Diagnostic criteria for schwannomatosis.

The neurofibromatoses are a diverse group of genetic conditions that share a predisposition to the development of tumors of the nerve sheath. Schwannomatosis is a recently recognized third major form of neurofibromatosis (NF) that causes multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with schwannomatosis represent 2.4 to 5% of all patients requiring schwannoma resection and approximately one third of patients with schwannomatosis have anatomically localized disease with tumors limited to a single limb or segment of spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2, but that familial occurrence is inexplicably rare. Patients with schwannomatosis overwhelmingly present with pain, and pain remains the primary clinical problem and indication for surgery. Diagnostic criteria for schwannomatosis are needed for both clinicians and researchers, but final diagnostic certainly will await the identification of the schwannomatosis locus itself.

Changes in phosphorylation of the NMDA receptor in the rat hippocampus induced by status epilepticus.

Systemic administration of pilocarpine preceded by lithium induces status epilepticus (SE) that results in neurodegeneration and may lead to the development of spontaneous recurrent seizures. We investigated the effect of Li/pilocarpine-induced SE on phosphorylation of the NMDA receptor in rat hippocampus. Phosphorylation of NR1 by PKC on Ser890 was decreased to 45% of control values immediately following 1 h of SE. During the first 3 h following the termination of SE, phosphorylation of Ser890 increased 4-fold before declining to control values by 24 h. Phosphorylation of NR1 by PKA was also depressed relative to controls immediately following SE and transiently increased above control values upon the termination of SE. SE was accompanied by a general increase in tyrosine phosphorylation of hippocampal proteins that lasted for several hours following the termination of seizures. Tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDAR increased 3-4-fold over control values during SE, continued to increase during the first hour following SE and then declined to control levels by 24 h. SE resulted in the activation of Src and Pyk2 associated with the postsynaptic apparatus, suggesting a role for these enzymes in the SE-induced increase in tyrosine phosphorylation. Changes in phosphorylation of the NMDA receptor may play a role in the pathophysiological consequences of SE.

A case of galactosialidosis.

Galactosialidosis is a lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, caused by a defect of another lysosomal protein, the protective protein. Three subtypes are recognized: the early infantile form, the late infantile form and the juvenile/adult form. We saw a patient with galactosialidosis of the juvenile/adult form, a 51-year-old Japanese man with angiokeratomas on both elbows and knees, myoclonus, ataxia, mental retardation and macular cherry-red spots. An electron-microscopic study of a skin biopsy showed membrane-limited vacuoles in the cytoplasm of the endothelial cells, pericytes and fibroblasts. Assays of enzymatic activity in cultured fibroblasts showed a marked decrease in both beta-galactosidase and neuraminidase (sialidase). The substance contained in the cytoplasmic vacuoles appears to be glycoproteins with sialic acid, which is a terminal glycosyl residue, because the cytoplasm of the endothelial cells of the vessels and pericytes are stained by the Limax flavus agglutinin, a lectin that binds specifically with sialic acid. This technology may be useful for easy investigation of the distribution of the accumulation of such substances in the central nervous system.

A case of febrile ulceronecrotic Mucha-Habermann disease requiring debridement of necrotic skin and epidermal autograft.

We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization.

Measurement of absolute cross sections for excitation of the 3s(2)3p(5) 2P(o)(3/2)- 3s(2)3p(5) 2P(o)(1/2) fine-structure transition in Fe9+.

Experimental cross sections are reported for the 3s(2)3p(5) 2P(o)(3/2)- 3s(2)3p(5) 2P(o)(1/2) transition in Fe9+ located at 1.945 eV. The center-of-mass interaction energies are in the range of 1.72 eV (below threshold) through threshold, to 5.6 eV (2.9 x threshold). Data are compared with results of a 49-state Breit-Pauli R-matrix theory. The experiment detects structures at 3.5 and 4.6 eV corresponding to enhancement of the direct excitation via many narrow, closely spaced resonances about these energies calculated by the theory. Iron is present in practically every astrophysical object, as well as being an impurity in fusion plasmas. Present data are the first electron-energy-loss measurements on a highly charged iron ion.

Use of a wrist activity monitor for the measurement of nocturnal scratching in patients with atopic dermatitis.

BACKGROUND: The amount of nocturnal scratching can be an indirect correlate of itch in pruritic dermatoses. We have previously used an infrared video camera to measure nocturnal scratching in atopic dermatitis (AD). Although this is a reliable method of measuring nocturnal scratching, it is not suitable for routine monitoring in clinical use. OBJECTIVES: To find a simplified way of monitoring itch. METHODS: We tried using a wrist activity monitor (ActiTrac) for the measurement of nocturnal scratching in patients with AD. ActiTrac is a wristwatch-shaped device that contains a piezoceramic sensor to measure and record limb movement over a pre-set time interval. The acceleration signal produced by motion of the hands is stored and downloaded into a personal computer. The average value of acceleration (AVA, 10(-3) g min(-1)) was calculated and compared with total scratching time as a percentage of total recording time (TST%) measured with the use of an infrared video camera in 63 recordings of 21 patients with AD. For 261 recordings in 29 patients with AD, the AVA was measured and correlated with disease severity, and compared with the AVA of five non-itchy controls. RESULTS: There was a significant correlation between the AVA and TST% (r = 0.91, P < 0.001), and a regression equation of y = 0.44x - 2.5 was obtained. The AVA correlated well with the severity of AD and definitely differed from the results observed in normal controls. The AVA (mean +/- SD) was 44.4 +/- 19.1 for 115 recordings in patients with severe AD, 23.2 +/- 10.9 for 89 recordings in patients with moderate AD, 8.9 +/- 6.0 for 57 recordings in patients with mild AD and 4.1 +/- 1.9 for 25 recordings in five normal controls. The units used here are arbitrary units min-1 with a range of 0--250, which corresponds to 0-75 x 10(-6) g min(-1). CONCLUSIONS: A wrist activity monitor is able to measure nocturnal scratching. However, further methods of analysis should be sought to select scratching activity exclusively.

Cutaneous lymphomas in Tokyo: analysis of 62 cases in a dermatology clinic.

BACKGROUND: The epidemiology of cutaneous lymphomas revealed that the incidence of lymphomas differed depending on various factors including area, race, and sex, among others. OBJECTIVE: This study was undertaken to analyse the incidence of cutaneous lymphomas in Tokyo. METHODS: The clinical records and histologic material from 50 patients with lymphomas of the skin and 12 patients with lymphomatoid papulosis seen during the last 10 years at the Department of Dermatology, The Jikei University School of Medicine, Tokyo, have been reviewed. RESULTS: T-cell lymphomas including mycosis fungoides (MF)-Sézary's syndrome (SS) complex and adult T-cell leukemia/lymphoma (ATL) were more frequent than B-cell lymphomas. The incidence of ATL is associated with the number of human T-cell lymphotropic virus type 1 (HTLV-1) carriers in the general population. Cutaneous B-cell lymphoma (CBCL) is not as rare as previously thought in Japan. CONCLUSIONS: Although the frequency of these cases depends on many unrelated factors, these values can provide a rough indication of the incidence of cutaneous lymphomas in Tokyo. The incidence of cutaneous lymphomas may be influenced by changes in environmental factors including viral infections.

High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH.

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder whose hallmark is bilateral vestibular schwannoma. It displays a pronounced clinical heterogeneity with mild to severe forms. The NF2 tumor suppressor (merlin/schwannomin) has been cloned and extensively analyzed for mutations in patients with different clinical variants of the disease. Correlation between the type of the NF2 gene mutation and the patient phenotype has been suggested to exist. However, several independent studies have shown that a fraction of NF2 patients with various phenotypes have constitutional deletions that partly or entirely remove one copy of the NF2 gene. The purpose of this study was to examine a 7 Mb interval in the vicinity of the NF2 gene in a large series of NF2 patients in order to determine the frequency and extent of deletions. A total of 116 NF2 patients were analyzed using high-resolution array-comparative genomic hybridization (CGH) on an array covering at least 90% of this region of 22q around the NF2 locus. Deletions, which remove one copy of the entire gene or are predicted to truncate the schwannomin protein, were detected in 8 severe, 10 moderate and 6 mild patients. This result does not support the correlation between the type of mutation affecting the NF2 gene and the disease phenotype. This work also demonstrates the general usefulness of the array-CGH methodology for rapid and comprehensive detection of small (down to 40 kb) heterozygous and/or homozygous deletions occurring in constitutional or tumor-derived DNA.

Prolonged herpes zoster in a patient infected with the human immunodeficiency virus.

In 1983, varicella zoster virus (VZV) disease was first recognized in the context of infection with the human immunodeficiency virus (HIV). Since that time, there have been many reports discussing the occurrence and clinical manifestations of hepes zoster in HIV-infected patients. We describe the development of prolonged herpes zoster in a patient with acquired immunodeficiency syndrome (AIDS) over the course of 104 days. Viral isolates at the three different clinical stages of the skin lesions were sensitive in vitro to acyclovir, and supposed to be a same strain by polymerase chain reaction (PCR) analysis. We also discuss an effective treatment for prolonged cases of zoster.

Effect of long-term, low-dose acyclovir suppressive therapy on susceptibility to acyclovir and frequency of acyclovir resistance of herpes simplex virus type 2.

We have examined the susceptibility to acyclovir and frequency of acyclovir-resistant viruses in herpes simplex virus type (HSV) 2 clones isolated directly from genital lesions of 11 patients who had taken suppressive therapy (200 mg/day) for 1-9 years and 15 patients naive to acyclovir. Suppressive therapy significantly reduced the incidence of recurrence and the severity of the skin lesions. HSV samples from genital lesions were directly inoculated into Vero cells, and viral clones were isolated in the absence and presence of 10 microg/ml acyclovir. Five-hundred-and-ninety-two clones, isolated in the absence of acyclovir, were subjected to the acyclovir susceptibility test, and 155 clones isolated in the presence of acyclovir were analysed for the mechanisms of resistance to acyclovir. There were no significant differences in the susceptibility to acyclovir, the frequency of acyclovir-resistant virus and the ratio of thymidine kinase-deficient viruses in acyclovir-resistant viruses between the two groups. The frequency of acyclovir-resistant clones was about three per 10000 plaque forming units (PFU), and genital lesions contained up to 3x10(6) PFU of replicating virus in the specimens from the patients with genital herpes with or without acyclovir-suppressive therapy. Thus, the low dose of acyclovir suppressive therapy did not affect the susceptibility to acyclovir or increase the frequency of acyclovir-resistant viruses in the genital lesions.

Distinctive distribution of human papillomavirus type 16 and type 20 DNA in the tonsillar and the skin carcinomas of a patient with epidermodysplasia verruciformis.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by disseminated pityriasis versicolor-like or flat wart-like lesions and by the development of skin carcinomas. It is well established that specific cutaneous human papillomaviruses (EV-HPVs) are associated with both benign and malignant skin lesions in EV patients. However, little is known of the relationship between HPV and the mucosal lesions of EV patients. OBJECTIVES: To detect and identify HPV types associated with skin and mucosal lesions of an EV patient. PATIENT/METHODS: We investigated the skin carcinoma and the coexisting tonsillar carcinoma of a 41-year-old man with EV. Histopathologically, both lesions were squamous cell carcinomas. We analysed these two lesions by immunohistochemistry, in situ hybridization, and by molecular virology. RESULTS: Neither skin nor tonsillar lesions exhibited positivity for HPV capsid antigen by immunohistochemistry. By Southern blot hybridization, however, the skin carcinoma harboured 'EV-specific' HPV20 DNA, while the tonsillar carcinoma harboured 'genital' HPV16 DNA. In addition, in situ hybridization localized the respective viral DNA in the corresponding lesion. CONCLUSIONS: The results indicate that EV-HPV could be responsible for the development of the skin carcinoma, but not the mucosal carcinoma in this patient.

Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1.

Although it is well recognized that a peripheral vasculopathy may occur in patients with neurofibromatosis 1 (NF1), it is unclear whether cardiovascular abnormalities are more common. We reviewed the frequency of cardiovascular abnormalities, in particular, cardiovascular malformations (CVMs), among 2322 patients with definite NF1 in the National Neurofibromatosis Foundation International Database from 1991-98. Cardiovascular malformations were reported in 54/2322 (2.3%) of the NF1 patients, only 4 of whom had Watson syndrome or NF1-Noonan syndrome. There was a predominance of Class II "flow" defects [Clark, 1995: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. p 60-70] (43/54, 80%) among the NF1 patients with CVMs. Pulmonic stenosis, that was present in 25 NF1 patients, and aortic coarctation, that occurred in 5, constitute much larger proportions of all CVMs than expected. Of interest was the paucity of Class I conotruncal defects (2 patients with tetralogy of Fallot), and the absence of atrioventricular canal, anomalous pulmonary venous return, complex single ventricle and laterality defects. Besides the 54 patients with CVMs, there were 27 patients with other cardiac abnormalities (16 with murmur, 5 with mitral valve prolapse, 1 with intracardiac tumor, and 5 with electrocardiogram abnormalities). No patient in this study had hypertrophic cardiomyopathy. There were 16 patients who had a peripheral vascular abnormality without an intracardiac CVM, plus an additional 4 patients among those with a CVM who also had a peripheral vascular abnormality.

A case of pemphigus vulgaris successfully treated with single filtration plasmapheresis: a correlation of clinical disease activity with serum antibody levels.

We report a patient with pemphigus vulgaris (PV) successfully treated with single filtration plasmapheresis. A 40-year-old man with PV was started on therapy with prednisolone (PSL). Although the dosage of PSL was doubled, and both cyclosporin A (CyA) and pulse therapy were added, the disease was not controlled. After single filtration plasmapheresis began, most of the eroded lesions on the trunk reepithelialized. A switch to double filtration was followed by recurrence. Finally, additional treatments with single filtration plasmapheresis were required to obtain remission. To evaluate the efficacy of the treatment, circulating antibodies were measured by immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) using recombinant desmoglein (Dsg) 3. IIF titer and the ELISA scores correlated with the clinical disease activity. It is suggested that ELISA was more sensitive than IIF.

[Alphaherpesvininae--dermatology].

The subfamily alphaherpesuvirinae contains herpes simplex virus(HSV) and varicella-zoster virus(VZV) in the Dermatology. HSV infectious diseases are herpetic gingivostomatitis, herpes labialis, facial herpes simplex, Kaposi's varicelliform eruption, genital herpes, lumbosacral herpes simplex, and herpetic whitlow. The primary form of VZV infection is varicella, and the reactivation form is herpes zoster. These infectious diseases in the dermatological clinics usually occur in adult. In this paper we mention clinical manifestations and treatment.

Coexistence of psoriasis and linear IgA bullous dermatosis.

Linear IgA bullous dermatosis (LABD) is characterized by IgA autoantibodies against components of the basement membrane zone (BMZ). A 97-kDa protein is one of the major autoantigens associated with this disease. We report a 68-year-old man who developed LABD after a 3-year history of psoriasis and in the context of active hepatitis C virus infection. He had been treated with cyclosporin for psoriasis for about 9 months. Histologically, there was a subepidermal blister containing neutrophils and eosinophils with lymphocytes infiltrating predominantly in the dermis. Direct immunofluorescent staining showed linear IgA deposition at the BMZ. The patient's IgA autoantibodies bound exclusively to the epidermal side of 1 mol/L salt-split normal human skin. Immunoblot analysis identified a 97-kDa autoantigen in epidermal extracts. This appears to be the first case of LABD with IgA autoantibodies against a 97-kDa autoantigen, associated with psoriasis and hepatitis C virus infection.

The characteristics of nocturnal scratching in adults with atopic dermatitis.

Patients with atopic dermatitis (AD) are known to suffer from nocturnal itch, and the resultant scratching may worsen the skin lesions. We observed nocturnal scratching for 112 nights in 35 adult patients with AD, using an infrared video camera system. To quantify the amount of scratching, we counted scratching bouts lasting more than 5 s and calculated the duration of all the scratching bouts (total scratching time, TST). The percentage of TST in the total recording time (TST%) was used as an index of nocturnal scratching. Mean +/- SD TST% was 14.3 +/- 13.9 for patients with severe AD, 6.2 +/- 3.7 for those with moderate AD and 0.7 +/- 0.4 for those with mild AD. The higher TST% in the severely affected group was attributed mainly to a longer duration rather than a higher frequency of bouts. Patients scratched more in the first third of the night than in the later two-thirds. Both the group of patients whose disease distribution pattern was generalized and those who showed a head-neck-shoulder type distribution scratched their heads, faces and necks for longer than other parts of the body. Repeated measurement performed on individual subjects resulted in a similar TST% when there was little change in skin lesions. TST% reduced by 15 +/- 21% when the patients showed marked improvement. The measurement of nocturnal scratching helps to evaluate the severity of itch in AD. In addition, the infrared video successfully detected the location and nature of nocturnal scratching in AD.

Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1.

Five percent of individuals with neurofibromatosis type 1 (NF1) present with congenital long bone pseudarthrosis (PA). In large series, 50-80% of patients with congenital long bone PA also have NF1. Very little information exists on the natural history and pathogenesis of PA in NF1. This report is a descriptive analysis of a large series of patients with NF1 and tibial bowing or PA. Study A is a case-control study using the National Neurofibromatosis Foundation International Database (NNFFID). Eighty-five patients with PA were compared to a control group from the same database. There was a statistically significant male predominance of NF1 cases with PA (54 males to 31 females), compared to controls (85 males to 87 females) (chi2 = 4.0, P = 0.046, using a two-tailed test with Yates' correction). There was no significant difference in the clinical presentation of NF1 manifestations in NF1 patients with PA than in NF1 patients without PA. Of the affected individuals with PA, there were 24 de novo cases and 21 familial cases (9 through maternal and 12 through paternal inheritance). Questions that could not be answered by Study A were addressed by a partially overlapping case-series report, Study B, in which data on 75 cases ascertained through questionnaires completed by NF center directors were collected. From Study B we determined that half of the patients who had a fracture sustained it before age 2, and approximately 16% of the pseudarthrosis patients had an amputation. Our data indicate a male predominance and no parent-of-origin effect. Male gender may be a susceptibility factor for pseudarthrosis in NF1.

Paget's disease arising near a male areola without an underlying carcinoma.

We report a 56-year-old man with Paget's disease occurring near the left areola without any underlying breast carcinoma. Histologically, there was no evidence suggesting continuity with a lactiferous duct, accessory breast, or microscopic gynecomastia. We review previous case reports of Paget's disease occurring in unusual sites and discuss their nomenclature from the histogenetic point of view.