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Biomedical subjects

A Williams

Publications and source records attributed to A Williams.

At least 469 records · Page 26Linked to original sources

Towards a typology of general practitioners' attitudes to general practice.

Current knowledge about the origins of variations in general practitioners' (GPs') prescribing and referral behaviour is limited. Differences are as yet unexplained by demographic factors such as list size or geographic location. Drawing on social psychological theory it is suggested that attitudes towards general practice held by GPs may be predictive of GP behaviour. A classification of GP types on the basis of expressed attitudes may represent the first step towards this goal. This research demonstrates that GPs in Avon have identifiable attitudes to general practice which can be classified into separate types. Uses of such a classification and implications for further research are also discussed.

Adult↗

Infection during chronic epidural catheterization: diagnosis and treatment.

A potentially serious complication of long-term epidural catheterization in cancer patients is infection. The early signs of infection were studied in 350 patients in whom long-term epidural catheters were inserted. Three areas of the catheter track were found to be involved; exit site and superficial catheter track infection, and epidural space infection. The authors identified the early signs of infection in each area and the progress of the infection from the deep track to include the epidural space in four of these patients. All 19 patients who developed deep track or epidural infections were successfully treated with antibiotics and catheter removal. None of the patients required surgery for spinal cord decompression. Catheters were replaced in 15 of the 19 treated patients who requested them after treatment with no recurrent infections. It was concluded that use of long-term epidural catheterization is associated with a definable epidural infection rate. The use of epidural opioid analgesia is an effective and safe means of obtaining pain relief for terminally ill patients when patients are monitored for possible infection and receive prompt treatment when the diagnosis is established.

Analgesia, Epidural↗

Effects of chain-length and unsaturation on affinity and selectivity at muscarinic receptors.

1. Lengthening the chain in diphenylacetylcholine decreases affinity for muscarinic cholinoceptors in guinea-pig ileum. Diphenylacetoxypropyldimethylamine and its quaternary trimethylammonium salt are roughly equiactive: the dimethylamine and the piperidine have some selectivity for ileum compared with atria, but are not as active nor as selective as 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) methobromide (MeBr). With the weaker diphenylacetoxybutyl compounds the base is more active than the quaternary salt. 2. The diphenylacetoxybutyl-, cis-butenyl and trans-butenyl compounds have similar affinities. The quaternary salts are less active than the tertiary bases, but they are less selective than the butynyl analogues studied in earlier work. 3. 1,1-Diphenyl-1-hydroxy-2,4-hexadiynyl dimethylamine and its trimethylammonium salt are inactive in concentrations below 100 microM, as are the (+)-camphor-sulphonyl ester of 4-hydroxy-N-methyl piperidine and its methiodide. The (+/-)-phenylcyclopentylacetyl ester of 4-hydroxy-N-methylpiperidine methobromide is more active than its cyclohexyl analogue and than 4-DAMP MeBr but it is less selective than 4-DAMP MeBr. 4. The high selectivity of p-fluoro-hexahydrosila-diphenidol is confirmed but this compound has relatively low affinity (for ileum log K = 7.8). 5. The results indicate steric constraints to binding at muscarinic receptors which could be used to check molecular modelling of the receptor based on its known amino acid sequence. The group binding the charged nitrogen is probably at the mouth of a cavity which can accommodate two large rings (as in 4-DAMP MeBr) but with a depth less than about 7 A so that the rod-like hexadiynes cannot fit. Differences between types of receptor may only involve small changes in geometry secondary to differences in amino acids not directly involved in binding and the production of selectivity depends upon finding substituents which interfere with binding more at one type of receptor than at another.

Animals↗

Phase-variable lipopolysaccharide structures enhance the invasive capacity of Haemophilus influenzae.

Genes necessary for the expression and phase variation of lipopolysaccharide epitopes of a virulent Haemophilus influenzae type b isolate (RM.7004) are contained within two chromosomal loci designated lic-1 and lic-2. Mutations were introduced into both lic-1 and lic-2, and the virulence of the double mutant was compared with that of the wild type in infant rats. These mutations in RM.7004 resulted in a significantly reduced incidence of bacteremia following intranasal inoculation, although nasopharyngeal colonization was similar for the mutant and wild-type strains. In contrast, no differences in bacteremia were observed when the mutant and wild-type strains were inoculated intraperitoneally.

Animals↗

A study of the causes of non-compliance by patients prescribed eyedrops.

An investigation into the causes of non-compliance by patients using eyedrops has been undertaken by questionnaire, ability tests, and by tests on eyedrop bottles. The results indicate a high prevalence of non-compliance, compounded by an inability adequately to instill a drop into the eye. About half the patients had difficulty aiming the drop, and other problems including squeezing the bottle, blinking, and seeing the tip of the bottle. Ability tests included a measurement of the grip strength of patients to complement measurement of the force required to expel a drop from a bottle. Some patients, particularly those with arthritis, could not generate enough force to squeeze a bottle. These same patients also had difficulty with the other movements required to administer drops. While some attempts have been made to produce devices to assist with eyedrops which can improve the aim of the patient, none give assistance in expelling a drop. An additional problem found was the reluctance of patients to admit to medical staff that they experienced any difficulty with their drops.

Adolescent↗

Immunohistochemical and electron microscopic findings in benign fibroepithelial vaginal polyps.

Eleven classic benign "fibroepithelial polyps" of the vagina were examined using a panel of immunocytochemical agents. Two were also examined electron microscopically. In all cases the stellate and multinucleate stromal cells characteristic of these lesions stained strongly for desmin, indicating muscle intermediate filament production. In common with uterine fibroleiomyomata, numerous mast cells were also often seen. Myoglobin staining was negative. Electron microscopical examination confirmed that the stromal cells contained abundant thin filaments with focal densities and also showed the ultrastructural features usually associated with myofibroblasts. It is concluded that these tumours would be better designated polypoid myofibroblastomas in view of the above findings.

Adult↗

Prioritising waiting lists.

The 'top 22' patient conditions on the general surgical waiting list at Guy's Hospital were rated independently by five general surgeons. Each surgeon estimated the peri-operative mortality rates associated with each treatment; the proportion of patients who failed to benefit; the effect of successful treatment on life expectancy and on the patients' quality of life. the mean values were used to estimate the expected net benefits (in terms of quality-adjusted life-years) from treatment one year earlier than might otherwise have been the case. These benefits were then related to the operating times and length of stay associated with each treatment; this identified which treatments offered the greatest benefit per unit of each constrained resource. Of all conditions examined anal fissures where shown to be the least resource intensive in relation to the benefits generated, whilst varicose veins and epigastric hernias proved otherwise. For the full potential of this approach to be realised it needs to be repeated in other places and in other specialties. It nevertheless offers a more rational basis for interpreting waiting list data than presently exists and by using the short-cut methods is a relatively cheap way of generating much useful data.

Data Collection↗

Xamoterol in the treatment of orthostatic hypotension associated with multiple system atrophy (Shy-Drager syndrome).

The effect of xamoterol on the orthostatic hypotension associated with Shy-Drager syndrome was investigated in three patients. Intra-arterial blood pressure was measured during a control period and during treatment with xamoterol, both in a cardiovascular investigation laboratory and for 24 h of unrestricted activity using portable apparatus. Xamoterol lessened the total number of symptomatic episodes of orthostatic hypotension by 67 per cent. Average untreated 24-h intra-arterial blood pressure was 132/78 mmHg; during treatment with xamoterol it rose to 138/90 mmHg. However episodes of severe hypertension (defined as a systolic intra-arterial blood pressure above 200 mmHg) were more frequent with xamoterol. Although xamoterol attenuated orthostatic hypotension, careful monitoring of ambulatory blood pressure may be necessary, particularly at the start of treatment, because of the development of severe supine hypertension. Intravenous test doses of xamoterol did not predict either the attenuation of orthostatic hypotension or the development of supine hypertension in all patients.

Adrenergic beta-Agonists↗

Spanish experience with teicoplanin.

Teicoplanin, a narrow spectrum glycopeptide antibiotic was prospectively evaluated in an open, non-comparative manner in three Spanish university hospitals. A total of 65 patients were treated (25 females and 40 males: median age 45 years) for the following severe infections: endocarditis (5), bone and joint (9), lower respiratory (6), septicaemia (21), skin and soft tissue (13) and other miscellaneous infections (11). The median dose given was 6.8 mg/kg (range 1.0-15.1 mg/kg), for a median duration of 12 days. A total of 70 organisms were isolated, of which the most common was Staphylococcus aureus, followed by coagulase-negative staphylococci. Of these 70 organisms, 44 were eliminated by teicoplanin therapy, while 10 organisms persisted. Clinical cure was considered to have been achieved in 75% of patients, while 11% showed some improvement, leaving 11% in whom therapy had failed. The safety of teicoplanin was considered to be acceptable, only 16 out of 65 patients experiencing one or more adverse events. Of 23 adverse events, two were described as severe, the remainder being either moderate or mild. No effects due to age or dose on the safety of teicoplanin were noted. These results are in keeping with those previously reported by other groups in Western Europe, and confirm the good safety profile of teicoplanin at a dose of 6 mg/kg. Further studies are now needed to compare teicoplanin with standard antibiotic regimens.

Adolescent↗

Alpha 2-adrenergic receptor stimulation mobilizes intracellular Ca2+ in human erythroleukemia cells.

Human erythroleukemia cells are a model system for studies of alpha 2-adrenergic receptors and their coupling to inhibition of adenylate cyclase (McKernan, R. M., Howard, M. J., Motulsky, H. J., and Insel, P. A. (1987) Mol. Pharmacol. 32, 258-265). Using Fura-2, we show that alpha 2-adrenergic receptor stimulation also increases intracellular Ca2+ in these cells by 80-250 nM. Although epinephrine only inhibited forskolin-stimulated cAMP generation when beta-adrenergic receptors were blocked, the Ca2+ increase was not affected by beta-adrenergic receptor blockade. The Ca2+ increase was not affected by forskolin or 8-bromo-cAMP. Thus, alpha 2-adrenergic receptors independently couple to elevation of intracellular Ca2+ and adenylate cyclase inhibition. Chelating all extracellular Ca2+ did not reduce the response, demonstrating mobilization of intracellular, rather than influx of extracellular Ca2+. The epinephrine-stimulated Ca2+ mobilization occurred prior to any detectable increase in inositol-(1,4,5)-trisphosphate. It was abolished by pretreatment with pertussis toxin (which blocks some G protein-mediated processes), but not by aspirin and indomethacin (which inhibit cyclooxygenase), nordihydroguaiaretic acid (which inhibits lipoxygenase), or Na+-free buffer (to block any Na+H+ exchange). We conclude, therefore, that alpha 2-adrenergic receptors on human erythroleukemia cells couple to mobilization of intracellular Ca2+ via a (pertussis toxin-sensitive) G protein-mediated mechanism that is independent of inhibition of adenylate cyclase.

Adrenergic alpha-Agonists↗

Studies of lectin binding to the human cervix uteri: I. Normal cervix.

Lectins of Bauhinia purpurea (BPA), Canavalin ensiformis (Con A), Griffonia simplicifolia I (GS I), Griffonia simplicifolia II (GS II), Maclura pomifera (MPA), Arachis hypogaea (PNA), Glycine max (SBA), Ulex europaeus I (UEA I) and Triticum vulgaris (WGA) were used to evaluate cell surface carbohydrates in formalin-fixed paraffin-embedded tissue sections of normal human cervix uteri. Consistent patterns of staining of the squamous epithelium were obtained in all 30 cases with BPA, GS II, MPA, PNA, SBA and WGA. A variable distribution of lectin binding was seen in squamous epithelium with Con A, GS I and UEA I. The patterns of GS I and GS II binding reflected squamous epithelial maturation. Columnar epithelium did not stain with GS II, stained variably with Con A, and stained consistently with the remaining seven lectins in all cases. No association between lectin binding and blood group or phase of the menstrual cycle was found. These findings may be used as a baseline for evaluation of lectin binding in both preinvasive and invasive lesions of the cervix uteri.

Adult↗

Studies of lectin binding to the human cervix uteri: II. Cervical intraepithelial neoplasia and invasive squamous carcinoma.

The cell surface carbohydrate profile of formalin-fixed paraffin-embedded tissue sections of neoplastic cervical squamous epithelium was evaluated using lectins of Bauhinia purpurea (BPA), Canavalin ensiformis (Con A), Griffonia simplicifolia I (GS I), Griffonia simplicifolia II (GS II), Maclura pomifera (MPA), Archis hypogaea (PNA), Glycine max (SBA), Ulex europaeus I (UEA I) and Triticum vulgaris (WGA). Three lectins (BPA, Con A and PNA) showed a similar pattern of staining in both normal squamous epithelium and in cervical intraepithelial neoplasia (CIN). Variable alterations were seen in lectin-binding patterns in CIN with seven lectins (GS I, GS II, MPA, PNA, SBA, UEA I and WGA). A significant difference was seen between the intensity of staining of normal squamous epithelium and CIN with all lectins except WGA. The alteration in GS II-binding pattern and intensity was significantly related to grade of CIN. No correlation was found between lectin binding and the presence of koilocytes in squamous epithelium. Cases of invasive squamous carcinoma showed a heterogeneous lectin-binding pattern and no significant association was found between lectin binding and tumour differentiation of patient survival. These results indicate that neoplasia in cervical squamous epithelium is associated with alterations in terminal alpha-Man residues, alpha- and beta-GalNAc residues, alpha- and beta-GlcNAc residues, alpha- and beta-Gal residues, and alpha-Fuc-containing residues, present in the outer parts of both N-linked and O-linked glycoconjugates. The implications of these findings are discussed.

Carbohydrates↗

Setting up an HIV screening program.

Human immunodeficiency virus-1 (HIV-1) screening programs currently are based primarily on the detection of specific HIV-1 antibodies by the commercially available enzyme immunoassay (EIA) combined with highly specific confirmation procedures. Factors to be considered in establishing a screening program include test performance characteristics, economy, confidentiality and notification procedures, legal and regulatory issues, proficiency and quality control measures, and laboratory safety. Commercial EIA screening in conjunction with a licensed Western blot assay permits the classification of all but a few serum samples into HIV-1-positive and HIV-1-negative categories. The occasional indeterminate results often can be resolved by following a defined retesting/resampling algorithm or by using research-level test procedures that may become available for diagnostic use in the future. Although screening of patient populations with an increased risk of HIV-1 exposure will improve the predictive accuracy of an initial screening assay, confirmation testing should nonetheless be performed for all EIA reactive sera regardless of the source. Local HIV-1 screening programs that meet minimum-volume requirements can result in considerable savings and flexibility for a moderate-size institution. However, before this type of program is undertaken, numerous technical and ethical considerations need to be addressed.

Algorithms↗