RESUMO
BACKGROUND: Phototesting is a technique that assesses the skin's sensitivity to UV radiation by determining the smallest dose of radiation capable of inducing erythema (minimal erythema dose [MED]) and anomalous responses to UV-A radiation. No phototesting protocol guidelines have been published to date. METHODOLOGY: This was a multicenter prospective cohort study in which 232 healthy volunteers were recruited at 9 hospitals. Phototests were carried out with solar simulators or fluorescent broadband UV-B lamps. Each individual received a total of 5 or 6 incremental doses of erythemal radiation and 4 doses of UV-A radiation. The results were read at 24hours. RESULTS: At hospitals where solar simulators were used, the mean (SD) MED values were 23 (8), 28 (4), 35 (4), and 51 (6) mJ/cm(2) for skin phototypes i to iv, respectively. At hospitals where broadband UV-B lamps were used, these values were 28 (5), 32 (3), and 34 (5) mJ/cm(2) for phototypes ii to iv, respectively. MED values lower than 7, 19, 27, and 38 mJ/cm(2) obtained with solar simulators were considered to indicate a pathologic response for phototypes I to IV, respectively. MED values lower than 18, 24, and 24mJ/cm(2) obtained with broadband UV-B lamps were considered to indicate a pathologic response for phototypes ii to iv, respectively. No anomalous responses were observed at UV-A radiation doses of up to 20J/cm(2). CONCLUSIONS: Results were homogeneous across centers, making it possible to standardize diagnostic phototesting for the various skin phototypes and establish threshold doses that define anomalous responses to UV radiation.
Assuntos
Eritema/classificação , Eritema/etiologia , Pele/efeitos da radiação , Raios Ultravioleta , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes Cutâneos , Luz Solar , Adulto JovemRESUMO
BACKGROUND: UV radiation and the presence of melanocytic nevi are the main risk factors of sporadic melanoma (MM). Protection of skin by an oral photoprotective agent would have substantial benefits. OBJECTIVE: We investigated the possible role of an oral Polypodium leucotomos (PL) extract to improve systemic photoprotection in patients at risk of skin cancer analyzing the ability to decrease UV-induced erythema. We also studied the interaction among MC1R polymorphisms and CDKN2A status with the minimal erythematous dose (MED) and their influence in the response after oral PL. METHODS: A total of 61 patients (25 with familial and/or multiple MM, 20 with sporadic MM and 16 with atypical mole syndrome without history of MM) were exposed to varying doses of artificial UVB radiation without and after oral administration of a total dose of 1080 mg of PL. RESULTS: Oral PL treatment significantly increased the MED mean in all group patients (0.123 to 0.161 J/cm(2) , p<0.05). Although not significant, we noticed a stronger effect of PL on the MED of patients with familial MM compared to those with MM (U=273, p=0.06). Among the patients with familial MM, those exhibiting a mutated CDKN2A and/or polymorphisms in MC1R had the bigger differences in response to treatment with PL. LIMITATIONS: Reduced number of patients. No control population. CONCLUSIONS: Administration of PL leads to a significant reduction of sensitivity to UVR (p<0.05) in all patients. Dark-eye patients and patients with higher UVR sensibility (lower basal MED) would be the most benefited from oral PL treatment.
Assuntos
Melanoma/prevenção & controle , Fitoterapia , Extratos Vegetais/administração & dosagem , Polypodium , Neoplasias Cutâneas/prevenção & controle , Administração Oral , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Melanoma/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/genética , Adulto JovemRESUMO
BACKGROUND: Patients with genodermatosis such as Gorlin syndrome (GS) and Xeroderma pigmentosum (XP) require a close follow-up for early diagnosis and treatment of skin cancer. We aimed to evaluate the efficacy of methyl-aminolevulinate (MAL) photodynamic therapy (PDT) in basal cell carcinomas (BCCs) from patients with GS and XP, and to determine the utility of reflectance confocal microscopy (RCM) in the diagnosis and the evaluation of therapeutic response. PATIENTS AND METHODS: We included four patients with GS and two siblings with XP. Single or multiple lesions in localized areas were treated with 1-3 cycles of MAL PDT. RCM was performed before and 3 months after the treatment in target lesions in all the patients. Patients were followed up for 3 years. RESULTS: In XP patients, we treated 13 pigmented BCCs on the face. All the lesions responded to the treatment and six lesions showed a complete clinical clearing. In GS patients, facial or trunk areas with multiple BCCs were treated (up to 200). Complete clinical remission was obtained in 25-67% of the lesions. Some nodular and pigmented lesions failed to achieve a complete remission. RCM could identify already described confocal features for BCC. Tumour remissions could be assessed by this technique. CONCLUSIONS: Methyl-aminolevulinate PDT may be useful for the treatment of superficial BCC in GS and XP. In some nodular lesions, PDT may complement surgery reducing tumour size. RCM may be regarded in the future as a complementary technique in BCC for the diagnosis and post-treatment assessment to non-invasive therapeutic modalities.
Assuntos
Predisposição Genética para Doença , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Microscopia Confocal , Fotoquimioterapia , Estudos Prospectivos , Neoplasias Cutâneas/genéticaRESUMO
UNLABELLED: Karnofsky Index (KI) is a widely used functional scale developed for oncology patients. It has proved useful as outcome predictor with cancer and geriatric patients. Theoretically, KI could be used to predict mortality in patients with home enteral nutrition (HEN). STUDY OBJECTIVES: To determine baseline KI and its 6-month evolution in HEN patients, and to assess its relation with the mortality rate. METHODOLOGY: Observational and prospective study carried out during 2002 and 2003 with tube feeding neurologic and cancer patients followed during 10 months since their HEN programme inclusion. RESULTS: 201 patients were included, 131 (65.2%) with neurological diseases and 70 (34.8%) with neoplasm. There were not significant differences between groups in age, days with HEN and mortality rate at the end of the study period (35.1% in neurologic patients and 40% in cancer ones). 27.1% of cancer patients had resumed full oral nutrition after ten months from the beginning of the study, whereas only 10.7% of neurologic patients did (p < 0.05). In the three measurement phases (initial, past-3 and past-6 months) KI values were higher for cancer patients than for neurologic ones (p < 0.001). In both groups we didn't found statistically significant differences in KI along the three measurements. A significant relation was observed overall between initial KI values and average survival after 10 months (p < 0.001), and an inverse relation was found between the former and mortality rate (p < 0.001). CONCLUSION: KI is a useful tool to predict mortality rate in cancer and neurologic patients under HEN.
Assuntos
Nutrição Enteral/mortalidade , Serviços de Assistência Domiciliar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neoplasias/terapia , Doenças do Sistema Nervoso/mortalidade , Doenças do Sistema Nervoso/terapia , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: To communicate the results from the registry of Home-Based Enteral Nutrition of the NADYASENPE group in 2007. MATERIAL AND METHODS: We included every patient in the registry with home enteral nutrition any time from January 1st to December 31st of 2007. RESULTS: The number of patients with home enteral nutrition in 2007 was 5,107 (52% male) from 28 different hospitals. 95.4% of them were 15 yr or older, with a mean age of 67.96 +/- 18.12, and 4.2 +/- 3.38 among patients aged 14 yr or less. The most common underlying diseases were neurological (37.8%) and neoplastic diseases (29.3%). Enteral nutrition was administered p.o. in most patients (63.5%), followed by nasogastric tube (25.9%), while gastrostomy was only used in 9.2%. The mean time in enteral nutrition support was 9.4 months and the most common reasons for withdrawal were death (58.7%) and switching to oral intake (32%). Activity was limited in 31.4% of patients and 36.01% were house-bound. Most patients needed partial (26.51%) or total (37.68%) care assistance. Enteral formula was provided by hospitals to 69.14% of patients and by pharmacies to 30.17% of them, while disposable material was provided by hospitals to 81.63% and by Primary Care to the remaining patients. CONCLUSIONS: In 2007, there has been an increase of more than 30% of patients registered with home enteral nutrition comparing with 2006, without any big difference in other data, but a higher proportion of patients with enteral nutrition p.o.
Assuntos
Nutrição Enteral , Assistência Domiciliar , Sistema de Registros , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Nutrição Enteral/métodos , Nutrição Enteral/estatística & dados numéricos , Nutrição Enteral/tendências , Feminino , Gastrostomia/estatística & dados numéricos , Assistência Domiciliar/estatística & dados numéricos , Humanos , Lactente , Intubação Gastrointestinal/estatística & dados numéricos , Jejunostomia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Neoplasias/terapia , Doenças do Sistema Nervoso/terapia , Espanha , Adulto JovemRESUMO
Three children (two boys and one girl) from the same family presented with photosensitivity, hyperpigmentation, hypertrichosis, mild skin fragility, blistering and scarring in childhood. On examination, the cutaneous lesions were found to have improved since their previous examinations. Laboratory tests showed raised plasma and urine carboxyporphyrins and decreased uroporphyrinogen decarboxylase enzyme activity in red blood cells. Triggering factors for porphyria were not detected except for a hepatitis C virus infection in the younger boy. The girl's clinical symptoms recurred in late adolescence, after iron and oestrogen treatments. Mutation analysis of the UROD gene detected two missense mutations, 19 A-->G M1V (novel) and 703C-->T P235S (previously reported), in an uncommon compound heterozygous manner in the three siblings.
Assuntos
Mutação de Sentido Incorreto/genética , Porfiria Cutânea Tardia/enzimologia , Uroporfirinogênio Descarboxilase/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Feminino , Heterozigoto , Humanos , Masculino , Linhagem , Uroporfirinogênio Descarboxilase/metabolismoRESUMO
OBJECTIVE: To communicate the results obtained from the registry of Home-Based Enteral Nutrition (HBEN) of the NADYA-SENPE group for the year 2006. MATERIAL AND METHODS: Recompilation of the data from the HBEN registry of the NADYA-SENPE group from January 1st to December 31st of 2006. RESULTS: During the year 2006, 3,921 patients (51% men) from 27 hospital centers were registered. Ninety-seven percent were older than 14 years. The mean age for those < 14 years was 4.9 +/- 3.9 (m +/- SD) and in those > or = 14 years, it was 68.5 +/- 18.2 years. The most common underlying disease was neurological pathology (42%), followed by cancer (28%). Enteral nutrition was administered p.o. in 44% of the patients, through nasogastric tube in 40%, gastrostomy in 14%, and jejunostomy in 1%. The average time of nutritional support was 8.8 months. The most common reasons for ending the therapy were patient's death (54%) and switching to oral feeding (32%). Thirty-one percent of the patients presented a limited activity and 40% were confined to bed/coach. Most of the patients required partial (25%) or total (43%) care assistance. The nutritional formula was provided by the hospital in 62% of the cases and from the reference pharmacy in 27%. The fungible material was provided by the hospital in 80% of the cases and by primary care in the remaining patients. CONCLUSIONS: Although the number of registered patients is slightly higher than that from the last years, there are no important changes in the patients characteristics, or way of administration and duration of enteral nutrition.
Assuntos
Nutrição Enteral/estatística & dados numéricos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Sistema de Registros , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
Acute intermittent porphyria (AIP) is a metabolic disease with a variable prevalence among different countries. In some areas of southern Europe it remains to be fully evaluated. We undertook a genetic and biochemical study of 16 unrelated Spanish AIP patients and relatives. The genetic analyses showed they harboured the following mutations in the porphobilinogen deaminase gene: R173W, G111R, L278P, L238P, R116W, R26C, 340insT, 730delCT, 691del30bp, and IVS14+1g>a. The mutation R173W was found in 6 patients (37.5%), including the only patients of our series with >3 recurrent porphyria attacks. While in clinical remission, all AIP patients exhibited sustained increased excretion of porphyrins and precursors. PBG excretion showed a high between-subject variation and was not related to erythrocyte PBG deaminase activity. The study of family members allowed the identification of 22 asymptomatic AIP carriers. These included 8 persons harbouring the R173W mutation belonging to four different families. Six of these latent AIP subjects showed increased PBG elimination, and in two the urinary levels were >10-fold the normal limit. These results reinforce the hypothesis that the R173W mutation may have a high biochemical and clinical penetrance among AIP patients.
Assuntos
Mutação , Porfiria Aguda Intermitente/genética , Porfiria Aguda Intermitente/metabolismo , Adolescente , Adulto , Análise Mutacional de DNA , Feminino , Humanos , Hidroximetilbilano Sintase/genética , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Polimorfismo Conformacional de Fita Simples , Porfobilinogênio/química , Porfiria Aguda Intermitente/urina , Porfirinas/urina , Sensibilidade e EspecificidadeRESUMO
GOAL: To communicate the information available by the NADYA-SENPE Working Group from patients on Home Enteral Nutrition (HEN) in our country during the year 2003. MATERIAL AND METHODS: The data were collected through a closed questionnaire included in the web site of the Working Group (www.nadya-senpe.com) available only by the authorized users. Variable included were: epidemiological information, the indication to prescribe this treatment, the access path, the specific nutritional formula used, the treatment duration, the complications and hospital readmission related to the nutritional treatment, the follow-up and the quality of life. RESULTS: We register 3,858 patients that belong to twenty-one hospitals. Mean age from those adults 66.2 +/- 18.9 years, and from those younger than 14, 6.0 +/- 4.3 years. Neurological and neoplasic diseases were the diagnostics more frequents (38.9% and 37.4%, respectively). Oral nutrition was the preferential rout used for the enteral nutrition (54.7%) followed by naso-enteral tube (26.6%), and only in 17.6% we used ostomy tubes. Polymeric was the enteral formula mainly utilized (80.1%). The mean time on HEN was 6.6 +/- 4.3 months; the 28.8% of patients stayed in the treatment for less than 3 months, 21.2 % between 3 and 6 months, and 50.0% more than 6 months. Patients were followed mainly by Nutritional Support Unit from the reference hospital (73.1%). While the reference hospital supplies the material (62.4%), reference hospital pharmacy (46.8%) and public pharmacies (32.0%) provides the enteral formula. Complications related to enteral nutrition included change of enteral tube (44.5%), gastrointestinal complications (30.5%), mechanical complications (21.7%), and the metabolic one (3.3%). These complications were followed by 0.02 hospitalizations/patient. At the end of the year, 54.7% of patients were in the HEN programme, and in 35.2 % HEN was finish due to accept oral conventional alimentation (49.2%) or by deceased of patients (40.9%). While 26.6% of the patients were confined to bed or armchair, 19.7 % no or light discapacity degree was observed. CONCLUSIONS: We found a persistence of these treatment in our country. Neurological and neoplasic diseases were the more frequent diagnosis in patients analysed. The high prevalence of cancer patients could be the main cause of oral access for enteral nutrition. Change of enteral tube was the more frequent complication observed during this treatment.
Assuntos
Nutrição Enteral , Serviços de Assistência Domiciliar , Sistema de Registros , Adolescente , Adulto , Idoso , Nutrição Enteral/métodos , Nutrição Enteral/estatística & dados numéricos , Feminino , Serviços de Assistência Domiciliar/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
AIM: To report on the results of the Registry on Home-based Parenteral Nutrition (HPN) of the NADYA-SENPE working group, corresponding to the year 2002. MATERIALS AND METHOD: Compilation of the registry data loaded by the Units in charge of HPN patients care. It consists of an on-line registry available to the registered users of the group's web page (www.nadya-senpe.com). Epidemiological, diagnostic, access route, complications, hospital admissions, degree of disability, and course until December 31st of 2002. RESULTS: Data from 74 patients were gathered (56.8% women and 43.2% men), from 18 hospital centers. Mean age of adult patients was 49.4 +/- 15.5 years and 2.3-1.1 years for patients younger than 14 years (n=3 patients). Diseases that prompted the use of HPN were mesenteric ischemia (29.7%), followed by neoplasms (16.2%), radiation enteritis (12.2%), motility impairments (8.1%), and Crohn's disease (5.4%). Tunneled catheters were used in 52.7% of cases, as compared to 36.5% of subcutaneous reservoirs. Mean treatment duration was 8.7 +/- 4.4 months; 68.9% of patients remained on HPN for a duration longer than 6 months, and in 41.9% longer than one year. Patients' follow-up was mainly done from the reference hospital (87.8%), and the remaining patients (12.5%) by the home care team. In no case patients were followed by the primary care team or other specialists than the ones that prescribed nutritional support. In 94 cases there were complications related to nutritional therapy. The more frequent complications presented were infectious. These complications represented 1.84 admissions per patient. The mean number of visits was 12.9 per patient (10.2 routinary visits and 2.7 emergency visits). At the end of the year, we observed that 74.3% patients stayed in the program, whereas in the remaining 23.6% HPN had been discontinued. The main causes for discontinuation were death (52.9%), and switch to oral diet (23.5%) or enteral nutrition (11.8%). With regards to disability degree, 16.1% were confined to a wheelchair or bed, and 17.6% had no disability at all or only a mild social disability. CONCLUSIONS: We observed a sustained HPN prevalence rate in Spain (1.8 patient pmp). The main cause for its use was short bowel syndrome secondary to vascular disease, followed by cancer. Complications associated to nutritional therapy were common, especially of infectious origin.
Assuntos
Nutrição Parenteral no Domicílio/estatística & dados numéricos , Sistema de Registros , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral no Domicílio/efeitos adversos , EspanhaRESUMO
GOAL: To communicate the information available by the NADYA-SENPE Working Group from patients on Home Enteral Nutrition (HEN) in our country during the year 2002. MATERIAL AND METHODS: The data were collected through a closed questionnaire included in the web site of the Working Group (www.nadya-senpe.com) available only by the authorized users. Variable included were: epidemiological information, the indication to prescribe this treatment, the access path, the specific nutritional formula used, the treatment duration, the complications and hospital readmission related to the nutritional treatment, the follow-up and the quality of life. RESULTS: We register 3967 patients that belong to twenty-one hospitals. Mean age from those adults 69.2 +/- 19.2 years, and from those younger than 14, 5.6 +/- 4.1 years. Neurological and neoplasic diseases were the diagnostics more frequents (39.2% and 34.6%, respectively). Oral nutrition was the preferential rout used for the enteral nutrition (53.6%) followed by naso-enteral tube (30.6%), and only in 15.8% we used ostomy tubes. Polymeric was the enteral formula mainly utilized (81.5%). The mean time on HEN was 5.8 +/- 4.4 months; the 35.7% of patients stayed in the treatment for less than 3 months, 22.4% between 3 and 6 months, and 41.6% more than 6 months. Patients were followed mainly by Nutritional Support Unit from the reference hospital (75.3%). While the reference hospital supplies the material (65.7%), reference hospital pharmacy (43%) and public pharmacies (37.3%) provides the enteral formula. Complications related to enteral nutrition included change of enteral tube (29.7%), mechanical complications (22.9%), gastrointestinal complications (22.9%), and the metabolic one (9.2%). These complications were followed by 0.02 hospitalizations/patient. At the end of the year, 49.3% of patients were in the HEN programme, and in 41.5% HEN was finish due to accept oral conventional alimentation (47.3%) or by deceased of patients. While 31.8% of the patients were confined to bed o armchair, 17.8% no o light discapacity degree was observed. CONCLUSIONS: We found a persistence of these treatment in our country (96.5 patients/million inhabitants. Neurological and neoplasic diseases were the more frequent diagnosis in patients analysed. The high prevalence of cancer patients could be the main cause of oral access for enteral nutrition. Change of enteral tube was the more frequent complication observed during this treatment.
Assuntos
Nutrição Enteral/estatística & dados numéricos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Sistema de Registros , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Nutrição Enteral/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , EspanhaRESUMO
Hepatoerythropoietic porphyria is a severe cutaneous porphyria caused by deficiency of uroporphyrinogen decarboxylase and is considered to be the homozygous form of familial (type II) porphyria cutanea tarda. To elucidate further the relation between these conditions, we studied five Spanish families with hepatoerythropoietic porphyria and nine unrelated Spanish patients with familial porphyria cutanea tarda. Immunoreactive and catalytic uroporphyrinogen decarboxylase was decreased by greater than 95% in the five patients with hepatoerythropoietic porphyria. Hepatic uroporphyrinogen decarboxylase activity was decreased to 22% of normal. Four patients were homozygous for a mutation (G281E) originally identified in a Tunisian family; the fifth patient was a compound heterozygote for this mutation. The calculated carrier frequency for G281E in Spain is one in 1800. None of the nine familial porphyria cutanea tarda patients carried the G281E mutation. However, one G281E heterozygote in a family with hepatoerythropoietic porphyria had overt porphyria cutanea tarda. These findings suggest that the G281E mutation is functionally less severe than erythrocyte measurements indicate, that its clinical penetrance is very low in heterozygotes, and that, for this particular mutation, hepatoerythropoietic porphyria is the homozygous form of familial porphyria cutanea tarda.
Assuntos
Mutação , Porfiria Cutânea Tardia/etiologia , Porfiria Hepatoeritropoética/etiologia , Uroporfirinogênio Descarboxilase/genética , Sequência de Bases , Humanos , Dados de Sequência Molecular , Porfiria Cutânea Tardia/genética , Porfiria Cutânea Tardia/metabolismo , Porfiria Hepatoeritropoética/genética , Porfiria Hepatoeritropoética/metabolismoRESUMO
Erythropoietic protoporphyria is a hereditary disorder of porphyrin metabolism caused by mutations in the ferrochelatase gene. Ferrochelatase catalyzes the chelation of ferrous iron into protoporphyrin IX to form heme. Mutation analysis was performed in four Spanish erythropoietic protoporphyria families resulting in the identification of four different mutations in the ferrochelatase gene. Two of them were novel mutations, a missense mutation (1157 A-->C, H386P) and a frameshift mutation (843delC) found in two Spanish families, respectively. The third and the forth Spanish patients carried already published ferrochelatase gene mutations, a nonsense mutation (343C-->T, R115X) and a missense mutation (557T-->C, I186T), respectively. The newly described frameshift mutation (843delC) predicted formation of an abrupt mRNA. The deleterious effect of His386 to Pro substitution as a result of mutation 1157 A-->C on the ferrochelatase activity was investigated by expressing the mutant ferrochelatase in Escherichia coli. The mutant ferrochelatase exhibited only 0.8% of the wild-type ferrochelatase activity. Prediction of the secondary structure of ferrochelatase suggested that the H386P mutation disrupted the original alpha-helical structure by way of introducing a turn, a rather drastic structural change of the enzyme sufficient to cause activity loss.
Assuntos
Ferroquelatase/genética , Porfiria Hepatoeritropoética/genética , Eletroforese em Gel de Poliacrilamida , Feminino , Mutação da Fase de Leitura , Humanos , Masculino , Mutação , Linhagem , Porfiria Hepatoeritropoética/enzimologia , Análise de Sequência de DNA , EspanhaRESUMO
BACKGROUND: Hepatoerythropoietic porphyria (HEP) is usually a severe form of cutaneous porphyria, characterized biochemically by an increased urinary excretion of polycarboxylated porphyrins. The disease is the result of a profound deficiency (<10% of normal activity) of uroporphyrinogen decarboxylase (UROD) activity. Hepatoerythropoietic porphyria is inherited as an autosomal recessive trait, whereas familial porphyria cutanea tarda is dominant. At least 30 different mutations of the UROD gene have been identified in patients with HEP and familial porphyria cutanea tarda, with 1 predominant missense mutation (glycine-to-glutamic acid substitution at codon 281) in Spanish patients with HEP. OBSERVATION: A 5-year-old patient with first-degree-related parents presented with HEP and mild symptomatology. We found low levels of UROD enzymatic activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine substitution at codon 46 (F46L). Both parents were healthy carriers of the mutation. The mother had reduced UROD activity (50% of normal), whereas the father had normal UROD activity. Prokaryotic expression of the F46L mutation using a pGEX vector has been used to confirm the deleterious effect of the mutation. When the mother started a new pregnancy, a prenatal study showed the absence of F46L mutation in the fetus and no accumulation of porphyrins in the amniotic fluid. CONCLUSIONS: A new mutation in the UROD gene causes a mild HEP phenotype. A normal UROD enzymatic activity was observed in the father, despite the presence of the heterozygous mutation. To our knowledge, this observation is the first description of a prenatal exclusion of HEP.
Assuntos
Homozigoto , Mutação/genética , Porfiria Eritropoética/genética , Diagnóstico Pré-Natal , Uroporfirinogênio Descarboxilase/genética , Substituição de Aminoácidos/genética , Pré-Escolar , Aberrações Cromossômicas , Códon , Consanguinidade , Feminino , Genes Recessivos , Triagem de Portadores Genéticos , Humanos , Leucina/genética , Masculino , Fenilalanina/genética , Porfiria Eritropoética/diagnóstico , Gravidez , Uroporfirinogênio Descarboxilase/deficiênciaRESUMO
BACKGROUND: Data from an epidemic reported in Turkey (1955-1959) is the only information about the relationship between hexachlorobenzene (HCB) intake and porphyria cutanea tarda in humans. No information is available on the HCB threshold exposure level to induce porphyria cutanea tarda. OBJECTIVES: To study HCB serum levels and urinary porphyrin excretion in the inhabitants of a village located near an organochlorine compound factory with high HCB concentrations in the air and to detect possible alterations in urinary porphyrin excretion and examine their relationship with HCB serum levels. DESIGN: Cross-sectional study. SETTING: Unit of Porphyrias of a tertiary care facility in Barcelona, Spain. PARTICIPANTS: Six hundred four inhabitants of the village who were older than 14 years provided serum and urine samples (185 participants were factory workers). MAIN OUTCOME MEASURES: Serum HCB was analyzed by gas chromatography coupled to electron capture detection. Quantification of urinary total porphyrins was performed by spectrofluorimetry. Porphyrin profile was determined by high-pressure liquid chromatography. RESULTS: Hexachlorobenzene was detected in all serum samples (mean, 39.8 ng/mL; range, 1.1-1616.0 ng/mL), and levels were higher in factory workers. Mean +/- SD level urinary total porphyrin average concentration was 98 +/- 69 nmol/L (range, 9-1009 nmol/L). Only the urine sample with the highest porphyrin concentration showed an increase of highly carboxylated porphyrins, with a typical profile of porphyria cutanea tarda. In the remaining 603 urine samples, coproporphyrin was the predominant fraction. CONCLUSION: The airborne exposure to and increased body burden of HCB in the Flix village population are not enough to trigger a significant alteration of the heme biosynthesis pathway.
Assuntos
Exposição Ambiental , Hexaclorobenzeno/sangue , Porfirinas/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Hexaclorobenzeno/efeitos adversos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Cutaneous malignant melanoma (CMM) is an aggressive tumour with a high metastatic potential. Deletions of chromosome 9p have been detected in CMM, some of which involve the CDKN2A/p14ARF genes. Loss of heterozygosity (LOH) of 16 microsatellite markers on 9p and mutations in the CDKN2A/p14ARF genes had been previously studied in 32 melanoma patients by our group. 9p deletions were detected in 15 primary tumours (45.5%) and are here correlated with the clinical outcome over 5 years and compared with classical prognostic factors. Eight of the 32 patients developed metastases (25%). The metastases were all detected within 768 days of the initial diagnosis. The patients without metastases were last monitored at least 1621 days after diagnosis. None of the 21 patients with more than eight microsatellites conserved developed metastases, whereas all of the eight patients who developed metastases had eight or more markers deleted. The sensitivity of this analysis to predict metastases was 100% (specificity 84%), whereas the sensitivity for the same sample using a Breslow thickness > 3 mm was 62.5% (specificity 68%). LOH of eight or more of the 9p microsatellite markers is therefore a useful prognostic factor to predict the development of metastases in the first 4.4-6.3 years (1621-2294 days).
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 9/genética , Melanoma/genética , Neoplasias Cutâneas/genética , Mapeamento Cromossômico , Análise Mutacional de DNA , DNA de Neoplasias/análise , Seguimentos , Marcadores Genéticos , Humanos , Perda de Heterozigosidade , Melanoma/secundário , Repetições de Microssatélites , Metástase Neoplásica , Sensibilidade e EspecificidadeRESUMO
The objective of this study was to establish normal reference ranges for porphyrins in healthy neonates. There is little information about urinary porphyrin excretion in this age group. This knowledge may provide an early diagnostic tool for detecting subtle alterations or latent forms in disorders of heme biosynthesis. Fifty healthy neonates were selected from the Department of Obstetrics. Total urinary porphyrins in random specimens were analysed by a spectrofluorometry method. The measurement of porphyrin fractions was made by fluorometric high-performance liquid chromatography (HPLC). The results were adjusted to urinary creatinine excretion to correct any imprecision and interindividual variation in body mass. The urinary total porphyrin had a median value of 331.50 (nmol/L). A statistically significant relationship between total porphyrin (nmol/L) and creatinine (mmol/L) was found (p < 0.01). The porphyrin/creatinine ratio showed a median value of 56.30 nmol/mmol creatinine. The study of individual porphyrins revealed that coproporphyrin and uroporphyrin were the major porphyrins excreted in neonates (coproporphyrin represents 81.98% and uroporphyrin 16.64% of total porphyrin); in both cases, isomer I was predominant with median values of 22.36 and 6.25 nmol/mmol creatinine, respectively. No significant relationships were found between porphyrin excretion and sex, gestational age, weight, or height. Our data provide the reference limits for porphyrins in neonates as a diagnostic guideline for evaluation of subtle alterations in heme biosynthesis.
Assuntos
Recém-Nascido/urina , Porfirinas/urina , Fatores Etários , Peso ao Nascer , Cromatografia Líquida de Alta Pressão , Coproporfirinas/urina , Creatinina/urina , Feminino , Idade Gestacional , Humanos , Masculino , Valores de Referência , Fatores Sexuais , Espectrometria de Fluorescência , Estatísticas não Paramétricas , Uroporfirinas/urinaRESUMO
BACKGROUND: To evaluate the highly active antiretroviral therapy (HAART) in the Kaposi's sarcoma evolution. PATIENTS AND METHOD: Retrospective analysis of a cohort of 126 HIV infected patients suffering from Kaposi's sarcoma with or without HAART. Clinical evolution, immunological status (CD4+ cell count) and response to therapy (HIV-RNA plasma viral load and human herpes-8 virus determination). RESULTS: All patients without HAART died and the cumulate probability survival (SD) among those who received HAART was 2.078 (74) days. The CD4+ count at baseline in the HAART group was 130 (125) * 106/l and the HIV-RNA viral load was 196,818 (244,195) copies/ml while at the moment of the clinical response was 235 (209) * 106/l CD4 + and 2,629 (6.444) copies/ml, respectively. CONCLUSION: HAART prolongs survival in HIV patients suffering from Kaposi's sarcoma. There is a clear relationship among clinical response, HAART and immunological recovery.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV , Sarcoma de Kaposi/etiologia , Adulto , Idoso , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Carga ViralRESUMO
The features and prognostic factors of 67 cases of Kaposi's sarcoma (KS) associated to the acquired immunodeficiency syndrome (AIDS) diagnosed at the Hospital Clinic, Barcelona, are analyzed. All the patients were male; mean age was 39.7 years, ranging from 22 and 62 years. 64 were homosexuals (95.5%), two were homosexual-drug addicts (3%) and one was drug addict (1.5%). Prevalence of cytomegalovirus and herpes virus infections were 91.1% and 89.5% respectively. In 42 cases (62.7%) KS was the initial AIDS presentation. The most common localization was the skin (89.5%), followed by the digestive tract (52.2%) and the lymph nodes (22.4%). Staging distribution was: 20 patients (29.8%) were in stage I, 11 patients (16.4%) in stage II, 7 patients (10.4%) in stage III, and 29 patients (43.2%) in stage IV. Constitutional symptoms associated to KS were found in 37 patients (55%). Overall 39 patients have already died, and the actuarial survival possibility of these 67 cases was 55% after 12 months. Univariant statistical analysis showed the presence of six variables with prognostic significance (p less than 0.05): staging, symptomatology, total white blood count, total lymphocyte count, T helper lymphocyte count and hemoglobin. Multivariant statistical analysis only chose the staging and symptomatology variables as independent (p less than 0.01 and p less than 0.001, respectively).
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Neoplasias do Sistema Digestório/etiologia , HIV-1 , Sarcoma de Kaposi/etiologia , Neoplasias Cutâneas/etiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Adulto , Neoplasias do Sistema Digestório/epidemiologia , Neoplasias do Sistema Digestório/mortalidade , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/mortalidade , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/mortalidade , Espanha/epidemiologia , Análise de SobrevidaRESUMO
Decisions have to be made about what data on patient characteristics and processes and outcome need to be collected, and standard definitions of these data items need to be developed to identify data quality concerns as promptly as possible and to establish ways to improve data quality. The usefulness of any clinical database depends strongly on the quality of the collected data. If the data quality is poor, the results of studies using the database might be biased and unreliable. Furthermore, if the quality of the database has not been verified, the results might be given little credence, especially if they are unwelcome or unexpected. To assure the quality of clinical database is essential the clear definition of the uses to which the database is going to be put; the database should to be developed that is comprehensive in terms of its usefulness but limited in its size.