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Biomedical subjects

B Woodward

Publications and source records attributed to B Woodward.

At least 19 recordsLinked to original sources
PubMed2001

Opportunities for improving the quality of hypertension care in a managed care setting.

Hypertension management practices and patient health outcomes in a managed care setting were evaluated. Health-system pharmacists analyzed plan medical and pharmacy claims data for September 1, 1998, to August 31, 1999, to identify hypertensive enrollees (n = 23,316). Reviews of pharmacy claims and medical charts of a sample of hypertensive patients (n = 374) determined blood pressure control status, prevalence of cardiovascular risk factors, and comorbidities. The majority of patients treated for hypertension (66%) did not achieve blood pressure control. Analysis revealed a high prevalence of cardiovascular risk factors among hypertensive patients, with 92.2% of study patients having two or more risk factors. Reviews of 132,512 pharmacy claims revealed that one half of all prescribed therapies were for monotherapy, and 21% of hypertensive patients were prescribed combination therapy with two different agents. Data from a large managed care organization revealed that more than half of all hypertensive patients had inadequate blood pressure control. A quality improvement program for hypertension care that can improve patient health outcomes must educate patients and health care providers about the implications of the disease, identify patients with compelling comorbidities, evaluate pharmacologic regimens, and recommend therapeutic changes when necessary.

Adult↗
PubMed2001

Retroviral labeling of Schwann cells: in vitro characterization and in vivo transplantation to improve peripheral nerve regeneration.

Transplantation of Schwann cells (SCs) is a promising treatment modality to improve neuronal regeneration. Identification of the transplanted cells is an important step when studying the development of this method. Genetic labeling is the most stable and reliable method of cell identification, but it is still unclear whether it has deleterious effect on SC characteristics. Our aim was to achieve a stable population of SCs transduced with the lacZ gene at a high frequency using a retroviral vector in vitro, and to follow the labeled SC in vitro to assess their viability and phenotypic marker expression. Furthermore, we transplanted lacZ-labeled SCs in a conduit to repair peripheral nerve to investigate their effect on nerve regeneration in vivo. Rat and human SCs were cultured and transduced with an MFG lacZ nls marker gene, achieving a transduction rate of 80% and 70%, respectively. Rat SCs were kept in culture for 27 weeks and examined every 4 weeks for expression of lacZ, viability, and phenotypic marker expression of GFAP, p75, MHC I and II. Throughout this period, transduced rat SCs remained viable and continued to proliferate. The proportion of cells expressing lacZ dropped only by 10% and the expression of phenotypic markers remained stable. Transduced human SCs were followed up for 4 weeks in culture. They proliferated and continued to express the lacZ gene and phenotypic marker expression of GFAP and p75 was preserved. Primary culture of transduced rat SCs were transplanted, syngeneically, in a conduit to bridge a 10 mm gap in sciatic nerve and the grafts were examined after 3 weeks for the presence and participation of labeled SCs and for axonal regeneration distance. Transplanted transduced rat SCs were clearly identified, taking part in the regeneration process and enhancing the axonal regeneration rate by 100% (at the optimal concentration) compared to conduits without SCs. Thus, retroviral introduction of lacZ gene has no deleterious effect on SCs in vitro and these SCs take part and enhance nerve regeneration in vivo.

Animals↗
PubMed2001

Demonstration of epidermal transfer from a polymer membrane using genetically marked porcine keratinocytes.

The culture of keratinocytes on flexible membranes has been proposed as a means to simplify, accelerate and improve the efficiency with which proliferating cells are delivered to full thickness or non-healing skin defects. However, there have been no studies that monitor the transfer of cells from such membranes to the wound bed. We have used a porcine model of lacZ gene marked cultured autologous keratinocyte grafting to demonstrate unambiguously the transfer of cultured cells to cutaneous wounds from the EpiGen polymer membrane developed by Smith & Nephew Group plc. Full thickness wounds enclosed within rigid chambers were first grafted with autologous de-epidermalised dermis (DED). Keratinocytes were cultured on EpiGen membranes and applied to the wound beds 7 days after the DED grafts. Epidermal remnants persist within the DED and the resultant epidermis is therefore, a mixture of wound regeneration and delivered cultured cells. Unequivocal evidence for keratinocyte transfer from the membrane was obtained through the observed macroscopic surface staining for lacZ transduced cells and lacZ positive cells detected in sections through deeper layers of epidermal tissue. This method offers a general approach for evaluating the efficiency of keratinocyte delivery using upside-down flexible membrane transfer.

Animals↗
PubMed2001

Confidentiality, consent and autonomy in the physician-patient relationship.

In the practice of medicine there has long been a conflict between patient management and respect for patient autonomy. In recent years this conflict has taken on a new form as patient management has increasingly been shifted from physicians to insurers, employers, and health care bureaucracies. The consequence has been a diminishment of both physician and patient autonomy and a parallel diminishment of medical record confidentiality. Although the new managers pay lip service to the rights of patients to confidentiality of their records, in fact they advocate very liberal medical records access policies. They argue that a wide range of parties has a need to know the contents of individually identifiable medical records in order to control costs, promote quality of care, and undertake research in the public interest. Broad interpretations of the need to know, however, are at odds with strict interpretations of the right to confidentiality. Strict confidentiality policies require that, with few exceptions, patient consent be obtained whenever a patient's record is used outside the treatment context. The traditional criterion for overriding the consent requirement has been that without the override some harm would directly result. This rule is now challenged by the claim that patients have a duty to make their records available for a wide range of research and public health purposes. The longstanding tension between physician responsibility for patient welfare and respect for patient autonomy is being replaced by a debatable requirement that both physician and patient autonomy be subordinated to the goals of data collection and analysis.

Access to Information↗
PubMed2001

Design of a telemedicine system using a mobile telephone.

This paper describes the design of a prototype integrated mobile telemedicine system that is compatible with existing mobile telecommunications networks and upgradable for use with third-generation networks. The system, when fully developed, will enable a doctor to monitor remotely a patient who is free to move around for sports medicine and for emergency situations.

Electrocardiography↗
PubMed2001

Contractile function in vitro of slow-twitch skeletal muscle from weanling mice subjected to wasting malnutrition.

Our hypothesis was that malnutrition sufficient to produce weight loss in weanling mice would decrease the ability of slow-twitch skeletal muscle to develop and maintain force. We isolated muscles from 3 groups (n = 5) of weanling C57BL/6J mice of both sexes (i) mice at 19 days of age serving as zero-time or baseline controls (CONT) (ii) mice fed for the next 14 days with a low-protein diet that produces features of incipient kwashiorkor (LPD) and (iii) mice fed for the next 14 days with a complete diet (NORM). Muscles were also obtained from 5 adult mice 7-9 months of age (MAT). We stimulated the soleus at 50 Hz for 500 ms at 0.6 tetanic contractions per min (tet x min(-1)), 6 tet x min(-1), and 30 tet x min(-1) in Krebs-Henseleit bicarbonate buffer at 27 degrees C gassed with 95% O2 and 5% CO2. The initial developed force (mN x mm(-2)) at 0.6 tet x min(-1) did not differ across groups (CONT 211.7 +/- 16.0, LPD 274.2 +/- 41.6, NORM 246.8 +/- 38.0, MAT 210.8 +/- 10.6). The fatigue rate (mN x mm(-2) x min(-1)) at 6 tet x min(-1) was significantly slower in muscles from CONT (0.6 +/- 0.3) and LPD (0.6 +/- 0.4) than in NORM (2.4 +/- 0.6) and MAT (2.3 +/- 0.2). At 30 tet x min(-1), the fatigue rate (mN x mm(-2) x min(-1)) did not differ across groups (CONT 2.4 +/- 0.5, LPD 2.7 +/- 0.5, NORM 2.5 +/- 0.4, MAT 2.0 +/- 0.2). After stimulation at 6 tet x min(-1) and 30 tet x min(-1), only muscles from CONT and LPD recovered to 100%. Because muscles from LPD mice developed equal force, fatigued less, and recovered from fatigue to a greater extent than muscles from NORM mice, we rejected the hypothesis. The function of the tissue remaining in the muscles from LPD mice approximated that of muscles from mice at 19 days of age rather than muscles from either mice of the same age fed a complete diet or adult mice.

Animals↗
PubMed2001

Initial experience with in-vitro fertilization technology in the English-speaking Caribbean.

This audit documents the first experience with in-vitro Fertilization technology in the English-speaking Caribbean. From 1996 to 2000, 121 cycles have been performed in 99 couples utilizing these techniques. After ovarian stimulation, 1,103 oocytes were retrieved (average 9.1) and of these, 65% fertilized normally, with embryo transfer possible in 111 cycles. Twenty-one pregnancies were recorded (21.2% per patient and 18.9% per embryo transfer) and the live birth rate per patient was 12.1%. The trend was for the success rate to be better in patients under age 36 years.

Adult↗
PubMed2000

Hypoxia augments conversion of big-endothelin-1 and endothelin ET(B) receptor-mediated actions in rat lungs.

We have examined the effect of endothelin-1, sarafotoxin-6C, big-endothelin-1 and other agents on perfused lungs from chronically hypoxic rats. Increases in pulmonary perfusion pressure induced by big-endothelin-1, endothelin-1, phenylephrine and potassium chloride were enhanced in hypoxic lungs, while the constrictor action of sarafotoxin-6C was not increased. When basal pulmonary perfusion pressure was raised, low doses of endothelin-1 and sarafotoxin-6C produced decreases in pulmonary perfusion pressure which were significantly greater in chronically hypoxic lungs, whereas responses to sodium nitroprusside were unchanged. Endothelin ET(B) receptor-mediated bronchoconstrictor responses were also potentiated in hypoxic lungs, whereas responses to carbachol were not. In hypoxic lungs, conversion of big-endothelin-1 to endothelin-1 was significantly increased. These data provide evidence for a generalised increase in vasomotor activity in chronically hypoxic lungs, and a more selective increase in endothelin ET(B) receptor-mediated vasodilator and bronchoconstrictor responses. Hypoxia also augments the conversion of big-endothelin-1 to endothelin-1.

Animals↗
PubMed2000

Long-term effect of vital labelling on mixed Schwann cell cultures.

Schwann cell transplantation following neuronal injury could encourage regeneration of spinal cord as well as improving peripheral nerve gap repair. In order to gain a better understanding of the role of transplanted Schwann cells in vivo, it is essential to be able to follow their behaviour after transplantation. Our aim was to evaluate the suitability of two vital fluorescent labels on the proliferation rate and phenotypic stability of Schwann cells, in either pure culture or mixed co-culture. Primary cultures of Schwann cells were obtained from Dark Agouti and Lewis neonatal rats and labelled with H33342 and PKH26, respectively. In mixed cultures, a 50: 50 mixture of Dark Agouti and Lewis Schwann cells was present. Labelled cultured cells were examined at 1, 2 and 4 weeks for viability and phenotypic marker expression of S100, GFAP, p75, MHC I, MHC II and compared with corresponding unlabelled cells. The results showed that although there was no deleterious interaction in the mixed cultures, the viability was reduced by the labelling after 2 weeks. Labelled cells could be distinguished up to 4 weeks, but there was leakage of H33342 label after 2 weeks. Labelled Schwann cells showed reduced expression of phenotypic markers, especially p75 when labelled with H33342. In conclusion, H33342 and PKH26 can be used as fluorescent markers of Schwann cells for short-term studies, for a maximum of 2 weeks, but different markers may be needed for longer experiments.

Animals↗
PubMed1999

Challenges to human subject protections in US medical research.

United States regulations governing federally supported research with human subjects derive in part from 2 international codes, the Nuremberg Code and the Declaration of Helsinki. The Declaration of Helsinki states that "concern for the interests of the subject must always prevail over the interests of science and society." The concept of minimal risk and the principle of informed consent are the key means by which US federal regulations seek to protect the rights and welfare of the individual in the research setting. Current trends in medical research-including increased funding, ever-greater capabilities of computers, development of new clinical tools that can also be used in research, and new research tools developed through research itself are creating greater demand for human subjects, for easier recruitment and conscription of these subjects, and for unimpeded access to patient medical records and human biological materials. Nationally and internationally, there are new pressures to subordinate the interests of the subject to those of science and society. The National Bioethics Advisory Commission, which is about to undertake a comprehensive review of the US system of human subject protections, faces a daunting task.

Advisory Committees↗
PubMed1999

Chronic hypoxia differentially alters the responses of pulmonary arteries and veins to endothelin-1 and other agents.

The effects of chronic hypoxia on the responses of rat large pulmonary arteries and veins to vasoactive agents have been examined. Endothelin-1-induced contractions of pulmonary arteries and pulmonary veins were reduced by chronic hypoxia. In contrast, chronic hypoxia augmented sarafotoxin 6c-induced contractile responses in pulmonary veins but not in pulmonary arteries. Chronic hypoxia augmented the constrictor effect of phenylephrine in pulmonary arteries, but not in pulmonary veins. The thromboxane receptor agonist, U46619 (9,11-dideoxy-9alpha,11alpha-epoxy-methanoprostaglandin++ + f2alpha) contracted pulmonary arteries and pulmonary veins, and although maximal responses were not altered in chronically hypoxic preparations, the EC50 value in pulmonary arteries was increased following chronic hypoxia. The relaxant effects of acetylcholine and isoprenaline on pulmonary arteries were potentiated by chronic hypoxia. In contrast, ionomycin-mediated relaxations of pulmonary arteries and pulmonary veins were reduced, while sodium nitroprusside-induced relaxation of pulmonary arteries and veins were not altered by chronic hypoxia. Previous studied have looked primarily at the effects of chronic hypoxia on pulmonary arteries. This data provides evidence that chronic hypoxia also causes selective changes in the reactivity of large pulmonary veins.

Animals↗
PubMed1999

Evidence for oxygenation-induced endothelin release from isolated lungs of chronically hypoxic rats.

In lungs from chronically hypoxic (CH, 3 weeks at 10% inspired O2) rats, oxygenation (20% O2, 5% CO2, 75% N2; PO2 121 mmHg) of the perfusate increases pulmonary perfusion pressure (PPP) and lung weight (LW). Hypoxic perfusate (95% N2, 5% CO2; PO2 5.5 mmHg) had no effect on PPP in lungs from CH rats. Indomethacin and nitro-L-arginine (L-NOARG) augmented the oxygen-induced increase in PPP. In contrast, the free radical scavengers superoxide dismutase (SOD) plus catalase delayed the onset of oxygen-induced vasoconstriction, while the endothelin (ET)B receptor antagonist BQ788 inhibited it. The ET(A) receptor antagonist BQ123 did not affect the PPP changes. This suggests a role for endogenous endothelins and ET(B) receptors in mediating the oxygenation-induced pulmonary vasoconstriction. Indomethacin had no effect on oxygen-induced lung weight (LW) changes while BQ788 and L-NOARG reduced the LW increase. This evidence shows that ET(B) receptor activation and NO generation are involved in the LW changes. In conclusion, oxygenation of the perfusate in isolated lungs from CH rats leads to pulmonary vasoconstriction which involves endothelins and activation of ET(B) receptors. In addition, increased NO production associated with ET(B) receptor activation is the prime stimulus for observed LW increase.

Adrenergic alpha-Antagonists↗
PubMed1999

Acidosis-induced coronary constriction in the rat heart: evidence for the activation of L-type calcium channels.

Perfused rat hearts were used to study the effects of acidosis on coronary tone. When pH was decreased, over the range pH 7.4 to pH 6.2, by reducing perfusate bicarbonate levels, under constant flow conditions, there was a transient decrease in coronary perfusion pressure (CPP), followed by a sustained acidosis-dependent increase in CPP, which reversed when pH was returned to pH 7.4. This increase in CPP was seen at perfusion rates of 5, 10, and 20 ml/min(-1). When using constant pressure perfusion acidosis reduced coronary flow. In a HEPES-buffered bicarbonate-free solution, acidosis did not cause a transient fall in CPP but it did produce a sustained increase in CPP. Addition of ammonium chloride (10 mM) reduced CPP, while washout of ammonium chloride increased CPP. The acidosis-induced increase in CPP was not affected by indomethacin, nitro-L-arginine, the nonselective adenosine receptor antagonist, 8-phenyl theophylline, or the thromboxane receptor antagonist, ZD 1542. The acidosis-induced increase in CPP was independent of the myocardial depressant effects of acidosis, but was attenuated by three different L-type calcium channel blockers. These results demonstrate that the coronary circulation of the rat constricts in response to acidosis. Experiments performed with L-type calcium channel blockers, and the calcium channel activator BAY K8644, suggest that constriction occurs via activation of L-type calcium channels. This would not be expected on the basis of electrophysiological studies, which have shown an inhibition of L-type calcium channels by acidosis.

Acidosis↗
PubMed1999

Effects of tumour necrosis factor-alpha on left ventricular function in the rat isolated perfused heart: possible mechanisms for a decline in cardiac function.

1. The cardiac depressant actions of TNF were investigated in the isolated perfused rat heart under constant flow (10 ml min(-1)) and constant pressure (70 mmHg) conditions, using a recirculating (50 ml) mode of perfusion. 2. Under constant flow conditions TNF (20 ng ml(-1)) caused an early (< 25 min) decrease in left ventricular developed pressure (LVDP), which was maintained for 90 min (LVDP after 90 min: control vs TNF; 110 +/- 4 vs 82 +/- 10 mmHg, P < 0.01). 3. The depression in cardiac function seen with TNF under constant flow conditions, was blocked by the ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, (LVDP after 90 min: TNF vs TNF with NOE; 82 +/- 10 vs 11 +/- 5 mmHg, P < 0.05). 4. In hearts perfused at constant pressure, TNF caused a decrease in coronary flow rate (change in flow 20 min after TNF: control vs TNF; -3.0 +/- 0.9 vs -8.7 +/- 1.2 ml min(-1), P < 0.01). This was paralleled by a negative inotropic effect (change in LVDP 20 min after TNF: control vs TNF; -17 +/- 7 vs -46 +/- 6 mmHg, P < 0.01). The decline in function was more rapid and more severe than that seen under conditions of constant flow. 5. These data indicate that cardiac function can be disrupted by TNF on two levels, firstly via a direct, ceramidase dependant negative inotropic effect, and secondly via an indirect coronary vasoconstriction.

Animals↗
PubMed1999

T cells with a quiescent phenotype (CD45RA+) are overabundant in the blood and involuted lymphoid tissues in wasting protein and energy deficiencies.

The objective of this investigation was to determine the influence of distinct forms of acute weight loss on the expression of the quiescence marker, CD45RA, by T cells in several lymphoid compartments including the blood. Male and female weanling mice, CBA/J and C57BL/6J strains, were allocated to the following groups: ad libitum intake of a complete purified diet; restricted intake of the complete diet; and ad libitum intake of an isocaloric low-protein diet. The restricted intake protocol produced weight loss through energy deficiency (marasmic-type malnutrition), whereas the low-protein diet caused wasting through inadequate protein nitrogen and induced a condition mimicking incipient kwashiorkor. In one experiment, weanling mice of both strains were maintained for 14 days according to each of these dietary protocols and, in a supplementary study, C57BL/6J weanlings consumed either the complete diet or the low-protein diet ad libitum for 21 days. Zero-time control groups (19-days old and 23-days old in C57BL/6J and CBA/J strains, respectively) were included in the first experiment to control for ontogeny-related change. Expression of CD45RA was assessed by two-colour flow cytometry in CD4+ and CD8+ T cells from the spleen, mesenteric lymph nodes and blood. Within 14 days, energy-restricted mice exhibited a high percentage of CD4+ T cells expressing CD45RA in all three lymphoid compartments in both mouse strains (an average of 50% CD45RA+ versus 9% in well-nourished controls), and a similar outcome was apparent in the CD8+ subset (93% CD45RA+ versus 63%). Mice fed the low-protein diet required up to 21 days to exhibit the same imbalance within the CD4+ T-cell subset (33% CD45RA+ versus 4% in well-nourished controls). A shift toward a quiescent phenotype occurs throughout the peripheral T-cell system in acute wasting disease. Consequently, the quiescence-activation phenotype of blood T cells reflects the same index in secondary lymphoid organs in such pathologies. Naive-type quiescence among T cells is implicated as a component of depressed adaptive immunocompetence in the advanced stages of diverse forms of acute weight loss.

Acute Disease↗
PubMed1999

The comparative performance of mobile telemedical systems based on the IS-54 and GSM cellular telephone standards.

The performance of mobile telemedical communications links based on the IS-54 and GSM cellular telephone standards (the most widely used commercial systems in North America and Europe, respectively) was studied by computer simulations. A photoplethysmography signal was used to investigate the transmission of medical data over simulated mobile phone channels. Various conditions were simulated in the communications path between a mobile transmitter and receiver, from perfect to distorted conditions. The results showed successful transmission, with bit error rates of better than 10(-7) at the receiver for the IS-54 standard. The performance of the IS-54 standard was superior to that of GSM in terms of minimum path delay variations, especially in built-up (urban) areas.

Computer Simulation↗
PubMed1998

Effects of prostaglandin F2 alpha on intracellular pH, intracellular calcium, cell shortening and L-type calcium currents in rat myocytes.

OBJECTIVE: We have studied the mechanisms underlying the positive inotropic action of prostaglandin F2 alpha (PGF2 alpha) by monitoring intracellular calcium transients, intracellular pH, L-type calcium currents and cell shortening in isolated ventricular myocytes. METHODS: Rat myocytes were loaded with fura-2AM for intracellular calcium measurements, or BCECF-AM for pH measurements. Cell shortening was recorded using an edge detection system, and L-type calcium currents measured using whole cell patch clamping. RESULTS: PGF2 alpha (3 nmol l-1-3 mumol l-1 increased single myocyte shortening and reduced resting cell length in a concentration-dependent manner. While myocyte shortening was increased by PGF2 alpha, this was not associated with any change in the amplitude of intracellular calcium transients, diastolic calcium, or L-type calcium currents. However, the same myocytes were capable of responding to catecholamines with increases in calcium transient amplitude and L-type calcium currents. PGF2 alpha (3 mumol l-1 caused a reversible rise in intracellular pH of 0.08 +/- 0.01 pH units (n = 5, p < 0.05). The Na(+)-H+ exchanger inhibitor, HOE 694 (10 mumol l-1, abolished the PGF2 alpha-induced rise in pH and the increase in cell shortening. PGF2 alpha-induced increases in cell shortening and intracellular pH were also attenuated by the protein kinase C (PKC) inhibitor, chelerythrine (2 mumol l-1. CONCLUSION: The positive inotropic action of PGF2 alpha appears to be mediated via activation of the Na(+)-H+ exchanger with the possible involvement of PKC. This suggests that PGF2 alpha-produces intracellular alkalosis, which then sensitizes cardiac myofilaments to calcium.

Alkaloids↗