[Immune thrombocytopenic purpura and HIV infection. Presentation of 3 cases].
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Biomedical subjects
Publications and source records attributed to S Brunet.
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A case with features of both multiple myeloma and non-Hodgkin's lymphoma at the moment of diagnosis is presented. The patient had lytic bone lesions and biclonal gammopathy, IgM kappa and IgA kappa. In the bone marrow biopsy, there was a diffuse infiltration by atypical plasma cells coexisting with an interstitial and nodular infiltration by poorly differentiated lymphoid cells. Immunofluorescence studies showed positive staining with alpha and kappa antisera in the cytoplasm of plasma cells and with mu and kappa antisera on the surface of lymphoid cells. After the beginning of chemotherapy, the IgA kappa monoclonal protein disappeared and the IgM kappa monoclonal protein remained constant.
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In the presence of amyloid enhancing factor, a variety of inflammatory stimuli, many of them nonantigenic, trigger amyloid deposition in 48 hours. There is a striking correlation between the extent of splenic amyloid deposition and the severity of inflammation at the injection site of the various irritants. Sublethal irradiation results in a parallel effect on the local inflammatory response and the accompanying extent of amyloid deposition produced in the spleen. Evidence that a product of local acute inflammatory responses is related to the deposition of amyloid is also presented. It is proposed that this product is a protease derived from the infiltrating polymorphonuclear leukocytes.
Using polyacrylamide gel electrophoresis and radioiodinated plasma proteins, data on the rate constant for synthesis and fractional degradation rates for albumin, alpha1-, alpha2-, beta-, and gamma-globulins were obtained during accelerated amyloid induction in a murine model. The results indicate that during amyloid induction there is an increased rate of synthesis of alpha2-, beta-, and gamma-globulins but only the alpha2-globulin degradation rate is accelerated. In this experimental system, should amyloid protein be a degradation product of a plasma fraction, the alpha2-globulin appears as the most likely precursor. The implications of our findings are discussed, and a new general mechanism of amyloid production is proposed.
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Specific binding for the serotonin 5-HT4 receptor (5-HT4R) radioligand [3H]GR 113808 was identified in pig caudate nucleus and characterized by serotonin subtype selective drugs. Binding was inhibited by serotonin and by synthetic indoles, benzamides and benzimidazolones known to characterize the 5-HT4R in functional tests. Rank order of potency of 5-HT4R antagonists was: GR 125487 (Ki, 0.19 nM) > GR 113808 >> SC 53606 > SDZ 205,557 > RS 235971/190 > DAU 6285 > tropisetron > DAU 6215. GR 125487 and GR 113808 were highly selective with respect to the 5-HT3 receptor (5-HT3R). Rank order of potency of 5-HT4R agonists was: SC 53116 (Ki, 21 nM) > BIMU 1 > cisapride > BIMU 8 > serotonin > renzapride > S-zacopride > metoclopramide > R-zacopride > 5-methoxytryptamine >> 5-carboxamidotryptamine. BIMU 8, renzapride, metoclopramide and the zacopride enantiomers gave shallow competition curves. The agonists were substantially less selective than the antagonists with respect to the 5-HT3R. With only two exceptions, SCH 23390 and metergoline, which bound with sub-microM affinity to the 5-HT4R, binding was not inhibited by compounds selective for other G-protein-coupled or channel-gated receptors. Highly significant correlations in affinities of compounds for 5-HT4R in caudata of pigs, guinea pigs and humans were found suggesting no difference among mammalian species.
Patient selection and optimal timing for implantation are unsettled issues in candidates for a bridge to cardiac transplantation. A prospective evaluation of a strategy based on enoximone (E) given IV, in addition to sympathomimetic drugs, permitting to buy time, and delay by hours or days the decisions, has been performed from 1985 to 1988. Thirty-four patients in cardiogenic shock with hemodynamical criteria for TAH implantation have been included: Cl was 1.8 +/- 0.2 L/min/m2 PCWP 29 +/- 7 mmHg, diuresis less than 20 ml/hr. The protocol permitted to postpone decisions of implantation in 30 cases. The 4 unresponsive patients were implanted immediately with TAH (3) or VAD (1). Three were transplanted, two successfully. For 30, time given permitted discovery of hidden contraindications to transplantation in 17 patients. In 13, indication for transplantation was confirmed and performed in 11 within 6 hrs to 8 days (survival 64%). In two, sudden deterioration led to an unsuccessful TAH implantation. Multifactorial analysis showed that a 50% rise in Cl together with a 50% drop in PCWP, a 50% drop in PVR 30 min after IV E has a high predictive value of survival. These data suggest that enoximone IV bolus given in addition to maximal sympathomimetics to patients in cardiogenic shock reduces by 88% the need for TAH or VAD. It also permits a better selection of the candidates.
We studied the safety of low-dose amphotericin B lipid complex (ABLC, at 1 mg/kg/day) in 30 persistently febrile (>38 degrees C for at least 5 days or with recurrent fever after 3 days of apyrexia) and neutropenic (<0.5 x 10(9)/l) adult patients with hematologic malignancies. The median age was 45 years (range 18-67), most (60%) had an acute leukemia and all had fever of unknown origin (FUO). The total duration of neutropenia was a median of 17 days (range 9-33), and the total number of days with fever 10 days (range 6-39). Seven patients experienced mild-to- moderate infusion-related adverse events (IRAE). The serum creatinine and urea increased from baseline to end of therapy in 76 and 63% of cases, but the maximum levels reached were <130 micromol/l and <11 mmol/l, respectively, in all cases. Liver enzymes showed modest but significant increases in most patients during therapy, while bilirubin decreased in 74% of cases. Response to treatment (defervescence within 6 days without developing a fungal or nonfungal infection) was seen in 22 cases (73%, 95% CI 58-89%), while 8 episodes were considered treatment failures: 2 due to persistent FUO, 1 withdrew due to IRAE, 2 developed nonfungal infections and 3 developed a presumed or definite invasive mycosis. We conclude that low-dose ABLC is very safe and well tolerated and seems as effective as c-AmB for this indication. Thus, randomized trials at this dose level appear justified to demonstrate any real benefit over c-AmB or other lipid formulations for the treatment of FUO in neutropenic patients.
Chronic primary autoimmune neutropenia (AIN) is a distinct clinical entity seen mostly in young children, characterized by persistent neutropenia with circulating anti-neutrophil antibodies and no associated disorders known to produce AIN. Herein we report a 22-year-old male who spontaneously developed severe chronic neutropenia with recurrent episodes of high fever and oral aphthous ulcers. Laboratory evaluations detected the presence of anti-granulocyte autoantibodies directed against the NA1 neutrophil-specific antigen. Clinical, laboratory and roentgenographic testing did not reveal any disorder known to be associated with AIN. The patient' s severe neutropenia did not respond to therapy with prednisone alone, but resolved following treatment with prednisone and high-dose cyclosporin A.
We report a case of disseminated infection produced by Trichosporon beigelii in a woman with acute leukemia and we review the cases described in the literature. In our patient the agent was isolated in the blood and in the bronchoalveolar aspirate. The infection was detected at the time the patient was under granulocytopenia produced by cytostatic therapy with involvement of the bones, kidney, lung, and skin. Although this mycotic agent is commonly sensitive in vitro to amphotericin B, there is not experience enough to recommend it and the mortality is high. Infection by Trichosporon beigelii should be considered in the differential diagnosis of patients with granulocytopenia and infection. This might contribute to improve the prognosis of the disease since and appropriate diagnosis and treatment would be established.
Parotid saliva secretion was studied in conscious dogs in which a chronic fistula of the parotid duct was provoked by a simple surgical procedure. To validate the technique employed, the responsiveness of the gland to various stimuli was examined. The volume of secretion was measured as well as the concentrations of Na+, K+ and calcium. Secretion was elicited by administering bethanechol i.v. or by feeding a meat meal. These stimuli, applied repetitively in the same animal, evoked reproducible secretory responses. In addition, the dose-response curve to bethanechol could also be constructed. The parotid secretion is controlled by muscarinic receptor activation, as illustrated by atropine blockade and its insensitivity to adrenergic drugs. The preparation is a versatile model which allows to investigate secretion evoked by both direct and reflex activation. The advantages of the preparation, which avoids invasive techniques, are accurate measurements and reproducible responses over long periods in a conscious animal.
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BACKGROUND: Allogeneic stem cell transplantation is being increasingly used to treat young patients with poor-prognosis low-grade lymphoproliferative disorders. We report our single-center experience. PATIENTS AND METHODS: Six adults (four with advanced chronic lymphocytic leukemia, one follicular center cell lymphoma and one mantle cell lymphoma) underwent allogeneic stem cell transplantation (SCT). Five received bone marrow while one received peripheral blood stem cells. Donors were HLA-identical siblings in five cases and an HLA-haploidentical sibling in one. The conditioning regimen included in five cases cyclophosphamide, TB1 and high-dose chlorambucil, without the latter in the patient with follicular lymphoma. RESULTS: Five patients successfully engrafted, while the patient who received the haploidentical marrow suffered primary graft failure. There were two cases of grade 2 acute GVHD and one limited chronic GVHD. Four patients are alive in complete remission (CR) with a follow-up of 17+ to 118+ months. Additionally, there is no evidence of residual disease by immunologic and molecular techniques in three cases, while one patient has residual disease assessed by molecular methods. CONCLUSIONS: These results suggest that allogeneic SCT can achieve prolonged remissions in advanced chronic lymphoproliferative disorders.
BACKGROUND: Patients with hematologic malignancies and a history of an invasive fungal infection are considered to be at high risk of suffering reactivation of the infection during subsequent intensive chemotherapy. PATIENTS AND METHODS: From January 1993 to September 1996, nine patients with a hematologic malignancy and previous invasive pulmonary aspergillosis (IPA) or Pseudallescheria boydii pneumonia and five with invasive candidiasis received further intensive chemotherapy (n = 3) or a bone marrow or peripheral blood stem cell transplant (n = 11) four days to 13 months (median three months) from the start of therapy for the fungal infection. Five patients with IPA and all five with invasive candidiasis showed complete or good partial radiologic resolution of the infection with the primary antifungal therapy given, which was continued before, during and after the period(s) of subsequent neutropenia. RESULTS: Twelve of the 14 patients showed no signs of progression or reactivation of the fungal infection during therapy, while two patients with active IPA died with progressive aspergillosis shortly after an allogeneic transplant. A review of the literature revealed that in both types of infections the risk of reactivation and dissemination appears low after achieving clinical and radiologic signs of response, which takes several weeks or months before proceeding to further antileukemic therapy. INTERPRETATION AND CONCLUSIONS: Despite lack of definite evidence, administration of an active antifungal drug before, during and after the period of neutropenia appears to be useful. In IPA, residual masses, nodules or cavities in the lung usually contain viable invasive fungal elements and should be resected whenever possible. On the other hand, the risk of reactivation and progression of an active fungal infection during intensive chemoradiotherapy is very high, and novel therapeutic strategies appear warranted in this setting.