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Biomedical subjects

J Kohler

Publications and source records attributed to J Kohler.

At least 19 recordsLinked to original sources
PubMed1992

Cytokine production after intravenous or peritoneal gram-negative bacterial challenge in mice. Comparative protective efficacy of antibodies to tumor necrosis factor-alpha and to lipopolysaccharide.

The production of TNF-alpha, IL-1, and IL-6 was measured in mice after bolus i.v. Escherichia coli O111 LPS injections and during bacteremia induced either by bolus i.v. or by i.p. challenges of live E. coli O111. High but transient TNF-alpha peaks were observed after bolus i.v. LPS or bacterial challenges. In contrast, the levels during lethal peritonitis increased progressively to values 50- to 100-fold lower than the peak values observed after i.v. injections, and remained sustained until death. Whereas after i.v. challenge with 1000 LD50 of LPS, anti-TNF-alpha antibody fully protected mice from death and reduced serum IL-1 and IL-6 levels, anti-TNF-alpha antibody did not improve the survival of mice nor reduced serum IL-1 and IL-6 levels after i.p. bacterial challenge. In contrast to anti-TNF-alpha antibodies, anti-LPS antibodies were protective in the peritonitis model. Protection was accompanied by a striking reduction of bacterial numbers and of TNF-alpha, IL-1, and IL-6 levels in the serum, but the levels of these cytokines were only marginally affected in the peritoneal lavage fluid. This latter observation demonstrates that the local peritoneal cytokines did not diffuse readily into the circulation, thus suggesting that at least part of the circulating cytokines are produced systemically. In conclusion, the striking differences between cytokine profiles as well as the divergent efficacy of anti-TNF-alpha antibody after i.v. bolus and after i.p. challenges suggest that TNF-alpha may not be as important in the pathogenesis of lethal peritonitis than after lethal acute bacteremia.

Animals↗
PubMed1992

[Neurologic complications of Q-fever (Coxiella burnetii)].

We report on fifteen patients with a typical syndrome of Q-fever. Four patients (= 27%) showed signs of nervous system involvement. One patient developed a meningitic syndrome, another patient had a passing psychosis. In two patients, severe cerebellar deficits were predominant. It is pointed out that these two patients were under lithium therapy because of manic-depressive illness. A synergetic neurotoxic effect of cociella burneti infection and lithium is discussed as a possible cause of the severe cerebellar pattern of symptoms.

Adult↗
PubMed1990

Induction and activity of NO synthase in bone-marrow-derived macrophages are independent of Ca2+.

The aim of the present study was to analyse whether an increase in the intracellular free Ca2+ concentration ([Ca2+]i) plays a role as a signal mediating synthesis of nitric oxide (NO) in bone-marrow-derived macrophages, either by stimulating induction of NO synthase or by regulating the activity of the enzyme. Therefore we compared the effects of various synthetic analogues of bacterial lipopeptide and of lipopolysaccharide (LPS) on NO production (assessed as nitrite formation during an incubation for 24 h) and on [Ca2+]i [measured with the fluorescent probe indo-1 (1-[2-amino-5-(6-carboxyindol-2-yl)phenoxy]-2- 2-(2'-amino-5'-methylphenoxy)ethane-NNN'N'-tetra-acetic acid)]. Strongly dissociating effects were evoked on nitrite formation and on [Ca2+]i by the stimuli. LPS was preferentially effective on nitrite formation, whereas the Ca2+ ionophore ionomycin and AlF3 induced increases only in [Ca2+]i. The lipopeptides N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)-(2RS)- propyl]-(R)-cysteinylalanylglycine, N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)- (2RS)-propyl]-(R)-cysteinylseryl-lysyl-lysyl-lysine and (S)-(1,2- dicarboxyhexadecyl)ethyl-N-palmitoylcysteinylseryl-lysyl-lys yl-lysine stimulated both parameters, but the maximal effects on nitrite formation and the shape of the dose-response curves did not parallel the effects on [Ca2+]i. Reduction of extracellular Ca2+ with EGTA significantly inhibited increases in [Ca2+]i, but did not change nitrite formation. Furthermore, NO synthesis in the cytosolic fraction of stimulated macrophages was not affected by Ca2+ over the concentration range 10 nM-2 microM. We conclude that increases in [Ca2+]i are not required for NO production in bone-marrow-derived macrophages. Thus the cellular regulation of NO production strikingly differs from that in the vascular endothelium, brain and adrenal gland.

Aluminum↗
PubMed1990

[Lyme borreliosis in neurology and psychiatry].

Neurological manifestations of Lyme disease are as multifarious as the entire spectrum of this common infection. In stage I, fibromyalgia and, more rarely, painful muscular fasciculation, dominate the clinical picture. In the individual case, mild psychic abnormalities may already be observed. Characteristic of the 2nd stage is lymphocytic meningopolyneuritis. Involvements of the CNS are expressed not so much in focal deficits, as in diffuse psychopathological disorders. In stage 3, CNS manifestations are characterized by chronic, in part multifocal, encephalitides and encephalomyelitides, isolated transverse myelitides and cerebral vasculitic disorders. The clinical symptomatology may be dominated by severe psychiatric syndromes. Connatal and subclinical latent infections of the nervous system with Borrelia represent special forms.

Diagnosis, Differential↗
PubMed1990

A magnetic measurement device for the kinematic analysis of unrestrained human hand movements.

A magnetic measurement device is described which was constructed to study human hand- and finger-movements. The system overcomes some problems frequently arising in the study of finger grip movements. It allows the simultaneous recording of several positions which cannot be observed with optical devices because they are hidden by other parts of the limb. Trajectories are recorded using small receiver coils moving in an alternating magnetic field of 3 transmitter coils. The performance of subject's movements is not significantly disturbed. A high sampling rate and a lack of mechanical damping permit a high temporal resolution which can analyze rapid movements. Subjects are not exposed to any biological risk or discomfort. Thus, a recording session can be repeated numerous times. The results obtained from this type of apparatus may allow quantification of the course of progressing diseases and to study the effects of remediation.

Electromagnetic Fields↗
PubMed1990

Ischemic stroke due to protein C deficiency.

Plasma protein C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis has been only rarely observed. We describe a young patient with heterozygous protein C deficiency who experienced a severe stroke due to thrombotic occlusion of the left middle cerebral artery.

Adult↗
PubMed1989

The role of short-term visuo-spatial memory in control of rapid multi-joint prehensive movements.

How memorized visuo-spatial information influences motor control and whether this information is able to replace the feedback processing in cases of visual deprivation was studied using an unrestrained finger- and hand-movement paradigm. Nineteen right-handed subjects were asked to grasp and lift a small block with the index finger and thumb of the right hand, as quickly as possible. The efficiency of motor performance was analysed by measuring the grasping time derived from tangential velocity profiles of the fingertips. The data revealed significantly shorter grasping times under continuous visual guidance than during blind grasping. Grasping times increased under conditions with stepwise prolongation of visual deprivation time prior to the movement onset. The results support the general concept that within the first seconds of visual deprivation, stored visuo-spatial information can partly compensate for the lack of continuous visual feedback.

Adult↗
PubMed1989

Increasing methotrexate effect with increasing dose in the treatment of resistant rheumatoid arthritis.

Forty-six patients with recalcitrant rheumatoid arthritis entered a trial encompassing a 2-week inpatient period plus a 16-week, randomized double blind, parallel study comparing placebo, 5 mg/m2 and 10 mg/m2 oral weekly methotrexate (MTX). An additional 6 patients, given 20 mg/m2 MTX, contributed to the toxicity, but not the efficacy analysis. All patients had "failed" either gold or D-penicillamine. A linear dose response relationship (placebo vs 5 mg/m2 vs 10 mg/m2) was found for 5 of 11 outcome variables: patient pain and patient global scale, physician global scale, joint tenderness count and activity of daily living scale (p less than 0.05 for each). Gastrointestinal toxicity (p = 0.002), dyspepsia (p less than 0.03) and stomatitis (p less than 0.09) occurred more commonly with MTX, and a general trend, although not significant, was found toward a dose toxicity relationship.

Activities of Daily Living↗
PubMed1989

Insect cells as substrates for biologicals.

Various methods for the growth of insect cells and the production of recombinant human beta-interferon (rHu beta-IFN) by insects cells, Spodoptera frugiperda, IPL-Sf-21AE after infection with recombinant AcNPV are described. Using a suspension perfusion Biospin filter culture system, an IPL-Sf-21AE cell line was propagated in a semi-controlled environment. To obtain and maintain high cell densities and viabilities in this system, the culture medium for suspension methods was modified by supplementing with ZnSO4, ALCl3, methyl cellulose and Darvan #2. Using these improved conditions, multiple harvests of rHu beta-IFN were collected in the cell culture supernatant for downstream processing.

Animals↗
PubMed1988

Computed tomography in cases of multiple sclerosis: problems of differential diagnosis in cases with atypical findings.

The value of computed tomography in the diagnosis of multiple sclerosis is undisputed. The examination is usually carried out as a routine part of the examination program. We report on the CT results of 112 patients with confirmed or suspected MS. Seventy-three patients were examined without, 39 with intravenous administration of a contrast medium. In 41% of the patients, isolated or multiple hypodense foci were found as a manifestation of a multilocular demyelinization process. In 17.8%, only cerebro-atrophic changes were encountered. In 30.3% of the cases the CT showed normal results. In the group of patients examined with a contrast medium, a pathological contrast medium concentration was found in 30.7%. The differential diagnostic demarcation against other diseases of the CNS with similar CT findings and problems of differential diagnosis with MRI are discussed.

Adult↗
PubMed1988

Left ventricular function at rest and during exercise in acute hypothyroidism.

The effect of hypothyroidism on left ventricular function at rest and during exercise was studied in nine patients without demonstrable cardiovascular disease who had had total thyroidectomy and ablative radioiodine treatment for thyroid cancer. Radionuclide ventriculography and simultaneous right heart catheterisation were performed while the patients were hypothyroid two weeks after stopping triiodothyronine treatment (to permit routine screening for metastases) and while they were euthyroid on thyroxine replacement treatment. When the patients were hypothyroid, cardiac output, stroke volume, and end diastolic volume at rest were all lower and peripheral resistance was higher than when they were euthyroid. Pulmonary capillary wedge pressure, right atrial pressure, heart rate, left ventricular ejection fraction, and the systolic pressure:volume relation of the left ventricle, which was used as an estimate of the contractile state, were not significantly different when the patients were hypothyroid or euthyroid. During exercise, heart rate, cardiac output, end diastolic volume, and stroke volume were higher when the patients were euthyroid than when they were hypothyroid. Again, pulmonary capillary wedge pressure, ejection fraction, and the systolic pressure:volume relation were similar in both thyroid states. The data suggest that the alterations in cardiac performance seen in short term hypothyroidism are primarily related to changes in loading conditions and exercise heart rate; they do not suggest that acute thyroid hormone deficiency has a major effect on the contractile properties of the myocardium.

Acute Disease↗
PubMed1988

Multiple sclerosis presenting as chronic atypical psychosis.

Two patients with multiple sclerosis are reported in whom psychopathological symptoms were present for many years. An exact psychiatric classification of the clinical syndrome was not possible. At no time during the illness were abnormal neurological findings observed. Multiple sclerosis was proven following necropsy in one patient. In the second patient a possible diagnosis of multiple sclerosis was made. This patient was found to have multiple lesions in the white matter which were evident on MRI and in the isoelectric focusing (IEF) of cerebrospinal fluid oligoclonal bands were found.

Adult↗
PubMed1988

Chronic central nervous system involvement in Lyme borreliosis.

We describe four patients with marked chronic meningoencephalomyelitis caused by tick-transmitted Borrelia burgdorferi infection. Imaging techniques showed either MS-like lesions or evidence of vascular involvement, as in other spirochetal infections, especially in meningovascular syphilis.

Adult↗
PubMed1988

Relation of noninvasive parameters and pulmonary artery mean pressure in patients with chronic obstructive lung disease.

A series of 31 patients with various degrees of chronic obstructive pulmonary disease (COPD) underwent radionuclide ventriculography with right heart catheterization. The patients were divided into 2 groups on the basis of their reduction in forced expiratory volume in 1 s (FEV1). In patients with FEV1 greater than or equal to 1,300 ml (group 1) the oxygen partial pressure (PaO2) did not significantly change with exercise, while in patients with FEV1 less than or equal to 1,200 ml (group 2) the PaO2 significantly decreased (p less than 0.05) with exercise. The groups were significantly different from each other as to the correlation between hemodynamic and noninvasive parameters. In the resting state, the correlation between pulmonary artery mean pressure (PAP) and both residual volume to total lung capacity (RV/TLC) and PaO2 was close only in group 2. By contrast, the right ventricular end diastolic wall thickness (RWD) correlated closely with PAP in both groups. With exercise close correlations were observed between PAP and the noninvasive parameters: RWD, PaO2 and right ventricular ejection fraction in both groups. Arterial CO2 partial pressure (PaCO2) was only increased (greater than or equal to 45 mm Hg) in group 2. This parameter correlated moderately closely with PAP both in the resting and the exercise state only in group 2. The predictive value of PaCO2 greater than or equal to 45 mm Hg for estimation of PAP greater than 35 mm Hg during exercise was 100%. We conclude that separation of patients with COPD into groups with different impairments of the lung function parameter FEV1 can improve the correlation coefficients between noninvasive and invasive parameters. The exercise values obviously correlate more closely than the resting values. An increased value of echocardiographically determined RWD seems to be a reliable parameter for prediction of PAP.

Adult↗