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Biomedical subjects

L J Smith

Publications and source records attributed to L J Smith.

At least 109 records · Page 6Linked to original sources
PubMed1994

A behavioural approach to retraining bowel function after long-standing constipation and faecal impaction in people with learning disabilities.

The authors describe a behavioural programme--involving prompted toilet-sitting after meals, rewards for appropriate evacuation and increased fibre--for four people with severe learning disabilities. Although treatment times were long, such training resulted in near-normal bowel function. While this behavioural approach does not ignore the biological aspects of the problem, soiling in intellectually disabled people should not be attributed to the handicapping condition alone. Training at an earlier age should be considered.

Adolescent↗
PubMed1994

Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. ACCOLATE Asthma Trialists Group.

The efficacy of 6 wk of therapy with oral ICI 204,219, a selective leukotriene D4 (LTD4) receptor antagonist, was evaluated in subjects with moderate asthma during a multicenter, double-blind, randomized, placebo-controlled, dose-ranging study. Subjects who entered the trial had been chronically treated for asthma with beta agonist alone or in combination with theophylline. Subjects were randomized to treatment with twice daily doses of ICI 204,219 (5, 10, or 20 mg) or placebo if they had an FEV1 between 40 and 75% of predicted values without bronchodilator therapy and a daytime asthma score > 10 (range 0 to 21 per wk) for 7 consecutive d. Efficacy was evaluated from the results of symptom assessments, pulmonary function tests, and rescue medication use. Of 276 subjects randomized to treatment, 266 (10 mg, n = 66; 20 mg, n = 67; 40 mg, n = 67; placebo, n = 66) were analyzed for efficacy. Diary card assessments showed that treatment with increasing doses of ICI 204,219 linearly improved five efficacy criteria without increasing the number or severity of adverse events. The 40 mg dose was more effective than placebo (p < 0.05) in reducing nighttime awakenings, first morning asthma symptoms, the daytime asthma score, and albuterol use and in increasing evening peak expiratory flow (PEF) rates as well as FEV1. Compared with baseline measurements, the 40 mg dose decreased awakenings by 46%, albuterol use by 30%, and daytime symptoms by 26% and increased FEV1 by 11%. ICI 204,219 improves objective and subjective measures of asthma severity in moderately ill asthmatic subjects and may provide a new treatment option for the disease.

Administration, Oral↗
PubMed1994

Selective cytotoxicity to human leukemic myeloblasts produced by oligodeoxyribonucleotide phosphorothioates complementary to p53 nucleotide sequences.

Cells were treated in vitro with oligodeoxyribonucleotide phosphorothioates (ODNs) complementary to sites common to both wild-type and mutant p53 nucleotide sequences. Acute myelogenous leukemia (AML) blasts from peripheral blood were exposed to four different p53 ODNs and showed anti-leukemic effects in suspension culture. This effect continued after removal of the ODN from the medium. Blocking of self-renewal of the leukemic blast stem cells in secondary plating of cells from cloning assays by two of the p53 ODNs was also observed. Control ODNs had no effect on leukemic blasts. Treatment of normal bone marrow cells with the four p53 ODNs did not influence their growth, nor was there any effect by the p53 ODNs on the leukemic cell-line, HL60, that does not express p53. These data suggest that p53 ODNs are selectively toxic to primary myelogenous blasts and may be therapeutically useful in AML.

Blast Crisis↗
PubMed1994

Strategic considerations for capital formation and development.

It is the role of healthcare financial managers to maximize their organizations' return on equity, not only for the short term, but also with an eye to the future. This article explores the financial and managerial factors financial managers should consider when planning the strategic sources of capital funds and asset acquisitions for an organization, then examines the factors comprising return on equity-margin, leverage, and turnover-in light of current and projected industry trends.

Capital Financing↗
PubMed1994

Intraoperative vecuronium anaphylaxis compounded by latex hypersensitivity.

BACKGROUND: Anaphylaxis to latex or muscle relaxant drugs has been demonstrated in the perioperative period but there are no reports of a patient with anaphylaxis to both of these substances. METHODS: We report a patient with meningomyelocele who was initially thought to have anaphylaxis to latex during induction of anesthesia. After recurrence of anaphylaxis following removal of latex as the suspected agent, the muscle relaxant vecuronium was found to be the actual etiology. RESULTS: Skin testing to several muscle relaxants and other anesthetic medications confirmed a hypersensitivity to vecuronium. Skin testing and subsequent physical contact with latex also established a hypersensitivity to this substance. CONCLUSIONS: This report demonstrates the need to scrutinize closely every notation in the anesthesia record when evaluating perioperative anaphylaxis and to consider that hypersensitivity to more than one substance may be present.

Anaphylaxis↗
PubMed1994

Effects of altered arterial carbon dioxide tension on quantitative electroencephalography in halothane-anesthetized dogs.

Quantitative electroencephalography was assessed in 6 dogs anesthetized with 1.8% end-tidal halothane, under conditions of eucapnia, hypocapnia, and hypercapnia. Ventilation was controlled in each condition. Heart rate, arterial blood pressure, core body temperature, arterial pH, blood gas tensions, end-tidal CO2 tension, and end-tidal halothane concentration were monitored throughout the study. A 21-lead linked-ear montage was used for recording the EEG. Quantitative electroencephalographic data were stored on an optical disk for analysis at a later date. Values for absolute power of the EEG were determined for delta, theta, alpha, and beta frequencies. Hypocapnia was achieved by hyperventilation. Hypercapnia was achieved by titration of 5% CO2 to the inspired gas mixture. Hypercapnia was associated with an increase in the absolute power of the delta band. Hypocapnia caused an increase in the absolute power of delta, theta, and alpha frequencies. Quantitative electroencephalographic data appear to be altered by abnormalities in arterial carbon dioxide tension. Respiratory acidosis or alkalosis in halothane-anesthetized dogs may obscure or mimic electroencephalographic abnormalities caused by intracranial disease.

Animals↗
PubMed1993

Expression and characterization of the N-terminal domain of an oleosin protein from sunflower.

Oil bodies of plant seeds contain a triacylglycerol matrix surrounded by a monolayer of phospholipids embedded with alkaline proteins termed oleosins. Although oleosins are amphipathic proteins, they are unlike bilayer membrane proteins since they are associated with a single lipid:water interface at the oil body surface. Oleosins are unusual proteins because they contain a 70-80-residue uninterrupted nonpolar domain, flanked by relative polar C- and N-terminal domains. In the present study, we report the expression of the N-terminal domain of the 18-kDa oleosin isoform from sunflower as a recombinant fusion protein in Escherichia coli and the determination of its secondary structure using CD and Fourier transform infrared spectroscopy either as a purified but partially denatured peptide or reconstituted into liposomes. The structure derived from physical studies was then compared and assigned with those predicted from analysis of the primary sequence of the N-terminal domain. Based on data derived from CD spectroscopy analysis of purified and partially renatured N-terminal polypeptide, it contains about 10% alpha-helical structure, 20-30% beta-strand structure, approximately 8% beta-turn structure, and 60% random coil structure. However, analysis of the polypeptide reconstituted into liposomes showed an increased content of alpha-helical structure to about 20% and an increased beta-strand structure content to about 30-40%. Data derived from Fourier transform infrared spectroscopy studies and compared with the data predicted from the primary sequence showed the peptide is well structured with some antiparallel beta-strand structure from residues 2-9, parallel beta-strand structure from residues 30-37 and/or 42-49, and alpha-helical structure from residues 10-23 and/or 43-49. There is potential amphipathic alpha-helix from residues 10-23. Based on these results, the following model for the secondary structure of the N-terminal domain of sunflower oleosin can be proposed. Residues 2-9 would produce amphipathic antiparallel beta-strand structure. Residues 10-23 would produce an amphipathic alpha-helical structure. Residues 30-37 and/or 42-49 would give parallel beta-strand structure, or residues 42-49 could form a nonpolar alpha-helical structure that would insert into the oil matrix.

Amino Acid Sequence↗
PubMed1993

Structure of hen lysozyme in solution.

The structure of the 129-residue protein hen lysozyme has been determined in solution by two-dimensional 1H nuclear magnetic resonance methods. 1158 NOE distance restraints, and 68 phi and 24 chi 1 dihedral angle restraints were employed in conjunction with distance geometry and simulated annealing procedures. The overall C alpha root-mean-square deviation from the average for 16 calculated structures is 1.8(+/- 0.2) A, but excluding 14 residues in exposed disordered regions, this value reduces to 1.3(+/- 0.2) A. Regions of secondary structure, and the four alpha-helices in particular, are well defined (C alpha root-mean-square deviation 0.8(+/- 0.3) A for helices). The main-chain fold is closely similar to structures of the protein in the crystalline state. Furthermore, many of the internal side-chains are found in well-defined conformational states in the solution structures, and these correspond well with the conformational states found in the crystal. The general high level of definition of mainchain and many internal side-chains in the solution structures is reinforced by the results of an analysis of coupling constants and ring current shifts. Many side-chains on the surface, however, are highly disordered amongst the set of solution structures. In certain cases this disorder has been shown to be dynamic in origin by the examination of 3J alpha beta coupling constants.

Animals↗
PubMed1993

Ventricular tachycardia and psychiatric depression in patients with coronary artery disease.

PURPOSE: The purpose of this study was to examine the relationship between psychiatric depression and ventricular arrhythmias in patients with coronary artery disease (CAD). The hypothesis was that depressed patients with CAD would have a higher prevalence of ventricular tachycardia (VT) than nondepressed patients with CAD. PATIENTS AND METHODS: One hundred three patients who were found to have significant CAD by elective diagnostic cardiac catheterization were administered a standardized psychiatric interview and underwent 24-hour Holter monitoring. RESULTS: Twenty-one patients (20%) met the criteria for either major or minor depression. There were no significant differences between depressed and nondepressed patients with CAD in severity of CAD or in ventricular function. Five (23.8%) of the depressed patients and three (3.7%) of the nondepressed patients exhibited episodes of VT during 24 hours of Holter monitoring (p < 0.008). This difference remained significant even after controlling for relevant covariates. CONCLUSIONS: We conclude that there is a higher prevalence of VT among patients with CAD and depression than among those CAD patients without depression. This may help to explain the increased risk for cardiac mortality in depressed patients with CAD.

Aged↗
PubMed1993

Effect of angiotensin II blockade on dietary protein-induced renal growth.

Dietary protein provokes renal growth and synthesis of renin. Because angiotensin II (AII) has growth-promoting properties, we tested the possibility that protein-induced renal growth depends on angiotensin II. Normal adult male rats placed on a high-protein diet (50%) developed significant renal and glomerular growth over 6 days compared with rats on a low-protein diet (6%). However, neither angiotensin converting enzyme inhibition with enalapril nor angiotensin receptor antagonism with losartan influenced the degree of whole-kidney, cortical tubular, or glomerular growth. Thus, angiotensin II is not a necessary factor in dietary protein-induced renal growth in normal adult rats.

Angiotensin II↗
PubMed1993

Inhibition of leukotriene D4-induced bronchoconstriction in subjects with asthma: a concentration-effect study of ICI 204,219.

The peptide-leukotriene antagonist, ICI 204,219 [4-(5-cyclopentyloxycarbonylamino-lmethylindol-3-ylmethyl )-3-methoxy-n-o-tolylsulfonyl benzamide], was administered 12 hours before an inhaled leukotriene D4 (LTD4) challenge during a double-blind, placebo-controlled, randomized, two-period crossover trial. Subjects with mild asthma were randomized into five treatment groups (six subjects each) and received single oral doses of placebo and either 5, 10, 20, 40, or 100 mg of ICI 204,219 on day 1 of each treatment period. ICI 204,219 was tolerated well by all subjects. A progressive dose response was observed for doses of ICI 204,219 from 5 mg through 100 mg. Compared with placebo, ICI 204,219 increased the concentration (PC20FEV1) and dose of LTD4 needed to reduce forced expiratory volume in 1 second (FEV1) by 20%. Mean LTD4 PC20FEV1 for groups that received placebo and 10, 40, or 100 mg ICI 204,219 increased by tenfold or more (p < 0.05). An association was found between the plasma concentration and protective effect of ICI 204,219 (p < 0.01). ICI 204,219 is the first leukotriene receptor antagonist for which a relationship has been established between drug plasma levels and its protective effect in subjects with asthma.

Adolescent↗
PubMed1993

Lung retention of phosphatidylcholine and cholesterol from liposomes: effects of oxygen exposure and fasting.

Antioxidants such as glutathione may play a role in prevention and treatment of several lung diseases. Liposomes can be used to deliver antioxidants to the lung and increase their retention. In addition, liposomes alone may protect against oxidant-induced damage. In addition, liposomes alone may protect against oxidant-induced damage. This study was designed to characterize the retention and distribution of liposomes in the lung under normal circumstances and during either fasting, exposure to 100% oxygen, or a combination of the two. Positively charged liposomes, consisting of phosphatidylcholine (PC), cholesterol, and stearylamine plus either [14C]cholesterol or [3H]PC, were instilled intratracheally. Five minutes to 5 days later the lungs were removed and the radioactivity determined. Both [14C]cholesterol and [3H]PC labels had prolonged and equal retention in the lung, but their distribution within lung compartments differed. The cholesterol label increased in lung tissue over time, comprising 78% of the remaining label after 5 days, whereas the PC label persisted at high levels in lavage fluid and became equally distributed between lung tissue and bronchoalveolar lavage fluid. Fasting had little effect on the retention of the labels and no effect on their distribution within the lung. Exposure to 100% oxygen increased lung retention of both radiolabels and altered their distribution such that [14C]cholesterol label decreased and [3H]PC label increased in lung tissue. These results demonstrate the prolonged retention of intratracheally administered liposomes or their components in the lung and the effects of two clinically relevant conditions, fasting and hyperoxic exposure. Furthermore, they provide a basis for designing future studies using liposomes.

Animals↗
PubMed1993

Increased levels of glutathione in bronchoalveolar lavage fluid from patients with asthma.

Patients with asthma generate increased amounts of reactive oxygen species (ROS) from peripheral blood cells and cells recovered by bronchoalveolar lavage (BAL). ROS produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. Although antioxidant defenses inhibit the changes produced by ROS, no data are available on local antioxidant defenses in asthma. The present study was designed to begin to explore these defenses by measuring superoxide dismutase (SOD) and catalase activities and total glutathione (GSH) levels in BAL fluid from normal subjects and patients with mild asthma. Baseline pulmonary function and methacholine bronchoprovocation tests were performed on all subjects. BAL was achieved by instilling five 20-ml aliquots of phosphate-buffered saline in each of three lung segments. The fluids recovered from the first 20-ml aliquot and that from the next four aliquots were labeled bronchial and alveolar fluid, respectively. Patients with asthma had a lower FEV1 (p < 0.005), less BAL fluid recovered (p < 0.05), and an increased percentage of bronchial eosinophils (p < 0.05). There were no differences in BAL total cell count or protein concentration. Catalase activity was not consistently detected in the unconcentrated BAL fluid from either group. SOD activity was found in both bronchial and alveolar samples, but it was similar in the two groups of subjects. The GSH concentration in bronchial fluid was higher in the patients with asthma (23.9 +/- 6.2 vs 13.0 +/- 1.8 microM/mg protein; p < 0.05); a similar trend was seen in the alveolar fluid (36.5 +/- 9.4 vs 23.3 +/- 3.0 microM/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of leukotriene D4 and platelet-activating factor on human alveolar macrophage eicosanoid and PAF synthesis.

Leukotrienes (LT) and platelet-activating factor (PAF) can increase nonspecific airway reactivity in normal subjects, and they have been proposed as putative mediators of asthma. Alveolar macrophages (AM), which have receptors for and synthesize leukotrienes and PAF, also may play a role in the pathogenesis of asthma. The present study was designed to determine the effects LTD4 and PAF have on bronchoalveolar lavage (BAL) fluid and cells, including AM eicosanoid and PAF synthesis, and to relate them to changes in nonspecific airway reactivity. Airway reactivity to methacholine was measured in healthy, male volunteers at least 2 days before and 6 h, 1, 3, and 7 days after inhaling either LTD4 or PAF. At least 3 wk later subjects inhaled in random order either methacholine or the mediator to which they were previously exposed, and BAL was performed the next day. This sequence was repeated with the other chemical 3 wk or more later. LTD4 inhalation increased airway reactivity and stimulated AM thromboxane synthesis while it reduced stimulated AM LTB4 synthesis. LTD4 did not affect the number of percentage of BAL cells or the BAL fluid protein and histamine concentrations. PAF inhalation increased airway reactivity and the proportion of neutrophils and eosinophils recovered by BAL, but it did not alter AM eicosanoid and PAF synthesis or the BAL fluid protein and histamine concentrations. A relationship was identified between the PAF-induced increase in airway reactivity and the percentage of BAL neutrophils, but no correlation was found between LTD4- or PAF-induced changes in airway reactivity and stimulated AM eicosanoid or PAF synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Treatment options in the child with a chronic cough.

Chronic cough is a common symptom in many different disease processes. Because the most effective way to eliminate a chronic cough is to identify and treat the underlying disease, the physician must approach the paediatric patient based on his or her knowledge of the differential diagnosis. The most common causes of cough in children are upper respiratory tract infections, asthma, rhinitis, sinusitis, and gastroesophageal reflux. By using a systematic approach, the cause of a chronic cough can almost always be found, and the cough successfully treated. Asthma is the cause of most undiagnosed chronic coughs but sinusitis, rhinitis, and gastroesophageal reflux must also be considered in difficult patients.

Antitussive Agents↗
PubMed1993

Intraventricular alpha interferon therapy for Rasmussen's syndrome.

A 4-year-old boy developed Rasmussen's syndrome and was treated with alpha interferon intraventricularly. An improvement in the epileptic and neurologic syndrome was noted for several weeks following interferon. No adverse side effects were encountered. Since hemispherectomy is the only established therapy in Rasmussen's Syndrome, further studies are needed to establish if intraventricular alpha interferon may halt the clinical progression of the syndrome.

Atrophy↗
PubMed1993

Cervical neoplasia. Its association with human papillomavirus infection.

Almost 70 human papillomavirus (HPV) types have been identified. An estimated one-third are anogenital associated. Their presence in the genital tract is associated with cancer, and certain particular types have a high correlation with cervical intraepithelial neoplasia (CIN) and carcinoma. Although a spectrum of histopathologic features within the epithelium characterize changes caused by HPV infection, only DNA analysis accurately detects and determines the type of infection. The variety of molecular methods for detection of HPV DNA primarily reveal whether or not a lesion is in fact associated with HPV infection. For minor grade cervical squamous lesions or equivocal Pap smear results, HPV detection and typing can help identify patients at increased risk for cervical carcinoma. Cervical colposcopy and biopsy are indicated for definitive diagnosis.

Female↗