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J J Grob

Publications and source records attributed to J J Grob.

At least 37 records · Page 2Linked to original sources

Identification by cDNA microarray technology of genes modulated by artificial ultraviolet radiation in normal human melanocytes: relation to melanocarcinogenesis.

Target genes of ultraviolet stress response in cutaneous melanocytes, potentially associated with solar-induced melanocarcinogenesis, were characterized by cDNA microarray technology. In cultured normal human melanocytes, 198 genes out of approximately 9000 arrayed were found modulated > or = 1.9 times following artificial ultraviolet minus sign mainly ultraviolet-B minus sign irradiation (100 mJ per cm(2)). Among them, 159 corresponded to known sequences, the encoded proteins being mostly involved in DNA or RNA binding/synthesis/modification, or ribosomal proteins. The others were transcription factors, receptors, tumor suppressors, and (proto)oncogenes. Members of these families have already been linked to melanoma. In addition, some of the modulated genes were borne by chromosomes harboring candidate melanoma loci. Comparisons with genes modified in melanoma samples reported in previous studies with similar microarray platform showed that 59% of the known genes sensitive to ultraviolet were modulated in the same way. Furthermore, 39 expressed sequence tags were modulated, and preliminary experiments showed that two expressed sequence tags displayed differential expressions both in melanoma cell lines and in melanoma tumors. These results provide a basis for further studies on the role of modulated genes in ultraviolet-induced melanoma. Because some of these genes are potential markers of the disease, they might help for developing new molecular-based strategies for risk prediction in patients.

Chromosomes↗

Pancreatitis associated protein I (PAP-I) alters adhesion and motility of human melanocytes and melanoma cells.

Pancreatitis associated protein I is a secretory stress protein first characterized in pancreas during pancreatitis but also expressed in several tissues including hepatic, gastric, and colon cancer. Its concentration in serum can be significant. The relationship of pancreatitis associated protein I to skin cancers was investigated in normal melanocytes, melanoma tumors, and melanoma cell lines. None of them expressed pancreatitis associated protein I, even after stress induction. Adenovirus-mediated pancreatitis associated protein I expression, however, reduced cell adhesion to laminin-1 and fibronectin with a loss of integrin participation. Pancreatitis associated protein I expression stimulated haptotactic and directed migrations of some melanoma cells, but only directed migration was activated in normal melanocytes. Importantly, directed migration and spreading on fibronectin of the responsive melanoma cells were also enhanced when purified rat pancreatitis associated protein I was added to the culture medium of noninfected cells. This indicates that effects in infected cells were elicited by pancreatitis associated protein I after its secretion. Exogenous pancreatitis associated protein I can therefore modify the adhesion and motility of normal and transformed melanocytes, suggesting a potential interaction with melanoma invasivity.

Acute-Phase Proteins↗

[Urticaria in the child].

Most cases of urticaria in children are short-lived and related to viral infections and/or medicine. By comparison, allergic etiologies, particularly food allergy, are relatively rare, and are mainly observed in infancy and early childhood. Chronic urticaria is even rarer and has many similarities with adulthood chronic urticaria, including unclear physiopathology. Treatment has been much improved in recent years due to the availability of new antihistaminic drugs with better efficiency and tolerance. The management of urticaria in children requires above all a methodical approach, giving the priority to the history in order to orientate the etiological diagnosis.

Child↗

Delays in diagnosis and melanoma prognosis (II): the role of doctors.

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.

Attitude of Health Personnel↗

Delays in diagnosis and melanoma prognosis (I): the role of patients.

A prospective survey was conducted to assess the role of patients in the melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a comprehensive questionnaire including a psychological instrument. Main outcome measures were the delay before medical intervention and the tumor thickness. Of 590 melanomas, 70.8% were detected by patients and this proportion was higher in females. Relatives were involved in the detection of half of the cases. Median delays before the patient realized he had a suspicious lesion, before this lesion was seen by a doctor, and before the melanoma was removed were 4 months, 2 months, and 1 week, respectively. Delays up to several years were observed in some cases. The rate of self-detection tended to be lower, the delays before seeking medical advice to be longer, and the tumor thickness to be higher in old people, in males, in lower-educated individuals, in those living out of towns, and in people with a low awareness about melanocytic tumors than in other cases. Conversely, individuals with a high number of atypical nevi, those who were aware to be at risk, and those who regularly visited a dermatologist tended to detect their melanoma more rapidly. No specific psychological traits were associated with a late reaction, although negligence and anxiety tended to prolong the delays. Knowledge about melanoma was poor in many patients, especially in males, and wrong beliefs were widespread. This study provides the targets of future education programs.

Adolescent↗

Skin tolerance and effectiveness of two hand decontamination procedures in everyday hospital use.

BACKGROUND: Hand decontamination is crucial to control nosocomial infections. The utility of hand decontamination is related not only to its antimicrobial effectiveness, but also to its acceptability by hospital staff. OBJECTIVES: We aimed to assess skin tolerance and antimicrobial effects of two widely accepted hand hygiene measures under in-use conditions. METHODS: Fifty-two nurses were randomly assigned for an 8-day period to either an alcohol-based disinfectant or a hand wash with a non-antiseptic soap. At baseline and at the end of the test period, microbiological hand samples were obtained both before and after a hand hygiene procedure, and skin tolerance was assessed using clinical scores and measurement of transepidermal water loss. RESULTS: Self-assessment of skin condition and grade of skin damage worsened significantly more in the group using soap than in the group using alcoholic disinfectant (P = 0.004 and P = 0.01, respectively). The alcohol-based rinse was significantly more effective than liquid soap in removing transient contaminant micro-organisms (P = 0.016). Twenty of 50 hand washes with non-antiseptic soap apparently resulted in bacterial contamination of the hands. At the end of the study, the total bacterial count increased with the increasing number of hand washes in the soap group (P = 0.003), and with the degree of skin damage (P = 0.005) in the antiseptic group. CONCLUSIONS: In everyday hospital practice, alcohol-based disinfectant is more effective and better tolerated than non-antiseptic soap; soap is at risk of spreading contamination; and skin comfort strongly influences the number and the quality of hand hygiene procedures.

Alcohols↗

Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma.

PURPOSE: To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m(2)/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m(2)/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P =.012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.

Adult↗

[Congenital hypotrichosis and milia with spontaneous regression during adolescence or Oley syndrome: a variant of Bazex-Dupré-Christol syndrome].

BACKGROUND: We report a family presenting the syndrome initially described by Oley characterized by congenital profus milia and hypotrichosis that regress during adolescence. CASE REPORT: A female infant with severe congenital hypotrichosis had profus milia involving the entire face. The remainder of the physical examination was normal. The mother had normal skin and hair but indicated she had had the same signs as a child. The patient's condition regressed from the age of 10 to 15 years but she has undergone several surgical resections for basocellular carcinoma since the age of 20. The maternal grandfather had spontaneously regressive typical follicular atrophodermia involving the back and the hands and also had several milium grains and several basocellular carcinomas. He had never presented hypotrichosis. DISCUSSION: Oley syndrome is defined as an association of congenital hypotrichosis and milia spontaneously regressive during adolescence. The symptoms presented by our patient and her mother are similar to this genodermatosis. Concomitant hypotrichosis, milia, basocellular carcinomas and follicular atrophodermia define the Bazex-Dupré-Christol syndrome. The grandfather's condition would be closer to this syndrome than Oley syndrome despite the spontaneous regression of certain anomalies during adolescence. This family study would suggest that the Bazex-Dupré-Christol syndrome and the Oley syndrome are two variants of the same condition.

Adolescent↗

White blood cell count: a prognostic factor and possible subset indicator of optimal treatment with low-dose adjuvant interferon in primary melanoma.

AlphaIFN has recently been recognized as an adjuvant therapy to surgery in melanoma patients. A major issue is to select patients who will benefit from this therapy and to avoid toxicity in those who will not respond. The aim of this exploratory analysis was to identify the predictive factors of response to alphaIFN. The French cooperative group has recently shown that adjuvant therapy of melanoma patients with low-dose alphaIFN provides a benefit on disease-free interval (DFI). Using this database, predictors of DFI were investigated using Cox models and treatment-covariate interactions were sought. Gender, age, Breslow thickness, and baseline WBC count, given an alphaIFN-WBC interaction, were independent predictors of DFI. Baseline WBC count was the only variable for which there was an interaction with alphaIFN, whatever the Breslow: patients with low WBC count (<6.8 x 10(9)/liter = median) did not benefit from alphaIFN (HR=1.27 (95%CI: 0.84-1.91); P = 0.26) whereas the DFI of patients with high WBC was prolonged (P = 0.0001) with a hazard ratio of 0.50 (95% confidence interval, 0.35-0.71). The estimated values of WBC count for which IFN was significantly superior to no-treatment were those > or = 7.2 x 10(9)/liter. The baseline WBC count was correlated to baseline neutrophils but not to Breslow thickness or to time since last melanoma surgery. AlphaIFN prolonged DFI in patients with a high WBC count but not in those with a low WBC count. The results of this exploratory analysis, if confirmed by other studies, may help to identify patients who are most likely to benefit from alphaIFN.

Age Factors↗

Risk factors for erysipelas of the leg (cellulitis): case-control study.

OBJECTIVE: To assess risk factors for erysipelas of the leg (cellulitis). DESIGN: Case-control study. SETTING: 7 hospital centres in France. SUBJECTS: 167 patients admitted to hospital for erysipelas of the leg and 294 controls. RESULTS: In multivariate analysis, a disruption of the cutaneous barrier (leg ulcer, wound, fissurated toe-web intertrigo, pressure ulcer, or leg dermatosis) (odds ratio 23.8, 95% confidence interval 10.7 to 52.5), lymphoedema (71.2, 5.6 to 908), venous insufficiency (2.9, 1.0 to 8.7), leg oedema (2.5, 1.2 to 5.1) and being overweight (2.0, 1.1 to 3.7) were independently associated with erysipelas of the leg. No association was observed with diabetes, alcohol, or smoking. Population attributable risk for toe-web intertrigo was 61%. CONCLUSION: This first case-control study highlights the major role of local risk factors (mainly lymphoedema and site of entry) in erysipelas of the leg. From a public health perspective, detecting and treating toe-web intertrigo should be evaluated in the secondary prevention of erysipelas of the leg.

Analysis of Variance↗

[Prevention of skin cancers].

Skin cancer should be the ideal cancer for prevention. The environmental risk factors subject to modification by primary prevention are known for melanoma and cutaneous carcinoma. Some precursors have been identified, opening the possibility of secondary prevention. In addition, skin cancers are easily visualised, facilitating diagnosis.

Humans↗

Melanoma and tumor thickness: challenges of early diagnosis.

OBJECTIVE: To test the basic assumption of campaigns for early diagnosis of melanoma, ie, prognosis is correlated with the delay in the diagnosis. DESIGN: Prospective study of the correlation between delays to diagnosis, assessed using a questionnaire, and the Breslow thickness as a prognosis marker. SETTING: Dermatology departments in France. PATIENTS: Five hundred ninety consecutive patients, referred within 12 weeks after resection of cutaneous melanoma. MAIN OUTCOME MEASURES: Assessment of 5 successive time intervals from the first time the patients realized that they had a lesion until the resection of the melanoma, and results of the correlation between each time interval and tumor thickness (Breslow). RESULTS: There is a positive but weak correlation between tumor thickness and the delay to identify a lesion as suspicious (r = 0.17; P = .009). However, this delay tends to be short for the thickest tumors. There is a negative correlation between tumor thickness and the delay to seek medical attention (r = -0.20; P<.001). This delay was shorter for nodular melanoma. No correlation is found between melanoma thickness and physicians' delays. CONCLUSIONS: Poor prognosis can be accounted for by aggressive rapidly growing tumors rather than by delays. In well-informed populations, campaigns for early diagnosis of melanoma may thus no longer have a major impact on prognosis, unless they are focused on subgroups less accessible to information and medical care.

Female↗

Melanoma prevention: evaluation of a health education campaign for primary schools.

OBJECTIVE: To evaluate the effectiveness of an educational campaign aimed toward limiting children's sun exposure. DESIGN: Prospective, multicenter trial with before-after comparison. A school-based campaign was presented as a game during a 4-week period (May 25 to June 1992) with primary school teachers as game hosts. Children were interviewed with a standardized questionnaire in September before (1991) and after (1992) the campaign. Comparisons between the children's answers before and after the campaign were made using paired chi2 tests and analysis of variance. SETTING: Five French primary schools. SUBJECTS: All children in their fourth year of primary school (228 children aged 9 years). MAIN OUTCOME MEASURES: Changes after the campaign in children's answers concerning their knowledge, attitude, and behavior toward the sun during summer holidays. RESULTS: Compared with the precampaign answers, more children after the campaign claimed to protect themselves from the sun with a hat (33.7% vs 23.8%; P = .01) or sunscreen (34.8% vs 25.4%; P = .03), avoided going outside during the sunniest hours (76.8% vs 66.0%; P = .02), reapplied sunscreens (22.1% vs 10.6%; P<.001), considered that a T-shirt and shade provided better protection than sunscreen (82.7% vs 74.8%; P = .05), considered sunlight as a risk factor for skin cancer (74.9% vs 50.7%; P<.001), and spent significantly less time in the sun with their arms (P = .005), trunk, legs, and head uncovered (P<.001). Children with a fair complexion, who were the target of this campaign, showed the best improvement in their responses. CONCLUSION: Health education campaigns can be effective in terms of improving the knowledge, attitude, and behavior of young children.

Child↗

Humour and alarmism in melanoma prevention: a randomized controlled study of three types of information leaflet.

Effectiveness of melanoma prevention depends on how it is accepted by the population. Humour and alarmism are often used in campaigns, but no information is available about how much they may improve or limit the impact of a campaign. Three different leaflets containing the same information about sun exposure and skin cancers were developed using three different tones of presentation: humoristic (H-leaflet), alarmist (A-leaflet) or neutral information (N-leaflet). In this randomized controlled study, each type of leaflet was mailed to a sample of 300 subjects representative of the sociodemographic population of the South of France. A fourth sample to whom no leaflet was sent was used as a control. Fifteen days after the mailing, the 1200 individuals were interviewed by phone. Four hundred and forty-four of the 900 who received the mail read the leaflet. The percentage of individuals with a good awareness of melanoma was higher in leaflet groups than in controls. The percentage of individuals who read a leaflet was lower in the A-leaflet group and the percentage of individuals knowing what a melanoma is tended to be lower in the H-leaflet group. There was no significant difference between groups with regard to ability for self-assessment of skin sun sensitivity, risk factors and sun exposure. The tone of presentation seems to have a limited impact on the effect of a campaign, but alarmism tends to reduce the number of people reached by the message whereas humour tends to decrease the impact of the message.

Humans↗

Development and validation of a quality of life measurement for chronic skin disorders in french: VQ-Dermato. The RéseaudEpidémiolo gie en Dermatologie.

BACKGROUND: Quality of life (QoL) assessment is crucial to assess the severity of dermatological diseases. PURPOSE: To construct and validate the first dermatology-specific instrument in French. METHODS: Items were generated from the interview of patients. The final self-administered questionnaire, the VQ-Dermato, included 28 questions. Validity in terms of content and construct, reliability in terms of reproducibility and internal consistency, responsiveness and acceptability were tested in a population of 231 patients with 12 categories of chronic skin disorders, who were recruited and followed in hospital and private practice in France. RESULTS: Item analysis revealed that discrimination indices were high. After factor analysis, 7 dimensions were retained, which accounted for 72% of the total variance. Cronbach's alpha coefficient ranged between 0. 67 and 0.88. A strong correlation was found between dimensions of the VQ-Dermato and the corresponding dimensions of the SF36. Scores were significantly different in each category of chronic skin disease and significantly higher when there was a function restriction or when the lesions were visible to others. The scale was proven to be stable by test-retest correlation. The VQ-Dermato was more responsive to clinical improvement after a 1- or 2-month treatment than the SF36. The percentage of missing responses was under 10 and the time for completing the questionnaire always under 13 min. CONCLUSION: The VQ-Dermato is the first valid and reliable dermatology-specific QoL instrument in French, and the first based on the concept of 'chronic skin disorders'. It is acceptable for routine use and has a better responsiveness than a general health instrument.

Adult↗