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Biomedical subjects

D Hill

Publications and source records attributed to D Hill.

At least 73 records · Page 4Linked to original sources

Substance use disorder in hospitalized severely mentally ill psychiatric patients: prevalence, correlates, and subgroups.

The prevalence and demographic and clinical correlates of lifetime substance use disorders were examined in a cohort of 325 recently hospitalized psychiatric patients (53% schizophrenia or schizoaffective disorder). Alcohol use was the most common type of substance use disorder, followed by cannabis and cocaine use. Univariate analyses indicated that gender (male), age (younger), education (less), history of time in jail, conduct disorder symptoms, and antisocial personality disorder symptoms were predictive of substance use disorders. Lifetime cannabis use disorder was uniquely predicted by marital status (never married) and fewer psychiatric hospitalizations during the previous 6 months. Optimal classification tree analysis, an exploratory, nonlinear method of identifying patient subgroups, was successful in predicting 74 percent to 86 percent of the alcohol, cannabis, and cocaine use disorders. The implications of this method for identifying specific patient subgroups and service needs are discussed.

Adult↗

Effects of fosinopril or sustained-release verapamil on blood pressure and serum catecholamine concentrations in elderly hypertensive men.

A randomized, double-blind, placebo-controlled clinical trial showed 14 of 18 (78%) of the elderly hypertensive men in this study had an uncomplicated and beneficial response to either fosinopril or verapamil. There was a well-tolerated reduction in systolic blood pressure (SBP) and diastolic blood pressure (DRP). There were no significant adverse drug events. Only the sitting SBP and the sitting DBP were significantly lowered by fosinopril and verapamil SR. Because reduction in both SBP and DBP in elderly hypertensives has been shown to be beneficial, these findings take on further importance when considering the choice of medication for antihypertensive therapy in the elderly. The increase in norepinephrine in the fosinopril-treated patients may explain why patients treated with long-term angiotensin-converting enzyme inhibitors alone or in combination with diuretics rarely complain of orthostatic symptoms.

Aged↗

Do women have equitable access to quality breast prosthesis services?

Although up to 90% of women who have had a mastectomy use breast prostheses, significant gaps exist around current breast prosthesis services for Australian women. These gaps include the timeliness and quality of information provision, the disparity in financial assistance, and the lack of knowledge regarding the determinants of what constitutes a "quality" breast prosthesis. Revised policy initiatives are central to addressing these gaps to ensure equitable access to quality breast prosthesis services.

Australia↗

Challenges and strategies for initiating a nursing facility practice.

PURPOSE: To provide a summary analysis of five case reports describing the challenges and strategies of nurse practitioners' (NPs') first-year experiences on initiating an effective role in a nursing facility practice. DATA SOURCES: Original qualitative research analyzing written journals of five NPs and written notes from two loosely structured group discussions among project participants. CONCLUSIONS: Two broad themes emerged: Figuring it Out and Responding/Getting a Handle on Things. Common sense and good resources were identified as critical. IMPLICATIONS FOR PRACTICE: Strategies to promote ease of role transition are essential for NPs in the nursing facility. Further, in addition to a focus on care of frail older adults, emphasis on the culture of and strategies for nursing facility visits, ethical issues, and ethical decision making are important components of NP educational programs.

Career Mobility↗

The neurochemical basis for the behavioral effects of triadimefon.

Administration of triadimefon (TDF) [1-(4-chlorophenoxy)-3,3-dimethyl-1-(1-H-1,2,4-triazol-1-yl)-2-butanone] in rodents incites heightened locomotor and stereotypy response, primarily through potentiation of dopaminergic activity. In the present study, 8 male Sprague-Dawley rats received repeated injections, on alternate days (100 mg/kg, 14 days) of TDF or corn oil. Enhanced locomotor and stereotypy behavioral patterns occurred in response to TDF injections, lasting until the 12th day of injection. Tolerance to this effect was evident by a lack of response to TDF injection by the 14th day. Similarly, a withdrawal period and challenge dose of TDF (5 days, 25 mg/kg) was ineffective in espousing locomotor or stereotypy behavioral changes. Cross sensitization to cocaine was also evident, since withdrawal and a challenge dose (8 days, 5 mg/kg) was also ineffective. Adaptative biochemical changes in dopaminergic function were examined after both acute (100 mg/kg) and repeated administration of TDF (100 mg/kg, 14 days) by examining [3H]dopamine (DA) uptake and DA release in both striatal (ST) and nucleus accumbens (NA) tissue. In corroboration with behavioral pattern indicating development of tolerance, there were significant changes in dopaminergic function. Repeated TDF exposure in vivo resulted in significant attenuation of ST and NA DA uptake in response to TDF (10(-4) to 10(-7) M) or cocaine (10(-5) to 10(-8) M) in vitro. Acute exposure to TDF in vivo also attenuated ST DA inhibitory effects of cocaine and TDF. Repetitive administration of TDF in vivo had no effect on in vitro TDF- or amphetamine-stimulated release of ST or NA DA. However, there was a significant reduction in amphetamine-stimulated DA release in animals after acute exposure to TDF in vivo. It was concluded from this study that the effects of chronic TDF exposure may primarily involve effects on DA uptake in the ST and NA.

Amphetamine↗

Developmental instability and working memory ability in children: a magnetic resonance spectroscopy investigation.

This study of children (ages 7 through 12) wishes to determine (a) whether variation in frontal lobe brain chemistry, determined from proton magnetic resonance spectroscopy (1H-MRS), is related to performance on a working memory task in children, and (b) whether developmental instability (DI; the imprecise expression of the genetic plan for development due to several known genetic and environmental effects) underlies phenotypic variation in brain chemistry. 1H-MRS assessed neurometabolites in a right frontal white matter voxel. The Visual Two-Back test assessed working memory. A composite measure of DI was created from measures of minor physical anomalies, fluctuating asymmetry of body characteristics, and fluctuating asymmetry of dermatoglyphic features. Greater DI strongly predicted lower concentrations of creatine-phosphocreatine (Cre) and choline-containing compounds, whereas Cre and N-acetyl-aspartate positively correlated with working memory skills. Working memory skills thus seem related to frontal lobe energy metabolism, which in turn is related to DI.

Aspartic Acid↗

Percutaneous vascular surgery after aortic valvuloplasty: initial clinical experience.

Percutaneous balloon aortic valvuloplasty can be associated with significant vascular morbidity. Often, managing the access site prolongs the length of hospitalization. Three patients were successfully treated with percutaneous femoral arterial vascular surgery immediately after aortic valvuloplasty. These patients did not suffer early or late vascular complications. The access site care was dramatically improved when compared to our usual experience.

Aged↗

Expression and characterization of elastase inhibitors from the ascarid nematodes Anisakis simplex and Ascaris suum.

Two elastase inhibitors, ASPI-1 and ASPI-2, from the parasitic nematode Anisakis simplex, have been isolated and characterized. Because these inhibitors are similar in size (60 amino acids in length) and primary sequence (52 and 47% identical) to the Ascaris suum chymotrypsin/elastase inhibitor-1 (AsC/E-1), we suggest that these Anisakis elastase inhibitors belong to the same unique class of canonical inhibitors formed by the family of Ascaris inhibitors (Huang K, Strynadka NCJ, Bernard VD, Peanasky RJ, James MG. Structure 1994;2:679-689). To compare ASPI-1 with AsC/E-1, we expressed both inhibitors in Pichia pastoris and found that: (1) the association constant of rASPI-1 with porcine pancreatic elastase (PPE) is similar to native inhibitor (Ka = 4.5 x 10(9) and 6.4 x 10(9) M(-1), respectively); (2) rASPI-1 is a potent inhibitor of PPE and human leukocyte elastase (Ka = 1.6 x 10(9) M(-1)); and (3) it is only a very weak inhibitor of chymotrypsin (CHYM) (Ka = 1.2 x 10(6) M(-1)). In contrast to the Anisakis inhibitor, however, rAsC/E inhibitor-1 is a very strong inhibitor of both PPE (Ka = 3.5 x 10(10) M(-1)) and CHYM (Ka = 3.6 x 10(12) M(-1)). We also found that the determined reactive sites (P1-P'1) of rASPI-1 and rAsC/E-1, as recognized by PPE, are Ala 28-Met 29 and Leu 31-Met 32, respectively. These P1-P'1 residues of AsC/E-1 constitute the same reactive site as that also recognized by CHYM (Peanasky RJ, Bentz Y, Homandberg GA, Minor ST, Babin DR. Arch Biochem Biophys 1994;232:135-142). The difference in specificities of ASPI-1 and AsC/E-1 toward their cognate serine proteases may be attributed to the P1 and P'3 residues in the inhibitors. Elastase, which recognizes both alanine and leucine, canaccommodate both ascarid inhibitors, whereas chymotrypsin, which prefers bulky, hydrophobic residues, only recognizes the Ascaris C/E inhibitor-1.

Amino Acid Sequence↗

Recombinant rat fibroblast growth factor-16: structure and biological activity.

Fibroblast growth factor-16 (FGF-16) is the most recent member of the FGF family to be cloned. Since the biologic activity of rat FGF-16 (rFGF-16) was unknown, and this protein has no apparent signal sequence, we transformed its entire cDNA into Escherichia coli for high-level expression and further characterization of this novel protein. An attempt was made to purify the expressed protein from the supernatant of mechanically lysed cells using sequential cation-exchange chromatography. This resulted in a gradual loss of the protein as precipitate throughout the purification process. In addition to precipitation during purification, sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that the partially purified materials showed a cluster of protein bands around 20k to 29k. Sequence analysis of the major bands indicated that two N-terminal truncations had occurred, during E. coli fermentation, purification, or both. The largest truncation resulted in the removal of the 34 N-terminal amino acids, including the initiation codon methionine. We cloned d34 rFGF-16, expressed the gene in E. coli, and developed a purification process for this form. Even with this truncated form, precipitation was a problem. We were largely able to overcome this problem, however, by including EDTA throughout the purification process. We have characterized the structure of purified d34 rFGF-16 extensively using circular dichroism, Fourier transform infrared spectroscopy, and sedimentation velocity analysis. These studies revealed that the protein has a distinct tertiary structure, consists primarily of beta-strands, has a weak tendency to self-associate, and is fairly extended. We then performed biologic assays which showed that d34 rFGF-16 induces oligodendrocyte proliferation in vitro, and induces hepatocellular proliferation and increased liver weight in vivo. In summary, FGF-16, a novel FGF family member, has both unique structural and biological properties.

3T3 Cells↗

Sun protection and sunburn in primary school children: the influence of age, gender, and coloring.

BACKGROUND: Childhood is a high-risk period for skin damage due to excessive sun exposure. This damage may lead to skin cancer later in life. METHODS: The present study measured children's knowledge and attitudes, and reported usual behavior relevant to sun protection and parents' encouragement of their children's sun protection among a sample of 735 primary school students and their parents, in Victoria, Australia. The incidence of sunburn among the children over late spring and early summer was monitored weekly for 8 weeks. RESULTS: The results indicate that children's knowledge of sun protection is moderately high and that positive sun protection attitudes, reported frequency of parents encouraging protection, and children carrying out sun protection are generally high. Trends for age indicate that while knowledge of sun protection increases with age, attitudes and behaviors supportive of sun protection decline. Sunburn rates increase with age. There was some evidence to suggest that children with fairer coloring receive greater encouragement from parents to protect themselves and are marginally better protected than children with darker coloring. However, this highly susceptible group still suffers more burns. There was little variation based on children's gender. CONCLUSIONS: The mid-primary school years may be a critical time for interventions promoting sun protection.

Adolescent↗

Identifying genes predisposing to atopic eczema.

BACKGROUND: Genetic and environmental factors are known to play a role in the development of atopic diseases, such as asthma, eczema, and rhinitis. However, the atopy gene (or genes) has yet to be defined. Studies of familial asthma have identified several regions that may contain genes predisposing to atopy, but the data for candidate regions do not show agreement, which may be due to heterogeneity, ascertainment bias, or stochastic factors. Factors such as an early age of onset, a positive family history, and a clearly defined phenotype favor a genetic origin and improve the chance of identifying genes that predispose to atopy. OBJECTIVE: We sought to define genes that predispose to the development of atopic eczema. METHODS: We have studied nuclear families with multiple cases of early-onset atopic eczema for involvement of the candidate regions on chromosomes 5q31 (IL gene cluster), 11q13 (high-affinity FCepsilon receptor), 14q11.2 (mast cell chymase), and 16p12 (IL-4 receptor alpha-chain, IL4RA gene). RESULTS: Using a recessive model, we find a maximum parametric log of the odds of linkage score of 2. 25 and nonparametric score of 2.54 (P =.006) for a region on chromosome 5q31, which we postulate contains a gene predisposing to atopic eczema, but lack of support for linkage to 11q13. Transmission disequilibrium tests do not support an association with candidate polymorphisms in the mast cell chymase and IL4RA genes. CONCLUSION: We have identified a clinically homogeneous cohort of patients with atopic eczema to identify genetic factors predisposing to the development of atopy. We postulate that there are certain loci that predispose to atopy in general and other loci that determine which of the atopic phenotypes is expressed.

Adolescent↗

Ectopic overexpression of c-mpl by retroviral-mediated gene transfer suppressed megakaryopoiesis but enhanced erythropoiesis in mice.

In this report, we tested whether ectopic overexpression of a cell surface receptor cDNA could be used to explore the physiological roles of that receptor. We generated c-mpl overexpressing animals by reconstituting mice with retroviral vector-transduced bone marrow (BM) cells. We observed that platelet counts in the c-mpl overexpressing mice failed to recover to normal levels and remained at <200 x 10(6)/mL post-transplantation, while platelet numbers in the control mice returned to > 800 x 10(6)/mL by 4 weeks post-transplantation. However, platelet counts in the c-mpl overexpressing mice could be stimulated to normal levels after administration of rhMGDF. No significant changes in peripheral leukocyte counts were observed, although the number of CFU-E, GM-CFC, and CFC-multi were reduced two- to threefold in the BM of the c-mpl overexpressing mice. In addition, enhanced erythropoiesis was observed in the c-mpl overexpressing mice. The mpl receptors on erythroid cells were functional as demonstrated by tyrosine-phosphorylation of mpl receptor on RBC and by in vitro erythroid colony-formation in response to MGDF stimulation, respectively. These results suggested that ectopically expressed mpl receptors competed for ligand in vivo leading to an insufficient amount of circulating thrombopoietin (Tpo) for the development of megakaryocytic lineage. These results further suggest that, in addition to sequestering circulating Tpo, overexpression of the mpl receptor on erythroid progenitors may directly contribute to enhanced erythropoiesis in vivo. Our studies demonstrate that ectopic overexpression of a receptor by retroviral-mediated gene transfer provides an approach to explore the biological roles of novel receptors.

Animals↗

ED echocardiography for peripartum cardiomyopathy.

Although peripartum cardiomyopathy is uncommon, emergency physicians should be knowledgeable of it because of its high morbidity and mortality. Emergency physicians should be alert to the fact that the clinical presentation of peripartum cardiomyopathy is nonspecific. Its clinical manifestations are found in other medical conditions that can present in the late prepartum or postpartum patient. We present a case of peripartum cardiomyopathy that illustrates how its nonspecific respiratory signs and symptoms led to an initial diagnosis of pulmonary embolism. The case also highlights the need for echocardiography in the evaluation of peripartum cardiomyopathy. We discuss the clinical presentation, diagnosis, and treatment of peripartum cardiomyopathy.

Adult↗

Is intracytoplasmic sperm injection necessary for couples undergoing in vitro fertilization-embryo transfer with normal semen analyses but failing hamster egg penetration assays?

PURPOSE: Our purpose was to assess whether in vitro fertilization (IVF)-embryo transfer (ET) candidate couples with basically normal semen analyses but failing zona-free hamster egg penetration assay (HEPA) scores benefit from intracytoplasmic sperm injection (ICSI). METHODS: Twenty consecutive IVF candidate couples with normal-borderline semen analyses and failing HEPA scores were recruited. Mature oocytes obtained from each woman were randomly divided between ICSI (group I; n = 126 oocytes) and standard insemination techniques (group II; 138 oocytes). Fertilization (two pronuclei) and cleavage (2-4 cells) rates were assessed for both groups. RESULTS: There were no statistically significant differences between the two groups with respect to (mean +/- standard error of the mean) fertilization (group I, 63.1 +/- 7.75; group II, 77.8 +/- 4.7%) or cleavage (group I, 87.3 +/- 2.4%; group II, 91.2 +/- 3.5%) rates. CONCLUSIONS: ICSI is not beneficial for IVF-ET when sperm samples demonstrate a failing HEPA score but have normal or minimally compromised semen analysis parameters.

Adult↗

Cytokines in alcoholic liver disease.

Cytokines are low-molecular-weight mediators of cellular communication produced by multiple cell types in the liver, with the Kupffer cell critically important. Inflammatory cytokines such as tumor necrosis factor, interleukin-1, and interleukin-8, and hepatic acute-phase cytokines such as interleukin-6 play a role in modulating certain metabolic complications in alcoholic liver disease and probably play a role in the liver injury of alcoholic liver disease. Two potential inducers of cytokine production in alcoholic liver disease are endotoxin and reactive oxygen species generated after ethanol metabolism. Cytotoxic cytokines likely induce liver cell death by both necrosis and apoptosis in alcoholic liver disease. Anticytokine therapy has been highly successful in attenuating cell injury/death in a variety of toxin-induced models of liver injury, including alcohol-related liver injury. Anticytokine therapy has been used successfully in humans in disease processes such as Crohn's disease and rheumatoid arthritis. There is an emerging rationale for use of anticytokine therapy in alcoholic liver disease, with the goal of maintaining beneficial effects of cytokines and inhibition of the deleterious effects of these potentially toxic agents.

Animals↗

Serum level of maternal human immunodeficiency virus (HIV) RNA, infant mortality, and vertical transmission of HIV in Zimbabwe.

Maternal human immunodeficiency virus (HIV) RNA load, vertical transmission of subtype C HIV, and infant mortality were examined in 251 HIV-seropositive women and their infants in Zimbabwe. Demographic characteristics, health and medical histories, serum HIV RNA loads, and CD4+ lymphocyte counts for mothers were examined by logistic regression analysis to determine significant risk factors and their odds ratios for transmission and infant mortality. Tenfold (1 log10) incremental increases in maternal HIV RNA were associated with a 1.9-fold increase (95% confidence interval [CI], 1.2-2.9) in transmission and a 2.1-fold increase (95% CI, 1.3-3.5) in infant mortality (P<.01). Maternal CD4 cell counts and demographic and medical characteristics were not significant predictors of transmission. However, maternal CD4 cell counts below the median (400/mm3) were significantly associated with infant mortality (P=. 035, Fisher's exact test). The maternal level of serum HIV is an important determinant of vertical transmission and infant mortality in subtype C infection in Zimbabwe.

CD4 Lymphocyte Count↗