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Biomedical subjects

D Seger

Publications and source records attributed to D Seger.

36 records · Page 2Linked to original sources
PubMed1994

Drug therapy during pregnancy and lactation.

This article reviews the altered physiology of pregnancy and its impact on drug pharmacokinetics together with the pharmacokinetics of drug transport across the placenta and into the breast milk. Also reviewed are the potential adverse effects of maternal drug therapy on the fetus and neonate and the difficulties in assessing the potential risks of therapy. Finally, these principles are applied in the discussion of a number of specific drugs frequently prescribed in the emergency department setting.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1993

The structure of a bovine lung cGMP-binding, cGMP-specific phosphodiesterase deduced from a cDNA clone.

Polymerase chain reaction (PCR) methodology and cDNA library screening were used to isolate a cDNA clone encoding a cGMP-binding, cGMP-specific phosphodiesterase (cGB-PDE) from bovine lung. Degenerate oligonucleotides based on cGB-PDE peptide sequences were used as primers for a PCR reaction with bovine lung cDNA as the template. An 824-base pair PCR product was recovered and used as a probe to screen a bovine lung cDNA library. A 4.5-kilobase pair cDNA clone encoding a full-length cGB-PDE was isolated. The open reading frame of this cDNA predicted an 875 amino acid (AA), 99,525-Da polypeptide. By Northern analysis, the cGB-PDE cDNA hybridized to a single lung 6.9-kilobase mRNA. The identity of the cGB-PDE cDNA was verified by comparison of the deduced AA sequence with several peptide sequences obtained from cGB-PDE. COS-7 cells transfected with cGB-PDE cDNA overexpressed cGMP-binding and cGMP-PDE activities characteristic of lung cGB-PDE. The sequence of cGB-PDE contained a segment (AA 578-812) that was homologous to the putative catalytic region conserved among all mammalian PDEs and a segment (AA 142-526) that was homologous to the putative cGMP binding region of the cGMP-stimulated PDE and the photoreceptor PDEs. As noted also for these PDEs, two internally homologous repeats were contained within the putative cGMP binding region of cGB-PDE. The amino-terminal 142 residues of cGB-PDE showed no significant homology to other PDEs and contained the serine (AA 92) which is phosphorylated by cGMP-dependent protein kinase.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1993

Molecular cloning of a cDNA encoding the "61-kDa" calmodulin-stimulated cyclic nucleotide phosphodiesterase. Tissue-specific expression of structurally related isoforms.

We have isolated a 2287-bp cDNA encoding the 61-kDa calmodulin-stimulated cyclic nucleotide phosphodiesterase (CaM PDE) from a bovine brain library. A large open reading frame within the cDNA encodes a 530-residue polypeptide which is identical to the sequence of the purified protein previously determined by direct amino acid sequencing. Moreover, COS cells transfected with the cDNA express a cAMP and cGMP hydrolytic activity that is stimulated by calcium and calmodulin, confirming that the cDNA represents a mRNA species encoding a CaM PDE isozyme. RNase protection analyses indicate that either 61-kDa CaM PDE mRNA or structurally related transcripts encoding different CaM PDE isoforms are expressed in a tissue-specific manner. Total RNA isolated from brain (cerebral cortex, basal ganglia, hippocampus, cerebellum, and medulla/spinal cord), heart, aorta, liver, kidney outer medulla, kidney papilla, trachea, and lung completely protected a 410-base antisense riboprobe corresponding to sequence encoding a portion of the catalytic domain. Little or no protection was detected using adrenal cortex, adrenal medulla, liver, kidney cortex, spleen, or T-lymphocyte total RNA. Only brain RNA completely protected a 240-base antisense riboprobe corresponding to the 61-kDa CaM PDE amino terminus encompassing a putative calmodulin-binding domain. However, heart, aorta, liver, kidney, trachea, and lung RNA protected 150 bases of this riboprobe suggesting that these tissues express an isoform structurally related to the 61-kDa CaM PDE. Northern analysis of mRNA isolated from brain, heart, aorta, liver, kidney, lung, and trachea revealed that the cDNA hybridizes with a 3.8- and a 4.4-kb (kilobase) mRNA species. Interestingly, Northern blots of bovine cerebral cortex and heart mRNA probed under stringent conditions with antisense transcripts corresponding to either the 5'- or 3'-untranslated sequence of the 61-kDa CaM PDE cDNA hybridized with only the 4.4-kb mRNA from both tissues. Since different, yet structurally similar CaM PDE isoforms are expressed in brain and in heart, this result, in addition to the RNase protection data, is consistent with the idea that the mRNAs encoding these two CaM PDE isoforms are products of an alternately spliced gene.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1993

Safety assessment of high-dose narcotic analgesia for emergency department procedures.

STUDY OBJECTIVE: To evaluate the safety of high-dose IV narcotics in patients requiring analgesia for painful emergency department procedures. DESIGN: Prospective multicenter clinical trial. SETTING: Five adult urban EDs. METHODS AND MEASUREMENTS: All patients received IV meperidine (1.5 to 3.0 mg/kg) titrated to analgesia followed by a painful procedure. Vital signs and alertness scale were recorded at regular intervals, and patients were observed for four hours. Adverse events were monitored and documented. Comparisons between baseline and postanalgesia intervals were made with a repeated measures ANOVA (Dunnett's test). RESULTS: Although statistically significant changes in vital signs and alertness scale occurred, they were not clinically significant. Opiate reversal with naloxone was not needed in any patient, and no significant respiratory or circulatory compromise occurred. CONCLUSION: This study of 72 patients demonstrates that high-dose narcotic analgesia is appropriate, well tolerated, and safe when used in selected patients before painful procedures in the ED. Narcotic antagonists and resuscitation equipment nonetheless should be available to maximize safety.

Adolescent↗
PubMed1992

Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases.

Mitogen-activated protein (MAP) kinase kinases, intermediates in a growth factor-stimulated protein kinase cascade, are dual specificity protein kinases that specifically phosphorylate and activate MAP kinases in response to extracellular signals. Here, we report the cloning of two forms of cDNA that encode this protein from human T-cells. MKK1a encodes a protein with predicted molecular size of 43,439 Da. Overexpression of this clone in COS cells led to elevated levels of protein and phorbol ester-stimulated MAP kinase kinase activity, confirming that MKK1a encodes the predicted protein. MKK1b, which appears to be an alternatively spliced form of the MKK1a gene, encodes a protein with predicted molecular size of 40,745 Da. Northern analysis revealed that the MKK1 cDNA hybridizes with a single 2.6-kilobase mRNA species in all human tissues examined. Sequence comparison shows homology to a group of yeast kinases that participate in signal transduction and to subdomain XI of other dual specificity kinase.

Amino Acid Sequence↗
PubMed1992

Molecular cloning of cDNA encoding a "63"-kDa calmodulin-stimulated phosphodiesterase from bovine brain.

Partially degenerate oligonucleotides based on peptide sequence were used to isolate cDNA to a 63-kDa bovine brain calmodulin-stimulated phosphodiesterase (CaM-PDE) isozyme. A 412-base pair polymerase chain reaction fragment was obtained and used along with the oligonucleotides to isolate several cDNAs each encoding sequence identical to known peptide sequences from the 63-kDa CaM-PDE. The largest cDNA contained a full-length open reading frame (ORF) encoding a 534 amino acid, 61,005-dalton protein. It had 59% amino acid identity to the 61-kDa bovine brain CaM-PDE and included a carboxyl-terminal conserved domain containing the PDE catalytic domain consensus sequences. The NH2-terminal region fits the criteria for a calmodulin-binding domain. When its expression was driven by a cytomegalovirus promoter on a pCDM8 vector in COS-7 cells, the cDNA encoded a catalytically active, calmodulin-stimulated PDE. Northern analysis of RNA from several tissues with a probe containing much of the conserved PDE catalytic domain showed only a single band of 4.0 kilobases. Hybridization was seen in mRNA from several regions of the central nervous system with the greatest signal in basal ganglia. Strong signals also were seen in other tissues including kidney papilla and adrenal medulla. Antisense RNA probes were used in RNase-protection assays to look for evidence of multiple 63-kDa CaM-PDE transcripts. A catalytic domain probe was fully protected by RNA from cerebral cortex, basal ganglia, cerebellum, hippocampus, adrenal medulla, and kidney papilla. However, a probe to the NH2-terminal region was fully protected only by brain and adrenal medullary RNA indicating the likelihood of one or more isozyme(s) divergent in this region in the kidney papilla.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Duration of antagonistic effects of nalmefene and naloxone in opiate-induced sedation for emergency department procedures.

Naloxone is an effective opiate antagonist, but its short half-life limits its usefulness. For outpatient procedures, a longer acting opiate antagonist could eliminate two to four hours of nursing observation in patients postoperatively. A controlled, randomized, double-blind trial comparing the effects of nalmefene, naloxone, and placebo in reversing opiate-induced sedation was carried out to determine efficacy, duration of action, and adverse effects in patients undergoing outpatient procedures. Each patient received 1.5 to 3.0 mg/kg meperidine intravenously before the procedure. After the procedure, each patient received either nalmefene, 1.0 mg; naloxone, 1.0 mg; or saline, 1.0 mL intravenously. Vital signs and assessments for alertness were performed for four hours. Naloxone significantly reversed sedation for only 15 minutes, whereas nalmefene was significantly effective (P less than .05) for up to 210 minutes. Nalmefene was significantly more effective than naloxone in reversing sedation at 60, 90, and 120 minutes. Nalmefene is an effective agent for the reversal of opiate-induced sedation after outpatient procedures.

Adolescent↗
PubMed1987

Transition of chromatin from the "10 nm" lower order structure, to the "30 nm" higher order structure as followed by small angle X-ray scattering.

Chromatin oligomers undergo a conformational change from a "10 nm" lower order structure at low concentration of salt to a "30 nm" higher order structure, with increasing NaCl or MgCl2 concentration. We have extended our previously reported hydrodynamic and light-scattering measurements of the folding of well-defined chicken erythrocyte chromatin fractions to include a study of the low angle X-ray scattering in solution. We show that it is feasible to identify the folding process with gradual compaction of a chain of freely joined filaments or a worm-like chain, within the limits of all the experimental data obtained. As the ionic strength is raised, the filament length of the oligomer, composed of Nz nucleosomes, decreases. At 75 mM-NaCl, the compacted model chains (Nz = 53) form structures that are, on average, cylindrically shaped with mean diameter 30 nm and length 104 nm. Helical symmetry need not be invoked in the modelling of the folding process and may, in particular, be difficult to establish in chicken erythrocyte chromatin, due to the non-uniform length of the DNA linker connecting the nucleosomes. Concerning the shape of the X-ray scattering profiles at various salt concentrations, it is possible in this way to rationalize two-slope cross-sectional plots, which have also been reported by other workers. Though this description represents a satisfactory conceptual presentation of a wealth of experimental data, it by no means represents a definitive solution to an exceedingly difficult problem.

Animals↗
PubMed1986

Rapid assay of serum theophylline levels.

Many patients with chronic obstructive pulmonary disease (COPD) are symptom free when they receive an oral theophylline regimen. When these patients present to the emergency department with an acute exacerbation of their disease, the emergency physician faces a dilemma regarding appropriate therapy with IV aminophylline. The patient's serum theophylline level is unknown. A blind loading dose may result in inadequate treatment or iatrogenic toxicity. The Ames Seralyzer is an immunoassay photometer that determines serum theophylline levels. We studied 90 patients with uncomplicated exacerbations of COPD treated in our ED before and after the installation of the Seralyzer. Theophylline levels measured by the Seralyzer had a high correlation with those measured by the hospital laboratory Abbott TDX (r = 0.914). Obtaining the theophylline level took a mean of only 0.46 hours with the Seralyzer, compared with 2.13 hours with the hospital laboratory. The time from presentation to theophylline loading was 1.87 hours, compared with 3.28 hours with the hospital laboratory group, resulting in significantly greater relief of respiratory distress at three hours after arrival in the Seralyzer group. The measured theophylline level was very poorly correlated with the physician's estimate of the level based on history (r = 0.353). We conclude that the Seralyzer provided accurate assessment of levels, enabled earlier theophylline loading of patients and lessened delays, and decreased the probability of theophylline toxicity.

Adult↗
PubMed1985

Central anticholinergic syndrome in a child: a case report.

A 2-year-old boy developed classical signs and symptoms of the central anticholinergic syndrome after ingesting twenty 4-mg tablets of the antihistamine cyproheptadine (Periactin). His symptoms were dramatically reversed by the intravenous administration of physostigmine. The physiology of the anticholinergic system and physostigmine are discussed along with the indications, toxicity, and dosing of physostigmine.

Child, Preschool↗
PubMed1985

Acquired immunodeficiency syndrome manifested as disseminated cryptococcosis.

A 32-year-old male homosexual presented to the emergency department (ED) with the clinical picture of a nonspecific illness. While in the ED, he experienced a first-time seizure. Computed tomography (CT) showed an enhancing mass lesion. Antibacterial therapy was started and continued until a second lumbar puncture (LP), 36 hours after admission, showed distinct yeast forms. Subsequent institution of appropriate therapy did not prevent the patient's death. The cause of death was disseminated cryptococcosis secondary to acquired immunodeficiency syndrome (AIDS).

Acquired Immunodeficiency Syndrome↗
PubMed1984

Interaction of chromatin with NaCl and MgCl2. Solubility and binding studies, transition to and characterization of the higher-order structure.

Chicken erythrocyte chromatin containing histones H1 and H5 was carefully separated into a number of well-characterized fractions. A distinction could be made between chromatin insoluble in NaCl above about 80 mM, and chromatin soluble at all NaCl concentrations. Both chromatin forms were indistinguishable electrophoretically and both underwent the transition from the low salt "10 nm" coil to the "30 nm" higher-order structure solenoid by either raising the MgCl2 concentration to about 0.3 mM or the NaCl concentration to about 75 mM. The transitions were examined in detail by elastic light-scattering procedures. It could be shown that the 10 nm form is a flexible coil. For the 30 nm solenoid, the assumption of a rigid cylindrical structure was in good agreement with 5.7 nucleosomes per helical turn. However, disagreement of calculated frictional parameters with values derived from quasielastic light-scattering and sedimentation introduced the possibility that the higher-order structure, under these conditions, is more extended, flexible, or perhaps a mixture of structures. Values for density and refractive index increments of chromatin are also given. To understand the interaction of chromatin with NaCl and with MgCl2, a number of experiments were undertaken to study solubility, precipitation, conformational transitions and binding of ions over a wide range of experimental conditions, including chromatin concentration.

Animals↗
PubMed1984

Nucleosome core particle stability and conformational change. Effect of temperature, particle and NaCl concentrations, and crosslinking of histone H3 sulfhydryl groups.

We have studied the reversible dissociation of core size DNA from chicken erythrocyte nucleosome core particles in solutions containing 0 X 1 M to 0 X 6 M-NaCl. Dissociation increases with increasing NaCl concentration, increasing temperature and decreasing particle concentration. At high particle concentrations, no free DNA is observed below 0 X 3 M-NaCl, whereas above 0 X 3 M-NaCl a lower limit of dissociation is reached. A theoretical analysis based on the migrating-octamer mechanism of Stein is in disagreement with his conclusions concerning dependence of core particle dissociation on particle concentration, but provides a good explanation for our observations, and those of others, using salt concentrations up to 1 M-NaCl. It appears that the core particle is not stabilized primarily by electrostatic interactions. DNA length is not critical for core particle stabilization. The conformation of remaining intact nucleosome core particles changes only moderately within the range of NaCl concentrations studied. Crosslinking by copper phenanthroline of the Cys110 histone H3 single sulfhydryl groups in the intact nucleosome core particle leads to a decrease in stability, yet essentially unchanged hydrodynamic properties are maintained at 0 X 6 M-NaCl, confirming conclusions derived from the behavior of the native core particles. Values for density increments of nucleosome core particles over a range of NaCl concentrations are also given. A method is described for studying binding of histones to nucleosome core particles in the ultracentrifuge by scanning at 230 and 260 nm.

Centrifugation, Density Gradient↗
PubMed1984

Acquired immune deficiency syndrome.

Acquired Immune Deficiency Syndrome (AIDS) occurs as a result of a defect in cell mediated immunity with a comparatively normal humoral immunity. Originally diagnosed in four distinct groups, AIDS is now recognized in six high-risk groups. Many theories of etiology exist; the most accepted etiologic agent is the Human T-lymphotropic retrovirus (HTLV). Clinical presentations are that of an opportunistic infection or a nonspecific illness. Once AIDS is diagnosed, medicine has little to offer the AIDS victim. CDC recommendations for health personnel and AIDS patients are reviewed.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Toxic emergencies of endocrine and metabolic therapeutic agents.

Treatment recommendations for insulin, sulfonylurea, and thyroid hormone poisoning are widely divergent. Recent research data indicates a standard approach to management of these poisonings. Clinical practice may now incorporate recent findings.

Humans↗
PubMedDate not supplied

The impact of computerized physician order entry on medication error prevention.

BACKGROUND: Medication errors are common, and while most such errors have little potential for harm they cause substantial extra work in hospitals. A small proportion do have the potential to cause injury, and some cause preventable adverse drug events. OBJECTIVE: To evaluate the impact of computerized physician order entry (POE) with decision support in reducing the number of medication errors. DESIGN: Prospective time series analysis, with four periods. SETTING AND PARTICIPANTS: All patients admitted to three medical units were studied for seven to ten-week periods in four different years. The baseline period was before implementation of POE, and the remaining three were after. Sophistication of POE increased with each successive period. INTERVENTION: Physician order entry with decision support features such as drug allergy and drug-drug interaction warnings. MAIN OUTCOME MEASURE: Medication errors, excluding missed dose errors. RESULTS: During the study, the non-missed-dose medication error rate fell 81 percent, from 142 per 1,000 patient-days in the baseline period to 26.6 per 1,000 patient-days in the final period (P < 0.0001). Non-intercepted serious medication errors (those with the potential to cause injury) fell 86 percent from baseline to period 3, the final period (P = 0.0003). Large differences were seen for all main types of medication errors: dose errors, frequency errors, route errors, substitution errors, and allergies. For example, in the baseline period there were ten allergy errors, but only two in the following three periods combined (P < 0.0001). CONCLUSIONS: Computerized POE substantially decreased the rate of non-missed-dose medication errors. A major reduction in errors was achieved with the initial version of the system, and further reductions were found with addition of decision support features.

Clinical Pharmacy Information Systems↗