An obstetric patient with neurocadiogenic syncope.

We report the peripartum management of a 29-year-old primigravid patient with neurocardiogenic syncope, which had been diagnosed six years previously on tilt-table testing. General principles were applied to minimise the risk of precipitating syncopal episodes. She had an uneventful ventouse-assisted vaginal delivery under epidural anaesthesia in our obstetric high dependency unit. The optimum management of these patients has yet to be established.

Factor XII deficiency acquired by orthotopic liver transplantation: case report and review of the literature.

Transmission of congenital clotting factor deficiencies after orthotopic liver transplantation is rare. There are published reports of liver donor-to-recipient transmission of protein C deficiency with dysfibrinogenemia, protein S, factor VII and factor XI deficiencies. We report a case of transmission of factor XII deficiency with liver transplantation in a patient with Budd-Chiari syndrome. There was a persistent elevation of the activated partial thromboplastin time (aPTT), but no evidence of bleeding while the patient was maintained on warfarin. The presence of a persistently abnormal aPTT may raise suspicion for the presence of a clotting factor deficiency; however, deficiencies of other clotting factors may not be readily apparent on routine blood tests performed in a donor. Being aware of the possibilities of transmission of these inherited deficiencies of coagulation factors will aid in their early detection and management in the transplant donor and recipient.

Predominance of brain tumors in an extended Li-Fraumeni (SBLA) kindred, including a case of Sturge-Weber syndrome.

BACKGROUND: Li-Fraumeni syndrome (LFS) is characterized by a plethora of cancers, most prominent of which is carcinoma of the breast followed by sarcomas, brain tumors, leukemia, lymphoma, lung carcinoma, and adrenocortical carcinoma (therefore, also referred to by the acronym SBLA syndrome). METHODS: The family reported herein was first described 2 decades ago. Now extensive follow-up has shown the predictable occurrence of these tumor types, in addition to an excess of brain tumors and the finding of Sturge-Weber syndrome (SWS) in an LFS-affected family member. RESULTS: A possible new feature of the disorder, suggestive of SWS, was identified in a patient in the direct genetic lineage. This patient had a rhabdomyosarcoma of the eyelid at age 29 months and at age 14 years was diagnosed with lymphoblastic lymphoma/acute lymphoblastic leukemia. A remarkable excess of brain tumors was identified in this family through this current update. The p53 germ-line mutation was not identified in any affected member of this family. CONCLUSIONS: To the authors' knowledge, this is the first example of SWS in the context of LFS. Brain tumors appear to be an important component of the tumor spectrum of LFS, as evidenced in this family.

The laryngeal mask airway as an aid to training in fibreoptic nasotracheal endoscopy.

We have investigated the extent to which the laryngeal mask airway, when used as an aid to fibreoptic nasotracheal video-endoscopy training, could reduce endoscopy apnoeic time in anaesthetised, paralysed oral surgery patients. Twenty anaesthetic trainees were randomly allocated to the laryngeal mask airway or control group. Laryngeal mask airway group endoscopies were performed in three stages following insertion of the laryngeal mask airway; stage 1: nasendoscopy, with the lungs ventilated automatically through the laryngeal mask airway; stage 2: removal of the laryngeal mask airway; stage 3: pharyngoscopy, larygoscopy and tracheoscopy. Control group endoscopies were performed conventionally, in one stage. Each trainee performed five nasotracheal intubations. Though total endoscopy time in the laryngeal mask airway group (stage 1 + stage 2 + stage 3 times) was significantly longer (average 136 s vs. 108 s), apnoeic time (stage 2 + stage 3 times) was significantly shorter (average 59 s vs. 108 s) than endoscopy time in the control group. This application of the laryngeal mask airway may have a useful role to play in ensuring patient safety during early fibreoptic training.

Learning fibreoptic skills in ear, nose and throat clinics.

We have compared the progress of anaesthetists taught fibreoptic techniques on awake patients in ear, nose and throat clinics with that of anaesthetists taught by traditional methods. Twelve anaesthetists participated in the study and were randomly allocated to the ear, nose and throat group or to the traditional training group. Each individual in the ear, nose and throat group attended the outpatient clinic and performed ten nasendoscopies on awake patient, whose upper airway had been anaesthetised with cocaine, under the supervision of an ear, nose and throat surgeon. Each individual in the traditional roup performed ten nasendoscopies on anaesthetised oral surgery inpatients under the supervision of an anaesthetist. To assess the effectiveness of the two training methods, each anaesthetist in each group then attempted ten fibreoptic nasotracheal intubations on anaesthetised oral surgery patients. There was no significant difference between either the success rates or mean successful tracheoscopy times between the two groups. Nasendoscopy training in the ear, nose and throat clinic appears to be good way of learning fibreoptic skills, which can then be readily applied to fibreoptic tracheal intubation in anaesthetic practice.

Cooperativity between non-polar and ionic forces in the binding of bacterial cell wall analogues by vancomycin in aqueous solution.

The clinically important glycopeptide antibiotic vancomycin binds to bacterial cell wall peptides of Gram-positive bacteria which terminate in -Lys-D-Ala-D-Ala, thereby inhibiting cell wall synthesis resulting in cell death. We have removed the N-terminal leucine residue of vancomycin by an Edman degradation and acylated the exposed amino group of residue 2 with N-Me-Gly, N-Me-D-Ala, acetyl, butyl, and isohexyl groups to generate novel vancomycin analogues. The binding of vancomycin and these vancomycin analogues to the bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala (DALAA) was studied by NMR techniques and UV spectroscopy. The effects that these structural modifications of the carboxylate binding pocket of vancomycin have on the antibiotic-DALAA recognition process show that a cooperative effect between non-polar and ionic forces appears to be partly responsible for the highly efficient sequestering of the DALAA C-terminal carboxylate from aqueous solution.

Ubiquitinated protein conjugates are specifically enriched in the lysosomal system of fibroblasts.

Ubiquitin-protein conjugates are found by immunogold electron microscopy to be enriched (12-fold) in the lysosomal compartment of 3T3-L1 fibroblasts. Treatment of fibroblasts with the cysteine protease inhibitor E-64 leads to an expansion of the lysosomal compartment and as a result an increase in the cellular content of ubiquitin-protein conjugates. There is no change in the specific enrichment of ubiquitin-protein conjugates in the lysosomal compartment following E-64 treatment. The results suggest that some ubiquitin-protein conjugates may normally be degraded lysosomally following sequestration by microautophagy and imply that protein ubiquitination may be one of the signals for protein uptake into lysosomes.

Insoluble disulfide cross-linked polypeptides accumulate in the functionally compromised lysosomes of fibroblasts treated with the cysteine protease inhibitor E-64.

Mouse fibroblasts (3T3-L1 cells) accumulate pulse-labeled long-lived polypeptides in detergent- and salt-insoluble aggregates when chased in the presence of inhibitors of lysosomal cysteine cathepsins, including E-64. Proteins found in the detergent- and salt-insoluble fraction include polypeptides which are disulfide cross-linked. E-64-induced polypeptide aggregates cofractionate with lysosomal enzyme markers on density gradients and are found in multivesicular dense bodies which by electron microscopy appear to be engaged in microautophagy. The results are discussed in relation to the possible role of polypeptide aggregation in the sequestration or trapping of cytoplasmic proteins by the lysosomal system.

Ubiquitin-protein conjugates accumulate in the lysosomal system of fibroblasts treated with cysteine proteinase inhibitors.

Mouse fibroblasts (3T3-L1 cells) accumulate detergent- and salt-insoluble aggregates of proteins conjugated to ubiquitin when incubated in the presence of inhibitors of lysosomal cysteine cathepsins, including E-64. These ubiquitin-protein conjugates co-fractionate with lysosomes on density gradients and are found in multivesicular dense bodies which by electron microscopy appear to be engaged in microautophagy. Both E-64 and ammonium chloride increase the intracellular concentration of free ubiquitin, but only E-64 leads to the formation of insoluble lysosomal ubiquitin-protein conjugates. The results are discussed in relation to the possible intracellular roles of ubiquitin conjugation.