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Biomedical subjects

L Smith

Publications and source records attributed to L Smith.

At least 217 records · Page 12Linked to original sources
PubMed1997

Tumour necrosis factor-alpha expression and cell recruitment in Sephadex particle-induced lung inflammation: effects of dexamethasone and cyclosporin A.

1. Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with diverse properties consistent with a possible role in inflammatory disease. We investigated whether TNF-alpha is induced during the progression of lung inflammation elicited by a particulate non-antigenic stimulus, and whether pharmacological control of TNF-alpha expression influences recruitment of specific inflammatory cell types. 2. A single intravenous injection of Sephadex particles into rats led to extensive granulomatous inflammation in lung alveolar and bronchial tissue that peaked in intensity after 24-72 h. Mononuclear cells were the principal component of granulomas, but neutrophils and eosinophils were also abundant. Numbers of mononuclear cells, neutrophils and eosinophils recovered by bronchoalveolar lavage (BAL) peaked at 72 h, 48 h and 72 h, respectively. 3. Messenger RNA encoding TNF-alpha was induced in lung epithelial cells, lung granulomas and BAL cells 6 h after Sephadex administration and remained elevated for 72 h before declining to baseline by 7 days. In BAL cell populations TNF-alpha protein was localized to mononuclear cells at all times points pre- and post-Sephadex administration. 4. Treatment of rats with dexamethasone significantly reduced the Sephadex-induced recruitment of mononuclear cells, neutrophils and eosinophils into the bronchoalveolar cavity, and significantly reduced TNF-alpha mRNA expression by BAL cells. 5. Treatment of rats with cyclosporin A was without effect on Sephadex-induced elevations of mononuclear cell numbers and expression of TNF-alpha, but did reduce significantly recruitment of neutrophils and eosinophils to BAL cell populations. 6. These results show that a sequential asthma-like recruitment of neutrophils, eosinophils and mononuclear cells into lung tissue can be induced by single exposure to a non-antigenic stimulus. Pharmacological and histological studies reveal that mononuclear cell mobilization relates closely to induced TNF-alpha expression, whereas mobilization of neutrophils and eosinophils appears secondary to expression of the cytokine.

Animals↗
PubMed1997

An investigation of hospital generated pharmaceutical care when patients are discharged home from hospital.

AIMS: To investigate how seamless pharmaceutical care could be delivered. METHODS: Elderly patients discharged from hospital, to their own home, were randomized into control and study groups. Control and study group patients received the normal discharge information. The study group were also counselled about their medicines and informed about their pharmaceutical care plan. Copies of the plan were given to the study patients. All patients received a domiciliary visit between 7 and 10 days after discharge. Their current medication was compared with that on discharge and contact was made with the General Practitioner as appropriate. RESULTS: Twenty-eight study and 25 control patients with a mean (s.d.) age of 77.5 (7.3) and 77.6 (6.1) years completed the study. A pharmaceutical domiciliary visit was necessary for 21 (75%) and 24 (96%) of the study and control patients respectively. Compliance was better (P < 0.01) in the study group. Unintentional changes to the medication of 31 (14 study and 17 control) patients were found during the visit and after contact with the prescriber all but one prescription was restored to that on discharge. CONCLUSIONS: At present it is difficult to ensure seamless pharmaceutical care. A pharmaceutical domiciliary visit may be useful to ensure seamless therapeutic care and thus avoid unnecessary healthcare events and costs after a patient is discharged home.

Aged↗
PubMed1997

A literature review of adolescence and cancer.

Cancer is a relatively rare phenomenon in adolescents and a traumatic experience which arouses feelings of anger, anxiety, fear and sadness. For the adolescent with cancer, there are missed opportunities, not only in daily life but also through lost social events such as dances or football games with friends. Adolescent cancer patients may understand the implications of the diagnosis of cancer but lack the personal resources or life event experience which could equip them to cope and make sense of the many potential problems which may accompany cancer. This paper reviews and explores the literature associated with the adolescent with cancer.

Activities of Daily Living↗
PubMed1997

Construction and characterization of retroviral vectors for interleukin-2 gene therapy.

Several investigators have employed interleukin-2 (IL-2) gene transfer to enhance the immunogenicity of tumor cell vaccines. We describe in this report the construction and characterization of retroviral vectors for IL-2 gene therapy. Human IL-2 cDNA with a chimeric rat preproinsulin/IL-2 DNA leader sequence was subcloned into the pLXSN (long terminal repeat promoter) and pLNCX (cytomegalovirus [CMV] promoter) vectors to generate the plasmids pLXSN-iIL2 and pLNCX-iIL2, respectively. Human IL-2 cDNA with a chimeric human tissue factor/IL-2 DNA leader sequence was utilized to construct the vector pLXSN-tIL2. The levels of IL-2 secreted by transduced tumor cells and fibroblasts were evaluated by enzyme-linked immunosorbent assay (ELISA) of culture supernatants and compared with those of normal peripheral blood mononuclear cells (PBMC) activated in vitro with calcium ionophore and phorbol 12-myristate 13-acetate. The highest levels of IL-2 secreted by transduced tumor cells (760 units/10(6) cells/24 h), adult fibroblasts (625 units/10(6) cells/24 h), and embryonic fibroblasts (3,975 units/10(6) cells/24 h) were 150- to 1,000-fold higher than than secreted by the activated PBMC (4 units/10(6) cells/24 h). Similar levels of IL-2 were expressed by human fibroblasts transduced with pLXSN vectors employing the preproinsulin (pLXSN-iIL2) or tissue factor (pLXSN-tIL2) leader sequences (range in IL-2 units/10(6) cells/24 h pLXSN-iIL2 = 375-625 vs. pLXSN-tIL2 = 90-440). Because IL-2-transduced cells for clinical applications are generally irradiated to prevent cellular proliferation, we evaluated the effects of radiation on IL-2 production. Radiation doses between 1,500 and 10,000 cGy resulted in gradual decreases in IL-2 secretion by transduced cells. The range of the decrease in IL-2 secretion was 7-11% by day 7, 0-29% by day 14, and 25-50% by day 35. For clinical applications, stable production of the vector in high concentrations is an important consideration. The retroviral vector pLXSN-tIL2 produced the highest viral titer and was chosen for further characterization. Southern blot analysis of SacI-digested genomic DNA from the LXSN-tIL2 producer cell line and SacI-digested pLXSN-tIL2 plasmid DNA revealed the expected 3.2-kbp fragment, suggesting the absence of transgene rearrangement and the suitability of this vector as a candidate for clinical applications.

3T3 Cells↗
PubMed1997

Cisapride in pediatric gastroesophageal reflux.

BACKGROUND: Gastroesophageal reflux is a common condition that in infants may lead to serious complication. This study assessed the efficacy and safety of oral cisapride suspension in the treatment of children 6 weeks to 2 years old with daily regurgitant reflux. METHODS: A randomized, prospective, double-blind, placebo-controlled clinical trial was conducted at three study sites. After a 1 week baseline assessment, 45 infants 6 weeks to 2 years old were randomized to a double-blind trial in which they received a 6 week course of cisapride (0.2 mg/kg q6h) or a placebo suspension. Efficacy was assessed with 24 hour esophageal pH monitoring, esophageal manometry, and esophageal biopsy before and after the treatment period. A diary of regurgitation frequency and severity was kept by the parents. Safety was assessed by adverse event monitoring and standard laboratory measurements. RESULTS: Compared with placebo, cisapride significantly (p < 0.05) reduced the mean duration of upright and supine reflux episodes. Compared to baseline, cisapride significantly reduced the mean duration of the longest reflux episode, and placebo increased the mean number of reflux episodes longer than 5 minutes. Cisapride was not significantly different from placebo for the following mean measurements: percent of total time pH < 4, number of reflux episodes, lower esophageal sphincter pressure, swallow pressure, regurgitation frequency or global evaluation scores. CONCLUSIONS: Cisapride is a safe, well tolerated prokinetic agent that improves the esophageal clearance of refluxed gastric acid in children under the age of 2 years.

Biopsy↗
PubMed1997

Partial dominance of a keratin 14 mutation in epidermolysis bullosa simplex--increased severity of disease in a homozygote.

Epidermolysis bullosa simplex is a disease in which keratin gene mutations cause the production of defective intermediate filaments, which leads in turn to epidermal basal cell fragility and blistering. The inheritance in nearly all kindreds is autosomal dominant, most kindreds have missense mutations, and the encoded proteins appear to exert a dominant negative function. One previously reported patient with generalized blistering had a fully dominant mutation of keratin 5; in that kindred a homozygote was affected no more severely than the heterozygotes. By contrast we report here a keratin 14 mutation that causes blistering limited to the hands and feet in heterozygotes, but homozygotes have more severe, widespread blistering of the skin and mucous membranes. Thus keratin gene mutations may be not only fully recessive or fully dominant but also partially dominant as well.

Adolescent↗
PubMed1997

Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes.

Erythrokeratodermias are a clinically heterogeneous group of rare autosomal dominant disorders of cornification with overlapping features including hyperkeratosis and erythema. We ascertained five extended pedigrees with different phenotypes for a linkage study. Three families presented with localized erythrokeratodermia variabilis, and one with erythrokeratodermia and ataxia. Another family had Greither disease associated with variable hyperkeratotic plaques. Despite their phenotypic differences, both erythrokeratodermia variabilis and erythrokeratodermia with ataxia map to a common region in 1p34-p35. Multipoint linkage and haplotype analyses place erythrokeratodermia variabilis between the marker D1S496 and D1S186 with a maximum LOD score of 12.88. Our linkage results provide compelling evidence for genetic homogeneity among families of mixed European and French-Canadian origin. In contrast, results excluded Greither's disease from the established erythrokeratodermia variabilis gene region indicating genetic heterogeneity of erythrokeratodermias. Based on recombinations, two genes assigned to 1p34-p35 were excluded: cartilage matrix protein and avian myelocytosis viral oncogene. Connexin-37 (GJA4), a member of the connexin gene family, maps within the erythrokeratodermia variabilis region and is an attractive candidate gene. Direct sequencing of the coding region of GJA4 in four patients revealed several variations, including a novel polymorphism within the 5' cytoplasmic domain, but no pathogenic mutations were found, thus excluding Connexin-37 as a candidate. There is evidence, however, that other epidermally expressed connexins cluster in this region, and one may yet be determined to play a role in the pathogenesis of erythrokeratodermia variabilis.

Chromosome Mapping↗
PubMed1997

Aberrant semantic activation in schizophrenia: a neurophysiological study.

OBJECTIVE: Schizophrenia has long been thought to be characterized by a fundamental disturbance in semantic associations, which has often been presumed to be of neurobiological origin. The authors examined the neurophysiological characteristics of semantic processing in schizophrenic patients. METHOD: During EEG recording, 15 schizophrenic patients and 15 age-matched comparison subjects read sentences that had either sensible or nonsensical endings. The authors recorded the N400 component, a specific negative event-related brain potential occurring approximately 400 msec after the final word in the sentence. N400 is highly, if not uniquely, sensitive to semantic expectancy and context, and larger, more negative N400 amplitude is associated with increased semantic unexpectancy. RESULTS: In relation to the normal comparison subjects, the schizophrenic patients demonstrated prolonged N400 latency after nonsensical sentence endings and also showed enhanced N400 negativity, regardless of the sense of the sentence ending. CONCLUSIONS: These findings suggest slower and more diffuse semantic activation in patients with schizophrenia, perhaps reflective of a disease-related failure to maintain and to use semantic context.

Adult↗
PubMed1997

Comparing costs of monitoring glaucoma patients: hospital ophthalmologists versus community optometrists.

OBJECTIVES: To compare the costs of monitoring stable glaucoma patients by community optometrists and hospital ophthalmologists. METHODS: A cost analysis was conducted alongside a randomised controlled trial which compared the accuracy and acceptability of measurement in each form of care. The viewpoints of the health service and of patients were considered. Costs were assessed using a number of different methods. Sensitivity analysis was conducted for key variables. RESULTS: The baseline analysis reflected heavily the different length of time between follow-up in the two arms of the trial (10 months (average) for hospital, 6 months for optometrists). It showed annual cost per patient for hospital ophthalmologists varied from 14.50 pounds to 59.95 pounds, and community optometrist costs varied from 68.98 pounds to 108.98 pounds. Assuming a 6-month follow-up interval for the hospital ophthalmologists, costs varied from 24.16 pounds to 99.92 pounds. CONCLUSIONS: Recommendations about the least costly form of follow-up must depend on the context in which the decision is being taken and the scale of change envisaged. If the aim is to recoup resources from hospitals in order to pay for monitoring in the community, community monitoring is unlikely to be the least costly option.

Community Health Services↗
PubMed1997

Evaluating critical thinking skills of baccalaureate nursing students.

This study evaluates the critical thinking skills of students enrolled in a baccalaureate nursing program, using the WGCTA, for the classes of 1993 through 1996. Scores were obtained at entry and at end of junior and senior years. The mean entry WGCTA score was 56 for all four classes; however, the 1995 and 1996 classes had significantly higher scores than the class of 1994. Critical thinking scores were higher at entry for older students and students who had completed another education degree; however, critical thinking scores were lower for students who had previous nursing experience. After adapting for age, previous degree, and nursing experience, no significant differences in the WGCTA scores from entry to end of junior and senior years emerged for the classes of 1993, 1994, 1995. Critical thinking skills have become the hallmark of education. The National Education Goal Panel has advocated for an increase in the ability to think critically, communicate effectively and solve problems (Banta, 1993). In turn, the nursing profession has incorporated these goals of higher education into its educational programs. The National League for Nursing (NLN) includes the measurement of critical thinking as a required outcome in the evaluation and accreditation of baccalaureate and higher degree programs in nursing. This critical thinking outcome must reflect the student's skill in analysis, reasoning, research, or decision making as these skills relate to the nursing discipline (National League for Nursing, 1992). To meet the NLN's critical thinking outcome criterion, nursing programs must have a method of evaluating this skill. Many programs use the Watson-Glaser Critical Thinking Appraisal (WGCTA), which is a standardized instrument. The College of Nursing at the University of Arkansas for Medical Sciences (UAMS) adopted this instrument to evaluate the critical thinking skills of students in the baccalaureate nursing program.

Adult↗
PubMed1997

Bryostatin 1 and phorbol ester down-modulate protein kinase C-alpha and -epsilon via the ubiquitin/proteasome pathway in human fibroblasts.

We evaluated the possibility that distinct proteolytic pathways contribute to the down-regulation of a novel (epsilon) or conventional (alpha) isoform of protein kinase C (PKC) in nonimmortalized human fibroblasts. Inhibitors of calpains and other cysteine proteinases, vesicle trafficking, or lysosomal proteolysis did not affect the down-regulation of PKC-alpha or -epsilon produced by bryostatin 1 (Bryo). Lactacystin (Lacta) and certain terminal aldehyde tripeptides or tetrapeptides, which selectively inhibit the proteasome, preserved substantial PKC-alpha and -epsilon protein from down-regulation by Bryo or phorbol-12-myristate-13-acetate. Lacta preserved active kinase in vivo, as shown by the retention of Bryo-induced autophosphorylated PKC-alpha. Concomitant with down-regulation, Bryo produced PKC-alpha and -epsilon species that were larger than the native proteins (80 and 90 kDa, respectively). Western blot analysis showed that the larger PKC-alpha species were ubiquitinylated. Treatment with Bryo plus Lacta synergistically increased multiubiquitinylated PKC-alpha, as expected if Bryo induces ubiquitinylation of PKC-alpha and Lacta blocks its degradation. Bryo also produced a 76-kDa, nonphosphorylated form of PKC-alpha and an 86-kDa form of PKC-epsilon. Phosphatase inhibitors decreased production of 76- and 86-kDa PKC-alpha and -epsilon by Bryo and preserved 80- and 90-kDa PKC-alpha and -epsilon, respectively. Our results suggest that the down-modulation of PKC-alpha and -epsilon occurs principally via the ubiquitin/ proteasome pathway. Dephosphorylation seems to predispose PKC to ubiquitinylation.

Acetylcysteine↗
PubMed1997

Factors associated with elective Norplant removal in black and white women.

Premature removal of contraceptive implants (Norplant [levonorgestrel implants], Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) is a cause of a sizable national medical expenditure in the United States. Understanding the factors that influence the decision to remove the implants and being able to predict which users are likely to elect discontinuation prematurely could provide useful information for counseling patients as they are considering contraceptive implants so that potentially enormous long-term savings could be achieved. This study surveyed 98 women who had Norplant inserted and removed between January 1991 and December 1994. Data were collected from chart review, and when necessary, a questionnaire was used to extract information not found in the chart. The chi-squared statistic and t-test were used to compare demographic variables. All but one subject received comprehensive pre-implant counseling. The main reason given for electively removing the Norplant prematurely was irregular menstrual bleeding (60%). Pre-implant counseling did not influence the decision for removal. These results indicate the importance of clarifying patients' doubts regarding menstrual bleeding irregularities during follow-up visits rather than relying on the information patients received during preimplant counseling.

Adult↗
PubMed1997

Docetaxel in combination with fluorouracil: study design and preliminary results.

The relatively recent introduction of a new class of chemotherapeutic agents--the taxoids--has raised hope of improved survival for patients with advanced or metastatic cancer. Following encouraging preclinical results of taxoid combinations, this phase I, nonrandomized trial was designed to evaluate a 1-hour intravenous infusion of docetaxel (Taxotere) on day 1 combined with fluorouracil (5-FU) as a daily intravenous bolus for 5 consecutive days. To date, 27 patients with advanced solid neoplasms have received 86 courses of docetaxel/5-FU at the following dose levels: 25/100, 35/150, 50/200, 60/200, and 60/300 mg/m2. Preliminary results showed no unexpected toxicities, and the principal toxicity was neutropenia of short duration. A treatment regimen of 60 mg/m2 docetaxel on day 1 and 300 mg/m2 of 5-FU given for 5 days, with a single course length of 28 days, is projected as the maximum tolerated dose.

Adult↗
PubMed1997

Critical thinking, health policy, and the Hmong culture group, Part I.

The author discusses the historical connection between the Hmong and the U.S. military operations in South Eastern Asia; gives an overview of Hmong culture health traditions, such as efficacious, neutral and harmful; socioeconomic data; immigration and the local community; and health problems specific to the Hmong.

Death, Sudden↗