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Biomedical subjects

R Kalb

Publications and source records attributed to R Kalb.

At least 19 recordsLinked to original sources

Partial liquid ventilation: effects of closed breathing systems, heat-and-moisture-exchangers and sodalime absorbers on perfluorocarbon evaporation.

BACKGROUND AND OBJECTIVES: During partial liquid ventilation perfluorocarbons are instilled into the airways from where they subsequently evaporate via the bronchial system. This process is influenced by multiple factors, such as the vapour pressure of the perfluorocarbons, the instilled volume, intrapulmonary perfluorocarbon distribution, postural positioning and ventilatory settings. In our study we compared the effects of open and closed breathing systems, a heat-and-moisture-exchanger and a sodalime absorber on perfluorocarbon evaporation during partial liquid ventilation. METHODS: Isolated rat lungs were suspended from a force transducer. After intratracheal perfluorocarbon instillation (10 mL kg(-1)) the lungs were either ventilated with an open breathing system (n = 6), a closed breathing system (n = 6), an open breathing system with an integrated heat-and-moisture-exchanger (n = 6), an open breathing system with an integrated sodalime absorber (n = 6), or a closed breathing system with an integrated heat-and-moisture-exchanger and a sodalime absorber (n = 6). Evaporative perfluorocarbon elimination was determined gravimetrically. RESULTS: When compared to the elimination half-life in an open breathing system (1.2 +/- 0.07 h), elimination half-life was longer with a closed system (6.4 +/- 0.9 h, P 0.05) when compared to a closed system. CONCLUSIONS: Evaporative perfluorocarbon loss can be reduced effectively with closed breathing systems, followed by the use of sodalime absorbers and heat-and-moisture-exchangers.

Absorption↗

Partial liquid ventilation in acute salt water-induced lung injury.

BACKGROUND AND OBJECTIVES: Salt-water aspiration results in pulmonary oedema and hypoxia. We tested the hypothesis that partial liquid ventilation has beneficial effects on gas exchange and rate of survival in acute and extended salt water-induced lung injury. METHODS: Anaesthetized, ventilated rats (tidal volume 6 mL kg(-1), PEEP 5 cmH2O) received a tracheal salt-water instillation (3%, 8 mL kg(-1) body weight) and were randomly assigned to three groups (n = 10 per group). While lungs of Group 1 were gas-ventilated, lungs of Group 2 received a single perfluorocarbon instillation (30 min after the injury, 5 mL kg(-1) perfluorocarbon) and lungs of Group 3 received an additional continuous perfluorocarbon application into the treachea (5 mL kg(-1) h(-1)) Arterial blood gases were measured with an intravascular blood gas sensor. RESULTS: Salt-water instillation resulted in a marked decrease in PaO2 values within 30 min (from 432 +/- 65 to 83 +/- 40 mmHg, FiO2 = 1.0, P < 0.01). Arterial oxygenation improved in all three groups irrespective of treatment. We observed no significant differences between groups in peak PaO2 and PaCO2 values. CONCLUSIONS: Our results suggest that partial liquid ventilation has no additional beneficial effects on gas exchange after life-threatening salt water-induced lung injury when compared to conventional gas ventilation with positive end-expiratory pressure.

Anesthesia↗

Screening Fanconi anemia lymphoid cell lines of non-A, C, D2, E, F, G subtypes for defects in BRCA2/FANCD1.

Biallelic mutations in BRCA2/FANCD1 were recently recognized as a rare cause of Fanconi anemia (FA). Using immunodetection with an antiserum directed against the carboxyterminus of the BRCA2 protein, we screened 38 lymphoid cell lines from FA patients whom we could not previously assign, via retroviral complementation analysis, to any of six known FA complementation groups (FA-A, -C, -D2, -E, -F, or -G). Three of these 38 cell lines lacked the 380-kDa BRCA2 signal on immunoblots. DNA sequencing showed biallelic compound and truncating mutations in two of the immuno-negative cell lines, whereas a monoallelic frameshift mutation and an amino acid substitution were detected in the third cell line. Our data show that less than 10% of unassigned FA cell lines harbor truncating mutations in BRCA2/FANCD1. This finding strongly suggests the existence of (an) additional, as yet unknown FA gene(s).

Cell Line, Transformed↗

Paired comparison of apheresis platelet function after storage in two containers.

Platelet quality after storage strongly depends on the pre-storage quality as well as on the storage conditions determined by the storage container. In this paired study, we evaluated two different containers (MedSep CLX and Delmed DPL-110). The Fresenius AS104 cell separator was used to prepare 17 platelet concentrates that were split and distributed into the containers to be compared. Cell counts, blood gas analysis, morphological scores, glucose and lactate levels, platelet activation, and platelet aggregation were measured before splitting at the day of preparation and after storage at day 3 and day 5. At day 3, there was no significant difference between the two bags apart from increased lactate and decreased pCO(2) concentrations in the CLX bags. At day 5 there were significantly higher lactate concentrations, pO(2) levels, and aggregation after stimulation in the CLX group, while the glucose and pCO(2) concentrations were significantly lower in these platelet concentrates as compared to the DPL-110 group. However, these parameters did not influence the functional parameters tested. While the platelet quality decreased during storage in all bags, the functional changes were nearly identical in both bags tested. We conclude that both bags are equivalent for 5-day storage of platelet concentrates.

Blood Preservation↗

Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial.

We have investigated the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS5572 in a double-blind, placebo-controlled multicenter clinical trial. 72 patients (WS 5572: 37, placebo: 35) with a diagnosis of mild to moderate major depressive disorder (according to DSM-IV criteria) were randomized in 42 days of treatment with either 300 mg WS5572 t.i.d. or placebo. The primary efficacy variable was the change of the 17-item Hamilton Depression Scale (HAMD) total score between baseline and double-blind treatment. The study was conducted with an adaptive interim analysis, which led to early stopping because convincing treatment efficacy could already be demonstrated. Group differences in favor of WS 5572 were descriptively apparent as early as day 7 of randomized treatment and were statistically significant at days 28 (p = 0.011) and day 42 (p < 0.001). Between baseline and treatment end, the HAMD total score decreased from 19.7 +/- 3.4 to 8.9 +/- 4.3 points in the Hypericum group and from 20.1 +/- 2.6 to 14.4 +/- 6.8 points in the placebo group (mean +/- SD). Responder rates were consistently higher in the Hypericum group. Comparable group differences in favor of WS 5572 were also found for von Zerssen's Depression Scale (D-S; self-rating), Clinical Global Impressions (CGI) and a global patient's self-assessment (GPA). Tolerability was very good in both groups, with no adverse drug reactions and no clinically relevant changes in safety parameters. The results indicate that Hypericum extract WS 5572 is an effective and well-tolerated drug for the treatment of mild to moderate major depressive disorder.

Adult↗

[Inspiration-triggered vasoconstrictive episodes in healthy subjects, in patients with diabetes mellitus and in patients with clinically manifest polyneuropathy of variable origin. A simple Doppler ultrasound test to assess the autonomic vascular functional unit of the upper extremity].

BACKGROUND: A cost- and time efficient ultrasound-Doppler-test is introduced to evaluate the function of autonomic innervation of the upper limb. A voluntary inspiratory vasoconstrictor episode (VICE) after a provoked deep inspiration, transmitted via sympathetic nervous system, can be demonstrated at the radial artery using basic Doppler equipment. PATIENTS AND METHOD: VICEs were investigated in 30 healthy subjects (group A), in 20 patients with diabetes mellitus without clinical signs of polyneuropathy (group B) and in 20 patients with clinically manifest polyneuropathy (group C). RESULTS: In all healthy subjects a two minutes arterial occlusion led to a decrease of resistance index (RI) lower than 0.9 indicating sufficient hyperemia. RI during VICE increased to 1.0 in all healthy subjects. In 50% of the patients of group B as well as in 50% of the patients of group C the test revealed abnormal findings suggesting a disorder of the functional peripheral neurovascular unity.

Adult↗

Leukocyte filtration of single-donor platelet units through an integrated filter system for the Fresenius AS 104 blood cell separator.

BACKGROUND AND OBJECTIVES: White cell depletion of platelet concentrates is widely applied to reduce the incidence of transfusion complications. We investigated a new plateletpheresis kit with an integrated filter for leukocyte depletion of platelets. MATERIALS AND METHODS: Parameters of product quality were investigated before and after in-line filtration of 70 single-donor platelet (SDP) units obtained by apheresis. We studied three different filter batches manufactured for the Fresenius AS 104 blood cell separator, and evaluated different softwares and interface positions with respect to platelet (PLT) yield and white blood cell (WBC) contamination. RESULTS: PLT yields before and after filtration was not statistically different in the protocols studied. WBC contamination after WBC depletion was in the range of 10(4)/SDP unit. Glucose, lactate dehydrogenase, and the morphology score were not statistically different before and after filtration. CONCLUSIONS: In-line WBC filtration of SDP units sufficiently reduced WBC below 5 x 10(6)/unit. The study allowed definition of the filter composition and apheresis parameters to optimize PLT yield and minimize WBC contamination.

Filtration↗

Influence of season on manifestation of schizophrenic subtypes.

In the modern classification systems ICD-10 and DSM-III-R, the term seasonality has been given a separate significance in the diagnostic categorization of affective disorders. Its definition is oriented not merely to the increased seasonal prevalence in the autumn and winter months, but also to symptoms that do not occur in nonseasonal attacks. To date, research work on seasonality in schizophrenia has concentrated on birth seasonality, while no results based on large populations of patients have yet become available on the manifestation seasonality of schizophrenic subtypes. Within the framework of a retrospective study carried out in the period between 1983 and 1995, involving 2, 119 patients suffering from recurrent attacks of schizophrenia, seasonal manifestations were recorded in accordance with the criteria defined in DSM-III-R. It was found that the two subtypes of paranoid hallucinatory and schizoaffective psychoses met the criterion of seasonality significantly more frequently than did the subtypes disorganized and catatonic disorders. In addition, seasonal courses within the groups just mentioned clearly differed from the nonseasonal forms in terms of their symptomatology.

Adult↗

[Psychiatric consultation before liver transplantation].

BASIC REMARKS: Since the long-term results of transplantations are highly dependent on patient compliance, prior to the decision to undertake such an operation, the psychiatrist is often asked whether there are any conditions presenting that would militate against the necessary cooperation. METHOD: Between 1992 and 1993, 35 patients were sent for psychiatric counselling prior to liver transplantation, and were evaluated using a standardised questionnaire. 23 of the 35 patients were submitted to psychological testing. RESULTS: in 23 cases, a psychiatric diagnosis was established in accordance with the ICD-10 criteria. The largest group was formed by the addictive diseases in this study, in particular alcohol dependence. Eight patients proved to have organ-related mental disturbances, other diagnoses such as depressive disorders or personality disorders were less common. In four cases, the psychiatrist was unable to recommend the liver transplantation. In such cases as these, the tasks of the psychiatrist is not restricted simply to a diagnostic assessment, but must also include a therapeutic approach intended to enable the patient to cope with the coming stresses and requirements.

Adaptation, Psychological↗

Genomic RFLP typing of human platelet alloantigens Zw(PlA), Ko, Bak and Br (HPA-1, 2, 3, 5).

The diallelic human platelet alloantigen systems 1-5 have been found to result from single base pair substitutions in the encoding genes of platelet membrane glycoproteins IIIa, Ib, IIb and Ia. This is the basis of DNA methods for determination of platelet alloantigens. In this study, 98 blood donors were typed in the HPA-1, 2, 3 systems and, for the first time, in the HPA-5 system. Serologically obtained data (MAIPA and platelet agglutination) were compared with results from analysis of restriction fragment length polymorphisms (RFLP). Discordances were found in the HPA-2 and 3 systems and can be ascribed to false typing results in both the serological and genomic methods. In the HPA-1, 2 and 5 systems, all samples were typed correctly with RFLP analysis. Serologically, two donors were falsely typed positive with anti-HPA-2b in platelet agglutination and one donor with anti-HPA-3a in MAIPA assay. In the HPA-3 system, another four donors were misinterpreted to be HPA-3a negative in RFLP analysis. Possible technical problems in PCR-RFLP-typing are discussed and another strategy of HPA-1 typing using the restriction enzyme Scr FI is evaluated.

Antigens, Human Platelet↗

A point mutation leads to an unpaired cysteine residue and a molecular weight polymorphism of a functional platelet beta 3 integrin subunit. The Sra alloantigen system of GPIIIa.

Recently, we described a low frequency platelet alloantigen on human platelet membrane glycoprotein (GP) IIIa, termed Sra, that was involved in neonatal alloimmune thrombocytopenia. To identify the molecular nature of the Sra alloantigen, we analyzed the nucleotide sequence of polymerase chain reaction-amplified GPIIIa mRNA, and found a C2004-->T substitution in seven Sra positive individuals which results in an Arg636-->Cys polymorphism within the cysteine-rich region of GPIIIa. Analysis of allele-specific recombinant forms of GPIIIa that differed only at amino acid residue 636 showed that anti-Sra alloantibodies reacted with the Cys636, but not the Arg636, recombinant form of GPIIIa. Interestingly, under reducing conditions, the Cys636 form of GPIIIa migrated with a slightly increased apparent molecular weight compared with the Arg636 form. Following treatment with Endoglycosidase H, both allelic forms of GPIIIa exhibited the same mobility, however the Sra epitope was lost. Sra positive platelets express the same number of GPIIb-IIIa complexes on their surface as wild-type Sra negative platelets, and also aggregate normally in response to a variety of platelet agonists. Based upon these results, we conclude that 1) GPIIIa residue 636 specifically controls the formation and expression of the Sra alloantigenic determinant, and 2) an unpaired cysteine residue alters the N-linked glycosylation pattern of the extracellular domain of GPIIIa, but affects neither the degree of surface expression nor the adhesive function of the GPIIb-IIIa complex.

Amino Acid Sequence↗

New polymorphism on platelet glycoprotein IIIa gene recognized by endonuclease Msp I: implications for PlA typing by allele-specific restriction analysis.

BACKGROUND: Five human platelet alloantigen systems have been shown to result from single base pair substitutions in encoding regions of platelet glycoprotein genes IIIa, Ib, IIb, and Ia. For each of the diallelic systems, at least one restriction enzyme is known to cut only one of the two haplotypes. In the PlA system, restriction endonucleases Nci I and Msp I both recognize the PlA2 allele. STUDY DESIGN AND METHODS: A causal observation of an unexpected Msp I restriction pattern of a PlA2/PlA2 individual was made. Samples from 261 blood donors were then typed for antigens of the PlA system by restriction fragment length polymorphism analysis using the Nci I and Msp I restriction enzymes. RESULTS: Applying both enzymes, concordant restriction patterns were found in 258 of 261 blood donors. Three donors had a base pair mutation on the PlA2 allele, which creates an additional restriction site for Msp I 20 base pairs downstream from the PlA polymorphic site. Nucleotide sequence analysis revealed a CT217-->CG217G base exchange resulting in a Leu40-->Arg40 polymorphism of glycoprotein IIIa. CONCLUSION: Presuming that the mutation is not a singular phenomenon and also occurs with the PlA1 haplotype, it could lead to false interpretations of restriction analysis with Msp I. To exclude that possibility, Nci I is preferred for restriction fragment length polymorphism typing in the PlA system.

Antigens, Human Platelet↗

Localization of the Br polymorphism on a 144 bp exon of the GPIa gene and its application in platelet DNA typing.

Alloimmunization against the human platelet alloantigen system Br (HPA-5) is the second most common cause of neonatal alloimmune thrombocytopenia (NAIT) in Caucasian populations. We have recently shown that a single base polymorphism at position 1648 on platelet mRNA coding for GPIa results in an aminoacid substitution at position 505 on the mature GPIa which is associated with the two serological defined Br phenotypes. Since DNA-typing of platelet alloantigens offers possibilities for useful clinical applications, we designed genomic DNA-based restriction fragment length polymorphism (RFLP) typing for Br alloantigens. To establish this technique we analyzed the genomic organization of GPIa adjacent to the polymorphic base. Using the polymerase chain reaction (PCR) of blood cell DNA we have identified two introns (approximately 1.7 and 1.9 kb) flanking a 144 bp coding sequence of the GPIa gene encompassing the polymorphic base 1648. Based on the intron sequence, a PCR primer was constructed to amplify a 274 bp fragment which was used for allele-specific RFLP to determine the Br genotypes. The results of RFLP analysis using MnlI endonuclease obtained from 15 donors (2 Bra/a, 2 Bra/b and 11 Brb/b) correlate perfectly with serological typing by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay.

Base Sequence↗