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Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 307 records · Page 17Linked to original sources

The use of decision-analytical modelling in economic evaluation of patch testing in allergic contact dermatitis.

OBJECTIVE: The objective of this observational prospective study was to demonstrate the cost effectiveness of patch testing in patients suspected of allergic contact dermatitis (ACD) and to determine the order in which different severity groups rank in terms of cost effectiveness. DESIGN AND SETTING: This observational study was conducted on 567 patients from 10 investigator sites in the US over a period of 1 year. All patients with a suspicion of contact allergy who exhibited at least moderate disease activity were included in the study and were stratified according to disease severity and whether or not they were patch tested. In each severity category, the cost effectiveness of patch testing was evaluated. Patients who were ruled out for contact allergy (without the use of patch test) by the first 6 months after admission were excluded. A validated dermatology-specific quality of life (DSQL) instrument was administered to all patients at the start of the study, and at 6 and 12 months thereafter. The cost-effectiveness analysis is demonstrated using a decision-analytical model. Costs included office visits and prescription costs without generic substitution. The cost of patch testing was not included due to the large variation in price among commercially available products. MAIN OUTCOME MEASURES AND RESULTS: Patch testing was performed on 22% of patients with mild disease, 41% of patients with moderate disease and 50% of those with severe disease. There was a significant difference between the patch-tested and non-patch-tested groups in terms of the time to obtain a confirmed diagnosis (medians = 8 and 175 days, respectively) and a significant difference in the ratio of patients who had a confirmed diagnosis (88 and 69%, respectively). As a result of changes made in their lifestyle, 66% of patients in the patch-tested group and 51% in the non-patch-tested group reported 75% or more improvement in their disease symptoms after 6 months. Early confirmation of diagnosis helped reduce the prediagnosis cost of treatment which was mostly based on preliminary diagnosis. The greatest quality-of-life (QOL) benefits from patch testing relative to nonpatch testing occurred in patients with recurrent/chronic ACD. CONCLUSIONS: Patch testing is most cost effective and reduces the cost of therapy in patients with severe ACD. Greater improvements in quality of life were seen in patients with recurrent/chronic ACD who were patch tested than patients who were not patch tested within the same group. Results were not sensitive to changes due to the addition of indirect costs or costs using generic substitution.

Anti-Allergic Agents↗

Mental health nursing support during Operation Sea Signal: Cuban/Haitian humanitarian mission.

Joint military humanitarian missions provide challenges and rewards for mental health nursing not found in the garrison mission. A primary challenge is to develop and implement programs that benefit the various populations inherent in such missions. During Operation Sea Signal, several programs, such as migrant adult day treatment, halfway house, outreach, and inpatient, led to the overall enhancement of mental health nursing care for the Cuban and Haitian migrants. It also gave the participating mental health nursing team of professionals and enlisted technicians the opportunity to develop their nursing expertise and sensitivity in a culturally diverse situation.

Cuba↗

An economic evaluation of patch testing in the diagnosis and management of allergic contact dermatitis.

BACKGROUND: A previous retrospective study indicated that patch testing is cost-effective and well accepted by patients. OBJECTIVE: The objective of this observational prospective study was to show the cost-effectiveness of patch testing in patients suspected of allergic contact dermatitis (ACD) and to determine the order in which different severity groups rank in terms of cost-effectiveness. METHODS: This observational study was conducted in 567 patients from 10 investigator sites over a period of 1 year. All patients with a suspicion of contact allergy who exhibited at least moderate disease activity were included in the study and were stratified according to disease severity and whether or not they were patch tested. In each severity category, the cost-effectiveness of patch testing was evaluated. Patients who were ruled out for contact allergy by the first 6 months after admission were excluded. A validated dermatology-specific quality of life instrument was administered to all the patients at entrance into the study and at 6 and 12 months after that. The cost-effectiveness analysis is shown using a decision analysis model. RESULTS: Patch testing was performed on 22% of patients with mild disease, 41% of patients with moderate disease, and 50% of patients with severe disease. As a result of changes made in their lifestyle, 66% in the patch-tested group and 51% in the non-patch-tested group reported 75% or more improvement in disease symptoms after 6 months. Early confirmation of diagnosis helped reduce the prediagnosis costs of treatment, which was mostly based on preliminary diagnosis. The greatest quality of life benefits from patch testing, relative to no patch testing, occurred in subjects with recurrent or chronic ACD. CONCLUSION: Patch testing is most cost-effective and reduces the cost of therapy in patients with severe ACD.

Chronic Disease↗

Technique of, and complications attributable to, repeated hyperosmotic blood-brain barrier disruption in dogs.

OBJECTIVE: To design a repeatable technique for reversible, hyperosmotic blood-brain barrier disruption (BBBD) in dogs and evaluate clinical effects of multiple BBBD. ANIMALS: 10 healthy adult dogs. PROCEDURE: Using fluoroscopic guidance, an arterial catheter was directed into the internal carotid artery via the femoral artery of 10 dogs. Blood-brain barrier disruption was achieved in 5 dogs, using intracarotid infusion of mannitol. Five control dogs received only saline solution. After recovery, dogs were monitored for clinical signs of disease before a second, nonsurvival procedure was performed 2 to 3 weeks later. BBBD was estimated, using computed tomographic (CT) densitometry values, as well as Evan's blue dye staining on necropsy specimens. RESULTS: Seven dogs completed the entire study. Two treatment dogs were lost after the first infusion because of deteriorating neurologic function attributed to CNS edema and increased intracranial pressure. One control dog was lost because of vessel wall damage during catheterization. The remaining dogs had only transient neurologic, ocular, and vasculature injuries. Successful BBBD was documented in all treated dogs by use of CT and Evan's blue dye evaluation. CONCLUSION: Repeated catheterization of the internal carotid artery and disruption of the blood- brain barrier is possible in dogs. CLINICAL RELEVANCE: Refinement of this technique would be useful not only for improved delivery of chemotherapeutic agents in patients with brain tumors, but also would allow further investigation of new treatments involving genetically engineered retroviruses and monoclonal antibodies.

Animals↗

Designing HeartCare: custom computerized home care for patients recovering from CABG surgery.

With the current trend toward discharge of cardiac artery bypass graft (CABG) patients from the hospital after 5 days, clinicians must make effective use of existing computer technology to provide more efficiently the services once available during the patient's lengthier hospital stay. This paper describes the design of the HeartCare initiative, a computerized cardiac recovery service designed to provide home-care support for patients in the first three months following CABG surgery. Capitalizing on the expansion in health resources on the Internet, and building on the lessons from the ComputerLink projects, HeartCare will employ the World Wide Web platform in the generation of personalized in-home computerized access to recovery resources. Key implementation decisions include selection of WebTV/ as the home-based device, and application of Metadata to organizing health-related knowledge resources on the WWW.

Computers↗

Perforin is activated by a proteolytic cleavage during biosynthesis which reveals a phospholipid-binding C2 domain.

Perforin is a secreted protein synthesized by activated cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. It is a key component of the lytic machinery of these cells, being able to insert into the plasma membrane of targeted cells, forming a pore which leads to their destruction. Here we analyse the synthesis, processing and intracellular transport of perforin in the NK cell line YT. Perforin is synthesized as a 70 kDa inactive precursor which is cleaved at the C-terminus to yield a 60 kDa active form. This proteolytic cleavage occurs in an acidic compartment and can be inhibited by incubation of the cells in ammonium chloride, concanamycin A, leupeptin and E-64. The increased lytic activity of the cleaved form can be demonstrated by killing assays in which cleavage of the pro-piece is inhibited. Epitope mapping reveals that cleavage of the pro-piece occurs at the boundary of a C2 domain, which we show is able to bind phospholipid membranes in a calcium-dependent manner. We propose that removal of the pro-piece, which contains a bulky glycan, allows the C2 domain to interact with phospholipid membranes and initiate perforin pore formation.

Amino Acid Sequence↗

Differential expression of XAP5, a candidate disease gene.

We have isolated a full-length cDNA corresponding to the XAP5 gene in Xq28. An unusual feature of the cDNA is that it contains runs of CCG repeats in the 5' untranslated region, typical of genes that exhibit anticipation. It has a striking pattern of differential expression and is greatly enhanced in various fetal tissues. This predicted protein encodes a unique 339-amino-acid polypeptide that contains a large percentage of highly charged residues and a possible nuclear localization signal. A comparison to genomic sequence shows that XAP-5 comprises 13 exons spanning 6.5 kb. An examination of the human population indicates that the longest CCG run is polymorphic and varies in length from 8 to 12 repeats.

Amino Acid Sequence↗

Identification of T-cell epitopes on the Rhesus polypeptides in autoimmune hemolytic anemia.

We have shown previously that the Rhesus (Rh) polypeptides are the commonest targets for pathogenic anti-red blood cell (RBC) autoantibodies in patients with autoimmune hemolytic anemia (AIHA). The aim of the current work was to determine whether activated T cells from such patients also mount recall responses to epitopes on these proteins. Two panels of overlapping 15-mer peptides, corresponding to the sequences of the 30-kD Rh proteins associated with expression of the D and Cc/Ee blood group antigens, were synthesized and screened for the ability to stimulate the in vitro proliferation of mononuclear cells from the peripheral blood or spleen of nine AIHA cases. Culture conditions were chosen that favor recall proliferation by previously activated T cells, rather than primary responses. In seven of the patients, including all four cases with autoantibody to the Rh proteins, two or more peptides elicited proliferation, but cells from eight of nine patients with other anemias and seven of nine healthy donors failed to respond to the panels. Multiple peptides were also stimulatory in two positive control donors who had been alloimmunized with Rh D-positive RBCs. Six different profiles of peptides elicited responses in the AIHA patients, and this variation may reflect the different HLA types in the group. Stimulatory peptides were identified throughout domains shared between, or specific to, each of the related 30-kD Rh proteins, but T cells that responded to nonconserved regions did not cross-react with the alternative sequences. Anti-major histocompatibility complex class II antibodies blocked the responses and depletion experiments confirmed that the proliferating mononuclear cells were T cells. Notably, splenic T cells that proliferated against multiple Rh peptides also responded to intact RBCs. We propose that pathogenic autoantibody production in many cases of AIHA is driven by the activation of T-helper cells specific for previously cryptic epitopes on the Rh proteins.

Adult↗

Protecting adolescents from harm. Findings from the National Longitudinal Study on Adolescent Health.

CONTEXT: The main threats to adolescents' health are the risk behaviors they choose. How their social context shapes their behaviors is poorly understood. OBJECTIVE: To identify risk and protective factors at the family, school, and individual levels as they relate to 4 domains of adolescent health and morbidity: emotional health, violence, substance use, and sexuality. DESIGN: Cross-sectional analysis of interview data from the National Longitudinal Study of Adolescent Health. PARTICIPANTS: A total of 12118 adolescents in grades 7 through 12 drawn from an initial national school survey of 90118 adolescents from 80 high schools plus their feeder middle schools. SETTING: The interview was completed in the subject's home. MAIN OUTCOME MEASURES: Eight areas were assessed: emotional distress; suicidal thoughts and behaviors; violence; use of 3 substances (cigarettes, alcohol, marijuana); and 2 types of sexual behaviors (age of sexual debut and pregnancy history). Independent variables included measures of family context, school context, and individual characteristics. RESULTS: Parent-family connectedness and perceived school connectedness were protective against every health risk behavior measure except history of pregnancy. Conversely, ease of access to guns at home was associated with suicidality (grades 9-12: P<.001) and violence (grades 7-8: P<.001; grades 9-12: P<.001). Access to substances in the home was associated with use of cigarettes (P<.001), alcohol (P<.001), and marijuana (P<.001) among all students. Working 20 or more hours a week was associated with emotional distress of high school students (P<.01), cigarette use (P<.001), alcohol use (P<.001), and marijuana use (P<.001). Appearing "older than most" in class was associated with emotional distress and suicidal thoughts and behaviors among high school students (P<.001); it was also associated with substance use and an earlier age of sexual debut among both junior and senior high students. Repeating a grade in school was associated with emotional distress among students in junior high (P<.001) and high school (P<.01) and with tobacco use among junior high students (P<.001). On the other hand, parental expectations regarding school achievement were associated with lower levels of health risk behaviors; parental disapproval of early sexual debut was associated with a later age of onset of intercourse (P<.001). CONCLUSIONS: Family and school contexts as well as individual characteristics are associated with health and risky behaviors in adolescents. The results should assist health and social service providers, educators, and others in taking the first steps to diminish risk factors and enhance protective factors for our young people.

Adolescent↗

Central venous catheters coated with minocycline and rifampin for the prevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. The Texas Medical Center Catheter Study Group.

BACKGROUND: Central venous catheters are a principal source of nosocomial bloodstream infections, which are difficult to control. OBJECTIVE: To determine the efficacy of catheters coated with minocycline and rifampin in preventing catheter-related colonization and bloodstream infections. DESIGN: Multicenter, randomized clinical trial. SETTING: Five university-based medical centers. PATIENTS: 281 hospitalized patients who required 298 triple-lumen, polyurethane venous catheters. INTERVENTION: 147 catheters were pretreated with tridodecylmethyl-ammonium chloride and coated with minocycline and rifampin. Untreated, uncoated catheters (n = 151) were used as controls. MEASUREMENTS: Quantitative catheter cultures, blood cultures, and molecular typing of organisms to determine catheter-related colonization and bloodstream infections. RESULTS: The group with coated catheters and the group with uncoated catheters were similar with respect to age, sex, underlying diseases, degree of immunosuppression, therapeutic interventions, and risk factors for catheter infections. Colonization occurred in 36 (26%) uncoated catheters and 11 (8%) coated catheters (P < 0.001). Catheter-related bloodstream infection developed in 7 patients (5%) with uncoated catheters and no patients with coated catheters (P < 0.01). Multivariate logistic regression analysis showed that coating catheters with minocycline and rifampin was an independent protective factor against catheter-related colonization (P < 0.05). No adverse effects related to the coated catheters or antimicrobial resistance were seen. An estimate showed that the use of coated catheters could save costs. CONCLUSIONS: Central venous catheters coated with minocycline and rifampin can significantly reduce the risk for catheter-related colonization and bloodstream infections. The use of these catheters may save costs.

Adolescent↗

Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth.

A prospective observational study of 104 women was performed to study whether the insulin-like growth factor (IGF) system in pregnancy before labour is associated with reduced fetal growth. Fetal blood was obtained by cordocentesis for prenatal diagnosis or at elective caesarean delivery and a maternal sample was also obtained, IGF-1 and IGF-2 and their binding proteins -1 and -3 were measured by RIA. The 35 case were smaller than -2S.D.s by ultrasound abdominal circumference and birthweight and were subdivided into fetal growth retardation (FGR, n = 20) and small for gestational age (SGA, n = 15) by Doppler velocimetry and neonatal outcome. Controls (n = 69) were normally grown. Control maternal IGF-1 (r = 0.65, P < 0.0001) and IGFBP-3 (r = 0.46, P = 0.001) increased with advancing gestational age. In FGR cases, maternal IGF-1 was low (P = 0.0001) and IGFBP-1 was high (P = 0.03) and maternal IGF-2 was low in SGA (P = 0.005). In the SGA fetus, IGF-2 was low (P = 0.0009) and IGFBP-3 (P = 0.02) was high. In FGR, IGFBP-1 (P < 0.0001) and IGFBP-3 (P = 0.002) were both elevated. These data do not support the hypothesis that fetal IGF-1 deficiency is a common cause of FGR. Elevated binding proteins may lead to a relative deficiency of free IGF but changes in binding proteins may be secondary to metabolic changes. In FGR, maternal IGF-1 was low with high binding proteins, so this system may be important in controlling placental transfer.

Embryonic and Fetal Development↗

Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGF-binding protein-1 in chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is characterized by severe physical and mental fatigue of central origin. Similar clinical features may occur in disorders of the hypothalamopituitary axis. The aim of the study was to determine whether patients with CFS have abnormalities of the growth hormone/insulinlike growth factor (GH-IGF) axis basally or following hypothalamic stimulation with insulin-induced hypoglycemia. We compared levels of GH, IGF-I, IGF-II, IGF-binding protein-1 (IGFBP-1), insulin, and C-peptide in nondepressed CFS patients and normal controls. We found attenuated basal levels of IGF-I (214 +/- 17 vs. 263.4 +/- 13.4 micrograms/L, p = .036) and IGF-II (420 +/- 19.8 vs. 536 +/- 24.3 micrograms/L, p = .02) in CFS patients and a reduced GH response to hypoglycemia (peak GH; 41.9 +/- 11.5 vs. 106.0 +/- 25.6 mU/L, p = .017). Insulin levels were higher (7.6 +/- 1.0 vs. 4.3 +/- 0.8 mU/L, p = .02) and IGFBP-1 levels were lower (19.7 +/- 4.6 vs. 43.2 +/- 2.7 mg/L, p = .004) in CFS patients compared with controls. This study provides preliminary data abnormalities of the GH-IGF axis in CFS. It is not apparent whether these changes are components of a primary pathological process or are acquired secondary to behavioral aspects of CFS such as reduced physical activity.

Adult↗

Intraendosomal degradation of transforming growth factor alpha.

Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) bind to the same receptor, but have different potencies and actions. A possible mechanism is that differences in processing may be responsible for their divergent properties. We have examined TGF alpha and EGF processing in isolated rat hepatocytes with and without various protease inhibitors and inhibitors of endosomal processing. Our results show that EGF undergoes limited degradation in endosomes and is primarily degraded in lysosomes. In contrast, TGF alpha is rapidly degraded in endosomes by insulin-degrading enzyme (EC 3.4.24.56), possibly allowing rapid return of the receptor to the cell surface. Incubation of isolated endosomes preloaded with labeled TGF alpha reveals that degradation can occur whether the vesicles are acidified or not, as is also the case for insulin. We conclude that TGF alpha is degraded immediately after internalization, at least partly before acidification has occurred, while EGF requires prolonged intracellular residence and lysosomal degradation. The different degradation pathways may play a role in the different activities of the two hormones.

Animals↗

Juvenile rheumatoid arthritis. Effects of disease activity and recombinant human growth hormone on insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, and osteocalcin.

OBJECTIVE: To investigate possible mechanisms of growth impairment in children with juvenile rheumatoid arthritis (JRA). METHODS: Eighteen prepubertal children with JRA and growth retardation received recombinant human growth hormone (rHuGH) for 1 year. Growth hormone profiles over 24 hours were obtained before treatment in 12 patients; the levels did not differ from those in "short normal" children. Levels of insulin-like growth factor 1 (IGF-1), IGF binding proteins (IGFBPs) 1 and 3, insulin, osteocalcin, and C-reactive protein (CRP), as well as the erythrocyte sedimentation rate were measured serially. Pretreatment levels were compared with control levels. RESULTS: In JRA patients, IGF-1, IGFBP-3, and osteocalcin levels were significantly lower and insulin levels significantly higher than those in controls, but there was no significant difference in the level of IGFBP-1. With rHuGH treatment, height velocity and mean levels of IGF-1, osteocalcin, and insulin increased significantly, while mean levels of IGFBP-1 fell significantly. Levels of IGFBP-3 correlated with those of IGF-1. The height velocity correlated positively with IGF-1 and osteocalcin, and negatively with IGFBP-1. Levels of IGFBP-1 were inversely related to those of insulin and IGF-1. There was a significant negative correlation between the CRP and height velocity, IGF-1 level, and osteocalcin level. CONCLUSION: IGF-1 production is impaired in children with active JRA. Treatment with a therapeutic dose of rHuGH can rectify the IGF-1 deficiency within 4 days, but its effect is adversely influenced by the acute-phase response, as reflected by an elevated CRP level.

Analysis of Variance↗

A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R-03.

PURPOSE: National Surgical Adjuvant Breast and Bowel Project Protocol R-03 was designed to determine the worth of preoperative chemotherapy and radiation therapy in the management of operable rectal cancer. METHODS: Thus far, 116 patients of an eventual 900 with primary operable rectal cancer have been randomized to receive multimodality therapy to begin preoperatively (59 patients) or identical therapy beginning after curative surgery (57). All patients received seven cycles of 5-fluorouracil (FU)/leucovorin (LV) chemotherapy. Cycles 1 and 4 through 7 used a high-dose weekly FU regimen. In Cycles 2 and 3, FU and low-dose LV chemotherapy was given during the first and fifth week of radiation therapy (5,040 cGy). The preoperative arm (Group 1) received the first three cycles of chemotherapy and all radiation therapy before surgery. The postoperative arm (Group 2) received all radiation and chemotherapy after surgery. Primary study end points included disease-free survival and survival. Secondary end points included local recurrence, primary tumor response to combination therapy, tumor downstaging, and sphincter preservation. RESULTS: Overall treatment-related toxicity was similar in both groups. Although seven preoperative patients had events after randomization that precluded surgery, eight events occurred during an equivalent follow-up period in the postoperative group. No patient was deemed inoperable because of progressive local disease. Sphincter-saving surgery was intended in 31 percent of Group 1 patients and 33 percent of Group 2 patients at the time of randomization. Such surgery was actually performed in 50 percent of the preoperatively treated patients and 33 percent of the postoperatively treated patients. The use of protective colostomy in patients undergoing sphincter-sparing surgery and the development of perioperative complications in all surgical patients were similar in both groups. There was evidence of tumor downstaging in evaluable patients undergoing preoperative therapy, with 8 percent of Group 1 patients having had a pathologic complete response. CONCLUSION: These data do suggest that the preoperative chemotherapy and radiation therapy regimen used are, at least, as safe and tolerable as standard postoperative treatment. There is presently a trend to tumor downstaging and sphincter preservation in the preoperative arm. Whether this arm will have greater or lesser survival and long-term toxicity awaits the completion of this relevant study.

Adenocarcinoma↗

The mouse chromosome 7 distal imprinting domain maps to G-bands F4/F5.

Mouse Chromosome (Chr) 7 distal to band F3 on the physical map is known to be subject to imprinting, maternal duplication (MatDp) of the region leading to a late embryonic lethality, while paternal duplication (PatDp) causes death in utero before 11.5 dpc. Using a new mouse reciprocal translocation T(7;11)65H to produce MatDp for distal Chr 7, we have mapped the region subject to imprinting more precisely to bands 7F4/F5 on the cytogenetic map. Fluorescence in situ hybridization (FISH) studies on mitotic and meiotic chromosomes of a T65H heterozygote show that the imprinted gene Igf2 is located in the same region. This was confirmed by the finding that embryos with MatDp of bands 7F4/F5 did not express Igf2. We suggest that other members of the imprinted domain containing Igf2, namely Mash2, H19, Ins2, and p57(K1P2), are also located in 7F4/F5 and that some or all of these genes may be responsible for the two imprinting lethalities seen with MatDp and PatDp for this region.

Animals↗