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Biomedical subjects

K Johnson

Publications and source records attributed to K Johnson.

At least 217 records · Page 12Linked to original sources

A randomized controlled prospective outcome study of a psychological and pharmacological intervention protocol for procedural distress in pediatric leukemia.

Evaluated distress during invasive procedures in childhood leukemia. Child and parent distress, assessed by questionnaires and ratings, were compared in two arms of a randomized, controlled prospective study, one a pharmacologic only (PO) (n = 45) and the other a combined pharmacologic and psychological intervention (Cl) (n = 47), at 1, 2, and 6 months after diagnosis. The cross-sectional control group (CC) consisted of parents of 70 patients in first remission prior to the prospective study. Mothers' and nurses' ratings of child distress indicated less child distress in the Cl group than the PO. When contrasted with the CC group, the Cl group showed lower levels of child distress. Data showed decreases over time in distress and concurrent improvements in quality of life and parenting stress and supported an inverse association between distress and child age.

Adaptation, Psychological↗

Evaluation of gas exchange, pulmonary compliance, and lung injury during total and partial liquid ventilation in the acute respiratory distress syndrome.

OBJECTIVE: To investigate whether pulmonary compliance and gas exchange will be sustained during "total" perfluorocarbon liquid ventilation followed by "partial" perfluorocarbon liquid ventilation when compared with gas ventilation in the setting of the acute respiratory distress syndrome (ARDS). STUDY DESIGN: A prospective, controlled, laboratory study. SETTING: A university research laboratory. SUBJECTS: Ten sheep, weighing 12.7 to 25.0 kg. INTERVENTIONS: Lung injury was induced in ten young sheep, utilizing a right atrial injection of 0.07 mL/kg of oleic acid followed by saline pulmonary lavage. Bijugular venovenous extracorporeal life support access, a pulmonary artery catheter, and a carotid artery catheter were placed. When the alveolar-arterial O2 gradient was >/= 600 torr and PaO2 </= 50 torr (</= 6.7 kPa) with an FIO2 of 1.0, extracorporeal life support was instituted. For the first 30 mins on extracorporeal life support, all animals were ventilated with gas. Animals were then ventilated with equal tidal volumes of 15 mL/kg during gas ventilation (n=5) over the ensuing 2.5 hrs, or with total liquid ventilation for 1 hr, followed by partial liquid ventilation for 1.5 hrs (total/partial liquid ventilation, n=5). MEASUREMENTS AND MAIN RESULTS: An increase in physiologic shunt (gas ventilation = 69 +/- 11%, total/partial liquid ventilation = 71 +/- 3%) and a decrease in static total pulmonary compliance measured at 20 mL/kg inflation volume (gas ventilation = O.48 +/- 0.03 mL/cm H2O/kg, total/partial liquid ventilation = 0.50 +/- 0.17 mL/cm H2O/kg) were observed in both groups with induction of lung injury. Physiologic shunt was significantly reduced during total and partial liquid ventilation when compared with physiologic shunt observed in the gas ventilation animals (gas ventilation = 93 +/- 8%, total liquid ventilation = 45 +/- 11%, p<.001; gas ventilation = 95 +/- 3%, partial liquid ventilation = 61 +/- 12%, p<.001), while static compliance was significantly increased in the total, but not the partial liquid ventilated animals when compared with the gas ventilated group (gas ventilation = 0.43 +/- 0.03 mL/cm H2O/kg, total liquid ventilation = 1.13 +/- 18 mL/cm H2O/kg, p <.001; gas ventilation = 0.41 +/- 0.02 mL/cm H2O/kg, partial liquid ventilation = 0.47 +/- 0.08, p = .151). In addition, the extracorporeal life support flow rate required to maintain adequate oxygenation was significantly lower in the total/partial liquid ventilation group when compared with that of the gas ventilation group (gas ventilation = 89 +/- 7 mL/kg/min, total liquid ventilation = 22 +/- 10 mL/kg/min, p <.001; gas ventilation = 91 +/- 12 mL/kg/min, partial liquid ventilation = 41 +/- 11 mL/kg/min, p < .001). Lung biopsy light microscopy demonstrated a marked reduction in alveolar hemorrhage, lung fluid accumulation, and inflammatory infiltration in the total/partial liquid ventilation animals when compared with the gas ventilation animals. CONCLUSIONS: In a model of severe ARDS, pulmonary gas exchange is improved during total followed by partial liquid ventilation. Pulmonary compliance is improved during total, but not during partial liquid ventilation. Total followed by partial liquid ventilation was associated with a reduction in alveolar hemorrhage, pulmonary edema, and lung inflammatory infiltration.

Animals↗

Case study: risperidone treatment of children and adolescents with developmental disorders.

In a clinical trial, 20 children and adolescents with developmental disorders (age range 8 through 17 years) refractory to previous psychotropic treatments were administered the atypical neuroleptic risperidone (dose range 1.5 to 10 mg/day). In a follow-up period ranging from 8 to 15 months, risperidone demonstrated clinical efficacy in 13 children. Twelve patients were free of side effects and two had minor ones. Three patients had marked weight increase, and galactorrhea developed in two adolescent girls. In this open study, risperidone was associated with clinical improvement. However, controlled studies are needed to determine its relative efficacy and safety in this special population.

Adolescent↗

Perfluorocarbon protects lung epithelial cells from neutrophil-mediated injury in an in vitro model of liquid ventilation therapy.

Liquid ventilation with perfluorocarbon has been effective in improving gas exchange and pulmonary function in the setting of acute respiratory failure. How improvement is brought about remains unknown. In the present study, we examined perfluorocarbon for effects on neutrophil function and for effects on neutrophil-epithelial cell interactions that could underlie its in vivo activity. Exposure of neutrophils in vitro to perfluorocarbon followed by washing did not interfere with their ability to generate oxidants or release proteolytic enzymes upon subsequent stimulation. Likewise, such treatment did not interfere with subsequent adhesion of the neutrophils to monolayers of epithelial cells or with neutrophil-induced injury to these cells. In contrast, when perfluorocarbon was added to neutrophils and epithelial cells together and the neutrophils then stimulated, it reduced their adhesive interaction with the target cells and concomitantly reduced target cell injury. In companion studies, cells were obtained by bronchial lavage of perfluorocarbon-treated patients with acute respiratory distress syndrome (ARDS) and analyzed for oxidant production. Oxidant-generating capacity by the cells obtained from the bronchial lavage fluid was similar to that of peripheral blood neutrophils. These data are consistent with the suggestion that perfluorocarbon protects cells in vitro from neutrophil-mediated injury, at least in part, by acting as a mechanical barrier. These findings are consistent with a potential mechanism of action in vivo.

Bronchoalveolar Lavage Fluid↗

X-linked exudative vitreoretinopathy caused by an arginine to leucine substitution (R121L) in the Norrie disease protein.

We report the cosegregation of an arginine to leucine substitution at position 121 of the Norrie disease protein in a large kindred where exudative vitreoretinopathy segregates as an X-linked recessive trait. The clinical phenotype and rate of disease progression were extremely variable, with progression to total retinal detachment from less than age 2 years to more than 21 years. To date, all mutations in X-linked vitreoretinopathy have been missense mutations, presumably not affecting the three-dimensional structure of the NDP gene product, and clustered around residues 121-126 of the Norrie protein. This contrasts with the diversity of mutations seen in the more severe, allelic Norrie disease.

Arginine↗

Long-term cyclosporine therapy for pediatric nephrotic syndrome: a clinical and histologic analysis.

Cyclosporine (CsA) is effective in treating steroid-dependent (SDNS) and steroid-resistant (SRNS) nephrotic syndrome (NS) in children, but because of the potential for chronic nephrotoxicity, its long-term use is controversial. This study reports the results of long-term CsA treatment in 22 children with idiopathic NS. Indications for treatment included SDNS (N = 7) and SRNS (N = 15) children. Pre-CsA histology showed minimal change disease in three patients, immunoglobulin M nephropathy (IgM) in 14 patients, and focal segmental glomerulosclerosis (FSGS) in five patients. All patients had normal initial serum creatinine values. CsA was added to prednisone at 6.3 +/- 0.4 mg/kg per day (mean +/- SE) and adjusted to maintain whole blood trough HPLC levels of 70 to 120 ng/mL for a period of 6 to 53 months (mean, 22 months). Analysis by clinical course revealed that 13 of 15 patients with SRNS (87%) entered remission after a mean duration of CsA treatment of 58 days, whereas seven of seven patients with SDNS were able to be weaned off of daily prednisone therapy. Histologic analysis showed that all five patients with FSGS and 13 of 14 patients with IgM nephropathy either entered remission or were weaned off of daily steroids. Ten of the 22 patients (45%) with complete remission required CsA plus low-dose alternate-day prednisone to maintain remission. Hypertension was seen in eight of 22 patients (36%). No patient had a significant increase in serum creatinine concentration. Renal biopsies performed in 12 patients after 12 to 41 months (mean, 21 months) of CsA therapy showed no nephrotoxicity or disease progression in ten patients. Progression of the previous interstitial fibrosis and tubular atrophy was noted in two patients, suggesting a 17% incidence of CsA nephrotoxicity. This analysis of the long-term risks and benefits of CsA for childhood NS has identified two important findings: (1) combined CsA and alternate-day steroids can be highly effective in inducing complete remission in patients with SRNS and biopsy-proven IgM nephropathy, and (2) long-term use of CsA in moderate doses with closely monitored levels can result in a relatively low incidence of nephrotoxicity.

Adolescent↗

Involvement of the ventral tegmental area in locomotion elicited from the nucleus accumbens or ventral pallidum.

This study was designed to evaluate the role of the circuit containing the nucleus accumbens, ventral pallidum (VP) and ventral tegmental area (VTA) in the motor stimulation produced by the microinjection of dopamine, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) or [D-Ala2, MePhe4,Gly-ol5]enkephalin (DAMGO) into VP or the shell and core compartments of the nucleus accumbens. Initial dose-response curves revealed that dopamine was approximately equipotent at producing motor activity after microinjection into the core and shell, AMPA was more effective in the core, whereas DAMGO was more potent in the shell. A role for the VTA in the motor responses elicited by dopamine, AMPA or DAMGO microinjection into the shell, core or VP was evaluated by microinjecting the tau-aminobutyric acidB agonist baclofen into the VTA to inhibit neuronal activity. Baclofen treatment abolished the motor responses elicited by AMPA from the shell, core and VP. The motor effect of DAMGO in the VP was abolished by baclofen, whereas the response in the shell was attenuated. The motor response to dopamine was unaltered by baclofen, regardless of the injection site. These data indicate that there exist differences between the core and shell of the nucleus accumbens in the capacity of neurotransmitter analogs to elicit motor activity, and that although AMPA-induced motor activity is dependent upon neurotransmission in the VTA after microinjection into the core, shell and VP, DAMGO-induced locomotion only requires such tone after microinjection into the VP and shell.

Animals↗

All-trans retinoic acid reduces membrane fluidity of human dermal fibroblasts. Assessment by fluorescence redistribution after photobleaching.

All-trans retinoic acid (RA) preserves human dermal fibroblast viability and stimulates proliferation in vitro. These effects are mediated, at least in part, by reducing the extracellular Ca2+ requirement. The same concentrations of RA that reduce the extracellular Ca2+ requirement also interrupt movement of Ca 2+ across the fibroblast plasma membrane. Based on these observations, we have examined the effects of RA on membrane properties that could influence Ca2+ movement. Fibroblasts were labeled with 1-acyl-2-(N-4- nitrobenzo-2-oxa-1,3 diazole)-amino-caproyl phosphatidyl-choline (a fluorescent phospholipid analogue) and examined for fluorescence redistribution after photobleaching (FRAP) with a pulse of intense light as a measure of membrane fluidity. Using this approach, we observed that membrane fluidity was higher when the cells were incubated in medium containing a low (sub-optimal) level of extracellular Ca2+ (0.15 mmol/L) than in a medium containing an optimal concentration (1.4 mmol/L). Treatment of the cells with 3 micromol/L RA reduced membrane fluidity of the cells under both high- and low-Ca2+ conditions. These findings demonstrate that RA has a direct effect on the plasma membrane of human dermal fibroblasts. This provides a possible mechanism for the previously identified inhibition of Ca2+ movement across the membrane of the same cells and for the previously identified protective effects against lysis under low-Ca2+ conditions.

Calcium↗

Dermatofibrosarcoma protuberans of the vulva. A case report.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous malignancy that is uncommon anywhere on the body but is especially uncommon on the vulva. This cancer rarely metastasizes but has a high incidence of local recurrence because of its tendency to grow in fingerlike projections away from the primary tumor. CASE: A 36-year-old, black woman was the 10th and youngest patient with DFSP of the vulva to be reported. Treatment of the 5-cm, mobile, well-circumscribed lesion consisted of local excision. Several adjacent microscopic lesions showing DFSP were found in the pathologic specimen, however, so an even wider excision was performed. Twenty-seven months following removal, there was no evidence of recurrence. CONCLUSION: Survival rates for DFSP of the skin range from 91% to 100% in reported series, but local recurrence rates of 20-49% have also been noted. The reported deaths from the disease have resulted from extensive local spread due to inadequate excision and, only rarely, metastases. Because DFSP tends to spread to microscopic projections away from the visible lesions, very wide local excision is required for tumor control.

Adult↗

Efficacy assessment in trials of combination therapy for rheumatoid arthritis.

The comparison of a combination disease modifying antirheumatic drug (DMARD) regimen with a single DMARD, or one combination with another, raises the same issues encountered when studying rheumatoid arthritis: how to design, conduct, and analyze randomized controlled trials. However, these claims of comparison are unique in that the setting to show primary efficacy is the same as that showing the primary therapeutic placement relative to standard therapy. Ordinarily standard therapy is not determined prior to approval. Accordingly, any combination DMARD trial presupposes agreement on what constitutes standard therapy and, if the intent is to show equivalence, on what (small) difference can be condoned to grant the claim. I address some important considerations regarding the rigor and credibility of designs for these claims, problems far less significant with simple drug vs placebo strategies. These can be grouped into 3 categories: (1) choice of controls/designs/patients to ensure a fair comparison; (2) sufficiently broad design formulations to yield controlled assessments of safety that are as thorough as those for efficacy in the past, and (3) maintaining blinding despite new design features that threaten it.

Antirheumatic Agents↗

Multidisciplinary discharge planning: developing a process.

In today's health care environment, Frankford Health Care System identified the need for a discharge planning process. A multidisciplinary task force developed and implemented a system that decreased length of stay and duplication of services, improved timeliness of intervention and fostered communication and respect among team members. The process included assessment of patient/family needs and coordination of care, services and referrals for all patients.

Continuity of Patient Care↗

Application of two-dimensional total correlation spectroscopy for structure determination of individual inositol phosphates in a mixture.

The discovery of the second messenger role of myoinositol (1,4,5)trisphosphate has triggered tremendous interest in investigating the structures and metabolism of inositol phosphates. The structures of these compounds are established by first purifying the compounds of interest and then identifying the structures through chemical degradation or NMR analysis. In this paper we describe a method that allows simultaneous determination, without separation, of the structures of multiple inositol phosphates in a mixture. The use of two-dimensional total correlation spectroscopy (2D TOCSY) experiments together with subspectra extracted from 2D TOCSY data allowed us to determine, in 3 to 4 h, the structures of five compounds in a mixture, without prior separation.

6-Phytase↗

How one hospital association became the Healthcare Forum. Interview by Terese Hudson.

In 1987, the Association of Western Hospitals, a San Francisco-based educational organization became the Healthcare Forum, directed at improving the leadership skills of senior management teams. More recently, the organization has put an emphasis on training leaders in methods to make their communities healthier. While the Forum has fewer members than it did as a 13-state association, they are more far-flung: members reside in all 50 states and 38 counties. Forum CEO Kathryn Johnson told senior writer Terese Hudson about how and why the group reinvented itself.

California↗