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Biomedical subjects

R Bellomo

Publications and source records attributed to R Bellomo.

At least 217 records · Page 12Linked to original sources

Human melanoma cell line M14 secretes a functional interleukin 2.

Interleukin 2 (IL2) is an important regulator of the immune system. In this report, we have analysed five human melanoma cell lines expressing the IL2R for their ability to secrete IL2. In the M14 melanoma cell line, we observed the appearance of the 0.9 kb transcript specific for the IL2 gene, 72 h after subculture, and the secretion of a biologically active IL2 which specifically sustains the proliferation of the IL2 dependent murine lymphoid cell line CTLL2. In M14 cells, IL2 gene activation is transient as in lymphoid cells but is not inhibited by the immunosuppressive drugs cyclosporine-A and FK506 which are effective on PHA-blasts. In M14 cells, recombinant IL2 (36 pM) induces the down modulation of ICAM-1 expression at the surface of M14 cells. Overnight incubation of these cells with polyclonal anti-IL2 antibodies leads to an increased expression of ICAM-1 and a decreased membrane detection of the IL2R alpha, suggesting the existence of an autocrine/paracrine loop involved in the surface expression of these antigens. A decreased expression of the ICAM-1 protein could help some melanoma cells to escape from cytolytic recognition and therefore favour their metastasis.

Cell Adhesion Molecules↗

[Extraskeletal myxoid chondrosarcoma of the abdominal wall. A clinical, histological, ultrastructural and cytofluorimetric case study].

The authors present a case of extraskeletal myxoid chondrosarcoma of the abdominal wall, an unusual localization and specific presentation. According to the literature, the clinical characters of this kind of tumor, the diagnostic iter and the therapeutic indications are being examined. The actual anatomopathological patterns used for the diagnosis of this neoplasm are being underlined.

Abdominal Muscles↗

Two consecutive thunderstorm associated epidemics of asthma in the city of Melbourne. The possible role of rye grass pollen.

OBJECTIVE: To document the clinical impact and identify the meteorological and environmental circumstances surrounding two epidemics of asthma exacerbations associated with thunderstorms in the city of Melbourne and to find a possible aetiology for these events. DESIGN: Collection of meteorological and environmental data from the Victorian Bureau of Meteorology and the Environment Protection Authority; collection of clinical data from metropolitan emergency departments and the Victorian Ambulance Service; and study of a cohort of affected patients with asthma and a control group of asthmatics who were not affected by the storms. SETTING: Tertiary institution. PATIENTS: Twelve storm-affected patients with asthma and 16 asthmatics not affected by the storms. INTERVENTION: Administration of a questionnaire, medical interview, pulmonary function tests and skin prick tests with common allergens. MAIN OUTCOME AND RESULTS: Both epidemics caused a major increase in the number of hospital attendances and admissions because of asthma exacerbation (five to ten fold rise). These events could not be related to atmospheric pollution or specific meteorological features of the storms. Patients affected by the second storm were significantly more likely to suffer from hay fever (P less than 0.05), rye grass pollen allergy (P less than 0.05) and allergy to rainfall released rye grass starch granules (P less than 0.025). CONCLUSIONS: Late spring thunderstorms in the city of Melbourne can trigger epidemics of asthma attacks. The seasonal nature of the phenomenon and the pattern of allergic responses found in affected patients suggest a possible aetiological role for rye grass pollen.

Air Pollution↗

Mechanism of grass-pollen-induced asthma.

Many asthmatics are sensitive to rye-grass pollen, but pollen grains are too large to penetrate the lower airways. Our aim was to investigate the mechanism by which rye-grass pollen causes asthma. A major allergen of rye-grass pollen, Lol pIX, is located in intracellular starch granules within pollen grains. In-vitro tests showed that pollen grains are ruptured in rainwater by osmotic shock, each grain releasing about 700 starch granules into the environment. These granules are small enough to enter the airways (less than 3 microns in diameter). The starch granules were present in atmospheric samples taken during the pollen season, and showed a 50-fold increase in atmospheric concentration on days following rainfall. Isolated granules elicited IgE-mediated responses in asthmatic patients, and 4 patients with rainfall-associated asthma who underwent an inhalation challenge test had striking bronchial constriction after exposure to starch granules. Starch granules released from rye-grass pollen seem to be capable of causing asthma.

Allergens↗

Renal allograft scintigraphy with Tc-99M-DTPA--its role during cyclosporine therapy.

There are no accurate noninvasive methods to distinguish renal allograft dysfunction due to rejection or cyclosporine nephrotoxicity. We have studied the value of Tc-99M-DTPA renal scanning in 90 episodes of renal allograft dysfunction occurring in 44 patients subjected to 57 renal biopsies in whom a clear diagnosis could be established. Renal scintigrams were assessed qualitatively and quantitatively by a blinded observer. Rejection was diagnosed when deterioration in perfusion occurred in the presence of maintained or declining radionuclide excretion. The diagnosis of cyclosporine nephrotoxicity was made by exclusion. The final diagnosis was based on the clinical response to therapy and/or the findings on renal biopsy. The scintigraphic diagnosis of rejection had a specificity of 87.9% and significantly contributed to the exclusion of cyclosporine nephrotoxicity (negative predictive value of 90.6%). Furthermore, a scintigraphic diagnosis compatible with cyclosporine nephrotoxicity, in the presence of a drug level above the therapeutic range, indicated a 90.4% probability of true nephrotoxicity. We conclude that, even in cyclosporine-treated renal transplant patients, Tc-99M-DTPA scintigraphy is of clinical value and can be incorporated into an effective diagnostic algorithm for allograft dysfunction.

Cyclosporine↗

Use of continuous haemodiafiltration: an approach to the management of acute renal failure in the critically ill.

We have prospectively investigated the effect of a flexible approach to the management of acute renal failure in critically ill patients based on continuous haemodiafiltration (CHD). Fifty critically ill patients (mean APACHE II score 28.1, range 18-37), with a mean age of 59.5 years, were treated with continuous arteriovenous haemodiafiltration (CAVHD) and/or continuous venovenous haemodiafiltration (CVVHD). CHD achieved excellent haemodynamic stability and control of azotaemia in all patients and permitted aggressive parenteral nutrition. The mean blood urea concentration fell from 33.9 mmol/l (95% confidence interval, CI, 29.1-38.7) to a plateau of 17 mmol/l (95% CI 14.3-19.7) after 72 h of therapy despite persistent anuria and the parenteral administration of 0.3 g/kday of protein nitrogen (mean urea clearance: 24.2 ml/min; 95% CI 22.9-25.5). No supplemental dialytic therapy was required during the 9,485 h of treatment. All clinically significant complications related to vascular access (14%). Twenty-two patients (44%) survived to be discharged from the ICU. CHD is relatively safe and effective in the management of acute renal failure in the critically ill.

Acute Kidney Injury↗

The cytokine network in the critically ill.

There is increasing experimental and clinical evidence that a number of cytokines play a major role in the response to injury and infection and in the development of organ damage in critically ill patients. Tumour necrosis factor (TNF) is now proposed to be a key mediator of organ injury during sepsis. It is elevated early in the course of septic shock and high levels correlate with unfavourable outcome. In animals it can produce the effects of endotoxin. The prophylactic administration of anti-TNF antisera protects mice and rabbits from lethal effects of lipopolysaccharide. Interleukin-1 (IL-1) is an endogenous pyrogen which induces leukocytosis and muscle catabolism. It causes hypotension and tachycardia by reducing smooth muscle contractility. IL-1 receptor blockers have been shown to diminish mortality in experimental endotoxic shock. Interleukin-6 (IL-6) is a pyrogen and lymphocyte activator. It is the major stimulus to acute phase protein production by the liver. A recently described neutrophil-activating peptide (Interleukin-8; IL-8) may be involved in the pathogenesis of ARDS. High blood levels of IL-8 have been found in patients with septic shock. Platelet-derived growth factor (PDGF) has been shown to stimulate TNF production, leukocyte chemotaxis and pulmonary vasoconstriction in response to endotoxin. Other cytokines and growth factors have not yet been studied in critical illness. The cytokine network can be either protective or damaging. Its activation during critical illness triggers complex and still poorly understood interactions. A better comprehension of its role in protection from infection and in the pathogenesis of multiple organ failure may allow therapeutic manipulations aimed at minimising adverse effects while retaining immunological protection.

Chemokine CCL2↗

Fibreoptic bronchoscopy in the critically ill: a prospective study of its diagnostic and therapeutic value.

AIM: A prospective study was undertaken to assess the diagnostic value and therapeutic usefulness of fibreoptic bronchoscopy in the critically ill. METHOD: Fifty-six bronchoscopies were performed in fifty patients. Biochemical, radiological, microbiological and clinical assessments were made before and after each procedure. RESULTS: Eighteen fibreoptic bronchoscopies were performed for therapeutic indications (32.1%) of which ten (55.6%) yielded a useful outcome. Thirty-eight bronchoscopies were for diagnostic purposes (67.8%) of which 22 (57.9%) were clinically useful. Broncho-alveolar lavage was performed in twenty-eight cases (50%) and it led to a clinically useful diagnosis in 17 (60.7%). There was no major complication. A subgroup of patients was defined (persistent left lower lobe collapse or consolidation following thoracic or abdominal surgery) in whom fibreoptic bronchoscopy usually did not yield a useful outcome. CONCLUSION: The use of fibreoptic bronchoscopy in the Intensive Care Unit, in combination with the technique of broncho-alveolar lavage, results in a clinically useful outcome in the majority of cases. Fibreoptic bronchoscopy is an effective and safe diagnostic and therapeutic tool in critically ill patients.

Adolescent↗

Management of acute renal failure in the critically ill with continuous venovenous hemodiafiltration.

Continuous venovenous hemodiafiltration (CVVHD) has been increasingly utilized for renal replacement therapy in the critically ill. We report details of a prospective study of CVVHD in 12 critically ill patients (7 males, 5 females; mean age 60 years, range 30-72 years; Apache II score mean 27.4, range 21-35) with oligoanuric acute renal failure supported on CVVHD. Vascular access was obtained via double lumen subclavian or femoral cannulae. The mean pretreatment urea was 35.9 mM/L and the mean pretreatment creatinine was 559 microM/L. After 24 h of treatment on CVVHD these fell to a urea mean of 20.3 mM/L and a creatinine mean of 298 microM/L and remained stable at these values for the duration of CVVHD. The mean net ultrafiltrate volume was 551 mL/h, with a urea clearance mean of 26.6 mL/min and a creatinine clearance mean of 23.7 mL/min. There were no complications related to use of the blood pump module or extracorporeal circuit. Excellent hemodynamic stability, control of fluid and electrolyte balance, and azotaemia control were maintained while on CVVHD. Technique survival was 100%. Patient survival was 42%. We conclude that CVVHD is a safe, effective, and durable therapy for the treatment of acute renal failure in the critically ill and that it offers outstanding metabolic control and cardiovascular stability.

Acute Kidney Injury↗

[Polycystic retroperitoneal leiomyosarcoma. A clinical and anatomo-pathological contribution].

The Authors report an unusual case of retroperitoneal leiomyosarcoma, multicystic, resembling an ovarian cystoma in a patient with simultaneous subclavian-axillary thrombosis. They analyze anatomo-pathological and clinical aspects of this kind of tumor and underline the possible errors they themselves faced. To they come to the conclusion that a careful diagnostic iter of this kind of tumor must be carried out and that the surgical approach must be radical.

Aged↗

Acute continuous hemofiltration with dialysis: effect on insulin concentrations and glycemic control in critically ill patients.

OBJECTIVES: To quantitate insulin losses and glucose absorption during acute continuous hemofiltration with dialysis and to assess the clinical importance of these changes. DESIGN: Prospective collection of serum and ultradiafiltrate fluid in patients receiving acute continuous hemofiltration with dialysis. Measurements of serum and ultradiafiltrate insulin and glucose concentrations. Calculations of insulin excretion and glucose absorption. Correlation of findings with patient outcome. SETTING: University medical center. PATIENTS: Sixteen ICU patients with acute renal failure. MEASUREMENTS AND MAIN RESULTS: The mean serum glucose concentration before acute continuous hemofiltration with dialysis was 178 mg/dL (9.9 mmol/L) (95% confidence interval 112 to 244 mg/dL [6.2 to 13.6 mmol/L]), increasing to 257 mg/dL (14.3 mmol/L) (95% confidence interval 167 to 347 mg/dL [9.3 to 19.3 mmol/L]) after 4 hrs of acute continuous hemofiltration with dialysis, and stabilizing at 207 mg/dL (11.5 mmol/L) (95% confidence interval 160 to 254 mg/dL [8.9 to 14.1 mmol/L]) at 24 hrs. Mean plasma insulin concentration before acute continuous hemofiltration with dialysis was 34.4 mU/L (95% confidence interval 8.6 to 60.2 mU/L), increasing to 54.4 mU/L at 4 hrs (95% confidence interval 25 to 83.8 mU/L; NS). There was no significant decrease in mean insulin concentration across the filter (51.8 mU/L before filtration vs. 51.9 mU/L after filtration). Insulin was detected in the ultradiafiltrate but its overall mean clearance rate was only 6.2 mL/min, with mean daily losses of 689 mU/day (95% confidence interval 325 to 1053 mU/day). During acute continuous hemofiltration with dialysis, glucose absorption through the filter averaged 134 g/day (95% confidence interval 96.2 to 171.8 g/day). Plasma insulin concentrations were significantly (p < .05) lower in survivors than nonsurvivors (51.7 vs. 123.6 mU/L). CONCLUSIONS: Significant glucose absorption occurs during acute continuous hemofiltration with dialysis and is coupled with minor insulin losses (< 1 U/day) through the filter. These events do not appear to have major clinical impact. A low plasma insulin concentration is associated with diminished mortality rates in this group of patients.

Acute Kidney Injury↗

In vitro proliferation and cloning of CD3- CD16+ cells from human thymocyte precursors.

Purified CD3-4- thymocytes were obtained by depletion of CD3+ and CD4+ cells from fresh thymocyte suspensions. 5-15% of these cells were found to express CD16 antigen, while other natural killer (NK) cell markers were virtually absent. Double fluorescence analysis revealed that 20-40% of thymic CD16+ cells coexpressed CD1, while approximately half were cyCD3+. When cultured in the presence of peripheral blood lymphocytes and H9 leukemia cell line as a source of irradiated feeder cells and interleukin 2 (IL-2), CD3-4- thymocytes underwent extensive proliferation. In addition, after 1-2 wk of culture, 30-50% of these cells were found to express CD16 surface antigen. Cloning under limiting dilution conditions of either CD3-4- or CD3-4-16- thymocytes in the presence of irradiated H9 cells resulted in large proportions (approximately 50%) of CD16+ clones. On the basis of the expression of surface CD16 and/or cyCD3 antigen, clones could be grouped in the following subsets: CD16+ cyCD3+; CD16+ cyCD3-; CD16- cyCD3+; and CD16- cyCD3-. All clones expressed CD56 surface antigen, displayed a strong cytolytic activity against NK sensitive (K562) and NK-resistant (M14) target cells, and produced IFN-gamma and tumor necrosis factor, but not IL-2. Similar to peripheral NK cells, thymic CD16+ cells expressed transcripts for CD16 and for CD3 epsilon (Biassoni, R., S. Ferrini, I. Prigione, A. Moretta, and E.O. Long, 1988. J. Immunol. 140:1685.) and zeta chains (Anderson, P., M. Caligiuri, J. Ritz, and S.F. Schlossman. 1989. Nature [Lond.]. 341:159). Therefore, it appears that cells that are phenotypically and functionally similar to CD3- CD16+ NK cells may arise from immature thymocytes.

Antigens, CD↗

Continuous arteriovenous haemodiafiltration in the critically ill: influence on major nutrient balances.

The impact of continuous arteriovenous haemodiafiltration (CAVHD) on nitrogen, lipid and carbohydrate balance was studied in 9 parenterally fed critically ill patients with acute renal failure. The effects on carbohydrate delivery of varying dialysate glucose concentrations or flow rates were also investigated. The total daily nitrogen loss was a mean of 24.1 g (95% CI 20.9-27.3 g/24 h) with non-urea nitrogen losses of 7.6 g (95% CI 5.6-9.6 g/24 h). Glucose delivery was a mean 5.8 g/h with a dialysate glucose concentration of 1.5% and a flow rate of 1 l/h (95% CI 4.5-7.0 g/h). Carbohydrate delivery increased with increased dialysate glucose concentration (mean 11.4 g/h with 2.5% glucose: 95% CI 9.6-13.1 g/h; mean 14.9 g/h with a 4.25% concentration: 95% CI 10.9-19; and with increased dialysate flow rates (mean 9.6 g/h, 95% CI 6.8-12.4 g/h, using 2 l/h of 1.5% glucose). Only trace amounts of cholesterol and/or triglycerides were detected in occasional ultradiafiltrate samples. CAVHD has an important impact on nitrogen and carbohydrate balance, but not on lipid status. Knowledge of these interactions is crucial for the rational planning of nutritional strategies in the critically ill.

Acute Kidney Injury↗

Thymic origin of some natural killer cells: clonal proliferation of human CD3-16+ cells from CD3-4-8- thymocyte precursors requires the presence of H9 leukemic cells.

Purified CD3-4- thymocyte populations were cultured in the presence of interleukin-2 (IL-2) and peripheral blood lymphocytes (PBL) and/or tumor cell lines as a source of irradiated feeder cells. Maximal cell proliferation was obtained in the presence of a mixture of H9 leukemic cells and normal PBL. More importantly, under these culture conditions, 30%-50% of these cells were found to express CD16 surface antigen after 1-2 weeks of culture. Similar proportions of CD16+ cells could be detected in CD3-4- thymocyte populations that had been further depleted of CD16+ cells. Cloning of CD3-4-16- thymocytes under limiting dilution conditions resulted, in the presence of H9 cells, in more than 50% of CD16+ clones (cloning efficiency 3%-8%). Since some of the surface CD3- clones expressed cytoplasmic CD3 antigen, it has been possible to identify four distinct phenotypic groups of clones (CD16+cyCD3+, CD16+cyCD3-, CD16-cyCD3+, CD16-cyCD3-). Independently of their phenotype, all thymus-derived CD3- clones expressed a strong cytolytic activity against natural killer (NK)-sensitive and NK-resistant tumour target cells. In addition, following stimulation with phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (or PHA alone) all clones released interferon-gamma and tumour necrosis factor-alpha, but not IL-2. Taken together, our data provide evidence that cells which share their phenotypic and functional properties with CD3-CD16+ NK cells can be derived from thymic precursors.

Antigens, CD↗