New optical technologies for earlier endoscopic diagnosis of premalignant gastrointestinal lesions

Gastrointestinal malignancies continue to be the second leading cause of cancer-related deaths in the developed world. The early detection and treatment of gastrointestinal preneoplasms has been demonstrated to significantly improve patient survival. Conventional screening tools include standard white light endoscopy (WLE) and frequent surveillance with biopsy. Well-defined endoscopic surveillance biopsy protocols aimed at early detection of dysplasia and malignancy have been undertaken for groups at high risk. Unfortunately, the poor sensitivity associated with WLE is a significant limitation. In this regard, major efforts continue in the development and evaluation of alternative diagnostic techniques. This review will focus on notable developments made at the forefront of research in modern gastrointestinal endoscopy based on novel optical endoscopic modalities, which rely on the interactions of light with tissues. Here we present the 'state - of - the - art' in fluorescence endoscopic imaging and spectroscopy, Raman spectroscopy, optical coherence tomography, light scattering spectroscopy, chromoendoscopy, confocal fluorescence endoscopy, and immunofluorescence endoscopy. These new developments may offer significant improvements in the diagnosis of early lesions by allowing for targeted mucosal excisional biopsies, and perhaps may even provide 'optical biopsies' of equivalent histological accuracy. This enhancement of the endoscopist's ability to detect subtle preneoplastic changes in the gastrointestional mucosa in real time and improved staging of lesions could lead to curative endoscopic ablation of these lesions and, in the long term, improve patient survival and quality of life.     

A Familial Hemorrhagic Diathesis due to an Antithrombin

1) A familial hemorrhagic diathesis has been found to be due to an antithrombin.

2) This antithrombin is not fibrinogen, antithrombin II, III, or IV, and isnot similar in its characteristics to the antithrombins described in secondaryhemorrhagic conditions.

3) The inheritance of this disorder is not sex-linked but is otherwise notclear. The factor may be a dominant, the expression of which is modified byunknown factors.

Submitted on July 6, 1962 Accepted on October 17, 1962     

Donor lymphocyte infusion for childhood acute lymphoblastic leukaemia relapsing after bone marrow transplantation

Four children with acute lymphoblastic leukaemia (ALL) who relapsed after allogeneic bone marrow transplantation (BMT) were treated with donor lymphocyte infusion (DLI) without prior conditioning. Three patients had previously received a non-T-cell-depleted matched sibling BMT and the fourth had a T-cell-depleted matched unrelated BMT. Two patients developed grade III–IV acute graft-versus-host-disease (GVHD) of the skin, which required intervention. Both are alive in complete haematological remission 7 and 10 months from DLI with chronic GVHD of the skin requiring immunosuppressive therapy. A third patient went into haematological remission 6 weeks after DLI, but with no clinical evidence of GVHD. His bone marrow remained in remission 11 months post-DLI despite the disease (ALL) relapsing in extramedullary sites. The fourth patient showed no clinical or haematological response to three consecutive doses of DLI given at 4-weekly intervals and died from progressive disease 11 months after relapse. These preliminary observations indicate that in constrast to experience in adult ALL, DLI may be effective in inducing sustained remission in children with ALL relapsing after BMT, and a response may occur even in the absence of clinical evidence of GVHD.     

Phenotypic and functional properties of Th lines and clones recognizing larval antigens of Schistosoma mansoni

Five T cell clones and two lines were derived from the lymph nodes (LN) of C57BL/6 mice immunized with radiation-attenuated lung-stage larvae of Schistosoma mansoni. All seven clones/lines were CD4⁺, CD^8- and expressed high levels of CD44 and CD45RB surface markers. After prolonged maintenance in-vitro, with soluble antigen from 18 h schistosomula (SSP), five retained the ability to proliferate readily and release IFNg in response to conca-navalin A (Con-A) and to SSP and/or soluble adult worm antigen (SWAP). These Th clones/lines induced significant footpad DTH reactions when injected with SWAP, but were unable to confer protective immunity after transfer to naïve recipient mice. This result could be explained by the antigen specificity of the clones/lines, since they were not able to release IFNg when cultured in-vitro with living lung-stage larvae. A second possibility is that the high level of CD45RB expression, which is not seen on the surface of pulmonary CD⁴⁺ memory/effector cells isolated directly from protectively-vaccinated mice, alters the ability of the clones/lines to release IFNg and to induce a DTH response in the lungs when they encounter antigen released from migrating schistosomula.     

SERUM FREE 1,25-DIHYDROXYVITAMIN D AND THE FREE 1,25-DIHYDROXYVITAMIN D INDEX DURING A LONGITUDINAL STUDY OF HUMAN PREGNANCY AND LACTATION

The changes in three different indices of 1,25-dihydroxyvitamin D (1,25(OH)2D) biological activity were studied longitudinally in 35 women during late pregnancy and lactation and in 26 control women. Measurements were made of maternal serum total 1,25(OH)2D and free 1,25(OH)2D concentration (by centrifugal ultrafiltration) and the free 1,25(OH)2D index (the molar ratio of total 1,25(OH)2D and vitamin D binding protein (DBP]. During late pregnancy total 1,25(OH)2D concentrations were significantly elevated when compared to controls, as were free 1,25(OH)2D and DBP concentrations and the free 1,25(OH)2D index. Serum total 1,25(OH)2D, free 1,25(OH)2D and DBP concentrations all fell dramatically during the first 2 weeks of lactation with total 1,25(OH)2D and free 1,25(OH)2D concentrations falling to levels below those of controls. During the course of lactation both total 1,25(OH)2D and free 1,25(OH)2D levels rose significantly although they were not different from controls at 18 weeks of lactation. In contrast, the free 1,25(OH)2D index fell during the first 2 weeks of lactation, but remained at this level, significantly lower than controls. Neither urinary calcium excretion nor dietary calcium intake correlated with total or free 1,25(OH)2D, DBP, or the free 1,25(OH)2D index. The disagreement in the results of free 1,25(OH)2D concentration and free 1,25(OH)2D index demonstrates that these two approaches to measuring biologically active 1,25(OH)2D are not equivalent. In attempting to account for the increased calcium requirements of human reproduction we conclude that in pregnancy any of the 1,25(OH)2D measurements may be appropriate. In lactation, however, either 1,25(OH)2D is not a major factor or 1,25(OH)2D biological activity is inadequately represented by any of the currently available methods.     

Risk assessment of intravenous dose presentation in secondary care

□ The Breckenridge report highlighted that intravenous drug additions were aseptic procedures and should be conducted under the direct control of a pharmacist □ This study attempts to determine the extent of intravenous drug preparation at ward level and apply a risk assessment model □ Observation and risk assessment of intravenous drug preparation was carried out in two clinical areas within a large hospital □ Two thirds of the intravenous drug administration events were graded as high risk □ In the absence of a centralised intravenous additive service, the use of ready to administer forms or novel reconstitution systems may significantly reduce the risks associated with intravenous administration events