The Lesch-Nyhan syndrome

Metabolic studies in a case of Lesch-Nyhan syndrome are presented. De novo synthesis of purine was shown to be inhibited upon adenine administration. The excretion of oxypurines is elevated, however, by an increased incorporation of the administered adenine into purine bases. A side effect of adenine administration is the production of the slightly soluble and highly nephrotoxic 2,8-dioxyadenine, which can cause renal damage.     

The combination of Hirschsprung's disease and achalasia

The unusual combination of Hirschsprung's disease and Achalasia in one case treated by standard procedures led to the discussion about RET germ-line mutations and consequently to the speculation about higher risk for multiple endocrine neoplasia syndrome type 2-related tumors. Although a mutation could be excluded by sequence analysis in this case, the correlation of these specific diseases affords additive investigations to make sure that no further prophylactic procedures were necessary.     

Human immunodeficiency virus type 1 latency model for high-throughput screening

Human immunodeficiency virus type 1 (HIV-1) is not eliminated from patients even after years of antiretroviral therapy, apparently due to the presence of latently infected cells. Here we describe the development of a cell-based system of latency that can be used for high-throughput screening aimed at novel drug discovery to eradicate HIV-1 infection.     

Quantification of myocardial perfusion defects using three different software packages

Software packages are widely used for quantification of myocardial perfusion defects. The quantification is used to assist the physician in his/her interpretation of the study. The purpose of this study was to compare the quantification of reversible perfusion defects by three different commercially available software packages. We included 50 consecutive patients who underwent myocardial perfusion single-photon emission tomography (SPET) with a 2-day technetium-99m tetrofosmin protocol. Two experienced technologists processed the studies using the following three software packages: Cedars Quantitative Perfusion SPECT, Emory Cardiac Toolbox and 4D-MSPECT. The same sets of short axis slices were used as input to all three software packages. Myocardial uptake was scored in 20 segments for both the rest and the stress studies. The summed difference score (SDS) was calculated for each patient and the SDS values were classified into: normal (<4), mildly abnormal (4–8), moderately abnormal (9–13), and severely abnormal (>13). All three software packages were in agreement that 21 patients had a normal SDS, four patients had a mildly abnormal SDS and one patient had a severely abnormal SDS. In the remaining 24 patients (48%) there was disagreement between the software packages regarding SDS classification. A difference in classification of more than one step between the highest and lowest scores, for example from normal to moderately abnormal or from mildly to severely abnormal, was found in six of these 24 patients. Widely used software packages commonly differ in their quantification of myocardial perfusion defects. The interpreting physician should be aware of these differences when using scoring systems.     

Prospective randomized controlled trial of acute normovolaemic haemodilution in major gastrointestinal surgery

Background. The efficacy of acute normovolaemic haemodilution(ANH) remains uncertain because of a lack of well-designed prospectiverandomized controlled trials. The aim of this study was to assessthe effects of ANH on allogeneic transfusion, postoperativecomplications, and duration of stay. Methods. Consecutive patients undergoing major gastrointestinalsurgery were randomized to a planned 3-unit ANH, or no ANH.Both groups underwent identical management including adherenceto a transfusion protocol after surgery. Outcome measures includedthe number of patients receiving allogeneic blood, complications,and duration of stay. Results. 380 patients were screened of which 160 were includedin the study, median age was 62 yr (range 23–90), ‘ANH’n=78, ‘no ANH’ n=82. There was no significant differencebetween groups in the number of patients receiving allogeneicblood 22/78 (28%) vs 25/82 (30%), the total number of allogeneicunits transfused (90 vs 93), complication rate, or durationof stay. Haemodilution significantly increased anaesthetic time,median 55 (range 15–90) vs 40 min (range 17–80)(P<0.001). Significantly fewer patients in the ANH groupexperienced oliguria in the immediate postoperative period 37/78(47%) vs 55/82 (67%) (P=0.012). The most significant factorsaffecting transfusion were blood loss, starting haemoglobin,and age. When compared with ASA-matched historical controls,the introduction of a transfusion protocol reduced the transfusionrate in colorectal patients from 136/333 (41%) to 37/138 (27%),P=0.004. Conclusions. In this large pragmatic study, ANH did not affectallogeneic transfusion rate in major gastrointestinal surgery.Preoperative haemoglobin, blood loss, and transfusion protocolare the key factors influencing allogeneic transfusion.     

Factors influencing community nurses' treatment of leg ulcers

Clinical effectiveness and evidence-based practice are a central feature of the clinical governance framework. Few studies have examined factors that motivate nurses to change practice in line with evidence-based guidelines. The overall aim of this exploratory study was to examine community nurses' experience of taking part in a clinical effectiveness programme for the management of leg ulcers in the community and to identify factors most likely to ensure a change in practice. The implementation programme was conducted in the general practices within one district of a primary care audit group. Face-to-face interviews were conducted with all practice nurses and district nurses involved in the care of patients with leg ulcers from the participating practices. Nurses identified the presence of a credible facilitator, visible benefits for patients and a desire to carry out their work in an evidence-based way as factors likely to influence change. However, the degree of change achieved was not uniform across all participants and three typologies of nurses were identified according to their attitudes and level of involvement.     

A web-based presentation of an undergraduate clinical skills curriculum

AIMS: The aim of this study was to use information and communications technology to present a curriculum of clinical skills in a user-friendly format. SETTING: A UK undergraduate medical school with a problem-based curriculum and a strong emphasis on proficiency in clinical skills. STUDY DESIGN: Case study describing the qualitative analysis of users' requirements and development of a web-based learning portfolio. EVALUATION: The study involved direct observation of users during a 'think-aloud' protocol, a validated software users' measurement inventory and a 17-item questionnaire designed to test whether 'SkillsBase' met its users' requirements. RESULTS: Students wanted a clear and flexible presentation of their skills curriculum that was easy to navigate, offered instructional material and standards for self- and peer assessment, offered useful Internet links, allowed them to compare their progress with school standards and peer norms, and could be used as a learning portfolio. During the think-aloud protocol, students made very few errors in data interpretation or navigation, and found SkillsBase easy to learn and aesthetically pleasing to use. They rated it higher on all measures of usability than standard commercial software. The questionnaire showed that it met most aspects of its design specification, although many students were doubtful that they would use its reflective function. It is available for inspection at http://www.skillsbase.man.ac.uk/. CONCLUSIONS: SkillsBase meets the design specification for a training and reflective aid to learning clinical skills and is very usable.     

Fluid dynamics in man of an intraperitoneal drug delivery solution: 4% icodextrin

Interest in targeting drugs into the peritoneal cavity for intra-abdominal cancers or infections is undergoing a revival as recent clinical trials have demonstrated, not only a regional advantage in concentration of the active agent, but also improved long-term outcomes. Solutions currently used for intraperitoneal (IP) drug delivery have short residence times, however, which can limit the exposure of all areas of the peritoneum to the active agent. Icodextrin 4% solution was compared with saline and a glucose-based peritoneal dialysis solution in a clinical study of IP residence time. The study was carried out during the fortnightly rest phase in 9 patients undergoing 5-fluorouracil (5-Fu) IP treatment for colorectal cancer. The volume remaining in the peritoneal cavity was measured at 0, 12, 24, 48, 72, and 96 hr after an instillation of 2 liters of each fluid. Saline (n = 3 dwells) and glucose (n = 3 dwells) peritoneal dialysis solutions were almost fully absorbed by 24 hr, and the patients experienced discomfort when using these solutions. In contrast, icodextrin 4% solution (n = 188 dwells) maintained its instilled volume for up to 48 hr, and half the instilled volume remained after 72 and 96 hr. This result would allow extensive and prolonged coverage of the peritoneal surface. Icodextrin 4% solution may be an effective vehicle to deliver therapeutic agents into the peritoneal cavity.