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J M Richard

Publications and source records attributed to J M Richard.

At least 19 recordsLinked to original sources
PubMed2001

[Cortinarius poisoning. Analysis of cases in the literature].

UNLABELLED: Cortinarius spp. poisoning is characterized by a delayed acute renal failure (ARF). The main features of this severe poisoning are still poorly known and often overlooked. The aim of this review of the literature was a better description of Cortinarius spp. poisoning. METHODS: The main medical databases were searched and analysed. RESULTS: 245 cases were collected and 90 cases could be analysed in details. Gastrointestinal disorders appeared a few days after the ingestion of the mushrooms (median: three days). The renal phase is delayed (median: 8.5 days). Hepatic failure and muscular lesions are highly questionable. Treatment is supportive in half of the cases, ARF progressed towards chronic renal failure, which progressed in 70% of the cases towards terminal renal failure. CONCLUSION: Cortinarius spp. poisoning is severe. Ingestion of Cortinarius species must be systematically suspected whenever tubulo-interstitial nephritis is diagnosed.

Acute Kidney Injury↗
PubMed2000

DNA strand scission by the nephrotoxin [2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide and related compounds in the presence of iron.

The capacity of non-illuminated nephrotoxin orellanine ([2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide) to induce DNA damage in the presence of ferrous iron and dioxygen has been evaluated. Maximal single-strand breaks in plasmid DNA were obtained with a metal to ligand ratio 1:3. Instantaneous oxidation of Fe2+ in presence of orellanine under air was responsible for oxy-radical production concomitant to a stable ferric complex Fe(III)Or3 formation, leading to oxidative DNA breakage at physiological pH. DNA damage was lowered in the presence of SOD and catalase or DMSO, indicating a set of reactions that leads to oxy-radical generation. Iron chelators such as DTPA and EDTA had no protecting effect, Desferal slightly protected. GSH acted as an oxy-radical scavenger, whereas cysteine induced stronger damage. Closely related bipyridine compounds were also studied in presence of Fe2+ and O2 using a combination of spin-trapping and DNA-nicking experiments, none of which were able to chelate iron and induce damage at pH 7. Both catecholic moieties and aminoxide groups are required for observing breakage at physiological pH.

2,2'-Dipyridyl↗
PubMed1998

Randomized trial of induction chemotherapy in larynx carcinoma.

We conducted a randomized study in patients with previously untreated advanced (T3) larynx carcinoma to compare total laryngectomy followed by radiotherapy to induction chemotherapy, followed by radiotherapy in good responders, and by total laryngectomy plus radiotherapy in poor responders. A total of 68 patients were included in the study, 36 in the induction chemotherapy group and 32 in the no chemotherapy group. 15 of the 36 patients in the induction chemotherapy group did not have a laryngectomy. Survival and disease-free survival were significantly worse in the induction chemotherapy group than in the no chemotherapy group (P = 0.006 and P = 0.02, respectively). The 2-year survival rates were 69% in the induction chemotherapy group and 84% in the no chemotherapy group. Larynx preservation for patients, selected on the basis of having responded to induction chemotherapy, cannot be considered a standard treatment at the present time.

Aged↗
PubMed1998

Peroxidase-mediated oxidation, a possible pathway for activation of the fungal nephrotoxin orellanine and related compounds. ESR and spin-trapping studies.

Orellanine is the tetrahydroxylated and di-N-oxidized bipyridine toxin extracted from several Cortinarius mushrooms among them C. orellanus. The pathogenic mechanism involved in the C. orellanus-poisoning by orellanine leading to kidney impairment is not yet fully understood until now. Electron spin resonance (ESR) spectroscopy has been used to study the activation of orellanine by horseradish peroxidase/H2O2 system at physiological pH. Evidence for a one-electron oxidation of the toxin by this enzymatic system to an ortho-semiquinone radical intermediate is presented. The orellanine ortho-semiquinone generated by the peroxidase/H2O2 system abstracts hydrogen from glutathione, generating the glutathionyl radical which is spin-trapped by 5,5'-dimethyl-1-pyrroline N-oxide (DMPO) and subsequently detected by ESR spectroscopy. Similarly, the ortho-semiquinone abstracts hydrogen from ascorbic acid to generate the ascorbyl radical which is detected by direct ESR. The peroxidatic oxidation of orellanine to semiquinone followed by its reduction by glutathione or ascorbic acid does not induce dioxygen uptake. The relationship between chemical structure and HRP oxidation of orellanine-related molecules, namely orelline and DHBPO2 (the parent molecule lacking of hydroxyl groups in 3 and 3' position) has been investigated in absence or in presence of reducing agents. None of the orellanine-related compounds can be oxidized by the HRP/H2O2 system, showing that both catecholic moieties and aminoxide groups are necessary for observing the formation of the ortho-semiquinone form of orellanine. As shown for the (photo)chemical oxidation of orellanine, the mechanism of toxicity could be correlated with a depletion of glutathione and ascorbate levels which are implicated in the defence against oxidative damage.

2,2'-Dipyridyl↗
PubMed1998

Generation of oxygen radicals from iron complex of orellanine, a mushroom nephrotoxin; preliminary ESR and spin-trapping studies.

Orellanine, [2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide, is the toxin responsible for the lethal nephrotoxicity of some Cortinarius mushrooms. Our present ESR and spin-trapping studies of the redox properties of the system of non-illuminated orellanine, ferrous iron and dioxygen contribute to understanding the molecular mechanism of its toxicity. UV-visible spectrophotometry, cyclic voltammetry and ESR in frozen medium showed the formation of a wine-red tris complex, Fe(III)Or3. This ferric complex is easily reducible (Ep = -565 mV vs Ag/AgCl/3M KCl at pH 7), involving a one-electron reversible process. Spin-trapping using DMPO is employed to detect the generation of superoxide anion and hydroxyl radicals. The instantaneous one-electron oxidation of ferrous ions in the presence of the toxin under air is concomitant with dioxygen consumption as supported by dioxygen consumption. GSH involves the toxin and ferrous ions under air in a redox cycling process resulting in the production of glutathionyl and oxygen free radicals, observed for the first time with an iron complex of a mushroom toxin. In most cases, EDTA is not able to prevent the Fe(III)Or3 and radical formation. The ortho-dihydroxylated groups borne by the di-N-oxidized bipyridine structure and not the bipyridine structure itself, are responsible for the formation of a stable ferric complex at pH 7, as they are for the generation of an apparently stable ortho-semiquinone anion radical. These one-electron mechanisms may play a major role in some of the known toxic effects of orellanine.

2,2'-Dipyridyl↗
PubMed1997

Novel methods for identification and quantification of the mushroom nephrotoxin orellanine. Thin-layer chromatography and electrophoresis screening of mushrooms with electron spin resonance determination of the toxin.

Orellanine, (2,2'-bipyridine)-3,3',4,4'-tetrol-1,1'-dioxide, the toxin from several Cortinariace species, induces an acute renal failure which can be very severe or even irreversible and fatal. It is therefore important to be able to quickly and simply identify orellanine in mushroom samples with classical methods, readily available in any laboratory, such as anti-poison centers. This article reports the results of three analytical methods: classical TLC on cellulose plates in n-butanol--acetic acid--water and two original methods, electrophoresis on agarose gel and direct electron spin resonance (ESR) after enzymatic oxidation. They were applied to detect orellanine in 34 Cortinariaceae and 4 other species of toadstools. Our three sets of results are convergent. TLC (detection limit: 15 ng with fluorescence densitometry), electrophoresis (25 ng) and even ESR (5 micrograms), are sensitive enough for our purpose, and a sophisticated method like HPLC (detection limit: 50 pg) is not required. As the ESR spectrum of the toxin semiquinone is highly specific, TLC or electrophoresis coupled with ESR are a convenient alternative to liquid chromatography coupled with mass spectrometry, with the same specificity, for a confirmation or with samples such as ours with high toxin contents. ESR unambiguously confirms the relatively high contents of orellanine, from 0.45% (C. henrici) to 1.1-1.4% (C. orellanus), found in five Cortinarius from the subgenus Leprocybe, section Orellani. The five species, though they are from different geographic origins, have a more or less common pattern of fluorescent compounds, among which orellinine and orelline beside orellanine. It can be useful to note that orellanine semiquinone can be easily detected by ESR directly in the fresh mushroom. The toxin is absent in the other mushrooms we tested, especially in D. cinnamomea and C. splendens, which have been claimed as toxic and suspected to contain orellanine.

2,2'-Dipyridyl↗
PubMed1995

First electron spin resonance evidence for the production of semiquinone and oxygen free radicals from orellanine, a mushroom nephrotoxin.

Orellanine is the tetrahydroxylated and di-N-oxidized bipyridine toxin from several Cortinarius mushrooms. The mechanism responsible for its lethal nephrotoxicity was unknown until now. Our present ESR spectroscopic study of the redox properties of the toxin is an original contribution to the knowledge of its toxicity. It was achieved in particular by comparison of the properties of orellanine to that of other bipyridine compounds. After a one-electron oxidation (e.g., photochemical oxidation upon visible light), a radical form of orellanine is observed at physiological pH under aerobic or anaerobic conditions. This radical, identified as ortho-semiquinone anion radical, can also be generated by oxidation with biological oxidizing agents or enzymatic systems. Production of superoxide and hydroxyl radicals is shown by the spin-trapping method using DMPO as a spin trap. Bioreducing agents like GSH and cysteine involve in vitro the semiquinone radical and orellanine in a redox cycling process resulting in the production of glutathionyl and oxygen free radicals. This process leads in vitro to a large oxygen consumption and to a dramatic depletion of glutathione level. The formation of an apparently stable ortho-semiquinone anion radical and of reactive oxygen radical species is observed for the first time with a mushroom toxin. It is due to the catechol-like functions borne by the di-N-oxidized bipyridine structure of the toxin and may at least partly explain the toxicity of orellanine.

2,2'-Dipyridyl↗
PubMed1994

Tortuosity of the retinal vessels in Aarskog syndrome (faciogenital dysplasia).

Aarskog syndrome (faciogenital dysplasia) is a genetic growth disorder characterized by short stature, cryptorchidism, shawl scrotum, and dysmorphic facial features. Ophthalmic findings include hypertelorism, blepharoptosis, strabismus, and ophthalmoplegia. The authors report a patient with Aarskog syndrome and bilateral retinal vessel tortuosity. This is the first retinal anomaly associated with Aarskog syndrome.

Abnormalities, Multiple↗
PubMed1993

Retinoblastoma in the state of Oklahoma: a clinicopathologic review.

This is a retrospective review of 56 patients diagnosed with retinoblastoma (Rb) from 1970 to 1990 at either the Dean A. McGee Eye Institute or Children's Hospital of Oklahoma. Twenty-six (46%) patients had somatic Rb and thirty (54%) had germinal Rb. On average, somatic disease presented at 20.5 months and germinal disease at 11.7 months. Nine (16%) of our patients have died; of these, metastatic disease was the cause of death in six patients, whereas a midline pineal tumor (trilateral retinoblastoma) was the cause of death in three patients. Metastatic disease presented an average of 17.5 months after the diagnosis of Rb, and death occurred an average of 10.3 months after the diagnosis of metastasis. Trilateral Rb presented an average of 18 months after the diagnosis of retinoblastoma, and on average death occurred 2 months later. Histopathology was available on forty-nine of our patients. Poorly differentiated tumor histology, optic nerve invasion of tumor cells past the surgical plane of transection, and choroidal invasion of tumor cells appear to be significant histological markers for developing metastatic disease. The cytogenetics, current therapy, and related management of retinoblastoma are reviewed.

Eye Enucleation↗
PubMed1992

An expansion prosthesis for the microphthalmic socket.

An expansion prosthesis has been developed for the anophthalmic or microphthalmic socket. Orthodontic wire covered with silicone tubing is fused onto a conventional methyl-methacrylate ocular prosthesis. The use of this device is illustrated in a case report.

Eye, Artificial↗
PubMed1991

Neoadjuvant chemotherapy consisting of cisplatin and continuous infusions of bleomycin and 5-fluorouracil for advanced head and neck cancer. The need for a new stratification for stage IV (M0) disease.

A Phase II study of cisplatin (100 mg/m2 on day 1) and bleomycin (15 mg intravenous push day 1) followed by 5 days of continuous intravenous infusions of 5-fluorouracil (5-FU) (650 mg/m2/d) and bleomycin (16 mg/m2/d) repeated at 21-day intervals was performed in 54 previously untreated patients with nonmetastatic (M0), locoregionally advanced head and neck squamous cell carcinoma (SCC). The aim of this study was to increase the complete response rate to chemotherapy and to identify prognostic factors that may influence local control and disease-free survival. From April 1986 until August 1988, 5 patients with Stage III and 49 with Stage IV (International Union Against Cancer-American Joint Committee on Cancer 1986 [UICC-AJCC]) disease received this regimen. Thirty (61%) patients with Stage IV disease had bulky nodal disease (9 N2c and 21 N3) and 29 (53%) had T4 primary lesions. The response rate was 59% (95% confidence interval, 47% to 71%) and the complete response rate to chemotherapy was 13% (95% confidence interval, 0% to 26%). The response rate was greatly influenced by tumoral volume and performance status (PS). The complete response rate to chemotherapy was 40% for patients with Stage III disease (2 of 5 patients) versus 10% for patients with Stage IV disease (5 of 49 patients; P = 0.02). The response rate for patients with Stage III disease was 100% (5 of 5 patients) versus 55% for patients with Stage IV disease (27 of 49 patients; P = 0.14). For patients with Stage IV bulky nodal disease (N2c-N3), the response rate was 43% (13 of 30 patients) and the complete response rate to chemotherapy was 3% (1 of 30 patients) versus 68% (13 of 19 patients; P = 0.13) and 21% (4 of 19 patients; P = 0.07), respectively, for patients with Stage IV less than N2b disease. The local control rate after definitive therapy was 100% for patients with Stage III disease, 70% (17 of 24 patients) for patients with Stage IV less than N2b disease, and 17% (5 of 30 patients) for patients with bulky nodal disease (P = 0.0005). As of February 1991, with a median follow-up time of 38 months (range, 30 to 53 months), 4 of 5 patients with Stage III disease and 7 of 19 patients with Stage IV less than N2b disease were alive with no evidence of disease (37%) versus 0 of 30 patients with bulky nodal disease (P = 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Orellanine inhibits protein synthesis in Madin-Darby canine kidney cells, in rat liver mitochondria, and in vitro: indication for its activation prior to in vitro inhibition.

Pure orellanine, a nephrotoxic compound extracted from the mushroom Cortinarius orellanus, which is known to induce severe kidney damage several days or weeks after ingestion, is found to inhibit strongly the synthesis of macromolecules (proteins, RNA and DNA) in Madin-Darby canine kidney (MDCK) cells and in rat liver mitochondria, although the uptake of labelled precursors of the above macromolecules is not significantly altered. Direct addition of orellanine to a cell-free system of rabbit reticulocyte lysate does not produce any inhibition of protein synthesis. However, when orellanine is pre-incubated with activating rat liver microsomal systems, this inhibition occurs. Thus, the in vivo inhibition of protein synthesis is most likely due to a metabolite of orellanine.

2,2'-Dipyridyl↗
PubMed1991

Hypopharyngeal sebaceous carcinoma: a case report.

A hypopharyngeal squamous-cell carcinoma with sebaceous differentiation is reported. In the primary as well as the metastatic lymph nodes, the tumor showed basaloid, squamous, and sebaceous cells. In addition, immunostaining for S-100 protein and vimentin manifested scattered cells showing cytoplasmic processes suggesting myoepithelial cells. An exhaustive review of the literature revealed only one similar case previously reported. The probable origin from the minor salivary glands is discussed.

Adenocarcinoma↗
PubMed1991

Randomised EORTC head and neck cooperative group trial of preoperative intra-arterial chemotherapy in oral cavity and oropharynx carcinoma.

Between February 1978 and January 1984, 222 eligible patients were randomised in a multicentre trial of preoperative intra-arterial chemotherapy in the treatment of oral cavity and oropharynx carcinoma. Patients were randomised between either surgery or preoperative chemotherapy. This latter group received vincristine and bleomycin for 12 days. Patients were stratified according to the primary site: floor of the mouth (FM) versus posterior oral cavity or oropharynx (POC) and institution. The FM group received postoperative radiotherapy depending upon quality of the margins and lymph-node pathological involvement, when it was systematically applied in the POC group. Tumour regression after chemotherapy either complete (CR) or partial (PR greater than 50%) was observed in 48% in the FM group and 41% in the POC group, and lymph-node regression (CR + PR) was respectively 15% and 23%. Some discrepancies appeared between clinical regression and pathological response, and the number of cases without histological response was clearly higher than the number of cases without clinical response. The overall survival showed a statistically significant difference (P = 0.048) between FM and POC groups. In the FM group, median survival in the chemotherapy arm was estimated at 7 years compared with 3 years in the surgery arm. In the POC group, median survival was estimated at 3 years in both treatment arms. Chemotherapy lowered the uncontrolled disease and local recurrence in the FM group. These differences do not exist in the POC group, which may be due to the systematically postoperative radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Recurrent and/or metastatic head and neck squamous cell carcinoma: a clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy.

One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cisplatinum (C-DDP, 100 mg/m2/cycle)-based. The two combinations tried were C-DDP, bleomycin, and fluorouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C-DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96-hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease-free interval (DFI), distant metastases, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedimentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR + PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 vs. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C-DDPci 7 (30%) of 23, CFB C-DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age less than 60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythrosedimentation rate (ESR) of less than 30 mm/1st hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease-free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas.

The c-Ha-ras gene was analysed by Southern blot hybridisation in 67 specimens of lymph node metastases and in 25 specimens of primary tumours obtained from 85 untreated patients with head and neck squamous cell carcinoma. The loss of one c-Ha-ras allele was observed in 10/46 (22%) tumours from heterozygous patients for this locus. Different genes, located as the c-Ha-ras gene on the short arm of chromosome 11, were also found to be deleted suggesting that the deletion of other genes could play a role in aggressiveness of head and neck carcinomas. Using polymerase chain reaction, mutation at codon 12 was detected in only 2/54 (3.8%) tumours but no mutation involving codon 61 was found. Neither gene amplification nor gene rearrangement could be observed. Total RNA was prepared from 79 of these tumour specimens and analysed by Northern and slot blot hybridisation. A 1.2 kb c-Ha-ras transcript band was detected in all the RNA preparations. Relatively high c-Ha-ras transcript levels were found in 18% of lymph node metastases and in 21% of primary tumours, indicating no significant differences between these cancers. Moreover, the c-Ha-ras mRNA levels were not significantly greater in the primary tumours than in the normal mucosae in 10/12 cases for which both tissues were analysed. These data indicate that c-Ha-ras gene does not seem to be strongly involved in head and neck carcinomas at that advanced stage of the disease, as this was previously reported for earlier clinical stages.

Blotting, Northern↗
PubMed1990

Glutathione and cysteine levels in human tumour biopsies.

There is evidence that some human tumours could be treated with a combination of buthionine sulfoximine and hypoxic cell sensitizers. However, clinical application of this technique requires a prior knowledge of the level of non-protein bound sulfhydryl (NPSH) compounds in these tumours. The present study provides data on the levels of glutathione (GSH) and cysteine (CYS) in human tumour biopsies from the cervix and from the head and neck. The NPSH compounds were measured by high performance liquid chromatography. The median GSH values were 20.5 nmol/mg protein (cervix) and 23 nmol/mg protein (head and neck) while the median CYS values were 4.4 (cervix) and 4.2 nmol/mg protein (head and neck). The values varied widely from one patient to another.

Chromatography, High Pressure Liquid↗