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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 397 records · Page 22Linked to original sources

Pharmacokinetics and tissue penetration of rufloxacin, a long acting quinolone antimicrobial agent.

The pharmacokinetics of rufloxacin after a single 400 mg oral dose were studied in eight volunteers, measuring plasma, inflammatory fluid and urine concentrations. Mean peak plasma concentrations of 4.4 mg/L were achieved at a mean time of 1.9 h after administration. The mean plasma elimination half-life was 28.2 h. Mean peak levels in inflammatory fluid reached 3.2 mg/L after 3.5 h, and 30.7% of the dose was eliminated in urine by 96 h. The apparent mean volume of distribution of rufloxacin, at steady state, was 109.5 L. The mean percentage penetration of rufloxacin into the inflammatory exudate, as measured by ratios of AUC0-50 h was 90%.

Administration, Oral↗

Effect of chemical form of selenium on tissue glutathione peroxidase activity in developing rats.

Two experiments were conducted to determine the effect of various forms of selenium (Se) on the activity of glutathione peroxidase (GSHPx) in liver, heart, kidney and eyes of the developing rat. In experiment 1, throughout mating, pregnancy and lactation, female rats consumed one of three diets: basal (less than 0.05 microgram Se/g); selenite (0.15 microgram Se/g) and selenomethionine (0.15 microgram Se/g). Some pups born to dams in the basal group were also given intraperitoneal doses of saline, selenite or selenomethionine. GSHPx activity was measured in tissues from fetuses, 7-d-old and 14-d-old nursing pups and the dams. In all tissues studied, GSHPx activity was highest in the 14-d-old pups whose mothers were in the selenomethionine group. Rat pups given intraperitoneal selenite (3 micrograms/kg body weight) had higher liver and kidney GSHPx activity than pups given the same amount of selenium as intraperitoneal selenomethionine. In experiment 2, all dams were fed the same basal diet, and pups were weaned to diets containing one of two levels of selenium (0.1 or 0.2 microgram/g), one of three forms of selenium (selenite, selenomethionine or selenocystine) or no added selenium. After 14 d of repletion, the highest level of hepatic GSHPx activity occurred in the selenite group and the lowest in the basal diet group. After 21 d of repletion, renal GSHPx activity was lowest in the basal group followed by the selenocystine group. The highest tissue selenium concentration was found in kidney tissues of the selenocystine group. These data support the hypothesis that these dietary forms of selenium are differentially available for GSHPx activity.

Animals↗

Establishing pregnancies after follicular stimulation for IVF with clomiphene citrate and human menopausal gonadotrophin only.

Data are presented on establishing pregnancies by IVF during 1987 using only clomiphene citrate and human menopausal gonadotrophin for follicular stimulation. Of the 562 patients undergoing follicular stimulation, 80% reached oocyte recovery and 70% had at least one conceptus replaced. Patients having one or more (up to a maximum of four) conceptuses replaced demonstrated a significant increase in the establishment of pregnancies from one to two (14-29%: P = 0.035) and from two to three conceptuses (29-42%: P = 0.037). There was a significant decline in pregnancies when four conceptuses were replaced compared with three (P = 0.004). The data were also analysed according to the cause of infertility, specifically tubal, endometriosis, unexplained infertility and male factors only. After the replacement of conceptuses, the incidence of implantation and abortion was not significantly different. The incidence of pregnancy declined significantly after 35 years (26%) compared with women under 31 years (43%; P = 0.043). Of 129 women having three conceptuses replaced, in those greater than 35 years (63 patients) 23 (37%) became pregnant whereas in those less than 31 years (65 patients), 34 (52%; P = 0.05) became pregnant. Twenty-two per cent of stimulated cycles resulted in an endogenous LH surge and the incidence of patients having three conceptuses replaced in this group was lower than those in the HCG group (P = 0.007). Fertilization per oocyte was also significantly reduced (P less than 0.001) in patients with an LH surge. In total, 2824 oocytes were recovered and 57% fertilized with 54% of patients having three conceptuses replaced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Presentation of six pregnancies established by sub-zonal insemination (SUZI).

Clinical trials were undertaken to evaluate sub-zonal insemination (SUZI) for the procurement of fertilization in infertile couples. We present here the six pregnancies resulting from this work. Insemination of multiple sperm was used, with a mean of 3.7 +/- 2.1 (SD) per oocyte. One hundred and thirty patients presented either with previous failures of fertilization in vitro and/or with severe seminal defects, including oligo-, astheno-, oligo-astheno- or necro-zoospermia. Forty-one (31.5%) patients achieved fertilization and 39 had replacement of conceptuses. Six patients achieved a pregnancy (4.6% overall, 15.4% per replacement), four have delivered and two have miscarried. The implantation rate was nine conceptuses from a total of 61 replaced (14.8%); and of the six women who conceived, nine of 11 replaced conceptuses implanted. Of the oocytes recovered, 539 were used for SUZI, of which 69 (12.8%) fertilized. Three singleton pregnancies resulted, two from patients having one conceptus replaced, the other from the replacement of three conceptuses. Two twin pregnancies were produced, both in patients having two conceptuses replaced. The sixth pregnancy, a triplet, occurred in a patient having three conceptuses replaced, one conceived after standard in-vitro fertilization (IVF), the other two after SUZI. Two sets of non-identical twins, both one male and one female, a singleton female and female (non-identical) triplets have been born, normal and healthy.

Adult↗

The use of the GnRH analogue buserelin for IVF--does it improve fertility?

OBJECTIVE: To determine the effect of a short course of the GnRH analogue buserelin and human menopausal gonadotrophin (hMG), for ovarian stimulation in our IVF programme, on reproductive endocrinology and pregnancy rates compared with conventional clomiphene citrate and hMG treatment. DESIGN: Prospective randomized allocation to one of two ovulation stimulation regimens. SETTING: Fertility clinic. SUBJECTS: 373 infertile couples with various factors associated with their subfertility. All the women were less than 46 years of age and had normal menstrual cycles. INTERVENTION: The first group (n = 151) was given clomiphene citrate (CC) from days 2-6 of the menstrual cycle and hMG from day 5 onwards (CC/hMG). The second group (n = 222) was given buserelin from days 1-3 and hMG from day 2 (buserelin/hMG). MAIN OUTCOME MEASURES: Concentration of plasma luteinizing hormone (LH), oestradiol (E2) and progesterone, number of ovulatory follicles induced and the occurrence of pregnancy. RESULTS: Plasma LH, E2 and progesterone concentrations were reduced in the late follicular phase after buserelin/hMG compared with CC/hMG. Buserelin/hMG promoted the development of more follicles than CC/hMG. The overall pregnancy rate after buserelin/hMG was not significantly different from that following CC/hMG treatment. CONCLUSION: The chance of pregnancy is not improved by the short-term use of buserelin with hMG, provided adequate follicular phase management is maintained.

Adult↗

Effects of FP2 and a mercury resistance plasmid from Pseudomonas aeruginosa PA103 on exoenzyme production.

Plasmids encoding mercury resistance carried by Pseudomonas aeruginosa PAO1161 and PA103 were found to be involved in regulating the secretion of protease, phospholipase C, and alkaline phosphatase. Previously, mutations in Pseudomonas strains that caused pleiotropic effects on the production of extracellular enzymes were mapped to the bacterial chromosome. We show that pleiotropic changes in extracellular enzyme production can also be regulated by plasmids. In this study, the effects on secretion of exoenzymes by two mercury resistance plasmids, FP2 from PAO1161 and pRLW103 from PA103, were assayed in P. aeruginosa PAO1 and PAO18. The introduction of either plasmid into PAO1 resulted in a significant decrease in exoprotease production. Additionally, pRLW103 significantly increased the production of alkaline phosphatase by both strains. Phospholipase C was produced only in strain PAO18 containing the pRLW103 plasmid. FP2 had no effect on alkaline phosphatase or phospholipase C production in either strain and was found to decrease exoprotease secretion only in strain PAO1. The results indicate the P. aeruginosa mercury resistance plasmids vary in their ability to modify exoenzyme expression, and this ability is influenced by the host strain.

Alkaline Phosphatase↗

Morphologic changes in lungs of anesthetized sheep following intravenous infusion of recombinant tumor necrosis factor alpha.

Tumor necrosis factor alpha (TNF alpha) is a monokine released in response to endotoxin and has been suggested as a primary mediator of endotoxic shock. We have recently demonstrated that infusion of recombinant human tumor necrosis factor alpha (rTNF alpha) into sheep elicits a physiologic response in the lung that closely resembles endotoxemia. The present study examines the morphologic changes that accompany these alterations in pulmonary physiology. Five anesthetized, open-chest sheep received 0.01 mg/kg of protein (2.24 x 10(7) U rTNF alpha/mg) intravenously over 30 min. Lung biopsy tissue for light and electron microscopy was obtained from random lobes 7.5, 15, 30, 60, 120, 180, and 240 min after beginning the infusion. Pulmonary (Ppa) and systemic arterial pressures, cardiac output, and peripheral blood leukocyte number and differential counts were monitored throughout the study. Three control animals were treated in a similar manner but received either saline (n = 1) or rTNF alpha denatured by boiling for 30 min (n = 2). rTNF alpha caused an early increase in Ppa and peripheral blood leukopenia. Light microscopy revealed a threefold increase in the number of granulocytes per 100 alveolar profiles by 30 min and a fivefold increase by 2 h. From 60 min, increased alveolar wall thickness, red cell congestion, and peribronchovascular edema were apparent; from 2 h, there was increased cellularity of the alveolar walls and mononuclear cell infiltration of perivascular connective tissue. Electron microscopy revealed damage to alveolar Type I and II pneumonocytes and progressive endothelial injury from 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Bipolar affective disorder following head injury.

A patient developed distinct episodes of major depressive illness, schizophreniform psychoses and mania as well as focal epilepsy following head injury. Head injury may be directly causative in the development of affective psychoses, in this case secondary bipolar (mixed) disorder.

Adult↗

Bovine parathyroid glands secrete a 26-kDa N-terminal fragment of chromogranin-A which inhibits parathyroid cell secretion.

Chromogranin-A (CgA) is a ubiquitous protein which colocalizes in secretory granules of multiple endocrine tissues and cosecretes with peptide hormones from these tissues. Although the function of CgA has remained unknown, there has been recent interest in its potential role as a prohormone for smaller, biologically active peptides. We isolated and characterized a 26-kDa N-terminal fragment of CgA which is a natural breakdown product of bovine parathyroid CgA in storage. A similar, if not identical, fragment of CgA is secreted by bovine parathyroid glands. The secreted fragment elutes on HPLC and migrates on both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and acid-urea gels in the same position as the 26-kDa N-terminal fragment. When added to the incubation medium of dispersed bovine parathyroid cells, the 26-kDa N-terminal fragment of CgA inhibits the low calcium-stimulated secretion of both PTH and CgA. This N-terminal fragment is homologous to betagranin, which is a 21-kDa N-terminal fragment of CgA that is generated from CgA in rat insulin granules. Thus, a naturally occurring betagranin-like N-terminal fragment of bovine parathyroid CgA is not only secreted itself, but can inhibit the secretion of PTH and intact CgA by bovine parathyroid cells. The processing of intact CgA to fragments such as the N-terminal fragment that we describe may be important in the autocrine or paracrine regulation of secretion.

Amino Acid Sequence↗

The association of laryngoceles with squamous cell carcinoma of the larynx.

The clinical diagnosis of laryngoceles simultaneously occurring with squamous cell carcinoma of the larynx is infrequent; however, when specimens from patients with laryngeal cancer have been examined closely, the two entities have been associated in 4.9% to 28.8% of cases. Despite this apparent relationship, the literature has failed to address the potential impact of a concurrent laryngocele on surgical decision making. Also, the wide variation in the reported rates of simultaneous occurrence of these two entities is unexplained. We performed whole-organ histopathologic analysis on a laryngeal specimen with bilateral external laryngoceles associated with squamous cell carcinoma and correlated this to computed tomography findings. Based on this information and other reports concerning the pattern of spread of carcinoma within laryngoceles, it appears that supraglottic laryngectomy is oncologically sound in the presence of a laryngocele as long as the usual criteria for this procedure are met.

Aged↗

The Basic HIV Disease Knowledge Questionnaire: a Rasch-scaled instrument to measure essential HIV knowledge.

The need for improvement in HIV disease-related psychometric questionnaires is noted. In response to this need a Rasch-scaled measure to ascertain basic HIV disease knowledge was developed and calibrated on 1092 subjects. Four studies conducted with the measure suggest adequate test-retest reliability. Three validity studies also conducted with this questionnaire suggest that the measure is sensitive to knowledge obtained from HIV-related training and education. Potential uses and limitations of this new questionnaire are discussed.

Adult↗

Job strain and ambulatory blood pressure profiles.

Occupational characteristics were used to study the role of job stress in the pathogenesis of hypertension. Ambulatory 24-h recordings of blood pressure were made for 161 men with borderline hypertension. From the occupational classification system scores for psychological demands, control, support, physical demands, and occupational hazards were obtained. The results indicated that the ratio between psychological demands and control (strain) was significantly associated with diastolic (but not systolic) blood pressure at night and during work. The association between job strain and diastolic blood pressure at night and during work was greatly strengthened when the subjects with occupations classified as physically demanding were excluded from the analysis. The conclusion was reached that a measure of job strain derived from the occupational classification is useful in predicting variations in diastolic blood pressure levels during sleep and work for men with borderline hypertension.

Adult↗

Quality assurance: the team approach.

Measuring quality has become an integral part of nursing facility operations. This cover story examines the components of a successful quality assurance program and how facilities across the country have implemented programs that meet the needs of facility residents and staff.

Institutional Management Teams↗

The structure and characteristics of rural hospital consortia.

Rural hospital consortia are relatively new organizations that have been developed to help improve the viability of participating hospitals. This paper describes the characteristics of rural hospital consortia in the United States and develops and tests a measurement model of their underlying structure. The measurement model, which characterized consortia structure in terms of degree of member commitment, degree of complexity, scale of operations, and degree of formalization, provided a good fit to the sample data. Most consortia appear to have followed a relatively conservative course that involved the development of programs that had limited sensitivity and financial risk for individual hospitals. This suggests that rural hospital consortia may not become a model for major structural change in the rural health care system. Future research should examine the evolution of rural hospital consortia from an organizational life cycle perspective.

Data Collection↗

Scintigraphic portrayal of beta receptors in the heart.

Myocardial beta adrenergic receptors play important roles in physiology and disease, but the receptors have not before been portrayed. The beta antagonist, iodocyanopindolol (ICYP), was used to develop a scintigraphic method for depicting the receptors in the living heart. Labeled with 125I, ICYP bound firmly to beta receptors in the rat heart; the data conformed to a mathematical model. In vivo saturation kinetics indicated binding sites with two affinities. Inhibition of ICYP binding by beta antagonists of different potency and different selectivity for beta-1 and beta-2 receptors produced the expected pharmacologic effects. Inhibition by lipophilic and hydrophilic antagonists gave no evidence that ICYP was appreciably bound to internalized receptors. Fractional binding by tracer quantities of (-) ICYP and (+/-) ICYP demonstrated stereospecificity. Labeled with 123I, ICYP bound to the hearts of intact dogs so that scintigraphic tomographs depicted ventricular myocardium. Small doses of beta antagonists selectively reduced the binding of ICYP to lung enabling better visualization of the heart. Thus, 123I-ICYP appears to portray the beta receptors in the living heart, and the characteristics of binding permit the development of mathematical models and lay the basis for quantifying this receptor binding.

Animals↗

A human epidermal differentiation-specific keratin gene is regulated by calcium but not negative modulators of differentiation in transgenic mouse keratinocytes.

Keratins K1 and K10 represent the major differentiation products of the maturing epidermal keratinocytes. Primary epidermal cell cultures from newborn K1 transgenic mice containing a 12-kilobase human K1 genomic fragment were established in order to examine the expression of both human and mouse K1 in the presence of known modulators of epidermal differentiation. Elevated levels of Ca2+ in the culture medium induced both mouse K1 and human K1. Supplementing the medium with retinoic acid or 12-O-tetradecanoylphorbol-13-acetate or introducing a Harvey viral ras oncogene (v-rasHa) into the cells completely suppressed mouse K1 but not human K1. Our results suggest that: (a) the human 12-kilobase insert contains all the necessary cis-acting elements to respond to the Ca2+ signal, and (b) other cis-acting elements, not present within this insert, may function independently to regulate the response of K1 to retinoids, 12-O-tetradecanoylphorbol-13-acetate, and v-rasHa transformation. This transgenic model provides an approach to identify elements required for the regulation of an epidermal differentiation-specific gene.

Animals↗

Optimized recirculation survival of mouse carrier erythrocytes.

Carrier mouse erythrocytes prepared by a hypotonic dialysis technique and reinjected into mice have a 24 hour survival of approximately 50%. Twenty-four hour survival can be improved substantially to 74% by removing the more fragile erythrocytes by a hypotonic wash treatment. The mean cell volume of the carriers prepared by this modification is significantly (p less than 0.01) different from cells prepared by the standard method with a isotonic wash treatment. Carriers prepared by the hypotonic treatment wash modification exhibit a different 50% hemolytic value (15% difference) from isotonically prepared carriers, and normal erythrocytes. Carrier-erythrocytes removed from mice 24 hour post-injection exhibit an osmotic profile that is independent of the treatment. Carriers were also prepared by another modification of the encapsulation procedure and held in a permeable state overnight before resealing and annealing. Carriers prepared in this manner showed a much lower 24 hour survival (13%).

Animals↗

Drug use and abuse in five US communities.

Data from the five-site Epidemiologic Catchment Area study (ECA), a probability sample of 18,571 adults, were used to describe the prevalence of drug abuse in the United States and to evaluate the hypothesis that multiple prescription regulations are effective in reducing drug abuse and drug diversion. The five sites surveyed were New Haven, Connecticut; Baltimore, Maryland; St. Louis, Missouri; Durham, North Carolina; and Los Angeles, California. The California triplicate prescription law was established in 1939 and is the longest continuously running triplicate prescription program in the country (Schedule II drugs). None of the other ECA sites had multiple prescription regulations in effect at the time the study was conducted. In general, the rates of drug use, abuse, and dependence were significantly higher in Los Angeles as compared with the other sites, both before and after controlling for sociodemographic differences. The proportion of users who go on to become abusers was consistent across sites (about 20%). The vast majority of those with a DSM-III diagnosis of abuse of prescription drugs reported that they obtained the drugs from a source other than their physician, suggesting that "diversion" of prescriptions from legal channels occurred at all sites. Limitations of the study design with respect to conclusions are discussed.

Drug Prescriptions↗