Technetium-99m labelled liposomes to image experimental arthritis

OBJECTIVES—Liposomes sterically stabilised with polyethylene glycol (PEG) labelled with technetium-99m were tested for their ability to image adjuvant arthritis in a rat model.
METHODS—Adjuvant arthritis was induced in the ankle joint of the left hind foot by injection of Mycobacterium butyricum in Freund's incomplete adjuvant in the foot pad. Seven days later animals received the following radiopharmaceuticals labelled with ^99mTc (a) non-PEG-liposomes, (b) PEG-liposomes or (c) non-specific human polyclonal IgG. For each of the radiopharmaceuticals the in vivo distribution of the radiolabel was monitored both scintigraphically as well as by counting the dissected tissues at two, eight, and 24 hours after injection.
RESULTS—The pharmacokinetics of the radiopharmaceuticals differed considerably (half life in the blood: PEG-liposomes (18 hours) > ^99mTc-IgG (3 hours) > non-PEG liposomes (1 hour)). The inflamed focus was visualised with each of the agents. The uptake of each of the radiopharmaceuticals in the inflamed ankle region correlated with their residence time in the blood (inflamed joint uptake: PEG liposomes (1.15% injected dose (ID)/g)>^99mTc-IgG (0.35% ID/g)>non-PEG-liposomes (0.05% ID/g)). Quantitative analysis of the images showed that the inflamed ankle to background ratio was highest with the PEG-liposomes (7.5 at 24 hours after injection), while with the other two agents this ratio did not exceed 4.
CONCLUSION—This study shows that ^99mTc-labelled PEG-liposomes may be an excellent agent to visualise arthritis. Increased label uptake in the inflamed joint and increased target to background ratios can be obtained with PEG-liposomes because of their long circulating properties. In addition to their use as vehicles for scintigraphic imaging of arthritis PEG-liposomes might also be used for the site specific delivery of antirheumatic drugs.

     

Doing it right the first time: quality improvement and the contaminant blood culture.

The aim of the project was to determine whether the rate of contaminant blood cultures could be reduced by using a team of dedicated phlebotomists. Comparisons were made between adult patients requiring blood cultures for suspected bacteremia on medical and surgical units before and after the introduction and withdrawal of a dedicated blood culture team. The results showed that a significant reduction in the contaminant blood culture rate was achieved by the blood culture team (P < 0.001; chi(2) test). Therefore, in our experience, the rate of contaminant blood cultures can be reduced in a teaching hospital by using a team of dedicated phlebotomists. Calculations made with our data and those published by others suggest that cost savings from reducing false-positive blood cultures are greater than the cost of the blood culture team.     

Location and geometric description of carpal bones in CT images

The carpal regions of ten cadaver extremities were imaged by CT. The images were combined into a 3-dimensional model of the carpus using a technique based on a dynamic programming algorithm to find an optimal estimate of the location of the bone boundaries in the CT images. The resulting set of surface points on each bone was used to compute volumes and principal and antipodal axes for the bones. A spatial coordinate system was established based on the positions of the centroids of three bones in the distal carpal row. The angular orientations of all carpal bones were determined with respect to this system. The principal axes for the same bone among ten wrist specimens proved to be more widely dispersed than the antipodal axes for the same bones. The antipodal axes also correspond more closely to an intuitive notion of the “longest axis” of the bones. We conclude that the antipodal axis is a more reliable and useful measure of bone orientation than the principal axis.     

Death due to anaesthesia at Groote Schuur Hospital, Cape Town--1956-1987. Part II. Causes and changes in aetiological pattern of anaesthetic-contributory death

A general analysis of the clinical failures that were responsible for deaths attributable to anaesthesia over a 30-year period, 1956-1987, is presented. Four particular general failures in clinical management were responsible for 80% of anaesthetic-contributory deaths (ACD). These were in descending order of frequency: (i) failures in airway management, of which the majority were associated with the complications of endotracheal intubation (27% of ACD); (ii) failures in pulmonary ventilation management (20% of ACD); (iii) failures in blood volume control (19% of ACD); and (iv) failures in arrhythmia control (17% of ACD). Computation of these groups of causes by the decade reveals a distinct and progressive change in the aetiological pattern of these deaths with time. While the incidence of ACD over the period decreased 6-fold from 0.43 to 0.07/1,000 anaesthetics, that proportion due to failures in airway management, in general, and complications of intubation, in particular, has progressively increased. This has been accompanied by a reciprocal decrease in deaths due to circulatory factors. It is postulated that this change arises from the fact that the physical skills, manual dexterity and clinical judgement demanded by the former have not changed with time, whereas the latter depend on intellectual responses to information derived from ever-improving vital function monitoring.     

The in vitro fertilisation programme at Tygerberg Hospital and the University of Stellenbosch. Five years' experience, April 1983-January 1988

The results of the in vitro fertilisation programme at Tygerberg Hospital for the period April 1983 to January 1988 are presented. Of the 1117 laparoscopies performed, 825 patients reached the transfer stage. A live-birth rate of 9.3% was achieved. The pregnancy rate after transfer of 4 embryos was 25.9% compared with 15.4% after 2 embryos and 10.8% after 3 embryos (P = less than 0.0001). The multiple pregnancy rate was 2.8% in the group receiving 2 embryos and 11.7% and 10.4% in those receiving 3 and 4 embryos, respectively. Of the 77 successful pregnancies (90 babies), 1 baby died at 34 weeks' gestation as the result of abruptio placentae due to preeclampsia and 1 cot death occurred. The only congenital abnormality encountered was a cleft palate.     

The role of the high dependency unit in postoperative care: an update.

The current experience of a high dependency unit established 5 years ago for the postoperative care of high-risk patients undergoing surgery is reported. The resource implications and contributions to the safety and quality of post-operative care, particularly pain relief, are described.     

Liquid silicone as a lunate prosthesis

Eleven patients with lunatomalacia were treated by excision of the lunate and instillation of liquid silicone. The silicone vulcanised and formed an in-situ molded prosthesis. The patients were reexamined after a mean of 7.1 years. Four patients were pain-free and two had pain only at work; three had not been improved by the operation and two had undergone arthrodesis. The patients with good results all belonged to group IV pre-operatively. Surprisingly, no patient showed any sign of silicone synovitis, although all the prostheses except one had either fractured or deformed. The reasons for this are discussed and the indications for the operation established.     

Erythropoietin and anemia in the progression of Balkan endemic nephropathy and other renal diseases

We have investigated anemia in patients at different stages of the evolution of three chronic renal diseases: Balkan endemic nephropathy (BEN), chronic pyelonephritis (PN) and chronic glomerulonephritis (GN). A total of 88 patients with creatinine clearances from 9 to 118 ml/min and hemoglobin concentrations from 70 to 160 g/l were studied with regard to the relationship, if any, between erythropoietin production and the type and stage of nephropathy. Anemia in BEN was a particular focus of interest since it had been stated that in BEN, anemia precedes renal failure. Our data neither prove nor disprove this statement. A significant positive correlation between creatinine clearance and hemoglobin concentration was found in all three nephropathies, indicating that in the patients studied the severity of anemia increased with the impairment of renal function regardless of the underlying disease. Serum levels of immunoreactive erythropoietin were in the normal range in 54 patients, moderately increased in 20 and slightly decreased in 14. The erythropoietin level appears to be unrelated to the stage of renal failure or the type of nephropathy. The only exception was the subgroup where the patients with glomerulonephritis and normal renal function had increased serum erythropoietin levels and significantly higher parameters of red blood cell concentration than the patients from the same subgroup with tubulointerstitial nephropathies. In patients with severe renal failure and anemia, serum erythropoietin levels were inappropriately low for the degree of anemia, indicating that erythropoietin plays a role in the pathogenesis of the anemia.