ABSTRACT
UV-induced DNA repair was studied in peripheral blood lymphocytes from patients with multiple actinic keratoses (AK) requiring surgical therapy and from age-matched normal control individuals. The DNA repair activity in lymphocytes from AK patients at 4 h after UV-irradiation was 50% of that in control lymphocytes, but at 21 h the extent of DNA repair synthesis was similar to that in control cells.
Subject(s)
DNA Repair , Keratosis/blood , Lymphocytes/metabolism , Ultraviolet Rays/adverse effects , Humans , Keratosis/etiology , Keratosis/physiopathology , Kinetics , Thymine Nucleotides/metabolismABSTRACT
Much of our knowledge about the relationship between micronutrients and cancer comes from studies in which plasma (serum) micronutrient levels have been correlated with cancer incidence; however, the relationship between the concentrations of micronutrients in the plasma and in the target tissues has not been established. Ninety-three subjects (62 males and 31 females ages 42-86, median age 69) with actinic keratoses were recruited for investigation of this relationship. The subjects were randomly assigned and received placebo or retinol (25,000 IU/day) intervention for 48 to 65 months as part of a skin cancer chemoprevention trial. Shortly before the end of the trial, three fasting plasma samples and one skin biopsy were obtained from each subject. The concentrations of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, retinol, retinyl palmitate, alpha-tocopherol and gamma-tocopherol in the plasma and skin were simultaneously measured using HPLC. The profiles of the eleven micronutrients in the plasma and skin were similar. Lycopene, beta-carotene and alpha-tocopherol were the predominant micronutrients in both plasma and skin, but the ratio of retinyl palmitate to retinol was much greater in the skin than plasma. The three fasting plasma concentrations from the same subject during a one-month period were very consistent; however, the between-person variations were very large. The retinol supplementation caused a significant increase in the plasma concentrations of retinol, retinyl palmitate, lutein and alpha-tocopherol, especially retinyl palmitate as well as the skin concentrations of retinol and retinyl palmitate.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Carotenoids/analysis , Carotenoids/blood , Keratosis/blood , Keratosis/metabolism , Retinoids/analysis , Retinoids/blood , Skin/chemistry , Vitamin A/therapeutic use , Vitamin E/analysis , Vitamin E/blood , Adult , Aged , Aged, 80 and over , Chromatography, High Pressure Liquid , Diterpenes , Female , Humans , Keratosis/drug therapy , Lycopene , Male , Middle Aged , Placebos , Retinyl Esters , Skin Neoplasms/prevention & control , Vitamin A/administration & dosage , Vitamin A/analogs & derivatives , Vitamin A/analysis , Vitamin A/blood , beta CaroteneABSTRACT
Eighteen patients with facial actinic keratoses were treated with the retinoid fenretinide (4-HPR), applied topically twice-daily for 3 months. After 3 months of treatment, complete regression was observed in 56% and partial regression in 44% of cases. Eight patients relapsed within 3 months after drug discontinuation. Six months later, only two patients (11%) showed a treatment response (complete regression). Blood samples showed that 4-HPR was not absorbed and no local or distant adverse effects were observed. Baseline plasma retinol levels were lower than in healthy subjects, thus suggesting that reduced retinol levels might be involved in this pathology. These encouraging preliminary results suggest the need for further studies to evaluate the best dosage schedules and duration of 4-HPR topical application in actinic keratoses.
Subject(s)
Anticarcinogenic Agents/therapeutic use , Facial Dermatoses/drug therapy , Fenretinide/therapeutic use , Keratosis/drug therapy , Precancerous Conditions/drug therapy , Administration, Topical , Adult , Facial Dermatoses/blood , Female , Humans , Keratosis/blood , Male , Middle Aged , Precancerous Conditions/blood , Remission Induction , Vitamin A/bloodABSTRACT
BACKGROUND AND DESIGN: After the chance of observation of an elevated parathyroid hormone (PTH) value in a patient with pityriasis rubra pilaris, the serum PTH level was measured in the next 14 patients seen with disorders of keratinization. Calcium metabolism in three affected patients was then studied in depth. RESULTS: Five of 15 patients had twofold or greater elevations in serum PTH values. The patients had four different disorders of keratinization: bullous congenital ichthyosiform erythroderma (two patients); lamellar ichthyosis (one patient); pityriasis rubra pilaris (one patient); and ichthyosis linearis circumflexa (one patient). At least one other patient with each diagnosis had normal PTH values. Two of three patients who were studied further had clear evidence of increased, biologically active PTH, consistent with secondary hyperparathyroidism. An elevated PTH level spontaneously became normal in one patient, and in a second patient it became normal with a high-calcium diet. CONCLUSIONS: These data provide the first indication that patients with various disorders of keratinization have an increased risk for secondary hyperparathyroidism. The exact prevalence, origin, and physiologic significance of this finding remain to be elucidated.
Subject(s)
Keratosis/blood , Parathyroid Hormone/blood , Adolescent , Adult , Calcium/blood , Cyclic AMP/analysis , Female , Humans , Hydroxycholecalciferols/blood , Hyperparathyroidism, Secondary/complications , Ichthyosis/blood , Keratosis/complications , Male , Middle Aged , Pityriasis Rubra Pilaris/bloodABSTRACT
PURPOSE: To report nine cases of tyrosinemia type II, with ocular signs and symptoms. METHODS: Participants included nine patients (18 eyes) who were followed for a mean follow-up period of 6.5 years (range, 2 to 8 years). Intervention included dietary restriction of tyrosine and phenylalanine, which led to resolution of ocular and cutaneous lesions, improved behavior in one patient, and may have prevented developmental delay in others. The main outcome measures were visual acuity and serum tyrosine levels to determine the response to dietary therapy. Intelligence testing and developmental screening were performed when appropriate. RESULTS: All patients presented with ocular signs and symptoms as the primary manifestation of disease and serve to illustrate the typical ocular findings of this syndrome. Three patients presented with cutaneous manifestations, and one patient had mild mental impairment at the time of diagnosis. CONCLUSIONS: Recalcitrant pseudodendritic keratitis may be the presenting sign in tyrosinemia type II. Awareness of the presenting signs and symptoms may accelerate the diagnosis and dietary intervention. Initiation of a tyrosine-restricted and phenylalanine-restricted diet in infancy is most effective in preventing cognitive impairment.
Subject(s)
Cornea/pathology , Keratitis/diagnosis , Tyrosinemias/diagnosis , Child , Child, Preschool , Diet, Protein-Restricted , Female , Humans , Infant , Keratitis/blood , Keratitis/diet therapy , Keratosis/blood , Keratosis/diagnosis , Keratosis/diet therapy , Male , Mental Disorders/blood , Mental Disorders/diagnosis , Mental Disorders/diet therapy , Tyrosine/blood , Tyrosinemias/blood , Tyrosinemias/diet therapy , Visual AcuityABSTRACT
The authors have studied--in the plasma--the changes of zinc, retinol binding protein (RBP), retinol and retinoic acid with reference to the dermatological status of fifty chronically haemodialysed renal insufficiency patients divided into four subgroups (normal skin, dry skin, dry skin with keratosis, and only keratosis). The results of these groups were compared to those of thirty healthy subjects. The values of these variables do not show any significant difference in function of the dermatological subgroups; but, despite the considerable rise in the retinol binding protein and retinol levels in comparison with the controls (haemodialysis patients: RBP = 11.77 +/- 2.83 mumol X l(-1), retinol = 7 +/- 2.57 mumol X l(-1); controls; RBP = 2.76 +/- 0.62 mumol X l(-1), retinol = 2.16 +/- 0.53 mumol X l(-1] the electromicroscopic examination of skin biopsy samples from some of the patients did not reveal any sign of hypervitaminosis A in the lesions.
Subject(s)
Hypervitaminosis A , Renal Dialysis/adverse effects , Retinol-Binding Proteins/blood , Skin Diseases/etiology , Tretinoin/blood , Vitamin A/blood , Zinc/blood , Humans , Keratosis/blood , Keratosis/etiology , Retinol-Binding Proteins, Plasma , Skin/pathology , Skin Diseases/bloodABSTRACT
The clinical response to various therapeutic agents was evaluated in 31 patients with phrynoderma. A complete clinical response with vitamin B-complex was noted in an average period of 5.7 weeks. In patients treated with vitamin E, partial or total improvement was seen in an average period of 12.3 and 10.7 weeks respectively. Patients treated with safflower oil showed a partial improvement in an average period of 13.2 weeks. The essential fatty acid (EFA) nutriture of 30 patients was compared with 7 controls. Plasma phospholipid fatty acid composition was used as an indicator of EFA nutriture. The patients with phrynoderma fell into two groups. In the 23 children in one group (pattern A), the mean levels of linoleic (18:2 omega 6), arachidonic (20:4 omega 6) and eicosatrienoic (20:3 omega 9) acids were similar to the levels in the controls. The ratio of eicosatrienoic to arachidonic acids (20:3 omega 9/20:4 omega 6), which is considered an accurate measure of EFA nutritional status, was 0.12 and in the normal range, suggesting that the EFA nutriture is normal in phrynoderma. The ratio of linoleic to arachidonic acids (18:2 omega 6/20:4 omega 6) was also found to be normal, suggesting that the metabolism of linoleic to arachidonic acid is not affected in phrynoderma. In seven children in a second group (pattern B), the fatty acid profile was different from patients with pattern A. In these two groups no obvious differences were noted in clinical features and severity. In patients treated with safflower oil, the mean levels of vitamin E were elevated. On all the three treatment schedules, the levels of other fatty acids were not altered. The biochemical and clinical evidence obtained indicate that phrynoderma may not be directly associated with EFA deficiency but that vitamin B-complex may have an important role. The plasma phospholipid fatty acid profile seems to reflect neither the clinical situation nor the response to therapy.
Subject(s)
Keratosis/etiology , Adolescent , Child , Child, Preschool , Fatty Acids, Essential/blood , Fatty Acids, Essential/deficiency , Female , Humans , Keratosis/blood , Keratosis/drug therapy , Male , Nutritional Status , Phospholipids/blood , Vitamin B Complex/administration & dosage , Vitamin B Complex/blood , Vitamin E/administration & dosage , Vitamin E/bloodABSTRACT
DNA repair activity was measured in peripheral blood lymphocytes from 18 patients with Actinic Keratosis and 18 age-matched control subjects, by comparing the incorporation of 3H-thymidine into cells after irradiation with ultraviolet light with that into unirradiated cells. The incorporation was followed autoradiographically or by measuring acid insoluble radioactivity in cells labelled in the presence of hydroxyurea. The repair activity in lymphocytes from Actinic keratosis patients was only 47.1 percent (+/- 6.5%) of that in cells from the control subjects.
Subject(s)
DNA Repair , Keratosis/blood , Lymphocytes/metabolism , Aged , DNA Repair/radiation effects , Dose-Response Relationship, Radiation , Humans , Keratosis/etiology , Lymphocytes/radiation effects , Middle Aged , Skin/radiation effects , Sunlight , Thymidine/blood , Ultraviolet Rays/adverse effectsSubject(s)
Antineoplastic Agents/adverse effects , Drug Eruptions/diagnosis , Keratosis/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Molecular Targeted Therapy/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Administration, Cutaneous , Aged , Antineoplastic Agents/therapeutic use , Drug Eruptions/blood , Drug Eruptions/drug therapy , Drug Eruptions/pathology , Female , Fusion Proteins, bcr-abl/antagonists & inhibitors , Humans , Keratolytic Agents/administration & dosage , Keratolytic Agents/therapeutic use , Keratosis/blood , Keratosis/chemically induced , Keratosis/drug therapy , Lower Extremity , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Salicylic Acid/administration & dosage , Salicylic Acid/therapeutic use , Torso , Upper ExtremitySubject(s)
Keratosis/drug therapy , Vitamin A/therapeutic use , Adult , Biopsy , Child , Female , Humans , Hydrocortisone/blood , Keratosis/blood , Keratosis/genetics , Male , Microscopy, Electron, Scanning , Placebos , Skin/drug effects , Skin/pathology , Skin Absorption , Triamcinolone Acetonide/therapeutic useSubject(s)
Carotenoids/blood , Dark Adaptation , Vitamin A/blood , Conjunctivitis/blood , Female , Gingivitis/blood , Humans , Keratosis/blood , MaleABSTRACT
Actinic keratosis (AK) can be treated by photodynamic therapy (PDT), which is becoming a well-established tool in dermatology. Normally a precursor of the photosensitiser is applied topically and converted into protoporphyrin IX (PPIX) in the cells. By activating PPIX with light, the dysplastic cells will be destroyed. We report the results of two clinical studies investigating the properties of a novel self-adhesive 5-ALA-patch (PD P 506 A) intended for PDT of mild to moderate AK on the face and head. The studies investigated the influence of patch application duration on PPIX-specific fluorescence and the pharmacokinetic properties of the 5-ALA patch. The PPIX fluorescence in AK lesions and normal skin after patch application (intraindividual comparison; application for 2, 3, 4, 5 h) was investigated in 13 patients using DYADERM Professional (Biocam). In the subsequent pharmacokinetic study 12 patients were treated with 8 patches each (4 h application). 5-ALA and PPIX were analysed in plasma (over 24 h) and urine (over 12 h). PPIX-specific fluorescence measured immediately after patch removal increased with increasing application duration to a maximum at 4-h application. The fluorescence in AK lesions was more intense than in normal skin. A small increase of 5-ALA plasma concentrations was observed in 10 of 12 patients after applying 8 patches for 4 h, which rapidly declined to normal values after patch removal. The maximum increase was 3.7-fold of the pre-dose 5-ALA plasma concentration. No PPIX-concentrations above the lower limit of quantification were observed. PPIX-specific fluorescence in AK lesions can be steered by application duration of this novel 5-ALA patch. Application is safe and well tolerable. The observed small rise in 5-ALA plasma concentrations is regarded clinically irrelevant. Clinical efficacy of the patch in PDT will be investigated in further clinical trials.
Subject(s)
Aminolevulinic Acid/pharmacokinetics , Keratosis/drug therapy , Photochemotherapy , Photosensitizing Agents/pharmacokinetics , Protoporphyrins/administration & dosage , Adhesives/administration & dosage , Adhesives/pharmacokinetics , Administration, Cutaneous , Aged , Aged, 80 and over , Aminolevulinic Acid/administration & dosage , Aminolevulinic Acid/analogs & derivatives , Case-Control Studies , Dosage Forms , Dose-Response Relationship, Drug , Environmental Exposure/adverse effects , Female , Fluorescence , Humans , Keratosis/blood , Keratosis/chemically induced , Keratosis/urine , Male , Middle Aged , Photosensitizing Agents/administration & dosage , Prospective Studies , Protoporphyrins/blood , Protoporphyrins/urine , Time Factors , Ultraviolet Rays/adverse effectsABSTRACT
No significant difference was found between the plasma vitamin A levels of patients with dyskeratoti skin disease and those of comparable control subjects.
Subject(s)
Keratosis/blood , Pityriasis Rubra Pilaris/blood , Vitamin A/blood , Adolescent , Adult , Aged , Darier Disease/blood , Female , Humans , Ichthyosis/blood , Male , Middle AgedABSTRACT
Of 108 renal transplant recipients (53 men and 55 women) treated with azathioprine (0.8-2.9 mg/kg/day) and prednisolone (10 mg daily), 10 men had actinic keratoses, and five of these had squamous cell carcinoma, on light-exposed areas of skin. The time from transplantation to diagnosis of these skin lesions varied from 1.2 to 9.0 (mean 5.1) years. The concentration of the active azathioprine metabolite 6-thioguanine nucleotide was 120-425 (mean 276) pmol per 8 X 10(8) red blood cells in the transplant patients who developed skin lesions and 54-203 (mean 130) pmol per 8 X 10(8) red blood cells in a matched control group of renal transplant recipients. This difference was statistically significant (P = 0.005). There was no statistically significant difference between patients and controls in azathioprine dosage, clinical features of immunosuppression, sunlight exposure or infection with human papilloma virus. The association of raised 6-thioguanine nucleotide concentrations in red blood cells with actinic keratoses and malignant skin tumours in these patients supports chemical carcinogenesis as a possible cause.
Subject(s)
Carcinoma, Squamous Cell/blood , Erythrocytes/analysis , Guanine Nucleotides/blood , Kidney Transplantation , Skin Neoplasms/blood , Thionucleotides/blood , Adult , Azathioprine/administration & dosage , Azathioprine/adverse effects , Carcinoma, Squamous Cell/chemically induced , Drug Administration Schedule , Female , Humans , Keratosis/blood , Male , Middle Aged , Photosensitivity Disorders/blood , Skin Neoplasms/chemically inducedABSTRACT
Dyskeratosis congenita is a rare genodermatosis whose hematologic complications include pancytopenia of variable time of onset, a propensity for opportunistic infections, and neoplasia. A family in which the disorder segregated in 3 generations and involved 9 members is reported, and the hematologic data of the 46 previously reported cases are reviewed.
Subject(s)
Keratosis/congenital , Leukoplakia/congenital , Nails , Pancytopenia/complications , Skin Diseases/congenital , Adult , Alkaline Phosphatase/blood , Blood Coagulation , Bone Marrow/pathology , Fetal Hemoglobin , Folic Acid/blood , Humans , Keratosis/blood , Keratosis/immunology , Male , Pedigree , Pigmentation Disorders/complications , Vitamin B 12/bloodABSTRACT
1. A study was undertaken to investigate the role of vitamin E in the aetiology of phrynoderma (follicular hyperkeratosis). Fifty-six children with the disease and twenty-one normal children were investigated for this purpose. 2. Plasma vitamin E levels (mean +/- SE; mg/l) were found to be low in phrynoderma (3.7 +/- 0.19) in contrast with normal children (6.6 +/- 0.40) and therapy with a combination of vitamin E and B-complex brought about complete cure. 3. The increase in plasma vitamin E levels after the administration of vitamin E at a dose of 100 mg three times daily for 4 weeks was higher than that obtained when vitamin E at the same dose was administered together with vitamin B-complex for 4 weeks, suggesting an interaction between the two vitamins. Further studies are necessary to find out the exact nature of this interrelationship.
Subject(s)
Keratosis/etiology , Vitamin E Deficiency/complications , Adolescent , Child , Child, Preschool , Drug Therapy, Combination , Female , Humans , Keratosis/blood , Keratosis/drug therapy , Male , Vitamin B Complex/therapeutic use , Vitamin E/blood , Vitamin E/therapeutic useABSTRACT
BACKGROUND: Reactive oxygen species and lipid peroxides have been implicated in the pathogenesis of a variety of diseases, particularly cancer. There may be an inverse correlation between lipid peroxidation and antioxidant defense mechanisms. The aim of this study was to investigate whether certain plasma antioxidants (ascorbic acid, alpha-tocopherol, total thiol groups, ceruloplasmin, urate, albumin and erythrocyte glutathione) are altered in actinic keratosis (AK) and basal cell carcinoma (BCC). METHODS: Plasma samples and red blood cells (RBC) of 13 patients with AK, 12 with BCC and 16 healthy controls were investigated. RESULTS: Data analysis indicates significant decrease of ascorbic acid (P < 0.001), alpha-tocopherol (P < 0.05 and P < 0.001), total thiol groups (P < 0.001), ceruloplasmin (P < 0.001 and P < 0.05), and RBC glutathione (P < 0.05) values in both AK and BCC groups compared to controls. Comparison of AK and BCC groups evidenced a significant decrease of alpha-tocopherol and RBC glutathione (P < 0.05) in BCC patient. CONCLUSION: Plasma antioxidants are decreased in the AK and BCC, probably due to the long exposure to UV irradiation which is one of the most important factors in the etiology of AK and BCC and alpha-tocopherol and RBC glutathione (P < 0.05) are most altered in BCC.
Subject(s)
Antioxidants/metabolism , Carcinoma, Basal Cell/blood , Keratosis/blood , Skin Neoplasms/blood , Adult , Aged , Antioxidants/analysis , Ascorbic Acid/blood , Ceruloplasmin/analysis , Erythrocytes/metabolism , Female , Glutathione/blood , Humans , Male , Middle Aged , Reference Values , Serum Albumin/analysis , Sulfhydryl Compounds/blood , Uric Acid/blood , Vitamin E/bloodABSTRACT
The distribution of A, B, and H blood group antigens was studied by means of peroxidase-antiperoxidase technique in normal skin and in lesions of carcinomas in situ (solar keratoses, Bowen's disease), squamous cell carcinoma, keratoacanthomas, and verrucae. In normal skin, the epidermis of persons of blood group O showed H antigens throughout the epidermis; of blood group A, H and A antigens; and of blood group B, H and B antigens. In lesions of solar keratoses, there were no antigens of blood groups in the irregular downward proliferations. In five of 11 cases of Bowen's disease, there were no antigens of blood groups in the epidermis. In eight out of 10 cases of squamous cell carcinoma, no antigens of blood groups were found in the islands of the neoplastic process, but in two cases they were present in a patchy distribution. In the benign lesions examined, the antigens of A, B, and H blood groups were always present, although in verrucae the staining was confined to the upper layers of the epidermis only.