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Biomedical subjects

R H Moore

Publications and source records attributed to R H Moore.

At least 37 records · Page 2Linked to original sources
PubMed1996

Positive predictive value of breast biopsy performed as a result of mammography: there is no abrupt change at age 50 years.

PURPOSE: To determine if the positive predictive value (PPV) of a biopsy initiated because of an abnormal mammogram changes abruptly at age 50 years. MATERIALS AND METHODS: The PPV and its variation with age was analyzed for 4,778 women who underwent biopsy for a clinically occult abnormality detected at mammography. The relationship of the results to the patient's age was analyzed with age represented as a continuous and two-categorized (< 50, > 50) measure. The latter measure represented an abrupt change, which distinguished those aged 49 years and younger from those aged 50 years and over. With this measure, the patients in each of the two age groups were statistically indistinguishable. RESULTS: The results were consistent with a steady increase in PPV and the yield of cancers with age, and there was no abrupt change at age 50 years. The modeled PPV for all cancers for these 4,778 patients was approximately 12% for women aged 40 years and increased to 46% by age 79 years. CONCLUSION: The PPV did not change abruptly at any age for women aged 40-79 years but increased steadily, which reflects the prior probability of breast cancer at each age. Inappropriate grouping of data can lead to misinterpretation of results. Screening guidelines should not be predicated on the false assumption that this variable changes at age 50 years.

Adult↗
PubMed1996

Physicians' opinions on the delivery of mammographic screening services: immediate interpretation versus double reading.

OBJECTIVE: Mammographic services are delivered in many ways. Emphasis has been placed on providing women with immediate reports of their screening mammograms. We believe that double reading of mammograms is more important than an immediate report. We sought to determine physicians' attitudes toward this issue and if education affects their opinions. MATERIALS AND METHODS: Questionnaires were mailed to 1000 physicians in Massachusetts who were randomly selected from 16,000 members of the state medical society. The questionnaire had four sections, of which two were pertinent to this subject. The first section collected general information on the physician's practice and experience. The second section described two common delivery systems for mammographic screening services and asked physicians to choose the delivery system that would most benefit their patients. RESULTS: Of the 1000 physicians, 294 returned the questionnaire, giving a response rate of 29%. Of these, 16 physicians returned blank surveys, leaving 278 for analysis. Two hundred forty-nine (90%) valued off-site, delayed interpretation of mammographic screening for their patients over on-site reading by a single radiologist if an off-site, delayed reading made double reading possible. CONCLUSION: An off-site, double-reading delivery system for mammographic screening services is preferred by many physicians for their patients once they are educated as to the benefits of double reading.

Adult↗
PubMed1996

Cytomegalovirus involving gastrointestinal tract in renal transplant recipients.

Infection due to cytomegalovirus (CMV) is a substantial cause of mortality and morbidity among renal transplant recipients but the prognosis of the disease has changed dramatically since the introduction of ganciclovir (GAN). During a period of 5 years we treated 54 patients who developed CMV disease. From this group of patients we identified 7 patients with primary gastrointestinal tract (GIT) CMV disease who received treatment with GAN. Tissue diagnosis was made by endoscopy of the upper GIT (6 patients) or sigmoidoscopy (one patient) and histological examination. All patients improved after treatment with GAN; three patients required additional treatment for recurrent CMV disease and recovered, and 1 patient relapsed without GIT involvement (P = 0.014). Recurrent CMV disease was more severe (mean score of 15 in relapse compared to 7 in the first episode). We believe relapse to be more common and the disease to be more severe in the presence of GIT involvement suggesting that a longer duration of treatment with GAN may be required in this clinical manifestation of CMV disease.

Adolescent↗
PubMed1996

Repetitive endocytosis and recycling of the beta 2-adrenergic receptor during agonist-induced steady state redistribution.

The human beta 2-adrenergic receptor (beta 2AR) rapidly internalizes after binding agonist, resulting in a dramatic redistribution of receptors from the plasma membrane and into endocytic vesicles. We sought to determine whether intracellular receptors constitute a static pool or represent a fraction of dynamically internalizing and recycling receptors. Using cells expressing a beta 2AR with an epitope tag at its amino-terminal ectodomain, changes in surface receptor levels were measured by flow cytometry and radioligand binding assays. The addition of a saturating level of a strong agonist (isoproterenol) caused the endocytosis of receptors with first-order kinetics (ke for naive cells, 0.222 min-1). After 10 min, the level of surface receptors remained stable at approximately 20% that of untreated cells, even though endocytosis continued with similar kinetics (ke for pretreated cells, 0.258 min-1), suggesting that internalized receptors were cycling in steady state with surface receptors. This prediction was confirmed directly by showing that internalized beta 2ARs recycled to the cell surface in the continued presence of agonist. The calculated transit times (1/k) in the presence of isoproterenol were 3.9 min for endocytosis and 11.2 min for recycling. The endocytic rate constant and the steady state redistribution to the internal pool were much lower after treatment with the partial agonist albuterol, suggesting a correlation between the efficiency of endocytosis and that of receptor coupling to the downstream signal transduction pathway. These findings indicate that in the presence of agonist, beta 2ARs are in a dynamic steady state between the plasma membrane and endosomes that is regulated principally by agonist efficacy.

Adrenergic beta-Agonists↗
PubMed1996

Foolers: things that look like pneumonia in children.

Pulmonary infiltrates on chest radiographs are common findings in the pediatric age group and are generally associated with acute infectious pneumonias. Occasionally, however, these "pneumonias" fail to respond to appropriate antibiotic therapy. Under these circumstances, noninfectious conditions that may be associated with pulmonary infiltrates should be considered. Thus, it is important that physicians who care for children have some knowledge of these potential "mimickers" of childhood pneumonia.

Asthma↗
PubMed1995

Blood lead surveys of communities in proximity to lead-containing mill tailings.

In former mining communities tailings containing up to 2% (20,000 ppm) lead (Pb), frequently as galena (lead sulfide), may be present in large piles near residences, as landfill under homes, or mixed with residential soils. The impact of tailings on blood lead was assessed by comparing blood lead values obtained from residents and environmental lead measured in soils and tailings piles. Data from 13 communities were compiled. Approximately 2995 blood lead measurements were available from persons residing on or near tailings, with the majority of samples from children. Blood lead levels were compared to 1806 controls from nearby communities, national norms, and communities with active smelters. Data comparisons indicated that blood lead values in tailings residents were usually comparable to controls. These data suggest that lead present in mill tailings is not readily bioavailable, even to children who played in dirt or tailings piles. Consequently, the hazard of lead in soils appears to be site-specific and influenced by bioavailability; the bioavailability of galena tailings to humans is low. When health risks of lead soils are predicted, factors affecting the bioavailability of lead present in tailings need to be taken into account.

Biological Availability↗
PubMed1995

Ligand-stimulated beta 2-adrenergic receptor internalization via the constitutive endocytic pathway into rab5-containing endosomes.

The small GTPase rab5 appears to be rate-limiting for the constitutive internalization of transferrin receptor and for fluid-phase endocytosis. However, it is unknown whether rab5 regulates receptors whose internalization is stimulated by the binding of ligand, and whether such receptors change the underlying rate of the endocytic pathways they utilize. As a model for ligand-stimulated endocytosis, we used transfected HEK293 cells expressing high levels of an epitope-tagged human beta 2-adrenergic receptor. Nearly all receptors were on the cell surface in the absence of agonist, but within ten minutes of agonist addition > 50% of receptors internalized and colocalized extensively with rab5. Hypertonic sucrose blocked beta 2-adrenergic receptor internalization, as well as that of transferrin receptor, suggesting a clathrin-mediated process. In contrast, an inhibitor of potocytosis had little effect upon beta 2-adrenergic receptor internalization, suggesting that this process did not require active caveolae. Consistent with this finding, caveolin was not detectable in the 12 beta 6 line, as assessed by western blotting with a polyclonal anti-caveolin antibody. Stimulated receptor internalization did not affect the rate or capacity of the constitutive endocytic pathway since there was no detectable increase in fluid-phase endocytosis after addition of beta-agonist, nor was there a significant change in the amount of surface transferrin receptor. Altogether, these data suggest that beta 2-adrenergic receptors internalize by a clathrin-mediated and rab5-regulated constitutive endocytic pathway. Further, agonist-stimulated receptor internalization has no detectable effect upon the function of this pathway.

Adrenergic beta-2 Receptor Agonists↗
PubMed1995

Real-time monitoring of renal function during ischemic injury in the rhesus monkey.

The presence of delayed graft function (DGF) following cadaver donor renal transplantation is associated with inferior graft survival as well as decreased patient survival. Delay in onset of function eliminates a valuable indicator of allograft viability, which is not easily replaced by standard diagnostic procedures. The purpose of this study was to demonstrate that a new clearance technique could be used to measure renal function minute to minute and under conditions similar to those observed in humans in the immediate posttransplantation period. A monkey model was used to provide controlled conditions. Increasing levels of ischemic injury were produced in 12 Rhesus monkeys by renal hilum cross-clamping. Real-time measurements of glomerular filtration rate (GFR) were obtained from the rate of clearance of the extracellular fluid of the GFR agent 99mTc-DTPA, as measured with a specially designed external radioactivity counting device called the ambulatory renal monitor, or ARM. GRF was measured every 2-5 min as the slope (k) of the log of activity measured minute to minute versus time. GFR measurements were correlated with blood urea nitrogen (BUN), plasma creatinine (Cr), routine light microscopy, and measurement of proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Large changes in renal function due to ischemia or ureteral obstruction were observed within minutes. In addition, the rate constant on Day 1 was predictive of peak serum Cr(R =--0.86, R2=.74, p = .0001). Acute tubular necrosis (ATN) resolution was reflected more quickly when using the rate constant (Day 1) than when using either BUN or plasma Cr (Day 3-4). Because of renal functional reserve, BUN and plasma Cr were relatively insensitive indicators of mild to moderate reductions in GFR as compared with the rate constant. We conclude that ARM is a simple method which provide an accurate, near real-time GFR readout with potential applications not only for the clinical management of patients with DGF, but also as a research tool in acute renal failure (ARF).

Animals↗
PubMed1994

Underage female DUI offenders: personality characteristics, psychosocial stressors, alcohol and other drug use, and driving-risk.

164 underage female DUI offenders were evaluated on measures of personality, driving-risk, psychosocial stressors, alcohol and other drug use, alcohol abuse, and symptoms of depression. Empirical classification of 10 groups represented five distinct types. 31 youth who were classified as Antisocial exhibited highest rates of alcohol misuse, other drug use, deviant driving behavior, traffic offenses and accidents, and psychosocial stressors. About 56% or 92 appeared to experience impaired functioning serious enough to warrant interventions more intense than educational classes. A measure of driving-risk developed and used in studies of male adults, the Donovan Research Questionnaire, did not appear to differentiate driving-risk among the young women. In contrast to male drivers, who often expressed anger or aggression through driving, most subjects appeared to react to emotion-eliciting stimuli with feelings of low self-worth or dysphoric affect rather than anger. Specialized screening suitable for young female DUI offenders should be considered.

Accidents, Traffic↗
PubMed1993

Is there an optimal time for the first cyclosporin dose in renal transplantation?

It is customary for patients undergoing kidney transplantation to receive their first dose of cyclosporin either just before or during the transplant operation. This ensures the early establishment of good levels of immunosuppression but might depress early graft function and contribute towards the development of acute tubular necrosis. In a controlled clinical trial, we have studied the effects of withholding cyclosporin for 12 h in patients undergoing cadaveric renal transplantation. Consecutive adult recipients of a cadaveric renal transplant were randomised to receive their first dose of cyclosporin (10 mg/kg p.o.) 6 h prior to transplant surgery or 12 h afterwards. All patients received azathioprine (1.5 mg/kg i.v.) and methylprednisolone (0.5 g i.v.) in addition during surgery. From the 2nd day onwards both groups were treated with an identical triple immunosuppressive regimen. The 27 patients who received their first dose of cyclosporin post-operatively had significantly better immediate and subsequent function than did the 26 patients who received their cyclosporin at the time of surgery. The delayed dosing was associated with improved graft survival and no increase in the frequency of rejection episodes. This regimen is recommended for all patients receiving triple therapy.

Adult↗
PubMed1993

Autoimmune renal disease and tumour necrosis factor beta gene polymorphism.

The genes encoding tumour necrosis factors (TNF) are located within the major histocompatibility complex. Since TNF may be involved in the pathogenesis of autoimmune disease the purpose of the present study was to investigate TNF beta gene polymorphism in two types of immune complex mediated glomerulonephritis, IgA nephropathy (IgAN) and idiopathic membranous glomerulonephritis (IMN) and to compare them with IDDM and healthy controls. DNA was studied by Southern-blot hybridisation methods using Nco I digestion and a TNF beta probe; two alleles were detected size 5.5 kb and 10.5 kb. In healthy controls (n = 107), 9% were 5.5 homozygotes, 47% heterozygotes and 44% 10.5 homozygotes. The corresponding figures in IMN (n = 51) were 21.5%, 61% and 17.5% (p = 0.002), in IDDM (n = 42) 24%, 50% and 26% (p = 0.027) and in IgAN (n = 77) 2.5%, 65% and 32.5% (p = 0.025). The increase in 5.5 homozygotes in both IMN and IDDM was found to be due to an increased frequency of the haplotype A1-B8-TNF beta 5.5-DR3 seen in both these diseases; whereas in IgAN the increased frequency of the 10.5 kb allele can be explained by an association of a Taq 1DQB1-T2 allele with the TNF beta 10.5 allele. These results demonstrate an association of TNF beta gene polymorphism with IMN and IgAN and confirm the associations found in IDDM. Although these disease associations can be explained by linkage disequilibrium with extended MHC haplotypes, a direct role of genetically determined TNF production in the etiology of these diseases remains to be excluded.

Alleles↗