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Biomedical subjects

M Carol

Publications and source records attributed to M Carol.

At least 19 recordsLinked to original sources

Increased mucosal tumour necrosis factor alpha production in Crohn's disease can be downregulated ex vivo by probiotic bacteria.

BACKGROUND AND AIMS: Tumour necrosis factor alpha (TNF-alpha) plays a key role in the pathogenesis of intestinal inflammation in Crohn's disease. The effect of bacteria on TNF-alpha release by intestinal mucosa was investigated. METHODS: Ileal specimens were obtained at surgery from 10 patients with Crohn's disease (ileal stricture) and five disease controls undergoing right hemicolectomy (caecal cancer). Mucosal explants from each specimen were cultured for 24 hours with either non-pathogenic Escherichia coli, Lactobacillus casei DN-114001, L bulgaricus LB10, or L crispatus (each study contained blank wells with no bacteria). Tissue and bacterial viability was confirmed by lactate dehydrogenase (LDH) release and culture. Concentrations of TNF-alpha were measured in supernatants and the phenotype of the intestinal lymphocytes was analysed by flow cytometry. RESULTS: Coculture of mucosa with bacteria did not modify LDH release. Release of TNF-alpha by inflamed Crohn's disease mucosa was significantly reduced by coculture with L casei or L bulgaricus; changes induced by L crispatus or E coli were not significant. The effect of L casei and L bulgaricus was not prevented by protease inhibitors. Coculture with L casei and L bulgaricus reduced the number of CD4 cells as well as TNF-alpha expression among intraepithelial lymphocytes from Crohn's disease mucosa. None of the bacteria induced changes in non-inflamed mucosa. CONCLUSIONS: Probiotics interact with immunocompetent cells using the mucosal interface and modulate locally the production of proinflammatory cytokines.

Adult↗

Comparison of intensity-modulated radiotherapy with conventional conformal radiotherapy for complex-shaped tumors.

PURPOSE: Conformal and intensity-modulated radiotherapy (IMRT) plans for 9 patients were compared based on characterization of plan quality and effects on the oncology department. METHODS AND MATERIALS: These clinical cases, treated originally with conformal radiotherapy (CRT), required extraordinary effort to produce conformal treatment plans using nonmodulated, shaped noncoplanar fields with multileaf collimators (MLCs). IMRT plans created for comparison included rotational treatments with slit collimator, and fixed-field MLC treatments using equispaced coplanar, and noncoplanar fields. Plans were compared based upon target coverage, target conformality, dose homogeneity, monitor units (MU), user-interactive planning time, and treatment delivery time. The results were subjected to a statistical analysis. RESULTS: IMRT increased target coverage an average of 36% and conformality by 10%. Where dose escalation was a goal, IMRT increased mean dose by 4-6 Gy and target coverage by 19% with the same degree of conformality. Rotational IMRT was slightly superior to fixed-field IMRT. All IMRT techniques increased integral dose and target dose heterogeneity. IMRT planning times were significantly less, whereas MU increased significantly; estimated delivery times were similar. CONCLUSION: IMRT techniques increase dose and target coverage while continuing to spare organs-at-risk, and can be delivered in a time frame comparable to other sophisticated techniques.

Carcinoma, Adenoid Cystic↗

Immunohistochemical study of lymphoid tissues in adjuvant arthritis (AA) by image analysis; relationship with synovial lesions.

The aim of this study was to examine leucocyte populations in lymphoid organs during AA and to ascertain the relationship with lesions in synovial joints. Popliteal lymph nodes, spleen and knee synovial membranes were removed from both healthy and AA rats at intervals of 3-4 days over a 3-week period. Cryostat sections were stained with MoAbs directed against lymphocyte and macrophage subpopulations, and studied by image analysis. Throughout the arthritic period, high numbers of ED1+ and ED3+ macrophages were seen in both lymphoid compartments and intercellular adhesion molecule-1 (ICAM-1) expression also increased in some zones of lymph nodes and spleen. The percentages of CD4+ and CD8+ cells rose in the splenic zones studied but fell in the lymph node cortex. Very few natural killer (NK) cells were found in lymphoid tissues, but the number rose after AA induction. In synovia from AA rats, ED2+ macrophages proliferated but alpha/beta T cell infiltration was only occasionally observed, accompanied by ED1+ cells and ICAM-1 expression. In conclusion, synovitis developing after AA induction seems to be caused directly by macrophages and indirectly by lymphocytes placed both in popliteal lymph nodes and spleen.

Animals↗

Diversion of intestinal flow decreases the numbers of interleukin 4 secreting and interferon gamma secreting T lymphocytes in small bowel mucosa.

BACKGROUND/AIMS: The intestinal immune system faces large amounts of antigens, and its regulation is tightly balanced by cytokines. In this study, the effect of intestinal flow diversion on spontaneous secretion of interleukin (IL)-4 and interferon (IFN)- gamma was analysed. METHODS: Eight patients (two with Crohn's disease, four with ulcerative colitis, and two with previous colon cancer) carrying a double lumen small bowel stoma after a total colectomy procedure were included in the study. For each patient, eight biopsy samples were taken endoscopically from both the diverted and non-diverted part of the small bowel. Intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) were isolated separately and assayed for numbers of cells spontaneously secreting IL-4 and/or IFN-gamma by an ELISPOT technique. RESULTS: Compared with the non-diverted mucosa, a significant decrease in the number of spontaneously IFN-gamma secreting CD3 lymphocytes was observed in the diverted small bowel mucosa among both IELs (p = 0.008) and LPLs (p = 0.007). The same results, although less significant, were obtained for IL-4, especially in LPLs (p = 0.01). CONCLUSION: The intestinal content influences the spontaneous secretion of IFN-gamma and IL-4 by intestinal lymphocytes. These results could help to elucidate the anti-inflammatory role of split ileostomy in patients suffering from inflammatory bowel diseases.

Adult↗

An image analysis strategy to determine the distribution of cell types in spleen sections.

An image analysis strategy was designed to objectively determine distribution patterns of cell types in spleen sections. The strategy was applied to rat spleen cryostat sections that were strained immunohistochemically by means of monoclonal antibodies against different populations of lymphocytes and macrophages. The strategy revealed three segments of the spleen beginning in the middle of a central arteriole and ending within the red pulp. In each of these segments, three consecutive zones were established: the white pulp, the marginal zone, and the red pulp. In each tissue section, three segments were selected starting in two different arterioles. Consequently, six segments were analysed in each section. Special software was used to calculate percentages of positive staining in all zones in each segment. Image analysis data for each monoclonal antibody tested correlated closely with microscopical observations. The proposed strategy allows objective quantification of lymphocyte and macrophage populations and their distribution patterns. It is an useful tool for studying imbalances in cell populations in the spleen due to immune challenges.

Animals↗

Persistent T cell and B cell activities in the duodenal mucosa of AIDS patients.

OBJECTIVE: As HIV infection most commonly occurs via a mucosal surface, and as gastrointestinal symptoms are very frequent among HIV-infected patients, we investigated the functional properties of residual lymphocytes in the duodenal mucosa from HIV-infected individuals. DESIGN: Duodenal biopsies and blood samples were obtained from 19 HIV-infected patients [Centers for Disease Control and Prevention (CDC) stage III] and from 19 controls. METHODS: Phenotypic analysis of lymphocytes was performed by flow cytometry and/or immunocytochemistry. Interferon gamma (IFN-gamma), interleukin (IL) 4 and immunoglobulin secretions were analysed by enzyme-linked immunospot techniques. The phenotype of cytokine-producing cells was analysed by flow cytometry. RESULTS: The proportions of duodenal T lymphocytes from HIV-infected patients spontaneously secreting IFN-gamma or IL-4 were not lower than those from healthy controls. In patients with a high intestinal mucosal viral load, they were higher than in controls (P < 0.05). The proportions of immunoglobulin-secreting cells were significantly raised in HIV-infected patients for the three main isotypes. CONCLUSIONS: T- and B-cell populations of the intestinal mucosa remain functional or are even activated in patients with AIDS, even when the numbers of both mucosal and circulating CD4+ lymphocytes are strongly decreased.

Adult↗

Spontaneous secretion of interferon gamma and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes.

BACKGROUND: Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses. AIMS: To quantify interferon gamma (IFN-gamma) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation. PATIENTS: Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa. METHODS: Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-gamma and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT). RESULTS: The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-gamma (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-gamma SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-gamma and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-gamma in the basal state, and 0.1% secreted IL-4. CONCLUSIONS: Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-gamma and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases.

Adult↗

Modulated beam conformal therapy for head and neck tumors.

PURPOSE: The goal of modulated-beam conformal therapy is to reduce the dose to healthy tissue and sensitive structures around a uniformly irradiated target volume. Multiple intensity-modulated fields offer improved tissue-sparing dose distributions. New computer-based systems for planning and delivering such treatments may soon be available from different commercial sources that will make the formulation of an intensity-modulated treatment plan and its execution widely available at any treatment facility that has the resources to acquire the necessary equipment. This work reports on a study of the integration of two such systems. METHODS AND MATERIALS: Treatment planning was done using a commercially available inverse planning algorithm based on simulated annealing. The plans arbitrarily assumed nine coplanar x-ray beams at nonopposed gantry angles. Intensity modulation was computed for each beam. The modulated field at each gantry angle was broken down into a series of uniform (nonmodulated) subfields, which could be delivered as a sequence to produce the desired dose distribution. Because a large number of subfields was delivered, a multileaf collimator (MLC) was used for field shaping. This allowed rapid and accurate field shaping for treatments made up of several hundred subfields. Computer control of the MLC and linear accelerator allowed delivery of doses less than .01 Gy per subfield. Treatment was delivered on a prototype, computer-controlled accelerator and MLC system. Resulting dose distributions were analyzed using film and an anatomically specific, homogeneous phantom. RESULTS: The treatment plans were evaluated using dose-volume histogram analysis. The plans provided acceptably uniform irradiation of the target volume without exceeding dose tolerances for nearby critical structures. The plans were successfully delivered by a prototype dynamic MLC. The time needed to deliver a sequence of subfields at one gantry angle ranged from 0.7 to 2.0 min. Isodoses from film agreed reasonably well with planned isodose distributions. CONCLUSIONS: It is feasible to plan and deliver fixed gantry, modulated-beam conformal therapy for head and neck tumors with systems being developed commercially. The planned dose distributions exhibit significant potential for sparing closely spaced normal tissue structures in the head and neck.

Algorithms↗

A comparison of intensity modulated conformal therapy with a conventional external beam stereotactic radiosurgery system for the treatment of single and multiple intracranial lesions.

PURPOSE: To compare the stereotactic radiosurgery treatment plans generated by a conventional radiosurgery treatment system with the plan generated by a system using intensity modulated beams. METHODS AND MATERIALS: Optimized conformal radiation treatment plans were generated for both single and multiple intracranial lesions using a conventional radiosurgery treatment-planning system computer and the Peacock treatment-planning computer. The Peacock system is a conformal therapy system that uses intensity modulated beams, back projection, and the simulated annealing optimization technique. The dose delivered to critical structures and the target volume were compared by means of dose volume histograms between plans generated by the two different systems. The Radiation Therapy Oncology Group (RTOG) stereotactic radiosurgery criteria were also used to evaluate each plan. RESULTS: (a) For a single small target, radiosurgery plans generated by the conventional radiosurgery system and the Peacock system were comparable. (b) For two separate small targets, where nonoverlapping arcs could be used, plans generated by the two systems were also comparable. (c) For a single large (>4 cm) irregular-shaped target, the Peacock system appeared to be able to generate a treatment plan superior to that of the conventional radiosurgery system. CONCLUSIONS: A treatment plan generated using intensity modulated beams appears to be superior to a multiple isocenter plan using a conventional radiosurgery system, for the treatment of a large irregular shaped intracranial target.

Radiosurgery↗

The field-matching problem as it applies to the peacock three dimensional conformal system for intensity modulation.

PURPOSE: Intensity modulated beam systems have been developed as a means of creating a high-dose region that closely conforms to the prescribed target volume while also providing specific sparing of organs at risk within complex treatment geometries. The slice-by-slice treatment paradigm used by one such system for delivering intensity modulated fields introduces regions of dose nonuniformity where each pair of treatment slices abut. A study was designed to evaluate whether or not the magnitude of the nonuniformity that results from this segmental delivery paradigm is significant relative to the overall dose nonuniformity present in the intensity modulation technique itself. An assessment was also made as to the increase in nonuniformity that would result if errors were made in indexing during treatment delivery. METHODS AND MATERIALS: Treatment plans were generated to simulate correctly indexed and incorrectly indexed treatments of 4, 10, and 18 cm diameter targets. Indexing errors of from 0.1 to 2.0 mm were studied. Treatment plans were also generated for targets of the same diameter but of lengths that did not require indexing of the treatment couch. RESULTS: The nonuniformity that results from the intensity modulation delivery paradigm is 11-16% for targets where indexing is not required. Correct indexing of the couch adds an additional 1-2% in nonuniformity. However, a couch indexing error of as little as 1 mm can increase the total nonuniformity to as much as 25%. All increases in nonuniformity from indexing are essentially independent of target diameter. CONCLUSIONS: The dose nonuniformity introduced by the segmental strip delivery paradigm is small relative to the nonuniformity present in the intensity modulation paradigm itself. A positioning accuracy of better than 0.5 mm appears to be required when implementing segmental intensity modulated treatment plans.

Algorithms↗

Initial clinical experience with the Peacock intensity modulation of a 3-D conformal radiation therapy system.

Peacock is a 3-D conformal treatment planning and delivery system for conformal radiation therapy which delivers intensity-modulated fields. A group of 13 patients were treated between March and February, 1995. Patient age ranged from 10 to 74. Six of the patients had previously received radiation therapy. Target volume was from 2.5 to 70 cm3: all treatments were fractionated, using single table angle plan with 270 degrees of rotation. A removable invasive cranial screw fixation device was used in all cases. Treated isodose line averaged 85%; conformality index was better than 2, with 0-5% of critical structure volume exceeding dose limits. Setup time averaged 8 min per fraction: treatment time ranged from 10 to 80 min. There were two equipment failures in 200 fractions/1,000 gantry rotations. Patient position averaged about 1 mm within initial setup. Follow-up has revealed no complications from the radiation.

Adolescent↗

Experience with the Pelorus stereotactic system.

The Pelorus stereotactic system, by its unique approach, alleviates the need for the traditional head frame and computer-generated coordinates which are common to most other systems. Despite its simplicity, it sacrifices nothing in terms of the range of problems for which it can be used to diagnose and treat. In fact, its unencumbered design may make it more appropriate for advanced procedures than conventional systems.

Humans↗

Percutaneous placement of ventriculoatrial shunts: four-year case experience.

During the past 4 years, we have used percutaneous placement of the atrial catheter in 39 patients who have undergone ventriculoatrial shunting. The age range of our patients has been from 9 to 74 years of age, with routine indications existing. Both subclavian and internal jugular venous access have been utilized, with the latter being our preferred route of access for reasons of safety. Average operative time has been approximately 35 to 40 minutes. Both traditional and split-sheath introducer catheters have been used. Patient follow-up has been up to 4 years. Intraoperative complications have been limited to puncture of the carotid artery on two occasions; neither affected the ultimate performance of the procedure. Postoperative complications have been limited to those peculiar to shunt procedures in general and have required revision in four instances. One patient suffered an infection secondary to shunting. The benefits of this procedure seem to include safety, decreased operative site exposure, and decreased operative time, all factors that may contribute to a lower than normal infection rate and may warrant consideration of this procedure in adolescents and adults for whom ventriculoatrial shunting is indicated.

Adolescent↗

A true 'advanced imaging assisted' skull-mounted stereotactic system.

A stereotactic system has been designed based upon a series of interlocking discs secured to the skull with self-tapping screws. Unlike previous skull-mounted systems, this system is a true, advanced imaging based stereotactic device with the capabilities and accuracy of more traditional, frame based devices. It has been used in a range of applications, from simple biopsies to interstitial radiation implant procedures. Well tolerated by the patient, it allows reaccess to the intracranial target without rescanning. It is convenient for the physician to utilize, both mechanically and timewise, is adaptable to MRI, DSA, and conventional X-ray techniques without modification, and is affordable.

Brain Diseases↗

Immediate mini-myelography in acute cervical cord injuries.

The use of contrast myelography in the evaluation of acute cervical spinal cord trauma is controversial. The purpose of employing such a technique is to demonstrate any persistent extradural cord compression after the spine is realigned by skeletal traction. The surgical correction of such compression may result in enhanced neurological recovery. The "mini-myelogram" is accomplished by performing a lateral C1/C2 spinal puncture and injecting a low volume of Pantopaque into the subarachnoid space. Demonstration of significant extradural compression results in emergency surgery for appropriate decompression. A small percentage of patients may enjoy enhanced recovery due to the decompression. A description of the technique and results of 90 patients undergoing mini-myelography are presented.

Adult↗

Minimyelogram in cervical spinal cord trauma.

Fifty-eight patients with a clinical or radiographic diagnosis of cervical spinal cord injury underwent Pantopaque myelography on an emergency basis. Twenty-five per cent of these patients demonstrated evidence of spinal cord compression after reduction by spinal traction, as evidenced by the presence of a myelographic defect. Less than half of these patients had a defect that the authors thought required emergency surgical decompression. Two of the five patients so operated upon demonstrated an improvement in neurological function after operation that was much greater than that which would have been predicted before operation. The finding of these few patients who made a significant improvement after operation may justify the myelographic investigation of all patients with evidence of serious cervical spinal cord injury. Based on our experience, Pantopaque myelography may offer adequate, accurate, and useful information for the immediate management of spinal cord-injured patients.

Arachnoiditis↗

Test for oral and postingestional factors mediating differential acceptability of morphine, methamphetamine, and chlordiazepoxide drinking solutions.

The relative degrees to which aversive oral (presumably gustatory) and postingestional variables attenuate the voluntary drinking of morphine, methamphetamine, and chlordiazepoxide solutions by rats were assessed by comparing immediate acceptability with subsequent acceptability. Results indicated that morphine solutions (0.01--0.05%) are avoided primarily because of unpalatability, while methamphetamine (0.005--0.02%) and chlordiazepoxide solutions (0.02--0.08%) are avoided primarily because of aversive postingestional effects.

Administration, Oral↗