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PubMed2006

A prospective study of upper aerodigestive tract manifestations of mucous membrane pemphigoid.

We conducted a prospective study between 1995 and 2002 to investigate nose and throat (NT) manifestations of mucous membrane pemphigoid (MMP). One hundred ten consecutive patients with clinical, histologic, and immunologic criteria of MMP were seen in 2 referral centers for bullous diseases. They were systematically asked about the existence of persistent NT symptoms. Patients who had any were examined with a flexible nasopharyngolaryngoscope by the same otorhinolaryngologist. When possible, NT mucous membrane (MM) biopsies were taken for direct immunofluorescence (IF) assays to determine lesion specificity. Thirty-eight (35%) patients (23 F/15 M; mean age, 58.5 yr) had the following NT symptoms: 35 (92%) nasal, 19 (50%) pharyngeal, and 10 (26%) laryngeal. Five (13%) had acute dyspnea. Thirty-three (87%) of the 38 symptomatic patients had lesions at physical examination: 30 (79%) nasal, 6 (16%) pharyngeal, and 19 (50%) laryngeal. Laryngeal involvement was asymptomatic in 11 patients. Lesions were mainly atrophic rhinitis and oropharyngeal and epiglottal erosions. Nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 (18%) patients, causing the death of 3. Direct IF showed malpighian epithelium associated with linear immune deposits (IgG, IgA, or C3) along the chorioepithelial junction in all 18 biopsies performed, including those of 4 symptomatic patients without lesions at physical examination. The presence of severe ophthalmologic lesions (p = 0.02) and > or =3 sites involved other than NT (p = 0.02) were predictive of laryngeal involvement. In contrast, laryngeal symptoms, disease duration, HLA DQB1*0301, and smoking were not significantly associated with laryngeal lesions. In conclusion, at least 35% of MMP patients had NT involvement. Atrophic rhinitis was the most frequent lesion. The most severe were the laryngeal lesions that were significantly associated with severe ocular involvement and disseminated disease, and could be fatal. Our results highlight the necessity of a multidisciplinary approach to MMP management to assure early diagnosis of NT involvement, to guide therapeutic choices, and to improve patient survival and functional outcomes.

Adolescent↗

PubMed2005

A volumetric analysis of soft-tissue changes in the aging midface using high-resolution MRI: implications for facial rejuvenation.

BACKGROUND: The present study evaluated volumetric changes in the aging midface. Both young and old living subjects were studied using high-resolution magnetic resonance imaging (MRI) to investigate the distribution and volume of the muscle and subcutaneous components of the midface. METHODS: MRI with a customized radiofrequency coil was performed in 20 healthy Caucasian female volunteers equally divided between young (16 to 30 years) and old (>59 years) age groups. Sagittal oblique images were obtained at 1-mm intervals through the midface, perpendicular to the nasolabial fold. Quantitative analyses of the cheek fat pad overlying the levator labii superioris and zygomaticus major muscles were performed separately. RESULTS: For both mimetic muscles, there were no significant differences between young and old subjects in muscle length, thickness, or volume from muscle origin to nasolabial fold. In addition, there were no significant differences between age groups in fatty infiltration of the muscles. The volumes of the medial and lateral aspects of the cheek fat pad were significantly greater in old than in young subjects (p < 0.05). In young subjects the greatest distribution of fat pad volume was found in the middle third of the cheek mass. There was a significant reduction in that portion of the fat pad distributed in the upper third and a further reduction in the lower third (p < 0.01). In old subjects, because of the increased distribution of fat in the upper third of the cheek fat pad, there was no significant difference in volume between the upper and middle thirds of the cheek fat pad. The percentage increase in fat in the upper third relative to the remainder of the midface was significantly greater in old compared with young subjects (p < 0.01). In contrast, the volume of the lower third of the midface was not significantly different between young and old subjects. CONCLUSIONS: The present study indicates that ptosis alone does not account for the changes observed in the aging midface. Selective hypertrophy of the upper portion of the cheek fat pad was also observed. The mimetic muscles, on the other hand, showed no significant differences with aging. To attain maximum precision in facial rejuvenation, these data suggest that after suspension of the ptotic cheek fat pad, each patient should be evaluated for excess bulk in the upper portion of the cheek fat pad. If excess bulk is present, patients may benefit further from selective reduction directed to the upper portion of the cheek fat pad, remaining superficial to the mimetic muscles of the face.

Adipose Tissue↗

PubMed2005

Experimental heatstroke in baboon: analysis of the systemic inflammatory response.

The objective of this study was to analyze the pattern of the inflammatory response to heatstroke in an experimental baboon model with a view to identifying potential target for therapeutic interventions. Blinded analysis of plasma collected from 12 juvenile baboons (Papio hamadryas) in heatstroke was used. Eight anesthetized animals were heat-stressed in an incubator at 44 degrees C to 47 degrees C until rectal temperature was 42.5 degrees C (moderate heatstroke; n = 4) or systolic arterial pressure fell to <90 mmHg (severe heatstroke; n = 4) and were allowed to recover at room temperature. Four sham-heated animals served as a control group. We performed sequential measurement of cytokines. The rectal temperature on completion of heat stress was 42.5 degrees C +/- 0.0 degrees C and 43.3 degrees C +/- 0.1 degrees C in moderate and severe heatstroke, respectively. Heat stress elicited early, simultaneous release of anti-inflammatory cytokines and chemokines (IL-10, IL-1ra, sTNFr I and II, and IL-8). Circulating levels of IL-12p40 were significantly decreased, whereas TNFalpha, IL-1beta, and IL-4 were below the detection limit in all animals. No baboon survived severe heatstroke; there was neurological morbidity without mortality in moderate heatstroke. Nonsurvivors displayed significantly greater activity/alterations in inflammation markers than survivors. Sham-heated animals had no evidence of inflammation activation. These results show that heatstroke activates complex systemic inflammatory and regulatory responses associated with outcome. Further definition of this ambivalent response is needed before identification of target of successful modulation may become possible.

Animals↗

PubMed2004

Renal-transplant recipients and sun protection.

BACKGROUND: The incidence of skin carcinomas in organ-transplant recipients is high. The main factors implicated in carcinogenesis are immune suppression and ultraviolet radiation. Only the second is avoidable. We have evaluated knowledge of and compliance with sun protection measures among renal-transplant recipients (RTR). METHODS: A survey by means of a questionnaire including questions about clinical data, knowledge of, and compliance with sun protection was given. The questionnaire was given to 520 consecutive RTR followed up in a single center, and 445 (86%) answered. RESULTS: Of the responders, 91% have been informed of the need for sun protection, in 80% of cases by dermatologists. Sixty-eight percent used more protective measures abroad than at home, 63% avoided going outside during the hottest midday hours, 63% used sunscreen regularly, but 46% used one or less tube of sunscreen a year. A hat was always worn in the sun by 35% and long sleeves by 36%. Women and fair-skinned individuals complied better with protective measures. A minority of patients knew that ultraviolet radiation carries a risk of skin cancer. CONCLUSIONS: This survey shows that most RTR are aware of the need for sun protection, but only a minority take adequate protection measures. The better results observed in this study than in previous published investigations may be caused by the great involvement of dermatologists in the care of RTR in our institution. The results of this survey underline the need to inform RTR better about sun-protection measures and the importance of cooperation between transplant physicians and dermatologists.

Clothing↗

PubMed2005

Cutaneous adverse events in renal transplant recipients receiving sirolimus-based therapy.

BACKGROUND: Sirolimus is an immunosuppressive drug recently developed for organ transplantation. Its mechanism of action, independent of calcineurin, is different from that of cyclosporine and tacrolimus, two calcineurin inhibitors (CIs). Because the toxicity of CIs is partly the result of calcineurin blockade, sirolimus exhibits a different toxicity profile. In this study, we evaluated the profile, frequency, and severity of cutaneous adverse events in renal transplant recipients receiving sirolimus-based therapy. PATIENTS AND METHODS: A systematic and in-depth evaluation of skin, mucous membranes, nails, and hair was performed in 80 renal transplant recipients receiving sirolimus-based therapy. The mean duration of the graft was 6 years and of sirolimus treatment was 18 months. Mycophenolate mofetil and steroids were combined with sirolimus for 74 patients. Sirolimus was used as first immunosuppressive therapy for 36 patients, and 44 patients were switched from CIs to sirolimus. RESULTS: Seventy-nine patients (99%) experienced cutaneous adverse events. Twenty patients (25%) demonstrated serious adverse events, and six patients (7%) stopped sirolimus during the 3 months after the study because of cutaneous events. The most frequent of these were pilosebaceous apparatus involvement, including acne-like eruptions (46%), scalp folliculitis (26%), and hidradenitis suppurativa (12%); edematous complaints, including chronic edemas (55%) and angioedema (15%); mucous membrane disorders, including aphthous ulceration (60%), epistaxis (60%), chronic gingivitis (20%), and chronic fissure of the lips (11%); and last, nail disorders including chronic onychopathy (74%) and periungual infections (16%). CONCLUSIONS: Skin disorders are frequent in renal transplant recipients receiving sirolimus as a long-term therapy. Despite the usually mild nature of skin events, they are often the reason for stopping sirolimus.

Adult↗

PubMed2001

Genotypes of JC virus in East, Central and Southwest Europe.

Distinctive genotypes of JC virus have been described for the major continental landmasses. Studies on European-Americans and small cohorts in Europe showed predominantly Type 1. Types 2 and 7 are found in Asia, and Types 3 and 6 in Africa. These genotypes differ in sequence by about 1--3%. Each genotype may have several subtypes which differ from each other by about 0.5--1%. The genotypes can be defined by a distinctive pattern of nucleotides in a typing region of the VP1 gene. This genotyping approach has been confirmed by phylogenetic reconstruction using the entire genome exclusive of the rearranging regulatory region. In this first large European study, we report on the urinary excretion of JCV DNA of 350 individuals from Poland, Hungary, Germany and Spain. We included Gypsy cohorts in Hungary (Roma), Germany (Sinti), and Spain (Gitano), as well as Basques in Spain. We show that while Type 1 predominates in Europe, the proportions of Type 1A and 1B may differ from East to Southwest Europe. Type 4, closely related to the Type 1 sequence (only approximately 1% difference) was a minor genotype in Germany, Poland and Spain, but represented the majority in Basques. The Gitanos in Spain showed a variant Type 4 sequence termed 'Rom-1'. Interestingly, neither the Gitanos in Spain, nor Sinti or Roma in Germany or Hungary showed the Type 2 or Type 7 genotype that might be expected if their origins were in an Asian population.

Adolescent↗

PubMed1988

Role of the oocyte nucleus in determination of the dorsoventral polarity of Drosophila as revealed by molecular analysis of the K10 gene.

In Drosophila, the establishment of dorsoventral polarity of the developing embryo depends on the expression of at least 11 maternally acting genes. Mutant females that lack any of these gene activities produce normally shaped eggs that develop into dorsalized embryos. The female sterile K10 mutation differs from these mutants, because in addition to the dorsalized development of the embryo, it causes a dorsalization of the egg shape. During oogenesis, the K10 gene is specifically expressed in the oocyte. Antibodies raised against a beta-galactosidase-K10 fusion protein were used to visualize the K10 product in ovaries by indirect immunofluorescence. The protein, which contains a putative DNA recognition helix, accumulates in the nucleus of the oocyte, where it is assumed to have a regulatory function. Our results thus indicate that the controlled expression of some of the genes of the oocyte nucleus is essential for the determination of the dorsoventral polarity of the oocyte and possibility of the developing embryo.

Amino Acid Sequence↗

PubMed1987