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Biomedical subjects

C Webster

Publications and source records attributed to C Webster.

At least 19 recordsLinked to original sources

Results after colectomy for colonic inertia: a sixteen-year experience.

BACKGROUND: Colonic inertia (CI) is a disturbance of colonic motility characterized by severe constipation and abdominal pain. This study was conducted to assess the results of total abdominal colectomy (TAC) in the management of CI. METHODS: A retrospective chart review of 55 patients who underwent TAC for CI was conducted. RESULTS: Forty-eight patients (87%) were female with an average age of 40; severe constipation existed 2 years prior to surgery. Symptoms included severe constipation (100%) and abdominal pain (84%); diagnostic workup included sitz marker study, anal manometry, and Gastrografin enema. In all cases, sitz marker studies were abnormal and anal manometry was normal. Histologically, no patient had absence of neuroenteric plexuses. Complications included prolonged ileus (24%) and small bowel obstruction (8%). Some 49 patients (89%) had "good" or "excellent" results and 6 patients (11%) had "poor" results. Postoperative stool frequency was 5, 4, and 3 per day at 1, 2, and 12 months, respectively. CONCLUSIONS: TAC results in resolution of constipation in most patients. We conclude that TAC is effective treatment in patients with CI.

Adolescent↗

An improved method for isolation of unconjugated bilirubin from rat and dog bile.

Radiolabeled unconjugated bilirubin (UCB) is currently prepared by biosynthetic labeling of bilirubin in fistula bile from precursor-labeled delta-aminolevulinic acid (ALA) in rats or dogs. With existing methods, yields of labeled UCB from the bile are generally less than 50%. We here report modifications of the original method of Ostrow et al (Ostrow JD, Hammaker L, Schmid R. The preparation of crystalline bilirubin-C(14). J Clin Invest 1961;40:1442-52) that result in improvement of yields to 72% from both dog and rat bile. The modifications include the initial deproteination of bile with a reverse-phase C18 cartridge, removal of ethanol before alkaline hydro-lysis to avoid esterification of UCB, and adjustments for the high proportion of non-glucuronide UCB conjugates in dog bile not precipitated as lead salts. These improvements should save significantly on both costs and animal usage.

Alkalies↗

Pitfalls in preparation of (3)H-unconjugated bilirubin by biosynthetic labeling from precursor (3)H-5-aminolevulinic acid in the dog.

We report problems encountered during preparation of tritium-labeled unconjugated bilirubin ((3)H-UCB) from precursor (3)H-5-aminolevulinic acid ((3)H-ALA) in 2 dogs with external biliary drainage installed into the animals under general anesthesia. Under prolonged sedation, 12.9 or 14.0 mCi of (3)H-ALA was administered intravenously in two divided doses, and bile was collected for 9 hours. In one animal, taurocholate (TC) infusion was needed to maintain bile flow. (3)H-UCB was isolated from the bile and recrystallized with the improved method of Webster et al (Webster CC, Tiribelli C, Ostrow JD. J Lab Clin Med 2001;137:370-3). Based on radioactivity and pigment content, hourly bile collections were pooled to optimize specific activities. Surprisingly, in the first dog, only 2.9% of injected radioactivity was recovered in bile and only 14.1% in urine, and the specific activities of the crystalline (3)H-UCB from the two pools were only 39.5 and 30.0 x 10(3) dpm/microg. High-performance liquid chromatography analysis revealed that only 4% of ALA degraded during 5 minutes in injection solution at pH 6.8. The low incorporation of (3)H-ALA and low specific activity of (3)H-UCB was apparently caused mainly by prior degradation and exchange of labile tritium of the (3)H-ALA and probably by enhanced endogenous ALA synthesis caused by the anesthetic/sedative agents. Revised procedures in the second dog improved the incorporation of (3)H-ALA to 11.9% excreted in bile and the specific activity of the crystalline (3)H-UCB to 122.0 and 50.8 x 10(3) dpm/microg, while urinary excretion of tritium increased to 28.5%. These experiences emphasize possible pitfalls in preparing (3)H-UCB by biosynthetic labeling from (3)H-ALA administered to dogs.

Aminolevulinic Acid↗

A methodology for web-enabling a computer-based patient record with contributions from cognitive science.

Cognitive science is a rich source of insight for creative use of new Web technologies by medical informatics workers. I outline a project to Web-enable an existing computer-based patient record (CPR) in the context of ideas from philosophy, linguistics, artificial intelligence, and cognitive psychology. Web prototypes play an important role (a) because Web technology lends itself to rapid prototype development, and (b) because prototypes help team members bridge among disparate medical, computing, and business ontologies. Six Web-enabled CPR prototypes were created and ranked. User scenarios were generated using a user communication matrix. Resulting prototypes were compared according to the degree to which they satisfied medical, computing, and business constraints. In a different organization, or at different time, candidate prototypes and their ranking might have been different. However, prototype generation and comparison are fundamentally influenced by factors usefully understood in a cognitive science framework.

Cognitive Science↗

Efficacy and tolerability of subcutaneous sumatriptan for acute migraine: a comparison between ethnic groups.

OBJECTIVE: To evaluate efficacy and tolerability of subcutaneous sumatriptan 6 mg versus placebo for acute migraine between ethnic groups. BACKGROUND: Patients in previous sumatriptan studies have been predominantly Caucasian and the effects of sumatriptan between different ethnic groups are unknown. METHODS: This was a multicenter, 3-phase, 12-attack study. Phases I and III (inclinic) were randomized, double-blind, placebo-controlled, crossover designs. Phase II (outpatient) was a single-blind design. Sumatriptan was compared to placebo across 2 groups (non-Caucasian and Caucasian) and individual ethnic subgroups (black, Hispanic, and others). Headache response, pain-free response, associated symptoms, and clinical disability were assessed. Tolerability assessments included the incidence of adverse events, physical examinations, vital signs, electrocardiograms, and clinical laboratory data. RESULTS: Two hundred patients treated at least one migraine attack (150 non-Caucasians: 46 blacks, 68 Hispanics, 36 others). Two hours postdose, significantly more inclinic sumatriptan-treated patients reported headache response (non-Caucasians, 81% versus 37% placebo; Caucasians, 87% versus 19% placebo; P<.001) and mild or no clinical disability, compared with placebo (non-Caucasians, 87% versus 50% placebo; Caucasians, 90% versus 38% placebo; P<.001). Blacks (80%), Hispanics (83%), and others (74%) reported similar patterns of headache response at 2 hours. Similar results were reported during the outpatient phase. The incidence of adverse events following sumatriptan during the inclinic phase was similar between ethnic groups (non-Caucasian, 75%; Caucasian, 79%) and higher than placebo (non-Caucasian, 51%; Caucasian, 31%). Overall, adverse events in the outpatient phase of the study were lower than in the inclinic phase. CONCLUSION: Sumatriptan injection is effective and well tolerated in non-Caucasians and Caucasians for the treatment of acute migraine attacks. Only minor differences in efficacy or tolerability were observed between blacks, Hispanics, and others.

Acute Disease↗

Identification of natural ligands for SH2 domains from a phage display cDNA library.

The cytoplasmic domain of the Fc gamma receptor IIB (FcgammaRIIB) can be successfully displayed on the surface of filamentous phage, and after phosphorylation in vitro, can interact specifically with the SH2 domains of SHP-2, a cytoplasmic tyrosine phosphatase. When full-length FcgammaRIIB is expressed on phage, however, this interaction is greatly compromised, illustrating that characteristics of the full-length sequence are not well tolerated by the phage display system. Many associations in cell physiology are driven by similar interactions involving small modular binding domains or ligands, and so a fragmented cDNA library will facilitate display of such domains free of sequences which compromise their expression. A fragmented leukocyte cDNA display library of 10(8) clones was constructed. This library was phosphorylated in vitro with fyn kinase and was selected against the tandem SH2 domains of SHP-2 in the search for additional ligands. A depletion strategy to remove non-specific clones was employed, using SHP-2 Sepharose, prior to in vitro phosphorylation and selection. This permitted the emergence of clones encoding the cytoplasmic domain of PECAM-1, another natural ligand for SHP-2. The importance of dual phosphorylation of tyrosine residues at positions 663 and 686 was confirmed in competition ELISA experiments using phosphorylated phage and synthetic peptides. Thus, phage display of fragmented cDNA libraries permits the identification and characterisation of phosphorylated ligands of modular binding domains based on their functional interaction.

Amino Acid Sequence↗

Minimally invasive treatment for localized adenocarcinoma of the prostate: review of 1048 patients treated with ultrasound-guided palladium-103 brachytherapy.

PURPOSE: To assess the effectiveness of palladium-103 brachytherapy in stage T1 and T2 adenocarcinoma of the prostate. PATIENTS AND METHODS: The charts of 1048 patients treated between 1991 and 1999 with transperineal realtime ultrasound-guided (103)Pd (Theraseed) implants were reviewed to assess the effects on serum prostate specific antigen (PSA) values and tissue (biopsy). Of the 1048 patients, 780 had sufficient data for this report. Preoperative total androgen blockade (leuprolide and flutamide) was used selectively in patients whose prostate size was >50 cc and those whose tumors had a Gleason score of >7. RESULTS: At 1 year, 86% of the evaluable 766 patients had stable PSA concentration <1.5 ng/mL; at 5 years, 86% of the 166 patients with data available had stable PSA values <1.5 ng/mL. Biopsies were negative in 92% of the patients studied at 2 years. Patients with pretreatment PSA values <10 ng/mL had the best outcomes, and those treated with (103)Pd plus hormone ablation achieved PSA reduction more rapidly than those treated with radioisotope monotherapy. There was one disease-related death; the principal morbidity was short-term bladder and bowel irritation without permanent sequelae. Impotence occurred in approximately 15% of patients, and incontinence occurred in 5% of those who had undergone prior transurethral resection of the prostate. CONCLUSION: The technique used in this study proved effective in reducing PSA concentrations to <1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. These results are comparable to those of external-beam radiation therapy and radical prostatectomy while demonstrating a significant reduction in morbidity.

Adenocarcinoma↗

Patterns of protein synthesis and tolerance of anoxia in root tips of maize seedlings acclimated to a low-oxygen environment, and identification of proteins by mass spectrometry.

Tolerance of anoxia in maize root tips is greatly improved when seedlings are pretreated with 2 to 4 h of hypoxia. We describe the patterns of protein synthesis during hypoxic acclimation and anoxia. We quantified the incorporation of [(35)S]methionine into total protein and 262 individual proteins under different oxygen tensions. Proteins synthesized most rapidly under normoxic conditions continued to account for most of the proteins synthesized during hypoxic acclimation, while the production of a very few proteins was selectively enhanced. When acclimated root tips were placed under anoxia, protein synthesis was depressed and no "new" proteins were detected. We present evidence that protein synthesis during acclimation, but not during subsequent anoxia, is crucial for acclimation. The complex and quantitative changes in protein synthesis during acclimation necessitate identification of large numbers of individual proteins. We show that mass spectrometry can be effectively used to identify plant proteins arrayed by two-dimensional gel electrophoresis. Of the 48 protein spots analyzed, 46 were identified by matching to the protein database. We describe the expression of proteins involved in a wide range of cellular functions, including previously reported anaerobic proteins, and discuss their possible roles in adaptation of plants to low-oxygen stress.

Adaptation, Physiological↗

Evolution of techniques for ultrasound-guided palladium 103 brachytherapy in 950 patients with prostate cancer.

PURPOSE: Brachytherapy is an effective, low-morbidity, cost-effective treatment for adenocarcinoma of the prostate. Although both iodine 125 and palladium 103 have been used extensively over the last 14 years, 103Pd (Theraseed) provides a more rapid initial dose and therefore better control of higher Gleason grade tumors. We assessed a highly refined methodology for 103Pd brachytherapy in patients with prostate cancer and compared outcomes before and after making adjustments in technique. MATERIALS AND METHODS: Standard brachytherapy techniques were modified to include combination of preplanning with real-time adjustment, placing all needles at once to minimize prostate movement, using monitored anesthesia control sedation during preoperative volume study and cystoscopy, and several other small but important changes. Charts were reviewed from 950 patients treated with 103Pd implants from 1991 through 1999. Prostate-specific antigen (PSA) and biopsy data before and after 1993 were compared for 733 patients whose data qualified for analysis. RESULTS: At 1 and 5 years after treatment, 85-88% of patients had stable PSA <1.5 ng/mL. Biopsies were negative in 90-94% at 2 years. CONCLUSION: The modification in techniques provides positive results that remain stable over time.

Adenocarcinoma↗

The early NHS and the crisis of public health nursing.

Establishment of the NHS in 1948 is rightly seen as a major turning point in health care in the United Kingdom. Notwithstanding conditions of severe austerity, the NHS succeeded remarkably well in its basic remit to make all essential medical care available to the entire population, free at point of delivery. The benefits of the new system extended across the entire front of its services. However, it is important to recognise that the reforms of 1948 were uniformly advantageous. It has for instance long been recognised that the NHS failed to bring about the expected transformation in standards of general medical practice. In this short paper the author argues that public health represented a further major sphere of underdevelopment. The fact that, with minor exceptions, public health is the least studied aspect of the early NHS is itself suggestive of its status as the Cinderella of the modern health services. The author also underlines the adverse implications of this inferior position for domiciliary midwifery, district nursing and health visiting. These constituted small but strategically important sectors of nursing, all of which fell under public health administration in the new health service. The author concentrates on the first phase of the NHS, the period between 1948 and 1974, now often regarded as its golden age. For the purposes of this discussion, most of the evidence relates to the formative phase of the new service, when many major policy questions relating to public health were first confronted. It is suggested that the early neglect of public health and its constituent nursing functions has left a legacy of problems that have still not entirely been resolved. For the purposes of this paper the term will be used to embrace the totality of health functions administered by departments of local government in the period from 1948 to 1974. Most of these services fell within the public health departments of local government, headed by the Medical Office of Health (MOH). However, some important functions involving the nurses were located in other departments. Especially important was the School Health Service, which was reformed in 1944, ahead of the NHS. This was a largely independent service under the administration of Local Education Authorities. Some of the problems of public health nursing related to this fragmentation of responsibility.

History, 20th Century↗

Identification of a nucleic acid binding domain in eukaryotic initiation factor eIFiso4G from wheat.

Higher plants have two complexes that bind the m7G-cap structure of mRNA and mediate interactions between mRNA and ribosomal subunits, designated eIF4F and eIFiso4F. Both complexes contain a small subunit that binds the 5'-cap structure of mRNA, and a large subunit, eIF4G or eIFiso4G, that binds other translation factors and RNA. Sequence-specific proteases were used to cleave native cap-binding complexes into structural domains, which were purified by affinity chromatography. We show here that eIFiso4G contains a central protease-resistant domain that binds specifically to nucleic acids. This domain spans Gln170 to Glu443 and includes four of the six homology blocks shared by eIFiso4G and eIF4G. A slightly shorter overlapping sequence, from Gly202 to Lys445, had no nucleic acid binding activity, indicating that the N-terminal end of the nucleic acid binding site lies within Gln170 to Arg201. The binding of the central domain and native eIFiso4F to RNA homopolymers and double- and single-stranded DNAs was studied. Both molecules had highest affinity for poly(G) and recognized single- and double-stranded sequences.

Amino Acid Sequence↗

Team leadership: network differences in women's and men's instrumental and expressive relations.

Recent studies have emphasised differences in leadership styles between women and men. Women have an "interactive" leadership style while men are more "directive" and "authoritative." Social network analysis is used to examine differences in eight mental health case management teams, half formally supervised by women and half by men. The techniques used are graphical displays and measures of centrality. Results show male leaders as the most central team member for both instrumental and expressive relations. Female leaders, however, do not adhere to a single leadership style. Team centralisation also differs with gender composition of teams influencing leadership differences.

Adult↗

Health-related hardiness and the effect of a psycho-educational group on clients' symptoms.

In the health literature, an individual's ability to resist illness when under stress has been referred to as 'hardiness'. Resources, which may be used to sustain a sense of well being, can be categorized by two broad domains, 'control' and 'commitment and challenge'. In this research, a quasi-experimental nonequivalent control group design was used to determine the impact of a specific clinical nursing intervention (the Wellness Program) in terms of its usefulness in fostering the development of health-related hardiness. Findings demonstrated a significant reduction in symptoms related to obsessive compulsiveness, hostility, psychoticism and average level of distress after subjects completed a relatively short psycho-educational health promotion group. Subjectively, the treatment group subjects also described positive changes in thoughts, feelings and behaviours. This research has implications for clinical interventions using small groups to promote health.

Adult↗