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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 325 records · Page 18Linked to original sources

IBC's conference on antibody engineering; new technology, application and commercialisation.

This was the first antibody engineering conference held by IBC Conferences in the UK, and was the European equivalent of the annual US meeting held in San Diego. The conference provided a forum for an update on progress in all aspects of antibody engineering. Topics covered ranged from the design of libraries and new selection techniques to news of the first engineered antibodies to enter clinical trials. Library size and diversity were shown to have increased dramatically in the last few years, and new formats have been introduced. In parallel, improvements to existing applications and the development of novel selection technologies were shown to improve accessibility to new targets. Exciting developments included phenotypic selections, ribosome display, improvements to bispecific design and the design of active intracellular antibodies. The data generated for recombinant antibodies in the clinic are very promising, with some antibodies demonstrating improvements over conventional therapies and others targeting diseases where no treatment is currently available. Presented below is a summary of the highlights of the conference, with particular focus on natural antibody phage libraries, and lead candidates derived from these libraries currently in clinical trials.

Journal Article↗

A phase I/II study of the protease inhibitor indinavir in children with HIV infection.

BACKGROUND: Indinavir, an inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, is approved for the treatment of HIV infection in adults when antiretroviral therapy is indicated. We evaluated the safety and pharmacokinetic profile of the indinavir free-base liquid suspension and the sulfate salt dry-filled capsules in HIV-infected children, and studied its preliminary antiviral and clinical activity in this patient population. In addition, we evaluated the pharmacokinetic profile of a jet-milled suspension after a single dose. METHODS: Previously untreated children or patients with progressive HIV disease despite antiretroviral therapy or with treatment-associated toxicity were eligible for this phase I/II study. Three dose levels (250 mg/m2, 350 mg/m2, and 500 mg/m2 per dose given orally every 8 h) were evaluated in 2 age groups (<12 years and >/=12 years). Indinavir was initially administered as monotherapy and then in combination with zidovudine and lamivudine after 16 weeks. RESULTS: Fifty-four HIV-infected children (ages 3.1 to 18.9 years) were enrolled. The indinavir free-base suspension was less bioavailable than the dry-filled capsule formulation, and therapy was changed to capsules in all children. Hematuria was the most common side effect, occurring in 7 (13%) children, and associated with nephrolithiasis in 1 patient. The combination of indinavir, lamivudine, and zidovudine was well tolerated. The median CD4 cell count increased after 2 weeks of indinavir monotherapy by 64 cells/mm3, and this was sustained at all dose levels. Plasma ribonucleic acid levels decreased rapidly in a dose-dependent way, but increased toward baseline after a few weeks of indinavir monotherapy. CONCLUSIONS: Indinavir dry-filled capsules are relatively well tolerated by children with HIV infection, although hematuria occurs at higher doses. Future studies need to evaluate the efficacy of indinavir when combined de novo with zidovudine and lamivudine.

Adolescent↗

Model behaviour.

Explore the source record for details and available documents.

Decision Making, Organizational↗

Aquarius: transitioning to an unmanned life support buoy.

The Aquarius underwater laboratory (or habitat) is the world's only operational saturation facility currently supporting scientific research and is operated by the University of North Carolina at Wilmington. The underwater laboratory accommodates and supports six aquanauts (scientists and habitat technicians) at habitat depth for 10-30-day missions. In the past, life support systems were provided by a manned support barge or Mobile Support Base (MSB) moored directly above Aquarius. The MSB was manned 24 h a day during saturation missions, which required 12 support staff in three separate shifts. A new unmanned Life Support Buoy (LSB) replaces the MSB and provides life support systems and is the voice, video, and data communications bridge from the habitat to the shore base. The LSB transmits status of all life support systems to the habitat and the shore base, thus minimizing the need for support staff to be present overtop of Aquarius during missions.

Automation↗

Reinfusion of discard blood from venous access devices.

PURPOSE/OBJECTIVES: To determine if clots are present in the initial 10 ml of blood routinely discarded from venous access devices (VADs) prior to blood sampling, and to determine if clots form in the discard blood specimen during the five minutes required to complete blood specimen sampling. DESIGN: A pretest/post-test design. SETTING: A large, mid-Atlantic research institution. SAMPLE: A convenience sample of 50 adult patients with cancer (27 males and 23 females) with a median age of 60. A large sampling size variation existed among the different VADs. METHOD: Two 5 ml discard specimens were drawn into separate syringes. Syringe #1 was filtered immediately, and syringe #2 was filtered after a five-minute dwell time. Both samples were filtered through a 40 micron filter. MAIN RESEARCH VARIABLE: The presence or absence of clots. FINDINGS: Fifty percent (n = 25) of the VADs had clots present on the filter from syringe #1. The clots varied in length, width, depth, and diameter, which precluded a consistent measurement. The investigators were able to measure either the diameter or length, depending on the shape of the clots. The majority of the clots (n = 17) appeared to be shaped like the lumen of a catheter and varied from 0.1 cm to 1.2 cm in length. Six clots were round and varied in diameter from 1.6 mm to 2.8 mm. Only 4% (n = 2) of the VADs had clots in syringe #2, but those clots were much larger, measuring 8.3 mm and 18.4 mm. CONCLUSIONS: The study addresses concerns of the investigators regarding the clinical practice of reinfusing discard blood obtained from VADs. Whether the clots present in the catheter and their reinfusion represent a significant risk to patient outcome is unclear. IMPLICATIONS FOR NURSING PRACTICE: Until further research is conducted and the degree of risk can be better defined, methods of drawing blood that require reinfusion of discard blood from VADs are not recommended.

Adult↗

Lower extremity paralysis after operative laparoscopy from conversion disorder. A case report.

BACKGROUND: Neurologic complications are rarely associated with laparoscopic procedures, and most nerve injuries are transient palsies. We present the first case of paraplegia following gynecologic laparoscopy. CASE: A 34-year-old woman, gravida 2, para 0-1-1-0, with long-standing infertility, underwent an uncomplicated laparoscopic ovarian cystectomy for a persistent ovarian cystadenoma. In the immediate postoperative period, the patient developed bilateral lower extremity paralysis. She regained her sensorimotor function in one extremity within hours, while both motor and sensory functions, but not proprioception, were deficient in the other extremity in a pattern of distribution that was inconsistent and paradoxical. Diagnostic studies to evaluate the patient's central and peripheral nervous systems and evoked sensory potentials were all normal. The patient's indifference to her persistent yet paradoxical neurologic deficits was a clue to her diagnosis. In the absence of an organic lesion to account for the patient's symptoms, the diagnosis of conversion disorder was made. CONCLUSION: Neurologic complications following laparoscopy are rare, generally involving nerve palsies from local injury. This is the first report of lower extremity paralysis after laparoscopy. Although conversion disorder is rare, it may occur in the gynecologic setting owing to its prevalence in women and especially in the presence of underlying affective disorders.

Adult↗

Characterization of the interthiol acyltransferase reaction catalyzed by the beta-ketoacyl synthase domain of the animal fatty acid synthase.

The enzyme activity responsible for translocation of saturated acyl chains from the 4'-phosphopantetheine of the acyl carrier protein to the active site cysteine of the beta-ketoacyl synthase in the animal fatty acid synthase has been identified. An enzyme assay was devised that allows uncoupling of the interthiol transfer step from the condensation reaction. Experiments with various fatty acid synthase mutants indicate clearly that catalysis of the transfer of saturated acyl moieties from the 4'-phosphopantetheine thiol to the active site cysteine thiol, Cys-161, is an inherent property of the beta-ketoacyl synthase domain. Catalytic efficiency of the interthiol transferase increases from C2 to C12 and decreases with increasing chain-lengths beyond C12. Malonyl, beta-hydroxybutyryl, and crotonyl thioesters are not substrates for the transferase, whereas the beta-ketobutyryl moiety is a poor substrate. These features of the substrate specificity are exactly as predicted for a transferase that fulfills the proposed role in the fatty acid synthase reaction sequence and indicate that this activity plays an important role in determining the overall specificity of the beta-ketoacyl synthase reaction.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

Effect of inhaled corticosteroids on episodes of wheezing associated with viral infection in school age children: randomised double blind placebo controlled trial.

OBJECTIVES: To determine the effect of regular prophylactic inhaled corticosteroids on wheezing episodes associated with viral infection in school age children. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: Community based study in Southampton. SUBJECTS: 104 children aged 7 to 9 years who had had wheezing in association with symptoms of upper and lower respiratory tract infection in the preceding 12 months. INTERVENTIONS: After a run in period of 2-6 weeks children were randomly allocated twice daily inhaled beclomethasone dipropionate 200 micrograms or placebo through a Diskhaler for 6 months with a wash out period of 2 months. Children were assessed monthly. MAIN OUTCOME MEASURES: Forced expiratory volume in 1 second (FEV1); bronchial responsiveness to methacholine (PD20); percentage of days with symptoms of upper and lower respiratory tract infection with frequency, severity, and duration of episodes of upper and lower respiratory symptoms and of reduced peak expiratory flow rate. RESULTS: During the treatment period there was a significant increase in mean FEV1 (1.63 v 1.53 1; adjusted difference 0.09 1 (95% confidence interval 0.04 to 0.14); P = 0.001) and methacholine PD20 12.8 v 7.2 mumol/l; adjusted ratio of means 1.7 (1.2 to 2.4); P = 0.007) in children receiving beclomethasone dipropionate compared with placebo. There were, however, no significant differences in the percentage of days with symptoms or in the frequency, severity, or duration of episodes of upper or lower respiratory symptoms or of reduced peak expiratory flow rate during the treatment period between the two groups. CONCLUSIONS: Although lung function is improved with regular beclomethasone dipropionate 400 micrograms/day, this treatment offers no clinically significant benefit in school age children with wheezing episodes associated with viral infection.

Administration, Inhalation↗

Temporal stability of polydipsia-hyponatremia.

We evaluated temporal stability and outcome predictors associated with polydipsia-hyponatremia (PH). Severity of PH was measured on two occasions separated by at least 1 year in 25 chronic psychiatric inpatients (24 with schizophrenia). Three-quarters of the sample had clinically evident PH on follow-up. Follow-up PH severity was significantly related to intake severity and hospitalization length. Our findings suggest that PH may be a persistent condition with specific outcome predictors.

Adult↗