Fusion of approaches to the treatment of organ failure

Because organ transplantation is the preferred treatment for organ failure, the demand for human organs for transplantation is large and growing. From this demand, several fields based on new technologies for the replacement or repair of damaged tissues and organs have emerged. These fields include stem cell biology, cloning, tissue engineering and xenotransplantation. Here we evaluate the potential contribution of these to the devising of alternative approaches to organ replacement. We present our vision for the development of two structurally complex organs – the lung and the kidney – based on a 'fusion' of new and established technologies.     

Anterior lumbar instrumentation improves correction of severe lumbar Lenke C curves in double major idiopathic scoliosis

Fifteen skeletally immature patients with double major adolescent idiopathic scoliosis with large lumbar curves and notable L4 and L5 coronal plane obliquity were retrospectively studied. Seven patients who underwent anterior release and fusion of the lumbar curve with segmental anterior instrumentation and subsequent posterior instrumentation ending at L3 were compared with eight patients treated with anterior release and fusion without anterior instrumentation followed by posterior instrumentation to L3 or L4. At 4.5 years follow-up (range 2.5-7 years), curve correction, coronal balance and fusion rate were not statistically different between the two groups; however, the group with anterior instrumentation had improved coronal plane, near normalangulation in the distal unfused segment compared with the group without anterior instrumentation. In cases involving severe lumbar curvatures in the context of double major scoliosis, when as a first stage anterior release is chosen, the addition of instrumentation appears to restore normal coronal alignment of the distal unfused lumbar segment, and may in certain cases save a level compared with traditional fusions to L4.     

Invited. Brain edema development after MRI-guided focused ultrasound treatment

The aim of this study was to investigate a potential technique for image-guided minimally invasive neurosurgical interventions. Focused ultrasound (FUS) delivers thermal energy without an invasive probe, penetrating the dura mater, entering through the cerebrospinal fluid (CSF) space, or harming intervening brain tissue. We applied continuous on-line monitoring by MRI to demonstrate the effect of the thermal intervention on the brain tissue. For this, seven rabbits had a part of their skull removed to create access for the FUS beam into the brain through an acoustic window of 11 mm in diameter. Dura was left intact and skin was sutured. One week later, the rabbits were sonicated for 3 seconds with 21 W acoustic power, and the FUS focus was visualized with a temperature-sensitive T1-weighted MRI pulse sequence. The tissue reaction was documented over 7 days with T2-weighted images of the brain. The initial area of the central low signal intensity in the axial plane was .4 ± .3 mm², and for the bright hyperintensity surrounding the lesion, it was 2.3 ± .6 mm² (n = 7). In the coronal plane, the corresponding values were .4 ± .1 mm² and 3.4 ± .9 mm² (n = 5). The developing brain edema culminated 48 hours later and thereafter diminished during the next 5 days. Histology revealed a central necrosis in the white matter surrounded by edematous tissue with inflammatory cells. In summary, the image-guided thermal ablation technique described here produced a relatively small lesion in the white matter at the targeted location. This was accomplished without opening the dura or the need for a stereotactical device. MRI allowed on-line monitoring of the lesion setting and the deposition of thermal energy and demonstrated the tissue damage after the thermal injury.     

Round table conference on clinical trials for the treatment of sepsis Brussels,March 12–14, 1994

The Proceedings of the Round Table Conference will be published as volume 19, in the series Update in Intensive Care and Emergency Medicine (Springer Verlag) in January, 1995.     

Phosphate poisoning by ingestion of clothes washing liquid and fabric conditioner

A case of deliberate ingestion of clothes washing liquid and fabric conditioner is described. Tracheal intubation and controlled ventilation became necessary because of respiratory muscle dysfunction associated with hypocalcaemia. We suggest that the phosphate component of the clothes washing liquid was responsible for the dramatic metabolic upset and subsequent need for admission to the Intensive Care Unit.     

Primary Health Care through a community based smoking-cessation program

The International Conference on Primary Health Care, meeting in Alma-Ata, in the Soviet Union, September 12, 1978, expressed the need for urgent action by all governments, all health and development workers and the world community, to protect and promote the health of all people of the world. The world was caught by the phrase which emerged from this conference, Health For All by the Year 2000 and many have examined the articles of the Alma-Ata declaration and tried to implement them in their corner of the world. This paper describes a community-based smoking-cessation program which was implemented in the province of Nova Scotia, Canada, during the years 1980–1984. Primary to this project was the belief that people have the right and the duty to participate individually and collectively in planning and implementing their health care. This paper describes one community's effort in putting this belief into practice.Carol Smillie, B.N. BE.d. M.S.c. is an Assistant Professor at the School of Nursing, Dalhousie University, Halifax, Nova Scotia, Canada B3H 3J5, Katherine Coffin, BA, MEd is the Program Officer, Nova Scotia Office, Health Promotion Directorate Health and Welfare Canada, 5251 Duke Street, Halifax, Nova Scotia. Canada B3J 1P3. Kathryn Porter, B.A. (Gen)., is the Information and Education Coordinator, Nova Scotia Division Canadian Cancer Society. Brenda Ryan, B.A., M.B.A. is Program Evaluation Analysist, Nova Scotia Department of Health, 6088 Hollis Street, Halifax. Nova Scotia, Canada. This Project was funded by Health and Welfare Canada, Nova Scotia Department of Health, Nova Scotia Division Canadian Cancer Society, Requests for reprints should be addressed to: Professor Carol Smillie.     

The pharmacokinetics and toxicity of the anthrapyrazole anti-cancer drug CI-941 in the mouse: a guide for rational dose escalation in patients

Summary CI-941 is a new synthetic DNA-binding agent selected for phase I clinical evaluation. The drug has broad-spectrum antitumour activity against a number of murine tumours and, in contrast to doxorubicin, is unlikely to induce cardiotoxicity by a free-radical-mediated mechanism. In this study the toxicity and pharmacokinetics of CI-941 were studied in the mouse to enable the implementation of a pharmacokinetically guided dose-escalation strategy in patients. Following a single i.v. bolus injection in mice, CI-941 induced dose-dependent leukopenia. The white blood cell counts were suppressed on day 3 by 18%, 50% and 65% of control, at doses of 10, 15 and 20 mg/kg CI-941, respectively. Other toxicities such as weight loss, alopecia, diarrhoea and convulsions were observed at doses >20 mg/kg. Lethality studies in female Balb-c mice resulted in an LD₁₀ value of 20 mg/kg (95% confidence limits; range, 19–21 mg/kg) and an LD₅₀ value of 22 mg/kg (95% confidence limits; range, 21–23 mg/kg). The pharmacokinetics of CI-941 were studied at four dose levels from 1/10 of the LD₁₀ to the LD₁₀ (20 mg/kg). The drug was rapidly cleared from the plasma (250–400 ml/min per kg) at a rate approaching the cardiac output of mice, displaying triphasic plasma pharmacokinetics. The area under the plasma CI-941 concentration vs time curve (AUC) was linear with respect to the dose, up to and including 15 mg/kg (AUC=110 M x min at 15 mg/kg), but became non-linear at 20 mg/kg (AUC=277 M x min). Despite 80%–84% plasma protein binding, CI-941 was rapidly and extensively distributed into tissues, especially the kidney. Following i.v. bolus injections at doses of 1.5 and 15 mg/kg, elimination of the parent compound by urinary excretion accounted for 12%–18% of the delivered dose. A phase-I starting dose (based on that equivalent to 1/10 of the LD₁₀ in the mouse) of 5 mg/m² CI-941 is recommended for single administration schedules. In addition, a pharmacokinetically guided dose-escalation strategy, based on achieving a target AUC of 110 M x min, is proposed.