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Biomedical subjects

D R Webb

Publications and source records attributed to D R Webb.

At least 19 recordsLinked to original sources
PubMed2001

Comparison of once-daily to twice-daily treatment with mometasone furoate dry powder inhaler.

BACKGROUND: Once-daily dosing with an effective inhaled corticosteroid (ICS) would likely enhance compliance and, therefore, aid in the management of asthma. OBJECTIVE: Several once-daily dosing regimens of mometasone furoate (MF) administered by dry powder inhaler (DPI) were compared with a twice-daily dosing regimen in 286 patients with mild to moderate persistent asthma who were previously being treated with ICS. METHODS: During a 2-week open-label phase, patients received MF-DPI, 200 microg twice daily. They were then randomized to continue MF-DPI, 200 microg twice-daily treatment or to receive MF-DPI, 200 microg once daily in the morning (AM), 200 microg once daily in the evening (PM), 400 microg once daily AM, or placebo as part of the 12-week, double-blind phase. The primary efficacy variable was the mean change from the baseline to endpoint (last evaluable observation) for FEV1. RESULTS: Once-daily MF-DPI, 400 microg, AM maintained FEV1, and morning peak expiratory flow rate, FVC, FEF25%-75%, and asthma symptom scores, at levels similar to those for MF-DPI, 200 microg twice daily and significantly better than placebo. Once-daily MF-DPI, 200 microg, PM was effective in maintaining pulmonary function, but was less effective on other efficacy measures. In comparison to the other MF-DPI groups, once-daily MF-DPI, 200 microg, AM was not as effective overall. The incidence of local adverse events, including oral candidiasis, was low with all dosages. CONCLUSIONS: Once-daily MF-DPI, 400 microg, AM was as effective as MF-DPI, 200 microg twice daily, whereas once-daily MF-DPI, 200 microg, was more effective when administered in the evening compared with morning, for patients receiving ICS therapy. Once-daily dosing offers an effective and convenient treatment that could aid compliance in the treatment of asthma.

Administration, Intranasal↗
PubMed2001

Use of a computer-controlled bipolar diathermy system in radical prostatectomies and other open urological surgery.

BACKGROUND: Ligasure is a computer-controlled bipolar diathermy system, designed to optimally seal vessels < or = 7 mm in diameter. The aim of the present study was to evaluate its application to open urological surgery. METHODS: The Ligasure device was used in 32 consecutive open surgical cases, including 25 radical prostatectomies, five radical nephrectomies, one partial nephrectomy and one nephro-ureterectomy. All procedures were performed using standard surgical techniques, with the exception that the Ligasure device was used for haemostasis. This included pelvic lymphatics and prostatic, adrenal, gonadal and aberrant obturator vessels, as well as vessels associated with the ureter, vasa, seminal vesicles, peri-renal fat, peritoneum and peri-adrenal tissues. Vessels > 7 mm in diameter, such as the renal artery, were ligated. In no patients were haemostatic clips used. RESULTS: In all procedures, vessels and other structures < 7 mm were successfully sealed using the Ligasure device. For some structures, such as the prostatic pedicles and the seminal vesicles, the Ligasure device was much easier to apply than haemostatic clips. Use of the Ligasure device reduced the operating time (mean: 113 min vs 135.5 min; P < 0.001) and blood loss (mean: 529 mL vs 642 mL; P < 0.02) for radical prostatectomies. No intraoperative or postoperative blood transfusions were required. There were no postoperative haemorrhages, lymph leakage or lymphocoeles. Median inpatient hospital stay was 7 days (range: 6-9 days) and no patients required readmission. CONCLUSION: The Ligasure, device was safe and easy to use in major urological procedures.

Aged↗
PubMed2000

Inhaled mometasone furoate reduces oral prednisone requirements while improving respiratory function and health-related quality of life in patients with severe persistent asthma.

BACKGROUND: Inhaled corticosteroid therapy in severe persistent asthma has been shown to reduce or eliminate oral corticosteroid (OCS) use while retaining effective asthma control. OBJECTIVE: We sought to evaluate the ability of mometasone furoate (MF) delivered by means of dry powder inhaler to reduce daily oral prednisone requirements in OCS-dependent patients with severe persistent asthma. METHODS: We performed a 12-week, double-blind, placebocontrolled trial (21 centers, 132 patients) comparing 2 doses of MF (400 and 800 microg administered twice daily) with placebo, followed by a 9-month open-label phase in which 128 patients received treatment with MF. RESULTS: At the endpoint of the double-blind trial, MF 400 and 800 mg twice daily reduced daily OCS requirements by 46.0% and 23.9%, respectively, whereas placebo increased OCS requirements by 164.4% (P <.01). Oral steroids were eliminated in 40%, 37%, and 0% of patients in the MF 400 and 800 mg twice daily and placebo groups, respectively. Pulmonary function and quality of life significantly increased for MF-treated patients. Further reductions in OCS requirements were achieved with long-term MF treatment in the open-label phase. CONCLUSION: MF inhaled orally as a dry powder is an effective alternative to systemic corticosteroids in patients with severe persistent asthma.

Administration, Inhalation↗
PubMed2000

CT analysis of caliceal anatomy in the supine and prone positions.

PURPOSE: To assess the effect of patient positioning on the position of the kidneys and their consequent projection onto plain radiographs, thus ascertaining the need for special preoperative imaging. PATIENTS AND METHODS: Fourteen patients were studied by obtaining fine (5-mm)-cut contrast-enhanced CT scans in the pyelogram phase in both the supine and prone position. The orientation of the kidneys relative to the midsagittal plane of the body and the orientation of the anterior and posterior calices relative to the axis of the kidney were measured from hardcopy images. Comparison was made between prone and supine positions for left and right kidneys separately, as well as overall. RESULTS: The position of the patient had a small effect on the orientation of the kidneys, with the mean angle changing from 56.6 degrees when supine to 61.6 degrees when prone (p < 0.05). However, no significant change in caliceal orientation or the relative projection of the anterior and posterior calices occurred as a result. CONCLUSION: There is no need to carry out special preoperative imaging in the operative or prone position.

Adult↗
PubMed1999

Selective A1-adenosine receptor antagonists identified using yeast Saccharomyces cerevisiae functional assays.

Evaluation of a biased "library" of pyrrolo[2,3-d]pyrimidines using yeast-based functional assays expressing human A1- and A2a-adenosine receptors, led to the A1 selective antagonist 4b. A direct correlation between yeast functional activity and binding data was established. Practical compounds with polar residues at C-4 of the pyrrolopyrimidine system required H-bond donor functionality for high potency.

Binding, Competitive↗
PubMed1999

Assessment of phylloquinone and dihydrophylloquinone dietary intakes among a nationally representative sample of US consumers using 14-day food diaries.

OBJECTIVE: To estimate dietary intakes of phylloquinone and dihydrophylloquinone in a representative sample of the American population using 14-day food diaries. DESIGN: Vitamin K food composition data were applied to 14-day food diaries completed by a nationally representative sample of approximately 2,000 households that participated in a Market Research Corporation of America menu census survey between July 1991 and June 1992. Dietary intakes were estimated for phylloquinone and dihydrophylloquinone. SUBJECTS: Subjects were 4,741 men, women and children with demographic characteristics similar to those of the US census population. STATISTICAL ANALYSIS PERFORMED: Descriptive statistics and 2-sample t tests. RESULTS: Mean reported intakes of phylloquinone among adults increased with age. Men and women in the 18- to 44-year-old groups reported mean phylloquinone intakes below the current Recommended Dietary Allowance for vitamin K. Of all study participants, 99.3% reported consumption of dihydrophylloquinone during the 14 days of diet recording; reported intakes peaked before the age of 6 years; after the age of 6 years intakes were constant. APPLICATIONS: The Market Research Corporation of America data provide a reference range for dietary intakes of 2 forms of vitamin K in the US diet: phylloquinone and dihydrophylloquinone. Given the putative role of vitamin K in bone mineralization, low intakes of phylloquinone reported among young adults highlight the need to educate the US population about the requirement for and sources of vitamin K. The abundance of dihydrophylloquinone in the US diet suggests the need for study of its biological activity relative to phylloquinone.

Adolescent↗
PubMed1999

Fluticasone propionate powder: oral corticosteroid-sparing effect and improved lung function and quality of life in patients with severe chronic asthma.

BACKGROUND: Many patients with severe asthma are dependent on oral corticosteroids for maintenance control of their disease. Treatments that allow patients to be weaned off oral corticosteroids may help to minimize the risk of side effects associated with their chronic use. OBJECTIVE: This study evaluated whether inhaled fluticasone propionate powder could maintain pulmonary function while reducing the dose of oral prednisone in patients with chronic, severe asthma. METHODS: Oral prednisone-dependent (5 to 40 mg/day) adolescents and adults with asthma (n = 111; mean FEV1 = 61% of predicted value) were randomized to placebo or twice daily fluticasone propionate 500 or 1000 microg administered by means of a multidose powder inhaler for 16 weeks in a double-blind, parallel-group study. Patients underwent controlled prednisone reduction on the basis of predetermined asthma stability criteria. RESULTS: Oral prednisone was eliminated by 75% and 89% of patients in the twice daily 500 and 1000 microg fluticasone propionate groups, respectively, versus 9% of the placebo group (P <.001). FEV1, morning and evening peak expiratory flow, asthma symptoms, albuterol use, and nighttime awakenings improved with fluticasone propionate treatment, achieving statistical significance (P </=.009) primarily in the 1000 microg twice daily group. Hypothalamic-pituitary-adrenal axis suppression observed at baseline improved when patients were weaned off oral prednisone to fluticasone propionate. Adverse events ascribed to drug treatment were primarily topical effects of inhaled corticosteroids or those associated with prednisone withdrawal. Patient quality of life assessed by means of the Asthma Quality of Life Questionnaire was clinically and significantly improved after fluticasone propionate treatment (P </=.003). CONCLUSION: Fluticasone propionate powder (500 or 1000 microg twice daily) effectively improved lung function, adrenal function, and asthma-specific quality of life in patients with severe chronic asthma previously treated with oral prednisone while allowing most patients to be weaned off oral corticosteroid therapy.

Administration, Inhalation↗
PubMed1999

Percutaneous management of caliceal diverticular calculi: technique and outcome.

OBJECTIVE: Symptomatic renal calculi found within caliceal diverticula are difficult to treat. We present a single-surgeon cohort of 21 consecutive patients undergoing percutaneous treatment of stones within caliceal diverticula over a 12-year period. PATIENTS AND METHODS: Each patient was managed by a one-stage percutaneous nephrolithotomy (PCNL). The majority of diverticula were situated at the upper pole. Access was gained via a direct target puncture, a Y puncture from a parallel calix, or through the diverticular stalk in the neighboring calix. The approach was commonly supracostal. A single-stage dilator was used to establish the track. Stones were removed intact or fragmented with ultrasonic lithotripsy, and the diverticular necks were treated with endoscopic division or dilation and splinted with a 22F nephrostomy tube for several days. RESULTS: Total stone clearance was obtained by PCNL alone in 95% of cases. The only case with incomplete clearance was cleared successfully with shockwave lithotripsy (SWL). Twenty patients were assessed with an intravenous urogram at 3 months and then annual plain films and clinical assessment. Further imaging was performed in selected cases. The diverticula were obliterated or had improved drainage in 85% of assessable cases. Three patients developed recurrent stones and were treated with SWL, laparoscopic diverticulectomy, on partial nephrectomy. One further patient required partial nephrectomy for poor drainage and ongoing pain. Of the 21 patients, 17 have remained stone, symptom, and infection free with clinical and radiologic follow-up ranging from 6 months to 12 years. CONCLUSIONS: This series demonstrates that percutaneous surgery can clear calculi from caliceal diverticula and, in most cases, correct or remove the underlying anatomic abnormality.

Adult↗
PubMed1998

Deletion of signaling molecule genes resembling the cytoplasmic domain of Igbeta in autoimmune-prone mice.

The P8.6 gene is encoded upstream of the mouse TCR Valpha1 gene in the anti-sense strand and its gene product contains the proline-rich region and tyrosine-isoleucine (Y-I) motif, which are consensus sequences for the SH2 and SH3 binding motifs respectively. It was found that this protein is highly homologous to Igbeta. We also found that the P8.6 protein associates with a 170 kDa phosphorylated protein in vivo. To examine the polymorphism of the P8.6 gene, we carried out a single-strand conformation polymorphism analysis and found that the P8.6 gene comprises a family of at least 13 independent genes arising from single or multiple mutations. The mutated P8.6 gene with the Y-L motif was deleted, especially in NZW and BXSB mice, whereas normal BALB/c mice have a P8.6 gene bearing both the Y-I and Y-L motifs, suggesting a dysregulation in signaling through the B cell receptor or TCR in these two autoimmune mice. Functional analysis using transfectant cells carrying P8.6-1 (Y-I motif) and P8.6-3 (Y-L motif) clearly demonstrated that P8.6-3 gene inhibited the signal transduction upon the stimulation of ionomycin and cell growth. The TANYSNI sequence has been proposed as the immunoreceptor tyrosine-based inhibitory motif, this motif is replaced by AANYSNI in the NZW mice. In conclusion, some P8.6 are deleted in particular autoimmune-prone mice.

Amino Acid Sequence↗
PubMed1998

Management of invasive penile cancer by synchronous penile lengthening and radical tumour excision to avoid perineal urethrostomy.

BACKGROUND: Adequate excision of invasive penile carcinoma often results in a penile stump of inadequate length to control the urinary stream. A simple technique to lengthen the stump and avoid urethrostomy is described here. METHODS: Additional corporal length is gained by dividing the dorsal suspensory ligaments through a transverse lower abdominal skin incision. Skin length is gained by vertical closure of this incision. RESULTS: This technique has been successful in two cases where the stump length after partial penectomy was borderline. Each patient has a functional stump with satisfactory cosmesis. CONCLUSIONS: In selected cases this technique may avert the need for perineal urethrostomy after adequate excision of a penile cancer.

Carcinoma, Squamous Cell↗
PubMed1997

Estimated consumption and eating frequency of olestra from savory snacks using menu census data.

Potential chronic (14-d average) and acute (single-day) estimated daily intakes (EDI) were computed for olestra, a fat replacement intended for use in preparing savory snacks. The EDI were computed from eating occasions reported during a 14-d Menu Census survey among 4741 consumers; values were increased by 10% for conservatism. The eating occasions included all meals and in-between meal occasions eaten at home or away. Data from only those individuals who ate savory snacks at least once during the 14 d were used; this included 3820 individuals (81% of the sample) and represented a total of 16,067 eating days (24% frequency). The estimated mean chronic intake ranged from 1.8 to 4.7 g/d, depending on age and gender; at the 90th percentile, the range was 4.1-11.0 g/d. For all ages and both genders, the estimated mean intake was 3.1 g/d. Estimated acute intakes at the mean and 90th percentile ranged from 5.5 to 16.5 g/d and from 10.2 to 24.0 g/d, respectively, depending on age and gender. For all ages and both genders, the estimated mean intake was 10.2 g/d. The lack of parity in the chronic and acute intake estimates indicates that savory snacks are not eaten on a daily basis by the majority of snack eaters. The survey data were analyzed to understand the potential temporal eating patterns of olestra from savory snacks. When snacks were consumed, on average, 69% of the eating occasions were with main meals and 31% were between meals. Savory snacks did not contribute a major fraction of total food to the diet; only 7 and 18% of main meals contained a savory snack food at the 50th and 90th percentile, respectively. For the 50th-percentile consumer (all ages, both genders), savory snacks were eaten four times during the 14-d survey period, and the eating occasions occurred on 3 d. Comparable results for 90th-percentile consumers were 10 eating occasions and 8 eating days.

Adolescent↗
PubMed1997

Evaluation of the potential for olestra to affect the availability of dietary phytochemicals.

It has been hypothesized that phytochemicals found in fruits and vegetables are responsible for the inverse association observed between diets high in fruits and vegetables and risk of certain chronic diseases and cancer. This paper assesses the potential for olestra to affect the absorption of dietary phytochemicals and estimates the effect of olestra on the availability of carotenoids when olestra-containing snacks and foods containing carotenoids are eaten in free-living diets. Experimental data compiled on the effects of olestra on the availability of 29 compounds, mainly nutrients and oral medications, showed that olestra affects the availability of only molecules having octanol-water partition coefficients greater than approximately 7.5. Partition coefficients compiled for 382 dietary phytochemicals showed that only two classes of phytochemicals, phytosterols and carotenoids, contain molecules with octanol-water partition coefficients in the range in which olestra could potentially affect bioavailability. The potential effect on the bioavailability of phytosterols would be <10% and would not be expected to be of concern inasmuch as the hypothesized benefit of consuming pharmacological amounts of phytosterols is to reduce cholesterol availability, a function also of olestra. A 5.9% reduction in the average effective beta-carotene intake was calculated for individuals eating olestra-containing snack foods in free-living diets. The calculation was made by assuming that carotenoid bioavailability would be reduced to the extent measured in human clinical studies each time olestra-containing snacks and carotenoid-containing foods are eaten together and that all snacks eaten are made with olestra. Among individuals with low carotenoid intakes (the lowest 10%) the calculated reduction was 6.0%; for heavy snack eaters (the top 10%) it was 9.5%. These effects on carotenoid bioavailability are similar to those that can occur with other dietary factors.

Adolescent↗
PubMed1997

Efficacy of inhaled fluticasone propionate in asthma results from topical and not from systemic activity.

The objective of this study was to determine whether the therapeutic benefits of inhaled fluticasone propionate are mediated through topical or systemic effects. Two hundred seventy-four patients with asthma receiving beclomethasone dipropionate or triamcinolone acetonide during a 2-wk, single-blind, run-in period were randomized to inhaled fluticasone propionate powder 100 or 500 micrograms twice daily, oral fluticasone propionate 20 mg once daily, or placebo during a 6-wk treatment period. Patients receiving inhaled fluticasone propionate had a significantly greater probability of remaining in the study over time compared with patients receiving oral fluticasone propionate or placebo (p = 0.001). FEV1 and PEF rates at end point were significantly higher with inhaled fluticasone propionate treatment regimens than with oral fluticasone propionate (with the exception of PEF rates for inhaled fluticasone propionate 100 micrograms) or placebo treatments (p < or = 0.004). Systemic exposure to fluticasone propionate as assessed by trough plasma concentrations and/or 12-hr plasma concentration area under the curve analyses (AUC12) was higher with the oral fluticasone propionate than with the two inhaled fluticasone propionate treatment groups. The results of this study suggest that the therapeutic benefits of inhaled fluticasone propionate are mediated through topical effects in the lungs and not through systemic effects.

Administration, Inhalation↗
PubMed1996

Extraperitoneal laparoscopy: anatomical dissections with experimental balloon dilators.

OBJECTIVES: To develop balloon dilators in vitro and in cadavers and to evaluate the anatomy of the extraperitoneal spaces and their surroundings created by such balloons. MATERIALS AND METHODS: Balloons of three different materials (condoms, fingers of surgical gloves, whole surgical gloves and 'party' balloons) were tested in an in vitro study and compared with a prototype balloon dilator used in cadavers. The balloon dilators were used to create extraperitoneal spaces in the pelvic, the loin and the iliac regions through stab incisions. The incisions were extended after dilatation to examine the spaces created and the consequent anatomical changes. RESULTS: In vitro, all balloons were found to have capacities of more than 10 L, except that made from the finger of a surgical glove. Early rupture after insertion and during dilatation was a problem in condom and party balloons. In cadavers, there was good exposure of anatomical structures within the extraperitoneal spaces created. Reflections of peritoneum in the loin and the iliac regions were unmoved by balloon dilatation. CONCLUSIONS: The prototype balloon dilator possessed all the characteristics desired of an ideal instrument for creating extraperitoneal spaces. Good exposure of anatomical structures by the balloon dilators allows a minimal dissection in extraperitoneal laparoscopic procedures in the aforementioned regions. That the peritoneal reflection was unmoved despite adequate expansion of the balloons also means that the exact placement of secondary laparoscopic ports is crucial in preventing peritoneal and colonic trauma.

Catheterization↗
PubMed1996

Extraperitoneal laparoscopic caliceal diverticulectomy.

Three women with symptomatic stone-containing caliceal diverticula in the right kidney were treated by extraperitoneal laparoscopic diverticulectomy. The diverticula measured 31 x 21 mm, 15 x 12 mm, and 12 x 9 mm, with the calculi measuring 10 x 8 mm, 5 x 4 mm, and 6 x 6 mm, respectively. The site of the diverticulum was identified by the presence of a depression on the surface of the kidney. The diverticulum was marsupialized, the lining fulgurated, and in the second and third patients, a flap of Gerota's fascia and perirenal fat inserted. The mean operating time was 127 minutes. The mean postoperative analgesic requirement was six doses of pethidine (meperidine). The median time to drainage tube removal was 3 days, and the median time to discharge after surgery was 4 days. Complications were minimal. On follow-up, all patients were stone free and asymptomatic. The first patient had a slight recurrence of the diverticulum, measuring 15 x 7 mm. Laparoscopic caliceal diverticulectomy has been successful in three patients.

Adult↗
PubMed1995

Phenotypic identification of specific and nonspecific suppressor T-cell populations involved in the in vivo response to alloantigen.

The monoclonal antibody 984.D4.6 (ma984) has been previously shown to recognize antigen-specific suppressor T-cells in an in vitro alloantigenic mixed-lymphocyte response system. In addition, an antiserum generated in rabbits to the N-terminal sequence of the nonspecific suppressor factor SIRS (soluble immune response suppressor) has been shown to block the suppressive activity of nonspecific, concanavalin A-activated suppressor cells. In the present studies we have used these antibodies to investigate the development of T-suppressor activity in mice immunized with alloantigen. These studies demonstrate the development of two populations of suppressor cells, one of which is antigen nonspecific and inhibitable with anti-SIRS and a second that is antigen-specific and sensitive to removal by lysis with ma984 plus complement. These populations of suppressor cells arise well after the peak of cytolytic T-cell activity in response to alloantigen indicating asynchrony in the development of the immune response to alloantigen.

Animals↗
PubMed1995

A 69-kDa membrane protein associated with lipopolysaccharide (LPS)-induced signal transduction in the human monocytic cell line THP-1.

Lipopolysaccharide (LPS) triggers a wide range of cellular responses in mammalian cells. Several proteins, including CD14, have been reported to possess LPS binding capacity. However, the signal transduction molecule(s) and pathway(s) through which LPS induces cellular responses have not been identified. A rabbit antiserum (5299), which had been made against the N-terminal 20-amino-acid sequence of the cytokine, soluble immune response suppressor, unexpectedly activated the human monocyte cell line THP-1 as assessed by tumor necrosis factor (TNF alpha) production. Normal rabbit serum or IgG caused no TNF production, while antiserum 5299 induced TNF at a 1:10(4) dilution. The activity of antiserum 5299 was not due to endotoxin contamination, since antiserum 5299 contained less endotoxin than required for activation of THP-1 and the TNF-inducing activity disappeared when the antiserum was boiled. Moreover, the activity was recovered in purified immunoglobulin G fraction from the antiserum (5299 IgG). These results suggest that antiserum 5299 contains an antibody which recognizes a signal-transducing molecule. THP-1 desensitized by incubation with LPS for 24 hr could not respond to LPS or antiserum 5299 while responsiveness to phorbol ester remained, suggesting that the signals induced by the antiserum 5299 and LPS are transduced through at least a partially common pathway. Western blotting with antiserum 5299 showed a 69-kDa protein which rapidly appeared in Triton X-100-insoluble fraction after stimulation with LPS or 5299 IgG, suggesting an association of 69-kDa protein with the cytoskeleton. Furthermore, two mutant cell lines were isolated (T-15 and T-25) from gamma-irradiated THP-1 which lack responsiveness to LPS. In these mutant cell lines, the 69-kDa protein was not observed in Triton X-100-insoluble fraction after stimulation with LPS. It is proposed that this protein may play an important role in LPS-stimulated signal transduction.

Blotting, Western↗