Mechanics and function in heart morphogenesis.

For years, biomechanical engineers have studied the physical forces involved in morphogenesis of the heart. In a parallel stream of research, molecular and developmental biologists have sought to identify the molecular pathways responsible for embryonic heart development. Recently, several studies have shown that these two avenues of research should be integrated to explain how genes expressed in the heart regulate early heart function and affect physical morphogenetic steps, as well as to conversely show how early heart function affects the expression of genes required for morphogenesis. This review combines the perspectives of biomechanical engineering and developmental biology to lay out an integrated view of the role of mechanical forces in heart development.     

Update on the management of neuromuscular block: focus on sugammadex

Steroidal neuromuscular blocking agents (NMBAs), such as rocuronium, are widely used in clinical anesthesia and emergency medicine to facilitate endotracheal intubation and artificial ventilation and to allow surgical access to body cavities. Reversal of neuromuscular blockade is important for the acceleration of patient recovery and prevention of postoperative residual neuromuscular blockade and reduces the incidence of severe morbidity and mortality associated with anesthesia management. Sugammadex is the first selective relaxant binding agent (SRBA) and has been designed to reverse the steroidal neuromuscular blocking drug rocuronium. Encapsulation of the rocuronium molecule by sugammadex results in a rapid decrease in free rocuronium in the plasma and subsequently at the nicotinic receptor at the motor endplate. After encapsulation, rocuronium is not available to bind to the nicotinic receptor in the neuromuscular junction. This promotes the liberation of acetylcholine receptors, and muscle activity reappears. This new concept of reversal of neuromuscular block induced by rocuronium (or vecuronium) led to impressive results in animal and phase 1 and 2 studies. Sugammadex is currently in phase 3 clinical studies and may be commercially available by 2008.     

Analysis of Deaths Related to Anesthesia in the Period 1996-2004 from Closed Claims Registered by the Danish Patient Insurance Association

Background: Anesthesia is associated with complications, and some of them may be fatal. The authors investigated the circumstances under which deaths were associated with anesthesia. In Denmark, the specialty anesthesiology encompasses emergency medicine, chronic and acute pain medicine, anesthetic procedures, perioperative care medicine, and intensive care medicine.

Methods: The authors retrospectively investigated anesthesia related deaths registered by the Danish Patient Insurance Association.

Results: From 1996 to 2004, 27,971 claims were made by the Danish Patient Insurance Association covering all medical specialties, of which 1,256 files (4.5%) were related to anesthesia. In 24 cases, the patient's death was considered to result from the anesthetic procedure: 4 deaths were related to airway management, 2 to ventilation management, 4 to central venous catheter placement, 4 as a result of medication errors, 4 from infusion pump problems, and 4 after complications from regional blockades. Severe hemorrhage caused 1 death, and in 1 case the cause was uncertain.     

Incompatibility of contrast agents with intravascular medications. Work in progress

In vitro and in vivo precipitation of iodinated contrast agents when ioxaglate and papaverine are given together has been reported. To verify these reports and to investigate other medications not previously tested, the authors analyzed mixtures of contrast agents and medications in vitro with a light spectrophotometer and observed them for visible precipitates for up to 120 minutes. Previously reported incompatibilities between ionic or low-osmolality contrast media and medications were verified, and several new incompatibilities were discovered. No incompatibilities were found when the drugs tested were mixed with the new nonionic contrast media.     

A new CD43 monoclonal antibody induces homotypic aggregation of human leucocytes through a CD11a/CD18-dependent and -independent mechanism.

We describe a monoclonal antibody (mAb), designated 1.C1, that causes rapid and vigorous aggregation among normal leucocytes and among T and myeloid/monocytic cell lines. As shown by competitive binding and sequential immunoprecipitation experiments, the antigen recognized by mAb 1.C1 is a 115,000 MW sialoglycoprotein, that corresponds to the human CD43 antigen, also known as leukosialin or sialophorin. The aggregation process starts within minutes and reaches maximum level 6-18 hr after addition of the antibody. It is dependent on active cell metabolism (inhibited at low temperatures and by a mixture of the metabolic poisons azide and 2-deoxy-D-glucose), a fluid plasma membrane (inhibited by pretreatment of the cells with paraformaldehyde) and an intact cytoskeleton (inhibited by cytochalasin B). Two reference CD43 antibodies (MEM-59 and DF-T1), both binding the same or closely related sialic acid-dependent epitope as mAb 1.C1, are also capable of inducing cell clump formation. CD11a/CD18 mAb block the 1.C1-induced adhesion of resting peripheral blood leucocytes, but not of haematopoietic cell line cells. In addition, mAb 1.C1 induces homotypic aggregation of K-562 cells, which do not express members of the beta 2 integrin subfamily on their surface. These data suggest that triggering of the CD43 antigen promotes homotypic cell adhesion that is mediated by both CD11a/CD18-dependent and -independent pathways.     

Evaluation and audit in a paediatric disability service

Parental and professional responses to questionnaires evaluating a paediatric disability service are reported and the viability of auditing structural, process, and outcome aspects of clinical practice are discussed. Expectations of waiting time to first appointment (met for only 52% of consumers) illustrate structural issues. Process issues are reflected in consumer reactions to outreach work (for example, 94% of parents and 84% of professionals found this supportive). Outcome measures such as consumer satisfaction with the service (76% of consumers reported being 'very satisfied' and 20% 'fairly satisfied') suggest that service aims are being met. Good concurrence of service aims with consumer needs is indicated by parental reasons for referral (for example, 75% for diagnostic help, 73% for a better understanding of the disorder, 88% for practical help), referrers' reasons (for example, 55% for a second diagnostic opinion, 45% due to lack of local expertise), and reports from most other professionals involved with the case that a similar service was not provided locally.     

Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome

Two siblings from a consanguineous family presented with a poikiloderma of limbs and face, plantar keratoderma, and toenail pachyonychia. Neutropenia and neutrophil dysfunction with impairment of the respiratory burst and bacterial killing resulted in frequent respiratory tract infections. A bronchocentric granulomatous pneumonia was a fatal complication. The clinical presentation is consistent with Clericuzio type poikiloderma with neutropenia. Literature review identified several additional probable patients. Genetic linkage analysis excluded the locus of the RECQL4 gene, mutations in which have been described in some patients with the Rothmund-Thomson poikiloderma syndrome. This report confirms the clinical and genetic identity of the Clericuzio type of poikiloderma with neutropenia syndrome.