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Biomedical subjects

S Hill

Publications and source records attributed to S Hill.

At least 127 records · Page 7Linked to original sources

Comparison between the phenotype and function of maturing dendritic cells from spleen and lymph nodes.

We compared the capacity of mature dendritic cells (DC) from lymph nodes and maturing DC from spleens in their capacity to stimulate responses to the small hapten picryl sulphonic acid (PIC) and to the same hapten conjugated to ovalbumin (PIC-OVA) and requiring processing. Surface expression of major histocompatibility complex (MHC) class II molecules, which are upregulated during maturation of splenic DC, were studied as an independent marker of maturation. Freshly isolated lymph node DC had a veiled appearance and high levels of class II expression. DC separated from suspensions of spleen cells expressed the DC-specific marker NLDC-145, but were small, had low levels of MHC class II molecules and expressed stem cell antigen. Those DC from spleen cells cultured for 24 and 48 hr showed the development of typical veiled DC morphology and high class II expression. Lymph node DC stimulated high levels of primary T-cell proliferation to PIC, but failed to stimulate primary responses to PIC-OVA. Splenic DC isolated immediately failed to stimulate primary responses to either antigen. More mature spleen DC stimulated responses both to PIC and PIC-OVA. Surprisingly, development of the capacity to stimulate responses to PIC preceded that of stimulating PIC-OVA responses. The capacity of the DC to process and present PIC-OVA was maintained during the culture period. The results indicate that both the form of the antigen and the source and maturity of the DC are critical in determining the responses stimulated in T lymphocytes.

Animals↗

Feasibility of national benchmarking of patient satisfaction with Australian hospitals.

PURPOSE: This paper discusses the feasibility of developing national benchmark questions on patient satisfaction with hospital care in Australian hospitals. The research was undertaken for the Australian government under the National Health Outcomes Programme. DATA SOURCES AND SELECTION: The paper draws on a review of research with consumers to identify issues of importance to them about hospital care. The Australian sources were reports by consumer and community organizations, research reports by hospitals, governments and academics, and data from complaints authorities. The emphasis was on consumers' own views. The main debates on patient satisfaction methodology were reviewed. Published material from the USA and Britain highlighting organizational policy issues was reviewed, as well as literature on benchmarking. Material was obtained through journal searches and identification of organizations which undertake consumer-oriented or service development research. CONCLUSIONS: The paper argues that national benchmarking of patient satisfaction is not reliable because patient satisfaction is a poorly understood concept and not a unitary concept. Also, the paper argues that benchmarking is about processes, and that the link between survey results and hospital processes is not well researched or understood. While patient satisfaction surveys appear to promote consumer perspectives, they remain caught within a passive approach to consumer participation in shaping service development and improving the quality of hospital care. The task of government is to mandate consumer feedback, resource the development of expertise and technologies, trial and evaluate approaches to obtaining feedback, disseminate research and effective models, and resource consumer organizations to be participants at all stages. This is described as providing the resources for benchmarking at local levels.

Australia↗

The kinetics of skin thinning induced by topical fluticasone propionate 0.05% cream in volunteer subjects.

Fluticasone propionate (FP) 0.05% (CutivateTM) cream is a novel corticosteroid used for the treatment of corticosteroid-responsive dermatoses. To date there are no published data concerning its effect on cutaneous atrophy. This randomized, double-blind study of 40 volunteer subjects was performed to investigate the kinetics of skin thinning induced by topical 0.05% FP cream vs. placebo after once-daily application for 2-8 weeks. The results of this study showed no significant effect on the skin thickness of subjects after 8 weeks' treatment with 0.05% FP cream compared with placebo.

Administration, Cutaneous↗

Ultrasound: a noninvasive screening test for detrusor instability.

OBJECTIVE: To determine whether transvaginal ultrasound measurement of bladder wall thickness can be used as a screening test for detrusor instability in women with urinary symptoms. DESIGN: A blinded prospective study. SETTING: A London teaching hospital. PARTICIPANTS: One hundred and eight-four symptomatic women presenting to a urodynamic clinic. MAIN OUTCOME MEASURE: The detection of detrusor instability by means of videocystourethrography (VCU) and ambulatory urodynamics in women with a mean bladder wall thickness of greater than 5 mm measured by transvaginal ultrasound. RESULTS: One hundred and eight women had a mean bladder wall thickness of greater than 5 mm. Ninety-four percent (102) of these women had detrusor instability either when undergoing VCU or ambulatory urodynamics. Seventeen women had a bladder wall thickness of less than 3.5 mm of whom three were found to have detrusor instability on VCU. CONCLUSION: The measurement of a mean bladder wall thickness greater than 5 mm with transvaginal ultrasound is a sensitive screening method for diagnosing detrusor instability in symptomatic women without outflow obstruction.

Adult↗

Is the short form 36 (SF-36) suitable for routine health outcomes assessment in health care for older people? Evidence from preliminary work in community based health services in England.

STUDY OBJECTIVE: To examine the short form 36 (SF-36) health status measure when used to assess older people's views of the outcome of community based health care. DESIGN: Completion of a structured questionnaire, before and after intervention alongside in-depth interviews with a subsample of the interviewees. SETTING: Community based continence and mental health services in two health authorities in the North West Health Region. PATIENTS: Forty seven older people newly referred to mental health services or continence services between December 1992 and April 1993 participated. MAIN RESULTS: The SF-36 showed minimal change over time for both patient groups. The more detailed in-depth interviews showed that people experienced positive changes and derived value from contact with services in a number of important ways. For many reasons these benefits were not reflected in their SF-36 scores. CONCLUSIONS: The SF-36 is not likely to be the "measure of choice" for this type of evaluation, particularly where it involves older patient groups who have high levels of comorbidity. The content of the SF-36 and its lack of detail for individual assessment of change means it masks rather than illuminates patients' views of outcome.

Aged↗

A preliminary study of flutamide, testolactone, and reduced hydrocortisone dose in the treatment of congenital adrenal hyperplasia.

Treatment outcome in congenital adrenal hyperplasia is often suboptimal due to hyperandrogenism, treatment-induced hypercortisolism, or both. As a new approach, we hypothesized that the effects of androgen could be blocked by an antiandrogen (flutamide) and an inhibitor androgen to estrogen conversion (testolactone), thus allowing the hydrocortisone dose to be reduced. We conducted a short term pilot study in 12 children with congenital adrenal hyperplasia in a randomised cross-over open design to determine whether flutamide, testolactone, reduced hydrocortisone dose, and fludrocortisone are more effective than hydrocortisone and fludrocortisone treatment in normalizing linear growth, weight gain, and bone maturation. Each regimen was administered for 6 months, with a 3-month washout period, consisting of hydrocortisone and fludrocortisone treatment, between regimens. Compared to hydrocortisone and fludrocortisone treatment, the regimen of flutamide, testolactone, reduced hydrocortisone dose (from 12.9 to 7.9 mg/m2 day), and fludrocortisone produced an increase in plasma 17-hydroxyprogesterone levels (P < 0.05) and a decline in urinary cortisol (P < 0.01), linear growth rate (-0.9 +/- 0.5 vs. 1.4 +/- 0.6 SD U; P = 0.003), weight velocity (-0.80 +/- 4.0 vs 0.6 +/- 0.4 SD U; P = 0.01), and bone maturation (0.6 +/- 0.6 vs. 1.4 +/- 0.9 yr bone age/yr chronological age; P = 0.02). Although no important adverse effects were observed, the known potential for flutamide-induced hepatotoxicity made frequent monitoring essential. We conclude that the regimen of flutamide, testolactone, reduced hydrocortisone does, and fludrocortisone improve the short term control of growth and bone maturation in children with congenital adrenal hyperplasia. Long term studies are required to determine whether this approach can improve these children's growth and development.

17-alpha-Hydroxyprogesterone↗

Waterborne cryptosporidiosis associated with a borehole supply.

From 1 April to 31 May 1993, 64 cases of cryptosporidiosis were diagnosed within one district health authority. Forty were classified as primary cases, 35 of whom were clustered in an area supplied by a discrete public water supply that supplied the majority of homes in a large town. Most of the water in this supply is abstracted from boreholes and some is filtered before distribution. Households that received mains water from this supply were 15 times more likely to be affected than households nearby that received water from other sources. A case control study demonstrated a dose response relationship between consumption of water obtained from the town supply and risk of illness. Very low concentrations of cryptosporidial oocysts were detected in the water supply on four occasions several weeks after the outbreak. Environmental investigation failed to reveal a likely mechanism for contamination of the water supply.

Adolescent↗

Comparing treatments.

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Clinical Trials as Topic↗

High-resolution solution structure of siamycin II: novel amphipathic character of a 21-residue peptide that inhibits HIV fusion.

The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has a valine residue at position 4. In both peptides, disulfide bonds link Cys1 with Cys13 and Cys7 with Cys19, and the side chain of Asp9 forms an amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50 mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers of cross peaks for a peptide of this size. We have used 335 NOE distance constraints and 13 dihedral angle constraints to generate an ensemble of 30 siamycin II structures; these have average backbone atom and all heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 A, respectively. The peptide displays an unusual wedge-shaped structure, with one face being predominantly hydrophobic and the other being predominantly hydrophilic. Chemical shift and NOE data show that the siamycin I structure is essentially identical to siamycin II. These peptides may act by preventing oligomerization of the HIV transmembrane glycoprotein gp41, or by interfering with interactions between gp41 and the envelope glycoprotein gp120, the cell membrane or membrane-bound proteins [Frèchet, D. et al. (1994) Biochemistry, 33, 42-50]. The amphipathic nature of siamycin II and siamycin I suggests that a polar (or apolar) site on the target protein may be masked by the apolar (or polar) face of the peptide upon peptide/protein complexation.

Amino Acid Sequence↗

Combined endoscopic ultrasound and stimulated biliary drainage in cholecystitis and microlithiasis--diagnoses and outcomes.

BACKGROUND AND STUDY AIMS: It is becoming increasingly evident from a number of studies that endoscopic ultrasound (EUS) is much more sensitive in the diagnosis of cholecystitis than transabdominal ultrasound (TUS). The present study was undertaken to further evaluate this relative sensitivity. PATIENTS AND METHODS: Sixty-six patients with biliary-type pain and a negative transabdominal ultrasound examination underwent combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD). Stimulated biliary drainage was obtained following intraduodenal infusion of magnesium sulfate or intravenous sincalide, a CCK analogue. EUS was considered positive if sludge or small stones were seen in the gallbladder. Stimulated biliary drainage was considered positive if calcium bilirubinate granules or cholesterol crystals were seen on microscopic examination of aspirated bile. RESULTS: At operation, 61 of the patients had cholecystitis documented histologically. Fifty-eight of the patients had gallbladder sludge or small stones on EUS. One patient had a negative EUS, but had calcium bilirubinate granules in the bile. Twenty-one patients were followed post-operatively for a period of seven to 17 months, with an average of 10.5 months. Nineteen patients (90.5%) remain free of biliary pain. CONCLUSIONS: Combined endoscopic ultrasound and stimulated biliary drainage (EUS/SBD) had a high sensitivity of 92.4% and a positive predictive value of 100% in the diagnosis of cholecystitis when transabdominal ultrasound was negative. A significant majority (90.5%) of patients with positive EUS/SBD who underwent cholecystectomy had resolution of their biliary pain.

Cathartics↗

On the clustered exchanges of the RecBCD pathway operating on phage lambda.

Lytic cycle crosses of Red- Gam- phage lambda were conducted in rec+ Escherichia coli carrying one or another plasmid with homology to lambda. Lambda x lambda recombinants and lambda x plasmid recombinants were formed by RecBCD-mediated recombination. We showed previously that the act of recombining with a plasmid alters the disposition of selected lambda x lambda exchanges. This work reports that the relationships between the lambda x plasmid and the lambda x lambda exchanges is unaltered by the removal from one lambda parent of the homology shared with the plasmid. This result supports our view that a reciprocal exchange, allowing for cointegrate formation, is associated with but mechanistically separable from a (presumably) nonreciprocal lambda x lambda exchange. The nature of this relationship is independent of lambda's Rap function, which is shown to alter the ratio of cointegrate formation (splices) to marker pick-up (patches) in lambda x plasmid recombination mediated by the RecBCD pathway.

Bacteriophage lambda↗

A Sorangium cellulosum (myxobacterium) gene cluster for the biosynthesis of the macrolide antibiotic soraphen A: cloning, characterization, and homology to polyketide synthase genes from actinomycetes.

A 40-kb region of DNA from Sorangium cellulosum So ce26, which contains polyketide synthase (PKS) genes for synthesis of the antifungal macrolide antibiotic soraphen A, was cloned. These genes were detected by homology to Streptomyces violaceoruber genes encoding components of granaticin PKS, thus extending this powerful technique for the identification of bacterial PKS genes, which has so far been applied only to actinomycetes, to the gram-negative myxobacteria. Functional analysis by gene disruption has indicated that about 32 kb of contiguous DNA of the cloned region contains genes involved in soraphen A biosynthesis. The nucleotide sequence of a 6.4-kb DNA fragment, derived from the region with homology to granaticin PKS genes, was determined. Analysis of this sequence has revealed the presence of a single large open reading frame beginning and ending outside the 6.4-kb fragment. The deduced amino acid sequence indicates the presence of a domain with a high level of similarity to beta-ketoacyl synthases that are involved in polyketide synthesis. Other domains with high levels of similarity to regions of known polyketide biosynthetic functions were identified, including those for acyl transferase, acyl carrier protein, ketoreductase, and dehydratase. We present data which indicate that soraphen A biosynthesis is catalyzed by large, multifunctional enzymes analogous to other bacterial PKSs of type I.

Actinomycetales↗

The oxygen affinity of cytochrome bo' in Escherichia coli determined by the deoxygenation of oxyleghemoglobin and oxymyoglobin: Km values for oxygen are in the submicromolar range.

Apparent oxygen affinities for Escherichia coli cells and membranes containing a terminal oxidase with only one type of ligand-binding heme, cytochrome o', were measured with oxyleghemoglobin and oxymyoglobin as sensitive oxygen reporters. Two Km values (0.15 to 0.35 microM and 0.016 to 0.085 microM) were detected, well below values determined for the purified oxidase by insensitive electrode methods.

Cytochrome a Group↗