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Biomedical subjects

C R Smith

Publications and source records attributed to C R Smith.

At least 181 records · Page 10Linked to original sources
PubMed1991

Four unusual cases of sudden and unexpected cardiovascular death in infancy and childhood.

Four unusual cases of sudden and unexpected cardiovascular death in infancy and early childhood that were found during a ten-year autopsy review at our institutions are presented. In Case 1, an asymptomatic 2-year-old male, sudden death resulted from an acute myocardial infarct due to occlusion of coronary arteries that had been previously damaged by unsuspected arteritis. Case 2, a previously well 7-month-old male, died from an acute myocardial infarct due to an unsuspected anomalous origin of the coronary arteries from a single, stenotic coronary ostium. Case 3, a previously well 21-month-old black male, died from a splenic sequestration crisis due to undiagnosed sickle cell disease. Case 4, a 2-month-old female with suspected Marfan syndrome, died from a ruptured dissecting aneurysm of a patent ductus arteriosus. Accuracy of diagnosis was of particular importance in the latter two cases because of the possible genetic implications.

Cardiovascular Diseases↗
PubMed1991

High-dose oral baclofen: experience in patients with multiple sclerosis.

We reviewed a 10% random sample of charts from an outpatient clinic for multiple sclerosis to determine the frequency with which baclofen was prescribed for spasticity in high doses (greater than 80 mg/d). About 20% of patients had taken high-dose baclofen, and 15% were still receiving a high dose. Taking a high dose was not associated with discontinuing treatment.

Administration, Oral↗
PubMed1991

Permeabilized hepatocyte couplets. Adenosine triphosphate-dependent bile canalicular contractions and a circumferential pericanalicular microfilament belt demonstrated.

The motility of bile canaliculi was examined in hepatocyte couplets permeabilized with palmitoyl lysophosphatidyl choline in a dosage regimen that drastically affected secretory function, yet maintained relative integrity of the cellular cytoskeleton. The permeabilized cells showed no exclusion of trypan blue, notable cytoplasmic organelle and membrane damage, and no uptake or secretion of either fluorescein diacetate or sodium fluorescein. However, bile canalicular structure remained relatively intact and actin and myosin were localized immunocytochemically in the pericanalicular region. Coincident with the administration of 1 mM ATP, 2 mM Mg2+, and 1 microM Ca2+, the canaliculi contracted with partial or complete luminal closure. ADP, AMP, or AMP-PCP could not be substituted for ATP. A dose-dependent relationship was shown between ATP concentration and canalicular contraction rate. The permeabilization procedure also provided enhanced visualization of pericanalicular microfilaments, believed to be actin filaments, and their organization into two layers: an inner membrane-associated network, and an outer filament bundle that inserted into belt junctions (zonulae adherentes). The organization of the microfilament belt of contiguous hepatocytes was such that it formed a circumferential band of microfilaments around the canaliculus. It is analogous to contractile filament belts found in the apical terminal web region of other epithelia. It was also observed that with canalicular luminal closure, there was a change in the organization of the pericanalicular microfilaments. It is concluded that in hepatocyte couplets, differential sensitivity of cell components to permeabilization can be achieved with palmitoyl lysophosphatidyl choline. In addition, the results provide evidence that the bile canaliculus has the capacity to be a contractile structure even in the absence of secretion, that canalicular contraction is ATP-dependent, and hence is a dynamic process.

Actin Cytoskeleton↗
PubMed1991

Pediatric heart transplantation after operations involving the pulmonary arteries.

A prohibitive perioperative mortality has been previously ascribed to pediatric heart transplantation after palliative operations for congenital heart disease involving the pulmonary arteries. Of 46 children who have undergone heart transplantation at our institution between June 1984 and February 1990, 7 (15%; mean age 8 +/- 3 years; range 1 to 18 years) have previously undergone such operations: right ventricle to pulmonary artery conduit/homograft for levo-transposition of the great arteries (2), Waterston shunt for tricuspid and pulmonary atresia (1), pulmonary artery banding for single ventricle (1), Fontan procedure for single ventricle (1), first-stage Norwood procedure for hypoplastic left heart syndrome (1), and classic right Blalock-Taussig shunt for atrioventricular canal with pulmonic stenosis (1). Three categories of pulmonary artery anatomy that require different approaches to reconstruction at the time of transplantation are recognized: abnormalities of position, pulmonary outflow obstruction, and previous systemic- or atrial-pulmonary connections. At operation, individualized pulmonary arterial reconstruction was employed, including use of previously created right ventricular-pulmonary artery conduits/homografts and angioplasty (with and without pericardial patches). Transplantation was successful in all patients. Posttransplant right ventricular-pulmonary artery pressure gradients and pulmonary vascular resistance indices were acceptable, with a tendency to decrease with time. Two patients had critical right ventricular failure postoperatively; one of them required support with extracorporeal membrane oxygenation. There was no perioperative mortality, with three deaths occurring from 5 to 39 months after transplantation. All surviving patients are in New York Heart Association functional class I. Techniques borrowed from the repair of congenital cardiac lesions can be applied to subgroups of children undergoing heart transplantation. Additional length of donor aorta and pulmonary artery should be harvested for possible use in designing pulmonary artery connections. Previous palliative operations involving the pulmonary arteries with associated complex pulmonary artery anatomy are not of themselves an insurmountable obstacle to successful heart transplantation.

Actuarial Analysis↗
PubMed1991

Improved heart preservation with University of Wisconsin solution: experimental and preliminary human experience.

We tested the ability of University of Wisconsin solution (UWS) to extend hypothermic nonperfused heart preservation in baboons and then proceeded to human transplantation. Orthotopic transplantation was performed in five baboons (UWS cardioplegia and storage [4 degrees C]; preservation time 10.3 +/- 0.6 hours). Four survivors were immunosuppressed for 45 days and killed. One animal died from disruption of the aortic anastomosis due to technical error. Preservation did not alter histology under light and electron microscopy or heart weight (at harvest, 51.4 +/- 11.6 g; before implant, 52.5 +/- 11.1 g). Animals were weaned from bypass (mean, 23 +/- 12 minutes) and returned to their cages without intravenous support within 3.6 +/- 0.6 hours. Weekly biopsy, electrocardiogram, enzyme analysis, echocardiogram, and right heart catheterization demonstrated excellent cardiac function. Following success in baboons, UWS was applied to human transplantation (n = 2, UWS cardioplegia and storage [4 degrees C]; preservation time 4.2 and 2.1 hours). The hearts returned to sinus rhythm within 4 minutes of reperfusion without defibrillation, and enzymatic and hemodynamic data reveal excellent heart preservation. Preliminary data suggest the ability of UWS to prolong heart preservation in baboons and be used safely in humans. Further studies are required to compare UWS with crystalloid cardioplegia and saline storage and to prolong donor heart preservation in humans.

Adenosine↗
PubMed1990

Unsuspected diaphragmatic hernia: a potential cause of sudden and unexpected death in infancy and early childhood.

Congenital diaphragmatic hernias are usually found in neonates who present with respiratory distress. However, a significant number may remain clinically undiagnosed until much later in life. Of interest, the prognosis is felt to be better in this latter group. We describe three previously well patients (aged 2, 4, and 24 months) who suffered unexpected cardiorespiratory arrests due to unsuspected congenital diaphragmatic defects with intestinal herniation. Deaths resulted from cardiovascular and respiratory compromise due to visceral herniation that caused mediastinal and pulmonary compression.

Child, Preschool↗
PubMed1990

Type IV Ehlers-Danlos syndrome presenting as sudden infant death.

A previously healthy 5-month-old female infant presented with sudden death due to spontaneous subarachnoid hemorrhage associated with minor multifocal visceral hemorrhages. The clinical diagnosis had been sudden infant death syndrome. Although the family history was noncontributory and other features of type IV Ehlers-Danlos syndrome (EDS) were absent, the pattern of hemorrhage was consistent with this type of connective tissue disorder. The diagnosis was confirmed after postmortem analysis of skin and aorta showed less than 5% type III collagen (normal greater than 15%). Extensive literature review failed to find any other reported cases of sudden death in infancy due to intracranial hemorrhage in patients with previously unsuspected type IV EDS. The authors suggest that collagen analysis should be performed in cases of unexplained multifocal spontaneous hemorrhage in infancy so that this rare diagnosis will not be missed.

Collagen↗
PubMed1990

Clostridium difficile invasion and toxin circulation in fatal pediatric pseudomembranous colitis.

The direct involvement of Clostridium difficile in the lesional tissue of pseudomembranous colitis has not been demonstrated; the organism's effects have been assumed to be strictly toxin mediated. Because C. difficile cytotoxin may be found incidentally in the intestinal lumina of asymptomatic infants, the role of the organism in a variety of pediatric intestinal diseases is uncertain. The authors studied seven cases of fatal pediatric pseudomembranous colitis in which the presence of C. difficile was uniformly demonstrable in lesional tissues with the use of both an intestinal spore stain and a specific immunostain. The patients had either underlying Hirschsprung's disease or hematologic malignancy; the striking pathologic features peculiar to these patients were altered mucosal mucin and immunologic barriers in the former group and neutropenia in the latter. Two patients had demonstrable circulating cytotoxin in serum or ascitic fluid, and C. difficile was identified invading colonic mucosa or submucosa. Such phenomena did not occur in control pediatric patients with multiple other intestinal lesions. Altered host factors may be responsible for the intestinal invasion of C. difficile and its systemic toxin circulation in cases of fatal pediatric pseudomembranous colitis.

Adolescent↗
PubMed1990

Lesions of the mid-shaft of the humerus presenting as shoulder capsulitis.

We describe three patients who presented with pain and restriction of movement at the shoulder suggestive of capsulitis, but proved to have lesions of the mid-shaft of the humerus. It is important to be aware of the possibility of this cause of a 'frozen shoulder', since radiographs of the shoulder are usually cropped at the mid-humerus and lesions at this level may easily be missed. A radiograph of the entire humerus, or an isotope bone scan, may be more useful than repeated shoulder radiographs in patients whose shoulder symptoms do not respond to standard treatment.

Adult↗
PubMed1990

Initial evaluation of human monoclonal anti-lipid A antibody (HA-1A) in patients with sepsis syndrome.

HA-1A, a human monoclonal immunoglobulin M antibody that binds specifically to the lipid A domain of endotoxin, was administered to septic patients to evaluate the safety, pharmacokinetics, and immunogenicity of the antibody. Thirty-four patients received a single infusion of either 25 mg, 100 mg, or 250 mg, and were followed clinically for 14 to 21 days after treatment. HA-1A serum levels were measured before infusion and frequently after infusion with a radiometric assay. A one-compartment pharmacokinetic model was fit to the measured serum levels, and accurately described the changes in HA-1A level over time in each dose group (r2 = .99). The mean +/- SEM apparent volume of distribution of HA-1A was 48.5 +/- 4.5 ml/kg, and the mean serum clearance was 2.8 +/- 0.4 ml/kg.h. The mean serum half-life of HA-1A was 15.9 +/- 1.5 h. The mean serum level one hour after a 100-mg dose was 33.2 +/- 2.4 micrograms/ml, and the mean concentration 24 h later was 9.1 +/- 1.6 micrograms/ml. The dose administered and presence of Gram-negative bacterial infection did not significantly influence the volume of distribution or serum clearance. No adverse reactions to HA-1A were observed, and no antibodies against HA-1A were detected in any patient. These data indicate that the pharmacokinetics of HA-1A are well described by a one-compartment pharmacokinetic model, and that HA-1A is safe and nonimmunogenic in patients with sepsis.

Adult↗
PubMed1990

Congenital teratomas of the neck and nasopharynx: a clinical and pathological study of 18 cases.

Congenital teratomas of the neck and nasopharynx are unusual tumours that seldom metastasize. Due to their rarity, reviews often have relied upon compilations of isolated case reports. We report our experience of the early outcome of 18 cases (14 cervical, four nasopharyngeal) to demonstrate the high morbidity and mortality that these benign but critically placed lesions have because of local mass effects. Six patients (33%) either were stillborn or died of disease within 2 days of birth; of the survivors, four (22%) had significant respiratory obstruction requiring surgery. Tumour location and size rather than histologic grading were the most significant features affecting the immediate clinical course. All but one of the patients who underwent early surgical resection had a favourable outcome.

Cause of Death↗
PubMed1990

Serum prolactin bioactivity and immunoactivity in hyperprolactinaemic states.

Serum prolactin concentrations were measured using a sensitive bioassay (Nb2 assay) and by radioimmunoassay in 11 patients with prolactin-secreting pituitary tumours (median serum immunoactive prolactin 5150 mU/L), and in 58 normal control subjects (median prolactin 190 mU/L). The mean ratio of serum prolactin bioactivity to immunoactivity was significantly lower in patients with prolactinomas than in normoprolactinaemic controls. Ten lactating women in the early post-partum period (median prolactin 3800 mU/L), studied as a model of physiological hyperprolactinaemia, also had reduced bioactivity to immunoactivity ratios. Overall, there was a significant negative correlation between bioactivity:immunoactivity ratio and serum immunoactive prolactin. The change in relative bioactivity of prolactin in serum samples from patients with prolactinomas and in women with physiological hyperprolactinaemia may reflect changes in the molecular heterogeneity of the hormone. Such changes may affect activity in both bioassays and radioimmunoassays.

Adult↗
PubMed1990

Prolactin and growth hormone: molecular heterogeneity and measurement in serum.

The pituitary hormones prolactin and growth hormone are related single-chain polypeptides. Both hormones exist in the circulation in several molecular forms, and this heterogeneity may account for some of the complex and sometimes contradictory actions, in vivo and in vitro, of both hormones. It may also lead to problems with quantitation by immunoassays and discrepancies between the results given by assays using different antibodies. Modified forms of the hormones may have markedly different activity in bioassays from that of the parent hormone, but the clinical significance of this is unclear. In this review we summarize what is known about the molecular heterogeneity of the hormones and briefly discuss the implications for clinical biochemists.

Genetic Variation↗
PubMed1990

The proportion of glycosylated prolactin in serum is decreased in hyperprolactinemic states.

The proportion of serum PRL that is glycosylated has been determined, and the effects of physiological and pathological hyperprolactinaemia on this proportion have been examined. Glycosylated and nonglycosylated PRL were immunoprecipitated from serum and subjected to polyacrylamide gel electrophoresis under reducing and dissociating conditions. Separated proteins were then transferred to nitrocellulose paper by electroblotting and detected immunologically with anti-PRL antiserum and 125I-labeled protein-A, followed by autoradiography. The proportion of total monomeric PRL present in the glycosylated form was then estimated by densitometric scanning of autoradiograms. In normal individuals glycosylated PRL was predominant, accounting for about 72% of the circulating monomeric PRL. This proportion was markedly decreased (ranging from undetectable to about 60%) in the serum of women who were pregnant or were lactating postpartum and also in patients with hyperprolactinemia caused by a pituitary tumor. The results suggest that under basal conditions the majority of PRL secreted from the pituitary is glycosylated, but with physiological or pathological hyperprolactinemia the capacity for glycosylation is exceeded.

Adult↗