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Biomedical subjects

F W Bowen

Publications and source records attributed to F W Bowen.

At least 19 recordsLinked to original sources
PubMed2001

Reappearance of myocytes in ovine infarcts produced by six hours of complete ischemia followed by reperfusion.

BACKGROUND: In this study we tested the hypothesis that delayed reperfusion of ischemic myocardium-too late to save myocytes-attenuates infarct expansion and improves collagen synthesis. METHODS: The hypothesis was tested in a sheep model of anteroapical infarction that has no collateral blood flow to the area at risk. After coronary ligation or arterial occlusion for 1 or 6 hours, sheep had serial hemodynamic and quantitative echocardiographic studies before and after infarction and 2, 5, 8, and 12 weeks later. Hearts were examined by light and electron microscopy at 2 and 12 weeks; hydroxyproline and ratios of type I/III collagen were measured at 12 weeks. RESULTS: After coronary occlusion, left ventricular (LV) function progressively decreased and size increased to form an anteroapical aneurysm. After 1 hour of ischemia, neither resting LV size nor function changed; the infarct contained a midmyocardial scar between epicardial and endocardial muscle. After 6 hours of ischemia, LV function was significantly better than that in nonperfused sheep. Two weeks after 6 hours of ischemia, no viable myocytes were visible by light microscopy, but electron micrographs showed rare intact nucleated myocytes with scarce cytoplasmic myofibrils. At the 12th week epicardial and endocardial myocytes reappeared in the infarct. Infarct collagen type I/III ratios were 1.2 in reperfused groups and 0.7 in nonperfused sheep. CONCLUSIONS: Delayed reperfusion causes loss and subsequent reappearance of ovine epicardial myocytes, improves collagen type I/III ratios, and attenuates LV dilatation and loss of function. One hypothesis to explain the reappearance of myocytes is that reperfusion partially reverses an incomplete apoptotic process.

Animals↗
PubMed2001

Application of "double bridge mechanical" resuscitation for profound cardiogenic shock leading to cardiac transplantation.

BACKGROUND: In patients with acute profound cardiogenic circulatory failure unresponsive to conventional resuscitation, we instituted immediate aggressive application of extracorporeal membrane oxygenation (ECMO) to restore circulatory stability. Long-term hemodynamic support was accomplished with an early "bridge" to ventricular assist device (VAD) before definitive treatment with cardiac transplantation. METHODS: A respective review of ECMO and VAD data registries was instituted. RESULTS: From May 1996 to July 2000, 23 patients were placed on ECMO support for profound cardiogenic circulatory failure. Eleven patients (47%) were withdrawn from support due to severe neurologic injury or multisystem organ failure. Three patients (13%) were weaned off ECMO with good outcome. Nine patients (39%) were transferred to a VAD. Two patients expired while on VAD support, and 7 of the VAD-supported patients (78%) survived to transplantation. Overall survival was 43%. CONCLUSIONS: Emergent ECMO support is a salvage approach for cardiac resuscitation once conventional measures have failed. In neurologically intact patients, the early transfer to a VAD quickly stabilizes hemodynamics, avoids complications, and is essential for long-term circulatory support before definitive treatment with cardiac transplantation.

Adolescent↗
PubMed2001

Restraining acute infarct expansion decreases collagenase activity in borderzone myocardium.

BACKGROUND: After acute myocardial infarction, regional myocardial wall strains and stresses change and a complex cellular and biochemical response is initiated to remodel the ventricle. This study tests the hypothesis that changes in regional ventricular wall strains affect regional collagen accumulation and collagenase activity. METHODS: Fourteen sheep had acute anteroapical infarction that progressively expands into left ventricular aneurysm within 8 weeks. In 7 sheep, infarct expansion was restrained by prior placement of mesh over the area at risk. Fourteen days after infarction, and after hemodynamic and echocardiographic measurements, animals were euthanized for histology, measurements of hydroxyproline, matrix metalloproteinase-1 (MMP-1 or collagenase) and MMP-2 (gelatinase) activity, as well as collagen type I and III in infarcted, borderzone, and remote myocardium. RESULTS: Restraining infarct expansion does not change collagen content or MMP-1 or MMP-2 activity in the infarct, but significantly increases the ratio of collagen I/III. In borderzone and remote myocardium infarct, restraint significantly increases collagen content and significantly reduces MMP-1 activity. MMP-2 activity is reduced (p = 0.059) in borderzone myocardium only. Between groups, the ratio of type I/III fibrillar collagen does not change in borderzone myocardium. CONCLUSIONS: Fourteen days after acute myocardial infarction, restraining infarct expansion increases collagen accumulation in borderzone and remote myocardium, which may prevent expansion of hypocontractile, fully perfused "remodeling myocardium" adjacent to the infarct. This study demonstrates that changes in regional myocardial wall strain alter the cellular and biochemical processes involved in postinfarction ventricular remodeling.

Animals↗
PubMed2000

Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons.

Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug.

Animals↗
PubMed1998

Principles of disease management in neonatology.

This article emphasizes the emerging facets of disease-management practice that impact directly on establishing a measured care system that can produce the information needed to establish a continuous quality improvement program. The areas discussed are risk assessment, clinical management guidelines and carepaths, and the measurement of system output known as clinical outcomes. The remainder of the article details the aspects of risk assessment, guideline function, and outcome assessment, critical in a disease-managed measured care system.

Disease Management↗
PubMed1996

Management issues for the neonatal patient.

Immediate management needs of the neonate are defined in terms of the physiology of maternal-fetal gas transport and the oxyradical hypothesis of cellular injury as it pertains to hypoemic-ischemic encephalopathy. Resuscitation, stabilization, and assessment needs are defined as related to outcome and factors of information systems. Psychosocial and legal issues are included as factors in neonatal management.

Asphyxia Neonatorum↗
PubMed1995

Severe retinopathy of prematurity in infants with birth weights less than 1250 grams: incidence and outcome of treatment with pharmacologic serum levels of vitamin E in addition to cryotherapy from 1985 to 1991.

OBJECTIVE: To determine the effect of vitamin E prophylaxis and treatment on the sequelae of severe (threshold) retinopathy of prematurity (ROP) in infants treated with cryotherapy at Pennsylvania Hospital from 1985 to 1991. STUDY DESIGN: Beginning on day 0, all infants with birth weights < or = 1250 gm received supplements of vitamin E using standard preparations. Serum E levels of 23 to 58 mumol/L (1 to 2.5 mg/dl) were targeted for infants with immature retinal vasculature or ROP of stage 2 or less in severity, and levels of 58 to 81 mumol/L (2.5 to 3.5 mg/dl) for infants with prethreshold ROP. At diagnosis of threshold ROP, treatment with a parenteral investigational new drug preparation of alpha-tocopherol was begun to raise serum levels to the pharmacologic range (93 to 116 mumol/L or 4 to 5 mg/dl). Within 3 days of diagnosis, and at the discretion of the retinal specialist, one or both eyes were treated with cryotherapy. Visual outcome at 4 years was compared with the 42-month outcome reported for eyes in the infants randomly assigned to treatment in the 1986-1987 Multicenter Trial of Cryotherapy for ROP (CRYO-ROP). RESULTS: Threshold ROP developed in 22 of 450 surviving infants (age 3 months). All were treated with pharmacologic serum levels of vitamin E; 17 infants were also treated with cryotherapy (10 in one eye and 7 in both eyes). These 17 infants, in comparison with infants in the CRYO-ROP trial (n = 187), were at least at equal risk for poor visual outcome on the basis of birth weight, gestational age, the percentage of zone 1 ROP, and mean interval from appearance of ROP to diagnosis of prethreshold ROP, which was shorter at Pennsylvania Hospital (4.1 days for the Pennsylvania Hospital group, 10.3 days for the CRYO-ROP group). However, on the basis of the mean number of days from diagnosis of prethreshold to threshold ROP (12.5 days for Pennsylvania Hospital, 10.5 days for CRYO-ROP) and the extent of extraretinal neovascularization at threshold (mean 7.9 sectors for Pennsylvania Hospital, 9.7 for CRYO-ROP), progression of retinopathy beyond the prethreshold stage had slowed and visual outcome in the eyes of infants at Pennsylvania Hospital treated with both cryotherapy and vitamin E (worse eye used for those treated with bilateral cryotherapy) was better than that reported for the treated eye of infants in the CRYO-ROP group (percentage of favorable visual acuity, 76% vs 48%, p = 0.04; percentage of normal structure posterior retinal pole, 71% vs 38%, p < or = 0.02). CONCLUSIONS: In this small case series, the combination of cryotherapy with anti-oxidant prophylaxis and treatment appeared to decrease the severity and sequelae of threshold ROP. This hypothesis deserves testing in a large, randomized clinical trial.

Combined Modality Therapy↗
PubMed1992

The high-risk infant environment. Part 2. The role of caregiving and the social environment.

Neonatal intensive care units are essential for the successful care of very immature and sick infants. The technology of NICUs has contributed significantly to the reduction of neonatal mortality and improvement of neonatal outcome. While the outcome for high-risk neonates has vastly improved over the past three decades, a number of infants sustain injuries and complications that result in long-term disabilities. It is now clear that some of the long-term problems of high-risk infants are a result of the environment and care practices and are not attributable to the original disease or condition that necessitated intensive care. There is accumulating evidence that environmental factors and care practices can interact with disease processes in ways that can increase morbidity, and possibly mortality. In addition to developmental and behavioral problems, there is growing evidence of effects on visual function and perhaps other sensory systems. Many of the environmental and care factors may cause delay in recovery and increase NICU time or unnecessary discomfort, yet not produce long-term disabilities or problems, as currently assessed. Many of the potential behavioral and developmental problems, as well as many of the potential problems with visual, auditory, and other modes of sensory discrimination, are not included in the usual follow-up assessments. The absence of data or the limitations of existing studies are not a cause for comfort or the assumption that the environment and care practices are safe or not harmful.(ABSTRACT TRUNCATED AT 250 WORDS)

Environment↗
PubMed1991

Variation of initial serum bilirubin rise in newborn infants with type of illness.

Hyperbilirubinaemia in newborn infants is generally regarded as a problem, and bilirubin itself as toxic metabolic waste, but the high frequency in newborn infants suggests that the excess of neonatal bilirubin may have a positive function. To investigate the hypothesis that bilirubin has a role as a free-radical scavenger, the rate of rise in serum bilirubin in the first few days of life was measured in 44 infants with five illnesses thought to enhance free-radical production and in 58 control infants. The infants were selected from 2700 consecutive births by exclusion of those with factors known to affect bilirubin metabolism, including enteral feeding. The control infants were those who seemed to be ill and received treatment, including restriction of enteral feeds, but in whom no illness, or disorders not related to free-radical production, were found. The mean serum bilirubin rise was significantly lower in the combined illness group than in the control group (36.1 [95% Cl 26.9-45.3] vs 66.7 [55.9-77.5] mumol.l-1.day-1; p less than 0.0001). In subgroup analyses the mean rises in infants with circulatory failure, neonatal depression/asphyxia, aspiration syndromes, and proven sepsis were significantly lower than in controls matched for gestational age and birthweight, but rises in infants with respiratory distress and their matched controls did not differ. These findings are consistent with the hypothesis that bilirubin is consumed in vivo as an antioxidant. Such consumption may operate in vivo in addition to the standard pathways for bilirubin metabolism (production, isomerisation, and excretion).

Antioxidants↗
PubMed1990

Retinopathy of prematurity: prevalence and treatment over a 20 year period at Pennsylvania Hospital.

This paper presents the results of a 20 year survey of ROP among less than or equal to 2000 g BW infants cared for at Pennsylvania Hospital. It relates changes in perinatal care and nutrition, survival rates, and serial serum E levels with incidence and severity of ROP. It includes our protocol for monitoring E nutrition so as to optimize its effectiveness at physiologic serum levels for prophylaxis for ROP. Also presented are the promising results of our experience with vitamin E at pharmacologic serum levels as a treatment for severe ROP (defined as in the Cryo ROP Trial). These indicate the need for a multicenter trial to assess the effect of pharmacologic Vitamin E therapy as an alternative or supplement to therapy of severe ROP with laser or cryo surgery.

Clinical Trials as Topic↗