Studies on the metabolism and toxicological detection of the amphetamine-like anorectic mefenorex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay

Studies on the metabolism and on the toxicological analysis of mefenorex [R,S-N-(3-chloropropyl)-alpha-methylphenethylamine, MF] using gas chromatography-mass spectrometry (GC-MS) and fluorescence polarization immunoassay (FPIA) are described. The metabolites were identified in urine samples of volunteers by GC-MS. Besides MF, thirteen metabolites including amphetamine (AM) could be identified and three partially overlapping metabolic pathways could be postulated. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for MF and 100 ng/ml for AM). Excretion studies showed, that only AM but neither MF nor its specific metabolites were detectable between 32 and 68 h after ingestion of 80 mg of MF. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 68 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.     

Arthroscopic-assisted reduction of distal radius fractures

The outcomes of seven patients with severe comminuted intraarticular fractures of the distal radius treated by arthroscopic reduction and percutaneous external fixation (ARPEF) were retrospectively reviewed. All of the fractures were classified as C3 types using the AO classification scheme. Outcomes were evaluated using the Gartland and Werley functional criteria, an objective wrist examination, a radiographic analysis, and a self-assessment outcome form at an average follow-up of 27 months (range, 12 to 45 months). All patients were free of pain and had returned to their prior occupations. No patient had articular incongruency of greater than 1 mm, and there was no evidence of radiocarpal degenerative change. Active range of motion and maximal grip strength averaged 92% and 98%, respectively, of the uninjured wrist. The technique of arthroscope-assisted reduction and percutaneous external fixation yielded excellent results in a small group of patients, with minimal complications.     

Bilateral lower limb oedema due to a distended urinary bladder

A 91-year-old Chinese man developed bilateral lower limb oedema due to venous obstruction resulting from a distended urinary bladder. After the bladder was decompressed by urethral catheterisation, the bilateral lower limb oedema promptly subsided. Although a distended urinary bladder is a rare cause of bilateral lower limb oedema, it can be easily recognised by palpation of the lower abdomen and the relief of symptoms by urethral catheterisation is most rewarding.     

Prediction of pulmonary capillary wedge pressure and assessment of stroke volume by noninvasive impedance cardiography

Early recognition of heart failure is important because early treatment reduces mortality and hospitalization rates. In screening for this disease, there is a need for a simple, safe, and cost-effective method to obtain cardiovascular variables. Therefore we developed a noninvasive impedance cardiographic method to predict the pulmonary capillary wedge pressure (PCWP) from the impedance cardiogram. The impedance cardiographic technique, though, was originally designed for stroke volume (SV) determination. The objectives of this study were to validate both variables by comparison with the paired, invasively obtained equivalents. PCWP, measured with a pulmonary artery catheter, was related to the O/C ratio from the impedance cardiogram. The O/C ratio was calculated as the amplitude of the impedance cardiogram during diastole (O) divided by the maximum height during systole (C). Stroke volume was also calculated from the impedance cardiogram according to the equation of Kubicek (SVIC) and compared with thermodilution (SVTD). Data analysis was performed in 24 stable patients who underwent diagnostic heart catheterization. Linear regression analysis showed that the O/C ratio was strongly related to the invasively measured PCWP over a range of 3 to 30 mm Hg (r = 0.92, standard error of the estimate, 3.2 mm Hg). Between SVIC and SVTD a moderate correlation was established (r = 0.69), but after exclusion of the data from patients with an aortic valve disorder (n = 5), the correlation increased considerably (r = 0.87). No significant differences between SVIC and SVTD were found (mean difference +/- 2 SD = 1.8 +/- 28.8 ml). These preliminary observations suggest that impedance cardiography can predict PCWP and measure SV over a wide range of clinically relevant values. The combined measurement of SV and PCWP by impedance cardiography might be a clinical useful tool in screening for heart failure.     

UDP-GlcNAc:Ser-protein N-acetylglucosamine-1-phosphotransferase from Dictyostelium discoideum recognizes serine-containing peptides and eukaryotic cysteine proteinases

Phosphoglycosylation catalyzed by UDP-GlcNAc:Ser-protein N-acetylglucosamine-1-phosphotransferase (Ser:GlcNAc phosphotransferase) adds GlcNAcalpha-1-P to peptidyl-Ser of selected Dictyostelium discoideum proteins. Lysosomal cysteine proteinase (CP), proteinase-1(CP7), is the major phosphoglycosylated protein in bacterially grown amoebae. GlcNAc-1-P is added within a Ser-rich domain containing SSS, SGSG, or SGSQ repeated motifs that are not found in other papain-like CPs. We studied the substrate specificity of the transferase using peptides containing these motifs and 12 other peptides with one or more Ser residues. Phosphoglycosylation is comparable for all three Dictyostelium CP motifs, but it is not restricted to them. Flanking residues in the other peptides strongly influence phosphoglycosylation efficiency. Dictyostelium microsomal membranes also phosphoglycosylate endogenous acceptors, and some of these acceptors occur as an 18 S complex with the transferase. CP-serine motif peptides inhibit endogenous acceptor phosphoglycosylation weakly (30-40%) at 800 microM, whereas catalytically inactive proteinase-1(CP7) and other non-phosphoglycosylated eukaryotic CPs, lacking the serine domain, inhibit transferase activity at 1-4 microM. SDS denaturation destroys the inhibitory potential of all CPs showing that transferase recognizes a conformation-dependent feature that is shared by all. Proteinase-1(CP7) expressed in Escherichia coli lacks GlcNAc-1-P, but it is a substrate for Ser:GlcNAc phosphotransferase, Km = 5.6 microM. Thus, Ser:GlcNAc phosphotransferase recognizes both acceptor peptide sequences and a conformational feature of eukaryotic CPs. This may be physiologically important for establishing or maintaining non-overlapping groups of GlcNAc-1-P- and Man-6-P-modified Dictyostelium proteins that reside in functionally distinct endo-lysosomal vesicles.     

Unbalanced chromosomal aberrations in neuroendocrine lung tumors as detected by comparative genomic hybridization

Typical and atypical carcinoids (TC, ATC) and small (SCLC) and large cell neuroendocrine carcinomas (LCNEC) constitute the spectrum of neuroendocrine lung tumors. Chromosomal aberrations have not been studied in LCNEC and only rarely in carcinoids. Only SCLCs have been investigated frequently for chromosomal aberrations. We compared three typical and four atypical carcinoids, one atypical carcinoid/SCLC mixed type, three SCLC, and three LCNEC for chromosomal gains and losses using comparative genomic hybridization. Typical carcinoids showed either no changes or only few chromosomal gains. Atypical carcinoids appeared genetically heterogeneous: One case had no aberrations, and three cases had few aberrations; two of them showed a deletion of 11q. SCLC and LCNEC were characterized by many gains and losses, especially similar changes of 3p, 5q, 5p, and 13q. Although ATC resemble LCNEC morphologically, there were no similarities at the genetic level. We have found a reciprocal relationship of prognosis and the amount of aberrations. TCs and ATCs with few chromosomal changes have the best prognosis, whereas SCLCs and LCNECs were generally characterized by a great amount of aberrations and worst prognosis. There was no unbalanced aberration common in all types of neuroendocrine tumors of the lung.     

Amoxicillin and its excretion into bronchial secretion (author's transl)

Various dates on amoxicillin (resorption, distribution, elimination, tissue passage, urinary excretion) are presented. The bacterial spectrum is more fully discussed. Amoxicillin is compared with ampicillin. Dosage and therapeutical results are presented. Within repeated bronchoscopic examinations necessary on account of bronchopulmonary affections determination of germs were done in 88 children. At the same time examination of ampicillin levels in bronchial secretions were performed after amoxicillin therapy with different high doses (3 x 125 mg to 3 x 750 mg) for 7 days. It could be shown that good antibiotic levels could be found in secretion specimens above all obtained 2 to 4 hours after the last amoxicillin administration. They could be found too, if there did not exist any purulent secretion or stronger inflammation. There are relations between the amount of dosage, the level in secretion as well as the influence on germs.     

Diagnosis of idiopathic myositis: value of 99mtechnetium pyrophosphate muscle scintigraphy and magnetic resonance imaging in targeted muscle biopsy

The widespread use and dramatic success of prosthetic joint implant surgery (arthroplasty) has greatly improved the quality of life for many individuals suffering from degenerative, arthritic, or injured joints. However, in a number of cases, recipients experience discomfort at the arthroplasty site that can signal biomechanical failure, or periprosthetic infection of the joint, or both. In fact, infection remains a devastating obstacle, preventing arthroplasty from being an almost perfect medical procedure. Existing tests for the diagnosis of infection in orthopedics are disappointing because of the relatively high frequency of false negative results. To overcome this shortcoming, and to reduce the number of infected revision arthroplasties, a methodology based on molecular biology has been established. The method allows the rapid, sensitive and accurate diagnosis of orthopedic infections, and should aid the clinician with treatment regimens, surgical decisions, and overall patient management in the growing arthroplasty population.