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Biomedical subjects

L Palmer

Publications and source records attributed to L Palmer.

At least 19 recordsLinked to original sources
PubMed2005

Stabilized plasmid-lipid particles containing PEG-diacylglycerols exhibit extended circulation lifetimes and tumor selective gene expression.

Stabilized plasmid lipid particles (SPLP) consist of a single copy of DNA surrounded by a lipid bilayer. The particles are small ( approximately 100 nm), stable, monodisperse and have a low surface charge. A diffusible polyethylene glycol (PEG) coating attached to a lipid anchor is critical to the SPLP's functionality. The PEG-lipid exchanges out of the bilayer at a rate determined by the size of the lipid anchor. Here we show that SPLP can be prepared using a series of PEG-diacylglycerol lipids (PEG-S-DAGs). SPLP were prepared incorporating PEG-dimyristoylglycerol (C14), PEG-dipalmitoylglycerol (C16) or PEG-distearoylglycerol (C18) and the rate of PEG-lipid diffusion from the bi-layer determined using a FRET assay. SPLP pharmacokinetics confirm a correlation between the stability of the PEG-lipid component and circulation lifetime. PEG-S-DAGs with longer lipid anchors yield more stable SPLP particles with longer circulation half-lives yielding an increase in tumor delivery and gene expression. PEG-distearoylglycerol (C18) containing SPLP bypass so-called 'first pass' organs, including the lung, and elicit levels of gene expression in distal tumor tissue 100- to 1000-fold greater than that observed in any other tissue. The incorporation of PEG-S-DAG in SPLP confirms that small size, low surface charge and extended circulation lifetimes are prerequisite to the accumulation and tumor selective expression of plasmid DNA following systemic administration.

Diglycerides↗
PubMed2005

LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women.

Postmenopausal osteoporosis and bone mass are influenced by multiple factors including genetic variation. The importance of LDL receptor-related protein 5 (LRP5) for the regulation of bone mass has recently been established, where loss of function mutations is followed by severe osteoporosis and gain of function is related to increased bone mass. The aim of this study was to evaluate the role of polymorphisms in the LRP5 gene in regulating bone mass and influencing prospective fracture frequency in a well-described, large cohort of normal, ambulatory Australian women. A total of 1301 women were genotyped for seven different single nucleotide polymorphisms (SNPs) within the LRP5 gene of which five were potentially informative. The effects of these gene polymorphisms on calcaneal quantitative ultrasound measurements (QUS), osteodensitometry of the hip and bone-related biochemistry was examined. One SNP located in exon 15 was found to be associated with fracture rate and bone mineral density. Homozygosity for the less frequent allele of c.3357 A > G was associated with significant reduction in bone mass at most femoral sites. The subjects with the GG genotype, compared to the AA/AG genotypes showed a significant reduction in BUA and total hip, femoral neck and trochanter BMD (1.5% P = 0.032; 2.7% P = 0.047; 3.6% P = 0.008; 3.1% P = 0.050, respectively). In the 5-year follow-up period, 227 subjects experienced a total of 290 radiologically confirmed fractures. The incident fracture rate was significantly increased in subjects homozygous for the GG polymorphism (RR of fracture = 1.61, 95% CI [1.06-2.45], P = 0.027). After adjusting for total hip BMD, the fracture rate was still increased (RR = 1.67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures.

Absorptiometry, Photon↗
PubMed2004

Effects of manipulating intrauterine growth on post natal adrenocortical development and other parameters of maturity in neonatal foals.

REASONS FOR PERFORMING STUDY: Intrauterine growth retardation (IUGR) impairs post natal adaptive responses and is associated with increased adrenocortical activity in many species. OBJECTIVES: To determine whether a restricted or enhanced intrauterine environment affects neonatal adaptation and adrenocortical function in horses. METHODS: Embryos from large (577 kg) Thoroughbred (TB) mares were transferred to smaller (343 kg) pony (P) mares and vice versa, to create a restricted (TB-in-P, n = 11) or enhanced (P-in-TB, n = 8) intrauterine environment. Control groups (TB-in-TB, n = 8; P-in-P, n = 7) were also included. RESULTS: Thirty foals were born live at full term (range 314-348 days) and 4 (3 TB-in-P, 1 P-in-TB) were stillborn between 275 and 335 days. TB-in-P foals were significantly (P<0.05) lighter than TB-in-TB, but heavier than P-in-P foals. TB-in-P foals took longer to first stand and suck and some had fetlock hyperextension and low (<4 g/l) plasma immunoglobulin G concentrations. Other foal groups showed normal behavioural responses. Haematological parameters were normal in all 4 groups of foals. Plasma ACTH levels were high at birth and plasma cortisol concentrations increased after delivery and returned to baseline within 6 h post partum in all but the TB-in-P foals, which had elevated levels until 48 h post partum. Plasma cortisol concentrations increased in all groups following exogenous ACTH administered on Days 1 and 5 postpartum. CONCLUSIONS: The TB-in-P foals showed IUGR and impaired post natal adaptive responses with basal hypercortisolaemia. POTENTIAL RELEVANCE: Foals born following IUGR may require clinical assistance in the early post natal period, but appear mature with respect to adrenocortical function.

Adrenal Cortex↗
PubMed2003

Evolution and microsynteny of the apyrase gene family in three legume genomes.

Apyrases have been suggested to play important roles in plant nutrition, photomorphogenesis, and nodulation. To help trace the evolution of these genes in the legumes--and possibly, the acquisition of new functions for nodulation--apyrase-containing BACs were sequenced from three legume genomes. Genomic sequences from Medicago truncatula, Glycine max and Lotus japonicus were compared to one another and to corresponding regions in Arabidopsis thaliana. A phylogenetic analysis of apyrase homologs from these regions and sequences from other legume species, as well as other plant families, identified a potentially legume-specific clade that contains a well-characterized soybean ( G. soja) apyrase, Gs52, as well as homologs from Dolichos, Lotus, Medicago and Pisum. Sister clades contain homologs from members of Brassicaceae, Solanaceae, Poaceae and Fabaceae. Comparisons of rates of change at synonymous and nonsynonymous sites in the Gs52 and sister clades show rapid evolution in the potentially legume-specific Gs52 clade. The genomic organization of the apyrase-containing BACs shows evidence of gene duplication, genomic rearrangement, and gene conversion among Gs52 homologs. Taken together, these results suggest a scenario of local apyrase gene duplication in an ancestor of the legumes, followed by functional diversification and increased rates of change in the new genes, and further duplications in the Galegae (which include the genera Medicago and Pisum). The study also provides a detailed comparison of genomic regions between two model genomes which are now being sequenced ( M. truncatulaand L. japonicus), and a genome from an economically important legume species ( G. max).

Apyrase↗
PubMed2001

Patient preferences versus physician perceptions of treatment decisions in cancer care.

PURPOSE: To examine patient preferences as well as physician perceptions of these preferences for decision making and communication in palliative care. PATIENTS AND METHODS: Medical decision-making preferences (DMPs) were prospectively studied in 78 assessable cancer patients after initial assessment at a palliative care outpatient clinic. DMPs were assessed with a questionnaire using five possible choices ranging from 1 (patient prefers to make the treatment decision) to 5 (patient prefers the physician to make the decision). In addition, the physician's perception of this preference was assessed. RESULTS: Full concordance between the physician and the patient was seen in 30 (38%) of 78 cases; when the five original categories were recombined to cover active, shared, and passive decision making, there was concordance in 35 (45%) of 78 cases. The kappa coefficient for agreement between physician and patient was poor at 0.14 (95% confidence limit, -0.01 to 0.30) for simple kappa and 0.17 (95% confidence interval [CI], 0.00 to 0.34) for weighted kappa (calculated on the three regrouped categories). Active, shared, and passive DMPs were chosen by 16 (20%) of 78, 49 (63%) of 78, and 13 (17%) of 78 patients, and by 23 (29%) of 78, 30 (39%) of 78, and 25 (32%) of 78 physicians, respectively. The majority of patients (49 [63%] of 78; 95% CI, 0.51 to 0.74) preferred a shared approach with physicians. Physicians predicted that patients preferred a less shared approach than they in fact did. Patient age or sex did not significantly alter DMP. CONCLUSION: An individual approach is needed and each patient should be assessed prospectively for DMP.

Adult↗
PubMed2001

Endothelial dysfunction, nitric oxide and platelet activation in hypertensive and diabetic type II patients.

Alterations in the synthesis or enhanced inactivation of nitric oxide (NO) and an increase in endothelin-1 production lead to an imbalance that can induce arterial hypertension. Type II diabetes is characterized by impaired endothelium-dependent vasodilation and vascular disease. NO is produced through L-arginine pathway by three different isoforms of nitric oxide synthase (NOS), an inducible form that can be activated by cytokines such as tumor necrosis factor alpha (TNFalpha). We evaluated NO plasmatic levels, endothelial damage markers such as von Willebrand factor (vWF), platelet activation, soluble P-selectin (sP-Sel), TNFalpha levels, insulinaemia (I), glycosylated haemoglobin (HbA1c), glycaemia and blood pressure in 32 hypertensive diabetic type II patients (Group A), 37 hypertensive patients (Group B) and 35 healthy subjects (Group C) matched in sex, age, body mass index and dietary habits. The level of I was increased in patients compared to the controls and correlated with their NO levels. vWF plasmatic levels were increased in Group A compared to Groups B and C. We also found significant differences in platelet activation among all the groups. In diabetic patients, increased NO levels correlated with TNFalpha, HbA1c and platelet activation showed greater endothelial damage than in Group B. These parameters described a prothrombotic state associated with an insulin resistance state, an increased vWF release, raised sP-Sel and TNFalpha levels and, maybe, low NO bioavailability, which could lead to a higher risk of development of thrombotic events in hypertensive diabetic patients (Group A) than in the hypertensive patients in Group B.

Aged↗
PubMed2001

Physician sex and other factors associated with type of breast cancer surgery in older women.

HYPOTHESIS: Physician-related factors as well as patient characteristics may explain why women aged 65 years or older with early-stage breast cancer undergo lumpectomy less often than younger women, despite National Institutes of Health recommendations favoring lumpectomy over mastectomy. DESIGN: A descriptive and analytical retrospective computer-assisted telephone survey. SETTING: A population-based random sample of breast cancer survivors in Colorado, identified from the Colorado Central Cancer Registry. PATIENTS: Women aged 65 to 84 years when diagnosed as having stage I or II breast cancer, treated 1 to 6 years previously with mastectomy or lumpectomy, and without recurrence or second primary cancers. Among women contacted, 58% participated. Results of 198 interviews are reported. METHODS: Survey questions included patient decision-making participation and physician recommendations, sources and amount of treatment information provided by physicians, physician characteristics, and patient surgery preferences and demographic characteristics. A multivariate logistic regression model identified factors independently associated with lumpectomy. RESULTS: Lumpectomy was strongly associated with higher patient education, female physician sex, patient age 75 years or older, and amount of physician-provided information. The number of physician-provided information sources was associated with surgery explanations, and female physicians provided more sources of information. A physician decision or recommendation for surgery type was reported by 61% of women, of whom 93% underwent the recommended procedure. A subset of patients (13%) reported deferring the surgery decision to someone else. CONCLUSIONS: These results suggest that better-educated and better-informed older women are more likely to undergo lumpectomy, and that physicians may influence breast cancer patients' decisions about surgery type.

Age Factors↗
PubMed2001

Aerosols and anti-infectious agents.

Anti-infectious agents such as pentamidine, antibiotics (mainly colistine and aminoglycosides), and amphotericin B can be administered by aerosol. Apart from pentamidine and Tobi, this route of administration is not officially approved and it constitutes an empirical approach, which has benefited from recent research summarized hereafter. The most fundamental question is related to the potentially deleterious effects of nebulization processes, especially ultrasound, on the anti-infectious properties of the drugs. Colimycin, which was chosen as a reference because its polypeptide structure makes it unstable a priori, proved to be resistant to high frequency ultrasound, which is encouraging for other molecules such as aminoglycosides or betalactamins. The nebulizer characteristics also have to be taken into account. An aerosol can be produced from an amphotericin B suspension and from colistine using both an ultrasonic nebulizer and a jet nebulizer. Differentiating between good and bad nebulizers is not dependent upon the physical process involved to nebulize the drug, but on the intrinsic characteristics of the device and its performance with a known drug. The inhaled mass of an aerosol in the respirable range must be high and dosimetric nebulizers represent significant progress. Finally, administration of anti-infectious aerosols requires a new pharmacological approach to monitor treatment, and urinary assays are promising for this purpose.

Administration, Inhalation↗
PubMed2001

Cost analysis of telehomecare.

The demand for home health care has skyrocketed in recent years. The aging population and the push for more efficient delivery of hospital services have fueled this growing demand. However, health care financing reforms have constrained the industry's growth. Home health agencies struggle to deliver high-quality services while staying within the financial limitations imposed by reimbursement changes. Telehomecare is one way to provide cost-effective care in the current environment. Personal computers and video equipment can transmit data over ordinary telephone lines and allow home health providers to monitor patients and provide care at a much lower cost than earlier technologies that required wider bandwidth telephone lines and more complex equipment. But can telehomecare yield cost-savings for home health agencies? This article addresses the costs associated with a telehomecare intervention in a large, urban, home health agency. The purpose of the study was two-fold: (1) to test the effects of telehomecare on clinical outcomes, and (2) to estimate the financial costs associated with providing telehomecare services. Our results show that, while telehomecare imposes additional expenses for care delivery, it contributes substantial savings without compromising quality. Additionally, we found that the financial benefit increases exponentially as the duration of the patient care episode increases.

Aged↗
PubMed2001

Measurement of serum amyloid A in the neonatal foal using a latex agglutination immunoturbidimetric assay: determination of the normal range, variation with age and response to disease.

This paper describes the use of a latex agglutination assay to measure serum amyloid A (SAA) in the neonatal foal. The normal range and response to clinical disease was determined. This retrospective study evaluated SAA concentrations over the first 3 days postpartum of 226 Thoroughbred foals judged to be clinically healthy. The normal range for each day was determined; levels were found to be significantly highest on Day 2 (Day 1 vs. Day 2 P<0.0001). The 95th percentile for Days 1-3 was 27.1 mg/l. Clinical records of 133 foals, presented as first or second opinion cases, were evaluated. Foals were divided into 4 groups; septicaemia (S), focal infection (FI), failure of passive transfer (FPT) and noninfectious disease (NI). There was a statistically significant difference (P<0.0001) between SAA concentrations of control foals compared to Groups S and FI. There was no statistically significant difference between controls and Groups FPT and NI. When Group NI was compared to Groups S and FI, there was a statistically significant difference (P<0.0001). The authors suggest that SAA determined by this latex agglutination assay might be a helpful aid in the diagnosis of septicaemia and focal infection in neonatal foals; levels >100 mg/l are highly suggestive of infection in young foals.

Age Factors↗
PubMed2000

Hyperhomocyst(e)inemia induces multiorgan damage.

Hyperhomocyst(e)inemia has been associated with the development of hypertension, stroke, and cardiovascular, cerebral/neuronal, renal, and liver diseases. To test the hypothesis that homocyst(e)ine plays an integrated role in multiorgan injury in hypertension, we employed: (1) spontaneously hypertensive rats (SHR) in which endogenous homocyst(e)ine levels are moderately high (18.1 +/- ().5 microM); (2) control age- and sex-matched Wistar Kyoto (WKY) rats in which homocyst(e)ine levels are normal (3.7 +/- 0.3 microM). To create the pathophysiological condition of hyperhomocyst(e)inemia, 20 mg/day homocyst(e)ine was administered for 12 weeks in (3) SHR (SHR-H) and in (4) WKY (WKY-H) rats. (5) Endogenous homocyst(e)ine levels were reduced slightly but not significantly from 18.1 +/- 0.5 microM to 12.5 +/- 0.7 microM in SHR by folic acid administration (SHR-F). Plasma and tissue levels of homocyst(e)ine were determined by HPLC and spectrophotometric methods. Plasma and sympathetic ganglion (neuronal) matrix metalloproteinase (MMP) activity was measured by zymography. Activity of neuronal MMP was increased in hyperhomocyst(e)inemic rats as compared with controls. Mean arterial pressure (mmHg) was 95 +/- 5, 126 +/- 8,157 +/- 10, 188 +/- 5, and 165 +/- 12 in WKY, WKY-H, SHR, SHR-H, and SHR-F, respectively. Urinary protein (mg/day) was 0.11 +/- 0.03, 0.88 +/- 0.22, 0.47 +/- 0.10, 0.89 +/- 0.21, and 0.81 +/- 0.21 in WKY, WKY-H. SHR, SHR-H, and SHR-F, respectively, as measured by the Bio-Rad dye binding assay. The relationships between increased arterial pressure, plasma homocyst(e)ine, and urinary protein were delineated. Plasma and neuronal creatinine phosphokinase (CK) isoenzymes were measured by agarose gel electrophoresis. All three CK isoenzymes, i.e., MM, MB, and BB, specific for skeletal, cardiac, and nerve tissue, respectively, were induced following 12 weeks' hyperhomocyst(e)inemia, suggesting multiorgan injury by homocyst(e)ine. Homocyst(e)ine induces endocardial endothelial cell (capillary) apoptosis and may reduce capillary cell density. Structural damage to aorta, myocardium, kidney, and renalureter was analyzed by histology. Results suggested an integrated physiological role of homocyst(e)ine in injury to the endothelial/epithelial cell lining in the respective organs.

Animals↗
PubMed2000

Use of archival tissue in epidemiologic studies: collection procedures and assessment of potential sources of bias.

Collection and analyses of archival tumor tissue as a means to increase our understanding of disease pathways is becoming an important avenue of epidemiologic research. In this paper, we present methods of collection and processing of archival tissue and assess the population characteristics of those for whom we were able to and unable to obtain tumor DNA. Cases of colon cancer diagnosed between September, 1991 and October, 1994 living in Utah, Northern California, or the Twin Cities Metropolitan area of Minnesota were targeted for this study. Of the 2477 people for whom we had permission to obtain tumor blocks, we were able to collect blocks and extract DNA for 2117 (85.5%). There were no differences in age, tumor site, or diet and lifestyle characteristics between those with and without DNA extracted. However, we were less likely to be able to extract DNA if the case was diagnosed at a more advanced disease stage or at the earliest disease. Potential bias from exclusion of those with the most advanced disease stage is discussed.

Adult↗
PubMed2000

An investigation of the clinical use of the house-tree-person projective drawings in the psychological evaluation of child sexual abuse.

Identification and evaluation of child sexual abuse is an integral task for clinicians. To aid these processes, it is necessary to have reliable and valid psychological measures. This is an investigation of the clinical validity and use of the House-Tree-Person (HTP) projective drawing, a widely used diagnostic tool, in the assessment of child sexual abuse. HTP drawings were collected archivally from a sample of sexually abused children (n = 47) and a nonabused comparison sample (n = 82). The two samples were grossly matched for gender, ethnicity, age, and socioeconomic status. The protocols were scored using a quantitative scoring system. The data were analyzed using a discriminant function analysis. Group membership could not be predicted based on a total HTP score.

Age Factors↗
PubMed2000

Major histocompatibility class I gene transcription in thyrocytes: a series of interacting regulatory DNA sequence elements mediate thyrotropin/cyclic adenosine 3',5'-monophosphate repression.

In response to TSH, thyroid cells decrease major histocompatibility (MHC) class I expression and transcription, providing an excellent model for studying the dynamic modulation of transcription of MHC class I genes. Here we show that protein kinase A (PKA), a downstream effector of the TSH/cAMP pathway, reproduces the effects of TSH in repressing class I transcription. PKA/cAMP-mediated repression of transcription involves multiple interacting upstream response elements in the class I promoter: an element extending from -127 to -90 bp containing a CRE-like core, and at least two elements within an upstream 30-bp segment (-160 to -130 bp), which overlaps with the interferon regulatory element. ICER (inducible cAMP early response), a transcriptional repressor induced by TSH/cAMP can decrease class I promoter activity when introduced into FRTL-5 thyroid cells in the absence of TSH/cAMP. ICER binds to both the CRE-like element and the upstream 30-bp segment, generating a novel TSH-induced ternary complex. The present studies led to the proposal that TSH-mediated repression of class I transcription is the result of integrating signals from transcription factors through the higher order interactions of multiple regulatory elements.

Animals↗
PubMed2000

Effects of maternally administered depot ACTH(1-24) on fetal maturation and the timing of parturition in the mare.

The aims of this study were to ascertain 1) whether fetal maturation could be induced precociously by maternal administration with adrenocorticotrophic hormone (ACTH) and 2) whether maturation could be achieved without significant risk to mare or fetus. Twenty-two mares received either 1 mg (low dose, LD, n = 6) or 4 or 5 mg (higher dose, HD, n = 16) synthetic Depot ACTH(1-24) at 300, 301 and 302 days gestation. Because, during the course of the study, ACTH appeared to have a greater influence on mares mated during the later part of the breeding season, the HD group were divided retrospectively into those mated before (HDE, n = 6), or after (HDL, n = 10), 1st July. All LD mares were mated before 1st July. Control injections were not performed but gestational data were compared retrospectively with 64 untreated, spontaneously foaling pony mares mated between May and October. Plasma progestagen and cortisol concentrations increased significantly (P<0.05) following ACTH administration in all groups, but progestagens were higher and cortisol elevated for longer in HD mares. ACTH stimulated mammary development and milk electrolyte changes in HD mares. Mean +/- s.e. gestation period (days) was significantly (P<0.01) shorter in HDL mares (318 +/- 1.8) compared with LD (335 +/- 3.7), HDE (340 +/- 4.3) and untreated mares mated after 1st July (327 +/- 1.3). All foals were mature except 2 HDL foals which were stillborn. HDL foals had a higher MCV and lower mean bodyweight, indicating they were delivered before full term. In conclusion, maternal ACTH administration appears to accelerate fetal maturation and delivery in pony mares given high doses and mated late in the breeding season. Further work is required to establish the optimal gestational age and dosage for maternal ACTH administration before clinical recommendations can be given for this therapy.

Animals↗