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Biomedical subjects

J A Smith

Publications and source records attributed to J A Smith.

At least 127 records · Page 7Linked to original sources
PubMed2000

The prognostic significance of S-phase analysis in stage Ta/T1 bladder cancer. A Southwest Oncology Group Study.

OBJECTIVES: An intergroup study (SWOG 8795) comparing two forms of adjunctive therapy (immuno and chemo), bacillus Calmette-Guerin (BCG) and mitomycin C (MMC), furnished preregistration index tumors for 244 patients with superficial, papillary stage Ta/T1 TCC. These were examined by flow cytometry to learn whether DNA ploidy or proliferation (low vs high S-phase fraction (SPF) helped to predict disease recurrence or progression. METHODS: Cell cycle analysis using commercially available (Multicycle) programs was performed on 249 Ta/T1 bladder cancers. Tumor grade, available for 223 cases, was assigned by a single study pathologist. The SWOG statistical office reviewed follow-up information and other data and performed statistical analysis. RESULTS: Disease recurrence occurred in half the cases studied. The most parsimonious model predictive of recurrence included only treatment arm and tumor grade, with the MMC arm and tumor grade greater than I indicating worse prognosis (p = 0. 014). Neither ploidy nor SPF predicted recurrence-free survival or contributed prognostic information that was additive to tumor grade. Within 5 years of follow-up, disease progression or death from bladder cancer occurred for 29/223 (13%) of patients. The most parsimonious model for progression-free survival included only grade greater than I (p<0.001) and high SPF (p = 0.029) (relative risk: tumor grade, 4.3, high SPF, 1.9). CONCLUSIONS: Knowledge of tumor proliferation (low versus high SPF) contributes prognostic information about tumor progression that is additive to tumor grade.

Cell Division↗
PubMed2000

Comparable efficacy of administration with face mask or mouthpiece of nebulized budesonide inhalation suspension for infants and young children with persistent asthma.

A randomized, double-blind, placebo-controlled, parallel-group study including 481 children at 37 centers in the United States demonstrated the efficacy and safety of budesonide inhalation suspension in doses of 0.25 mg once daily, 0.25 mg twice daily, 0.5 mg twice daily, and 1.0 mg daily in infants and young children with persistent asthma. The retrospective analysis presented here compares the efficacy of treatment with the suspension administered through a face mask or mouthpiece. All patients receiving budesonide inhalation suspension via face mask or mouthpiece showed clinical improvements in nighttime and daytime asthma symptoms as compared with administration of a placebo. The improvements were of similar magnitude as those observed in an analysis of all patients treated. Improvements in nighttime asthma symptoms were statistically significant with budesonide at 0.25 mg daily (p = 0.040), 0.25 mg twice daily (p = 0.008), and 0.5 mg twice daily (p = 0.046) delivered by face mask. In patients using mouthpieces, nighttime asthma symptoms improved significantly in the 0.25-mg twice-daily (p = 0.005) and 1.0-mg daily (p = 0.035) groups. Patients receiving budesonide at 0.5 mg twice daily via a face mask improved significantly in daytime asthma symptoms (p = 0.009). The use of breakthrough medication was reduced in patients receiving budesonide via face masks or mouthpieces relative to placebo, and treatment was well tolerated in all study groups. This retrospective analysis suggests that nebulized budesonide inhalation suspension can be administered effectively by either face mask or mouthpiece to young children with persistent asthma.

Administration, Inhalation↗
PubMed2000

Enteroaggregative Escherichia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells.

Enteroaggregative Escherichia coli (EAEC) is an emerging cause of acute and persistent diarrhea worldwide. EAEC infections are associated with intestinal inflammation and growth impairment in infected children, even in the absence of diarrhea. We previously reported that prototype EAEC strains rapidly induce IL-8 production by Caco-2 intestinal epithelial cells, and that this effect is mediated by a soluble, heat-stable factor released by these bacteria in culture. We herein report the cloning, sequencing, and expression of this biologically active IL-8-releasing factor from EAEC, and its identification as a flagellin that is unique among known expressed proteins. Flagella purified from EAEC 042 and several other EAEC isolates potently release IL-8 from Caco-2 cells; an engineered aflagellar mutant of 042 does not release IL-8. Finally, cloned EAEC flagellin expressed in nonpathogenic E. coli as a polyhistidine-tagged fusion protein maintains its proinflammatory activity. These findings demonstrate a major new means by which EAEC may cause intestinal inflammation, persistent diarrhea, and growth impairment that characterize human infection with these organisms. Furthermore, they open new approaches for diagnosis and vaccine development. This novel pathogenic mechanism of EAEC extends an emerging paradigm of bacterial flagella as inflammatory stimuli.

Amino Acid Sequence↗
PubMed2000

Is Intranet technology the low cost, quick fix solution for Scotland's clinical information technology chaos? Results of a pilot study.

For health care professional staff immediate access to recent clinical documents is seen as the first priority for developments in Information Technology. Large amounts of clinical data are held on computer systems to which staff have little or no access. A pilot study has been undertaken to evaluate the use of Intranet technology, electronically extracting large volumes of data from various feeder systems in real time and allowing access via standard Internet browsers. Over 700,000 reports have been successfully transferred from three differing sources with more than 2000 new records added per week. Intranet technology would seem to be a low cost solution, capable of rapid implementation, that could overcome the most important bottleneck in clinical computing.

Cost Control↗
PubMed2000

The Southampton Needs Assessment Questionnaire (SNAQ): a valid tool for assessing the rehabilitation needs of disabled people.

OBJECTIVE: To validate the Southampton Needs Assessment Questionnaire (SNAQ) for use with disabled people during face-to-face interviews. DESIGN: The SNAQ was designed to be used in a cross-sectional survey of disabled people with a physical disability with a follow-up study one year later. Content and criterion validity was examined using 32 disabled people who took part in the pilot study. Construct validity and internal reliability was examined using data from 93 disabled people who took part in the main survey. Responsiveness of the questionnaire was evaluated using the data gathered during a follow-up study of 77 people had taken part in the original study. OUTCOME MEASURES: The OPCS Disability Severity Scales (OPCS) and the Functional Independence Measure (FIM) were used to measure level of disability of participants, the Nottingham Health Profile (NHP) and the UK version of the SF-36 to examine perceived health status. PARTICIPANTS: People with a primary physical disability, aged 16-65, randomly selected from two disability registers in southern England. MAIN RESULTS: Content and criterion validity were established. Construct validity and internal reliability of the SNAQ was good. Inter-rater reliability was not tested since only one researcher conducted the interviews. Test-retest reliability was not formally tested because of the probability that participants would learn from the first needs assessment questionnaire and that different results on a retest occasion could arise from this. The SNAQ was sensitive in picking up changes over time. CONCLUSION: The SNAQ has shown good validity (content, coverage and construct), internal reliability, sensitivity and responsiveness. Further studies are needed to define the consequences of meeting or not meeting the rehabilitation needs of disabled people. Inter-rater reliability remains to be established.

Adolescent↗
PubMed2000

Functional lower urinary tract voiding outcomes after cystectomy and orthotopic neobladder.

PURPOSE: We reviewed our experience with orthotopic continent urinary reconstruction after radical cystectomy to determine the functional voiding patterns and compare different methods of reservoir construction. MATERIALS AND METHODS: The study included 100 consecutive patients who underwent cystectomy and orthotopic neobladder. Reservoir construction consisted of a W-shaped ileal reservoir in 40 patients, ileal reservoir with afferent limb in 26, a Padua ileal reservoir in 18, right colon in 14 and sigmoid colon in 2. The functional voiding outcome was determined by a detailed patient interview and chart review. RESULTS: There were no perioperative deaths. All patients regained good daytime urinary control and none required protective pads, although 18% used protective padding at night because of nocturnal leakage. Eight patients (8%) performed self-intermittent catheterization because of poor reservoir emptying. There were no substantial differences in outcomes among the various methods of reservoir construction. CONCLUSIONS: Excellent functional voiding outcomes are obtained with radical cystectomy and orthotopic bladder reconstruction. Comparable results can be achieved with use of either large bowel or ileum and with various methods of bowel folding as long as principles of preservation of the periurethral sphincter muscle, and construction of an adequate capacity and low pressure reservoir are maintained.

Adult↗
PubMed2000

Early post-prostatectomy pelvic floor biofeedback.

PURPOSE: We determined whether biofeedback enhanced pelvic floor exercises begun 6 weeks after radical prostatectomy improve the early recovery of continence. MATERIALS AND METHODS: We randomized 30 patients who underwent radical retropubic prostatectomy into a group that received 5 biofeedback sessions and a control group. RESULTS: Overall 87% of patients were pad-free at 6 months with similar results in the treatment and control groups (86% versus 88%). There was no statistically significant difference in pad test results or voiding diary records in the 2 groups. CONCLUSIONS: A treatment program of biofeedback enhanced pelvic floor exercises begun 6 weeks after radical retropubic prostatectomy did not significantly affect continence in this study.

Biofeedback, Psychology↗
PubMed2000

Radical prostatectomy and collaborative care pathways.

The purpose of this study was to describe the development, implementation, and evaluation of a collaborative care pathway for radical retropubic prostatectomy. The experience of Vanderbilt University Medical Center is described, and the literature was reviewed. In addition, an example of the radical prostatectomy care pathway is provided for an illustration of a care path. The experience of using collaborative care pathways at Vanderbilt Medical Center has resulted in decreased length of stays, decreased blood utilization, and decreased overall costs. Also, staff satisfaction has improved all without compromising patient care. Collaborative care pathways have been shown to be a cost effective way of standardizing patient care without sacrificing the quality of patient care. In addition, they allow for an easier way to critically evaluate outcomes, costs, and patient and staff satisfaction.

Cost-Benefit Analysis↗
PubMed2000

African American female physicians in South Carolina: role models and career satisfaction.

BACKGROUND: This study examined the factors that influenced African American women to select medicine as a career and their satisfaction with their career choice. METHODS: Of 132 African American female physicians in South Carolina, 62 responded to a survey of open-ended questions about why they chose medicine, what they liked and disliked about their career, and who influenced their decision to become a physician. RESULTS: The majority chose medicine for altruistic reasons and found that medicine provided challenge and the opportunity to make a positive difference. Family members, teachers, and physicians served as the common external influences in their decision to become a physician. Managed care, paper work, and time demands constituted the most disliked aspects of medicine. CONCLUSION: Altruistic reasons and/or an interest in science motivated most of these African American female physicians to study medicine. Family members most often were their principal role models.

Black or African American↗
PubMed1999

Regulation of renal adenosine A(1) receptors: effect of dietary sodium chloride.

The influence of dietary NaCl on the regulation of renal adenosine A(1) receptors was investigated in the rat. Renal membranes from rats fed on a diet low (0.04%) in NaCl showed a 46% increase in B(max) for the binding of [3H]-1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX), a selective adenosine A(1) receptor antagonist, compared to membranes from rats fed on a normal diet (0.4% NaCl). Conversely, a high NaCl diet (4.0%) resulted in a 37% decrease in B(max). Levels of renal adenosine A(1) receptor mRNA were 65% lower in rats on a high salt diet. Autoradiographic studies showed that, for the inner medullary collecting ducts, a low NaCl diet resulted in a 30% increase in [3H]DPCPX binding with a 39% decrease noted in rats maintained on a high salt diet. The results indicate that changes in adenosine A(1) receptor density may represent a novel mechanism whereby the kidneys adapt to changes in salt load.

Animals↗
PubMed1999

Mild autosomal dominant hypophosphatasia: in utero presentation in two families.

We describe four pregnancies in two families in which mild hypophosphatasia, apparently transmitted as an autosomal dominant trait, manifested in utero as severe long bone bowing. Postnatally, there was spontaneous improvement of the skeletal defects. Recognition of this presentation for hypophosphatasia by family investigation and assessment of the fetal skeleton for degree of ossification and chest size using ultrasonography is important. The prognosis for this condition is considerably better than for more severe forms of hypophosphatasia and for many other disorders that cause skeletal defects with long bone bowing in utero.

Adult↗
PubMed1999

Angiotensin II inhibits insulin-induced egr-1 expression in mesangial cells.

The gene early growth response gene-1 (egr-1) encodes a zinc transcription factor involved in cell proliferation. Increased expression of egr-1 has been linked to heart and kidney disease. In mouse mesangial cells, insulin stimulated egr-1 expression more than angiotensin II, suggesting that insulin may play an important role in stimulating cell proliferation, leading to glomerulonephritis and diabetic nephropathy. Angiotensin II inhibited insulin-induced egr-1 expression but not c-fos expression, and the decrease in egr-1 expression was concurrent with a decrease in insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation. These results suggest that insulin-induced egr-1 expression in mouse mesangial cells is downstream of tyrosine phosphorylation of IRS-1 and activation of the MAP kinase pathway and that crosstalk between angiotensin II and insulin signaling pathways led to an inhibition of IRS-1 tyrosine phosphorylation and egr-1 expression.

Angiotensin II↗
PubMed1999

Generation of constitutively active p90 ribosomal S6 kinase in vivo. Implications for the mitogen-activated protein kinase-activated protein kinase family.

p90 ribosomal S6 kinases (RSKs), containing two distinct kinase catalytic domains, are phosphorylated and activated by extracellular signal-regulated kinase (ERK). The amino-terminal kinase domain (NTD) of RSK phosphorylates exogenous substrates, whereas the carboxyl-terminal kinase domain (CTD) autophosphorylates Ser-386. A conserved putative autoinhibitory alpha helix is present in the carboxyl-terminal tail of the RSK isozymes ((697)HLVKGAMAATYSALNR(712) of RSK2). Here, we demonstrate that truncation (Delta alpha) or mutation (Y707A) of this helix in RSK2 resulted in constitutive activation of the CTD. In vivo, both mutants enhanced basal Ser-386 autophosphorylation by the CTD above that of wild type (WT). The enhanced Ser-386 autophosphorylation was attributed to disinhibition of the CTD because a CTD dead mutation (K451A) eliminated Ser-386 autophosphorylation even in conjunction with Delta alpha and Y707A. Constitutive activity of the CTD appears to enhance NTD activity even in the absence of ERK phosphorylation because basal phosphorylation of S6 peptide by Delta alpha and Y707A was approximately 4-fold above that of WT. A RSK phosphorylation motif antibody detected a 140-kDa protein (pp140) that was phosphorylated upon epidermal growth factor or insulin treatment. Ectopic expression of Delta alpha or Y707A resulted in increased basal phosphorylation of pp140 compared with that of WT, presenting the possibility that pp140 is a novel RSK substrate. Thus, it is clear that the CTD regulates NTD activity in vivo as well as in vitro.

Amino Acid Sequence↗
PubMed1999

Heritable variation in resistance to gastro-intestinal nematodes in an unmanaged mammal population.

The impact of parasites on natural populations has received considerable attention from evolutionary biologists in recent years. Central to a number of theoretical developments during this period is the assumption of additive genetic variation in resistance to parasites. However, very few studies have estimated the heritability of parasite resistance under field conditions, and those that have are mainly restricted to birds and their ectoparasites. In this paper, to our knowledge, we show for the first time in a free-ranging mammal population, Soay sheep (Ovis aries) living on the islands of St Kilda, that there is significant heritable variation in resistance to gastrointestinal nematodes. This result is consistent with earlier studies on this population which have indicated locus-specific associations with parasite resistance. We discuss our results in the context of current studies examining heritable resistance to parasites in domestic sheep and the possible mechanisms of selective maintenance of genetic variation for resistance to gastrointestinal nematodes in the St Kilda Soay sheep population.

Animals↗
PubMed1999

Edible mushroom (Agaricus bisporus) lectin, which reversibly inhibits epithelial cell proliferation, blocks nuclear localization sequence-dependent nuclear protein import.

The Galbeta1-3GalNAcalpha (TF antigen)-binding lectin (ABL) from the common edible mushroom (Agaricus bisporus) has a potent anti-proliferative effect without any apparent cytotoxicity. This unusual combination of properties prompted investigation of its mechanism of action. In contrast to soluble lectin, agarose-immobilized, and hence noninternalizable ABL had no effect on proliferation of HT29 colon cancer cells. Electron microscopy of HT29 cells incubated with fluorescein- and gold-conjugated ABL showed internalization of the lectin into endocytotic vesicles and multivesicular bodies. Confocal microscopy showed perinuclear accumulation of fluorescein isothiocyanate-conjugated lectin, which also inhibits HT29 cell proliferation, raising the possibility that the lectin might interfere with nuclear pore function. Transport of heat shock protein 70 into the nucleus in response to heat shock was blocked by preincubation of HT29 cells for 6 h with 40 micrograms/ml ABL. In digitonin-permeabilized cells, nuclear uptake of bovine albumin conjugated to a nuclear localization sequence (NLS)-containing peptide was also inhibited by a 15-min preincubation with 40-100 micrograms/ml ABL. In contrast, serum-stimulated nuclear translocation of mitogen-activated protein kinase, which is NLS-independent, was not affected by pretreatment of cells with the lectin. These results suggest that the anti-proliferative effect of ABL is likely to be a consequence of the lectin trafficking to the nuclear periphery, where it blocks NLS-dependent protein uptake into the nucleus.

Adult↗