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Biomedical subjects

S Guy

Publications and source records attributed to S Guy.

At least 19 recordsLinked to original sources

Composting under controlled conditions.

Three cylindrical reactors, each with a working capacity of approximately 200 litres, were used to investigate composting. The process was optimised and conditions were controlled so that composting on a laboratory-scale thermally resembled that occurring in the core of large open heaps. A baseline flow of humidified air aerated the reactors in five-minute bursts. The reactors operated as closed systems with facilities to analyse the composition of the off-gas for ammonia, oxygen and carbon dioxide. Temperature was used to monitor the progress of the process. Heat loss from the reactor surface was compensated for with an external heat source. A basic model of radial conductive heat losses showed that 53 watts per square-metre would be the maximum heat flux needed to keep the temperature difference across the reactor to within a degree when running at 60 degrees C. A heating cable was used, which could supply 150 watts per square-metre, and the radial temperature difference was reduced to within a degree in more than 60% of the recorded temperatures in the case studies presented. The temperature of the composting material was held at 60 degrees C using a high flow rate 'cooling' aeration with temperature feedback. This, however, led to a mean vertical temperature difference of at least 10 degrees C. The aeration strategy resulted in a well-aerated material, which favoured aerobic microbial activity and the temperature increased as a result of the internally generated heat associated with composting. Three-quarters of the ammonia was emitted in the first week.

Bacteria, Aerobic↗

Safety and security policies on psychiatric acute admission wards: results from a London-wide survey.

Very little research evidence is available regarding current safety and security procedures on acute psychiatric wards. This includes controversial areas such as the temporary removal of personal property, the searching of patients and visitors, the use of alarms and modern technology, and locking of entrances to regulate those entering and leaving. This is also despite widening dismay over increasing violence within a variety of hospital settings, the comparatively high risk of physical assault faced by mental health professionals and an abundance of literature and training in regards to violence management and prevention. To gain an understanding of current safety and security measures, a London-wide survey of acute admission wards was undertaken revealing a wide variety of measures and policies in operation. Over 100 NHS and private wards were sent questionnaires; there was a response rate of 70%. Results show that a significant proportion of acute admission wards are now locked at all times and a small proportion of units have 24-hour security/reception staff on-site and a low level of modern technology usage such as CCTV and electronic access systems. There is wide variation in items banned, restrictions placed on inpatients, and the searching of patients and visitors. Two independently varying emphases of ward security policies were identifiable, the first aimed at preventing harm to patients using door security, banning of item and restrictions on inpatients. The other is aimed at reducing risks to staff via searching of patients, use of security guards and sophisticated alarm systems. There is some preliminary evidence that these security policies are differentially associated with levels of absconding and violent incidents. Further research to guide practice is urgently required.

Admitting Department, Hospital↗

Who writes guidelines, and who should?

AIM: To confirm or refute the impression that diagnostic radiology was often not represented on guideline writing committees, despite the fact that guidelines often made statements with implications for radiological practice. MATERIALS AND METHODS: We took two approaches. Firstly we examined all published Scottish Intercollegiate Guidelines Network (SIGN) guidelines and extracted the disease topic, the number of authors and peer reviewers, the number that were radiologists, and independently decided whether, given the content, radiologist input at the writing or review stage was necessary. We also searched for all guidelines on management of stroke worldwide (a single disease topic with major radiological implications) and extracted the proportion of authors that were radiologists. RESULTS: Of 47 SIGN guidelines on different diseases, 11 (23%) had a radiologist in the authorship (13/594, 2.2% total authors), and 5/47 (11%) had a radiologist specialist reviewer (10/529, 1.8% total reviewers). Independent review of the guidelines' content suggested that 76% of guidelines should have had a radiologist author and 91% a radiologist reviewer (discrepancy 53% and 80% respectively). Amongst 22 guidelines on acute stroke management in the world literature with 202 authors (where stated), there were only two radiologists (1%), both on one guideline which was specifically to do with imaging of stroke (5% of all stroke guidelines identified). CONCLUSION: Diagnostic radiology is poorly represented on guideline writing committees, although frequently guidelines have implications for radiological practice. Radiologists should try to be more involved in guideline production.

Authorship↗

Simultaneous heart and kidney transplantation in patients with end-stage heart and renal failure.

Combined simultaneous organ transplantation has become more common as selection criteria for transplantation have broadened. Broadening selection criteria is secondary to improved immunosuppression and surgical techniques. The kidney is the most common extrathoracic organ to be simultaneously transplanted with the heart. A series of 13 patients suffering from both end-stage heart and renal failure underwent 14 simultaneous heart and kidney transplantations at Temple University Hospital between 1990 and 1999. This is the largest series reported from a single center. Three patients died during the initial hospitalization for an in-hospital mortality of 21%. Of 10 patients who left the hospital, 1-year survival was 100% and 2-year survival 75%. One patient required retransplant for rejection within the first year. Overall mortality at 1 and 2 years was 25 and 41%, respectively. Four out of nine (44%) patients greater than 5 years post-transplant were alive. Of the 10 patients who left the hospital, 66% were alive at 5 years. One patient succumbed to primary nonfunction of the cardiac allograft, while the four other deaths were secondary to bacterial or fungal sepsis. The patient's racial backgrounds were equally divided between African-American and white. These results are similar to those reported in a United Network of Organ Sharing Database (UNOS) registry analysis of 84 simultaneous heart and kidney transplants that found 1- and 2-year survival to be 76 and 67%, respectively. Simultaneous heart and kidney transplantation continues to be a viable option for patients suffering from failure of these two organ systems, although the results do not match those of heart transplant alone.

Cause of Death↗

Frequent attenders in general practice: a retrospective 20-year follow-up study.

We describe a 20-year retrospective study of 58 patients with a cross-matched control group in one practice, who initially attended more than 12 times in 1975. The study establishes that frequent attendance is not consistent; the majority of high-attending patients in general practice revert over a short period of time to a normal consulting pattern. Diseases, rather than patients, appear to dictate high consulting rates. Consistent high attendance is largely owing to multiple pathology.

Adult↗

Characterization of two members of the maize gene family, Incw3 and Incw4, encoding cell-wall invertases.

Two maize putative cell-wall invertase genes (Incw3 and Incw4) have been isolated by screening a genomic DNA library (Zea mays L. W22) using the cDNA probes encoding the two maize cell-wall invertases Incw1 and Incw2. The Incw3 and Incw4 genes contain six exons/five introns and five exons/four introns, respectively. The protein sequences deduced from both genes revealed a beta-fructosidase motif and a cysteine catalytic site known to be conserved in invertase genes. A detailed analysis of the protein and nucleotide sequences provides evidence that the Incw3 and the Incw4 genes encode putative cell-wall invertases. Furthermore, the isoelectric point deduced from the INCW4 protein sequence suggested that the Incw4 gene may encode a unique type of cell-wall invertase unbound in the apoplast. Gene expression studies using RT-PCR and in-situ RT-PCR hybridization showed that the Incw3 expression is organ/tissue-specific and developmentally regulated. In contrast, the Incw4 gene is constitutively expressed in all vegetative and reproductive tissues tested.

Amino Acid Sequence↗

Inhibitory activity of anti-interleukin-4 and anti-interleukin-10 antibodies on Toxoplasma gondii proliferation in mouse peritoneal macrophages cocultured with splenocytes from infected mice.

Cocultures of splenocytes from Toxoplasma gondii-immunized mice or from naive mice, separated by a transwell membrane from naive macrophage layers, induced a decrease in T. gondii proliferation in macrophages in comparison with cultures without splenocytes or cocultures with splenocytes from infected mice. Interleukin 4 (IL-4) and IL-10 levels increased in cocultures of splenocytes from infected mice with naive macrophages. In contrast, the levels of these cytokines decreased in cocultures with splenocytes from immunized mice. No correlation was found between the release of interferon-gamma (IFN-gamma) and the inhibition of parasite multiplication. Cocultures with splenocytes from immunized mice induced an increase in tumor necrosis factor-alpha (TNF-alpha) levels. In contrast, in cocultures with splenocytes from infected mice, TNF-alpha production decreased. In cocultures with splenocytes from infected mice, T. gondii proliferation in macrophages was neutralized by anti-IL4 or anti-IL10 antibodies and was associated with increased TNF-alpha production. Moreover, this study demonstrates the significant combined effect of IL-4 and IL-10 on the down-regulation of macrophage-effector functions. A soluble positive signal was given by splenocytes to induce the production of TNF-alpha by macrophages. This signal was inhibited by IL4 and IL10. This process is biologically relevant in the regulation of T. gondii proliferation.

Animals↗

Toxoplasma gondii secretes a calcium-independent phospholipase A(2).

Phospholipases A(2) (PLA(2)) play an important role in Toxoplasma gondii host cell penetration. They are also key enzymes in the host cell response to the parasite invasion. PLA(2) hydrolyse cellular phospholipids, releasing multiple inflammatory lipidic mediators. We have investigated the biochemical characterisation of T. gondii PLA(2) activity in a mouse-cultured tachyzoite homogenate and in the peritoneal exudate from infected mice, using the hydrolysis of a fluorescent phosphatidylglycerol labelled at the sn-2 position. Spectrofluorimetry and thin-layer chromatography showed a PLA(2) activity (about 0.5-2 nmol/min per mg), calcium-independent, secreted into infected mice peritoneal exudate, with a broad pH activity ranging between 6.5 and 9.5 and resistant to a great number of potential PLA(2) inhibitors except dithio-nitrobenzoic acid (1 mM). An associated phospholipase A(1) activity was also displayed. These results suggest that Toxoplasma gondii displays specific phospholipases different from host enzymes and probably involved at critical steps of infectious cycle.

Animals↗

Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients.

OKT3 , a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFalpha and IL1beta. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance. We sought to analyze the role of proinflammatory and Th-1 cytokines in T cell recovery and rejection after liver transplantation with OKT3 prophylaxis. In plasma samples from 32 patients, we measured TNFalpha, IL1beta and IL6 (before transplant and on postoperative days 1, 2 and 3) and IL2, IFNgamma, sIL2R and slCAM (postoperative days 5, 7 and 10) and examined possible correlations with T-cell recovery and occurrence of rejection within 3 weeks. TNFalpha, IL1beta, and IL6 did not correlate with T-cell recovery. In patients who rejected, IL2 and IFNgamma on postoperative days 5 and 7 correlated with degree of T-cell recovery by day 10; a significant rise in sIL2R over time also correlated with T-cell recovery in this group. Our results emphasize the role of Th-1 cytokines in rejection following OKT3 induction and suggest that markers of T cell activation may predict risk.

Animals↗

Th1/Th2 cytokines and ICAM-1 levels post-liver transplant do not predict early rejection.

Th1 derived cytokines IFN-gamma and IL-2, Th2 cytokine IL-4, and ICAM-1 have been implicated in liver allograft rejection. In order to determine whether monitoring of cytokine profiles during the first days post-liver transplant can predict early rejection we measured IFN-gg, IL-2, sIL-2 receptor, IL-4 and ICAM-1 in 22 patients, in plasma samples obtained within 4 h after liver perfusion (baseline) and between postoperative days (POD) 3-6. ICAM-1 and sIL-2R levels at POD 3-6 were significantly higher than at baseline but did not differ in presence or absence of rejection. Mean percentage increase of ICAM-1 levels was significantly lower in patients with Muromonab-C3 Orthoclone OKT3 (J.C. Health Care) (OKT3) whereas percentage increase of sIL-2R levels was higher in OKT3-treated patients. IFN-gamma levels at POD 3-6 increased from baseline while IL-4 levels were unchanged. Levels of IFN-gamma, IL-4 and their ratios did not correlate with rejection or immunosuppressive therapy. Thus, Th1/Th2 cytokine monitoring during the first week post-transplant does not predict early rejection and immunosuppressive therapy is the predominant factor affecting ICAM and sIL-2R levels after liver transplantation.

Female↗

Ivr2, a candidate gene for a QTL of vacuolar invertase activity in maize leaves. Gene-specific expression under water stress.

Water shortage produced an early and large stimulation of acid-soluble invertase activity in adult maize leaves whereas cell wall invertase activity remained constant. This response was closely related to the mRNA level for only one of the invertase gene (Ivr2), encoding a vacuolar isoform. In parallel, four quantitative trait loci (QTLs) were detected for invertase activity under control and nine under stressful conditions. One QTL in control and one in stressed plants was located near to the Ivr2 gene on chromosome 5. Other QTLs for invertase activity were found close to carbohydrate QTLs; some of them formed 'stress clusters'.

DNA, Plant↗

Correlation between von Willebrand factor levels and early graft function in clinical liver transplantation.

Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC) activation and damage in nearly every liver transplantation; the extent of these changes influences early graft function. Upon reperfusion, activated SEC show increased expression of adhesion molecules, including von Willebrand factor (vWF) which is released into the circulation. This study was designed to evaluate the levels of vWF measured in the caval effluent and correlate these findings with known markers of SEC damage and early graft function. Data were obtained from 35 patients undergoing orthotopic liver transplantation (LTx). Two samples were taken from each patient for measurement of vWF: a) from the portal vein immediately prior to reperfusion; and b) from the first 50 ml of the caval effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid (HA), thrombomodulin (TM), IL-1 beta, IL-6, IL-8 and TNF-alpha. Patients were divided into two groups based on early graft function. Poor early graft function (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase (ALT) level > 2500 U/L during the first three postoperative days (POD) and a prothrombin time (PT) > 16 s on POD 2 (n = 8). The remaining 27 patients had good early graft function (GEGF). In patients with GEGF, vWF levels dropped significantly between the two time points. This change was not observed in those with PEGF. A positive linear correlation was observed in the PEGF group between vWF and HA and IL-6. The different pattern of change in vWF between the two groups, as well as the positive correlation between HA, IL-6 and vWF in PEGF, suggest that vWF may be a useful marker of early graft function.

Adult↗

Donor des-gamma-carboxy prothrombin positivity is a risk factor for poor early graft function in liver transplantation.

Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin that lacks coagulating activity. The aim of this study was to determine if the presence of DCP in the donor could be used as a marker of post-transplant graft function. We collected data and serum samples on 90 organ donors. DCP level was correlated with donor-specific factors and with graft function intraoperatively and in the early post-transplant period. Twenty-seven donors (30.0%) had positive DCP levels before harvesting. Although recipients were similar in demographics, preoperative liver function, and primary disease distribution, patients transplanted with livers from DCP-positive donors needed significantly more intraoperative transfusion. Furthermore, donor DCP positivity was identified as a preoperative risk factor for poor early graft function based on multivariate analysis (odds ratio = 6.58, P = 0.0032). Our findings suggest that DCP is another valuable marker for evaluating the quality of donor livers.

Adolescent↗

Assessment of liver allograft function by hyaluronic acid and endothelin levels.

BACKGROUND: Sinusoidal endothelial cells are considered the primary site of preservation-reperfusion injury occurring during cold storage and reperfusion. Hyaluronic acid (HA) and endothelin-1 (ET) are markers of endothelial cell integrity. The aim of this study was to evaluate the possible correlation between these markers and early graft function following liver transplantation. MATERIALS AND METHODS: Blood samples were collected from 85 adult orthotopic liver transplant recipients at the following time points: before surgery, just before reperfusion, first and last 20 cc of caval effluent, 30, 60, and 120 min after reperfusion, and on postoperative day (POD) 1. Levels of both HA and ET were measured by sandwich enzyme-binding assay. HA uptake was also defined for every sample as the ratio of the actual measurement to the value obtained just before reperfusion. RESULTS: Patients with severe liver disease displayed significantly higher pretransplant HA and ET levels compared with those of less advanced illness. Poor early graft function (PEGF) was defined as peak enzyme levels on the first three PODs higher than 2500 U/L and prothrombin time longer than 16 s on POD 2. Patients with PEGF (n = 9) showed significantly lower HA uptake than patients with good graft function (n = 76) at 60 and 120 min after reperfusion. There was also a significant difference in the average uptake values measured in the last 20 cc of caval effluent between the two groups. We could not find any difference in ET levels between these two groups. CONCLUSIONS: Perioperative HA uptake measurement may be an additional marker to evaluate early graft function.

Adult↗

Effects of beta-adrenoceptor agonists and antagonists on heart-rate variability in normal subjects assessed using summary statistics and nonlinear procedures.

The influence of celiprolol (beta1- and beta2-adrenoceptor partial agonist), propranolol (beta1- and beta2-adrenoceptor antagonist), and atenolol (beta1-adrenoceptor antagonist) on heart-rate variability (HRV) was assessed from Holter records in 12 normal volunteers. A combination of summary statistics and nonlinear procedures was used to assess HRV and autonomic balance. Under double-blind and randomised conditions (Latin-square design), subjects received placebo, celiprolol (200 and 800 mg), propranolol (160 mg), atenolol (50 mg), and combinations of these agents. Single oral doses of medication (at weekly intervals) were administered at 22:30 h with sleeping heart rates (HRs) recorded overnight. Compared with placebo, celiprolol (200 and 800 mg) increased the sleeping HR, the HR effect of celiprolol was different from the bradycardia after propranolol, 160 mg, and atenolol, 50 mg. Dose-response effects on HR with celiprolol were evident in the presence of atenolol, unlike those with propranolol that abolished the HR increase between celiprolol, 200 mg and 800 mg. These data were consistent with beta1-selective adrenoceptor agonism with 200 mg but agonism at both the beta1- and beta2-adrenoceptor with celiprolol, 800 mg. The action of the drugs on short-term HRV indices (rMSSD and pNN50) closely followed their effects on HR. The longer-term HRV indices (global SD, SDANN) were reduced by celiprolol but increased by propranolol and atenolol. At a fixed HR, the data dispersion (SDNN5) was higher with propranolol compared with celiprolol; however, the dispersion was not merely an HR-dependent phenomenon. A novel nonlinear approach (quadrant analysis) revealed the sequencing of cardiac accelerations and decelerations after the high correlation between adjacent intervals had been removed. Celiprolol increased the frequency of consecutive cardiac accelerations; the duration between and variance of these beat-to-beat differences shortened after celiprolol but lengthened with increased variance after propranolol and atenolol. These results demonstrated reduced HRV indices and a shift toward sympathetic dominance after the beta-adrenoceptor agonist celiprolol contrasting with increased HRV indices and parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and atenolol. The implications of these findings for the treatment of patients with cardiovascular disease warrant further study.

Adrenergic beta-Agonists↗

Effluent levels of thrombomodulin predict early graft function in clinical liver transplantation.

Thrombomodulin is a surface protein on vascular endothelial cells that serves as a binding site for thrombin and plays an important role as an anticoagulant factor. We correlated plasma thrombomodulin levels with early graft function after liver transplant in 58 recipients. Blood samples were collected at the following time points: before surgery, just before reperfusion, 30, 60, 120 min after reperfusion, and post-operative day 1. The first and last 20 cc of caval effluent were also collected. Plasma thrombomodulin levels were measured by a sandwich enzyme-binding assay in the blood samples; tissue expression was determined by immunohistochemistry. Poor early graft function was defined as peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2500 U/l during the first 3 post-operative days and prothrombin time >16 s on post-operative day 2. Thrombomodulin levels in the first 20 cc of caval effluent ranged from 1.33 to 91 FU/ml and showed a significant positive correlation with ischemic time, intra-operative blood transfusion requirement, and early graft function. In grafts with high effluent thrombomodulin (>20 FU/ml, n=12), the incidence of poor early graft function and primary nonfunction was 66.7% and 25.0%, respectively; in grafts with low effluent thrombomodulin (<20 FU/ml, n=46), graft function was not impaired. By immunohistochemistry, thrombomodulin was detected in large vessels of every donor liver. Sinusoidal cells, however, showed positive staining only in livers with poor early graft function. Effluent thrombomodulin levels reflect the extent of preservation injury and might be a useful marker for predicting graft function after liver transplantation.

Adult↗