Soluble transferrin receptor: a discriminating assay for iron deficiency.

The distinction between iron deficiency anaemia (IDA) and the anaemia that accompanies infection, inflammation or malignancy, commonly termed the anaemia of chronic disease (ACD), is often difficult, as the conventional laboratory indices of iron status are often influenced by acute phase responses. In recent years, the soluble transferrin receptor (sTfR) has been introduced as a sensitive, early and highly quantitative new marker of iron depletion, increasing in proportion to tissue iron deficit. Unlike conventional laboratory tests, the sTfR is not an acute phase reactant and remains normal in patients with chronic disease. In this study TfR concentrations were compared with the gold standard of iron stores, bone marrow iron. The sTfR concentration was shown to be the most efficient test in predicting bone marrow iron stores in 20 patients with ACD (75% efficiency) and in 18 patients with rheumatoid arthritis (RA) (94% efficiency). Measurement of sTfR may be a useful addition in the differential diagnosis of ACD and IDA.

Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow transplant recipients.

The pharmacokinetics of fluconazole was investigated in 20 bone marrow transplant patients following oral administration of 200 mg of this drug. Blood samples were collected from each patient at different time intervals within 48 h after the first dose, and fluconazole was measured in plasma by high-performance liquid chromatography with UV detection. Urine was collected from 14 of these patients and analyzed similarly. The plasma concentration-time data exhibited the characteristics of the one-compartment model with first-order absorption quite well. The means +/- standard deviations of half-lives for absorption and elimination, peak concentration, time to peak, mean residence time, apparent volumes of distribution, area under the curve, and apparent oral clearance observed in these patients were 2.84 +/- 1.34 h, 19.94 +/- 18.7 h, 4.45 +/- 1.86 microg/ml, 8.34 +/- 5.97 h, 39.57 +/- 20.5 h, 0.874 +/- 0.48 liter/kg, 156.0 +/- 60.6 microg x h/ml, and 0.0256 +/- 0.0138 liter/h x kg, respectively. The amount of fluconazole excreted in urine in 24 h was 67.1 +/- 83 mg, which represents 33.55% +/- 41.6% of the dose administered. Patients who developed hemorrhagic cystitis excreted significantly (P < or = 0.0094) more fluconazole in 24 h than did those who did not.

Effect of repeated dosing on the pharmacokinetics of oral fluconazole in bone marrow transplant patients.

We examined the pharmacokinetics of fluconazole in 11 bone marrow transplant patients after multiple oral daily dose of 200 mg of this drug. Blood was sampled at different intervals on day 1, day 13, and day 27. No dose was given on day 2, day 14, and day 28 to allow the concentration-time data to be collected over 48 hours. The 24 hour urine was also collected, and fluconazole was analyzed in both plasma and urine by a high performance liquid chromatography. The plasma concentration-time data were best described by the one-compartment model with first-order absorption. The overall inter-day change and the difference between day 1 and day 27 in the rate constant for absorption (ka), peak plasma concentration (Cmax), through plasma concentration (Cmin), time-to-peak (tmax), area-under-the-curve 0-24 (AUC0-24), rate constant for elimination (ka), mean residence time after oral administration (MRTor), and fraction of the dose excreted unchanged in urine 24 hours (fu24) were significant (P < or = 0.0029 and P < or = 0.01, respectively). However, the difference between day 1 and day 13 was significant (P < or = 0.05) only in ka, tmax, Cmax, Cmin, and AUC0-24, and between day 13 and day 27 was significant (P < or = 0.05) only in ka, Cmin, ka, and MRTor. There was no significant inter-day change in the renal clearance. The significant (P < or = 0.05) increases in Cmax, Cmin, and AUC0-24 after the dose given on day 13 as compared with day 1, and in Cmin on day 27 as compared with day 13 indicate that, in contrast to volunteers, the steady state condition was not reached on day 13 and possibly not on day 27 in these patients. This perhaps should be taken into account when prescribing fluconazole to seriously ill patients.

High incidence of line-related infection and mechanical failure of an antiseptic impregnated central venous catheter in highly immunocompromised patients.

Prolonged central venous catheterisation is associated with a substantial risk of line related infection, which may be reduced when a chlorhexidine/silver-sulfadiazine coated catheter (ARROWgard Blue(TM)) is used in medical or surgical ICU patients. However, no data is available from severely immunocompromised patients. We therefore performed an initial exploratory study among patients with haematological malignancy, aplastic anaemia or bone marrow transplantation. The study was terminated after the 12th catheter insertion. Eight of 11 assessable catheters developed a notable degree of mechanical dysfunction, which directly led to catheter removal in 2 patients. Six of the 11 catheters were unstable. Catheter-related infection occurred in 5 instances. Only 1 catheter functioned normally and was unassociated with infection. The ARROWgard Blue(TM) catheter cannot be recommended for prolonged use in these patients.

Systemic amphotericin B versus fluconazole in the management of antibiotic resistant neutropenic fever--preliminary observations from a pilot, exploratory study.

A pilot exploratory study was undertaken to collect preliminary information relating to safety and overall outcome in using intravenous fluconazole (FLUC) for managing antibiotic resistant neutropenic fever (ARNF), with the objective of assessing feasibility of performing a larger prospective controlled study. Patients who were neutropenic from treatment for leukaemia or bone marrow transplantation, received either fluconazole (FLUC) or amphotericin B (AB). Eight of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/- 6.3 days for AB, and a similar proportion in each treatment group defervesced within 5 days (50% vs. 52%), respectively. Six of 16 patients (37.5%) on FLUC and three of 25 patients (12%) on AB developed overt invasive fungal disease, including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive candidiasis (FLUC 2 cases, AB 0 cases). The mean time to these events was 19.5 +/- 13.4 (FLUC) and 9.0 +/- 3.6 (AB) days. The fungal related mortality rates were higher in the FLUC group: five of 16 patients (31%) vs. two of 25 patients (18%) died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/- 18.4 (AB) days. This tendency towards a more favourable outcome in patients on AB may have been due to absence of prior fluconazole prophylaxis in patients subsequently receiving IV FLUC. Analysis of a small subgroup of patients who had all received prior prophylaxis with clotrimazole only, indicated that a greater number of patients subsequently receiving IV FLUC died from fungal disease (5/16 vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Trauma outcome analysis of two Canadian centres using the TRISS method.

In this retrospective study, the TRISS method of trauma care analysis is used to compare trauma care at the Hamilton General Hospital (HGH) and the Ottawa Civic Hospital (OCH) with the standards reported in the Major Trauma Outcome Study (MTOS). A total of 274 adult patients with multiple-system injuries were studied; their demographic data, Trauma Scores (TS) on arrival to the Emergency Room, and Injury Severity Scores (ISS) were reviewed. The TRISS scores and Z and M statistics were then calculated. In the Hamilton group, 106 consecutive patients from April through July 1987 were studied. The majority of patients (72%) were male, and the median age was 26 years. The majority of patients (96.2%) sustained blunt trauma, with motor vehicle accidents (MVA) being the most common (76.4%) mechanisms of injury. Fifty-four (51%) of the patients were transferred from outlying hospitals. The Z and M statistics were -0.05 and 0.92, respectively. In the Ottawa group, 168 consecutive patients from April 1987 through October 1988 were studied. The majority of patients (73%) were male, and the median age was 39 years. Blunt trauma accounted for the majority (91.7%) of injuries, with MVAs being responsible for 58% of injuries. Most patients (63.5%) were transferred from regional hospitals. The Z and M statistics were 1.20 and 0.56, respectively. We conclude that the survival statistics of trauma patients treated at both centres are comparable to those of trauma patients in the MTOS.

Pneumatic antishock trousers.

While pneumatic antishock trousers are a useful adjunct for the initial management of hypotension, they do not replace, but can augment, fluid replacement and other resuscitative procedures. They can be applied quickly and are relatively safe when used in the manner recommended. They must not be used in a patient with congestive heart failure. Finally, it is imperative that they are not removed suddenly from the hypovolemic, hypotensive patient.