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K Lewandowski

Publications and source records attributed to K Lewandowski.

At least 37 records · Page 2Linked to original sources
PubMed1999

On-bead combinatorial approach to the design of chiral stationary phases for HPLC.

A library of 36 L-amino acid anilides, which are potential selectors for chiral HPLC, was synthesized in solution and attached to functionalized macroporous polymer beads. The best selector from the library was identified by a deconvolution process using the HPLC separation of several racemic N-(3,5-dinitrobenzoyl)-alpha-amino acid alkylamides as a probe. In each deconvolution step, a series of chiral stationary phases (CSPs) containing a subset of the amino acid anilide selector library was screened for enantioselectivity. After the best CSP was chosen, the library was further deconvoluted until the single best selector was found. The highest selectivity was obtained with a L-proline-1-indananilide that exhibited alpha values up to 23 under normal-phase HPLC conditions. In addition, six CSPs were prepared using individual selectors from the library, and screening results indicate that the deconvolution process indeed led to the most selective receptor.

Amino Acids↗
PubMed1999

A combinatorial approach to recognition of chirality: preparation of highly enantioselective aryl-dihydropyrimidine selectors for chiral HPLC.

A parallel library of 108 4-aryl-1,4-dihydropyrimidine (DHPM) enantiomers, which are potential selectors for chiral HPLC separations, was synthesized using the single-step Biginelli multicomponent condensation. The individual compounds were screened by observing the enantioselectivity for resolution on a "brush-type" L-(3,5-dinitrobenzoyl)leucine-based chiral stationary phase, and separation factors alpha up to 12 were achieved. The best candidates from the library contained an ortho-substituted aromatic group at C4 carbon atom of the pyrimidine ring and an alkyl substituent at N1 nitrogen atom. Resolution of the enantiomers of the lead compound, 4-(9-phenanthryl)-DHPM 8, using semipreparative chiral HPLC followed by attachment to monodisperse macroporous aminomethacrylate beads, provided the novel polymer based chiral stationary phase with good enantioselectivities in the resolution of several pi-acidic aryl-dihydropyrimidines and derivatized profens. In addition, 3,5-dinitrobenzamido derivatives of alpha-amino acids could be resolved under normal phase HPLC conditions with separation factors up to 8.

Chromatography, High Pressure Liquid↗
PubMed1999

[Knowledge-based diagnosis and therapeutic recommendations with fuzzy-set theory methods in patients with acute lung failure (ARDS)].

OBJECTIVE: Since the treatment of patients with severe ARDS using the extracorporal lung assist (ECLA) methods remains a cost intensive and speculative procedure, a knowledge based computer system should be created and evaluated in order to support clinical decisions. METHODS: The model was based on the fuzzy set theory and therefore able to give decisions between yes and no, that means that a criterion could also be fulfilled to 35% or 80% for example. The development of this computer program consists of two steps: first, the entry criteria for the ECLA therapy were established within a framework of an international evaluation of clinical data from 3 centres (Berlin, Marburg, Vienna). Here, inherent vagueness, uncertainty of the occurrence and limited availability of medical data are to be considered to establish a useful tool. Secondly, this was done by grouping and weighting of parameters by the system and the status of each patient or patient group was assigned by the percentage of fulfillment of the criterion. RESULTS: By using a mixed sample of patients from these three centres, the fulfillment of entry criteria according either to definitions of Berlin or to definition of Marburg was different (68% versus 36%). Other differences (36% vs. 22% and 68% vs. 60%) were found between the fuzzy based score and the crisp score which represents the usually performed method. CONCLUSIONS: This now preevaluated minimal data set to describe severe ARDS patients based on the fuzzy set theory may be useful to evaluate patients for ECLA therapy or for another controlled ARDS-therapy.

Acute Disease↗
PubMed1999

Effect of a 2-hour infusion of 2-chlorodeoxyadenosine in the treatment of refractory or previously untreated Waldenström's macroglobulinemia.

2-Chlorodeoxyadenosine (2-CdA) is a new purine analogue active in indolent lymphoid malignancies. In this retrospective study 22 patients with Waldenström's macroglobulinemia (MW) were treated with 2-CdA given in 2-h intravenous infusions. Nine of them were untreated and 13 relapsed or were refractory to previous therapeutic modalities with chlorambucil/prednisone (11 patients) or COP (2 patients). The patients were given 1-11 (median 4) courses of 2-CdA at the dose of 0.14 mg/kg daily in 2-h intravenous infusion for 5 consecutive days. The courses were repeated every 28-35 d. If severe myelosuppression or infection developed, 2-CdA therapy was stopped until the haematological parameters increased. The effectiveness of the treatment was evaluated after the 3 cycles and after completion of therapy. None of the patients has achieved complete response (CR) after 3 courses of treatment and only one (4.5%) has obtained CR after 5 courses. Partial response (PR) was achieved in 8 (36.4%) patients, giving an overall response rate of 40.9%. Ten further patients (45.4%) responded to the treatment with less than 50% decrease in monoclonal protein (defined as stabilisation). There was no significant difference between the response rate in previously pretreated (38.5%) and untreated (44.4%) patients (p>0.05). Mean observed decrease in monoclonal protein was 41%. In the group of 9 patients responding to 2-CdA treatment mean duration of response was 12 months (range 3-34). Myelosuppression was the most prominent side-effect. Neutropenia was present in 17 (77.3%) and thrombocytopenia in 7 (31.8%) patients. In 6 patients myelosuppression was the reason for treatment discontinuation after 1 or 2 courses without significant therapeutic effect. Seven patients died, including 4 from the responding group and all three non-responding patients. Treatment-related thrombocytopenia and fatal haemorrhage was the course of death in 1 patient. In conclusion, the results of our study show that 2-CdA given in 2-h infusions is an effective agent in WM and may be given on an outpatient basis. However, myelosuppression is frequent and the drug must be administered with caution.

Adult↗
PubMed1999

Childhood asthma: exhaled nitric oxide in relation to clinical symptoms.

Bronchial asthma is associated with increased levels of exhaled nitric oxide which are suppressible by glucocorticosteroid inhalation. Children with bronchial asthma were studied to elucidate the relation between endogenous NO release and recent symptoms of bronchial obstruction. Twenty-five children with atopic asthma and 11 healthy control subjects were enrolled and exhaled NO was studied using chemiluminescence analysis. The subjects breathed purified air (<0.5 parts per billion (ppb) NO) exclusively through their mouths. Orally expired NO was measured during continuous nasal aspiration (1.3 L x min(-1)) to remove nasally produced NO. Nasal NO concentration was determined within the aspirated gas. Orally expired NO concentration was 2.5+/-0.3 ppb (mean +/-SEM) in healthy control subjects, 3.19+/-0.88 ppb (NS) in symptom-free children, and 8.28+/-0.81 ppb (p< or =0.01) in children with bronchial asthma who had had recent symptoms of bronchial obstruction. Similarly, in the subgroup of children treated regularly with inhaled glucocorticosteroids those with recent symptoms had significantly higher orally exhaled NO concentrations than healthy control subjects (9.5+/-1.5 ppb, p<0.05). The nasal NO concentration was 152.8+/-12.7 ppb in healthy control subjects and not significantly different in asthmatic children. In this group of asthmatic children, recent symptoms of bronchial obstruction were linked to significantly higher concentrations of NO in orally exhaled gas and to increased oral NO excretion rates. If substantiated by further studies, measurement of orally exhaled NO during nasal aspiration may become useful to monitor disease control in asthmatic children.

Asthma↗
PubMed1999

Free leptin, bound leptin, and soluble leptin receptor in normal and diabetic pregnancies.

We measured serum levels of free leptin, bound leptin, and soluble leptin receptor by specific RIA methods in 20 normal and 19 insulin-dependent diabetes mellitus subjects at 20 and 30 weeks gestation and postpartum, and analyzed the data using hierarchical statistical models. Total leptin levels rise from 20-30 weeks gestation (688 +/- 58 to 785 +/- 62 pmol/L, mean +/- SEM; P = 0.009). There is a significant postpartum fall to 445 +/- 47 pmol/L (P < 0.001). This rise is caused by the rise in the bound leptin levels, as there is no significant change in free leptin levels between 20 and 30 weeks (P = 0.17). There is a significant postpartum fall in free leptin levels (P < 0.001). Insulin requirements rise in the third trimester, but despite this there was no significant difference in free or bound leptin levels between the normal and diabetic subjects at any stage [free leptin, 223 +/- 35 and 266 +/- 24, 237 +/- 45 and 223 +/- 27, and 109 +/- 16 and 104 +/- 24 (P = 0.34); bound leptin, 410 +/- 73 and 428 +/- 54, 501 +/- 78 and 562 +/- 71, and 330 +/- 47 and 271 +/- 46 (P = 0.84); for normals and diabetics at 20 and 30 weeks gestation and postpartum, respectively]. Diabetic subjects, however, had significantly higher soluble leptin receptor levels at all stages (P << 0.001), which rose further in the third trimester from 3742 +/- 268 (mean +/- SEM) to 4134 +/- 239 pmol/L, whereas in the normal group there was a fall from 3149 +/- 169 to 2712 +/- 123 (P = 0.05). There is a linear relationship between the soluble leptin receptor levels and the body mass index in the diabetic group only. We conclude that there is no significant difference in free or bound leptin levels between the normal and insulin-dependent diabetic subjects either during pregnancy or postpartum, but female insulin-dependent diabetic subjects have significantly higher soluble leptin receptor levels. We speculate that high soluble leptin receptor levels might be implicated in the development of the leptin resistance in this group.

Adult↗
PubMed1998

The design of chiral separation media using monodisperse functionalized macroporous beads: effects of polymer matrix, tether, and linkage chemistry.

Porous size monodisperse methacrylate beads containing amino and hydroxyl groups, which can be used as a platform for the production of chiral separation media, have been prepared using the staged templated suspension polymerization process. The monomers 2-hydroxyethyl methacrylate and several tert-butoxycarbonyl-protected aminoalkyl methacrylates were used for the preparation of both hydroxyl- and amino-functionalized beads. Attachment of a chiral selector based on L-valine-3,5-dimethylanilide through a carbamate and a urea linkage, respectively, provides chiral stationary phases with excellent enantioselectivities in the separation of the enantiomers of 3,5-dinitrobenzamido derivatives of alpha-amino acids. For comparison purposes, a separation medium was also prepared by the direct polymerization of a chiral monomer analogous to the hydroxyethyl methacrylate-based stationary phase. The chiral stationary phases prepared with the N-methyl-2-aminoethyl methacrylate platform exhibit the best selectivity, and separation factors as high as 15 were achieved under normal-phase HPLC conditions.

Carbamates↗
PubMed1998

Exhaled nitric oxide in preterm infants.

Nitric oxide (NO) is detectable in the exhaled gas of adults during spontaneous respiration and, according to current knowledge, mainly originates from the paranasal sinuses. We studied total NO excretion rates by chemiluminescence in preterm infants whose paranasal sinuses are known to be only partially pneumatized. NO excretion was 7.15 +/- 1.13 nl/min (mean +/- SD, range 6.33-9.36 nl/min) measured from spontaneously exhaled nasal gas (n = 6) and 0.3 +/- 0.05 nl/min (range 0.26-0.36 nl/min) measured from the lower airways in intubated individuals (n = 3). These values are considerably lower than those reported for older children and adults. Body weight-related amounts of NO excretion, however, seem comparable between infants and adults.

Body Weight↗
PubMed1998

Low nitric oxide concentrations in exhaled gas and nasal airways of mammals without paranasal sinuses.

To investigate whether relevant levels of nasal nitric oxide (NO) are produced in the absence of paranasal sinuses, we studied 17 healthy baboons, mammals without any paranasal sinuses. The animals were anesthetized with ketamine hydrochloride and breathed spontaneously. While the baboons breathed through a face mask (mouths closed) connected to a respirator, NO concentrations in exhaled gas were sampled from the expiratory limb and analyzed by chemiluminescence. While the animals were breathing ambient air, nasal gas was sampled via a thin plastic tube and analyzed for NO concentrations by chemiluminescence. Mean NO concentration in the exhaled gas was 1.00 +/- 0.59 parts/billion, and NO release was 4.28 +/- 2.72 nl/min. A NO concentration of 4.79 +/- 2.08 parts/billion was found in the nasal gas (NO release: 7.18 +/- 3.13 nl/min). An age-dependent increase in nasal NO levels was not observed. Exhaled and nasal NO concentrations in baboons were markedly lower than in mammals with paranasal sinuses, suggesting that paranasal sinuses might be an anatomic requirement for production of relevant nasal NO levels.

Animals↗
PubMed1998

[Allogenic blood stem cell transplants: characteristics of transplantation material and clinical transplantation course].

We have analysed the clinical course of the 14 consecutive allogeneic peripheral blood stem cell transplantations (PBSCT) and cellular composition of the grafts. Donors were HLA-identical siblings except for the one donor who was only HLA-phenotypically identical brother. Nine of them were sex-mismatched to their recipient. Donors received filgrastim (G-CSF) at a dose of 10 microkilograms/kg for 5 days (4-6). Leukaphereses were started at 5 day to obtain the target dose 4 x 10(6) CD34+ cells/kg recipient weight. Median 24 l of blood (24-36) was processed collecting: 10.3 x 10(8)/kg (6.69-18.8) WBC, 9.9 x 10(8)/kg (5.87-16.02) MNC, 9.72 x 10(6)/kg (0.74-18.98) CD34+ cells, 242.5 x 10(6)/kg (77.9-422) T lymphocytes (CD4+ to CD8+ ratio was 1.5), 76 x 10(6)/kg (24-113) B lymphocytes, 33 x 10(6)/kg (14-88) NK cells and 168.8 x 104/kg (23.1-271.4) CFU-GM with 131.7 x 10(4)/kg (8.4-297.6) BFU-E. Engraftment times to a neutrophil count (ANC) > 0.5 x 10(9)/l was achieved at a median of 15 days (range 10-23) in all patients whereas the platelet count > 20 x 10(9)/l at a median of 14 days (9-19) in all but one patient who received the smallest dose of CD34+ cells. Acute graft versus host disease (GvHD) developed in 8 patients who survived more than 30 days. Most of them (75%) were patients with chronic myeloid leukaemia (CML). In 4 of them GvHD was steroid resistant. Chronic GvHD developed in 3 of 6 evaluable patients. We confirm that allogeneic PBSCT result in rapid and longterm trilineage engraftment. However, the observation of the increasing incidence and severity of acute GvHD in patients with CML will require verification in the larger setting of patients after completion of ongoing clinical trials.

Adult↗
PubMed1998

[Combined hemostatic defects in family members of symptomatic carriers of Leiden mutations of factor V].

The aim of the study was to determine the frequency of additional prothrombotic defect in family members of 14 symptomatic, heterozygous carriers of factor V Leiden mutation (FV Leiden). The FV Leiden was found in fifty-five from among 127 persons (43%). Thirty-two from 53 (68%) family carriers of FV Leiden had venous thromboembolic disease at the time of examination. Combined defects were found in 6 out of 14 families (in 4 families coexistence of FV Leiden mutation with protein S deficiency, in 1 with G20210 A mutation of prothrombin gene and in 1 with antithrombin III deficiency). Until now 63% (7/11) of combined defect carriers (mean age 48.5 years) and 59% (24/42) of heterozygous FV Leiden carriers (mean age 52.2 years) have been symptomatic. The thrombosis-free survival (Kaplan-Maier analysis) was comparable in combined and in single defect carriers groups.

Antithrombin III Deficiency↗
PubMed1997

An alternative method for identifying the factor V gene Leiden mutation.

The recently described point mutation of nucleotide 1691 of the factor V gene is responsible for the factor V resistance to a cleavage with an activated protein C (APC-resistance). Despite the high sensitivity and specificity of the APC-resistance test as a screening method for the detection of the factor V APC-resistance, there is still a necessity to develop a simple, cheap and accurate DNA-based assay. Herein, two different ASO-PCR methods were used for the detection of the Leiden mutation. The first involved a direct ASO-PCR with a consensus FV N1 primer and a sequence specific primer for the 1691 bp "G" normal allele (FV G1) or a specific primer for the 1691 bp "A" mutant allele (FV A1). The second method consisted of direct ASO-PCR by using the consensus FV N1 primer and one of two primers with an additional T-->G mismatch at the penultimate position from the 3'-end. One primer was specific for the 1691 bp "G" normal allele (FV G2) and the other was specific for the 1691 bp "A" mutant allele (FV A2). These permit clear and easy distinctions between homozygous normal and heterozygous and homozygous mutant probands. We also tested a T-->A mismatched primer to compare our method with that recently reported by Bellisimo et al. We found that within a large range of PCR conditions, T-->G mismatched oligonucleotides discriminated better than T-->A mismatched between three factor V 1691 position genotypes. We therefore recommend our method for the screening of a single 1691G-->A nucleotide mutation in the factor V gene.

Alleles↗
PubMed1997

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.

OBJECTIVE: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). DESIGN: Uncontrolled prospective trial. SETTING: One university hospital intensive care department. PATIENTS AND PARTICIPANTS: 122 patients with ARDS, consecutively admitted to the ICU. INTERVENTIONS: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) groups (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. MEASUREMENTS AND RESULTS: The groups differed in both APACHE II (16 +/- 5 vs 18 +/- 5 points, p = 0.01) and Murray scores (3.2 +/- 0.3 vs 3.4 +/- 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 +/- 9 vs 13 +/- 9 days, p = 0.0151), and length of ICU stay in Berlin (31 +/- 17 vs 50 +/- 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 +/- 27 mm Hg in AT-sine-ECMO patients that improved to 165 +/- 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 +/- 28 mm Hg and improvement to 160 +/- 102 mm Hg was not reached until ICU day 13. QS/QT was significantly higher in the ECMO-treated group and exceeded 50% during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75%. Survival rates were 89% in the AT-sine ECMO group and 55% in the ECMO treatment group (p = 0.0000). CONCLUSIONS: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.

Adult↗