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Biomedical subjects

C Patterson

Publications and source records attributed to C Patterson.

At least 145 records · Page 8Linked to original sources

Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine safety and immunogenicity.

OBJECTIVE: To address the issues of immunogenicity and local and systemic reactions to vaccination with influenza vaccine in patients with rheumatoid arthritis (RA). METHODS: One hundred and twenty-six patients with RA were stratified into 3 groups: (1) those with a history of vaccination with influenza vaccine within 24 months who were receiving usual therapy for RA, (2) those receiving usual therapy for RA but without prior vaccine, and (3) those receiving immunosuppressive medication or prednisone > or = 7.5 mg/day, irrespective of their prior immunization status. Within each group, patients were randomized to receive vaccine or placebo. A group of age matched, healthy controls were also vaccinated. RESULTS: During a one month followup period, adverse reactions occurred with equal frequency among patients with RA and healthy controls. Similar significant increases in titers to the vaccine were seen in all groups of patients with arthritis and in the controls. CONCLUSION: The potential increase in susceptibility to influenza and death from respiratory illness in patients with RA and the demonstrated safety and immunogenicity of influenza vaccine should require the inclusion of patients with RA in standard immunization programs.

Arthritis, Rheumatoid↗

The St. Jude Medical prosthesis. A thirteen-year experience.

From May 1979 until July 1992, 1184 patients, 2 to 86 years of age (median = 59 years), received 1367 St. Jude Medical prostheses (578 aortic, 440 mitral, 3 tricuspid, and 170 multiple). Overall early mortality was 4% with 2.4%, 4.3%, and 8.2% after aortic, mitral and multiple valve replacement, respectively. Follow-up was 100% complete (4936 patient-years). Actuarial survival at 10 years (including both early and late deaths) was 71% +/- 4.1% after aortic valve replacement, 58.8% +/- 5.1% after mitral valve replacement, and 58.9% +/- 9.6% after multiple valve replacement. Multivariate analysis identified age, previous operations, diabetes mellitus, extent of coronary artery disease, preoperative New York Heart Association class, and additional procedures as independent prognostic factors for overall survival. All patients including 20 children (2 to 18 years of age) received sodium warfarin. The linearized risk per 100 patient-years for all embolic events (major and minor) was 2.4, 4.4, and 5.0 after aortic, mitral, and multiple valve replacement, respectively; when only major events were considered, the linearized risks were 0.33, 1.17, 1.54, respectively. Freedom from major systemic embolism at 10 years was 96% +/- 2% after aortic valve replacement, 88% +/- 4% after mitral valve replacement, and 89% +/- 3% after multiple valve replacement. Five patients had valve thrombosis, four of whom definitely received inadequate anticoagulation therapy. Ninety-seven patients had 107 episodes of anticoagulant-related hemorrhage (2.2/100 patient-years) accounting for 17 late deaths; 14 of the deaths involved an international normalized ratio in excess of 3.5. To reduce the rate of thromboembolism without increasing the rate of anticoagulant-related hemorrhage, we propose that the international normalized ratio should be kept between 2.5 and 3.0. No recorded structural failure or significant hemolysis was found in the absence of periprosthetic leak. This experience encourages us to continue using the St. Jude Medical prosthesis.

Actuarial Analysis↗

Report of the Canadian Hypertension Society Consensus Conference: 4. Hypertension in the elderly.

Several knowledge gaps, which made evidence-based guidelines impossible in 1985, have since been filled. There is now unequivocal evidence that treatment of isolated systolic hypertension benefits elderly patients, as does treatment beyond the age of 75 years. Pseudohypertension, although occasionally problematic, is not common and is not a reason to neglect the treatment of elderly patients, including those with isolated systolic hypertension. In general, long-term antihypertensive treatment of the elderly is well tolerated and does not cause important decreases in mental function. Comparative drug studies continue to accumulate; most show no clinically significant general differences between drugs, aside from the somewhat decreased efficacy and tolerability of beta-blockade in elderly patients. As in the young, certain drugs may be preferred in the presence of other conditions--e.g., congestive heart failure or diabetes.

Aged↗

Screening for abdominal aortic aneurysm in men ages 60 to 80 years. A cost-effectiveness analysis.

PURPOSE: To evaluate the cost-effectiveness of screening by physical examination or abdominal ultrasonography for abdominal aortic aneurysm (AAA) in men aged 60 to 80 years. DATA SOURCES: A systematic review of the pertinent literature by the Canadian Task Force on the Periodic Health Examination, augmented by an additional computerized search (MEDLINE) and references identified from bibliographies of pertinent articles. Several experts reviewed the data for completeness. STUDY SELECTION: Published English-language studies that present data relevant to screening for abdominal aortic aneurysm. DATA EXTRACTION: Several reviewers determined a range of data and the most probable value for each parameter. DATA SYNTHESIS: A computer spreadsheet model was constructed to simulate the costs and effectiveness of various screening protocols in a cohort of 10,000 men during a period of 20 years. The primary cost-effectiveness measure computed was incremental present-value dollar expenditures for screening and treatment per incremental present-value life-year saved by the screening program. Using the "most probable" values for the simulation parameters, a single screening procedure of abdominal palpation followed by abdominal ultrasound scan for patients with positive screening results is estimated to gain 20 life-years at a cost of $28,741 per life-year. A single ultrasound screen gains 57 life-years at a cost of $41,550 per life-year. A repeated ultrasound screen after 5 years gains 1 additional life-year at a cost of $906,769. CONCLUSIONS: A single screen for AAA by abdominal palpation in men from age 60 to 80 years might be considered cost-effective but of small benefit. A single screen with ultrasonography is at the high end of the cost-per-life-year range that might be considered cost-effective and also is of modest benefit. Repeated screening is not cost-effective.

Aged↗

Structure-function relationship of human neutrophil collagenase: identification of regions responsible for substrate specificity and general proteinase activity.

The family of matrix metalloproteinases is a family of closely related enzymes that play an important role in physiological and pathological processes of matrix degradation. The most distinctive characteristic of interstitial collagenases (fibroblast and neutrophil collagenases) is their ability to cleave interstitial collagens at a single peptide bond; however, the precise region of the enzyme responsible for this substrate specificity remains to be defined. To address this question, we generated truncated mutants of neutrophil collagenase with various deletions in the COOH-terminal domain and chimeric molecules between neutrophil collagenase and stromelysin and assayed the expressed enzymes against type I collagen and the general substrate, casein. Our data suggest that substrate specificity for interstitial collagen is determined by a 16-aa sequence in the COOH-terminal domain of neutrophil collagenase and is influenced by the integrity of a disulfide-defined loop at the COOH terminus for maximal activity. It was found that a relatively large region of 62-aa residues influenced the relative efficiency of collagenolytic activity. In addition to the region that conferred this specificity, a site at the COOH side of the presumptive zinc-binding locus was found to be necessary for general catalytic activity. Mutation of a critical aspartic residue at position 253 within this area resulted in complete loss of proteolytic activity, suggesting that Asp-253 might function as one of the ligands for divalent cations, which are essential for enzymatic activity.

Amino Acid Sequence↗

Thrombin receptor activating peptides induce Ca2+ mobilization, barrier dysfunction, prostaglandin synthesis, and platelet-derived growth factor mRNA expression in cultured endothelium.

Endothelial cell activation by thrombin is a key event in wound healing, inflammation, and hemostasis. To better define thrombin-endothelial cell interactions we synthesized several peptides of varying length corresponding to the initial 14 amino acid sequence of the cloned human platelet thrombin receptor after cleavage at an arginine41 site (R/SFLLRNPNDKYEPF). Thrombin receptor activating peptides (TRAPs) as short as 5 amino acids induced significant levels of PGI2 synthesis and expression of PDGF mRNA in human endothelium and produced dose-dependent cellular contraction and permeability of confluent human umbilical vein and bovine pulmonary artery endothelial monolayers. To explore whether TRAPs utilized similar signal transducing pathways as alpha-thrombin to accomplish endothelial cell activation, phospholipase C production of the Ca2+ secretagogue IP3 was measured and detected 10 seconds after either TRAP 7 or alpha-thrombin. Furthermore, TRAPs ranging from 5-14 residues induced significant dose-dependent increases in Fura-2 fluorescence indicative of Ca2+(1) mobilization. These results indicate that thrombin-mediated proteolytic cleavage of the human and bovine thrombin receptor initiates stimulus/coupling responses such phospholipase C activation, Ca2+ mobilization, and protein kinase C activation. The functional consequence of this cellular activation via the cleaved receptor is enhanced cellular contraction, barrier dysfunction, PGI2 synthesis, and expression of PDGF mRNA.

Amino Acid Sequence↗

The probability of correctly predicting subglottic penetration from clinical observations.

It is difficult to predict from clinical signs and symptoms which patients suffer from subglottic penetration of foods. Most investigators attempting to predict aspiration have used small numbers of patients and relatively unsophisticated statistical techniques. In this study, we utilized 249 patients to examine the predictive value of several clinical factors thought to be suggestive of subglottic penetration with discriminant analysis. Using this approach we were able to correctly predict about 2/3 of both those who aspirate and those who do not aspirate. This is better than others have reported but still inadequate for clinical purposes.

Aged↗

Inactivated hepatitis A vaccine in childhood: implications for disease control.

The experience to date with the Merck inactivated hepatitis A vaccine in healthy children 2-16 years old is reviewed. Comparison of response to increasing doses indicates that an intramuscular dose of 25 units results in seroconversion of 99% of children by week 4 following a single dose. Antibody persistence rate is nearly 100% six months later, whether or not a second priming dose is given at week 8. This vaccine has proven highly immunogenic in children and has a favourable safety/tolerability profile. It should be useful for pre-exposure prophylaxis and control of hepatitis A, and should eventually replace immune globulin (Ig) for this indication.

Adolescent↗

Worldwide experience with the CR326F-derived inactivated hepatitis A virus vaccine in pediatric and adult populations: an overview.

The worldwide experience to date with VAQTA, a highly purified formalin-inactivated hepatitis A vaccine containing alum-adjuvant, is reviewed. No serious adverse experience related to vaccination has been reported. The vaccine has proven highly immunogenic, with seroconversion detectable after a single dose in 90-99% of children 2-16 years old, and of adults under 77 kg (170 lb) body weight. There is a trend toward lower one-dose seroconversion rates with increasing age and with weight > 77 kg. Early seroconversion in the latter groups may require two 25-unit doses given 2, 4 or 8 weeks apart, or a higher priming dose. Seroconversion induced by this vaccine has been shown to signify protection from clinical hepatitis A disease. The few vaccines whose titers have waned to borderline levels responded anamnestically to a booster, suggesting that the vaccine induces an immune memory response and should provide long-term protection.

Adolescent↗

Safety, tolerability and immunogenicity of a formalin-inactivated hepatitis A vaccine (VAQTA) in rural Kentucky children.

This study evaluated the immunogenicity and safety/tolerability profile of an investigational formalin-inactivated hepatitis A virus vaccine (VAQTA; Merck Research Laboratories) in 150 seronegative healthy children, 4 to 12 years old. The vaccine was derived from virus grown in infected MRC-5 cells in either roller bottles or Nunc cell factories (Nunc, Denmark). Subjects were vaccinated intramuscularly in a two dose regimen initially and at 24 weeks: Group A (n = 50) with a 12-unit dose from a roller bottle lot; Group B (n = 50) with a 25-unit dose from another roller bottle lot; and Group C (n = 50) with a 25-unit dose from a Nunc cell lot. Sera for anti-hepatitis A virus antibodies were drawn 3 weeks before vaccination and 4, 24 and 28 weeks after the first dose. Seroconversion from < 10 mIU/ml to > or = 10 mIU/ml by modified HAVAB (Abbott Laboratories) was observed in 99% of subjects at week 4 and persisted in 100% of subjects at week 28 (4 weeks after the second dose). The ranges of geometric mean titers of anti-HAV for all subjects at weeks 4, 24 and 28 were 31 to 49, 51 to 79 and 7059 to 29,609 mIU/ml, respectively. The 12- and 25-unit dose levels of roller bottle yielded similar geometric mean titers. The rise in geometric mean titers after the booster dose was > 120-fold and was highest in the recipients of the 25-unit Nunc cell lot (P < 0.05 for Group C vs. B).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Uncertainty, and appraisal in patients diagnosed with abdominal aortic aneurysms.

The purpose of this study was to describe the uncertainty of subjects diagnosed with abdominal aortic aneurysms and to examine the relationship between uncertainty and subjects', positive or negative appraisals of uncertainty. Twenty-seven subjects who had a definitive diagnosis of abdominal aortic aneurysms were surveyed using the Mishel Uncertainty in Illness Scale (MUIS), the Folkman and Lazarus Restructured Appraisal Scale, and a demographic questionnaire. Findings from the study suggested that the level of uncertainty among patients with abdominal aortic aneurysms was similar or higher than the level of uncertainty that has been reported for patients with myocardial infarctions (M = 91.9, S.D. = 19.56). There was no significant relationship between uncertainty and appraisal of uncertainty as a danger (r = .21, p = .14) or opportunity (r = .14, p = .25). Implications for further research include examining patients uncertainty levels and appraisal at repeated intervals during their illness trajectory.

Adaptation, Psychological↗

Telomere length predicts replicative capacity of human fibroblasts.

When human fibroblasts from different donors are grown in vitro, only a small fraction of the variation in their finite replicative capacity is explained by the chronological age of the donor. Because we had previously shown that telomeres, the terminal guanine-rich sequences of chromosomes, shorten throughout the life-span of cultured cells, we wished to determine whether variation in initial telomere length would account for the unexplained variation in replicative capacity. Analysis of cells from 31 donors (aged 0-93 yr) indicated relatively weak correlations between proliferative ability and donor age (m = -0.2 doubling per yr; r = -0.42; P = 0.02) and between telomeric DNA and donor age (m = -15 base pairs per yr; r = -0.43; P = 0.02). However, there was a striking correlation, valid over the entire age range of the donors, between replicative capacity and initial telomere length (m = 10 doublings per kilobase pair; r = 0.76; P = 0.004), indicating that cell strains with shorter telomeres underwent significantly fewer doublings than those with longer telomeres. These observations suggest that telomere length is a biomarker of somatic cell aging in humans and are consistent with a causal role for telomere loss in this process. We also found that fibroblasts from Hutchinson-Gilford progeria donors had short telomeres, consistent with their reduced division potential in vitro. In contrast, telomeres from sperm DNA did not decrease with age of the donor, suggesting that a mechanism for maintaining telomere length, such as telomerase expression, may be active in germ-line tissue.

Base Sequence↗

Extraadrenal myelolipoma. A report of two cases.

Two cases of extraadrenal myelolipoma with unusual clinicopathologic features are described. The patient in case 1 had multifocal myelolipomas, involving both the lung and retroperitoneum, that mimicked malignancy, and the patient in case 2 had a single diffuse retroperitoneal myelolipoma without circumscription. Of possible etiologic significance is the fact that both patients were treated with exogenous steroids.

Aged↗

Effectiveness of a geriatric day hospital.

OBJECTIVE: To determine whether there is a difference in the quality of life between elderly patients managed in a day hospital and those receiving conventional care. DESIGN: Randomized controlled trial; assessment upon entry to study and at 3, 6 and 12 months afterward. SETTING: Geriatrician referral-based secondary care. PATIENTS: A total of 113 consecutively referred elderly patients with deteriorating functional status believed to have rehabilitation potential; 55 were assessed and treated by an interdisciplinary team in a day hospital (treatment group), and 58 were assessed in an inpatient unit or an outpatient clinic or were discharged early with appropriate community services (control group). OUTCOME MEASURES: Barthel Index, Rand Questionnaire, Global Health Question and Geriatric Quality of Life Questionnaire (GQLQ). MAIN RESULTS: Eight study subjects and four control subjects died; the difference was insignificant. Functional status deteriorated over time in the two groups; although the difference was not significant there was less deterioration in the control group. The GQLQ scores indicated no significant difference between the two groups in the ability to perform daily living activities and in the alleviation of symptoms over time but did show a trend favouring the control group. The GQLQ scores did indicate a significant difference in favour of the control group in the effect of treatment on emotions (p = 0.009). CONCLUSION: The care received at the day hospital did not improve functional status or quality of life of elderly patients as compared with the otherwise excellent geriatric outpatient care.

Activities of Daily Living↗

Iron deficiency anemia in the elderly: the diagnostic process.

OBJECTIVE: To determine the effectiveness of physician probability estimates calculated on the basis of findings from history-taking and physical examination in the diagnosis of iron deficiency anemia in elderly patients. DESIGN: Prospective study. SETTING: Two community hospitals offering secondary and tertiary care. PATIENTS: A total of 259 patients over 65 years of age found to have previously undiagnosed anemia. MEASURES: Physician estimates of the likelihood of iron deficiency before (pretest probability) and after (post-test probability) the laboratory test results were available. The hemogram was available to the physicians when they made their pretest probability estimates. Because the serum ferritin level proved to be the most powerful of the laboratory test results studied, the likelihood ratios associated with the post-test estimates were compared with the ratios associated with the serum ferritin level. MAIN RESULTS: The post-test probability estimates were influenced by the serum ferritin level and the pretest estimates. The post-test estimates derived from the findings obtained through history-taking and physical examination and the laboratory test results (including the serum ferritin level) were slightly less accurate in predicting iron deficiency than the serum ferritin level alone. Nevertheless, a model in which the pretest estimates were used in addition to the serum ferritin level to predict iron deficiency proved to be more powerful than the serum ferritin level alone (p = 0.006). This indicated that the limitations of the post-test estimates were due to a misinterpretation of the serum ferritin level and that the findings from history-taking and physical examination added important diagnostic information. CONCLUSIONS: Physicians must be aware of test properties to provide optimal care to their patients. If test results are properly interpreted, pretest probabilities derived from findings obtained through history-taking and physical examination can add useful information that will lead to more accurate diagnoses.

Aged↗

Comparative increases of lead and barium with age in human tooth enamel, rib and ulna.

Lead and Ba in postmortem tooth enamel, rib and ulna of six contemporary people (67-96 years; ave. 80) were shown to exhibit similar accumulations with age in the three different types of osseous tissue: Pb/Ca (wt) = 3.0, 5.2, and 3.9 x 10(-5) in rib, ulna, and tooth enamel; and Ba/Ca (wt) = 2.4, 2.4, and 1.8 x 10(-5) in rib, ulna, and tooth enamel, respectively. Mean concentrations of Pb were 11, 19, and 14 micrograms g-1 in rib (ash), ulna (ash), and enamel (dry), respectively. Means for Ba were 8.7, 8.9, and 6.4 micrograms g-1 in rib (ash), ulna (ash), and enamel (dry), respectively. Comparison of Ba in ulna of our 80-year-old subjects with Ba determined by other investigators in bones of younger contemporary populations indicated that Ba accumulates with age at about half the rate of Pb accumulation in bone. Concentrations of Ba in rib, ulna and enamel were positively correlated and similar within an individual, but varied among subjects in proportion to variations in absorptive uptake in portal blood. Barium may diffuse from a blood-dentine source into enamel, where it replaces Ca and accumulates with age. Because of extreme Pb pollution of our 80-year-old subjects and its variation of intake with age, the correlation of Pb in tooth enamel with Pb in bone was more scattered than for Ba. It is shown by means of stable Pb isotopic tracers that: (i) among the three types of osseous tissue, the residence time of Pb is longest in enamel, where it apparently accumulates with age by diffusion with little loss through exchange; and (ii) the residence time of Pb is longer in compact ulna than in trabecular rib, as it accompanies Ca in its osteoblastic transfer from blood to bone and then in its osteoclastic transfer back to blood from bone.

Aged↗