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Biomedical subjects

S Sharp

Publications and source records attributed to S Sharp.

At least 37 records · Page 2Linked to original sources
PubMed1998

Cartilage protective agent (CPA) Ro 32-3555, a new matrix metalloproteinase inhibitor for the treatment of rheumatoid arthritis.

CPA was well tolerated at all dose levels (10-150 mg) following single oral dose administration to healthy male volunteers. There was no relationship between the intensity, duration and number of adverse events reported and the dose of CPA. There was a dose-related increase in exposure as measured by AUC0-infinity and Cmax. Administration of 10 mg CPA following food resulted in a delayed tmax, and a significant decrease in Cmax but not AUC0-infinity.

Adult↗
PubMed1998

Follow-up care in general practice of patients with myocardial infarction or angina pectoris: initial results of the SHIP trial. Southampton Heart Integrated Care Project.

OBJECTIVE: We aimed to assess the effectiveness of a nurse-led programme to ensure that follow-up care is provided in general practice after hospital diagnosis of myocardial infarction (MI) or angina pectoris. METHODS: We conducted a randomized controlled trial with stratified random allocation of practices to intervention and control groups within all 67 practices in Southampton and South-West Hampshire, England. The subjects were 422 adult patients with a MI and 175 patients with a new diagnosis of angina recruited during hospital admission or chest pain clinic attendance between April 1995 and September 1996. Intervention involved a programme of secondary preventive care led by specialist liaison nurses in which we sought to improve communication between hospital and general practice and to encourage general practice nurses to provide structured follow-up. The main outcome measures were: extent of general practice follow-up; attendance for cardiac rehabilitation; medication prescribed at hospital discharge; self-reported smoking, diet and exercise; and symptoms of chest pain and shortness of breath. Follow-ups of 90.1 % of subjects at 1 month and 80.6% at 4 months were carried out. RESULTS: Median attendance for nurse follow-up in the 4 months following diagnosis was 3 (IQR 2-5) in intervention practices and 0 (IQR 0-1) in control practices; the median number of visits to a doctor was the same in both groups. At hospital discharge, levels of prescribing of preventive medication were low in both intervention and control groups: aspirin 77 versus 74% (P = 0.32), cholesterol lowering agents 9 versus 10% (P = 0.8). Conversely, 1 month after diagnosis, the vast majority of patients in both groups reported healthy lifestyles: 90 versus 84% reported eating healthy food (P = 0.53); 73 versus 67% taking regular exercise (P = 0.13); 89 versus 92% not smoking (P = 0.77). Take up of cardiac rehabilitation was 37% in the intervention group and 22% in the control group (P = 0.001); the median number of sessions attended was also higher (5 versus 3 out of 6). CONCLUSIONS: The intervention of a liaison nurse is effective in ensuring that general practice nurses follow-up patients after hospital discharge. It does not alter the number of follow-up visits made by the patient to the doctor. Levels of prescribing and reported changes in behaviour at hospital discharge indicate that the main tasks facing practice nurses during follow-up are to help patients to sustain changes in behaviour, to encourage doctors to prescribe appropriate medication and to encourage patients to adhere to medication while returning to an active life. These are very different tasks to those traditionally undertaken by practice nurses in relation to primary prevention, where the emphasis has been on identifying risk and motivating change. Assessment of the effectiveness of practice nurses in undertaking these new tasks requires a longer follow-up.

Adult↗
PubMed1997

3-D histo-radiographic comparison of surgical clearances of microcalcified lesions in breast localization biopsies.

There is controversy as to the value of the radiological or pathological estimation of surgical clearance of microcalcifying breast lesions. An important part of this issue has been addressed by coordinated three-dimensional radiographic and histological examination of a prospective consecutive series of 40 benign and malignant mammographically detected lesions in surgical breast biopsy specimens containing microcalcifications, including 20 cases of ductal carcinoma in situ. They were radiographed from four viewpoints by means of rotation in a radiolucent tetrahedral container. The planes of histological examination were then chosen to correspond to the radiographic view showing the minimum separation of the edge of the specimen and the outermost microcalcification. There was a close correlation (Spearman ranked) between the least tetrahedral radiographic distance and the corresponding histological distance separating the surgical margin of excision. There were, however, incompatible Wilcoxon signed ranking orders when comparing the least tetrahedral distance or the histological distance with all four single radiographic views, including the conventional specimen radiographic view. Two-dimensional specimen mammography and standardized histological examination are suboptimal and may thus have contributed to confusion as to the value of determining adequate surgical excision of ductal carcinoma in situ of the breast. Although labour-intensive, use of four-view radiography and choice of the appropriate plane of histological examination give a better correlation of the radiographic estimates of surgical clearance with histology than single-view specimen radiography and arbitrary histological sectioning.

Biopsy↗
PubMed1997

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part I--The effects of heparin, protamine and propofol.

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) (Sangtec Medical, Sweden) assays are designed for clotted samples, but when studying cerebral damage following cardiac surgery, perioperative samples will contain heparin and/or protamine. The lipid emulsion propofol is also frequently used during cardiac surgery and could affect the assays. We, therefore, studied the effects of heparin, protamine and propofol on the accuracy of NSE and S-100 assays in five healthy patients. Blood samples were taken and divided into four groups: normal saline was added to group A; heparin to group B; heparin followed by protamine to group C; and propofol to group D. NSE and S-100 concentrations were measured for all samples. Neither heparin, protamine nor propofol affected the accuracy of S-100 and NSE assays; therefore, samples can be taken throughout operations involving cardiopulmonary bypass without influencing the results.

Anesthetics, Intravenous↗
PubMed1997

Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: Part III--Dose haemolysis affect their accuracy?

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) are useful for detecting cerebral damage during cardiopulmonary bypass (CPB). However, red cells contain NSE, and the haemolysis frequently caused by CPB could produce a false rise in NSE; S-100 is not found in red cells and should not be affected. We, therefore, compared the effects of haemolysis on NSE and S-100 to see if correction was necessary and possible. From seven patients, serial dilutions of haemolysed red cells were added to plasma (1/64-1/2048), measured for absorption at 540 nm and assayed for NSE and S-100. S-100 concentrations showed no change with haemolysis. Measured NSE increased significantly with haemolysis > 1/512 (an increase of 6.6 micrograms/ml): a correction formula is presented. In 39/48 patients after CPB, mean haemolysis was < 1/256 and would not need any correction. NSE and S-100 assay can, therefore, be used throughout CPB, which allows both glial and neuronal damage to be studied.

Artifacts↗
PubMed1996

Heterogeneous expression of sulphotransferases in periportal and perivenous hepatocytes prepared from male and female rat liver.

Sulphotransferase (ST) is a family of enzymes responsible for metabolism and detoxication of endobiotics and xenobiotics. We investigated the hepatic acinar distribution of three sulphotransferases: phenol sulphotransferase (PST), oestrogen sulphotransferase (EST), and hydroxysteroid sulphotransferase (HST) in male and female rat livers by measurement of enzyme activities in isolated periportal and perivenous hepatocytes. The distribution was confirmed by immunohistochemistry. EST activity was located predominantly in the perivenous hepatocytes in male rats but not in female rats, where residual activity is catalysed by another ST. HST activity was not significantly different in periportal and perivenous hepatocytes in either male or female rats. For PST, a more widespread distribution was observed, with slight predominance in the periportal regions. The results indicate heterogeneous distribution of ST isoenzymes in the periportal and perivenous hepatocytes isolated from male and female rat livers.

Animals↗
PubMed1996

Egg-sharing in assisted conception: ethical and practical considerations.

The present acute shortage of eggs for donation cannot be overcome unless adequate guidelines are set to alleviate the anxieties regarding payments, in cash or kind, to donors. The current Human Fertilisation and Embryology Authority (HFEA) guidelines do not allow direct payment to donors but accept the provision of lower cost or free in vitro fertilization (IVF) treatment to women in recognition of oocyte donation to anonymous recipients. Egg-sharing achieved in this way enables two infertile couples to benefit from a single surgical procedure. However, the practical guidelines related to this approach are ill-defined at the present time leading to some justifiable uncertainty. A pilot study was therefore undertaken in order to establish the place of egg-sharing in an assisted conception programme. The current HFEA guidelines on medical screening of patients, counselling, age and rigid anonymity between the donor and recipient were followed. The study involved 55 women (25 donors and 30 recipients) in 73 treatment cycles involving fresh and frozen-thawed embryos. Donors were previous IVF patients who, regardless of their ability to pay, shared their eggs equally with matched anonymous recipients. They paid only for their consultations and tests right up to the point of being matched with a recipient. The sole recipient paid the cost applicable in egg donation of a single egg collection, although both received embryo transfers. The results indicate that although the recipients were older than the donors (41.4 +/- 0.9 versus 31.6 +/- 0.5 years), and there was no difference in the mean number of eggs allocated, the percentage fertilization rates, or the mean number of embryos transferred, there were more births per patient amongst recipients than amongst donors (30 versus 20%). We conclude that providing the donors are selected carefully, this scheme whereby a sub-fertile donor helps a sub-fertile recipient is a very constructive way of solving the problem of the shortage of eggs for donation. There are also the advantages of including a group of women who would otherwise be denied treatment. Problems related to 'patient coercion' can, in our view, be fully overcome by the application of strict common-sense safeguards. The ideal of pure altruism is not without its medical and moral risk. The success of egg-sharing depends on shared interests and a degree of altruism between the donor, the recipient and the centre. The current HFEA guidelines should be applauded for enabling a highly effective concept of mutual help to develop.

Adult↗
PubMed1996

Optimal lead selection for detection of ST segment shifts.

A comparison was made to determine the ability of optimal sets of 2-6 unipolar leads and a normal Holter lead set to estimate ST potential distributions changes induced by balloon inflation during angioplasty. The performance of these lead sets was compared to measurements observed in recorded 32-lead body surface maps. Unipolar lead potentials were estimated using a linear, least mean squared error estimator of the total body surface map. The correlation between maximum ST potential change in the body surface map and that predicted by the unipolar lead sets ranged from 0.84-0.93. The correlation between maximum ST segment change measured from the body surface map and measured from the Holter leads was 0.29. Therefore, shifts in ST segment potentials can accurately be estimated from a small number of unipolar leads. In contrast, current bipolar ambulatory recording techniques may introduce significant bias to such estimates.

Angioplasty, Balloon, Coronary↗
PubMed1996

Design, production and characterization of antibodies discriminating between the phenol- and monoamine-sulphating forms of human phenol sulphotransferase.

1. Phenol sulphotransferases (PSTs) are important enzymes in xenobiotic and endobiotic detoxication, and a key component of the body's chemical defence mechanism. 2. Human phenol-(P-PST) and monoamine-(M-PST) sulphating forms of PST share 93% amino acid sequence identity, and to date the various antibodies produced against PSTs all recognize both enzymes. 3. We have identified two peptides based on the cDNA-derived amino acid sequences of human P-PST and M-PST, which elicited for the first time antibodies capable of discriminating between these highly homologous enzymes. 4. These antibodies represent valuable tools for studying the expression, distribution and function of human phenol sulphotransferases.

Amino Acid Sequence↗
PubMed1995

Preparation and characterization of anti-peptide antibodies directed against human phenol and hydroxysteroid sulphotransferases.

Sulphotransferases (STs) catalyze the sulphation and, in general, detoxication of a large number of xenobiotics and endogenous compounds. A total of six synthetic peptides derived from the cDNA-derived amino acid sequences of the human phenol-sulphating form of phenosulphotransferase (P-PST) and human hydroxysteroid sulphotransferase (HST)--three from each sequence--were separately conjugated to the carrier protein keyhole limpet hemocyanin, and used to immunize rabbits. One successful antibody preparation was produced from among the P-PST peptides, and two from the HST peptides. On immunoblot analysis following SDS/PAGE, the anti-P-PST antibodies recognized two major forms of phenol ST in man, P-PST and the monoamine-sulphating form of PST, M-PST, and the two antibody preparations against HST recognized the human HST. These experiments demonstrate that it is possible to design specific antibodies against human sulphotransferases based on their amino acid sequences.

Adjuvants, Immunologic↗
PubMed1994

Sulfation of endogenous compounds and xenobiotics--interactions and function in health and disease.

Sulfation is a major detoxication mechanism for endogenous compounds and xenobiotics performed by a family of sulfotransferase isoenzymes. Understanding the normal cellular functions of these different sulfotransferases and the way in which endogenous and exogenous factors are able to influence their activity and expression will provide us with the information necessary to develop novel therapeutic strategies for conditions where sulfation may be implicated. This concept is discussed and is illustrated by examples including adverse drug reactions, fetal development and cancer.

Amino Acid Sequence↗
PubMed1994

Immunohistochemical localisation of hydroxysteroid sulphotransferase in human breast carcinoma tissue: a preliminary study.

Understanding the function and regulation of the metabolism of steroid hormones by breast tumours will be instrumental to the development of novel treatments for this widespread disease. We have examined the expression of hydroxysteroid sulphotransferase, an enzyme which inactivates many steroids, in particular androgens, in normal breast tissue and in six ductal-type mammary carcinomas using immunohistochemistry. The enzyme is not expressed in the epithelial cells which line the normal breast duct, but is present in significant amounts in neoplastic cells, suggesting that the gene encoding this protein is activated at some stage of the neoplastic transformation. The implications of this finding for the role of steroid metabolism in breast cancer are discussed.

Breast↗
PubMed1994

Mobilisation of Ph-negative peripheral blood stem cells in CML with idarubicin and cytarabine.

Recent interest in autologous transplantation in chronic myeloid leukaemia (CML) has focused on attempts to select out putatively normal Ph-negative progenitor cells for subsequent reinfusion after high dose therapy. One way in which this may be achieved is by collecting peripheral blood stem cells (PBSCs) during the early regenerative phase following chemotherapy when Ph-negative cells seem to have a short term proliferative advantage. Data now suggest that it is possible to collect Ph-negative (and occasionally PCR negative) progenitor cells in a significant number of CML patients, a proportion of whom will go on to achieve a cytogenetic remission post-autografting. The durability of these remissions and the effect on long term survival remain to be established and at present this form of therapy should be reserved for those unsuitable for allogeneic transplantation who have failed to achieve a major cytogenetic response to interferon-alpha.

Cell Separation↗
PubMed1993

Immunochemical characterisation of a dehydroepiandrosterone sulfotransferase in rats and humans.

A member of the rat liver hydroxysteroid sulfotransferase (ST) enzyme family metabolising dehydroepiandrosterone (DHEA) was purified from female rats and used to raise rabbit polyclonal antibodies. Characterisation of this antibody preparation demonstrated that it was specific for DHEA ST, and recognised a single 30-kDa protein on immunoblot analysis of rat liver cytosol which was expressed preferentially in female rat liver, and immunohistochemical localisation of the protein in female rat liver determined that DHEA ST was distributed homogeneously in the cytoplasm of hepatocytes. Examination of the extrahepatic expression of this protein showed it to be located predominantly in the liver, although a small amount of enzyme activity was found in the kidney which was not apparently subject to the same sex difference as the hepatic activity. Immunological analysis suggested that this activity was not due to the action of DHEA ST, but to another, unidentified ST isozyme. The antibody cross-reacted strongly with adult human liver DHEA ST, recognising a protein of 35 kDa on immunoblotting. Using this antibody preparation, the distribution of DHEA ST in mid-trimester human fetal tissues was examined, and it was shown that the enzyme is expressed in the adrenal and liver, but not to any significant extent in the kidney or lung. This antibody therefore provides a powerful tool for investigating the function of DHEA ST.

Adrenal Glands↗
PubMed1992

Inhibition of human and rabbit liver steroid and xenobiotic UDP-glucuronosyltransferases by tertiary amine drugs--implications for adverse drug reactions.

1. To investigate the hypothesis that disruption of glucuronidation of endogenous compounds by drugs represents a potential mechanism for pathogenesis of adverse drug reactions, the effects of a range of tertiary amine and amide drugs (many with effects on sex hormone function) on steroid hormone and xenobiotic UDP-glucuronosyltransferase activities in human and rabbit liver microsomes were studied in vitro. 2. Chlorpromazine, amitriptyline, imipramine, promethazine and cyproheptadine were consistently the most potent inhibitors of the glucuronidation of testosterone, androsterone, oestriol and 1-naphthol, the steroid activities being more susceptible to inhibition (up to 90%). 3. Carbamazepine, diphenhydramine, sulphadimethoxine, dimenhydrinate and (+/-)-chlorpheniramine had little effect on the UDPGT activities measured. 4. The structural features within this group of compounds required for inhibitory potency were the presence of a rigid tricyclic ring (e.g. phenothiazine) and either a dimethylaminopropyl or a methylpiperidine side-chain. 5. The implications of these data for involvement of disruption of the normal cellular function of glucuronidation in the pathogenesis of frequently observed adverse side-effects associated with these compounds are discussed.

Amines↗
PubMed1991

Glucuronidation of imipramine in rabbit and human liver microsomes: assay conditions and interaction with other tertiary amine drugs.

The present work confirms that rabbit liver microsomes afford a good in vitro model for studying the glucuronidation of drugs containing tertiary amino groups. Furthermore, the availability of the assay procedure described above will allow us to understand further the basis for the inter-species differences in the metabolism of tertiary amines, and will eventually aid in our identification of the UDPGT isozyme(s) responsible for the conjugation of these compounds in man.

Amines↗
PubMed1991

Histologic comparison of regeneration in human intrabony defects when osteogenin is combined with demineralized freeze-dried bone allograft and with purified bovine collagen.

A bone-inductive protein, osteogenin, has been isolated from long bones of humans and offers promise as a grafting material. Studies, however, suggest that osteogenin must be combined with a bone-derived matrix in order to initiate bone differentiation. The purpose of this study was to determine if osteogenin combined with demineralized freeze dried bone allograft (DFDBA), a bone-derived matrix, and with a bovine tendon-derived matrix will enhanced regeneration of intrabony defects in humans. The tendon-derived matrix and DFDBA used alone served as controls. The ability of each material to form a new attachment apparatus was evaluated independently in submerged and nonsubmerged environments in 2 patient populations. Lymphocyte testing was performed to assess development of an immune reaction to osteogenin. The most apical level of calculus on the root served as the histologic reference point to measure regeneration. Biopsies were obtained at 6 months and regeneration was measured histomorphometrically by 2 blinded evaluators. Serial sections from 36 submerged defects in 8 patients and 50 nonsubmerged defects in 6 patients were submitted for statistical analysis. Mean results indicate that osteogenin combined with DFDBA significantly enhanced regeneration of a new attachment apparatus and component tissues in a submerged environment. DFDBA plus osteogenin and DFDBA alone formed significantly more new attachment apparatus and component tissues than either the tendon-derived matrix plus osteogenin or the tendon-derived matrix alone in both submerged and nonsubmerged environments. There were no significant differences between the tendon-derived matrix plus osteogenin and the tendon-derived matrix alone in either the submerged or nonsubmerged environment. Osteogenin does not impair normal lymphocyte blastogenesis at 6 months postsurgical challenge.

Alveolar Bone Loss↗