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Biomedical subjects

G Langer

Publications and source records attributed to G Langer.

At least 37 records · Page 2Linked to original sources
PubMed1992

Plasminogen activators from the saliva of Desmodus rotundus (common vampire bat): unique fibrin specificity.

The saliva of D. rotundus contains at least four plasminogen activators (PAs) which all require fibrin as a cofactor. D. rotundus salivary PAs (DSPAs) exhibit a sequential array of structural motifs such as "Finger" (F), "EGF" (E), "Kringle" (K) and "Protease" (P) which was elucidated by cDNA cloning and sequencing. The respective domain organizations are: FEKP (DSPA alpha 1 and DSPA alpha 2), EKP (DSPA beta) and KP (DSPA gamma). In all four forms the plasmin-sensitive site of tPA is obliterated, indicating that they function as single-chain enzymes. DSPA alpha 1 differs from alpha 2 by amino acid substitutions found mainly in the F, E and K domain, 11% of the total sequence. DSPA beta and gamma, while being closely related to alpha 2, still exhibit 2 and 13 amino acid exchanges, respectively. These sequence heterogeneities, together with results of Southern blot hybridization experiments, strongly suggest that the four DSPA mRNA species originate from different genes. All four forms of DSPA have been expressed in animal cell culture and DSPA alpha 1 was chosen for a detailed pharmacological characterization. In vitro DSPA alpha 1 activity is enhanced 50,000-fold in the presence of fibrin, whereas the activity of single chain tPA is only enhanced 100-fold. At equally effective thrombolytic doses DSPA causes lower bleeding incidence in a rat mesenteric vein model and exhibits high potency, clot selectivity, and speed in the dissolution of fibrin embolized into the lung of anesthetized rats. In the copper coil-induced dog coronary heart infarction model, at doses that achieve patency at equal rates, reocclusion is significantly less frequent than with tPA. These results indicate that DSPA alpha 1 may be a safer and more efficacious thrombolytic agent than the PAs currently in clinical use.

Amino Acid Sequence↗
PubMed1992

Mechanisms of spontaneous shift of surface electrocardiographic configuration during ventricular tachycardia.

OBJECTIVES: The aim of this study was to examine, with multichannel direct cardiac mapping techniques, the mechanisms of spontaneous shift of the QRS configuration in the surface electrocardiogram during episodes of ventricular tachycardia. BACKGROUND: Ventricular tachycardias demonstrating a spontaneous shift in their surface electrocardiographic (ECG) features are occasionally encountered. It is not known whether such changes in configuration are primarily due to a significant change in the tachycardia site of origin or represent alterations in patterns of endocardial and epicardial activation. Knowledge of these features would be helpful, particularly when ablative therapy is considered for the arrhythmias. METHODS: During map-directed cardiac surgery, episodes of ventricular tachycardia were mapped from 224 epicardial and endocardial sites. Episodes of pleomorphic tachycardia were identified and isochronal maps of endocardial and epicardial activation were constructed from representative beats before and after the change in configuration. RESULTS: From 52 consecutive patients who underwent detailed intraoperative mapping, 9 patients with pleomorphic ventricular tachycardia were identified in whom 14 episodes of spontaneous shift occurred. An analysis of the epicardial activation patterns revealed that the sites of earliest epicardial breakthrough showed significant alteration at the time of QRS shift in all occurrences. In 10 of these shift episodes, however, the sites of tachycardia origin, located on the endocardial surface, remained closely adjacent (< 2 cm apart). Although these sites of origin remained relatively constant, significant alterations in the patterns of endocardial activation were seen in most episodes. These included changes in the direction of propagation of the wave front of activation and shifts between monoregional and figure eight patterns of activation. CONCLUSIONS: In most episodes of pleomorphic ventricular tachycardia, the arrhythmia site of origin remains relatively constant. However, patterns of epicardial activation do undergo significant change and appear to be the major determinant of the QRS configuration on the surface ECG.

Cardiac Pacing, Artificial↗
PubMed1991

The plasminogen activator family from the salivary gland of the vampire bat Desmodus rotundus: cloning and expression.

Complementary DNAs coding for four Desmodus rotundus salivary plasminogen activators (DSPAs) were isolated and characterized. The predicted amino acid sequences display structural features also found in tissue-type plasminogen activator. The largest forms (DSPA alpha 1 and -alpha 2) contain a signal peptide, a finger (F), an epidermal growth factor (EGF), a kringle, and a serine protease domain, whereas DSPA beta and -gamma lack the F and F-EGF domains, respectively. Additional differences between the four forms suggest that distinct genes code for the members of the DSPA family. Transfection of DSPA-encoding cDNAs, placed under the control of the simian virus 40 late promoter, into COS-1 cells resulted in the secretion of highly fibrin-dependent PAs.

Amino Acid Sequence↗
PubMed1990

Myocarditis and myocardial hemorrhage associated with thrombotic thrombocytopenic purpura.

Four patients with thrombotic thrombocytopenic purpura (TTP) developed severe cardiac dysfunction. Endomyocardial biopsy in one patient demonstrated focal myocarditis associated with platelet microthrombi. Cardiac function and TTP improved after plasmapheresis therapy in this as well as in two other patients. A fourth patient died owing to extensive intramyocardial confluent hemorrhages. Cardiac involvement in TTP may be due to microvascular thrombosis, hemorrhage, or myocarditis. Severe myocardial dysfunction may improve with treatment aimed at the underlying hematologic disorder.

Adult↗
PubMed1988

Prolactin responses to haloperidol in normal young women.

The prolactin (PRL) responses to intramuscular haloperidol (HPD) (0.5, 1.0, and 1.5 mg) were evaluated in six normal premenopausal women during the follicular and luteal phases of their menstrual cycles. These were compared to the PRL responses to these doses of HPD in normal young men. PRL responses to HPD did not differ between the follicular and luteal phases. The mean log-transformed PRL response to the lowest HPD dose (0.5 mg) in women was less than that in the men, but the women had greater PRL responses than the men to the higher haloperidol doses (1.0 mg and 1.5 mg).

Adult↗
PubMed1988

Plasma concentrations of haloperidol and prolactin and clinical outcome in acutely psychotic patients.

This study was aimed at disclosing possible relationships between short term therapeutic outcome and certain ranges in plasma concentrations of haloperidol and of prolactin. Acutely psychotic patients (n = 28) were diagnosed (by RDC) as schizophrenics acute subtype (n = 17), schizoaffectives manic type, acute subtype (n = 8) and manics (n = 3). Parenteral haloperidol was the pharmacological treatment mostly given; the dose was kept constant intraindividually but varied between patients from 5 to 40 mg/d (median 15 mg/d). Data for statistical analyses of possible psychobiological relationships were analyzed at 12 days (median) of haloperidol regimen, that is at a relatively early cut-off in treatment. Keeping the methodological difficulties in mind, certain ranges in plasma concentrations of haloperidol (16-26.9 mg/ml; (Fig. 1) and of prolactin (64-159.9 mg/ml; (Fig. 2) were found to be associated-statistically independently-with a favourable therapeutic outcome. The rate of recovery was best if a patient came to lie with both plasma levels within these therapeutic ranges (Fig. 3). It is concluded that the combination of pharmacological and neuroendocrinological techniques in psychiatric research may be of substantial use for clinical purposes.

Acute Disease↗
PubMed1987

[The placebo: beyond pretense and the nuisance variable. Arguments in favor of re-evaluating a significant protherapeutic concept ("aura curae")].

In this theoretical paper the concept of placebo is being investigated within a field of tension: on one side the conventional understanding of "placebo", that is empirically inconsistent and scientifically and ethically unsatisfactory, and on the other side the upgraded concept of "aura curae" as suggested by the author, that appears to be less contradictory and also richer in heuristic potential and, conceivably, may be closer to the essence of "placebo" itself. This statement is being corroborated by six main arguments. The first three arguments are meant to weaken the conventional concept of "placebo": The first argument deals with the empirical inconsistencies of the traditional placebo concept; the second addresses the possible distortion of scientific conclusions drawn from a conventional "placebo-controlled" trial; the third argument deals with the ethical problems of "pretense" and of "withholding adequate medication". The following three corresponding arguments are put forward in support of the upgraded placebo-concept of "aura curae" (Latin: "air of care"; "unspecific healing context"). The fourth argument introduces the concept of "aura curae" itself; the fifth argument deals with two alternatives to the conventional placebo-controlled trial, namely the "placebo-integration" and the "value added efficacy"; the sixth argument concludes with a discussion of the ethical advantages of implementing the concept of "aura curae" in clinical and research practice. The purpose of this paper is to contribute to a comprehensive "healing context", that would better fit the patient's needs; i.e., in addition to the various traditional "therapies" of specific influence (biological and psychosocial), the "protherapeutic" and unspecific effects of the "aura curae" should be integrated into a systemic patient care.

Clinical Trials as Topic↗
PubMed1987

[Placebo-controlled studies with mianserin. Discussion from the viewpoint of a re-evaluated placebo concept].

In this paper the literature on placebo-controlled studies with Mianserin is being commented in view of the enclosed discourse "Placebo: Beyond pretense and nuisance variable." This paper's purpose is to enrich the understanding of the effect of a drug under everyday therapeutic conditions, an understanding, that derives from the physicians synthesis of personal uncontrolled observations of a drug's profile and the reported "mean-effect" in placebo-controlled studies.

Clinical Trials as Topic↗
PubMed1986

[Psychotherapeutic effects of psychotropic drugs: principle considerations from the psychobiologic viewpoint].

The paper presents, from a psychobiological perspective, a critical and pragmatic discussion on fundamental questions related to the psychotherapeutic effects of psychopharmacological drugs. A series of definitions of the terms "psychopharmacological drugs", "cerebrotropic" and "psychotropic", "psychoactive and psychotherapeutic effects" and psychobiological" are initially given and set within a psychobiological framework of reference. The purpose of this is to reduce inherent contradictions of conventional definitions and to prove the heuristic value of the new concept. The epistemological basis of the presented reasoning is the psycho-physical identity theory that is based on the theories of systems and biological evolution. The author further discusses questions on the neurobiological and psychotherapeutical effects of psychopharmacological drugs, their locus and mechanism of action and other aspects related to the theme. Finally, the problem is raised as to how to separate from each other the multidimensional therapeutic factors, which alltogether result in the final psychotherapeutic effect of the drugs. Among these therapeutic factors, the so-called placebo is of prominent importance; the author presents a definition of placebo that fit the conceptual framework of the paper.

Brain↗
PubMed1986

[Possibilities of endoprosthetic joint replacement].

Nowadays arthroplastic operations determine the everyday work in the orthopaedic clinic. The good primary results show a distinct change of indications in favour of the artificial joint replacement. After a longer duration of implantation is to be reckoned with a failure quote of 10% and more. Here the problems of the durable anchoring of the prosthesis, the late infection and the exhaustion of the material are in the foreground. In the development of endoprosthesis in the GDR as carriers of the power the nickel-free cobalt-basis alloy Prothecast and as sliding partner the highly pure Hermsdorf aluminum oxide ceramic material were used as implant materials. These biomaterials best stood the test.

Biocompatible Materials↗
PubMed1986

Response of thyrotropin to thyrotropin-releasing hormone as predictor of treatment outcome. Prediction of recovery and relapse in treatment with antidepressants and neuroleptics.

We determined whether the response of thyrotropin (TSH) to thyrotropin-releasing hormone could predict the outcome of treatment with antidepressant and neuroleptic drugs. We studied 114 female patients diagnosed as having major and minor depressive, manic, schizoaffective, and schizophrenic disorders. A blunted TSH response (less than 5 microU/mL [less than 5 mU/L]) at admission was associated with recovery after nine weeks of inpatient treatment using clomipramine hydrochloride for depression and haloperidol for psychosis. A blunted TSH response at discharge was associated with early relapse in depressives receiving clomipramine maintenance therapy. Our findings support the notion that the thyrotropin-releasing hormone test is a "state" marker that may be of use in predicting the outcome of treatment with antidepressant and neuroleptic drugs.

Adolescent↗
PubMed1986

[Comparison of the bioavailability of two diazepam preparations. Clinical comparison between a new commercial preparation and a standard preparation after oral and intramuscular administration].

The following pharmacokinetic study was aimed at a comparison of the bioavailability of two different preparations of diazepam (Gewacalm and a further wellknown formulation). 40 healthy volunteers were subjected to a cross-over design in which plasma levels of diazepam were assayed after oral and intramuscular application of 10 mg of a preparation. In the comparison (N = 30) of oral bioavailability (rate and completeness of enteral absorption) no statistical difference between both preparations was observed. In the study of intramuscular bioavailability (N = 10), a trend of quicker and more complete resorption of Gewacalm was of statistical significance (p less than 0.05), however, because of the small number of subjects tested in the intramuscular study a replication study is advisable.

Administration, Oral↗
PubMed1985

[Long-term administration of antidepressive agents: maintenance therapy and phase prevention].

Long-term regimen of psychotropic drugs in depression is particularly indicated in those patients who benefit most from the drugs, namely patients of the "endogenous" or "endogenomorphic" type. Medication over months or even years is indicated for two frequently concurrent reasons: firstly for "maintenance therapy", i.e., medication should be continued after remission of the depressive syndrome because of not yet identifiable "vulnerability" to relapse in many patients and, secondly, for "prophylactic therapy", i.e. medication can be given during apparent psychological health and in the absence of any imminent risk in order to prevent a possible new episode of depression. Long-term regimen of both types of medication is different, though not decisively so. Neither can cure a patient of depression; however, recurrence of the psychopathological syndrome can be successfully prevented. This paper presents a practical and updated discussion of various questions related to long-term regimen with psychotropic drugs used in depression: tricyclic antidepressants, lithium, carbamazepine and others.

Antidepressive Agents, Tricyclic↗
PubMed1985

Release of human neurophysin I during insulin-induced hypoglycemia in depressed patients is abolished after recovery with clomipramine treatment.

Release of human neurophysin I (hNp I) and neurophysin II (hNp II) during insulin-induced hypoglycemia was studied in 10 unipolar depressed women before and after 4-5 weeks of standard antidepressant drug treatment with daily intravenous infusions of clomipramine. Before treatment, a significant increase of hNp I but not of hNp II serum levels in response to hypoglycemia was observed. At retest during clomipramine administration, a marked clinical amelioration occurred in all patients as determined with the Hamilton Rating Scale for Depression; the hNp I response to insulin was abolished, but no effect on hNp II concentration could be demonstrated. No correlation was found between the degree of the depression score decrease and the amplitude of the inhibition of hNp I release or serum levels of clomipramine or its metabolite, desmethylclomipramine. The meaning of this difference in reactivity of the neurohypophyseal system in the course of depressive illness, based on the pharmacological and biochemical profiles of clomipramine action, is discussed.

Blood Glucose↗
PubMed1985

Rapid psychotherapeutic effects of anesthesia with isoflurane (ES narcotherapy) in treatment-refractory depressed patients.

Treatment-refractory depressed patients who objected to electroconvulsive therapy (ECT) were given a series of anesthesias with isoflurane (Forane), a modern and established inhalation anesthetic. According to our hypothesis to be tested, the brief period of electrocerebral silence (ES), which can be observed shortly after the grand mal seizure in ECT, may be in itself a crucial biological determinant for the therapeutic effects of ECT. Isoflurane is the only drug known to effect an ES in the EEG in nontoxic concentrations, which does not result in adverse effects on any body organ including the brain; no seizure activity can be observed. Eleven depressed patients received a total of 36 anesthesias with isoflurane (ES narcotherapy). Rapid antidepressant effects were observed in 9 patients (p less than 0.0001). Effects were reproducible and lasted up to several weeks. No adverse effects of anesthesia were noticed.

Adult↗