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Biomedical subjects

J Johnston

Publications and source records attributed to J Johnston.

At least 91 records · Page 5Linked to original sources
PubMed1997

Radiation therapy for rhabdomyosarcoma: local failure risk for Clinical Group III patients on Intergroup Rhabdomyosarcoma Study II.

PURPOSE: A subset of 362 pediatric patients with rhabdomyosarcoma was selected from a total of 532 eligible IRS-II patients in Clinical Group III to assess the local and regional failure rates following radiotherapy and to determine patient, tumor, and treatment factors contributing to the risk for local and regional failure. METHODS AND MATERIALS: The study population was selected from all eligible IRS-II Clinical Group III patients. Excluded patients were those with "special pelvic" primary sites whose protocol management restricted radiotherapy (n = 123), and those who were removed from the study before radiotherapy was to begin, or because it was omitted (n = 47). A binary recursive partitioning model was used to identify subgroups of the remaining 362 patients at risk of local or regional failure. RESULTS: The local (only) failure rate was 17% (95% confidence interval, 13-21%), and the local (all) failure rate was 20% (95% confidence interval, 16-24%). The 5-year actuarial risk of local (all) failure was 22% (95% confidence interval, 18-27%). The risk of regional (nodal) failure was between 2% and 23%. Increasing tumor size predicted an increased local failure risk. Primary tumors located above the clavicle had a reduced risk of local failure. The binary recursive partitioning model identified a subset of patients at high risk of local failure. Those patients had primary tumors in the chest, pelvic region, extremity, or trunk, or tumors > 10 cm in diameter. Their local failure rate was 35% (compared to 15% for the remaining patients). The subset of patients at high risk for regional (nodal) failure had node involvement at diagnosis and a primary tumor originating at a site other than orbit, parameningeal, or trunk. Compliance with radiation treatment guidelines approached but did not achieve statistical significance as a predictive factor for local failure. By univariate analysis, factors not influencing local failure risk were age, race, gender, adenopathy, and histology. CONCLUSION: Radiation therapy and chemotherapy administered to Clinical Group III patients entered into the IRS-II protocol produced sustained local control in most cases. Knowledge of the factors which predict an increased risk of local or regional failure will facilitate the design of new treatment strategies.

Adult↗
PubMed1997

Origin of respiratory sinus arrhythmia in conscious humans. An important role for arterial carotid baroreceptors.

BACKGROUND: We investigated whether respiratory sinus arrhythmia (RSA) in healthy humans originated from central neuronal oscillations or from peripheral baroreceptors responding to respiratory changes in venous return. METHODS AND RESULTS: During subjects' controlled breathing we used sinusoidal neck suction to influence RSA (spectral analysis of RR interval). In 11 subjects, 20-second apnea greatly reduced RSA, which was restored by neck suction at the frequency of respiration. Counteracting the respiration-induced cycles of carotid blood pressure decreased RSA in 13 subjects (from 2136 +/- 682 to 1372 +/- 561 ms2, P < .01). The critical phase of this neck suction was constant for each subject at around the phase shift (with regard to respiration-related fluctuations of blood pressure) best for smoothing respiratory (mechanical) changes in blood pressure. Suction of a non-baroreceptor area (the thigh) did not affect RSA. In 4 subjects, to separate the effects of peripheral baroreceptor afferents from respiration-entrained central oscillation (15 breaths/min), we cycled the neck suction at 12 cycles/min. Increasing neck suction from -7 to -30 mm Hg increased the ratio of the power of the 12 cycles compared with the 15-cycle RSA oscillation in RR interval spectral analysis from 0.26 to 2.57. A 12-cycle/min suction of an area other than the neck had little effect on the RR interval spectrum. CONCLUSIONS: RSA can be mimicked or reduced by stimulation of arterial baroreceptors with cycles of appropriately phased neck suction at the frequency of respiration. This suggests an important influence of the arterial baroreceptors in the generation of RSA in conscious humans.

Adult↗
PubMed1997

Left ventricular hypertrophy in hypertensive patients is associated with abnormal rate adaptation of QT interval.

OBJECTIVES: This study sought to examine whether the responses of the QT interval to changes in the heart rate were altered in left ventricular hypertrophy (LVH). BACKGROUND: The QT interval has been shown to have a delayed adaptation to sudden changes in heart rate in normal subjects. Abnormalities in the adaptation of the QT interval to changes in the RR interval may facilitate the development of ventricular arrhythmias. METHODS: Consecutive newly diagnosed hypertensive subjects, not taking any medications, were age and gender matched for LVH (n = 21) versus on LVH (n = 16). QT interval dynamics were analyzed under visual control using a validated algorithm with automatic QT measurements at the end of the T wave. A computerized Holter system was developed to study the QT interval response to changes in the RR interval. The adaptive response of the QT interval was measured as the ratio of the slope from 10% to 90% of the QT change relative to the RR interval change (dQT/dRR10-90). Steady state adaptation was also studied as the percent shortening and lengthening of the QT interval during acceleration and deceleration of heart rate. RESULTS: The adaptive response of the QT interval measured as dQT/dRR10-90 was increased in the LVH group compared with that in the control subjects during both acceleration (0.33 +/- 0.06 vs. 0.18 +/- 0.02, p = 0.02) and deceleration phases (0.23 +/- 0.04 vs. 0.16 +/- 0.02, p = 0.03). In the LVH group, the percent lengthening of the QT interval was greater (7.6 +/- 0.7 vs. 5.1 +/- 0.2, p = 0.03), whereas the percent shortening was not significantly different (5.71 +/- 0.5 vs. 4.6 +/- 0.3, p = 0.43), than that in control subjects. CONCLUSIONS: The QT interval response to changes in the RR interval is rapid and exaggerated in LVH. These abnormalities of the QT interval response demonstrate that there are altered repolarization dynamics in patients with LVH that may make them vulnerable to serious ventricular arrhythmias.

Adaptation, Physiological↗
PubMed1997

Evaluating a statewide partnership for reducing risks for chronic diseases.

We describe a case study evaluation of Kansas LEAN, a statewide partnership with the mission of reducing risks for chronic diseases through dietary and exercise modification. We used a case study design to examine five primary questions related to process and outcome: (a) were the goals of the partnership important to constituents? (process), (b) were constituents satisfied with the partnership (process), (c) were community or systems changes (new or modified programs, policies, or practices) facilitated by partnership efforts (outcome)?, (d) were these changes important to the partnership's mission (outcome)?, and (e) what critical events helped facilitate community changes (outcome)? several measurement instruments--a monitoring and feedback system, constituent surveys, and semistructured interviews--were used to address key evaluation questions. Kansas LEAN is a strong statewide partnership with involvement from key representatives throughout Kansas. It is an ongoing, comprehensive health promotion program that plans and implements multiple components, in a variety of settings, to create awareness, behavior change, and a supportive environment. Kansas LEAN has facilitated several important community or systems changes related to its mission. We conclude with a discussion of the challenges of evaluating partnerships that seek to reduce risks for chronic diseases.

Acute Disease↗
PubMed1997

Mutation characterization and genotype-phenotype correlation in Barth syndrome.

Barth syndrome is an X-linked cardiomyopathy with neutropenia and 3-methylglutaconic aciduria. Recently, mutations in the G4.5 gene, located in Xq28, have been described in four probands with Barth syndrome. We have now evaluated 14 Barth syndrome pedigrees for mutations in G4.5 and have identified unique mutations in all, including four splice-site mutations, three deletions, one insertion, five missense mutations, and one nonsense mutation. Nine of the 14 mutations are predicted to significantly disrupt the protein products of G4.5. The occurrence of missense mutations in exons 3 and 8 suggests that these exons encode essential portions of the G4. 5 proteins, whose functions remain unknown. We found no correlation between the location or type of mutation and any of the clinical or laboratory abnormalities of Barth syndrome, which suggests that additional factors modify the expression of the Barth phenotype. The characterization of mutations of the G4.5 gene will be useful for carrier detection, genetic counseling, and the identification of patients with Barth syndrome who do not manifest all of the cardinal features of this disorder.

Acyltransferases↗
PubMed1997

Syntactic bootstrapping in children with specific language impairment.

Syntactic bootstrapping was assessed in six children with normally developing language (NL) and six children with specific language impairment (SLI), ages 6 and 8, respectively. Children earned normal range non-verbal IQs and were matched by raw scores on a test of sentence comprehension. They were asked to listen to sentences containing novel verbs and to act out the meanings with toys. The SLI children earned reliably lower scores, but their errors suggested processing limitations rather than deficits in syntactic representation.

Child↗
PubMed1997

Birth balls.

Explore the source record for details and available documents.

Delivery, Obstetric↗
PubMed1996

Hepatic expression of macrophage inflammatory protein-1 alpha and macrophage inflammatory protein-1 beta after liver transplantation.

Two local events that are crucial for T cell emigration into tissue are (1) activation of T cell integrins to permit binding to endothelial counter-receptors and (2) directed migration through the endothelium and into tissue in response to chemotactic factors. Because the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta can activate adhesion and induce migration of T cells in vitro, we investigated their expression in human liver allografts to determine whether they might be involved in regulating the recruitment of T cells to allografts in vivo. Both chemokines were expressed strongly by infiltrating leukocytes during rejection and could be detected immunohistochemically on biliary epithelium, an important target for T cell mediated graft damage. Both chemokines, but particularly MIP-1 beta, were detected on the vascular and sinusoidal endothelium of rejecting liver allografts, where they were coexpressed with the T cell beta 1-integrin receptor vascular cell adhesion molecule-1. In situ hybridization with complementary ribonucleic acid probes showed no MIP-1 alpha or MIP-1 beta mRNA in normal liver but dramatic expression of both chemokines in infiltrating leukocytes and graft endothelium during rejection. Expression was reduced after successful corticosteroid treatment of rejection but persisted in patients progressing to chronic rejection. Increased MIP-1 alpha and MIP-1 beta mRNA expression was already found in biopsies taken at the end of the transplant operation, suggesting that early induction of chemokines, possibly in response to graft reperfusion, might promote the subsequent development of graft rejection. These data demonstrate for the first time that MIP-1 alpha and MIP-1 beta are (1) expressed in human liver allografts, (2) produced by endothelial cells in vivo, and (3) induced early after transplantation. They suggest that MIP-1 alpha and MIP-1 beta produced by graft infiltrating leukocytes and graft endothelium might play a crucial role in regulating T cell recruitment to liver allografts in vivo.

Bile Ducts↗
PubMed1996

The effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene.

The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on the elimination of nalmefene and nalmefene glucuronide also was assessed. Participants with normal renal function received a single intravenous dose of 2 mg, and patients with ESRD received two separate doses of 1 mg nalmefene hydrochloride. Terminal elimination half-life (t1/2) of both nalmefene and nalmefene glucuronide was prolonged in patients with ESRD compared with that in participants with normal renal function. The steady-state volume of distribution (Vdss) of nalmefene was significantly higher and total body clearance lower in patients with ESRD than in participants with normal renal function. Hemodialysis clearance of nalmefene was approximately 3.3% of total body clearance. Although the hemodialysis clearance of nalmefene glucuronide was 179.3 +/- 24.1 mL/min and its t1/2 was significantly reduced during dialysis to 5.2 +/- 2.3 hours, a dramatic rebound of nalmefene glucuronide concentrations of 75.7% was observed 7.7 +/- 5.4 hours after the end of hemodialysis. Thus, hemodialysis does not result in clinically significant alterations in the disposition of nalmefene or its primary metabolite, nalmefene glucuronide. These data suggest that there is no pharmacokinetic basis for modification of the initial dosage, but maintenance doses, if needed, should be administered less frequently due to the prolonged elimination of the active moiety, nalmefene.

Adult↗
PubMed1996

Midwives, breastfeeding, and Baby Friendly Australia.

Breastfeeding is a fundamental practice area for all midwives in Australia, and most midwives and maternity units claim that they recommend breastfeeding. Midwives have the opportunity to support women, or to erect barriers to the early establishment of breastfeeding. The author contends that through an understanding of the Baby Friendly Hospital Initiative's "Ten steps to successful breastfeeding", within the social/holistic model of midwifery care, long term health and social benefits will ensue.

Australia↗
PubMed1996

Is respiratory sinus arrhythmia a good index of cardiac vagal tone in exercise?

To assess the relative roles of neural and nonneural mechanisms in respiratory sinus arrhythmia (RSA) at rest and during exercise (steady-state supine cycle ergometry at 25% of peak oxygen uptake), we studied 10 healthy men (mean age 21 +/- 1 yr) before (control) and during ganglion blockade (GB) with trimetaphan camsylate (3-5 mg/min i.v.). GB was confirmed by the abolition of the reflex bradycardia in response to intravenous phenylephrine and of the blood pressure rise with the cold pressor test. RSA was calculated from the power of the spectral component of the R-R interval variability centered at the breathing frequency. GB decreased but did not abolish RSA. At rest, this nonneural component of RSA was negligible, accounting for < 1% of the control RSA. During GB, exercise did not affect RSA significantly. However, because control RSA was decreased by exercise, the proportion of nonneural RSA increased by 32% (range from 17 to 75%). These results indicate that as the vagal tone decreases with exercise, an increasing proportion of RSA is due to nonneural mechanisms.

Adolescent↗
PubMed1996

Health marketing in the supermarket: using prompting, product sampling, and price reduction to increase customer purchases of lower-fat items.

Reducing purchase and consumption of higher-fat foods is an important health objective for the nation since these behaviors are associated with cardiovascular disease and some cancers. Public health agents attempt to promote health-related behaviors, such as purchases of lower-fat foods, by changing key features of relevant environments. This study examined the effects of a marketing intervention in a supermarket on customer purchases of lower-fat products. Customers of one store of a major supermarket chain participated in this study. Direct observations of customer purchases of lower-fat milk, salad dressings, and frozen desserts were conducted. The supermarket intervention consisted of prompting, product sampling, and price reduction (store coupons). Using an interrupted time series design with switching replications, we found low to moderate increases for the lower-fat counterparts of milk, frozen desserts, and salad dressing. The greatest increase in purchases was found with frozen desserts. Findings from this study suggest that prompting, product sampling, and price reduction can increase customer purchases of some lower-fat products. Implications of these findings for the development and evaluation of health marketing interventions are discussed.

Advertising↗
PubMed1996

Elbow injuries to the throwing athlete.

Elbow injuries in the throwing athlete are common. Because of the tremendous medial tensile forces and lateral compressive forces borne by the elbow, there is a wide array of injuries that occur. A detailed history and physical examination are necessary for an accurate diagnosis. Many of the injuries discussed can be treated successfully with conservative measures followed by aggressive physical therapy. Prompt recognition and early treatment is mandatory. In those conditions in which conservative treatment tends to fail, the detailed surgical options have been discussed. It is important to select highly motivated patients for those procedures that require extensive rehabilitation postoperatively. The keys to success in elbow surgery are a compliant patient and a well-regimented rehabilitation program.

Athletic Injuries↗
PubMed1995

Health care report cards. Validity of case definitions.

Administrative databases are increasingly being used to construct health care report cards. We analyzed information from one of the original report cards, the Medicare Hospital Information Project. Assessment of mortality statistics for three clinical entities--coronary artery bypass surgery, hip reconstruction, and treatment of sepsis--demonstrated widespread outcome variances that reflected imperfect definitions rather than performance issues in clinical care. The use of administrative data sets to design report cards requires clinical expertise to ensure validity of the data. Designers of report card measures should share preliminary data with providers to enable feedback in methods and uncover definitional and validity concerns before widespread dissemination.

Bias↗
PubMed1995

Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils.

The diversity of monocyte chemotactic protein (MCP)3 target cell types, as well as the capacity of MCP3 to desensitize leukocyte responses to other CC chemokines, suggested that MCP3 may interact with multiple CC chemokine receptors. The purpose of this study is to establish how MCP3 binds and activates monocytes and neutrophils. We show that human monocytes exhibit high-affinity binding for 125I-MCP3 with an estimated Kd of 1-3 nM and about 10,000 binding sites/cell. The binding of 125I-MCP3 to monocytes was progressively less well competed by CC chemokines macrophage inflammatory protein (MIP)1 alpha (Kd = 5-10 nM), RANTES (Kd = 5-10 nM), MCP1 (monocyte chemoattractant and activating factor, or MCAF) (Kd = 60 nM) and MIP1 beta (Kd > 100 nM). On the other hand, unlabeled MCP3 displaced the binding of radiolabeled MIP1 alpha, RANTES, MCP1 and MIP1 beta as effectively as the isologous CC chemokines. In agreement with the binding data, pretreatment of monocytes with MCP3 completely desensitized the calcium flux in response to MIP1 alpha and RANTES. However, MIP1 alpha and RANTES failed to desensitize the response of monocytes to MCP3. MCP3 and MCP1 partially desensitized each other's effects on monocytes. These binding and cross-desensitization results suggest that MCP3 binds and signals through other binding sites in addition to those shared with MIP1 alpha, RANTES and MCP1. The unidirectional competition for MIP1 beta binding and signaling by MCP3 suggests the existence of an as-yet unidentified site for MCP3 shared with MIP1 beta. The existence of another unique binding site(s) for MCP3 was further shown by the failure of any of the other CC chemokines to compete effectively for MCP3 binding on neutrophils. MCP3 in our study was also the only human CC chemokine that consistently chemoattracted neutrophils. These results suggest that MCP3 is a ligand that can bind and activate a broad range of target cells through receptors shared by other CC chemokines as well as its own receptor.

Calcium↗