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Biomedical subjects

A Thyss

Publications and source records attributed to A Thyss.

At least 109 records · Page 6Linked to original sources

Invasive mixed growth hormone/prolactin secreting pituitary tumour: complete shrinking by octreotide and bromocriptine, and lack of tumour growth relapse 20 months after octreotide withdrawal.

Octreotide and bromocriptine were used to treat an acromegalic patient harbouring an invasive pituitary tumour secreting growth hormone and prolactin. Octreotide (100 micrograms, subcutaneously, three times daily) and bromocriptine (15 mg orally, daily) rapidly improved clinical signs and symptoms, including diabetes that initially required insulin. Complete control of growth hormone and prolactin secretion was obtained and maintained by this treatment protocol for 12 months without affecting the other pituitary functions. A major tumour shrinkage was apparent by magnetic resonance imaging after six months, and was considered to be complete after 12 months of treatment. Octreotide was then discontinued without any relapse in either growth hormone secretion or tumour growth over a 20-month period following withdrawal. Attempts were made to discontinue bromocriptine, but a maintenance therapy (2.5 mg daily) was required to control rebounds of prolactin hypersecretion. Two months after octreotide withdrawal, acute pancreatitis secondary to cholelithiasis required surgery; this complication was attributed to octreotide (pre-treatment ultrasonography was normal). These findings suggest that combination therapy with octreotide and bromocriptine may be considered in pituitary macroadenomas secreting growth hormone and prolactin. They also emphasize the need for a close monitoring of cholelithiasis, not only during octreotide therapy but also after the drug's withdrawal.

Adenoma↗

[Dihydropyrimidine dehydrogenase activity in lymphocytes: predictive factor for 5-fluorouracil clearance].

We previously have shown that pharmacokinetic monitoring of 5-fluorouracil (5-FU) could significantly improve the 5-FU therapeutic index when given in continuous venous infusion (Br J Cancer 59, 287-290, 1989). However, the more rational approach would be to find individual biological factors which could predict 5-FU clearance. Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme in the catabolism of 5-FU. DPD activity was measured in 57 head and neck cancer patients receiving CDDP (100 mg/m2, day 1) plus 5-FU (1 g/m2/day x 5, day 2-day 6). DPD activity was measured in lymphocytes using a radioenzymatic assay (2.5 mM MgCl2, 250 microM NADPH, 20 microM 14C-5-FU) with separation of 14C-5-FU from 14C-5-FUH2 by HPLC coupled with a radiodetector. The average DPD activity measured in lymphocytes was 0.186 +/- 0.068 nmol/min/mg protein (range 0.058-0.357) and the average 5-FU clearance (Cl) was 2,523 +/- 684 ml/min/m2 (range 1,052-4,029). A significant linear correlation was demonstrated between DPD activity and 5-FU clearance (Cl = 1,099 + 7,580 DPD, r2 = 0.613, P < 0.0001). In patients evaluated for more than one cycle (n = 18), variations in 5-FU clearance were associated with corresponding variations in DPD activity. The individual determination of DPD activity measured in lymphocytes could be useful for identifying patients at risk for altered 5-FU pharmacokinetics and could be used to adjust the optimal 5-FU dose for each patient before starting the treatment.

Adult↗

Expression of integrin receptors on 45 clinical neuroblastoma specimens.

Immunohistological expression of integrins has been analyzed on 45 neuroblastoma specimens representative of the different clinical and histological forms of the tumor. None of the specimens expressed the alpha 5 chain of the integrins. The beta 1 chain was expressed on all specimens, the alpha 1 chain on 44 specimens and the alpha 3 chain on 42; the 4 specimens which lacked alpha 1 or alpha 3 were stage-4 neuroblastomas. The alpha 2 chain was expressed on 18 specimens, and the alpha 6 chain on 17; 15 reacted with both. Their reactivity was related to the maturation of the tumor rather than the stage of the disease: they were expressed on low-grade, well-differentiated specimens; stage 3-4 neuroblastoma specimens analyzed at diagnosis were negative, but usually expressed both chains when analyzed after in vivo differentiation by chemotherapy. alpha v reacted with 18 specimens and beta 3 with 12, without strict relation with the stage of the disease and/or its degree of differentiation; 9 well-differentiated specimens expressed the beta 4 chain; only 4 well-differentiated specimens expressed the alpha 4 chain. The 4 specimens which lacked alpha 1-beta 1 or alpha 3-beta 1 expression had n-myc amplification, whereas those which expressed either alpha 4, beta 4, beta 3 or alpha v had no amplification. Furthermore, the expression of the 3 heterodimers alpha 4-beta 1, alpha v-beta 3 and alpha 6-beta 4 was essentially observed on primary tumors which developed in the mediastinum. The expression of alpha 2-beta 1 and alpha 6-beta 1 was observed on both n-myc-positive and -negative specimens. beta 1 and alpha 3 were diffusely expressed on all counterparts of these tumors, from undifferentiated neuroblasts to ganglion and Schwann cells. The alpha 1 chain reacted with undifferentiated and intermediate neuroblasts as well as with Schwann cells, but ganglion cells were negative. alpha 2 and alpha 6 chains were negative on undifferentiated neuroblasts, variably expressed on intermediate neuroblasts, and restricted to Schwann cells in ganglioneuroma. The expression of alpha 4 and beta 4 was restricted to Schwann cells. alpha v and beta 3 occasionally reacted with undifferentiated and intermediate neuroblasts; alpha v was strongly positive on Schwann cells but negative on ganglion cells, whereas beta 3 was positive on both neuronal and non-neuronal populations.

Ganglioneuroma↗

Expression of P-glycoprotein restricted to normal cells in neuroblastoma biopsies.

Immunohistological detection of P-glycoprotein (P-gp) with monoclonal antibody C219 was performed on serial sections of 37 neuroblastoma specimens representative of the different forms of the disease, from stage 1 ganglioneuroma to stage 4 neuroblastoma. Malignant cells, irrespective of their degree of maturation varying from neuroblasts to ganglion cells, were negative on all specimens. The expression of P-glycoprotein was detected in nine specimens, but it was restricted to normal cells within the tumour. In four specimens, C219 reacted with normal infiltrating cells in the stroma (i.e. monocytes, histiocytes or fibroblasts) representing 5 to 10% of the total population within the section; in three specimens, the residual adrenal gland was strongly positive, and in two ganglioneuromas, a weak reactivity of C219 was observed on a few satellite cells and schwann cells. Three of 15 biopsies obtained at diagnosis contained normal P-gp positive cells: two were classified as stage 1 ganglioneuromas; one was a typical stage 4 composite tumours with positive histiocytes and fibroblasts in the well-differentiated counterpart. Six of 22 biopsies obtained after patients had received our current protocol of chemotherapy contained normal P-gp positive cells: five were partially differentiated and necrotic under the effect of chemotherapy; only one positive specimen was classified as undifferentiated neuroblastoma. Among negative specimens from previously treated patients, one was obtained from a patient in relapse after high-dose chemotherapy and ABMT, two were obtained from patients who had not responded to induction therapy, and six from patients in partial remission after induction therapy. The clinical evolution was very similar in both groups of patients with P-gp negative or positive biopsies. These findings suggest that the quantitative assessment of MDR RNA by northern blotting on fresh homogenates is likely to overestimate its expression on neuroblastoma cells, and that the mechanism of chemoresistance in widespread neuroblastoma is less likely to be associated with P-gp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A study of nineteen immunocompromised patients with extensive skin lesions caused by Pseudomonas aeruginosa with and without bacteremia.

Nineteen immunocompromised patients with extensive skin lesions caused by Pseudomonas aeruginosa with or without P. aeruginosa bacteremia were analysed. Patients whose lesions originated in the skin were in the majority (14 patients). Skin lesions were located at the site of entry of bacteria (apocrine areas in 12 patients). Cutaneous lesions were pleomorphic but the typical picture of ecthyma gangrenosum was common in this group of patients. Only 2 of them developed P. aeruginosa septicemia and the prognosis was relatively good (7.5% mortality rate). These observations confirm that ecthyma gangrenosum may be a primary cutaneous disorder not systematically associated with bacteremia.

Acquired Immunodeficiency Syndrome↗

[Primary mammary focus of malignant non-Hodgkin's lymphoma. Apropos of 10 cases].

The authors describe 10 cases of malignant non-Hodgkin's lymphoma in a mammary site in women aged 38 to 82 years. The clinical examination and the sometimes suggest an adenocarcinomatous lesion, thus leading to a useless surgical exeresis. An initial histological study provides the diagnosis. A complete assessment of extension allows an accurate staging and the refinement of the therapeutic schedule. Exclusive radiation therapy seems to be justified in low-malignancy forms remaining strictly confined to the breast. For the high- and medium-malignancy forms, the essential weapon is chemotherapy, which seems to improve the duration and rate of remission.

Adult↗

[Non-Hodgkin's lymphoma in HIV infection. A multicenter retrospective study of 21 cases].

The incidence of non-Hodgkin's malignant lymphoma is known to be increased in patients who are seropositive for the human immunodeficiency virus (HIV). We report here a multicentre retrospective study of 21 HIV-positive patients with non-Hodgkin's lymphoma seen between 1985 and 1987. All phenotype B lymphomas of intermediate or high malignancy grade according to the Working Formulation are difficult to classify histologically. Because of this problem, reexamination of the specimens by several pathologists and perhaps also the use of other morphological prognostic criteria, such as mitotic index, seem to be desirable. In more than one-third of our patients the presence of a lymphoma led to the finding of HIV seropositivity in subjects who were all issued from populations at risk. Median age was 39 years. Spread evaluation showed stage III or IV in most cases with, in 4 out of 5 patients, extranodal sites, notably the neuromeningeal system, liver, gastrointestinal tract and bone marrow. The median overall survival was 5 months, but in April 1989 2 patients had survived for more than 30 months. Obtaining complete remission (11/21 cases) was imperative for a 10 months' survival. Eight of the 11 patients in whom complete remission was obtained had received the heavy induction chemotherapy required by the degree of malignancy, but no death due to drug toxicity was recorded. 17 patients died, with active lymphoma (12 cases) and/or infection (8 cases) being documented at the time of death. The finding of more than 500/sq. mm CD4 lymphocytes in peripheral blood in 10 cases while the lymphoma was developing, and the heterogeneity of the Epstein-Barr virus (EBV) profile in serum raise the question of the role played by T-cell immunodeficiency and by EBV infection in the physiopathogenesis of these lymphomas.

Adult↗

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

Adolescent↗

Biochemical and pharmacological consequences of the interaction between methotrexate and ketoprofen in the rabbit.

Severe methotrexate (MTX) toxicity is a proven complication of associations of MTX and non-steroidal anti-inflammatory drugs (NSAIDs). This study investigated the interaction between MTX (50 or 100 mg kg-1) and ketoprofen (KP) (3 mg kg-1 day-1, pretreatment for 8 days) in the rabbit. The drug association induced a reversible increase in blood urea and creatinine. The severity degree of renal dysfunction was significantly related to the MTX dose; it was not modified by prolonged exposure to KP after MTX administration. The biological markers of haematopoietic and hepatic functions were unchanged. Pretreatment by KP induced a marked reduction (70%) in the urinary excretion of the prostaglandin 6-keto-PGF1 alpha. MTX dose-related alterations in MTX pharmacokinetics were also observed with the drug association: at a MTX dose of 100 mg kg-1, the presence of KP significantly reduced the total body clearance, the renal clearance and the fraction of MTX eliminated in urine as compared to controls. An appreciable reduction in the plasma binding of MTX was also noted in vivo when KP was associated. This experimental study confirms the existence of an interaction between MTX and KP and demonstrates its renal origin.

6-Ketoprostaglandin F1 alpha↗

Spontaneous hematoma of the kidney simulating a nephroblastoma. Report of two cases.

The International Society of Pediatric Oncology (SIOP) 6 clinical trial for Wilms' tumor (WT) includes preoperative chemotherapy for all nonmetastatic patients. Approximately 50% of patients treated in this manner can be classed stage 1 after surgery. This strategy requires a positive diagnosis in the absence of histologic data. Diagnostic errors are very rare: Only 1.5% of the first 856 cases entered in the SIOP 6 trial were found to be benign. This article reports two very similar cases of spontaneous hematoma of the kidney that were initially misdiagnosed as hemorrhagic WT. Unusual severe acute anemia was a feature of both cases. Even the most modern state-of-the-art imaging techniques were unable to rule out the possibility of a tumor subjacent to a voluminous renal hematoma. The patients' courses during preoperative chemotherapy were of no formal diagnostic value, and the correct diagnosis was not made until surgery.

Antineoplastic Combined Chemotherapy Protocols↗

Dermatomyositis-like syndrome in X-linked hypogammaglobulinemia. Case-report and review of the literature.

A case of dermatomyositis-like syndrome is described in a 19-year-old man with a history of Bruton's hypogammaglobulinemia. Although the patient had central-nervous-system manifestations (seizures), no echovirus was isolated in the cerebrospinal fluid, in contrast to previously reported cases. Data for our case and the 15 cases previously reported in the literature are reviewed. HLA typing of our patient revealed the presence of HLA B8 and DR3, which seems to play a major role in juvenile dermatomyositis.

Adult↗

[Malignant maxillofacial non-Hodgkin's lymphoma. Apropos of 15 cases involving the naso-sinus cavities].

Non-Hodgkin's lymphomas include malignant conditions developing within lymphoid tissue, both lymph nodes and extranodal lymphoid tissue. Due to its rich lymphatic supply, the cervico-facial region is frequently involved: 10 to 15% of all NHL (1, 2, 8, 15), i.e. a similar incidence to primary GI involvement (4). The cervical glands and lymphatic structures of the Waldeyer ring are most often and most classically involved. The nasosinusal cavities may be involved, producing diagnostic problems which have to be resolved by the specialist (6). Between 1972 and 1989, 20 cases of NHL involving the bony cavities of the face were seen at the Centre Antoine-Lacassagne. These include the 15 cases reported below involving the naso-sinusal cavities.

Adolescent↗