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Biomedical subjects

J J Grob

Publications and source records attributed to J J Grob.

At least 55 records · Page 3Linked to original sources
PubMed1998

Randomised trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma.

BACKGROUND: Owing to the limited efficacy of therapy on melanoma at the stage of distant metastases, a well-tolerated adjuvant therapy is needed for patients with high-risk primary melanoma. Our hypothesis was that an adjuvant treatment with low doses of interferon alpha could be effective in patients with localised melanoma. METHODS: After resection of a primary cutaneous melanoma thicker than 1.5 mm, patients without clinically detectable node metastases were randomly assigned to receive either 3x10(6) IU interferon alpha-2a, three-times weekly for 18 months, or no treatment. The primary endpoint was the relapse-free interval. FINDINGS: 499 patients were enrolled, of whom 489 were eligible. When used as part of a sequential procedure, interferon alpha-2a was of significant benefit for relapse-free interval (p=0.038). A long-term analysis, after a median follow-up of 5 years, showed a significant extension of relapse-free interval (p=0.035) and a clear trend towards an increase in overall survival (p=0.059) in interferon alpha-2a-treated patients compared with controls. There were 100 relapses and 59 deaths among the 244 interferon alpha-2a-treated patients compared with 119 relapses and 76 deaths among the 245 controls. The estimated 3-year-relapse rates were 32% in the interferon alpha-2a group and 44% in controls; the 3-year death rates were 15% and 21%, respectively. Only 10% of patients experienced WHO grade 3 or 4 adverse events. Treatment was compatible with normal daily life. INTERPRETATION: Adjuvant therapy of high-risk melanoma with low doses of interferon alpha-2a for 18 months is safe and is beneficial when started before clinically detectable node metastases develop.

Antineoplastic Agents↗
PubMed1998

Radiosurgery without whole brain radiotherapy in melanoma brain metastases. Club de Cancérologie Cutanée.

To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life.

Adult↗
PubMed1998

Antiinflammatory properties of cetirizine in a human contact dermatitis model. Clinical evaluation of patch tests is not hampered by antihistamines.

The aim of this double-blind, placebo-controlled, randomized, cross-over pilot study was to assess the antiinflammatory properties of cetirizine. A group of 27 patients with a positive patch test to an allergen consecutively received cetirizine 10 mg o.d. or placebo during a 14-day period, respectively. At day 11 of each period, patch testing was performed with the allergen. The image analysis showed a skin reaction significantly reduced under cetirizine (p = 0.03), but the clinical recording and the standardized chromatometry did not show any difference between groups. In the cross-over analysis the results of image analysis were influenced by the period, but this effect disappeared after adjustment of the ambient temperature during the 3 days of the test. These results demonstrate that cetirizine has an impact on the inflammatory process in a clinical model of cell-mediated allergic reaction, although this effect is only detected with a very sensitive technique. They also show that it is useless to stop antihistamines before patch testing, since clinical evaluation of tests is not hampered by a potent antihistamine. Additionally this study suggests that ambient temperature has an influence on the results of tests.

Adult↗
PubMed1998

Combined treatment with dacarbazine, cisplatin, fotemustine and tamoxifen in metastatic malignant melanoma.

The combination of dacarbazine (DTIC), cisplatin (DDP), carmustine and tamoxifen (TAM) has been reported to yield a high rate of response in patients with metastatic melanoma, but responders often experience intracranial recurrences. As fotemustine (FOT) has demonstrated activity on cerebral metastases, the rationale of this study was to replace carmustine by FOT in this four-drug regimen. Twenty patients with metastatic melanoma received FOT (100 mg/m2) on days 1 and 8, DTIC (220 mg/m2 per day) and DDP (25 mg/m2 per day) from day 1 to day 3 and from day 28 to day 30, and continuous daily treatment with TAM (20 mg/day). If stabilization or response was observed at the end of the 8th week, patients received maintenance courses of FOT on day 1, and DTIC (220 mg/m2 per day) and DDP (25 mg/m2 per day) on days 1 to 3. Nineteen patients were evaluable. Of these, six had brain metastases. The overall response rate was 10.5% (two out of 19); both of the responders had only partial responses. The best responding site was lung. No response was obtained in the four patients with evaluable brain metastases, but no patient had therapy failure due to new brain metastases. The median overall survival was 5 months (range 1-45 months). Toxicity was mainly haematological. The use of this combination is not recommended.

Adult↗
PubMed1998

Physiopathogenic investigations in a case of familial stiff-skin syndrome.

BACKGROUND: Stiff-skin syndrome (SSS) is a rare cutaneous syndrome characterized by stony-hard skin and limitation of joint mobility. Its cause is still unknown. OBJECTIVE: Biological investigations were performed in a new case of SSS. METHODS: Collagen production and DNA biosynthesis were studied from fibroblast culture. Proinflammatory cytokines (TNF-alpha, IL-6 and TGF-beta2) were measured in the patient's serum. Results were compared with pathological findings. RESULTS: Collagen production and DNA biosynthesis were normal whereas the level of circulating cytokines was high. Histological examination of the skin showed mild fibrosis in the dermis whereas the fascia was not thickened. CONCLUSION: Our clinical and biological findings suggest that in this case, cutaneous changes may be related to an inflammatory process rather than to a primary fibroblast defect or a fascial abnormality as previously hypothesized.

Collagen↗
PubMed1998

[Plasma tryptophan bioavailability during chronic urticaria].

OBJECTIVES: Chronic idiopathic urticaria is known to have psychogenic component with a triggering or favoring effect. Different tests or evaluation scales have been unable to identify a specific psychological profile. Erythrocyte-specific membrane transport of tyrptophan (TRP), the main plasma precursor of cerebral serotonin synthesis, controls, by a erythrocyte-specific storage and release mechanism, circulating TRP homeostasis. Bioavailability of circulating TRP is a factor controlling serotonin synthesis in the brain. An evaluation of the rate of TRP transfer could be a biochemical approach to chronic urticaria more informative than psychological tests. PATIENTS AND METHODS: A kinetic study of L-TRP influx into circulating erythrocytes was conducted in 17 patients with chronic urticaria with no detectable cause and in 35 healthy controls. Blood samples were marked with 3H-TRP. Maximum L-TRP-specific influx (Vmax) was expressed in mumol/cell/min. The urticaria patients also underwent psychological testing to determine anxiety and depression scores using standardized scales (Hamilton). RESULTS: Mean Vmax was not significantly difference between the two groups. Vmax values were quite similar in all the control subjects but showed wide dispersion in the urticaria group. Three subgroups were found in the urticaria patients depending on Vmax: those with Vmax equivalent in control levels (+2 SD), those with Vmax less then 2 SD (29% of the patients) and those with Vmax greater than 2 SD of control levels (23% of the patients). Thus more than 50% of the urticaria patients had perturbed erythrocyte-specific L-TRP influx. The anxiety and depression scores obtained from the psychological evaluation were not correlated with Vmax. DISCUSSION: Erythrocyte-specific TRP membrane transport, evaluated by Vmax. Would not appear to be perturbed in chronic urticaria. Even though the urticaria patients could be divided into three groups according to their Vmax, the mean value was not significantly different from that in controls. These findings do not allow a conclusion concerning a perturbation of bioavailability of plasmatic TRP and any possible central serotoninergic dysfunction in chronic urticaria.

Adolescent↗
PubMed1996

Expression of FGF1 and FGFR1 in human melanoma tissues.

Fibroblast growth factor 2 (FGF2) has been implicated in the pathogenesis of malignant melanoma (MM), but the role of other FGFs and their receptors (FGFRs) is not elucidated. To determine whether FGF1 and FGFR1 may be involved in MM growth in vivo, we have studied the expression of the FGF1 and FGFR1 genes in 77 fresh MM biopsy samples, using RT-PCR analysis. Samples of benign nevi, normal skin and carcinoma cell lines were included as controls. Using RT-PCR analysis, expression of FGF1 and FGFR1 was observed in 69/77 and 68/77 cases, respectively. Immunohistochemical detection of the FGFR1 protein was positive in reactive stromal cells and at a much lower level in neoplastic cells. In situ hybridization experiments demonstrated FGFR1 mRNA mainly located in the stromal component. Southern blot analysis of genomic DNA prepared from MM tumors did not show any structural alteration of the FGFR1 gene. There was no correlation between FGF1/FGFR1 expression and the usual clinicopathological parameters of MM. We conclude that FGF1 and FGFR1 are frequently co-expressed in MM, a situation that may contribute to aberrant autocrine and paracrine pathways. Due to the absence of correlation with clinico-pathological parameters, this expression cannot be used as a marker of prognosis in the management of MM patients.

Actins↗
PubMed1996

Adhesive and migratory behaviors of nevus cells differ from those of epidermal melanocytes and are not linked to the histological type of nevus.

It has been postulated that acquired nevi undergo life span continuous evolution from junctional, presumably in radial expanding phase at the dermal epidermal junction, to compound and then to dermal nested nevi. In an attempt to correlate the morphology of nevi with biological data, we have investigated whether migratory and adhesive phenotypes of nevus cells could account for histological patterns and possible spatiotemporal changes in nevi. Nevus cells were cultured from compound and dermal nevi and compared to normal epidermal cultured melanocytes from children and adults. AR nevus cells showed similar in vitro adhesive and migratory indexes on laminin-1, laminin-5/nicein, fibronectin, or collagen IV substrates, suggesting that these intrinsic characteristics do not account for the tendency to dermal nesting and/or to radial growth along the dermal-epidermal junction. The cells from epidermal and dermal parts of compound nevi migrated similarly across a reconstituted basement membrane. The results show that intrinsic adhesive and migratory behaviors of nevus cells were not associated with a histological type of nevus. Interestingly, differences in migratory phenotype and intercellular adhesion capacities between nevus cells and normal melanocytes indicated that they could represent different melanocytic cell subpopulations. Finally, melanocytes from adults and children expressed similar levels of the same integrins as all nevus cells but showed differences in function of both alpha3 and alpha6 integrin subunits and in migratory/adhesive behaviors, which may suggest different states of melanocyte maturation.

Adult↗
PubMed1996

Excess of nevi related to immunodeficiency: a study in HIV-infected patients and renal transplant recipients.

To assess the relationship between immune system and nevi, we studied two models of immunodeficiency caused by different mechanisms, i.e., virus and drug. Our rationale was that if an excess of nevi was found in these two epidemiologic models, it could be concluded that the excess was due to immunodeficiency itself rather than its cause. One hundred ten renal transplant recipients (RTR) were compared with age-, sex-, and phenotype-matched controls. Eighty four HIV-positive patients (HIV+) were compared with similarly matched controls. Nevi < 5 mm (N < 5) or > or = 5 mm (N > or = 5) were counted in three sites representative of regularly, intermittently, and never sun-exposed sites. The number of N < 5 was higher in RTR (p < 0.001) and in HIV+ (p < 0.001) than in respective controls. N > or = 5 were significantly higher only in RTR. These differences tended to be the same for all sites and persisted after adjustment for possible confounding factors. The incidence of atypical nevus was higher in RTR than in controls. Immunodeficiency seems to promote the occurrence of nevi. This supports the concept of immune surveillance of nevi and raises the question of whether sun-induced immune suppression plays a role in the development of nevi. As nevi are risk markers for melanoma, a higher incidence of melanoma could be expected in immunocompromised patients.

Adult↗
PubMed1996

Insulin-induced lipoatrophy in type I diabetes. A possible tumor necrosis factor-alpha-mediated dedifferentiation of adipocytes.

OBJECTIVE: To test the hypothesis that tumor necrosis factor (TNF)-alpha may mediate the loss and the dedifferentiation of subcutaneous fat tissue in the insulin-induced lipoatrophies of a diabetic patient who presented extensive lesions. RESEARCH DESIGN AND METHODS: An in vitro exploration of cytokine production by peripheral blood mononuclear cells (PBMC) from the reported case was performed and compared with the same explorations of PBMC from three nondiabetic subjects and three diabetic patients without lipoatrophic lesions. A proliferation test and an evaluation of TNF-alpha and interleukin (IL)-6 production from PBMC in presence of insulin were studied. RESULTS: The production of TNF-alpha and IL-6 by the macrophages of the patient in presence of insulin were dramatically increased in comparison with control subjects. This process needed cooperation with other lymphoid cells and was abrogated by dexamethasone. CONCLUSIONS: In our reported case, a local hyperproduction of TNF-alpha from macrophages that was induced by the injected insulin could explain the dedifferentiation of the adipocytes of the subcutaneous tissue and the reversion that was induced by the local injection of dexamethasone.

Adipocytes↗
PubMed1996

[Experience in the screening of melanoma].

Melanoma is theoretically an ideal model for prevention campaigns. However a detailed analysis of this model shows that we do not yet have reliable tools to identify the high risk population and that prevention campaigns have a limited impact. However, any campaign which can increase the notoriety of melanoma in the public can probably improve early diagnosis. Detailed evaluation of messages and cost-effectiveness ratio of campaigns is needed.

Cost-Benefit Analysis↗
PubMed1995

Cost-effectiveness of surveillance of stage I melanoma. A retrospective appraisal based on a 10-year experience in a dermatology department in France.

BACKGROUND: There is no agreement about surveillance after resection of a stage I melanoma. OBJECTIVE: We assessed the cost-effectiveness of this surveillance. METHODS: Out of 912 patients with stage I (and Clark's level > or = II) melanoma examined from 1981 to 1991, only 528 were regularly followed in our department. RESULTS: 115 out of 528 relapsed; 33% were detected by the patient himself, 16% by the referring physician and 39% were detected in our department. Chest X-ray or abdomen ultrasonography revealed only 10% of relapses; CT scans were useless. There was a huge gap between the cost-effectiveness of clinical examinations and radiology. The time between relapse and the last check-up in our department was less than 4 months in one third of the metastases. CONCLUSIONS: In stage I melanoma, only clinical examination is really cost-effective in the detection of metastases. However, many metastases are likely to become prominent between two examinations if patients are examined less than 3 times a year. A progressive decrease in frequency is thus not advisable, until the risk is considered low enough to stop follow-up.

Cost-Benefit Analysis↗