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Biomedical subjects

P Morel

Publications and source records attributed to P Morel.

At least 19 recordsLinked to original sources

All-transretinoic acid followed by intensive chemotherapy gives a high complete remission rate and may prolong remissions in newly diagnosed acute promyelocytic leukemia: a pilot study on 26 cases.

We entered 26 patients with newly diagnosed acute promyelocytic leukemia (APL) in a pilot study of all-transretinoic acid (ATRA) followed by intensive chemotherapy. Median age was 46 (range 25 to 63). No patient presented with leukocytes > 10 x 10(9)/L or had the microgranular APL variant. Cytogenetic analysis (25 patients) found a t(15;17) in 24 cases. Patients were scheduled to receive ATRA (45 mg/m2/d) until complete remission, followed by an intensive daunorubicin (DNR) + Ara C course ("4 + 7" course), then three "2 + 5" DNR + Ara C courses and maintenance chemotheapy. However, the "4 + 7" course was administered in emergency if hyperleukocytosis rapidly developed to prevent leukostasis. Twenty-five patients (96%) achieved CR, 14 with ATRA alone and 11 after the addition of the "4 + 7" course on day 2 to 30 of treatment, because leukocytes rapidly increased (9 cases), because of resistance to ATRA (1 case), and development of organomegaly (1 case). The remaining patient died on day 6, from CNS bleeding. Apart from hyperleukocytosis, side effects were usually moderate. In the 11 patients who could be studied in vitro, a very good correlation was found between in vivo and vitro differentiation and proliferation of APL blasts with ATRA. Three patients were allografted after the "4 + 7" course. Four patients did not receive this course but received the subsequent "2 + 5" courses and maintenance. The remaining patients followed the scheduled protocol. Three patients relapsed after 8, 11, and 15 months (including one allografted patient). Two patients died in CR, after 6 and 17 months. The other 20 patients remained in CR after 18+ to 34+ months (median 21). Actuarial disease free interval (DFI) and event free survival (EFS) were 87% and 77%, respectively, after 18 months. These results were compared to those obtained in our previous APL 84 trial with chemotherapy alone in newly diagnosed APL (after excluding patients included in this trial who presented with hyperleukocytosis). In APL 84 trial, the CR rate was 76%, the actuarial DFI and EFS were 59% and 48% after 18 months, respectively. Differences with the pilot study of ATRA followed by chemotherapy were significant for DFI (P = .02), EFS (P = .006), but not for CR rate (P = .08). Although this is a historical comparison, these results suggest that ATRA followed by chemotherapy may prove superior to chemotherapy alone in newly diagnosed APL, by slightly increasing the CR rate, but perhaps more importantly by reducing the relapse rate.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis

[Asymptomatic carriage of Chlamydia trachomatis in men consulting for condylomata acuminata].

A search for Chlamydia trachomatis by cell culture was carried out in the urethra of 82 male patients consulting for condyloma acuminata at the Clinical and Biological Centre for Sexually Transmissible Diseases of the Saint-Louis hospital, Paris. Three patients had discreet urethral signs, but none had urethral discharge. Cell culture was positive for C. trachomatis in 36 of the 82 patients (44 percent). This high prevalence suggests that C. trachomatis should systematically be looked for in the urethra of male patients consulting for condylomata acuminata. If this cannot be done, then a systematic treatment with tetracyclines should be instituted.

Adult

[Liver transplantation for primary biliary cirrhosis].

Primary biliary cirrhosis (PBC) is regarded as one of the optimal indications for orthotopic liver transplantation (OLT) in adults. Between July 1987 and August 1991, 7 patients had PBC as the indication for OLT. 6 were transplanted and one patient is still on the waiting list. The patients' mean age was 47 years (range: 39 to 59) and the time from diagnosis to indication for OLT was 4, 7, 8, 10, 12, 15 and 17 years. Variceal hemorrhage episodes treated by sclerotherapy (plus porta-caval shunt in one patient) occurred in 3 patients before OLT. All suffered from jaundice (mean bilirubin 232 mumol/l, range 116 to 536), weakness, anorexia and pruritus. There were no deaths in this series during a mean follow-up time of 26 months (range 6 to 43). With the exception of osteopenia, all complications of chronic liver disease were reversed by OLT. Despite numerous postoperative problems (e.g. reoperations, intense rejection episodes, cytomegalovirus infections and lumbar column fractures), the quality of life is excellent for these 6 patients. Mean bilirubin at time of last follow-up was 18 mumol/l (range 8 to 26). No evidence of PBC recurrence was found. Based on international experience confirmed by this series, we support the notion that no patient suffering from advanced PBC should be denied OLT whenever possible.

Adult

The cutaneous form of adult T-cell leukemia/lymphoma in a woman from the Ivory Coast. Clinical, immunovirologic studies and a review of the African adult T-cell leukemia/lymphoma cases.

A 36-year-old woman from Ivory Coast, who has lived in France since 1976, had multiple cutaneous nodules and tumors in 1988. Histopathologic studies showed a massive infiltration of the dermis and hypodermis by a diffuse proliferation of mature activated T-cells (CD4-positive, CD25-positive, HLA-DR-positive) with irregular nuclei. The patient did not present with a leukemic picture and only few lymphoid cells with abnormally shaped nuclei were present in the blood. Human T leukemia/lymphoma virus type I (HTLV-I) antibodies were present in the serum and specific HTLV-I pol sequences were detected in the DNA extracted from the tumor nodules and peripheral blood mononuclear cells (PBMC) using the polymerase chain reaction technique. Whereas only a polyclonal integration of HTLV-I provirus was detectable in the PBMC, a clonal integration of three HTLV-I proviruses was demonstrated in the tumor nodules DNA, establishing with certainty the diagnosis of HTLV-I-induced adult T-cell leukemia/lymphoma (ATL). This case illustrates the need for molecular studies to differentiate without ambiguity an ATL from any other type of cutaneous lymphoproliferation, even when it occurs in a HTLV-I-seropositive individual. The situation of HTLV-I-associated ATL in Africa is reviewed.

Adult

Secondary acute lymphoblastic leukemia with t (4;11): report on two cases and review of the literature.

We report two cases of secondary acute lymphoblastic leukemia (ALL) with t (4;11) (q21;q23) translocation occurring after chemotherapy and radiotherapy for a prior cancer. Seven previously published cases of secondary ALL with t (4;11) (q21;q23) are also reviewed. Most patients had received a combination of topoisomerase II inhibitors (anthracyclines, mitoxantrone, or the epipodophillotoxin derivatives VP16 or VM26) and cyclophosphamide, which have also been implicated in the pathogenesis of secondary acute myeloid leukemia (AML) with 11q23 rearrangements. These observations give further support to the existence of a subgroup of secondary acute leukemias with cytogenetic findings "specific" for de novo ALL and AML, especially those with translocations involving the 11q23 region.

Antigens, Differentiation

Evaluation of a chemiluminometric immunoassay for detection of Chlamydia trachomatis in the urine of male and female patients.

A chemiluminometric immunoassay (Magic Lite Chlamydia) for detection of Chlamydia trachomatis antigens in first-void urine samples was compared with cell culture using urogenital swabs from 221 men and 242 women. The rate of isolation of Chlamydia trachomatis was 23.5% in men, nearly 80% of whom had symptoms of urethritis, and 8.3% in women, in whom both cervix and urethra samples were tested. In urine sediments from men and women respectively the chemiluminometric assay showed a sensitivity of 80.8% and 70%, a specificity of 97% and 95%, a positive predictive value of 89.4% and 58.3%, and a negative predictive value of 94.3% and 97.2%. Discrepancies between results obtained with the chemiluminometric assay and cell culture were resolved using two polymerase chain reaction techniques to test urogenital samples. The detection of Chlamydia trachomatis in urine samples with the chemiluminometric assay was confirmed to be superior for screening symptomatic men with urogenital infections than women as a lower prevalence population.

Adolescent

Down-regulation of cell surface CD4 molecule expression induced by anti-CD4 antibodies in human T lymphocytes.

Antigenic modulation was defined as the down-regulation of a cell surface antigen expression induced by exposure to specific antibody. We investigated the modulation of CD4 surface expression in human peripheral blood lymphocytes incubated in vitro with anti-CD4 monoclonal antibodies (mAbs). Modulation of surface CD4 was achieved at 37 degrees C, but not at 4 degrees C, with five different murine anti-CD4 mAbs of IgG1 and IgG2a subclasses, with different epitope specificities. Modulation was dose dependent with a maximum at nonsaturating mAb concentration. It was reversible upon culture in mAb-free medium. It was accelerated and amplified in the presence of monocytes or after cross-linking of anti-CD4 mAbs. It could be induced with solid phase anti-CD4 mAbs, but not with soluble F(ab')2 fragments. Its magnitude was identical on all CD4+ lymphocytes. It was associated with a moderate down-regulation of CD2 and CD3 but not of CD8 and HLA class I surface expression. Modulation was slightly augmented by addition of inhibitors of the endosome/lysosome pathway but not by protein synthesis inhibitors. The anti-CD4 mAb initially bound to cell surface was no longer detectable after 24 hr of culture. Most of surface CD4 proteins complexed with antibody were rapidly internalized and transiently replaced by CD4 from an intracytoplasmic pool and then no longer were expressed. CD4 mRNA was moderately decreased in cells incubated with anti-CD4 mAb while beta-actin and beta 2-microglobulin mRNAs remained at stable levels. It was concluded that down-regulation of CD4 surface expression induced by anti-CD4 mAb concerned only a part of CD4 molecules and was associated with a decreased synthesis. The delay required to achieve maximal modulation is likely to reflect exhaustion of the intracytoplasmic recycling pool of CD4 molecules.

Animals

Down-regulation of lymphocyte CD4 antigen expression by administration of anti-CD4 monoclonal antibody.

Modulation of surface CD4 antigen expression was assessed by flow cytometry after calibration with 125I-labeled anti-CD4 monoclonal antibodies (mAbs). Three patients with severe psoriasis treated with BB14 (anti-CD4 mouse IgG1) and five patients with rheumatoid arthritis treated with BL4 (anti-CD4 mouse IgG2a) were analyzed for sequential changes in surface CD4 expression on CD4+ blood lymphocytes. Anti-CD4 mAb treatment induced a decrease of 50 to 80% of CD4 expression, with slow and partial recovery after cessation of mAb administration. CD4 modulation was related to mAb dosage and mAb concentration in plasma. It was achieved at nonsaturating concentration. In vitro incubation of blood mononuclear cells induced CD4 modulation of similar kinetics and magnitude, associated with decrease of 5-10% of CD3 expression. CD4 modulation required both an intact Fc part of the antibody and the presence of monocytes. The possible role of CD4 modulation should be considered along with other functional activities of anti-CD4 mAbs in analyzing the mechanisms of the clinical effects of these antibodies.

Antibodies, Monoclonal

Localized pretibial pemphigoid and pemphigoid nodularis.

We describe a 75-year-old woman with a chronic, blistering eruption on the left leg whose clinical and immunopathologic features were consistent with a diagnosis of localized pretibial pemphigoid. After a disease-free interval of 5 years she developed a generalized prurigo nodularis-like eruption. Immunofluorescence studies revealed deposition of IgG and C3 along the dermoepidermal junction, and circulating autoantibodies against the dermoepidermal junction were demonstrated. Indirect immunoelectron microscopic examination of saponin-treated skin samples showed deposits of immunoreactants over the intracellular part of the hemidesmosomes. By Western immunoblotting the 230 kd bullous pemphigoid antigen was recognized by circulating autoantibodies. Thus our patient had two unusual clinical variants of bullous pemphigoid: localized pretibial pemphigoid and pemphigoid nodularis.

Aged

Anti-CD4 monoclonal antibody therapy in severe psoriasis.

We report here the treatment of psoriasis, a chronic inflammatory skin disease characterized by uncontrolled keratinocyte proliferation, with BB14, a CD4 murine IgG1 antibody. Three patients with severe psoriasis were treated with anti-CD4 mAb infusions (0.2 mg/kg/day for the first patient, 0.4 mg/kg/day for 2 days and 0.8 mg/kg/day during the following days for the 2 others) for 7 or 8 days, without other therapy. Rapid clinical improvement, with major reduction of the Psoriasis Area Severity Index, was observed during 1 month after treatment. Moderate decreases in CD4+ blood cells occurred in the last two patients but not in the first one. Circulating T cells coated with anti-CD4 mAb were detectable during the first 48 h in the first patient and from day 1/2 to day 7/8 in the two others. The density of CD4 molecules on the surfaces of peripheral blood lymphocytes was decreased in all patients and remained low as long as anti-CD4 mAb was detectable in patient serum. The maximal 24 h residual mAb levels ranged from 0.3 microgram/ml in the first patient to 3.8 and 7.0 microgram/ml in the two others. The three patients produced IgM antibodies against the anti-CD4 mAb at day 7/8 or 15 and two patients had IgG antibodies at day 15. Lesional skin samples demonstrated (1) gradual improvement in parakeratosis, papillomatosis and acanthosis, (2) decreased expression of ICAM-1 and HLA-DR by keratinocytes, (3) an increase in CD1a+ Langerhans cell number, (4) partial decrease in epidermal T cell infiltrate and (5) no major change in the dermal infiltrate composed of CD3+, TcR alpha beta+, CD45Ro+, HLA-DR+ T cells. We conclude that anti-CD4 mAb administration can induce a rapid and major improvement in psoriatic lesions, with immunohistochemical changes different from those induced by cyclosporin A or 8-methoxypsoralen plus long wave UV light (PUVA) therapy. Our data provide strong evidence for a critical role of CD4+ lymphocytes in psoriasis.

Adult

Differential effects of preexisting uremia and a synchronous kidney graft on pancreas allograft functional survival in rats.

Pancreas transplant results have been better in uremic recipients of a simultaneous kidney than in nonuremic recipients of a pancreas alone. We studied the relative effect of uremia versus a double transplant on functional survival by performing bladder-drained pancreas transplants alone (PTA), kidney transplants alone (KTA), and simultaneous pancreas/kidney (SPK) transplants from Buffalo donors to diabetic Lewis rat recipients that were or were not made uremic 2-3 weeks before by 1 4/5 native nephrectomy. Pancreas graft exocrine function was monitored by urinary amylase (UA). In the PTA and SPK recipients made diabetic by streptozotocin, endocrine function was monitored by measuring nonfasting plasma glucose (PG) levels. Kidney graft function was monitored by plasma creatinine (Cr). Rejection of the endocrine pancreas was defined as an increase of PG to greater than 200 mg/dl; of the exocrine pancreas, as a decline in UA to less than 6000 U/L or to less than 100 U/24 hr; and of the kidney, as an elevation of Cr to greater than 3 mg/dl. The mean functional survival times (MST) of both the endocrine (12.0 +/- 2.1 versus 10.1 +/- 1.1 days, P = 0.036) and exocrine (8.0 +/- 2.1 versus 6.3 +/- 1.3 days, P = 0.016) components of the pancreas grafts were significantly longer in SPK than in PTA recipients. The MST of kidney allografts, however, was not significantly longer in nonuremic SPK than nonuremic KTA recipients (6.7 +/- 1.4 versus 5.7 +/- 0.7 days, P = 0.13). In parallel experiments in recipients immunosuppressed with cyclosporine, the graft survival times were longer, but the relative differences between the PTA, SPK, and KTA groups persisted. Histologically, lymphocyte infiltration began in the two organs almost simultaneously, but the severity of the rejection was more vigorous in the kidney than in the pancreas in doubly grafted rats, and destruction of pancreas grafts progressed more slowly in SPK than in PTA recipients. Preexisting uremia delayed pancreas rejection in both SPK (exocrine 10.6 +/- 2.3, P = 0.032, and endocrine 14.8 +/- 3.4 days, P = 0.065, versus nonuremics) and PTA (exocrine 8.5 +/- 1.7, P = 0.007, and endocrine 12.6 +/- 2.5, P = 0.026, versus nonuremics) nonimmunosuppressed recipients. The MST of kidney grafts was not significantly longer in uremic (8.9 +/- 2.8 days) than in nonuremic (6.7 +/- 1.4 days) SPK recipients (P = 0.081). A synchronous kidney transplant and uremia independently down-modulate the rejection response to a pancreas graft, and a simultaneous pancreas graft has no detrimental effect on the survival of a kidney graft.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Hereditary benign telangiectasia: two case reports.

We present two cases of hereditary benign telangiectasia (HBT) in which the genetic findings are compatible with an autosomal dominant hypothesis. The lesions persisted indefinitely for many years without effect on the general health of the patients. The term hereditary benign telangiectasia distinguishes the disorder from the more serious hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber). The etiology remains unknown. The condition causes only cosmetic disability and is not associated with any other diseases.

Adolescent

Oral intraepidermal IgA pustulosis and Crohn's disease.

A case is reported of a 60-year-old woman with Crohn's disease who developed recurrent oral blisters and erosions. The histopathology of the buccal mucosa showed intraepidermal bullae and clefts with an intense accumulation of neutrophils in the epithelium. Direct immunofluorescence revealed intercellular IgA predominantly in the basal and suprabasal layers and in one biopsy concurrent deposits of IgG. No circulating autoantibodies were detected.

Crohn Disease

Prognosis and treatment of lymphoblastic lymphoma in adults: a report on 80 patients.

PURPOSE: We analyzed prognostic factors in 80 adult patients with lymphoblastic lymphoma (LBL). PATIENTS AND METHODS: Twenty-one patients received six monthly courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and maintenance chemotherapy for 12 months. The LNH-84 protocol (30 patients) consisted of four courses of high-dose CHOP followed by consolidation for 4 months. Both FRALLE (22 patients) and LALA (seven patients) protocols were two intensive chemotherapy regimens for acute lymphoblastic leukemia (ALL) that included an induction with daunorubicin, vincristine, cyclophosphamide, prednisolone (and asparaginase for the FRALLE regimen), consolidation, and maintenance chemotherapy that lasted for 2 years. RESULTS: Sixty-six patients (82%) achieved a complete remission (CR). The CR duration rate and overall survival rate at 30 months were estimated to be 46% and 51%, respectively, with a median follow-up of 55 months. Only two of 37 relapses occurred after 26 months. Chemotherapy protocol did not influence CR rate, CR duration, and survival. A higher CR rate was associated with an age of less than 40 years, lactic dehydrogenase (LDH) level of less than two times the upper limits of normal, and no or one extranodal site of disease. Short survival was associated with a failure to achieve CR, age older than 40 years, B symptoms, LDH level more than two times the upper limits of normal, and hemoglobin level of less than 100 g/L. Bone marrow involvement had no prognostic value. We could not evaluate precisely the prognostic value of Ann Arbor stage because inclusion criteria differed among treatment groups. CONCLUSION: Our findings suggest that age and LDH are two important pretreatment prognostic factors for adult LBL, and that the optimal prognostic staging system remains a controversial issue.

Adolescent