Effects of human i.v. immunoglobulin on bacterial clearance and granulocyte function in endotoxinemia

PURPOSE: The therapeutic impact of intravenous immunoglobulins (ivIG) in septic patients remains controversial. Until now, the mechanisms of action have not been fully elucidated. Since polymorphonuclear neutrophils (PMN) play a key role in host defence, this study focuses on the effects of ivIG on bacterial clearance and PMN respiratory burst activity during endotoxinaemia. For this purpose, it was investigated whether ivIG improves blood clearance and organ colonisation as well as PMN functions after experimentally induced bacteraemia in rabbits. METHODS: The experiments were performed in 30 anaesthetised rabbits. To determine quantification of bacterial killing in vivo, defined numbers of exogenous Escherichia (E.) coli 1.3 x 10(8) CFU) were injected intravenously in untreated animals (n = 10) or 60 min after infusion of endotoxin (LPS: 40 micrograms/kg/h) in groups without (n = 10), and after pretreatment with ivIG (Sandoglobulin, 0.5 g/kg body weight, n = 10), respectively. Parameters monitored were rates of bacterial elimination from the blood, LPS clearance, arterial pressure, blood gases and white blood cell counts, PMN burst activity was determined using a flow cytometry assay. Samples of liver, kidney, spleen and lung were collected for bacterial counts 180 min following E. coli injection. RESULTS: Compared to controls, endotoxinaemia resulted in a prolonged elimination of the injected E. coli out of the blood associated with a significantly (p < 0.01) higher colonisation of all organs. Pretreatment with ivIG improved LPS clearance and significantly reduced bacterial colonisation of lung and kidney (p < 0.01). This was paralleled by an enhanced PMN respiratory burst activity compared to untreated animals (p < 0.05). CONCLUSION: The reduced bacterial colonisation of lung and kidney in correlation with an increased PMN bactericidal activity in endotoxinaemia suggest an improved granulocyte-dependent bacterial killing due to ivIG application.     

Red cell aplasia caused by parvovirus B19 in AIDS: use of i.v. immunoglobulin

We describe the case of a 34-year-old man with AIDS who developed severe anemia due to chronic pure red cell aplasia (PRCA) caused by parvovirus B19. Following initial treatment with an infusion of intravenous immunoglobulin (IVIg), 1 g/kg, PRCA resolved, but there was a recurrence of severe anemia in 3 months. Retreatment with 2 g/kg IVIg over 2 days resulted in normalization of hemoglobin and a significantly longer remission duration. Two doses of 0.4 g/kg IVIg q 4 wk failed to prevent a relapse of PRCA in our patient. The dose and schedule of IVIg in the treatment of PRCA caused by parvovirus B19 in AIDS requires further definition.     

Intramuscular high-dose triamcinolone acetonide in the treatment of severe chronic asthma

We describe our experience with administering intramuscular triamcinolone acetonide to 22 steroid-dependent patients with asthma. These patients represent the minority of those with asthma whose disease is characterized by frequent emergency department visits, hospital admissions, and long-term dependency on oral corticosteroid therapy. The participants were randomly assigned to 2 treatment groups, one group receiving 120 mg of intramuscular triamcinolone acetonide, the second receiving 360 mg as a series of three 120-mg daily doses. We determined relative efficacy by comparing peak expiratory flow rates and incidents of emergency department visits, hospital admissions, and ventilatory failure of the study and during the 12 months before enrollment. Peak expiratory flow rates improved significantly in both groups. The mean (+/- standard deviation [SD]) monthly percentage of predicted peak expiratory flow on the study was 88.6 +/- 3.7% and 91.2 +/- 3.9% compared with 63 +/- 15.1% and 64 +/- 14.5% at entry in patients receiving 120 and 360 mg, respectively (P < 0.02). Patients receiving 120 mg required 8 hospital stays and 8 emergency department visits compared with 27 hospital stays and 72 emergency department visits in the previous year (P < 0.05). Patients receiving 360 mg required 5 hospital stays and 5 emergency department visits compared with 33 hospital stays and 34 emergency department visits in the previous year (P < 0.05). The average monthly interval (+/- SD) between exacerbations was 2.7 +/- 2.3 and 7.8 +/- 3.5 for patients receiving 120 mg and 360 mg, respectively. A total of 25 intubations was required in the previous year and only 1 during the study. The incidence of cushingoid facies, weight gain, and hypertension was reduced in both groups (P < 0.05). Total steroid use was reduced in both groups (P < 0.02). A dose of 360 mg produced a longer exacerbation-free period than 120 mg (P < 0.02).     

Soft laser therapy in combination with tebonin i.v. in tinnitus

Lymph node tuberculosis is the most frequent tuberculous manifestation in the otorhinolaryngological area. In 13 patients with histologically verified tuberculous lymphadenitis cervical sonographic examinations revealed characteristic findings. The sonographic features typical for this disease were multiple, enlarged, conglomerating roundish and oval lymph nodes. These lymph nodes were hypoechoic, exhibited dorsal sound amplification and had sharp margins. With caseation, however, there were blurred borders. In cold abscesses an inhomogeneous texture with inhomogeneous shadows was found. Differential diagnosis included non-specific abscess-forming lymphadenitis, lymph node metastases and malignant lymphoma. A tentative diagnosis of cervical lymph node tuberculosis may be made due to the polymorphous sonographic pattern if history and clinical findings are taken into account. A proper histological and microbiological work-up is still essential for confirmation of the sonographic diagnosis.     

Safety and cost of rapid i.v. injection of famotidine in critically ill patients

The safety and cost of famotidine in intensive care patients given the drug by rapid i.v. injection or slow i.v. infusion were studied. All patients admitted to the medical-coronary care and surgical intensive care units (ICUs) at a university teaching hospital over a two-month period who had orders for at least one dose of famotidine injection for any indication were randomly assigned to receive the drug by rapid i.v. injection or slow i.v. infusion via volumetric chamber. Data on patient demographics, drug administration time, adverse effects, cardiovascular variables, and costs (including drug acquisition, supply, and nursing personnel costs) were collected prospectively. Fifty-three patients received famotidine by i.v. injection (a total of 1041 doses) and 52 by i.v. infusion (1006 doses). The mean +/- S.D. duration of famotidine administration was 44 +/- 12 seconds in the i.v.-injection group and 19 +/- 5 minutes in the i.v.-infusion group. Adverse effects possibly related to famotidine occurred in three injection-group patients and two infusion-group patients. No significant difference between the groups in cardiovascular variables (mean arterial pressure, heart rate, and respiratory rate) was noted. Cost savings for the injection group relative to the infusion group totaled $2886 for the two-month study period. Half of the savings came from reduced supply costs and half from reduced personnel costs. The annualized savings to the institution would be about $17,300. Rapid i.v. injection of famotidine appeared to be as safe in ICU patients as giving the drug by slow i.v. infusion and was less costly.     

The effect of i.v. enalaprilat in chronically treated hypertensive patients during cardiac surgery

In areas where hepatitis B virus (HBV) is prevalent, HBV carriers negative for hepatitis B surface antigen (HbsAg) by enzyme-linked immunosorbent assay (ELISA) have been reported. Moreover, even after screening donor blood for HbsAg and hepatitis B core antibody (HBcAb), post-transfusion hepatitis B continues to occur, though with a decreasing frequency. Therefore, screening tests far more sensitive for detecting HBsAg than those currently available are needed. We developed a highly sensitive method for HBsAg detection. It is based on the recognition of peroxidase activity through measuring the formation of stable nitroxide radical with electron spin resonance (ESR) spectroscopy in the presence of hydrogen peroxide, p-acetamidophenol (p-AP), and 4-hydrazonomethyl-1-hydroxy-2,2,5,5,-tetramethyl-3-imidazoline-3-o xide (HHTIO). A cut-off value was established by testing of 186 healthy adults and 50 HBsAg-positive individuals. The signal to noise (S/N) ratio of less than 1.488 obtained by ESR spectroscopy was considered to be negative and more than 2.181, positive. The p-AP/HHTIO method was found to be 10 times more sensitive than the standard ELISA and reproducibility was excellent. Additional investigations were made on the HBsAg levels in the serum from 26 healthy subjects, in whom cut-off index levels on ELISA were negative but relatively high (range: 0.6 to 1.0); and on 15 patients with non B non C hepatitis. Three of 26 cases and 3 of 15 with non B non C hepatitis were judged to be HBsAg positive. Of these, 5 were found to be positive for HBV DNA by polymerase chain reaction (PCR). It was shown in this study that the p-AP/HHTIO method is practical and useful in screening HBV carriers because of the sensitivity in HBsAg detection, which is comparable to PCR analysis.     

Haemostatic changes caused by i.v. regional anaesthesia with lignocaine

The various components of i.v. regional anaesthesia (IVRA), that is ischaemia, tourniquet compression and the presence of high concentrations of local anaesthetics in the blood vessels of the extremity, may affect haemostatic mechanisms. We performed a cross-over study in 10 healthy male volunteers to examine the role of lignocaine in IVRA on several haemostatic variables, and those indicating fibrinolysis and platelet function in particular. Venous blood samples were obtained from the test arm and the opposite arm before IVRA, at the time of tourniquet cuff deflation and 30 min thereafter. Metal needle punctures were used, and for the sample from the test arm at the time of cuff deflation, cuff pressure was reduced from 300 mm Hg to individual mean arterial pressure. The IVRA technique included exsanguination by arm elevation and axillary artery compression, inflation of the tourniquet cuff for 20 min and deflation of the cuff in one step (after obtaining the venous sample). Each subject received, in random order, either 0.5% lignocaine 3 mg kg-1 or the corresponding volume of saline i.v. All fibrinolysis markers, that is, D-dimer, tissue plasminogen activator antigen (t-PA antigen), tissue plasminogen activator activity (t-PA activity), plasminogen activator inhibitor activity (PAI) and protein C indicated enhanced fibrinolysis by IVRA, but only t-PA antigen and PAI showed greater changes in the lignocaine compared with the saline group in the exposed arm at the time of cuff deflation. Platelet function tests (ADP-induced platelet aggregation, beta-thromboglobulin and thrombelastogram (TEG)) indicated no differences between the lignocaine and saline groups. Although IVRA appeared to induce some platelet dysfunction, there was a small increase in TEG amplitude indicative of improved fibrin-platelet interaction in the lignocaine-exposed arm at the time of cuff deflation. We conclude that the presence of high i.v. lignocaine concentrations (median 144.4 micrograms ml-1 in cubital veins at the end of the tourniquet time) potentiated ischaemia-induced fibrinolysis activation during IVRA. Concomitant platelet dysfunction was not aggravated by lignocaine.     

Evaluation of saline for i.v. locks in children

A practice change to saline for peripheral IV maintenance was evaluated in a large teaching hospital in the Midwest. Subjects (N = 126) were children over 28 days of age, with peripherally placed IVs. Group I (n = 68) were children randomly selected to receive saline flush in an experimental study. Group II (n = 58) consisted of children receiving the saline flush after the change in practice was made. There was no significant difference between groups for either of two measures of IV duration. The mean duration of the IV from first flush was 35.38 hours for Group I and 44.09 hours for Group II; the time from insertion to discontinuation was 60.86 and 60.03 hours respectively. Patient age, site location, number of flushes, number of irritating medications, and site complications did not differ significantly between groups. The results of this clinical evaluation support previous findings that saline is efficacious for maintaining the patency of peripheral IVs in children over 28 days of age.     

Audit pinpoints i.v. drug administration pitfalls

This paper describes an approach to auditing the time spent by nurses giving intravenous drugs. The results of the audit, carried out at Wycombe General Hospital, are reported and discussed together with the measures taken to address practical and medico-legal issues. The authors conclude that much nursing time could be saved with closer adherence to guidelines for practice.     

Interaction of i.v. anaesthetic agents with 5-HT3 receptors

Using N1E-115 neuroblastoma cells as an experimental model, we have examined if four commonly used i.v. anaesthetic induction agents interact with 5-HT3 receptors. Specifically, we tested the hypothesis that the antiemetic effects of propofol may result from 5-HT3 receptor antagonism. Binding of tropisetron (a 5-HT3 selective reference compound), etomidate, ketamine, thiopentone and propofol to 5-HT3 receptors was assessed by measuring the displacement of [3H]BRL 43694 from whole N1E-115 cells. The rank order potency (Ki) was tropisetron (1.7 (SEM 0.2) nmol litre-1) > etomidate (83.(4) mumol litre-1) > or = ketamine (97 (4) mumol litre-1) > thiopentone (177 (9) mumol litre-1) > propofol (819 (171) mumol litre-1). With the exception of thiopentone these effects were outside the clinical range and suggest that anaesthetic agents are unlikely to interact directly with 5-HT3 receptors, and that other mechanism(s) must underlie the antiemetic effects of propofol.     

Impaired perception of dyspnea in patients with severe asthma. Relation to sputum eosinophils

Poor dyspnea perception might be a risk factor for developing asthma exacerbations. We investigated whether severe asthmatics with recurrent exacerbations (brittle asthma) have different dyspnea perception and sputum cells compared with equally severe, but stable asthmatics, or patients with mild steroid-naive asthma. Fifteen brittle asthmatics (13 female, median age 28 yr [range, 20 to 47 yr]), 15 matched severe-stable asthmatics (14 female, median age 26 yr [range, 17 to 52 yr]), and 11 mild asthmatics (8 female, median age 25 yr [range, 19 to 43 yr]) underwent inhalation tests with methacholine (MCh), and hypertonic saline combined with sputum induction. Dyspnea was assessed by Borg and Visual Analogue Scale (VAS), plotted against the percent fall in FEV1, and expressed as the slope of the regression line (Slope-Borg and Slope-VAS). The brittle and stable asthmatics had poorer perception than patients with mild asthma (Slope-Borg [p = 0.036], Slope-VAS [p < 0.001] for MCh). In patients with brittle asthma the perception was less as compared with severe-stable asthma (Slope-Borg for MCh: p = 0.05). In the severe asthmatics there was an inverse correlation between sputum eosinophilia and Slope-Borg and Slope-VAS (R = -0.55, p = 0. 002 and R = -0.37, p = 0.049), whereas this correlation was a positive one in the mild asthmatics (R = 0.79, p = 0.012 and R = 0. 67, p = 0.05). In conclusion, patients with severe asthma, particularly those with recurrent exacerbations, have blunted perception of dyspnea, which is related to the degree of sputum eosinophilia. This suggests that increased sputum eosinophilia is an indicator of clinical instabililty, and that eosinophilic airways inflammation might affect dyspnea perception in severe asthma.     

Pulmonary atresia with intact i.v. septum (author''s transl)

Eight cases of pulmonary atresia with intact ventricular septum, are reviewed. Three corresponded to the group with small or hypoplastic right ventricle and five to the one with normal or enlarged right ventricular cavity. The electrocardiogram was of less value than plain chest radiography for the differential diagnosis of both groups. Cardiac catheterization revealed a right to left atrial shunt and the suprasystemic level of the right ventricular pressure. Selective angiocardiography demonstrates the stop of contrast at the level of pulmonary valve. Five patients were operated. An ascending aorta to right pulmonary artery anastomosis, Waterston type, was performed in three patients. Pulmonary valvotomy was carried out in the others.     

Hormonal and metabolic effects of somatostatin in diabetic patients submitted to an i.v. arginine infusion

In French-speaking Quebec, implantation of behaviour therapy in psychiatric hospitals has been difficult because psychiatrists' training was and still is almost exclusively based on psychoanalytic therory. For this reason, many psychotherapists do not use the knowledge derived from laboratory experiments and only rely on their clinical judgement. Prejudiced by their professional identity, many psychiatrists believe that behaviorists manipulate and control patients, mechanize therapy, deny the importance of interpersonal relationships and only use punitive techniques. After refuting these arguments, the author describes the practical difficulties encountered when implanting behaviour therapy in a psychoanalytic milieu, as well as the advantages of a better understanding between these two schools, which might lead to psychiatry becoming more scientific, more human and closer to daily reality.