Tumour VEGF/non tumour VEGF protein expression ratio as a biomarker for survival in colorectal cancer patients.

AIMS: Vascular endothelial growth factor (VEGF) over-expression is frequently considered as a marker of both, a poor prognosis and of an aggressive tumour phenotype. Colorectal carcinoma is still one of the most lethal malignancies. Thus, our purpose was to study the expression of VEGF in tumour tissue (VEGF(t)) and in the tissue surrounding tumours (VEGF(nt)) and analyse its correlation with clinico-pathological features and overall survival. METHODS: The study was designed to determine the concentration of vascular endothelial growth factor in tumour (n = 87) and non-tumour tissue (n = 230) obtained form the colorectal cancer patients. Accordingly, VEGF expression was studied in tissue homogenates by a quantitative sandwich ELISA method. RESULTS: The study was performed on 317 colorectal samples from 87 colorectal cancer patients. VEGF expression was higher in the tumour than in the non-tumour area (P < 0.0005). In areas of 5-10 cm around the tumours, VEGF expression was higher than the expression obtained in proximal or distal edge of the resection. VEGF(t) expression was lower in patients with stage I than in patients with stage II, III, or IV. However, a shorter overall survival time was evident when the ratio obtained between VEGF expression in the tumour and mean VEGF expression in the non-tumour areas of the same patient (VEGF(t)/VEGF(nt) ratio) was ≤2 (P = 0.019). CONCLUSIONS: VEGF expression in colorectal cancer tissue was higher in tumour than in non-tumour areas. VEGF(t) expression was lower in initial clinical stages. Indeed, patients who presented a VEGF(t)/VEGF(nt) ratio >2 survived longer. This is the first report showing that the clinical outcome could be related to the VEGF(nt) over-expression in colorectal cancer patients.

Epidermal growth factor receptor ligands in murine models for erythropoietic protoporphyria: potential novel players in the progression of liver injury.

Activation of the epidermal growth factor receptor (EGFR) plays an important role in liver regeneration and resistance to acute injury. However its chronic activation participates in the progression of liver disease, including fibrogenesis and malignant transformation. Hepatobiliary disease represents a constant feature in the clinically relevant Fechm1pas/Fechm1pas genetic model of erythropoietic protoporphyria (EPP). Similarly, chronic administration of griseofulvin to mice induces pathological changes similar to those found in patients with EPP-associated liver injury. We investigated the hepatic expression of the EGFR and its seven most relevant ligands in Fechm1pas/Fechm1pas mice bred in three different backgrounds, and in griseofulvin-induced protoporphyria. We observed that the expression of amphiregulin, betacellulin and epiregulin was significantly increased in young EPP mice when compared to aged-matched controls in all genetic backgrounds. The expression of these ligands was also tested in older (11 months) BALB/cJ EPP mice, and it was found to remain induced, while that of the EGFR was downregulated. Griseofulvin feeding also increased the expression of amphiregulin, betacellulin and epiregulin. Interestingly, protoporphyrin accumulation in cultured hepatic AML-12 cells readily elicited the expression of these three EGFR ligands. Our findings suggest that protoporphyrin could directly induce the hepatic expression of EGFR ligands, and that their chronic upregulation might participate in the pathogenesis of EPP-associated liver disease.

Induction of hepatic aminolevulinate acid synthetase activity by isoflurane in a genetic model for erythropoietic protoporphyria.

Erythropoietic Protoporphyria (EPP) is an inherited deficiency of ferrochelatase, the last enzyme of the heme pathway. Under general anaesthesia, some patients develop neurological dysfunction suggesting upregulation in heme biosynthesis similar to that described for acute porphyrias after xenobiotic administration. Our aim has been to evaluate whether Isoflurane induces alterations in the heme pathway in a mouse model for EPP. Administration of Isoflurane (a single dose of 2 ml/kg, i.p) to wild-type (+/+), heterozygous (+/Fechm1Pas) and homozygous (Fechm1Pas/Fechm1Pas) mice, was evaluated by measuring the activity of delta-aminolevulinic acid synthetase (ALA-S) and Porphobilinogen-deaminase (PBG-D) in different tissues, as well as Heme oxygenase (HO), cytochrome P-450, CYP2E1 and glutathione levels in liver. Porphyrin precursors were measured in 24 h-urine samples. Fechm1Pas/Fechm1Pas mice receiving anaesthesia show enhanced ALA-S and CYP2E1 activities in the liver and increased urinary excretion of porphyrin precursors. No alterations were found in either PBG-D or HO activities. Diminished glutathione levels suggest that anaesthesia may produce oxidative stress in these animals. In conclusion, Isoflurane induces ALA-S activity and increased excretion of porphyrin precursors in EPP mice. These findings appear to confirm our previous hypothesis and indicate that Isoflurane may be an unsafe anaesthetic not only for patients with acute porphyrias but also for individuals with non acute porphyrias.

Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells.

Erythropoietic protoporphyria is characterized clinically by skin photosensitivity and biochemically by a ferrochelatase deficiency resulting in an excessive accumulation of photoreactive protoporphyrin in erythrocytes, plasma and other organs. The availability of the Fech(m1Pas)/Fech(m1Pas) murine model allowed us to test a gene therapy protocol to correct the porphyric phenotype. Gene therapy was performed by ex vivo transfer of human ferrochelatase cDNA with a retroviral vector to deficient hematopoietic cells, followed by re-injection of the transduced cells with or without selection in the porphyric mouse. Genetically corrected cells were separated by FACS from deficient ones by the absence of fluorescence when illuminated under ultraviolet light. Five months after transplantation, the number of fluorescent erythrocytes decreased from 61% (EPP mice) to 19% for EPP mice engrafted with low fluorescent selected BM cells. Absence of skin photosensitivity was observed in mice with less than 20% of fluorescent RBC. A partial phenotypic correction was found for animals with 20 to 40% of fluorescent RBC. In conclusion, a partial correction of bone marrow cells is sufficient to reverse the porphyric phenotype and restore normal hematopoiesis. This selection system represents a rapid and efficient procedure and an excellent alternative to the use of potentially harmful gene markers in retroviral vectors.

Survival of patients with colorectal carcinoma: possible prognostic value of tissular carbohydrate antigen 19.9 determination.

BACKGROUND: An important goal of serum tumor marker research is to provide a test for detecting cancer in early stages. Expression of carbohydrate antigen (CA) 19.9 has been described in various malignancies. METHODS: The possible prognostic value measuring cytosol CA 19.9 expression in tumors was evaluated in a study of 63 colorectal carcinoma (CRC) patients who were followed for at least 2 years. CA 19.9 expression in cytosol was determined by enzyme-linked immunoadsorbant assay, and measurement of this protein achieved by quantitative assay. RESULTS: Mean levels of cytosol CA 19.9 found in tumor samples were significantly higher than those in nontumoral areas in CRC patients (P<0.0005). Patients with more than 3 positive lymph nodes had a higher expression of the marker (P<0.05). Univariate and multivariate analyses revealed that cytosol CA 19.9 concentration was an independent prognostic variable for relapse. Furthermore, the probability of relapse increased 4.2 times for every increase in cytosol tumor marker of 5000 U/mg, and tumors located in the rectum had a probability of relapse 9.5 times greater. CONCLUSIONS: Cystol CA 19.9 expression in CRC can be an independent prognostic factor for relapse. Patients with high levels of CA 19.9 have worse prognosis than those with lower values. Therefore, this group of patients should receive special management with regard to their follow-up and treatment. Moreover, quantitative cytosol tumor marker measurement is an easy and highly effective method for determining the prognoses of CRC patients.

The photodynamic and non-photodynamic actions of porphyrins

Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture

Porfiria cutanea tarda esclerodermiforme / Porphyria cutane tarda sclerodermoid

La porfiria cutánea tarda (PTC) es un desorden del metabolismo del hemo caracterizado por una masiva pofirinuria e incremento de porfirinas plasmáticas, como consecuencia de una disminución en la actividad de la enzima uroporfirinógeno decarboxilasa. El signo clínico salente es una típica fotosensibilización cutánea. En este trabajo se realiza una revisión de la PCT como entidad clínica, considerando en particular la variante esclerodermiforme(PCTE). Se ha llevado a cabo un estudio bioquimico clínico completop de 16 pacientes argentinos y 3 españoles, entre un total de 102 y 35 PCT respectivamente. En el momento del diagnóstico, los valores de porfirinas urinarias oscilaron entre 400 y 10000 ug/24 h(VN=50-250 ug/24h), con un patron cromatográfico típico: 40-50 por ciento uroporfirinas; (VN= 100 por ciento coproporfirionas) e indice de porfirinas plasmáticas (IPP) entre 1,6 y 5,3 con =618nm (VN<1,3). La aparición de lesiones esclerodermiformes fue más frecuente en el grupo argentino (15,58 por ciento) que en el español (8,57 por ciento) y a su vez más común en hombres que en mujeres. Un 35,7 por ciento de las PCTE argentinas presentaron lesiones de calcinosis en las zonas típicas, pre y retro auriculares, cuero cabelludo cuello y triángulo de escote; en un solo caso calcificación en helix y antihelix del pabellon auricular. En un 80 por ciento se hallo alopecía porfírica cicatricial y en un 72 por ciento placas de esclerosis. En un 35 por ciento de las PCTE argentinas las lesiones esclerodérmicas mejoraron con el tratamiento. En un 25 por ciento de los casos, las lesiones fueron previas a la aparición de los signos clásicos de la PCT en otro 25 por ciento casi concomitantes y en el 50 por ciento a 1 año después. En conclusión, se ha observado una alta incidencia de la PCTE en la población de pacientes argentinos , mucho mayor que en la serie española y qu en las descriptas en la literatura, sin poderse establecer ninguna correlación con los nivelrs de porfirinas plasmáticas o urinarias, ni con el tiempo de evolución de la enfermedad y la aparición de las lesiones esclerodérmicas. Cabe notar que los resultados terapéuticos fueron más satisfactorios que los esperados

[Prevalence of porphyria cutanea tarda in Madrid and relationship between urine porphyrin and ethanol intake in a multiple linear regression model]. / Prevalencia de porfiria cutánea tarda en Madrid y asociación entre la porfirinuria y el consumo de etanol en un modelo de regresión lineal múltiple.

BACKGROUND: The application of a simple fluorometric analytical method enabled us to quantify the urinary porphyrin excretion and to establish the prevalence of porphyria cutanea tarda (PCT) in the town of Madrid, Spain, in a cross-sectional study. PATIENTS AND METHODS: The study assessed 1,613 subjects from three districts in Madrid, in whom further variables potentially related to porphyrinuria such as ethanol intake or -in women-oral contraceptive use were measured and recorded. RESULTS: The estimated prevalence of the disease was 1.24 cases per 1,000 inhabitants (95% confidence interval 0.15-4.47 per thousand). After excluding from the study sample all cases with existent disease, an analysis was performed to ascertain an unilateral tolerance interval for urinary porphyrin concentration in the adult population; this level was established at 181.2 micrograms/l. The effect of ethanol intake on porphyrinuria was considered significant using a multiple linear regression model adjusted for the control variables gender, age and body mass index. In fertile women, contraceptive use did not attain statistical significance when that variable was included in a multiple regression model. CONCLUSIONS: A high prevalence has been estimated for PCT in the Madrid population. A significant association was further found between alcohol intake and porphyrinuria in non-porphyric adults.

Urodecarboxilasa en sangre de pacientes hemodializados / Decarboxylase in blood in hemodialysed patients

En la porfiria cutánea tarda(PCT) hay una falla en la uroporfirinógeno decarboxilasa (Uro-D) hepática, como consecuencia se incrementa la concentración de porfirinas altamente carboxiladas. Enla PCT hereditaria la Uro-D está disminuída en sangre y es normal en la PCT adquirida. Parte de la población hemodializada presenta signos cutáneos que son histológica y morfológicamente semejantes a la PCT, asociado a niveles aumentados de porfirias plasmáticas. Se estudió el contenido de porfirinas plasmáticas y la actividad de la Uro-D eritrocitaria, en 12 pacientes hemodializados sin lesiones cutáneas, uno de ellos portador de PCT hereditaria. El contenido de porfirias en plasma estuvo aumentado(0,084 mas igual 0,,10 ug/ml; uroporfirina igual 80 por ciento, cproporfirina igual 20 por ciento) en 30 por ciento de los pacientes estudiados( valor normal: 0,048 mas igual 0,010 ug/ml; coproporfirina igual 100 por ciento). Las porfirinas plasmáticas del paciente PCT al inicio del tratamiento con S-adenosil-L-metionina fue: 1,71 ug/ml; uroporfirina igual 48 por ciento, firiaporfirina igual 41 por ciento hexaporfirina igual 7 por ciento, pentaporfirina igual 3 por ciento y coproporfirina igual 1 por ciento) y luego de 6 años, al final del tratamiento, los valores fueron: 0,089 ug/ml; uriporfirina igual 80 por ciento, firiaporfirina igual 20 por ciento. La remisión clínica se correlacionó con la bioquímica. En los pacientes hemodializados la actividad de URO_D estuvo dentro de los valores normales(12,45 mas igual 1,o U/ml GR), excepto en el portador de la PCT hereditaria en el cual la actividad estuvodisminuída al 50 por ciento. Estos resultados sugieren que la hemodialisis per se no modificaria a la actividad de URO-D eritrocitaria.

[Adenosine deaminase (ADA) and beta 2-microglobulin (beta 2M) as discriminating serum markers of progression to AIDS]. / Adenosina desaminasa (ADA) y beta 2-microglobulina (beta 2 M) como marcadores séricos discriminantes de progresión al SIDA.

BACKGROUND: To establish the discriminatory value of ADA and beta 2M serum levels as markers of AIDS progression. METHODS: We have followed quarterly during two years a cohort of 24 patients with HIV infection; 103 clinical and laboratory evaluations were done (CDC/93 classification). In each of those blood samples we determined ADA, beta 2M, IgG, IgA, IgM, and CD4+ and CD8+ lymphocytes. RESULTS: 26 evaluations belong to cases that kept stable in the clinic category A or B, CDC/93, ("stables": ADA = 19.05 +/- 10.79 U/L; beta 2M = 2.95 +/- 1.1 mg/L); the remaining 77 evaluations are from patients who clinical progressed to AIDS ("progressors": ADA = 32.03 +/- 13.2 U/L; beta 2M = 4.74 +/- 1.94 mg/L). When we compared statistically (RSIGMA software) the ADA and beta 2M means of both groups (Student t) and the means of all the variables in a block (multivariate analysis: Hotelling T2), very significant differences were appreciated (p < 0.001). CONCLUSIONS: ADA and beta 2M are significantly increased in serum of HIV infected patients who clinical progress to AIDS. ADA and beta 2M can be used as serum markers of AIDS progression with a mistaken classification probability in the discriminatory analysis of 0.25; this probability decreases to 0.06 when immunoglobulins and lymphocytes subpopulations are evaluated too.

Mechanistic studies on uroporphyrin I-induced photoinactivation of some heme-enzymes.

Aerobic and anaerobic studies have demonstrated that uroporphyrin I-induced inactivation of delta-aminolevulinic acid dehydratase, porphobilinogenase, deaminase and uroporphyrinogen decarboxylase was dependent on oxygen and mediated by reactive oxygen species. The mechanism of photoinactivation of those heme-enzymes from human erythrocytes by uroporphyrin I by u.v. light was investigated. Enzymes of the heme pathway were preincubated in the presence of specific scavengers for several reactive oxygen species and then exposed to uroporphyrin I and u.v. light. Upon exposure of the enzymes to the porphyrin under u.v. light, and in an aerobic atmosphere, the percentage of enzyme activities with respect to the corresponding controls were 50.2 +/- 5.1 (SD, n = 6), 25.3 +/- 3.0 (SD, n = 6), 25.9 +/- 2.8 (SD, n = 6) and 49.7 +/- 7.5 (SD, n = 8) for delta-aminolevulinic acid dehydratase, porphobilinogenase, deaminase and uroporphyrinogen decarboxylase, respectively. The presence of sodium azide, histidine or superoxide dismutase did not protect the enzymes against the effects of uroporphyrin I. However, both cysteine and potassium ferrycyanide prevented the enzyme photoinactivation induced by uroporphyrin I. In the presence of either catalase or GSH, the enzyme photoinactivation was lower. Ethanol, glucose and dimethylsulfoxide had no effect on enzyme activity, while ion chelators had variable effects. This study shows that the type II mechanism is not the predominant reaction mediating the uroporphyrin I effect and enzyme photoinactivation would involve an electron transfer. Hydrogen peroxide and hydroxyl radicals could possibly mediate the uroporphyrin I-induced enzyme photoinactivation.

Uroporphyrinogen decarboxylase: complete human gene sequence and molecular study of three families with hepatoerythropoietic porphyria.

A deficiency in uroporphyrinogen decarboxylase (UROD) enzyme activity, the fifth enzyme of the heme biosynthetic pathway, is found in patients with sporadic porphyria cutanea tarda (s-PCT), familial porphyria cutanea tarda (f-PCT), and hepatoerythropoietic porphyria (HEP). Subnormal UROD activity is due to mutations of the UROD gene in both f-PCT and HEP, but no mutations have been found in s-PCT. Genetic analysis has determined that f-PCT is transmitted as an autosomal dominant trait. In contrast, HEP, a severe form of cutaneous porphyria, is transmitted as an autosomal recessive trait. HEP is characterized by a profound deficiency of UROD activity, and the disease is usually manifest in childhood. In this study, a strategy was designed to identify alleles responsible for the HEP phenotype in three unrelated families. Mutations of UROD were identified by direct sequencing of four amplified fragments that contained the entire coding sequence of the UROD gene. Two new missense mutations were observed at the homoallelic state: P62L (proline-to-leucine substitution at codon 62) in a Portuguese family and Y311C (tyrosine-to-cysteine substitution at codon 311) in an Italian family. A third mutation, G281E, was observed in a Spanish family. This mutation has been previously described in three families from Spain and one from Tunisia. In the Spanish family described in this report, a paternal uncle of the proband developed clinically overt PCT as an adult and proved to be heterozygous for the G281E mutation. Mutant cDNAs corresponding to the P62L and Y311C changes detected in these families were created by site-directed mutagenesis. Recombinant proteins proved to have subnormal enzyme activity, and the Y311C mutant was thermolabile.

[Role of hepatitis C virus in porphyria cutanea tarda hepatopathy]. / Papel del virus de la hepatitis C en la hepatopatía de la porfiria cutánea tarda.

BACKGROUND: Porphyria cutanea tarda has been classically considered as an acquired disorder due to the exerted influence of several factors (such as viral infections) on its fenotipic expression. The aim of the present study has been focussed on the prevalence analysis and the hepatotoxic role of the hepatitis C virus (HCV). PATIENTS AND METHODS: By means of a second generation ELISA test, serum antibodies against hepatitis C virus was studied in 132 patients with porphyria cutanea tarda. The polymerase chain reaction (PCR) was assayed in 55 cases to detect serum viral RNA. A liver biopsy was performed in 93 cases. RESULTS: The 64.4% of the studied patients were seropositive and PCR for HCV was positive in the 83% out of the 55 studied cases. The group of 19 patients suffering from familial porphyria cutanea tarda showed a similar prevalence to the group of 113 patients with sporadic porphyria (47.3% vs 67.2%). In 82% out of the total cases, risk factors for HCV infection were not found. In seropositive cases, both transaminases were more frequently altered than in seronegative ones. The univariant study was not able to demonstrate the relationship between seropositivity, and transaminases, urinary porphyrins alcohol consumption, frequency of antibodies against hepatitis B virus, relevance of the histological hepatic damage or incidence of porphyria relapses. Nevertheless, a multivariant analysis on 93 patients with liver biopsy showed that the risk to suffer from severe liver disease increases 2.8 times in seropositive patients, 3.13 times in those presenting high levels of serum ferritin and 9.25 times in patients up to 65 years old. CONCLUSIONS: The frequent hepatitis C virus infection in patients with porphyria cutanea tarda must be considered as a precipitating factor for the disease and as an aggravating factor of its associated liver damage.

Low-dose oral chloroquine in patients with porphyria cutanea tarda and low-moderate iron overload.

OBJECTIVE: to assess the efficacy, tolerance and determinants for relapse in patients with porphyria cutanea tarda treated with low-dose oral chloroquine. DESIGN: open trial with a median follow-up of 3 years. SETTING: outpatient referral unit of a university hospital. PATIENTS: 53 patients with low-moderate iron overload or intolerance to phlebotomies. INTERVENTION: 250 mg twice weekly oral chloroquine diphosphate until remission or failure to respond. MEASUREMENTS: porphyrin excretion, biochemical changes and development of side effects. RESULTS: after administration of a median dose of 23.5 g of chloroquine (limits 12.6-56 g) during a median time of 8 months (limits: 1-26 months), 50 patients (94%) reached a metabolic remission (urinary uroporphyrin excretion < 100 micrograms/l). In 14 of these patients (28%), porphyrin excretion further decreased after finishing chloroquine therapy. Metabolic remission persisted during 24 months (limits 6-97 months). Side-effects (severe pruritus) appeared only in one patient. Twenty-two patients relapsed, the relapses being associated with greater basal values of serum AST, ALT, gammaglobulin, urinary uroporphyrin and to the time needed to achieve remission. One year and three years after finishing therapy the probabilities of relapse were 12% (95% C.I.: 5-27%) and 49% (95% C.I.: 34-67%), respectively. Time to achieve remission was the only independent predictor of relapse (hazard ratio: 1.2, 95% C.I.: 1.05-1.21, P < 0.01). CONCLUSION: low-dose oral chloroquine is a safe therapy that promotes a high proportion of remission and sustained control of porphyria cutanea tarda associated with low-moderate iron overload.

[The usefulness and limitations of adenosine deaminase in the diagnosis of tubercular pleurisy. A meta-analytical study]. / Utilidad y limitaciones de la adenosina desaminasa en el diagnóstico de la pleuresía tuberculosa. Estudio metaanalítico.

To assess the yield of adenosine deaminase (ADA) measurement in the diagnosis of tuberculous pleuritis and to afford parameters applicable to different populations and risk groups, a meta-analysis was performed in this study. National and anglo-saxon studies included in the Index Medicus from 1980 to march of 1990 were reviewed. The estimated incidence of tuberculous pleuritis in our medium was about 0.18 (confidence intervals for 95%-95% CI: 15-0.21). The diagnostic yield of ADA was as follows: sensitivity of 0.99 (95% CI: 0.98-0.99) and specificity of 0.93 (95% CI: 0.91-0.94). The quotients of probability (parameters that measure the predictive values of the tests at any given prevalence) were 14.31 and 0.004 for the positive and negative tests, respectively. In or medium the positive and negative predictive values were 0.74 (95% CI: 0.68-0.81) and 0.99 (95% CI: 0.98-0.99), respectively. An ADA value below the discriminative level nearly rules out the existence of tuberculous pleuritis, whereas at the contrary, and ADA value above the discriminative point offers a limited information about the etiology of the pleural effusion.

[Adenosine deaminase in pleural effusions. Its usefulness in the diagnosis of tuberculous pleurisy]. / Adenosina desaminasa (ADA) en los derrames pleurales. Su utilidad en el diagnóstico de la pleuresia tuberculosa.

The activity of adenosine deaminase was determined in 79 pleural effusions in order to evaluate the utility and reliability in diagnosing tuberculous effusions. The effusions were grouped by the etiology: 26 were tuberculous (group I); 22 were neoplastic (group II); 11 were pneumonic (group III); 10 were non-infections exudates of different causes (group IV); and 10 transudates (group V). Group I presented the higher median value of AD (MED = 81.92; DE: 29.02) the difference being statistically significant (p less than 0.0001) compared with the results of the other groups. We found 2 cases of pleural tuberculosis histologically demonstrated with AD levels under the amount of 40 U/L. In our experience, AD determination had a sensitivity of 92% and specificity of 94%; with a predictive value of 89% and a negative predictive value of 96%, this being considered useful but non specific of tuberculosis.

Porphyria cutanea tarda and hepatocellular carcinoma. Frequency of occurrence and related factors.

In order to assess the incidence of hepatocellular carcinoma (HCC) in porphyria cutanea tarda (PCT), 83 patients (77 males, 6 females, mean age 57.4 years) were studied. Thirteen patients (15.7%) had HCC, all of whom were male and cirrhotics with a mean age of 58.5 years. HCC patients showed a statistically significant (P less than 0.0005) longer evolution time (23 years since onset of the cutaneous disease) than patients without HCC (9.4 years), while the age of onset was similar in both groups. Differences in alcohol intake and hepatitis B virus (HBV) markers were non-significant, although high prevalence (54%) of past HBV infection was found in both groups. In HCC development, attributable risks of 100% were found for cirrhosis (P less than 0.001), male sex (P = NS) and for age over 51 (P less than 0.025). Therefore, PCT harbours a high incidence of HCC; evolution time, cirrhosis and age over 51 appear to be the most important contributing factors.