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Biomedical subjects

R J Anderson

Publications and source records attributed to R J Anderson.

At least 163 records · Page 9Linked to original sources
PubMed1992

Hypervitaminosis A and reproductive disorders in rabbits.

Reproductive abnormalities in New Zealand White rabbits at a large commercial rabbitry were linked to an excess of dietary retinyl acetate. Fetal resorptions, abortions, and stillbirths were common in pregnant does. Examination of aborted and stillborn fetuses disclosed hydrocephalus, microencephaly, and cleft palate. Analysis of the commercially prepared feed disclosed a total vitamin A content of 102,278 IU/kg, of which 97,618 IU was retinyl acetate (recommended total vitamin A concentrations are 6,000 to 12,000 IU/kg). Levels of vitamin A in the plasma of does with reproductive disorders were 517 to 1,667 ng/ml (normal level is 300 ng/ml), and liver levels were 2,070 to 12,854 micrograms/g (normal range is 50 to 300 micrograms/g).

Abortion, Incomplete↗
PubMed1992

Marketing dentistry: a pilot study in Dudley.

This study was an attempt to persuade non-users or irregular users of dental services to change their behaviour and visit the dentist more regularly. The task was divided into two main parts. One was a promotion campaign undertaken in the Borough of Dudley in the West Midlands and the other a professional development programme for the dentists practising in the same area. The professional development campaign was designed to make the practitioners aware of the barriers to dental care which are perceived by patients. It was undertaken through a series of workshops on various aspects of practice development and promotion to which the staff of all the dental practices in Dudley were invited. Thirty-nine out of a total of forty-one accepted the invitation and attended some or all of the programme. In addition to the workshops members of the research team visited each of the participating practices regularly to discuss aspects of the programme and to record progress. The practitioners had varied attitudes to marketing and varied learning styles, and therefore they had different expectations of the nature and purpose of professional development. The majority attended solely to learn about the promotion campaign. There were also varying perceptions of patient recruitment and retention. None saw this as a serious problem. However, even before the new National Health Service contract for general dental practitioners there was the growing realisation that in the future there would be competition between practices and that this could be a reason for considering recruitment and the retention of patients more carefully. This was considered by many of the dentists, but not all, to be a problem of patient behaviour, linked with a degree of fatalism, and that nothing much could be done about it. There was a reluctance to change and the fear of the risks involved led a number of the general dental practitioners to identify and emphasise the difficulties in making new developments rather than their benefits. Only one quarter of the practices made any changes and they tended to prefer quick solutions rather than basic development. The experience gained in this part of the study indicated that in the future professional development should be considered in terms of the dentist's perception of the costs and the benefits; direct costs, opportunity costs, and the prospect of effecting change.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Medical apartheid. An American perspective.

The suppressive policies and practices of apartheid in South Africa have directly contributed to preventable morbidity and mortality in black Africans. Due to socioeconomic segregation ("functional apartheid"), America's citizens of color also suffer excess death and disability. Health status measurements in the United States confirm the failure of the current fragmented health care system to recognize or respond to the unmet need or the barriers that exist. Predictably, the changes needed to improve the health status of black South Africans are similar to those that are necessary to remedy the situation in the United States. Community-Oriented Primary Care is a health service provision model that holds promise as a comprehensive community-based strategy that can begin to address some of the shortcomings of the current medical care systems of both nations.

Black or African American↗
PubMed1991

Regulation by forskolin of cyclic AMP phosphodiesterase and protein kinase C activity in LLC-PK1 cells.

Forskolin, a naturally occurring activator of adenylate cyclase, inhibits total and high-affinity cyclic AMP phosphodiesterase activity in soluble and particulate fractions of cultured LLC-PK1 renal epithelial cells. The naturally occurring forskolin analogue 1,9-dideoxyforskolin, which does not stimulate adenylate cyclase activity, is a more potent inhibitor of cyclic AMP phosphodiesterase activity than forskolin. To clarify the structural feature of the forskolin molecule responsible for inhibition of cyclic AMP phosphodiesterase activity, the effects of two agents which share structural identity with portions of the forskolin ring were tested. The steroid 5-pregnenolone, but not the hexose alpha-D-galactose, inhibited cyclic AMP phosphodiesterase activity in LLC-PK1 cells. Forskolin and 1,9-dideoxyforskolin both stimulate protein kinase C activity in LLC-PK1 cells. The effect of 1,9-dideoxyforskolin in stimulating LLC-PK1 protein kinase C activity can be attenuated by staurosporine. Both 5-pregnenolone and alpha-D-galactose also stimulate protein kinase C activity in LLC-PK1 cells. 5-Pregnenolone and the phorbol ester phorbol 12-myristate 13-acetate cause translocation of protein kinase C from a soluble to a particulate fraction, while both 1,9-dideoxyforskolin and alpha-D-galactose increase protein kinase C activity in both soluble and particulate fractions. Our results demonstrate that forskolin exerts diverse enzymic effects in cultured LLC-PK1 cells.

1-Methyl-3-isobutylxanthine↗
PubMed1991

A method for the purification of DNA/protein complexes applied to DNA topoisomerase II cleavage sites.

The object of this study was to devise a purification method for DNA/topoisomerase II complexes, with which to examine the enzyme's cleavage site specificity in cellular differentiation. Retinoic acid-induced differentiation involves topoisomerase II-mediated transient changes in DNA supercoiling, but it is not known whether this occurs at specific sites in the genome. Topoisomerase II forms a covalent DNA enzyme complex as it acts, which can be recovered by the sodium dodecyl sulfate (SDS)/KCl precipitation method, but this method fails to recover significantly more DNA from cells induced to differentiate. This may in part reflect the low numbers of retinoic acid-induced protein-linked breaks in DNA and also the method's relative inefficiency for DNA with few attached topoisomerase molecules. This suggested that an additional purification method would be required to enrich sufficiently for cleavage site DNA to address the issue of site specificity. The principle of our method is to couple poly(ethylene glycol) (PEG) to topoisomerase while it is covalently attached to DNA and then to use phase partitioning in an aqueous two-phase system of PEG and phosphate to separate free DNA from DNA bound to PEG-modified topoisomerases (which have high affinities for the phosphate-rich and PEG-rich phases, respectively). The method can be used in conjunction with DNase protection and, unlike the SDS/KCl method, can fractionate short fragments of DNA to which single protein molecules are attached. Using the SDS/KCl precipitation and new method in series, we have recovered protein-linked DNA from HL60 cells induced to differentiate to the granulocyte lineage (by retinoic acid) or to the monocyte/macrophage lineage (by phorbol myristate acetate) and have demonstrated that specific sequences become protein linked, probably to topoisomerase II, during induced differentiation.

Chemical Fractionation↗
PubMed1991

Separation of cell mixtures by immunoaffinity cell partitioning: strategies for low abundance cells.

The partitioning of cells in aqueous two-phase systems formed by poly(ethylene glycol) (PEG) and dextran can be changed by incubating the cells with a PEG-modified antibody directed specifically against its surface. We have developed a new approach for immunoaffinity cell partitioning (IACP) in which the antibodies are first reacted with tresylated monomethoxy PEG (TMPEG) in sodium phosphate buffer, pH 7.5, the excess TMPEG is quenched by reaction with bovine serum albumin, and the resulting preparation is used directly for incubation with the cells without any isolation of the monomethoxyPEG (MPEG)-antibody conjugates. We have demonstrated the specificity of this IACP method by showing that MPEG-modified anti-human red blood cell antibody increases the partition of human erythrocytes from the interface to the PEG-rich top phase (up to 100%) but not the partitioning of either neutrophils or HL60 cells. Irrelevant antibodies do not affect the partitioning of red blood cells. The partitioning behaviors of erythrocytes and HL60 cells in mixtures varying from 75 to 10% red blood cells subjected to IACP are similar to those of the pure cell population, i.e., erythrocytes ca. 100% and HL60 cells 3% in top phase. Thus, the population of erythrocytes can be almost completely extracted into the top phase in a single step. The contaminant cells represent only a small percentage (less than 5% in most of the cases) of the cell mixture recovered in top phase. Both cell populations can be completely separated by countercurrent distribution (CCD).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Affinity↗
PubMed1991

Carotid endarterectomy for asymptomatic carotid stenosis: a ten-year experience with 120 procedures in a fellowship training program.

Performance of carotid endarterectomy for asymptomatic carotid stenosis has been restricted during recent years because of concern of reported complications in as high as 10-15% of patients, as well as limited long-term data on stroke protection. During the last 10 years, we have studied immediate and long-term results of carotid endarterectomy for asymptomatic disease in 120 patients. Operations were performed by a clinical vascular fellow with a staff surgeon in attendance in 113 (94%) cases with the remainder performed by the staff surgeon. Patients' mean age was 66 years; 82% were men. Risk factors included hypertension (56%), smoking (52%), coronary artery disease (32%), diabetes (24%), and hypercholesterolemia (6%). Arteriographic severity of stenoses was 80-99% in 74%, 60-79% in 22%, and 40-59% in 4% of cases. Postoperative complications included two transient neurological events (1.7%). No permanent strokes or deaths occurred. Using the life table method, cumulative stroke rate was 4.5% for ipsilateral events and 7.3% for contralateral events, confirming the high degree of stroke protection afforded by carotid endarterectomy in this population. Since these results were accomplished in a fellowship training program, we regard adequacy of this experience as the most influential factor in accomplishing this record. Surgeons who are unable to achieve comparable results should consider abandonment of the procedure or an extended period of additional training.

Aged↗
PubMed1991

Leukocyte activation in ischemia-reperfusion injury of skeletal muscle.

Polymorphonuclear leukocyte (PMN) participation in the pathophysiology of the reperfusion injury following skeletal muscle ischemia has become recognized. We measured the activation of PMNs as evidenced by production of superoxide anion (O2-) in the isolated canine gracilis muscle preparation of ischemia-reperfusion injury. PMNs were isolated from the gracilis muscle venous effluent and central venous blood after 6 hr of bilateral gracilis ischemia and 1 hr of reperfusion in five dogs. Baseline samples were obtained prior to ischemia from the central venous circulation. Liberation of O2- from PMNs and from PMNs stimulated by opsonized zymosan was determined by measuring ferricytochrome reduction. Results are expressed as nanomoles of O2- produced/2 x 10(6) PMN +/- SEM. O2- production by unstimulated cells was increased from 0.33 +/- 0.15 nmole in the baseline samples to 0.96 +/- 0.08 nmole in the central venous sample (P less than 0.01). With stimulation by zymosan, production increased from 10.3 +/- 1.4 nmole in the baseline samples to 15.2 +/- 1.1 nmole in the central venous sample (P less than 0.05) and to 15.5 +/- 0.9 nmole in the gracilis venous sample (P less than 0.01). These increases in superoxide production were not seen in the three sham-operated animals. Mean infarct size determined by planimetry was 55%. O2- produced by PMNs from central venous blood correlated with infarct size (r = 0.934, P = 0.02). These data imply that PMNs are activated by muscular ischemia, and the degree of activation is directly related to the extent of the muscle infarction.

Animals↗
PubMed1991

Alcohol consumption in men exposed to the military draft lottery: a natural experiment.

The randomized natural experiment provided by the military draft lotteries of 1970, 1971, and 1972 is used to compare alcohol consumption in men born in the years 1950, 1951, and 1952. Alcohol consumption data are derived from the National Health Interview Survey supplements for 1977, 1983, and 1985. The analysis follows an intention-to-draft paradigm, where draft eligibility is determined solely by randomly assigned lottery numbers. Draft eligibility status is found to be unassociated with alcohol consumption, despite the fact that eligibility for the draft significantly increased the likelihood of military service and that veterans are more likely to report increased alcohol consumption compared to nonveterans. The randomized draft lottery provides an elegant natural experiment that potentially obviates the problem of confounding by premilitary service factors found in previous studies of alcohol consumption among veterans and nonveterans. However, the indirect association between draft eligibility and any health outcome (where military service is an intervening variable), together with the failure of the draft to produce a higher percent of veterans, prohibits application in all but the largest samples.

Alcoholism↗
PubMed1991

Community responsive medicine: defining an academic discipline.

Academic medicine is entering a period of introspection created by changing patterns of health and disease and changing patterns in reimbursement and health policy. To respond to existing health challenges, innovative strategies for health care delivery and education must be devised. The migration of medical education and health care delivery into centralized and frequently difficult-to-access campuses is being reviewed by payors, policy analysts, and purchasers of care. One proposed solution to this problem responds to the identified shortcomings in medical education and some of the failures of our health care delivery system. Community Oriented Primary Care (COPC) and the related discipline of Community Responsive Medicine define health-oriented strategies that blend traditional primary care and public health. The classroom in Community Responsive Medicine is the community. The curriculum is defined by the elements and skills necessary to improve the health status of the target community. The model allows the student and resident to appreciate and experience the entire spectrum of health and disease and to understand the sequence of events that may lead to illness. Tertiary care is a critical curriculum component, but in Community Responsive Medicine the curriculum is balanced between the ambulatory and tertiary care settings. Community Responsive Medicine defines a role for new leadership that can create responsive educational and health care delivery systems accountable to the communities they serve.

Community Medicine↗
PubMed1991

Incidence and neurodevelopmental outcome of periventricular hemorrhage and hydrocephalus in a regional population of very low birth weight infants.

During the years 1984 to 1987, 459 very low birth weight (VLBW) infants were admitted to a state-designated Level III Neonatal Intensive Care Unit. Cerebral sonography performed in a standardized sequence and graded with the Papile scale diagnosed 97 (21.1%) children with periventricular hemorrhage (PVH). The incidence of PVH declined from a peak of 26.6% in 1985 to 16.4% in 1987, associated with an increase in the incidence of inborn admissions (including maternal transport) from 62.0% in 1984 to 80.4% in 1987. During initial hospitalization, the occurrence of both low-grade (Grades I and II) and high-grade PVH was associated with a significantly higher incidence of perinatal risk factors compared with a concurrent population of VLBW infants without PVH. Developmental follow-up was achieved in 93.3% of VLBW infants without PVH and 95.7% of VLBW infants with PVH who survived their initial hospitalization. The incidence of abnormal outcome ranged from 7 of 37 infants with Grade I PVH to 7 of 8 VLBW infants with Grade IV PVH. Only 1 of 16 VLBW infants with high-grade PVH demonstrated normal motor and cognitive development. Active hydrocephalus developed in 12 infants; 11 sustained a high-grade PVH. Appropriate treatment of intracranial hypertension did not modify the neurodevelopmental outcome. In conclusion, this regional population of VLBW infants demonstrated a decline in the incidence of PVH during the years 1984 to 1987 associated with an increase in the incidence of inborn admissions. The risk of abnormal neurodevelopmental outcome was elevated for all grades of PVH. A 12.0% incidence of hydrocephalus was associated with high-grade PVH, and appropriate treatment did not alter the poor prognosis.

Cerebral Hemorrhage↗
PubMed1991

cAMP stimulates protein kinase C activity in cultured renal LLC-PK1 cells.

Exposure of intact LLC-PK1 cells to the phorbol ester 4-phorbol 12-myristate 13-acetate (PMA) increases basal, arginine vasopressin-stimulated, and forskolin-stimulated adenylate cyclase activity in LLC-PK1 membranes. This observation suggests that protein kinase C can increase adenosine 3',5'-cyclic monophosphate (cAMP) in LLC-PK1 cells. To determine whether cAMP regulates protein kinase C activity in LLC-PK1 cells, intact cells were exposed to either forskolin or to soluble cAMP analogues. Acute (5 and 30 min) exposure to either forskolin or cAMP analogues increases protein kinase C activity as observed by two different methods for measuring protein kinase C. Acute exposure to PMA translocates protein kinase C from a soluble to a particulate cell fraction, whereas acute exposure to cAMP increases both soluble and particulate forms of protein kinase C. Longer exposure (18 h) to PMA results in a loss of protein kinase C activity, whereas 18-h exposure to cAMP results in a further increase in protein kinase C activity. The effect of cAMP but not of PMA to stimulate protein kinase C activity can be attenuated by the pro-R diastereoisomer of adenosine 3',5'-cyclic phosphorothioate, suggesting a protein kinase A-mediated effect. These results suggest the presence of a monodirectional mode of signal transduction system interaction in LLC-PK1 cells in which protein kinase C and protein kinase A can potentiate each other.

Adenylyl Cyclases↗
PubMed1991

Once-daily fosinopril in the treatment of hypertension.

This multicenter, dose-ranging study evaluated the antihypertensive effectiveness of once-daily administration of fosinopril sodium in 220 patients with supine diastolic blood pressure of 95-115 mm Hg. After a 4-week placebo period, patients were randomly assigned to double-blind therapy with either placebo or 10, 40, or 80 mg fosinopril once daily for 4 weeks. If treatment goals were not met, chlorthalidone 25 mg/day was added for weeks 5 to 8. Thereafter, patients could enter the long-term, open-label phase and receive 10-80 mg/day fosinopril plus chlorthalidone, if needed. After 4 weeks of monotherapy, the average decreases in supine diastolic blood pressure were 9% (10 mg), 11.5% (40 mg), and 12.5% (80 mg) compared with 6% in the placebo group. After 8 weeks, the average decreases, with or without diuretic therapy, were 12.5-18.2%, compared with 10.8% with placebo. Blood pressure continued to be well controlled, and the patients showed no evidence of tachyphylaxis or tolerance through 12-15 months of treatment. Fosinopril was well tolerated. During the short-term phase, no patient withdrew because of adverse events possibly related to fosinopril; during the long-term phase, nine of 148 patients (6.1%) withdrew for that reason. In patients with mild-to-moderate hypertension, once-daily fosinopril (40 and 80 mg) provided significant antihypertensive effects with or without diuretic therapy. The 10 mg dose was effective in some patients and may be considered a starting dose.

Antihypertensive Agents↗
PubMed1991

ATP receptor regulation of adenylate cyclase and protein kinase C activity in cultured renal LLC-PK1 cells.

In cultured intact LLC-PK1 renal epithelial cells, a nonhydrolyzable ATP analogue, ATP gamma S, inhibits AVP-stimulated cAMP formation. In LLC-PK1 membranes, several ATP analogues inhibit basal, GTP-, forskolin-, and AVP-stimulated adenylate cyclase activity in a dose-dependent manner. The rank order potency of inhibition by ATP analogues suggests that a P2y type of ATP receptor is involved in this inhibition. The compound ATP gamma S inhibits agonist-stimulated adenylate cyclase activity in solubilized and in isobutylmethylxanthine (IBMX) and quinacrine pretreated membranes, suggesting that ATP gamma S inhibition occurs independent of AVP and A1 adenosine receptors and of phospholipase A2 activity. The ATP gamma S inhibition of AVP-stimulated adenylate cyclase activity is not affected by pertussis toxin but is attenuated by GDP beta S, suggesting a possible role for a pertussis toxin insensitive G protein in the inhibition. Exposure of intact LLC-PK cells to ATP gamma S results in a significant increase in protein kinase C activity. However, neither of two protein kinase C inhibitors (staurosporine and H-7) prevents ATP gamma S inhibition of AVP-stimulated adenylate cyclase activity, suggesting that this inhibition occurs by a protein kinase C independent mechanism. These findings suggest the presence of functional P2y purinoceptors coupled to two signal transduction pathways in cultured renal epithelial cells. The effect of P2y purinoceptors to inhibit AVP-stimulated adenylate cyclase activity may be mediated, at least in part, by a pertussis toxin insensitive G protein.

3',5'-Cyclic-AMP Phosphodiesterases↗