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B Guillot

Publications and source records attributed to B Guillot.

At least 73 records · Page 4Linked to original sources

[Leg ulcer].

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Humans↗

[Local cutaneous side effects of interferons].

UNDERESTIMATED SIDE EFFECTS: Skin reactions to interferon (INF) treatment are uncommon in the larger series in the literature and are usually considered to be minor. They account for 5 to 12% of adverse effects to IFN and are encountered increasingly in patients with active chronic hepatitis C. Reactions may be local, occurring exclusively at the site of injection, or general. REPORTED EFFECTS AND TREATMENTS: We reviewed the literature on local skin reactions at the site of injection of the different interferons to study the underlying pathophysiological mechanisms and management schemes used. TWO TYPES OF REACTIONS: Local skin reactions can be divided into two types depending on the potential gravity and management. Minor reactions (transient erythema, eczema, depilation) have few clinical or therapeutic implications. More serious reactions, necrosis, vasculitis or injection can be potentially severe and require definitive interruption of treatment. PREVENTION: Preventive measures include careful education concerning self-injections using proper asepsia, variation of injection sites, and self-assessment of persistent skin reactions.

Drug Eruptions↗

High-resolution neutron structure of nicotinamide adenine dinucleotide.

The structure of the free-acid form of the coenzyme NAD(+) was determined at 100 K from a single-crystal neutron experiment. NAD(+) is the oxidized form of the coenzyme redox pair NAD(+)/NADH and plays an important role in the catalysis of biological processes. The molecule crystallizes in space group P1 with one NAD(+) and four water molecules per unit cell. The structure is compared with the previous X-ray models of NAD(+) [Reddy et al. (1981), J. Am. Chem. Soc. 103, 907-914; Parthasarathy & Fridey (1984b), Science, 226, 969-971; Guillot et al. (2000), Acta Cryst. C56, 726-728]. The crystal packing and the hydrogen-bond pattern are discussed as well as four short C-H.O contacts involving the pyridine and adenine rings. The structure displays stereochemical distortions owing to the hydrogen bonding and crystal-packing constraints, reflecting the adaptability of the NAD(+) molecule in various chemical environments.

Crystallography, X-Ray↗

HFE mutations and transferrin receptor polymorphism analysis in porphyria cutanea tarda: a prospective study of 36 cases from southern France.

BACKGROUND: Porphyria cutanea tarda (PCT) is associated in most cases with iron overload, which may participate in decreased activity of uroporphyrinogen decarboxylase in the liver. The aetiology of this iron overload remains unknown; however, it has been demonstrated that mutations of HFE, the genetic haemochromatosis gene, might be present in a significant proportion of Anglo-Saxon and Italian patients. Furthermore, transferrin receptor polymorphism may influence the affinity of this receptor to its ligand with a subsequent increase of cellular iron absorption and storage. OBJECTIVES: To evaluate the incidence and spectrum of HFE mutations and the relative frequency of the two main alleles of transferrin receptor in patients with PCT originating from southern France, and to evaluate the relationship of these genetic data with iron status, and with hepatitis B and C and human immunodeficiency virus (HIV) infections. METHODS: Thirty-six consecutive patients with either sporadic or familial PCT were prospectively included between 1997 and 2000. Search for the presence of the three main mutations of the HFE gene and identification of the transferrin receptor alleles were performed using polymerase chain reaction followed by enzymatic digestion. Iron parameters and viral status for hepatitis B and C viruses and HIV were determined. RESULTS: Seven patients (19%) showed heterozygous C282Y mutation, but no C282Y homozygote was present; five patients (14%) carried homozygous H63D mutation, while eight (22%) were heterozygous for this mutation. One patient was heterozygous for the S65C mutation (3%). Iron parameters demonstrated overload in all patients, without a clear difference between patients with and without deleterious mutations of the HFE gene. Infection by hepatitis C virus was documented in 20 patients (56%), and was significantly less frequent in patients with deleterious HFE mutations. The profile of transferrin receptor alleles in PCT patients did not show significant variation compared with the general population. CONCLUSIONS: This study confirms the high frequency of HFE mutations in patients with PCT and supports the hypothesis that HFE gene abnormalities might play a significant part in the PCT pathomechanism, probably through iron overload; by contrast, transferrin receptor polymorphisms do not appear to play a significant part in iron overload in PCT.

Adult↗

[Metastatic melanoma of unknown primary site].

INTRODUCTION: Melanomas of unknown primary site are rare. To establish their diagnosis the metastatic nature of the lesion must be confirmed clinically and histologically, the melanoid nature by histology and immunohistochemistry. Any primary melanoma must be eliminated by careful examination of the skin and mucosa, and the absence of past surgical excision of skin lesions must be confirmed. We studied the epidemiological, clinic and prognostic characteristics of 19 melanomas of unknown primary site in a series of 646 melanomas. MATERIAL AND METHODS: This retrospective study was conducted on a series of 646 melanomas recruited over a period of 14 years. The epidemiological (age, gender, phototype and family history of melanoma), clinical and prognostic parameters (relapse and global survival rate) were analyzed in 19 patients. Clinical and epidemiological data were compared with the 646 melanomas of the series. The prognostic parameters were compared with the melanomas of the series at the same stage. RESULTS: The melanomas with unknown primary site represented 2.94 p. 100 of our series and concerned 10 men and 9 women with a median age of 60 years. Eight patients presented stage III melanomas, according to MD Anderson's classification and 11 stage IV. Relapse after surgery was observed in 63 p. 100 of patients and 9 deceased during the observation period. In stage III patients the probability of survival after 2 years was of 51 p. 100 and for stage IV 34 p. 100. DISCUSSION: In our series the frequency of melanomas of unknown primary site is comparable to that observed in other studies. Compared to melanomas of known primary site, there was a preponderance in men and in slightly older patients. There was a majority of single glandular localizations and no particular site was preponderant. Survival of Stage III patients was comparable to that of melanomas of know primary site. However, for stage IV patients it appeared better, as has been noted in other series. Treatment of metastatic melanomas of unknown primary site should therefore be the same as that of classical forms. Whenever possible, surgery remains the first indication. Search for the primary site must be orientated by clinical examination including complete examination of the skin and mucosa (ENT, ophthalmologic and genito-urinary), eventually associated with paraclinical investigations, depending on the symptoms.

Adolescent↗

[Cutaneous angiosarcoma of the breast after treatment with conservative surgery and radiotherapy of breast carcinoma].

Secondary cutaneous angiosarcoma of the breast is uncommon. This tumor develops after conservative treatment of breast cancer. We present a case that developed seven years after conservative treatment with surgery and radiotherapy for breast cancer. Several factors may be implicated in the pathogenesis of this tumor (carcinogenic effect of radiotherapy, HHV8 infection), but the essential factor appears to be chronic edema. Prognosis is poor but initial wide surgical resection can achieve prolonged remission. Early diagnosis and treatment are the main prognostic factors.

Aged↗

Delays in diagnosis and melanoma prognosis (II): the role of doctors.

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.

Attitude of Health Personnel↗

Delays in diagnosis and melanoma prognosis (I): the role of patients.

A prospective survey was conducted to assess the role of patients in the melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a comprehensive questionnaire including a psychological instrument. Main outcome measures were the delay before medical intervention and the tumor thickness. Of 590 melanomas, 70.8% were detected by patients and this proportion was higher in females. Relatives were involved in the detection of half of the cases. Median delays before the patient realized he had a suspicious lesion, before this lesion was seen by a doctor, and before the melanoma was removed were 4 months, 2 months, and 1 week, respectively. Delays up to several years were observed in some cases. The rate of self-detection tended to be lower, the delays before seeking medical advice to be longer, and the tumor thickness to be higher in old people, in males, in lower-educated individuals, in those living out of towns, and in people with a low awareness about melanocytic tumors than in other cases. Conversely, individuals with a high number of atypical nevi, those who were aware to be at risk, and those who regularly visited a dermatologist tended to detect their melanoma more rapidly. No specific psychological traits were associated with a late reaction, although negligence and anxiety tended to prolong the delays. Knowledge about melanoma was poor in many patients, especially in males, and wrong beliefs were widespread. This study provides the targets of future education programs.

Adolescent↗

A new model for 20-hydroxyecdysone and dibenzoylhydrazine binding: a homology modeling and docking approach.

The ecdysone receptor (ECR), a nuclear transcription factor controlling insect development, is a novel target for insecticides such as dibenzoylhydrazines with low environmental and toxicological impacts. To understand the high selectivity of such synthetic molecules toward ECR, two homology models of the Chironomus tentans ECR ligand-binding domain (LDB) have been constructed by taking as templates the known LBD crystal structures of the retinoic acid and vitamin D receptors. Docking of 20-hydroxyecdysone (20E) and dibenzoylhydrazines to the receptor suggests a novel superposition of the natural and synthetic molecules; the N-tert-butyl substituent of the dibenzoylhydrazines extends significantly beyond the 20E volume. Our ECR-LBD protein models rationalize how 20E and dibenzoylhydrazines interact with the ligand-binding pocket. The homology model complexes provide new insights that can be exploited in the rational design of new environmentally safe insecticides.

Amino Acid Sequence↗

Treatment of Old World cutaneous leishmaniasis by pentamidine isethionate. An open study of 11 patients.

BACKGROUND: Pentavalent antimonial derivatives (PAD), especially meglumine antimoniate (Glucantime((R))), are usually considered as the first-line drugs for Old World leishmaniasis, but their potential toxicity and the number of required injection, either intralesional or intramuscular, prompt to search for alternative treatments. OBJECTIVE: To evaluate the efficiency and tolerance of pentamidine isethionate in Old World leishmaniasis. METHODS: An open pilot study included 11 patients from two regional academic centers, with varied parasitological forms of Old World leishmaniasis, treated with three strictly intramuscular injections of 4 mg/kg of base-pentamidine every other day. RESULTS: Tolerance was good overall, and 8/11 (73%) of patients responded well with a quick healing of their lesions, little scarring and no relapse. CONCLUSION: Pentamidine isethionate is a safe and effective first-line treatment for Old World leishmaniasis. Larger-scale prospective studies comparing several dosage regimens of pentamidine and pentamidine isethionate to PAD are warranted.

Adolescent↗

Residues in the ligand binding domain that confer progestin or glucocorticoid specificity and modulate the receptor transactivation capacity.

To localize regions conferring ligand binding specificity of the human glucocorticoid (hGR) and progesterone (hPR) receptors, we constructed chimeras comprising the DNA-binding domain of the yeast transcription factor GAL4, linked to the ligand binding domain of hGR or hPR. Replacement of a sequence of hGR encompassing helices H6 and H7 with the homologous sequence from hPR creates a chimeric protein GP3, which binds the progestin RU 27987 with high affinity, and results in a concomitant loss of glucocorticoid binding [dexamethasone (DEX), RU 43044]. Moreover, GP3 is not able to mediate RU 27987-induced transactivation. A detailed mutational analysis of this sequence and the study of the recently solved hPR crystal structure revealed five residues that confer progestin responsiveness to GR or modulate ligand binding and transcriptional activation. Notably, the simultaneous presence of residues Ser637 and Phe639 on GP3, lining the ligand binding pocket, is specifically involved in RU 27987 binding. The absence of residues Asp641, Gln642, and Leu647 on GP3 is accountable for the lack of glucocorticoids binding on GP3. Unlike residue 642, residues 641 and 647 are not in direct contact with the ligand and most likely act through steric-mediated interactions. The presence of Gln642 and Leu647 are determinant for transcriptional activation in response to DEX and RU 27987, respectively. DEX-dependent transactivation is further enhanced by the presence of Leu647.

Amino Acid Sequence↗

Angiosarcoma of the scalp and face: failure of an interferon alpha treatment.

Angiosarcoma of the scalp and face is a rare malignant endothelial tumor arising in elderly people. Treatment is disappointing and prognosis remains poor. We report two cases of angiosarcoma of the scalp and face relapsing after classical therapy with surgery and radiotherapy and treated with interferon alpha. The tolerance was poor and the disease progressed 2 and 5 months after the onset of the treatment. When used alone, interferon alpha does not appear as an effective treatment in this kind of angiosarcoma.

Aged↗