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Biomedical subjects

F Keller

Publications and source records attributed to F Keller.

At least 217 records · Page 12Linked to original sources
PubMed1989

Gentamicin volume of distribution as a power function of body weight.

Gentamicin volume of distribution (V) was related to body weight (W) in 183 obese, normal weight and infant patients as reported in five published studies. In contrast to the usually postulated simple proportionality (V = bW) a linear function was found (V = a + bW) with an intercept (a = 2.5 +/- 0.49) significantly different from zero (P = 0.0001) and a slope (b = 0.19 +/- 0.10) significantly different (P = 0.0001) from the mean factor of proportion (b = 0.35 +/- 0.19). As compared with the linear function, a power function (V = 0.57 W 0.79) approximated even more closely the dependence of gentamicin volume on body weight (r = 0.94 vs r = 0.81). The difference between both functions was more than 50% only for body weight less than 5 kg. It is concluded that the relation between gentamicin volume of distribution and body weight is non-linear.

Adult↗
PubMed1989

Respiratory sinus arrhythmia in the denervated human heart.

We performed this study to test whether the denervated human heart has the ability to manifest respiratory sinus arrhythmia (RSA). With the use of a highly sensitive spectral analysis technique (cross correlation) to define beat-to-beat coupling between respiratory frequency and heart rate period (R-R) and hence RSA, we compared the effects of patterned breathing at defined respiratory frequency and tidal volumes (VT), Valsalva and Mueller maneuvers, single deep breaths, and unpatterned spontaneous breathing on RSA in 12 normal volunteers and 8 cardiac allograft transplant recipients. In normal subjects R-R changes closely followed changes in respiratory frequency (P less than 0.001) but were little affected by changes in VT. On the R-R spectrum, an oscillation peak synchronous with respiration was found in heart transplant patients. However, the average magnitude of the respiration-related oscillations was 1.7-7.9% that seen in normal subjects and was proportionally more influenced by changes in VT. Changes in R-R induced by Valsalva and Mueller maneuvers were 3.8 and 4.9% of those seen in normal subjects, respectively, whereas changes in R-R induced by single deep breaths were 14.3% of those seen in normal subjects. The magnitude of RSA was not related to time since the heart transplantation, neither was it related to patient age or sex. Thus the heart has the intrinsic ability to vary heart rate in synchrony with ventilation, consistent with the hypothesis that changes, or rate of changes, in myocardial wall stretch might alter intrinsic heart rate independent of autonomic tone.

Adult↗
PubMed1989

Factors influencing the response to hepatitis B vaccination of hemodialysis patients.

The response rate and HBsAG antibody concentrations were examined after hepatitis B vaccination in 78 hemodialysis patients aged between 29 and 79 years. The values were related to age, duration of hemodialysis, body weight, creatinine, urea nitrogen, serum concentrations of beta 2-microglobulin and soluble interleukin-2 receptor (IL-2R). Patients with low anti-HBsAG antibody concentrations (10-100 mU/ml) had significantly higher IL-2R serum concentrations than those with high anti-HBsAG antibody concentrations (greater than 3,000 mU/ml; p less than 0.05). Discriminant multivariate analysis (p = 0.032) revealed the influence (62%) of IL-2R on the response rate while other factors were similar in all patient groups. It is concluded that preactivation of T cells with an increased release of IL-2R may contribute to impaired immune response after hepatitis B vaccination.

Adult↗
PubMed1989

Progression of renal failure in analgesic-associated nephropathy.

The factors that influence the progression of renal failure in analgesic-associated nephropathy (AAN) still remain to be clarified. In this study, the actual analgesic intake (N-acetyl-p-aminophenol, NAPAP, i.e. acetaminophen in urine) and progression of renal failure (1/crea method) in 127 outpatients with various renal diseases were investigated over a period of 7-150 months. AAN was diagnosed in 57 of the 127 patients (44%). The NAPAP test was positive in 21% of the 57 AAN patients and in 3% of the 70 control patients with other renal diseases (p = 0.0001). The AAN patients presented with more advanced renal insufficiency, lost more weight, and had more severe hypertension as well as a higher mortality rate than the control patients (univariate analysis). Progression of renal insufficiency, as measured by regression analysis of the reciprocal of serum creatinine versus time and expressed as clearance loss per year, was more rapid in the AAN patients who were found positive for NAPAP (6.9 +/- 5.5 ml/min/year) than in the AAN patients who were found negative (4.1 +/- 11.0 ml/min/year) or in control patients with other renal diseases (5.1 +/- 14.9 ml/min/year). Multivariate analysis showed the more rapid clearance loss to be the most discriminating factor between the AAN patients who continued analgesic abuse of phenacetin-or acetaminophen-containing drugs and AAN patients who stopped. We therefore conclude that continued analgesic abuse promotes renal insufficiency in AAN. The progression of renal failure in AAN patients who stopped abusing analgesics, however, cannot be explained within the parameters investigated, i.e. urinary tract infection, hypertension, hyperalimentation, or papillary necrosis.

Acetaminophen↗
PubMed1989

Multivariate analysis of aminoglycoside levels in hemodialysis patients.

Multivariate discriminant analysis was performed on data for 50 consecutive hemodialysis patients who had received aminoglycoside treatment because of severe bacterial infections. The 10 of the 60 clinical parameters considered to be most important were survival of patients (28/50 patients), success of treatment (27/50 patients), acute or chronic renal failure (15 vs. 35), age (54 +/- 17 years), creatinine level (675 +/- 298 mumol/l), artificial ventilation (21/50 patients), need for catecholamines (19/50 patients), continuous arteriovenous hemofiltration (9/50 patients), duration of therapy (12 +/- 8 days) as well as aminoglycoside peak (7.5 +/- 2.7 mg/l) and trough levels (3.6 +/- 1.3 mg/l). The 4 of the 10 parameters investigated by multivariate analysis significantly contributing to survival of patients were clinical success of aminoglycoside treatment (p = 0.0001), no need for catecholamines (p = 0.0001), duration of dosage (p = 0.003) and aminoglycoside peak levels (p = 0.009).

Adolescent↗
PubMed1989

Treatment of carbamazepine poisoning by combined hemodialysis/hemoperfusion.

A severe carbamazepine intoxication in a 45-year-old woman was treated with combined hemodialysis/hemoperfusion. The ingested dose was estimated as 4-36 g. Serum carbamazepine levels were determined by fluorescence polarization immunoassay. The detoxication was performed 18 h after admission and resulted in a 50 percent reduction in serum drug levels accompanied by rapid clinical improvement.

Carbamazepine↗
PubMed1989

Long-term treatment and prognosis of rapidly progressive glomerulonephritis.

Short-term prognosis of rapidly progressive glomerulonephritis (RPGN) has improved since immunosuppressive therapy was introduced. The long-term course of the disease was investigated in 46 consecutive and unselected patients over a period of 15 years (1970-1986) with a mean observation time of five years (+/- 45 months). Most of the 46 patients had idiopathic RPGN (61%). Initially, hemodialysis needed 25 of the 46 patients (54%). Immunosuppressive therapy (plasma exchange, methylprednisolone pulses, steroids, cyclophosphamide, azathioprine) was administered in 36 of the 46 patients (78%). A remission was achieved in only 19 of the 36 patients who received immunosuppression (53%) and no spontaneous improvement was seen. Factors indicating poor prognosis were initial high serum creatinine, high percentage of crescents in glomeruli, glomerular sclerosis, and immunohistologic staining of the IgG at the tubuli. In 11 patients with remission, immunosuppression was discontinued and 6 had a relapse. Long-term immunosuppression was given to 8 patients with remission. Their renal function was not normal (creatinine 240 +/- 77 mumol/l), but none had a relapse (p = 0.01). It is concluded that the treatment of RPGN requires long-term attendance and repeated immunosuppression comparable to a systemic immune disease.

Adult↗
PubMed1988

Strain-specific development of the mossy fiber system in organotypic cultures of the mouse hippocampus.

The postnatal development of the hippocampus of the inbred mice strains BALB/c, C57BL/6, and DBA/2 was studied in organotypic explant cultures using the roller-tube technique. In vivo, mice exhibit strain-specific mossy fiber distribution patterns. As a main result we found, that after cultivation of 3-4 weeks, similar strain-specific patterns became apparent in vitro, as visualized by a modified Timm staining. From this experiment we can conclude that a postnatal extrinsic influence cannot be the cause of the strain-specific hippocampal features.

Animals↗
PubMed1988

[Cumulative functional rates of orthoptic dialysis fistulas and interposition grafts].

The function of 221 dialysis shunts was investigated retrospectively in 111 patients of an outpatient haemodialysis centre. The mean age of the patients was 58 years. Of 221 recorded shunts, 171 were direct arteriovenous fistulas, while 50 were interposition grafts. The longest observation period was almost 20 years (227 months). The cumulative function rate was evaluated by the life table method; primary patency (until first revision) was differentiated from total function (revisions included). The direct fistulas as compared to the grafts had a significantly (P less than 0.05) higher primary function rate (median 35 vs. 13 months) and after 36 months also a significantly longer total function (median 76 vs. 28 months). Complications were significantly (P less than 0.05) more frequent in grafts than in fistulas (61/50 vs 120/171). Surgical revisions of fistulas failed significantly more often (P less than 0.05) than revisions of grafts (137/171 versus 26/50). Grafts on the forearm had significantly worse results as compared to grafts or fistulas on the upper arm (P = 0.03). In contrast to age, sex and underlying disease of patients a blood pressure less than 130/70 mmHg was a significant risk factor for shunt failure (P = 0.002). Analysis of primary function shows (clearer than the total patency rate) that a direct fistula is a better vascular access in haemodialysis patients than a graft.

Actuarial Analysis↗
PubMed1988

Organotypic culture of central histamine neurons.

Organotypic cultures of histaminergic tuberomammillary (TM) neurons were grown using explants obtained from newborn rats. The cultures were examined after immunohistochemical localization of the histamine synthetic enzyme, L-histidine decarboxylase (HDC). The morphological properties of the somata, dendrites and axons of HDC-immunoreactive TM neurons in organotypic culture were virtually indistinguishable from those seen in situ. Extensive plexuses of HDC-immunopositive axons, including growth cones, were seen within the hypothalamus, the plasma surrounding the explant and co-cultured hippocampus. Organotypic cultures of TM histamine neurons, and co-cultures with their targets, provide a useful model system for studying several aspects of central histaminergic neurobiology.

Animals↗
PubMed1988

Dynamic instability and motile events of native microtubules from squid axoplasm.

Native microtubules from extruded axoplasm of squid giant axons were used as a paradigm to characterize the motion of organelles along free microtubules and to study the dynamics of microtubule length changes. The motion of large round organelles was visualized by AVEC-DIC microscopy and analyzed at a temporal resolution of 10 frames per second. The movements were smooth and showed no major changes in velocity or direction. During translocation, the organelles paused very rarely. Superimposed on the rather constant mean velocity was a velocity fluctuation, which indicated that the organelles are subject to considerable thermal motion during translocation. Evidence for a regular low-frequency oscillation was not found. The thermal motion was anisotropic such that axial motion was less restricted than lateral motion. We conclude that the crossbridge connecting the moving organelle to the microtubule has a flexible region that behaves like a hinge, which permits preferential movement in the direction parallel to the microtubule. The dynamic changes in length of native microtubules were studied at a temporal resolution of 1 Hz. About 98% of the native microtubules maintained their length ("stable" microtubules), while 2% showed phases of growing and/or shrinking typical for dynamic instability ("dynamic" microtubules). Gliding and organelle motion were not influenced by dynamic length changes. Transitions between growing and shrinking phases were low-frequency events (1-10 minutes per cycle). However, a new type of microtubule length fluctuation, which occurred at a high frequency (a few seconds per cycle), was detected. The length changes were in the 1-3 micron range. The latter events were very prominent at the (+) ends. It appears that the native axonal microtubules are much more stable than the purified microtubules and the microtubules of cultured cells that have been studied thus far. Potential mechanisms accounting for the three states of microtubule stability are discussed. These studies show that the native microtubules from squid giant axons are a very useful paradigm for studying microtubule-related motility events and microtubule dynamics.

Animals↗
PubMed1988

Transport and subcellular localization of polyamines in carrot protoplasts and vacuoles.

Putrescine and spermidine uptake in carrot (Daucus carota L., cv "Tip top") protoplasts and isolated vacuoles was studied. Protoplasts and vacuoles accumulated polyamines very quickly, with maximum absorption within 1 to 2 minutes. The insertion of a washing layer containing 100 millimolar unlabeled putrescine or spermidine did not change this pattern, but strongly reduced the uptake of putrescine and spermidine in protoplasts and in vacuoles. The dependence of spermidine uptake on the external concentration was linear up to the highest concentrations tested in protoplasts, while that in vacuoles showed saturation kinetics below 1 millimolar (K(m) = 61.8 micromolar) and a linear component from 1 to 50 millimolar. Spermidine uptake in protoplasts increased linearly between pH 5.5 and 7.0, while there was a distinct optimum at pH 7.0 for vacuoles. Preincubation of protoplasts with 1 millimolar Ca(2+) affected only surface binding but not transport into the cells. Nonpermeant polycations such as La(3+) and polylysine inhibited spermidine uptake into protoplasts. Compartmentation studies showed that putrescine and spermidine were partly vacuolar in location and that exogenously applied spermidine could be recovered inside the cells. The characteristics of the protoplast and vacuolar uptake system induce us to put forward the hypothesis of a passive influx of polyamines through the plasmalemma and of the presence of a carrier-mediated transport system localized in the tonoplast.

Journal Article↗
PubMed1988

Sucrose Synthase, a Cytosolic Enzyme in Protoplasts of Jerusalem Artichoke Tubers (Helianthus tuberosus L.).

The exact subcellular location of sucrose synthase (UDP-d-glucose: d-fructose 2-alpha-d-glucosyltransferase, EC 2.4.1.13) in Helianthus tuberosus tubers was studied by comparison of its activity in protoplasts with that of vacuoles isolated from them. Assuming 100% of the beta-N-acetylglucosaminidase activity to be of vacuolar origin, less than 5% of both the sucrose synthase activity and the extravacuolar marker NAD-malate dehydrogenase was detected in the vacuole preparations. Sucrose synthase is therefore an extravacuolar enzyme. Its role in the inulin metabolism of H. tuberosus is discussed.

Journal Article↗
PubMed1988

Pathogenic and non-pathogenic Entamoeba: pore formation and hemolytic activity.

Pore-forming activity in planar lipid bilayers and liposomes of extracts from differentially pathogenic Entamoeba and the capacity of trophozoites and subcellular fractions to lyse human red blood cells (hrbc) were investigated. In all amebas studied, the two activities paralleled each other. They were high in E. histolytica irrespective of the virulence of the particular strain, but low in non-pathogenic E. histolytica-like amebas of human origin as well as in E. invadens, which is pathogenic for reptiles, and in E. moshkovskii isolated from sewage. We conclude that the capacities to insert pores and to lyse are not sufficient for virulence although they may be necessary. The subcellular distribution of the hemolytic activity of E. histolytica and its sensitivity to a variety of inhibitors and activators differ from those of other known amebic cytotoxic activities including pore formation. Therefore, there may be an additional constituent of E. histolytica involved in the cytotoxicity of the parasite.

Animals↗
PubMed1988

Interaction of mouse hepatitis virus 3 with Kupffer cells explanted from susceptible and resistant mouse strains. Antiviral activity, interleukin-1 synthesis.

The genetic sensitivity of mouse strains to mouse hepatitis virus 3 (MHV 3) has been related in vitro to a delay of virus replication in liver sinusoidal cells. In vivo immuno-histochemical studies of the liver from infected mice have demonstrated that mechanisms other than direct viral injury are in operation. To examine potential mechanisms, the interaction of lipopolysaccharide (LPS)-stimulated Kupffer cells with MHV 3 was studied. We first observed a dramatic inhibition in viral replication in LPS-treated Kupffer cells explanted from A/J resistant mice. Second, we demonstrated that MHV 3 induced a dose-dependent interleukin 1 (IL-1) activity in the supernatants of infected Kupffer cells of both strains. These results led us finally to examine the antigen-processing function of the Kupffer cells of both strains of mice. No striking differences were observed in the ability of Kupffer cells from resistant or sensitive mice to collaborate with immunocompetent lymphocytes. Our data suggest that Kupffer cells play a double role which is crucial in the pathogenesis of MHV 3-induced hepatitis. First, they act directly as the genetically determined sensitivity of mice to MHV 3 infection is correlated with the efficiency of the antiviral activity induced in Kupffer cells by LPS. Second, they act indirectly through the synthesis of different amounts of IL-1 induced by MHV 3. This hypothesis is further borne out by the effects of indomethacin treatment on the course of MHV 3 infection in A/J resistant mice in vivo.

Animals↗
PubMed1988

Clinical evaluation of diagnostic hemoperfusion for in vivo enrichment of bacteria and fungi in comparison with a conventional blood culture technique.

The hemoperfusion module, a newly developed technique for recovering pathogenic microorganisms from patients suffering from septicemia, was compared with conventional blood cultures. The module was interconnected with the extracorporeal circulation of 92 predominantly hemodialyzed patients. Nearly 12 liters of flowing blood (up to 200 ml min-1; mean running time, 60 min) came in contact with the coated charcoal. Of 99 modules examined, 44 (44.7%) yielded positive cultures and contained 54 potentially pathogenic bacteria or fungi (22 species). Only 32 of 190 (16.8%) conventional blood cultures were positive and contained 37 microorganisms (10 species). Even when patients were receiving antibiotic treatment, the frequency of isolation was significantly higher in hemoperfusion (21 of 44 modules positive, 47.7%) than in conventional blood cultures (10 of 88 cultures positive, 11.4%). In contrast, 23 of 55 modules (41.8%) and 22 of 102 conventional blood cultures (21.6%) were positive when patients were not treated with antibiotics prior to blood sampling. Altogether, hemoperfusion modules appeared to be superior to and more sensitive than the conventional blood cultures used and seemed to be a valuable tool for detecting septicemia.

Adult↗