Point-of-care blood gas analysers: a performance evaluation.

Neonates represent a group with unusual sample characteristics and tend to have high hematocrits (Hct). The critically ill patient is also far from ideal with respect to sample type, being prone to either hemodilution or hemoconcentration. Prior to the selection of a point-of-care testing (POCT) analyser for blood gases and electrolytes, we therefore undertook a careful evaluation of some of the performance characteristics of selected instruments. We also conducted an evaluation of one of these systems using patients in the operating room (OR) and the pediatric Intensive Care Unit (ICU). Overall performance for hematocrit determination was acceptable in middle ranges but showed bias at high and low extremes. One system showed significant bias for electrolytes. For the patient evaluation, the system tested, the ABL70 (Radiometer, Copenhagen), showed a small positive bias for Na determinations. It also showed an important bias for pO(2) at levels that are clinically significant. The possibility of operator-related effects on test results has to be eliminated. In terms of ease of use and client satisfaction, the system was well received.

Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplant recipients.

To assess the relationship between serum cytokines and cytomegalovirus (CMV) reactivation, 75 allogeneic bone marrow transplant patients underwent weekly measurements of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha, CMV blood cultures, and antigenemia tests. Of the patients, 44 (58.7%) developed CMV infection, and 19 (25.3%) developed clinical CMV disease. The mean maximum levels of all three cytokines were significantly increased in patients with CMV infection compared with levels in those without. Maximum levels of IL-6 were significantly higher in patients with active CMV disease than in those who did not develop CMV disease (281.2+/-85.5 vs. 95.7+/-15.0 pg/mL; P=.034). Levels of IL-8 and TNF-alpha were also elevated in patients who developed active disease. In a multivariate logistic regression model, IL-6 levels were independently associated with CMV disease (odds ratio=1.70 per 100-pg/mL increase in IL-6; P=.009). Cytokines may play an important role in the pathogenesis of CMV after bone marrow transplantation and may be a useful predictor for CMV.

The efficacy of diazepam in the treatment of acute iron overload in rats.

While conducting studies on the prevention of mortality from acute iron intoxication in rats, diazepam, given to prevent animal suffering, was observed to be associated with reduced mortality in a limited number of animals. The objective was to assess whether diazepam reduces mortality following acute iron intoxication in rats. Survival of rats was compared among groups receiving (i) orally 612 mg/kg iron alone (LD60), (ii) iron with a subcutaneous injection of 2.5 mg/kg diazepam (DZ), or (iii) iron, DZ with 800 mg/kg deferiprone intraperitoneal injections. The administration of DZ decreased mortality from 60 to 16% (p < 0.001). The addition of deferiprone to DZ resulted in zero mortality (p < 0.05 compared with the DZ group) over the study period. The administration of DZ was not associated with decreased iron absorption or increased urinary iron excretion, whereas the administration of deferiprone did result in urinary iron excretion. Microscopic examination suggests that diazepam administration may be associated with lower intracellular accumulation of iron. In conclusion, diazepam reduces mortality from iron overdose in rats through a yet unidentified mechanism, although the drug does not inhibit iron absorption or enhance urinary iron removal.

Efficacy of deferiprone in the treatment of acute iron intoxication in rats.

BACKGROUND: Deferiprone [(1,2-dimethyl-3-hydroxypyrid-4-one) (L1)], is the first orally active iron chelating agent to reach clinical trials in patients with chronic iron overload. Its efficacy in preventing morbidity and mortality in acute iron poisoning has not been tested. OBJECTIVE: To determine whether deferiprone can reduce the mortality of rats following toxic oral doses of iron. METHODS: Rats were administered 612 mg/kg elemental iron by gavage, corresponding to the LD58. A parallel group received the same oral dose of iron followed by deferiprone intraperitoneally at 400 mg/kg (loading dose), followed by additional intraperitoneal injections of 200 mg/kg, 100 mg/kg and 100 mg/kg of deferiprone at one hour intervals. RESULTS: Coadministering deferiprone with the iron decreased mortality from 58% (11/19) to 15% (3/20) (p = 0.013). The administration of deferiprone was associated with urinary excretion of iron (which did not occur with iron alone) and the production of the red deferiprone-iron complex. On histological examination there appeared to be less iron in the liver and gastrointestinal tract. CONCLUSION: The coadministration of deferiprone can decrease morbidity and mortality caused by acute iron overdose. Deferiprone holds promise for the treatment of iron poisoning but additional study is required.

Primary sclerosing cholangitis in 32 children: clinical, laboratory, and radiographic features, with survival analysis.

The clinical presentation and outcome of 32 children with primary sclerosing cholangitis (PSC) are reviewed, the largest North American series. The majority of patients were diagnosed in their second decade (median age: 13 years). Four children presented before the age of 2 years, but none in the neonatal period. Seventeen patients had inflammatory bowel disease (IBD), all with colitis, 14 ulcerative colitis, and 3 Crohn's disease. Eight patients presented with chronic liver disease before clinical onset of IBD. Only 8 of 32 patients were jaundiced at presentation. Fifteen of 32 had a normal serum alkaline phosphatase (ALP) level at presentation. Nine children presented with features similar to those of autoimmune hepatitis. Cholangiography was performed in all cases and classified by a scoring system specifically developed for pediatric patients. Intrahepatic disease predominated; in only three cases a common bile duct stricture was identified requiring stenting. Findings on the initial liver biopsy were classified according to Ludwig's criteria for staging PSC: there were 15 biopsies in stages 1 to 2 and 17 biopsies stages 3 to 4. HLA class I and II antigens were determined in 27 patients. An increased incidence of HLA B8 and DR2(15) but not DRw52a (DRB3*0101) was found. Anti-neutrophil cytoplasmic antibody (ANCA) was positive in 10 of 24 patients tested. Survival analysis indicated that a later age at presentation, splenomegaly, and prolonged prothrombin time (PT) at presentation were significant contributors to the prediction of poor outcome (i.e., death or listing for transplantation). Liver transplantation was successfully performed in seven children. Physicians must maintain a high index of suspicion of PSC in any child or young adult presenting with chronic liver disease, especially in the presence of IBD, even with a normal serum alkaline phosphatase level.

Cardiac contusion and creatine kinase-MB: a pertinent case history and brief review of the utility of CK-MB.

Cardiac contusion is defined as the myocardial cellular damage that can result from nonpenetrating chest trauma. However the noninvasive diagnosis of this lesion is problematic. Among the criteria suggested for the diagnosis of cardiac contusion is an elevation of serum levels of the heart-specific isoform of the enzyme creatine kinase (CK-MB). We present here the case of a patient who, on the basis of an initial elevation of CK-MB, was suspected of having cardiac contusion as a result of a motor vehicle accident. The patient was clinically stable and there were no other signs to support this diagnosis. Serial analyses showed a fall in total CK to below the upper limit of the reference interval but, as a percent of total activity, CK-MB was constantly slightly elevated (values 5.1-6.5%, upper limit of normal = 4%). At the same time the patient appeared to be improving clinically. The patient's status deteriorated suddenly and he eventually went to surgery where a large intramural haematoma and a left ventricular aneurysm were discovered. The significance of the elevations of serum CK-MB is discussed and a brief review of the literature is presented.

Determination of bupivacaine in plasma by high-performance liquid chromatography. Levels after scalp infiltration in children.

The local anaesthetic bupivacaine could be very useful for analgesia in pediatric neurosurgery. Since systemic toxic reactions to bupivacaine are correlated with high plasma levels it was important, as an adjunct to clinical evaluation, to measure plasma bupivacaine. This report describes a high-performance liquid chromatography (HPLC) method for the quantitation of plasma bupivacaine. Sample preparation involves extraction into ether followed by back-extraction into HCl. After evaporation, the acid extract is redissolved and separated by reversed-phase chromatography. The assay is linear to 5 mg bupivacaine/L and shows excellent recovery and precision. With samples from children undergoing brain surgery following scalp infiltration with either 0.125% or 0.25% bupivacaine, plasma levels peak within 10 min, then fall rapidly to a plateau by 30 min. This plateau is maintained for at least 120 min. In no case did we find supposed toxic levels of bupivacaine.

Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia.

Single-dose and steady-state pharmacokinetics of the new oral iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1) were studied in 14 patients with thalassemia and correlated with iron excretion. Food prolongs the rate of absorption of L1, but it does not affect significantly the extent of absorption measured by the area under the plasma concentration-time curve. Similarly, it does not affect the chelation potential of the drug. The mean elimination half-life of the drug is 3 hours, suggesting that a divided dose every 8 hours may assure better chelation. Our steady-state studies reveal that urinary iron excretion is independently influenced by body iron load (measured by ferritin levels) and by steady-state trough concentrations of the drug. While patients were receiving an unchanged regimen of 75 mg/kg/day, we have detected a gradual and significant decrease in trough concentrations in the presence of unchanged patients' compliance monitored by the Medication Event Monitoring System, diaries, and pill count. These findings suggest self-induction of L1 metabolism or decreased absorption during long-term therapy. Because of the concentration-dependent iron excretion, patients may need increasing doses to achieve negative iron balance.

Scalp infiltration with bupivacaine in pediatric brain surgery.

To evaluate whether local anesthetic scalp infiltration blunts hemodynamic responses to craniotomy in anesthetized children (age, 2-18 yr), two concentrations of bupivacaine (0.125% and 0.25%) with vasoconstrictor (epinephrine 1:400,000) were compared with control data when a solution of vasoconstrictor alone was injected. Arterial plasma levels of bupivacaine were measured by high-pressure liquid chromatography. Statistically significant increases in mean arterial pressure and heart rate above baseline measurements occurred in the control group during the period between scalp incision and dural reflection (P less than 0.05). Both concentrations of bupivacaine prevented these increases. Mean arterial pressure and heart rate during scalp incision and scalp reflection were significantly higher in the control group than in both bupivacaine groups (P less than 0.05). Peak bupivacaine plasma levels (mean +/- SD) occurred either 5 or 10 min after infiltration and were significantly higher in the 0.25% group (0.48 +/- 0.31 microgram/mL) than the 0.125% group (0.14 +/- 0.13 microgram/mL) (P less than 0.05). These results suggest that bupivacaine infiltration blocks the hemodynamic response to craniotomy. A concentration of 0.125% bupivacaine with 1:400,000 epinephrine is as effective as 0.25% bupivacaine with 1:400,000 epinephrine at reducing the hemodynamic response to craniotomy. Because the lower concentration of bupivacaine produces lower blood levels, we recommend 0.125% bupivacaine with 1:400,000 epinephrine as a useful, safe adjunct to general anesthesia in children undergoing craniotomy.

Coffee and alcohol as determinants of risk of pancreas cancer: a case-control study from Toronto.

Results are reported from a population-based study of 249 cases of pancreas cancer and 505 controls carried out in Toronto, Canada, between 1983 and 1986. Lifetime consumption of coffee and alcohol and medical histories were assessed by personal interviews. No evidence of any association was found with different types of coffee or alcohol after adjusting for smoking, calories and fibre intake. There was a significant increased risk associated with a history of diabetes mellitus within 5 years of cancer development. A protective effect of a history of some allergic conditions, hay fever, eczema and asthma, was observed, although the relative risks were not significant (p value greater than 0.10).

Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients.

The efficacy of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) was compared with that of subcutaneous desferrioxamine in 26 patients with transfusional iron overload. Immediately after red-cell transfusion, 20 patients were randomised to receive either desferrioxamine (50 mg/kg daily as a 12 h subcutaneous infusion), or L1 (50 mg/kg daily by mouth). Patients were evaluated during treatment with the other drug after transfusion the next month. Mean (SD) daily urinary iron excretion was lower during L1 than during desferrioxamine (12.3 [6.7] vs 18.2 [15.3] mg/day). In 5 patients the dose of L1 was raised from 50 to 75 mg/kg daily; mean urinary iron excretion rose from 13.8 (7.0) mg/day to 26.7 (17.8) mg/day, comparable with that during desferrioxamine (24.9 [24.3] mg/day). Faecal iron excretion rose slightly over baseline in 6 patients studied during L1 administration (from 8.5 [0.9] mg/day to 12.2 [0.9] mg/day). Pharmacokinetic studies showed an elimination half-life for L1 of 117-237 min. Studies in dogs and in volunteers showed no absorption of the L1-iron complex, excluding a contribution of absorption of intraluminal complexes of L1 and food iron to urinary iron excretion. Further animal toxicity testing is needed before L1 can be studied in a broader group of patients.

Protein analysis of cardiac sarcolemma: effects of membrane-perturbing agents on membrane proteins and calcium transport.

Protein composition of cardiac sarcolemmal membranes was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Membranes were observed to contain about 20 polypeptide bands ranging from 18000 to 200 000 dalton mass. Out of these, six bands were prominent and together comprised 57% of the membrane protein. When sarcolemmal membranes, phosphorylated by [gamma-(32)P] ATP in the presence of Ca(2+) or Na+ with and without K+, were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis at pH 2.4, the band III region (Mr 105 000) of gels was found to contain active sites of monomeric Ca-ATPase and (Na,K)ATPase. Bands I (Mr greater than 200 000), II (Mr 150 000), III (Mr 105 000), and VI (Mr 47 000) were accesible to trypsin; the extent of proteolysis was dependent on the time of exposure to, and the concentration of, trypsin (i.e, ratio of sarcolemmal protein/trypsin). Addition of molar sucrose protected sarcolemmal proteins from the tryptic proteolysis. Calcium transport was reduced by the action of trypsin; the degree of reduction was influenced by the time of exposure of membranes to trypsin as well as the concentration of trypsin. (Mg,Ca)ATPase activity, on the other hand, was elevated moderately at lower concentration and reduced at higher concentration of trypsin. Treatment with phospholipase C cium transport and (Mg,Ca)ATPase activity; electrophoretic patterns were unaffected by this treatment. Addition of lecithin to phospholipase C treated membranes produced a moderate increase in calcium transport. Exposure to Triton X-100 (1%) specifically solubilized three protein bands (Mr90 000, 67 000, and 57 000), whereas exposure to deoxycholate (1%) preferentially solubilized high-molecular-weight proteins, including band III (Mr 105 000); Lubrol-PX (1%) caused nonspecific solubilization of proteins, although the extent of solubilization with Lubrol-PX was considerably less than with either Triton or deoxycholate.

Stimulation of cardiac sarcolemmal (Na+--K+) ATPase activity by phosphorylase kinase.

Following preincubation with phosphorylase kinase, ATPase activities of heart sarcolemmal membranes were increased: total ATPase from 9.38+/-0.65 to 15.25+/-0.90 and ouabain-sensitive (Na+--K+)ATPase from 1.67+/-0.17 to 3.12+/-0.33 micron moles Pi/mg protein/h (mean +/- S.E. of 3 experiments); (Ca2+)ATPase and (Mg2+--Ca2+)-ATPase activities were not significantly altered due to phosphorylase kinase. Under these conditions, phosphorylase kinase catalyzed phosphorylation of sarcolemmal membranes. The kinase-catalyzed phosphorylation of membranes was increased by Ca2+ ions: at pH 6.8, 30% increase in phosphorylation was observed whereas at pH 8.5, 267% increase was noted due to this action. These findings support the view that Ca2+-dependent phosphorylation of membranes regulates (Na+--K+)ATPase.

Adenosine triphosphate - dependent calcium binding and accumulation by guinea pig cardiac sarcolemma.

Sarcolemma isolated from guinea pig heart ventricles possessed ATP-dependent Ca2+ binding and accumulation (+ oxalate) activities which were not inhibited by sodium azide, oligomycin, or ruthenium red. Ca2+ binding and accumulation by sarcolemma were sensitive to pH, the optimum being about pH 6.8. The concentrations of ATP required for half-maximal binding and accumulation were 94.3 and 172 muM, respectively. Mg2+ up to 5 mM significantly enhanced both activities but was inhibitory at higher concentrations (greater than 10 mM). Sarcolemmal Ca2+ binding and accumulation were stimulated 100% by K+, half-maximal enhancement occurring at 5-10 mM K+. Ca2+ binding and accumulation were both saturable processes and the respective apparent Km values for Ca2+ were 16.4 and 14.3 muM. Ca2+ binding by sarcolemma was a rapid process and the bound Ca2+ was released upon depletion of ATP in the medium. It is suggested that the sarcolemmal Ca2+ transport system may well be of significance in regulation of the contraction-relaxation cycle of cardiac muscle.