Biomedical subjects

C A Johnson

Publications and source records attributed to C A Johnson.

At least 217 records · Page 12Linked to original sources

PubMed1993

Pharmacokinetics of intraperitoneal, intravenous, and subcutaneous recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis.

The pharmacokinetics of recombinant human erythropoietin (Epo) were compared after mean single 99.1 U/kg intraperitoneal (IP), intravenous (i.v.), and subcutaneous (SC) doses in eight noninfected patients on peritoneal dialysis in a randomized, three-way, cross-over fashion. Continuous ambulatory peritoneal dialysis was performed in all patients on the days of the study. The IP dose was instilled into an empty peritoneum; total dwell time was 10 hours (4 hours dry, 6 hours with 2 L of peritoneal dialysis fluid). Blood samples were collected for 96 hours following IP and SC Epo, and for 72 hours following i.v. Epo. For the IP dose, a 10-hour effluent dialysate sample was collected to determine Epo recovery. Enzyme immunoassay was used for Epo analysis. The mean apparent volume of distribution was 0.05 L/kg, equivalent to 4.5% of total body weight; the mean total body clearance was 0.08 mL/min/kg. All eight patients exhibited multiexponential decay in serum Epo concentrations following i.v. Epo. Absorption of IP Epo was significantly greater than previous reports, presumably due to its administration into a dry peritoneum. The maximum concentrations following the IP and SC doses were nearly identical, but amounted to only 5% of the maximum concentrations for the i.v. dose. Subcutaneous Epo took nearly twice as long as IP Epo to achieve peak serum concentrations (17.1 +/- 5.0 hours v 9.4 +/- 1.9 hours). Compared with the IP route, the SC dose achieved a higher area under the serum concentration time curve from time 0 to 96 hours (AUC0-96; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1993

Anaplastic large-cell Ki-1 lymphoma. Pulmonary presentation mimicking miliary tuberculosis.

An unusual presentation of anaplastic large-cell (ALC) Ki-1 lymphoma is described, in which pulmonary involvement mimicked miliary tuberculosis. Lung involvement is uncommon in this type of lymphoma, and it is not clear from previous reports whether this was a presenting feature. Bone marrow involvement, rare in Ki-1 lymphoma, also was present in this case. Despite therapy skin involvement subsequently developed, and the patient died 3 months after presentation. Postmortem examination revealed lymphomatous involvement of the heart, liver, kidneys, stomach, and lymph nodes. This case highlights the need for awareness of ALC Ki-1 lymphoma particularly when it presents at uncommon extranodal sites.

Adult↗

PubMed1993

Role of automation in new instrumentation.

In recent years there has been an unprecedented increase in the development of automated instrumentation for ophthalmic diagnostic and assessment purposes. An important part of this growth in automated clinical ophthalmic instrumentation has been directed to perimetry and visual field testing. In less than 15 years automated perimetry has advanced from a laboratory curiosity to become the standard for clinical visual field testing. This paper will provide a brief overview of the impact that automated perimetry has had on current clinical ophthalmic practice and patient management. It is presented as a general example of the influence that automated instrumentation has exerted on the clinical environment.

Automation↗

PubMed1993

A noninvasive video-based method for measuring lens transmission properties of the human eye.

The Lens Absorption Monitor (LAM) is an automated video-based system for obtaining rapid objective noninvasive measurements of the spectral transmission properties of the human lens. The technique is based on intensity measurements of the 4th Purkinje image for different wavelengths, and incorporates several features that overcome some of the difficulties associated with previous studies using this approach. LAM transmission measures for the visible spectrum can be obtained in approximately 2 s, and in most instances can be obtained without having to dilate the subject's eye. This paper describes the technique and presents our initial findings for 40 normal observers between the ages of 24 and 77 years. Results of the LAM technique show that it is able to measure the wavelength-dependent properties of the lens accurately and to identify age-related changes in "yellowing" of the lens. Test-retest reliability of the LAM is better than for psychophysical estimates of ocular media transmission. LAM and psychophysical measures in the same subjects were found to be correlated, although LAM measures produced consistently lower values of lens density than the psychophysical determinations. There was only moderate agreement between LAM and psychophysical measures of lens density. Possible explanations for these differences are discussed. Future research will determine whether this technique is able to detect and quantify early cataract development.

Adult↗

PubMed1993

Placenta praevia: does uterine activity cause bleeding?

Twenty-two women > 24 weeks' gestation with a central placenta praevia were monitored to determine if an increase in uterine activity precedes bleeding in patients with central praevias. Monitoring of all subjects began at 26.3 +/- 4.4 weeks and continued until 37 weeks (or delivery if preterm). All subjects had at least one haemorrhage, 7 women had 2, and 4 subjects had 3 episodes of bleeding. Only 3 patients delivered at term while the remainder (86%) delivered preterm. The gestational age at first episode of bleeding was 29.1 +/- 3.6 weeks and at delivery was 34.3 +/- 3.3 weeks. Nine women (41%) had an increase in uterine activity above baseline the day or the day preceding the first haemorrhage. The increase in uterine activity was not statistically significant when compared to the 6 days prior to bleeding when all 22 patients were considered.

Adult↗

PubMed1993

Pharmacokinetics and ex vivo susceptibility of cefpodoxime proxetil in patients receiving continuous ambulatory peritoneal dialysis.

Pharmacokinetics of cefpodoxime, an extended-spectrum cephalosporin, were determined for eight noninfected patients on continuous ambulatory peritoneal dialysis (CAPD) and eight healthy volunteers. Subjects were matched for sex, age (+/- 6 years), and body weight (+/- 10 kg, except for one pair) and received a single 200-mg (cefpodoxime equivalents) oral dose of the prodrug cefpodoxime proxetil in an open-label, paired-design fashion. Dialysate (CAPD group only), plasma, and urine samples were collected and assayed for cefpodoxime by a microbiologic method. In addition, mean bactericidal titers of the effluent dialysate against selected bacterial strains often associated with CAPD-related peritonitis were determined at 6 and 24 h after the dose. There was a significant difference (P < 0.05) in all pharmacokinetic parameters between healthy and CAPD subjects, except for lag time to absorption. The mean peak plasma cefpodoxime concentration of 1.88 +/- 0.6 micrograms/ml occurred at 2.44 +/- 0.5 h for healthy volunteers, while the peak concentration of 3.25 +/- 1.4 micrograms/ml occurred at 12.0 +/- 4.2 h for patients on CAPD. The average elimination half-life in CAPD patients was approximately 12 times greater than that seen in healthy volunteers. Peritoneal dialysis had a minimal effect on cefpodoxime clearance. In healthy volunteers, 24.2% +/- 13% of the dose was recovered from the urine, in contrast to only 5.59% +/- 6.9% for CAPD patients. The mean bactericidal titers for all CAPD patients, at 6 and 24 h, were mostly less than 1:2 and did not exceed 1:4 for any of the isolates. Because of the decreased renal clearance and negligible dialysate clearance of cefpodoxime, and delayed drug absorption, the dosage interval for cefpodoxime proxetil may need to be extended in CAPD patients.

Administration, Oral↗

PubMed1993

Longitudinal comparison of temporal-modulation perimetry with white-on-white and blue-on-yellow perimetry in ocular hypertension and early glaucoma.

We obtained data over 3 years on temporal-modulation perimetry (TMP), standard automated [white-on-white (W/W)] perimetry, and short-wavelength-sensitive [blue-on-yellow (B/Y)] perimetry in ocular hypertensive (OH) patients and patients with early glaucomatous visual-field loss (EG). Evidence of visual-field defects was obtained with the use of both B/Y perimetry and TMP in the majority of OH and EG eyes that demonstrated progression on W/W perimetry as well as in all stable EG eyes. Using the nerve-fiber-bundle pattern to compare testing procedures, we determined that these defects were generally as extensive or more extensive than the concurrent W/W abnormalities. In terms of location over the 3 years of testing, TMP and B/Y defects were reasonably consistent in the EG eyes, somewhat less consistent in the OH eyes demonstrating progression, and both inconsistent and infrequent in the stable OH eyes. The greatest degree of overlap occurred between the location of defects obtained by use of the higher TMP frequencies (8 and 16 Hz) and that of defects obtained by use of B/Y perimetry. Since these two methods are thought to isolate different visual mechanisms subserved by different visual pathways, these results suggest that early glaucomatous visual-field damage as revealed by TMP and B/Y perimetry may not be specific to a single visual pathway.

Color Perception Tests↗

PubMed1993

Relations of coping effort, coping strategies, perceived stress, and cigarette smoking among adolescents.

Coping strategies may influence adolescent smoking behaviour because they provide alternative behavioral and cognitive outlets which facilitate or inhibit smoking, or because they are expressions of general coping effort to smoke or not smoke. The present investigation examined three possibilities regarding how coping strategies versus coping effort compare as predictors of adolescent smoking: (1) general coping effort to not smoke may be a better predictor of adolescent smoking behaviors than are specific coping strategies; (2) coping strategies may be relatively better predictors of smoking behaviors; or (3) these two constructs may be relatively better predictors of different parameters of smoking behavior. Analytic strategies included calculation of a series of multiple regression models, involving (a) 11 coping strategies previously studied in adolescent smoking research, (b) a new simple measure of coping effort to not smoke, and (c) perceived stress, as concurrent predictors of four smoking-related items. Of the 11 coping strategies, partying, relaxation, seeking spiritual guidance, and getting revenge were related to at least one of the four cigarette smoking items. Only coping effort was directly related to recent smoking behavior, whereas only the coping strategies were related to cumulative smoking. Both types of items predicted refusal self-efficacy and intention to smoke in the future. Apparently, these two types of items show unique as well as common predictive variance. These results suggest that coping strategies are related to cumulative smoking for reasons other than motivation to not smoke.

Adaptation, Psychological↗

PubMed1993

Modern developments in clinical perimetry.

Recent developments in automated perimetry have emphasized the adaptation of specialized psychophysical procedures for visual field testing to measure visual properties other than the detection of light. In addition, many new methods to quantitatively analyze visual field data have been generated. These new developments are promising for enhancing the diagnostic capabilities of automated perimetry in patients with glaucoma and patients suspected of having glaucoma. A review of some of the most recent advances in automated perimetry are presented.

Glaucoma↗

PubMed1993

An incidental finding of extreme self-limited thrombocytosis of unknown cause.

This report describes an 11-year-old male who presented to his pediatrician at the Bowman Gray School of Medicine in Winston-Salem, N.C., because of long standing enuresis. During evaluation and the following two-week period, this patient was found to have extreme thrombocytosis ranging from 2,175 x 10(9)/L to 3,700 x 10(9)/L. In the absence of any apparent reactive cause, a presumptive diagnosis of essential thrombocythemia was made. Although chemotherapy was considered, the patient was temporarily lost to follow-up before there was a final decision about therapy. One year later, this patient's platelet count had spontaneously decreased to normal (273 x 10(9)/L), and has remained normal during a follow-up period of seven years, although only sporadic platelet counts have been obtained. His most recent physical examination revealed no abnormalities. The case is presented as further evidence that extremely high platelet counts are not necessarily dangerous and do not all require therapy.

Child↗

PubMed1993

Anatomic features and radiographic observations of gastric emptying and small intestinal motility in the rat.

This study presents the first report of the identification of anatomic structures on survey radiographs of the abdomen of the rat, along with detailed barium contrast studies of the gastrointestinal tract in normal rats. The rats (49 to 112 days old) were chemically restrained with a combination of 0.71 mg ketamine hydrochloride/g of body weight and 0.5 mg of acetylpromazine maleate injected intramuscularly. Following sedation, a 36% (wt/vol) micropulverized barium sulfate suspension was administered via a stomach tube at a dose of 0.02 ml/g of body weight. The radiographic features of the gastrointestinal tract were enhanced after coating of the mucosal surfaces with the high-density barium suspension. Internal structures of the stomach and mucosal surfaces of the intestine were clearly identified. The barium contrast study was used to establish gastrointestinal transit times. The mean gastric emptying time was 11 +/- 4.27 (SEM) min and mean intestinal transit time was 5 +/- 0.75 (SEM) h. Image intensification fluoroscopy was used to observe patterns of small intestinal motility and to establish small intestinal contraction rates. Prominent cluster of circular contractions were primarily observed in the jejunum, and wave-type peristalsis was primarily observed in the duodenum. Isolated circular contractions and weak segmentation patterns were observed in the ileum. The mean contraction rate per minute was observed to be 14 +/- 2.12 (SEM) in the jejunum. We propose that under the conditions of the current study, radiographic investigation of gastrointestinal function in rats is a feasible and inexpensive procedure.

Animals↗

PubMed1993

Effect of peritonitis on plasma and dialysate alpha 1-acid glycoprotein concentrations in peritoneal dialysis patients.

The effect of peritonitis on plasma and dialysate alpha 1-acid glycoprotein (AAG) concentrations was determined. Plasma and dialysate samples were obtained at the onset of infection and one month after treatment from 10 peritoneal dialysis patients with peritonitis. Plasma and dialysate samples were also obtained from 10 noninfected matched controls. Sampling was repeated after a minimum of one month. Samples were assayed for AAG by radial immunodiffusion. The mean +/- S.D. plasma AAG concentrations for patients with peritonitis and for control patients were 152.4 +/- 30.9 mg/dL and 146.6 +/- 45.0 mg/dL, respectively (p > 0.05). The dialysate AAG concentrations for nine control patients were below the limit of detection. The mean +/- S.D. dialysate concentration for the nine infected patients with detectable AAG concentrations was 15.4 +/- 9.5 mg/dL. After successful antimicrobial therapy, dialysate AAG concentrations declined. There was no obvious correlation between dialysate white blood cell count and dialysate AAG concentration during peritonitis. Peritonitis increased dialysate AAG concentrations but had no effect on plasma AAG concentrations.

Bacterial Infections↗

PubMed1993

Quality of laboratory performance in testing for human immunodeficiency virus type 1 antibody. Identification of variables associated with laboratory performance.

To identify factors that may affect the quality of laboratory performance of human immunodeficiency virus type 1 (HIV-1) antibody testing, the Centers for Disease Control and Prevention Model Performance Evaluation Program surveyed laboratories in 1989 that performed enzyme immunoassay (EIA) and Western blot tests for HIV-1 antibody. Panels of 10 HIV-1-antibody-positive and antibody-negative plasma samples, some of which were duplicates, were mailed to program-participating laboratories. Laboratories were also mailed survey questionnaires to ascertain their laboratory characteristics and testing practices. Using 1988 data, researchers previously found that the overall analytic performance of laboratories performing HIV-1 antibody testing was independently associated with the following: (1) requiring a minimum degree of testing personnel; (2) having written criteria for identifying unsatisfactory specimens; (3) requiring in-house training for testing personnel; (4) having tested more than 10,000 specimens; (5) being identified as an "other" laboratory type; (6) having more than 24 months of testing experience; (7) laboratory uses specific (Abbott) materials for EIA; and (8) testing specimens collected by family-planning clinics. To verify these findings, we performed multivariate analysis on 1989 performance data. For the 1989 EIA analytic sensitivity, significant positive (P < or = .05) associations were detected with having written criteria for identifying unsatisfactory specimens and with having tested more than 10,000 specimens. For the 1989 overall EIA analytic performance, a significant negative (P < or = .05) association was found with using specific (Abbott) EIA materials, and a significant positive (P < or = .05) association was found with having tested more than 10,000 specimens. For Western blot results, the only significant (P < or = .05) associations were for both analytic sensitivity and overall analytic performance and having tested more than 10,000 specimens.

Blotting, Western↗

PubMed1993

Temporal modulation perimetry: the effects of aging and eccentricity on sensitivity in normals.

PURPOSE: Temporal modulation perimetry (TMP) is a new test procedure designed to measure sensitivity to sinusoidal flickering stimuli throughout the central 27 degrees visual field. The purpose of this investigation was to determine the effect of age and visual field eccentricity on temporal modulation sensitivity. METHOD: In its present form, TMP is used to determine modulation sensitivity for three temporal frequencies (2, 8, and 16 Hz) at 45 visual field locations. Both eyes of 43 normal observers between 20 and 75 years of age were examined. RESULTS: Our results indicate that sensitivity to all temporal frequencies tested showed a decline with age, particularly in the peripheral visual field. Furthermore, the age-related sensitivity loss was more pronounced for 16 Hz than for 2 or 8 Hz. CONCLUSIONS: These data demonstrate an age-related loss in temporal modulation sensitivity in the peripheral visual field. They also provide a baseline comparison standard for evaluation of clinical patient populations.

Adult↗

PubMed1993

Helicobacter pylori and peptic ulcer disease.

The role played by Helicobacter pylori in the pathogenesis of peptic ulcer disease (PUD) is discussed, and the epidemiology, identification, diagnosis, eradication, and treatment of H. pylori infection are reviewed. Isolation of H. pylori from up to 100% of patients with duodenal ulcer and 80% of patients with gastric ulcer establishes a strong association between H. pylori and idiopathic PUD, although other factors also may be essential for the development of PUD. Invasive procedures for diagnosis of H. pylori infection include upper endoscopy and biopsy of gastroduodenal tissues followed by culture or the rapid urea test; noninvasive tests include the urea breath tests and serology. Although H. pylori is susceptible to a number of antimicrobials, eradication (as opposed to suppression) of this organism has been a major challenge. The most important predictive factor for clinical and microbiological efficacy is the pretreatment susceptibility of H. pylori to nitroimidazoles. Triple therapy with bismuth, metronidazole, and either amoxicillin or tetracycline has resulted in better clinical and microbiological outcomes than either monotherapy or dual therapy. Possible adverse effects of this regimen include nausea, vomiting, taste disturbance, and diarrhea. Anti-H. pylori therapy should be reserved for those patients who have recurrent symptomatic or intractable PUD. Currently, the regimen of choice includes bismuth, metronidazole, and either amoxicillin or tetracycline given for at least two weeks.

Anti-Bacterial Agents↗

PubMed1992

Synthesis and antifolate evaluation of 10-ethyl-5-methyl-5,10- dideazaaminopterin and an alternative synthesis of 10-ethyl-10- deazaaminopterin (edatrexate).

Previous findings suggesting that 5,10-dialkyl-substituted derivatives of 5,10-dideazaaminopterin warranted study as potential antifolates prompted synthesis of 10-ethyl-5-methyl-5,10- dideazaaminopterin (12a). The key step in the synthetic route to 12a was Wittig condensation of the tributylphosphorane derived from 6-(bromomethyl)-2,4-diamino-5-methylpyrido[2,3-d]pyrimidine (7a) with methyl 4-propionylbenzoate. Reaction conditions for the Wittig condensation were developed using the tributylphosphorane prepared from 6-(bromomethyl)-2,4-pteridinediamine (7b) as a model. Each of the respective Wittig products 8a and 8b was obtained in 75-80% yield. Hydrogenation of 8a and 8b at their 9,10-double bond afforded 4-amino-4-deoxy-10-ethyl-5-methyl-5,10-dideazapteroic acid methyl ester (9a) and 4-amino-4-deoxy-10-ethyl-10-deazapteroic acid methyl ester (9b). This route to 9b intersects reported synthetic approaches leading to 10-ethyl-10-deazaaminopterin (10-EDAM, edatrexate), an agent now in advanced clinical trials. Thus the Wittig approach affords an alternative synthetic route to 10-EDAM. Remaining steps were ester hydrolysis of 9a,b to give carboxylic acids 10a,b followed by standard peptide coupling with diethyl L-glutamate to produce diethyl esters 11a,b, which on hydrolysis gave 12a and 10-EDAM (12b), respectively. The relative influx of 12a was enhanced about 3.2-fold over MTX, but as an inhibitor of dihydrofolate reductase (DHFR) from L1210 cells and in the inhibition of L1210 cell growth in vitro, this compound was approximately 20-fold less effective than MTX (DHFR inhibition, Ki = 4.82 +/- 0.60 pM for MTX, 100 pM for 12a; cell growth, IC50 = 3.4 +/- 1.0 nM for MTX, 65 +/- 18 nM for 12a).

Aminopterin↗

PubMed1992

Hydroxyurea induces apoptosis and regular DNA fragmentation in a Burkitt's lymphoma cell line.

Hydroxyurea (HU) is an S-phase-specific cytotoxic drug used in the clinical treatment of haematological malignancies. HU treatment has been shown to lead to accumulation of short DNA fragments which show direct correlation with cytotoxicity. Specific regular DNA fragmentation is a biochemical feature of apoptosis (programmed cell death) in some systems. We investigated the effect of HU on a neoplastic (Burkitt's lymphoma) cell line (BM13674) in vitro to determine the role of apoptosis in HU action. HU produced growth inhibition and cell death by apoptosis in BM13674 cells. Low dose HU (66 and 131 mumol/l) gave a growth inhibition effect only with no apoptosis being induced. Higher doses (0.66-13 mmol/l) induced apoptosis in a dose-dependent manner. Regular DNA fragmentation was detected by agarose gel electrophoresis of DNA and this correlated in time with the onset of apoptosis detected by light and electron microscopy. The results do not exclude the possibility that HU directly induces DNA strand breaks, which then initiate apoptosis and accompanying regular fragmentation of DNA in the apoptotic cells.

Burkitt Lymphoma↗

PubMed1992

Type I human complement C2 deficiency. A 28-base pair gene deletion causes skipping of exon 6 during RNA splicing.

Two variants of a genetic deficiency of complement protein C2 (C2D) have been previously identified. No C2 protein translation is detected in type I deficiency, while type II deficiency is characterized by a selective block in C2 secretion. Type I C2 deficiency was described in a family in which the C2 null allele (C2Q0) is associated with the major histocompatibility haplotype/complotype HLA-A25,B18,C2Q0,BfS,C4A4, C4B2,Drw2; this extended haplotype occurs in over 90% of C2-deficient individuals (common complotype/haplotype). To determine the molecular basis of type I C2 deficiency, the C2 gene and cDNA were characterized from a homozygous type I C2-deficient individual with the common associated haplotype/complotype. We found a 28-base pair deletion in the type I C2Q0 gene, beginning 9 base pairs upstream of the 3'-end of exon 6, that generates a C2 transcript with a complete deletion of exon 6 (134 base pair) and a premature termination codon. In studies of eight kindred, the 28-base pair deletion was observed in all C2Q0 alleles associated with the common type I deficient complotype/haplotype; this deletion was not present in normal C2 nor in type II C2-deficient genes. These data demonstrate that: 1) type I human complement C2 deficiency is caused by a 28-base pair genomic deletion that causes skipping of exon 6 during RNA splicing, resulting in generation of a premature termination codon, 2) the 28-base pair deletion in the type I C2Q0 gene is strongly associated with the HLA haplotype/complotype A25,B18,C2Q0,BfS,C4A4,C4B2,Drw2, suggesting that all C2-deficient individuals with this haplotype/complotype will harbor the 28-base pair C2 gene deletion, and 3) type II C2 deficiency is caused by a different, as yet uncharacterized, molecular genetic defect.

Amino Acid Sequence↗