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Biomedical subjects

D W Johnson

Publications and source records attributed to D W Johnson.

At least 91 records · Page 5Linked to original sources

Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with doxycycline.

OBJECTIVE: To examine ocular signs, symptoms, and results of tear analysis in patients with cutaneous rosacea before, during, and after doxycycline therapy. DESIGN: Before-after trial. SETTING: General community. PATIENTS OR OTHER PARTICIPANTS: Thirty-nine patients with cutaneous rosacea underwent dermatologic and ocular examinations, testing of tear break-up time, and Schirmer testing at baseline and 4, 8, and 12 weeks. Six patients did not complete the study. Baseline tear break-up time and results of Schirmer test were compared with those of 13 patients without rosacea who were matched for age and sex. INTERVENTION: Patients with rosacea were given doxycycline, 100 mg daily for 12 weeks. MAIN OUTCOME MEASURE: Statistically significant (P, .05) improvement in tear break-up time. RESULT: The most frequent ocular symptoms were dryness, itching, blurred vision, and photosensitivity, all of which improved significantly with treatment. All patients had signs of ocular disease, most commonly erythema and telangiectasia, meibomian gland dysfunction, and ciliary base injection. Significant improvement (P,.05) for scales, erythema and telangiectasia, ciliary base injection, bulbar injection, papillary hypertrophy, and punctate epithelial erosions was seen. Average tear break-up time for the patients with rosacea was 5.7 seconds, which improved to 10.8 seconds after 12 weeks of treatment (P = .007). Baseline tear break-up time was significantly lower than for the comparison group of normal subjects (P = .001). There was no correlation between severity of cutaneous disease and ocular disease. CONCLUSIONS: All patients with cutaneous rosacea had some degree of ocular involvement. Tear break-up time is abnormal in patients with rosacea. Ocular erythema and telangiectasia, meibomian gland dysfunction, and short tear break-up time in patients with cutaneous rosacea are indicators of ocular rosacea. Doxycycline, 100 mg daily, will improve ocular disease and increase the tear break-up time.

Adult↗

Infectious posterior scleritis caused by Pseudallescheria boydii. Clinicopathologic findings.

PURPOSE: The purpose of the study is to describe an unusual case of infectious posterior scleritis after excision of a pterygium. METHODS: The case history of a patient in whom anterior and posterior scleritis developed after excision of a pterygium is reviewed. Histopathologic findings are presented. RESULTS: Pathologic examination results of a scleral biopsy site and the eye showed extensive involvement of the posterior sclera with fungi that on culture grew Pseudallescheria boydii. The development of posterior scleral thickening and intrascleral abscesses gave the clinical impression of autoimmune posterior scleritis or possible tumor. Ultrasonography and computed tomography scan of the eye and orbit proved particularly helpful in following progression of scleral involvement. CONCLUSIONS: Pseudallescheria boydii is capable of causing an infectious posterior scleritis, which can mimic autoimmune posterior scleritis. The use of systemic immunosuppressive agents contributed to this unusual clinical presentation. Progression of posterior scleritis in the face of apparent adequate immunosuppressive therapy always should suggest the possibility of tumor or infection.

Aged↗

Human renal fibroblasts modulate proximal tubule cell growth and transport via the IGF-I axis.

To determine the paracrine interactions involved in the tubulointerstitial response to progressive renal disease, the role of insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBPs) in in vitro interactions between human proximal tubule cells (PTC) and renal cortical fibroblasts (CF) were studied in primary cell culture. PTC growth and transport were increased in the presence of CF-conditioned media (CF-CM), as shown by increased thymidine incorporation, cellular protein content and sodium-hydrogen exchange (NHE) activity, to 185 +/- 31% (P < 0.01), 150 +/- 18% (P < 0.05) and 195 +/- 27% (P < 0.01) of the control values, respectively. IGF-I was produced by cultured CF at a rate of 64.6 +/- 7.5 ng/mg protein/day. Exogenous IGF-I applied to PTC provoked similar enhancement of growth and NHE activity as CF-CM and the stimulatory effect of CF-CM was blocked by specific immunoneutralization of IGF-I receptors. These receptors were threefold more abundant on PTC basolateral versus apical membranes. IGF binding proteins (IGFBP)-2 and IGFBP-3 were secreted by CF at rates of 694 +/- 88 and 1769 +/- 45 ng/mg/day, with the release of IGFBP-3 being enhanced in the presence of PTC-CM (120.0 +/- 9.7% of control, P < 0.01). Moreover, the addition of CF-CM to PTC increased cell-associated IGFBP-3 on PTC surfaces, without changes in IGF-I receptor numbers or affinity and without changes in PTC mRNA for IGFBP-3. Des(1-3)IGF-I, an analog that binds to the IGF-I receptor but not to IGFBPs, provided a less potent stimulus for PTC growth compared with IGF-I, indicating that cell-associated IGFBP-3 facilitates the action of IGF-I on PTC. The results support important paracrine roles for both IGF-I and IGFBPs in the interstitial regulation of proximal tubule growth and transport.

Antibodies↗

Using cooperative learning to enhance the academic and social experiences of freshman student athletes.

One hundred seven freshman student athletes in 17 different women's and men's intercollegiate sports were required to attend evening study sessions. The student athletes completed academic assignments and studied for tests primarily in cooperative learning groups. As gauges of the program's impact on the participants, 3 questionnaires were administered to a sample of 50 (25 women and 25 men). The respondents reported that (a) they worked cooperatively on academic assignments, (b) the program staff provided both academic and personal support while structuring and facilitating cooperative learning groups, and (c) they themselves were highly task oriented, confident of their academic ability, and involved in positive and supportive relationships with their fellow participants.

Achievement↗

The activin receptor-like kinase 1 gene: genomic structure and mutations in hereditary hemorrhagic telangiectasia type 2.

The activin receptor-like kinase 1 gene (ALK-1) is the second locus for the autosomal dominant vascular disease hereditary hemorrhagic telangiectasia (HHT). In this paper we present the genomic structure of the ALK-1 gene, a type I serine-threonine kinase receptor expressed predominantly in endothelial cells. The coding region is contained within nine exons, spanning < 15 kb of genomic DNA. All introns follow the GT-AG rule, except for intron 6, which has a TAG/gcaag 5' splice junction. The positions of introns in the intracellular domain are almost identical to those of the mouse serine-threonine kinase receptor TSK-7L. By sequencing ALK-1 from genomic DNA, mutations were found in six of six families with HHT either shown to link to chromosome 12q13 or in which linkage of HHT to chromosome 9q33 had been excluded. Mutations were also found in three of six patients from families in which available linkage data were insufficient to allow certainty with regard to the locus involved. The high rate of detection of mutations by genomic sequencing of ALK-1 suggests that this will be a useful diagnostic test for HHT2, particularly where preliminary linkage to chromosome 12q13 can be established. In two cases in which premature termination codons were found in genomic DNA, the mutant mRNA was either not present or present at barely detectable levels. These data suggest that mutations in ALK-1 are functionally null alleles.

Activin Receptors↗

Insulin-like growth factor I stimulates apical sodium/hydrogen exchange in human proximal tubule cells.

To determine whether insulin-like growth factor I (IGF-I) stimulated apical sodium/hydrogen exchange (NHE), confluent primary human proximal tubule cells (PTC) were incubated for 48 h in serum-free media in the presence or absence of 100 ng/ml IGF-I. Cells incubated in IGF-I demonstrated significant increases in thymidine incorporation (181.2 +/- 30.3% of control values; n = 12, P = 0.01) and in resting intracellular pH (pHi) (7.52 +/- 0.08 vs. 7.30 +/- 0.06; n = 20, P < 0.05), as determined by 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein quantitative microspectrofluorometry. Following intracellular acid loading, ethylisopropylamiloride (EIPA)-inhibitable H+ efflux and 22Na+ influx after 1 min were both significantly enhanced in IGF-I-treated cells compared with controls (8.78 +/- 1.69 vs. 3.03 +/- 0.72 mM/min and 3.47 +/- 0.49 vs. 1.55 +/- 0.35 nmol x mg protein(-1) x min(-1), respectively). 22Na+ uptake studies in PTC grown on permeable supports demonstrated preferential stimulation of apical vs. basolateral NHE. The 50% inhibitory concentrations (IC50) in IGF-I-treated and control cells for EIPA (0.5 and 1.1 microM, respectively) and for HOE-694 (4.0 and 10.0 microM, respectively) were also consistent with predominant activation of apical, rather than basolateral, NHE activity. Kinetic analysis revealed an increase in maximal transport velocity (Vmax, 15.50 +/- 1.50 vs. 7.26 +/- 3.07 mM/min; n = 10, P < 0.05), without a significant change in antiporter affinity for extracellular Na+. Incubation of PTC with 100 ng/ml IGF-I produced an acute, reversible, and EIPA-inhibitable pHi increase of 0.05 +/- 0.01 pH units (n = 5, P < 0.05). The results suggest that IGF-I may contribute to the metachronous stimulation of apical NHE and PTC growth observed in many physiological and pathological conditions involving the human kidney.

Adult↗

Studies on the mechanism of phosphatidylinositol 3-kinase inhibition by wortmannin and related analogs.

Wortmannin, a fungal metabolite, was identified as a potent inhibitor (IC50 = 4.2 nM) of phosphatidylinositol 3-kinase (PI 3-kinase). Due to the importance of PI 3-kinase in several intracellular signaling pathways, structure-activities studies on wortmannin analogs were performed in an effort to understand the structural requirements necessary for PI 3-kinase inhibition. Since wortmannin is an irreversible inhibitor of PI 3-kinase, it was postulated that covalent attachment at the electrophilic C-21 site was a possible mode of action for PI 3-kinase inhibition. We have prepared various wortmannin analogs which address the possibility of this mechanism. Of particular interest are compounds which affect the C-21 position of wortaminnin either sterically or electronically. Our results support the conclusion that nucleophilic addition by the kinase onto the C-21 position of wortmannin is required for inhibition of PI 3-kinase by wortmannin analogs. Additionally, we have prepared several D-ring analogs of wortmannin, and their activities are reported herein. We conclude that the wortmannin D ring is an important recognition site since modifications have such a dramatic effect on inhibitor potency. Finally, the identification of 17beta-hydroxywortmannin represents the first reported subnanomolar inhibitor of PI 3-kinase. These studies, along with in vivo antitumor experiments, suggest that the mechanism of PI 3-kinase inhibition correlates to the associated toxicity observed with wortmannin-based inhibitors of PI 3-kinase.

Androstadienes↗

Outpatient treatment of croup with nebulized dexamethasone.

PURPOSE: To determine if treating children who have acute, moderate croup with nebulized dexamethasone sodium phosphate in the emergency department results in clinical improvement by 4 hours and a decrease in the hospitalization rate. DESIGN: Randomized, double-blind, placebo controlled trial. SETTING: Emergency department, children's hospital. PATIENTS: Fifty-five children with croup who were in moderate respiratory distress after treatment with mist for 30 minutes who met inclusion and exclusion criteria. MEASUREMENTS: Croup score, respiratory rate, heart rate, and oxygen saturation were assessed by one of us (D.W.J. or S.S.) before treatment and 2 and 4 hours after treatment. A staff pediatrician or senior pediatric resident, also "blind" to treatment, decided on admission to or discharge from the hospital. The differences between groups for change in croup score and hospitalization rate after treatment were analyzed. RESULTS: Evaluation of the croup scores disclosed a significant improvement in the dexamethasone-treated group compared with the placebo group at 4 hours (P=.005, Mann-Whitney U). However, the hospitalization rate was not statistically different at the end of treatment (33% vs 52%, P=.28) or after 24 hours (48% vs 60%, P=.56, Yates corrected chi(2)). Our study has 80% power to detect a two-thirds reduction in hospitalization rate. Two patients with neutropenia treated with dexamethasone had a clinical course consistent with bacterial tracheitis. CONCLUSIONS: Treatment of moderate croup with nebulized dexamethasone results in clinical improvement within 4 hours. We did not show a decrease in hospitalization rates, although our sample size was only large enough to detect a 67% reduction in the rate of hospitalization. Given the infectious complications and the absence of evidence for a sustained clinical effect, we do not recommend that patients with croup be treated with nebulized dexamethasone.

Acute Disease↗

Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2.

Hereditary haemorrhagic telangiectasia, or Osler-Rendu-Weber (ORW) syndrome, is an autosomal dominant vascular dysplasia. So far, two loci have been demonstrated for ORW. Linkage studies established an ORW locus at chromosome 9q3; endoglin was subsequently identified as the ORW1 gene. A second locus, designated ORW2, was mapped to chromosome 12. Here we report a new 4 cM interval for ORW2 that does not overlap with any previously defined. A 1.38-Mb YAC contig spans the entire interval. It includes the activin receptor like kinase 1 gene (ACVRLK1 or ALK1), a member of the serine-threonine kinase receptor family expressed in endothelium. We report three mutations in the coding sequence of the ALK1 gene in those families which show linkage of the ORW phenotype to chromosome 12. Our data suggest a critical role for ALK1 in the control of blood vessel development or repair.

Activin Receptors↗

Cooperative learning and peer acceptance of students with learning disabilities.

The effects of cooperative learning on 417 regular-education students, acceptance of 41 of their special-education classmates were examined in an 8-month study. The participants were in Grades 5-8 in 21 classes in 2 U.S. schools. The 3 conditions were cooperative learning and competitive learning, taught by the same teachers, and competitive learning, taught by a random sample of teachers. In October and in May, the regular-education students rated each classmate's desirability as a work partner. The students' peer ratings were generally very stable, for both their regular-education classmates and their special-education classmates. Positive changes in peer ratings for both types of classmates occurred more frequently in the cooperative-learning condition than in the competitive-learning conditions.

Adolescent↗

Impact of a gonorrhea control program, including selective mass treatment, in female sex workers.

A gonorrhea control program initiated in 1967 in registered female sex workers (FSWs) in the Philippines involved weekly endocervical cultures for Neisseria gonorrhoeae, with treatment of FSWs found infected or named as contacts by US Navy servicemen. Gonorrhea prevalence in FSWs in Olongapo city fell from 11.9% to 4.0% within 4 months, and gonorrhea incidence in servicemen at nearby Subic Bay fell by half. Selective mass treatment (SMT) with oral ampicillin-probenecid or tetracycline was then given to registered FSWs in an attempt to further reduce gonorrhea rates. N. gonorrhoeae was isolated from 105 (4.0%) of 2640 FSWs before SMT and from 43 (1.6%) 1 week later (P < .001). However, gonorrhea incidence among servicemen fell no lower, and gonorrhea prevalence in FSWs quickly returned to higher levels. Thus, after implementation of weekly screening and treatment of FSWs found infected or named as contacts, SMT of FSWs (without increasing condom use or treating regular partners) contributed nothing further to gonorrhea control.

Female↗

Monitoring of extracellular and total body water during haemodialysis using multifrequency bio-electrical impedance analysis.

Multifrequency bio-electrical impedance analysis (MFBIA) was evaluated as a technique for monitoring changes in extracellular and total body water (ECW and TBW, respectively) of 15 subjects during dialysis. Dilution analysis, using deuterium oxide and sodium bromide, was also performed on each subject before dialysis so that prediction equations for ECW and TBW based on the MFBIA measures could be developed. These prediction equations were then used to estimate water compartment volume changes during dialysis and compared with volumetric measures of the dialysate removed. The results show that MFBIA does not accurately measure ECW and TBW changes during dialysis. The MFBIA measures tend to overestimate the changes and are not sufficiently precise to be clinically useful.

Adult↗

Take two classes and call me in the morning: the case for training wellness.

The purpose of this article is to show how a well-conducted needs assessment coupled with a well-conceived training plan can improve training and, indeed, total organizational wellness. This is important on two fronts--organizational and individual. Conceptually, providing training is not much different than providing any other product or service. We often have no idea of how to get the ¿right stuff to the right people at the right time under the right conditions.¿ Thus, this article will provide a framework for ¿getting it right¿ (the first time)! The message? Make your training time and dollars count, no training simply for the sake of training; we must apply it to the training wellness equation.

Decision Making, Organizational↗

A randomized trial comparing 1.25 mmol/l calcium dialysate to 1.75 mmol/l calcium dialysate in CAPD patients.

BACKGROUND: Effective control of hyperparathyroidism and renal osteodystrophy in CAPD patients requires a combination of calcitriol and calcium carbonate (CaCO3), but is frequently limited by hypercalcaemia. Reducing dialysate calcium (Ca) concentration may overcome this problem, but had not been examined in a controlled trial. METHODS: 45 stable CAPD patients were randomly assigned in a prospective double-blind trial to either a study group (1.25 mmol/l Ca dialysate) or a control group (1.75 mmol/l Ca dialysate) for 12 months. Clinical, biochemical and radiological parameters of secondary hyperparathyroidism were followed. RESULTS: Twenty-three patients did not complete the study due to death (9), transplantation (7) or conversion to haemodialysis (7). Eleven patients in each group completed the study. Mean serum Ca, phosphate, ionized Ca, aluminium, alkaline phosphatase (AP), and bone mineral density (BMD) Z-scores did not differ significantly at any time within or between the two groups. Severe hypercalcaemia was more common in the control group (11 vs. 2, P = 0.027). Mean serum intact parathyroid hormone (PTH) and osteocalcin (OCN) initially rose in the study group relative to controls at 3 months (40 +/- 7 vs 12 +/- 3 pmol/l, P = 0.004, and 33 +/- 5 vs 15 +/- 2 micrograms/l, P = 0.002 respectively), but were not sustained. Median weekly dosages of calcitriol and daily dosages of CaCO3 increased significantly in the study group (O microgram to 1 microgram P = 0.014 and 1260 mg to 2520 mg P = 0.002 respectively), but not in the control group. Supplementary aluminium hydroxide (A1, (OH)3) was required for phosphate control in both study (n = 5) and control patients (n = 4). CONCLUSIONS: Lowering dialysate calcium concentration reduced the frequency of severe hypercalcaemia and allowed prescription of larger quantities of calcitriol and CaCO3. However, in this study it offered no advantage in terms of A1(OH)3 requirement, while bone mass density did and may have initially exacerbated secondary hyperparathyroidism not change.

Aluminum Hydroxide↗

Percutaneous biopsy of the thoracic spine.

Percutaneous biopsy of the thoracic spine has become the procedure of choice for biopsy of the thoracic spine. Familiarity with triangulation and using biplane fluoroscopy or the CT scan is a requirement, however. Once these techniques have been mastered, biopsy of the thoracic spine is safe and effective for obtaining diagnostic tissue and only under rare circumstances is opened biopsy necessary. The technique is described as is a review of the results.

Biopsy, Needle↗