IgM-enriched immunoglobulin (pentaglobin) positively influences the course of post-surgical intra-abdominal infections.

BACKGROUND: Polyvalent IgM-enriched intravenous human immunoglobulin (IVIG) preparations are discussed to be beneficial regarding sepsis outcome. MATERIALS AND METHODS: Sixty-four patients with abdominal infection were treated with Pentaglobin or Albumin. Serum levels of endotoxin and chemokines were determined. RESULTS: Incidence of fever was 19/28 in the pentaglobin and 18/26 in the albumin group, the percentage of days with fever was 34 +/- 26 for pentaglobin and 43 +/- 25 for albumin (mean +/-SD). Procalcitonin levels of the pentaglobin treated patients fell under the upper limit of normal on day six whereas levels of albumin patients remained elevated. CONCLUSION: Pentaglobin has a positive influence on the course of post-surgery intra-abdominal infection.

Ultrastructural localization of type VI collagen in normal adult and osteoarthritic human articular cartilage.

OBJECTIVE: Type VI collagen is a major component of the pericellular matrix compartment in articular cartilage and shows severe alterations in osteoarthritic cartilage degeneration. In this study, we analysed the exact localization of type VI collagen in its relationship to the chondrocyte and the (inter)territorial cartilage matrix. Additionally, we were interested in its ultrastructural appearance in normal and osteoarthritic cartilage. DESIGN: Distribution and molecular appearance was investigated by conventional immunostaining, by multilabeling confocal scanning microscopy, conventional transmission, and immunoelectron microscopy. RESULTS: Our analysis confirmed the pericellular concentration of type VI collagen in normal and degenerated cartilage. Type VI collagen formed an interface in between the cell surface and the type II collagen network. The type VI collagen and the type II collagen networks appeared to have a slight physical overlap in both normal and diseased cartilage. Additionally, some epitope staining was observed in the cell-associated interterritorial cartilage matrix, which did not appear to have an immediate relation to the type II collagen fibrillar network as evaluated by immunoelectron microscopy. In osteoarthritic cartilage, significant differences were found compared with normal articular cartilage: the overall dimension of the lacunar volume increased, and a significantly increased type VI collagen epitope staining was observed in the interterritorial cartilage matrix. Also, the banded isoform of type VI collagen was found around many chondrocytes. CONCLUSIONS: Our study confirms the close association of type VI collagen with both, the chondrocyte cell surface and the territorial cartilage matrix. They show severe alterations in type VI collagen distribution and appearance in osteoarthritic cartilage. Our immunohistochemical and ultrastructural data are compatible with two ways of degradation of type VI collagen in osteoarthritic cartilage: (1) the pathologically increased physiological molecular degradation leading to the complete loss of type VI collagen filaments from the pericellular chondrocyte matrix and (2) the transformation of the fine filaments to the band-like form of type VI collagen. Both might implicate a significant loss of function of the pericellular microenvironment in osteoarthritic cartilage.

Pharmacokinetics of viral antibodies after administration of intravenous immunoglobulin in patients with chronic lymphocytic leukaemia or multiple myeloma.

OBJECTIVE: Intravenous immunoglobulin (IVIG) preparations are derived from human pooled plasma and should fulfil high standards of purity and viral safety. Introduction of additional purification steps, however, may result in modulation of the biological properties of immunoglobulins. Since cleavage of the Fab-fragment leads to a significant decrease in half-life, the latter provides information about the integrity of the immunoglobulin G (IgG) molecules. Therefore, a pharmacokinetic study of a novel preparation is required to determine safety and disposition in the target population. METHODS: Twenty-seven patients with chronic lymphocytic leukaemia (CLL) and 12 with multiple myeloma received intravenous infusions of IVIG containing antibodies against hepatitis B virus (anti-HBs; n= 15; 8960 IU), cytomegalovirus (anti-CMV; n = 9; 14,250 U) or varizella-zoster-virus (anti-VZV; n = 15; 6000 IU), respectively. Serum concentrations of viral antibodies were determined for 71 days during and after infusion. RESULTS: Maximum serum concentrations of anti-HBs, anti-CMV and anti-VZV were observed at about 4 h (median) after start of the infusion. Total body clearances came to 0.14 +/- 0.08 ml/min (anti-HBs), 0.10 +/- 0.02 ml/ min (anti-CMV) and 0.14 +/- 0.07 ml/min (anti-VZV). The terminal elimination half-lives were determined to be 25.34 +/- 8.34 days (anti-HBs), 24.66 7.28 days (anti-CMV) and 31.79 +/- 12.47 days (anti-VZV). Clinical chemistry parameters including C3- and C4-complement serum concentrations revealed no pathological changes, seroconversion for hepatitis B and C and HIV did not occur. CONCLUSIONS: The pharmacokinetic parameters of the IgG antibodies calculated after administration of the novel IVIG preparations to patients with CLL and multiple myeloma are in close agreement with data obtained from healthy volunteers and with values of native IgG, suggesting that the production process did not impair clinically relevant characteristics of the viral antibodies.

Bovine colostrum ameliorates diarrhea in infection with diarrheagenic Escherichia coli, shiga toxin-producing E. Coli, and E. coli expressing intimin and hemolysin.

BACKGROUND: Diarrheagenic Escherichia coli may cause serious extraintestinal complications, but there is no specific treatment. METHODS: Patients with diarrhea caused by diarrheagenic E. coli, specifically Shiga toxin-producing E. coli and E. coli-expressing intimin and enterohemorrhagic E. coli-hemolysin were treated by administration of pooled bovine colostrum, rich in antibodies to Shiga toxin and enterohemorrhagic E. coli-hemolysin, in a placebo-controlled, double-blind study. Symptom resolution and fecal excretion of infecting strains were assessed. RESULTS: No side effects were attributable to colostrum. Stool frequencies in the group treated with bovine colostrum were significantly reduced compared with those in the placebo group. No effect of therapy on the carriage of the pathogens or on complications of the infection could be demonstrated. CONCLUSIONS: Bovine colostrum is well tolerated and diminishes frequency of loose stools in children with E. coli-associated diarrhea. A prospective study should be conducted among a larger number of children with Shiga toxin-producing E. coli identified early in illness, to determine the effectiveness of colostrum therapy.

Pharmacokinetics of oxypolygelatine in healthy volunteers.

OBJECTIVE/METHODS: The pharmacokinetics of the plasma substitute oxypolygelatine (OPG) were studied in 12 healthy volunteers after single-dose administration of 27 ml x kg(-1) body weight, with a maximum of 2000 ml. OPG was determined in plasma and urine over 48 h after the infusion. Peak plasma OPG concentrations at the end of the infusion were determined to 4.600 (623) microg x ml(-1), the area under the plasma concentration/time curve (AUC(0-infinity)) was calculated to 70.135 (15.861) microg x h x ml(-1). RESULTS: The model-independently calculated volume of distribution came to 23.1 (4.8) 1 with a clearance total is (Cl(tot)) of 24.6 (6.8) ml x min(-1). The initial half-life according to a three-compartment model came to 0.3 (0.2) h, followed by a distribution half-life of 3.1 (2.6) h and a terminal elimination half-life of 13.4 (2.2) h. Cumulative urinary excretion of OPG was 64% after 48 h. CONCLUSION: This low recovery rate may be explained by the distribution of OPG into the extravascular space and subsequent degradation in tissue sites.

Efficacy and potential clinical applications of Pentaglobin, an IgM-enriched immunoglobulin concentrate suitable for intravenous infusion.

OBJECTIVE: Characterisation of the antibodies against important human pathogens in two immunoglobulin preparations: Intraglobin F and IgM-enriched Pentaglobin. DESIGN: In vitro assay of antibody titre using bacterial outer-membrane proteins, lipopolysaccharides (LPS), and exotoxins of clinically relevant bacteria. METHODS: Antibody reactivities measured by ELISA and immunoblot techniques against antigens from bacteria that cause sepsis, antibiotic-resistant nosocomial pathogens, and enteric pathogens. RESULTS: IgG anti-LPS reactivity was present in both study drugs. Specific IgM antibodies against LPS of gram-negative bacteria that cause sepsis were also detected in the IgM-enriched Pentaglobin. IgG-reactivity against gram-positive multiresistant strains of Staphylococcus aureus (S. aureus) were detectable in both preparations. IgG and IgM antibodies present against Yersinia outer proteins and Campylobacter jejuni (C. jejuni) outer membrane proteins were detected in Pentaglobin. Both preparations reacted against alpha toxin of S. aureus and streptolysin of Streptococcus pyogenes. Pentaglobin showed a strong IgM-reactivity against alpha-haemolysin. CONCLUSION: Our data suggest that infusion of well characterised immunoglobulin preparations might be beneficial for patients with severe infections. This is highly relevant in view of the high pathogenicity of bacteria that cause infections in patients in hospital and the continually increasing antibiotic resistance (particularly methicillin-resistant S. aureus).

Antibody reactivity and fecal recovery of bovine immunoglobulins following oral administration of a colostrum concentrate from cows (Lactobin) to healthy volunteers.

Using immunoblot techniques, we investigated the immunoglobulin G (IG) reactivity present in Lactobin, an immunoglobulin concentrate (prepared from colostrum pools from non-immunized cows) against potential pathogenicity factors from Yersinia enterocolitica and Campylobacter jejuni. A strong reactivity against Yersinia outer proteins (Yops), against the Yersinia adhesin A (Yad A) as well as a high reactivity against flagellin and the outer membrane proteins (OMP) of C. jejuni was demonstrated. The IgG antibody reactivity against these antigens was also assessed in vitro after incubation of IG with stools from healthy adults for different time intervals. Minimal loss occurred within 2 hours of incubation at 37 degrees C and complete loss after 24 hours. In a clinical study stool specimens from 8 healthy volunteers were analyzed 1-4 days after oral administration of the drug for the presence of bovine IgG and its antibody reactivity against Yersinia antigens. Small amounts of the bovine immunoglobulins were detected in stools from 3 of the 8 subjects, however, without antibody reactivity. Additional pharmacokinetic investigations in patients with gastrointestinal diseases are necessary to determine the optimal therapeutic regimen for these patients.

Inhibition of Helicobacter pylori and Helicobacter mustelae binding to lipid receptors by bovine colostrum.

Helicobacter pylori, the etiologic agent of chronic-active gastritis and duodenal ulcers in humans, and Helicobacter mustelae, a gastric pathogen in ferrets, bind to phosphatidylethanolamine (PE), a constituent of host gastric mucosal cells, and to gangliotetraosylceramide (Gg4) and gangliotriaosylceramide (Gg3). The effect of a bovine colostrum concentrate (BCC) on the interaction of H. pylori and H. mustelae to their lipid receptors was examined. BCC blocked attachment of both species to Gg4, Gg3, and PE. Partial inhibition of binding was observed with native bovine and human colostra. BCC lacked detectable antibodies (by immunoblotting) to H. pylori surface proteins (adhesins). However, colostral lipid extracts contained PE and lyso-PE that bound H. pylori in vitro. These results indicate that colostrum can block the binding of Helicobacter species to select lipids and that binding inhibition is conferred, in part, by colostral PE or PE derivatives. Colostral lipids may modulate the interaction of H. pylori and other adhesin-expressing pathogens with their target tissues.

A standard immunoglobulin preparation produced from bovine colostra shows antibody reactivity and neutralization activity against Shiga-like toxins and EHEC-hemolysin of Escherichia coli O157:H7.

Enterohemorrhagic Escherichia coli (EHEC) causes a variety of clinical conditions, the most important being hemorrhagic colitis and hemolytic uremic syndrome. A curative therapy of EHEC diseases is not yet feasible. This study investigates the antibody reactivity of Lactobin, a standardized immunoglobulin (Ig) preparation, obtained from the colostra of non-immunized cows. Three different batches of Lactobin exhibited equally high titers of specific antibodies against Shiga-like toxins (SLTs, verocytotoxins) and EHEC hemolysin (EHEC-Hly) produced by E. coli O157. In addition, Lactobin blocked the cytotoxic effect of SLT-I and SLT-II on Vero cell monolayers and inhibited the cytolytic effects of EHEC-Hly on human erythrocytes. Since Lactobin contains high levels of antibodies and neutralizing activity against important virulence factors of EHEC O157, this drug has potential use in the treatment of diarrhea and the prevention of EHEC-associated hemolytic uremic syndrome.

Importance of simultaneous active cytomegalovirus and Epstein-Barr virus infection in renal transplantation.

BACKGROUND: Although being the most common infective complication after transplantation, cytomegalovirus (CMV) infection does not always produce disease symptoms in immunosuppressed patients. Development of CMV disease may depend on different factors such as virulence of particular CMV strains and impairment of CMV-specific immune reactions. OBJECTIVE: Demonstration of the importance of simultaneous Epstein-Barr virus (EBV) activation for development of symptomatic CMV infections. STUDY DESIGN: 208 renal transplantation patients were monitored for 3 years with respect to (i) CMV and EBV replications, and (ii) clinical symptoms associated with combined and single infections, respectively. RESULTS: CMV and EBV replications were observed in 22% and 19% of the patients, respectively. Many of these active virus infections were found to overlap in time (59% and 74% of all active CMV and EBV infections, respectively). The increased detection of combined CMV and EBV infections probably does not result from higher initial immunosuppression in these patients, since the percentage of patients receiving OKT3 or ATG was almost identical in the groups of single and combined infections. In 18 cases of combined infections, CMV replication preceeded EBV replication, while EBV replication prior to CMV replication was observed in one case only, indicating that activation of latent EBV infection may be induced during active CMV infection. CONCLUSIONS: Simultaneous replication of both viruses seems to be clinically important, since severe clinical symptoms were observed only in the group of combined CMV and EBV infections. Symptoms were similar to the clinical pictures of CMV disease. Thus, simultaneous EBV replication may be an important co-factor for the development of CMV disease, possibly by further decreasing the number of functional CD4 T cells or enhancing the CD8-positive cytolytic/suppressor T-cell subset as reflected by the comparatively stronger decrease of CD4/CD8 ratio during simultaneous CMV and EBV replication, particularly in the case of symptomatic infections.

Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects.

Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.

Bactericidal properties of Campylobacter jejuni-specific immunoglobulin M antibodies in commercial immunoglobulin preparations.

Campylobacter jejuni is one of the most common enterocolitis-causing microorganisms worldwide. It is of particular importance in immunodeficient patients, who frequently are prone to develop extraintestinal manifestations. Since these cases respond poorly to antibiotic treatment, a supportive immunomodulating therapy including the administration of C. jejuni-specific immunoglobulins would be desirable. In the present study, nine commercial immunoglobulin preparations for intravenous use were tested for the presence of C. jejuni lipopolysaccharide (LPS)- and outer membrane protein (OMP)-specific antibodies by using immunoblot and enzyme-linked immunosorbent assay techniques. The immunoglobulin G (IgG) antibody reactivities against these antigens were comparable in eight of nine tested immunoglobulin preparations. Only in one preparation were C. jejuni OMP- and LPS-specific IgM antibodies found. In this preparation the immunoblot test revealed a strong reactivity against both flagellin and a major OMP. Moreover, all immunoglobulin preparations recognized OMPs of C. jejuni serotypes Lior 4, 9, 11, and 29 equally strongly, while the reactivity to an anti-Lior 36 isolate was less marked. Furthermore, the bactericidal properties of three immunoglobulin preparations were tested by means of chemiluminescence signaling in and bacterial killing by human polymorphonuclear leukocytes (PMNL). The results show that the IgM preparation enhanced Campylobacter-triggered chemiluminescence signaling in PMNL as well as killing of C. jejuni by PMNL, while the other immunoglobulin preparations did not do so. These results suggest that the administration of immunoglobulin preparations containing C. jejuni-specific IgM antibodies would be beneficial for patients with severe C. jejuni infections.

[Animal experiment, pharmacokinetic and clinical studies of intraperitoneal therapy with interleukin-2 (n Il-2) in patients with ovarian carcinoma]. / Tierexperimentelle, pharmakokinetische und klinische Untersuchungen zur intraperitonealen Therapie mit Interleukin-2 (n IL-2) bei Patientinnen mit Ovarialkarzinom.

OBJECTIVE: In an orthotopic transplantation model using human ovarian cancer xenografts we evaluated antitumor effects of nIL-2 as well as its side effects in a clinical phase I/II study. METHODS: In patients with advanced ovarian cancer nIL-2 was administered i.p. in escalating doses every two days by means of a Tenckhoff-catheter. RESULTS: Considerable stimulation of intraperitoneal immune cells was observed without severe toxic side effect WHO grade III/IV. CONCLUSIONS: Due to pharmacological-pharmacokinetic advantages using the i.p. route nIL-2 was very well tolerated and showed considerable stimulation of local immune cells.

Pharmacokinetic characteristics and tolerability of a novel intravenous immunoglobulin preparation.

In two independent trials 10 and 12 healthy volunteers received the novel intravenous immunoglobulin (IVIG) preparations BT 511 and BT 507, respectively. BT 511 contains 5 g human plasma proteins per 100 ml, more than 95% of which are immunoglobulins of the G class (IgG). BT 507 contains in addition 61 IU antibody against hepatitis B surface antigen (anti-HBs).ml-1. In trial I volunteers received 4.0 ml/kg (n = 4) and 8.0 ml.kg-1 (n = 6) BT 511 to study the tolerability and the magnitude of the increase in immunoglobulins in plasma as well as their decline over 1 month. After administration of the lower dose, plasma IgG increased from 10.7 to 14.7 g.l-1 directly after the infusion. Following the 8.0 ml.kg-1 dose a more pronounced increase from 12.4 to 21.2 g.l-1 was observed. No adverse events occurred. After 1 month IgG concentrations had almost reached baseline values at 12.2 g.l-1 in the 4.0 ml.kg-1 group, but were still significantly increased at 15.2 g.l-1 after the high dose. There was a linear correlation between the maximal IgG plasma concentration and the subsequent decline of IgG during the 29-day observation period. After administration of BT 507 maximal anti-HBs concentrations of 1778 mU.ml-1 occurred 1.4 h after termination of the infusion. The terminal elimination half-life was 22.4 days, and total clearance and volume of distribution were determined to be 0.122 ml.min-1 and 5.41, respectively. The pharmacokinetic parameters calculated for anti-HBs as an indicator of IgG were in accordance with the pharmacokinetic behaviour of native IgG.

Tolerance and cerebrospinal fluid pharmacokinetics of intrathecally administered human natural interleukin-2: a phase I trial.

Recombinant interleukin-2 (rIL-2) is at present widely applied in the immunotherapy of various advanced cancers. As a number of side effects following the administration of rIL-2, either alone or in combination with lymphokine-activated killer (LAK-) cells, have been reported, a preparation of human leukocyte-derived and fully glycosylated interleukin-2 was used in the present study. We have recently demonstrated in cats that this natural IL-2 (nIL-2) is well tolerated and that the distribution and elimination half-lifes following intrathecal (i.th.) application are considerably longer than those after intravenous (i.v.) injection. To determine whether these long half-lifes and the good tolerance of i.th. given nIL-2 are also found in man, four patients with meningeosis neoplastica received repeated injections of human nIL-2 i.th.. Cerebrospinal fluid samples were drawn at different time intervals from either the lateral ventricle or lumbar subarachnoid space. The doses of nIL-2 ranged from 2 x 10(4) to 4 x 10(5) IU per injection. Only minor side effects were noted in one patient. The half-lifes for distribution and elimination of i.th. given nIL-2 ranged between 0.5-1.7 hours and 4.9-14.4 hours respectively. A linear relationship exists between the i.th. dose of nIL-2 and the area under the cerebrospinal fluid activity time profile curve.

Functional analysis of tumor-associated lymphocytes from gynecological tumors.

Tumor-Associated Lymphocytes (TAL) were isolated from peritoneal fluids of six ovarian cancer patients and pleural effusion from eight breast cancer patients, respectively. In one case we obtained ascitic fluid as well as pleural effusion because of intraabdominal metastatic breast carcinoma. The collected cells were cultured in a complete medium and supplemented with human interleukin-2 (nIL-2) in a concentration of 1000 Units/ml. Phenotyping was not always possible due to rapid decay of the cells. Cytotoxicity was determined with a fluorescence-based assay, in some cases at different stages of cell growth. In two cases TAL from ascitic fluids showed increased cytotoxic activity after a longer cultivation period. TAL from pleural effusions showed cytotoxic activity against the target cell lines in two cases only. Some of these TAL did not proliferate any more but died within 24 h. With the functional analysis we wanted to investigate the cytotoxic potential against natural killer (NK)-sensitive and NK-resistant (Raji) cell lines. The results demonstrate the ability of some of the TAL populations to destroy tumor cells.

Interleukin-2 and blood brain barrier in cats: pharmacokinetics and tolerance following intrathecal and intravenous administration.

Single bolus doses of glycosylated human interleukin-2 (n IL-2) in the range of 2.8 x 10(3) to 2.0 x 10(6) IU/kg were administered to anesthesized cats via the cephalic vein (n = 10) or using suboccipital puncture (n = 8). CSF (cerebrospinal fluid) and blood samples were collected by repeated puncture. The n IL-2 concentration in four cats was determined on the basis of its biologic activity using 3H-thymidine incorporation into human ConA-blasts and by radioimmunoassay. In additional experiments radioactivity was determined in cerebrospinal fluid and serum after intravenous and intrathecal (i.th.) application of 5.8 x 10(3) - 3.2 x 10(3) IU/kg of 14C-acetyl-n IL-2 in regular time intervals. CSF and serum concentration time-profiles show a biexponential decline in the plasma elimination phase with half-lives of 4 min (alpha-phase) and 90 min (beta-phase) after intravenous and 20-120 min (alpha-phase) and 2-16 hours (beta-phase) after intrathecal application. There is a trend towards longer terminal elimination half-lives with increasing doses. Interleukin-2 is able to penetrate the blood brain barrier from the circulation into the cerebrospinal fluid and vice versa. Due to a slow rate of penetration and rapid elimination from blood only traces of n IL-2 (2-8 IU/ml) are detected in CSF after i.v. injection of 2 x 10(6) IU/kg, whereas concentrations between 400 and 1600 IU/ml are maintained in CSF for several hours following i.th. administration of 2-10 x 10(5) IU/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian rhythm of soluble interleukin-2 receptor in healthy individuals.

The cytokine levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6) and tumor-necrosis-factor alpha (TNF-alpha) were studied in 12 healthy volunteers at 11 different times of day. TNF-alpha levels were below the detection limit, and IL-6 levels were at baseline values of the respective assay used. Interindividual variations were found for the plasma levels of sIL-2R (179-524 U/ml). Shedded IL-2 receptors displayed a pronounced circadian phase-dependency (p less than 0.0001) with a peak value at 12:29 h and a trough at 4:14 h when a complex cosine function (period lengths: 24 h plus 12 h) was fitted to the data. These findings may be of importance when using sIL-2R as a diagnostic tool as well as in controlling efficacy of drug treatment.

The effect of antenatal intravenous immunoglobulin on ascending intrauterine infection after preterm premature rupture of the membranes: a pilot study.

Ascending infection is a serious threat in pregnancies complicated by preterm premature rupture of the membranes (PROM). In a controlled randomized prospective pilot study (n = 18) we have evaluated the effect of intravenous IgM enriched immunoglobulin given to the mothers 24-48 hours after preterm PROM in reducing ascending infection. Using a validated infection score from laboratory and clinical data at birth, we found a significant reduction of probable infection in the neonates of the treatment group compared to the control group (p = 0.0022). Histopathological investigation of the placentas, membranes and umbilical cords revealed significantly lower stages and grades of chorioamnionitis in the treatment group (p = 0.036). From these preliminary results we conclude, that intravenous broad spectrum immunoglobulin given antenatally to patients with preterm PROM may reduce ascending infection. However, studies with a much larger cohort of patients are necessary to confirm these preliminary results and to detect potential clinical benefits from this treatment mode.

Elimination of pyridoxylated polyhemoglobin after partial exchange transfusion in chimpanzees.

Partial exchange transfusion with 8.5% pyridoxylated polyhemoglobin solution [PolyHb-PPa] was performed in five male chimpanzees weighing 22-30 kg. Serial blood and urine samples were obtained for 3 days. Percutaneous liver biopsies were performed on the 3rd to 4th, and the 9th to 11th days after PolyHb-PPa administration. Mean exchange volume was 42.5 +/- 10.7 ml/kg BW (26.8-54.6 ml/kg), mean Hb dose 3.7 +/- 0.9 g PolyHb-PPa/kg BW (2.4-4.8 g/kg), mean exchange rate 56.7 +/- 7.1% (48.2-67.4%). All animals survived long-term. Analysis of the plasma Hb concentration-time data showed a first order decline at a plasma level of 3.7 +/- 0.9 g PolyHb-PPa/kg BW. Mean intravascular half-life was 14.6 +/- 3.2 h. Total renal elimination of PolyHb-PPa was about 7%. PolyHb-PPa was absorbed and stored by Kupffer cells and transformed into hemosiderin. Siderosis of Kupffer cells and renal tubules had largely subsided 10 days after PolyHb-PPa indicating subsequent in vivo degradation and metabolization of the polymerized Hb fractions.