[Principles and concepts of immunosuppressive therapy of glomerulonephritis].
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Glomerulonephritis↗
Biomedical subjects
F Keller
Publications and source records attributed to F Keller.
Modulation of an NCAM-related adhesion molecule with long-term synaptic plasticity in Aplysia.
A form of learning in the marine mollusk Aplysia, long-term sensitization of the gill- and siphon-withdrawal reflex, results in the formation of new synaptic connections between the presynaptic siphon sensory neurons and their target cells. These structural changes can be mimicked, when the cells are maintained in culture, by application of serotonin, an endogenous facilitating neurotransmitter in Aplysia. A group of cell surface proteins, designated Aplysia cell adhesion molecules (apCAM's) was down-regulated in the sensory neurons in response to serotonin. The deduced amino acid sequence obtained from complementary DNA clones indicated that the apCAM's are a family of proteins that seem to arise from a single gene. The apCAM's are members of the immunoglobulin class of cell adhesion molecules and resemble two neural cell adhesion molecules, NCAM and fasciclin II. In addition to regulating newly synthesized apCAM, serotonin also altered the amount of preexisting apCAM on the cell surface of the presynaptic sensory neurons. By contrast, the apCAM on the surface of the postsynaptic motor neuron was not modulated by serotonin. This rapid, transmitter-mediated down-regulation of a cell adhesion molecule in the sensory neurons may be one of the early molecular changes in long-term synaptic facilitation.
Amino Acid Sequence↗
Serotonin-mediated endocytosis of apCAM: an early step of learning-related synaptic growth in Aplysia.
The long-term facilitation of synaptic efficacy that is induced by serotonin in dissociated cell cultures of sensory and motor neurons of Aplysia is accompanied by the growth of new synaptic connections. This growth is associated with a down-regulation in the sensory neuron of Aplysia cell adhesion molecules (apCAMs). To examine the mechanisms of this down-regulation, thin-section electron microscopy was combined with immunolabeling by gold-conjugated monoclonal antibodies specific to apCAM. Within 1 hour, serotonin led to a 50% decrease in the density of gold-labeled complexes at the surface membrane of the sensory neuron. This down-regulation was achieved by a heterologous, protein synthesis-dependent activation of the endosomal pathway, which leads to internalization and apparent degradation of apCAM. The internalization is particularly prominent at sites where the processes of the sensory neurons contact one another and may act there to destabilize process-to-process contacts that normally inhibit growth. In turn, the endocytic activation may lead to a redistribution of membrane components to sites where new synapses form.
Animals↗
Significance and quantitative analysis of von Willebrand factor in human platelets.
The von Willebrand factor (vWF) is found in plasma and in platelets. The concentration and multimeric composition of the vWF in platelets of 160 patients with bleeding tendency were examined since very little is known about the platelet vWF. For quantitative analysis of the platelet vWF, a modified ELISA was established. A reference range from 70%-130% of platelet vWF concentration considered normal was established by examining 80 healthy blood donors. 16.9% of the 160 patients showed a decreased vWF concentration in platelets only, while all the other coagulation parameters were normal. 3 of our patients belong to the same family and suggesting an autosomal dominant genetic transmission for the von Willebrand disease type 1-3. The data also suggests, that a quantitative and qualitative analysis of the vWF in plasma and platelets is required for an exact diagnosis of the von Willebrand disease.
Blood Donors↗
Effects of long-term treatment with lovastatin on the clotting system and blood platelets.
In a study of 20 patients with hypercholesterolemia (type IIa) the effects of lovastatin (20-80 mg/day) on various clotting and thrombosis parameters were monitored for 12 months. On 11 occasions various cholesterol fractions and clotting parameters were determined in each patient. In addition, the clotting inhibitors AT III, protein C, protein S, and C1-esterase inhibitor and the fibrinolysis parameters plasminogen and alpha 2-antiplasmin were examined. Platelet function was monitored on the basis of spontaneous and induced (collagen, ADP, epinephrine, ristocetin) aggregation. Lovastatin in the above dosage brought about a 66 mg/dl (from 320 +/- 12.6 to 254 +/- 12.0 mg/dl) reduction in the total cholesterol level and a 56 mg/dl (from 244 +/- 11.4 to 188 +/- 12.1 mg/dl) reduction in LDL cholesterol at the end of the study. Fibrinogen showed a significance decrease during the study period, whereas PT and aPTT remained unaffected. The initial slopes of the ADP-induced platelet aggregation revealed a significant decrease. C-reactive protein and platelet count remained within the normal range, indicating no significant change. Thrombin clotting time, AT III, C1-esterase inhibitor, plasminogen, and alpha 2-antiplasmin were not modified. Protein C and S behaved in a contradictory way, but remained within the normal range. Long-term treatment with lovastatin was associated with a significant reduction of fibrinogen levels and platelet aggregation induced by ADP in type-IIa hypercholesterolemic patients. These alterations, as well as their role in cardiovascular disease, should be the subject of further investigations.
Adolescent↗
[Personality, motivation and affect as modulating factors in suicidal behavior of depressed women].
From a psychological point of view, we would expect that motivational rather than biological dysfunctions mediate initiation of violent and non-violent suicidal actions. To prove this assumption we classified depressed women in four groups according to their suicidal behaviour and matched them to age: suicide ideators, violent suicide attempters, non-violent suicide attempters, non-suicidal depressed controls. We then tested group differences in respect of aggression, impulsivity, introversion, affective lability, anxiety, depression and electrodermal activity (EDA). To take a closer look at motivational dysfunctions, we implemented the Action Control Scale (corresponding to Kuhls theory of action and state orientation), since we regard chronic state orientation as a risk factor for suicidal behaviour. Results show few differences in violent attempters compared with controls. In contrast to non-violent attempters, they show a greater tendency to achievement and action oriented behaviour being less introverted. Non-violent attempters, however, show most significant differences to their controls: Corresponding to a high state orientation, they are more depressed, anxious, less stable in respect of affectiveness, and more introverted, with low scores in aggression and contentedness in life. In contrast to some other studies, nonreactivity in the electrodermal system dominates in all groups. Results demonstrate that motivational dysfunctions like state orientation allow better prediction and understanding of violent or non-violent suicidal behaviour in depressed women than does electrodermal reactivity.
Adult↗
Acute endocrine failure after brain death?
After brain death, 32 potential organ donors were studied to determine serum and plasma concentrations of hypothalamic-pituitary hormones, thyroid hormones, and cortisol over a period of up to 80 hr. Diagnosis of brain death was established either on the basis of clinical criteria (n = 16) or by angiography (n = 16). While 78% of the organ donors developed diabetes insipidus, none of the circulating hormones of the anterior pituitary gland showed a progressive decline in concentration according to their plasma half-lives. With the exception of arginine vasopressin (AVP), no hormone concentration was found to be subnormal due to the onset of brain death. The subnormal free triiodothyronine (FT3) values in 62% of cases (median FT3 of 2.2 pmol/L within the first 24 hr) and the cortisol concentration of 6.9 micrograms/dl correlate with the frequency of similar findings in patients with severe head injuries. While the adrenocorticotropic hormone (ACTH) concentrations of 10-53 pg/ml remained constant during the study period, thyroid-stimulating hormone (TSH) and human growth hormone (hGH) concentrations showed a 12- and 35-fold increase from baseline values after 30-40 hr. These results suggest that, despite the now generally accepted criteria of brain death, there is still some residual function, and thus also perfusion of the hypothalamic-pituitary neuroendocrine system. This residual function appears to be sufficient to maintain hormonal plasma levels at least in the low reference range in most donors. Hormonal depletion in organ donors subsequent to brain death, as suggested repeatedly in the literature, could not be confirmed. The analysis of serum or plasma concentration patterns of a number of hormonal parameters following brain death does not support the rationale for a routine replacement therapy of total triiodothyronine (TT3) or cortisol to maintain endocrine homeostasis prior to organ harvest. However, dexamethasone therapy may be followed by suppression of the adrenal cortex of the organ donor. In these cases, cortisol substitution may be indicated.
Adrenocorticotropic Hormone↗
Raised concentrations of the carboxy terminal propeptide of type IV (basement membrane) procollagen (NC1) in serum and urine of patients with glomerulonephritis.
Type IV collagen is a major component of the glomerular and tubular basement membrane. We used a specific radioimmunoassay to determine (mean +/- SD) the concentration of carboxy terminal non-collagenous fragment (NC1) of type IV procollagen in the serum (normal 6.0 +/- 1.2 ng ml-1) and urine (normal 1.5 +/- 2.0 ng ml-1) of 142 patients with various kidney diseases. The 15 patients with active glomerulonephritis displayed (ANOVA, Scheffé test) significantly elevated NCl values in their serum (14 +/- 8.2 ng ml-1) as compared with the 32 patients with chronic interstitial nephritis (7.8 +/- 3.0 ng ml-1), the 17 patients with various other chronic kidney diseases (8.1 +/- 2.4 ng ml-1) and the 23 ambulatory kidney transplant patients (9.1 +/- 1.7 ng ml-1). The highest serum NCl concentrations were found in nine patients with membranoproliferative glomerulonephritis (16 +/- 9.4 ng ml-1). Sequential serum NCl concentrations in the one patient with active Goodpasture's syndrome were marginally elevated (less than 11 ng ml-1). Serum NCl did not increase with acute interstitial rejection episodes in six kidney transplant patients. The highest urinary NCl concentrations were found in seven patients with minimal change glomerulonephritis (7.5 +/- 3.2 ng ml-1). No correlation was found between serum NCl and serum creatinine, NCl and creatinine clearance, or renal NCl clearance and creatinine clearance. There was a significant correlation between serum NCl and proteinuria. Serum and urinary NCl concentrations were elevated independently from renal function, thus indicating intrinsic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Interstitial nephritis with reversible renal failure due to a copper-containing intrauterine contraceptive device.
A 41-year-old woman was admitted to the hospital because of renal failure requiring hemodialysis treatment. Renal biopsy revealed active chronic interstitial nephritis. Renal function nearly normalized after removal of a copper-containing intrauterine device (IUCD). We conclude that copper-IUCDs may lead to renal failure in women with copper allergy.
Acute Kidney Injury↗
[Psychosocial factors and follow-up of depressive disease].
In a one-year follow-up study 187 inpatients were studied using structured and semistructured interviews (Diagnostic Interview Schedule, Münchner Ereignisliste, Social Interview Schedule). In order to predict the course of depression we focused on psychosocial factors and their influence on the course of depression. The severity of depression at discharge and negative life events during the follow-up period could be identified as the main influence factors. Results suggest reciprocal influence between illness and social conditions, especially illness and marital relations. Marital dysfunctioning at follow-up was reported significantly more often by patients with unfavourable outcome, whereas patients who recovered did not differ from the control group in their marital conditions. The results suppose the value of social variables in the prediction of the course of illness. A few implications on these findings for therapeutic process are discussed.
Adult↗
[Diagnostic strategies for detection of the von Willebrand syndrome].
The von Willebrand disease (vWD) is the most severe coagulopathy. Because of the complex biochemical structure of the von Willebrand factor (vWF), a great number of types and subtypes of the vWD were found. A screening of vWD can only be done by examining the bleeding time, the ristocetin cofactor activity (risto) and by an immunological determination of the vWF concentration. Examinations of 200 patients with a bleeding tendency showed that the ratio vWF/risto < 0.7 indicates a high probability for an abnormal multimeric structure of vWF. The exact determination of the vWD subtype then has to be done by a SDS-agarose gel electrophoresis. In 16.8% of our patients we found a decreased vWF concentration in the platelets. These patients showed normal plasmatic coagulation factors, but a bleeding tendency and a prolonged bleeding time. For diagnosis of vWD the bleeding time, immunological determination of the vWF and the risto should be done first. If a ratio vWF/risto < 0.7 or a prolonged bleeding time with a bleeding tendency is found, the separation of the vWF multimers into plasma and platelets and the determination of the vWF concentration in platelets should be carried out for an exact diagnosis of vWD.
Blood Coagulation Tests↗
Analgesic nephropathy and renal transplantation.
Analgesic nephropathy was the most frequent diagnosis in 324 haemodialysis patients (30%) and the second most frequent diagnosis in 900 transplant patients (17%) at the Klinikum Steglitz, Berlin. Analgesic patients were the oldest group among haemodialysis and transplanted patients; the analgesic patients on haemodialysis were significantly older than the transplanted analgesic patients (55.9 +/- 11.2 versus 50.5 +/- 7.5 years, P = 10(-6)). Patient and graft survival under cyclosporin treatment are not statistically different in 125 transplantations of 109 patients with analgesic nephropathy compared to 508 transplantations of 423 patients with other renal diseases (5-year patient survival, 83.3 +/- 5.1% versus 88.4 +/- 2.4%; 5-year graft survival, 53.5 +/- 7.4% versus 56.8 +/- 3.8%; NS). Acetaminophen in urine was found in two of 30 analgesic and in one of 54 other patients with a functioning transplant (6.7% versus 1.9%; NS). As a sign of compliance, the mean cyclosporin trough level of 17 patients with analgesic nephropathy did not differ significantly from that of 14 patients with polycystic kidney disease (136.4 +/- 16.4 versus 139.4 +/- 17.3 ng/ml; NS), nor did the mean standard deviation of the individual measurements (36.7 +/- 36.8 versus 27.5 +/- 20.7 ng/ml; NS). Urothelial carcinoma was significantly more frequent in patients with analgesic nephropathy than in those with other renal diseases despite cystoscopy and retrograde pyelography before transplantation (3.7% versus 0.32%; P = 0.001). Vascular disease was the cause of death in 19 of 44 analgesic transplant patients who died (43.2%).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Multicentre evaluation of the Boehringer Mannheim/Hitachi 747 analysis system.
Analytical performance and practicability of the new Boehringer Mannheim/Hitachi 747 analysis system were assessed in a multicentre evaluation involving four laboratories. The analytical performance was evaluated according to a protocol similar to the ECCLS guidelines and comprised 13 analytes including enzymes, substrates and electrolytes. About 65,000 results were obtained within three months. The evaluation was planned and supported by a program system called "Computer Aided Evaluation". Acceptance criteria have been established for judging the results. The median of the within-run coefficients of variation (CVs) in control sera of all methods was below 1%, being far below the acceptance limit of 2%. The median of CVs of between-days imprecision was below 2% (acceptance criterion 3%). The high degree of precision prompted us to set up a biometrical model suitable for the differentiation between deviant points, outliers and measurements that can still be explained by the system performance. No relevant drift effects were observed during eight hours. The methods were linear over a wide range, avoiding rerun analysis in most cases. No sample-related carry-over was found. Reagent-dependent carry-over outside the acceptance limits was measured from uric acid to phosphorus to a slight extent, and from triacylglycerols to lipase, as well as from total protein to bilirubin to a perceptible degree. It can be avoided by separating these reagent combinations in the channel arrangement. Taking a systematic deviation of more than 10% as unacceptable, four of the 13 analytes suffered from interference by haemoglobin, one by bilirubin and one by turbidity. The Boehringer Mannheim/Hitachi 747 analysis system is capable of determining serum indices which in combination with the interferogram allow an assessment of the interference. With the exception of chloride the recovery of the assigned values for all control sera showed values between 95 and 105%. Out of 40 method comparison studies for enzymes and substrates, 31 yielded regression equations with less than 5% proportional errors and less than 5% constant errors. Deviations exceeding these acceptance criteria can be explained by differences in the reagent formulation, in the method employed or in calibration. The agreement of the ISE method comparisons was within a +/- 5% deviation over a wide analytical range. Practicability of the Boehringer Mannheim/Hitachi 747 analysis system was assessed with the help of a questionnaire, in which properties of the instrument were quantified, thus permitting a relatively objective rating. The 190 questions were placed in 14 groups, each dealing with an attribute of the instrument.(ABSTRACT TRUNCATED AT 400 WORDS)
Autoanalysis↗
Renal transplant hypertension caused by iliac artery stenosis.
A captopril renal study performed with both radiohippuran and 99mTc-MAG3 demonstrated the typical changes of a hemodynamically significant renal artery stenosis in a hypertensive renal allograft recipient. Arteriography demonstrated high grade stenosis not of the renal artery but of the iliac artery. After successful angioplasty, the patient's hypertension resolved.
Captopril↗
[Complete anuria in unilateral renal artery obstruction and ischemic nephropathy].
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Acute Kidney Injury↗
Combined haemoperfusion, haemofiltration and haemodialysis for systemic detoxification in locoregional 5-fluorouracil therapy.
Combined haemoperfusion, haemofiltration and haemodialysis (HPFD) was examined for its systemic effect on 5-fluorouracil (5-FU) kinetics after locoregional application to one female patient with liver metastases of a colon carcinoma. During each HPFD treatment, which lasted 4 h, 5-FU was given via a port-a-cath system into the hepatic artery on 4 separate days. The HPFD extraction rate was 99%. Extracorporal 5-FU clearance (89 ml/min) was 9% of total body clearance (1094 ml/min). The fraction eliminated within 4 h was only 6% of the applied dose (3500-4000 mg 5-FU). Sufficient extracorporal detoxification during combined HPFD can thus not be guaranteed in locoregional chemotherapy with a high dose of 5-FU.
Colonic Neoplasms↗
Outcome prediction of acute renal failure in medical intensive care.
Data acquired prospectively from 134 patients with acute renal failure requiring dialysis in a medical intensive care unit (ICU) were analysed in order to derive indicators predicting ICU-survival. Mortality in the ICU was 56.7%. Linear discriminant analysis correctly predicted outcome in 79.9% at the start of dialysis, and 84.7% at 48 h after the first dialysis. The most important predictive variables were mechanical ventilation and low blood pressure. On the other hand, the total correct classification rates achieved by a standardised system for scoring ICU-patients (APACHE II) did not exceed 58.2%. It is concluded that outcome prediction by APACHE II and even by the discriminant functions is too inaccurate to become the basis for clinical decisions either concerning the initiation or the continuation of dialysis treatment in ARF.
Acute Kidney Injury↗
Recurrent and de novo renal disease after kidney transplantation with or without cyclosporine A.
We evaluated the clinical course of 700 renal transplantations, including 1,305 transplant histologies performed in 611 patients between 1970 and 1988, to estimate the influence of cyclosporine A (CsA) after kidney transplantation on the incidence of recurrent or de novo renal disease. Primary renal disease recurred in 11 of 583 functioning transplants (1.9%) with transplant loss in seven patients (1.2%): focal segmental glomerulosclerosis (FSGS, three patients); membranous glomerulonephritis (GN, one patient); mesangiocapillary GN (one patient); rapidly progressive IgA nephropathy (one patient); hemolytic-uremic syndrome (HUS, three patients); and oxalosis in two transplants (one patient). De novo renal disease occurred in six patients (1.0%), including mesangiocapillary GN type I (three patients); nonpurulent focal GN in septicemia (one patient); HUS (one patient); and nodular glomerulosclerosis in steroid diabetes (one patient). De novo membranous GN was seen in 14 additional cases (2.4%). No statistically significant difference could be established between the treatment groups without (n = 225) and with (n = 358) CsA in recurrent and de novo renal disease (n = 7/225 v 10/358, NS); in recurrent and de novo GN (n = 4/225 v 6/358, NS); in recurrent FSGS (n = 1/7 v 2/8, NS); in recurrent and de novo HUS (n - 1/1 v 2/7, NS); and in de novo membranous GN (n = 7/225 v 7/358, NS). Transplant loss by recurrent and de novo GN was higher without than with CsA (n = 4/4 v 1/6, P = 0.004). On the basis of our investigation, we conclude that recurrent and de novo renal disease in the transplant occur rarely and are not prevented by CsA. However, even if the incidence of transplant GN is unchanged by CsA treatment, its clinical course seems to be mitigated. CsA treatment also does not increase the incidence of HUS.
Adolescent↗