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Biomedical subjects

J Chapman

Publications and source records attributed to J Chapman.

At least 469 records · Page 26Linked to original sources
PubMedDate not supplied

Delayed graft function: risk factors, consequences and parameters affecting outcome-results from MOST, A Multinational Observational Study.

BACKGROUND: Delayed graft function (DGF) is a common complication after renal transplantation, and may affect graft function. The aim of this analysis was to evaluate risk factors for DGF, as well as parameters and events influencing graft function after DGF. We analyzed data collected in an ongoing international, prospective; observational study, the Neoral-MOST (Multinational Observational Study in renal Transplantation), and included in the analysis all patients with cadaveric kidney transplants for whom renal function at 1 year posttransplantation was documented (N = 8950). Logistic regression was used to evaluate the risk factors for DGF occurrence, and multifactorial analysis of variance (ANCOVA) to assess the relevance of different factors for GFR at 1 year. RESULTS: Higher donor age, longer CIT, male recipients, Caucasian recipients, high recipients body mass index, and PRA were all associated with a higher risk for DGF. Renal function of former DGF kidneys at 1 year was lower in kidneys of elder donors, or which had experienced rejection or CMV infection. Variations of the maintenance regimen at 1 year posttransplantation were not associated with better graft function. Multifactorial analysis showed donor age and acute rejection as significant independent factors. CONCLUSIONS: Most factors increasing the risk for DGF or having a negative impact on renal function at 1 year in grafts with DGF are predetermined. Additional posttransplant damage by acute rejection was associated with further reductions in GFR. Preventing acute rejection is an important step in achieving optimal function of DGF grafts.

Adult↗
PubMedDate not supplied

Impact of mycophenolate mofetil dose posttransplantation on 12-month renal function: analysis of the MOST database.

INTRODUCTION: Mycophenolate mofetil (MMF) has greatly reduced the risk of acute rejection episodes (ARE) after renal transplantation, but dose reductions/withdrawals could jeopardize long-term results. METHODS: The MOST database of "de novo" patients treated with MMF at month 1 and functioning grafts at month 12 were divided into 2 groups: groups 1, 2 g MMF at month 1 and month 12; and group 2, 2 g MMF at month 1 but MMF <2 g at month 12 to evaluate renal function glonerular filtration rate (GFR). RESULTS: In this study, 1136 patients were receiving 2 g MMF at month 1. On month 12, 645 were on 2 g (56.8%, group 1) and 431 were on <2 g (43.2%, group 2). Group 1 included younger recipients of younger donors with fewer patients with delayed graft function (DGF). Group 1 showed more ARE during month 1 and more patients who received induction. Mean Neoral daily doses at month 1/month 12 were 5.3/3.0 and 5.3/3.1 mg/kg in group 1 and group 2, respectively (P = .05 at month 12). GFR in group 1 and group 2 were 59.06 (CI 57.10-60.60) and 53.81 (CI 52-55.7) at month 1 (P < .001); 63.7 (CI 62.1-65.30) and 55.9 (CI 54.1-57.7) mL/min*1.73 m(2) at month 12 (P < .001). The mean increases in GFR between month 1 and month 12 were 4.64 and 1.94 mL/min*1.73 m(2), respectively (P < .05). A multivariate analysis also included 795 patients from the "maintenance" patient database with retrospective detailed information. The following parameters were highly predictive for good renal function at month 12: donor age younger than 60 years, recipient age younger than 60 years, immediate graft function, 12-month MMF dose = 2 g, absence of CMV infection, and 12-month Neoral dose <3 mg/kg/d. CONCLUSIONS: Maintenance of MMF dose at 2 g/d during the first year appears to facilitate the attainment of optimal renal function at 12-months after kidney transplantation.

Analysis of Variance↗
PubMedDate not supplied

Germline mutational analysis of presenilin 1 and APP genes in Jewish-Israeli individuals with familial or early-onset Alzheimer disease using denaturing gradient gel electrophoresis (DGGE).

Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2). The relative proportions in which mutations in these genes occur among AD patients in Israel has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with AD: 22 with sporadic, early-onset disease (below 65 years), and 30 with FAD. Mutation screen employed denaturing gradient gel electrophoresis (DGGE) of exon-specific PCRs and restriction enzyme digest. Five patients from three different families displayed mutations within the PS-1 gene: three patients of one family showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated patients showed an identical mis-sense mutation in codon 318 (Glu318Gly). No patient showed an abnormal migration on DGGE (for APP) or mutant restriction digest pattern (for PS-2) genes. These data may indicate the existence of another familial Alzheimer disease (FAD) gene locus in the Israeli Jewish population.

Adult↗
PubMedDate not supplied

Viral-mediated gene delivery of constitutively activated G alpha s alters vasoreactivity.

1. Decline in beta-adrenoceptor (beta-AR)-mediated function occurs with increasing age, as well as in multiple disease conditions. The mechanisms responsible for this decline include alterations in beta-AR itself, beta-AR coupling proteins, such as G-proteins, or other beta-AR-linked proteins, such as G-protein receptor kinases and/or phosphatases. 2. The present study examines the physiological effects of in vitro transfer of constitutively activated G alpha s (G alpha s-Q227L) to both cultured vascular smooth muscle cells (VSMC) and whole aortic tissue of 6-month-old (adult) animals via a replication-deficient Herpes simplex virus (HSV) vector. These studies were conducted to provide a model for future examination of the role of G alpha s in the age-related decline in beta-AR-mediated vasorelaxation. 3. Gene transfer was confirmed by western blotting for specific proteins. Aortic tissue infected with HSV-G alpha s-Q227L had reduced phenylephrine-induced contraction and enhanced isoproterenol-stimulated vasorelaxation. Infection of cultured VSMC with HSV-G alpha s-Q227L increased both basal- and isoproterenol-stimulated cAMP accumulation, whereas forskolin-stimulated cAMP production was unchanged. 4. These results implicate G alpha s as a target for further investigation in age-related changes in vascular reactivity and support the use of viral-mediated gene transfer as an effective tool to study adrenergic signal transduction and physiology in vascular tissue.

Animals↗
PubMedDate not supplied

Survival from primary breast cancer after routine clinical use of mammography.

Clinical trials indicate that mammography provides a substantial breast cancer survival benefit; however, there is a need to demonstrate that this benefit extends to clinical practice and to determine the extent that current reductions in mortality are attributable to regular screening or adjuvant systemic therapy. Mammography was used routinely at our institution across a broad age range, in an era when most patients received no adjuvant systemic therapy. We examined breast cancer survival for a cohort of 678 stage I-III primary invasive breast cancer patients accrued from 1971 to 1990, and followed to 1996; 18% received adjuvant hormonal therapy and 15% received adjuvant chemotherapy. There were 61 women less than 40 years old; 136, 40-49 years; 341, 50-69 years; 140, > or =70 years. Factors available for multivariate investigations were age (years), tumor size (cm), nodal status (N-, Nx, N+), ER (fmol/mg protein), PgR (fmol/mg protein), adjuvant radiotherapy (no, yes), adjuvant hormonal therapy (no, yes), and adjuvant chemotherapy (no, yes). Forward stepwise multivariate regression with log-normal survival analysis was used to examine the effects of these factors on disease-specific survival. Ten-year survival by tumor size was adjusted for the effects of other significant factors. For women less than 40 years of age, 10-year survival at the T1a, T1b, T1c, and T2 cut-points for tumor size is, respectively, 0.77, 0.74, 0.67, 0.44; for 40-49 years it is 0.92, 0.90, 0.85, 0.62; for 50-69 years it is 0.81, 0.79, 0.75, 0.62; for > or =70 years it is 0.84, 0.81, 0.73, 0.44. With routine use of clinical mammography and up to 26 years of follow-up, we found breast cancer survival to be significantly better (p< or = 0.05) for all women with smaller tumors and that survival indicated a change in natural disease history with early detection. The Canadian National Breast Screening Study (NBSS) controls had significantly smaller tumors (p < 0.001) than our patients, which may indicate access to mammography outside of the NBSS that reduced the apparent survival benefit for clinical trial mammography.

Adult↗
PubMedDate not supplied

Invasive mucinous (colloid) adenocarcinoma of ectopic breast tissue in the vulva: a case report.

We present the first case of primary vulvar mucinous adenocarcinoma of ectopic breast origin. The patient is an 84-year-old woman with a mass on the left side of her vulva. A left partial vulvectomy with bilateral inguinal lymph node dissections revealed a mucinous adenocarcinoma that involved the dermis and subcutaneous tissue. The tumor cells were positive for estrogen receptors (ERs), progesterone receptors (PRs), and BRST-1 markers. The clinical and pathologic features, differential diagnosis, and treatment are discussed.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

The use of intravenous immunoglobulin as maintenance therapy in myasthenia gravis.

The standard therapy for myasthenia gravis (MG) includes steroids and immunosuppressants, which have delayed onset of action and significant side effects. Plasmapheresis and intravenous immunoglobulin have been used mostly for the treatment of severe exacerbations. In the present study we examined the use of intravenous immunoglobulin as maintenance treatment in MG. We included 11 patients with generalized myasthenia gravis. All had severe bulbar and respiratory involvement that required mechanical ventilation in three patients. Intravenous immunoglobulin treatment was initiated at a dose of 400 mg/kg/d for 5 days and followed by maintenance with 400 mg/kg once monthly. Regular medications were continued as necessary. There was significant improvement in all patients, and none required mechanical ventilation over the treatment period of 20.3 months +/- 8.3 (mean +/- SD, total patient years of treatment = 18.7). Steroid and pyridostigmine doses were reduced significantly and steroids were discontinued in two patients. There were no serious side effects related to intravenous immunoglobulin. These results suggest that intravenous immunoglobulin maintenance therapy is a valid modality in patients with MG.

Adult↗
PubMedDate not supplied

The effect of moderate exercise training on oxygen uptake post-aortic/mitral valve surgery.

BACKGROUND: This study determined the response of aortic and/or mitral valve replacement/reconstruction (AVR/MVR) surgery patients to a 3-month exercise rehabilitation program (ERP) of moderate intensity, frequency, and duration that commenced approximately 9 weeks post-operatively. METHODS: Based on geographic proximity and availability of transportation to attend ERP classes, 29 experimental subjects were enrolled in the ERP and 20 control subjects received standard care that did not include the ERP, but did not prohibit activity/exercise. Exercise tolerance was determined from estimated oxygen uptake (VO2) during exercise tolerance testing (GXT) before and after standard care or the ERP. RESULTS: VO2 at the maximum stage of the GXT increased significantly (P < or = 05) for the experimental (4.89 +/- 5.07 mL/kg/min) and control (5.11 +/- 4.48 mL/kg/min) groups. No significant between-group differences were noted in VO2 at the maximum stage of the exercise testing or at the target heart rate (HR). Furthermore, reported exercise levels of subjects in both groups were comparable and sufficient for training effects to occur. CONCLUSION: Alternate strategies to improve exercise tolerance such as home-based rehabilitation programs should be investigated for relatively healthy aortic and/or mitral valve surgical patients.

Aortic Valve Insufficiency↗
PubMedDate not supplied

Penetrance and phenotypic expression of a mutation linked to Creutzfeldt-Jakob disease in the elderly.

We have previously reported several carriers of the PRNP E200K point mutation among subjects aged over 65 years. In order to examine the prevalence of this mutation among demented subjects of Libyan and Tunisian origin and the clinical characteristics associated with it, we screened 58 elderly subjects belonging to this ethnic group. Five mutation carriers were identified, all of whom had cognitive deterioration consistent with primary degenerative dementia. All had low Hachinski ischemic scores (0.8 +/- 0.8, mean +/- SD) as compared with noncarriers (6.7 +/- 3.0; p = 0.011, Wilcoxon rank sum test). In addition to the cognitive decline, 4 carriers had additional cerebellar, pyramidal, or extrapyramidal findings compatible with the diagnosis of possible or probable Creutzfeldt-Jakob disease.

Aged↗
PubMedDate not supplied

Dementia and antiphospholipid antibodies.

Antiphospholipid antibodies (aPLAb) may cause both focal ischemic and diffuse brain damage and may be associated with dementia. We have examined the relationship of aPLAb to dementia in the elderly. Blood samples were obtained from 87 consecutive patients with dementia (74 +/- 11 years old) and 69 controls (78 +/- 9 years old), residents of an old age home who were not overtly demented. Levels of aPLAb were measured by a standardized ELISA, utilizing cardiolipin as antigen, and we considered levels above 20 IgG antiphospholipid units (GPLU) as significantly elevated. We found that 5 of the 87 demented patients (6%), but none of the 69 controls, had significantly elevated aPLAb levels (p = 0.03, one-tailed Fisher's exact test). All the patients with high aPLAb levels were diagnosed clinically as having dementia of the Alzheimer type, except for 1 who had mixed dementia, and none had features of an immune-mediated disease. Thus, a small but significant number of patients with dementia have high levels of aPLAb. The role of the aPLAb in these patients, with apparently diffuse brain disease, is currently unknown.

Aged↗
PubMedDate not supplied

Lipoprotein(a) impairs generation of plasmin by fibrin-bound tissue-type plasminogen activator. In vitro studies in a plasma milieu.

Apoprotein(a), (apo[a]), the specific antigen of lipoprotein(a) (Lp[a]), consists of structural domains (a serine protease unit, kringles 4 and 5) with marked homology to those of the corresponding domains in plasminogen. In this study, we have investigated the impact of this unique structural mimicry on the binding and activation of plasminogen by fibrin-bound tissue-type plasminogen activator at the plasma-fibrin interface. We found that the total amount of plasmin generated on the surface of fibrin was decreased in the presence of high concentrations of Lp(a): 197 +/- 65 fmol in plasmas with greater than 60 mg/dl Lp(a) versus 287 +/- 112 fmol in control plasmas. A similar effect was also apparent in the corresponding euglobulin fractions (554 +/- 169 fmol versus 754 +/- 310 fmol), the latter lacking the plasminogen-binding proteins alpha 2-antiplasmin and histidine-rich glycoprotein, but containing Lp(a). The difference between plasma samples was significant (p less than 0.05) as calculated from the percent decrease in plasmin generated from plasmas with high levels of Lp(a) relative to that generated in the paired controls with low Lp(a) levels. The involvement of Lp(a) was verified in a reconstituted system consisting of normal human plasma supplemented with 100 mg/dl of either purified Lp(a) or low density lipoprotein. Lp(a) produced a decrease of 30% in the generation of plasmin (180 fmol versus 255 fmol in plasma, and 485 fmol versus 705 fmol in the euglobulin fraction). Moreover, using a radiolabeled sheep antibody against human apo(a), we were able to demonstrate the binding of 40 fmol Lp(a) to fibrin during ongoing plasminogen activation. These results indicate that Lp(a) impairs the binding of plasminogen to fibrin and thereby decreases the generation of plasmin by occupying C-terminal lysine residues unveiled on the fibrin surface by plasmin degradation as recently reported (Circulation 1990;82[suppl III]:III-92). In consequence, impairment of fibrinolysis and accumulation of Lp(a) at sites of vascular injury may occur, factors that may be important in the development of atherosclerosis and associated thrombosis.

Blood↗
PubMedDate not supplied

Pharmacokinetics of intravenous procaine infusion in humans.

Pharmacokinetic data during and following the continuous intravenous infusion of procaine are lacking. We studied 12 women undergoing hysterectomy during N2O-O2 and narcotic anesthesia. A constant infusion of 2% procaine was administered at a rate of 1 mg/kg/min to six patients (group I) and at a rate of 1.5 mg/kg/min to the other six (group II). Procaine plasma levels were determined by flame ionization gas-liquid chromatography. Using a two-compartment pharmacokinetic model, disposition kinetics were studied. Steady-state plasma levels were achieved within 20 to 30 minutes after commencement of the infusion. Following termination of the infusion the drug disappeared with a distribution half-life (t1/2 alpha) of 2.49 +/- 0.36 minutes and an elimination half-life (t1/2 beta) of 7.69 +/- 0.99 minutes at both infusion rates. In group I, the fraction of drug in the central compartment was 65%, the volume of distribution at steady-state was 0.79 +/- 0.14 L/kg, and total body clearance 0.08 +/- 0.01 L/kg/min. In group II, the fraction of drug in the central compartment was 82%, the volume of distribution at steady-state 0.34 +/- 0.07 L/kg, and the total body clearance 0.04 +/- 0.01 L/kg/min. These data indicate that procaine is a drug of limited distribution and tissue uptake with a short duration of action.

Adult↗
PubMedDate not supplied

Induction of cognitive deficits by immunization with cholinergic cell bodies: the influence of age and integrity of the blood-brain barrier.

We have recently shown that prolonged immunization of young rats for one year with cholinergic cell bodies (perikarya, PK) purified from Torpedo electric lobe results in the accumulation of IgG in specific brain areas such as the hippocampus and induces behavioral deficits in spatial orientation and short term memory /1, 7/. We presently studied the rate of development of the cognitive deficit in older (12 months old) Sprague Dawley rats which were immunized for periods of up to one year with either Torpedo cholinergic PK or adjuvant (controls). T-maze alternation and Morris swim maze tests revealed a small deficit in the performance of the PK immunized rats after 6 months whereas significant deficits were observed after 12 months of immunization. These results suggest that the duration of immunization is a more significant factor than the age of the animals in the development of the behavioral deficit. In order to examine whether permeability of the blood-brain barrier to IgG influences the rate of development of the cognitive deficit, we disrupted the blood-brain barrier of PK immunized rats by hypercapnia. This treatment repeated weekly for 2 months was found not to accelerate the rate of appearance of deficits in performance of the rats in the T-maze alternation and Morris swim test. These results suggest that penetration of IgG via the blood-brain barrier does not determine the rate of appearance of the cognitive deficits.

Age Factors↗
PubMedDate not supplied

Acupressure for nausea: results of a pilot study.

PURPOSE/OBJECTIVES: To compare differences in nausea experience and intensity in women undergoing chemotherapy for breast cancer between those receiving usual care plus acupressure training and treatment and those receiving only usual care. DESIGN: Single-cycle, randomized clinical trial. SETTING: Outpatient oncology clinic in a major teaching medical center and a private outpatient oncology practice. SAMPLE: Seventeen women participated in the study. The typical participant was 49.5 years old (SD = 6.0), Caucasian (59%), not married/partnered (76%), on disability (53%), born a U.S. citizen (76%), and heterosexual (88%); lived alone (59%); had at least graduated from high school (100%); and had an annual personal income of $50,000 or greater (65%). METHODS: The intervention included finger acupressure bilaterally at P6 and ST36, acupressure points located on the forearm and by the knee. Baseline and poststudy questionnaires plus a daily log were used to collect data. MAIN RESEARCH VARIABLES: Nausea experience measured by the Rhodes inventory of Nausea, Vomiting, and Retching and nausea intensity. FINDINGS: Significant differences existed between the two groups in regard to nausea experience (p < 0.01) and nausea intensity (p < 0.04) during the first 10 days of the chemotherapy cycle, with the acupressure group reporting less intensity and experience of nausea. CONCLUSIONS: Finger acupressure may decrease nausea among women undergoing chemotherapy for breast cancer. IMPLICATIONS FOR NURSING PRACTICE: This study must be replicated prior to advising patients about the efficacy of acupressure for the treatment of nausea.

Acupressure↗