PubMed HealthSearch

Biomedical subjects

W Samtleben

Publications and source records attributed to W Samtleben.

At least 19 recordsLinked to original sources

[Progressive multifocal leukoencephalopathy as a result of immunosuppressive therapy].

HISTORY AND ADMISSION FINDINGS: A 62-year-old woman developed paresis in her right arm within several weeks. She was being treated with methylprednisolone (4 mg daily) and chlorambucil (2 mg every other day) for systemic lupus erythematodes (SLE), which was now in remission. Neurological examination on admission revealed a right flaccid hemiparesis, predominantly of the right arm. The physical examination was otherwise unremarkable. INVESTIGATIONS: Magnetic resonance imaging (MRI) (T2 weighted) showed hyperintense changes in the subcortical medullary layer of the left precentral gyrus without perifocal oedema or abnormal contrast medium uptake, which argued against progressive cerebral ischaemia or tumour. Blood and cerebrospinal fluid (CSF) showed no abnormalities except leukopenia and a raised antinuclear antibody titre. Progressive paralysis of the right side of the body after 2 years of immunosuppressive treatment, the MRI findings and an essentially normal CSE suggested progressive multifocal leucoencephalopathy (PML), confirmed by polymerase chain reaction (PCR) demonstrating JC-virus DNA in serum and CSF. TREATMENT AND COURSE: As a result of the CNS infection with papovavirus JC, an opportunistic infection of the central nervous system, which is usually fatal, occurred. The cerebral changes spread within a few weeks, despite of the immunosuppressive drugs having been discontinued. The pareses progressed further and a marked personality disorder of organic origin ensued. CONCLUSION: While efficacious immunosuppressive drugs against autoimmune disease are available, their use risks the occurrence of life-threatening opportunistic infections.

Brain

Therapeutic plasma exchange in patients with chylomicronemia syndrome complicated by acute pancreatitis.

Chylomicronemia syndrome (CMS) is a rare disorder characterized by the presence of chylomicrons in the fasting state causing a milky appearance of plasma, eruptive xanthomas, and hepatosplenomegaly; an acute and potentially life threatening complication is severe acute pancreatitis. The underlying defects are inborn errors of metabolism such as deficiencies of lipoprotein lipase (LPL) or apoprotein C-II (apo C-II) as well as familial hypertriglyceridemia. Moreover, CMS can be precipitated when mild hypertriglyceridemia is exacerbated by additional factors such diabetes mellitus, ethanol abuse, or pregnancy. The purpose of the present study was to retrospectively analyze the results of therapeutic plasma exchange (TPE) in 5 patients transferred to our hospital for severe acute pancreatitis due to chylomicronemia syndrome. In a total of 7 TPE sessions, on average 3,286 +/- 247 ml of plasma (i.e., about 1 patient plasma volume) were treated per session. Triglyceride (TG) levels were decreased from 4,972 +/- 2,469 mg/dl on admission to 1,614 +/- 1,276 mg/dl (-70%) after the TPE sessions, and a further decrease was achieved by conservative treatment. Part of the TG reducing effect of the treatment was probably due to heparin induced lipolysis. Acute pancreatitis was resolved in all cases, and 1 pregnant patient delivered without problems at term. In summary, 1 or 2 TPE sessions sufficed to substantially decrease the bulk of triglycerides in acutely exacerbated chylomicronemia syndrome causing a rapid resolution of acute severe pancreatitis.

Acute Disease

Low density lipoprotein hemoperfusion by direct adsorption of lipoproteins from whole blood (DALI apheresis): clinical experience from a single center.

The elimination of low density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) by conventional LDL apheresis techniques can only be achieved in a cell-free medium and thus requires the initial separation of plasma from the blood cells. The present paper describes the first LDL hemoperfusion system which is able to adsorb LDL and Lp(a) directly from whole blood. This simplifies the procedure substantially. The adsorber consists of polyacrylate ligands linked to a modified polyacrylamide matrix. These negatively charged polyacrylate ligands interact with the positively charged apoprotein B moiety of LDL and Lp(a), which results in selective adsorption of these lipoproteins onto the column. Three hypercholesterolemic patients suffering from overt atherosclerotic complications were treated weekly by direct adsorption of lipoproteins (DALI) (n = 20 sessions each). All patients were on the highest tolerated dose of cholesterol synthesis enzyme (CSE) inhibitors. About 1.3 patient blood volumes were treated per session. The anticoagulation was performed with acid citrate dextrose (ACD-A). The following acute reductions were achieved: LDL: 66%; Lp(a): 63%; and triglycerides: 29%. High density lipoprotein (HDL) (-13%) and fibrinogen (-16%) were not substantially reduced. The sessions were essentially uneventful. Due to a low ACD-A infusion rate, no hypocalcemic episodes were registered. One patient on enalapril was treated without complications when this angiotensin converting enzyme (ACE) inhibitor was withdrawn 2 days prior to apheresis. In summary, in our hands, DALI apheresis proved to be a simple, safe, and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid lowering therapy.

Adsorption

Therapeutic plasma exchange in patients suffering from thrombotic microangiopathy after allogeneic bone marrow transplantation.

Thrombotic microangiopathy (TM) is a potentially fatal complication of allogeneic bone marrow transplantation (BMT). The underlying pathophysiology is thought to be generalized endothelial cell damage caused by several factors including conditioning treatment, cyclosporin A (CsA), or graft versus host disease (GVHD). In the present retrospective study, 6 patients suffering from Grade 2 BMT-TM at a mean of 62 days post BMT were treated by 3-15 daily sessions of therapeutic plasma exchange (TPE). In most sessions, cryosupernatant (CSN) of plasma, in some fresh frozen plasma (FFP) was used as the substitution fluid. All patients suffered from acute graft versus host disease (aGVHD) of the skin, which was treated by CsA. CsA was withdrawn in all patients. TPE caused a response in 4 of 6 patients evidenced by a decrease to Grade 0 (n = 3) or 1 (n = 1) BMT-TM. Only 1 patient had mild renal insufficiency which did not improve during TPE. While all patients were dependent on platelet transfusions at baseline, the platelet counts improved in 2 of 6 patients after the TPE course. One patient did not show any response to TPE with FFP, and his disease improved only after CSN was introduced as substitution fluid (Grade 0). Four patients were still alive 175-495 days post BMT, and 2 patients died about 2-3 weeks after the end of the TPE course, 1 from cachexia and 1 from systemic aspergillosis. In summary, in this pilot study, TPE positively influenced BMT-TM, especially if CSN was used as the substitution fluid.

Adult

Early loss of renal transplants in patients with thrombophilia.

BACKGROUND: We considered the possibility that thrombophilia may propagate graft thrombosis and therefore we evaluated the protein C system, which is a natural anticoagulant. Potential alterations in this system include protein C or protein S deficiency, inhibition through a lupus anticoagulant (LA), or a resistance to activated protein C due to the factor V Leiden (FVL) mutation. METHODS: One hundred thirty-two consecutive renal transplant patients, not known to have abnormal thrombostasis, in whom 1-year graft survival could be assessed, underwent laboratory testing for protein C or S activity, LA, and FVL. Transplant survival and demographic data were extracted from the hospital record. RESULTS: We identified 18 patients with thrombophilia (FVL, 10; LA, 6; protein S, 2) who had received a total of 28 renal transplants. Of these 28 transplant recipients, 11 transplants were lost within the first year, compared with 21 of 155 transplants to 114 patients without thrombophilia (P=0.0003). Median graft survival for patients with thrombophilia was 30 months (range: 0 to 166), compared with 86 months (range: 0 to 212) for patients without thrombophilia (P<0.01). The presence of thrombophilia represented a 3.5-fold (95% confidence interval, 2.3-5.3-fold) risk for 1-year graft loss. CONCLUSION: In this retrospective study, patients with thrombophilia had a significantly higher risk of early transplant failure. These data point toward a potential contribution of thrombophilia to transplant loss, a hypothesis that needs further study.

Adult

[Chronic HIV- and chronic HBV infection with hematuria and proteinuria].

HISTORY AND CLINICAL FINDINGS: A medical examination, undertaken in an apparently healthy 30-year-old man because of his occupational exposure to chemicals, revealed haematuria and proteinuria. Physical examination was unremarkable except for oral hair-leukoplakia and swelling of the cervical, supraclavicular, axillary and inguinal lymph nodes. INVESTIGATIONS: Examination of the urine demonstrated selective glomerular proteins (1.5 g/24 h) and dysmorphic erythrocytes. SGOT and SGPT activities were raised (73 and 129 IU/l, respectively). Active hepatitis B virus (HBV) and human immunodeficiency virus (HIV-1) infections were demonstrated virologically. The CD4+ count in blood was reduced to 200 cells/microliter. Renal biopsy showed an IgA nephropathy. TREATMENT AND COURSE: Antiretroviral treatment with zidovudine and lamivudine were started. SGOT and SGPT activities and HIV load fell steadily, while CD4+ cell count rose markedly. Renal functions have remained stable during the past 6 months. CONCLUSION: Signs of glomerular damage are not unusual in systemic diseases, tumors or infections (Hepatitis B and HIV in this case) and they may be the first manifestations of the underlying disease.

Acquired Immunodeficiency Syndrome

Down-regulation of surface monocyte lipopolysaccharide-receptor CD14 in patients on cardiopulmonary bypass undergoing aorta-coronary bypass operation.

OBJECTIVES: Major operative trauma like aorta-coronary bypass operation may lead to postoperative immunodisturbance, putting the patient at an increased risk for infection and sepsis. The monocyte/macrophage system and the endotoxin receptor CD14 are important in the early recognition and elimination of invading bacteria. The aim of this study was to analyze changes in membrane-associated CD14 and soluble CD14 during and after cardiac involving cardiopulmonary bypass. METHODS: We studied numbers of leukocytes, monocytes, and monocyte subpopulations, expression of monocyte membrane-associated CD14 and plasma levels of soluble CD14 in 10 patients (63 +/- 8 years of age), who underwent elective cardiopulmonary bypass. RESULTS: Cardiopulmonary bypass induced marked postoperative monocytosis, which was maximal 20 hours after the operation (485 +/- 242 cells/microl before, 1080 +/- 264 cells/microl 20 hours after surgery). Expression of membrane-associated CD14 on classical CD14++ monocytes decreased significantly by 40%, reaching a nadir 20 hours after surgery (p < 0.05). At the time of maximal membrane-associated CD14 suppression, the levels of soluble CD14 measured by enzyme-linked immunosorbent assay were clearly increased (3.2 +/- 1.0 microg/ml before versus 5.6 +/- 1.0 microg/ml 20 hours after, p < 0.001). No significant change of the percentage of small (alpha) and large (beta) forms of soluble CD14 was found. CONCLUSIONS: Cardiopulmonary bypass leads to reduced membrane-associated CD14 expression on peripheral blood monocytes and increased levels of soluble CD14 through shedding or secretion of membrane-associated CD14 from the cell surface. These findings indicate that bypass is associated with significant monocyte activation.

Blotting, Western

HELP apheresis in the treatment of sepsis.

Heparin induced extracorporeal lipoprotein fibrinogen precipitation (HELP) is an established procedure for removal of low-density lipoprotein (LDL) cholesterol, lipoprotein (a), and fibrinogen in patients with severe hypercholesterolemia. In vitro studies revealed that HELP also removes endotoxin, tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP). With the intention to treat, we applied this procedure to 4 patients with severe gram-negative sepsis with highly elevated endotoxin blood levels. Nine treatments were performed, 6 using the standard HELP precipitating buffer and 3 without addition of heparin to the precipitating buffer. Heparin was omitted from the precipitating buffer to avoid fibrinogen depletion in patients at risk (low fibrinogen, postoperative). The average processed plasma volume was 3,386 ml in the standard and 2,963 ml in the modified treatment. Mean reductions (%) in plasma solute concentrations were (standard/ modified procedure) as follows: endotoxin, 50/57; TNF-alpha, 25/5; CRP, 49/55; fibrinogen, 49/6; total cholesterol, 38/5; and apolipoprotein B (Apo B), 41/2. Both treatment modalities were equally effective in removing endotoxin and CRP. With the modified precipitation buffer, fibrinogen was not removed. To further simplify the extracorporeal treatment, we have designed a closed-loop circuit with 2 adsorbers in series, one for removal of TNF-alpha (dextran sulfate modified cellulose) and the other for removal of endotoxin (DEAE-cellulose). In vitro evaluation confirmed very efficient endotoxin and TNF-alpha removal from plasma. This system is very simple, operates at physiological pH, and uses adsorbers already in clinical use for other purposes.

Apolipoproteins B

Clinical and biochemical findings in uremic patients with and without restless legs syndrome.

The restless legs syndrome (RLS) is one of the most common and unpleasant complaints of uremic patients. The pathophysiology of the RLS is still unclear. Various factors, including anemia and iron deficiency, are proposed to play a major role. We determined the prevalence of RLS in all stable hemodialysis patients under long-term treatment in two dialysis centers (n = 136) and compared the clinical and biochemical findings of patients with RLS and without RLS. Twenty-three percent of all patients investigated fulfilled the diagnostic criteria of RLS according to the International Restless Legs Syndrome Study Group. There were no statistical differences between the two groups regarding age, duration of uremia and need for dialysis, time on dialysis per week, hemoglobin, hematocrit, erythrocytes, s-ferritin, s-transferrin, s-iron, calcium, and standard biochemical indices, except for intact parathyroid hormone (iPTH) levels. Uremic patients with RLS showed significantly lower iPTH (P < 0.01) concentrations. In addition, the RLS group received a significantly higher number and dosage of psychopharmacological drugs, (ie, L-DOPA), than patients without RLS. These biochemical findings suggest that neither the severity of anemia nor that of iron deficiency has to be considered a major pathophysiological factor in established RLS. The significantly lower iPTH secretion in uremic patients with RLS, however, is a new finding, and further investigations will be necessary to determine whether this result is of any clinical significance to this group of patients. The significantly higher number of psychopharmacological drugs prescribed to uremic patients with RLS may be related to the symptoms of RLS.

Adult

[ARDS and Wegener granulomatosis].

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.

Acute Kidney Injury

LDL hemoperfusion--a new procedure for LDL apheresis: biocompatibility results from a first pilot study in hypercholesterolemic atherosclerosis patients.

Current lipid apheresis techniques can remove atherogenic lipoproteins only from plasma. The initial mandatory separation of plasma and blood cells renders the extracorporeal circuit complex. We recently described the first clinical application of a new lipid adsorber that adsorbs low-density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) directly from whole blood. In continuation of our work, this paper describes the clinical biocompatibility of this new LDL hemoperfusion system. In a 2 center phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation protocol consisted of an initial heparin bolus followed by an acid citrate dextrose-A (ACD-A) infusion during the treatment. One patient blood volume was treated per session. All sessions were clinically uneventful. No signs of hemolysis or extracorporeal clot formation could be detected, and cell counts remained virtually constant. In a subgroup of patients (n = 4-6), further biocompatibility parameters were studied. Activation of leukocytes (elastase release), thrombocytes (beta-thromboglobulin [beta-TG] extrusion), and monocytes (interleukin (IL)-1beta and IL-6) were minimal. Complement activation (C3a and C5a generation) was negligible. The chosen anticoagulation protocol was both safe (constant ionized calcium levels) and effective (low thrombin-antithrombin formation). In summary, within the scope of a first pilot study, this new LDL hemoperfusion procedure combined the features of excellent clinical tolerance, good biocompatibility, and ease of handling. Phase III clinical trials will have to show whether these encouraging preliminary results can be corroborated in a larger patient population.

Acrylic Resins

Plasma therapy at Klinikum Grosshadern: a 15-year retrospective.

Immediately after the availability of highly permeable membranes in 1979, membrane plasma separation was introduced as a mode of extracorporeal blood purification by the nephrology group at Klinikum Grosshadern of the Ludwig Maximilians University of Munich (F.R.G.). The new therapy was applied primarily in the management of immunologically mediated renal and extrarenal disorders as well as in paraproteinemias. We also have witnessed a widespread application of this extracorporeal treatment as a last resort in otherwise refractory clinical conditions. Over the years, the group at Grosshadern has contributed to the development, as well as to the laboratory and clinical testing, of new plasma separation membranes, simplified plasmapheresis formats (e.g., spontaneous membrane plasma separation), and several plasma fractionation procedures (e.g., cascade filtration, adsorption). Whenever indicated and possible, plasma fractionation procedures, rather than unselective plasma exchange, are performed in an appropriate clinical situation.

Chemical Fractionation