Anticoagulation of older patients.
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Age Factors↗
Biomedical subjects
J Barrett
Publications and source records attributed to J Barrett.
Non-tuberculous respiratory infections.
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Aged↗
Hyperthermic resuscitation is safe and effective after hemorrhagic shock in dogs.
OBJECTIVE: To show that resuscitation from hypothermic, hemorrhagic shock using 65 degrees C intravenous fluid results in a more rapid return to euthermia compared with 40 degrees C intravenous fluid, without significant endothelial or hemolytic injury. DESIGN: Fourteen anesthetized beagles (10-12 kg) were cooled to a core temperature of 30 degrees C and hemorrhaged to a mean arterial pressure of 40 to 45 mm Hg for 30 minutes. The animals were randomized to receive either 65 degrees C or 40 degrees C intravenous fluid through a specially designed catheter at a rate of 80% of their blood volume per hour until euthermic (37 degrees C) or for 2 hours. MATERIALS AND METHODS: Blood pressure, pulmonary artery pressure, heart rate, and core temperature were continuously monitored. Blood samples were collected at baseline, after hemorrhage, 2 hours of resuscitation, and at postmortem examination after 7 days of survival. Laboratory measurements included complete blood count, plasma-free hemoglobin, and osmotic fragility. Values were compared using the Student's paired or unpaired t test with p approximately 0.05 indicating significance. Postmortem examination included light microscopy of the proximal superior vena cava or right atrium. RESULTS: Animals receiving 65 degrees C intravenous fluid warmed 3.6 degrees C/hour, significantly faster than the 40 degrees C animals (1.9 degrees C/hour). There were no significant differences in plasma-free hemoglobin or osmotic fragility. Endothelial injuries were found in two animals in each group. These defects occurred along the path of catheter insertion and not at the infusion site. CONCLUSIONS: Central intravenous fluid at 65 degrees C is a more rapid means of treating hypothermia than standard 40 degrees C intravenous fluid. It is safe even in hypovolemic animals.
Animals↗
Prognosis of penetrating trauma in elderly patients: a comparison with younger patients.
BACKGROUND: It has previously been shown that elderly patients have a worse prognosis than their younger counterparts after sustaining blunt trauma. This is due in part to a higher incidence of comorbid conditions as well as less physiologic reserve in an elderly population sustaining largely blunt trauma. We compared the outcome after penetrating trauma in elderly patients to matched "younger" patients to determine whether they had a similarly poor prognosis. METHODS: Elderly patients (> or = 65 years) were identified from our trauma registry. Sex, mechanism of injury, and Abbreviated Injury Score/Injury Severity Score were determined from the registry. Patients presenting with traumatic arrest were excluded. The registry was then searched for patients aged 15 to 40 years with the same sex, mechanism of injury, and Abbreviated Injury Score in each region. A chart review was then performed to determine additional details of their hospital stay. The two groups were then compared using Student's t test and Fisher's exact chi2 test, as appropriate. RESULTS: Eighty-five elderly patients (OLD group) were admitted with penetrating trauma between 1983 and 1998. They were compared with 85 matched young patients (YOUNG group). Each group included 66 male and 19 female patients. In each group, gunshot wounds occurred in 45.9%, stab wounds in 52.9%, and shotgun wounds in 1.2% of patients. The average Injury Severity Score in each group was 5.5 +/- 5.6 (range, 1-29) and the regional Abbreviated Injury Scores were likewise equal in both groups. The OLD patients had an average hospital stay of 6.9 +/- 9.1 days compared with 4.3 +/- 5.7 days in the YOUNG patients (p < 0.05). Twenty-seven OLD patients spent 7.3 +/- 9.2 days in the intensive care unit compared with 19 YOUNG patients who stayed 3.4 +/- 3.2 days (p < .05). A total of 91 comorbidities were identified in 58 OLD patients compared with 18 in 15 YOUNG patients (p < .0001). Eighty-six invasive procedures were performed in the OLD group compared with 96 in the YOUNG group (p = not significant). Nineteen OLD patients (22.3%) and 15 YOUNG patients (17.6%) suffered one or more complications, including death (p = not significant). A total of 91% of surviving OLD patients were discharged to home compared with 100% of surviving YOUNG patients (p < .01). CONCLUSION: Elderly patients who sustain penetrating trauma have more comorbidities than their younger counterparts. This may account for their longer hospital stay and lesser ability to be discharged home. These patients do not have an increased complication rate and should continue to be managed aggressively.
Adolescent↗
Hemosuccus pancreaticus after penetrating trauma to the abdomen.
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Abdominal Injuries↗
Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action.
Chemokines are involved in recruitment and activation of hematopoietic cells at sites of infection and inflammation. The M3 gene of gammaHV68, a gamma-2 herpesvirus that infects and establishes a lifelong latent infection and chronic vasculitis in mice, encodes an abundant secreted protein during productive infection. The M3 gene is located in a region of the genome that is transcribed during latency. We report here that the M3 protein is a high-affinity broad-spectrum chemokine scavenger. The M3 protein bound the CC chemokines human regulated upon activation of normal T-cell expressed and secreted (RANTES), murine macrophage inflammatory protein 1alpha (MIP-1alpha), and murine monocyte chemoattractant protein 1 (MCP-1), as well as the human CXC chemokine interleukin-8, the murine C chemokine lymphotactin, and the murine CX(3)C chemokine fractalkine with high affinity (K(d) = 1. 6 to 18.7 nM). M3 protein chemokine binding was selective, since the protein did not bind seven other CXC chemokines (K(d) > 1 microM). Furthermore, the M3 protein abolished calcium signaling in response to murine MIP-1alpha and murine MCP-1 and not to murine KC or human stromal cell-derived factor 1 (SDF-1), consistent with the binding data. The M3 protein was also capable of blocking the function of human CC and CXC chemokines, indicating the potential for therapeutic applications. Since the M3 protein lacks homology to known chemokines, chemokine receptors, or chemokine binding proteins, these studies suggest a novel herpesvirus mechanism of immune evasion.
Animals↗
Antiplatelet effects of MK-852, a platelet fibrinogen receptor antagonist, in healthy volunteers.
MK-852, a cyclic heptapeptide, is a potent platelet fibrinogen receptor antagonist. When administered to normal healthy male subjects by 1- and 4-hour constant rate intravenous infusions, it provides a generally well-tolerated and reversible means of inhibition of platelet function. At infusion rates of 1 microgram/kg/min for 1 hour and 0.44 microgram/kg/min for 4 hours, respectively, MK-852 extended baseline bleeding time by greater than 2.2-fold and 2.6-fold, inhibited ADP-induced platelet aggregation by 76% and 69%, and inhibited collagen-induced platelet aggregation by 65% and 67%, respectively. The pharmacokinetics of MK-852 include an elimination half-life of approximately 2 hours, total clearance of about 150 ml/min, and volume of distribution of about 18 liters. Examination of the relationship between MK-852 whole-blood concentration in vitro and inhibition of platelet aggregation showed an EC50 of about 55 ng/ml and a Hill coefficient of 1.55. The infusions were generally well tolerated, with no study drug-related changes in blood counts or biochemical profiles.
Adenosine Diphosphate↗
Maternal-fetal HLA incompatibility and the course of inflammatory arthritis during pregnancy.
OBJECTIVE: Studies indicate that maternal-fetal incompatibility of HLA-DR and DQ antigens may be associated with a decreased risk of disease activity during pregnancy in women with rheumatoid arthritis. We attempted to replicate these findings in a large cohort of women with inflammatory polyarthritis. METHODS: Women with an inflammatory polyarthritis were recruited during the last trimester of pregnancy and were interviewed and examined in their homes by a research nurse. Each woman provided a sample of blood as well as permission for a sample of cord blood to be taken at the time of birth. DNA was extracted from both maternal and cord blood and HLA-DRB1 and DQB1 typing performed. On the basis of known haplotypes found in Caucasian populations, DQA1 type was inferred wherever possible. RESULTS: Based on 110 or more maternal-fetal pairs, there was no increased occurrence of disease remission associated with maternal-fetal incompatibility of DRB1 alleles (remission ratio 0.7, 95% confidence interval 0.2-2.8), DQB1 alleles (remission ratio 1.2, 0.3-6.5), or DQA1 alleles (remission ratio 0.8,0.3-1.9). Results were similar whether maternal-fetal sharing was defined by broad allelic group or by specific alleles. CONCLUSION: Our results do not support the hypothesis that maternal-fetal HLA incompatibility contributes to remission of inflammatory arthritis during pregnancy.
Adult↗
Costs of care for HIV infection in a managed care population from 1995 to 1997.
OBJECTIVE: To determine costs of drug and nondrug treatment of HIV-infected patients during introduction of protease inhibitors and combination therapy. STUDY DESIGN: Longitudinal, observational study of insurance claims data. PATIENTS AND METHODS: Data from managed care organizations in Texas and California contracting with an HIV case management group were reviewed for all non-Medicaid/non-MediCal adults infected with HIV for costs of drugs and nondrug treatment per HIV-infected member per month from January 1995 to December 1997. Costs of care for patients with and without undetectable viral loads (< 400 copies/mL) were quantified. RESULTS: Per HIV-infected member, average monthly drug costs increased, nondrug costs decreased, and total costs remained stable. Quarterly mortality rates decreased from 4.8% to 0.25%. From the first quarter of 1996 to the last quarter of 1997, the proportion of patients with undetectable viral loads increased from 6% to 56%. Increasing drug costs and decreasing nondrug costs were observed in patients with and without undetectable viral loads, but costs were higher for the latter: after the second quarter of 1996, drug costs were $67 to $277 higher for patients without undetectable viral loads, nondrug costs were $185 to $741 higher, and total costs were $333 to $808 higher. CONCLUSIONS: Reduced mortality rates and increased viral suppression to undetectable levels were observed during introduction of protease inhibitors and combination therapy in this MCO setting. Increased average monthly drug costs per HIV-infected patient were offset by decreased average monthly nondrug costs, and both costs were lower when patients achieved undetectable viral loads.
California↗
Use of chemokine receptors by poxviruses.
Chemokine receptors serve as portals of entry for certain intracellular pathogens, most notably human immunodeficiency virus (HIV). Myxoma virus is a member of the poxvirus family that induces a lethal systemic disease in rabbits, but no poxvirus receptor has ever been defined. Rodent fibroblasts (3T3) that cannot be infected with myxoma virus could be made fully permissive for myxoma virus infection by expression of any one of several human chemokine receptors, including CCR1, CCR5, and CXCR4. Conversely, infection of 3T3-CCR5 cells can be inhibited by RANTES, anti-CCR5 polyclonal antibody, or herbimycin A but not by monoclonal antibodies that block HIV-1 infection or by pertussis toxin. These findings suggest that poxviruses, like HIV, are able to use chemokine receptors to infect specific cell subtypes, notably migratory leukocytes, but that their mechanisms of receptor interactions are distinct.
3T3 Cells↗
The complete DNA sequence of myxoma virus.
Myxomatosis in European rabbits is a severely debilitating disease characterized by profound systemic cellular immunosuppression and a high rate of mortality. The causative agent, myxoma virus, is a member of the poxvirus family and prototype of the Leporipoxvirus genus. As a major step toward defining the genetic strategies by which the virus circumvents host antiviral responses, the genomic DNA sequence of myxoma virus, strain Lausanne, was determined. A total of 171 open reading frames were assigned to cover the 161.8-kb genome, including two copies each of the 12 genes that map within the 11.5-kb terminal inverted repeats. Database searches revealed a central core of approximately 120 kb that encodes more than 100 genes that exhibit close relationships to the conserved genes of members of other poxvirus genera. Open reading frames with predicted signal sequences, localization motifs, or homology to known proteins with immunomodulatory or host-range functions were examined more extensively for predicted features such as hydrophobic regions, nucleic acid binding domains, ankyrin repeats, serpin signatures, lectin domains. and structural cysteine spacings. As a result, several novel, potentially immunomodulatory proteins have been identified, including a family with multiple ankyrin-repeat domains, an OX-2 like member of the neural cell adhesion molecule family, a third myxoma serpin, a putative chemokine receptor fragment, two natural killer receptor-like species, and a variety of species with domains closely related to diverse host immune regulatory proteins. Coupled with the genomic sequencing of the related leporipoxvirus Shope fibroma virus, this work affirms the existence of a conserved complement of poxvirus-specific core genes and expands the growing repertoire of virus genes that confer the unique capacity of each poxvirus family member to counter the immune responses of the infected host.
Amino Acid Sequence↗
From concept to market in industrial impedance applications.
This paper discusses some of the technical aspects of converting a laboratory idea into a commercial product. The example used is the development of the Aber Instruments Biomass Monitor, which is now used worldwide in industry for the pitching of yeast in breweries and for biomass measurements in the pharmaceutical industry. Although the issues raised will relate to instrumentation in a production environment, many of the themes will be equally applicable to medical instruments.
Biomass↗
Isoenzyme activities of different strains of Cryptosporidium parvum.
Different isoenzyme activities have been assayed in three strains of Cryptosporidium parvum, C1 (C. parvum from infected calves, UK), C2 (C. parvum from infected calves, Egypt) and C3 (C. parvum from infected goats, Egypt). The electrophoretic variations of five enzymes; lactate dehydrogenase (LDH), glucose phosphate isomerase (GPI), hexokinase (HK), malate dehydrogenase (MDH) and glutamate dehydrogenase (GLDH) were compared among the three different isolates using native polyacrylamide gel-electrophoresis. LDH showed an identical pattern in the three isolates. GPI showed two different bands in C3 and C1, with both bands present in C2. HK activity showed a weak band in C1 but no reaction was detected with C2 and C3. Malate dehydrogenase (MDH) showed no reaction in C1, but similar bands in C2 and C3. Glutamate dehydrogenase (GLDH) showed two different patterns, C2 and C3 had one pattern and C1 showed additional zones of reaction. Rat liver homogenate was run at the same time as the parasite extracts as a positive control. This investigation suggests that GPI, HK and GLDH could be used to characterise different Cryptosporidium isolates.
Animals↗
Quantifying the exact role of HLA-DRB1 alleles in susceptibility to inflammatory polyarthritis: results from a large, population-based study.
OBJECTIVE: To accurately determine the contributions of HLA-DRB1 alleles in explaining susceptibility to inflammatory polyarthritis in a large, true population-based cohort of new-onset cases. METHODS: A cohort of 680 consecutive patients with inflammatory polyarthritis, of whom 404 satisfied the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), was recruited from the population-based Norfolk Arthritis Register. All cases were compared with 286 local population controls. A standardized clinical assessment was performed on all patients. HLA-DRB1 phenotypes, including DR4 subtypes, were determined using a semiautomated, reverse dot-blot method. Results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: There was only a modest association (OR 1.8, 95% CI 1.4-2.4) between inflammatory polyarthritis and the presence of any shared epitope (SE) allele; the strongest individual risk was with DRB1*0404 (OR 3.5, 95% CI 1.8-6.8). Comparison of the genotypes demonstrated that the effect of being SE homozygous (OR 2.1, 95% CI 1.5-3.0) was only moderately greater than the effect of being SE heterozygous (OR 1.3, 95% CI 1.1-1.6). The exception to this was genotypic combinations that included HLA-DRB1*0404, which exhibited ORs ranging up to 18.0. There were no differences between either the phenotype or genotype data when the patients were stratified by RA status (defined by the ACR criteria). In contrast, the associations were substantially stronger in patients who were positive for rheumatoid factor. CONCLUSION: Previous studies had not been able to clarify whether the influence of HLA-DRB1 on RA was related to disease susceptibility or to disease severity and progression. These data on a unique population-based incident cohort suggest only weak effects on susceptibility, with the exception of the clearly distinct influence of HLA-DRB1*0404.
Alleles↗
Diurnal variation in saliva estriol level during pregnancy: a pilot study.
OBJECTIVE: The object of the study was to characterize daily values and patterns of salivary estriol levels during normal pregnancy at mid to late gestation. STUDY DESIGN: We measured salivary estriol levels in a clinical research center setting with an established enzyme-linked immunosorbent assay. Fourteen pregnant women (24-36 weeks' gestation) submitted unstimulated saliva samples hourly from 10:00 am until 10:00 pm and at midnight and 2:00, 4:00, 6:00, and 8:00 am. RESULTS: Each subject demonstrated greater salivary estriol levels at night (10:00 pm-6:00 am) than in the daytime (8:00 am-9:00 pm, P <.001). Salivary estriol levels consistently increased at 10:00 pm, peaked at 4:00 am, and returned to daytime levels between 6:00 and 7:00 am. Salivary estriol concentrations were stable during daylight hours. CONCLUSIONS: (1) There was a dramatic diurnal variation in salivary estriol levels (nadir during daylight with nighttime apogee). (2) Diurnal patterns and salivary estriol levels were consistent in each of 14 subjects evaluated in the latter half of pregnancy. Samples for baseline measurements of salivary estriol level should be obtained during daylight hours (8:00 am-8:00 pm).
Adolescent↗
Effect of Fasciola gigantica somatic extracts and excretory/secretory products on superoxide production by activated neutrophils.
Somatic extracts and excretory/secretory (ES) products from Fasciola gigantica suppress the release of toxic oxygen intermediates by activated sheep neutrophils. At the concentrations used both the somatic extracts and ES products had no effect on neutrophil viability and in both cases the inhibitory effect was reversible. In the somatic extracts, heating or treatment with trypsin destroyed the inhibitory effect. However, the ES products contained at least two immunomodulatory factors. One was less than 10 kDa, the other greater than 50 kDa and both factors were heat and trypsin stable. By acting locally and only causing temporary inhibition of neutrophil function F. gigantica can protect itself from immune mediated oxidative damage without compromising the host's response elsewhere.
Animals↗
Thapar and barrett reply
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Journal Article↗
Human G-CSF-mobilized CD34-positive peripheral blood progenitor cells can stimulate allogeneic T-cell responses: implications for graft rejection in mismatched transplantation.
To investigate mechanisms of stem cell graft rejection we studied the allo-stimulatory potential of G-CSF mobilized peripheral blood progenitor cells (PBPC). CD34+ cells were purified (>95%) in a two-step procedure using immunoaffinity columns for CD34 selection and T-depletion. The capacity of CD34+ cells to stimulate allogeneic T-cell responses was compared with other cells from the same individual. CD34+ cells induced potent proliferative responses at stimulator:responder ratios of 1:20, but were approximately 50-fold less efficient compared to dendritic cells. Furthermore, CD34+ cells primed responses from partially matched allogeneic T cells in bulk cultures. Dual-colour flow cytometry showed that the co-stimulatory molecules B7.1, CD40 and ICAM-1 were absent on resting CD34-positive progenitor cells, but were induced during incubation with allogeneic lymphocytes due to a cytokine-mediated effect. Up-regulation of accessory molecules on CD34+ cells was reproduced by incubation with interferon-gamma or GM-CSF which enhanced the allo-stimulatory activity of CD34+ cells. Blocking studies with inhibitory antibodies suggested co-stimulatory functions for B7.2, ICAM-3, CD40 and LFA-3. CD34+ cells were more efficient in inducing allogeneic T-cell responses when compared to the unprocessed leukapheresis products. The reduced allo-stimulatory ability of G-CSF mobilized PBPC could be explained by the presence of CD3+ 4+ and CD3+ 8+ lymphocytes with suppressor activity. We conclude that current methods of stem cell selection for transplantation do not avoid allosensitization of the recipient and that further graft manipulation with add-back of lymphocytes or selection of subsets of CD34+ cells with reduced allo-stimulatory ability may reduce graft rejection.
Antibodies, Blocking↗