Corneal confocal microscopy : a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy

OBJECTIVE: The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies. ---------- RESEARCH DESIGN AND METHODS: A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM). ---------- RESULTS: Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = −0.475, P < 0.0001; NBD r = −0.511, P < 0.0001; and NFL r = −0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm2 with a sensitivity of 0.82 (95% CI 0.68–0.92) and specificity of 0.52 (0.40–0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm2 with a sensitivity of 0.71 (0.42–0.92) and specificity of 0.64 (0.54–0.74). ---------- CONCLUSIONS: CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity. Established diabetic neuropathy leads to pain and foot ulceration. Detecting neuropathy early may allow intervention with treatments to slow or reverse this condition (1). Recent studies suggested that small unmyelinated C-fibers are damaged early in diabetic neuropathy (2–4) but can only be detected using invasive procedures such as sural nerve biopsy (4,5) or skin-punch biopsy (6–8). Our studies have shown that corneal confocal microscopy (CCM) can identify early small nerve fiber damage and accurately quantify the severity of diabetic neuropathy (9–11). We have also shown that CCM relates to intraepidermal nerve fiber loss (12) and a reduction in corneal sensitivity (13) and detects early nerve fiber regeneration after pancreas transplantation (14). Recently we have also shown that CCM detects nerve fiber damage in patients with Fabry disease (15) and idiopathic small fiber neuropathy (16) when results of electrophysiology tests and quantitative sensory testing (QST) are normal. In this study we assessed corneal sensitivity and corneal nerve morphology using CCM in diabetic patients stratified for the severity of diabetic neuropathy using neurological evaluation, electrophysiology tests, and QST. This enabled us to compare CCM and corneal esthesiometry with established tests of diabetic neuropathy and define their sensitivity and specificity to detect diabetic patients with early neuropathy and those at risk of foot ulceration.

Staphylococcus sp na produção primária de leite: aspectos de saúde pública

Staphylococcus is one of the more important causes of the called Foodborne Disease(FD), being that from the 40 species described from genus, the more important is Staphylococcus aureus. During years believed that the S. aureus was the only specie from genus able to produce enterotoxins, responsable for the clinical frame in humans, but latest studies report the isolation of other species both positive coagulase (PC) as negative with enterotoxigenic potential. The symptoms of this intoxication appear after a short period of incubation (2-6 hours) and usually characterized by nausea, vomits, abdominal ache, diarrhea, and rarely is fatal. For the toxin to be formed in food is necessary that bacteria population to be at least 105 UFC/g, being that such toxins characterized by presenting great resistance front of gastrointestinal proteases and of homemade termical treatment. Among the main foods that might carry the microorganism, the milk and its derivatives have highlights. The contamination of the product might happen as from the milk from cows with clinical and/or subclinical mastitis, as the Staphylococcus genus is one of the main agents etiologic from this disease, equipments utensils badly sanitized equipments and utensils and from the manipulators. The control of these factors configures as fundamental condition for the achievement of a safe, quality product, which doesn’t offer risk to the consumers

Relationship between aetiology and left ventricular systolic dysfunction in hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a common cardiac disease caused by a range of genetic and acquired disorders. The most common cause is genetic variation in sarcomeric proteins genes. Current ESC guidelines suggest that particular clinical features (‘red flags’) assist in differential diagnosis. Aims: To test the hypothesis that left ventricular (LV) systolic dysfunction in the presence of increased wall thickness is an age-specific ‘red flag’ for aetiological diagnosis and to determine long-term outcomes in adult patients with various types of HCM. Methods: A cohort of 1697 adult patients with HCM followed at two European referral centres were studied. Aetiological diagnosis was based on clinical examination, cardiac imaging and targeted genetic and biochemical testing. Main outcomes were: all-cause mortality or heart transplantation (HTx) and heart failure (HF) related-death. All-cause mortality included sudden cardiac death or equivalents, HF and stroke-related death and non-cardiovascular death. Results: Prevalence of different aetiologies was as follows: sarcomeric HCM 1288 (76%); AL amyloidosis 115 (7%), hereditary TTR amyloidosis 86 (5%), Anderson-Fabry disease 85 (5%), wild-type TTR amyloidosis 48 (3%), Noonan syndrome 15 (0.9%), mitochondrial disease 23 (1%), Friedreich’s ataxia 11 (0.6%), glycogen storage disease 16 (0.9%), LEOPARD syndrome 7 (0.4%), FHL1 2 (0.1%) and CPT II deficiency 1 (0.1%). Systolic dysfunction at first evaluation was significantly more frequent in phenocopies than sarcomeric HCM [105/409 (26%) versus 40/1288 (3%), (p<0.0001)]. All-cause mortality/HTx and HF-related death were higher in phenocopies compared to sarcomeric HCM (p<0.001, respectively). When considering specific aetiologies, all-cause mortality and HF-related death were higher in cardiac amyloidosis (p<0.001, respectively). Conclusion: Systolic dysfunction at first evaluation is more common in phenocopies compared to sarcomeric HCM representing an age-specific ‘red flag’ for differential diagnosis. Long-term prognosis was more severe in phenocopies compared to sarcomeric HCM and when comparing specific aetiologies, cardiac amyloidosis showed the worse outcomes.

Risk factors, aetiology and outcome of ischaemic stroke in young adults: the Swiss Young Stroke Study (SYSS).

Ischaemic stroke (IS) in young adults has been increasingly recognized as a serious health condition. Stroke aetiology is different in young adults than in the older population. This study aimed to investigate aetiology and risk factors, and to search for predictors of outcome and recurrence in young IS patients. We conducted a prospective multicentre study of consecutive IS patients aged 16-55 years. Baseline demographic data, risk factors, stroke aetiology including systematic genetic screening for Fabry disease and severity were assessed and related to functional neurological outcome (modified Rankin Scale, mRS), case fatality, employment status, place of residence, and recurrent cerebrovascular events at 3 months. In 624 IS patients (60 % men), median age was 46 (IQR 39-51) years and median NIHSS on admission 3 (IQR 1-8). Modifiable vascular risk factors were found in 73 %. Stroke aetiology was mostly cardioembolism (32 %) and of other defined origin (24 %), including cervicocerebral artery dissection (17 %). Fabry disease was diagnosed in 2 patients (0.3 %). Aetiology remained unknown in 20 %. Outcome at 3 months was favourable (mRS 0-1) in 61 % and fatal in 2.9 %. Stroke severity (p < 0.001) and diabetes mellitus (p = 0.023) predicted unfavourable outcome. Stroke recurrence rate at 3 months was 2.7 %. Previous stroke or TIA predicted recurrent cerebrovascular events (p = 0.012). In conclusion, most young adults with IS had modifiable vascular risk factors, emphasizing the importance of prevention strategies. Outcome was unfavourable in more than a third of patients and was associated with initial stroke severity and diabetes mellitus. Previous cerebrovascular events predicted recurrent ones.

Fabry's disease: otoneurologic findings in twelve members of one family

Fabry's disease corresponds to an inherited disorder transmitted by an X-linked recessive gene. It generates a dysfunction of glycosphingolipid metabolism due to an enzymatic deficiency of alpha-galactosidase activity, resulting in glycosphingolipid deposits in all areas of the body. The clinical (heart, kidney, and central nervous system) manifestations are more severe in hemizygous boys than in heterozygous girls. They appear during childhood or adolescence: acroparesthesia, joint pain, angiokeratoma, corneal dystrophy, hypohydrosis or anhydrosis, and renal failure. The otoneurologic symptoms consist of hearing fluctuation, progressive unilateral or bilateral hearing loss, and episodes of vertigo or dizziness. Otoneurologic findings in 12 of 26 members of the same family are presented: the mother and 9 of her 12 children, as well as 2 of her 14 grandchildren: 4 healthy persons, 4 heterozygous female carriers, and 4 hemizygous male patients. Three of the male patients had fluctuation of hearing, sudden hearing loss, and episodes of vertigo and dizziness. The otoneurologic examinations showed a bilateral cochleovestibular deficit (n = 1), a right cochleovestibular deficit (n = 1), and a bilateral hearing loss combined with a right vestibular deficit (n = 1). Histopathologic evidence of glycosphingolipid accumulation in vascular endothelial and ganglion cells, as well as atrophy of the stria and spiral ligament, might explain the otoneurologic symptoms and findings.

Obtenção de hibridos lapdesf fur-fd e atividade anti-inflamatória com potencial atividade neuroprotetora

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

ADAMTS13 activity in sickle cell disease

Sickle red blood cell (SRBC)-endothelial adhesion plays a central role in sickle cell disease (SCD)-related vaso-occlusion. As unusually large von Willebrand factor (ULVWF) multimers mediate SRBC-endothelial adhesion, we investigated the activity of ADAMTS13, the metalloprotease responsible for cleaving ULVWF multimers, in SCD. ADAMTS13 activity was determined using a quantitative immunoblotting assay. VWF:Ag and VWF:RCo were determined using commercial assays. The high-molecular-weight VWF multimer percentage was determined by employing gel electrophoresis. ADAMTS13 activity was similar among asymptomatic patients (n = 8), patients at presentation with a painful crisis (n = 23), and healthy controls. ADAMTS13/VWF:Ag ratios were lower in patients compared to healthy HbAA controls, with the lowest values at presentation with a painful crisis (P = 0.02). Division of samples in those with VWF:RCo/VWF:Ag ratios < 0.70 and those with ratios >or= 0.70 revealed significantly more samples with ratios >or= 0.70 (P = 0.01) collected during painful crises. ULVWF multimers were detected in 6 patient samples and in 1 control sample. ADAMTS13/VWF:Ag ratios were inversely related to the duration of symptoms at presentation with an acute vaso-occlusive event (r(s)-0.67, P = 0.002). Although SCD is characterized by elevated VWF:Ag levels, no severe ADAMTS13 deficiency was detected in our patients.

Ferroportin Disease (Haemochromatosis-type IV): a case report

Introdution: Haemochromatosis-type IV, the ferroportin disease, is characterized by an autosomal-dominant transmission and early iron accumulation in macrophages. It is caused by mutations in the transmembrane iron exporter protein ferroportin1 (SLC40A1 gene). In form A (classic), ferroportin loss of function mutants are unable to export iron from cells leading to cellular iron accumulation with decreased availability of iron for serum transferrin (TS). We present a Portuguese rare clinical case of HH-IV. Materials and Methods: A 41-year-old woman with hyperferritinemia and normal TS. Causes of hyperferritinemia (inflammation, chronic alcohol consumption, metabolic syndrome, cell necrosis, non-alcoholic fatty liver disease and aceruloplasminemia) were assessed. Liver iron, evaluated by magnetic resonance imaging (MRI) was carried out. Screening for mutation in HFE and SCL40A1 genes were performed by Sanger sequencing. Baseline: Ferritin:708ng/ml; TS: 27%; MRI:85µmol/g; Hb:13,6g/dl. Therapy: weekly 450ml Therapeutic Phlebotomies (TP) until ferritin≤50ng/ml. Results: Hyperferritinemia comorbidities and common genetic mutations for haemochromatosis were negative. However, sequencing of the patient SLC40A1 gene has revealed the presence in heterozygosity of the variant c.238G>A; p.Gly80Ser. Due to low tolerance to TP, we adopted smaller phlebotomies every three weeks. Conclusion: This patient has a rare autosomal-dominant Ferroportin disease due to a mutated ferroportin which is predicted to be defective in iron cellular export. In agreement, she presents hyperferritinemia, with normal TS and liver iron overload. The genotype/phenotype association allowed to diagnosis this rare FD case. Although a mild form A, we decided to start TP. Her father also has been treated for iron overload.

Weather variability, tides, and Barmah Forest Virus Disease in the Gladstone region, Australia

In this study we examined the impact of weather variability and tides on the transmission of Barmah Forest virus (BFV) disease and developed a weather-based forecasting model for BFV disease in the Gladstone region, Australia. We used seasonal autoregressive integrated moving-average (SARIMA) models to determine the contribution of weather variables to BFV transmission after the time-series data of response and explanatory variables were made stationary through seasonal differencing. We obtained data on the monthly counts of BFV cases, weather variables (e.g., mean minimum and maximum temperature, total rainfall, and mean relative humidity), high and low tides, and the population size in the Gladstone region between January 1992 and December 2001 from the Queensland Department of Health, Australian Bureau of Meteorology, Queensland Department of Transport, and Australian Bureau of Statistics, respectively. The SARIMA model shows that the 5-month moving average of minimum temperature (β = 0.15, p-value < 0.001) was statistically significantly and positively associated with BFV disease, whereas high tide in the current month (β = −1.03, p-value = 0.04) was statistically significantly and inversely associated with it. However, no significant association was found for other variables. These results may be applied to forecast the occurrence of BFV disease and to use public health resources in BFV control and prevention.