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Biomedical subjects

D M Cohen

Publications and source records attributed to D M Cohen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Transcriptional responses to tubule challenges.

Adaptation to physiological stimuli often involves changes in gene transcription. Studies of hyperosmolar stress in renal epithelial cells have provided an ideal paradigm for understanding regulation of gene expression. Renal epithelial cells respond very differently to hyperosmolar NaCl and urea and several strategies including cloning based on known biological function, candidate gene analysis, and differential display analysis have successfully identified many genes induced by these hyperosmolar challenges. Hyperosmolar NaCl produces adverse effects on cellular biosynthetic processes and compensatory increases are observed in transcription of transporters, stress proteins, and metabolic enzymes. In contrast, hyperosmolar urea fails to inhibit biosynthetic processes but, nonetheless, initiates a very specific program of gene expression in renal epithelial cells. This program appears to involve a urea sensor/receptor system which activates transcription and translation of the zinc-finger transcription factor Egr-1. This work highlights the concept that rapid analysis of differential gene expression will enable one to define cellular programs of gene expression involving up- and down-regulation of functionally-related gene families.

Animals↗
PubMed1996

Transfusion patterns in pediatric open heart surgery.

BACKGROUND: Transfusions in pediatric open heart surgery were analyzed to determine the percentage of patients transfused, the types and volumes of blood components used, and the relationships among transfusions, patient characteristics, surgeon, and surgical procedure. STUDY DESIGN AND METHODS: In a 9-month period, 122 patients, aged 12 or less (median, 1 year; 31% <4 months old), underwent 126 procedures (37 routine, 60 complex, 29 repeat operations). Bypass circuit size and priming solution, target intraoperative hematocrit, heparinization, protamine reversal, and transfusion indications and doses were standardized. The number of full "adult" units of packed red cells (RBCs), units of fresh-frozen plasma (FFP), and platelet concentrates (PCs) transfused in the operating room through postoperative Day 3 were tabulated. RESULTS: RBCs, FFPs, and PCs were transfused in 98, 54, and 58 percent of cases, respectively. Twenty-two percent of components were transfused postoperatively. The average numbers of components transfused for complex procedures (3.4 RBCs, 6.1 total) and repeat operations (4.0 RBCs, 8.1 total) were greater than those for routine procedures (1.8 RBCs, 2.1 total) (p<0.01). The average total number of components transfused did not correlate with surgeon or patient age; patients <4 months old used the largest mean numbers of RBCs and total components of all types. For four procedures, preoperative crossmatch and directed-donation collection orders that would be expected to produce acceptable utilization rates and a <15-percent chance of needing additional components were determined. CONCLUSION: Blood order protocols for pediatric open heart surgery can be procedure-specific, should address the use of non-red cell components, and should cover early postoperative transfusions.

Blood Transfusion↗
PubMed1996

Intraosseous needle: use of the miniature C-arm imaging device to confirm placement.

Intraosseous infusions are commonly used in pediatric emergencies. Although this technique is often lifesaving, significant complications can develop from incorrect needle placement. Current methods of evaluating needle position rely on the operator's experience with the procedure. We describe the use of a miniature C-arm imaging device to accurately confirm proper needle placement.

Cardiopulmonary Resuscitation↗
PubMed1996

NaCl but not urea activates p38 and jun kinase in mIMCD3 murine inner medullary cells.

The mitogen-activated protein kinases (MAPKs), p38 and jun kinase (JNK), are activated by diverse stressors in cells of nonrenal medullary origin. Epithelial cells of the renal medulla are among the very few cells of higher eukaryotes routinely subjected to hyperosmotic stress, composed of principally NaCl and urea. Hyperosmotic NaCl activated p38 and JNK in a time- and dose-dependent fashion in cells of the murine terminal inner medullary collecting duct cell line (mIMCD3) as determined by immune complex kinase assay. Hyperosmotic urea exerted a minimal effect upon only p38 activation, which was evident only at 5 min. The NaCl effect was dose dependent to 800 mosmol/kgH2O; 800 mosmol/kgH2O urea, in contrast, exerted no effect. Consistent with these observations, NaCl (800 mosmol/kgH2O) but not urea (800 mosmol/kgH2O) increased tyrosine phosphorylation of p38 and JNK at 10 min. Therefore, even in the extremely osmotolerant renal medullary mIMCD3 cell line, derived from a tissue adapted for routine exposure to elevated osmolality, hypertonic NaCl activated two stress-responsive MAPKs. Urea, in contrast, exerted virtually no effect; therefore, cellular protection from urea stress operates through a mechanism distinct from the stress-responsive MAPKs.

Animals↗
PubMed1995

Clinical pathways can be based on acuity, not diagnosis.

The standardization of medical practice is gaining acceptance as a technique for controlling length of stay and hospital charges, while maintaining quality. Most clinical pathways address specific diagnoses or procedures, but we have developed a new approach in which pathways for cardiac care are based on acuity. All congenital cardiac surgical care rendered at Columbus Children's Hospital now falls within one of four such clinical pathways. This simplified approach is easy to use and has been well accepted. Our experience in a group of 107 consecutive patients treated in this fashion is described. The results of variance analyses, along with length of stay and charge data, are presented to demonstrate the degree to which resource utilization can be standardized in this widely variable group of patients whose problems were made cohesive by classification according to acuity level. We conclude that the resultant standardization offers considerable advantages for the managed care environment.

Cardiac Surgical Procedures↗
PubMed1995

Electrical injuries in a pediatric emergency department.

STUDY OBJECTIVE: To examine the spectrum of electrical injuries and develop guidelines for management. DESIGN: Retrospective review of charts compiled during a 6-year period (1988 through 1993). SETTING: Pediatric emergency department. PARTICIPANTS: Seventy-eight patients seen for electrical injuries. RESULTS: Fifty-four percent of patients were boys, and the mean age of the patients was 5.3 years. Eighty-two percent sustained burns. We divided patients into those who were involved in major electrical current events (n = 8) (water contact and high voltage) and minor electrical current events (n = 70) (injury sustained while placing an object in an outlet or touching/plugging in a cord or during oral contact with a cord). Of the minor events, all burns (n = 61) involved less than 1% of body surface area. Eighteen patients sustained second-degree burns, and 19 sustained third-degree burns. Of the eight major-event patients, one had abnormal ECG/rhythm strip findings, two had abnormal urinalysis results, and six had abnormal levels of creatine phosphokinase. All eight were admitted. Of the 70 minor-event patients, 2 of 53 had abnormal ECG/rhythm strip findings, 1 of 48 had abnormal urinalysis results, and 2 of 40 had abnormal creatine phosphokinase levels. Thirty-six of the 70 minor-event patients were admitted. Patients involved in major events were more likely to undergo studies (P = .002), to have an abnormal result (P = .000008), and to be hospitalized (P = .008). In minor-event patients, hospitalization was limited to observation and the fitting of oral appliances. CONCLUSION: Children involved in electrical events are usually exposed to low-voltage household current resulting in minor injury. Asymptomatic children with minor electrical injuries do not require laboratory evaluation or hospitalization.

Accidents, Home↗
PubMed1995

Pediatric patients requiring CPR in the prehospital setting.

STUDY OBJECTIVE: To determine the outcome of pediatric patients with prehospital cardiopulmonary arrest. DESIGN: Chart review of all patients with prehospital cardiopulmonary arrest who were subsequently admitted to a pediatric emergency department from January 1988 to January 1993. Cardiopulmonary arrest was considered to have been present if assisted ventilation and chest compressions were performed on an apneic, pulseless patient. SETTING: Pediatric ED. PARTICIPANTS: Pediatric patients in prehospital cardiac arrest. RESULTS: In all, 95 patients were identified. Fifty-six had initial hospital care at the pediatric ED (primary patients). The remaining 39 were transported to the pediatric ED after initial care of another institution (secondary patients). Forty-one percent of patients were younger than 1 year. Most arrests were respiratory in origin; asystole was the most common dysrhythmia. Fifteen patients (27%) survived to discharge. Fourteen of the survivors had return of spontaneous circulation before ED arrival. Thirty-three patients were in arrest on ED arrival; in 16 (48%) of these, return of spontaneous circulation subsequently developed in the ED, and 1 survived to discharge. Two survivors, including the survivor with return of spontaneous circulation in the ED, had severe neurologic sequelae. Ten (26%) of the secondary patients survived. All survivors had return of spontaneous circulation before arrival in the ED. Two survivors had severe neurologic sequelae. CONCLUSION: Most successfully resuscitated pediatric arrest victims are resuscitated in the prehospital setting and do not suffer severe neurologic injury. Most patients who present to the ED in continued arrest and survive to discharge have severe neurologic injury.

Age Factors↗
PubMed1995

Protection of human polymorphonuclear leukocyte function from the deleterious effects of isolation, irradiation, and storage by interferon-gamma and granulocyte-colony-stimulating factor.

BACKGROUND: Fungal infections represent a difficult challenge to clinicians caring for neutropenic patients with hematologic malignancies, as antifungal therapy often has limited success in that setting. One promising yet problematic alternative approach is leukocyte transfusion. The isolation of polymorphonuclear leukocytes (PMNs) induces apoptosis and functional deterioration, and irradiation to prevent transfusion-associated graft-versus-host disease causes further functional deterioration. STUDY DESIGN AND METHODS: The ability of interferon-gamma and granulocyte-colony-stimulating factor (G-CSF), used both alone and in combination, to protect PMNs after 0 or 20 hours' storage in cell culture (as a model for function after transfusion) and irradiation with 0, 5, or 30 Gy was studied. RESULTS: Without cytokine treatment, 20-hour-old PMNs showed marked apoptosis, no appreciable chemotaxis, and no ability to kill Candida albicans. In contrast, cytokine treatment significantly reduced apoptosis and protected chemotaxis, C. albicans killing, and surface-receptor expression from both storage and irradiation. Although the majority of the benefit appeared to be due to G-CSF, consistent trends suggested better function of PMNs after combined treatment with interferon-gamma and G-CSF. CONCLUSION: Judicious use of cytokines may preserve PMN function. These findings have important implications for the transfusion of PMNs to cytopenic patients.

Apoptosis↗
PubMed1995

Estimation of TCA cycle flux, aminotransferase flux, and anaplerosis in heart: validation with syntactic model.

Weiss et al. (Circ. Res. 70: 392-408, 1992) proposed a model of the citric acid cycle (CAC) in myocytes and a system of 17 differential equations that can be used to describe the changes over time in enrichment of carbons C-2 and C-4 of glutamate under conditions of metabolic steady state. They also proposed an empirical measure (KT) of flux through the CAC, which has been shown to be correlated to O2 consumption in rat hearts perfused with acetate or a mixture of glucose and acetate. We report a new method for estimation of the absolute rate of the flux through the CAC in heart (vTCA), without the numerical solution of differential equations. Unlike KT, our estimate is equal to the rate of flux catalyzed by the alpha-ketoglutarate dehydrogenase complex (vTCA), not merely correlated with it. We also estimate the rate of flux catalyzed by aspartate aminotransferase (vTA) and by NADP(+)-dependent malic enzyme (an anaplerotic reaction). The formula for vTCA during administration of [2-13C]acetate is as follows: vTCA = M[(C-2ssLC-4)/[C-4ss(LC-4-LC-2)]], where C-2ss and C-4ss represent steady-state fractional enrichment, LC-2 and LC-4 represent dominant rate constants of C-2 and C-4 of glutamate, respectively, and M is the sum of concentrations of aspartate, glutamate, and intermediates of the CAC. The assumptions underlying our formula are as follows: 1) metabolic steady state is maintained, 2) exchange of molecules between cytosolic and mitochondrial compartments is rapid, 3) 13C enters pools of the CAC only from acetyl CoA via citrate synthase, 4) [citrate]/[glutamate] < 1 + (vTCA/vTA), and 5) (m-[glutamate])/M < C-2ss/C-4ss.

Aspartate Aminotransferases↗
PubMed1995

Healthcare in transition. Labor law impact on nurse-supervisor roles.

The United States Supreme Court has issued a new decision concerning the representation rights of nurses who exercise supervisory authority on behalf of their employers. However, the holding of the decision may reflect a view of labor-management relations that is outdated, given the massive changes that healthcare is going through in the 1990s.

Health Care Reform↗
PubMed1994

Hyperosmotic urea increases transcription and synthesis of Egr-1 in murine inner medullary collecting duct (mIMCD3) cells.

It was previously shown that when cells of renal epithelial origin are exposed to hyperosmotic urea in concentrations unique to the renal medulla, abundance of mRNA encoding the immediate-early gene product Egr-1 is up-regulated. This phenomenon appears restricted to cells of renal epithelial origin. In the present study, the newly isolated murine renal inner medullary cell line mIMCD3 was used to determine whether the urea-induced increase in Egr-1 mRNA abundance is associated with increased expression of functional protein product, and whether this increase is transcriptionally mediated. In Western analysis, urea (200 mM) increased Egr-1 immunoreactivity 3-fold relative to sham-treated cells. [35S]Methionine pulse-labeling followed by immunoprecipitation confirmed that this increased immunoreactivity was associated with increased de novo Egr-1 protein synthesis. Electrophoretic mobility shift assay demonstrated that urea treatment induced a commensurate increase in specific DNA binding activity for the Egr-1 consensus sequence. In addition, the increase in Egr-1 mRNA expression accompanying urea treatment was a consequence of enhanced transcription, as determined by nuclear run-off assay. Taken together, these data indicate that hyperosmotic urea increases both Egr-1 transcription and new protein synthesis in renal epithelial cells in culture, and that this newly synthesized Egr-1 is a functional DNA-binding protein. To our knowledge, this is the first example of urea-inducible gene transcription. In addition, Egr-1 represents the first eukaryotic transcription factor transcriptionally activated by a hyperosmotic stressor.

Animals↗
PubMed1994

SYNTAX: a rule-based stochastic simulation of the time-varying concentrations of positional isotopomers of metabolic intermediates.

We present a new approach to simulation of metabolic pathways. The syntactic approach combines a rule-based description of biochemical reactions with a stochastic model of chemical kinetics. Each syntactic rule describes the location in a product molecule to which a particular carbon of a reactant molecule will be transferred. Using specifically labeled substrates and known rates of chemical reactions, our simulation predicts the time-dependent changes in concentration of positional isotopomers of metabolic intermediates. (A positional isotopomer of a compound is an isomer that is determined by the positions of isotopes within the molecule, e.g., [1,2-13C]glucose and [1,3,5-13C]glucose). For the simulation of the 13C-positional isotopomers of the citric acid cycle in heart cells we require only 39 syntactic rules, compared to the 176 ordinary differential equations required by the traditional approach. Addition of chemical reactions to the simulation does not require changing the program code for the existing reactions. In comparison, addition of a reaction to a system described by differential equations requires altering the equations for all isotopomers of all reactants and products of the new chemical reaction.

Carbon Isotopes↗
PubMed1994

Coronary artery fistula in the pediatric age group: a 19-year institutional experience.

Ten patients with coronary artery fistulae were identified from records at Columbus Children's Hospital between 1974 and 1993. Clinical presentations of patients were quite variable, from 1 day to 20 years of age. Symptoms ranged from none to severe cardiorespiratory failure requiring extracorporeal membrane oxygenation. Long term follow-up revealed one sudden death and one spontaneous closure of the fistula. This lesion should be ruled out in patients who present as extracorporeal membrane oxygenation candidates. Patients with mild forms of this lesion may be followed up medically if the left to right shunt is inconsequential, because spontaneous closure is a possibility. Because of the risk of sudden death, close long-term follow-up is mandatory even for operated patients, and antiplatelet therapy should be considered for these patients.

Adult↗
PubMed1994

Use of cardiac catheterization in pediatric cardiac surgical decisions.

Current practice patterns relating to pediatric cardiac catheterization (Cath) have considerable economic implications. The decreased cost and risk of noninvasive methods such as echocardiography (ECHO) and magnetic resonance imaging (MRI) make them attractive alternative diagnostic methods if they can sufficiently define cardiac anatomy and the need for surgical intervention. We reviewed a recent cardiac surgical series of 465 cases in 1.5 years to determine how often a Cath was performed prior to surgery. Overall, 59.4% of the procedures were preceded by a Cath (76% of open heart operations, and 26.7% of closed heart operations). We specify the situations where we feel enough information is available for preoperative decision making from non-invasive testing, and we present some diagnostic pitfalls that have been encountered.

Cardiac Catheterization↗