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Biomedical subjects

E Martin

Publications and source records attributed to E Martin.

At least 433 records · Page 24Linked to original sources
PubMed1993

Ceftriaxone--bilirubin-albumin interactions in the neonate: an in vivo study.

The in vivo bilirubin-albumin binding interaction of ceftriaxone (CRO) was investigated in 14 non-jaundiced newborns, aged 33-42 weeks of gestation, during the first few days of life after they had reached stable clinical condition. CRO (50 mg/kg) was infused intravenously over 30 min. The competitive binding effect of CRO on the bilirubin-albumin complex was estimated by determining the reserve albumin concentration (RAC) at baseline, at the end of CRO infusion, and at 15 and 60 min thereafter. Immediately after the end of drug administration, RAC decreased from 91.9 (+/- 25.1) mumol/l to 38.6 (+/- 10.1) mumol/l (P = 0.0001). At the same time the plasma bilirubin toxicity index (PBTI) increased from 0.64 (+/- 0.40) before drug infusion to 0.96 (+/- 0.44) thereafter (P = 0.0001). The highest displacement factor (DF) was calculated to be 2.8 (+/- 0.6) at the end of drug infusion. Average total serum bilirubin concentrations decreased from a baseline value of 59.6 (+/- 27.0) mumol/l to 55.2 (+/- 27.1) mumol/l (P = 0.026). Sixty minutes after the end of CRO infusion, RAC was 58.3 (+/- 21.7) mumol/l, PBTI regained baseline, but DF was still 1.9 (+/- 0.2). No adverse events were recorded. Our results demonstrate significant competitive interaction of CRO with bilirubin-albumin binding in vivo. Thus, ceftriaxone should not be given to the neonate at risk of developing bilirubin encephalopathy.

Bilirubin↗
PubMed1993

Pituitary stalk thickening with diabetes insipidus preceding typical manifestations of Langerhans cell histiocytosis in children.

In up to 25% of cases of children with central diabetes insipidus no organic cause can be documented. We present three boys (age 2.2, 2.3 and 6 years at diagnosis) with acute onset central diabetes insipidus, in whom the only pathological finding using MRI was a thickened central part of the pituitary stalk (> 2.5 mm). Recent reports demonstrate similar MRI findings in adults with Langerhans cell histiocytosis (LCH), sarcoidosis, or tuberculosis, and in children with proven LCH and diabetes insipidus. In those adults with LCH, the pituitary stalk lesion has been histologically verified as a sequela of LCH. In contrast, in two of our three patients pituitary stalk thickening preceded the typical peripheral lesions of LCH by several months, whereas in the third patient there is as yet no evidence of systemic disease. We conclude that thickening of the central part of the pituitary stalk might represent the first manifestations of LCH clinically presenting with diabetes insipidus. MRI investigation of the pituitary stalk in children with unexplained central diabetes insipidus and accurate follow up in patients with thickening of the pituitary stalk in necessary to avoid missing other manifestations of a systemic disease.

Acute Disease↗
PubMed1993

Regulatory role of enteric kappa opioid receptors in human colonic motility.

The effects of different kappa opioid agonists and antagonists on spontaneous mechanical activities and responses to electrical transmural nerve stimulation of both longitudinal and circular muscle strips from the human sigmoid colon were studied. A superfusion apparatus was used to record isometric contractions. Exogenously added kappa agonists did not modify spontaneous contractile activities on either type of strip. Nerve stimulation induced a triphasic response composed of a first contraction (C1) followed by a relaxation (C2) and an off-contraction (C3); this response was mediated by cholinergic excitatory nerves and non-adrenergic, non-cholinergic excitatory and inhibitory nerves. Dynorphin 1-13 and the synthetic kappa agonist trans-3,4-dichloro-N-methyl-N-(2- [1pyrolidinyl]-cyclohexyl) dramatically decreased the amplitude of the excitatory components C1 and C3. The effects of both kappa agonists were blocked in presence of the kappa antagonist Nor-Binaltorphimine. The delta antagonist ICI 174864 did not prevent the inhibition of the contractions C1 and C3 induced by dynorphin. Therefore, these data suggest that kappa receptors are involved in the neuroregulation of smooth muscle of human colon and mediate inhibition of cholinergic and non-cholinergic excitatory transmission within myenteric plexus.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Congenital hemiplegia: morphology of cerebral lesions and pathogenetic aspects from MRI.

We have analyzed the MRI findings from the brains of 33 children with congenital hemiplegia. Referral of these children to our hospital was either because of neurological problems or a history of complicated birth. According to maturation-dependent pathophysiological mechanisms we have classified the lesions into the following five groups: 1. malformations/prenatal encephalo-clastic lesions, 2. periventricular leukomalacia or atrophy, 3. diencephalic lesions, 4. subcortical and cortical lesions, and 5. normal findings. Combination of lesions was not uncommon. The neuroradiologically most prominent and most expanded lesions determined the classification to the different groups. We detected malformations/encephalo-clastic lesions (Group 1) in 5 children; one of these children also presented additional lesions of Groups 2 and 3. Six children displayed periventricular leukomalacia (Group 2), and in one child in combination with diencephalic and subcortical lesions. Ten children exhibited diencephalic lesions (Group 3), in one case combined with periventricular leukomalacia. The MRI of seven children showed subcortical/cortical lesions (Group 4), in four cases extending into diencephalic structures. Two children had a combination of evenly matched periventricular, diencephalic and subcortical/cortical lesions, where it was impossible to define a principal lesion. Three children had normal MRI findings. Significantly, 8 of 33 children had bilateral lesions although presenting with hemiplegia. The large proportion of diencephalic lesions, not described in similar CT studies, and the small number of normal MRI findings show the value of MRI in evaluation of congenital hemiplegia. The ability to correlate, to some extent, neuroradiological findings of damage to developmental stage affords the conclusion that at least a third of the children in our series with congenital hemiplegia suffered prenatal damage.

Brain↗
PubMed1993

Changes in the peritoneum during the development of the testis, epididymis and ductus deferens in the pig.

The development of the peritoneal folds of the testis, epididymis and ductus deferens of the pig prior to testicular descent was studied in 18 to 82 days-old embryos/fetuses. The parietal attachment of the mesonephros, mesonephric and paramesonephric ducts and gubernaculum constituted the urogenital mesentery. This could be divided in a cranial and a caudal part. The first fixed the mesonephros and had a mesogonad as a secondary fold. The second had two branches, one laterally to the umbilical artery belonging to the gubernaculum (Plica gubernacularis) and the medial to the artery contained the meso- and paramesonephric ducts. The mesogonad was related caudally with Plica gubernacularis. The fold of the meso- and paramesonephric ducts could also be divided in two parts. The caudal was a primary component of the urogenital mesentery, while the cranial was first ventral and later lateral to the mesogonad (mesorchium) and appeared as a secondary fold of the urogenital mesentery (cranial part). A vascular fold contributed to separate the suspensory ligament of the testis from the developing mesorchium. The proposed meaning of the terms used might be useful for comparative studies.

Animals↗
PubMed1993

Inhibition of hepatic microsomal drug metabolism by atracurium administration in the rat.

The muscle relaxant atracurium is known to undergo extrahepatic degradation via Hofmann elimination and ester hydrolysis. The purpose of the present study was to evaluate the effects of atracurium on hepatic P450-dependent enzyme activities. Thirty-two male Sprague-Dawley rats were anaesthetized, mechanically ventilated, and randomly allocated to one of four study groups: group 1 received saline, group 2 atracurium, group 3 vecuronium, and group 4 pancuronium intravenously for a period of 3 hr. Equipotent doses of the muscle relaxants were applied; the doses had been obtained in a pilot study using evoked electromyography. At the end of the study period, the livers were removed and analyzed. All three muscle relaxants may lead to inhibition of hepatic drug metabolism. Atracurium influences hepatic P450, although it is predominantly degraded in extrahepatic tissues. Further studies are needed to evaluate the contribution of the major metabolite laudanosine to this inhibitory action.

Aminopyrine N-Demethylase↗
PubMed1993

Staphylococcal alpha-toxin kills human keratinocytes by permeabilizing the plasma membrane for monovalent ions.

Incubation of human keratinocytes with nanomolar concentrations of Staphylococcus aureus alpha-toxin leads to irreversible depletion of cellular ATP. The toxin forms hexamers in the target cell membranes, and rapid transmembrane flux of K+, Na+, and 86Rb+ is observed. Unexpectedly, pores formed in keratinocytes through application of low but lethal doses of alpha-toxin appeared to be considerably smaller than those formed in erythrocyte membranes. They permitted neither rapid influx of Ca2+ or propidium iodide, nor efflux of carboxyfluorescein. Larger pores allowing flux of all three markers did form when the toxin was applied at high concentrations. Flux of monovalent ions and reduction in cellular ATP levels evoked by low toxin doses correlated temporally with a fall in oxygen consumption, which was interpreted to reflect breakdown of mitochondrial respiration. The lethal event could not be thwarted by manipulating the extracellular K+ or Ca2+ concentrations. Realization that alpha-toxin may form very small pores in nucleated cells is important for future research on cellular toxin effects and membrane repair processes.

Bacterial Toxins↗
PubMed1993

Can analysts agree? The problems of consensus and the psychoanalytic mannequin: II. Empirical tests.

The present investigation reports on the execution of an empirical strategy for testing agreement in complex clinical psychoanalytic propositions, and for testing whether stereotypical assumptions are overridden (revised) by the specific character of the patient's narrative. The findings reveal that, in general, for the several domains of psychoanalytic formulation, psychoanalyst judges reach superior levels of ordinal agreement, and modest to good levels for agreement on magnitude. Moreover, formulations based on verbatim psychoanalytic sessions pass the "test of the mannequin" in most domains, i.e., surpass stereotypical psychoanalytic assumptions about the patient's dynamics. The mannequin concept, here operationalized, introduces a new and epistemically crucial consideration for the making of psychodynamic formulations. Other novel contributions of these studies include the development of operationalized measures of (reconstructive) historical linkage, and the introduction of magnitudinal agreement in this empirical area.

Adult↗
PubMed1993

Non-opioid peptides for analgesia.

Amongst the spinal peptide candidates believed to be involved in the mediation of analgesia, only somatostatin fulfills the criterium of a real analgesia substance. Spinal somatostatin specifically blocks the transmission of painful stimuli. Spinal calcitonin may lower the opioid dose requirement in patients with bone metastases but it fails to relieve acute pain. The usefulness of ACTH and CRF for treatment of pain remains to be established. The role of CCK-8, vasopressin and neurotensin is unclear. The contradictory findings on antinociception using simple rodent withdrawal reflex tests (e.g. the tail flick test), or more complex behavioral tests in which supraspinal sensory processing is involved, (e.g. the hot plate test), indicate that these tests are inappropriate when neuropeptides are employed. Furthermore, due to their inability to predict analgesia in humans, they do not fulfill the guidelines proposed by the IASP that animal test procedures have to be for the benefit of humans.

Analgesia↗
PubMed1993

[Acute thromboembolism of the lung. Clinical picture--pathophysiology--diagnosis--therapy].

Pulmonary embolism must often be considered as a differential diagnosis, especially in the perioperative period. Only prompt therapeutic measures can reduce the high early mortality in the acute phase of this condition. Diagnostic and therapeutic measures are dependent on the severity of the symptoms. If pulmonary embolism is suspected, heparin is administered. In the case of cardiovascular deterioration, other measures have to be taken. Following confirmation of the diagnosis of pulmonary embolism, several thrombolytic regimens are applicable. Low-dose urokinase (bolus 250,000 U followed by 60,000-80,000 U/h) is associated with a relatively low incidence of bleeding complications. A more rapid reduction of the right ventricular afterload will be achieved via short-term thrombolysis. Newer findings suggest that bolus thrombolysis with 3 million U urokinase is as effective as 100 mg tissue plasminogen activator (rt-PA) administered over a 2-h period. When the patient is found to be in a state of shock, confirmation of the diagnosis has to be delayed. Recommendations include the bolus application of 1.5-3 million U urokinase when right ventricular decompensation is prominent or during cardiopulmonary resuscitation. In case of existing contraindications or postoperatively, low-dose urokinase treatment (bolus 250,000 U followed by 40,000-60,000 U/h, rarely up to 2,200 U/kg per hour) may be initiated when the situation is urgent and there are no treatment alternatives. Bolus application of 1-2 million U urokinase should be considered depending on the severity of the symptoms and the underlying disease. In some hospitals, alternative treatment modalities include catheter-assisted procedures with subsequent local thrombolysis and surgical embolectomy. Pathophysiological aspects as well as therapeutic options in the intensive care unit are discussed in depth. In addition to adequate oxygenation, right ventricular coronary perfusion and contractility may be maintained using various catecholamine infusions. The importance of phosphodiesterase inhibitors, mediator antagonists such as acetylsalicylic acid or ketanserin, and dilators of the pulmonary vascular bed are discussed.

Acute Disease↗
PubMed1993

Oral clonidine premedication prevents the rise in intraocular pressure following succinylcholine administration.

The objective of the study was to assess the effects of premedication with clonidine on intraocular pressure (IOP) after the administration of succinylcholine. Fifty elderly patients undergoing ophthalmic surgery were randomly allocated to two study groups. Group 1 patients (n = 25) received clonidine, 300 micrograms p.o. In group 2 (n = 25), the benzodiazepine dipotassium clorazepate was given p.o. at a dose of 0.3 mg.kg-1. Anesthesia was induced with thiopental 3-4 mg.kg-1, alfentanil 10 micrograms.kg-1, atracurium 0.07 mg.kg-1, and succinylcholine 1 mg.kg-1. Nine IOP measurements were taken in each patient starting before premedication and ending 3 min after endotracheal intubation. In both groups, there was a decrease in IOP after induction of anesthesia with thiopental and alfentanil. Succinylcholine administration and endotracheal intubation had no further effect on IOP in the clonidine group. In group 2, succinylcholine caused an increase in IOP when compared with the post induction value. We conclude that clonidine premedication can prevent the increase in IOP following succinylcholine administration.

Administration, Oral↗
PubMed1992

Genetic dissection of the transcription cycle. A mutant RNA polymerase that cannot hold onto a promoter.

Deletion of 10 amino acids from a conserved motif in the beta subunit of Escherichia coli RNA polymerase (RNAP) leads to an interrupted transcription cycle and lethal phenotype. RNAP carrying the mutant subunit retains catalytic function and specificity of promoter recognition but is unable to efficiently hold onto DNA in the binary complex, resulting in a diminished initiation frequency. However, inefficient initiation by the mutant enzyme leads to processive and stable ternary elongating complex. Thus, the mutation dissects the traits of promoter selectivity, binary complex stability, and ternary complex processivity reflecting compartmentalization of function within the RNAP molecule.

Amino Acid Sequence↗
PubMed1992

Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo.

Complement plays a role in activating the inflammatory response and has been implicated in the pathogenesis of some inflammatory diseases. With a view toward controlling unwanted C activation, we evaluated the C regulator, human decay accelerating factor (DAF). Three forms of recombinant DAF were purified from transfected Chinese hamster ovary cells: glycophosphatidylinositol (GPI)-linked membrane DAF (mDAF) extracted from cell membranes; spontaneously shed soluble DAF (sDAF) derived from mDAF; and a novel secreted protein (seDAF), generated by deletion of the signal for GPI attachment. We show that all three molecules inhibit both the classical and alternative pathways of C activation. The following observations indicate that mDAF extracted from Chinese hamster ovary cells reincorporates into RBC membranes via its GPI anchor: 1) cells that are preincubated with mDAF and then washed remain fully protected from C-mediated hemolysis; 2) incubation with phosphatidylinositol-specific phospholipase C abolishes this protection; and 3) sDAF and seDAF, which lack a GPI anchor, do not associate with cell membranes. mDAF is a more potent inhibitor of C-mediated hemolysis than either sDAF or seDAF, suggesting that incorporation into cell membranes greatly enhances the efficiency with which DAF inhibits C activation on the cell surface. In contrast, C activation in the fluid phase is inhibited by sDAF and seDAF, but not by mDAF, possibly due to interference by serum lipoproteins. A reversed passive Arthus reaction in guinea pigs was used to evaluate the ability of recombinant seDAF to inhibit C activation in vivo. When administered at dermal sites, seDAF reduced the severity of immune complex-mediated inflammatory reactions induced by a reversed passive Arthus reaction, as judged by both gross and histologic examination. These data indicate that seDAF may be useful as an anti-inflammatory therapeutic.

Animals↗