Biomedical subjects

P Späth

Publications and source records attributed to P Späth.

At least 19 recordsLinked to original sources

PubMed2003

Efficacy, tolerability, safety and pharmacokinetics of a nanofiltered intravenous immunoglobulin: studies in patients with immune thrombocytopenic purpura and primary immunodeficiencies.

BACKGROUND AND OBJECTIVES: A nanofiltration step with the capacity to reduce blood-borne pathogens was introduced into the manufacturing process of intravenous immunoglobulin (IVIG). In order to demonstrate the efficacy, safety and pharmacokinetics of the modified product, we conducted Phase II/III studies comparing the nanofiltered IVIG (IVIG-N) with its parent product, Sandoglobulin, in patients with chronic immune thrombocytopenic purpura (ITP) and primary immunodeficiencies (PID). MATERIALS AND METHODS: Patients with ITP (n = 27) with platelet counts of < 20 x 10(9)/l were treated with Sandoglobulin or IVIG-N infusions at a dose of 0.4 g/kg body weight on five consecutive days. The primary efficacy end-point was the number of patients with an increase in platelet counts to > 50 x 10(9)/l. Secondary end-points were time to and duration of response, and regression of bleeding. Patients with PID (n = 36) were treated for 6 months with Sandoglobulin or IVIG-N at doses of 0.2-0.8 g/kg, infused at 3- or 4-week intervals. The primary end-point was the number of days absent from school/work. Secondary end-points were hospitalization, use of antibiotics and feeling of well-being. In both studies, tolerability was assessed by recording of adverse events and laboratory determinations. Viral safety was ascertained by serology supplemented with nucleic acid detection methods. Pharmacokinetics were analysed in patients with PID using serum concentration-time data for immunoglobulin G (IgG), and IgG antibodies to hepatitis B surface antigen (anti-HBsAg). RESULTS: In the ITP study, the primary end-point was met by 12/16 patients on IVIG-N and by 10/10 patients on Sandoglobulin (P = 0.123). A shift towards lesser bleeding intensity was seen in both groups. In the PID study, seven of 18 patients on IVIG-N and six of 16 patients on Sandoglobulin missed days at work/school, with monthly mean absences of 0.4 and 0.5 days (P = 0.805). The feeling of well-being was comparable in both groups. In the ITP study, adverse events with a causal relationship to medication were suspected in six patients on IVIG-N and in seven on Sandoglobulin. In the PID study, three patients on IVIG-N and two on Sandoglobulin experienced possible drug-related adverse events. In both studies, serological and polymerase chain reaction (PCR) tests gave evidence for virus safety. Pharmacokinetics showed constant peak and trough serum IgG levels in all patients, indicating almost steady-state conditions for both formulations. The overall half-life (t1/2) for total IgG was 33 +/- 17 days in the IVIG-N arm and 25 +/- 16 days in the Sandoglobulin arm; for anti-HBsAg t1/2, values were 17 +/- 7 and 17 +/- 9 days, respectively. CONCLUSIONS: IVIG-N is efficacious, well tolerated and safe in patients with ITP and PID. Its pharmacokinetic properties were comparable to those of Sandoglobulin.

Adolescent↗

PubMed2001

Anaphylactic reactions to aprotinin reexposure in cardiac surgery: relation to antiaprotinin immunoglobulin G and E antibodies.

BACKGROUND: Aprotinin, a serine proteinase inhibitor, reduces bleeding during cardiac surgery. As aprotinin is derived from bovine lung, it has antigenic properties. This investigation examined the incidence of anaphylactic reactions in patients reexposed to aprotinin and the relation to preformed antiaprotinin immunoglobulin (Ig)G and IgE antibodies. METHODS: This prospective observational study conducted at five centers in Germany evaluated patients undergoing repeat cardiac surgery reexposed to aprotinin between 1995 and 1996. Antiaprotinin IgG and IgE antibody measurements, using a noncommercial enzyme-linked immunosorbent assay and an immunofluorescence assay, respectively, were performed preoperatively and postoperatively. An anaphylactic reaction was defined as major changes from baseline within 10 min of aprotinin administration of systolic pressure 20% or greater, heart rate 20% or greater, inspiratory pressure greater than 5 cm H2O, or a skin reaction. RESULTS: In 121 cases (71 adults, 46 children), a mean aprotinin reexposure interval of 1,654 days (range, 16-7,136 days) was observed. Preoperative antiaprotinin IgG (optical density ratio > 3) and IgE antibodies (radioallergosorbent test [RAST] score < 3) were detected in 18 and 9 patients, respectively. High concentrations of each (IgG, optical density ratio > 10; IgE, RAST score > or = 3) were detected in five patients. Three patients (2.5%; 95% confidence interval, 0.51-7.1%) experienced an anaphylactic reaction after aprotinin exposure, followed by full recovery; these patients had reexposure intervals less than 6 months (22, 25, and 25 days) and the highest preoperative IgG concentrations of all patients (P < 0.05). Assay sensitivity was 100%, as no anaphylactic reactions occurred in IgG-negative patients (95% confidence interval, 0.0-3.1%); assay specificity was 98%. Preoperative IgE measurements were quantifiable in two of three reactive patients and in three nonreacting patients. CONCLUSIONS: Quantitative detection of antiaprotinin IgE and IgG lacks specificity for predictive purposes; however, quantitation of antiaprotinin IgG may identify patients at risk for developing an anaphylactic reaction to aprotinin reexposure.

Adolescent↗

PubMed1999

Monomeric complement-activating IgG paraproteins.

Three patients presented a unique syndrome of recurrent panniculitis with an IgGkappa paraprotein and depletion of the early components of the classical pathway of complement. The IgGkappa paraproteins were monomers with a normal structure, and with no evidence for aggregation, as assessed by electron microscopy and ultracentrifugation. Both heavy and light chains were of normal molecular size (SDS-PAGE), and the paraproteins were not heavily glycosylated. However, the paraproteins from all three patients had unusual features that included abnormal behavior on gel filtration chromatography and a heavy chain of high pI. When analyzed by fast protein liquid chromatography (Superdex 200), elution of the paraproteins was retarded, particularly when the ionic strength was increased. This retardation was partially reversed in 20% alcohol, and fully reversed in 6 M guanidine-HCl. Neither anti-C1 inhibitor nor anti-C1q autoantibodies were found in any of the patients' sera. However, the paraproteins bound to the globular heads of C1q at normal ionic strength. They activated C4 in normal human serum, but not in C1q-deficient serum. Activation led to the formation of C1s-C1 inhibitor complexes. Taken together, the data suggest that the unusual paraproteins have the capacity to bind C1q, which then leads to activation of C1. The ability of these paraproteins to activate C1, in spite of their being soluble monomers, is likely to be related to their unique physicochemical features.

Chromatography, Gel↗

PubMed1999

[Hereditary or acquired angioedema caused by functional deficiency of C1 inhibitor--a still unfamiliar disease picture].

Hereditary angioneurotic oedema or hereditary angiooedema (HAE) and acquired angiooedema (AAE) are disorders of the C1-inhibitor (C1-INH) protein, caused by the lack, dysfunction or exhaustion of the C1-INH molecule. Inadequate function of C1-INH results in inappropriate control of various enzymes of the fibrinolytic, complement and kinin systems as well as of factor XII, being the initial enzyme of the kinin and contact coagulation systems. As C1-INH functional deficiency is rare and the clinical manifestation little known, even nowadays the most feared complication of the deficiency may evolve: death from acute airway obstruction. Patients deficient in C1-INH function whose clinical manifestations are misinterpreted as allergic angiooedema are most at risk for fatal laryngeal oedema. The therapy of allergic and C1-INH-related angiooedema is fundamentally different. The background for the hereditary form of inadequate C1-INH function is a gene defect. The predominant primary underlying disease of the acquired form of the deficiency (AAE) is a lymphoproliferative process.

Angioedema↗

PubMed1999

Natural killer cell activity and cytokine production after in vitro immunoglobulin treatment of lymphocytes derived from pregnant women with or without risk for spontaneous abortion.

OBJECTIVE: To investigate the possible mechanism of action effective in immunoglobulin G (IgG) treatment of recurrent spontaneous abortion (RSA). The effect in vitro of a commercially available intravenous immunoglobulin (IvIg) on the rate of interleukin (IL)-10 and IL-12 positive cells (Th1/Th2 balance) and on natural killer (NK) cell activity in populations of peripheral lymphocytes of healthy pregnant women and women at risk for premature pregnancy termination was studied. Primary habitual aborters as well as women showing clinical symptoms (bleeding or regular uterine contractions) of threatened premature pregnancy termination were included. METHODS: Lymphocytes of 20 pregnant women were tested. Five different batches of an IvIg with reported immunomodulatory potential were used at a concentration of 10 mg/mL. Cytokine profiles of the lymphocytes were determined by immunocytochemistry. For testing of NK cell activity, the 4 hr single cell cytotoxicity assay was used. RESULTS: Incubation with IgG of lymphocytes from recurrent spontaneous aborters concomitantly and significantly decreased the rate of IL-12 positive cells (P < 0.01) and increased the rate of IL-10 positive cells (P < 0.01), whereas such treatment had no significant effect on lymphocytes of pregnant women not at risk of abortion. Dialysis or heat treatment (56 degrees C, 30 min) of the IgG preparations did not modify the effect. Elevated NK cell activity of women at risk for premature pregnancy termination significantly decreased after IgG incubation of cells in all cases, whereas NK cell activity of normal pregnancy lymphocytes was not altered. CONCLUSION: This study suggests that incubation of peripheral lymphocytes from RSA patients with polyclonal polyspecific IgG alters cytokine profiles and NK activity while the same treatment does not affect lymphocytes of healthy pregnant women. These data might add to the understanding of mechanisms of action of IvIg in prevention of recurrent pregnancy loss.

Abortion, Habitual↗

PubMed1998

[Hereditary angioedema. A rare cause of acute abdominal pain with ascites].

HISTORY AND CLINICAL FINDINGS: Since the age of 16 years a now 25-year-old woman had been known to have C1-inhibitor (C1-INH) deficiency. She presented herself at the emergency department because of acute severe lower abdominal cramps. A urinary infection had been treated with antibiotics for the previous 4 days. There was marked pain on pressure over the lower abdomen, but there were no signs of peritonitis and bowel sound were normal. There had been no nausea or vomiting and the stools had been normal. INVESTIGATIONS: There was a leukocytosis of 10,200/microliter, moderately elevated C-reactive protein (44.8 mg/l), haemoglobin concentration of 17 g/dl and haematocrit of 51%. Radiology revealed oedema of the duodenum and sonography showed free fluid in the abdomen. TREATMENT AND COURSE: After excluding an acute abdomen and in view of the C1-INH deficiency treatment was symptomatic. All symptoms completely disappeared after 2 days. CONCLUSIONS: Exclusively gastrointestinal symptoms and ascites are rare in patients with hereditary angioedema. But knowledge of this manifestation of the disease is important because patients are sometimes operated under the false diagnosis of acute abdomen. In severe cases symptomatic treatment may have to be supplemented by C1-INH administration. Prevention with attenuated androgens should be started or modified, respectively.

Abdominal Pain↗

PubMed1997

Prevalence of anaphylactic reactions to aprotinin: analysis of two hundred forty-eight reexposures to aprotinin in heart operations.

The efficacy of aprotinin to reduce intraoperative bleeding tendency in cardiac operations has been demonstrated in several studies. Aprotinin is a polybasic polypeptide and has antigenic properties. Anaphylactic reactions to aprotinin have been described. The aim of the present study was to evaluate the prevalence of adverse reactions to reexposure to high-dose aprotinin. The clinical outcome of all patients undergoing heart operations in our institution between 1988 and 1995 with at least two exposures to aprotinin was investigated. There were 248 reexposures to aprotinin in 240 patients: 101 adult and 147 pediatric cases. The total aprotinin doses were 4.9 x 10(6) (interquartile range 2 x 10(6)) KIU (adults) and 1.3 x 10(6) (interquartile range 1.2 x 10(6)) KIU (pediatric patients). The time between the first and second aprotinin exposures was 344 (interquartile range 1039) days. Seven adverse reactions to aprotinin were found (2.8%). The severity of the reaction ranged from mild (no intervention) to severe (longer-lasting circulatory depression despite vasopressor therapy). All patients survived the event. Patients with an interval less than 6 months since the previous exposure had a statistically higher incidence of adverse reactions than patients with a longer interval (5/111 or 4.5% vs 2/137 or 1.5%, p < 0.05). Two patients reacted to a test dose of 10,000 KIU aprotinin. Pretreatment with antihistaminics was done in 60% of the patients. We recommend the following procedure for reexposure with high-dose aprotinin: (1) delay of the first bolus injection of aprotinin until the surgeon is ready to begin cardiopulmonary bypass, (2) test dose of 10,000 KIU aprotinin in all patients with aprotinin treatment, (3) H1/H2 blockade in known or possible reexposures, and (4) avoidance of reexposure within the first 6 months after the previous exposure to aprotinin. With these precautions a reexposure to aprotinin in patients with a high risk of bleeding is justified, because the benefits of aprotinin treatment outweigh the relative risk of a serious allergic reaction.

Adolescent↗

PubMed1997

Type I hereditary angio-oedema. Variability of clinical presentation and course within two large kindreds.

OBJECTIVES: Hereditary angio-oedema (C1-inhibitor deficiency) is a disease with protean manifestations which is often misdiagnosed initially. The purpose of this study was to delineate the clinical spectrum and course of this potentially life-threatening disease. SETTING: Ten members of two unrelated affected kindreds were repeatedly hospitalized in our service with attacks of angio-oedema. Among the 271 members of the two kindreds 69 were identified who reported typical attacks. DESIGN AND SUBJECTS: Detailed information on the clinical course and laboratory data (C1-inhibitor concentration and activity, C4 concentration) were obtained from 59 of the 69 affected subjects. RESULTS: C1-inhibitor concentration and activity were low in all affected patients. The disease had become manifest by age 30 years in 98%. Most patients suffered from attacks of subcutaneous swellings and abdominal pain, and half of the patients have had attacks affecting the airways. The frequency of attacks ranged from less than one to over 26 per year. Forty-two per cent had to be hospitalized at least once. Four have died of acute airway obstruction. Thirty-eight attacks in 10 patients hospitalized in our service were all treated successfully with fresh frozen plasma or with C1-inhibitor concentrate. Trauma, stress, insect stings and foodstuff were triggering factors, but the majority of attacks occurred without an identifiable trigger. Oral contraceptives and pregnancy led to worsening of symptoms. Nonetheless, all 36 pregnancies reported were carried to term. Twenty-five patients were on continuous treatment with attenuated androgens or tranexamic acid, but only seven were free of attacks in the year preceding the survey. CONCLUSION: Hereditary angio-oedema is an autosomal dominant disease with great variability of clinical expression and severity, even within a single kindred. It often goes unrecognized over years, and it may lead to death if, in case of impending airway obstruction, specific therapy is not instituted.

Acute Disease↗

PubMed1997

Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection.

OBJECTIVE: To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-ADE) of HIV infection which may play a significant role in the progression of HIV-disease. METHODS: In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1IIIB and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources. RESULTS: All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum. CONCLUSION: These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.

Antibodies, Monoclonal↗

PubMed1995

In vitro complement activation by ragweed allergen extract in the sera of ragweed allergic and non-allergic persons.

Ragweed allergen (RWA)-induced complement activation in sera of 40 RW allergic patients and of 40 non-allergic controls was investigated. After treatment of the sera with RWA, levels of C3a, C5a, C3bBbP, C1rC1sClinh, SC5b-9 and granulocyte-aggregating activity were determined. Concentration of RW-specific IgG was also measured. After RWA treatment dose-dependent complement activation was detected in sera of RW allergic and non-allergic persons. C3a generation was observed mostly in the sera of RW allergic individuals, while levels of C3bBbP and of RW-specific IgG were significantly higher in sera of allergics, and a strong correlation was found between these two parameters. In a prospective clinical study, a significant positive correlation was observed between the extent of RWA-induced alternative pathway (AP) activation and the severity of symptoms of allergic rhinoconjunctivitis that were developed in a 4-week period subsequent to blood sampling. These observations suggest that complement activation has a role in the development of the symptoms of RW allergy.

Complement Activation↗

PubMed1995

Crucial residues in the carboxy-terminal end of C1 inhibitor revealed by pathogenic mutants impaired in secretion or function.

The last exon of the C1-1NH gene was screened for point mutations in 36 unrelated hereditary angioedema patients. Mutations were found in eight patients, predicting changes in the short COOH-terminal region which anchors the reactive site loop on its COOH-terminal side. The effects of each of these mutations were examined in transiently transfected Cos-7 cells. Complete intracellular retention or degradation was observed with substitutions in the COOH-terminal strands 4B or 5B: Leu459-->Pro, Leu459-->Arg, and Pro467-->Arg were all blocked at early stages of intracellular transport, but differences in the immunofluorescence patterns indicated that a significant fraction of the Leu459-->Pro and of the Pro467-->Arg proteins reached a compartment distinct from the endoplasmic reticulum. In line with previous findings with alpha 1-antitrypsin, chain termination within strand 5B resulted in rapid degradation. Mutant Val451-->Met, in strand 1C, and mutant Pro476-->Ser, replacing the invariant proline near the COOH terminus, yielded reduced secretion, but these extracellular proteins were unable to bind the target protease C1s. Presence of low levels of both dysfunctional proteins in patient plasmas defies the conventional classification of C1 inhibitor deficiencies as type I or type II. These data point to a key role of certain residues in the conserved COOH-terminal region of serpins in determining the protein foldings compatible with transport and proper exposure of the reactive site loop.

Amino Acid Sequence↗

PubMed1994

Treatment of autoimmune disease by immunomodulation through extracorporeal elimination and intravenous immunoglobulin.

If customary drug mediated immunosuppressive therapy leads to intolerable side effects or is inefficient, extracorporeal elimination and untargeted or targeted immunoglobin therapy modulating the immune response are taken into consideration for the treatment of patients with autoimmune diseases. Both elimination and immunoglobulin therapy, are not alternatives but appear to act complementary, if sequentially applied. Selective immunoadsorption is increasingly applied for extracorporeal elimination and is able to replace plasma exchange therapy. Both, hydrophobic interaction chromatography and affinity chromatography are effective in given clinical conditions. Therapeutic affinity chromatography appears to be superior to hydrophobic interaction chromatography, if an effective, rapid elimination of the disease promoting agent is desired. Experience with therapeutic chromatography collected in the past, indicates that a rapid elimination of immunoglobulins and the subsequent intravenous infusion of 7S immunoglobulin is superior to elimination or untargeted immunomodulation alone. These experimental approaches lead to an extension of the available treatment modalities. However, controlled trials rather than anecdotal reports are needed, to provide substantial information.

Adsorption↗

PubMed1994

Comparison of the effects of aprotinin and tranexamic acid on blood loss and related variables after cardiopulmonary bypass.

Aprotinin reduces blood loss after cardiopulmonary bypass, but may sensitize recipients and is expensive. Tranexamic acid, a synthetic antifibrinolytic, has less disadvantages, but opinions differ regarding its efficacy. We studied three groups of patients undergoing cardiopulmonary bypass for coronary disease: recipients of aprotinin (total dose 4.2 x 10(6) kallikrein inhibiting units, n = 14), recipients of tranexamic acid (total dose 20 mg/kg body weight, n = 15), and nonmedicated controls (n = 14) during 24 hours after cardiopulmonary bypass. Compared with controls, aprotinin reduced blood loss, the number of patients requiring transfusions, and the mean number of transfused red cell units (all with p < 0.05), whereas the recipients of tranexamic acid did not differ either from aprotinin recipients or from controls. Aprotinin and tranexamic acid both mitigated the early postoperative reduction of adenosine diphosphate-induced platelet aggregation seen in the controls (p < 0.05). Postoperative increases of plasma concentrations of the prothrombin activation fragment F1 + 2 and the thrombin-antithrombin III complex showed an activation of intravascular coagulation, without any intergroup differences. The balance between concentrations of tissue plasminogen activator and the type 1 plasminogen activator inhibitor disclosed an activation of fibrinolysis, without differences between the groups. The concentrations of D-dimer, a breakdown product of cross-linked fibrin, remained at baseline in the recipients of aprotinin and tranexamic acid but tripled in the controls (p < 0.05). By contrast, the plasma antiplasmin activity was equally depressed in the tranexamic acid and the control groups but decreased less in the recipients of aprotinin (p < 0.05). This discrepancy may reflect the different modes of action of the two agents, which may make aprotinin more efficacious than tranexamic acid in the "nonfibrinolytic" act of protecting platelet function against attack by plasmin during cardiopulmonary bypass.

Aged↗

PubMed1994

[Selective adsorption of cryoglobulins from plasma of three patients with mixed type II cryoglobulinemia].

A new immunoadsorption column using Sepharose CL 4B as carrier material and IgG as covalently bound ligand was applied for the treatment of three patients with mixed type II kryoglobulinaemia. The titers of rheumatoid factors and cryoglobulins could be significantly decreased during each treatment. The removal of both correlated with the clinical improvement. Skin ulcers, refractory to conventional therapy and arthropathical complaints decreased considerably or disappeared. Further studies evaluating the pathomechanisms and the predictivity of the results must be performed.

Cryoglobulinemia↗

PubMed1993

Genetic basis of human complement C8 beta deficiency.

The eighth component of human complement (C8) is a serum protein consisting of three chains (alpha, beta, and gamma) and encoded by three different genes, C8A, C8B, and C8G. C8A and C8B are closely linked on chromosome 1p, whereas C8G is located on chromosome 9q. In the serum the beta subunit is non-covalently bound to the disulfide-linked alpha-gamma subunit. Patients with C8 beta deficiency suffer from recurrent neisserial infections such as meningitis. Exon-specific polymerase chain reaction (PCR) amplification with primer pairs from the flanking intron sequences was used to amplify all 12 C8B exons separately. No difference regarding the exon sizes was observed in a C8 beta-deficient patient compared with a normal person. Therefore, direct sequence analysis of all exon-specific PCR products from normal and C8 beta-deficient individuals was carried out. As a cause for C8 beta deficiency, we found a single C-T exchange in exon 9 leading to a stop codon. An allele-specific PCR system was designed to detect the normal and the deficiency allele simultaneously. Using this approach as well as PCR typing of the Taql polymorphism located in intron 11, five families with 7 C8 beta-deficient members were investigated. The mutation was not found to be restricted to one of the two Taql RFLP alleles. The mutant allele was observed in all families investigated and can therefore be regarded as a major cause of C8 beta deficiency in the Caucasian population. In addition, two C8 beta-deficient patients were found to be heterozygous for the C-T exchange. The molecular basis of the alleles without this point mutation also causing deficiency has not yet been defined.

Base Sequence↗

PubMed1993

Autoimmune C1 inhibitor deficiency: report of eight patients.

PURPOSE: In this study, we investigated the clinical and biochemical features and the responses to treatment of eight patients with auto-antibody-mediated C1 inhibitor (C1-INH) deficiency and symptoms of angioedema. PATIENTS AND METHODS: In addition to the 8 patients with acquired angioedema (AAE), we also studied 36 subjects with hereditary angioedema (HAE), 15 of them treated with C1-INH plasma concentrate, and 26 patients with different autoantibodies in their plasma (10 with systemic lupus erythematosus, 6 with lupus-like anticoagulant, and 10 with chronic liver disease). Functional C1-INH was measured with the reagent kit of Immuno (Vienna, Austria); C1-INH, C4, and C1q antigen were determined by radial immunodiffusion; and autoantibodies to C1-INH were detected by an enzyme-linked immunosorbent assay method. RESULTS: Four patients with AAE had no other diseases, one had breast cancer, one liver hydatidosis, one Waldenström's disease, and one a benign M component. Functional C1-INH levels were below 30% of normal, and C1q plasma levels were low in seven patients but normal in one. Autoantibodies to C1-INH were detectable in all eight AAE patients but in none of the others. Prophylactic treatment with attenuated androgens was successful in one of four patients, and with antifibrinolytic agents (tranexamic acid) in six of seven patients. Laryngeal attacks in five patients were treated with C1-INH plasma concentrate; two patients had marked clinical and biochemical responses. In three, the symptoms resolved only with high doses, and the biochemical parameters did not significantly increase. CONCLUSIONS: Our results suggest that patients with autoimmune AAE are clinically and biochemically heterogeneous. They have different responses to treatment that seem to be related to variable C1-INH consumption.

Aged↗

PubMed1992

Central venous catheterization in infants and children with congenital heart diseases: experiences with 500 consecutive catheter placements.

In a prospective study results of central venous catheter (CVC) placements in a consecutive group of 500 patients with less than 20 kg body weight undergoing cardiac surgery were evaluated. The incidence of previous cardiac surgery was 21% and the incidence of factors preventing the primary puncture of the right jugular or innominate vein was 13.4%. The anesthesiologists were free to select the catheterization technique, site of puncture, and catheter type. All CVC insertions were performed prior to surgery under continuous circulatory monitoring and optimal positioning of the anesthetized patient. Ninety-six percent of all catheterizations were successful, 81% of them on the first attempt. In the 4% of cases where catheterization failed, a CVC had to be placed by the surgeon. Of all catheters, 66% were positioned via the right internal jugular (IJV) or innominate vein (IV), 8% via the left, 16% via an external jugular vein (EJV), and 5% via other veins. Seventy-six percent of CVC insertions were performed with the Seldinger technique. Of the four catheter types used in this study, double lumen catheters were most frequently selected (38%). Placement of 22-ga single lumen catheters was preferred in infants with less than 5 kg body weight, in spite of their tendency to kink. Observed complications (10% arterial puncture, 4% hematoma, and 1% intrathoracic bleeding) never required immediate surgical intervention. Careful selection of appropriate catheters, as well as extensive experience and knowledge of the anatomical structures involved in special heart defects, helped to keep the risk of complications low.

Body Weight↗

PubMed1992

Total intravenous anesthesia for infants and children undergoing correction of tetralogy of Fallot: sufentanil versus sufentanil-flunitrazepam technique.

The effects of two total intravenous anesthetic techniques were compared in 20 infants and children undergoing primary correction of tetralogy of Fallot (TOF). All patients (mean body weight, 11.4 +/- 4.2 kg; range, 6 to 20 kg; mean age, 32 +/- 21 months, range, 7 to 85 months) were premedicated with atropine, 0.02, mg/kg, morphine, 0.2, mg/kg, and flunitrazepam, 0.04 mg/kg, intramuscularly, 1 hour preoperatively. Anesthesia was induced with 1 microgram/kg of sufentanil (S) and pancuronium, 0.1 mg/kg, intravenously. Patients were ventilated with 100% oxygen. Hemodynamic parameters, heart rate (HR), systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP), central venous pressure (CVP), and peripheral arterial blood oxygen saturation (SaO2) were recorded. Plasma concentrations of S, epinephrine (E), norepinephrine (NE), and blood gases were determined. To obtain a further depth of anesthesia, 10 patients (SM group) received 4 micrograms/kg of S and 10 patients (SF group) received 4 micrograms/kg of S in combination with flunitrazepam, 40 micrograms/kg, in a randomized manner. Measurements were made before and after induction of anesthesia, before and after anesthetic loading, 2 minutes after sternotomy, 15 minutes after initiation of extracorporeal circulation (ECC), and at sternal closure. Peak values for plasma S concentrations of 3.14 +/- 1.13 (SM group) and 3.45 +/- 97 ng/mL (SF group) were found before sternotomy. Following intubation HR, SBP, DBP, and MAP remained close to values measured before induction, but SaO2 increased significantly (P less than 0.01) in all patients. HR, SBP, and MAP decreased during anesthetic loading in both groups. Hemodynamics and plasma E and NE remained essentially unchanged after sternotomy in the SF group.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗