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J J Grob

Publications and source records attributed to J J Grob.

At least 73 records · Page 4Linked to original sources

Polymerase chain reaction detection of circulating melanocytes as a prognostic marker in patients with melanoma.

BACKGROUND AND DESIGN: Polymerase chain reaction (PCR) detection of circulating tumor cells from malignant melanoma (MM) was recently described, but the prognostic value of this method in the treatment of patients with MM remained unclear. In the present prospective study, blood samples (n = 193) were collected from 93 patients with MM: 10 stage I patients after primary tumor resection, 18 patients with regional lymph node metastases before node resection, 33 disease-free but high-risk patients (previously treated for node metastases), and 32 patients with distant metastases. Circulating melanocytes were detected using a reverse transcriptase PCR method that analyzes tyrosinase gene expression. All patients were kept under regular surveillance. RESULTS: The PCR assay was always negative in normal individuals and in subjects with non-MM metastatic cancer, while it was positive in 16 of 32 patients with disseminated MM. Five of eight patients who were PCR-positive before node dissection vs one of 10 who were PCR-negative relapsed within 6 months after surgery. In high-risk but apparently disease-free patients, the risk of relapse within the next 6 months was 3.8 times higher after a positive test result. In patients with distant metastases, a positive PCR predicted rapid disease progression. CONCLUSIONS: These data suggest that PCR detection of circulating melanocytes can be considered as a marker for rapid postoperative relapse after node dissection in patients with MM with regional node metastases, for short-term relapse in high-risk disease-free patients, and for rapid and severe progression in patients with distant metastases. This test may have a crucial interest in the treatment of patients with MM.

Base Sequence↗

NM23 expression in metastasis of malignant melanoma is a predictive prognostic parameter correlated with survival.

The management of patients presenting with metastatic malignant melanoma (MM) is hampered by the substantial variability in survival of these patients and the lack of prognostic markers. In the search for a reliable predictive parameter, we have investigated the expression of the nm23 gene, considered to be a major regulator of the metastatic process. We have analysed by Northern blot the nm23 mRNA level in tumour tissue obtained from metastases of 20 stage II and ten stage III patients with MM. Normal human tissues and benign naevi were simultaneously examined. The level of nm23 expression was highly heterogeneous in MM metastases, with a mean value which was higher than the mean level in normal tissues and naevi. Correlative study was focused on the overall survival following resection of the metastasis in which nm23 Northern blot analysis was performed. Patients displaying higher nm23 expression in metastatic tissue (above the mean level) tended to have a longer survival than others (P = 0.08), and this difference was significant for patients presenting with isolated regional lymph node involvement (P = 0.035). The time from biopsy of the primary MM to the appearance of the first lymph node metastasis also showed a positive correlation with the nm23 mRNA level in this metastasis. The present study is not only in accordance with previous reports showing that the nm23 gene may be implicated in MM progression, but also suggests the reliable value of nm23 expression as a prognostic marker for patients presenting with metastatic MM.

Female↗

[Sneddon syndrome].

Sneddon's syndrome is a rare disease characterised by cerebrovascular ischaemic attacks and generalised livedo. Since previous observations, other symptoms were described: involvement of heart, of kidney, arterial hypertension, complicated obstetric or gynaecologic history in women. Prognosis is highly variable, depending on extent and speed of progression of cerebrovascular changes, which can lead to severe permanent mental deterioration. In livedo, histopathology shows pathological changes of small to medium-sized dermal arteries in a distinct time sequence: an early phase localized in endothelium followed by a late fibrotic phase. No specific laboratory findings are found. Recently some cases were reported in association with antiphospholipids antibodies. The etiopathogeny of Sneddon's syndrome is still unknown and could result from different processes: progression to an autoimmune disease such as lupus erythematosus, primitive endarteritis obliterans, or a new clinical expression of the antiphospholipid antibodies syndrome. At present, none of the therapeutic modalities provides significant improvement.

Cerebrovascular Disorders↗

[Role of sun exposure on benign melanocytic nevi. A first study in populations controlled for age, sex and phenotype].

BACKGROUND: These studies were designed to assess the influence of sun exposure on nevi in white people. In order to eliminate the confounding effect of age, sex and phenotype, two parallel studies were conducted in people of the same age (17 to 24 years), sex (males) and phenotype: one in people with "red" phenotype and one in people with "dark" phenotype. RESULTS: In both groups, comparison of nevus counts on the inner and outer side of the upper extremities and comparison of mean density of nevi (number per square meter) in always-exposed and never-exposed skin show that number of nevi is higher in sun exposed areas. In both groups the density of large and atypical nevi was maximal on intermittently sun-exposed skin while the density of small nevi was maximal on always-exposed skin. The number of large nevi on intermittently-exposed skin correlated with cumulative intensive exposure during beach recreation in the red phenotype group. The number of large nevi was significantly higher in red phenotypes who repeatedly experienced severe sunburns in their first 20 years of life. CONCLUSIONS: The number of nevi at the end of the second decade is influenced by cumulative sun exposure from birth. "Traumatizing" sun exposure, which is more frequent in "red" phenotype than in "dark" one, has an influence on the number of large nevi and is therefore likely to make small nevi grow.

Adult↗

Large keratoacanthomas treated with intralesional interferon alfa-2a.

BACKGROUND: Spontaneous involution of giant keratoacanthomas (KAs) can leave large scars or cause mutilation. Human papillomaviruses have recently been demonstrated in KAs. Intralesional interferon alfa-2a (IFN alfa-2a) has been shown to have activity against different epithelial tumors and to have an antiviral effect. OBJECTIVE: This study was conducted to determine whether it was possible to stop extension of large KAs, to accelerate healing, and to obtain good cosmetic results with intralesional IFN alfa-2a. METHODS: Six large KAs were treated with intralesional IFN alfa-2a. RESULTS: Regression was obtained in five cases in 3 to 7 weeks with excellent cosmetic results. The main side effect was pain during injection. CONCLUSION: Our results suggest that this treatment hastens healing and limits scarring.

Aged↗

Tyrosinase gene expression in human tissues.

The occasional occurrence of primary extra-cutaneous malignant melanomas (MM) has led to the hypothesis that melanocytes derived from the neural crest may be arrested in their migration and may undergo an in situ malignant transformation. However, aggregates of nevus cells have only rarely been identified by histological examination in a few organs other than skin and eye. Tyrosinase is a melanin biosynthetic enzyme that is considered one of the most specific markers of melanocytic differentiation. We have attempted to detect cells committed to the melanocytic lineage, in human tissues, by means of tyrosinase gene expression. Total RNA was extracted from normal and neoplastic tissues and analyzed using a highly sensitive reverse transcription PCR assay with primers specific for the tyrosinase gene. Peripheral blood mononuclear cells (PBMC) from healthy subjects were used as negative controls. Tyrosinase transcripts were identified in a wide range of normal organs such as skin, lymph nodes, antrum, colon, kidney, lung, testis, ovary, breast, and peripheral nerve. Tyrosinase RNA was also detected in neoplastic samples including benign cutaneous nevi, lymph nodes involved by MM, breast carcinoma, liposarcoma, malignant lymphoma, and schwannoma. PBMC from patients with metastatic MM were also positive, while no positivity was detected in blood specimens from patients with other cancers. Therefore, it appears likely that cells expressing the tyrosinase gene are present in a wide range of human tissues. Although these cells still have to be accurately identified, one could propose that they might correspond to either fully differentiated melanocytes, melanocytic precursors, or Schwann cells bearing potentialities of melanocytic differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Study of sunbathing habits in children and adolescents: application to the prevention of melanoma.

Excessive sun exposure in the first 15 years of life has been shown to be a determinant risk factor for melanoma. This study was conducted on a randomly selected sample of 200 adolescents (13-14 years old) and 150 children (3 years old) in Marseille (South of France). Children and adolescents were examined and interviewed (mothers answered for young children). Our results show that a large number of highly sensitive children were not identified as such by their parents and most adolescents do not realize or at least admit being highly sun sensitive. Adequate sun protection measures were used in only 63% of 3-year-olds and 38% of adolescents. With reference to their constitutional skin sensitivity and taking into account their possible use of effective sun protection measures, 33% of the children and 62% of the adolescents were highly overexposed. Only good sun protection habits of the mother were predictive of acceptable sun exposure in children. In the adolescents the predictive variables were sun protection habits of the father and sunbathing only to obtain a tan. The main reason why adolescents sunbathed was embellishment. Conversely, most mothers said that they exposed their young children to the sun for health. Many adolescents and mothers were reasonably well informed but considered the risk of sun exposure to be exaggerated by the media. These results may be important to determine the targets of future melanoma prevention campaigns.

Adolescent↗

[Erosive pustulosis of the scalp. A spongiform pustular dermatosis?].

A case of erosive pustular dermatosis of the scalp is reported. The lesions were eroded with crusting and pustule formation and were localised on the scalp. Investigations for infection, autoimmunity, vascular or tumoral aetiology were negative. Skin biopsy revealed non specific inflammation as usually, but also showed spongiform pustule formations which had not previously been described. Topical corticosteroid therapy dramatically improved the lesions. The pathogenesis of this disease is discussed.

Administration, Topical↗

Role of sun exposure on nevus. First study in age-sex phenotype-controlled populations.

BACKGROUND: These studies were designed to assess the influence of sun exposure on nevi in white people. To eliminate the confounding effect of age, sex, and phenotype, two parallel studies were conducted on people of the same age (17 to 24 years; median, 20 years old), sex (male), and phenotype: one in people with "red" phenotype (red or red-blond hair, white complexion on the inner part of the arm, and inability to tan) and one in people with "dark" phenotype (brown or black hair, dark complexion on the inner part of the arm, absence of freckles, and easy tanning without burning). RESULTS: In both groups, comparison of nevus counts on the inner and outer side of the upper extremities and comparison of mean density of nevi (number per square meter) in always-exposed and never-exposed skin show that the number of nevi is higher in sun-exposed areas. The density of large and atypical nevi was maximal on intermittently sun-exposed skin while the density of small nevi was maximal on always-exposed skin. The number of large nevi on intermittently exposed skin correlated with cumulative intensive exposure during beach recreation in the red phenotype group. The number of large nevi was significantly higher in red phenotypes who repeatedly experienced severe sunburns in their first 20 years of life. CONCLUSIONS: The number of nevi at the end of the second decade is influenced by cumulative sun exposure from birth. "Traumatizing" sun exposure, which is more frequent in the red phenotype than in the dark phenotype, has an influence on the number of large nevi and is therefore likely to make small nevi grow.

Adolescent↗

Fotemustine plus dacarbazine for malignant melanoma.

119 patients with metastatic melanoma received fotemustine 100 mg/m2 on days 1 and 8 and dacarbazine 250 mg/m2 on days 15-18. After a 5-week rest, fotemustine 100 mg/m2 on day 1 and dacarbazine 250 mg/m2 on days 2-5 was given every 3-4 weeks. 12 complete responses (11.6%) and 16 partial responses were observed in 103 evaluable patients (response rate 27.2%). The median duration of response was 21.5+ weeks (8+ to 53+). The response rate was 26.3% in CNS, 18.2% in visceral sites and 37.5% in non-visceral sites. The toxicity was mainly haematological: grade III-IV leukopenia in 27.4% and thrombocytopenia in 23.4%. The response rate was lower than that in 63 patients previously reported. The present series had a higher median age (54 vs. 40 years) without any differences in other population variables. However, activity on CNS metastases and on non-visceral sites was confirmed. Haematological toxicity was about 50% lower than that with fotemustine alone. Hence, this is an active outpatient regimen for metastatic melanoma, especially against cerebral and non-visceral metastases.

Adult↗

Palmoplantar orthokeratotic filiform hyperkeratosis in a patient with associated Darier's disease. Classification of filiform hyperkeratosis.

We present here the third published case of palmoplantar orthokeratotic filiform hyperkeratosis of particular clinical interest because of associated Darier's disease. We propose a classification of filiform hyperkeratosis in three groups on the basis of the topography (i.e. palmar and plantar, disseminated with palmoplantar sparing and linear) and the histology (i.e. porokeratosis or orthokeratosis) of the lesions. This keratinization disorder does not seem to be a specific disease entity but rather a syndrome secondary to various disorders.

Aged↗

[Trigeminal neurotrophic ulcer and vascular disorders of the brain stem. A clinico-electrophysiological study].

Torpid facial ulcerations may occur as a result of lesions involving the trigeminal fibers. These neurotrophic ulcerations have usually been observed after alcohol injection in the trigeminal ganglion. We report two cases associated with brainstem infarction. In both patients, the blink reflex was studied. The masseter inhibitory reflex was studied in one case. Analysis of these electrophysiological recordings can be of particular value in localizing the site of the lesion along the trigeminal pathway.

Adult↗

[Multiple trichoepithelioma, cylindroma, miliaria and carcinomatous transformation].

We report a new case of multiple trichoepitheliomas, milia and cylindromas syndrome. This new case differed from the others in that it was complicated by the occurrence of a basal cell carcinoma presenting as an ulcus rodens affecting the nasal pyramid. In such cases, the main differential diagnosis to be excluded is basal cell naevomatosis.

Aged↗

[Campaign of early detection of melanoma in the Provence-Alpes-Côte-d'Azur area 1989. Lessons of an experience].

The prognosis of melanoma is closely related to tumor thickness at the time of surgical excision. Thickness depends on the duration of disease before diagnosis. This underlines the importance of information campaigns to promote early diagnosis of melanoma. The purpose of this study was to estimate the cost and effectiveness of a media campaign for the early screening of malignant melanoma (MM) at national level. This trial, the first of its kind in France, was conducted in the spring of 1989 in the Provence-Alpes-Côte d'Azur-Corse region. The campaign combined an effort to inform and heighten awareness in the medical community and the broadcast of an information movie for the general population on a regional TV channel. Following the campaign, the number of MM diagnosed in a representative selection of pathology laboratories increased significantly compared with the same period of the previous year: + 108 p. 100 over the 10 first weeks, + 47.6 p. 100 over 6 months. This increase was mostly for MM of low thickness (less than 1 mm) which have a good prognosis: + 74 p. 100 over 6 months. However MM distribution by thickness was not significantly different from one year to the next. Although the number of added cost generated by this campaign could not be precisely determined, these positive initial results argue for a national prevention campaign based on the lessons of this experience.

Costs and Cost Analysis↗