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.     

Manifestation of the Wolff-Parkinson-White syndrome during isoprenaline infusion and carotid sinus massage

Fully susceptible cross-bred calves, six to nine months of age, were immunised by tick-induced Theileria annulata infection treated with chlortetracycline at 16 mg/kg body weight for four, eight or 16 days. The infections were induced with 10 ticks (Hyalomma anatolicum anatolicum) or 30 ticks (H dromedarii). The recovered calves were tested for immunity to homologous severe challenge, 50 or 73 days after the first infection. The reaction of the calves to infections was evaluated by noting the prepatent period, symptoms, degree of anaemia, rate of parasitisation of lymphocytes and erythrocytes. It was observed that untreated calves developed acute theileriasis characterised by typical symptoms and lesions and 56 to 66 per cent mortality. The medicated calves, however, developed a mild form of the disease. Calves which recovered from treated or untreated infections were solidly resistant to subsequent severe homologous infection. Judged from the severity of anaemia in the infected calves, eight day and 16 day medication provided slightly better protection than four day medication. It was concluded that eight day medication afforded adequate protection against the severe immunising infection, and allowed the development of solid resistance to severe homologous challenge.     

The relative effects of selective intra-arterial and intravenous vasopressin infusion

The relative effects of selective intra-arterial and intravenous infusions of vasopressin were evaluated in 16 normotesive dogs. One group was infused via the left gastric artery, one was infused via a peripheral vein, and a control group was not infused. Flow to the stomach and bowel was reduced by an average of 73% and 45%, respectively. There was no significant difference between selective intra-arterial and intravenous infusions with regard to their effects on visceral flow or their systemic parameters. Control animals demonstrated only minor variations from base-line flow.     

Sustained response to intravenous alendronate in postmenopausal osteoporosis

We studied the effects of alendronate (amino-hydroxybutylidene bisphosphonate) on biochemical indices of bone turnover and on lumbar spinal bone mineral density in 15 postmenopausal women with vertebral osteoporosis. Alendronate 7.5 mg daily was administered intravenously as a slow infusion for four consecutive days. Treatment was associated with a significant decrease in serum calcium (p < 0.01), fasting urinary calcium excretion (p < 0.01) and hydroxyproline excretion within several days followed a later decrease in serum alkaline phosphatase activity that showed a significant reduction at two months after treatment (p < 0.05). Serum calcium reverted to pretreatment values by the second week after infusion, but the decrease in alkaline phosphatase, urinary calcium, and hydroxyproline excretion persisted to six months after infusion. There was a 3% mean increase in lumbar bone mineral density at six months (p < 0.01). A transient lymphopenia or leucopenia was noted in eight patients and a short-lived fever in six. No other side effects were observed. This study demonstrates that shortterm exposure to high intravenous doses of alendronate induces suppression of bone resorption in osteoporosis that persists for at least 6 months after infusion. We conclude that a short exposure to high intravenous doses induces sustained effects on bone turnover in much the same manner as that observed in Paget's disease of bone.     

Mood response to levodopa infusion in early Parkinson's disease

Mood response to levodopa infusion was studied in 18 Parkinson's disease (PD) patients during the first year of levodopa therapy before and after 2-hour (1.0 mg/kg/h) levodopa infusions at baseline and 6- and 12-month follow-up. Mood elevation was greatest after a 2-day levodopa holiday at the 6- and 12-month assessments. Age, sex, duration and severity of PD, and ongoing oral levodopa dose did not correlate with mood response. Mood response in these patients differs from that seen in advanced patients, possibly because of sensitization to levodopa's mood effects.     

舒适护理在门诊静脉输液患者中的应用研究

目的:探讨舒适护理对门诊静脉输液患者的影响,总结护理经验,提高护理质量.方法:将400例符合入组标准的静脉输液患者随机分为观察组和对照组各200例.对照组接受常规输液护理,干预组在常规护理基础上加强舒适护理措施,比较二者的护理效果.结果:两组患者在满意度、健康教育效果和不良反应发生率比较,差异有统计学意义(P＜0.05).结论:门诊静脉输液患者采用舒适护理,提高患者身心舒适程度的同时,还能确保患者的安全,促进护理服务质量的提高,值得临床推广应用.     

Heterogeneity of antibody response to human platelet transfusion

To study the antibody response to human platelet transfusions, nine thrombocytopenia patients with bone marrow failure were given 6 U (3X10(11)) of random platelet concentrates twice a week. Before transfusion, none of the patients had preexisting antibodies detectable with lymphocytotoxicity, platelet aggregation, or capillary leukoagglutination techniques. After receiving 18-78 U of platelets, they became refractory to further transfusions of random platelets and alloantibodies were detectable. Two patterns of antibody response could be identified. In three patients, the sera were not lymphocytotoxic with a panel of standard cells in which all the known HLA antigens in the first and second series were represented at least once. Yet, they caused platelet aggregation with 30, 24, and 60%, respectively, of a donor population studied. The aggregating activities were inhibited by antihuman IgG but not by antihuman IgA or antihuman IgM antiserum. The aggregating antibodies could be absorbed out with donor platelets but not lymphocytes or granulocytes. Antibodies from two of these patients aggregated platelets of their respective siblings matched for both HLA haplotypes. Transfusion of platelets from these two siblings did not increase the platelet count while platelets obtained from aggregation-negative donors did. The sera from the remaining six patients were lymphocytotoxic with 15-100% of the panel of standard cells. They also had aggregating antibodies, which could be absorbed out by both platelets and lymphocytes, suggesting that they were HLA antibodies. These data suggest that the development of platelet-specific antibodies may play an important role in the immunological rejection of isologous platelets, and should be considered in the selection of donors for patients who are refractory to platelets from random donors.     

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.     

Pharmacokinetics of theophylline in patients following short-term intravenous infusion

Serum theophylline concentrations after intravenous administration of a new short-term infusion (Euphyllin Kurzzeitinfusion) were measured in 50 out-patients with chronic obstructive airways disease (COAD). An intravenous infusion of theophylline ethylenediamine 480 mg (corresponding to approximately 350 mg anhydrous theophylline) in 50 ml isotonic solution was given in 20 min. Blood samples were taken beforehand and 25 to 30 min and 1, 3 and 6 h after starting the infusion. 86% of the patients had a one-hour serum level in he therapeutic range of 8.20 mg/l, and 2 h later, this was true of 64% of the patients. The short-term infusion was well tolerated, even in cases with unknown high pre-infusion serum levels. Pertinent pharmacokinetic parameters were determined, such as total body clearance, apparent volume of distribution, and half-life of elimination. Geometric mean an 95%-confidence limits, derived from the log-normal distribution of these parameters, were: Cl = 0.044 (0.018-0.190) l/h/kg ideal body weight, Vd = 0.451 (0.258-0.789) l/kg ideal body weight, and t 1/2(el) = 7.1 (2.6-19.1) h.     

The effects of large volume intravenous fluid infusion on neonatal renal function

Twenty healthy infants weighing less than 2,000 gm were studied at low (3.6 ml/kg/hr) or high (10.3 ml/kg/hr) rates of intravenous infusion. Inulin clearance determined by the constant infusion method was greater at the high rate of infusion (p = less than 0.05). Inulin clearance in two groups of infants over 2,000 gm studies at the same low or high rates of infusion did not increase at the higher rate of infusion. Since the GFR in infants less than 2,000 gm depends partially on the rate of intravenous infusion, small, healthy preterm infants may benefit from a rate of fluid administration greater than the low rate. When studies at low and high rates of infusion were compared in the 20 infants less than 2,000 gm, the fractional urinary sodium excretion increased with the increased fluid load. Delivery of fluid from the proximal tubule (CH2O =Na per dl GFR) increased (p less than 0.005). Free-water clearance and the absolute volume of urine increased at the high rate of infusion. These data indicate that the healthy preterm infant less than 2,000 gm, like the adult, compensates by increasing free-water clearance and urine volume when challenged with a large fluid load. Although fluid changes of short duration are appropriately handled, the effect of continuous rapid infusion on water and sodium balance in infants of this size remains to be determined.     

Metabolic factors in the renal response to amino acid infusion

A mechanism of mate selection in humans is proposed and elaborated. It is further proposed that this mechanism constitutes one of the important factors for stability and the necessary longevity of the procreational dyad and therefore the procreational success of humans as a species. The concepts and mechanisms of assortative mating (homogamy) and that of complementarity of temperaments of the mates (heterogamy) which guide such selections are described, the relationships between the two are explored, and finally their possible early developmental origins are proposed. Evidence from a small study of 20 married couples' responses in temperament tests is offered as well as some illustrative case histories all pointing to those mechanisms. The argument is based mainly on principles of evolutionary psychology.     

The use of anti-D to improve post-transfusion platelet response: a randomized trial

Patients undergoing induction chemotherapy for acute leukaemia often become refractory to platelet transfusions. Increased clearance of transfused platelets due to alloimmune destruction has been identified as one of the primary mechanisms contributing to this refractory state. We performed a double-blind randomized trial to determine whether the administration of anti-D to Rh-positive individuals could prevent the refractory state and improve post-transfusion platelet response. Rh-positive patients with acute leukaemia undergoing induction chemotherapy and requiring platelet transfusions were allocated to weekly intravenous anti-D (20 micrograms/kg) or placebo. Platelets and red cell concentrates were administered according to standardized transfusion guidelines. Outcome measures included platelet transfusion utilization, red cell utilization, platelet recovery 18-24 h post-infusion, and the percentage of patients refractory to platelet transfusion. There were 43 patients studied: 21 received anti-D and 22 saline placebo. The mean number of platelet concentrates required per day of observation was 0.59 (SD 0.22) in the anti-D group and 0.61 (SD 0.22) in the placebo group, P = 0.86. No difference was detected between groups in terms of platelet recovery post-infusion, refractoriness to platelet transfusion or frequency of infection (P = 0.97). Red cell concentrate utilization was significantly increased in the anti-D group compared to the placebo group, 0.58 units per day versus 0.37 units per day respectively, P = 0.005. We conclude that the use of anti-D did not improve post-transfusion platelet response in Rh positive patients with acute leukaemia, but did result in an increased need for red cell transfusion.     

Cultured adult rabbit myocytes: effect of adding supplements to the medium, and response to isoprenaline

INTRODUCTION: The aims of this study were to investigate: (1) the effect of supplementing the culture medium on preservation of L-type calcium channel current (1Ca,L) in adult rabbit ventricular myocytes cultured for 4 days; and (2) preservation of the ICa,L response in cultured myocytes to the beta-adrenergic agonist isoprenaline. METHODS AND RESULTS: Adult rabbit myocytes were cultured on laminin-pretreated glass coverslips. The basic, serum-free culture medium was supplemented with 2 mM L-carnitine, 5 mM creatine, and 5 mM taurine. Myocytes were whole cell patch-clamped, and the L-type Ca channel current was recorded selectively as Ba flux (IBa,L) via the channels. IBa,L density (i.e., IBa,L amplitude normalized to membrane capacitance) in myocytes maintained in supplemented medium did not change significantly during culture (P > 0.1). By comparison, IBa,L density in myocytes cultured in nonsupplemented medium declined by 36% after 24 hours in culture (day 1) and then recovered by the fourth day (day 4). There was no significant difference in the response to isoprenaline of acutely isolated myocytes and 4-day cultured myocytes. Isoprenaline 100 nM increased peak IBa,L by 149% +/- 32% (mean +/- SEM) in acutely isolated myocytes (n = 4 cells), and by 224% +/- 60% (n = 6 cells) and 159% +/- 24% (n = 8 cells) in day 1 and 4 cultured myocytes, respectively. CONCLUSIONS: Supplemented medium improved IBa,L density in cultured myocytes. beta-Adrenergic receptors and intracellular messenger pathways appear to remain intact in adult rabbit myocytes cultured for up to 4 days.     

Diazepam: intravenous infusion in the treatment of status epilepticus

A case of Pierre Robin-Syndrome with associated rib gap defects is reported. Rib defects are described still now only in childs with micrognathia. Respiratory embrassement may be caused.     

Acute insulin response to intravenous glucagon in polycystic ovary syndrome

In order to evaluate the acute insulin response after i.v. injection of glucagon in polycystic ovary syndrome (PCOS), 35 women affected by PCOS and 11 normo-ovulatory controls underwent a 75 g oral glucose tolerance test (OGTT) and, 2 days later, a glucagon test (1 mg i.v.). Patients were analysed according to their degree of obesity; the insulin release after glucagon injection for lean PCOS subjects and control women was not statistically significantly different. Conversely obese PCOS patients had higher insulin secretion after both i.v. glucagon and OGTT when compared to the other groups. Moreover the insulin secretory patterns were heterogeneously represented in lean and obese PCOS women. When the patients were analysed according to their insulinaemic response to OGTT, normoinsulinaemic PCOS women and control subjects had a similar insulin response to i.v. glucagon whereas the hyperinsulinaemic PCOS group had a higher insulin response (P < 0.0001). Moreover, a highly significant relationship was found between the insulin response to OGTT and to glucagon administration in the PCOS population (P < 0.0001; r = 0.73), which was maintained also after controlling for obesity. Our results are consistent with the hypothesis that PCOS patients could have an insulin hyper-response to glucagon administration, that is partially independent from obesity and related to their insulinaemic status. Moreover, the glucagon test could represent an effective alternative to OGTT in screening insulin disorders of PCOS patients (at least in the absence of other risk factors), due to its reliability, simplicity, and speed of performance.     

Routine use of low-dose intravenous insulin infusion in severe hyperglycaemia

A review if presented of the use of low-dose insulin infusion in the management of 58 episodes of severe diabetic hyperglycaemia. Neutral insulin in a dosage of 2-4 units per hour is infused via a paediatric giving set to achieve a sustained physiological elevation of insulin levels. This method is safe, simple and rapidly effective in lowering the blood glucose level, the mean rate of fall (62 mg/100 ml/hr, or 11% per hour) being unaffected by prior insulin therapy, acidosis or ketonuria. Classification of the hyperglycaemia as ketoacidotic or hyperosmolar is unnecessary before insulin therapy is instituted, as the relative decline in glucose level is the same in the hyperosmolar non-ketotic group as in the others. Proven infection significantly lowers the rate of fall of glucose level. Hypoglycaemia and hypokalaemia are rare during low-dose infusion. Early and adequate replacement with potassium phosphate is recommended, oral potassium supplements being continued for several days. Bicarbonate therapy is rarely indicated in the management of acidosis. No patient had cerebral oedema during treatment, and one elderly patient with extensive pneumonia and empyema died during the infusion. It is suggested that continuation of low-dose insulin infusion, together with 5% dextrose solution, after the plasma glucose level reaches 200 mg/100 ml, may hasten the clearance of ketones, preventing relapse.     

Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain

Relative growth is often used as a phenotypic measure to distinguish mutant and wild-type yeast or bacterial strains. Differential growth as a function of temperature is a convenient and accurate means of analyzing differences between strains. Slight differences in the genotypes of two strains frequently result in differential growth of the two strains as a function of temperature. We have developed a chamber for the simultaneous growth of multiple strains in microtiter plates along a temperature gradient. Image analysis was used to determine colony area and number at various times as a function of temperature. This chamber reduces the time required and increases the accuracy in measuring growth as a function of temperature. This occurs by allowing relative growth to be measured along a temperature gradient where all other conditions are constant. Two strains of yeast (Saccharomyces cerevisiae) with a known difference in temperature dependence of growth were used to demonstrate the performance of this chamber.     

The peripheral intravenous cannula: a cause of venous air embolism

Venous air embolism has been reported as a complication of invasive diagnostic and therapeutic procedures or accidental trauma. Little is known about the incidence of air embolism after minimal intravenous manipulations, such as the insertion of a peripheral intravenous cannula. Small air emboli in the central veins, central arteries, and cardiac chambers can be detected during electron-beam computed tomography studies of the chest. Electron-beam computed tomography of the chest was performed on 208 patients after the insertion of a peripheral intravenous cannula. The images were analyzed using a digital workstation. Small air embolism was visible in 10 of 208 (4.8%) patients in the following locations: the pulmonary trunk in 6 patients, the right ventricle in 2, the right atrium in 1, and the left brachiocephalic vein in 1. The embolism was asymptomatic in each patient. Although the potential risks in patients with septal defects and shunts remain unclear, caution should be taken with minimal intravenous manipulations.     

Some peculiarities of the glucoregulatory response to glucose infusion in the rat

The glucoregulatory response to the i.v. infusion of different doses of glucose and glucose plus insulin was studied in anesthetized rats by using the primed constant infusion of glucose-2-3H. Infusion of glucose at the rate of 10 mg/kg/min induced a rise of about 100% in blood glucose, while the hepatic release of glucose showed only a small and transient decrease. A proportional increase of glycemia and glucose utilization (Rd) was observed without any appreciable change in the metabolic clearance rate (MCR) of glucose; a two-fold increase in plasma insulin was recorded at all times. In the group of rats receiving 20 mg/kg/min of glucose, changes in the above parameters were slightly greater; MCR showed a moderate increment in spite of the six-fold rise of plasma insulin. Finally, the influsion of large doses of insulin together with 20 mg/kg/min of glucose resulted in complete cessation of glucose release by the liver and in a remarkable increase of Rd and MCR. These results suggest a poor adaptability of the glucoregulatory system of the rat in response to glucose infusion as compared to other mammalian species.