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Biomedical subjects

R B Wallace

Publications and source records attributed to R B Wallace.

At least 127 records · Page 7Linked to original sources

Preimplantation alteration of adenine nucleotides in cryopreserved heart valves.

To assess the initial metabolic phase of cellular injury from cardiac valve processing, high-energy phosphate concentrations were analyzed in valve leaflets subsequent to critical processing steps. Using a porcine model, valves were processed in a manner identical to human homografts, with 58 randomly assigned to five groups representing distinct preparation phases. Group I (controls) sustained 40 minutes of warm ischemia concluded by liquid nitrogen immersion. Remaining groups similarly endured 40 minutes of ischemia, but were subsequently prepared according to stepwise design: II, warm ischemia + 24 hours of 4 degrees C ischemia; III, warm ischemia + 24 hours of 4 degrees C antibiotic disinfection; IV, warm ischemia + 24 hours at 4 degrees C (without antibiotics) + cryopreservation (-1 degrees C/min cryoprotected freezing); and V, warm ischemia+disinfection+cryopreservation. At each regimen's conclusion leaflet extracts were assayed by high-performance liquid chromatography for high-energy adenine nucleotides (adenosine triphosphate, adenosine diphosphate, adenosine monophosphate) and catabolites. A 47% and 86% decrease in cellular adenosine triphosphate level was observed in group III and group V leaflets, respectively. The level of total adenine nucleotides was maintained up to cryopreservation; thereafter a 74% decrease was noted. Catabolite analysis confirmed incomplete degradation of adenine nucleotides indicating cellular metabolic resilience throughout standard homograft preparation in valves previously exposed to 40 minutes of warm ischemia.

Adenine Nucleotides↗

Incorporation of nonbase residues into synthetic oligonucleotides and their use in the PCR.

Oligonucleotides containing the nonbase residues 1,3-propanediol or 1,4-anhydro-2-deoxy-D-ribitol were synthesized and used as primers for the polymerase chain reaction (PCR). Since these residues cannot be replicated by a DNA polymerase, the resulting PCR products have protruding 5' ends. Primers were designed with three regions, a 3' region complementary to the desired template, a 5' region complementary to a preselected nucleotide sequence, and a nonreplicable element interposed between these two containing 1-3 of the nonbase residues. The primers were used in a PCR and the products hybridized without denaturation to a solid support containing an immobilized preselected nucleotide sequence. Studies are reported showing the effects of the nonreplicable elements in primer extension reactions and the application to the capture of PCR products.

Base Sequence↗

Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors.

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion-associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one-way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA-GVHD.

Aged↗

Nonsteroidal anti-inflammatory drugs and blood pressure in an elderly population.

BACKGROUND: Short-term clinical studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with the effectiveness of antihypertensive therapies. We studied the joint effects of these two classes of drugs among subjects participating in the cross-sectional baseline interview from a population-based cohort study of community-dwelling elderly. METHODS: Blood pressure was recorded by interviewers using a standard sphygmomanometer after at least 5 minutes in the sitting position. Two recordings were made in rapid succession, using the first and fifth Korotkoff sounds. The second recording was used for this study. From respondents' medication container labels, interviewers recorded the name and dosage regimen of each medication used during the preceding two weeks. RESULTS: Persons on antihypertensive therapy taking NSAIDs had systolic blood pressures approximately 5 mmHg higher than those not taking NSAIDs, and were more likely to have systolic blood pressure above 140 mmHg (odds ratio = 2.19, 95% confidence interval 1.33, 3.61). These findings could not be explained by differences between NSAID users and nonusers in age, relative weight, or the type or dose of antihypertensive regimen. No significant effects of NSAIDs were seen for diastolic blood pressure or among persons not taking antihypertensive drugs. When analyses were restricted to non-indomethacin NSAID use, the findings were unchanged. CONCLUSION: These findings suggest that NSAID use may be an important community reason for loss of pharmacologic control of hypertension.

Aged↗

Iowa FICSIT trial: the feasibility of elderly wearing a hip joint protective garment to reduce hip fractures.

Hip fractures exact a heavy toll in the elderly population. While intervention strategies are being investigated to reduce the numbers of geriatric falls and to improve the body's resiliency, the geriatric population remains at risk for the mortality and morbidity associated with fractures. The Iowa FICSIT site is investigating the feasibility of passive protection of the proximal femur through the use of hip pads. The pad is designed to disperse throughout the pad the energy created in a fall. The focus of the Iowa trial is to determine if elderly will wear hip pads for the majority of their waking hours. Thirty subjects are being recruited from each of six elderly populations who are at high risk to fall and at increased risk of injury. To facilitate compliance, the following strategies are utilized: run-in period, graduated implementation, tailoring of wearing times, and self-report of compliance. Outcome measures include compliance rates and injuries sustained during falls.

Accidental Falls↗

Inhibition of adenosine deaminase and nucleoside transport. Utility in a model of homograft cardiac valve preimplantation processing.

Human cardiac valves are increasingly used in the reconstruction of ventricular outflow tracts and offer performance advantages over porcine and mechanical prostheses; the durability of these replacements has been associated with leaflet interstitial cell viability and a presumed sustained function after implantation. Preimplantation tissue preparation entails sequential steps that are potentially cytotoxic and may therefore affect functional cell survival at thaw. We defined the metabolic consequences of each interval using semilunar cusps from 118 porcine valves to model a homograft preparation with 40 minutes of fixed cadaveric (harvest) ischemia. Fifty-eight valves served as controls and were first processed according to standard cryopreservation protocol; nucleosides were extracted at the end of each step to differentiate independent contributions to high-energy phosphate depletion. Sixty simultaneously harvested leaflets were administered the nucleoside transport inhibitor p-nitrobenzy-thionosine (NBMPR) and the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) at procurement, to attempt adenosine salvage and restitution of processing-incurred adenine nucleotide losses. High-performance liquid chromatography was used to compare adenosine triphosphate, diphosphate, and monophosphate and diffusible nucleopurines of the control and EHNA/NBMPR-treated groups. Control results indicate that disruption of the adenosine triphosphate-diphosphate cycle occurs independently with antibiotic disinfection and cryopreservation. However, throughout all preparation steps, adenine nucleotides were maintained at harvest (baseline) concentrations in the EHNA/NBMPR valves. This suggests that salvage therapy may protect a significant number of cells from net high-energy phosphate catabolism. If, with further study, the durability of transplanted valves is concluded to benefit from retained leaflet interstitial cell viability, such enhancement of metabolic tolerance to the obligatory processing may facilitate functional recovery.

Adenine↗

Geriatric assessment and driver functioning.

In this article, the sensory, cognitive, and motor function relevant to driving, their measurement, the epidemiology of age-associated functional impairments, and the relationship of functional impairments to both self-reported driving and the imposition of legal restrictions are reviewed. A number of issues remain to be resolved before the scientific basis for public policy recommendations on aging drivers is sufficiently sound. For example, although an association between various functional impairments and the imposition of restrictions was found, with the exception of visual impairments, which under Iowa law may require the imposition of restrictions, those aspects of functional impairment that precipitate state-imposed license restrictions cannot be identified by the authors. The authors' measures of functional status may serve as surrogates for other, more important variables. If so, it has implications for both prevention of impairment-associated restrictions and interventions occurring after restrictions have been imposed. One of the most important issues confronting clinicians, researchers, and regulators is the development of appropriate tests to screen for dysfunctional driving with safety risks. Whether an appropriate battery could be created from already-existing tests and questionnaires is unclear. Certainly it seems desirable to consider the issue of face validity and explore items more clearly related to driving, such as self-reported loss of concentration or difficulty with manipulating controls. Many of the current tests focus on low levels of cognitive and physical performance. Relatively severe impairments are clearly related to driving behavior, as the authors found. Relatively minor impairments also may have an impact on driving performance, however, and it is important to explore tests sensitive to these mild impairments. Finally, it is critical to conduct appropriate studies of the reliability, validity, sensitivity, and specificity of any proposed batteries. These studies should include representative samples of drivers and not just clinic populations or community volunteers. It is also important to include a number of assessments of driving. Although state records of accidents and violations are useful, not all accidents or violations are included in state records. From a public health standpoint, crashes are the outcome of interest, but their relatively low rates require large number s of research participants or relatively long study periods. More detailed driver assessments similar to those included in state on-the-road testing or course testing are also important.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Self-reported adverse drug reactions and related resource use. A study of community-dwelling persons 65 years of age and older.

OBJECTIVE: To describe the incidence and health resource consequences of self-reported adverse drug reactions (ADRs) and their relation to self-perceived health, number of medications used, and age in a geographically based population 65 years of age and older. DESIGN: A survey of a defined population. PARTICIPANTS: Three thousand, one hundred seventy noninstitutionalized persons 65 years of age and older residing in two Iowa counties. MEASUREMENTS: Reports of ADRs (elicited using an open-ended questionnaire); names of drugs involved; descriptions of reactions and related health resource use; self-perceived health status (at the first annual follow-up); and number of medications (from the baseline interview). RESULTS: Ten percent (95% CI, 8.97 to 11.09) of respondents reported one or more ADRs. Three quarters of respondents who reported ADRs contacted a physician. Of these, half indicated that a laboratory test had been ordered, and 7% reported a hospitalization due to the reaction. Advanced age alone was associated with decreased risk in women; a similar trend in men was not statistically significant. However, persons with poorer health status and those who reported the greatest prior use of medications were most likely to report reactions. CONCLUSIONS: In this study of noninstitutionalized elderly persons, advanced age did not appear to be associated with increased risk for self-reported ADRs. We could not determine whether the decrease in ADR reports among the oldest respondents represented true diminished ADR occurrence or altered ADR detection and reporting capabilities. When projected to the elderly community-dwelling U.S. population, 2.2 million annual physician visits, 1.1 million laboratory tests, and 146,000 hospitalizations may result from ADRs.

Age Factors↗

Genetic markers associated with high density lipoprotein cholesterol levels in a biracial population sample.

An explanation for the consistently documented finding of higher levels of high density lipoprotein-cholesterol in black men relative to white men was sought by comparing the frequency of restriction fragment length polymorphism markers present in blacks and in whites at the gene loci coding for the two major apolipoprotein constituents of high density lipoprotein, apolipoproteins AI and AII. The measurements were made in population-based samples of 45 to 54-year-old black (n = 190) and white (n = 370) subjects from the Minnesota Heart Survey for whom lipoprotein levels were available. The mean high density lipoprotein-cholesterol level for black men in the sample (47 +/- 1.5 mg/dl) was higher (P less than 0.05) than that for white men (42 +/- 0.9 mg/dl), while levels in women were not different between races. While the SacI and MspI markers at the apolipoprotein AI-CIII-AIV gene locus showed similar frequencies in blacks compared to whites, the degree of the linkage disequilibrium previously noted between these markers in white subjects was altered in blacks and the minor allele of the PstI marker at this locus was virtually absent in the black subjects (P less than 0.005 vs whites). For black men, there were significant associations of the M2 allele and the S2M2 haplotype at the apolipoprotein AI locus with lower high density lipoprotein-cholesterol levels. The results are consistent with the hypothesis that DNA sequence variations in the vicinity of the apolipoprotein AI-CIII-AIV gene locus are associated with the difference in high density lipoprotein-cholesterol levels between blacks and whites.

Adult↗

Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss.

Radial bone mineral density (BMD) of 217 white women aged 22-54 years from a single rural community was evaluated in 1984 using single-photon absorptiometry. BMD was measured at a site one-third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was -5.6%. The average rate of loss was -4.5% for women retaining positive estrogen status at follow-up (n = 108) and -7.4% for women who were in negative estrogen status at follow-up (n = 73). Baseline radial BMD measures were highly predictive of the follow-up BMD values (r = 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone-specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a "peak age" in the baseline and follow-up BMD measures. Based on rates of BMD change, "peak" bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast-feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adjusted for age or estrogen status.

Adult↗

Platelet activating factor antagonist enhances lung preservation.

Platelet activating factor (PAF) is a potent phospholipid mediator of the immune and inflammatory responses, which causes physiologic effects similar to post-transplant pulmonary dysfunction. This study investigates the hypothesis that the use of a specific PAF antagonist (PAFA), BN 52021, in canine lung transplantation improves lung preservation. Twelve pairs of canines underwent left lung allotransplantation after pulmonary artery flushing with modified Euro-Collins (EC) solution (40 ml/kg). The experimental group (N = 6) received EC with BN 52021 (10 mg/kg). BN 52021 was administered to donors prior to harvest and to recipients prior to reperfusion. The preservation interval was 20 hr and the study period was 12 hr post-transplant. Differential pulmonary function and hemodynamics were monitored, comparing the transplanted left lung and the native right lung. Recipients were ventilated on 100% O2. Administration of the platelet activating factor antagonist, BN 52021, was associated with improvement in transplant lung oxygenation, pulmonary vascular resistance, and compliance. At 12 hr, transplant lung pulmonary venous oxygen tension in the treatment group (EC + BN 52021) was 154 +/- 21 mm Hg versus 87 +/- 10 mm Hg in the control group (EC) (P less than 0.05). Pulmonary vascular resistance of the transplant lung at 12 hr was 146 +/- 24 Dynes.sec.cm-5 in the EC + BN 52021 group as compared to 320 +/- 51 Dynes.sec.cm-5 in the EC group (P less than 0.05). Dynamic pulmonary compliance of the transplant lung at 12 hr was 32 +/- 2.9 ml/cm H2O in the EC + BN 52021 group versus 13 +/- 2.0 ml/cm H2O in the EC group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

High energy phosphate depletion in leaflet matrix cells during processing of cryopreserved cardiac valves.

Preimplantation preparation of cardiac valves includes three major steps: (1) harvesting with accompanying ischemia (warm time from cessation of donor heart beat), (2) antibiotic disinfection, and (3) controlled-rate cryopreservation. To define the interdependent injury effects of these manipulations on leaflet matrix cells and specifically the potential for prolonged harvest-related ischemia to predispose greater injury by the subsequent steps, 96 semilunar valves were harvested from pigs in a manner analogous to human heart valve retrievals and randomly allocated to study groups as follows: 48 control valves were exposed to increasing harvested-related ischemic times, (2, 6, 12, 24 hr) and immersed in liquid nitrogen to arrest metabolic activity (i.e., prior to cryopreservation) and conclude the ischemia; another 48 were similarly harvested, subjected to identical ischemic times, then disinfected in 4 degrees C RPMI medium with standard antibiotics for 24 hr and dimethylsulfoxide cryopreserved at -1 degrees C/min to -170 degrees C (i.e., formal cryopreservation protocol). At thawing, each valve was extracted in 12% trichloroacetic acid and assayed by high performance liquid chromatography for components of the adenine nucleotide pool including ATP, lower energy nucleotides (total adenine nucleotides, [TAN] = [ATP] + [ADP] + [AMP]), adenosine, and the diffusible purines. Results are reported as nanomoles metabolite/milligram of leaflet cell protein (Lowry) and reflect a maintenance of total high energy phosphates in the control groups (5.41 +/- 0.29 nmole TAN at 2 hr; 8.34 +/- 0.67 nmole TAN at 24 hr), which fell significantly in all cryopreserved groups (1.27 +/- 0.33 nmole TAN at 2 hr; 0.34 +/- 0.22 nmole TAN at 24 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Application of an allele-specific polymerase chain reaction to the direct determination of ABO blood group genotypes.

The allele-specific polymerase chain reaction (ASPCR) procedure has proven a powerful tool for the detection and analysis of known genetic polymorphisms. Here, we present a novel application of the ASPCR technique to determine the ABO genotypes of individuals without the need of family analysis. The method introduces a new strategy for primer design that permits the identification of the different ABO genotypes according to the molecular size of allele-specific amplification products. Four primer sets, each specific for a different set of ABO alleles, are mixed in one reaction and the amplification products are resolved on a polyacrylamide gel. Forty-one individuals belonging to various families, whose ABO phenotypes were previously determined serologically, were typed with this new variation of the ASPCR technique. A 100% correlation between the serology and the ASPCR data was found. The Mendelian segregation of ABO alleles was also demonstrated in families. The method is rapid, simple, reproducible, and specific. Potential applications include gene mapping, genetic disease diagnosis, HLA typing, paternity testing, and forensic science.

ABO Blood-Group System↗

Serum albumin in older persons: relationship with age and health status.

We analyzed data from 4115 persons aged 71 years and older who had blood drawn at a home visit in three communities to examine the cross-sectional distribution of serum albumin and correlates of hypoalbuminemia. Mean albumin was lower among older persons, from 41.6 g/l in men aged 71-74 years to 38.5 g/l in men 90 years or older, and from 41.1 g/l to 38.9 g/l in women of the same ages, respectively. Hypoalbuminemia (albumin less than 35 g/l) was observed in 3.1% of subjects. Hypoalbuminemia and lower serum albumin were independently associated with anemia, recent diagnosis of cancer, two or more limitations in activities of daily living, residence in a nursing home, heavy cigarette smoking (greater than 1 pack/day), and older age. A 10-year age increment was associated with 0.8 g/l lower serum albumin and odds ratio of 1.56 (95% CI 1.14, 2.13) for hypoalbuminemia after adjusting for demographic factors and health status. Characteristics associated with serum albumin may confound the reported relationship between serum albumin and mortality.

Activities of Daily Living↗

Conceptual problems in identifying risk factors for functional decline in the elderly: a commentary.

Assessment of risk factors for chronic disease and disability among the elderly is a complex issue. Findings may be affected by the age at which the putative risk factor was measured, interval between the time of measurement of risk and outcome, possibility of changing patterns of exposure throughout the life span, and selective survival. We illustrate the complexity of risk assessment with findings from the Iowa 65+ Rural Health Study on the relationship between body mass and changing physical function. In baseline cross-sectional analyses, both high and low body mass were associated with poorer function. In 6-year longitudinal analyses limited to persons who were functionally intact at baseline, high body mass was associated with poorer lower-extremity function but relatively preserved upper-extremity function. High body mass was also associated with elevated rates of transient impairments. Extremes of teenage body habitus were associated with impaired physical function in old age. Function was poorest among those with a lifetime history of high body mass, and changes in body mass were complexly associated with subsequent function. Thus conceptual and analytic models of chronic illness and disability need to consider multiple, changing exposures over the lifetime, as well as the impact of illness, disability, and their treatment on subsequent risk factor exposure.

Activities of Daily Living↗

Detection of specific alleles by using allele-specific primer extension followed by capture on solid support.

This article describes a method for determining whether a particular nucleic acid sequence is present in a sample and for discriminating between any two nucleic acid sequences if such sequences differ only by a single nucleotide. The method entails extension of a novel two-component primer on templates that may or may not include a target nucleic acid sequence. The 3' portion of the primer is complementary to a portion of the template adjacent to the target sequence (for example, the polymorphic nucleotide). The 5' portion of the primer is complementary to a different preselected nucleic acid sequence. Extension of the 3' portion of the primer with a labeled deoxynucleoside triphosphate yields a labeled extension product, but only if the template includes the target sequence. The presence of such a labeled primer-extension product is detected by hybridization of the 5' portion to the preselected sequence. The preselected sequence is immobilized on a solid support. The method has been applied to genotyping individuals for the two-allele polymorphism of the human tyrosinase gene.

Alleles↗

Use of medications by persons 65 and over: data from the established populations for epidemiologic studies of the elderly.

Data were analyzed from household interviews of four population-based cohorts comprising the Established Populations for Epidemiologic Studies of the Elderly to estimate the prevalence of prescription and nonprescription medication use among community-living elderly and to examine sociodemographic and health factors related to medication use. Prescription drugs were used by 60-68% of men and 68-78% of women. Nonprescription drugs were used by 52-68% of men and 64-76% of women. Use of prescription medications generally increased with age although use of nonprescription drugs was not associated with age. Men and women who smoked or used alcohol in the preceding year frequently took medications. Those who reported more depressive symptoms, impairments in physical functioning, hospitalizations, and had poorer self-perceived health status were most likely to take medications. However, 10-29% of respondents with fair or poor self-perceived health took no prescription medications, and 3-13% took neither prescription nor nonprescription medications. While further research appears warranted into potential overmedication of elders, particularly those with many depressive symptoms, these data suggest that studies of potential underuse among elders with poor health are equally important.

Activities of Daily Living↗

Infected aortic aneurysms. A changing entity.

Infected (mycotic) aortic aneurysms are infrequent and, without surgical intervention, usually lead to uncontrolled sepsis or catastrophic hemorrhage. Symptoms are frequently absent or non-specific during the early stages, and a high index of suspicion is essential to make the diagnosis. Surgery performed after rupture carries high morbidity and mortality rates. Bacterial endocarditis with streptococcus pyogenes was the most common cause of infected aortic aneurysm in the pre-antibiotic era. Today, arterial trauma due to iatrogenic manipulation and depressed immunocompetence have become more common risk factors. Staphylococcus aureus and Salmonella are the most frequent bacteria identified. The authors' recent experience in six patients with infected aortic aneurysms who underwent arteriography and computed tomography was reviewed and these diagnostic methods compared. Computed tomography was found to be more sensitive in the diagnosis of the early stages of the disease, allowing for follow-up by serial scans in a noninvasive and less costly manner. Successful treatment, in four of these patients, was accomplished by aneurysmal resection and extra-anatomic bypass or in situ prosthetic reconstruction. A higher clinical awareness of this disease, leading to early computed tomography evaluation and prompt surgical intervention under appropriate and intensive antibiotic therapy, appears to offer the best chance of survival in patients with this difficult condition.

Aged↗