Thesis--University of Göteborg, 1970.

Thesis--University of Göteborg, 1970.

No description available.

Thesis (Ph.D.)--Brown University, 2005. / Vita. Thesis advisor: Samuel I. Beale. Includes bibliographical references (leaves 123-146). Also available online.

A thesis presented to the Faculty of Medicine, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Medicine / Since changes occur in size, shape and haemoglobin content of red cells in disease a classification of the anaemias based on the morphology of the red cell has been widely used ( Wintrobe, 1956 ) . While such classification has a limited usefulness from the diagnostic and therapeutic approach it has two serious defects.. / IT2018

This thesis was undertaken to determine if there is any interrelationship between the two terminal enzymes of the haem biosynthetic pathway, protoporphyrinogen oxidase (PPO) and ferrochelatase, with particular reference to porphyria variegata (PV) and erythropoietic protoporphyria (EPP)• It has previously been found that both enzymes were deficient in PV and EPP, there being a qualitative difference in so far as ferrochelatase deficiency is concerned. / IT2018

La porfiria cutánea tarda (PCT) es la porfiria más frecuente y existen dos tipos: la forma esporádica y la forma familiar. Ambas suelen presentarse con fragilidad cutánea o ampollas en zonas fotoexpuestas. Clásicamente la PCT puede asociarse con otras enfermedades, entre ellas la diabetes mellitus. El objetivo principal del presente estudio es describir detalladamente las características clínicas, bioquímicas y los factores de riesgo de esta porfiria en ambos sexos de nuestra población. De esta forma podremos actualizar la sintomatología, diagnosticar mejor casos de presentación clínica atípica y detectar características que nos puedan predecir la posible existencia de un caso familiar o la posible asociación con diabetes. Se trata de un estudio observacional retrospectivo de pacientes diagnosticados de PCT en el Servicio de Dermatología del Hospital Clínic que han acudido para control durante el periodo 2004-2008. Primero se realiza revisión de las características clínicas, datos de laboratorio, datos genéticos y factores de riesgo de porfiria, comparando entre sexos y entre formas familiares y adquiridas. Posteriormente se seleccionan pacientes con PCT controlados estrictamente durante al menos 10 años y se analiza si han desarrollado trastornos del metabolismo de la glucosa (GMA) y se comparan las mismas variables de la primera fase junto con otras relacionadas con el riesgo de diabetes. Los principales resultados obtenidos han sido: 1)- Las mujeres presentaron con más frecuencia hipertricosis facial (84.8%; p=0,004), afectación de áreas diferentes a manos y cara (33,3%; p= 0,008) y prurito (27,3%; p=0,041) respecto de los hombres; 2)- De nuestros pacientes, 11,8% no presentaron el inicio clínico típico, siendo la hipertricosis e hiperpigmentación facial la manifestación más frecuente en estos casos; 3)- El análisis de los factores de riesgo mostró una alta prevalencia de infección por virus de la hepatitis C (65,8%) y abuso de alcohol (59,9%), siendo ambos mucho más frecuentes en los hombres (p< 0,001); 4)- En el análisis multivariante, la ausencia de infección por virus de la hepatitis C fue el único factor predictor de la presencia de formas familiares (odds ratio, 0.05; 95% intervalo confianza, 0.006-0.46); 5)- Se han identificado 33 pacientes (41%) con GMA, de los cuales 27 (82%) habían desarrollado estos trastornos un largo periodo después del diagnóstico de la PCT (media= 12,7 años); 6)- En el análisis bivariante, estos pacientes habían presentado cifras medias significativamente más altas de ferritina sérica en el momento del diagnóstico de la PCT (651 vs. 405 ng/mL, p= 0.005), una mayor frecuencia de ferritina persistentemente elevada (52% vs. 15%, p de tendencia < 0,001) y una prevalencia más alta de historia familiar de diabetes (48% vs. 15%, p= 0.004); 7)- En el análisis multivariante, la ferritina persistentemente elevada [odds ratio (OR), 10,66, 95% intervalo confianza (CI), 1,95-58,19, p= 0,006] y la historia familiar de diabetes (OR 4,82, CI 95%, 1,34-17,33, p= 0,016) continuaron asociándose significativamente con la presencia de GMA. En conclusión, las formas de presentación atípica de la PCT deben ser tenidas en cuenta de cara a prevenir un retraso en el diagnóstico. En nuestra población, la ausencia de infección por VHC en un paciente con PCT debe hacernos sospechar una forma familiar. La hiperferritinemia persistente parece ser un biomarcador de riesgo de desarrollo de diabetes en la PCT, probablemente en el contexto de la sobrecarga férrica y la inflamación hepática. Una estricta monitorización a largo plazo del metabolismo de la glucosa y de la ferritina sérica puede ser aconsejable en el seguimiento rutinario de los pacientes con PCT. / Porphyria cutanea tarda (PCT) occurs in both sporadic and familial forms and mostly presents with skin fragility and blisters. An association between porphyria cutanea tarda (PCT) and glucose metabolism alterations (GMA) is widely reported. This is a retrospective study including 152 Spanish patients with PCT attending the Porphyria Unit of the Hospital Clinic of Barcelona, Spain, in the period 2004–2008. A subset of 81 patients with a strict long-term follow-up was further selected to analyse the association with GMA. Our main results are: women more frequently had facial hypertrichosis (84.8%; p = 0.004), affected areas other than the hands and face (33.3%; p = 0.008), and pruritus (27.3%; p = 0.041) compared with men. Of our patients, 11.8% did not present the typical clinical onset of the disease, with facial hypertrichosis and hyperpigmentation the more frequent complaints. Analysis of risk factors showed a high prevalence of hepatitis C virus infection (HCV, 65.8%) and alcohol abuse (59.9%), both being more frequent in men (p < 0.001). HCV infection was the only risk factor that showed differences between the sporadic and familial forms in the logistic regression model (odds ratio, 0.05; 95% confidence interval, 0.006-0.46). Patients who developed GMA had significantly higher mean serum ferritin at diagnosis (651 vs. 405 ng/mL; P = 0.005), a higher prevalence of persistently elevated serum ferritin (52% vs. 15%; P < 0.001 for trend) and a higher prevalence of family history of DM (48% vs. 19%; P = 0.004). In multivariate analysis, persistently elevated serum ferritin [odds ratio (OR) 10.66, 95% confidence interval (CI) 1.95–58.19; P = 0.006] and family history of DM (OR 4.82, 95% CI 1.34–17.33; P = 0.016) remained significantly associated with the presence of GMA. In conclusion, atypical forms of presentation of PCT should be considered in order to prevent delayed diagnosis. In our population, the absence of HCV infection in a patient with PCT may suggest a possible familial case. Persistent hyperferritinaemia seems to be a risk biomarker of GMA in patients with PCT. Strict long-term monitoring of serum glucose and ferritin may be advisable in the routine follow-up of patients with PCT.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Thesis (MSc (Genetics))--University of Stellenbosch, 2008. / The porphyrias are a group of genetic diseases resulting from the accumulation of haem precursors due to defective enzyme activity in either one of the last seven enzymes in the haem biosynthesis pathway. One of the common hepatic porphyrias, porphyria cutanea tarda (PCT), arises from the inhibition of uroporphyrinogen decarboxylase (UROD) activity. It is characterised by excessive urinary and hepatic excretion of uroporphyrinogens and manifests cutaneously in the form of dermatitis. Two main forms of PCT have been described, namely familial PCT (fPCT) and sporadic PCT (sPCT). PCT is a complex disease and a few genetic (including modifier loci) and environmental precipitating factors have been implicated in the aetiology of PCT. An important exacerbating factor, iron overload, is observed in the majority of PCT patients. The aim of this study was to determine whether DNA sequence variation in the 5' untranslated regulatory region of four genes involved in iron metabolism i.e. CP, CYBRD1, HAMP and SLC40A1 may in any way be associated with PCT. The study cohort consisted of 74 patients from three diverse South African populations including 15 Black (eight males and seven females), 30 Caucasian (13 male and 17 females) and 29 Coloured (18 males and 11 females) individuals as well as 132 population-matched controls. The promoter region of the selected genes were screened for variation utilising the techniques of polymerase chain reaction (PCR) amplification, heteroduplex single-stranded conformational polymorphism (HEX-SCCP) analysis, restriction fragment length polymorphism (RFLP) analysis and bi-directional semi-automated DNA sequencing. Twenty three previously described and eleven novel variants were identified. The novel variants comprised CYBRD1: -1540G/A, -1474G/A, -1452T/C, -1346T/C, -1272T/C, -645T/C; G(T)8G(T)nG(T)nG(T)9; HAMP: -429G/T and SLC40A1: -1461T/C, -1399G/A, -524C/T. Statistically significant associations were observed at a number of loci. In silico analysis revealed several putative transcription factor binding sites (TFBSs) spanning the regions of variation. The disruption of an existing (or creation of a novel) TFBS is thought to occur in the presence of a variant in a number of instances. This may lead to the manipulation of transcription rates, thereby depicting a possible mechanism for gene dysregulation. The study presented here was undertaken as a preliminary investigation to determine the contribution (if any) of variants in the regulatory regions of candidate genes in iron metabolism in South African PCT patients. Considering the increasing incidence of PCT, in particular the Black South African population, it is necessary to elucidate the underlying mechanisms of iron overload in PCT patients. The propitious findings signified in the study, in conjunction with phenotypegenotype correlations, will assist in clarifying the association between iron overload and PCT. / jfl2010 / Imported from http://etd.sun.ac.za April 2010.

Porphyria is a rare metabolic disease which occurs as a result of accumulation of endogenous porphyrins due to specific enzyme deficiency in the biosynthetic pathway of heme. Chloroquine is currently used in the treatment of cutaneous porphyria, although its mechanism of action is not yet well understood. It is believed that chloroquine works in porphyria by forming complexes with excess porphyrin molecules and thus enhancing their elimination from the body. Previous reports of porphyrin-chloroquine complexes have been done mostly in aqueous models. In this study, UV/Visible optical absorbance difference spectroscopy was used to study the complexation of protoporphyrin IX with chloroquine and a range of acceptor molecules in hydrophobic models. The results show that chloroquine, mefloquine, amodiaquine, quinacrine, and pyronaridine formed relatively stronger complexes compared to other molecules such as quinine, duroquinone and caffeine. Therefore, relative to chloroquine, some of the molecules with comparable or greater binding affinity to protoporphyrin IX might also be useful in the treatment of porphyria.