Vulvar Basal Cell Carcinoma: Four Case Reports With Immunohistochemical Study.

Basal cell carcinomas (BCC) are the most frequent tumours in humans and normally appear in photoexposed areas of the skin. It is widely accepted that BCCs originate at follicular stem cells and consequently are very rare in nonhairy areas. Here, we report 4 cases of vulvar BCC, 3 of which were located in a vulvar semimucous area, a nonphotoexposed area, and a nonhairy area. We have determined the CK7 and CK19 profile of all cases; both are markers of simple epithelium with glandular differentiation. Interestingly, all cases were positively stained for CK7 and CK19. Considering that the vulvar region is rich in sebaceous and apocrine units, we hypothesise a glandular origin of BCCs situated in the vulvar region.

Core Content for Undergraduate Medical Education in Spain: Recommendations of the Instructors' Group of the Spanish Academy of Dermatology and Venereology (AEDV).

BACKGROUND: Skin problems are among the most frequent reasons for seeking medical attention in primary care. In recent years, as a result of the process of adapting medical curricula to the requirements of the European Higher Education Area, the amount of time students spend learning the concepts of dermatology has been reduced in many universities. MATERIAL AND METHODS: In order to reach a consensus on core content for undergraduate education in dermatology, we sent a survey to the 57 members of the instructors' group of the Spanish Academy of Dermatology and Venereology (AEDV), asking their opinions on what objectives should be set for a dermatology course in Spain. A total of 131 previously selected objectives were listed. We then applied the Delphi method to achieve consensus on which ones the respondents considered important or very important (score≥4 on a Likert scale). RESULTS: Nineteen responses (33%) were received. On the second round of the Delphi process, 68 objectives achieved average scores of at least 4. The respondents emphasized that graduates should understand the structure and functions of the skin and know about bacterial, viral, and fungal skin infections, the most common sexually transmitted diseases (STDs), and the 4 main inflammatory dermatoses. Students should also learn about common complaints, such as itching and bald patches; the management of dermatologic emergencies; purpura and erythema nodosum as signs of internal disease; and the prevention of STDs and skin cancer. During clinical clerkships students should acquire the communication skills they will need to interview patients, write up a patient's medical history, and refer the patient to a specialist. CONCLUSIONS: The AEDV's group of instructors have defined their recommendations on the core content that medical faculties should adopt for the undergraduate subject of dermatology in Spain.

Evaluating clinical dermatology practice in medical undergraduates.

The acquisition of competences (the set of knowledge, skills and attitudes required to perform a job to a professional level) is considered a fundamental part of medical training. Dermatology competences should include, in addition to effective clinical interviewing and detailed descriptions of skin lesions, appropriate management (diagnosis, differentiation, and treatment) of common skin disorders and tumors. Such competences can only be acquired during hospital clerkships. As a way of certifying these competences, we propose evaluating the different components as follows: knowledge, via clinical examinations or critical incident discussions; communication and certain instrumental skills, via structured workplace observation and scoring using a set of indicators; and attitudes, via joint evaluation by staff familiar with the student.

Unilateral milia-type intradermal tophi associated with underlying urate subcutaneous deposition: an uncommon cutaneous presentation of gout.

Tophi develop during the most advanced clinical stage of gout, and are usually located on or around the joints. However, unusual skin features caused by intradermal and/or subcutaneous deposition of tophaceous material at locations other than articular regions have been reported. We present the case of a patient with a condition that has been recently termed 'miliarial gout'. which is only the second such case, to our knowledge. A 51-year-old woman, who had a chronic joint disease that had been diagnosed and treated as psoriatic arthritis, presented with multiple asymptomatic, yellowish-white, firm papules (1-3 mm in size) on erythematous areas on the outside of her left leg. On histological examination of a skin biopsy, uric acid crystals were seen in the dermis and subcutis. The patient also had a raised level of serum urate, consistent with a diagnosis of gout. Treatment with allopurinol led to rapid improvement. Intake of corticosteroids and diuretics was a possible triggering factor for the development of cutaneous tophi in this patient.

[Oral acitretin and topical imiquimod as neoadjuvant treatment for giant basal cell carcinoma]. / Tratamiento neoadyuvante con acitretino oral e imiquimod tópico en el carcinoma basocelular gigante.

Giant basal cell carcinoma (BCC) is defined as a tumor with a diameter of 5 cm or more. Surgery, the treatment of choice for any type of BCC, can cause considerable anatomical damage in large tumors. In 2 patients with giant BCC we therefore provided neoadjuvant treatment with a combination of oral acitretin and topical 5% imiquimod. Acitretin is a systemic retinoid used for primary prevention of nonmelanoma skin cancer. Imiquimod is an immunomodulator whose approved indications include treatment of nonfacial superficial BCC less than 2 cm in diameter. Previous studies have demonstrated a synergic anticancer effect of both drugs in vitro and in vivo. This combination produced a marked reduction in tumor mass in our patients. Later we were able to provide definitive treatment, which achieved complete remission of the tumors.

[Guide to buying a camera for dermatological photography]. / Guía para la compra de una cámara fotográfica para Dermatología.

Choosing a camera for use in the dermatology office is difficult, particularly in the case of a digital camera because the market is constantly evolving. This article explains the features that should be taken into account, including camera type, sensor, lens and macro capability, aperture priority mode, screen, viewfinder, operating speed, flash, battery, memory card, and image format. The most recent advances in the field of digital photography relevant to the dermatologist are discussed.

[Portfolios: a tool for the training and assessment of residents in dermatology, part 1]. / El portafolio como herramienta de formación y evaluación de los residentes de Dermatología (I).

The medical resident's portfolio is a collection of materials that show reflective learning in the context of clinical practice. A portfolio contains documents (such as case histories and questionnaires the resident has used), images, and video recordings that reveal that an individual has acquired the competencies needed for professional practice. A portfolio is an assessment tool that simultaneously supports learning and gives evidence for certifying competence. It encourages independent continuing professional development that is incremental and centered on answering questions about what one has learned, how it might be applied, what still needs to be learned, and what must be done to reach one's goal. Answering such questions provides evidence of competencies that have been acquired and what is still lacking, allowing the trainee to develop a plan for personal improvement and evaluate subsequent achievements. The first step in creating a portfolio is to list required skills and abilities, along with the actions that will allow the resident to acquire them during each year of residency training. The ultimate goal is to define the resident's professional competence. We describe a model on which to base a training and assessment portfolio for residents in dermatology.

[Portfolios: a tool for the training and assessment of residents in dermatology, part 2]. / El portafolio como herramienta de formación y evaluación de los residentes de dermatología (II).

A portfolio is a collection of material documenting reflection about practice. It contains documents (eg, case histories and questionnaires the resident has used), images, and video recordings that reveal that an individual has acquired the competencies needed for professional practice. This assessment tool simultaneously supports learning and provides evidence for certifying competence. The adoption of portfolio use by a dermatology department requires the support of both the training supervisor and the chief of department. The learning objectives defined by the National Board for Medical-Surgical Dermatology and Venereology must be taken into consideration so that ways to assess each objective can be included; this approach supports holistic ongoing education as well as the certification of competencies the resident finally achieves. Use of portfolios in medical residency training can improve on current assessment methods, which we believe lack precision. We propose that portfolios gradually begin to replace the resident's training log. We are currently developing an online software application that will facilitate the use of portfolios.

Expression of somatostatin receptors in human melanoma cell lines: effect of two different somatostatin analogues, octreotide and SOM230, on cell proliferation.

Somatostatin analogues (SAs) are potential anticancer agents. This study was designed to investigate the expression of somatostatin receptors (SSTRs) in melanoma cells and the effect of two SAs on cell proliferation and viability. Eighteen primary and metastatic human cutaneous melanoma cell lines were treated with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was assessed by real-time polymerase chain reaction. Proliferation, viability and cell death were assessed using standard assays. Inhibition was modelled by mixed-effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited proliferation of most melanoma cell lines, but inhibition was < 50%. Neither SA affected cell viability or induced cell death. The results suggest that melanoma cell lines express SSTRs. The SAs investigated, under the conditions used in this study, did not, however, significantly inhibit melanoma growth or induce cell death. Novel SAs, combination therapy with SAs and their anti-angiogenic properties should be further investigated.

Microbe-Dependent Induction of IL-9 by CLA+ T Cells in Psoriasis and Relationship with IL-17A.

IL-9 is present in psoriatic lesions and is produced by lymphocytes. However, it is not known whether this cytokine is induced by relevant pathogenic triggers of psoriasis, such as Streptococcus pyogenes. Here we addressed the production of IL-9 in response to various pathogens in a psoriatic ex vivo model. Extracts of S. pyogenes and Candida albicans triggered the production of IL-9 and also IL-17A and IFN-γ. This induction was dependent on the interaction between CLA+ T cells and epidermal cells. Neutralization of IL-9 reduced S. pyogenes-induced IL-17A production by CLA+ T cells but had no effect on IFN-γ production. Also, IL-9 increased the survival of circulating psoriatic CLA+ T cells. Co-cultures from patients with guttate or plaque psoriasis with S. pyogenes produced similar amounts of IL-9. High cytokine responses in streptococcal-driven guttate patients paralleled peaks in Psoriasis Area Severity Index and anti-streptolysin O levels. Our results confirm that IL-9 promotes inflammation in psoriasis by up-regulating IL-17A production and support the clinical association of the immune response by streptococcal-sensitized CLA+ T cells with this cytokine, especially in guttate psoriasis.

Influence of infarct-related artery patency on the indexes of parasympathetic activity and prevalence of late potentials in survivors of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine whether infarct-related coronary artery patency influences myocardial electrical stability as measured by the prevalence of late potentials or heart rate variability. BACKGROUND: Several studies have suggested that loss of vagal activity is associated with an increased incidence of arrhythmic death after myocardial infarction. METHODS: A short-duration, high resolution electrocardiogram (ECG) was performed before hospital discharge in 175 patients with a first myocardial infarction. Seventy-three patients received thrombolytic therapy. All patients underwent coronary angiography. Coronary occlusion was defined as minimal or no anterograde flow. Eighty-eight patients (50.3%) had an occluded infarct-related artery. Sixty-two healthy subjects served as control subjects to determine the normal range of heart rate variability. RESULTS: Comparison between the control group and patients without patency of the infarct-related artery in the time domain and spectral analyses revealed in the latter patients a reduced heart rate variability (p < 0.0001) and a lower power spectrum density in both the 0.05- to 0.15-Hz band (p < 0.0001) and the 0.15- to 0.35-Hz band (p < 0.0001). The heart rate variability in patients with late potentials was lower than in those with a normal signal-averaged ECG. Those patients with spontaneous or thrombolysis-induced reperfusion have less occurrence of late potentials and higher parasympathetic activity than do patients with a closed artery. CONCLUSIONS: This study suggests that the patency of the infarct-related artery determines both the absence of late potentials and the preservation of vagal tone and may explain the reduction in mortality induced by thrombolytic therapy in myocardial infarction.

Behavior of the pulmonary circulation in the grossly obese patient. Pathogenesis of pulmonary arterial hypertension at an altitude of 2,240 meters.

Twenty persons living at an altitude of 2,240 meters were studied in order to examine the relative roles of passive and active factors in the genesis of pulmonary arterial hypertension in obesity (overweight, 75 +/- 39 percent). Pulmonary arterial hypertension was present in 80 percent (16) of the patients (mean pulmonary arterial systolic pressure, 45 +/- 17 mm Hg). In 95 percent (19) of the 20 patients, resistance to pulmonary flow at the end of diastole was increased (estimated mean pulmonary arteriolar resistance, 210 +/- 144 dynes.sec.cm-5; mean pulmonary arterial diastolic-pulmonary wedge pressure gradient 7.86 +/- 1.40 mm Hg). The mean arterial oxygen pressure was 50 +/- 9 mm Hg, the arterial carbon dioxide tension was 37 +/- 6 mm Hg and the arterial pH was 7.42 +/- 0.08. Since the pulmonary arterial systolic pressure has been reasonably predicted (r = 0.91; P < 0.001), it would appear that the compliance of the elastic pulmonary arteries in obese patients follows a normal pattern. The behavior of the right ventricular end-diastolic pressure at rest (mean change, 4.6 mm Hg; P < 0.001) and of the pulmonary wedge pressure (mean change, 4.7 mm Hg; P < 0.001) during passive lifting of the legs was indirect evidence of the increase in pulmonary blood volume. The presence of an abnormal resistance to pulmonary blood flow at the end of diastole is suggestive of a decrease in the distention of the pulmonary microcirculation. The pulmonary arterial diastolic-pulmonary wedge pressure gradient and the pulmonary arterial diastolic pressure were related to arterial oxygen unsaturation (r = 0.70; P < 0.05) but not to the concentration of hydrogen ions; thus hypercapnic acidemia appears as a secondary factor in the genesis of pulmonary arterial hypertension at high atitudes. The explanation could be the relative hyperventilation of high altitudes, with a compensatory metabolic alkalosis. The increased pulmonary blood volume and the alveolar hypoxia are the main causes in the pathogenesis of pulmonary arterial hypertension in the grossly obese patient at this altitude.

Skin lesions in the ICU.

OBJECTIVE: The objective of this study is to identify the dermatological disorders (DDs) responsible for the most common skin lesions in the ICU, their incidence and their impact on mortality, degree of severity and length of stay in the ICU. DESIGN AND SETTING: We performed a 2-year prospective study in a general medical and surgical ICU including, exceptionally, paediatric cases. PATIENTS: We included all patients who presented skin lesions upon admission or developed them during their ICU stay. RESULTS: Forty-six patients (10% of all admissions) were enrolled, with 51 DDs. SAPS II score (43) and mean length of stay (19 days) were significantly higher than in the general group of ICU admissions. Differences in mortality rates (26% versus 29%) were not statistically significant. CONCLUSIONS: DDs are entities that should be borne in mind in the critically ill patient; their incidence is by no means negligible and makes careful examination of the skin mandatory both on admission and during a patient's ICU stay.

Color Doppler-guided prostate biopsies in 591 patients with an elevated serum PSA level: impact on Gleason score for nonpalpable lesions.

OBJECTIVES: To compare results of color Doppler-guided ultrasonography (CDUS) versus those of systematic biopsies in 591 patients with an elevated serum PSA level and to correlate them with digital rectal examination (DRE) findings. METHODS: Biopsies were directed into hypervascularized (CDUS+) or hypovascularized (CDUS-) hypoechoic peripheral zone nodules (443 cases). When transrectal ultrasound (TRUS) was normal (148 cases), biopsies were directed into hypervascular area. Six additional posterior biopsies were also performed in every patient, together with four anterior biopsies in 117 patients with normal DRE and prostate weight above 40 g. RESULTS: Biopsies were positive in 339 patients (57%). Positive biopsy rate (PBR) of directed biopsies was 84% in hypervascular abnormalities (264 of 316) and 17% in hypovascular nodules (23 of 134) (P < 0.001). PBR of combined biopsies was 84% in CDUS+ patients (266 of 316) and 26% in CDUS- patients (73 of 275) (P < 0.001). Comparison of TRUS and CDUS showed a sensitivity of 0.9 and 0.78, respectively, and a specificity of 0.46 and 0.8, respectively. Of the 131 patients with a PSA level between 4 and 10 ng/mL and a normal DRE, PBR was 59% (22 of 37) when CDUS was positive and 11% (10 of 94) when it was negative, regardless of TRUS abnormalities (P < 0.001). Nonpalpable cancers with a negative CDUS showed a significantly (P < 0.001) lower Gleason score (5.5 +/- 0.9) than that of CDUS+ cancer (6.5 +/- 1.1). Eleven cancers were diagnosed by only anterior positive biopsies. All of them had a negative CDUS and a PSA level above 10 ng/mL. CONCLUSIONS: CDUS does not modify prostate biopsy policy except in patients with negative CDUS, normal DRE, and PSA level between 4 and 10 ng/mL, where deferment of biopsy can be advocated. Anterior biopsies are only useful in patients with a PSA level above 10 ng/mL and a negative CDUS.

Efficacy of pravastatin as a hypolipidemic agent in patients with polygenic hypercholesterolemia.

In Mexico, hypercholesterolemia has become a major public health problem particularly in the states of the north of the country and in Mexico City, where a prevalence of 20% has been reported. Schemes of treatment have now been reinforced by the appearance of new cholesterol reducing drugs. The objective of the study was to demonstrate efficacy and safety of a 10 mg daily dose of oral Pravastatin (a new 3-hydroxy-3-methyl glutaryl CoA inhibitor) in a group of patients positive for hyperlipidemia, after 6 months of treatment. Twenty-five patients were included (14 men, 11 women) with an average age of 54 and 50 years, respectively. The main outcome measure was total cholesterol (T-CHOL), low density lipoprotein-cholesterol (LDL-C), triglycerides (TGL), high density lipoprotein cholesterol (HDL-C) and adverse drug reactions report. Twenty-one out of 25 patients completed the study. T-CHOL diminished 21%, LDL-C was reduced by 28%, TGL decreased 6% and HDL-C increased 32%. No adverse reactions were observed throughout the study. Our study shows that the use of a low dose of Pravastatin satisfactorily reduced T-CHOL and LDL-C levels while significantly increasing HDL-C after 27 weeks of treatment, without untoward effects.

Risk stratification for malignant arrhythmic events in patients with an acute myocardial infarction: role of an open infarct-related artery and the signal-averaged ECG.

BACKGROUND: There is increasing evidence that an open infarct-related artery results in increased electrical stability of the heart and that this effect is at least in part responsible for the favorable outcome of these patients. In the thrombolytic era the optimal strategy for risk stratification remains controversial. This study examined the predictors of serious arrhythmic events during the first year after myocardial infarction. METHODS: A total of 222 patients with acute myocardial infarction, 41.4% of whom were treated with thrombolysis, were studied. At hospital discharge, signal-averaged electrocardiography was performed on 196 subjects and Holter monitoring on 200. One hundred and ninety-seven patients underwent coronary angiography. Left ventricular ejection fraction was determined in 201 subjects. RESULTS: An open infarct-related artery was documented in 106 patients. The incidence of late potentials was 34% (66 patients). Twenty-four patients (10.8%) had an arrhythmic event during follow-up (sudden death in seven, sustained ventricular tachyarrhythmias in 15, unexplained syncope in two). Signal-averaged electrocardiography had a sensitivity of 94% and a specificity of 72% for prediction of arrhythmic events. An occluded infarct-related artery was 78% sensitive and 58% specific, a left ventricular ejection fraction below 40% had a sensitivity of 71% and specificity of 80%, and Holter monitoring was only 38% sensitive and 92% specific. A combination of late potentials plus an occluded infarct-related artery was 68% sensitive and 84% specific. Positive predictive value was low for all variables examined, but could be improved by the combination of several risk factors. The highest positive predictive value was provided by the combination of an abnormal signal-averaged ECG and complex ventricular arrhythmias on ambulatory ECG. On multivariate analysis, in rank order, presence of late potentials, ejection fraction below 40%, high-grade ventricular ectopic activity and an occluded infarct-related artery were predictive of arrhythmic events. CONCLUSION: Among patients surviving an acute myocardial infarction, the occurrence of malignant arrhythmic events can be reliably predicted by the combination of an abnormal signal-averaged ECG, left ventricular dysfunction, complex ventricular arrhythmias on Holter monitoring and an occluded infarct-related artery at the time of hospital discharge.

Effects of verapamil in ventricular tachycardias. An experimental and clinical study.

To determine the effect of verapamil in ventricular tachycardias, we performed an experimental and clinical study. Experimental ventricular tachycardias (VT) were produced in dog hearts with minute aconitine crystals introduced into the periphery of a left ventricular area, damaged by intramural injection of 1.0-1.5 ml phenol. The response of these tachycardias to 0.2 mg/kg verapamil was analyzed. Verapamil was infused into the superior vena cava over 15-20 min. Leads II, aVL, intraventricular right and left unipolar records, as well as one of the superior vena cava, were registered under control conditions, in the presence of VT, and after application of verapamil. Recordings were obtained at constant intervals, waiting for the recovery of sinus rhythm (SR) and the posterior reappearance of tachycardia. Experiments were performed for 6 to 8 h under continuous infusion of Hartmann's solution. Throughout these periods, variations in systemic systolic pressure were recorded. From 75 animals submitted to this treatment, 30 (40%) recovered transiently the SR, whereas the drug exerted no antiarrhythmic effect in 19 (25%), and arterial systolic pressure fell importantly in 10 (13%) animals. In two more groups, of 15 dogs each, the VT response to verapamil was compared with the response to lidocaine and flecainide. Endovenous verapamil (5-10 mg) was administered to 10 patients, coursing with VT and having a structurally normal heart, after this arrhythmia was induced by electrical stimulation. The response to verapamil was satisfactory in nine patients (90%), in which VT originated in the septal and apical regions of the left ventricle. Verapamil seems to be effective in experimental and clinical ventricular tachycardias related to calcium-dependent potentials, in which the sustaining mechanism could either be triggered activity or reentry.

Tilt testing in neurocardiogenic syncope: isosorbide versus isoproterenol.

OBJECTIVE: To compare the diagnostic value of pharmacological stimulation with sublingual isosorbide dinitrate and intravenous isoproterenol during tilt testing in patients with neurocardiogenic syncope and with a negative tilt test without pharmacological provocation. METHODS AND RESULTS: One hundred and twenty patients with a history of neurocardiogenic syncope (aged 15 to 77 years) and 50 healthy volunteers (aged 25 to 70 years) were prospectively submitted to head-up tilt (HUT). Those who did not develop syncope or presyncope during passive HUT for 30 minutes underwent repeated HUT with isoproterenol infusion at 4 microg/min (ISOP HUT), for 10 minutes, and, subsequently, were tilted after sublingual administration of 5 mg of isosorbide dinitrate (ISDN HUT) for another 12 minutes. ISDN HUT was always performed after ISOP HUT. Sensitivity and specificity of passive HUT were 41% (95% C.I. 32.9% to 51.0%) and 100%, respectively. Sensitivity of ISOP HUT was 51.4% (95% C.I. 39.2% to 63.6%) and specificity 70% (95% C.I. 55.4% to 82.1%) and for ISDN HUT were 70% (95% C.I. 57.9% to 80.4%) and 88% (95% C.I. 75.7% to 95.5%), respectively. The accuracy of ISDN HUT was significantly higher than the accuracy of ISOP HUT 77.5% (95% C.I. 68.9% to 84.6%). There were fewer side effects during ISDN HUT. CONCLUSION: Sublingual isosorbide dinitrate is at least as sensitive as isoproterenol to assess patients with suspected neurocardiogenic syncope and with a negative tilt test without provocation. The low rate of side effects and the higher accuracy of ISDN HUT, along with the simplicity of this challenge compared to ISOP HUT, suggest that sublingual isosorbide dinitrate should be preferred as a provocative agent to evaluate neurocardiogenic syncope after a negative passive tilt test.

Gastric hemorrhage in dogs given high doses of methylprednisolone sodium succinate.

OBJECTIVE: To determine whether healthy dogs given high doses of methylprednisolone sodium succinate (MPSS) develop gastrointestinal tract ulcers and hemorrhage. ANIMALS: 19 healthy male hound-type dogs. PROCEDURE: Dogs were assigned randomly to intravenously receive high doses of MPSS (30 mg/kg of body weight, initially, then 15 mg/kg 2 and 6 hours later, and, subsequently, every 6 hours for a total of 48 hours; n = 10) or an equal volume of saline (0.9% NaCl) solution (9). Gastroduodenoscopy was performed before and after treatment. Endoscopic evidence of gross hemorrhage in the cardia, fundus, antrum, and duodenum of each dog was graded from none (0) to severe (3), and a total stomach score was calculated as the sum of the regional gastric scores. Number of ulcers were recorded. The pH of gastric fluid and evidence of occult gastric and fecal blood were measured. Food retention was recorded. RESULTS: Gastric hemorrhage was evident in all dogs after MPSS administration and was severe in 9 of 10 dogs but not visible in any dog after saline treatment. Occult gastric blood was detected more commonly (9/10 vs 2/9), median gastric acidity was greater (pH 1 vs pH 3), and food was retained more commonly (7/10 vs 1/9) in the stomach of MPSS-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE: High doses of MPSS cause gastric hemorrhage in dogs. All dogs treated with high doses of MPSS should be treated with mucosal protectants or antacids to prevent gastric hemorrhage.