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Biomedical subjects

P Sutton

Publications and source records attributed to P Sutton.

At least 37 records · Page 2Linked to original sources
PubMed1997

Reengineering a cardiovascular surgery service.

BACKGROUND: Reengineering, involving the radical redesign of business processes, has been used successfully in a variety of health care settings. In 1994 New York University (NYU) Medical Center (MC) launched its first reengineering team, whose purpose was to redesign the entire process of caring for patients-from referral to discharge-on the cardiovascular (CV) surgery service. REENIGINEERING TEAM: The multidisciplinary CV Surgery Reengineering Team was charged with two goals: improving customer (patient, family, and referring physician) satisfaction and improving profitability. The methodology to be used was based on a reengineering philosophy-discarding basic assumptions and designing the patient care process from the ground up. THE TRANSFER-IN INITIATIVE: A survey of NYU cardiologists, distributed in April 1994, suggested that the organization was considered a difficult place to transfer patients. The team's recommendations led to a new, streamlined transfer-in policy. The average waiting time from when a referring physician requested a patient transfer and the time when an NYUMC physician accepted the transfer decreased from an average of 9 hours under the old system to immediate acceptance. OTHER INITIATIVES: Three customer satisfaction task forces implemented multiple programs to make the service more user friendly. In addition, referrals increased and length of stay decreased, without an adverse impact on the mortality rate. CONCLUSION: For the first time at NYUMC, a multidisciplinary team was given the mandate to achieve major changes in an entire patient care process. Similar projects are now underway.

Cardiology Service, Hospital↗
PubMed1997

The endotoxin of Helicobacter pylori is a modulator of host-dependent gastritis.

Atrophic gastritis caused by Helicobacter pylori is the precursor lesion in the development of intestinal-type gastric adenocarcinoma. In animal models, atrophic gastritis induced by Helicobacter felis has been shown to be host dependent, developing in some mouse strains and not in others. The lipopolysaccharide (LPS) of H. pylori has been suggested to play a role in the induction of gastritis. The goal of this study was to compare the inflammation induced by long-term infection of the C3H/He and the C3H/HeJ strains of mice with H. felis. C3H/HeJ mice are unresponsive to LPS. Six months after infection, severe atrophic gastritis had developed in the body mucosae of all infected C3H/He mice, with replacement of parietal and chief cells. Atrophy was associated with a loss of the H. felis from the antral mucosa. In contrast, no atrophy was seen in the infected C3H/HeJ non-LPS responder animals, and heavy colonization of the antrum remained. There were no significant differences between both the quantitative and qualitative serum immunoglobulin G (IgG) and salivary IgA levels in both strains of mice. The main difference between the two strains of long-term-infected mice was a lack of macrophage infiltration in the lamina propria. Immunization induced good protective immunity to challenge with viable H. felis. Helicobacter-induced, host-dependent gastritis is likely to be cell mediated. The C3H/He and C3H/HeJ mouse model provides an excellent opportunity to investigate the cellular basis of atrophic gastritis.

Animals↗
PubMed1996

Exacerbation of invasive aspergillosis by the immunosuppressive fungal metabolite, gliotoxin.

Invasive aspergillosis is a significant cause of death in immunocompromised individuals. The majority of strains of the main causative agent, Aspergillus fumigatus, produce gliotoxin, a secondary metabolite with demonstrated in vitro immunosuppressive activity. Pretreatment of normally resistant mice with a single injection of a sublethal dose of gliotoxin was sufficient to make them susceptible to infection and subsequent death, after challenge with A. fumigatus spores. Animals infected with the non-gliotoxin producing strain survived significantly longer than those infected with a gliotoxin producer. We propose that the release of gliotoxin by A. fumigatus hyphae during infection can exacerbate the pathogenesis of aspergillosis.

Animals↗
PubMed1995

Evidence that gliotoxin enhances lymphocyte activation and induces apoptosis by effects on cyclic AMP levels.

Gliotoxin is a secondary metabolite produced by several pathogenic fungi. It has potential clinical applications as an immunosuppressive agent in preventing allograft rejection. At low doses (< 30 nM) gliotoxin displays co-mitogenic activity, but at higher doses induces apoptosis in cells. Here we demonstrate that gliotoxin, although not mitogenic in its own right, enhances activation in preactivated splenocytes by a calcium-independent mechanism. The enhancement in activation correlates with a decrease in intracellular cyclic AMP levels. This property is inhibited by dibutyryl-cAMP. Increasing the concentration of gliotoxin to levels that caused apoptosis produced a dose-related increase in cAMP levels. Thus, the effects of gliotoxin on cell activation and the induction of apoptosis may both be mediated by changed levels of cAMP.

Animals↗
PubMed1995

Investigation of the potential use of immunosuppressive agent gliotoxin in organ transplantation.

Gliotoxin is an immunosuppressive secondary metabolite produced by several pathogenic fungi. It has previously been shown to prevent graft-versus-host disease in transplantation of allogeneic mouse bone marrow and to reduce the immunogenicity of human fetal pancreas. We here report on the effect of gliotoxin on the prevention of rejection of allografts in two distinct models. Bathing mouse thyroid tissue in gliotoxin solution for 16 hr prolonged graft survival following transplantation into allogeneic recipients. In contrast the perfusion of rat kidneys with gliotoxin followed by 1 hr of incubation before orthotopic transplantation had little success with preventing allograft rejection. This disparity is most likely due to the incubation in the renal model not allowing sufficient time for the elimination of antigen presenting cells in the donor organ. However, the success with the thyroid grafts demonstrates the potential of gliotoxin as an immunomodulating agent in organ transplantation and warrants further investigation in other systems.

Animals↗
PubMed1995

Repolarization gradients derived by subtraction of monophasic action potential recordings in the human heart. Studies incorporating altered mechanical loading and ischemia.

Information derived from the analysis of the electrocardiographic waveform remains one of the most valuable diagnostic aids in modern cardiology. Paradoxically, although changes in the ST-T segment probably have the widest clinical application, it is the analysis of this repolarization phase that has been surrounded by the greatest difficulties in interpretation.

Action Potentials↗
PubMed1995

DNA synthesis precedes gliotoxin-induced apoptosis.

The toxin gliotoxin induces apoptosis or programmed cell death in a variety of immune cells including thymocytes. Apoptosis induced by gliotoxin in thymocytes is unaffected by protein synthesis inhibitors nor is it associated with early changes in intracellular calcium levels (Beaver and Waring, 1994). This work shows that the cell lines P815 and WEHI7 and murine thymocytes when treated with gliotoxin show an early incorporation of tritiated thymidine over the concentration range which causes apoptosis. Proliferating cell nuclear antigen (PCNA), a marker for S phase, is elevated in cells following gliotoxin treatment and S phase DNA content is increased. Thymidine incorporation is inhibited by hydroxyurea, an inhibitor of replicative DNA synthesis not repair. Free radical scavangers have no effect on apoptosis induced by gliotoxin in thymocytes. Hydrogen peroxide-treated cells showed no enhanced thymidine incorporation and no apoptosis. Thus oxidative stress does not appear to be a factor in gliotoxin-induced apoptosis. Thymocytes treated with gliotoxin show increased phosphorylation of a 16.3 kDa protein, and apoptosis is inhibited by the tyrosine kinase inhibitor genistein, which also inhibited the increased thymidine incorporation in P815 cells. We conclude that one mechanism by which gliotoxin can cause apoptosis may be the induction of inappropriate entry of cells into the cell cycle followed by death.

Journal Article↗
PubMed1994

Child growth monitoring: errors of measurement with the TALC direct recording scale.

Young children in the Seychelles were weighed and charted using both a beam balance with the standard growth chart and using the TALC direct recording scale with integral chart. The oscillating pointer and unwanted horizontal movement of the chart in the scale resulted in unacceptable misclassification of nutritional status equivalent to a weighing error in infants of +/- 2 kg. The electronic walk-on scale may provide the most important next step forward in low cost scale technology in primary health care.

Body Weight↗
PubMed1994

In vivo immunosuppressive activity of gliotoxin, a metabolite produced by human pathogenic fungi.

Aspergillosis is a disease caused by the opportunistic pathogen Aspergillus fumigatus and other related fungi. It occurs mainly in immunosuppressed people and causes very high mortality rates. A fumigatus and other pathogenic fungi have been shown to produce a metabolite, gliotoxin, which has immunosuppressive properties in vitro, but little is known about its in vivo activity. Here we report that gliotoxin has increased toxicity in mice after irradiation. A single injection of gliotoxin delayed the recovery of immune cells after immunosuppression by sublethal irradiation by 2 weeks. Study of the morphology of cells of the thymus, spleen, and mesenteric lymph nodes by light microscopy and electron microscopy and agarose gel electrophoresis of DNA from these organs showed that the injection of gliotoxin induced apoptosis in cells of the immune system in vivo. Thus, gliotoxin does have immunosuppressive activity in vivo and could potentially play a significant role in the pathogenesis of aspergillosis and other fungal diseases.

Animals↗
PubMed1993

Rapid re-expression of CD45RC on rat CD4 T cells in vitro correlates with a change in function.

Rat CD4+ T cells are divided phenotypically by the anti-CD45RC monoclonal antibody OX22 into subsets with contrasting functions. Stimulation of T cells in vitro is known to induce a change in isoform from CD45RC+ to CD45RC-. We have investigated the in vitro conditions which promote a switch in isoform in the opposite direction. We observed that a majority of CD45RC- CD4 T cells (> 90%) spontaneously re-expressed CD45RC during the first 1-3 days of culture in both the presence and absence of alloantigen. The T cells remained CD45RC+ when cultured for 7 days in serum-free growth medium. However, alloantigen-activated lymphocytes, expressing the interleukin-2 receptor (IL-2R), downregulated CD45RC by day 4 and remained CD45RC- during the course of the experiment. Using mixtures of allotype-marked CD45RC+ and CD45RC- T cells, it was demonstrated that each subset showed comparable survival, IL-2R expression and time courses of activation in response to alloantigen. The repertoire of neither subset was, therefore, deficient in terms of allorecognition. The rapid re-expression of CD45RC in culture was accompanied by a change in function: CD45RC+ "converts", obtained by overnight culture of CD45RC- T cells, induced significantly higher graft-versus-host responses. Thus, the transition in culture from CD45RC- to CD45RC+ reflects a major functional reprogramming of the cell and not a trivial modulation of a surface antigen.

Animals↗
PubMed1993

'Healthy living' and sulphonylurea therapy have different effects on glucose tolerance and risk factors for vascular disease in subjects with impaired glucose tolerance.

This study was undertaken to determine whether impaired glucose tolerance and associated risk factors for cardiovascular disease can be improved with 'healthy living' by diet and exercise or with sulphonylurea therapy. Patients were recruited by screening subjects with either a family history of type II diabetes, previous gestational diabetes, or a previously raised plasma glucose (5.6-6.6 mmol/l). Impaired glucose tolerance was defined as hyperglycaemia on two separate tests, an achieved glucose level after a glucose infusion test above the 90th percentile of an age-matched normal population (> 9.3 mmol/l) or a fasting plasma glucose above the 95th percentile (> 5.6 mmol/l). Thirty-seven subjects with impaired glucose tolerance were entered into a randomized, prospective study for 6 months with allocations to healthy living or double blind to sulphonylurea (gliclazide 40 mg twice daily) or placebo tablets. The study took place in an out-patient setting, with three times weekly exercise sessions at a Sports Centre. After 6 months the placebo group showed no change in plasma glucose, cholesterol and blood pressure. The subjects receiving gliclazide showed improved glucose levels (mean fasting plasma glucose levels fell from 5.8 to 5.1 mmol/l, p < 0.05) but no significant change in plasma cholesterol or blood pressure. The healthy living group, after exclusion of four non-compliant subjects, showed no change in glucose levels, but a decreased systolic blood pressure (fall in mean from 124 to 116 mmHg, p < 0.05) and plasma cholesterol levels (fall in mean from 5.2 to 4.5 mmol/l, p < 0.01). with an increase in HDL:LDL ratio (rise in mean from 0.39 to 0.46, p < 0.05). Subjects with impaired glucose tolerance may benefit in different ways from gliclazide and healthy living. The metabolic responses to each therapy may help to decrease the risk of developing diabetes and cardiovascular disease.

Adolescent↗
PubMed1992

Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

OBJECTIVE: The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS: Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS: 23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING: Tertiary referral centre for cardiology. RESULTS: In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal, and four showed no clear change. In those with myocardial infarction four out of five patients had changes that resembled those with normal ventricles but the changes were less pronounced. There were no differences in any of the three groups between the changes in monophasic action potential duration in patients taking beta blockers and those who were not. The changes in monophasic action potential duration in the transplanted heart resembled those in the group with normal ventricles. Inflections on the repolarisation phase of the monophasic action potential consistent with early afterdepolarisations were seen in three of the patients with abnormal wall motion and in none of those with normal wall motion. CONCLUSIONS: These results are further evidence that changes in ventricular loading influence repolarisation. When wall motion was abnormal the effects on regional endocardial repolarisation were often opposite in direction to those when it was normal. Thus regional differences in wall motion could generate local electrophysiological inhomogeneity which may be relevant to the association of arrhythmia with impaired left ventricular function.

Action Potentials↗
PubMed1992

Effect of abrupt changes in ventricular loading on repolarization induced by transient aortic occlusion in humans.

We have investigated the influence of ventricular loading on repolarization from beat to beat in the human heart. Sixteen patients undergoing routine coronary artery surgery were studied. Left ventricular epicardial monophasic action potentials and local electrograms were recorded during acute changes in ventricular loading induced by transient aortic occlusion. Monophasic action potential duration shortened (P less than 0.0001) and returned to control values within one or two beats after release (P less than 0.0001). Values at 90% repolarization were 325 +/- 31 ms preocclusion, 311 +/- 29 ms during occlusion, 326 +/- 32 ms postocclusion. The Q-T interval of the local epicardial electrogram shortened during occlusion (P less than 0.001) and returned to control values after release (P greater than 0.0001): 396 +/- 44 ms preocclusion, 379 +/- 41 ms during occlusion, and, 399 +/- 42 ms postocclusion. A significant correlation was obtained between changes in peak systolic pressure and changes in monophasic action potential duration (R = 0.96; P less than 0.0001 at 90% repolarization). A significant correlation was also observed between changes in peak systolic pressure and the Q-T interval of the local electrogram (R = 0.91; P less than 0.0001). This study shows that abrupt changes in ventricular loading from one beat to the next induce significant changes in the timing of ventricular repolarization. These results may well be relevant to the initiation of arrhythmia by a single ventricular ectopic beat, particularly under pathological conditions.

Action Potentials↗
PubMed1992

Altered patterns of glycosylation on rat lymphocytes associated with activation.

The expression of cell-surface carbohydrates on rat lymphocytes was investigated by flow cytometry using a panel of lectins. A small group of lectins was identified, all with a main binding requirement of N-acetylgalactosamine that bound to all B lymphocytes but only to activated T lymphocytes expressing the interleukin-2 (IL-2) receptor (as shown by staining with the monoclonal antibody OX39). Studies demonstrated that five of these lectins competed for the same binding site, while others did not. With the knowledge of the binding requirements of these lectins, a structure can be deduced for the carbohydrate moiety which appears on T lymphocytes when activated.

Animals↗