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Biomedical subjects

J Braun

Publications and source records attributed to J Braun.

At least 505 records · Page 28Linked to original sources

Pharmacokinetics of flecainide in patients with mild and moderate renal failure compared with patients with normal renal function.

We have studied the pharmacokinetics of flecainide after the oral administration of 100 mg to 8 patients without renal impairment and 8 patients with mild to moderate renal failure. Both groups gave comparable results with respect to the peak plasma concentrations and the time to peak. There was a significant correlation between renal flecainide clearance and endogenous creatinine clearance. The elimination half-time in the patients with impaired renal function was significantly longer (19.9, SD 9.9 h) than that in the patients with normal renal function (11.5, SD 4.2 h), but the variability in the elimination half-time in renal failure could not be explained on the basis of the available results.

Female↗

[Proctocolectomy with direct ileoanastomosis and superimposed small intestine pouch].

Our experiences with 26 patients show that total proctocolectomy with direct ileoanal pouch anastomosis and without maintenance of the rectal muscle cuff proves to be an excellent method for secure and lasting treatment of UC and ACR as well as of manifest cancer. The advantage of this method is the maintenance of normal continence function at a lower operative risk and few postoperative complications. Contraindication for this operative approach is still Crohn' disease. Furthermore the indication is limited by primary dysfunction of the anal sphincter.

Adenomatous Polyposis Coli↗

Bioavailability of disopyramide in normal volunteers using unbound concentration.

The pharmacokinetics of disopyramide were determined in 10 healthy volunteers after a 300 mg oral dose and again after a 2 mg/kg i.v. dose. The unbound clearance was 599 ml/min and the unbound renal clearance 310 ml/min. The terminal elimination rate constant of unbound drug was 0.180 h-1 after the i.v. dose and 0.203 h-1 after the oral dose. The absorption rate constant was 0.53(-1) and the maximum peak concentration occurred after 3.2 h. The bioavailability was 0.809 using the area under the unbound plasma concentration time curve. Although a saturable plasma protein binding was found in all subjects the bioavailability using the total concentration, in contrast to theoretical expectations, showed the same value (0.813) as the unbound concentrations.

Adult↗

Friend virus-infected long-term bone marrow cultures produce colony stimulating factor dependent and independent granulocyte-macrophage progenitor cells for over four years in vitro.

C3H/HeJ mouse long-term bone marrow cultures infected at initiation with a cloned polycythemic strain of Friend spleen focus forming virus in a cloned N-tropic murine leukemia virus helper virus coat, persistently produced: colony-forming unit spleen (CFUs) for 55 weeks that formed macroscopic spleen colonies in syngeneic or allogeneic C57B10.Br/J mice; and L-cell or WEHI-3 cell conditioned medium-dependent granulocyte-macrophage colony forming unit culture (GM-CFUc); and morphologically normal granulocytes for over 245 weeks. Colony stimulating factor (CSF)-independent colony forming progenitor cells were first detectably produced in vitro at 75 weeks, and when subcultured generated karyotypically distinct permanent factor-independent tumorigenic cell lines. Nonadherent cells removed from long-term marrow cultures at 19 but not at 77 weeks reconstituted donor origin hematopoiesis in C57B10.Br/J mice as measured by B-cell lineage surface immunoglobin allotype. Nonadherent cells removed at 77 weeks produced lethal splenomegaly and marrow infiltration with culture origin cells in C57B10.Br/J mice. Despite generation of clonal malignant cell lines, L-cell DSF (CSF-1, M-CSF) responsive GM-CFUc that were simultaneously produced over 4 years in the same long-term marrow cultures, grew to 7 day colonies in semisolid medium and terminally differentiated. Thus, adherent stromal cells in Friend virus-infected long-term bone marrow cultures simultaneously support CSF-responsive and malignant CSF-independent hematopoietic progenitor cells.

Animals↗

Nifedipine vasodilates human forearm arteries and dorsal hand veins constricted by specific alpha-adrenoceptor stimulation.

1. The local dilative effect of the calcium entry blocker nifedipine on forearm arteries and dorsal hand veins has been studied in 27 healthy male volunteers. 2. Nifedipine induced an increase of blood flow by 1190% (P less than 0.001) in the forearm. 3. The construction of the hand veins induced by stimulation of either postsynaptic alpha 1- or alpha 2-adrenoceptors was reduced (P less than 0.001) by nifedipine. 4. The calcium entry blocker nifedipine is a potent dilator of human forearm arteries as well as of dorsal hand veins.

Adrenergic alpha-Agonists↗

Lateral interactions among membrane proteins. Valid estimates based on freeze-fracture electron microscopy.

We consider the lateral distribution of intrinsic membrane proteins from the viewpoint of the statistical-mechanical theory of liquids. We connect the information in freeze-fracture electron micrographs--positions of proteins but not lipids or aqueous species--to a well developed theory of liquid mixtures. An algorithm, based on the Born-Green-Yvon integral equation, is presented for deducing forces between proteins from correlations among protein positions that are observed in micrographs. The algorithm is tested on simulated micrographs, obtained by Monte-Carlo methods, where forces between proteins are known analytically. We conclude that valid estimates of such forces, both attractions and repulsions, can be obtained from the positions of a few thousand proteins.

Algorithms↗

Lateral interactions among membrane proteins. Implications for the organization of gap junctions.

We have studied the relationship between interprotein forces and the lateral distribution of proteins in disordered mouse liver gap junctions. Data on protein positions are obtained from freeze-fracture electron micrographs. Short-ranged correlations in observed positions are characteristic of interacting particles in a fluid state. An analysis derived from statistical mechanics allows the determination of the magnitude and functional form of interprotein forces. We find that jap junction proteins are mutually repulsive, in a manner consistent with electrostatics and excluded volume. This dictates that long-ranged protein aggregation into jap junction plaques cannot arise solely from interparticle interactions. An alternative is the balance of lateral pressures between the junction and the surrounding glycocalyx. This idea is quantified into a model. Junctional pressure arises from protein-protein interactions and is computed from a pressure equation based on the force and a radial distribution function describing order. The pressure from the glycocalyx is assumed to arise from mixing, electrostatic, and elastic interactions of sugar residues, and is described with terms from Flory-Krigbaum and McMillan-Mayer theories. The results of this modeling are in reasonable agreement with available experimental data.

Animals↗

Effects of reactive hyperemia and nifedipine on forearm vascular resistance in essential hypertension: evidence for functional abnormality.

The aim of this study was to explore whether the increased forearm vascular resistance in patients with essential hypertension is predominantly due to structural or functional changes. We studied 22 male patients with moderate essential hypertension and 22 age- and weight-matched normotensive men (28-52 years). The effects of intraarterially infused nifedipine, reactive hyperemia after 10 min arterial occlusion combined with handgrip exercise and local heating, and arterial occlusion combined with nifedipine on forearm blood flow and blood pressure were investigated in random order. Blood pressure was measured directly in the brachial artery and forearm blood flow by venous occlusion plethysmography. The calculated resistance values reduced by nifedipine or following arterial occlusion remained significantly higher in hypertensives than in normotensives. However, the maximal vasodilation achieved by the combination of arterial occlusion and nifedipine resulted in a similar decrease of resistance in hypertensives and normotensives. These data suggest that there is an important functional component of the elevated vascular resistance in patients with essential hypertension.

Adult↗

[Effect of selected anesthetics on serum myoglobin levels after administration of succinylcholine. Comparison of halothane, enflurane and isoflurane with thiopental in adults].

The type of anesthetic agent used influences the extent of the increase in serum myoglobin concentrations brought about by succinylcholine (sch). The purpose of this study was to compare the inhalational agents halothane, isoflurane, and enflurane with i.v. thiopental with respect to their effects on serum myoglobin levels following sch. Twenty-four male adults undergoing surgical procedures involving no muscle trauma were randomized and divided into four groups of six each. Following induction of anesthesia with a bolus injection of thiopental 2.5-3.5 mg/kg, patients in the four groups received either repetitive doses of thiopental plus N2O/O2 (4 l/min; FiO2 0.3) or one of the inhalational agents in N2O/O2 in dosages necessary for maintenance. Ventilation was carried out according to clinical judgement. Following a pre-sch phase of 15 min, sch 1 mg/kg was injected intravenously. Blood samples for determining myoglobin (normal range 30-60 ng/ml) were taken immediately prior to (control values) and 5 and 15 min after sch injection. Increases were defined as the difference of two values 15 min prior to and after sch. Statistical analysis was carried out by way of ANOVAs, P less than 0.05 being considered significant. The mean values of myoglobin prior to sch ranged from 52.3 to 57.7 ng/ml according to group (Table 1). The increase in concentration normally ranged from 1 to 7 times pre-sch levels, in some cases to 20 times. Table 2 shows the mean values. The type of anesthetic agent exerted no significant influence on serum concentration.

Adult↗

[Bronchoalveolar lavage. The humoral parameter spectrum in bronchial carcinoma and chronic bronchitis].

The concentrations of tissue-polypeptide antigen (TPA), ferritin, alpha 1-acid glycoprotein (alpha 1-aGP), transthyretin (TBPA), alpha 1-antitrypsin (alpha 1-Pi), alpha 2-macroglobulin (alpha 2-MG), C-reactive protein and IgA were determined in broncho-alveolar lavage fluid of 13 patients with chronic bronchitis and 11 with bronchial carcinoma and accompanying bronchitis. Measurement of TPA, alpha 1-Pi, ferritin and transthyretin provides useful additional information in the diagnosis of bronchial carcinoma. The ratios of TPA/TBPA, alpha 1-Pi/TBPA and alpha 1-aGP/TBPA differentiate highly sensitively between bronchial carcinoma and chronic bronchitis.

Antibody Formation↗

Activity of phagocytic granulocytes in patients with prostatic cancer.

Chemilumenescence (CL) occurs due to the phagocytosis of bacteria and of tumor cells by polymorphonuclear neutrophils (PMN). Levels of CL were measured in patients with prostatic cancer and from normal subjects. Patients with advanced disease (stage C, D) showed no elevated CL levels as compared to healthy individuals or patients with minimal disease (stage A, B). Following external radiation therapy in patients with stage A-C prostatic carcinoma high levels of CL were recorded. Estrogen medication also resulted in increased CL levels, while estramustine did not affect phagocytic activity. Intradermal BCG vaccination caused increased PMN activity. Progressive prostatic cancer in hormone treated patients was associated with increased CL as compared to patients with stable or regressive disease.

Antineoplastic Agents↗

Repetitive visual images in severe war head injuries.

Out of 20 young inpatients who suffered missile head injuries, two (10%) presented repetitive visual images (RVI). The RVI appeared during wakefulness when relaxed with closed eyes and also at sleep stage I, II and REM, at sleep onset and at sleep end. When the two patients were compared neurologically and psychologically with the other eighteen, the coexistence of combat stress syndrome, diffuse brain lesions, right non-dominant associative area damage and homonymous hemianopia characterised the two RVI patients. RVI do not appear in the absence of the combat stress syndrome even in the presence of the other 3 factors. The sleep may be secondarily contaminated by wakefulness RVI. The presence of disturbed REM temporal distribution and short REM latency indicate the depressive state of these patients. It is hypothesised that a similar brain activity in wakefulness and REM sleep explain the wake dreaming or wakefulness RVI of those patients.

Adult↗

Lymphocyte killer activity in individuals sensitized against antigen-D assessed by direct ADCC lysis of O,Rh-positive erythrocytes.

Lymphocytes from individuals sensitized against the Rh-D antigen were found to lyse O,Rh-positive erythrocytes. The controls consisted of individuals non-sensitized against D antigen. The lytic effect in the absence of additional in vitro added specific antibody was very high in sensitized individuals, but low in the control group. Lytic effect decreased after treating the lymphocytes of sensitized donors with trypsin, but it remained unchanged in the control group. These results suggest that the sensitized donors possessed lymphocytes with specific antibodies in vivo. This phenomenon could prove a valuable diagnostic tool in recognizing responder and non-responder donors in the early phase of immunization.

ABO Blood-Group System↗

B-Ly1 cells: immortal Ly-1+ B lymphocyte cell lines spontaneously arising in murine splenic cultures.

We have surveyed the molecular and functional properties of B-Ly1 cells, spontaneously occurring Ly-1+ cell tissue cultures lines established from murine spleen. Several features are surprising when compared to the conventional understanding of B cell physiology: In contrast to the major B cell subpopulation, these cells establish stable in vitro lines in the absence of nominal growth factors. This outgrowth is consistently accompanied by c-myc amplification and deregulation, and resistance to the effects of an autoregulatory IgM species which normally curtails the growth of B cells. These properties may be relevant to the disproportionate occurrence of Ly-1+ B cell malignancies in vivo. B-Ly1 cell lines consistently delete immunoglobulin constant region genes, and uniformly express lambda light chains, a rare murine isotype. These features may be causally related, and may reflect a novel recombinational activity (see this volume). Immunoglobulin expression can be modulated by conventional stimuli. However, the response is transient, and includes production of mature heavy chain isotypes ("class switching") without apparent switch deletion. Moreover, unstimulated B-Ly1 cells show transcriptional activity throughout the heavy chain locus, and a novel hypermutation activity affecting the immunoglobulin variable region. The mechanisms underlying this surprising pattern of immunoglobulin expression are unknown. However, one wonders whether this expression pattern, if common to Ly-1+ B cell in vivo, might provide modes to escape idiotypic or isotypic immunoregulation. If so, this may be relevant to the prevalence of autoantibody production by this subpopulation. Thus, we are hopeful that some of these unique properties, if confirmed in the Ly-1+ B cells in vivo, will provide more definitive markers for this subpopulation, and disclose mechanisms accounting for their distinctive physiology and pathophysiology.

Animals↗

Does transurethral resection of prostatic carcinoma promote tumor spread?

122 patients with prostatic carcinoma treated by radiation therapy were reviewed. An actuarial analysis was done on survival comparing patients treated by transurethral resection (TURP) prior to radiation to those diagnosed by needle biopsy. Survival rates were not significantly different between groups. TURP was also without effect on interval free of distant or local recurrence. Survival and time to distant or local recurrence were analyzed by tumor stage and grade. A multivariate analysis with the Cox model was made by which the effects of TURP and tumor grade and stage were examined simultaneously. TURP was without effect on survival rates and interval to distant or local recurrence after adjustments had been made for the effects of stage and grade.

Actuarial Analysis↗

Recurrence of intracranial meningiomas: the role played by regional multicentricity. Part 2: Clinical and radiological aspects.

Globular single meningiomas are generally regarded as benign tumors that can be completely removed. Nevertheless, after a total macroscopic resection including the insertion zone (Grade 1 operation according to Simpson's classification), the incidence of recurrence ranged from 9% to 14% at the 5-year follow-up review. The authors have shown that single meningiomas represent only the visible predominant growth in the midst of a wide neoplastic field in the dura mater. Regional multiplicity in meningiomas would thus seem to be the rule. With this in mind, the authors propose to divide recurrences after Grade 1 operations into true local and false regional. A local recurrence is defined as a regrowth within the limits of the previous dural flap. Regional recurrence is when new growth develops outside the previous craniotomy site; this should not be considered as a recurrence but as a new primary site. These regional recurrences might explain some unexpected late tumor growth occurring after a Grade 1 operation. Five illustrative cases in which regional recurrence was detected by computerized tomography are presented. The authors also propose to add a supplementary grade to Simpson's surgical grading: Grade 0. This operation would entail a wide resection of the dura around the attachment zone of the meningioma. The authors hope that with a Grade 0 operation the incidence of recurrence might be reduced.

Adult↗