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Clozapine is an atypical antipsychotic agent with a novel pharmacological profile and multiple clinical properties. Because of its side effects, it is recommended in treatment of severe resistant schizophrenia for which purpose it is remarkably effective. Little is known about the safety profile of clozapine during pregnancy and labour and because it is now used more commonly to manage schizophrenia, it is important that we as anaesthetists are aware of its many interactions and potential side effects. We present a case of a successful emergency caesarean section in a schizophrenic patient on clozapine treatment.

Mucosal addressin cell-adhesion molecule (MAdCAM-1) is a membrane-bound leukocyte receptor regulating both the passage and retention of leukocytes in mucosal tissues. A crystal structure for the two extracellular amino-terminal domains of human MAdCAM-1 has previously been reported, confirming their expected immunoglobulin superfamily topology. In this study, a second crystal structure of this fragment is described. Although the overall structure is similar to that previously reported, one edge strand in the amino-terminal domain is instead located on the opposite sheet. This alters the arrangement and conformation of amino acids in this region that have previously been shown to be crucial for ligand binding. MAdCAM-1 is also seen to form dimers within the crystal lattice, raising the possibility that oligomerization may influence the biological role of this adhesion molecule.

The n -3 and n -6 fatty acids are transferred across the placenta with consistently higher 22:6 n -3 and lower 18:2 n -6 in fetal than maternal plasma. This study sought to determine whether maternal and fetal cord blood red blood cell (RBC) phospholipid fatty acids show similar saturation with 22:6 n -3, and also addressed the relationship between 18:2 n -6 and Δ6 desaturase product/precursor ratios for 97 mothers and newborns. Despite higher fetal than maternal plasma phospholipid 22:6 n -3, the maternal and fetal RBC phospholipid 22:6 n -3 showed similar curvilinear relationships to the plasma phospholipid 22:6 n -3. Risk of failure to achieve high RBC phospholipid 22:6 n -3 increased sharply below a plasma phospholipid 22:6 n -3 of 6.5g/100g fatty acids. Higher maternal and fetal 18:2 n -6 was associated with lower RBC phospholipid 22:6 n -3/22:5 n -3, 22:5 n -6/22:4 n -6 and 18:3 n -6/18:2 n -6. These findings suggest low placental transfer of 18:2 n -6 may be a specific mechanism to prevent inhibition of fetal Δ6 desaturase and facilitate fetal cellular phospholipid 22:6 n -3 accretion.

A congenital rhabdomyosarcoma presented as a partially necrotic mass on the left forearm on delivery at term. Ulceration and persistent bleeding were managed by primary curettage followed by local resection including partial excision of the muscles of the extensor compartment of the forearm. The defect was resurfaced with a split skin graft. The surgery was followed by chemotherapy according to the IVA regime. There was no recurrence at 2 years of age and the limb was fully functional. The presentation and management of rhabdomyosarcoma are discussed.

The crystal structure of a chimeric Fab' fragment of a monoclonal antibody is presented. The Fab' comprises the murine light chain and heavy chain variable domains of the carcinoma-binding antibody B72.3 fused to the constant domain of human kappa, and the first constant domain and hinge domain of human gamma 4, respectively. A model for the Fab' has been determined by molecular replacement and refined to a resolution of 3.1 A with an R-factor of 17.6%. The additional residues that distinguish a Fab' from a Fab fragment are seen to be disordered in the crystals. The H3 hypervariable loop is short and adopts a sharp hairpin turn in a conformation that results from an interaction between the lysine side-chain of H93 and the main-chain carbonyl group of H96. The remaining hypervariable loops display conformations similar to those predicted from the canonical structures approach, although loop H2 is apparently displaced by a salt-bridge formed between H55 Asp and the neighbouring H73 Lys. These and other features of the structure likely to be important in grafting the hypervariable loops to an otherwise human framework are discussed.

Crystals have been obtained of a chimaeric Fabt′ fragment that binds to a tumour-associated mucin-like glycoprotein TAG72. The Fab′ fragment comprises the variable heavy and light-chain domains of a murine monoclonal antibody, B72.3, coupled to human γ4 and κ constant regions. The crystals are orthorhombic and belong to the space group P212121, with unit cell dimensions a = 67.9 A , b = 94.2 A and c = 208.8 A . Diffraction to 2.6 A resolution was observed using synchrotron radiation. Despite the acute radiation sensitivity of the crystals a full native data set has been collected using the Weissenberg camera at the Photon Factory synchrotron. These data will be used for molecular replacement calculations in an attempt to elucidate the structure of this chimaeric Fab′ fragment.

The findings on gallium-67 scans were compared with the findings of standard techniques (X-ray chest, lymphangiography, clinical examination, and laparotomy findings) in patients with lymphoma, mainly at presentation, but sometimes on follow-up. The objective was to ascertain the reliability of this non-invasive technique in detecting lymphomatous deposits, and to assess its place in the battery of investigations which may be used in clinical staging of lymphomas. One hundred and sixty-six patients were studied, in whom 198 gallium-67 scans were performed. The results indicated that detection of mediastinal and upper para-aortic node involvement was the most significant function, and such detection might alter clinical staging, and, therefore, therapy. Gallium-67 was unhelpful in splenic scanning, being positive usually only in cases which had clinically detectable involvement. Unsuspected lung and bone lesions were found occasionally, and this was of considerable importance. Gallium-67 scanning is regarded as an important, non-traumatic additional investigation, clinically useful in staging lymphomas.

Many indoles can be assayed fluorimetrically either by measurement of their native fluorescence or by conversion to a suitable derivative, e.g., a norharman in the case of tryptamine and tryptophan (1, 2). For tryptophan the latter method has two main advantages over measurement of native fluorescense; first, separation between excitation and emission maxima is great enough for simple filter instruments to be used, and second, it possesses a much greater sensitivity. Furthermore, the excitation wavelength is in the visible region, whereas native fluorescence is measured in the ultraviolet region. It was the high sensitivity which prompted us to adapt the norhaman method for use on a small-scale to measure tryptophan in blood plasma in a clinical study which necessitated withdrawal of several blood samples in an 8-hour period. The method described, which can be applied to as little as 10 μ plasma, minimizes the inconvenience of repeated venupunctures.

Investigation of a 15-year-old white male patient with chronic granulomatous cheilitis revealed asymptomatic Crohn's disease of the lower gastrointestinal tract. This is reported to support the suggestion that chronic granulomatous cheilitis and Crohn's disease may be intimately related. Tests for nutritional status are shown to be important in the investigation and management of patients with this condition, being the first indication of any gastrointestinal pathology.

The cause of the renal failure that occurs in approximately 20 percent of patients following allogeneic bone marrow transplantation is poorly understood. A patient is described in whom acute renal failure occurred one week after allogeneic bone marrow transplantation. The onset of the renal failure was associated with the demonstration of anti-Lewis antibodies in the patient's serum, which could only have been derived from donor lymphocytes. Recovery of renal function coincided with the disappearance of the Lewis antibody. It is postulated that Lewis incompatibility between graft and host tissue may have contributed to the renal failure in this patient and that incompatibility associated with determinants present on renal cells may account for other instances of acute renal failure following allogeneic bone marrow transplantation.

In 40 patients assessed for splenic enlargement prior to splenectomy, clinical examination and ultrasonic scanning gave equally accurate results when compared with splenic weight after removal. In the 22 patients having staging laparotomy and splenectomy for Hodgkin's disease, ultrasound was unable to assess accurately the presence of tumour deposits.