Novel uses of laser therapy in Goltz syndrome.

Goltz syndrome is an X-linked dominant, multisystem birth defect due to PORCN mutation. The skin findings follow Blaschko's lines and often show epidermal atrophy and herniation of subcutaneous fatty tissue. Regarding treatment, light sources can offer a good therapeutic option for some manifestations of this rare disease and improve the aesthetic appearance of the skin lesions. We report two new cases of Goltz syndrome in which the cutaneous findings remarkably improved with pulsed dye laser and carbon dioxide laser.

Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2.

Hyperinsulinemic hypoglycemia (HI) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders. The co-occurrence of these disorders (HIPKD) in 17 children from 11 unrelated families suggested an unrecognized genetic disorder. Whole-genome linkage analysis in five informative families identified a single significant locus on chromosome 16p13.2 (logarithm of odds score 6.5). Sequencing of the coding regions of all linked genes failed to identify biallelic mutations. Instead, we found in all patients a promoter mutation (c.-167G>T) in the phosphomannomutase 2 gene (PMM2), either homozygous or in trans with PMM2 coding mutations. PMM2 encodes a key enzyme in N-glycosylation. Abnormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancreatic ß cells altered insulin secretion. Recessive coding mutations in PMM2 cause congenital disorder of glycosylation type 1a (CDG1A), a devastating multisystem disorder with prominent neurologic involvement. Yet our patients did not exhibit the typical clinical or diagnostic features of CDG1A. In vitro, the PMM2 promoter mutation associated with decreased transcriptional activity in patient kidney cells and impaired binding of the transcription factor ZNF143. In silico analysis suggested an important role of ZNF143 for the formation of a chromatin loop including PMM2 We propose that the PMM2 promoter mutation alters tissue-specific chromatin loop formation, with consequent organ-specific deficiency of PMM2 leading to the restricted phenotype of HIPKD. Our findings extend the spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 pleiotropy.

Effects of fungal inocula and habitat conditions on alder and eucalyptus leaf litter decomposition in streams of northern Spain.

We investigated how fungal decomposer (aquatic hyphomycetes) communities colonizing alder and eucalyptus leaf litter respond to changes in habitat characteristics (transplantation experiment). We examined the breakdown of leaf materials and the associated fungal communities at two contrasting sites, a headwater stream (H) and a midreach (M). Agroforestry increased from headwater to midreach. One month after the start of experiments at both sites, some leaf samples from the midreach site were transplanted to the headwater site (M-H treatment). Although both sites showed similar dissolved inorganic nutrient concentrations, eucalyptus leaves initially incubated at the midreach site (M, M-H) increased their breakdown rate compared to those incubated along the experiment at the headwater site (H). Alder breakdown rate was not enhanced, suggesting that their consumption was not limited by nutrient availability. Sporulation rates clearly differed between leaf types (alder > eucalyptus) and streams (H > M), but no transplantation effect was detected. When comparing conidial assemblages after transplantation, an inoculum effect (persistence of early colonizing species) was clear in both leaf species. Substrate preference and shifts in the relative importance of some fungal species along the process were also observed. Overall, our results support the determining role of the initial conditioning phase on the whole litter breakdown process, highlighting the importance of intrinsic leaf characteristics and those of the incubation habitat.

An immunohistochemical study of verrucous hemangiomas.

BACKGROUND: According to the International Society for the study of vascular Anomalies, vascular anomalies are classified as vascular neoplasms and vascular malformations. In some vascular lesions, categorization as a neoplasm or malformation has not been established with confidence so far. In order to further clarify the nosology of verrucous hemangioma, we studied 13 cases. OBJECTIVE: To analyze immunohistochemical characteristics of verrucous hemangiomas in order to gain further insight in its histogenesis. METHODS: We carried out a retrospective review. Immunohistochemical expression for Wilms tumor 1 (WT1), Glut-1 and D2-40 was performed in 13 cases. RESULTS: Immunohistochemistry performed with Glut-1 and WT1 showed positive staining in all lesions. All verrucous hemangiomas lacked D2-40 immunostaining. CONCLUSIONS: This is the first report in the literature investigating WT1 in verrucous hemangioma in order to further clarify the nosology of this vascular anomaly. Despite the clinical features of verrucous hemangioma, which are similar to those seen in vascular malformations, verrucous hemangioma exhibited an immunoprofile similar to vascular neoplasms, according to WT1 and Glut-1 positivity.

Circulating kisspeptin levels exhibit sexual dimorphism in adults, are increased in obese prepubertal girls and do not suffer modifications in girls with idiopathic central precocious puberty.

The system KISS1-KISS1R is one of the main regulators of the hypothalamic-pituitary-gonadal axis and constitutes a link between metabolism and reproduction through its interaction with leptin. The aim of this study was to clarify the possible utility of kisspeptin as a pubertal marker and/or the possible influence of nutritional status in kisspeptin levels. To this end, we have studied kisspeptin plasma levels throughout sexual development and in prepubertal obese girls and girls affected by idiopathic central precocious puberty (CPP). Plasma kisspeptin concentrations were analyzed by RIA. An increase in kisspeptin levels was observed in adult females compared to healthy prepubertal and pubertal girls (p<0.001) and to adult males (p<0.001). Additionally, kisspeptin was increased in prepubertal obese girls compared to healthy prepubertal girls (p<0.01) and girls with idiopathic CPP (p<0.05). As revealed by the regression analysis, in prepubertal healthy and obese girls and girls with idiopathic CCP, the parameters that influenced kisspeptin levels were BMI (R(2)=0.10, p<0.05) and leptin levels (R(2)=0.14, p<0.01). In conclusion, kisspeptin levels do not seem to be a good pubertal marker. The results obtained in prepubertal and idiopathic CCP girls point to a relationship between leptin, BMI and kisspeptin at least in this group, and suggest a possible role for adipose tissue in the modulation kisspeptin synthesis.

Identification of a Gypsy SHOX mutation (p.A170P) in Léri-Weill dyschondrosteosis and Langer mesomelic dysplasia.

We report the clinical and molecular characteristics of 12 Spanish families with multiple members affected with Léri-Weill dyschondrosteosis (LWD) or Langer mesomelic dysplasia (LMD), who present the SHOX (short stature homeobox gene) mutation p.A170P (c.508G>C) in heterozygosity or homozygosity, respectively. In all studied families, the A170P mutation co-segregated with the fully penetrant phenotype of mesomelic limb shortening and Madelung deformity. A shared haplotype around SHOX was observed by microsatellite analysis, confirming the presence of a common ancestor, probably of Gypsy origin, as 11 of the families were of this ethnic group. Mutation screening in 359 Eastern-European Gypsies failed to identify any carriers. For the first time, we have shown SHOX expression in the human growth plate of a 22-week LMD fetus, homozygous for the A170P mutation. Although the mutant SHOX protein was expressed in all zones of the growth plate, the chondrocyte columns in the proliferative zone were disorganized with the chondrocytes occurring in smaller columnal clusters. We have also identified a novel mutation at the same residue, c. 509C>A (p.A170D), in two unrelated Spanish LWD families, which similar to A170P mutation impedes nuclear localization of SHOX. In conclusion, we have identified A170P as the first frequent SHOX mutation in Gypsy LWD and LMD individuals.

Leukonychia totalis associated with multiple pilar cysts: report of a five-generation family: FLOTCH syndrome?

The association of familial totalis leukonychia with multiple pilar cysts is a rare condition that could represent a separate syndromic entity. Since Bauer described a family with totalis leukonychia and sebaceous cysts in 1920, only four new affected families have been reported. We report a five-generation family with a total leukonychia and multiple pilar cysts on the scalp. The hypothesis of a deficiency of a gene regulating the structure of keratin has been postulated but the exact genetic mechanism has not been yet determined. In our family, no other keratinizing structures were involved.

Capillary-lymphatic malformation, kaposiform hemangioendothelioma and delayed Kasabach-Merritt phenomenon.

According to International Society for the Study of Vascular Anomalies classification, vascular anomalies are mainly divided into two groups: vascular tumors and vascular malformations. Nevertheless, a small group of patients present clinical and/or histopathologic overlapping features. We report a case of a 4-month-old boy that presented a vascular lesion on his right buttock with involvement of abdominal wall muscles, abdominal cavity and drainage to primitive iliac by a tortuous drainage vein. Surgery was performed and histopathology demonstrated a combined vascular malformation. Six months later he developed a thrombocytopenia and repeat magnetic resonance imaging revealed a new solid mass involving the majority of the abdominal cavity. At 18 months of age the patient developed a Kasabach-Merrit phenomenon and treatment with vincristine, interferon and then acetyl-salicilic acid and dypiridamol was started. No response in platelet counts was obtained and one more surgery was perfomed. On this occasion a histopathologic study revealed vascular malformation areas intermingled with areas of kaposiform hemangioendothelioma. This patient demonstrates the Kasabach-Merritt phenomenon with kaposiform hemangioendothelioma arising within a pre-existing combined vascular malformation.

Variants of milia successfully treated with CO(2) laser vaporization.

BACKGROUND: Milia are a usual consultation in dermatologic practice and optimal treatment modalities are not established. OBJECTIVE: To evaluate the efficacy and the safety of CO(2) laser vaporization in the treatment of milia. METHODS: We report four patients, aged from 12 to 50 years old, with different variants of milia: milia en plaque, milia post-photodermatitis, multiple eruptive milia and milia post-trauma. They were treated with the CO(2) laser in superpulsed and focused mode at 2 W/cm(2), with two passes in each session. The follow-up was 12-36 months. RESULTS: All patients showed marked improvement after a few sessions of CO(2) laser. No-one had recurrence or noticeable side effects. CONCLUSION: The CO(2) laser is an option in adult and child patients with multiple milia lesions or milia en plaque, obtaining good cosmetic results with minimal side effects.

Keratosis pilaris atrophicans: treatment with intense pulsed light in four patients.

BACKGROUND: Keratosis pilaris atrophicans (KPA) is a group of disorders characterized by erythematous keratotic papules followed by atrophy on the face. The treatment is often unsatisfactory. METHODS: Four white women, with ages ranging from 14 to 20 years, were treated with an intense pulsed light (IPL) system with a cut filter of 570 nm. The power density was between 40 and 47 J/cm(2), divided into two pulses of 3 ms, with a delay between both of 20 ms. Patients received five to nine sessions. RESULTS: Clinical improvement was noted in all patients, with a reduction of erythema in treated areas of between 75% and 100%. Treatment was well tolerated and no adverse reactions were observed. After a follow-up of 10 months no recurrence was observed. In addition, in parallel mode to erythema improvement, a reduction of roughness was observed. CONCLUSION: Our results suggest IPL should be considered as a safe treatment option in patients with KPA.

Arteriovenous haemangioma in liver disease. Treatment with carbon dioxide laser vaporization in five cases.

BACKGROUND: Arteriovenous haemangioma (AVH) is considered a rare, benign, acquired, cutaneous tumour of vascular origin. Recently, a variant associated with chronic hepatic disease has been described. The usual treatment is surgical resection but no other treatments have been reported. OBJECTIVE: To evaluate the results obtained in the treatment of AVH with carbon dioxide laser vaporization. METHODS: Every patient with AVH related to chronic hepatic disease treated in the laser unit was reviewed. Five patients were treated with carbon dioxide laser vaporization. The first pass of treatment was performed in defocused mode at 2 W/cm(2). After this, several passes were performed in order to clear the entire lesion. One session of treatment was necessary for three patients, and the other two patients needed two sessions. RESULTS: The tumoral mass as well as the pulse disappeared in all lesions; total clearance was obtained in four of the five cases. In the postoperative time, no bleeding or haemorrhage were observed. No significant secondary effects of treatment were present. The cosmetic outcome was excellent in all cases. CONCLUSION: Carbon dioxide laser vaporization may be an alternative treatment for cases of AVH in chronic hepatic disease: the procedure is easy and with good cosmetic outcome.

Actinic cheilitis: evolution to squamous cell carcinoma after carbon dioxide laser vaporization. A study of 43 cases.

BACKGROUND: Actinic cheilitis (AC) is a precancerous lesion of the lip. Treatment of AC is indicated for prevention of squamous cell carcinoma (SCC), although the exact transition rate of AC to SCC is unknown. Carbon dioxide (CO(2)) laser vaporization seems to be an adequate therapy for AC, but there are no references about the evolution rate of AC to SCC after this treatment. OBJECTIVE: To evaluate the results obtained after treatment of AC by CO(2) laser vaporization in comparison with other treatment modalities and the evolution rate of AC to SCC after CO(2) laser treatment. METHODS: A retrospective review identified 43 patients with AC treated with CO(2) laser vaporization at our hospital from 2002 to 2006. Clinical and therapeutic information was evaluated. All patients were followed for more than 15 months after treatment. RESULTS: After a mean follow-up period of 29.4 months, 3/43 treated AC showed local recurrence. Another two patients developed SCC in the treated field. A residual scar was clinically evident in two patients. CONCLUSIONS: CO(2) laser vaporization with an adequate postoperative follow-up is an effective treatment for chronic AC. Nevertheless, some patients (4,6%) went on to develop lip SCC. The follow-up of these patients is mandatory.

Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism.

OBJECTIVE: To determine the influence of gestational age and fetal growth restriction on the cord blood adipokine profile, IGF1, and ghrelin levels, and their relationship with glucose metabolism. STUDY DESIGN: One hundred and ninety newborns (99 preterm and 91 full term) were studied and, according to their anthropometry at birth, classified as small (SGA) or adequate for gestational age (AGA). METHODS: Venous cord blood serum levels of IGF1, IGF binding protein 3 (IGFBP-3), adiponectin, resistin, leptin, soluble leptin receptor (sOB-R), tumoral necrosis factor-alpha, interleukin 6 (IL-6), total ghrelin, and acylated ghrelin were determined and compared between preterm and full-term, as well as between SGA and AGA, newborns. Correlations with newborn weight, gestational age, and homeostatic model assessment (HOMA) index, as an index of insulin resistance, were determined. RESULTS: Preterm newborns had higher HOMA, sOB-R, resistin, and IL-6 and lower IGF1, IGFBP-3, leptin, and adiponectin levels than full-term newborns. SGA had lower IGF1, IGFBP-3, leptin, IL-6, and adiponectin and higher sOB-R and total ghrelin than AGA newborns. Adiponectin and HOMA showed independent positive and negative correlations with gestational age respectively, but not with neonatal weight. Birth weight was correlated positively with IGF1 and leptin levels and negatively with total ghrelin ones. CONCLUSIONS: Our findings suggest that the lack of proper acquisition of adipose tissue by the fetus either due to prematurity or to fetal growth restriction is associated with changes in the cord blood adipokine profile that may contribute to the impairment of glucose metabolism.

Venous malformations with lip involvement: palliative treatment with carbon dioxide laser vaporization in five cases.

BACKGROUND: The treatment of venous malformations remains controversial. Traditional surgical excision is only possible in a few cases. Numerous sclerosing agents have been used, but none of them are ideal or absolutely safe for the treatment of venous disorders. In isolated cases, an expectative control would be a good option. OBJECTIVE: To report our experience with CO(2) laser vaporization as palliative treatment in five cases of head and neck venous malformations with lip involvement. METHODS: Five patients were treated with a CO(2) laser in superpulsed, focused mode at 2 W/cm(2), with several passes in each session. Patients were aged from 16 to 49 years old (mean: 36.6 years). Three sessions of treatment were performed in two patients while only one session was used in the rest. The follow-up was 6-36 months (mean: 22.8 months). RESULTS: Significant cosmetic improvement with flattening of the lip surface was achieved in all patients. CONCLUSION: Carbon dioxide laser vaporization can be considered as one method of choice for an effective palliative treatment of lip involvement in venous malformations.