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Biomedical subjects

L Wood

Publications and source records attributed to L Wood.

At least 73 records · Page 4Linked to original sources
PubMed1998

Results of a phase III, double-blind, placebo-controlled trial of megestrol acetate modulation of P-glycoprotein-mediated drug resistance in the first-line management of small-cell lung carcinoma.

The objective of this study was to determine if the addition of megestrol acetate (MA), a modulator of P-glycoprotein-mediated drug resistance, to first-line cytotoxic therapy in patients with limited and advanced stage small-cell lung cancer (SCLC) would improve median time to disease progression and median overall survival. Secondary outcomes evaluated were response rates and patient symptom profile. Between 1992 and 1995, 130 eligible patients were randomized in a double-blind fashion to receive standard first-line therapy consisting of alternating courses of cyclophosphamide/doxorubicin/vincristine and etoposide/cisplatin (and thoracic radiotherapy for limited stage patients), along with either placebo or MA 160 mg t.i.d. for 8 days commencing 3 days before initiation of each cycle of chemotherapy. Treatment was continued for a maximum of six cycles. A total of 130 eligible patients were randomized, 65 to each arm. Fifty-two per cent of patients had limited disease and 48% had advanced disease. The median time to disease progression in limited stage disease was 46 weeks in the placebo arm and 43 weeks in the MA arm (P = 0.71) and in advanced stage disease was 28 weeks in the placebo arm and 27 weeks in the MA arm (P = 0.92). The median overall survival in limited stage disease was 75 weeks in the placebo arm and 75 weeks in the MA arm (P = 0.56) and in advanced stage disease was 41 weeks in the placebo arm and 39 weeks in the MA arm (P = 0.96). There was no consistent statistical difference in response rates or patient symptom profiles between the two treatment arms. The addition of MA, in the dose and schedule used, to standard first-line cytotoxic therapy in SCLC did not result in a significant improvement in response rates, symptom profile, median time to disease progression or overall survival.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

The effects of skin brushing on H reflex amplitude in normal human subjects.

Experiments were performed on twenty-two neurologically normal subjects in order to investigate the effects of skin brushing on H reflex excitability in triceps surae. H reflex amplitude was observed to decrease during brushing of a 2 cm x 10 cm area of skin overlying triceps surae, returning to control levels when brushing ceased. Alterations in the duration of the brushing period did not affect the magnitude of the H reflex inhibition, although increased frequency of brush strokes per minute slightly increased the amount of inhibition observed. Brushing of smaller skin areas overlying the muscle only sometimes resulted in H reflex inhibition. Brushing over other skin areas of the lower limb produced only slight effects on triceps surae H reflex amplitude. Removal of cutaneous input from the skin overlying triceps surae abolished any effects of brushing in this area on H reflex amplitude. These results demonstrate an inhibitory effect of brushing on H reflex excitability in normal subjects. If such results are confirmed in subjects with neurological deficit, they could have implications for the use of brushing in clinical practice.

Adult↗
PubMed1997

Efficacy and safety of oral immunotherapy with short ragweed extract.

BACKGROUND: Oral immunotherapy, if proven safe and effective, could be an alternative to subcutaneous immunotherapy. OBJECTIVE: This pilot study investigated the clinic and immunologic effects of ragweed immunotherapy using a new microencapsulated, pH-sensitive, oral delivery system. METHODS: A double-blind, placebo-controlled trial was conducted in 23 patients with allergic rhinitis to short ragweed. Following a baseline nasal challenge with ragweed allergen, oral immunotherapy with encapsulated short ragweed extract or placebo was administered once daily, 6 days/week. Dosed began at 3 micrograms Amb a 1 per day and were increased by 3 micrograms every three days as tolerated, to a maximum daily maintenance dose of 24 micrograms. A nasal challenge was repeated 6 weeks, later, followed by the continuation of maintenance therapy through the natural ragweed season. Daily allergy symptoms and relief medication usage was recorded. A final nasal challenge was performed at the end of the natural season. Short ragweed-specific serum IgE, IgG, and IgG4 antibody levels were measured every 2 weeks during the study. RESULTS: Maximum tolerated doses ranged from 6 to 24 micrograms Amb a 1 per day (74% reached 24 micrograms). Adverse events were not serious or different between the active and placebo groups. The active group showed increased in short ragweed-specific serum IgG and IgG4 antibody levels. Symptom scores during the natural season were numerically but not statistically lower in the active treatment group. This group also experienced a greater reduction from baseline in nasal reactivity as assessed by nasal challenge. CONCLUSIONS: These pilot data suggest that the encapsulated, pH-sensitive oral immunotherapy delivery system was safe, induced a brisk serologic response, and attenuated the symptomatic response to both experimental and environmental ragweed exposure.

Administration, Oral↗
PubMed1997

Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers.

In a double-blind and randomized manner, 18 male and female junior competitive swimmers supplemented their diets with 21 g.day-1 of creatine monohydrate (Cr) or a maltodextrin placebo (P) for 9 days during training. Prior to and following supplementation, subjects performed three 100-m freestyle sprint swims (long course) with 60 s rest/recovery between heats. In addition, subjects performed three 20-s arm ergometer maximal-effort sprint tests in the prone position with 60 s rest/recovery between sprint tests. Significant differences were observed among swim times, with Cr subjects swimming significantly faster than P subjects following supplementation in Heat 1 and significantly decreasing swim time in the second 100-m sprint. There was also some evidence that cumulative time to perform the three 100-m swims was decreased in the Cr group. Results indicate that 9 days of Cr supplementation during swim training may provide some ergogenic value to competitive junior swimmers during repetitive sprint performance.

Adolescent↗
PubMed1997

Bone marrow contribution to eosinophilic inflammation.

Allergen-induced bone marrow responses are observable in human allergic asthmatics, involving specific increases in eosinophil-basophil progenitors (Eo/B-CFU), measured either by hemopoietic assays or by flow cytometric analyses of CD34-positive, IL-3R alpha-positive, and/or IL-5-responsive cell populations. The results are consistent with the upregulation of an IL-5-sensitive population of progenitors in allergen-induced late phase asthmatic responses. Studies in vitro on the phenotype of developing eosinophils and basophils suggest that the early acquisition of IL-5R alpha, as well as the capacity to produce cytokines such as GM-CSF and IL-5, are features of the differentiation process. These observations are consistent with findings in animal models, indicating that allergen-induced increases in bone marrow progenitor formation depend on hemopoietic factor(s) released post-allergen. The possibility that there is constitutive marrow upregulation of eosinophilopoiesis in allergic airways disease is also an area for future investigation.

Allergens↗
PubMed1997

Nurses preparing for change: their needs and concerns.

As a result of decreased lengths of stay and cost-containment initiatives, fewer nurses are needed in acute care settings. The trend for community-based health care is broadening employment opportunities for nurses to work in community settings. As nurses are considering options to base their practice in community settings, it is important to understand their concerns about making this transition. The results of a qualitative study conducted to examine the concerns and educational needs of acute care nurses related to working in the community are reported. Clinical, professional, and intrapersonal skills important for a successful transition to community-based practice are identified and discussed.

Acute Disease↗
PubMed1996

The interaction of an epidermal growth factor/transforming growth factor alpha tail chimera with the human epidermal growth factor receptor reveals unexpected complexities.

It has been assumed that substitution of homologous regions of transforming growth factor alpha (TGF-alpha) into epidermal growth factor (EGF) can be used to probe ligand-receptor recognition without detrimental effects on ligand characteristics for the human EGF receptor (EGFR). We show that a chimera of murine (m) EGF in which the carboxyl-terminal tail is substituted for that of TGF-alpha (mEGF/TGF-alpha44-50) results in complex features that belie this initial simplistic assumption. Comparison of EGF and mEGF/TGF-alpha44-50 in equilibrium binding assays showed that although the relative binding affinity of the chimera was reduced 80-200-fold, it was more potent than EGF in mitogenesis assays using NR6/HER cells. This superagonist activity could not be attributed to differences in ligand processing or to binding to other members of the c-erbB family. It appeared to be due, in part, to choice of an EGFR-overexpressing target cell where high receptor number compensated for the low affinity of the ligand; it also appeared to be related to the ability of the chimera to activate the EGFR tyrosine kinase. Thus, when EGFR autophosphorylation was measured, mEGF/TGF-alpha44-50 was more potent than EGF, despite its low affinity. When tested using chicken embryo fibroblasts, substitution of the TGF-alpha carboxyl-terminal tail into mEGF failed to enhance its binding affinity for chicken EGFRs; however, the chimera was intermediate in potency between TGF-alpha and mEGF in mitogenesis assays. Our results suggest a contextual requirement for EGFR recognition which is ligand-specific. Further, the unpredictable responses to chimeric ligands underline the complex nature of the processes of ligand recognition, receptor activation, and the ensuing cellular response.

Animals↗
PubMed1996

The significance of valine 33 as a ligand-specific epitope of transforming growth factor alpha.

Although binding of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) to the EGF receptor (EGFR) is mutually competitive, their binding is not identical, and their biological activities are not always equivalent. To probe for ligand-specific interactions, we have synthesized analogues of TGFalpha with modifications to the residue lying between the fourth and fifth cysteines (the "hinge"). Although this residue lies in a structurally conserved region of the protein, it is not conserved within the EGFR ligand family. Our results show that in TGFalpha there is a preference for a bulky hydrophobic hinge residue; this contrasts with EGF, for which a hydrogen bond donor functionality is preferred. Sequence analysis of the human EGFR ligands revealed that the nature of the hinge residue correlated with the sequence in the B-loop beta-sheet. As this region is an important determinant in recognition of TGFalpha by the chicken EGFR, we assessed the mitogenicity of the TGFalpha hinge mutants, as well as the other EGFR ligands, using chicken embryo fibroblasts. The preference of the chicken EGFR for TGFalpha hinge mutants with hydrophobic side chains paralleled that of the human EGFR. Betacellulin and heparin-binding EGF-like growth factor also possess an hydrophobic hinge; both were at least as potent as TGFalpha for chicken embryo fibroblasts. EGF and amphiregulin, both with hydrogen bond donor functionalities at their hinge, displayed markedly decreased in potency by comparison with TGFalpha. We propose that EGFR ligands can be subclassified into TGFalpha-like and EGF-like and that this is of functional significance, identifying a potential mechanism whereby EGFR can discriminate between its ligands.

Amino Acid Sequence↗
PubMed1996

Frequency and chronological distribution of linear enamel hypoplasia in a North American colonial skeletal sample.

A skeletal sample of 44 individuals born and raised in early 18th century frontier settlements of Northeastern United States is examined for the frequency and chronological distribution of linear enamel hypoplasia (LEH) on the maxillary and mandibular incisors and canines. The prevalence of LEH ranged from 31% on the I2 to 66% on the mandibular C and the mean number of defects ranged from .59 on the I2 to 1.08 on the mandibular C. These frequencies were generally lower than those reported for two later samples; the Monroe County Poorhouse sample and the Hammon-Todd sample. Individuals in these latter two samples were derived from the lowest socioeconomic stratum of their respective populations. Frequency differences are explained within the context of the changing availability of resources that resulted from the rise of industrialization, urbanization, and wage labor which took place during the 18th and 19th centuries. The frequency of LEH was low prior to 1.5 years of age and may result from attrition and/or decreased susceptibility in the relevant area of the crown or from low morbidity or high mortality. Peak frequencies are observed in all age categories ranging from 2.5 to 3.0 years up to 4.0 to 4.5 years and are too late to result from weaning. Instead, they may reflect the susceptibility of nonimmune children to diseases that were common in colonial North America. As the majority of these diseases were not fatal, most victims who survived may have had one or more LEHs as visible proof of their earlier encounter(s).

Age Distribution↗
PubMed1996

A risk-to-benefit analysis for central venous catheters.

Reliable venous access is an important consideration in the management of the cancer patient, where long-term intravenous therapy is needed. A single institution retrospective analysis of 205 catheter placements allowed comparison of different lines and techniques. This experience shows that surgical introduction under general anaesthetic of a double-lumen, 12 gauge, silastic catheter in the superior vena cava, via the internal jugular vein and using a 15 cm anterior chest wall tunnel, resulted in longest survival, fewest infections, and enjoyed a high patient acceptability. A substantial cost-saving, particularly in antibiotic usage, was observed as a result of the improved technique.

Antineoplastic Agents↗
PubMed1996

Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group.

The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens.

Adolescent↗
PubMed1996

Effects of ingesting supplements designed to promote lean tissue accretion on body composition during resistance training.

This study examined the effects of ingesting nutritional supplements designed to promote lean tissue accretion on body composition alterations during resistance training. Twenty-eight resistance-trained males blindly supplemented their diets with maltodextrin (M), Gainers Fuel 1000 (GF), or Phosphagain (P). No significant differences were observed in absolute or relative total body water among groups. Energy intake and body weight significantly increased in all groups combined throughout the study with no group or interaction differences observed. Dual energy x-ray absorptiometry-determined body mass significantly increased in each group throughout the study with significantly greater gains observed in the GF and P groups. Lean tissue mass (excluding bone) gain was significantly greater in the P group, while fat mass and percent body fat were significantly increased in the GF group. Results indicate that total body weight significantly increased in each group and that P supplementation resulted in significantly greater gains in lean tissue mass during resistance training.

Absorptiometry, Photon↗