M. Casado

Activation of High‐Affinity Uptake of Glutamate by Phorbol Esters in Primary Glial Cell Cultures

The effects of 12‐O‐tetradecanoylphorbol 13‐acetate (TPA), a potent activator of protein kinase C, on high‐affinity Na+‐dependent glutamate transport were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with TPA led to concentration‐ and time‐dependent increases in the glutamate transport that could be completely suppressed by the addition of the protein kinase C (PKC) inhibitor 1‐(5‐isoquinolinylsulfonyl)‐2‐methylpiperazine. The TPA effects could be mimicked by oleoylacetylglycerol and by the diacylglycerol kinase inhibitor R59022. The effects of TPA were potentiated by the Ca2+ ionophore A23187. Under the chosen experimental conditions TPA had no effect on glutamate transport in neurons. We conclude that PKC activates the sodium‐dependent high‐affinity glutamate transport in glial cells and that it has dissimilar effects on neurons and glial cells.

Postmenopausal frontal fibrosing alopecia

Recently a new entity, postmenopausal frontal fibrosing alopecia, was added to the established subtypes of scarring alopecias affecting postmenopausal women. This condition is characterized by a progressive frontal hairline recession associated with scarring. We studied the clinical and histopathologic features in four women with this disorder. Of note, a history of bilateral oophorectomy in two of them appears to be a new association. All four cases had frontoparietal recession of the hairline and two of them also had loss of their eyebrows. None of our four patients had any mucous membrane or other skin lesions. Histological examination showed perifollicular fibrosis and lymphocytic inflammation around the isthmus and infundibular areas of the follicles. No effective treatments have emerged for this type of postmenopausal alopecia, but progression of the hair loss and scarring appears to be self‐limiting. We believe that this condition is a distinct clinicopathological variant of lichen planopilaris.

High incidence of porokeratosis in renal transplant recipients

Immunosuppression is a well–documented precipitant of porokeratosis (PK). However, PK is not considered among the most common cutaneous disorders in immunosuppressed patients. We studied prospectively a series of 103 renal transplant patients and found 11 cases (10.68%) of PK. Our series represents the highest incidence of PK in transplant patients reported so far. Our findings suggest that PK in transplant recipients may be more frequent than previously thought.

Toenail onychomycosis in patients with acquired immune deficiency syndrome: treatment with terbinafine

Skin infections caused by dermatophytes are one of the most frequent dermatological complications in patients with acquired immunodeficiency syndrome (AIDS) resulting from infection with human immunodeficiency virus (HIV). Tinea unguium associated with AIDS is characterized by being clinically more aggressive and therapeutically more difficult to treat than in the general population. Terbinafine is considered to be a first‐choice option for the treatment of dermatophyte onychomycosis in immunocompetent individuals. This drug has been used in a series of 21 HIV‐positive patients diagnosed with tinea unguium for 1 year in the University Hospital La Paz, Madrid. All patients underwent a subsequent clinical follow‐up for 6 months. The results showed a high percentage of clinical and mycological cures, as well as maintenance of the response after follow‐up; no drug interactions or significant adverse effects related to the drug under study were recorded.

Successful treatment of aphthous ulcerations in AIDS patients using topical granulocyte-macrophage colony-stimulating factor.

Oral recurrent aphthous ulceration (RAU) is a well‐recognized complication in patients infected with human immunodeficiency virus. RAU can be progressive and destructive, causing dysphagia and secondary malnutrition. The aetiology of RAU remains unknown, and its response to available treatments is often unsatisfactory. We describe three patients with advanced AIDS who suffered from extensive RAU which failed to respond to several treatments, including topical viscous lidocaine and topical and systemic glucocorticoids. Owing to difficulties in using thalidomide (two patients had neurological conditions which precluded thalidomide use), all three patients were treated with an oral solution containing recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF, 400 μg in 5% glucose 200 mL). From the first application, all three patients showed significant improvement of their lesions and amelioration of pain, and they were completely cured in a few days. No adverse effects were recorded. The patients did not show relapses of RAU over a prolonged follow‐up. Controlled trials are warranted in order to establish the role of GM‐CSF as a valid, alternative option for aphthous ulcerations of the mouth in AIDS patients in whom corticosteroids or thalidomide are not suitable.

Destructive herpetic whitlow in AIDS : report of three cases

Summary Herpes simplex virus infection in immunocompromised individuals, including AIDS patients, is characterized by its tendency for atypical presentations and unusual locations, often resulting in delayed diagnosis and treatment. Three HIV‐infected patients who developed prolonged cutaneous lesions of the fingers are presented. These lesions were unmodified by previous antibiotic treatment, and rapidly progressed to the complete destruction of nail structures in two patients. Viral culture confirmed the diagnosis of herpetic whitlow in all cases, and treatment with oral aciclovir resulted in complete recovery. Surgical treatment was not necessary.

A Customized Pigmentation SNP Array Identifies a Novel SNP Associated with Melanoma Predisposition in the SLC45A2 Gene

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.

Extramedullary plasmacytoma and AIDS-related Kaposi's sarcoma

ities. They raise the possibility of a true association of urticaria pigmentosa either with a specific but variable Nager-like syndrome or with a community of syndromes with anomalies of the face, ears, and digits. Alternatively, urticaria pigmentosa may be a part of the Nager syndrome itself that has previously gone unrecognized. Finally, the possibility of a fortuitous association cannot be ignored.

ERYTHEMA ELEVATUM DIUTINUM AFTER LIVER TRANSPLANTATION: DISAPPEARANCE OF THE LESIONS ASSOCIATED WITH A REDUCTION IN CYCLOSPORIN DOSAGE

When Drs. Esterly and Enjolras talk about hemangiomas, they usually mean the problematic ones. When I talk about hemangiomas, I mainly mean the “harmless” superficial ones, and, in this group, mainly the singular elevated hemangiomas with a regular circumference, because they represent 80% of all hemangiomas (in my opinion). These hemangiomas are mostly harmless for us doctors, but are they really that harmless for the children and their parents? They are very annoying when located in the facial area (54%), and they tend to ulcerate when located in the anal-genital area (4%). If we have a therapy at hand which takes 10 seconds, can be done without anesthesia, and does not have any side effects, why should we not help these children and their parents? In 875 cases which were treated by contact surgery, I have only seen the development of scars in three cases, and all three cases did not belong to the group of singular elevated hemangioma with a regular circumference, but were telangiectatic patches. If treatment were necessary at all, they should have been treated by pulsed dye laser. Treating singular elevated hemangiomas with a regular circumference by contact surgery, especially when they are still small, is relatively easy. It is neither spectacular nor life saving, but it saves the parents and children a lot of grief. Of course, it has to be done properly. That means not using a spray (sprays often cause ulcerations) but using a metal stick which is cooled by liquid nitrogen until it has reached a temperature of -196°C. Contact surgery does not need to be done in a famous center, which is probably one of the reasons why the big names are not very interested. And rightly so, because this leaves more time for them to care for the rare, complicated, and serious cases. But this does not mean that therapy for the overwhelming number of “harmless” hemangiomas should be neglected.

Cutaneous calcinosis with transepithelial elimination in a patient with sarcoidosis.

A 44‐year‐old man who had worked as a plumber and was currently working as a bricklayer was referred to our hospital because of a 2‐year history of progressive dyspnea. Physical examination revealed cyanosis, clubbing of the fingers, and edema of the inferior extremities. Chest auscultation revealed bilateral inspiratory crackles predominantly at the lung bases. Remarkably, there were several painful, firm papules and nodular lesions over the fingertips of the hands, some with whitish crusts (Fig. 1). These lesions had appeared 2 years before and gradually increased in number and size.