The triad of bilateral retinoblastoma, dysplastic naevus syndrome and multiple cutaneous malignant melanomas: a case report and review of the literature

We report a case of a patient with the triad of retinoblastoma, dysplastic naevus syndrome (DNS) and multiple cutaneous melanomas. The combination of retinoblastoma and DNS is a significant risk factor for the development of cutaneous melanoma. This risk extends to family members. We recommend that survivors of (inherited) retinoblastoma and their relatives are closely screened for the presence of dysplastic naevi. (C) 2002 Lippincott Williams Wilkins.

Association of hypertension and hypokalemia with Cushing's syndrome caused by ectopic ACTH secretion: a series of 58 cases.

Cushing's syndrome is associated with hypertension in approximately 80% of cases. Hypertension contributes to the marked increased mortality risk of past or current Cushing's syndrome, largely because of increased cardiovascular risk. Observation of the pathophysiological effect of chronically elevated ACTH and cortisol values in patients with ectopic ACTH secretion complements the available data from acute studies of the effects of ACTH and glucocorticoid infusions in normal volunteers. In a retrospective case review, we identified 58 patients with Cushing's syndrome caused by ectopic ACTH secretion, who were treated at the National Institutes of Health between 1983-1997. The diagnosis of an ectopic ACTH cause was confirmed by inferior petrosal sinus sampling and/or pathologic examination of tumor. The commonest causes were bronchial carcinoid (40%) and thymic carcinoid (10%), but 18 of 58 (31%) patients had an unknown source of ectopic ACTH. Hypertension (systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg in adults) was noted in 45 of 58 (78%) ectopic Cushing's patients, a prevalence similar to that noted in other endogenous Cushing's syndrome etiologies. Hypertension was severe, deemed to require 3 or more drugs by the treating physicians, in 26 of 58 (45%) patients. Hypokalemia was much more prevalent than in patients with other causes of Cushing's syndrome, affecting 33 of 58 (57%) patients. The range of plasma ACTH (17-1557 pg/mL, normal

The morbidity of Guillain-Barré syndrome admitted to the intensive care unit

Patients with severe forms of Guillain-Barré syndrome (GBS) require intensive care. Specific treatment, catheterization, and devices may increase morbidity in the intensive care unit (ICU). To understand the spectrum of morbidity associated with ICU care, the authors studied 114 patients with GBS. Major morbidity occurred in 60% of patients. Complications were uncommon if ICU stay was less than 3 weeks. Respiratory complications such as pneumonia and tracheobronchitis occurred in half of the patients and were linked to mechanical ventilation. Systemic infection occurred in one-fifth of patients and was more frequent with increasing duration of ICU admission. Direct complications of treatment and invasive procedures occurred infrequently. Life-threatening complications such as gastrointestinal bleeding and pulmonary embolism were very uncommon. Pulmonary morbidity predominates in patients with severe GBS admitted to the ICU. Attention to management of mechanical ventilation and weaning is important to minimize this complication of GBS. Other causes of morbidity in a tertiary center ICU are uncommon.

Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm

Background - Marfan syndrome (MS) is a genetic disorder caused by a mutation in the fibrillin gene FBN1. Bicuspid aortic valve (BAV) is a congenital heart malformation of unknown cause. Both conditions are associated with ascending aortic aneurysm and premature death. This study examined the relationship among the secretion of extracellular matrix proteins fibrillin, fibronectin, tenascin, and vascular smooth muscle cell (VSMC) apoptosis. The role of matrix metalloproteinase (MMP)- 2 in VSMC apoptosis was studied in MS aneurysm. Methods and Results - Aneurysm tissue was obtained from patients undergoing surgery ( MS: 4 M, 1 F, age 27 - 45 years; BAV: 3 M, 2 F, age 28 - 65 years). Normal aorta from subjects with nonaneurysm disease was also collected ( 4 M, 1 F, age 23 - 93 years). MS and BAV aneurysm histology showed areas of cystic medial necrosis (CMN) without inflammatory infiltrate. Immunohistochemical study of cultured MS and BAV VSMC showed intracellular accumulation and reduction of extracellular distribution of fibrillin, fibronectin, and tenascin. Western blot showed no increase in expression of fibrillin, fibronectin, or tenascin in MS or BAV VSMC and increased expression of MMP-2 in MS VSMCs. There was 4-fold increase in loss of cultured VSMC incubated in serum-free medium for 24 hours in both MS ( 27 +/- 8%) and BAV ( 32 +/- 14%) compared with control ( 7 +/- 5%). Conclusions - In MS and BAV there is alteration in both the amount and quality of secreted proteins and an increased degree of VSMC apoptosis. Up-regulation of MMP-2 might play a role in VSMC apoptosis in MS VSMC. The findings suggest the presence of a fundamental cellular abnormality in BAV thoracic aorta, possibly of genetic origin.

Etiology of ovarian failure in blepharophimosis ptosis epicanthus inversus syndrome: FOXL2 is a conserved, early-acting gene in vertebrate ovarian development

Blepharophimosis ptosis epicanthus inversus syndrome (BPES) is a human disorder caused by mutations in the forkhead transcription factor gene FOXL2 and is characterized by facial dysmorphology combined in some cases with ovarian failure. To better understand the role of FOXL2 in the etiology of ovarian failure in BPES, we examined its expression in embryonic ovaries of mice, chickens, and red-eared slider turtles, representatives of three phylogenetically distant vertebrate groups that have different mechanisms of sex determination. Expression of Foxl2 was detected in early ovaries of all three species around the time of sex determination and was associated with both somatic and germ cell populations in mice. Expression was sexually dimorphic in all cases. Sequence analysis of turtle and chicken FoxL2 orthologues indicated an unusually high degree of structural conservation during evolution. FoxL2 was found to be autosomal in chickens, and therefore unlikely to represent the dominant ovarian-determining gene that has been postulated to exist as a possible explanation for female heterogamety in birds. Our observations suggest that BPES may result from early abnormalities in regulating the development of the fetal ovary, rather than premature degeneration of the postnatal or adult ovary. Further, our results suggest that FOXL2 is a highly conserved early regulator of vertebrate ovarian development.

Diagnostic and management protocols for equine Cushing's syndrome

Equine Cushing's syndrome is a common problem in aged horses and ponies. It presents with a variable combination of clinical signs; hirsutism is characteristic of the disease, with laminitis frequently being the most devastating consequence. This article describes the diagnostic protocols available and, in view of the fact that complete resolution of the disease is not achievable, discusses how the condition might be managed appropriately to improve the quality of life of affected animals.

Role of China in the quest to define and control severe acute respiratory syndrome

China holds the key to solving many questions crucial to global control of severe acute respiratory syndrome (SARS). The disease appears to have originated in Guangdong Province, and the causative agent, SARS coronavirus, is likely to have originated from an animal host, perhaps sold in public markets. Epidemiologic findings, integral to defining an animal-human linkage, may be confirmed by laboratory studies; once animal host(s) are confirmed, interventions may be needed to prevent further animal-to-human transmission. Community seroprevalence studies may help determine the basis for the decline in disease incidence in Guangdong Province after February 2002. China will also be able to contribute key data about how the causative agent is transmitted and how it is evolving, as well as identifying pivotal factors influencing disease outcome.

Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: Effects of environmental enrichment

Mental retardation in individuals with Down syndrome (DS) is thought to result from anomalous development and function of the brain; however, the underlying neuropathological processes have yet to be determined. Early implementation of special care programs result in limited, and temporary, cognitive improvements in DS individuals. In the present study, we investigated the possible neural correlates of these limited improvements. More specifically, we studied cortical pyramidal cells in the frontal cortex of Ts65Dn mice, a partial trisomy of murine chromosome 16 (MMU16) model characterized by cognitive deficits, hyperactivity, behavioral disruption and reduced attention levels similar to those observed in DS, and their control littermates. Animals were raised either in a standard or in an enriched environment. Environmental enrichment had a marked effect on pyramidal cell structure in control animals. Pyramidal cells in environmentally enriched control animals were significantly more branched and more spinous than non-enriched controls. However, environmental enrichment had little effect on pyramidal cell structure in Ts65Dn mice. As each dendritic spine receives at least one excitatory input, differences in the number of spines found in the dendritic arbors of pyramidal cells in the two groups reflect differences in the number of excitatory inputs they receive and, consequently, complexity in cortical circuitry. The present results suggest that behavioral deficits demonstrated in the Ts65Dn model could be attributed to abnormal circuit development.

Tympanometry and TEOAE testing of children with Down Syndrome in Special Schools

Despite widespread awareness that children with Down syndrome are particularly susceptible to hearing pathologies, the audiological status of students with Down syndrome in special schools is all too often unknown. Unfortunately, hearing screening for this population is unable to rely on standard, behavioural test batteries. To facilitate future improvements in screening protocols, this study investigated the results of tympanometry and transient evoked otoacoustic emission (TEOAE) testing for a group of children with Down syndrome. Assessments were not conducted in the artificial context of a clinic or laboratory, but within the school environment. Outcomes are reported for 27 subjects with a mean age of 10 years 5 months (SD = 4;11). Tympanometry testing was failed in at least one ear by 41.7% of subjects, while a failure rate of 81.5% of subjects was observed for TEOAE testing. Therefore, it is concluded that immediate review of hearing screening programs for students with Down syndrome is highly advisable.

Risk factors for sudden infant death syndrome in a developing country

OBJECTIVE: To analyze whether previously identified risk factors for sudden death syndrome have a significant impact in a developing country. METHODS: Retrospective longitudinal case-control study carried out in Porto Alegre, Southern Brazil. Cases (N=39) were infants born between 1996 and 2000 who died suddenly and unexpectedly at home during sleep and were diagnosed with sudden death syndrome. Controls (N=117) were infants matched by age and sex who died in hospitals due to other conditions. Data were collected from postmortem examination records and questionnaires answers. A conditional logistic model was used to identify factors associated with the outcome. RESULTS: Mean age at death of cases was 3.2 months. The frequencies of infants regarding gestational age, breastfeeding and regular medical visits were similar in both groups. Sleeping position for most cases and controls was the lateral one. Supine sleeping position was found for few infants in both groups. Maternal variables, age below 20 years (OR=2, 95% CI: 1.1; 5.1) and smoking of more than 10 cigarettes per day during pregnancy (OR=3, 95% CI: 1.3; 6.4), significantly increased the risk for the syndrome. Socioeconomic characteristics were similar in both groups and did not affect risk. CONCLUSIONS: Infant-maternal and socioeconomic profiles of cases in a developing country closely resembled the profile described in the literature, and risk factors were similar as well. However, individual characteristics were identified as risks in the population studied, such as smoking during pregnancy and maternal age below 20 years.

Metabolic syndrome in fixed-shift workers

OBJECTIVE To analyze if metabolic syndrome and its altered components are associated with demographic, socioeconomic and behavioral factors in fixed-shift workers.METHODS A cross-sectional study was conducted on a sample of 902 shift workers of both sexes in a poultry processing plant in Southern Brazil in 2010. The diagnosis of metabolic syndrome was determined according to the recommendations from Harmonizing the Metabolic Syndrome. Its frequency was evaluated according to the demographic (sex, skin color, age and marital status), socioeconomic (educational level, income and work shift), and behavioral characteristics (smoking, alcohol intake, leisure time physical activity, number of meals and sleep duration) of the sample. The multivariate analysis followed a theoretical framework for identifying metabolic syndrome in fixed-shift workers.RESULTS The prevalence of metabolic syndrome in the sample was 9.3% (95%CI 7.4;11.2). The most frequently altered component was waist circumference (PR 48.4%; 95%CI 45.5;51.2), followed by high-density lipoprotein. Work shift was not associated with metabolic syndrome and its altered components. After adjustment, the prevalence of metabolic syndrome was positively associated with women (PR 2.16; 95%CI 1.28;3.64), workers aged over 40 years (PR 3.90; 95%CI 1.78;8.93) and those who reported sleeping five hours or less per day (PR 1.70; 95%CI 1.09;2.24). On the other hand, metabolic syndrome was inversely associated with educational level and having more than three meals per day (PR 0.43; 95%CI 0.26;0.73).CONCLUSIONS Being female, older and deprived of sleep are probable risk factors for metabolic syndrome, whereas higher educational level and higher number of meals per day are protective factors for metabolic syndrome in fixed-shift workers.

Use of medicines recommended for secondary prevention of acute coronary syndrome

ABSTRACT OBJECTIVE : To analyze if the demographic and socioeconomic variables, as well as percutaneous coronary intervention are associated with the use of medicines for secondary prevention of acute coronary syndrome. METHODS : In this cohort study, we included 138 patients with acute coronary syndrome, aged 30 years or more and of both sexes. The data were collected at the time of hospital discharge, and after six and twelve months. The outcome of the study was the simultaneous use of medicines recommended for secondary prevention of acute coronary syndrome: platelet antiaggregant, beta-blockers, statins and angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker. The independent variables were: sex, age, education in years of attending, monthly income in tertiles and percutaneous coronary intervention. We described the prevalence of use of each group of medicines with their 95% confidence intervals, as well as the simultaneous use of the four medicines, in all analyzed periods. In the crude analysis, we verified the outcome with the independent variables for each period through the Chi-square test. The adjusted analysis was carried out using Poisson Regression. RESULTS : More than a third of patients (36.2%; 95%CI 28.2;44.3) had the four medicines prescribed at the same time, at the moment of discharge. We did not observe any differences in the prevalence of use in comparison with the two follow-up periods. The most prescribed class of medicines during discharge was platelet antiaggregant (91.3%). In the crude analysis, the demographic and socioeconomic variables were not associated to the outcome in any of the three periods. CONCLUSIONS : The prevalence of simultaneous use of medicines at discharge and in the follow-ups pointed to the under-utilization of this therapy in clinical practice. Intervention strategies are needed to improve the quality of care given to patients that extend beyond the hospital discharge, a critical point of transition in care.

ERICA: prevalence of metabolic syndrome in Brazilian adolescents

ABSTRACT OBJECTIVE To determine the prevalence of metabolic syndrome and its components in Brazilian adolescents. METHODS We evaluated 37,504 adolescents who were participants in the Study of Cardiovascular Risks in Adolescents (ERICA), a cross-sectional, school-based, national study. The adolescents, aged from 12 to 17 years, lived in cities with populations greater than 100,000 inhabitants. The sample was stratified and clustered into schools and classes. The criteria set out by the International Diabetes Federation were used to define metabolic syndrome. Prevalences of metabolic syndrome were estimated according to sex, age group, school type and nutritional status. RESULTS Of the 37,504 adolescents who were evaluated: 50.2% were female; 54.3% were aged from 15 to 17 years, and 73.3% were from public schools. The prevalence of metabolic syndrome was 2.6% (95%CI 2.3-2.9), slightly higher in males and in those aged from 15 to 17 years in most macro-regions. The prevalence was the highest in residents from the South macro-region, in the younger female adolescents and in the older male adolescents. The prevalence was higher in public schools (2.8% [95%CI 2.4-3.2]), when compared with private schools (1.9% [95%CI 1.4-2.4]) and higher in obese adolescents when compared with nonobese ones. The most common combinations of components, referring to 3/4 of combinations, were: enlarged waist circumference (WC), low HDL-cholesterol (HDL-c) and high blood pressure; followed by enlarged WC, low HDL-c and high triglycerides; and enlarged WC, low HDL-c, high triglycerides and blood pressure. Low HDL was the second most frequent component, but the highest prevalence of metabolic syndrome (26.8%) was observed in the presence of high triglycerides. CONCLUSIONS ERICA is the first Brazilian nation-wide study to present the prevalence of metabolic syndrome and describe the role of its components. Despite the prevalence of Metabolic Syndrome being low, the high prevalences of some components and participation of others in the syndrome composition shows the importance of early diagnosis of this changes, even if not grouped within the metabolic syndrome.