[Acute pancreatitis: sleeping with the enemy].
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Biomedical subjects
Publications and source records attributed to R Troiano.
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We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.
In a double-blind prospective randomized trial, we assessed the efficacy and safety of modified total lymphoid irradiation (TLI) plus low dose prednisone (TLI-LDP) as compared to sham TLI plus identical prednisone therapy (sham TLI-LDP) in 46 patients with progressive forms of multiple sclerosis (MS). No significant difference existed between groups at study entry in patient age, sex, duration of MS, or disability status. However, following treatment, significantly fewer TLI patients showed a sustained one point decline in the Expanded Disability Status Scale, the primary study endpoint, as compared to the sham TLI group using the Kaplan-Meier Product-limit survival analysis, (P<0.005). Risk for relapse requiring treatment with intravenous methylprednisolone was reduced by 54% in the TLI-treated group (P<0.05). Significantly fewer TLI-LDP patients had gadolinium enhancing plus new T2-weighted lesions (P=0.018) when compared to the sham group post-treatment. There was also a substantial and significant decrease in blood lymphocytes in the TLI-LDP group when compared to either pretreatment values or to sham TLI-LDP through at least 12 months post-therapy. Side effects secondary to TLI were generally mild and well-tolerated. These results further support the hypothesis that TLI and systemic immunosuppression have a beneficial effect in progressive forms of MS.
The good correlation between exposure to n-hexane and 2,5-hexanedione urinary excretion confers on this diketone an important toxicological meaning. this paper proposes a reversed-phase HPLC method which includes, after acid hydrolysis, a derivatization step of 2,5-hexanedione with 2,4-dinitrophenylhydrazine at 70 degrees C for 20 min. The reaction conditions, such as temperature, reagent concentration and time, are optimized so as to allow the condensation of a single carbonyl group. A linear response was obtained in the 0.19-20.0 mg/l range with a detection limit of 0.03 mg/l, corresponding to a signal-to-noise ratio of 3. A phosphate buffer (pH 3.3)-acetonitrile mixture (50:50) as the eluent and UV detection at 334 nm were used.
Total lymphoid irradiation (TLI) has been reported to delay deterioration in patients with progressive multiple sclerosis and other autoimmune disorders. METHODS--In an open trial, the effect of TLI combined with a one year course of low dose prednisone was compared to the effect of sham TLI and TLI only in a prior double-blind study of patients with progressive multiple sclerosis. RESULTS--Twenty-seven patients receiving TLI combined with corticosteroids had significantly greater lymphocytopenia in the year post-therapy than those receiving TLI only or sham TLI and Kaplan Meier product-limit survival analysis showed significantly less progression in the TLI plus steroid group over 4 years of follow-up. No difference in lymphocytopenia or progression was found with TLI plus corticosteroid therapy when the spleen was removed from the field of irradiation. CONCLUSION--These results lend further support to the hypothesis that TLI may be effective in progressive MS, and indicates that adding low-dose prednisone may enhance this effect. The study also suggests that TLI may be equally effective whether or not the spleen is irradiated.
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Gestation is a period of decreased risk for a relapse of MS, whereas the 3 months postpartum is a period of high risk. Taken together, the pregnancy year may also be a period of higher risk for relapse than non-pregnancy periods. However, the lifetime risk rate does not appear to change because of pregnancy, and on the basis of current retrospective studies, long-term disability is not higher in pregnant women or even women experiencing relapses during the pregnancy year. MS has little or no effect on the course of pregnancy or delivery, although patients with severe MS may have difficulty fully caring for their newborns. The decision to become pregnant should be made by the patient and her husband after they are appropriately informed about the risks involved.
This study compared change scores obtained on patient self-reported symptoms (MS-RS) with the neurological examination of the Kurtzke Functional Systems (FS) and change scores obtained on patient self-reported activities of daily living (ADL-MS) with the neurologist-determined Expanded Disability Status Scale (EDSS) that were obtained from two separate times separated by approximately seven months for 100 patients with multiple sclerosis. Percent agreement based on < or = 1 unit difference between patient and neurologists' change scores (Time 2-Time 1) ranged between 73% and 86% for MS-RS and FS measures and was 72% for ADL-MS and EDSS. Together, the ADL and MS-RS patient self-report scales provide health status information from the patient's perspective that can be useful in guiding the physical examination, in making comparisons from visit to visit and/or between visits, in assessing patients' quality of life, and in increasing patient satisfaction with medical care.
OBJECTIVE: The fast spin-echo pulse sequence allows T2-weighted MR images to be acquired more rapidly than is possible with conventional spin-echo sequences, and phased-array coils can provide a higher signal-to-noise ratio than is possible with the body coil. The combination of these methods permits higher resolution images to be obtained with more signal averages despite shorter imaging times. In this study, initial technical comparisons designed to confirm the advantage of combining fast spin-echo pulse sequences with a pelvic phased-array multicoil were followed by an assessment of the value of these methods for the localization and staging of prostatic carcinoma. SUBJECTS AND METHODS: Seventy-one men with known (60) or suspected (11) prostatic carcinoma were imaged with T2-weighted fast spin-echo pulse sequences in the axial and coronal planes with a phased array of four surface coils (multicoil) for signal reception. Four of these men also were imaged with fast spin-echo sequences and the body coil, and six of these men also were imaged with T2-weighted conventional spin echo sequences and the multicoil; image qualities achieved with these techniques were compared. The use of IV glucagon (42 of 71 studies) before fast spin-echo sequences was correlated with the subsequent presence or absence of peristaltic artifacts on MR images. MR images were analyzed for the presence or absence of prostatic cancer in the right and left sides of the gland and for evidence of spread either through the capsule, into the seminal vesicles, or to lymph nodes or bone. Findings at MR imaging were compared with results of radical prostatectomy (20), lymph node dissection without prostatectomy (seven), and biopsy (67). RESULTS: Image quality obtained with the combination of the fast spin-echo sequence with the multicoil was judged superior to that obtained with either the conventional spin-echo sequence with the multicoil or the fast spin-echo sequence with the body coil. Significant motion artifacts were noted in 45% of studies (13/29) performed without glucagon vs 7% of studies (3/42) performed with glucagon. In the 58 patients for whom information concerning the location of tumor in either the right or left side of the gland was obtained from biopsy (39) or surgery (19), MR images allowed cancer to be detected with 89% sensitivity and 77% specificity. Among the 20 patients undergoing prostatectomy and seven others undergoing lymph node dissection, MR imaging permitted high accuracies in predicting involvement of the seminal vesicles (100%), local transcapsular spread (85%), and involvement of pelvic lymph nodes (85%). CONCLUSION: Fast spin-echo imaging with a pelvic phased-array multicoil provides high-resolution images of the prostate that may obviate an endorectal coil for the detection, localization, and staging of prostatic carcinoma.
The chronic ingestion of fenfluramine results in a sustained depression in body weight despite the return of ad libitum food intake to normal levels. This chronic suppression of body weight is immediately reversed after discontinuation of the drug treatment. Such a phenomenon indicates that the drug must increase metabolic rate. However, studies in both humans and animals have failed to demonstrate an increase in metabolic rate after the administration of the drug. Instead, fenfluramine appears to potentiate the expenditure of energy whenever increases in energy expenditure occur. Fenfluramine potentiates the thermic effect of food (TEF) both in animals as well as in humans. Moreover, the energy cost of locomotor behavior also appears to be potentiated by this drug. Most importantly from a therapeutic perspective, unlike the anorectic effect of fenfluramine, tolerance does not appear to develop to its ability to potentiate energy expenditure.
In an attempt to prevent disease exacerbations, intravenous gamma globulin (500 mg to 2 g/kg) plus methylprednisolone was administered monthly to 14 patients with progressive multiple sclerosis, 11 of whom were steroid dependent. Seventeen exacerbations of disease activity were seen in 11 patients over a mean follow-up period of 7.8 months. Four exacerbations occurred in 3 patients within one month of receiving 1.6 to 2.0 g/kg of intravenous gamma globulin (IVGG). Most exacerbations occurred within 2 weeks of steroids being tapered; thus a steroid sparing effect of IVGG could not be demonstrated. We conclude that IVGG plus methylprednisolone can be given safely at monthly intervals for a prolonged period but in the dosage administered did not prevent exacerbations in 80% of patients with progressive multiple sclerosis.
PURPOSE: The aim of this study was to assess the utility of clinical assessment of respiratory muscle weakness in MS. PATIENTS AND METHODS: We studied 40 MS patients who performed pulmonary function tests using standard procedures and measures of respiratory muscle strength. Descriptive clinical indices included a history of detailed neurologic findings, including upper and lower extremity weakness, cerebellar signs, and evidence of cerebral lesions and other clinical signs including dependence in activities of daily living, shortness of breath, weak voice, dysarthria and dysphagia. We devised an index comprised of four clinical signs: the patient's report of difficulty in clearing pulmonary secretions and his report of a weakened cough, the examiner's observation of the patient's cough, and ability to count on a single exhalation. RESULTS: Mean values of TLC (95 percent +/- 14) VC (91 percent +/- 19), and RV (106 percent +/- 34) were normal. By contrast, MVV (68 percent +/- 20), PImax (74 percent +/- 27) and PEmax (51 percent +/- 22) were decreased. Stepwise multiple regression indicated that the best single predictor of expiratory muscle weakness was the index score; the combination of index score, upper extremity weakness, and maximal voluntary ventilation accounted for 60 percent of the variance in PEmax. CONCLUSION: We conclude that clinical assessment is a better predictor of respiratory muscle weakness than spirometry and that a systematic clinical assessment supplemented by respiratory muscle assessment and MVV can uncover subtle respiratory muscle weakness in patients with MS.
Serum levels of the soluble interleukin-2 receptor (sIL-2R), an indicator of T cell activation, were significantly elevated in chronic progressive MS (CPMS) patients, clinically stable MS patients and in patients with other neurological diseases (OND) as compared to healthy controls. Levels of sIL-2R in steroid treated CPMS patients were markedly lower than in untreated CPMS patients and were comparable to healthy controls. Thus, systemic T cell activation occurs in MS during clinically stable and progressive disease stages and in other neurological disorders. The ability of oral corticosteroids to depress serum sIL-2R levels in vivo may be one mechanism by which they exert their therapeutic effect.
Decreased numbers of CD4+CD45R+ suppressor-inducer T cells have been reported in patients with a variety of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis but not in patients with other neurological diseases. We now report our findings using murine monoclonal antibodies and two-color flow cytometric analysis on CD4+CD45R+ T cells in 22 patients with chronic progressive multiple sclerosis, 23 patients with other neurological diseases and 42 normal, healthy controls. Suppressor-inducer T cells were significantly reduced (p less than 0.001) in both patients with multiple sclerosis and other neurological diseases as compared to controls. Both patient populations had elevated helper T cell subset ratios. Thus, our data suggests that decreases in suppressor-inducer T cells may represent a common immunological defect among autoimmune and presumably non-autoimmune neurological disorders.
Twenty-seven young patients with multiple sclerosis (MS) were studied to determine if they had received prior measles vaccination. Fourteen patients whose immunization records were available had received measles vaccine in childhood. Eight other patients gave a history of receiving measles vaccine. These results suggest that infection by measles virus is probably not the sole cause of MS and that, unlike subacute sclerosing panencephalitis and postmeasles encephalitis, MS may not be preventable by measles vaccination given at an appropriate age.
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