Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families.

Inherited mutations in components of desmosomes result in a spectrum of syndromes characterized by variable abnormalities in the skin and its appendages, including blisters and erosions, palmoplantar hyperkeratosis, woolly hair or hypotrichosis and, in some cases, extracutaneous features such as cardiomyopathy. We investigated the molecular basis of two Brazilian patients presenting with clinical features consistent with ectodermal dysplasia-skin fragility syndrome. In patient 1 we identified a homozygous nonsense mutation, p.R672X, in the PKP1 gene (encoding plakophilin 1). This particular mutation has not been reported previously but is similar to the molecular pathology underlying other cases of this syndrome. In patient 2 we found compound heterozygosity for two frameshift mutations, c.2516del4 and c.3971del4, in the DSP gene (encoding desmoplakin). Although there was considerable clinical overlap in the skin and hair abnormalities in these two cases, patient 2 also had early-onset cardiomyopathy. The mutation c.3971del4 occurs in the longer desmoplakin-I isoform (which is the major cardiac transcript) but not in the more ubiquitous desmoplakin-II. In contrast, PKP1 is not expressed in the heart, which accounts for the lack of cardiomyopathy in patient 1. Collectively, these cases represent the first desmosomal genodermatoses to be reported from Brazil and add to genotype-phenotype correlation in this group of inherited disorders. Loss-of-function mutations in the DSP gene can result in a phenotype similar to ectodermal dysplasia-skin fragility syndrome resulting from PKP1 mutations but only DSP pathology is associated with cardiac disease.

GLUT-1 in oral benign vascular lesions.

AIM: To investigate the accuracy of histological diagnosis of oral hemangioma, oral vascular malformation and oral pyogenic granuloma according to immunohistochemical evaluation of the human erythrocyte-type glucose transporter protein (GLUT-1), and to observe the immunoexpression of this protein in oral varix. MATERIALS AND METHODS: Immunohistochemistry for GLUT-1 was performed in 93 histologically diagnosed cases of oral benign vascular lesions: 17 vascular malformations, 19 hemangiomas, nine varix, and 48 pyogenic granulomas. Descriptive analyses were performed. RESULTS: None of the cases of the oral benign vascular lesions evaluated were immunopositive to GLUT-1. The 19 cases histologically diagnosed as oral hemangioma that showed negative staining to GLUT-1 were reclassified as oral pyogenic granuloma or oral vascular malformations. The histological evaluation itself is not enough to obtain the correct diagnosis of oral HEM as none of the sample cases were true hemangioma. All sample cases with initial vascular malformation or pyogenic granulomas classification were negative to GLUT-1, demonstrating the accuracy of histological diagnosis of these lesions itself. Oral varix showed negative staining to GLUT-1 in blood vessels. CONCLUSIONS: GLUT-1 is an useful, effective and important auxiliary marker for the diagnosis of oral benign vascular lesions. CLINICAL RELEVANCE: This study showed that histological diagnosis alone is not sufficient to correct diagnoses of oral hemangioma. Moreover, immunohistochemistry to GLUT-1 is a useful and easy diagnostic method that may be used to avoid such misdiagnosis. Accurate diagnosis of these oral lesions has an important clinical relevance allowing: (1) correct management, (2) adequate communication among the multidisciplinary team (dentist, dermatologist, pediatrist, radiologist, pathologist, and surgeon), (3) understanding of the biological behavior of the lesions, and (4) facilitate the development of new therapeutic modalities. Thus, supporting the use of this marker in medical and dentistry communities is warranted.

Influence of narrow-band UVB phototherapy on cutaneous microbiota of children with atopic dermatitis.

OBJECTIVE: In the present work, the effect of narrow-band ultraviolet B (UVB) phototherapy on a cutaneous microbial population was evaluated in patients with atopic dermatitis (AD) and compared with control patients (vitiligo). METHODS: Count, isolation and identification of cutaneous microbiota from anticubital fossa were performed in 10 controls and 10 AD patients, both submitted to similar levels (P > 0.05) of UVB phototherapy (4.3 +/- 0.9 and 4.3 +/- 0.8 accumulated joules, respectively). Additionally, Staphylococcus aureus isolates were screened for the production of exotoxins. RESULTS: The total and staphylococcal cutaneous microbial population levels were higher (P < 0.05) in AD patients than in the controls. All these population levels decreased (P < 0.05) for both AD and control patients after UVB phototherapy, which also decreased the SCORAD for AD patients. All patients with AD and 50% of controls were carriers of S. aureus, and harboured the bacteria simultaneously on skin and anterior nares. All of the S. aureus strains recovered from AD patient skin produced toxin and the B type was the most frequently detected (70%), followed by C (20%) and A (10%) toxins. Only 40% of the S. aureus isolates from control patients produced toxin. After UVB treatment, microbial population levels of AD patients were similar (P > 0.05) to the ones found in control patients before phototherapy, and toxin production ability of S. aureus isolates decreased drastically. CONCLUSION: The results of the present study show the beneficial effect of UVB phototherapy on AD and suggest that this may be attributable not only to reduction of skin surface bacteria but also to the suppression of superantigen production from S. aureus.

Flow cytometric determination of cellular sources and frequencies of key cytokine-producing lymphocytes directed against recombinant LACK and soluble Leishmania antigen in human cutaneous leishmaniasis.

Leishmaniasis, caused by infection with the protozoan parasite Leishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-gamma) production by several different sources, listed in order of contribution: CD4(+) T lymphocytes, CD4(-), CD8(-) lymphocytes, and CD8(+) T lymphocytes. (ii) SLA induced a higher frequency of lymphocytes producing IFN-gamma and tumor necrosis factor alpha (TNF-alpha) than did LACK. (iii) LACK induced an activation of monocyte populations as reflected by an increased percentage of CD14-positive cells. (iv) Neither SLA nor LACK induced detectable frequencies of cells producing interleukin-4 (IL-4) or IL-5. These data demonstrated a multifaceted immune response to SLA in human leishmaniasis involving Th1 CD4(+) T lymphocytes (IFN-gamma(+) and IL-10(-)/IL-4(-)), Tc1 CD8(+) T cells (IFN-gamma(+), and IL-10(-)/IL-4(-)), and a high frequency of TNF-alpha-producing lymphocytes. Moreover, it was determined that the recombinant antigen LACK acts as a weak inducer of Th1-type lymphocyte responses compared to SLA.

[Neonatal dermatoses of relevant medical significance: their report in the newborn's file] / Dermatoses neonatais de importância clínica: notificação no prontuário do recém-nascido.

OBJECTIVE: To check the report of neonatal dermatoses of medical relevance (congenital melanocytic nevus, sebaceous nevus, cafe-au-lait spots, Port-wine stain, ash leaf maculas) in the newborn's file. METHODS: The authors carried out a cross-sectional study in two hospitals in the city of Belo Horizonte. All children born during a consecutive period of 4 months were examined within their 36 first hours of life by a dermatologist who reported all clinically relevant dermatoses (congenital melanocytic nevus, sebaceous nevus, cafeau- lait spots, Port-wine stain, ash leaf macules). Simultaneously, the dermatologist's report was cross checked with the pediatrician's. RESULTS: Neonatal dermatoses of clinical relevance were found in 42 (5.6%) out of 752 children examined during this period. However, the report in the neonate's file could be detected only in 5 (11,9%) out of 42 children. CONCLUSIONS: Clinically relevant dermatoses were underreported in the neonate's file in this study. There is a clear need to stimulate the detection and report of these skin disorders so that parental advice, treatment and genetic counseling can be adequately indicated.

Efficacy and safety of itraconazole pulse therapy: Brazilian multicentric study on toenail onychomycosis caused by dermatophytes.

BACKGROUND: Itraconazole is a large spectrum triazole with known efficacy in both continuous and pulse therapy for various mycoses. OBJECTIVES: Evaluate the efficacy and tolerability of itraconazole pulse therapy for onychomycosis of the toenails due to dermatophytes, in a prospective, open, non-comparative and multicentric investigation. Patients and methods The trial was completed by 72 patients of an initial total of 89. Treatment consisted of four cycles of itraconazole, 200 mg twice a day, for seven consecutive days each month. Patients were evaluated clinically, mycologically and biochemically before, during and at the end of the investigation, and were divided into two groups according to the measure of normal portion of the most affected nail (target nail), as follows: Group 1: 0-5.9 mm; and Group 2: more than 6 mm. RESULTS: Improvement was satisfactory and progressive. Results were statistically significant, when comparing the three moments of the study: pre-treatment, end of therapy (fourth month) and follow-up (ninth month) in both groups. CONCLUSIONS: Itraconazole pulse therapy was efficient and safe for the treatment of onychomycosis caused by dermatophytes, although a much higher daily dosage than the known continuous administration was used. Group 1, with nails initially more extensively affected, had a more evident improvement, by the mean variation in millimeters of normal portion of the target nail. This group showed a very satisfactory response, although not reaching total cure, thus demonstrating the great importance of early treatment of this disease. A residual therapeutic effect is maintained even after suspension of the drug. Group 2 obtained better total cure rates, and four pulses were, in general, sufficient, whereas more cycles would have been beneficial for the Group 1 patients with more extensive involvement.

Porcine stentless valve/bovine pericardial conduit for right ventricle to pulmonary artery.

BACKGROUND AND OBJECTIVES: We assessed the long-term outcome of a glutaraldehyde-preserved bovine pericardial conduit containing a stentless composite porcine aortic valve. METHODS: Between November 1985 and May 1995, 33 stentless porcine valves attached to bovine pericardial conduits were used in 33 patients with complex congenital cardiac malformations. These patients required a conduit between the right ventricle and the pulmonary artery because of an absent or inadequate pulmonic artery. All patients were approached by midsternotomy. One patient with pulmonic atresia and an interventricular septal defect required left thoracotomy for ligation of collaterals. RESULTS: Of the initial 33 patients, clinical follow-up was performed in 23 discharged patients (70%) for 1.7 to 10.5 years. The echo-Doppler analysis performed in each of the 23 followed patients showed excellent conduit and valve function in all but 4 patients, in whom a valve gradient of 60 mm Hg was noted. There was no tissue structural failure noticed in this study. CONCLUSIONS: The SJM Biocor (Belo Horizonte, Brazil) bovine pericardial stentless valved conduit performed well as a substitute for the right ventricle to pulmonary artery connection.

Porcine mitral stentless valve mid-term clinical results.

OBJECTIVES: Time testing is essential with any valvular procedure, especially when a new concept is introduced such as the mitral stentless valve. Our purpose is to evaluate the results obtained over 4 years with this operation, particularly to attest the impact of preservation of annulo ventricular continuity on the long term results of these patients. METHODS: From March 1992 to August 1996, 120 patients had their mitral valves replaced with a porcine stentless mitral valve. The observation period was 54 months with total patients follow-up of 3424 months with a mean of 28.5 months. The age ranged from 11 to 72 years (mean 35.22 +/- 14.98). There were 73 females (60.8%) and 47 males (39.2%). The predominant etiology was rheumatic heart disease. Associated procedures were performed in 12 patients (10%), and the great majority of the patients were in functional class III and IV (NYHA). RESULTS: Hospital mortality occurred in seven patients (5.83%) non valve related except for one early case of endocarditis. Early reoperation related to technical failure were necessary in 4 patients without mortality. Follow-up was accomplished in 101 patients and ranged from 2 to 54 months. Late reoperations were required in 16 patients (nine due to mitral insufficiency, five because of endocarditis and two for mitral stenosis). Most reoperations were related to technical failure. Among the 82 patients presently in control, 72 showed a competent mitral stentless valve, eight with stable mild mitral regurgitation and in two a decreased mitral orifice. Hemodynamic performance of the valve has been excellent in this group, particularly in patients with left ventricular dysfunction. CONCLUSION: Although technical complexity remains the main cause of reoperations with this valve, experience has shown that it not only provides preservation of the left ventricular function but also promised significant increase of the ejection fraction in patients with poor left ventricular function.

[Giant hemangioma treated with interferon alpha-2a]. / Hemangioma gigante tratado com Interferon Alfa-2a.

OBJECTIVE: The authors describe a case of giant hemangioma treated with interferon alpha-2a and review the role of this drug and other therapeutic modalities in the management of vascular lesions. METHODS: A seven month-old child with giant hemangioma and persistent bleeding, anemia and repeated infections was treated with interferon alpha-2a. The drug was administered at the dosage of 3 million units/m(2)/day, subcutaneously, for nine months. RESULTS: Response to treatment was considered excellent, with regression of 90% of the lesion, control of bleeding, infection and anemia, and catch-up growth. No untoward effects were observed. CONCLUSION: Interferon alpha-2a should be considered as a valid therapeutic option in selected cases of hemangioma in children.

Open clinical study of the efficacy and safety of terbinafine cream 1% in children with tinea corporis and tinea cruris.

BACKGROUND: Topical application of antifungal agents is considered the treatment of choice for dermatomycoses. Most of the available drugs are fungistatic, requiring long term treatment to prevent relapses. Terbinafine is a synthetic antifungal agent that, because of its fungicidal action, provides high cure rates and low relapse rates after short periods of treatment. METHODS: Ninety-seven children ages 2 to 15 years with a suspected diagnosis of tinea corporis and/or tinea cruris were enrolled in this open trial. After mycologic assessment to confirm diagnosis (culture and direct microscopy) terbinafine 1% cream was applied once daily during 1 week. Clinical and mycologic assessments were made at the baseline visit and on Days 7, 14 and 21. Efficacy assessment was based on 88 children (9 patients excluded by protocol violation). RESULTS: Therapy was considered effective in 92.0% (81 of 88) of patients (complete clinical and mycologic cure or mycologic cure with minimum signs and symptoms or clinical improvement, > or = 50%). Tolerability was assessed in 97 patients on an intention-to-treat basis. Adverse reactions were itching 3% (3 of 97), itching associated with erythema exacerbation 1% (1 of 97) and contact dermatitis 1% (1 of 97). CONCLUSION: Terbinafine 1% cream appears to be an effective and well-tolerated treatment for tinea corporis and tinea cruris in children.

Late complications after surgical exclusion of the thoracic aorta.

Two patients who underwent surgical exclusion of the thoracic aorta for chronic dissecting aneurysms of the descending aorta died 4 and 8 years after surgery due to complications in part related to the operative technique. One patient developed pseudoaneurysm of the proximal aortic stump with fatal exsanguination through an aortapulmonary fistula. The other patient developed progressive dilatation of the remaining abdominal aorta with subsequent rupture. The surgical approach in this case was extremely difficult because of the previous exclusion procedure which determined a highly demanding reoperation. Although surgical exclusion of the thoracic aortic may be a useful technique in some situations, we must be aware of its early and late complications and, in our opinion, it should be seen only as an alternative treatment for very special patients with diseases of the descending thoracic aorta.

[Ventricular fibrillation in a patient with the permanent form of junctional reciprocating tachycardia]. / Fibrilação ventricular em paciente com forma permanente da taquicardia juncional reciprocante.

A case of a 20 year old young man having the permanent form of junctional reciprocating tachycardia complicated by ventricular fibrillation (VF) is reported. A number of antiarrhythmic drugs either as single or combined therapy fail to control tachycardia. Paroxisms of a faster palpitation which never lasted longer than a few minutes were felt over the last six months before the occurrence of VF. At admission, a narrow QRS tachycardia 250 beats/min was recorded and soon degenerated into VF. After electrical shock with 350J permanent form of junctional tachycardia resumed. Electrophysiologic evaluation identified an accessory pathway with long conducting times in postero-septal location, enhanced atrioventricular node conduction and inducible atrial flutter. The patient underwent successful radiofrequency ablation and is doing well after 18 months of follow-up, being off antiarrhythmic drug and tachycardia free.

Surgical technique of implanting the stentless porcine mitral valve.

The new stentless porcine mitral valve was developed to serve as an anatomically correct substitute for a diseased mitral valve. Extensive acute animal experimentation was performed, and from this the logical sequence for selecting the correct valve size and the specific technique for implanting it were determined. The following are the major steps to successfully implant a mitral stentless valve: First, mitral valve complex analysis must be done to determine the correct procedure to be performed and the feasibility of using the stentless mitral valve. Second, the correct size of stentless mitral valve must be chosen. Third, the papillary muscle anatomy must be assessed to determine the site and number of sutures necessary for securely holding the new origin of the new chordae. Fourth, the papillary muscle sutures must be anchored to the free pericardial edge of the new chordal origin. Fifth, the chordal alignment with both trigonal areas must be perfect. Sixth, the annulus may be sutured using either continuous or interrupted sutures. Perioperative echocardiography, preferably transesophageal echocardiography, should be done in every patient. Although reoperation was necessary in 5 patients (non-valve-related), the results in 74 patients (3 early and 3 late non-valve-related deaths excluded) followed up for at most 26 months (mean, 14 months) have been excellent. The quality of the results obtained in this initial clinical trial has reinforced our current preference for this valve in patients requiring mitral valve replacement. Longer follow-up is required to confirm that these good results continue.

Porcine stentless aortic valve in re-replacements and acute aortic valve endocarditis.

Between June 1990 and June 1993, 135 patients received a porcine stentless aortic valve (PSAV) at our institution. In this group, there were 33 patients in whom the stentless valve was used to replace a previously inserted malfunctioning aortic valve prosthesis (n = 19) or to treat acute aortic valve endocarditis (n = 14, five native, nine prosthetic endocarditis). There was one hospital death caused by multiple organ failure in a patient with endocarditis and preoperative cerebral stroke. Two patients died after hospital discharge; one suffered sudden death following a pacemaker failure four month after surgery and the other died due to Candida albicans sepsis after a prolonged antibiotic treatment. There were two reoperations; one to correct a dehiscence of the proximal suture line and the other to replace a degenerated valve 3.5 years after implantation in a 14 year old boy. All operative survivors were followed clinically with serial color Doppler echocardiography. No recurrence of endocarditis was detected. Aortic root reconstruction was achieved even in the presence of multiple abscesses. All but one patients showed a normally functioning valve with none or minimal aortic insufficiency. In our opinion the PSAV is an excellent aortic valve substitute for patients with damaged aortic annulus, because it promotes aortic root remodeling, decreases the incidence of postoperative paravalvular leaks and helps to prevent endocarditis recurrence.

Heterologous mitral valve transplant: the first 50 patients clinical analysis.

From March 1992 to August 1993, 50 patients underwent mitral valve replacement with the new heterologous stentless mitral bioprosthesis in our institution. The development of this heart valve substitute, its technique of implantation and the results observed in the first group of 50 patients have had us to review the initial experience. The surgical protocol included an accurate mitral valve complex analysis, adequate valve size selection, attachment of the papillary muscle to the new chordal origin and approximation of the stentless mitral to the patient's annulus. There was one hospital death (2%), not related to the valve or to the technique and four reoperations: two due to endocarditis, one because of a perivalvular leak and one due to a mismatched stentless valve. The late mortality (4%) was not valve-related. The follow-up has shown excellent valve performance with improved left ventricular function in the great majority of the patients. Based on the current analysis, it can be stated that reproducibility of the surgical technique and the excellence of the clinical follow-up may contribute favorably to a better quality of life and longer valve durability in patients requiring mitral heart valve replacement.

Replacement of the ascending aorta and aortic arch with bovine pericardial grafts. A preliminary report.

Bovine pericardial (BP) grafts have been clinical use at Biocor Hospital since 1989 for replacement or repair of the ascending aorta (AsAo) and initial segment of the aortic arch (AoAr). The main advantages of BP grafts that have justified their clinical application are much easier surgical technique, perfect hemostasis and low cost. From Feb/89 to Feb/94, 88 BP grafts were implanted in the AsAo or the AoAr. There were 33 valved conduits, 47 non-valved conduits and 8 patches. The main indication for the procedure was acute dissection of the aorta, accounting for 50% of the cases. The total hospital mortality was 20.4%. Follow-up was obtained in all but two patients. Patients who survived 2 or more years postoperatively (n = 31) underwent either an echocardiographic or an angiographic study in order to access the behavior of the graft, which was perfect in all of them. The current follow-up is short and complications such as calcification may still develop. However the present study has clearly shown the superior handling and better hemostasis of BP grafts compared to the classical Dacron prosthesis.

Porcine stentless aortic heart valve substitute mid-term clinical follow-up.

From May 1990 to January 1994, 120 patients underwent aortic valve replacement with the use of the Biocor porcine aortic stentless heart valve (BPASHV). There were 83 male and 3 female patients. The age ranged from 11 seventy-six (76) years with a mean of 36. Eighty-five patients were under 40 years of age. Sixty-four patients underwent their first aortic valve replacement due to rheumatic heart disease, 30 because of prosthetic valve failure and of those: 20 were due to primary tissue failure and in 10 due to prosthetic endocarditis, native aortic bicuspid valve in 11 and senile calcificant aortic valve disease in four. Thirty-three patients had aortic annular related pathology. Their preoperative functional class revealed 61 patients in class III and 59 in class IV. The longest follow-up in this aortic group was 42 months with a mean of 26. The surgical technique used rendered consistent and reproducible results. There was a hospital mortality of six patients (5%). The mortality was not valve related. The hospital morbidity in 14 revealed full recovery of all patients. There were four late reoperations, in two due to recurrent endocarditis and in the last two because of paravalvar leak. There was a late mortality of four patients (non valve related). The follow-up of these patients revealed full competent aortic stentless valve in 97 patients and only minor jet in nine. Most patients are in functional class I and II. The Aortic stentless concept has proven to be outstanding with the use of the Biocor Aortic stentless valve throughout the current follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Porcine stentless mitral heart valve substitute: short term clinical data.

Beginning March 1992 to February 1994, 65 patients were submitted to mitral valve replacement using the porcine mitral stentless heart valve. This group took in 65 patients, their age ranged from four to 65 with a mean of 26 years. Forty patients were below years of age. The major indication was rheumatic heart disease sequelae in 50 patients, mitral valve endocarditis in six, myomatous degeneration in four and in five previous mitral prosthetic valve was replaced due to tissue failure. The preoperative functional class revealed 35 patients in class III and 30 in class IV. The longest follow-up was 23 months with a mean of 12. The surgical technique used rendered consistent and reproducible results. There was a hospital mortality of two patients or 3.1%. The hospital morbidity revealed full recovery of all patients. There were three patients reoperated because of valve endocarditis in two and in one due to partial dehiscence of the suture at the annular level. All three patients had full recovery after a reoperation. There was a late mortality of two patients, non valve related. The follow-up of these patients revealed full competent stentless mitral valve in 50 patients and in nine minor to mild jets were encountered by color echo-Doppler. Most patients are in functional class I and II. The stenless concept has prove to be outstanding in the mitral position throughout the current follow-up of close to 2 years.(ABSTRACT TRUNCATED AT 250 WORDS)