed that, by this time, both basal and stimulated renal renin release rates were impaired in older rats. Thus, both decreased renin synthesis and impaired renin release underlie the fall in plasma renin with normal aging. This decrease may act to lower intrarenal baseline levels of angiotensin II, an adaptation of likely importance in the modulation of intrarenal vascular tone and tubular function in the aging kidney.

Aging↗
PubMed1995

Caloric irrigators: air, open-loop water and closed-loop water.

Selective stimulation of the semicircular canal system of one ear by establishing a temperature gradient is still widely used in the clinic in the caloric test. The results obtained are noted for their imprecision and variability. This is, in part, due to a lack of uniformly applied standardized test protocols, as well as difficulties in applying a precise stimulus. The relative merit of the three types of irrigation are reviewed. Whilst some authors argue that both the closed-loop and air irrigators produce even more variability of response than open water systems, the present author believes that intratest replication studies indicate that the closed-loop irrigation stimulus is the least variable and best tolerated by the patient. In perhaps one-fifth of patients, response to the first irrigation is much stronger than subsequent stimulus applications. It is suggested that there may therefore be a case for routinely performing five irrigations in the bithermal caloric test, including a replication of the first irrigation. It is assumed that psychological factors, especially anxiety, may explain the phenomenon of enhanced initial response, and some of the variability of caloric test responses in general. Use of the closed-loop irrigator is advocated for ease of use, reduced routine maintenance and to minimize patient distress, thereby reducing anxiety and result variability.

Air↗
PubMed1995

Engraftment characteristics of peripheral blood stem cells mobilised with cyclophosphamide and the delayed addition of G-CSF.

The optimal protocol for the mobilisation of PBSC remains unknown. We present data on 42 patients mobilised with cyclophosphamide (3 or 4 g/m2) and the delayed addition of a standard 300 micrograms dose of G-CSF (Filgrastim) from day +5. The patients had received a median of 2 previous chemotherapy regimes, 38% had received prior radiotherapy and 38/42 had active disease at the time of mobilisation. The protocol was well tolerated and 38 patients proceeded to transplantation. The median number of CD34+ cells reinfused was 4.3 x 10(6)/kg (range 0.5-30) and CFU-GM 15.8 x 10(4)/kg (range 0-148). The total number of CD34+ cells harvested correlated with the total number of CFU-GM available for reinfusion (P = 0.008). Overall engraftment occurred within median days to neutrophils > 0.5 x 10(9)f/l or platelets > 20 x 10(9)/l of 14 and 13 days, respectively. Patients receiving more than 2.5 x 10(6)/kg CD34+ cells had even more rapid haemopoietic reconstitution with significant reductions in hospital stay and transfusion requirements. Those below this threshold had significantly delayed platelet engraftment. The mobilising dose of cyclophosphamide did not influence the achievement of the threshold CD34+ cell yield for optimal engraftment. The delayed addition of a standard 300 micrograms G-CSF dose after priming chemotherapy resulted in the use of a median 9 days hence 9 vials of G-CSF. This protocol presents the potential for cost saving without compromising the quality or success of PBSC mobilisation.

Adult↗
PubMed1995

An interlaboratory comparison of the FDA protocol for the evaluation of cavitation potential of mechanical heart valves.

Five laboratories carried out measurements of cavitation threshold for a common set of six mechanical prosthetic heart valves, two each from three different manufacturers. This study was intended to evaluate to what extent FDA's current guidance for cavitation testing would lead to consistent results in a variety of laboratory settings and to seek areas for improvement in the recommended test protocol. The inter-laboratory study protocol specified: (1) characterization of the test fluid by oxygen content and electrical conductivity, (2) location and frequency response of pressure sensors, (3) determination of ventricular and atrial pressures (P) and loading rates (dP/dt) averaged over the time period of valve closure and over the time periods of 1 ms, 5 ms, and 20 ms prior to video visualization. The protocol did not specify: (1) the fluid pumping equipment to be used to generate cavitation, (2) the pump or fluid parameters adjusted to raise or lower the loading rate, (3) the equipment, technique, or sensitivity used to visualize cavitation, and (4) a specific definition of the threshold for cavitation. Results from the five laboratories are reported. Significant differences in results were observed in dP/dt and in the pressure difference across the valves during closure at cavitation threshold. Specific differences in test systems included a wide range of ventricular compliance and single valved versus double valved test systems. Three single valve systems with compliant ventricles produced results in reasonable agreement with one another. Further similarity in test equipment should be specified to assure adequate interlaboratory reliability for cavitation testing. Areas needing better specification include the design of the valve mount, the design of the cavitation generators, and qualitative criteria for detection of threshold cavitation.

Biocompatible Materials↗
PubMed1994

Genetic Bit Analysis: a solid phase method for typing single nucleotide polymorphisms.

A new method for typing single nucleotide polymorphisms in DNA is described. In this method, specific fragments of genomic DNA containing the polymorphic site(s) are first amplified by the polymerase chain reaction (PCR) using one regular and one phosphorothioate-modified primer. The double-stranded PCR product is rendered single-stranded by treatment with the enzyme T7 gene 6 exonuclease, and captured onto individual wells of a 96 well polystyrene plate by hybridization to an immobilized oligonucleotide primer. This primer is designed to hybridize to the single-stranded target DNA immediately adjacent from the polymorphic site of interest. Using the Klenow fragment of E. coli DNA polymerase I or the modified T7 DNA polymerase (Sequenase), the 3' end of the capture oligonucleotide is extended by one base using a mixture of one biotin-labeled, one fluorescein-labeled, and two unlabeled dideoxynucleoside triphosphates. Antibody conjugates of alkaline phosphatase and horseradish peroxidase are then used to determine the nature of the extended base in an ELISA format. This paper describes biochemical features of this method in detail. A semi-automated version of the method, which we call Genetic Bit Analysis (GBA), is being used on a large scale for the parentage verification of thoroughbred horses using a predetermined set of 26 diallelic polymorphisms in the equine genome.

Autoanalysis↗
PubMed1994

Analysis of nucleotide pools in human lymphoma cells by capillary electrophoresis.

Capillary electrophoresis is applied to determine nucleotide pool levels in human Burkitt lymphoma cells. The analysis was performed on a 65 cm x 50 microns I.D. Ucon-coated column with on-column UV detector. The method requires only nanoliters of sample and a simple sample preparation procedure. Over 12 nucleotides were separated and quantitated with high resolution and reproducibility. The whole capillary electrophoretic separation time was only 35 min. These results demonstrate that capillary electrophoresis provides a useful and easy way to analyze nucleotide pools in cells.

Adenine Nucleotides↗
PubMed1994

Single- and multilocus DNA fingerprinting of communally breeding pukeko: do copulations or dominance ensure reproductive success?

In behavioral and ecological studies the "function" of dominance hierarchies is thought to be related to reproductive success. In particular, dominant males are regarded as likely to gain a reproductive advantage due to enhanced "access" to females. We compare the dominance status of adults with the frequency of copulations and the patterns of parentage in communally breeding pukeko or purple swamphen (Porphyrio porphyrio melanotus). This avian species has an unusual social system, often breeding in polygynandrous groups in which there is a strong dominance hierarchy. Typically, during the breeding season, there is considerable sexual activity, with heterosexual and homosexual copulations between adults being commonplace. Hae III-digested DNA from individuals belonging to breeding groups was hybridized to the minisatellite DNA probe YNH24, revealing putative single-locus profiles, while hybridization of the same DNA to the minisatellite probes pV47-2, 3'HVR, and per revealed typical multilocus profiles. The numbers of unattributable restriction fragments allowed the maternity and paternity of all individuals to be conclusively determined, despite high levels of band sharing among individuals within breeding groups. These close genetic similarities are a likely consequence of strong philopatry and inbreeding. We report instances of males which are high on the dominance hierarchy but have only a limited reproductive output in comparison with others and males which are subordinate but achieve a significant proportion of fertilizations. Generally these data reveal no consistent relationship between dominance, the frequency of copulations, and parentage among males. We conclude that pukeko highlight some difficulties with conventional explanations for the "function" of dominance.

Animals↗
PubMed1994

Involvement of protein kinase C in cAMP regulation of myelin basic protein gene expression.

Since synthesis of myelin components has been seen to be stimulated by cAMP in both oligodendrocytes and Schwann cells we have begun investigating the specific sequence(s) in the 5' flanking region of the myelin basic protein (MBP) gene that are responsible for the induction of MBP transcription by cAMP. Using stably transfected cell lines containing various deletions of the MBP promoter directing the bacterial chloramphenicol acetyltransferase (CAT) gene we have identified a region of the MBP gene that is inhibitory to stimulation by increased cAMP levels. This inhibition can be overcome by pretreating the cells with 12-O-tetradecanoylphorbol 13-acetate (TPA) for 48 hr. The effects on MBP gene expression modulated by TPA and cAMP involve altered DNA-protein interactions in the 5' end of the MBP promoter. The effect of TPA also appears to be mediated by down-regulation of protein kinase C.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Retention of B-cell-specific monoclonal antibodies by human lymphoma cells.

The rates of endocytosis, intracellular degradation, and cell-surface shedding of 125I-labeled monoclonal antibodies (MoAbs) HD-37 (anti-CD19), B1 (anti-CD20), MB-1 (anti-CD37), BC8 (anti-CD45), and DA4-4 (anti-mu) by B-lymphoma cells were compared by cellular radioimmunoassay, ultrastructural autoradiography, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and thin layer chromatography using biopsy specimens from 12 patients with non-Hodgkin's lymphomas. 125I-BC8 was stably retained on the surface of lymphoma cells without appreciable internalization or shedding, whereas 125I-DA4-4 underwent rapid endocytosis and degradation. 125I-B1 was not internalized or degraded by tumor cells, but rapidly dissociated from the cell surface in intact form. Moderate rates of endocytosis, intracellular metabolism, and cell-surface shedding were shown by 125I-HD37 and 125I-MB-1. The 3 patients with diffuse, small cleaved-cell lymphomas internalized and degraded antibodies more slowly than did patients with other histologic subtypes. These kinetic differences may be important in the selection of MoAbs for immunotoxin and radioimmunoconjugate therapy of B-cell malignancies.

Antibodies, Monoclonal↗
PubMed1994

Measuring switchability and prescribability: when is average bioequivalence sufficient?

Recent work, beginning with that of Anderson and Hauck in 1990, has led to a general acceptance of the need to ensure switchability in bioequivalence testing for approval of generic drugs. In other applications of bioequivalence testing, prescribability may be sufficient. However, there is less acceptance of the need to change statistical procedures and study designs from those currently used to assess the current criterion of average bioequivalence. We propose easily interpreted measures of switchability and prescribability. These measures provide bases for assessing conditions under which average bioequivalence is not sufficient to ensure switchability and prescribability, and hence for which a procedure for individual or population bioequivalence is required. The required conditions are sufficiently tight that they cannot be presumed to hold. Thus, there are reasonable conditions for which current practice is not sufficient. An outcome of this development is a connection between two current approaches for assessing individual bioequivalence.

Drug Prescriptions↗
PubMed1994

Corporal punishment in elementary education: views of Barbadian schoolchildren.

Most previous research has suggested that children often express little unconditional disapproval of the use of corporal punishment in schools. However, this might be expected to change when pupils become aware that such treatment is no longer permitted in many countries, or hear it labelled as "abuse." This paper reports on research conducted in elementary schools in the Caribbean island of Barbados, where head teachers (or their authorized deputies) are still permitted by law to use corporal punishment. Findings indicated that approximately three-quarters of pupils surveyed still approved use of corporal punishment with their own age group, although their comments also suggested that a considerable amount of routine (and illegal) "flogging" or "lashing" by regular classroom teachers occurred, which many wished to see stopped. The growing risk of clashes between parents and schools was also identified. While this and other recent studies in Barbados provide little evidence of support for the total abolition of corporal punishment within the educational system, it is hoped that research may have some role to play in exerting pressure on schools to eliminate some of their more ritualized and pedagogically counterproductive practices.

Attitude↗
PubMed1994

Blood donor counselling for HIV: results of a multi-country feasibility study.

A qualitative characterisation study was conducted by the World Health Organisation's Global Programme on AIDS, and the International Federation of Red Cross and Red Crescent Societies, in six developing countries in order to determine the feasibility of introducing blood donor counselling into procedures for blood donation at blood transfusion sites. After careful preparation of consultants, in-country visits were made to include structured discussions with key BTS and Red Cross, and national AIDS programme staff, and donors, and observations of relevant facilities. Necessary resources, management requirements, obstacles to and options for blood donor counselling were explicated, together with information on the role of HIV testing in motivating blood donation, and problems associated with this and with donor notification. Blood donor counselling is seen as feasible, provided minimum conditions can be established to ensure appropriate standards and availability of resources.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Modulation of glomerular hypertension defines susceptibility to progressive glomerular injury.

The fawn-hooded rat constitutes a spontaneous model for chronic renal failure with early systemic and glomerular hypertension, proteinuria (UpV) and high susceptibility to development of focal and segmental glomerular sclerosis (FGS). It has been argued that uninephrectomy (UNX) accelerates the development of glomerular injury by aggravation of glomerular hypertension and by an independent effect to promote glomerular enlargement. The present study was performed to further delineate the importance of these parameters for the development of FGS. At the age of eight weeks male rats were UNX and randomly assigned to either control (CON), enalapril (ENA) or Nw-nitro L-arginine methyl ester (NAME) treatment. In all groups glomerular hemodynamic studies were performed four weeks post-UNX. Systemic blood pressure and UpV were monitored for 4 to 12 weeks post-UNX. Kidneys were then prepared for morphologic study. ENA treatment achieved control of both systemic and glomerular hypertension, maintenance of glomerular hyperfiltration and hyperperfusion, increased ultrafiltration coefficient(Kf), and long-term protection against UpV and FGS. NAME rats showed aggravation of both systemic and glomerular hypertension, decreased renal perfusion and filtration with reduced Kf, and high filtration fraction. The incidence of FGS in NAME and CON groups was similar at 8 and 12 weeks post-UNX, respectively. Glomerular enlargement was present in CON and ENA rats, but did not correlate with injury, while glomerular tuft size was lowest in NAME rats, which displayed prominent glomerular injury. Systemic blood pressure correlated strongly with glomerular capillary pressure. We conclude that systemic and glomerular hypertension govern the development of UpV and FGS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Relevance of single nephron studies to human glomerular function.

The preceding article has illustrated a few of the many studies utilizing single nephron micropuncture techniques to identify intrarenal hemodynamic disease patterns, to identify the actions of various vasoactive mediators and thereby allow correlation with disease processes, and to explain the mechanisms underlying interventions which benefit the kidney. Many other uses of these techniques have provided insight into clinical disease pathophysiology, including: studies examining the importance of changes in tubuloglomerular feedback; the role of changes in tubular reabsorption; and studies correlating function with morphologic changes and with in vitro studies. While this review has concentrated on in vivo glomerular micropuncture techniques, a number of other innovative techniques are being used to approach these questions, including studies in isolated perfused tubules, afferent and efferent arterioles, and glomeruli. Accordingly, these studies will continue to provide the hemodynamic context in which other pathophysiologic processes and therapeutic mechanisms are revealed.

Animals↗
PubMed1994

The efficacy of recombinant human granulocyte colony-stimulating factor and recombinant human granulocyte macrophage colony-stimulating factor in permitting the administration of higher doses of cyclophosphamide in a doxorubicin-cyclophosphamide combination. An NSABP pilot study in patients with metastatic or high-risk primary breast cancer. National Surgical Adjuvant Breast and Bowel Project.

Colony-stimulating factors (CSFs) shorten the duration of myelosuppression following chemotherapy and, thus, allow the administration of higher doses. This study evaluates the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) in allowing administration of high-dose cyclophosphamide in combination with doxorubicin. Ninety women with metastatic, locally advanced, or high-risk (> or = 10 positive nodes) breast cancer and no prior anthracycline treatment were given doxorubicin (60 mg/m2) with progressively increased doses of cyclophosphamide (1,200 mg/m2, 1,800 mg/m2, and 2,400 mg/m2). The first 60 patients received GM-CSF; the remaining 30, G-CSF. The maximum tolerated dose was not reached with 2,400 mg/m2 of cyclophosphamide. When compared to GM-CSF, G-CSF significantly reduced the duration of granulocytopenia (P < .001). No differences in duration of thrombocytopenia were noted. The results were not sufficiently consistent to indicate a trend toward reduction in rates of febrile neutropenia with one CSF versus the other. However, patients who received G-CSF were hospitalized less frequently than those receiving GM-CSF. With CSFs, high-dose cyclophosphamide in combination with doxorubicin can be safely administered on an outpatient basis. A shorter duration of granulocytopenia resulted from the use of G-CSF than from GM-CSF.

Antineoplastic Combined Chemotherapy Protocols↗