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Biomedical subjects

K Armstrong

Publications and source records attributed to K Armstrong.

At least 19 recordsLinked to original sources
PubMed2005

Safety of recombinant human factor XIII in a cynomolgus monkey model of extracorporeal blood circulation.

Factor XIII (FXIII) is a thrombin-activated plasma coagulation factor critical for blood clot stabilization and longevity. Administration of exogenous FXIII to replenish depleted stores after major surgery, including cardiopulmonary bypass, may reduce bleeding complications and transfusion requirements. Thus, a model of extracorporeal circulation (ECC) was developed in adult male cynomolgus monkeys (Macaca fascicularis) to evaluate the nonclinical safety of recombinant human FXIII (rFXIII). The hematological and coagulation profile in study animals during and after 2 h of ECC was similar to that reported for humans during and after cardiopulmonary bypass, including observations of anemia, thrombocytopenia, and activation of coagulation and platelets. Intravenous slow bolus injection of 300 U/kg (2.1 mg/kg) or 1000 U/kg (7 mg/kg) rFXIII after 2 h of ECC was well tolerated in study animals, and was associated with a dose-dependent increase in FXIII activity. No clinically significant effects in respiration, ECG, heart rate, blood pressure, body temperature, clinical chemistry, hematology (including platelet counts), or indicators of thrombosis (thrombin:anti-thrombin complex and D-Dimer) or platelet activation (platelet factor 4 and beta-thromboglobulin) were related to rFXIII administration. Specific examination of brain, heart, lung, liver, and kidney from rFXIII-treated animals provided no evidence of histopathological alterations suggestive of subclinical hemorrhage or thrombosis. Taken as a whole, the results demonstrate the ECC model suitably replicated the clinical presentation reported for humans during and after cardiopulmonary bypass surgery, and do not suggest significant concerns regarding use of rFXIII in replacement therapy after extracorporeal circulation.

Animals↗
PubMed2004

A cytogenetic method for stacking gene pairs in common wheat.

The potential for non-reciprocal Robertsonian translocations of wheat (Triticum aestivum L.) to assist in the stacking of genes was assessed from a study of their cytological and genetic behaviour. To obtain translocations, a double monosomic (3B+5A; 2n=40=19ii+2i) was crossed reciprocally with a contrasting disomic. Individuals inheriting a broken monosome were identified from the loss of one arm-specific DNA marker coupled with retention of a marker for the opposite arm. No double breaks (potential translocations) were found in 180 cross progeny recovered from pollen of the double monosomic but two instances (loss of 5AL plus 3BS; loss of 5AL plus 3BL) were found in 251 progeny recovered from ovules. Meiotic pairing and multi-color genome-specific fluorescence in situ hybridization (mcGISH) showed that each plant with a double break contained one translocated chromosome between the A and B genomes that had rejoined at the centromere and that formed a trivalent (19ii+ liii) in about 83% of PMC. Most trivalents (approximately 92%) aligned at metaphase in a 'V' configuration(alternate disjunction) while the rest aligned in linear 'I'(adjacent disjunction) or ambiguous 'L' configurations. Genetic analysis of a testcross of these 'fusion monosomics' showed that this preferential co-orientation of the trivalent influenced the assortment of the chromosome arms involved. Loci that were located in the hemizygous ends of the 'V' trivalent showed strong quasi-linkage in that most ovules from the female testcross carried relevant DNA markers either from both standard chromosomes or from neither. This shows that, in most cases, the two standard chromosomes assorted to the same pole while the fused monosome segregated to the opposite pole. For heterozygous loci (present both on the fusion monosome and the standard chromosomes) assortment was either independent or showed partial linkage to the hemizygous arm depending on the reported recombination distance from centromere. Marker assortment was further distorted in male testcrosses and in doubled haploids (made from the fusion monosomics by the maize method) by the strong selective advantage of pollen or haploids that inherited the standard chromosomes rather than the deficiencies. This genetic data shows that under the combined influence of alternate disjunction and natural selection, progeny of fusion monosomics will revert to the standard disomic arrangement, fixing the gene content of both hemizygous arms in the process. Thus, any pair of genes could be targeted for joint fixation by isolating the fusion monosome that will link them temporarily in a segregating population.

Chromosome Mapping↗
PubMed2003

Characterization of six wheat x Thinopyrum intermedium derivatives by GISH, RFLP, and multicolor GISH.

Restriction fragment length polymorphism (RFLP) analysis and multicolor genomic in situ hybridization (GISH) are useful tools to precisely characterize genetic stocks derived from crosses of wheat (Triticum aestivum) with Thinopyrum intermedium and Thinopyrum elongatum. The wheat x Th. intermedium derived stocks designated Z1, Z2, Z3, Z4, Z5, and Z6 were initially screened by multicolor GISH using Aegilops speltoides genomic DNA for blocking and various combinations of genomic DNA from Th. intermedium, Triticum urartu, and Aegilops tauschii for probes. The probing (GISH) results indicated that lines Z1 and Z3 were alien disomic addition lines with chromosome numbers of 2n = 44. Z2 was a substitution line in which chromosome 2D was substituted by a pair of Th. intermedium chromosomes; this was confirmed by RFLP and muticolour GISH. Z4 (2n = 44) contained two pairs of wheat--Th. intermedium translocated chromosomes; one pair involved A-genome chromosomes, the other involved D- and A- genome chromosomes. Z5 (2n = 44) contained one pair of wheat--Th. intermedium translocated chromosomes involving the D- and A-genome chromosomes of wheat. Z6 (2n = 44) contained one pair of chromosomes derived from Th. intermedium plus another pair of translocated chromosomes involving B-genome chromosomes of wheat Line Z2 was of special interest because it has some resistance to infection by Fusarium graminearum.

Blotting, Southern↗
PubMed2001

Cost-effectiveness of raloxifene and hormone replacement therapy in postmenopausal women: impact of breast cancer risk.

OBJECTIVE: To examine the life expectancy and cost-effectiveness of hormone replacement therapy (HRT) and raloxifene therapy in healthy 50-year-old postmenopausal women. METHODS: We performed a cost-effectiveness analysis using a Markov model, discounting the value of future costs and benefits to account for their time of occurrence. RESULTS: Both HRT and raloxifene therapy increase life expectancy and are cost-effective relative to no therapy for 50-year-old postmenopausal women. For women at average breast cancer and coronary heart disease risk, lifetime HRT increases quality-adjusted life expectancy more (1.75 versus 1.32 quality-adjusted life years) and costs less ($3802 versus $12,968) than lifetime raloxifene therapy. However, raloxifene is more cost-effective than HRT for women at average coronary risk who have a lifetime breast cancer risk of 15% or higher or who receive 10 years or less of postmenopausal therapy. Raloxifene is also the more cost-effective alternative if HRT reduces coronary heart disease risk by less than 20%. CONCLUSIONS: Assuming the benefit of HRT in coronary heart disease prevention from observational studies, long-term HRT is the most cost-effective alternative for women at average breast cancer and coronary heart disease risk seeking to extend their quality-adjusted life expectancy after menopause. However, raloxifene is the more cost-effective alternative for women at average coronary risk with one or more major breast cancer risk factors (first-degree relative, prior breast biopsy, atypical hyperplasia or BRCA1/2 mutation). These results can help inform decisions about postmenopausal therapy until the results of large scale randomized trials of these therapies become available.

Breast Neoplasms↗
PubMed2001

Barriers to influenza immunization in a low-income urban population.

BACKGROUND: Although influenza immunization significantly reduces mortality from influenza, over one third of elderly Americans are not immunized each year. Low rates of immunization are particularly concerning among African-American low-income populations. Preliminary interviews suggested that fear of undisclosed ingredients in the influenza vaccine may impede vaccine acceptance in this vulnerable population. OBJECTIVES: To assess the role of concern about vaccine contents and other factors in the use of influenza immunization among a predominantly African-American low-income urban population. METHODS: Cross-sectional, health-system-population-based, telephone survey of a random sample of West Philadelphia residents aged > or =65 years. RESULTS: Of 659 eligible individuals, 486 (73.8%) were successfully interviewed. Concern about undisclosed shot contents was reported by 132 (20%) respondents and was inversely associated with vaccine receipt (OR 0. 49, 95% CI 0.26-0.91). This association was similar among African Americans and Caucasians. In addition, receipt of influenza vaccine was inversely associated with belief that immunization is inconvenient (OR 0.14, 95% CI 0.05-0.36), belief that immunization is painful (OR 0.21, 95% CI 0.08-0.54), and history of previous side effects (OR 0.33, 95% CI 0.18-0.60), and positively associated with physician recommendation (OR 3.22, 95% CI 1.76-5.93). CONCLUSIONS: In a low-income urban population, concern about undisclosed vaccine contents appears to impede acceptance of influenza immunization among both African Americans and Caucasians. Directly addressing this concern offers a new approach to increasing immunization in this vulnerable population.

Aged↗
PubMed2001

Using survival curve comparisons to inform patient decision making can a practice exercise improve understanding?

BACKGROUND: Patients often face medical decisions that involve outcomes that occur and change over time. Survival curves are a promising communication tool for patient decision support because they present information about the probability of an outcome over time in a simple graphic format. However, previous studies of survival curves did not measure comprehension, used face-to-face explanations, and focused on a VA population. METHODS: In this study, 246 individuals awaiting jury duty at the Philadelphia County Courthouse were randomized to receive one of two questionnaires. The control group received a questionnaire describing two hypothetical treatments and a graph with two survival curves showing the outcomes of each treatment. The practice group received the same questionnaire preceded by a practice exercise asking questions about a graph containing a single curve. Subjects' ability to interpret survival from a curve and ability to calculate change in survival over time were measured. RESULTS: Understanding of survival at a single point in time from a graph containing two survival curves was high overall, and was improved by the use of a single curve practice exercise. With a practice exercise, subjects were over 80% accurate in interpreting survival at a single point in time. Understanding of changes in survival over time was lower overall, and was not improved by the use of a practice exercise. With or without a practice exercise, subjects were only 55% accurate in calculating changes in survival. CONCLUSION: The majority of the general public can interpret survival at a point in time from self-administered survival curves. This understanding is improved by a single curve practice exercise. However, a significant proportion of the general public cannot calculate change in survival over time. Further research is necessary to determine the effectiveness of survival curves in improving risk communication and patient decision making.

Adult↗
PubMed2001

Fetal antecedents of male factor sub-fertility: how important is birthweight?

BACKGROUND: Severely reduced fetal growth has been linked to gonadal dysfunction. The aim of this study was to explore the link between birthweight and subsequent male infertility using the Aberdeen Maternity and Neonatal Databank (AMND). METHODS AND RESULTS: Assuming 80% power at the 5% significance level, a minimum of 126 men (63 in each group) was required to show a mean difference of 0.5 (SD = 1) in the standardized birthweight scores between cases and controls. Men born locally with unexplained male factor infertility (n = 79) were identified from the infertility clinic database. Men with normal semen parameters, born in Aberdeen and attending the infertility clinic with their partners (n = 104), served as controls. The pregnancy records of these men's mothers were obtained from the AMND and a standard case-control analysis performed. In addition to standardized birthweight scores, the following variables were studied: crude birthweight, social class, maternal age, parity, obstetric history, antepartum and peripartum events. CONCLUSIONS: No differences were found between the two groups, suggesting that low birthweight is unlikely to affect male fertility in later life.

Birth Weight↗
PubMed2001

Long-term effectiveness of a peer-based intervention to promote condom and contraceptive use among HIV-positive and at-risk women.

OBJECTIVE: The authors used data from a larger study to evaluate the long-term effects of a peer advocate intervention on condom and contraceptive use among HIV-infected women and women at high risk for HIV infection. METHODS: HIV-infected women in one study and women at high risk for HIV infection in a second study were selected from the Women and Infants Demonstration Project and assigned to a standard or an enhanced HIV prevention treatment group. The enhanced intervention included support groups and one-on-one contacts with peer advocates tailored to clients' needs. The authors interviewed women at baseline and at 6-, 12- and 18-months, and measured changes in consistency of condom and contraceptive use and in self-efficacy and perceived advantages and disadvantages of condom and contraceptive use. RESULTS: Of HIV-infected women, the enhanced group had improved consistency in condom use, increased perceived advantages of condom use, and increased level of self-efficacy compared with the standard group. Of women at risk, the enhanced intervention group at six months maintained consistent condom use with a main partner and perceived more benefit of condom use compared with the standard group. These differences diminished at 12 months. CONCLUSIONS: The enhanced intervention was generally effective in the HIV+ study. In the at-risk study, however, intervention effects were minimal and short-lived. Factors related to the theory, intervention design, and sample characteristics help explain these differences.

Adolescent↗
PubMed2001

Reproductive and contraceptive attitudes as predictors of condom use among women in an HIV prevention intervention.

This study prospectively evaluates the effect of childbearing motivation and contraceptive attitudes on consistency of condom use among at-risk women enrolled in an HIV prevention intervention. Women (age 15-40, 85% African-American) were recruited from homeless shelters, drug treatment facilities, and public housing developments and assigned to standard or enhanced intervention conditions. Among the eligible study group of nonsterilized women with a main partner (n = 312), 24.4% wanted to have a baby at baseline; 43.5% believed their partner wanted them to have a baby. Women who reported a desire for a baby, compared to all others, were less likely to be at a higher level of condom consistency six months later (OR = 0.66; .48-.90). Women who perceived partner support for contraceptive use showed a higher level of condom consistency (OR = 1.20; 1.03-1.41) at 6-month follow-up. Many women in this study wanted to have a baby and this desire interfered with subsequent consistency of condom use. We also found that condom use increased toward consistency of use among women whose partner supported contraceptive use. HIV prevention interventions should include screening for reproductive motivation, so that prevention messages can be tailored to the realities of women's lives. Women who want a baby can be educated about disease prevention in the context of pregnancy planning and linked with appropriate services. Women who want to avoid childbearing can be given messages that emphasize the contraceptive benefits of condom use and that help strengthen partner support.

Adolescent↗
PubMed2000

Ross syndrome plus: beyond horner, Holmes-Adie, and harlequin.

BACKGROUND: Ross syndrome is an uncommon disorder characterized by the triad of segmental anhidrosis, hyporeflexia, and tonic pupils. METHODS: The authors describe the clinical findings of five patients with Ross syndrome and detail the results of their pharmacologic and autonomic testing. RESULTS: In four patients, the classic findings of Ross syndrome were accompanied by Horner's syndrome. Other symptoms of dysautonomia were also common. CONCLUSIONS: These findings suggest that Ross syndrome is a dysautonomic condition of varying expression resulting from a generalized injury to ganglion cells or their projections.

Adolescent↗
PubMed2000

Effect of coronary angiography on use of lipid-lowering agents in women: a report from the Women's Ischemia Syndrome Evaluation (WISE) study. For the WISE Investigators.

We sought to assess the impact of coronary angiography results on use of lipid-lowering agents among women enrolled in the Women's Ischemia Syndrome Evaluation [WISE] study. WISE is a multicenter study designed to evaluate new diagnostic modalities among women undergoing angiography for suspected coronary artery disease (CAD). History of atherosclerosis, risk factors for CAD, and low-density lipoprotein (LDL) cholesterol are determined at baseline. The percentage of women at LDL cholesterol goal, use of lipid-lowering agents, and eligibility for lipid-lowering therapy were determined based on National Cholesterol Education Program II guidelines at baseline and 6-week follow-up. Among the 212 women for whom angiographic data were available, 84 had known atherosclerosis, 80 had no history of atherosclerosis but > or =2 risk factors (high risk), and 48 had no history of atherosclerosis and <2 risk factors (low risk). At baseline, LDL cholesterol goals were met in 24% women with atherosclerosis, in 56% high-risk women, and in 88% low-risk women. Angiography revealed previously undiagnosed CAD in 70% of the high-risk and in 42% of the low-risk women. After angiography results were available, 6 women started lipid-lowering therapy and 2 stopped. Based on National Cholesterol Education Program II guidelines, 63 additional women would have been eligible for pharmacologic lipid-lowering therapy. Intensification of lipid-lowering therapy was not apparent 6 weeks after coronary angiography in women with newly diagnosed CAD or among women whose diagnosis was confirmed.

Aged↗
PubMed2000

Cost-effectiveness of prophylaxis against Pneumocystis carinii pneumonia in patients with Wegner's granulomatosis undergoing immunosuppressive therapy.

OBJECTIVE: To assess the incremental cost-effectiveness of 3 Pneumocystis carinii pneumonia (PCP) prophylaxis strategies in patients with Wegener's granulomatosis (WG) receiving immunosuppressive therapies: 1) no prophylaxis; 2) trimethoprim/sulfamethoxazole (TMP/SMX) 160 mg/800 mg 3 times a week, which is discontinued if patients experience an adverse drug reaction (ADR); and 3) TMP/SMX 160 mg/800 mg 3 times a week, which is replaced by monthly aerosolized pentamidine (300 mg) if patients experience an ADR. METHODS: A Markov state-transition model was developed to follow a hypothetical cohort of WG patients over their lifetimes starting from the time of initial exposure to the immunosuppressive therapy. The effect of PCP prophylaxis on life expectancy, quality-adjusted life expectancy, average discounted lifetime cost (ADLC), and incremental cost-effectiveness was estimated based on data obtained from a literature review. Direct medical costs were examined from a societal perspective, and costs and benefits were discounted at 3% annually. RESULTS: No prophylaxis resulted in a life expectancy of 13.36 quality-adjusted life years (QALY) at an ADLC of $4,538. In comparison, prophylaxis with TMP/ SMX alone increased the QALY to 13.54 and was cost saving, with an ADLC of $3,304. The addition of pentamidine in patients who had an ADR to TMP/SMX resulted in 13.61 QALY, with an ADLC of $7,428. Compared with TMP/SMX alone, TMP/SMX followed by pentamidine increased the QALY by 0.07 at an incremental cost of $58,037 per QALY. Both TMP/SMX alone and TMP/SMX followed by pentamidine prophylaxis strategies dominated the no prophylaxis strategy until the incidence of PCP fell below 0.2% and 2.25%, respectively. Institution of pentamidine therapy for patients with a TMP/SMX ADR increased quality-adjusted life expectancy compared with that with TMP/ SMX alone until the incidence of PCP rose above 7.5%. CONCLUSION: Prophylaxis using TMP/SMX alone increased life expectancy and reduced cost for patients with WG receiving immunosuppressive therapy. Replacing TMP/SMX with monthly aerosolized pentamidine in cases of ADR further increased life expectancy, although at an increased cost.

Adult↗
PubMed2000

Medicalizing normality? Management of irritability in babies.

OBJECTIVE: The aims of this project were to identify the scources and quality of the health advice provided to parents with irritable infants; to assess the efficacy of a residential programme in the diagnosis and management of irritable infants; and to assess the intermediate term outcome for such infants and their mothers. METHODOLOGY: All mother-infant pairs admitted during a 3 month period to a residential setting with the primary concern of infant irritability were asked to participate in the study. Pre-admission and 3 month post-discharge health-care advice, investigations and treatment details were collected. Maternal mood at admission and 3 months post-discharge was measured using the Edinburgh Postnatal Depression Scale (EPDS). On admission, infant medication for proposed cause of excess irritability was ceased, with parental consent, if it was appropriate and following full medical assessment. Individual case plans were designed by the admitting child health nurse in consultation with the mother. These included education as to normal infant behaviour, settling techniques, and establishment of routine; family issues were also explored. RESULTS: Fifty-one consecutive mother-infant pairs consented to participate and formed the cohort, 48 (94%) were available for follow-up interview 3 months post-discharge. The average age on admission was 13 weeks (range 4-28 weeks), 32 (62.7%) were male, 34 (66.7%) were first born and 45 (88.2%) lived with both their parents. A multiplicity of health professionals had been involved in the pre-admission care, and 48 of the infants had been or were currently on medication for gastro-oesophageal reflux disease and or colic. At the end of admission, diagnoses made were predominantly behavioural (22) and feeding problems (20). Nine infants were felt to have an organic cause for their irritability. Maternal mood improved significantly on EPDS from the time of admission (45 (86.2%) of mothers with scores > or = 12, mean score 16.5) to post-admission follow up (9 (18. 8%) with scores > or = 12, mean score 7.2). CONCLUSIONS: There is evidence that a proportion of babies with 'normal' irritability are being incorrectly diagnosed as having an organic disorder exposing them inappropriately to medication, which may be harmful, and potentially creating lifelong problems for these infants and their families.

Colic↗