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Biomedical subjects

M O Doss

Publications and source records attributed to M O Doss.

At least 55 records · Page 3Linked to original sources
PubMed1995

Low prevalence of hepatitis C virus infection in porphyria cutanea tarda in Germany.

Previous studies from Spain, Italy, and France have demonstrated a high prevalence (71% to 91%) of antibodies against hepatitis C virus in patients with porphyria cutanea tarda (PCT). To determine the role of hepatitis C virus (HCV) in PCT in Germany, we have assessed the prevalence of antibodies against HCV and hepatitis B virus (HBV) in 106 patients (mean age, 60 +/- 14 years) with the disease. Eight of 106 patients (8%) were positive for HCV antibodies and HCV RNA using second-generation enzyme-linked immunosorbent assay (ELISA), recombinant immunoblot assay, and polymerase chain reaction. Antibodies against HBV core antigen were found in 14 patients (13%). Of the patients with antibodies against HCV alanine transaminase (ALT) (aspartate transaminase [AST]) levels above normal occurred in 71% (86%). Because elevated ALT (AST) levels were also found in 51% (64%) of 88 patients without markers of HCV or HBV, we suggest that liver damage in PCT may exist in absence of these viruses. This is supported by the finding that in patients without HCV or HBV markers, higher serum ALT and AST activities were found in patients with overt disease or relapse (ALT, 59 +/- 44 U/L; AST, 37 +/- 21 U/L), whereas patients in remission displayed significantly lower serum enzyme activities (ALT, 16 +/- 8 U/L; AST, 16 +/- 7 U/L), (P < .001). These results indicate that HCV infection does not play a major role in the pathogenesis of PCT in Germany.

Aged↗
PubMed1995

Hormonal oral contraceptives, urinary porphyrin excretion and porphyrias.

The influence of hormonal oral contraceptives on the urinary porphyrin excretion of 40 healthy females has been studied. Two different hormonal oral contraceptives (combinations of gestoden or desogestrel, respectively, and ethinylestradiol) were applied for half a year. In each case twenty women received one of these two combinations. Porphyrin precursors delta-aminolevulinic acid and porphobilinogen were normal in all subjects as well as the mean of uroporphyrin and coproporphyrin. One healthy female developed a mild secondary coproporphyrinuria. In this case coproporphyrin isomer I was slightly enhanced and isomer III slightly lowered. Furthermore it could be shown that three females with repeated premenstrual clinical expression of an acute hepatic porphyria (acute intermittent porphyria and hereditary coproporphyria) could be treated successfully with a hormonal oral contraceptive or other exogenous hormones to stabilize the latent, subclinical phase of the disease.

Adult↗
PubMed1995

Treatment of porphyria cutanea tarda by the effect of chloroquine on the liver.

Porphyria cutanea tarda (PCT) is characterized by cutaneous symptoms in association with hepatic accumulation and urinary excretion of mainly uro- and heptacarboxyporphyrins. 24 PCT patients excreting urinary porphyrins between 1.9 and 5.8 mumol/24 h (normal < 0.2) were treated with chloroquine at a dose of 125 mg twice a week. During the first phase of therapy urinary porphyrin excretion transiently increased 1.1- to 2.9-fold indicating a phase of mobilization. A slight initial elevation was also found regarding the activities of serum aminotransferases reflecting the hepatotoxic effect of chloroquine. The clinical symptoms disappeared after a period ranging from 2 to 6 months, and after an average of 12 months the porphyrin excretion in all patients had returned to nearly normal values.

Adult↗
PubMed1995

Excretion pattern of faecal coproporphyrin isomers I-IV in human porphyrias.

The relative proportions of the four coproporphyrin isomers I-IV were analysed in faeces of 20 healthy subjects and 60 patients suffering from one of the seven common types of hepatic or erythropoietic hereditary porphyrias. A newly developed, reliable method for sample preparation was applied, using reversed-phase thin layer chromatography for the isolation of naturally occurring coproporphyrin free carboxylic acids. Accurate separation and quantitation of the individual isomers I-IV were achieved with the help of ion-pair high-performance liquid chromatography. The four coproporphyrin isomers I-IV were positively identified by on-line scanning of their fluorescence spectra in the emission and excitation modes. Recovery rates with this new analytical procedure were between 90 and 100%, and coefficients of variation varied between 0.8 and 5.7% (N = 7). Diagnostically important findings were greatly increased proportions of isomer I and decreased proportions of isomers III, II and IV in erythropoietic porphyrias, such as congenital erythropoietic porphyria and protoporphyria. Significantly increased proportions of isomers III, II and IV, on the other hand, were observed in acute hepatic porphyrias, e.g. acute intermittent porphyria and porphobilinogen synthase deficiency porphyria, as compared with porphyria cutanea tarda (p < 0.005 and p < 0.03, respectively). Inversion of the faecal coproporphyrin III to I ratios and markedly elevated percentages of the atypical isomers II and IV were important diagnostic markers for variegate porphyria and hereditary coproporphyria. The highest proportions of isomer III were found in hereditary coproporphyria, where the amount of the isomers II and IV exceeded that of isomer I. Asymptomatic carriers of the relevant gene defect in families with hereditary coproporphyria could be detected by an increased faecal coproporphyrin III to I ratio. Our results clearly demonstrate the potential of faecal coproporphyrin I-IV isomer ratios for the diagnosis and differential diagnosis of hereditary porphyrias.

Adult↗
PubMed1995

Dual porphyria of coexisting variegata and cutanea tarda.

While porphyria cutanea tarda and porphyria variegata are independent diseases, we report on seven rare cases with a coincidence of these two different porphyrias in one individuum. The mutual clinical symptom was a cutaneous photosensitivity, which is a major symptom in porphyria cutanea tarda and a facultative one in porphyria variegata. Additionally, five patients had also experienced episodes of acute abdominal pain, which were in three cases accompanied by neurological symptoms, thus offering evidence for an acute hepatic porphyria, such as porphyria variegata. Determination of urinary porphyrin metabolites revealed a porphyria cutanea tarda-like excretion pattern with an elevation of uroporphyrin (mean 1134 nmol/24 h, range 563-4052, normal < or = 30) and heptacarboxyporphyrin (mean 389 nmol/24 h, range 64-830, normal < or = 4). In all patients, however, urinary coproporphyrin was also increased, reaching levels too high for porphyria cutanea tarda but typical for porphyria variegata (mean 1788 nmol/24 h, range 142-4168, normal < or = 120). Fecal porphyrin excretion also resembled the variegate-type with a high concentration especially of protoporphyrin (mean 628 nmol/g dry weight, range 401-1018, normal < or = 151), accompanied by an increase of coproporphyrin (mean 194 nmol/g dry weight, range 75-409, normal < or = 37). The urinary porphyrin precursors 5-aminolaevulinic acid and porphobilinogen were markedly elevated only in one patient, who was in an acute porphyric phase at the time of investigation. The activity of uroporphyrinogen decarboxylase in erythrocytes was considerably decreased in six of our cases (33-64%) and slightly diminished in the other one (83% of normal activity).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Liver cirrhosis in protoporphyria: bile acid therapy and liver transplantation].

Protoporphyria is an important differential diagnosis in patients with jaundice and cutaneous photosensitivity. In 1975 erythropoietic protoporphyria and liver damage of unknown origin were diagnosed in a 24 year old patient with photosensibility since early childhood. Laparoscopic liver biopsy confirmed protoporphyrin-associated liver cirrhosis in 1983. Therapy with ursodeoxycholic acid was initiated and liver function was stable during an 18 month period. In december 1989 the patient developed severe intrahepatic cholestasis with rapid deterioration of liver function. Liver transplantation was performed in 1990. The patient is now five years after transplantation in an excellent clinical condition. This 20 year observation period gives insight in the pathogenesis of protoporphyrin-induced hepatobiliary complications in a latent and overt phase. The relevant diagnostic and prognostic porphyrin parameters and therapy of protoporphyric liver disease are discussed.

Adult↗
PubMed1993

[Anesthesia with propofol during an exacerbated course of acute intermittent porphyria].

In the eighth week of pregnancy the medical indication for induced abortion was established due to an exacerbating acute intermittent porphyria with life-threatening neurological symptoms. delta-aminolaevulinic acid and porphobilinogen were excessively increased in urine prior to the operation. Anaesthesia was induced with a bolus of propofol, alfentanil and droperidol, maintained by 67% of nitrous oxide and small bolus injections of the three drugs. The patient regained consciousness immediately after the operation, and reached full orientation and cooperativeness within five minutes. The postoperative period remained uneventful and the neurological and psychological symptoms returned to the pre-exacerbation status. Chorion gonadotropins and porphyria markers decreased within the next four weeks accompanied by a simultaneously progressing clinical improvement. The use of propofol and the other drugs appears justified even in exacerbated porphyria.

Abortion, Therapeutic↗
PubMed1993

Composition of urinary coproporphyrin isomers I-IV in human porphyrias.

The urinary distribution and relative proportions of the four coproporphyrin isomers I-IV were investigated in 50 patients suffering from hepatic and erythropoietic types of hereditary porphyrias. A highly efficient sample preparation method was applied to isolate urinary coproporphyrins, the isomer ratios of which were quantitated by isocratic ion-pair high-performance liquid chromatography. Results showed a significant decrease (p < 0.001) of the proportion of coproporphyrin I in acute hepatic porphyria (acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, porphobilinogen synthase deficiency porphyria) as compared with chronic hepatic porphyria (porphyria cutanea tarda, chronic hepatic porphyria type B and C) (13.2 +/- 5.3%, mean +/- S.D., vs. 31.4 +/- 11.5%). Conversely, the proportion of isomer III was significantly higher (p < 0.001) in acute hepatic porphyria than in chronic hepatic porphyria (80.9 +/- 5.2% vs. 62.2 +/- 10.9%). As expected, the highest level of coproporphyrin I (90.0 +/- 1.9%) was found in congenital erythropoietic porphyria. The atypical coproporphyrins II and IV were detected in all types of porphyria analysed and ranged from 0.2 to 9.0%; no significant differences were seen between acute and chronic hepatic porphyrias. The diagnostic importance of the isomer ratios of coproporphyrins I and III has been confirmed in our study, while the significance of the atypical coproporphyrin isomers II and IV is still unclear at present.

Adult↗
PubMed1993

[Diagnostic porphyrinopathies in hereditary hyperbilirubinemia].

Secondary porphyrinopathias were investigated in hereditary hyperbilirubinemias of the types Dubin-Johnson syndrome (DJS), Rotor's syndrome (RS), Gilbert's syndrome (GS) and compared with the findings in alcohol-induced cholestasis. The determination of urinary coproporphyrin excretion including its isomer I and III relation allows to diagnose and differentiate DJS from the other two forms of hereditary hyperbilirubinemias. An isomer I proportion of > 80% (normal < 32%) in association with a normal coproporphyrin excretion is pathognomonic for DJS. An increased coproporphyrinuria with about 70% isomer I is found in RS; a normal urinary coproporphyrin excretion combined with an isomer I increase of about 50-70% indicates the frequent GS. Alcohol-related cholestasis reveals a distinct pathologic coproporphyrinuria and elevated isomer I proportions between 37-67%. Due to the overlapping of isomer alterations in DJS-gene carriers, patients with GS and patients with exogenous toxically-induced cholestasis, additional diagnostic criteria are required to clarify the porphyrinopathia in its clinical context.

Adolescent↗
PubMed1993

[Porphyrin-induced biliary cirrhosis in protoporphyria: indications for liver transplantation].

A 51-year-old patient, who had experienced photosensitivity from childhood on, fell ill with an icterus accompanied by abdominal complaints. At the age of 46 years an erythropoietic protoprophyria had been diagnosed by an excessive protoporphyrinemia. Meanwhile, in consequence of the protoporphyria's erythrohepatic progression, a biliary liver cirrhosis developed, associated with portal hypertension and marked splenomegalie. As a remission of the protoporphyria-induced hepatobiliary complication could not be achieved by conservative medical treatment, the indication for orthotopic liver transplantation was established. The operation proceeded without complications, and the postoperative course, too, revealed no problems. With primarily good bile production, bilirubin and aminotransferases soon declined to normal values. Urinary coproporphyrin excretion was found to be normal after transplantation, only a domination of isomer I still peristed. Furthermore, a distinct elevation of protoprophyrin continued to exist both in erythrocytes and plasma as expression of the immanent enzyme deficiency typical for the genodermatosis protoporphyria. In the liver explant a micronodular transformation of parenchyma was found besides a deposition of reddish-brown protoporphyrin pigment in hepatocellular cytoplasma and Kupffer's cells, in addition to pigment casts in the canaliculi and within single portal bile ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1993

[Cholestatic erythrohepatic protoporphyria: porphyrin metabolism before and after liver transplantation].

The ferrochelatase deficiency in protoporphyria leads to accumulation of protoporphyrin in erythrocytes and liver. Consequences are protoporphyrinemia with photosensitivity and liver damage (fibrosis, cirrhosis) with cholestasis. The latter are unpredictable and can be observed in about 10% of the patients. Protoporphyrin, the physiological main component of hepatocellular porphyrins, has a hepatotoxic effect in the high-concentrated crystalline storage form. The obligatory hepatobiliary excretion of the lipophil, erythropoietic increased accumulating protoporphyrin in protoporphyria strains the excretory function of the liver. Its restriction is followed by an exzessive protoporphyrin accumulation, which leads to protoporphyrin-induced, progressive cholestatic cirrhosis, icterus, and aggravation of the extrahepatic protoporphyrinemic cutaneous manifestation. In case of hepatobiliary complications a coproporphyria of diagnostic relevance develops with inversion of isomers. Simultaneously, the fecal protoporphyrin excretion decreases. After liver transplantation hyperbilirubinemia, protoporphyrinemia and coproporphyrinuria significantly went down. A protoporphyrinemia of about 20% of preoperative values reflects the persisting hereditary enzyme defect and the continuity of the metabolic disease.

Adult↗
PubMed1993

[Cimetidine in treatment of acute intermittent porphyria].

Two female patients with repeated exacerbations of acute intermittent porphyria (20 exacerbations in 44 and 5 in 34 months, respectively) were treated with cimetidine (2 x 400 mg/d) over 4 months. Therapeutical aim of the medication was to prevent further porphyria manifestations. In contrast to previous casuistic reports and experimental studies in laboratory animals cimetidine did not stabilize porphyrin biosynthesis. One patient had an acute attack during the period of treatment, while the other had no further exacerbations. However, cimetidine did not worsen the clinical course of our patients either and therefore can safely be applied as an H2-antagonist in patients with acute intermittent porphyria. While administration of glucose and heme-preparations is considered to be an effective form of therapy for the acute episodes, long-lasting as well as prophylactic therapies in order to stabilize the period of remission are not known so far.

Administration, Oral↗
PubMed1992

[Liver transplantation in erythrohepatic protoporphyria].

A 51-year-old man had for 5 years been known to have erythropoietic protoporphyria. GPT levels were raised up to 40 U/l, gamma-GT up to 120 U/l. After lengthy exposure to sun radiation an erythema with blisters, abdominal discomfort and jaundice developed (total bilirubin 7.3 mg/dl) and biliary liver cirrhosis with portal hypertension and splenomegaly were diagnosed. Because the acute hepatobiliary complications were not improved by conservative treatment (daily 750 mg ursodeoxycholic acid and 12 g colestyramine), an orthotopic liver transplantation was performed without complication. The excised liver showed small nodular parenchymal transformation and contained reddish brown protoporphyrin pigment in the hepatocellular cytoplasm, the Kupffer cells, the canaliculi and in some biliary ducts. Bilirubin and transaminase levels in blood became normal after the transplantation, as did the urinary excretion of coproporphyrin. However, isomer I was still dominant. The protoporphyrin level in erythrocytes and plasma remained elevated. After a symptom-free interval of one year biochemical and histological tests demonstrated protoporphyrin-induced damage in the transplanted liver.

Cholestyramine Resin↗
PubMed1991

Effect of alcohol on delta-aminolevulinic acid dehydratase and porphyrin metabolism in man.

The influence of alcohol on porphyrin metabolism was investigated in 6 healthy non-alcoholics and 19 patients with chronic alcohol abuse. In the healthy subjects, blood and urine samples were obtained before and after acute alcohol exposure, whereas in the chronic alcoholics only one examination was performed. In both groups a significant inhibition of delta-aminolevulinic acid dehydratase was demonstrated. The activity was partially restored in vitro by addition of zinc ions or dithiothreitol. A combination of both activators produced reactivation to normal levels. Coproporphyrinuria was more prominent in chronic alcoholics (373 nmol/24 h on average, upper norm 119 nmol/24 h) compared to non-alcoholics (140 nmol/24 h). Urinary porphobilinogen and delta-amino-levulinic acid were normal except for a moderately increased delta-aminolevulinic acid in four healthy individuals. In conclusion, alcohol causes reversible inhibition of delta-aminolevulinic acid dehydratase. The metabolic changes reflect both an inhibition of delta-aminolevulinic acid dehydratase and coproporphyrinogen oxidase; a simultaneous, moderate induction of hepatic delta-aminolevulinic acid synthase is suggested. Erythrocyte delta-aminolevulinic acid dehydratase activity could serve as a sensitive indicator for both acute and chronic alcohol consumption even better than coproporphyrinuria.

Adult↗