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Biomedical subjects

C Stephens

Publications and source records attributed to C Stephens.

At least 37 records · Page 2Linked to original sources

Complement activation during prolonged extracorporeal membrane oxygenation.

Short-term cardiopulmonary bypass activates the complement system, possibly resulting in pulmonary dysfunction from granulocyte aggregation and pulmonary endothelial damage. These effects may be inhibited by steroids. Prolonged extracorporeal membrane oxygenation (ECMO) is used for newborn respiratory failure, but the effects of ECMO on complement activation are unknown. Twenty-one newborn infants with respiratory failure treated with ECMO were randomly assigned to group I (control, no steroids) or group II (30 mg/kg intravenous methylprednisolone before ECMO). Depletion assays of C3 and C5 were performed in each group at intervals before and during ECMO (declining values indicate complement activation). The groups were compared for complement levels, survival, time on ECMO and on the ventilator, and total hospitalization time. Steroids significantly shortened the time on ECMO and time on the ventilator after ECMO but did not affect survival or total hospitalization time. Steroids also enhanced activation of C3 and C5. Complement activation occurs during ECMO. Steroid administration paradoxically causes earlier complement activation but shortens ECMO and ventilator times. Complement activation during ECMO is of questionable significance. The benefits of steroids during ECMO may be mediated through other mechanisms.

Birth Weight

Prognostic determinants in extracorporeal membrane oxygenation for respiratory failure in newborns.

Extracorporeal membrane oxygenation (ECMO) is becoming an accepted therapeutic modality for newborn respiratory failure, but there is little information available regarding the prognostic determinants with this technique. One hundred thirty-five newborns treated with ECMO over a 4-year period were critically analyzed with regard to the influence that birth weight, gestational age, age at initiation of ECMO, best blood gases before ECMO, number of hours on ECMO, renal failure, intracerebral hemorrhage, and long-distance air transport had on survival. Infants with meconium aspiration and those undergoing long-distance transfer showed significant differences in blood gases before ECMO, with survivors having more normal pH and carbon dioxide tension values. Intracerebral hemorrhage and renal failure that developed during ECMO were grave prognostic signs, with few survivors in either group. These data show that ability to ventilate patients before ECMO, giving normal carbon dioxide tension and pH values, is an important prognostic sign in infants with meconium aspiration and undergoing long-distance transfer for ECMO, whereas renal failure and intracerebral hemorrhage are usually lethal complications of ECMO. Each center performing ECMO should continually reevaluate this invasive technique and its results and complications.

Acute Kidney Injury

Holograms as substitutes for orthodontic study casts: a pilot clinical trial.

A pilot study of holograms as substitutes for study casts during routine clinical treatment was carried out by four clinicians on 56 patients over a 6-month period. Three of the clinicians found holograms to be as informative as study casts and equally or more convenient, but one clinician considered holograms to be inferior to study casts in both these respects. In addition, replicate quantification of malocclusions by means of the Summers index showed very similar rates of random error for holograms and for study casts and no significant systematic error between the scores obtained. Currently available holograms merit further investigation as alternatives to study casts. Refinement to further improve the convenience, informativeness, and economy of the holograms is also being undertaken.

Holography

A critical analysis of extracorporeal membrane oxygenation for congenital diaphragmatic hernia.

Despite advances made in the care of infants with congenital diaphragmatic hernia (CDH), survival remains poor. New therapy, such as extracorporeal membrane oxygenation (ECMO), is controversial but may improve survival. Thirty-two newborns with CDH were treated. Thirteen infants were treated with jugular vein-carotid artery ECMO after CDH repair elsewhere; six (46%) survived. Three of the remaining 19 were moribund shortly after birth and first received ECMO, then underwent repair; two (67%) survived. The other 16 underwent CDH repair; 8 of 9 (89%) recovered with conventional therapy, and 4 of 7 (57%) survived when ECMO was used after conventional therapy failed. Overall survival was 63%. Parameters with which physicians may attempt to predict survival or the need for ECMO after repair--such as A-aDO2, ventilatory index versus PCO2, presence of a "honeymoon period" (PaO2 greater than 100 mm Hg after repair), or oxygenation index--were unreliable. ECMO can improve survival in infants with CDH, probably through reversal of pulmonary hypertension. Presently available methods of predicting survival after CDH repair with or without ECMO are not accurate, and thus no infant should be excluded from repair or ECMO support.

Extracorporeal Membrane Oxygenation

Differential splicing yields novel adenovirus 5 E1A mRNAs that encode 30 kd and 35 kd proteins.

In addition to the protein products of the adenovirus E1A 13S and 12S mRNAs, monoclonal antibodies specific for the E1A proteins immunoprecipitate polypeptides with relative mol. wt of 30,000 (30 kd) and 35,000 (35 kd) from extracts of infected cells. The 30 kd and 35 kd proteins are encoded by novel mRNAs referred to as the 10S and 11S mRNAs, respectively. These two mRNAs arise from differential splicing of the E1A precursor RNA. For the 10S mRNA, the precursor is spliced twice, once removing the region between nucleotides 637 and 854 and once between 974 and 1229. The splice between nucleotides 974 and 1229 is identical to the one used for the processing of the 12S mRNA. Synthesis of the 11S mRNA also utilizes two splicing events. One of these is identical to the 637/854 splice of the 10S mRNA, and the other removes the region between nucleotides 1112 and 1229, a splice junction also found in the 13S mRNA. All four mRNAs used the same reading frame and, therefore, code for related proteins. The products of the 10S and 11S mRNAs are identical to the products of the 12S and 13S mRNAs, respectively, except for an internal stretch of 27 amino acids removed by the 637/854 splice. Within this segment is a group of amino acid residues that is highly conserved between different adenovirus serotypes. Mutant adenoviruses in which the wild-type E1A sequences have been replaced with cDNA copies of the 10S or 11S mRNAs are defective for growth on HeLa cells suggesting that this region is important for viral growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenovirus Early Proteins

Comparison of the stimulation of glycosaminoglycan synthesis in cultures of mononuclear cells from blood and of fibroblastic cells.

A small molecular weight factor, derived from bovine bone ('matrigenin'), stimulated glycosaminoglycan and proteoglycan synthesis of cultured human fibroblastic cells but not of mononuclear cells from human blood. However, proteoglycan synthesis and secretion by the mononuclear cells was stimulated by the addition of concanavalin A. The proteoglycan from the concanavalin-A-stimulated mononuclear cells was of smaller molecular weight than the proteoglycan from the 'matrigenin'-stimulated fibroblastic cells. The major increase in proteoglycan synthesis and secretion occurred much later during the culture period for concanavalin-A-stimulated mononuclear cells than for 'matrigenin'-stimulated fibroblastic cells.

Cells, Cultured

Electrophoresis of glycosaminoglycans isolated from normal human plasma. Direct evidence for the presence of a heparin-like molecule.

It has frequently been suggested that there may normally be small quantities of heparin in human blood, but amounts so small that their direct demonstration is not possible by available methods [1-4]. In this communication, we provide direct electrophoretic visualization that heparin or a closely related substance, is present in normal human plasma. After isolating glycosaminoglycans (GAGs) from 2-3 mls of plasma, a modification of the discontinuous high voltage electrophoretic method developed by Cappelletti et al. was used to successfully separate and identify the GAGs present in six normal adults (4 men and 2 women). In each case, in addition to chondroitin-4-SO4, chondroitin-6-SO4, and heparan-SO4, we were able to show the presence of a band which corresponds to that of heparin.

Electrophoresis, Cellulose Acetate

Characterization of tissue and plasma glycosaminoglycans during experimental AA amyloidosis and acute inflammation. Qualitative and quantitative analysis.

Qualitative and quantitative methods were used to determine changes in glycosaminoglycans (GAGs) in the spleen and plasma during initial stages of experimental amyloidosis and acute inflammation. GAG deposition in the spleen during the early stages of amyloidosis consists of a 16-fold heparin and heparan sulfate increase. Though splenic weights do increase during protracted inflammation only minor changes arise in splenic GAGs in the absence of amyloid deposition. An overall increase in plasma GAGs, consisting of a 4.5-fold chondroitin-4-sulphate increase, occurred at the time of GAG deposition in the tissues (spleen, liver) and probably accounts for the minor GAG changes seen in the spleen during inflammation. The time course of splenic heparin/heparan sulfate increase during amyloid deposition coincides with the histochemical changes previously described. Plasma GAG changes follow a pattern similar to that of acute phase protein reactants. The results suggest that GAG metabolism, in particular heparin/heparan sulfate, are intimately involved in the process of AA amyloidogenesis.

Acute Disease

The effect of "matrigenin" activity from bone on glycosaminoglycan and proteoglycan synthesis by cultured cells from articular tissues.

An activity that stimulates glycosaminoglycan and proteoglycan synthesis by confluent connective tissue cells in culture ("matrigenin" activity) has been partially purified from bovine bone. This activity is expressed on fibroblastic cells from several types of connective tissues, including synovium, and on cartilage tissue, but not on cells of unrelated origin. For synovial fibroblastic cells, matrigenin activity stimulated both hyaluronic acid and proteoglycan synthesis. The major proteoglycan whose synthesis was stimulated, contained primarily chondroitin-6-sulfate chains and eluted in the range of 400-600 Kdaltons. It is suggested that matrigenin activity in bone matrix has the potential to modulate remodelling (repair) in bone and in the synovial and cartilagenous regions abutting on bone.

Animals

The relationship between PaCO2 and ventilation parameters in predicting survival in congenital diaphragmatic hernia.

Fifty-eight infants with congenital diaphragmatic hernia presenting within the first 6 hours of life, who underwent surgical repair, were analysed prospectively in order to produce a reliable index of severity of disease that would reliably predict eventual outcome. All were treated with paralysis hyperventilation and intravenous (IV) isoproterenol for the first 48 hours. There were 30 survivors and 28 deaths in this series (mortality 48%). Using arterial PCO2 values measured 2 hours after surgical repair and correlating them with an index of mechanical ventilation (mean airway pressure and respiratory rate), we have been able to clearly define two groups of diaphragmatic hernia based on their response to IPPV. The first group, with CO2 retention and severe preductal shunting, was unresponsive to hyperventilation with high rates and pressures; the mortality was 90%. The second group responded well to hyperventilation and demonstrated reversable ductal shunting only. Survival in this group was 97%. Only four patients out of 58 exhibited the "honeymoon period," with a period of stability followed by severe ductal shunting. Arterial CO2 accurately reflects the degree of lung development in this disease and separates those patients with severe pulmonary hypoplasia, where the outcome is invariably fatal, from those with a well-developed contralateral lung where there is excellent potential for survival.

Carbon Dioxide

Hepatic hemangioma in childhood: medical management or surgical management?

Between 1955 and 1980 there were 14 patients treated at The Hospital for Sick Children with hemangiomas of the liver. Eight were seen at birth and 13 within the first 6 wk of life. The presenting clinical feature was that of massive hepatomegaly. Two children who had presented in the neonatal period were found to have had cardiac failure. Six patients were anemic and required blood transfusions. Before 1976 all patients who did not have cutaneous hemangiomas underwent laparotomy. Since 1976 only one laparotomy was done, the remaining 5 patients all having been treated symptomatically without operation. All the tumors involuted in the first year of life. Follow-up ranged from 1 to 20 yr and all are living and without symptoms. We recommend no active treatment if complications are absent. Steroids and radiotherapy are not used. If anemia and/or cardiac failure supervene, appropriate nonoperative management is necessary. Surgical treatment is indicated only if medical management fails or for rupture of the lesion.

Child

Utilization of Starea, urea, or soybean meal in complete rations for lactating dairy cows.

Three complete rations containing 15.8% of the dry matter as crude protein were compared to a 14.5% crude protein basal ration (dry matter basis) through eight Holstein cows in a replicated 4 times 4 Latin square design. The high protein rations contained supplemental nitrogen totally from soybean meal, urea, or Starea, the latter two providing 16 and 22% of total ration nitrogen, respectively. Concentrations were mixed with wilted alfalfa-bromegrass silage and complete rations fed ad libitum. Data were collected during the last week of each 28 days. Ration had no effect on milk yield, composition of fat or protein, or apparent digestibility of dry matter, crude protein, or acid detergent fiber. Weight gains and dry matter intake were greatest with the soybean meal ration. Intake of the low protein ration was depressed. There were no significant differences between the high protein rations for efficiency of nitrogen utilization.

Animal Feed