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Biomedical subjects

P Wolkenstein

Publications and source records attributed to P Wolkenstein.

At least 73 records · Page 4Linked to original sources
PubMed1998

Covalent binding of carbamazepine reactive metabolites to P450 isoforms present in the skin.

Carbamazepine is an anticonvulsant associated with a high risk for severe cutaneous reactions. Upon metabolism by cytochrome P450, carbamazepine may produce reactive metabolites. We evaluated in vitro the covalent binding of carbamazepine reactive metabolites on human P450s and then the presence of these P450s in human epidermis. Carbamazepine reactive metabolites covalent binding to human liver microsomes involved P450 subfamilies 1A, 2C and 3A. Specific covalent binding to yeasts expressing different P450s showed that carbamazepine reactive metabolites bound specifically to P450 1A2 and 3A4. We confirmed the constitutive presence of P450 3A in human epidermis and after induction with coaltar of P450 1A. Consequently, the production in epidermis of carbamazepine reactive metabolites is theoretically possible with formation of P450 adduct metabolites.

Adult↗
PubMed1998

Vulvovaginal involvement in toxic epidermal necrolysis: a retrospective study of 40 cases.

OBJECTIVE: To determine the incidence, features, and surgical treatment of vulvovaginal lesions in toxic epidermal necrolysis. METHODS: Acute genital lesions were studied retrospectively in 40 women hospitalized for toxic epidermal necrolysis in a dermatologic intensive care unit. A questionnaire was sent to evaluate sequelae and their effects on sexual activity. Examination and surgical treatment were proposed to patients with symptomatic sequelae. RESULTS: Twenty-eight of the 40 patients reported genital lesions during the acute phase of toxic epidermal necrolysis. No specific treatment was carried out during the acute period. Sequelae were observed in five cases, of which three involved the lower genital tract and two the vulva exclusively. The two patients with exclusive vulval involvement did not attempt any sexual activity. The other three patients with both vulval and vaginal lesions were unable to have normal sexual intercourse. Two of the three patients were treated surgically. One patient succeeded in having intercourse, but surgery failed to relieve dyspareunia. CONCLUSION: Genital involvement is frequent during toxic epidermal necrolysis but rarely leads to symptomatic sequelae. Surgery for synechiae is sometimes necessary to recover sexual activity because the vulvovaginal canal is stenotic. Because of the partial effect on pain relief after surgery, a preventive approach should be tried.

Adolescent↗
PubMed1998

Lichenoid erythrodermic bullous pemphigoid of the African patient.

BACKGROUND: Lichen planus (LP) pemphigoides is defined by the concurrence of bullous pemphigoid (BP) and LP lesions. However, other autoimmune bullous skin diseases such as paraneoplastic pemphigus or bullous lupus erythematosus may also be associated with lichenoid eruptions. OBJECTIVE: Our purpose was to describe 3 African patients with a similar form of lichenoid erythrodermic BP. METHODS: Medical records of the 3 patients were reviewed for clinical, histologic, and biologic data. The ultrastructural localization of autoantibody deposits was studied by direct and indirect immunoelectron microscopy. The antigenic specificities recognized by the patients' sera were analyzed by immunoblotting on human epidermal extracts. RESULTS: Three black African men had a severe lichenoid erythroderma associated with BP lesions involving the skin and mucosa. Histologic and direct immunofluorescence examination of skin and mucosal lesions were consistent with the diagnosis of BP associated with a lichenoid dermatitis. Immunoblot analysis of sera detected anti-BPAG1 and anti-BPAG2 antibodies and immunoelectron microscopy showed IgG deposits localized in the lamina lucida and the hemidesmosomes. The 3 patients were natives of an area near the Senegal River and had the common HLA-DR10 haplotype. CONCLUSION: The clinical and histologic features of these 3 patients were distinct from classic LP pemphigoides. Their common geographic origin and the presence of the HLA-DR10 haplotype suggest that these cases represent a particular type of lichenoid erythrodermic BP, which is probably determined by genetic factors.

Adult↗
PubMed1998

Radiosurgery without whole brain radiotherapy in melanoma brain metastases. Club de Cancérologie Cutanée.

To evaluate the effectiveness of radiosurgery without whole brain radiotherapy in the palliative treatment of melanoma brain metastases, we retrospectively assessed the results in 35 patients: 4 with a solitary brain metastasis, 13 with a single brain metastasis and metastases elsewhere and 18 with multiple brain metastases. The local control rate was 98.2% (55/56 metastases) at 3 months. Median survival was 22 months in patients with a solitary brain metastasis, 7.5 months in patients with a single brain metastasis and metastases elsewhere, and 4 months in patients with multiple brain metastases. Complications were unusual and surgery was required in 2 of 35 patients. These results show for the first time that melanoma patients with a unique brain metastasis with or without metastases elsewhere clearly benefit from tumour control easily obtained by radiosurgery. Although the comparison of radiosurgery with surgery and/or whole brain radiotherapy cannot be adequately addressed, radiosurgery alone seems to provide similar results with lower morbidity and impact on quality of life.

Adult↗
PubMed1998

Pulmonary embolism; lung scanning interpretation: about words.

OBJECTIVE: To assess clinicians' agreement on how they interpret lung scan reports with regard to the diagnosis of pulmonary embolism. DESIGN: In this prospective study, nuclear medicine physicians provided two types of reports for each lung scan: a routine descriptive report and a short form with a standardized conclusion on the likelihood of pulmonary embolism: "high probability," "no conclusion," and "diagnosis excluded." Three independent blinded senior clinicians reviewed all routine reports and chose one of the following conclusions: "high probability," "no conclusion," or "diagnosis excluded." SETTING: An acute care teaching hospital near Paris. SUBJECTS: Eighty-two lung scans were studied. MAIN OUTCOME MEASUREMENTS: Inter-clinician agreement and agreement between clinicians' conclusions and the nuclear medicine physicians' standardized reports were analyzed using the kappa index. RESULTS: The distribution of the clinicians' conclusions from routine reports strongly differed (p < 0.001). Agreement among the three clinicians was observed in 40.2% of the routine reports, and the inter-clinician agreement was poor to moderate (kappa range, 0.28 to 0.52). A complete agreement among the three clinicians and the nuclear medicine physicians' standardized conclusions was observed for 32.9% of the reports. The agreement between each clinician and the standardized conclusions was also poor to moderate (kappa range, 0.32 to 0.55). CONCLUSION: Reading the same routine reports, clinicians reached different conclusions. Furthermore these differed greatly from the nuclear medicine physicians' standardized conclusions. These results support the notion that physicians should be given standardized reports.

Adult↗
PubMed1998

[Neurofibromatosis].

Neurofibromatoses regroup at least two different autosomal dominant disorders, neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). NF1 gene and NF2 genes have been respectively localized on chromosomes 17 and 22. NF1 represents 95% of neurofibromatoses cases. Its incidence is 1 for 3,500 newborns, its prevalence 1 for 4,500. NF1 is characterized by its cutaneous manifestations, café au lait spots, lentigines and neurofibromas. NF2 incidence is 1 for 33,000-40,000 newborns. NF2 is characterized by bilateral vestibular schwannomas (former acoustic neurinomas) and other tumors of the central nervous system. The hallmark of schwannomatosis (neurilemmomatosis) is multiple cutaneous or subcutaneous schwannomas without vestibular schwannomas. Different neurofibromatoses are characterized by different prognosis, complications, and genetic counseling. Multidisciplinary centers with trained physicians are ideal structures for management of neurofibromatoses patients.

Diagnosis, Differential↗
PubMed1998

[Cutaneous manifestations of type 1 neurofibromatosis and their treatment].

After recalling the frequency and pathophysiology of type 1 neurofibromatosis, or Von Recklinghausen disease, the authors report the various cutaneous manifestations: café-au-lait spots, lentigines, cutaneous neurofibromas, plexiform neurofibromas. Treatment must be multidisciplinary, as surgery is difficult and often gives disappointing results. The various surgical treatments are considered according to the type and site of the lesions to be treated, with particular emphasis on the treatment plan, which must be discussed with the patient.

Adolescent↗
PubMed1997

Pulmonary complications in toxic epidermal necrolysis: a prospective clinical study.

OBJECTIVE: To evaluate the incidence, clinical features, and prognosis of pulmonary complications associated with toxic epidermal necrolysis DESIGN: Prospective study. SETTING: Dermatology intensive care unit in Mondor Hospital, France. PATIENTS: 41 consecutive patients. INTERVENTIONS: On admission, then daily, respiratory evaluation was based on clinical examination, chest X-ray, and arterial blood gas analysis. When clinical symptoms, X-ray abnormalities, or hypoxemia [partial pressure of oxygen (PO2) < 80 mm Hg] were present, fiberoptic bronchoscopy was performed. RESULTS: 10 patients presented early manifestations: dyspnea (n = 10), bronchial hypersecretion (n = 7), marked hypoxemia (n = 10) (PO2 = 59 +/- 8 mm Hg). Chest X-ray was normal (n = 8) or showed interstitial infiltrates (n = 2). In these 10 patients, fiberoptic bronchoscopy demonstrated sloughing of bronchial epithelium in proximal airways. Delayed pulmonary complications occurred in 6 of these 10 patients from day 7 to day 15: pulmonary edema (n = 2), atelectasis (n = 1), bacterial pneumonitis (n = 4). Mechanical ventilation was required in 9 patients. A fatal outcome occurred in 7 patients. Seven patients did not develop early pulmonary manifestations (PO2 on admission 87 +/- 6 mm Hg) but only delayed pulmonary symptoms related to atelectasis (n = 1), pulmonary edema (n = 4), and bacterial pneumonitis (n = 3); bronchial epithelial detachment was not observed. None of them required mechanical ventilation and all recovered with appropriate therapy. CONCLUSIONS: "Specific" involvement of bronchial epithelium was noted in 27% of cases and must be suspected when dyspnea, bronchial hypersecretion, normal chest X-ray, and marked hypoxemia are present during the early stages of toxic epidermal necrosis. Bronchial injury seems to indicate a poor prognosis, as mechanical ventilation was required for most of these patients and was associated with a high mortality.

Adolescent↗
PubMed1997

Schwannomatosis: a clinical entity distinct from neurofibromatosis type 2.

BACKGROUND: Schwannomatosis includes multiple cutaneous schwannomas, central nervous system tumors and various neurologic deficits. OBJECTIVE: To specify the clinical presentation of schwannomatosis, excluding neurofibromatosis type 2 (NF2). METHODS: Patients with at least 2 cutaneous schwannomas were evaluated for NF2 criteria. RESULTS: 5 men and 2 women (mean age 54 +/- 18 years) we included. Two cases were familial. Cutaneous schwannomas were tender nodules with onset above the age of 30 years. Four patients had paresthesias. Four patients had hypacusis, but auditory brainstem responses showed no retrocochlear involvement. No vestibular schwannoma or central nervous system tumor was found with magnetic resonance imaging in 6 patients. Spinal imaging performed in 6 patients was normal in 5 and showed a spinal schwannoma in the 6th patient. CONCLUSION: We strictly eliminated the diagnosis of NF2 in our patients. Exclusion of NF2 in suspected schwannomatosis is essential for further molecular genetic studies.

Adult↗
PubMed1997

Vulvovaginal sequelae in toxic epidermal necrolysis.

OBJECTIVE: To evaluate the incidence of vulvar lesions during the acute and healing periods in toxic epidermal necrolysis (TEN), to describe the clinical aspects and functional consequences, and to evaluate surgical treatment. STUDY DESIGN: During the acute period in 40 patients, cutaneous and mucous lesions were described on the day of hospitalization and daily thereafter. To evaluate the healing period, a questionnaire was sent to the same 40 patients to obtain information on symptomatology after the acute period, anatomic modifications, and the quality of sexual and other genital activity. RESULTS: During the acute period, genital lesions were present in 28 of the 40 patients studied (70%). In 24/28 (89%) the lesions were vulvar only, and in 3/28 (11%) they were vulvovaginal. In one case vaginal involvement could not be proven because the patient was a virgin. During the healing period, sequelae occurred in 5 of the 40 patients (12.5%): four cases were known since the patients had visited the Department of Gynecology because of secondary effects, and one case was detected by the questionnaire. The symptoms occurred during hospitalization in 1 case, at the end of the second month in 2, at the 12th month in 1 and unknown in 1. The site was the vulva in all five cases and was the vulva and vagina in three. Again, the virgin could not be examined. The average interval between secondary effects and the original gynecologic visit was 7 months (3-12). The sequelae were treated surgically in two of the five affected patients: on the vulva, nymphoplasty, posthectomy and median perineotomy; in the vagina, sharp and blunt dissection, with use of a soft mold. The first patient had a recurrence six months after surgery, and the second had no recurrence but has been unable to engage in intercourse. CONCLUSION: From our study of the involvement of the vulva and vagina during TEN and the sequelae, it is clear that detection from the questionnaire was insufficient. Some women can have synechiae without functional sequelae, and others can have minor involvement with important psychological repercussions. A prospective study with systematic examination of the vulvovaginal area and systematic follow-up for at least one year is needed. For therapy, a lubricant gel (perhaps topical steroids) could be useful. Placing a soft mold in the vagina as soon as possible, though difficult, and keeping it there until complete healing occurs can lead to infection. It is not clear that use of a mold would promote healing or be tolerated. Intercourse immediately after the acute period would be helpful but probably would not be welcome to the patients. However useful, a prospective survey would be difficult because it would entail many years of study.

Adolescent↗
PubMed1997

Drug-induced linear IgA disease: target antigens are heterogeneous.

No information is available concerning the target antigen(s) in drug-induced linear IgA disease. The purpose of this study was to define better drug-induced linear IgA disease by studying its immunopathological, immunoultrastructural and immunochemical characteristics in three patients. In the first patient, IgA deposits were seen in the lamina lucida. In the second and the third patients, IgA deposits were seen on each side of the lamina densa. Immunoblotting of the first patient's serum showed that IgA reacted with a protein of 230 kDa similar to the bullous pemphigoid-associated antigen 1 (BPAG 1). The second patient's serum did not react with specific bands. In the third patient IgA antibodies reacted with a protein of 97 kDa on epidermal extracts. Our findings suggest that, as in idiopathic forms, the target antigen is not unique in drug-induced linear IgA disease. In some patients, drug-induced linear IgA disease may represent an IgA class response to the BPAG 1.

Adult↗
PubMed1997

[Acute mast cell leukemia disclosed by vasomotor flushing].

INTRODUCTION: Acute mast cell leukemia is a rare and severe disease. We report herein a case associated with a flush syndrome. CASE REPORT: A 44-year-old man, presented with a flush of face and trunk. Bone marrow was infiltrated with immature mast cells. In spite of chemotherapy and bone marrow transplantation the patient deceased. DISCUSSION: Pheochromocytoma, carcinoid tumor, and mastocytosis are associated with a flush syndrome. In our patient the diagnosis was an acute mast cell leukemia. Acute mast cell leukemia can follow systemic mastocytosis or occur de novo. This disease is of poor prognosis. No treatment is available.

Adult↗
PubMed1996

Apoptosis as a mechanism of keratinocyte death in toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening diseases characterized by extensive epidermal destruction. The aim of our study was to investigate apoptosis in keratinocytes of patients with TEN and TEN/SJS overlap syndrome. Keratinocytes from TEN patients were found to undergo extensive apoptosis. These results suggest that cell destruction in TEN occurs as a result of apoptosis. Our findings suggest that apoptosis inhibitory agents may play an important part in the therapeutic strategy of TEN.

Adult↗
PubMed1996

Patch testing in severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Patch testing may help to assess the culpability of a drug in an adverse reaction. Our aim was to study patch testing in severe cutaneous adverse drug reactions (ADRs) (Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), acute generalized exanthematous pustulosis (AGEP), and other cutaneous ADRs). 59 patients with cutaneous ADRs were included: 22 had SJS/TEN, 14 AGEP, and 23 other cutaneous ADRs. Patients were patch tested with the suspect drug, and with a standard series of drugs. 2 patients among the 22 SJS/TEN cases had a relevant positive test. 7 patients among the 14 AGEP cases had a relevant positive test. 6 patients among the 23 other cutaneous ADRs had a relevant positive test. Our results suggest that patch testing has a weak sensitivity in SJS/TEN and is not appropriate in these diseases. Patch testing seems more adapted to other cutaneous ADRs, such as AGEP, in which the proportion of positive patch tests was significantly higher (p < 0.02). Nevertheless, the difference of sensitivity of patch testing in SJS/ TEN, AGEP or other cutaneous ADRs could be linked not only to the clinical type of eruption, but also to the different spectrum of culprit drugs in each type of eruption.

Adult↗
PubMed1996

Caseous necrosis in cutaneous leishmaniasis.

A case of late stage cutaneous leishmaniasis with focal caseous necrosis is reported. The patient, a 30 year old Tunisian man, presented with idiopathic bone marrow aplasia. Microscopically, minimal changes were observed in the epidermis: slight hyperkeratosis and moderate acanthosis. Lesions predominated in the dermis. Epithelioid granulomas were found in the lower dermis. Some of these lesions were clearly surrounded by a ring of lymphocytes and were rarely confluent. A peculiar histological feature was the presence of focal acidophilic and slightly granular necrosis at the centre of some the tuberculoid lesions. Focal fibrinoid necrosis was found in the upper dermis, outside granulomas. A mild to moderate infiltrate of histiocytes, lymphocytes and plasma cells, with scanty neutrophils, was observed mainly in the upper dermis. No intracellular or extracellular Leishman-Donovan bodies were observed. Acid fast mycobacteria, however, were not detected. Leishmaniasis was diagnosed on culture of skin biopsy specimens. The presence of caseous necrosis could lead to diagnostic confusion and result in an erroneous diagnosis of, for example, tuberculosis, syphilis, acne agminata, and sarcoidosis with fibrinoid necrosis. This is especially the case when parasites are scanty or absent.

Adult↗