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Biomedical subjects

C Johnson

Publications and source records attributed to C Johnson.

At least 217 records · Page 12Linked to original sources

Differential response in cell proliferation to beta estradiol in coronary arterial vascular smooth muscle cells obtained from mature female versus male animals.

Although the cardioprotective effect of estrogen is well recognized, the mechanisms by which this sex steroid provides a reduction in coronary artery disease are not fully understood. Vascular smooth muscle cells (VSMC) are present in early atherosclerosis and become the dominant cell type. VSMC contain estrogen receptors and may have specific responses to estrogen. We studied the effect of beta-estradiol on the proliferation of coronary VSMC obtained from sexually mature male, female, and oophorectomized pigs. Alpha-estradiol, an inactive isomer of estradiol, had no effect on cells obtained from male or female animals. In vascular smooth muscle cells obtained from sexually mature female animals, significant inhibition of proliferation of coronary vascular smooth muscle cells was noted at physiologic concentrations of beta-estradiol. Progesterone inhibited VSMC proliferation at concentrations of 10(-9)M. In contrast, beta-estradiol did not alter proliferation in porcine coronary vascular smooth muscle cells obtained from sexually mature male or from oophorectomized female animals. This study is the first to indicate, in an animal model, specific gender-related differences in cell proliferation in response to sex steroid hormones.

Analysis of Variance↗

Frequency of MBP and MBP peptide-reactive T cells in the HPRT mutant T-cell population of MS patients.

Somatic mutation as an index of in vivo T-cell amplification is a powerful tool to analyze the specificity and size of the autoreactive T-cell repertoire. Using this strategy, we determined the precursor frequency of T cells reactive to myelin basic protein (MBP) and overlapping MBP peptides spanning regions p84-168 in patients with MS and controls in the HPRT mutant T-cell population. Among 19 MS patients, nine had estimatable frequencies to MBP or MBP peptides, p93-112, p124-142 and p143-168 in the HPRT mutant T-cell population. Only one of the 10 controls showed measurable frequency to MBP in the HPRT mutant T-cell population. These studies suggest that increased frequency of T cells reactive to MBP and MBP peptides might indicate putative disease-related epitopes in MS.

Adolescent↗

Effects of 12-week administration of dornase alfa in patients with advanced cystic fibrosis lung disease. Pulmozyme Study Group.

STUDY OBJECTIVE: The 12-week efficacy and safety of aerosolized recombinant human DNase (dornase alfa) were evaluated in previously untreated patients with cystic fibrosis (CF) with advanced lung disease. DESIGN: In this multicenter, double-blind, placebo-controlled study, CF patients with advanced lung disease were randomized to receive either dornase alfa or placebo once a day for 12 weeks. PATIENTS: A total of 320 patients in clinically stable condition with documented CF and an FVC less than 40% of predicted were recruited from 65 CF Foundation care centers in the United States. The dornase alfa and placebo groups were comparable with respect to age (range, 7 to 57 years), height, and weight. Male subjects outnumbered female subjects (55% vs 45%) and few subjects were younger than 17 years of age (15%). The percentages of predicted FEV1 and FVC were significantly lower in the dornase alfa group at baseline (p < or = 0.05). INTERVENTIONS: Patients were randomly assigned to receive either 2.5 mg dornase alfa once daily (n = 158) or placebo once daily (n = 162). All patients continued to receive standard medications and treatments administered for CF. MEASUREMENTS AND RESULTS: Dornase alfa improved the mean percent change in FEV1 from baseline by 9.4% compared with 2.1% for placebo (p < 0.001). The actively treated group showed a 12.4% improvement in FVC compared with 7.3% for placebo (p < 0.01). There were no differences between the treatment groups in dyspnea score number of days receiving i.v. antibiotics, or length of hospital stay; the overall incidence of adverse events was comparable between treatment groups. Fifteen patients died: 9 in the dornase alfa group and 6 in the placebo group; no differentiating clinical characteristics were demonstrated. CONCLUSIONS: Pulmonary function as measured by FEV1 and FVC improved significantly in the dornase alfa-treated patients. Dornase alfa was found to be safe and well tolerated over the 12-week study period.

Adolescent↗

Melanoma of the foot in white South Africans.

There have been few studies that have compared the outcome of treatment of melanoma on the sole and dorsum of the foot or defined their prognostic factors. We describe 44 white patients (30 women and 14 men, mean age 53 years) with melanoma on the foot (sole, n = 25, dorsum, n = 19) seen over a 15 year period. Forty patients presented with stage I, two with stage II, one with stage III, and one with stage IV disease. The median Breslow depth of penetration was 2.8 mm (sole 3.3, dorsum 2.3). Of the 40 patients with stage I disease, 34 patients (17 dorsum, 17 sole) were treated by wide local excision (2 cm or more) and none developed local recurrence. Six patients (five sole, one dorsum) who had narrow excision margins (less than 1 cm, stage I disease) developed local recurrences. Ten patients underwent prophylactic hyperthermic limb perfusion. Sixteen patients with stage I disease (10 sole, six dorsum) developed metastases in the inguinal nodes. All 16 underwent block dissection of the nodes and five are alive. The overall survival for both dorsum (73%) and sole (66%) (stage I disease) was similar at 60 months. Both patients with stage II disease were alive at the time of writing, but the two patients with stage III and IV disease had died. The foot is an anatomical subsite associated with a poor prognosis for melanoma. There is little difference in prognostic factors and outcome between the sole and dorsum.

Adult↗

Education review: Meeting statewide needs for health information management education through distance education.

In 1990 a need was expressed for a baccalaureate degree in health information management (HIM) for HIM employees who could not leave their jobs and/or families to attend classes 150 miles away. Faculty from the Medical College of Georgia, the state's health sciences university, began teaching one class per quarter at St. Joseph Hospital in Atlanta in 1993. In conjunction with DeKalb College in Atlanta, the Medical College of Georgia now offers the entire HIM curriculum leading to a baccalaureate degree. Classes are taught by faculty at the Medical College of Georgia through the use of ¿electronic classrooms¿ equipped with two-way interactive video cameras and monitors, special detail cameras, and state-of-the-art computers. The Medical College of Georgia now offers the only baccalaureate degree in HIM in the state university system.

Georgia↗

Current concepts in postmenopausal hormone replacement therapy.

As more women are living longer, there is an increasing need for women to discuss hormone replacement therapy (HRT) with their physicians. This task is complicated by areas of scientific uncertainty and evolving data concerning the risks and benefits of HRT. Benefits of HRT that are supported by strong scientific evidence include relief from menopausal symptoms such as hot flashes, prevention of osteoporosis, cardioprotective effects, relief of urogenital atrophy, and decreased urinary incontinence. Benefits supported by observational evidence include improvement of emotional lability and depression, improved sense of well-being in patients with rheumatoid arthritis, increased dermal and total skin thickness, improved verbal memory skills, and decreased risk of colon cancer. Risks to consider include a possible increase in the incidence of breast cancer and an increase in endometrial cancer in women who have an intact uterus and do not receive a progestin. Women in various risk groups, such as those at risk for coronary artery disease, osteoporosis, or breast cancer, must consider the risk-to-benefit ratio for their own individual circumstances.

Breast Neoplasms↗

Diagnosis of vasa previa with ultrasound and color flow Doppler: a case report.

Ultrasound and Doppler imaging have proven to be valuable antepartum diagnostic tools for the early recognition of vasa previa. Recent reports have demonstrated that successful detection and timely management can subsequently reduce the risk of a life-threatening fetal hemorrhage. We present the fourth reported case of vasa previa detected antenatally by ultrasound. While conscientious attention to the risk factors and a high index of clinical suspicion remain important considerations, we believe that ultrasound and color Doppler flow analysis represent a highly sensitive diagnostic tool for those patients at risk. In the past, antenatal diagnosis has relied on insensitive and inconclusive means, often only after signs of fetal compromise have become apparent. Sonography has been demonstrated to offer reduced fetal mortality and therefore must be considered the new standard of care for management of suspected vasa previa.

Adult↗

Interpretation of facial expressions of emotion: the influence of eyebrows.

The contribution of the eyebrow component (eyebrow density and eyebrow position) in interpretation of facial displays of emotions was explored. In Study 1, college students (N = 60) and children (N = 60), ages 6-9 years, listened to vignettes consisting of one or two sentences and selected the facial expression that best matched the vignette. A main effect for eyebrow density as well as interactions for Density x Age and Density x Emotion were found. Also, a main effect for eyebrow position and interactions for Position x Age, Position x Emotion, and Position x Age x Emotion were significant. Study 2 was conducted to better understand whether findings regarding eyebrow position were a function of mistaking the intended emotion portrayed in the vignettes. Using a within-subject design, responses from 60 children, age 6-9 years, were compared for trials when the emotion was designated and when emotion was not designated. A main effect for designation of emotion was not found; however, an interaction effect for Designation x Emotion was significant.

Adolescent↗

Safety of autotransplants with high-dose melphalan in renal failure: a pharmacokinetic and toxicity study.

Melphalan (MEL) is probably the most effective chemotherapeutic agent in multiple myeloma (MM) with a clear dose-response effect. It can be escalated without excessive toxicity to 200 mg/m2, a myeloablative dose requiring hematopoietic stem cell support. Patients with marked renal insufficiency, not an infrequent finding in MM, have either received reduced doses or have been excluded from therapy with high-dose MEL. A prospective study was performed to evaluate the relationship between MEL pharmacokinetics and renal function in 20 patients with MM. Six patients had severe renal insufficiency (creatinine clearance, <40 ml/min), including five on chronic hemodialysis. Three patients with severe renal impairment first received a low test dose of MEL (16 mg/m2) for pharmacokinetic studies. All patients received 200 mg/m2 MEL divided into two equal doses of 100 mg/m2 i.v. on 2 consecutive days, followed by the administration of peripheral blood stem cells. MEL pharmacokinetics, performed after the first dose of 100 mg/m2, was not adversely affected by impaired renal function. The median half-life (t1/2), area under the concentration curve, and clearance of MEL were 1.1 h, 5.5 mg h/liter, and 27.5 liter/h, respectively, in patients with a creatinine clearance of <40 ml/min compared to 1.9, 7.9, and 23.6 for the others. Renal insufficiency also had no apparent negative impact on the quality of peripheral blood stem cell collections and did not adversely affect posttransplant engraftment, transfusion requirements, incidence of severe mucositis, or overall survival. However, it was associated with longer durations of fever (P = 0. 0005) and hospitalization (P = 0.004). No transplant-related deaths were observed. Plasma t1/2 and area under the concentration curve differed by a factor of 10 and MEL clearance by a factor of 5 between patients with the lowest and highest values. These large variations in MEL elimination could not be explained by patient or disease characteristics. We conclude that renal failure does not require dose reduction of MEL in autologous transplant. Due to marked interindividual variation in MEL elimination, pharmacokinetically guided dosing as well as cellular pharmacology studies may be helpful in achieving a more uniform antitumor effect.

Adult↗

Treatment of aggressive non-Hodgkin's lymphoma in the elderly.

A nonanthracycline-containing chemotherapeutic combination for the treatment of intermediate and high-grade non-Hodgkin's lymphoma was evaluated. Thirty-four consecutive and previously untreated patients, with a median age of 75 (range 54-86) years, with aggressive lymphoma, received daily etoposide (60 mg/m2 intravenous infusion [IVI]), cytosine arabinoside (50 mg/m2 subcutaneously), and methylprednisolone (60 mg/m2 IVI) on each of 5 consecutive days. Individuals with limited disease (stages I and II) (n = 9) received six, 3-day cycles of the same therapy and involved field radiation (36 Gy in 20 fractions) between the third and fourth courses. Patients with disseminated lymphoma (n = 25) received 10 cycles over 8 months of the same combination, with the addition of methotrexate (200 mg/m2 on days 8 and 15), followed by leucovorin rescue (10 mg/m2 orally every 6 hr for 8 doses). Of the 34 patients, 44% entered complete remission (CR), and 7 died before completing the first cycle of chemotherapy. Fifty-six percent of the patients with limited disease and 40% with disseminated lymphoma (P > 0.05) achieved CR. For all patients, median survival was 14 months (range 3 days- > 54 months), this being 12 and 15 months, respectively. For the entire population of responding patients, median survival has not been reached at a median follow-up of 39 months, while the median CR duration is 21 months. Ten of the 15 responders are alive in unmaintained CR at a median of 41 (range 30-54) months. Myelotoxicity was the major side effect, leading to adjustments in dose and schedule in two-thirds of the patients, although treatment changes did not affect outcome. Of the 15 deaths that occurred in this trial, in 53.3% it was unrelated to lymphoma or its therapy. Four patients that had achieved CR died of cardiovascular events (n = 2) or of progressive second malignancies (n = 2). It is concluded that cytosine arabinoside in combination regimens is effective in selected patients; this is particularly relevant in the elderly.

Aged↗

Antigen-based heteropolymers. A potential therapy for binding and clearing autoantibodies via erythrocyte CR1.

OBJECTIVE: To determine if complexes containing monoclonal antibodies to CR1 cross-linked with antigen (antigen-based heteropolymers [AHP]) can bind the corresponding autoantibody to primate erythrocyte CR1 and promote autoantibody clearance from the circulation. METHODS: AHP were constructed by cross-linking double-stranded DNA (dsDNA) to monoclonal antibodies to CR1. The ability of AHP to facilitate binding of human anti-dsDNA antibodies to primate erythrocytes was studied in vitro using a variety of radioimmunoassays (including Farr assays), enzyme immunoassays, and fluorescence-activated cell sorting. In addition, we used a monkey model to study in vivo the AHP-mediated clearance of passively infused human anti-dsDNA antibodies. RESULTS: Large amounts of lupus IgG anti-dsDNA antibodies can be specifically bound to human erythrocytes via the complexes, and studies in 2 rhesus monkeys indicate that the erythrocyte-bound antibodies are rapidly cleared from the circulation. CONCLUSION: This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.

Animals↗

Biodegradation of sorbed chemicals in soil.

Rates of biodegradation of sorbed chemicals are usually lower in soil than in aqueous systems, in part because sorption reduces the availability of the chemical to microorganisms. Biodegradation, sorption, and diffusion occur simultaneously and are tightly coupled. In soil, the rate of biodegradation is a function of a chemical's diffusion coefficient, sorption partition coefficient, the distance it must diffuse from the site of sorption to microbial populations that can degrade it, and its biodegradation rate constant. A model (DSB model) was developed that describes biodegradation of chemicals limited in the availability by sorption and diffusion. Different kinetics expressions describe biodegradation depending on whether the reaction is controlled by mass transfer (diffusion and sorption) or the intrinsic biodegradation rate, and whether biodegradation begins during or after the majority of sorption has occurred. We tested the hypothesis that there is a direct relationship between how strongly a chemical is sorbed and the chemical's biodegradation rate. In six soils with different organic carbon contents, there was no relationship between the extent or rate of biodegradation and the sorption partition coefficient for phenanthrene. Aging of phenanthrene residues in soil led to a substantial reduction in the rate of biodegradation compared to biodegradation rates of recently added phenanthrene. Considerable research has focused on identification and development of techniques for enhancing in situ biodegradation of sorbed chemicals. Development of such techniques, especially those involving inoculation with microbial strains, should consider physical mass transfer limitations and potential decreases in bioavailability over time.

Absorption↗

Comparison of three jet nebulizer aerosol delivery systems used to administer recombinant human DNase I to patients with cystic fibrosis. The Pulmozyme rhDNase Study Group.

STUDY OBJECTIVE: To compare the degree of improvement in pulmonary function achieved with recombinant human DNase I (rhDNase) administered by three different aerosol delivery systems: DeVilbiss Pulmo-Aide compressor with the Marquest Acorn II nebulizer, the Hudson T Up-draft nebulizer, and the Pari LC Jet Plus nebulizer with the Pari Inhalier Boy compressor. These produce similar aerosols in vitro in terms of size distribution and activity of delivered rhDNase. STUDY DESIGN: Multicenter, randomized, open-label, parallel-group comparison of changes from baseline in pulmonary function variables in each test group. Patients were treated with rhDNase (2.5 mg bid) for 15 days, administered with three different aerosol delivery systems. SETTING: Outpatient clinics at 26 sites in the United States. PATIENTS: 397 patients > 5 years of age with cystic fibrosis and baseline forced vital capacity (FVC) values between 40 and 70% of predicted values. RESULTS: All three nebulizers gave comparable improvements in pulmonary function. FEV1 increased by an average of 13.2 to 14.1%, FVC by 10.9 to 11.8% and forced midexpiratory flow (FEF25-75) by 16.5 to 17.1%. No unusual or unexpected adverse events were reported other than those that would be expected in patients with cystic fibrosis. CONCLUSIONS: Recombinant human DNase I produced a similar magnitude of improvement in the pulmonary function of patients with cystic fibrosis when the drug was administered using three different types of nebulizer systems with similar in vitro delivery and safety characteristics.

Adult↗

Clinical perspective of the treatment of fifth metatarsal fractures.

The authors present a retrospective study of fifth metatarsal fractures. These fractures include Jones fractures, avulsion fractures, spiral and oblique midshaft fractures, and the author-termed "tulip" fracture (impaction fracture of the fifth metatarsal head). These fractures were fixated with the cannulated screw, Kirschner wires, and cerclage loop wires combined with Kirschner wires. A one-way analysis of variance (ANOVA) was performed on the data to test for any significant difference in the fixation type used and the overall healing time. The ANOVA was found to be nonsignificant, F(2,10) = 0.379, p < 0.05. Therefore, it can be concluded that all three types of fixation work equally well. Other analyses were performed on each of the three specific types of fractures to see if there was any difference in fixating the fracture versus no fixation and immobilization. This information was significant for only the Jones fracture, F(1,5)2.23, p < 0.05, meaning that Jones fractures heal in a significantly shorter amount of time when some type of open reduction internal fixation is used. Since there was no difference in healing time between the different types of fixation, the authors advise that the cannulated screw be strongly considered because of its efficiency of insertion. In addition, because of the vascularity, muscle insertions, and motion related to the fifth metatarsal, the authors recommend that most Jones fractures be fixated for a more rapid return to function.

Adult↗