Excess benign melanocytic naevi after chemotherapy for malignancy in childhood.

OBJECTIVE--To see whether children who have had chemotherapy develop increased numbers of moles. DESIGN--Blind assessment of patients having chemotherapy and subsequent comparison with the first suitable patients matched for age and sex who were attending the clinic during the same period after having completed treatment. Controls were obtained the following year by taking the first suitable patients attending a routine dermatology outpatient clinic who matched the study groups for age and sex. SETTING--Referrals to a paediatric oncology clinic and a dermatology clinic at two city hospitals. PATIENTS--The group receiving chemotherapy comprised all 32 patients with acute lymphatic leukaemia, lymphoma, and rhabdomyosarcoma who were attending the paediatric oncology clinic on two mornings a week during October 1987 to March 1988. The group who had completed treatment comprised 32 patients who were attending for follow up during the same period and who matched the first group for age and sex. Thirty two other patients attending the dermatology outpatient clinic with unrelated skin conditions served as controls. END POINT--Definite increase in numbers of moles on children after a course of chemotherapy. MEASUREMENTS AND MAIN RESULTS--Moles were counted by one observer on defined areas of the body and divided into those less than 3 mm and greater than or equal to 3 mm diameter. Patients receiving chemotherapy had a similar number of moles to the control group. By contrast patients who had completed chemotherapy had significant increases both in moles less than 3 mm and greater than or equal to 3 mm and in the total number of moles. These patients were more likely to have moles on acral sites. CONCLUSIONS--Children with substantially increased numbers of moles (benign melanocytic naevi) after successful chemotherapy for malignancy may have an increased risk of melanoma. They should be offered prolonged surveillance and cautioned about exposure to ultraviolet light.     

Effect of maintenance chemotherapy in childhood on numbers of melanocytic naevi.

OBJECTIVE--(a) To determine whether children given chemotherapy for haematological malignancy have significantly more melanocytic naevi than age matched children in the local population; (b) to establish whether any observed variation in naevus counts from normal is seen at the start of maintenance chemotherapy. DESIGN--Follow up of 29 consecutive children starting maintenance chemotherapy, with parental interview and count of all melanocytic naevi > or = 2 mm on the child''s skin. Assessment repeated three years later after completion of maintenance chemotherapy. Other dermatological problems identified at either visit were also recorded. SETTING--Royal Hospital for Sick Children, Glasgow. RESULTS--At the start of maintenance chemotherapy all children had total body counts of melanocytic naevi within the normal range established for age matched children in the local population. Three years later total body naevus counts were significantly increased, the median increase being 66 naevi per child (95% confidence interval 57 to 94). The only other problem noted in these children was relatively poor regrowth of scalp hair. CONCLUSION--Children on maintenance chemotherapy for haematological malignancies develop an excessive number of melanocytic naevi. Excessive numbers of melanocytic naevi are the most important risk factor for melanoma in the general population. These children should have periodic skin examinations at their follow up visits, and both child and parent should be educated about clinical features of early melanoma.     

Loss of pannexin 1 attenuates melanoma progression by reversion to a melanocytic phenotype

Pannexin 1 (Panx1) is a channel-forming glycoprotein expressed in different cell types of mammalian skin. We examined the role of Panx1 in melanoma tumorigenesis and metastasis since qPCR and Western blots revealed that mouse melanocytes exhibited low levels of Panx1 while increased Panx1 expression was correlated with tumor cell aggressiveness in the isogenic melanoma cell lines (B16-F0, -F10, and -BL6). Panx1 shRNA knockdown (Panx1-KD) generated stable BL6 cell lines, with reduced dye uptake, that showed a marked increase in melanocyte-like cell characteristics including higher melanin production, decreased cell migration and enhanced formation of cellular projections. Western blotting and proteomic analyses using 2D-gel/mass spectroscopy identified vimentin and β-catenin as two of the markers of malignant melanoma that were down-regulated in Panx1-KD cells. Xenograft Panx1-KD cells grown within the chorioallantoic membrane of avian embryos developed tumors that were significantly smaller than controls. Mouse-Alu qPCR of the excised avian embryonic organs revealed that tumor metastasis to the liver was significantly reduced upon Panx1 knockdown. These data suggest that while Panx1 is present in skin melanocytes it is up-regulated during melanoma tumor progression, and tumorigenesis can be inhibited by the knockdown of Panx1 raising the possibility that Panx1 may be a viable target for the treatment of melanoma.     

Relation between nicotine intake and Alzheimer's disease.

OBJECTIVE--To study the association between Alzheimer''s disease and nicotine intake through smoking. DESIGN--Population based case-control study. SETTING--City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS--198 patients with early onset Alzheimer''s disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer''s disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES--Age of onset of dementia, relative risk of Alzheimer''s disease. RESULTS--89 of 193 patients with Alzheimer''s disease had a history of smoking compared with 102 of 195 controls. Among the patients and controls with a family history of dementia, smoking was significantly less common in those with dementia (40/95 with dementia v 55/96 controls; relative risk 0.35; 95% confidence interval 0.16 to 0.78). The risk of Alzheimer''s disease decreased with increasing daily number of cigarettes smoked before onset of disease (relative risk 0.3 in those smoking greater than 21/day v 1 in non-smokers). In six families in which the disease was apparently inherited as an autosomal dominant disorder, the mean age of onset was 4.17 years later in smoking patients than in non-smoking patients from the same family (p = 0.03). CONCLUSIONS--These findings suggest an inverse association between smoking and Alzheimer''s disease, although smoking cannot be advocated for other health reasons. We speculate that nicotine may have a role in the aetiology of both Alzheimer''s disease and Parkinson''s disease.     

Turner's syndrome--correlation between karyotype and phenotype

Turner's syndrome is defined as a congenital disease determining by quantitative and/or structural aberrations of one from two X chromosomes with frequent presence of mosaicism. Clinically it is characterized by growth and body proportion abnormalities, gonadal dysgenesis resulting in sexual infantilism, primary amenorrhoea, infertility, characteristic stigmata, anomalies of heart, renal and bones and the presence of some diseases like Hashimoto thyroiditis with hypothyroidism, diabetes mellitus type 2, osteoporosis, hypertension. Turner's syndrome occurs in 1:2000 to 1:2500 female livebirth. The most frequent X chromosome aberrations in patients with phenotype of Turner syndrome are as follows: X monosomy - 45,X; mosaicism (50-75%), including 45,X/46,XX (10-15%), 45,X/46,XY (2-6%), 45,X/46,X,i(Xq), 45,X/46,X,del(Xp), 45,X/46,XX/47,XXX; aberration of X structure: total or partial deletion of short arm of X chromosome (46,X,del(Xp)) isochromosom of long arm of X chromosome (46,X,(i(Xq)), ring chromosome (46, X,r(X)), marker chromosome (46,X+m). Searching of X chromosome and mapping and sequencing of genes located at this chromosome (such as SHOX, ODG2, VSPA, SOX 3) have made possible to look for linkage between phenotypes and adequate genes or regions of X chromosome. In this paper current data concerning correlation between phenotype and karyotype in patients with TS have been presented.     

DNA-cytophotometry of benign compound and intradermal naevi, Spitz epithelioid naevi and malignant melanomas

Single cell DNA cytophotometry was used to characterize seven compound, ten intradermal and six Spitz naevi as well as 23 primary cutaneous malignant melanomas. Compound and intradermal naevi were characterized by a smaller nuclear area than both Spitz naevi and malignant melanomas. Tumour ploidy could not be used as a single criterion of malignancy since both diploid and hyperdiploid melanomas were encountered. The very low mean optical density of Spitz naevi served to distinguish these lesions from malignant melanomas.     

Relation of coronary heart disease and apolipoprotein E phenotype in patients with non-insulin dependent diabetes.

OBJECTIVES--To examine the relation between coronary heart disease and the apolipoprotein E phenotypes in patients with non-insulin dependent diabetes mellitus. DESIGN--Cross sectional study. SETTING--District around Kuopio University Central Hospital, East Finland. SUBJECTS--138 men with non-insulin dependent diabetes and 64 men without diabetes as controls. MAIN OUTCOME MEASURE--Apolipoprotein E phenotype, electrocardiographic abnormalities, other signs of coronary heart disease. RESULTS--The prevalences of definite myocardial infarction and ischaemic electrocardiographic changes were highest in the diabetic men with the phenotypes E4/4 or E4/3 (25% (95% confidence interval 18% to 32%) and 50% (42% to 58%) respectively), although the difference between the phenotype groups was not significant. The prevalence of angina pectoris was 69% (61% to 77%) in men with the phenotypes E4/4 or E4/3 (p = 0.005 compared with other phenotypes), 41% (33% to 49%) in men with phenotype E3/3, and 47% (39% to 55%) in those with phenotypes E2/2 or E2/3. Similarly, the simultaneous presence of angina pectoris and ischaemic electrocardiographic changes was highest in the diabetic men with the phenotypes E4/4 or E4/3 (42% v 22% in those with E3/3 and 29% in those with E2/2, E2/3; p = 0.038). Overall, the prevalence of any evidence of coronary heart disease among the diabetic subjects with the phenotypes E4/4 or E4/3 was 81% (p = 0.011 compared with other phenotypes), 58% in those with phenotype E3/3, and 53% in those with phenotypes E2/2 or E3/3. CONCLUSION--Apolipoprotein E phenotypes E4/4 and E4/3 modulate the risk of coronary heart disease in men with non-insulin dependent diabetes.     

Relation between medicines sweetened with sucrose and dental disease.

The teeth of 44 children aged under 6 years who had been taking syrup medicines regularly for at least six months were compared with those of a control group of 47 children of similar ages. Dental disease was assessed by measuring dental caries, dental plaque, and gingivitis. The children who were receiving sucrose-based medicines had significantly more carious teeth and gingivitis. It is concluded that sucrose-based medicines continuously administered to children cause dental caries and gingivitis. Liquid medicines for children should be either unsweetened or sweetened with non-cariogenic substances.