Lactate clearance and survival following injury

Previous reports cite optimization of O2 delivery (DO2) to 660 mL/min/m2, O2 consumption (VO2) to 170 mL/min/m2, and cardiac index (CI) of 4.5 L/min as predicting survival. We prospectively evaluated 76 consecutive patients with multiple trauma admitted directly to the ICU from the operating room or emergency department. Patients had serum lactate levels and oxygen transport measured on ICU admission and at 8, 16, 24, 36, and 48 hours. Patients were analyzed with respect to survival (S) versus nonsurvival (NS), lactate clearance to normal (< or = 2 mmol/L) by 24 and 48 hours, hemodynamic optimization as defined above, as well as Injury Severity Score (ISS), ICU stay (LOS), and admission blood pressure. All patients achieved non-flow-dependent VO2. There was no difference in CI, DO2, VO2, or ISS when S was compared with NS. All 27 patients whose lactate level normalized in 24 hours survived. If lactate levels cleared to normal between 24 and 48 hours, the survival rate was 75%. Only 3 of the 22 patients who did not clear their lactate level to normal by 48 hours survived. Ten of the 25 nonsurvivors (40%) achieved the above arbitrary optimization criteria. Fifteen of the survivors never achieved any of these criteria. Optimization alone does not predict survival. However, the time needed to normalize serum lactate levels is an important prognostic factor for survival in severely injured patients.     

Plasma and platelet concentration and platelet uptake of serotonin in normal and pre-eclamptic pregnancies

Pharmacologic and methodologic advances over the last decade have resulted in a body of information implicating serotonin as a mediator in the genesis of pre-eclamptic hypertension. Platelets contain the largest storage of serotonin in peripheral blood and have the ability to take up this amine from surroundings, store and release it by several mechanisms. Plasma and platelet serotonin concentrations and platelet serotonin uptake have been measured in 8 non-pregnant women, 12 normal pregnant women and 8 women with severe pre-eclampsia. Plasma serotonin concentration was significantly higher in severely preeclamptic women, compared with age and gestation matched normal pregnant women. In addition, plasma serotonin concentration was directly related to systolic and diastolic blood pressure with severity of the syndrome. Furthermore, platelet serotonin concentration in women with pre-eclampsia was significantly higher than in non-pregnant controls, but it was not significantly different from the normal pregnant women. Moreover, serotonin is effectively taken up by platelets through a saturable transport process. The calculated apparent Km for serotonin uptake process did not differ significantly among non-pregnant women, normal pregnant women and women with pre-eclampsia. However, Vmax values were significantly higher in women with pre-eclampsia than in the normotensive pregnant women. As the actions of serotonin in the periphery could be terminated primarily by active uptake system by platelets and placenta, significant alterations in the rate of transport could result in physiologically significant changes in serotonin levels. These data raise the possibility that abnormal regulation of transporter function is involved in the etiology of pre-eclampsia.     

Current airway clearance techniques

In recent times, airway clearance has become an increasingly important part of the treatment of patients with excessive bronchial secretions, especially those with cystic fibrosis. The number of airway clearance techniques available has also grown considerably, becoming increasingly more specific. This has allowed patients a greater choice of treatment techniques and has led to a subsequent rise in independence. This paper gives a brief overview of the methods of airway clearance currently being used by physiotherapists in New Zealand. To date, no one method has been shown to be more effective than another. It is imperative therefore, that those involved in respiratory care have a clear understanding of the airway clearance techniques available. This will allow us to provide out patients with the best possible treatment option.     

Renal clearance of ifosfamide

Nephrotoxicity is an important clinical side effect of the chemotherapeutic agent ifosfamide. This medication is activated by the hepatic cytochrome P450 system with potentially toxic metabolites produced through both ring hydroxylation and chloroethyl side chain oxidation pathways. Using an isolated perfused rat kidney preparation, we examined the possibility that renal metabolism of ifosfamide also occurs. Renal function before and after addition of ifosfamide to perfusate was not significantly different. After addition of ifosfamike to the perfusate, the metabolites N2-dechloroethylifosfamide, N3-dechloroethylifosfamide, and isophasphoramide mustard were recovered from urine and renal venous effluent. These results provide the first demonstration of ifosfamide metabolism by the kidney and suggest the possibility that intrarenal metabolism may contribute to nephrotoxicity.     

Apheresis platelets: emerging issues related to donor platelet count, apheresis platelet yield, and platelet transfusion dose

The prevalence of atopic dermatitis and other allergic diseases is increasing in industrialized countries. Today we know that atopy is conditioned genetically, but the development of the atopic phenotype requires environmental factors. It is believed that the genetic factors have not changed and that the increased prevalence is due to the increase in exposure to allergenic and non-specific environmental factors. The potential for sensitization is greater in the early years of life, so it is necessary to reduce harmful environmental exposure at these ages. Atopic clinical manifestations develop sequentially, in many cases beginning with atopic dermatitis in the early months of life. We know that children with atopic dermatitis present non-specific bronchial hyperreactivity (58 to 82%), which is a risk factor for the later development of asthma. The presence of specific bronchial hyperreactivity for mites in atopic dermatitis with mite sensitization also has been described, and it has been demonstrated that signs of eczema can develop or become exacerbated by airway exposure during bronchial challenge tests. The evolution from atopic dermatitis to asthma is a possibility that must be kept in mind. Patients should be followed-up and study of hyperreactivity and sensitization to allergens should be carried out in order to prevent the development of clinical symptoms. Prevention should include pneumoallergens, food allergens, and non-specific environmental risk factors, such as parental smoking (particularly mothers), pollution inside and outside the home, etc. Prevention is particularly important in children at risk of allergy, as determined by a family history among first-degree relatives, as well as the presence of atopic dermatitis, particularly of early onset, because these patient are most at risk of developing bronchial asthma in later years. At present, pharmacological prevention is being studied, without overlooking environmental prevention, in children at high risk of atopic disease for the purpose of preventing chronic inflammations that will condition their future as adults. In our daily clinical experience, atopic dermatitis is responsible for 8% of visits to a pediatric allergology unit. We emphasize that 62.5% of our patients with dermatitis are referred when they already have bronchial asthma, which represents an important delay in diagnosis with respect to the onset of symptoms.     

Investigations of platelet aggregation and platelet counts from stored canine whole blood

The effects of the long term storage of canine blood at 4 to 6 degrees C in PVC-bags containing CPDA-1 as a stabiliser on platelet aggregation and platelet counts were investigated. Aggregation induced by collagen, adenosine diphosphate or a calcium ionophore was preserved well during the first six hours, but there was then a decrease of 24 to 46 per cent in the ability of the platelets to aggregate, after which during the next three to four weeks of storage there was no further decrease in their aggregation properties. The formation of aggregates of platelets reduced the numbers of platelets counted as single thrombocytes by more than 30 per cent during the first four days. The numbers of platelets recorded varied widely with the counting method used (counting chamber or automatically) and with the ethylenediamine tetra-acetic acid content of the dilution fluid.     

Effects of 2,2'-dipyridyl and related compounds on platelet prostaglandin synthesis and platelet function

2,2'-dipyridyl, a chelator of ferrous iron and inhibitor of platelet aggregation, was studied together with several similar compounds to determine the mechanism of their effects on platelets. All of these compounds were more potent inhibitors of arachidonic-acid-mediated aggregation (IC50, 0.17-1.8 mM) than of ADP-mediated aggregation (IC50, 7.6-19.7 mM). At low concentrations required to inhibit arachidonic-acid-mediated aggregation, 2,2'-dipyridyl, 4,4'-dipyridyl and 2-chloropyridine specifically inhibited the platelet cyclo-oxygenase. The mechanism of inhibition of ADP-induced aggregation was investigated, but was not explained. At concentrations needed to inhibit ADP-induced aggregation, 2,2'-dipyridyl did not alter cell ultrastructure, serotonin or nucleotide content or interfere with release of [14C]arachidonic acid or calcium movements. Therefore, our results indicate that 2,2'-dipyridyl and related compounds have two effects on platelets, both due to the unprotonated form. The inhibition of cyclo-oxygenase by low concentrations of these compounds is not due to bidentate iron chelation, since 4,4'-dipyridyl was almost as effective as 2,2'-dipyridyl, but is compatible with binding of these inhibitors to the iron in the heme of the cyclo-oxygenase.     

Economic impact of donor platelet count and platelet yield in apheresis products: relevance for emerging issues in platelet transfusion therapy

The apical membrane antigen 1 (AMA-1) family is a promising family of malaria blood-stage vaccine candidates that have induced protection in rodent and nonhuman primate models of malaria. Correct conformation of the protein appears to be essential for the induction of parasite-inhibitory responses, and these responses appear to be primarily antibody mediated. Here we describe for the first time high-level secreted expression (over 50 mg/liter) of the Plasmodium vivax AMA-1 (PV66/AMA-1) ectodomain by using the methylotrophic yeast Pichia pastoris. To prevent nonnative glycosylation, a conservatively mutagenized PV66/AMA-1 gene (PV66Deltaglyc) lacking N-glycosylation sites was also developed. Expression of the PV66Deltaglyc ectodomain yielded similar levels of a homogeneous product that was nonglycosylated and was readily purified by ion-exchange and gel filtration chromatographies. Recombinant PV66Deltaglyc43-487 was reactive with conformation-dependent monoclonal antibodies. With the SBAS2 adjuvant, Pichia-expressed PV66Deltaglyc43-487 was highly immunogenic in five rhesus monkeys, inducing immunoglobulin G enzyme-linked immunosorbent assay titers in excess of 1:200,000. This group of monkeys had a weak trend showing lower cumulative parasite loads following a Plasmodium cynomolgi infection than in the control group.     

Hepatic cirrhosis and clearance of fibrinolysis activators]

Strain differences in the antibody response to human IgG (HGG) were observed when aggregated HGG was injected intravenously. Lipopolysaccharide (LPS) administered subsequently markedly enhanced the antibody response to HGG in low responder C57BL/6 mice as compared with that in high responder DDD, C3H/He or (C57BL/6 X DDD)F1 mice. Aggregate-free preparation of HGG at a dose of 0.5 mg induced immunological tolerance in all strains of mice tested. LPS injected subsequently converted tolerogenic, aggregate-free HGG into immunogen in DDD mice but not in C57BL/6 mice. To determine the correlation between adjuvanticity and mitogenicity of LPS, spleen cells from normal mice were cultured in the presence of LPS and 3H-thymidine uptake was measured. Spleen cells of DDD mice incorporated three times as much 3H-thymidine as those of C57BL/6 mice. There seems no strong correlation between both activities of LPS. The data obtained are discussed in terms of strain differences in the macrophage function for processing the antigen.     

Mucociliary clearance and respiratory function in foundry workers

The aim of the study was to establish whether changes occur in respiratory function, particularly mucociliary clearance, among second fusion smeltery workers. The research covered 93 male smelters employed in steel forming and casting and 116 male workers of an electric power station, considered as non-exposed. Physiological, pathological and occupational histories of all subjects under study were available. An ECCS respiratory symptoms questionnaire was administered to all subjects ad the two groups also underwent a general medical examination, a spirometry and a chest X-ray. During the medical examination sputum was collected from the subjects to measure mucus transport rate on frog palate, expressed as Normalised Frog Palate Transport Rate (NFPTR). For the environmental research, dust, fumes and gas samplings were taken either at a fixed station or by means of personal dosimeters. Environmental research revealed very low concentrations of respiratory irritants (total dust: 0.2-6.8 mg/m3; respirable dust: 0.1-4.9 mg/m3; total silica: < 2-15.5%; respirable silica: < 0.004-0.3 mg/m3; iron: 0.008-0.085 mg/m3; chromium and manganese: < 0.001 mg/m3; fumes and gases: well below the TLV. The two groups were homogeneous with regard to age and smoking habits. Exposed workers showed rales, dyspnoea and spontaneous phlegm more frequently than non-exposed workers. NFPTR alterations were checked in 49 out of 81 exposed and in 18 out of 81 non-exposed subjects (chi squared = 22.9; p < 0.001). Stratification of the results according to smoking habits further confirmed the strong association between occupational exposure and NFPTR alterations. Smelters showed significantly lower mean NFPTR values compared to non-exposed subjects; also, the mean value of NFPTR in the exposed was below 0.70, which is considered the lowest individual limit in normal subjects. The only variable which explains a large part of the variability of NFPTR is past work in a smeltery rather than in an electric power station. The spirometries showed that only the mean PEF values were significantly lower among the exposed. Stratified analysis of the results according to smoking habits in the two groups revealed a close association between smeltery work and reduction of PEF to under 80% of the ECCS 1983 theoretical values, independently of smoking habits. We also compared the mean PEF values, both as measured values and as percent values of the ECCS 1983 theoretical values, stratified for occupational exposure and smoking; the results again showed that differences between these mean values were mainly due to current or past work in the foundry.(ABSTRACT TRUNCATED AT 400 WORDS)     

Nephrectomy decreases amylin and pramlintide clearance in rats

Amylin is a 37 amino acid hormone, co-secreted with insulin from the pancreatic beta-cell in response to nutrient stimuli. Because the human amylin analog, pramlintide, is being tested in patients with diabetes mellitus, a known risk factor for nephropathy, we examined the role of the kidney on amylin and pramlintide metabolism and action in functionally nephrectomized rats. Nephrectomy markedly altered amylin metabolism: it increased incremental area under the plasma amylin concentration curve 3.6-fold (P<0.001) and increased the elimination half-life from 17+/-1 to 26+/-2 minutes (P < 0.01) after subcutaneous injection of 100 microg amylin. Nephrectomy decreased plasma amylin clearance from 20.3+/-1.1 to 7.9+/-0.4 mL/min (P < 0.0001). Thus, at these doses in the rat, the kidney is important for metabolizing amylin and pramlintide.     

The omnipotent platelet

This information was derived from the increase in platelets of patients following fractures and/or bone surgery and in conjunction with a vast amount of published literature. The increase in numbers of platelets reflects the extent of bone involvement, especially noted in the hip, knee, post-coronary artery bypass graft, and multiple fractures. The role of the platelet in any and all tissues, i.e. soft tissue or bone, whether beneficial or detrimental, is multifunctional. The platelet responds to all physiologic and pathologic states and, if tissue involved is sufficient, the role of the platelet becomes obvious.