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Biomedical subjects

J Byers

Publications and source records attributed to J Byers.

16 recordsLinked to original sources

Prediction of in vivo hepatic clearance from in vitro data using cryopreserved human hepatocytes.

1. Cryopreserved human hepatocytes were used to predict in vivo hepatic clearance (CL(hepatic)) from estimates of in vitro intrinsic clearance (CL' int). 2. (CL' int) was estimated for phenytoin, valproic acid, carbamazepine, theophylline, quinidine and procainamide after their addition to hepatocytes suspended either in human serum or in serum-free media. (CL' int)was estimated from in vitro concentration versus time data fitted to a monoexponential decay model. (CL' int) was estimated from concentrations measured at four time points and from just two-point measures, namely the initial concentration (C(0)) and the final concentration measurement (C(last)). 3. Predicted CL(hepatic) was within twofold of reported in vivo values of CL(hepatic) for all substrates. Moreover, predictions were not significantly different whether derived from hepatocytes suspended in serum or in serum-free medium. 4. Two-point estimates of (CL' int) were just as accurate in predicting CL(hepatic) as were multipoint estimates of (CL' int). 5. Although the data set was limited, the findings suggest that the measurement of the disappearance of xenobiotics from serum or serum-free media in which primary human hepatocytes have been suspended provides a physiologically relevant estimate of hepatic clearance that can be employed early in the drug development process to eliminate xenobiotics with unacceptable clearances.

Cell Survival↗

Renal function and dysfunction.

Recent publications regarding perioperative renal dysfunction provide a 'potpourri' of topics worthy of discussion. The risk of perioperative renal dysfunction is higher in patients with heart failure, but other pre-existing conditions, such as genetic polymorphism, may have prognostic implications. Evaluation of renal risk and protective interventions are discussed for a number of specific operative entities, including cardiac surgery (with or without cardiopulmonary bypass), aortic surgery and renal revascularization. New publications on a wide variety of nephrotoxic insults are presented, including antifibrinolytic agents, obstructive jaundice, prostaglandin inhibitors, cyclosporine A, radiocontrast dyes and volatile anesthetic agents. Renal transplantation is discussed as a specific entity. Finally, we discuss recent papers describing outcome in patients in chronic renal failure undergoing cardiac surgery.

Journal Article↗

How to manage diuretic therapy.

All diuretics are not created equal. How they act, where they act, and how they interact with other drugs can make a big difference. Here are the ins and outs of diuretic therapy--and the crucial assessments you need to make.

Age Factors↗

Tissue-specific mosaicism among fetuses with prenatally diagnosed diaphragmatic hernia.

OBJECTIVE: Our purpose was to determine if cytogenetic discrepancies between fetal blood and amniotic fluid are present in fetuses with prenatally diagnosed diaphragmatic hernia. STUDY DESIGN: Chromosome analysis was performed on 15 fetuses with prenatally diagnosed diaphragmatic hernia. Fourteen had both amniotic fluid and fetal blood studies. One fetus had an amniocentesis followed by postnatal skin and peripheral lymphocyte chromosome analysis. RESULTS: In one fetus with a normal karyotype on fetal blood, amniotic fluid mosaicism for a supernumerary isochromosome 12p was identified. Another fetus had normal amniotic fluid chromosome analysis but was diagnosed with mosaic isochromosome 12p on skin biopsy after birth. Concordant aneuploidy in both fetal blood and amniocytes was found in five pregnancies (three with trisomy 18, one with an unbalanced translocation, and one with mosaic supernumerary isochromosome 12p). Eight fetuses had normal karyotypes. CONCLUSION: Because diaphragmatic hernia is a common component of mosaic isochromosome 12p syndrome and this chromosome abnormality is predominantly found in fibroblasts but not lymphocytes, an amniocentesis may be more accurate than fetal blood sampling in defining the true fetal chromosome status when diaphragmatic hernia is detected prenatally.

Adult↗

The complex CD44 transcriptional unit; alternative splicing of three internal exons generates the epithelial form of CD44.

We have utilized the polymerase chain reaction (PCR) to isolate a 3.5 kilobase pair (kb) genomic fragment that encodes the additional extracellular domain unique to the epithelial isoform of CD44 (CD44E). Nucleotide sequence was determined for this complete region and sequence comparison to our previously determined CD44R1 and CD44R2 cDNA sequences revealed the R region to be comprised of three exons of 102 bp, 90 bp, and 204 bp. Northern blot analysis of CD44 expressing cell lines confirmed the presence of CD44R1 transcripts and indicates that the epithelial domain may be inserted through alternative splicing into all CD44 transcript classes. Southern blot analysis of the CD44E genomic fragments is consistent with a single copy per human haploid genome. The data presented here further supports our model of the human CD44 transcriptional unit as a single gene complex that utilizes an invariant 5' initiation site, alternative internal and 3' end splicing, and multiple poly (A) sites to generate through RNA processing a diverse number of human CD44 isoforms.

Amino Acid Sequence↗

Nonimmune hydrops fetalis and fetal congenital syphilis. A case report.

Nonimmune hydrops fetalis occurred secondary to a syphilitic infection. Ultrasonographic evaluation and cordocentesis were used to confirm the antenatal infection. An IgM antibody specific for Treponema pallidum wall antigen (anti-47-kDa) was used to document the fetal infection. High-dose intravenous penicillin was administered in an attempt to achieve adequate fetal levels.

Adolescent↗

Computerized quantitative dynamic analysis of facial motion in the paralyzed and synkinetic face.

Diagnosis, treatment, prognosis, and the neurobiology of recovery of facial paralysis has been impeded by the inability to quantitate facial movement objectively. The purpose of this paper is to report our preliminary results in the study of the paralyzed face using a newly developed computerized quantitative dynamic analysis system. Five normal volunteer subjects, and 17 patients with facial paralysis or paresis, from a wide range of etiologies, were analyzed utilizing the computerized analysis system; eight of these patients had synkinesis. Raw data image-change intensity: duration curves, numeric and graphic displays of curve parameter descriptive statistics, and rank order correlation analyses showed high levels of correlation between the computerized facial motion analysis and the House-Brackmann facial nerve grading system and a clinical grading scale for synkinesis. These data suggest that it is possible to develop a computerized image-difference analysis system that approximates the human ability to access facial movement and, additionally, deliver an equal-interval continuous quantitative data scale dynamic over a spectrum of time during facial motion.

Adolescent↗

Trauma in patients influenced by drugs and alcohol.

To examine the relationship of drugs, alcohol, and trauma, we conducted a retrospective study of 66,099 patients seen in the emergency department at the University of Arizona Health Sciences Center from August 1975 to July 1978. Of 646 patients found to have acute drug intoxication, 33 (5.1%) had sustained traumatic injury. Examination of blood, urine, and gastric specimens revealed only alcohol present in 17 (49%) of these patients. No specific pattern of drug ingestion or injury was seen in the remaining patients. While no generalizations can be made regarding prevention, the data may sensitize the clinician to the complex interrelationship of drugs, alcohol, and trauma.

Adult↗

Demographic characteristics of elderly drug overdose patients admitted to a hospital emergency department.

This study was undertaken to identify the demographic characteristics of patients aged 55 or older in a drug-overdose group admitted to the Emergency Department of Arizona Health Sciences Center during the 3-year period, August 1975-July 1978. Of the 646 overdose patients observed, 60 (9.5 percent) were aged 55 or older; of these, 77 percent were women--a significantly higher proportion than in the rest of the overdose group. The majority of the overdose incidents were unintentional, and most patients required hospitalization. For the elderly, the drugs involved in the overdoses did not differ significantly from those ingested by others in the overdose group. Concurrent traumatic injury occurred more often in the older age group, necessitating a longer hospital stay and higher health care costs. Drug overdosage is a significant problem in the elderly population. Since many overdose are unintentional, elderly persons in particular require the counsel of physicians and pharmacists in the medication process.

Aged↗

Acetaminophen assay: the clinical consequences of a colorimetric vs a high-pressure liquid chromatography determination in the assessment of two potentially poisoned patients.

Following acetaminophen (APAP) overdosage, plasma half-life of APAP elimination appears to be a good prognostic indicator of potential hepatic toxicity. A half-life of greater than 4 hr is often associated with liver injury. In two patients who each allegedly ingested greater than 13 gm of APAP, serial assay procedures were performed using both a colorimetric (nitrous acid chromophore) method and HPLC for all samples. The data obtained were used to determine the plasma half life. A comparison of the results obtained from both methods revealed a significant variation. It appears that the colorimetric method, at lower plasma concentrations of APAP (less than 50 microgram/ml), overestimates the actual drug concentration, resulting in the calculation of a falsely prolonged plasma half-life. This may result in the unnecessary implementation of antidotal therapy. The HPLC method is considered to be more specific than the colorimetric analysis and to better reflect actual plasma APAP concentrations, especially at lower concentrations of APAP.

Acetaminophen↗

Phenobarbital pharmacokinetics and bioavailability in adults.

The pharmacokinetics and bioavailability of phenobarbital were examined in six healthy adult subjects after a 2.6 mg/kg intravenous and a 2.9 mg/kg oral dose. Serum concentrations of phenobarbital were followed by means of a high pressure liquid chromatographic assay for 21 days after drug administration. After the intravenous dose, the mean distribution half-life was 0.18 hour and the mean elimination half-life was 5.8 days. Mean total body clearance and mean renal clearance were 3.0 ml/hr/kg and 0.8 ml/hr/kg, respectively. The apparent volume of distribution was 0.60 liter/kg. After administration of phenobarbital tablets, the maximum phenobarbital serum concentration was 5.5 mg/liter at 2.3 hours after the dose. Adjusted absolute availability of phenobarbital from the tablets studied was 94.9 per cent (range 81-111.9 per cent). The elimination half-life averaged 5.1 days for the oral dose. There was no evidence of autoinduction of phenobarbital elimination over the study period.

Adult↗