Wiedemann‐Steiner syndrome in two patients from Portugal

Wiedemann‐Steiner syndrome (WSS) is a rare genetic disorder characterized by growth retardation, facial dysmorphism, hypertrichosis cubiti and neurodevelopment delay. It is caused by pathogenic variants in the KMT2A gene. This report describes two unrelated Portuguese patients, age 11 and 17 years, with a phenotype concordant with WSS and clinical and molecular diagnosis of WSS by the identification of two novel frameshift variants in the KMT2A gene. This work also highlights the presence of certain clinical features in patients with growth retardation and development delay and should draw attention to the diagnosis of WSS, when hirsutism, particularly hypertrichosis cubiti is present.     

Automated spoken dialogue system for hypertensive patient home management

Recent advances in automatic speech recognition and related technologies allow computers to carry on conversations by telephone. We developed an intelligent dialogue system that interacts with hypertensive patients to collect data about their health status. Patients thus avoid the inconvenience of traveling for frequent face to face visits to monitor the clinical variables they can easily measure at home; the physician is facilitated in acquiring patient information and cardiovascular risk, which is evaluated from the data according to noted guidelines. Controlled trials to assess the clinical efficacy are under way.     

Report on two patients with Costello syndrome and sialuria

We report on 2 unrelated patients with Costello syndrome. The first is a 5-year-old girl with “coarse” face, nasal papillomata, redundant skin of feet and hands, hyperextensible hand and finger joints, curly hair, feeding problems due to oral motor apraxia, growth and psychomotor retardation. The second is a 3-year-old boy with “coarse” face, loose skin on hands and feet, curly hair, oral motor apraxia, severe growth and psychomotor retardation. In both patients urine sialic acid levels were found to be repeatedly high. The meaning of this biochemical abnormality is discussed. © 1993 Wiley-Liss, Inc.     

Correlation between the course of the medial plantar artery and the morphology of the abductor hallucis muscle

The abductor hallucis muscle flap is commonly used as a proximally-based flap in the management of ankle, heel, and midfoot lesions, where it is ideally suited for closing defects. This study investigates the anatomical details of this muscle in 13 fresh male cadavers. The medial plantar artery (MPA) was studied by dissection and macroscopic analyses to document the relationship of its superficial and deep branches with respect to the abductor hallucis muscle (AHM). Three main patterns could be described. In Pattern A (54%) the MPA divides into two branches. The deep branch reaches the deep surface of the AHM, supplying its proximal part, and the superficial branch courses between the AHM and the flexor digitorum brevis, to end as the first plantar metatarsal artery. The latter supplies two to three small branches to the distal part of the AHM. The fibers of the AHM end symmetrically on the two sides of the tendon and the muscle presents an arciform shape. The MPA, in Pattern B (38%), lacks a deep branch and continues along the lateral border of the AHM as a superficial branch that supplies proximal and distal collaterals to the muscle. The muscle fibers of the AHM end mainly on the medial side of the tendon. The muscle belly presents an arciform shape and is located on the medial margin of the foot superomedially with respect to Pattern A. In Pattern C (8%) the MPA continues as a large deep branch on the deep surface of the AHM and ends as the medial collateral artery of the big toe. A smaller superficial branch of the MPA provides a few collaterals to the AHM from its proximal part and to the flexor digitorum brevis in its distal part. The AHM fibers end mainly on the lateral side of the tendon and morphologically the muscle presents a straight line on the sole of the foot compared to Pattern A. Although Patterns B and C, from a surgical point of view, necessitate interruption of the main trunk of the MPA, Pattern A may permit the vascularization of the muscles of the medial side of the sole of the foot by the superficial trunk of the MPA. Because preoperative radiological study of the plantar vessels correlate with the morphological characteristics of the AHM observed during surgery, such imaging may be useful in determining the appropriate flap design based on the patient's unique pattern of MPA branching.     

Blue rubber bleb nevus syndrome and pulmonary hypertension: an unusual association

INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital systemic angiodysplasia with multiple vascular malformations in the skin, gastrointestinal tract and, less often, in other internal organs and the brain. CASE REPORT: A 36-year-old man with past history of BRBNS was admitted to our hospital for progressive dyspnea and fatigue. Primary pulmonary hypertension (PPH) was diagnosed. He then developed acute abdominal pain and dyspnea, dying in a few hours due to sudden cardiac arrest. Postmortem examination demonstrated angiomatous lesions located in the skin, small bowel, heart, lungs, liver and thyroid. The lesions were slightly raised, soft and compressible and microscopically consisted of dilated vascular channels lined by a flattened endothelium. The vascular wall was formed by several layers of smooth muscle cells, intermixed with abundant aggregates of elastic lamellae and thin collagen fibers. Luminal thrombi were a frequent finding. In the small bowel, we identified the presence of an abnormally large artery directly opening into a thin-walled venous channel. The most striking finding in the lungs was the presence of thrombi of varying age in the lumen of segmental and elastic arteries, as well as muscular arteries and arterioles. Severe medial hypertrophy of muscular arteries and muscolarization of arterioles were also present. Intimal proliferative lesions and plexiform lesions were never observed. CONCLUSION: The pulmonary findings are consistent with recurrent thromboembolic events from shunts in the visceral lesions. To our knowledge, this is the first report of BRBNS with visceral arterovenous (AV) fistulae complicated by thromboembolic pulmonary hypertension (PH).     

Growth failure in Crohn’s disease children: may the first treatment have a role?

Introduction: Growth failure in children is a frequent feature of childhood-onset Crohn’s disease (CD), and stunting can persist into adulthood. Growth is an important outcome by which to judge the effectiveness of therapies in children; currently available studies in CD children have focused on the short-term impact of treatments on growth, and there are limited data regarding the long-term effects of treatments upon growth.

Areas covered: We designed the present article to review whether the first treatment performed in newly diagnosed CD children may have a role on the future growth course. We conducted a systematic literature search to identify relevant studies published on the PubMed database from January 2002 up to now. We found only six surveys that documented mid-term growth course in newly diagnosed CD patients.

Expert commentary: In the last years there have been relevant advances in the clinical management of CD children; however, there is a lack of knowledge about the best strategy to reverse growth failure. Children treated with enteral nutrition have appropriate height and weight gain but do not reverse the growth course. Further surveys are required to better explore not only clinical outcomes but also long-term growth course following each therapeutic strategy.     

Derivation of HLA-B*0702 transgenic mice: functional CTL repertoire and recognition of human B*0702-restricted CTL epitopes

Transgenic mice expressing chimeric human leukocyte antigen (HLA)-B*0702 and murine H-2K(b) class I molecules were evaluated as a model system to study the immunogenicity of human cytotoxic T lymphocyte epitopes. Immunization of these mice with six known HLA-B*0702-restricted cytotoxic T lymphocyte epitopes emulsified in incomplete Freund's adjuvant induced significant immune responses specific for all six epitopes. A comparison of the immune responses between HLA-B*0702/K(b) and HLA-A*0201/K(b) transgenic mice demonstrated that the HLA-B*0702/K(b) mice possess a T-cell receptor repertoire capable of recognizing human B*0702 epitopes. However, the magnitude of B*0702-specific responses induced in B*0702/K(b) mice were approximately tenfold lower than A*0201-specific responses induced in HLA-A*0201/K(b) transgenic mice. A panel of 24 B*0702 motif-bearing peptides was used to examine the relationship between immunogenicity and HLA-B*0702 binding capacity. All seven peptides with high binding affinities of 50% inhibitory concentration < or =50 NM (IC(50) 50 nM or less) were immunogenic. Similarly, 75% (9 of 12) of the intermediate binders (IC(50) nM of 50-500) were also immunogenic. Finally, only two of five peptides with binding capacity > 500 nM were found to have marginal immunogenicity, whereas the other three were completely negative. HLA-B*0702/K(b) transgenic mice were found to induce B*0702-specific responses after immunization with whole DNA genes or minigenes, suggesting that, at least to some degree, B*0702 epitopes were generated as a result of natural in vivo processing and presentation.     

Acute effects of light and darkness on sleep in the pigeon (Columba livia)

In addition to entraining circadian rhythms, light has acute effects on sleep and wakefulness in mammals. To determine whether light and darkness have similar effects in birds, the only non-mammalian group that displays sleep patterns comparable to mammals, we examined the effects of lighting changes on sleep and wakefulness in the pigeon. We quantified sleep behavior (i.e., bilateral or unilateral eye closure) in pigeons maintained under a 12:12 LD cycle, and immediately following a change from a 12:12 to a 3:3 LD cycle. During both LD cycles, sleep was most prevalent during dark periods. During the 3:3 LD cycle, darkness had the greatest sleep promoting effect during the hours corresponding to the subjective night of the preceding 12:12 LD cycle, whereas light suppressed sleep across circadian phases. As previously suggested, the light-induced decrease in sleep in the subjective night might be partly mediated by the suppression of melatonin by light. Although the sleep promoting effect of darkness was modulated by the circadian rhythm, sleep in darkness occurred during all circadian phases, suggesting that darkness per se may play a direct role in inducing sleep. In addition to the effects of lighting on behavioral state, we observed an overall bias toward more right eye closure under all lighting conditions, possibly reflecting a response to the novel testing environment.