Evaluation of dialysis membrane-blood compatibility: experimental methods.
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Animals↗
Biomedical subjects
B Schmidt
Publications and source records attributed to B Schmidt.
Neonatal thrombosis: report of a prospective Canadian and international registry.
OBJECTIVE: We sought to obtain representative data on the risk factors, diagnosis, current management, and short-term outcome of neonatal thrombosis. RESEARCH DESIGN: A case registry was established at McMaster University. Standardized questionnaires were mailed to collaborators at participating centers every 4 to 6 months. SETTING: Eighty-five level III and modified level II neonatal units in North America, Europe, and Australia were invited to join the registry. PATIENTS: Eligible infants were born between January 1990 and June 1993. Large-vessel thrombosis was diagnosed during the first month of life or up to 44 weeks post-conception after premature birth. The clinical impression of thrombotic vessel obstruction was confirmed using at least one imaging technique. RESULTS: Physicians in 64 centers expressed their willingness to participate. A total of 97 cases (excluding stroke) were registered from 29 centers. Spontaneous renal venous thrombosis (n = 21) was diagnosed at a median age of 2 days. The other venous (n = 39), arterial (n = 33), and mixed (n = 4) thromboses presented later; 89% of them were associated with an intravascular catheter and 29% with systemic infection. Doppler ultrasonography was the definitive diagnostic test in 68% of cases; contrast angiography was performed infrequently (14%). A third of all patients (but 62% of infants with renal venous thrombosis) received supportive therapy only. Thrombolytic agents were prescribed for 28% of catheter-associated venous thromboses and 30% of all arterial thromboses. The remainder of the patients were given heparin. Most patients (82%) survived to hospital discharge. Mortality rates were highest among infants with aortic thrombosis or central venous line-associated thrombosis affecting the right atrium or the superior vena cava (33%). CONCLUSIONS: Neonatal thrombosis is diagnosed fairly rarely. With the exception of spontaneous renal venous thrombosis, almost all cases are associated with indwelling catheters. Doppler ultrasound techniques are the most popular means of confirming the diagnosis in virtually all centers. Treatment varies greatly among different centers, probably because of the lack of scientific evidence about the optimum management of affected infants.
Canada↗
[Neurosyphilis. A case report and review of the literature on differential neuroborreliosis diagnosis].
A 35-year old man was presented with organic psychosyndrome. Anamnestic reports informed about changes in his behaviour like loss of interest, reduced concentration and short-term-memory loss within the last 2 years. The practicing psychiatrist diagnosed a depressive syndrome in conjunction with a borderline syndrome and administered antidepressive and neuroleptic therapy. Specific serologic tests were not done. Neurologically, there was a picture of influent and slurred speech, and ataxic gait. Muscle tonus was normal, muscle reflexes were of the same diminished intensity on both sides. The psychic status revealed a person mostly oriented in time, location and situation but with severe disorders of recognition, concentration, and memory. Laboratory diagnosis proved the suspected diagnosis of neurosyphilis. Additionally, there were antibodies to Borrelia burgdorferi (Bb) in serum and CSF and a positive CSF/serum index of 9.0 (threshold: 1.9). The neuroradiologic examination (CCT, NMR, SPECT) showed an intense, diffuse, frontotemporal atrophy of the cortex. By NMR, massive gliosis was found in both hippocampi. Angiographically, an aneurysma (1 cm in diameter) of the medial cerebral artery was demonstrated. Specific treatment was performed with Na penicillin (5 Mio. i.v./4 h over 21 days). No remission could be achieved.
Adult↗
Evidence in Latin America of recurrence of V388M, a phenylketonuria mutation with high in vitro residual activity.
Phenylketonuria mutation V388M is frequent in the Iberian Peninsula. In vitro, the V388M mutant enzyme has similar immunoreactive protein and phenylalanine hydroxylase mRNA and has 43% residual activity, which correlates well with the mild phenotype exhibited by the homozygous patients. In Spain it has been detected in 5.7% of the mutant alleles and is always associated with haplotype 1.7. This mutation is also present in high frequency in some Latin American countries (Brazil, 9%; Chile, 13%). It is interesting that in Chile most of the alleles bearing this mutation carry haplotype 4.3, although in Brazil it is found only on the background of haplotype 1.7. The origin of V388M in Spain on haplotype 1.7 and in Chile on haplotype 4.3 is clearly different. Recurrence is the most plausible explanation, because the mutation involves a CpG dinucleotide, and a recombination event transferring the mutation from haplotype 1 to 4 is unlikely.
Alleles↗
Encephalitic and myocardial toxoplasmosis masquerading as cytomegalovirus infection in a renal allograft recipient.
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Aged↗
Congenital melanocytic nevi and DNA content. An analysis by flow and image cytometry.
BACKGROUND: Potential risk factors for the development of melanoma in congenital melanocytic nevi (CMN) are not well established. DNA aneuploidy may constitute such a risk factor but has not been sufficiently studied in CMN. METHODS: In the present study, DNA analysis of eight giant CMN, nine medium CMN (1.5-20 cm), and eight small CMN (< 1.5 cm) was assessed by flow cytometry and selected lesions (six nevi) by DNA image cytometry. DNA content was correlated with patient age, nevus size, and degree of cytologic atypia. RESULTS: DNA aneuploidy was detected by flow cytometry in two giant CMN from adult patients and in a small CMN from a child. DNA aneuploidy was not observed in any of the six CMN studied by image cytometry, although an increased S-phase was noted in a markedly atypical giant CMN. No DNA aneuploidy was detected in medium-sized CMN or in the CMN of nine patients 1 year of age or younger. CONCLUSION: In contrast to previous studies, it was observed that abnormal DNA content does tend to correlate with cytologic atypia, particularly in giant CMN with atypia or melanoma, in adults. Conversely, frank DNA aneuploidy in any CMN in children younger than 1 year of age, irrespective of histologic findings, was not detected. Finally, based on these limited studies, greater sensitivity of image over flow cytometry for detection of DNA aneuploidy cannot be verified.
Adolescent↗
Cyclosporine pharmacokinetics and variability from a microemulsion formulation--a multicenter investigation in kidney transplant patients.
The steady-state pharmacokinetics and tolerability of a microemulsion formulation of cyclosporine (Sandimmune Neoral) were compared with the commercial formulation (Sandimmune) in 55 clinically stable renal allograft recipients. In study period I (2 weeks' duration), patients entered the study on a stable, individualized twice-daily dosage regimen of the commercial formulation. In period II (2 weeks), they were changed over to the microemulsion formulation at the same dose as at study entry. In period III (2 weeks), dose titration was subsequently allowed if necessary to provide comparable steady-state trough concentrations as at study entry. The commercial formulation was reinstituted during period IV (2 weeks). Safety and tolerability were assessed at weekly clinic visits, and the steady-state pharmacokinetics of cyclosporine in whole blood were characterized at the end of each study period. A milligram-to-milligram dose conversion was adequate when making the initial change between formulations in order to maintain steady-state trough concentrations in the target therapeutic range. Concomitant with this conversion, the steady-state peak concentration and area under the curve increased on average by 59% and 30%, respectively, due to absorption-related differences between the formulations. These increases were not associated with an increase in adverse experiences or changes in blood pressure or clinical laboratory parameters over the first four weeks after the change-over. Trough concentrations were more stable and were more strongly correlated with systemic exposure (area under the curve) during treatment with the microemulsion formulation. Intraindividual coefficients of variation in steady-state peak concentration, time to attain the peak, area under the curve, and percent peak-trough fluctuation ranged from 18% to 74% from the commercial formulation. Variability from the microemulsion formulation was significantly less, ranging from 10% to 22%.
Absorption↗
A homodimer represents an active species of the peptidyl-prolyl cis/trans isomerase FKBP25mem from Legionella pneumophila.
The molecular mass of the native FK506-binding peptidyl-prolyl cis/trans isomerase (PPIase) FKBP25mem from Legionella pneumophila (Mip (macrophage infectivity potentiator) protein) was determined by two methods. By gel-permeation chromatography we found no indication of the presence of the monomeric enzyme. However, an oligomeric state with a molecular mass of about 62 kDa was detected. By cross-linking with dimethyl pimelimidate and subsequent SDS-PAGE of either the surface proteins of intact L. pneumophila cells or the purified recombinant FKBP25mem in solution, we observed an immunoreactive band indicative of a mass in the dimer range. In contrast to human recombinant FKBP12, the enzymatic activity of Legionella FKBP25men was strongly dependent on the protein concentration, pointing to a dimer as the most active species. However, the inhibition by FK506 yielded a nearly constant value of Ki of about 250 nM when measured in the same range of FKBP25mem concentration. These results may be explained by the fact that monomeric FKBP25mem has little, if any, influence on enzymatic activity when compared with the homodimer.
Amino Acid Isomerases↗
Glycosylation and phosphorylation of arylsulfatase A.
The glycosylation and phosphorylation of the lysosomal enzyme arylsulfatase A was analyzed by a combination of metabolic labeling, tryptic fragmentation, mass spectrometry, and radiosequencing. The results demonstrate that all three potential N-glycosylation sites at Asn residues 158, 184, and 350 are utilized in arylsufatase A and carry high mannose or hybride type oligosaccharides. Phosphorylation of mannose residues is restricted to oligosaccharides at the first and third N-glycosylation site (Asn-158 and Asn-350). Both are phosphorylated with comparable efficiency. An earlier study had shown that a mutant arylsulfatase A containing only the second N-glycosylation site at Asn-184 folds correctly and is phosphorylated (Gieselmann, V., Schmidt, B., and von Figura, K. (1992) J. Biol. Chem. 267, 13262-13266). The lack of phosphorylation at Asn-184 in wild type arylsulfatase A therefore indicates that in vivo the presence of oligosaccharides can interfere with phosphorylation of other sites or that phosphorylation occurs in an ordered manner whereby phosphorylation of one site can affect the phosphorylation of another site.
Amino Acid Sequence↗
In vitro phosphorylation of the 46-kDa mannose 6-phosphate receptor by casein kinase II. Structural requirements for efficient phosphorylation.
Some steps in the receptor-mediated transport of newly synthesized mannose 6-phosphate-containing lysosomal enzymes are assumed to be accompanied by changes in the phosphorylation state of receptors. In vitro, the metabolically phosphorylated 46-kDa mannose 6-phosphate receptor (MPR 46) was dephosphorylated by protein phosphatase 2A. The synthetic cytoplasmic domain of MPR 46 was phosphorylated in vitro by casein kinase II. Tryptic phosphopeptide mapping showed that casein kinase II phosphorylates MPR 46 in vitro at the same site that is phosphorylated in vivo. Inhibition studies using synthetic peptides corresponding to different amino acid sequences of the cytoplasmic tail of MPR 46 revealed that the sequence 26-32 (ADGCDFV) contribute to efficient phosphorylation of serine 56. Baby hamster kidney cells were transfected with wild type human MPR 46 cDNA or cDNAs containing mutations in the cytoplasmic tail and assayed for their phosphorylation state in vivo. The phosphorylation of mutant receptors with deleted residues 23-28 (NLVADG) was strongly reduced. These data indicate that residues on the N-terminal side of the phosphorylatable serine 56 may influence the efficiency with which a casein-kinase II-like kinase phosphorylates MPR 46.
Amino Acid Sequence↗
Analysis of melanocytic lesions by DNA image cytometry.
BACKGROUND: There is increasing evidence that melanocytic nevi with architectural and/or cytologic atypia (dysplastic melanocytic nevi [DMN]) are lesions intermediate between banal nevi and malignant melanoma. Other studies have shown conflicting results regarding the DNA content in DMN. METHOD: In the present investigation, the authors measured DNA ploidy by image analysis (CAS-200 system, Cell Analysis Systems, Inc., Elmhurst, IL) using Feulgen staining in 54 melanocytic lesions. The lesions were categorized into 7 groups: compound nevus (CN) = 7; compound nevi with features of DMN (F) = 10; DMN with slight atypia = 8; DMN with moderate atypia = 9; DMN with severe atypia (S) = 8; melanoma in situ = 5; and malignant melanoma (CMM) = 7. The age distribution for these various lesions was also recorded. DNA histograms obtained by image analysis from these groups were examined for DNA aneuploidy by DNA index and classified according to Auer classifications (Auer I-IV). RESULTS: There was a progression of mean age for each group of melanocytic lesions, ranging from 39 years for ordinary nevi to 53 years for invasive melanoma. The Type I histogram, which is distinctly diploid, was seen in 4 of 7 cases of CN, 5 of 10 of nevi with features of dysplastic nevus, and 3 of 8 nevi with slight atypia. The Type I histogram was not observed at all in nevi with moderate atypia, severe atypia, melanoma in situ, and invasive melanoma. The Type IV histogram (aneuploid) was not identified in low grade lesions (CN, F, S), but was observed in two of nine nevi with moderate atypia, six of eight lesions with severe atypia, two of five melanomas in situ, and five of six invasive melanomas. Aneuploidy by DNA index was noted in one nevus with features of DMN, one DMN with slight atypia, one with moderate atypia, four of eight DMN with severe atypia, two of five in situ melanomas, and two of six invasive melanomas. CONCLUSION: The results show that DMN exhibit a spectrum of abnormal DNA content intermediate between banal nevi and CMM and that DNA content generally correlates with the age of patients and degree of atypia in melanocytic nevi.
Adult↗
Characterization of Mip proteins of Legionella pneumophila.
The Mip ('macrophage infectivity potentiator') protein of Legionella pneumophila has been shown to be an essential virulence factor, exhibiting peptidyl-prolyl cis/trans isomerase (PPIase) activity that can be inhibited by the immunosuppressant FK506. The cloning and sequencing of mip genes from three different L. pneumophila strains revealed a single amino acid substitution which did not affect the isomerase property of the enzyme. Mip proteins isolated from two wild-type L. pneumophila strains and from two corresponding Escherichia coli K-12 recombinant clones derived from these strains exhibited identical enzymatic properties and the precursor proteins are processed at identical cleavage sites. The mature Mip proteins exist in an oligomeric form. Site-directed mutagenesis demonstrated that a substitution of an Asp residue at position 142 by a Leu residue affects PPIase activity of Mip.
Amino Acid Isomerases↗
Reactive collisions as a signature for meltinglike transitions in clusters.
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Journal Article↗
[An unusual case of congenital trigger finger].
A rare case of the congenital digitus saltans is discussed. The differences between the more frequent adult form and the congenital form are reviewed according to the clinical signs. The literature is reviewed. The possible etiological factors are discussed.
Age Factors↗
Skeletal muscle involvement in tropical spastic paraparesis/HTLV-1-associated myelopathy.
The frequency of muscle involvement in TSP/HAM is not known, nor is the precise role that HTLV-1 and the diverse cytokines play in the genesis of HTLV-1-associated diseases. In order to better define the frequency and characteristics of the skeletal muscle involvement in TSP/HAM, we studied 11 affected patients. EMG was performed in 9 patients and muscle biopsy was performed in all 11. Muscle tissue was analyzed using: reverse transcriptase PCR for interleukin-1 in 8; PCR for HTLV-1 proviral DNA in 5; and electron microscopy for viral particles in 3. We found pathologic alterations in all 11 patients. Four patients (36%) had a neurogenic process, while a primary muscle involvement was observed in the rest (64%). Four patients (36%) had polymyositis, and 3 (27%) had a noninflammatory myopathy. Muscle weakness in the upper limbs was significantly associated with inflammation in the muscle biopsy. EMG was abnormal in only 2 of 9 patients. Reverse transcriptase PCR did not demonstrate message for interleukin-1 in any sample examined. PCR did identify HTLV-1 proviral DNA in the muscle of 3 patients. Retroviral-like particles were found, by EM, in only one biopsy. HTLV-1 may play an important role in the pathogenesis of the frequent myopathies associated with HAM/TSP.
Adult↗
Treatment of a high-flow arteriovenous malformation by direct puncture and coil embolization.
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Arteriovenous Malformations↗
Platelet-leukocyte aggregation during hemodialysis.
Hemodialysis is associated with simultaneous changes in leukocytes and platelets, but it is unclear whether these alterations affect the interactions between these cell types. To evaluate this process, we examined the appearance of platelet specific antigens (CD41) on leukocytes as an index of platelet-leukocyte aggregation during hemodialysis using three different synthetic membranes. Patients with end-stage renal disease (ESRD) on long-term hemodialysis treatment were enrolled. Flow cytometric techniques and platelet specific monoclonal antibodies (MoAb) that recognize the glycoprotein complex on resting and activated platelets (anti-CD41), the activated GPIIb-IIIa complex receptor (anti-LIBS1), and the p selectin GMP140, that is exposed on platelet plasma membrane after activation and platelet degranulation (anti-CD62), were used. Subjects with ESRD had a lower predialysis platelet surface expression of CD41 and LIBS1 compared to normal controls, but unchanged CD62 expression. In parallel, patients with ESRD manifested a uniformly reduced platelet-leukocyte microaggregates predialysis compared to normal controls. When examined across the dialyzer, however, an increase in platelet-neutrophil and platelet-monocyte microaggregates was observed with all three synthetic membranes at both 15 and 30 minutes after initiation of dialysis. This phenomenon could be duplicated in vitro by physiologic concentrations of the platelet specific agonist ADP, but not by the complement factors C3a or C5a. We conclude that platelet-leukocyte aggregates occur during dialysis likely related to a primary platelet activation mechanism. This phenomenon may serve as a new biocompatibility parameter and may shed light on some of the biologic consequences of hemodialysis.
Adolescent↗
Surgical strategies in very-low-birthweight neonates with necrotizing enterocolitis.
Very-low-birthweight (VLBW) neonates are more prone to complications and death than term infants are. In a 15-year period, 19 neonates with VLBW were operated on for necrotizing enterocolitis (NEC). Indications for operation were pneumoperitoneum in 12 and deterioration of general condition in 7. Bowel resection and intestinal diversion was performed in 12, a lateral enterostomy at the site of perforation was created in 5, and 2 neonates with necrosis of the whole bowel underwent an exploratory laparotomy without any further surgical treatment. Surgical complications were found in one-third of the patients. The mortality rate was significantly higher when the ileum was affected. The survival rate was 68%. Prior to 1984 the survival rate was 37% (3/8); subsequently, it has improved to 91% (10/11) as a result of improved intensive therapy.
Anastomosis, Surgical↗