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Biomedical subjects

C A Johnson

Publications and source records attributed to C A Johnson.

At least 307 records · Page 17Linked to original sources

Pharmacokinetics and pharmacodynamics of cefoperazone-sulbactam in patients on continuous ambulatory peritoneal dialysis.

This study was conducted to determine the pharmacokinetics of the fixed combination antibiotic cefoperazone-sulbactam in patients receiving continuous ambulatory peritoneal dialysis (CAPD). In addition, the pharmacodynamic profile of this combination was determined by the use of mean bactericidal titers against selected bacterial strains. Six noninfected CAPD patients were given a fixed dose of cefoperazone (2 g) and sulbactam (1 g) either intravenously or intraperitoneally over 10 min in a randomized, two-way crossover fashion. The mean peak cefoperazone concentration in serum after intravenous administration was 280.9 micrograms/ml. The mean peak concentration in serum after intraperitoneal cefoperazone administration was 38.9 micrograms/ml and occurred 2 to 4 h postdose. The mean peak sulbactam concentration in serum after intravenous administration was 82.2 micrograms/ml. The mean peak concentration in serum after intraperitoneal sulbactam administration was 24.4 micrograms/ml and occurred at 6 h. The absolute bioavailability of the intraperitoneal dose was 61% for cefoperazone and 70% for sulbactam. Cefoperazone total body and renal clearances were unaffected by renal failure and dialysis. However, both clearance values for sulbactam were reduced markedly. Only intraperitoneal dosing provided peak inhibitory and bactericidal titers in dialysate for all organisms tested. Intravenous dosing provided satisfactory dialysate titers only for very susceptible bacterial strains. End-stage renal disease and CAPD do not alter cefoperazone pharmacokinetics; however, sulbactam dosing may need to be adjusted.

Adult↗

Age-related changes in the central visual field for short-wavelength-sensitive pathways.

The sensitivity of short-wavelength-sensitive (SWS) cone pathways throughout the central 30-deg visual field was determined in both eyes of 62 normal volunteers between the ages of 20 and 72 years. We found an average SWS cone pathway sensitivity decrease with age of approximately 0.15 log unit per decade. The sensitivity reduction was approximately linear, with a slightly larger decrease beyond the age of 50 years. The age-related SWS cone pathway sensitivity reductions also became larger as a function of increasing stimulus eccentricity. Measurements of ocular-media absorption characteristics in each eye revealed that 30-40% of the age-related sensitivity loss could be attributed to reductions in transmission of short-wavelength light by the ocular media. After corrections for preretinal media transmission loss, the decrease in the sensitivity of SWS cone pathways with age was approximately 0.09 log unit per decade. This age-related loss is greater than age-related sensitivity decreases in the middle-wavelength-sensitive and/or long-wavelength-sensitive cones (approximately 0.06 to 0.07 log unit per decade). In the age group older than 60 years, there was an inverse relationship between media-corrected SWS cone pathway sensitivity and media absorption characteristics (i.e., media-corrected SWS cone pathway sensitivity was higher in eyes with lower media transmission of short wavelengths). This relationship was not so evident for younger subjects. A similar inverse relationship between transmission loss in the ocular media and SWS cone pathway sensitivity was found between left and right eyes of the same individual.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Naturally occurring human antibodies against two distinct functional domains in the heavy chain of FXI/FXIa.

We have isolated and probed the mechanism of action of two naturally occurring antibodies (Baltimore and Winston-Salem) against factor XI (FXI), that developed in patients congenitally deficient in FXI after replacement therapy. Purification on immobilized protein A and neutralization with monospecific antibodies against IgG heavy and light chain subtypes indicated that both antibodies were of restricted heterogeneity. Both Winston-Salem (IgG3 kappa) and Baltimore (IgG1 kappa) completely inhibited FXI coagulant activity at titers of 200 and 8 Bethesda units, respectively. Immunoaffinity columns prepared from each antibody were able to bind the heavy but not the light chain of reduced and alkylated activated FXI (FXIa). The activation of purified FXI by activated bovine factor XII (FXIIa), a reaction independent of high molecular weight kininogen (HK), was not inhibited by either antibody. The active site on the FXIa light chain was unaffected by either patient's IgG, as measured by its amidolytic activity. In contrast, one antibody (Baltimore) or its Fab' blocked the surface-mediated proteolytic activation of FXI by human FXIIa in a concentration-dependent fashion by preventing its binding to HK, but had no effect on the rate of activation of FIX by FXIa. In contrast, the other antibody (Winston-Salem) or its Fab' inhibited the activation of FIX by FXIa in a concentration-dependent fashion but did not inhibit binding of FXI to HK. We conclude that each of these two naturally occurring antibodies is directed against a specific, separate, and distinct epitope located in the heavy chain of FXIa, one near or at the domain essential for the activation of FIX by FXIa and the other close to the domain required for binding to HK.

Amides↗

Effects of various sedatives on air cystometry in dogs.

The effects of various sedatives on air cystometry in dogs were investigated. Oxymorphone plus acepromazine, xylazine alone, atropine plus xylazine, and diazepam plus ketamine were compared for interference with the detrusor reflex, adequacy of patient restraint, and development of adverse side effects. Atropine plus xylazine was the best of the 4 drug combinations tested, because it had the least interference with the detrusor reflex, bradycardia did not develop, and excellent restraint was obtained. Pain and hematuria were common whenever intravesicular pressure exceeded 40 cm of H2O, yet pressures that high were rarely necessary to stimulate the detrusor reflex.

Acepromazine↗

Pathophysiology and treatment of the anemia of renal failure.

The pathophysiology of anemia associated with renal failure and the major pharmacologic agents used in the treatment of this anemia are reviewed. Patients with renal failure are often anemic primarily because of diminished circulating erythropoietin and suppressed erythropoiesis in the bone marrow. The anemia may cause malaise, fatiguability, aggravated angina, and decreased exercise tolerance. Many patients require frequent red blood cell transfusions. Therapy has included anabolic androgen administration, iron and vitamin supplementation, and the administration of red blood cells. These approaches generally have not resulted in sustained improvement of the anemia. The recent development of recombinant human erythropoietin may represent a major therapeutic advance for the treatment of anemia associated with renal failure. Previously, erythropoietin therapy was not possible because of lack of sufficient quantities of the purified hormone. Clinical trials indicate, however, that recombinant human erythropoietin may improve erythropoiesis in most patients. Adverse effects have generally been mild and easily managed; however, increases in blood pressure and arteriovenous fistula clotting have been reported. Although initial reports are encouraging, larger and longer clinical trials are needed to determine proper dosing and to understand more completely the potential adverse effects of recombinant human erythropoietin. Previous pharmacologic attempts to improve the anemia associated with renal failure have been largely unsatisfactory; initial reports on the use of recombinant human erythropoietin are promising.

Anemia↗

Prenatal screening.

Routine obstetric screening for all patients should include a Pap smear, urinalysis and urine culture, complete blood count, blood type, Rh factor and direct Coombs' test. Patients should also be screened for syphilis, rubella, gonorrhea and diabetes. For patients at high risk for certain conditions, additional studies of value include obstetric ultrasound, amniocentesis, serum alpha-fetoprotein level and screening for sickle cell anemia, herpes, hepatitis B, Chlamydia and human immunodeficiency virus.

Diagnostic Tests, Routine↗

Congenital portosystemic shunts in dogs: 46 cases (1979-1986).

Congenital portosystemic shunts (CPSS) were diagnosed in 46 dogs. The historic, physical, and laboratory findings were tabulated. Half of the affected males were cryptorchid. Urolithiasis was detected in 20% of the dogs. The biochemical tests with the best sensitivity for the diagnosis of CPSS were sulfobromophthalein retention, fasting serum ammonia concentration, and serum alkaline phosphatase activity. The survival time and quality of life were assessed by physical and biochemical reevaluation of the dogs and by means of a questionnaire that was completed by the owners. Five dogs were treated medically. Thirty-three dogs were treated surgically. Dogs that had complete surgical occlusion of the CPSS became normal, and quality of life was excellent. Dogs that had partial occlusion of the CPSS improved, and some became clinically normal. Dogs that did not have surgical correction of the CPSS had continuation of signs, but several survived for years.

Animals↗

Abdominal tuberculosis in children. A survey of cases at the Red Cross War Memorial Children's Hospital, 1976-1985.

Fifty-nine cases of abdominal tuberculosis were seen at the Red Cross War Memorial Children's Hospital, Cape Town, during the period 1976-1985. More than half these patients were under 4 years of age and all were malnourished. Mesenteric adenitis and/or peritoneal involvement accounted for the majority of cases and only 8 patients with proven gastro-intestinal lesions were seen. The diagnosis of suspected abdominal tuberculosis is relatively easily made since abdominal distension occurs in almost all patients. More than half have an abdominal mass, a chest radiograph suggestive of tuberculosis, a positive Mantoux skin test or a combination of these as supportive evidence for the diagnosis. Over a quarter of the patients presented with signs suggestive of intestinal obstruction. Response to antituberculosis therapy is excellent. Stricture formation on healing may occur in a minority of patients with the enteric form of the disease. Providing it is not part of disseminated tuberculosis in a grossly malnourished young child, the prognosis with treatment for abdominal tuberculosis is satisfactory.

Age Factors↗

Optimal rates of movement for kinetic perimetry.

Duration, reliability, and sensitivity of kinetic thresholds were evaluated for the I/4e, I/2e, and I/1e Goldmann-equivalent targets as a function of stimulus velocity (1 degrees to 8 degrees/s) using the SQUID automated perimeter. For all targets, the average duration of kinetic meridional scans decreased significantly as stimulus velocity increased from 1 degrees to 4 degrees/s. Minimal reductions in kinetic scan times were present for stimulus velocities above 4 degrees/s. All targets appeared to have reductions in sensitivity at velocities above 4 degrees/s (target detection occurring at more central visual field locations) that were presumably related to the observers' reaction times. There were no consistent differences in the variability of kinetic thresholds for different stimulus velocities. When all factors were considered, a stimulus velocity of 4 degrees/s seemed to be optimal for kinetic scans of all targets in the central and peripheral visual field.

Adult↗

Contrast sensitivity after penetrating keratoplasty.

Contrast sensitivity testing in the corneal transplant patient may enhance our assessment of visual performance, which is traditionally evaluated using Snellen acuity only. To evaluate contrast sensitivity function after penetrating keratoplasty, we studied 29 patients with anatomically successful corneal grafts and a best corrected visual acuity of 20/50 or better. Graft patients were compared with an age-matched control group including persons with comparable visual acuities without ocular disease. In addition to a complete ophthalmic examination, all subjects underwent contrast sensitivity testing using a computer-generated sinusoidal grating system as well as a commercially available contrast sensitivity wall chart. Data indicate that, despite comparable Snellen visual acuity, the contrast sensitivity curves for graft patients were depressed overall compared with those of normal subjects except at the lowest spatial frequency. However, comparison of grafted eyes to contralateral eyes with corneal disease in a small subset of patients with bilateral disease shows a trend toward higher contrast sensitivity values in the eyes that had been operated on. These data suggest that despite an improvement in contrast sensitivity with penetrating keratoplasty, an eye with a corneal transplant is not entirely normal from a visual standpoint. Nonacuity parameters may be important indexes for assessing real-world visual function in the graft patient, although the clinical role of these tests is not yet completely defined.

Adult↗

The therapeutic use of azathioprine in renal transplantation.

This review discusses the pharmacokinetics, mechanism of action, clinical use, toxicities, drug interactions, and possible approaches for therapeutic monitoring of azathioprine (AZA). The drug has been used extensively in posttransplant immunosuppressive protocols. Its therapeutic use is hampered by the development of toxicities, however, especially leukopenia, which is a common criterion for dosage adjustment. Azathioprine is rapidly converted in the liver and erythrocytes to 6-mercaptopurine (6MP), which is eventually metabolized to inactive 6-thiouric acid (6TU). The terminal half-lives of AZA and 6MP are 50 and 74 minutes, respectively. While renal dysfunction does not alter the disposition of AZA, hepatic insufficiency attenuates the pharmacologic activity. Immunosuppression depends on the formation of active intracellular thiopurine ribonucleotides, although AZA itself may block antigen recognition. Individualization of AZA regimens by determining tissue concentrations of thioguanine nucleotides, and plasma concentrations of AZA, 6MP, or 6TU may improve the risk:benefit ratio.

Azathioprine↗

The consistency of peer and parent influences on tobacco, alcohol, and marijuana use among young adolescents.

The purpose of this study was to determine the degree to which the use of tobacco, alcohol, and marijuana by young adolescents can be described using a common theoretical model. Structural models were created in which psychosocial variables hierarchically predicted the use of each substance. The fit of a model in which paths from predictor variables were constrained to be equal was not inferior in any meaningful way to that of a model in which all path coefficients were freely estimated, thus suggesting that use of tobacco, alcohol, and marijuana by young adolescents may be considered to be a unitary phenomenon. A simplified model, in which these substances were combined into a single latent variable, showed a good fit. The results of these analyses suggest that it may be beneficial to consider adolescent substance use to be a unitary phenomenon.

Adolescent↗

The prevention of cigarette smoking in children: two- and three-year follow-up comparisons of four prevention strategies.

Recent studies have suggested that a prevention program that addresses the social influences that encourage smoking can be effective in deterring cigarette use by adolescents. This study presents 1-, 2-, and 3-year follow-up results from two studies which evaluated three variations of the social influences curriculum and compared them to a health consequences program and a usual-care comparison group. These results suggest that a peer-led, social influences program can restrain smoking among both baseline nonsmokers and baseline experimental smokers at 2 years postintervention. Analyses of attrition data suggest no evidence to threaten the internal validity of these findings, although their generalizability to baseline smokers may be limited.

Adolescent↗