Biomedical subjects

L Anderson

Publications and source records attributed to L Anderson.

At least 19 recordsLinked to original sources

PubMed2001

Pancreas transplantation: the histologic morphology of graft loss and clinical correlations.

BACKGROUND: Graft losses due to leaks, bleeding, thrombosis, infections, and early pancreatitis are grouped together under the category of technical failure. Among these complications, massive vascular thrombosis continues to be the most important cause of early graft loss due to technical failure. Pathological evaluation of most allografts lost early in the posttransplantation period shows vascular thrombosis with associated proportional parenchymal necrosis. The morphological findings in allografts that are considered to be lost due to technical failure has not been systematically addressed. In particular, the role of acute rejection in early graft loss has not been well studied. METHODS: Seventy-four consecutive pancreas graft pancreatectomies were studied histologically to evaluate for thrombosis (recent versus organized), type of vessel involved by thrombosis (arteries, veins, or both), acute rejection grade, chronic rejection grade, endotheliitis, transplant arteritis, coagulation necrosis, acute pancreatitis, presence of infectious organisms, transplant (obliterative) arteriopathy, neoplasia, relative proportions of alpha and beta islet cells, and immunoglobulin and complement deposition. The histological findings were correlated with donor and recipient data as well as clinical presentation. RESULTS: In 23 out of 39 grafts lost in the first 4 weeks posttransplantation, the only pathological changes found were vascular thrombosis and bland ischemic parenchymal necrosis. In these cases, no underlying vascular pathology or any other specific histological change was identified. Most of these grafts (78%) were lost in less than 48 hr and all in the first 2 weeks posttransplantation. Massive vascular thrombosis occurring in an otherwise histologically normal pancreas was the most common cause of graft loss in the first 4 weeks posttransplantation (59%). In most of the remaining cases (33%), although the clinical presentation suggested technical failure, there was clear histological evidence that the massive thrombosis resulted from vascular injury due to immune damage (acute and hyperacute rejection). Increased incidence of early graft thrombosis was seen in grafts from older donors and longer cold ischemia times. After the first month posttransplantation, graft pancreatectomies revealed a wider variety of pathological processes that included severe acute rejection, combined acute and chronic rejection, chronic rejection, and infections. Acute and chronic vascular thrombosis in large and small vessels was commonly seen at all times posttransplantation; chronic, organized thrombosis was strongly associated with chronic rejection. CONCLUSIONS: (a) Early acute thrombosis occurring in a histologically normal pancreas defines a true technical failure. This study showed that acute rejection leading to massive thrombosis, which clinically simulates technical failure, results in a significant proportion of early graft losses. (b) Systematic histological evaluation of failed grafts is absolutely necessary for the accurate classification of the cause of graft loss. (c) There is morphological evidence that chronically ongoing thrombosis is an important, common, contributing factor for late graft loss.

Adult↗

PubMed2001

Prevalence of diastolic dysfunction in normotensive, asymptomatic patients with well-controlled type 2 diabetes mellitus.

To evaluate the prevalence of left ventricular (LV) diastolic dysfunction in patients with type 2 diabetes mellitus free of cardiovascular disease, we studied 86 normotensive men and women (mean age 46 +/- 6 years) with Doppler echocardiography. All subjects were asymptomatic for ischemic heart disease or heart failure. The traditional transmitral filling patterns were used to characterize diastolic physiology. The Valsalva maneuver was used to differentiate normal from pseudonormal LV filling pattern. All patients had a normal electrocardiogram at rest and a negative result on exercise echocardiography for inducible wall motion abnormalities. Global LV systolic function was normal (mean LV ejection fraction 58%, range 53% to 76%). Diastolic dysfunction was found in 41 subjects (47%) of which 26 (30%) had impaired relaxation and 15 (17%) had a pseudonormal filling pattern. The mean LV mass index was 101 g/m2 (range 86 to 122). All patients with a normal-filling physiology had gender-adjusted normal LV mass index (mean 93 +/- 11 g/m2), whereas 62% of those with either abnormal relaxation (mean 103 +/- 12 g/m2, p <0.001) or a pseudonormal pattern (mean 110 +/- 12 g/m2, p <0.001) had increased LV mass index. No subject in this cohort had restrictive diastolic physiology. In conclusion, diastolic dysfunction in type 2 diabetes mellitus patients is often found despite adequate metabolic control and freedom from clinically detectable heart disease. The Valsalva maneuver can unmask an additional 17% of patients with subclinical abnormal LV filling pattern, who otherwise would be classified as having a normal diastolic physiology. Increased LV mass index is closely associated with abnormal LV filling characteristics.

Adult↗

PubMed2001

TAU as a susceptibility gene for amyotropic lateral sclerosis-parkinsonism dementia complex of Guam.

BACKGROUND: A Guam variant of amyotrophic lateral sclerosis (ALS-G) and parkinsonism dementia complex (PDC-G) are found in the Chamorro people of Guam. Both disorders have overlapping neuropathologic findings, with neurofibrillary tangles in spinal cord and brain. The cause of ALS-G-PDC-G is unknown, although inheritance and environment appear important. Because neurofibrillary tangles containing tau protein are present in ALS-G-PDC-G, and because mutations in the tau gene (TAU) cause autosomal dominant frontotemporal dementia, TAU was examined as a candidate gene for ALS-G-PDC-G. METHODS: TAU was evaluated by DNA sequence analysis in subjects with ALS-G-PDC-G, by linkage analysis of TAU polymorphisms in an extended pedigree from the village of Umatac, and by evaluation of linkage disequilibrium with polymorphic markers flanking and within TAU. RESULTS: Linkage disequilibrium between ALS-G-PDC-G and the TAU polymorphism CA3662 was observed. For this 2-allele system, PDC and ALS cases were significantly less likely than Guamanian controls to have the 1 allele (4.9% and 2% vs 11.5%, respectively; Fisher exact P =.007). DNA sequence analysis of TAU coding regions did not demonstrate a mutation responsible for ALS-G-PDC-G. Analysis of TAU genotypes in an extended pedigree of subjects from Umatac showed obligate recombinants between TAU and ALS-G-PDC-G. Linkage analysis of the Umatac pedigree indicates that TAU is not the major gene for ALS-G-PDC-G. CONCLUSIONS: The genetic association between ALS-G-PDC-G implicates TAU in the genetic susceptibility to ALS-G-PDC-G. TAU may be a modifying gene increasing risk for ALS-G-PDC-G in the presence of another, as yet, unidentified gene.

Adult↗

PubMed2001

Efficacy of adenoviral TNF alpha antisense is enhanced by a macrophage specific promoter.

Macrophage-derived TNF alpha is a critical mediator of inflammation and destruction in diseases such as rheumatoid arthritis and Crohn's disease. These studies were undertaken to develop an effective adenovirus-based strategy to specifically suppress TNF alpha in primary human macrophages. A variety of promoters and LTRs were evaluated for effective expression in the macrophage cell line RAW 264.7. The CMV promoter and the Visna LTR were the most strongly expressed and were therefore used to drive the expression of TNF alpha antisense fragments. In transient transfection assays, the antisense fragment terminating at the 3' end of the first exon (216 bp) was superior to the others (70 and 750 bp), when expressed under the control of either the CMV promoter or the Visna LTR. Adenoviral vectors expressing the 216 bp TNF alpha antisense fragment, controlled by the CMV promoter or the Visna LTR, were both effective at suppressing LPS-induced TNF alpha secretion by primary human macrophages. However, the Visna LTR was more effective not only at suppressing LPS-induced TNF alpha secretion, but also IL-6, which is highly sensitive to TNF alpha secretion. These results demonstrate that effective, specific, suppression of TNF alpha in macrophages is possible, employing a directed antisense approach and a promoter system that is highly efficient in human macrophages.

Adenoviridae↗

PubMed2001

GRASPing infection: a workload measurement tool for infection control nurses.

The GRASP nursing workload management system was used over a five-month period by both the infection control nurses (ICNs) in an infection control team (ICT) in a 1200-bedded university teaching hospital trust. GRASP data were used to quantify and qualify patient and Trust requirements for infection control (IC). The results indicated that care was being prioritised as the average daily patient care requirement was 15.9 h, whereas the ICNs were only able to provide 12.7 h to meet this. Infection control nurses spent 5.3 h dealing with methicillin-resistant Staphylococcus aureus (MRSA), and only 3.9 h in preparation and delivery of education. A 'fire brigade service' was being provided at the expense of developmental and strategic issues. GRASP provided a method of quantifying, recording and analysing workload. It was used to support recommendations from the Health Quality Service Organizational Audit (Kings Fund), the Department of Health (DoH), the National Audit Office (NAO), and the Health and Safety Executive (HSE) for an increased focus on education and risk management in IC. It was also used in a skill-mix exercise, and resulted in the appointment of additional staffing to the ICT. GRASP data could be used for benchmarking with other institutions to provide a flexible system which may be adapted to meet the changing demands of the health service. It provides a means for ICNs to measure and manage their workload, and may be adapted to other members of the ICT.

Hospitals, University↗

PubMed2001

Rate of injection through whitacre needles affects distribution of spinal anaesthesia.

A prospective, randomized, double-blind study was performed to investigate whether altering the rate of injection of local anaesthetic through a Whitacre needle had any effect on the spinal block achieved. Twenty patients scheduled for elective urological surgery under spinal anaesthesia received an injection of 3 ml of 0.5% plain bupivacaine either by hand (fast) over 10 s (18 ml min(-1)) or by infusion pump (slow) over 3 min (1 ml min(-1)). All patients were in the sitting position both during insertion of the spinal needle and for 3 min after the start of spinal injection, and they then changed to the supine position. The slow injection group achieved peak sensory block earlier, after a median interval of 20 (95% confidence interval 12.5-30) min vs 30 (22.5-45) min (P<0.05) for the fast group. The level of peak sensory block was similar: T3.5 (T2-T4.5) vs T4 (T1.5-T6.5). The time to lowest mean arterial pressure occurred earlier in the slow group, at 10 (8 to 18) vs 20 (15-31) min (P<0.05). Duration of the motor block was shorter in the slow group: 180 (152-242) vs 270 (225-300). We conclude that a slow spinal injection of plain bupivacaine results in a block of more rapid onset and recovery.

Aged↗

PubMed2001

Inside the routine general practice consultation: an observational study of consultations for sore throats.

OBJECTIVES: The aims of this study were to examine how GPs manage the consultation for upper resiratory tract infections (URTIs) and the prescribing of antibiotics, to understand what skills and strategies are used in managing URTIs without antibiotics, and to note evidence of pressure on doctors to prescribe and whether there are signs of overt disagreement about prescribing in the consultation. METHODS: A qualitative analysis of audiotaped consultations was carried out. The setting was a general practice in South Wales and the subjects were five GPs and 29 parents presenting children with URTIs over a 2-week period. The main outcome measures were skills and strategies identified from audiotapes of consultations. RESULTS: This group of GPs used a set of readily identifiable consulting skills for managing the consultation without prescribing. Their consultations had a highly routinized quality. There was little evidence of either conflict or overt pressure from parents to prescribe. The word 'antibiotics' was seldom mentioned. Clinicians did not elicit patient expectations for receiving antibiotics. CONCLUSIONS: Doctors use a set of readily identifiable skills in managing the URTI consultation. Avoiding the prescribing of antibiotics is not necessarily a simple and straightforward matter. Since patients apparently want antibiotics less than anticipated, eliciting expectations might be a way of reducing prescribing and broadening the approach to meeting patient needs. Whether doctors can adjust their routinized consulting patterns in the time-limited context of general practice remains an open question.

Anti-Bacterial Agents↗

PubMed2001

Attaining superior outcomes with joint replacement patients.

Wanting to improve the quality outcomes of their joint care program, a team approach was used to implement a program with integrated care across the continuum. The authors describe the joint care program and its outcomes that included a decrease in length of stay, fewer complications, improved functional status, higher discharge disposition to home, and lower variable costs per case.

Advisory Committees↗

PubMed2001

Surveillance of depleted uranium exposed Gulf War veterans: health effects observed in an enlarged "friendly fire" cohort.

To determine clinical health effects in a small group of US Gulf War veterans (n = 50) who were victims of depleted uranium (DU) "friendly fire," we performed periodic medical surveillance examinations. We obtained urine uranium determinations, clinical laboratory values, reproductive health measures, neurocognitive assessments, and genotoxicity measures. DU-exposed Gulf War veterans with retained metal shrapnel fragments were excreting elevated levels of urine uranium 8 years after their first exposure (range, 0.018 to 39.1 micrograms/g creatinine for DU-exposed Gulf War veterans with retained fragments vs 0.002 to 0.231 microgram/g creatinine in DU exposed but without fragments). The persistence of the elevated urine uranium suggests ongoing mobilization from the DU fragments and results in chronic systemic exposure. Clinical laboratory outcomes, including renal functioning, were essentially normal. Neurocognitive measures showing subtle differences between high and low uranium exposure groups, seen previously, have since diminished. Sister chromatid exchange frequency, a measure of mutation in peripheral lymphocytes, was related to urine uranium level (6.35 sister chromatid exchanges/cell in the high uranium exposure group vs 5.52 sister chromatid exchanges/cell in the low uranium exposure group; P = 0.03). Observed health effects were related to subtle but biologically plausible perturbations in central nervous system function and a general measure of mutagen exposure. The findings related to uranium's chemical rather than radiologic toxicity. Observations in this group of veterans prompt speculation about the health effects of DU in other exposure scenarios.

Adult↗

PubMed2001

Phosphorylation and rapid relocalization of 53BP1 to nuclear foci upon DNA damage.

53BP1 is a human BRCT protein that was originally identified as a p53-interacting protein by the Saccharomyces cerevisiae two-hybrid screen. Although the carboxyl-terminal BRCT domain shows similarity to Crb2, a DNA damage checkpoint protein in fission yeast, there is no evidence so far that implicates 53BP1 in the checkpoint. We have identified a Xenopus homologue of 53BP1 (XL53BP1). XL53BP1 is associated with chromatin and, in some cells, localized to a few large foci under normal conditions. Gamma-ray irradiation induces increased numbers of the nuclear foci in a dose-dependent manner. The damage-induced 53BP1 foci appear rapidly (in 30 min) after irradiation, and de novo protein synthesis is not required for this response. In human cells, 53BP1 foci colocalize with Mrel1 foci at later stages of the postirradiation period. XL53BP1 is hyperphosphorylated after X-ray irradiation, and inhibitors of ATM-related kinases delay the relocalization and reduce the phosphorylation of XL53BP1 in response to X-irradiation. In AT cells, which lack ATM kinase, the irradiation-induced responses of 53BP1 are similarly affected. These results suggest a role for 53BP1 in the DNA damage response and/or checkpoint control which may involve signaling of damage to p53.

Androstadienes↗

PubMed2001

Prevalence of mental retardation and developmental disabilities: estimates from the 1994/1995 national health interview survey disability supplements.

In 1994 and 1995, the National Health Interview Survey included a Disability Supplement (NHIS-D) to collect extensive information about disabilities among individuals sampled as part of annual census-based household interview surveys. Here we describe the development and application of operational definitions of mental retardation and developmental disabilities to items in the NHIS-D to estimate prevalence. In our analyses, we estimate the prevalence of mental retardation in the noninstitutionalized population of the United States to be 7.8 people per thousand (.78%); of developmental disabilities, 11.3 people per thousand (1.13%); and the combined prevalence of mental retardation and/or developmental disabilities to be 14.9 per thousand (1.49%). Differences in prevalence estimates for mental retardation and developmental disabilities and among people of various ages are explored.

Journal Article↗

PubMed2001

Prevalence of mental retardation and developmental disabilities: estimates from the 1994/1995 National Health Interview Survey Disability Supplements.

Adolescent↗

PubMed2001

Evaluation of a cervical cytology device (cell-sweep) based on comparison to colposcopic findings.

A new cytology sampling device, the CellSweep, identifies squamous intraepithelial lesions with a sensitivity of 75%. The purpose of this study was to evaluate the accuracy of cervical cytology using a new sampling device combining an endocervical brush and ectocervical spatula into one unit (CellSweep, patented by R. Mohajer, Troy, Michigan). From April 1995 to July 1995, 71 patients referred to the Allegheny University Hospitals Colposcopy Clinic had cervical cytology obtained with the CellSweep and underwent colposcopic evaluation of the cervix. The ability of the CellSweep to detect an abnormality confirmed by colposcopic evaluation was studied. Colposcopically directed ectocervical biopsies were obtained only in patients with identifiable lesions (n = 32). No random biopsies were obtained. The cytology smear was unsatisfactory for interpretation in one case. The remaining 70 Papanicolaou smears were read as normal in 17 (24%) cases and atypical squamous cells in 19 (27%). A squamous intraepithelial lesion (SIL) was detected in 34 (48%) smears. The colposcopic evaluation was normal in 50 patients who had satisfactory Papanicolaou smears, whereas SIL was detected in 20 cases. In 31 patients, SIL was not present in either colposcopy or cytology. In this preliminary study, the CellSweep identified SIL with a sensitivity of 75% and a specificity of 62%. The CellSweep, which combines an endocervical brush and an ectocervical spatula into a single unit, seems to be an acceptable device for obtaining cervical cells for cytologic screening.

Adolescent↗

PubMed2000

Interactions of conformationally biased north and south 2'-fluoro-2', 3'-dideoxynucleoside 5'-triphosphates with the active site of HIV-1 reverse transcriptase.

Molecular dynamics simulations of a ternary complex of HIV-1 reverse transcriptase (RT), double-stranded DNA, and bound dideoxynucleoside-5'-triphosphate (RT-DNA-ddNTP), utilizing the ddNTPs ddATP, betaFddATP, and alphaFddATP, explain the experimentally observed order of potency of these 5'-triphosphates as inhibitors of RT: ddATP > betaFddATP > alphaFddATP. On the basis of RT's known preference to bind the incoming dNTP (or ddNTP) with a north conformation at the polymerase site, alphaFddATP, which in solution prefers almost exclusively a north conformation, was predicted to be the most potent inhibitor. However, Tyr115, which appears to function as a steric gate to preclude the binding of ribonucleoside 5'-triphosphates, prevents the effective binding of alphaFddATP in its preferred north conformation. The south-biased betaFddATP, while able to bind to RT without hindrance by Tyr115, has to pay a high energy penalty to be flipped to the active north conformation at the polymerase site. Finally, the more flexible and less conformationally biased ddATP is able to switch to a north conformation at the RT site with a smaller energy penalty than betaFddATP. These results highlight the opposite conformational preferences of HIV-1 RT for alphaFddATP and betaFddATP and help establish conformational guidelines for optimal binding at the polymerase site of this enzyme.

Anti-HIV Agents↗

PubMed2000

High-dose-rate intraoperative radiation therapy (HDR-IORT) for retroperitoneal sarcomas.

PURPOSE: Retroperitoneal sarcomas represent a formidable challenge to the treating oncologist due to their location, large size, and poor prognosis. The purpose of this study was to determine if the addition of high-dose-rate intraoperative radiation therapy (HDR-IORT) to surgery and external beam radiotherapy (EBRT) would improve the outcome in these patients. METHODS AND MATERIALS: Thirty-two patients with retroperitoneal soft tissue sarcoma were prospectively treated according to a protocol that included maximal tumor resection, HDR-IORT, and postoperative EBRT when feasible. Twelve patients presented with primary and 20 with locally recurrent disease. The tumors were high-grade in 20 patients and low-grade in 12 patients. Complete gross resection was achieved in 30 patients. HDR-IORT was given to a dose of 12-15 Gy. Additional EBRT was given to 78% of patients to a dose of 45-50.4 Gy. The two patients with gross residual disease received an additional I-125 permanent implant to a median peripheral dose of 140-160 Gy. The median follow-up was 33 months (range 1-77 mo). RESULTS: The 5-year actuarial local control rate for the whole group was 62%. For patients with primary disease, the local control rate was 74% compared to 54% in patients with recurrent disease (p = 0.4). The overall 5-year distant metastasis-free survival rate was 82%. In patients with high-grade tumors the rate was 70% vs. 100% in those with low-grade tumors. This difference was statistically significant, p = 0.05. The 5-year disease-free and overall survival rates were 55% and 45%, respectively. The most common type of post-treatment complication was gastrointestinal obstruction (18%) followed by fistula formation (9%), peripheral neuropathy (6%), hydronephrosis (3%), and wound complication (3%). CONCLUSIONS: We are encouraged by the favorable local control rate and the acceptable morbidity with this new technique applied to a challenging patient population.

Adult↗

PubMed2000

Efficacy of doramectin against naturally acquired nematode infection in Iberian swine.

Studies were carried out to determine the therapeutic efficacy of doramectin, administered intramuscularly at a dose of 300 microg/kg live weight, against naturally acquired helminths of extensively farmed Iberian pigs. The first study (slaughter study) evaluated, through necropsy of the study animals, the product's efficacy against gastrointestinal and pulmonary nematodes (Ascaris suum, Oesophagostomum dentatum and Metastrongylus sp.) whilst the second, faecal egg count reduction study, (FECR study) evaluated the drug's efficacy only against gastrointestinal helminths (A. suum, Trichuris suis and Oesophagostomum sp.). The first study used 20 animals divided into two equal groups of 10 on the basis of body weight and faecal egg count. One group constituted saline treated controls and the other was doramectin treated. On Day 14 post treatment half of the animals in each group were necropsied and the number of parasites present counted. On Day 15 the remaining half of each group underwent the same procedure. The second study was carried out with 40 animals divided equally into two groups of 20. This study determined the effect of doramectin treatment on faecal egg counts as an indicator of parasite burden. The first study demonstrated an efficacy of 100% against adult Metastrongylus sp. and A. suum, whilst the efficacy against O.dentatum was 96.3%. The second study indicated that at Day 21 post treatment there was a 100% reduction in egg counts in faeces in comparison to untreated controls.

Animals↗

PubMed2000

Adenosine deaminase prefers a distinct sugar ring conformation for binding and catalysis: kinetic and structural studies.

Several recent X-ray crystal structures of adenosine deaminase (ADA) in complex with various adenosine surrogates have illustrated the preferred mode of substrate binding for this enzyme. To define more specific structural details of substrate preferences for binding and catalysis, we have studied the ADA binding efficiencies and deamination kinetics of several synthetic adenosine analogues in which the furanosyl ring is biased toward a particular conformation. NMR solution studies and pseudorotational analyses were used to ascertain the preferred furanose ring puckers (P, nu(MAX)) and rotamer distributions (chi and gamma) of the nucleoside analogues. It was shown that derivatives which are biased toward a "Northern" (3'-endo, N) sugar ring pucker were deaminated up to 65-fold faster and bound more tightly to the enzyme than those that preferred a "Southern" (2'-endo, S) conformation. This behavior, however, could be modulated by other structural factors. Similarly, purine riboside inhibitors of ADA that prefer the N hemisphere were more potent inhibitors than S analogues. These binding propensities were corroborated by detailed molecular modeling studies. Docking of both N- and S-type analogues into the ADA crystal structure coordinates showed that N-type substrates formed a stable complex with ADA, whereas for S-type substrates, it was necessary for the sugar pucker to adjust to a 3'-endo (N-type) conformation to remain in the ADA substrate binding site. These data outline the intricate structural details for optimum binding in the catalytic cleft of ADA.

Adenosine↗

PubMed2000

Efficacy of abciximab readministration in coronary intervention.

Abciximab, an Fab monoclonal antibody fragment that blocks the platelet glycoprotein IIb/IIIa receptor, is increasingly used as an adjunct to coronary intervention. Little is known, however, about the efficacy and safety of readministration of abciximab. This study examined and characterized outcomes of patients receiving abciximab for a second time. From April 1995 to June 1997, 164 consecutive patients were readministered abciximab at our 3 institutions. We retrospectively examined and analyzed in-hospital outcomes in this cohort. The median time to readministration was 95 days. The angiographic success rate of percutaneous intervention was 99.5%. Rates and 95% confidence intervals of in-hospital events were death 2% (0.7% to 6.1%), myocardial infarction 3% (1% to 7%), coronary bypass surgery 0% (0% to 2.2%), and intracranial hemorrhage 2% (0.4% to 5.3%). Severe thrombocytopenia was observed in 4% of patients (1.4% to 7.8%) after readministration. Allergic or anaphylactic reactions were not observed. Major bleeding was associated with excessive concomitant antithrombotic therapy. Patients undergoing readministration of abciximab within 2 weeks of first administration experienced a higher incidence of severe thrombocytopenia (12% vs. 2%, p = 0.046). Thus, abciximab remains clinically efficacious when readministered as an adjunct to percutaneous coronary intervention. However, concomitant heparin administration must be carefully monitored and warfarin therapy should be avoided. Vigilant surveillance for thrombocytopenia should be employed. Reduced dosing may be necessary when abciximab is readministered within days of the initial administration.

Abciximab↗