Basic isoferritin and hypercalcaemia in renal cell carcinoma

A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a “basic isoferritin”. The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture

We have recently shown using dansyl-L-lysine exclusion studies that the release of human chorionic gonadotrophin (HCG) in conjunction with L- lactate dehydrogenase (LDH) from first trimester villi during organ culture is symptomatic of syncytiotrophoblast degeneration. The purpose of this study was to examine chorionic villi at the ultrastructural level in order to determine events occurring during organ culture. The tissue was sampled after 0, 24, 48 and 120 h in culture and processed for electron microscopy. In addition to confirming the previously recorded syncytial degeneration, the electron micrographs showed clearly the generation of a new syncytiotrophoblast layer. The new layer, derived from differentiating cytotrophoblast cells, was largely formed by 48 h and was maintained for at least 120 h in culture. This study demonstrates a model which provides an opportunity to study the differentiation of cytotrophoblast cells whilst they retain their anatomical relationships within the villous structure.      

Lymphocyte proliferative responses to chlamydial antigens in human chlamydial eye infections.

In order to study the relationship between cell-mediated immune responses to Chlamydia trachomatis and the pathogenesis of human chlamydial eye disease, we have measured the peripheral blood lymphocyte proliferative responses to whole chlamydial elementary bodies in 40 subjects with oculogenital chlamydial infection of varying severity, 13 subjects with genital chlamydial infections and 12 healthy seronegative controls. The mean stimulation index was significantly higher in those with oculogenital infections than in controls. There was a strong correlation between the response to C. trachomatis serotypes B and L1. We studied the relationship between proliferative responses and four clinical parameters: follicular conjunctivitis, papillary hypertrophy, corneal pannus and epithelial punctate keratitis, but were unable to show a significant association with any of these. Nor was there any association between proliferative response and serum antibody titre to C. trachomatis (pooled serotypes D-K), duration of disease or quantitative isolation of chlamydia from the conjunctiva. The depletion of CD8+ cells had no consistent effect on proliferative responses to serotype L1 in 13 subjects.     

The use of intravenous lidocaine for postoperative pain and recovery: international consensus statement on efficacy and safety

Intravenous lidocaine is used widely for its effect on postoperative pain and recovery but it can be, and has been, fatal when used inappropriately and incorrectly. The risk-benefit ratio of i.v. lidocaine varies with type of surgery and with patient factors such as comorbidity (including pre-existing chronic pain). This consensus statement aims to address three questions. First, does i.v. lidocaine effectively reduce postoperative pain and facilitate recovery? Second, is i.v. lidocaine safe? Third, does the fact that i.v. lidocaine is not licensed for this indication affect its use? We suggest that i.v. lidocaine should be regarded as a ‘high-risk’ medicine. Individual anaesthetists may feel that, in selected patients, i.v. lidocaine may be beneficial as part of a multimodal peri-operative pain management strategy. This approach should be approved by hospital medication governance systems, and the individual clinical decision should be made with properly informed consent from the patient concerned. If i.v. lidocaine is used, we recommend an initial dose of no more than 1.5 mg.kg^-1, calculated using the patient’s ideal body weight and given as an infusion over 10 min. Thereafter, an infusion of no more than 1.5 mg.kg^-1.h^-1 for no longer than 24 h is recommended, subject to review and re-assessment. Intravenous lidocaine should not be used at the same time as, or within the period of action of, other local anaesthetic interventions. This includes not starting i.v. lidocaine within 4 h after any nerve block, and not performing any nerve block until 4 h after discontinuing an i.v. lidocaine infusion.     

Updates in our understanding of local anaesthetic systemic toxicity: a narrative review

Despite advances in clinical practice, local anaesthetic systemic toxicity continues to occur with the therapeutic use of local anaesthesia. Patterns of presentation have evolved over recent years due in part to the increasing use of ultrasound which has been demonstrated to reduce risk. Onset of toxicity is increasingly delayed, a greater proportion of clinical reports are secondary to fascial plane blocks, and cases are increasing where non-anaesthetist providers are involved. The evolving clinical context presents a challenge for diagnosis and requires education of all physicians, nurses and allied health professionals about these changing patterns and risks. This review discusses: mechanisms; prevention; diagnosis; and treatment of local anaesthetic systemic toxicity. The local anaesthetic and dose used, site of injection and block conduct and technique are all important determinants of local anaesthetic systemic toxicity, as are various patient factors. Risk mitigation is discussed including the care of at-risk groups, such as: those at the extremes of age; patients with cardiac, hepatic and specific metabolic diseases; and those who are pregnant. Advances in the changing clinical landscape with novel applications and settings for the use of local anaesthesia are also described. Finally, we signpost future directions to potentially improve the management of local anaesthetic systemic toxicity. The utility of local anaesthetics remains unquestionable in clinical practice, and thus maximising the safe and appropriate use of these drugs should translate to improvements in patient care.     

An analysis of an admissions system: can performance in the first year of the dental course be predicted?

The admissions process must be scrupulously fair and select the most suitable students. Data on applicants to the Manchester Dental School for the 1996/97 academic year were analysed. The aims of this project were to: describe the applicants using information from the UCAS (university entrance) form; to relate information from the UCAS form to interview performance and A-level results; and to evaluate whether these factors can predict performance during the first year of the course.     

APOE epsilon4 allele and amyloid beta-protein deposition in long term survivors of head injury

Head injury and APOE epsilon4 are risk factors for Alzheimer's disease (AD). We previously found that deposits of amyloid beta-protein (Abeta) occur in fatal head injury, more frequently in patients with APOE epsilon4. We postulated that Abeta deposits triggered by injury could, in survivors, lead to AD-like pathology later in life. Here, we compared Abeta deposits in 21 long term survivors of head injury (up to 20 years) with age and APOE genotype matched controls. In both groups Abeta deposits were more common among patients with APOE epsilon4. However, Abeta deposits were not more common among survivors of head injury than controls. The findings support previous studies associating APOE epsilon4 with deposition of Abeta. However pathogenetic mechanisms other than Abeta deposition may explain the association of head injury with AD.