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Biomedical subjects

P J Larson

Publications and source records attributed to P J Larson.

At least 37 records · Page 2Linked to original sources

Antibodies to low-incidence antigens and elimination of the antihuman globulin phase of the crossmatch-case report: anti-Wra.

An antibody to a low-incidence antigen was identified in the serum of a nontransfused male patient. The antibody was subsequently identified as anti-Wra and was only detectable at the antihuman globulin (AHG) phase of the crossmatch. Instances of severe hemolytic transfusion reactions have been reported following the transfusion of red blood cells containing low-incidence antigens in patients with antibodies directed toward these antigens (e.g., anti- Wra, -Cob, -Jsa, etc.). Elimination of the AHG phase of the crossmatch can result in either risks or benefits. Since patients seen at this facility primarily have been multitransfused or are multiparous females, the AHG phase of the crossmatch has been maintained.

Journal Article↗

Isolation and characterization of mouse coagulation factor X -- biophysical and enzymological properties.

Mouse factor X was highly purified from plasma using barium ion precipitation and chromatography on anion-exchange and heparin-agarose affinity chromatography columns. Intact and reduced patterns of mouse factor X in SDS-PAGE were similar to those of human factor X. The specific absorption E 1%/1 cm at 280 nm of mouse factor X was found to be 11.2. Content of carbohydrate moieties of mouse factor X, determined to be 10% by weight, differs both quantitatively and quantitatively from that of human factor X, while the gamma-carboxyglutamic acid (Gla) and beta-hydroxy-aspartic acid (beta-OH-Asp) content were essentially the same as for human factor X. The amino-terminal amino acid sequences of the light and heavy chains of mouse factor X separated by SDS-PAGE were ANSFF--FKK and SVALXTSDSE, respectively. Underlined residues are non-identical with those of human factor X. Clotting time-based assays using human factor X-deficient plasma as substrate exhibited the following apparent extents of activation of factor X in mouse plasma, using human plasma as the standard: 195% (intrinsic); 200% (extrinsic); and 190% (RVV-X). Using the purified proteins in the same assay systems, the following apparent activation of mouse factor X was demonstrated, compared with human factorX: 195% (intrinsic); 27% (extrinsic); and 41% (RVV-X). These activity profiles suggest that the human extrinsic coagulation pathway functions less efficiently than the corresponding mouse pathway in the activation of mouse factor X. Furthermore, mouse brain thromboplastin satisfactorily replaced rabbit brain thromboplastin in extrinsic activation of factor X in mouse plasma, but not of human plasma or purified mouse or human factor X, in line with studies by others suggesting that human factor VIIa poorly activates factor X in the presence of mouse tissue factor. While fully RVV-X-activated mouse factor X activated human prothrombin at a rate equal to about 117% of that for human factor X, it hydrolyzed the synthetic substrate, S-2222, at a rate of only about 18% of that for human factor X. These results are expected to be useful in making the mouse suitable for study of the mammalian blood coagulation pathways.

Amino Acids↗

Alloimmunization to platelets in heavily transfused patients with sickle cell disease.

Bone marrow transplantation (BMT) is now an option for some patients with sickle cell disease (SCD). Many SCD patients are multiply transfused with red blood cells (RBCs), and may be immunized to alloantigens other than erythrocyte antigens. Because platelet refractoriness is a significant complication during BMT, we wished to determine the prevalence of alloimmunization to platelets in transfused SCD patients. Sera collected from 47 transfused and 14 untransfused SCD patients were screened for HLA and platelet-specific antibodies. Transfusion and RBC antibody histories were reviewed. A subset of the patients were rescreened 1 year later. Eighty-five percent of patients with at least 50 RBC transfusions (22 of 26), 48% of patients with less than 50 transfusions (10 of 21), and none of 14 untransfused patients demonstrated platelet alloimmunization (P < .05). Platelet alloimmunization was more prevalent than RBC alloimmunization (20% to 30%). Half of the platelet reactivity was chloroquine-elutable. Eighteen of 22 patients (82%) on chronic RBC transfusion remained platelet-alloimmunized 11 to 22 months after initial testing. In summary, 85% of heavily transfused SCD patients are alloimmunized to HLA and/or platelet-specific antigens. These patients may be refractory to platelet transfusion, a condition that would increase their risk during BMT. Leukodepletion in the transfusion support of SCD patients should be considered to prevent platelet alloimmunization.

Adolescent↗

Structural integrity of the gamma-carboxyglutamic acid domain of human blood coagulation factor IXa Is required for its binding to cofactor VIIIa.

This report describes the analysis of a novel mutant human factor IX protein from a patient with hemophilia B (factor IX activity <1%; factor IX antigen 45%). Enzymatic amplification of all eight exons of the factor IX gene followed by direct sequence analysis reveals a single nucleotide change (a guanine --> adenine transition) in exon 2 at nucleotide 6409 which results in a glycine --> arginine substitution at amino acid 12 in the gamma-carboxyglutamic acid rich (Gla) domain of the mature protein. Factor IX was isolated by immunoaffinity chromatography from plasma obtained from the proband. The purified protein is indistinguishable from normal factor IX by polyacrylamide gel electrophoresis. Characterization of the variant in purified component assays reveals that it is activated normally by its physiologic activator factor XIa, but its phospholipid-dependent activation by the factor VIIa-tissue factor complex is diminished. In the presence of phospholipid and 5 mM Ca2+, the activities of variant and normal plasma-derived factor IX are similar; however, in the presence of activated factor VIIIa (intrinsic tenase complex), the normal augmentation of the cleavage of the specific substrate of factor IX, factor X, is not observed. The determination of the association constants for normal and variant factor IXa with factor VIIIa shows that the affinity of the activated variant factor IX for the cofactor factor VIIIa is 172-fold lower than normal. Competition studies using active site-inactivated factor IXas in the intrinsic tenase complex confirm that the defect in the variant protein is in its binding to factor VIIIa. We conclude that the structural integrity of the Gla domain of human factor IX is critical for the normal binding of factor IXa to factor VIIIa in the intrinsic tenase complex. In addition, a glycine at amino acid 12 is necessary for normal activation of factor IX by the factor VIIa-tissue factor complex.

Adenine↗

Delayed hemolytic transfusion reaction due to anti-Go(a), an antibody against the low-prevalence Gonzales antigen.

Go(a) (D(Cor)) is a low-frequency antigen in the Rh system found on red cells lacking part of the D mosaic (category IVa). Anti-Go(a) has not been previously reported to cause hemolytic transfusion reactions. A 27-year-old African American male with sickle-cell disease, maintained on chronic transfusion, was noted to have dark plasma during an erythrocytapheresis, procedure, and the pretransfusion hemoglobin was noted to be 1 g/dl lower than 4 weeks before (with hyperbilirubinemia and a significantly increased LDH). Polyspecific direct antiglobulin test (DAT) was weakly positive (C3-weak, IgG-weak), and indirect antiglobulin tests (IATs) performed on the serum (pre- and posttransfusion reaction) and a red blood cell (RBC) eluate from the postreaction sample were negative. A segment from one of the four implicated units from the prior month's transfusion was strongly reactive at 37 degrees C and using anti-human globulin (AHG) when crossmatched with the postreaction serum and the eluate. The postreaction serum, screened with a panel of red cells positive for low-prevalence antigens, reacted with three Go(a+) cells. The implicated unit was reactive with a previously identified anti-Go(a) serum.

Adult↗

Differences in nausea, vomiting, and retching between younger and older outpatients receiving cancer chemotherapy.

The purpose of this study was to determine whether there were differences in the side effects of nausea, vomiting, and retching (N, V, and R) between younger ( < 65 years, n = 102) and older ( > or = 65 years, n = 25) persons receiving outpatient chemotherapy. A longitudinal 4-month study was used for the 127 participants recruited from 18 settings. Participants completed two questionnaires (Inventory of N, V, and R and Behavior Checklist) over the course of the study. The pattern between the younger and older patients' N, V, and R subscale scores was consistent in that the younger patients' scores were consistently (except on one occasion) higher than the older patients' scores, but this difference was statistically insignificant. This study furthers our understanding of N, V, and R and has several clinical implications.

Adult↗

Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy.

PURPOSE/OBJECTIVES: To test the effectiveness of a nurse-initiated systematic oral hygiene teaching program-PRO-SELF: Mouth Aware (PSMA)-in conjunction with two mouthwashes (0.12% chlorhexidine or sterile water) in preventing chemotherapy-induced oral mucositis. DESIGN: Randomized, double-blind, placebo-controlled, clinical trial. SETTINGS: 23 outpatient clinics and office practices in California. SAMPLE: 222 patients who were starting a cycle of mucositis-inducing chemotherapy. METHOD: Participants were followed over three chemotherapy cycles. All patients were provided the PSMA program. Random assignment to a mouthwash occurred prior to the development of oral mucositis. Researchers used the Oral Assessment Guide to assess the patients oral cavities monthly (with the patients cycles of chemotherapy) and when patients reported any oral changes between cycles. MAIN RESEARCH VARIABLES: Type of mouthwash, incidence, days to onset, and severity of chemotherapy-induced oral mucositis. FINDINGS: No significant differences existed between the two mouthwashes in regard to incidence, days to onset, and severity of mucositis. CONCLUSIONS: Because chlorhexidine (S20 per pint) was no more effective than water, a substantial cost savings can be realized by rinsing with water. Interestingly, the PSMA program appeared to reduce the incidence of mucositis from on a prior estimate of 44% to less than 26%. IMPLICATIONS FOR NURSING PRACTICE: A nursing prescription of a systematic oral hygiene program using water as a mouth rinse is cost efficient and may be effective in preventing oral mucositis.

Adult↗

The monocyte monolayer assay: a noninvasive technique for predicting the severity of in utero hemolysis.

To test the noninvasive monocyte monolayer assay in predicting hemolytic severity in utero, we studied 18 patients from two institutions with significant erythrocyte alloantibodies. Serum samples were obtained from each patient. Each subject donated a serum sample during her pregnancy. Monocytes were harvested from a single healthy donor and grown in monolayer culture. Erythrocytes with the appropriate antigens were sensitized with maternal serum and incubated with the monocyte monolayers. Erythrophagocytosis was scored as a percentage of the positive control. Perinatal outcomes were assessed post hoc and cases were classified as unaffected or mildly, moderately, or severely affected using standard definitions. Prenatal management was conducted without knowledge of the results. Six of the 18 patients had severe disease and one of the 18 had moderately severe disease. At a cutoff level of 20, the assay generated the following results: sensitivity was 7 of 7 (100%), specificity was 10 of 11 (90.9%), positive predictive value was 7 of 8 (87.5%), and negative predictive value was 10 of 10 (100%). The monocyte monolayer assay appears to be a useful, noninvasive modality for predicting the severity of hemolytic disease in utero.

Erythroblastosis, Fetal↗

Comorbidity, nutritional intake, social support, weight, and functional status over time in older cancer patients receiving radiotherapy.

It is essential that nurses gain insight about the responses of older adults to standard anticancer therapies because there is ongoing concern about whether the elderly are affected adversely by the prescribed therapy. The purpose of this longitudinal prospective study was to describe selected outcomes and their relationships in a sample of 45 elderly (mean age 69.8 years; range 61-86) patients receiving radiotherapy for either breast (42%) or lung (58%) cancer. The outcome variables were weight and multidimensional functional status; moderator variables were co-morbidity, nutritional intake, estimated adequacy of intake, radiation dose, side effects, and social support. Data were collected at the beginning of radiation (T1), the middle of therapy (T2), the conclusion of therapy (T3), and three months post radiation (T4). Although 81.4% had some concurrent condition, those with a comorbid condition did not respond significantly differently from those without a comorbid condition on any of the major variables at any of the four times. At none of the four times was the caloric intake adequate to meet the estimated energy requirements for usual activity (range 67.9-71.5%). However, caloric intake was not significantly related to weight at any of the four times. There was a significant weight decrease from beginning of therapy to the middle of therapy and from the beginning of therapy to conclusion of therapy. The percentage of calories contributed by protein was significantly correlated with weight during radiotherapy, and protein calories consumed at the previous time were correlated with weight at T2 and T3. In contrast, the percentage of calories contributed by carbohydrate intake was significantly negatively correlated with two of the four functional status measures at each time, but was not related to weight. In addition carbohydrate calories consumed at the previous time also were related to one or more functional status measures at succeeding time points. Almost no relationships were found between social support and the outcome measures of weight and functional status. Scores on three of the four functional status measures suggest improvement over time from initiation of radiation to 3 months after therapy. Scores on the fourth measure, Overall Health Rating, suggest a slight decline; however, the average score reflects good overall health. These findings provide evidence that this group of elderly, the great majority of whom had at least one comorbid condition, tolerated the course of radiation with less than adequate intake for usual activity, a slight decrease in mean weight, but without major disruptions in functional status.(ABSTRACT TRUNCATED AT 400 WORDS)

Activities of Daily Living↗

Influence of age on problems experienced by patients with lung cancer undergoing radiation therapy.

The purpose of this prospective, longitudinal study was to determine if patients with lung cancer who are 65 years of age or older experience problems differently than do patients younger than age 65 during and following radiation treatment. The moderator and outcome variables selected for study were recognized attendant problems that may develop during lung cancer treatment and that may influence the treatment regimen and response. No statistically significant differences were found between patients age 65 or older and those younger than age 65 on caloric intake, adequacy of energy intake, total radiation dose, concurrent illnesses, and social support at any of four data-collection periods. Similarly, there were no significant differences on weight, body mass index, and multidimensional functional status. The relationship between the social support subscales and functional status measures for the 65-or-older group suggested that those subjects with lower social support perceived themselves to have better functional status. There was no relationship between social support and two functional status measures for the under-65 group. The significant relationships between social support and the overall health rating were in opposite directions for the two age groups. The results suggest that chronologic age alone may not be a sufficient criterion to determine therapeutic regimen or to suggest that unique problems may result.

Activities of Daily Living↗

Biology of inherited coagulopathies: factor IX.

Characterization of the functional domains of FIX and related vitamin K-dependent proteins has been enhanced by the isolation and characterization of the genes encoding these proteins. A better understanding of the interactions between FIX's activators, cofactors, and substrate, FX, has been gained through the study of naturally occurring variants isolated from patients with hemophilia B and genetically engineered recombinant molecules. With the determination of specific mutations in hemophilia B kindreds, and through advances in molecular techniques, especially the polymerase chain reaction, more accurate determination of carrier status and prenatal diagnosis can now be made.

Amino Acid Sequence↗

The relationship of visual acuity, tactile sensitivity, and mobility of the upper extremities to proficient breast self-examination in women 65 and older.

The purpose of this study was to describe the relationship of visual acuity, tactile sensitivity, and mobility of the upper extremities to the performance of proficient breast self-examination (BSE) in women 65 and older. A convenience sample of 32 women, ages 66-89, met with the investigator to have their visual acuity, tactile sensitivity, and upper extremity mobility tested. Their ability to perform the visual, tactile, and upper extremity components of proficient BSE also was tested by using simulated breast models (SBMs). Thirty of the women had adequate visual acuity (< or = 20/40 Snellen equivalent) but were unable to visually detect the abnormalities on the SBM. Thirty of the women had tactile sensitivity of 10 mm (1 cm) or better on the static two-point discrimination test of the second, third, and fourth digits of each hand. Yet, only 13 of these women were able to locate the 1 cm lump; only 12 were able to locate the 5 mm lumps; and none were able to locate the 3 mm lump. The subjects' ability to pass the upper extremity mobility component of proficient BSE was significantly related to their ability to pass the upper extremity range of motion criteria. Limitations and deficits, mostly of the hands and shoulders, were revealed. When teaching BSE to older women, nurses are responsible for assessing limitations and deficits in their ability to perform proficient BSE and, if necessary, for intervening with alternatives. The need for further research in this area is indicated to improve assessment and education of older women regarding the use of proficient BSE for early detection of breast cancer.

Age Factors↗

Comfort. Immigrant Hispanic cancer patients' views.

This study focuses on the meaning of comfort from the perspective of immigrant Hispanic cancer patients undergoing treatment at a large Western medical center. Patients (n = 10), in 30 ethnographical interviews conducted in Spanish by a culturally sensitive interviewer identified characteristics, needs, and sources of comfort. The characteristics of comfort were: feeling integrated, functioning and normalcy, care and nurturing, security and safety, control and "comodo." Comfort needs evolved into 6 categories: nurturing, familiar environment, safety, quality of life, normalcy, and "animo." Providers of comfort, as perceived by these Hispanic patients were: self, family, health care providers, and God. The characteristics of comfort most frequently talked about by the Hispanic participants were feeling integrated and nurtured. Integrated, a seemingly complex characteristic of comfort, reflected a sense of inner peace with oneself that went beyond the physical comfort. Function and normalcy were also perceived to be important aspects of comfort. It is important to note that the Hispanic patients on occasion used culturally relevant terms, such as comodo and animo (neither of which are readily translated into English) to convey their impressions of comfort. The study demonstrates that comfort is important in illness and cancer treatment situations, and that for these Hispanic patients it also had influence from their culture.

Adult↗

Working families and eldercare: a national perspective in an aging America.

The competing demands of employment and caring for a dependent elderly family member can create stress for families, and some employers are becoming concerned about the impact of eldercare on the workplace. This first national survey of workers examined the extent of eldercare and its impact on workers. In this article, the authors profile the employees who described themselves as caregivers, the older people they were caring for, the care they were giving, the extent to which they reported conflict between their work and caregiving responsibilities, and the workplace supports they would have found helpful in managing these roles. Women were devoting more time to caregiving and were more likely to report work and caregiving conflict than were men. Social workers in occupational and community settings can play a key role in providing information about eldercare services, in counseling caregivers, and in advocating for employee benefits and community services to help workers maintain both work and family roles.

Activities of Daily Living↗