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J C Deybach

Publications and source records attributed to J C Deybach.

At least 91 records · Page 5Linked to original sources
PubMed1989

A point mutation G----A in exon 12 of the porphobilinogen deaminase gene results in exon skipping and is responsible for acute intermittent porphyria.

We have determined the mutation in a patient with acute intermittent porphyria. The mRNA coding for porphobilinogen deaminase was reverse transcribed then the cDNA was enzymatically amplified in vitro. Upon sequencing of a polymerase chain reaction product of abnormal size we found that this fragment lacked exon 12 of the gene. We analysed a genomic fragment containing exon 12 and determined that the patient was heterozygous for a point mutation G A at the last position of exon 12. We propose that this base change is responsible for an abnormal processing of the mutant allele such that exon 12 is missing in the mature mRNA. The resulting aberrant mRNA encodes a truncated protein which is inactive but stable and can be detected using antibodies directed against the normal enzyme.

Acute Disease↗
PubMed1989

[Anesthesia and hepatic porphyria].

Three of the acute hepatic porphyrias, acute intermittent porphyria, variegata porphyria and hereditary coproporphyria, are characterized by an idiosyncratic reaction to many common drugs; the resulting excessive excretion of porphyrin precursors is responsible for episodes of acute neurological dysfunction. This review aimed to focus the attention of the anaesthesiologist on the porphyrinogenic properties of all the drugs used in anaesthesia and intensive care. An outline of the chemistry of porphyrins and the enzymatic pathways were recalled, so as to place the acute porphyrias in their proper perspective. There follows a reminder of the clinical aspect of acute porphyric crises. The part played by drugs is then assessed from clinical and laboratory data concerning their porphyrinogenicity. Those drugs for which there is conflicting evidence regarding their safe use in porphyric patients are discussed: propofol, ketamine, benzodiazepines, etomidate, local anaesthetics. Recommendations supported by clinical and experimental data are given, especially the results obtained with the chick embryo liver model. Treatment of the acute crisis is provided, with particular emphasis on the use of haematin. The anaesthetic management of hepatic porphyric patients is described. Those drugs which are well-known porphyrinogenic compounds in the chick embryo liver must be excluded from use for anaesthesia in the porphyric patients, even if they have been observed to be innocuous in rare cases of asymptomatic patients. Finally, recommendations for anaesthesia in symptomatic cutanea porphyria are given.

Alcuronium↗
PubMed1988

Radiological features in congenital erythropoietic porphyria (Gunther's disease). Report of 3 cases.

Gunther's disease or congenital erythropoietic porphyria is a rare and severe disorder comprising cutaneous and haemolytic symptoms. Photocutaneous lesions are responsible for scleroderma-like calcifications and deformities of the extremities visible on X-rays. Hemolytic manifestations lead to diffuse major osteopenia. Soft tissue calcifications of the fingers can be seen even in young patients. One case reported here is the first illustration of intracranial calcifications located on dura-mater and calvarium.

Bone Diseases, Metabolic↗
PubMed1987

[Drug risk of hepatic porphyria. Development of an animal experiment model].

Hepatic porphyrias (acute intermittent porphyria, coproporphyria, porphyria variegata and porphyria cutanea) are inherited diseases affecting porphyrin-heme metabolism in the liver. A situation analogous to the latent stage of human hepatic porphyria can be produced in chick embryos by injecting an inhibitor of ferrochelatase (the last enzyme in the heme biosynthesis pathway); the simultaneous injection of a porphyrinogenic drug (e.g. barbiturate) results in a strong increase of liver porphyrin levels, as is found in human hepatic porphyrias. This experimental model facilitates drug screening: drugs that are found to be porphyrinogenic in ovo are potentially dangerous to patients with hepatic porphyria and should be avoided.

Animals↗
PubMed1986

[Acute attacks of hepatic porphyria. Treatment with hematin. 5 cases].

The effectiveness of 2 hematins administered by intravenous infusion was compared in acute intermittent porphyria. Judging from subjective symptoms (abdominal pain), clinical improvement was complete and constant. There was a rapid decrease in urinary excretion of porphyrins precursors, with a clearer response of delta-aminolevulinic acid than of porphobilinogen. Urine levels of uroporphyrin often returned to normal after two infusions. The drugs were very well tolerated. Provided it is administered early, before neurological complications develop, treatment with hematin completely relieves abdominal symptoms and suppresses most of the biochemical changes associated with hepatic porphyria.

Acute Disease↗
PubMed1986

[Peridural anesthesia with procaine and fentanyl in a parturient with acute intermittent porphyria].

Acute intermittent porphyria is one of three severe hepatic porphyrias. Clinical manifestations include intermittent acute attacks of abdominal pain and neuropathy with an occasionally outcome. These attacks are often precipitated by endogenous (menstrual cycle and pregnancy in women) or exogenous factors (porphyrinogenic drugs). An epidural analgesia was performed during the labour of a pregnant woman with acute intermittent porphyria just after an acute attack of abdominal pain. Analgesia was obtained using procaine and fentanyl. The choice of drugs was based on available clinical reports and experimental studies of the porphyrinogenicity of drugs in animal models (rat in vivo and chick embryo in ovo).

Acute Disease↗
PubMed1985

The mitochondrial location of protoporphyrinogen oxidase.

Using the digitonin method and subsequent fractionation of rat liver mitochondria, protoporphyrinogen oxidase (penultimate enzyme in the heme biosynthesis pathway) was found to be closely associated with the mitochondrial inner membrane fraction. Chemical treatment with non-specific probes (trypsin and diazobenzene sulfonate) of either intact or inverted mitoplasts, indicated that protoporphyrinogen oxidase was anchored within the lipid bilayer of the inner membrane. Protoporphyrinogen had an equal access to the active site of the enzyme from both sides of the inner membrane and its transformation to protoporphyrin did not appear to be energy-dependent. Studies of protoporphyrinogen synthesis from exogenously added coproporphyrinogen in either intact or hypoosmotically treated mitochondria underlined the importance of the peculiar submitochondrial location of coproporphyrinogen oxidase and protoporphyrinogen oxidase for the transfer of substrates to the inner membrane.

Animals↗
PubMed1985

Renal disposition of gentamicin, dibekacin, tobramycin, netilmicin, and amikacin in humans.

The tubular disposition of five aminoglycosides was studied in humans to establish a possible relationship between tubular reabsorption and the nephrotoxicity that has been described in the literature. Thirty-three healthy male volunteers received a continuous intravenous infusion of isotonic saline with inulin, followed 1 h later by inulin plus gentamicin, dibekacin, tobramycin, netilmicin, or amikacin (1 mg/kg per h) or amikacin (4 mg/kg per h) over a period of 2 h. Brain-stem-evoked response audiometry was performed both before and at the end of each infusion. The latency of wave V remained constant whichever antibiotic was considered. The glomerular filtration rate did not vary significantly during the infusion of each drug. The percent fractional excretion was 79 +/- 6, 81 +/- 22, 85 +/- 5, and 99 +/- 9 for gentamicin, dibekacin, tobramycin, and netilmicin, respectively, and 83 +/- 4 and 124 +/- 13 for amikacin at concentrations of 1 and 4 mg/kg per h, respectively. Net balance and renal clearance were similar for the five aminoglycosides when administered at a rate of 1 mg/kg per h. With gentamicin only, fractional excretion was correlated with the urinary flow rate. We can conclude that (i) gentamicin, generally considered the most nephrotoxic agent, had the highest degree of net reabsorption; (ii) netilmicin exhibited a net zero tubular balance; (iii) amikacin had different patterns of tubular disposition according to the dose, i.e., reabsorption at 1 mg/kg per h and secretion at 4 mg/kg per h, raising the hypothesis of a saturable process of reabsorption; and (iv) these differences in tubular reabsorption could account at least in part for the known different nephrotoxic potentials of these five aminoglycosides in humans.

Adult↗
PubMed1984

Effects of succinylacetone on dimethylsulfoxide-mediated induction of heme pathway enzymes in mouse friend virus-transformed erythroleukemia cells.

Heme has been reported to exert a control over its own biosynthesis and to affect the erythroid differentiation process at different sites. In this study, succinylacetone, a powerful inhibitor of delta-aminolevulinic acid dehydrase was used to block heme synthesis and to study the effects of heme depletion on the dimethylsulfoxide (DMSO)-mediated induction of the heme pathway enzymes in Friend virus-transformed erythroleukemia cells. The presence of succinylacetone in the medium during the DMSO treatment (1) potentiates the induction of delta-aminolevulinic acid synthetase (the first enzyme of the pathway) and this effect is reversed by the addition of exogenous hemin; (2) does not affect the induction of delta-aminolevulinic acid dehydrase (the second enzyme); (3) prevents the induction of porphobilinogen deaminase (the third enzyme), since no increase could be detected in either the enzyme activity or the immunoreactive protein and this effect could not be reversed by the addition of exogenous hemin; (4) does not affect the induction of ferrochelatase. The possible role of heme or of intermediate metabolites of the pathway on the induction of these enzymes during the erythroid differentiation process is discussed.

5-Aminolevulinate Synthetase↗
PubMed1984

Enzymatic and immunological studies of uroporphyrinogen decarboxylase in familial porphyria cutanea tarda and hepatoerythropoietic porphyria.

Uroporphyrinogen decarboxylase activity was measured in hemoglobin-free lysates from two patients with hepatoerythropoietic porphyria (HEP) and from 12 unrelated patients with familial porphyria cutanea tarda (PCT). In HEP patients, enzyme activities were 5% of normal, and familial studies clearly confirmed that patients with HEP are cases of homozygous PCT. Immunoreactive uroporphyrinogen decarboxylase was measured by developing a direct and noncompetitive enzyme immunoassay (EIA). For the 12 familial PCT patients, we found an immunoreactive protein decreased (51%) to the same extent as the catalytic activity (48%) [cross-reactive immunological material ( CRIM ) negative]. The children from the HEP family were also CRIM negative, contrasting with another HEP family previously described as CRIM positive; our data support the hypothesis of a heterogeneity in familial uroporphyrinogen decarboxylase deficiency.

Carboxy-Lyases↗
PubMed1983

Study of anaesthetic agents for their ability to elicit porphyrin biosynthesis in chick embryo liver.

Effects of some anaesthetic drugs on the activity of delta-aminolevulinate synthetase and on the formation of porphyrins and cytochrome P-450 were studied in 18-day-old chick embryo livers in ovo. The drugs were either tested alone or with a small dose of 1,4-dihydro-3,5-dicarbethoxycollidine, which reproduces in the embryo liver a partial block in the heme biosynthesis pathway similar to that found in cells of human patients with porphyrias. Two series of local anaesthetics were tested: procaine and its derivatives (proxymetacaine, oxybuprocaine, butacaine and tetracaine) had no (or very slight) porphyrogenic effects. In contrast, lidocaine and its derivatives (bupivacaine, mepivacaine, etidocaine, pyrrocaine and prilocaine) were found to induce delta-aminolevulinate synthetase and to cause accumulation of porphyrins and cytochrome P-450. Some other drugs used in anaesthesiology were tested: fentanyl, morphine, sodium oxybate, pancuronium, pethidine and phenoperidine were found to be non-porphyrogenic; alcuronium was a slight inducer. It is suggested that the inducing drugs should be avoided in patients with hepatic porphyrias.

Anesthetics↗