Successful immunosuppressive treatment and long-term follow-up of anti-Ri-associated paraneoplastic myelitis.
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Biomedical subjects
Publications and source records attributed to P Eichhorn.
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We present the case of a 75-year-old female with weight loss, anemia, systemic signs of inflammation, mild renal insufficiency, microscopic hematuria, mixed glomerular and tubular proteinuria, and high titers of PR3-ANCA. Renal biopsy demonstrated interstitial nephritis with some sclerosed but otherwise normal glomeruli. Extensive work-up showed no signs of granulomatous inflammation or other vasculitic organ involvement. We presumed this to be a rare renal manifestation of ANCA-associated disease with the presence of sclerosed glomeruli suggesting a previous history of glomerular involvement. In view of the absence of active vasculitic or granulomatous disease, treatment was limited to low-dose corticosteroids with good response.
AIMS: The aims were to test whether Parvibaculum lavamentivoransT degraded commercial linear alkylbenzenesulphonate (LAS) surfactant via omega-oxygenation and beta-oxidation to sulphophenylcarboxylates (SPCs), whether the organism was widespread and reisolable, and whether the degradative community used the 4-sulphocatechol 1,2-dioxygenase to cleave the aromatic ring from LAS. METHODS AND RESULTS: Heterotrophic P. lavamentivoransT converted LAS (side chain length C10-C13) to SPCs (C4-C13), alpha,beta-unsaturated SPCs (C4-C13) and sulphophenyldicarboxylates (SPdCs) (at least C8-C12). Identifications came from high performance liquid chromatography (HPLC) separation, an electrospray interface and mass spectrometry. No evidence for other paths was found. The degradation of LAS in trickling filters inoculated with environmental samples always showed transient SPC intermediates (HPLC) and the presence of the P. lavamentivorans morphotype in the community. One new isolate was obtained. A community able to mineralize LAS contained 4-sulphocatechol-1,2-dioxygenase at high specific activity. CONCLUSIONS: Parvibaculum lavamentivoransT degrades commercial LAS via omega-oxygenation, oxidation and chain shortening through beta-oxidation to yield a wide range of SPCs. The latter are degraded in bacterial communities which contain organisms like P. lavamentivorans, and which utilize sulphocatechol dioxygenase for ring cleavage. SIGNIFICANCE AND IMPACT OF THE STUDY: There is one widespread pathway to degrade LAS. Any traces of LAS and larger amounts of SPCs in the effluent from sewage works are exposed to degradative organisms in acclimated and pristine environments. These degradative reactions can now be studied in pure cultures.
The aerobic biodegradability of an extensively used synthetic polymer was monitored the first time on a laboratory-scale fixed-bed bioreactor (FBBR) applying matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). Polymeric poly(vinylpyrrolidone) (PVP) was spiked at concentrations of 10 mg l(-1) onto the FBBR run with river water and the biodegradation monitored after lyophilization of aliquots of the test liquor applying MALDI-TOF-MS. The latter proved to be a powerful tool for qualitative screening purposes of PVP in a molecular mass range <20 kDa in particularly yielding a high sensitivity and shot-to-shot reproducibility. The sample-to-sample reproducibility was enhanced applying the anchor target device. Post-source decay-MALDI-TOF-MS fragmentation investigations determined the unknown end groups of PVP unambiguously. Poor biodegradability of PVP can be assumed, since even after 30 days, no oxidation of the terminal groups and no difference in the repeating units was observed. A decrease in the molecular mass distribution can be drawn back rather to adsorption of PVP in the FBBR other than to biodegradation. This was further investigated performing an adsorption experiment with sewage sludge as solid matrix and analyses of the aqueous phase and sludge samples. Extrapolating these results to the situation in wastewater treatment plants, it is highly likely that PVP is eliminated from the dissolved phase by adsorption onto sludge particles.
Laguna de Bay in the Philippines is one of the largest freshwater lakes in Asia and is considered a primary source of drinking water, but also receives daily discharges of effluent from both domestic and industrial activities. Branched alkylbenzenesulfonates (ABS), which were banned in Europe and withdrawn from the market in the U.S. since the mid-1960s, but not in Southeast Asia, and linear alkylbenzenesulfonates (LAS) are anionic surfactants used in detergent formulations and are therefore main components of effluent discharges. The presence of both LAS and ABS in several water streams in the catchment area of Laguna de Bay was determined using liquid chromatography-mass spectrometry (LC-MS). The concentration levels of LAS (1.2-73 and 2.2-102 microg l(-1)) and ABS (1.1-75 and 1-66 microg l(-1)) in some tributaries of Laguna de Bay and its outlet (Pasig River) to Manila Bay were assessed in December 1999 and March 2000, respectively. The LAS/ABS ratio was calculated as an indication of the extent of the distribution and fate of these surfactants in the surface water. The nearer the location to the metropolitan area of Manila, the higher the levels of LAS and ABS detected in the waters. Moreover, the extent of biodegradation was investigated by monitoring their alkyl homologue distribution and the presence of sulfophenylcarboxylate (SPC) metabolites. Similarly, differences in the levels of SPC and the homologues were apparent at the different sampling points. Presumably, even the quite recalcitrant ABS form SPCs under the conditions present in Southeast Asia. Since wastewater treatment facilities are not well established in developing countries like the Philippines, the call for the use of environmentally friendly chemicals is of even higher significance.
After liquid chromatographic (LC) separation, electrospray ionization mass spectrometry (ESI-MS) was investigated for the determination of the amphoteric surfactant cocamidopropylbetaine (CAPB). In the positive ion mode the molecule formed the adduct ions [M + H](+), [M + Na](+) and [M + K](+). Adducts of these cations were also detected with decreasing abundance as dimer and trimer clusters. Additionally, doubly charged molecular ions with different combinations of cations were identified. It was noticed that the relative abundances of individual cation adducts were not reproducible, apparently owing to varying contents of alkali metal ions originating from the solvent and the sample. Under negative ionization, the major molecular ion was [M - H](-). Higher clusters formed by two and three surfactant molecules, i.e. [2M - H](-) and [3M - H](-) were likewise registered. The tendency to form clusters in both positive and negative ion modes, even at 0.1 mg l(-1) levels, was attributed to strong electrostatic interactions between the zwitterionic head groups. Further evidence for this assumption was provided by the detection of a fragment formed from [2M - H](-) which contained the two charged head groups. Studies were undertaken in the negative ion mode on the concentration- and orifice voltage-dependent monomer, dimer and trimer formation of C(12)-CAPB in order to evaluate potential issues in using the ion [M - H](-) mode for quantitative analysis. Finally, the established (-)-LC/ESI-MS method was applied to follow up the primary degradation of CAPB in a laboratory-scale fixed-bed bioreactor (FBBR) spiked with a test concentration of 10 mg l(-1). Direct analysis without sample pretreatment revealed that higher alkyl homologues were more prone to adsorption. Primary biodegradation of all alkyl homologues was completed after a period of 4 days. Selected lyophilized FBBR samples were examined for the presence of transient or stable degradation intermediates, but no metabolite could be identified.
Seven laboratories participated in an inter-laboratory comparison exercise within the framework of the PRISTINE, SANDRINE and INEXsPORT European Union Projects. Solid-phase extraction (SPE) methodologies were used for the extraction of target analytes from wastewaters. The analytical strategies were based on liquid chromatography (LC) coupled to mass spectrometric (MS) or to fluorescent (FL) detection in all cases with the exception of one laboratory using a test-tube enzyme-linked immunosorbent assay kit. Samples were spiked with the surfactants nonylphenolpolyglycol ether, coconut diethanolamide, linear alkylbenzene sulfonate, nonylphenolpolyglycol ether sulfate, alkylpolyglycol ether and secondary alkane sulfonate. After enrichment on previously conditioned SPE cartridges, the SPE cartridges were distributed among the participating laboratories without the information about the amount of spiked surfactants. In addition, SPE cartridges loaded with a real-world environmental sample containing a tannery wastewater were also analyzed. The results of the programme showed that SPE followed by LC-MS techniques are reliable for the surfactants determination at submicrogram to microgram per liter levels in wastewaters. Inter-laboratory precision values were calculated as the reproducibility relative standard deviation (RSD(R)) which was determined from the reproducibility standard deviation (sR) and the average concentration at a particular concentration level. When data from all laboratories were pooled, the RSD(R) values ranged from 5.1 to 28.3% for the determination of target analytes. The most accurate result corresponded to that given for linear alkylbenzene sulfonates. Taking into account that different methodologies were used (including non-chromatographic techniques) and the complexity of the samples analyzed, it can be considered that acceptable reproducibility values were obtained in this inter-laboratory study.
Linear alkylbenzenesulfonates (LASs) were determined in wastewaters and coastal waters by solid-phase extraction, using two different sample preparation protocols depending on the sample treated, followed by capillary electrophoresis and ultraviolet detection (CE-UV). The linear range of the proposed method varied from 3 to 53 and from 25 to 495 microg/l, depending on the compound, with a limit of detection of 1 microg/l when 250 ml of coastal water was preconcentrated. [M-H]- ions were used for CE-MS confirmation after quantification by CE-UV. CE-MS diagnostic ions were the same ones used in LC-electrospray (ESI) MS and corresponded to m/z 297, 311, 325 and 339 for C10, C11, C12 and C13 LASs, respectively. LASs were determined in wastewater samples of the influent and effluent of three wastewater treatment plants (WWTPs), two of them using biological treatment with secondary settlement and receiving mainly domestic wastewaters whereas one of the plants was operated with physicochemical treatment and received mainly industrial wastewaters. LASs were also analyzed in two samples from coastal waters of the bay of Cadiz (Spain) receiving untreated domestic effluents. All samples were also analyzed by LC-ESI-MS and the results are compared with the CE-UV method developed in this work. The concentration levels of total LASs varied from 988 to 1309 microg/l in the influents of WWTPs, whereas in the effluents the concentrations varied from 136 to 197 microg/l. The levels of LASs in coastal wastewaters of the bay of Cadiz varied from 739 to 911 microg/l, indicating that the wastewaters discharged into the bay did not undergo any treatment at all.
Alkyl glucamides (AGs) were analyzed by reversed-phase liquid chromatography (LC) coupled to mass spectrometry with electrospray ionization (ESMS). Analytes were separated according to the chain length of two homologs, C12- and C14-glucamide. Mass spectrometric detection in the positive ion mode exhibited higher overall sensitivity where, apart from fragments, different molecular and quasi-molecular ions were obtained. However, application of the negative ion mode offered advantages in terms of reproducibility and extent of information when analyzing environmental samples. Therefore, a simple and sensitive analytical methodology was developed for the determination of AGs in municipal sewage treatment plant influent and effluent based on solid-phase enrichment, LC separation and negative ion ESMS quantification. After preconcentration of 100 ml of aqueous sample, the recoveries using polymeric LiChrolut EN cartridges exceeded 89%. A quantification limit of 0.1 microg l(-1) was achieved. Studies on the biodegradability and metabolic pathway of C10-glucamide were carried out on a laboratory-scale microbial test unit under aerobic conditions. A postulated metabolism including omega-oxidation of the alkyl chain followed by subsequent beta-oxidations was checked by LC/ESMS. Identification and formation of 'C4-glucamide acid' as a degradation intermediate was confirmed by mass spectrometric studies. Higher homolog acids such as C10-, C8- and C6-glucamide acids, which should be predicted precursors of C4-glucamide acid, and any other metabolites, were not detectable, presumably owing to rapid breakdown.
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Alkyl polyglucosides (APGs) were analyzed by reversed-phase liquid chromatography coupled to mass spectrometry with electrospray ionization. Analytes were separated according to the chain length of the alkyl homologues, whereas the separation of isomeric forms of the glucose moiety was achieved partially. Depending on the structure of the glucose ring the alkyl monoglucosides show a distinct affinity in terms of the formation of sodium and ammonium adduct ions. Metabolism of isomer pure alkyl monoglucosides was studied on a testfilter device to gather information about the degradation behavior and to obtain eventually poorly degradable metabolites. In spite of unsuccessful detection of any metabolites such as "polyglucoside alcanoic acids", a degradation pathway was proposed including the cleavage of the glucosidic bond as initial step. In addition, a method for the determination of APGs in municipal waste water effluent was developed using solid-phase extraction on reversed-phase material. Recovery rates were in the range of 66 to 98% for three spiked alkyl monoglucosides and a quantitation limit of 0.2 microg l(-1) was achieved.
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UNLABELLED: Wegener's granulomatosis is a distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tract and glomerulonephritis. This disease can present as a clinical picture which resembles sepsis and adult respiratory distress syndrome (ARDS). Wegener's disease requires immunosuppression which can have detrimental consequences when used in sepsis. The following case report illustrates the diagnostic difficulties encountered by intensive care physicians treating severe pulmonary failure and multiple organ dysfunction in Wegener's granulomatosis appearing as ARDS with sepsis. CASE REPORT: A 19-year-old female patient had developed acute respiratory and renal failure after a prolonged period (many months) of antibiotic resistant otitis, sinusitis and mastoiditis. The patient had required intubation at another hospital and there was a history of tension pneumothorax and cardiopulmonary resuscitation during mechanical ventilation. Emergency extracorporeal membrane oxygenation (ECMO) for acute hypercapnic and hypoxic respiratory failure was instituted and the patient was transported to our institution while on ECMO. The patient was treated empirically for suspected pulmonary and systemic infection and received hydrocortisone (0.18 mg/kg/h) as part of a protocol-driven treatment of septic shock in addition to antibiotic and antimycotic regime. The use of ECMO was required for 10 and mechanical ventilation for another 50 days after admission. After successful extubation, central nervous system dysfunction became evident with a somnolent and generally unresponsive patient. When the hydrocortisone dose was gradually tapered, the clinical status of the patient further deteriorated, pulmonary gas exchange worsened and she developed renal failure with proteinura and hematuria. A renal biopsy was performed demonstrating vasculitis and focal segmental glomerulonephritis, a systemic granulomatous vasculitis was suspected; the serum was tested for anti-proteinase 3 antibodies (PR3-ANCA) and turned out to be positive (17.5 U/ml; normal range < 7 U/ml). The morphologic findings from renal biopsy, the positive test for antiproteinase 3 antibodies and the pulmonary-renal involvement with evidence of multisystem disease established the diagnosis of Wegener's granulomatosis. Immunosuppressive therapy with cyclophosphamide and prednisolone was instituted resulting in rapid improvement with recovery of pulmonary, renal and central nervous system function within two weeks. The use of ECMO in this patient served as a life-saving immediate measure usefull to "buy time" until a definite diagnosis could be established. ARDS represents an uniform pulmonary reaction to a large number of different noxious stimuli and disease entities. This case demonstrates that intensive care physicians caring for critically ill patients with ARDS should include even rare causes of pulmonary injury into their differential diagnosis.
UNLABELLED: To classify interatrial septal anomalies in adults, 24,458 Doppler-echocardiographic studies performed between 1. 1. 1987 and 31. 12. 1992 were reviewed. Patients below 16 years of age or with complex congenital heart disease, or after surgical closure of an atrial septal defect, were excluded. Additionally, all 823 transesophageal echocardiographies done between 1. 1. 1993 and 31. 12. 1994 were analyzed to see whether a patent foramen ovale was present. Among 294 patients with interatrial septal anomalies (prevalence 1.2%; male:female = 1:1.4), 298 congenital anomalies of the interatrial septum were detected. 63% of interatrial septal anomalies constituted newly detected anomalies. Age ranged from 16 to 84 (median 43) years. In 21% of the patients the left-to-right shunt was > or = 50% (QP/QS > or = 2). In 25% pulmonary hypertension was present and 25% of the patients underwent surgery. A patent foramen ovale was present in 0.16% of all transthoracal and in 5.7% of all transesophageal echocardiographies. Secundum defects constituted 46%, atrial septal aneurysms 24%, patent foramen ovale 13%, atrioventricular canals 11%, and superior sinus venosus defects with anomalous pulmonary venous return 6% of all diagnoses. Associated anomalies were mitral valve prolapse in 14%, pulmonary valve stenosis in 3%, left-sided persistent vena cava superior and Chiari network in 2% each, anomalous pulmonary venous return, ventricular septal defect, bicuspid aortic valve, and Ebstein's anomaly in 1% each. 4% of the patients showed further cardiac lesions. CONCLUSIONS: Anomalies of the interatrial septum in adults were frequent and often newly detected. In a high percentage of patients with interatrial septum the left-to-right shunt was hemodynamically relevant.
Effects of alpha-melanocyte-stimulating hormone (alpha-MSH), beta-melanocyte-stimulating hormone (beta-MSH), beta-lipotropin (beta-LPH), and beta-endorphin (beta-EPH) at concentrations from 10(-9) M up to 10(-6) M on human adipose tissue lipoprotein lipase (LPL) were studied in a cell-free system. alpha-MSH and beta-MSH did not exert any effect on LPL; no degradation of these peptides in the incubation medium could be detected by HPLC analysis. beta-LPH and beta-EPH failed to alter enzyme activity. However, HPLC analysis revealed an unspecific rapid degradation of the peptides due to the activity of tissue proteases. Therefore, the protease inhibitors amastatin, antipain, APMSF, and TPCK were tested at concentrations of 10(-5), 10(-4), and 10(-3) M for their efficacy to inhibit degradation. None of the inhibitors was able to substantially reduce proteolysis of beta-LPH, as was the case with amastatin, APMSF, and TPCK for beta-EPH. However, antipain at 10(-4) M preserved at least 20% of the initial peptide concentration from proteolysis up to 150 min. Antipain caused a decrease in lipoprotein lipase activity (LPLA), which was dependent on concentration. The adverse effect of antipain at concentrations of 10(-4) M on LPL was completely abolished by beta-EPH at a concentration of 10(-6) M.
OBJECTIVES AND BACKGROUND: Severe primary tricuspid regurgitation in the adult is a rare finding. This study describes the diagnostic findings and the treatment of an isolated congenital cleft of the anterior leaflet of the tricuspid valve as the morphologic substrate for severe tricuspid regurgitation. METHODS: The clinical, echocardiographic findings and the follow-up findings of five patients (all male, 20 to 56 years old) with this disorder are described. Four of the five patients underwent cardiac surgery that confirmed the diagnosis. RESULTS: In three of five patients, exertional fatigue was the limiting symptom (New York Heart Association functional classes II and III). The clinical findings included a holosystolic murmur and supraventricular arrhythmias in all patients. Cardiac catheterization, performed in four patients, yielded the incorrect diagnosis of Ebstein's anomaly in three. In one patient the cleft was associated with an atrial septal defect of the secundum type. In four of five patients successful reconstruction of the tricuspid valve with a DeVega annuloplasty was performed. One patient had a partial excision of the right atrium, and one had a closure of a coexisting atrial septal defect. One patient refused operation. CONCLUSIONS: Tricuspid valve anomalies can be accurately identified by Doppler echocardiography. Surgical repair is the treatment of choice in patients with severe tricuspid regurgitation due to a congenital cleft of the anterior leaflet of the tricuspid valve.
In 12,576 consecutive Doppler-echocardiographic studies (DE) performed on 11,450 patients over 3 years (1987-1989), 183 newly diagnosed congenital heart abnormalities were detected in 161 patients. The age of the 161 patients (86 female, 75 male) ranged from 16 to 84 years (median 34.5). The highest incidences of pathologies were those of ASD II (29%) and VSD (11%). With decreasing frequency the following abnormalities were diagnosed: pulmonary valve disease (8%), interatrial septal aneurysms (7%), membranous subvalvular aortic stenosis (5%), anomalous pulmonary venous connections (4%), atrioventricular canal defects (4%), persistent left superior venae cavae (4%), patent ductus arteriosus (4%), aneurysms of the membranous septum (4%), and sinus venosus defects (3%). Less common findings were coarctation of the aorta (2.5%), persistent sinusoids (2.5%), arteriovenous fistulas (2.5%), congenital LV-aneurysms (2.5%), Ebstein's anomalies (1%), anomalies of the papillary muscles (1%) and RV-dysplasias (1%). Rare findings were a cor triatriatum, a tetralogy of Fallot, a partial defect of the pericardium, a pulmonic atresia with VSD, an isolated cleft of the tricuspid valve, and finally a connection of a hepatic vein to the right atrium. In conclusion, we found an incidence of 1.4% in newly diagnosed congenital heart disease in adolescents and adults undergoing DE. 32 of 159 patients (20%) were referred to surgery, while endocarditis prophylaxis was indicated in 45%.