Biomedical subjects

G B Wright

Publications and source records attributed to G B Wright.

18 recordsLinked to original sources

PubMed2001

Development of left ventricular hypertrophy in adults in hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations.

OBJECTIVES: We sought to determine whether the development of left ventricular hypertrophy (LVH) can be demonstrated during adulthood in genetically affected relatives with hypertrophic cardiomyopathy (HCM). BACKGROUND: Hypertrophic cardiomyopathy is a heterogeneous cardiac disease caused by mutations in nine genes that encode proteins of the sarcomere. Mutations in cardiac myosin-binding protein C (MyBPC) gene have been associated with age-related penetrance. METHODS: To further analyze dormancy of LVH in patients with HCM, we studied, using echocardiography and 12-lead electrocardiography, the phenotypic expression caused by MyBPC mutations in seven genotyped pedigrees. RESULTS: Of 119 family members studied, 61 were identified with a MyBPC mutation, including 21 genetically affected relatives (34%) who did not express the HCM morphologic phenotype (by virtue of showing normal left ventricular wall thickness). Of these 21 phenotype-negative individuals, 9 were children, presumably in the prehypertrophic phase, and 12 were adults. Of the 12 adults with normal wall thickness < or = 12 mm (7 also with normal electrocardiograms), 5 subsequently underwent serial echocardiography prospectively over four to six years. Of note, three of these five adults showed development of LVH in mid-life, appearing for the first time at 33, 34 and 42 years of age, respectively, not associated with outflow obstruction or significant symptoms. CONCLUSIONS: In adults with HCM, disease-causing MyBPC mutations are not uncommonly associated with absence of LVH on echocardiogram. Delayed remodeling with the development of LVH appearing de novo in adulthood, demonstrated here for the first time in individual patients with prospectively obtained serial echocardiograms, substantiates the principle of age-related penetrance for MyBPC mutations in HCM. These observations alter prevailing perceptions regarding the HCM clinical spectrum and family screening strategies and further characterize the evolution of LVH in this disease.

Adult↗

PubMed2001

Management of acute pulmonary hemorrhage in children.

OBJECTIVE: Acute pulmonary hemorrhage can result from a variety of causes. This report offers a diagnosis and treatment plan for children with acute, life-threatening pulmonary hemorrhage resulting from a variety of causes. METHODS: Retrospective review of children with acute pulmonary hemorrhage cared for at a tertiary care children's hospital during from January 1, 1993 to September 1, 1999. PATIENTS: Fourteen children were identified with life-threatening pulmonary hemorrhage during the study period. INTERVENTIONS: Bronchoscopy was the keystone to diagnosis of pulmonary hemorrhage in this series. All of the children underwent multiple procedures to stabilize the airway and control blood loss. These interventions included CO2 laser bronchoscopy, Nd-YAG laser bronchoscopy, endoscopic balloon occlusion of a lobe or main bronchus, topical airway vasoconstrictors, endoscopic tumor excision, transcatheter embolization of bronchial vessels, and lobectomy. OUTCOMES: Three children died and 11 survived without neurological sequelae. CONCLUSIONS: Control of acute pulmonary hemorrhage is a difficult problem and often requires multiple procedures. Endoscopic control is usually required for palliation until more definitive therapy can be undertaken.

Acute Disease↗

PubMed2000

Neurodevelopmental follow-up at 36 months' corrected age of preterm infants treated with prophylactic indomethacin.

BACKGROUND: Previous reports have suggested that prophylactic indomethacin decreases cerebral blood flow and may play a role in the development of ischemic brain injury and developmental handicaps. OBJECTIVE: To assess the neurodevelopmental outcome of subjects at 36 months' corrected age (CA) who, as low-birth-weight infants, received prophylactic low-dose indomethacin within the first 24 hours of life to prevent patent ductus arteriosus. SETTING: Newborn intensive care nursery and outpatient follow-up clinic at Children's Hospitals and Clinics of Minneapolis, Minneapolis, Minn. DESIGN: Ninety infants with birth weights of 600 to 1250 g were entered into a prospective, randomized, controlled trial to receive either prophylactic indomethacin, 0.1 mg/kg, or placebo in the first 24 hours and again every 24 hours for 6 doses to prevent patent ductus arteriosus. Nonresponders were treated with standard therapeutic indomethacin or ligation. Neurodevelopmental assessment at approximately 36 months' CA included medical and developmental histories, physical examinations, and developmental testing using the Bayley II Scales of Infant Development on subjects up to 42 months' CA. Subjects were classified as (1) normal, (2) mildly to moderately abnormal, or (3) severely impaired. RESULTS: Forty-two (98%) of 43 subjects who received prophylactic indomethacin survived compared with 46 (98%) of 47 who received placebo. Sixty-six (75%) of 88 survivors were seen for neurodevelopmental assessment at 36 months' CA. This group included 29 (69%) of 42 who received prophylactic indomethacin and 37 (80%) of 46 who received placebo. Twenty-three (79%) of 29 infants in the prophylactic indomethacin group had normal neurodevelopmental assessments at 36 months' CA compared with 26 (70%) of 37 placebo-treated subjects (P = .68). Of 4 significantly impaired subjects treated with prophylactic indomethacin, 1 had spastic diplegia; 1, spastic quadriplegia; 1, cognitive delay; and 1, significant motor delay. Of 8 significantly impaired placebo-treated subjects, 7 had spastic diplegia; 1, microcephaly. CONCLUSION: The use of prophylactic low-dose indomethacin when initiated in the first 24 hours of life in low-birth-weight infants to prevent patent ductus arteriosus is not associated with adverse neurodevelopmental outcome at 36 months' CA.

Cardiovascular Agents↗

PubMed1996

Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room.

OBJECTIVE: To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room. DESIGN: Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation. RESULTS: Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis. CONCLUSION: The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.

Birth Weight↗

PubMed1994

Control of Aedes albopictus larvae using time-release larvicide formulations in Louisiana.

The ability of time-release formulations of larvicides and insect growth regulators (IGRs) to provide long-term control of Aedes albopictus was investigated in the field. Larvicides used in the study were Bactimos pellets (Bacillus thuringiensis var. israelensis, active ingredient) and Abate pellets (temephos, active ingredient). The IGR Altosid (methoprene, active ingredient) was used in pellet and sand formulations. Application rates were higher than label recommendations. In a preliminary test, clay flower bowls were treated with 2 g of material. Bactimos pellets failed to provide control after 60 days. Abate pellets and the Altosid formulations provided essentially 100% control for 150 days. After 360 days in the field, the Abate pellets produced 100% larval mortality, and significant levels of control were provided by the Altosid formulations and the Bactimos pellets. In a small-scale operational trial of this technique, 1 g of Altosid pellets was applied to every container that could be located in 2 urban residential neighborhoods in Lake Charles, LA. Aedes albopictus biting populations were monitored weekly in the treated areas and in an untreated control area. Biting population densities declined significantly in treated areas compared with the control area. Results suggested that long-term control of Ae. albopictus populations can be achieved economically with one application of Altosid pellets or Abate pellets in containers.

Aedes↗

PubMed1992

Fixation of osteochondral fractures in rabbit knees. A comparison of Kirschner wires, fibrin sealant, and polydioxanone pins.

We compared fibrin sealant, polydioxanone (PDS) pins and Kirschner wires in the fixation of osteochondral fractures in rabbit knees. Standardised osteochondral fractures of the right medial femoral condyle were made in 56 adult New Zealand white rabbits. There were equal groups of control knees, and those which had Kirschner-wire, fibrin-sealant or PDS-pin fixation. No external immobilisation was used. One animal from each group was killed at two, three and four weeks. The remaining rabbits were killed at six weeks. A fracture which healed with less than 1 mm of displacement was considered a success. There was successful healing in 29% of the control group, in all of the Kirschner-wire group, in 50% of the fibrin-sealant group, and in 86% of the PDS-pin group. The use of PDS pins appears to be a reliable alternative to the use of metal in the fixation of osteochondral fractures in rabbits.

Animals↗

PubMed1990

Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin.

Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay.

Aspirin↗

PubMed1989

Calcium is rapidly exchangeable in cultured vascular smooth muscle cells from rabbit aorta.

Calcium exchange was measured in enzymatically isolated, cultured smooth muscle cells from the rabbit thoracic aorta. Cells were grown to confluence in monolayer on scintillator discs which were then inserted into a modified flow cell/spectrometer to measure 45Ca exchange in a continuous, on-line manner. This also allowed us to measure rapid movements of cellular Ca2+ without solubilizing the cells. Two components of Ca2+ exchange were detected: a La3+-displaceable, rapidly exchangeable fraction (t 1/2 = 15.6 s) and a slowly exchangeable fraction (t 1/2 = 34.5 min). The La3+ displaceable, rapidly exchangeable Ca2+ fraction represented 57 to 61% of the total exchangeable Ca2+. Multiple passaging of cells did not after the Ca2+ flux characteristics. Low Na+ perfusion increased smooth muscle cell Ca2+ flux by 6.71 mmol/kg dry weight. This increase was localized to both the rapidly and slowly exchangeable Ca2+ compartments. Ouabain, an inhibitor of the plasmalemmal Na+ -K+ pump, also increased net uptake of 45Ca. The results demonstrate that approximately 60% of exchangeable Ca2+ of smooth muscle cells is very rapidly exchangeable (t 1/2 less than 16 s). The results stress the importance of measuring 45Ca2+ movements in an on-line, continuous manner in order to ensure detection of the majority of total exchangeable Ca2+ in smooth muscle cells.

Animals↗

PubMed1989

Mortalities associated with use of a commercial suspension of polyvinyl alcohol.

Two cases of symptomatic neonatal hepatic arteriovenous malformation (AVM) are presented. Both were treated with percutaneous transcatheter embolization and a commercially available polyvinyl alcohol suspension. Both infants died soon after AVM embolization. The results of laboratory examination of particle-size homogeneity of this commercial suspension demonstrate marked inhomogeneity of particle size very probably contributed to the death of these patients. A protocol has been developed to help determine appropriate particle size in individual cases; this may help prevent such catastrophic results during transcatheter embolization.

Arteriovenous Malformations↗

PubMed1988

Adults with cyanotic congenital heart disease: hematologic management.

Hematologic management of adults with cyanotic congenital heart disease has received little recent attention. The lack of practical therapeutic guidelines prompted us to consolidate our observations on 124 cyanotic adults for general physicians, cardiologists, and hematologists who care for these patients. Specific attention focused on regulation of erythrocyte mass and concepts of compensated and decompensated erythrocytosis, symptoms of deficient tissue oxygen transport, hyperviscosity and iron deficiency, the potential relation between elevated hematocrit levels and brain injury, hemostasis, urate metabolism, and renal function. Cerebral infarction was not seen in any patient. Phlebotomy is best reserved for treatment of symptomatic hyperviscosity. Iron therapy is indicated for symptomatic iron deficient erythropoiesis. Abnormal hemostatic mechanisms are the rule. Antithrombotic medications have little or no role in treatment. Hyperuricemia is the result of abnormal renal uric acid excretion not urate overproduction, and serves as a marker of abnormal renal function. Drugs that promote urate excretion are the preferred maintenance treatment in symptomatic hyperuricemic patients.

Adolescent↗

PubMed1983

Fixed subaortic stenosis in the young: medical and surgical course in 83 patients.

Eighty-three patients aged 11 months to 25 years were followed up a median of 6.1 years (range 8 days to 24 years) after diagnosis of fixed subaortic stenosis (SAS). Fourteen (17%) had significant noncardiac defects and 47 (57%) had additional cardiac malformations. The left ventricular (LV) outflow gradient increased in 25 of 26 patients catheterized more than once before surgery. Of 15 patients less than 12 years old with gradients less than or equal to 40 mm Hg, 10 ultimately underwent operation after developing severe obstruction; another has progressed to a gradient of 45 mm Hg at 6 years of age. Before surgery (at a median age of 12 years), 55% had aortic regurgitation (AR), which was usually mild. Infective endocarditis occurred in 12% of the group, with a frequency of 14.3 cases per 1,000 patient-years. Seventy-four patients were operated on, with 6 early (8%) and 7 late (9%) deaths. Twelve underwent reoperation to relieve residual obstruction. Surgery reduced gradients in patients with discrete SAS from 83 +/- 33 to 29 +/- 30 mm Hg, but in 6 patients with tunnel SAS the reduction was less satisfactory. AR was absent or mild in most patients postoperatively. When the gradient was reduced to less than 80 mm Hg, infective endocarditis did not occur unless there were other residual lesions. These data suggest that it is reasonable to resect discrete SAS in children less than 10 to 12 years old with LV outflow gradients greater than or equal to 30 mm Hg.

Adolescent↗

PubMed1983

Characterization of the rabbit ventricular myocardial receptor for angiotensin II. Evidence for two sites of different affinities and specificities.

Angiotensin II binding sites in a rabbit ventricular myocardial particulate fraction were identified and characterized with the radioligand 125I-angiotensin II. The order of potency in competing with 125I-angiotensin II for these sites was similar to that observed in physiological studies. Computer-assisted analysis of the competition of binding sites for 0.3 nM 125I-angiotensin II by unlabeled angiotensin II (3 X 10(-11) M to 1 X 10(-5) M) demonstrated that optimal fitting of the competition curves was attained with a two-site model having one site of high affinity (KA1 = 2.4 +/- 0.6 X 10(9) M-1), low capacity (N1 = 7.8 +/- 0.8 fmoles/mg of protein) and a second site low affinity (KA2 = 9.6 +/- 0.6 X 10(6) M-1) and high capacity (N2 = 219 +/- 128 fmoles/mg of protein). Analysis of competition by Sar1-Ile8 angiotensin II for 125I-angiotensin II binding sites indicated that the antagonist interacted with the first site with high affinity (KA1 = 8 X 10(9) M-1), but interacted minimally with the second site (KA2 = 10(5) M-1). Monovalent cations (Na+, K+, Li+, NH4+) were roughly equipotent in decreasing 125I-angiotensin II binding by reducing the number of high-affinity sites (N1 = 2.6 +/- 0.7 fmoles/mg of protein with 100 mM Na+) without changing the affinity of either site or the number of low-affinity sites. The number of high-affinity sites was increased to 14.4 +/- 1.5 fmoles/mg of protein by 5 mM Mg2+. In the presence of divalent cations, nucleotides reduced binding of 125I-angiotensin II with the potency order guanosyl-5'-yl-imidodiphosphate greater than GTP greater than GDP greater than ATP greater than GMP. Guanosyl-5'yl-imidodiphosphate significantly reduced the affinity of the high-affinity site (KA1 = 1.0 +/- 0.2 X 10(9) M-1) and perhaps of the low-affinity site (KA2 = 1.0 +/- 2.2 X 10(6) M-1). Computer-assisted assessment of dissociation of 0.3 nM 125I-angiotensin II from rabbit myocardial membranes corroborated the equilibrium data: dissociation was biphasic (K-1 = 0.19 +/- 0.2 min-1 for a rapidly dissociating site, k-1 = 2.5 +/- 2.1 X 10(-3) min-1 for a slowly dissociating site); 5 mM Mg2+ did not significantly change either dissociation rate; but guanosyl-5'-yl-imidodiphosphate significantly increased dissociation rates from both sites. Despite the indirect evidence that these angiotensin II receptors interact with guanine nucleotide regulatory proteins, angiotensin II (10(-6) M) failed to influence adenylate cyclase activity. The physiological implications of the presence in ventricular myocardium of two distinct angiotensin II receptors and in particular the implications of a receptor-associated guanine nucleotide regulatory protein which does not couple to adenylate cyclase require further investigation.

Adenylyl Cyclases↗

PubMed1982