Stunting and wasting in a growing economy: biological living standards in Portugal during the twentieth century.

Portugal's real income per head grew by a factor of eight during the second half of the twentieth century, a period of fast convergence towards Western European living standards. We use a new sample of about 3,400 infants and children living in Lisbon to document trends in the prevalence of stunting and wasting between 1906 and 1994. We find that stunting and wasting fell quickly from around 1950, for both males and females. We additionally use a sample of more than 26,000 young adult males covering the entire country, which shows a consistent decrease in wasting and stunting with the expected time lag. We discuss these trends in relation to changes in income and public policy, which affected the ontogenetic environment of children. Sustained progress began well before the introduction of democracy.

Acquired von Willebrand Syndrome and Chronic Anaemia: A Different Diagnostic Approach.

Heyde's syndrome is a form of acquired von Willebrand syndrome that consists of bleeding from intestinal angiodysplasia in the presence of aortic stenosis (AS). An association with obstructive hypertrophic cardiomyopathy, rather than AS, by a similar mechanism has also been described. We report the case of a 78-year-old woman with chronic anaemia and hypertrophic obstructive cardiomyopathy in whom intestinal angiodysplasia with active bleeding was identified by an unconventional method. In this case, the authors describe a different approach to reach the correct diagnosis. LEARNING POINTS: In patients with anaemia due to gastrointestinal bleeding, a high level of suspicion is crucial to identify the haemorrhagic focus.Intestinal angiodysplasia is associated with acquired von Willebrand syndrome.Acquired von Willebrand syndrome secondary to hypertrophic obstructive cardiomyopathy occurs by the same mechanism of aortic stenosis.

Foodborne Botulism: Neglected Diagnosis.

Botulism is rare neuroparalytic disease caused by botulinum toxin, one of the most toxic substances known. Foodborne botulism is caused by consumption of foods contaminated with botulinum toxin. The clinical manifestations are flaccid, symmetrical, descending paralysis affecting cranial and peripheral nerves. The only specific treatment is botulinum antitoxin. We report the case of a 37-year-old man with gastrointestinal manifestations and posterior cranial nerve palsy who was diagnosed with botulism infection. Clinicians should be aware of rare causes of infection and determine the aetiology of symptoms. LEARNING POINTS: Botulism remains a diagnostic challenge.Misdiagnosis of early cases suggests sporadic cases are overlooked.Timely clinical diagnosis is critical for treatment decisions as botulinum antitoxin cannot reverse existing paralysis.

Disseminated Gonococcal Infection: A Case Report of Arthritis-Dermatitis Syndrome.

The bacteremic spread of the sexually transmitted pathogen, Neisseria gonorrhoeae (N. gonorrhoeae), results in disseminated gonococcal infection (DGI), which can lead to a variety of clinical signs and symptoms, such as multiple skin lesions, tenosynovitis and arthralgias/arthritis. The Centers for Disease Control and Prevention listed that drug-resistant N. gonorrhoeae (cephalosporin resistance) poses an urgent threat due to antimicrobial resistance. The authors describe the case of a young woman presenting in the emergency department (ED) with skin lesions and malaise. DGI was confirmed by blood cultures, nucleic acid amplification testing (NAAT) in cervical mucosa and urine gonococcal probe. One week of intravenous ceftriaxone was administrated with complete clinical and analytical resolution. The patient made a full clinical recovery. Clinicians must be aware of the signs and symptoms of this rare yet reemerging disease.

Pulmonary Arteriovenous Malformation can be Associated with Embolic Stroke of Undetermined Source (ESUS).

Pulmonary arteriovenous malformations (PAVMs) are rare vascular anomalies. Alternative designations are pulmonary arteriovenous fistulae or aneurysms. Although mostly asymptomatic, PAVMs can cause respiratory symptoms due to right-to-left shunt. The central nervous system is a potential target for complications, including stroke, as a result of paradoxical embolism. In this report, the authors describe an unusual case of cerebral emboli caused by paradoxical embolism through a PAVM, presenting with a broad pathology including orthodeoxia, central cyanosis and digital clubbing, which should be kept in mind since misdiagnosis may cause severe morbidity in young adults. LEARNING POINTS: Pulmonary arteriovenous fistulae, although rare, must be considered in the presence of dyspnoea, cyanosis, hypoxaemia/orthodeoxia and stroke.In young adults with embolic stroke of undetermined source (ESUS), paradoxical embolism has to be ruled out.Meticulous anamnesis and physical examination can guide diagnostic investigation, reducing hospitalization time and superfluous complementary examinations.

Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action.

Eslicarbazepine acetate (ESL) is a once daily antiepileptic drug (AED) approved by the European Medicines Agency (EMA), the Food and Drug Administration (FDA) and Health Canada as an adjunctive therapy in adults with partial-onset seizures (POS). In humans and in relevant animal laboratory species, ESL undergoes extensive first pass hydrolysis to its major active metabolite eslicarbazepine that represents ∼95% of circulating active moieties. ESL and eslicarbazepine showed anticonvulsant activity in animal models. ESL may not only suppress seizure activity but may also inhibit the generation of a hyperexcitable network. Data reviewed here suggest that ESL and eslicarbazepine demonstrated the following in animal models: (1) the selectivity of interaction with the inactive state of the voltage-gated sodium channel (VGSC), (2) reduction in VGSC availability through enhancement of slow inactivation, instead of alteration of fast inactivation of VGSC, (3) the failure to cause a paradoxical upregulation of persistent Na(+) current (I NaP), and (4) the reduction in firing frequencies of excitatory neurons in dissociated hippocampal cells from patients with epilepsy who were pharmacoresistant to carbamazepine (CBZ). In addition, eslicarbazepine effectively inhibited high- and low-affinity hCaV3.2 inward currents with greater affinity than CBZ. These preclinical findings may suggest the potential for antiepileptogenic effects; furthermore, the lack of effect upon KV7.2 outward currents may translate into a reduced potential for eslicarbazepine to facilitate repetitive firing.

Characterization of the interaction of the novel antihypertensive etamicastat with human dopamine-ß-hydroxylase: comparison with nepicastat.

The interaction of etamicastat, a novel peripherally acting dopamine-ß-hydroxylase (DBH) inhibitor, with the enzyme was studied using a classical kinetic approach and the pharmacodynamics effect of the compound upon administration to rats was also evaluated. SK-N-SH cell homogenates convert tyramine into octopamine with a Km value of 9 mM, and a Vmax of 1747 nmol/mg protein/h. The K(m) value for ascorbate was 3 mM. The inhibition of DBH by etamicastat and nepicastat, a known centrally acting DBH inhibitor, with IC50 values of 107 and 40 nM, respectively, was fully reversed by dilution. Non-linear fitting of the velocities, determined at various concentrations of substrate (tyramine) and co-substrate (ascorbic acid), and of etamicastat and nepicastat, indicated that the inhibition of DBH by both compounds follows a mixed-model inhibition mechanism, approaching competitive behavior with regards to the substrate tyramine, with K(i) values of 34 and 11 nM, respectively. Relatively to ascorbate, both compounds followed a mixed-model inhibition mechanism, approaching uncompetitive behavior. Oral administration of both compounds (at 30 mg/kg) inhibited adrenal DBH activity over time and significantly decreased noradrenaline levels in the heart. Nepicastat also decreased noradrenaline levels in the parietal cortex, but not etamicastat. Both compounds significantly decreased systolic and diastolic blood pressure in spontaneously hypertensive rats. In conclusion, etamicastat and nepicastat behave as multisubstrate DBH inhibitors, binding reversibly and preferentially to the reduced form of the enzyme, and simultaneously at the substrate and oxygen binding sites. Etamicastat, in contrast to nepicastat, offers the advantage of peripheral selectivity without central effects.

Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide.

This study aimed at evaluating the effects of eslicarbazepine, carbamazepine (CBZ), oxcarbazepine (OXC) and lacosamide (LCM) on the fast and slow inactivated states of voltage-gated sodium channels (VGSC). The anti-epileptiform activity was evaluated in mouse isolated hippocampal slices. The anticonvulsant effects were evaluated in MES and the 6-Hz psychomotor tests. The whole-cell patch-clamp technique was used to investigate the effects of eslicarbazepine, CBZ, OXC and LCM on sodium channels endogenously expressed in N1E-115 mouse neuroblastoma cells. CBZ and eslicarbazepine exhibit similar concentration dependent suppression of epileptiform activity in hippocampal slices. In N1E-115 mouse neuroblastoma cells, at a concentration of 250 µM, the voltage dependence of the fast inactivation was not influenced by eslicarbazepine, whereas LCM, CBZ and OXC shifted the V0.5 value (mV) by -4.8, -12.0 and -16.6, respectively. Eslicarbazepine- and LCM-treated fast-inactivated channels recovered similarly to control conditions, whereas CBZ- and OXC-treated channels required longer pulses to recover. CBZ, eslicarbazepine and LCM shifted the voltage dependence of the slow inactivation (V0.5, mV) by -4.6, -31.2 and -53.3, respectively. For eslicarbazepine, LCM, CBZ and OXC, the affinity to the slow inactivated state was 5.9, 10.4, 1.7 and 1.8 times higher than to the channels in the resting state, respectively. In conclusion, eslicarbazepine did not share with CBZ and OXC the ability to alter fast inactivation of VGSC. Both eslicarbazepine and LCM reduce VGSC availability through enhancement of slow inactivation, but LCM demonstrated higher interaction with VGSC in the resting state and with fast inactivation gating.