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Biomedical subjects

J F Hartmann

Publications and source records attributed to J F Hartmann.

At least 37 records · Page 2Linked to original sources

Hemodynamic patterns of meningococcal shock in children.

Meningococcal shock still is associated with high mortality. Along with antibiotics and control of metabolic derangements, standard therapy involves monitoring and maintaining numerous cardiorespiratory variables. From 1980 to 1985, 39 children with meningococcal shock were treated in our pediatric ICU. We obtained full hemodynamic monitoring in 18 (12 survivors, six nonsurvivors). Two hemodynamic patterns were observed: hypovolemia and cardiac failure. Early death was generally related to refractory hypovolemia, probably secondary to severe capillary leak. Survival usually occurred when noticeable cardiac failure was controlled with early use of catecholamines and judicious fluid management. Because cardiac failure only slowly recovered, a therapeutic approach that aims not at normal variables but, rather, at survival variables seems appropriate.

Blood Volume↗

Effects of the angiotensin converting enzyme inhibitor, lisinopril, on normal and diabetic rats.

The comparative effects of lisinopril, a third generation angiotensin converting enzyme (ACE) inhibitor, on components of the renin-angiotensin system were assessed in normal and in an animal model of diabetes-related hypertension, the streptozotocin-diabetic rat. Two weeks after injection of streptozotocin the mean systolic blood pressure of diabetic rats was elevated 11% above that of normal rats. This effect was prevented by daily injection of insulin. The mean serum ACE activity was elevated 71% above that of normal rats. Lisinopril reduced systolic blood pressure and inhibited serum ACE activity in both normal and diabetic rats in a dose-response fashion. In normal rats maximum inhibition of blood pressure occurred at a mean dose of 1.0 mg/kg and in the diabetic rat at a mean dose of 5.0 mg/kg. At a mean dose of 5 mg/kg, ACE was inhibited by 100 and 92% in normal and diabetic rats, respectively. Plasma renin activity (PRA) increased sharply in both groups of rats treated with the lower doses of lisinopril, only to decrease at the 5 mg/kg level. At 20 mg/kg, PRA continued to decline in normal animals, but not in diabetic rats. Formation of angiotensin II (Ang II) in both normal and diabetic rats was maximally inhibited at doses of 1.0 and 0.1 mg/kg of lisinopril, respectively without a significantly greater effect at the higher doses of the drug. In separate experiments the effects of chronic treatment with lisinopril at two dosage levels on various physiological parameters of streptozotocin-diabetic rats were compared with the effects of another hypotensive agent, hydralazine, an arteriolar vasodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

[Agglutination of intravenous lipid emulsions by acute phase proteins of inflammation].

Agglutination of intravenous fat emulsions (IVFE) by sera of acutely ill children was studied in vitro in 23 patients. C-Reactive protein (CRP) has been showed to agglutinate with IVFE; after discarding CRP, serum of acutely ill patients still agglutinate with IVFE. The agglutination score in generalized sepsis is significantly highest than in localized sepsis. We studied agglutination during three periods: first days of treatment by antibiotics (period 1), between the fourth day and the end of treatment (period 2), and after the end of treatment (period 3). In period 2, when orosomucoid concentrations; nevertheless, the observation of an agglutination in periods 1 and 3 where the mean orosomucoid level is within normal range, strongly suggests that one or more others acute phase proteins are also involved in occurrence of agglutination.

Agglutination↗

[Immune response in splenectomized children to anti-pneumococcal vaccination].

The antibody response following anti-pneumococcal immunization with a 14-valent vaccine was studied in 54 children, aged 2 to 18 years after splenectomy. Splenectomy had been performed for traumatic, hematologic or immunologic reasons. Antibody titration with respect to 12 serotypes was performed by radioimmunoassay immediately before and one month after immunization. Changes in responses were studied according to the indication for splenectomy and to the vaccine serotype. The main conclusions of this study are the excellent tolerance of immunization, the lack of significant difference between the average responses according to the indications for splenectomy, the obtainment of a titer probably protective for 80% of the patient studied and the confirmation of the low immunogenic character of serotype 6A. These results suggest that anti-pneumococcal prophylaxis by immunization can be highly recommended before splenectomy but it can also be performed after surgery.

Adolescent↗

[Neonatal syphilis despite erythromycin treatment of the mother].

A one-month old infant whose mother had been treated with erythromycin during pregnancy exhibited signs of severe congenital syphilis with collapse requiring admission to an intensive care unit. Erythromycin has low placental transfer and other treatments would have probably been more adequate. Some authors advocate the use of the latest tetracyclines and doxycycline could also be administered. The WHO's recommendations that all children born of mothers who were not treated with penicillin should receive this antibiotic after birth is still valid.

Erythromycin↗

Application of an in vitro semi-microtest to the study of drug sensitivity of 66 Plasmodium falciparum isolates from 15 countries.

The activity of four antimalarial drugs against 66 Plasmodium falciparum isolates from 15 countries was assessed by an in vitro semi-microtest. Median inhibitory concentrations (IC50) for chloroquine were less than 120 nM in 22 isolates from patients successfully treated with chloroquine, and more than 250 nM in six isolates from patients with chloroquine-resistant malaria. 10 of 15 isolates from Brazil (Amazonia), 7 of 12 isolates from Madagascar, two from Kenya and two from Thailand had IC50 for chloroquine of more than 250 nM. None of the 35 isolates from West and Central Africa had IC50 of more than 120 nM. Very different levels of sensitivity were observed in Brazil and Madagascar. 27 of 28 isolates (including two that were chloroquine-resistant in vivo) had IC50 of less than 50 nM for dichlorquinazine, a 4-aminoquinoline. The IC50 for mefloquine was less than 160 nM in 55 isolates including ten from patients who were successfully treated with mefloquine. IC50 for quinine were between 140 and 660 nM for 30 isolates. This test has proved useful in epidemiological studies, therapeutic monitoring of clinical cases and in the evaluation of new drugs.

Animals↗

Pig bronchial mucous membrane: a model system for assessing respiratory mucus release in vitro.

A convenient organ culture system is described in which fragments of mucous membrane isolated from bronchi of the pig were maintained in either screw-cap tubes or multiwell tissue culture plates. The mucous membrane of the pig bronchus, like that of the human, is rich in mucus-secreting submucosal glands and can respond to cholinergic stimulation in vitro by releasing either L-[3H]fucose- or L-[3H]serine-labeled acid-precipitable macromolecules. Reproducible cholinergic-mediated release of labeled macromolecules was attained by first washing the mucous membrane fragments in serum-free modified Earles medium (Dulbecco's) for 120 min at 4 degrees C. Maximum stimulation was obtained when the incubation medium was supplemented with 0.5-2.0% horse serum. Approximately 50% of L-[3H]fucose-labeled macromolecules were eluted in the void volume from a column of Sepharose CL-6B in 6 M urea. Cochromatography of L-[3H]- and L-[14C]fucose-labeled glycoproteins released by mucous membranes of control and methacholine-treated tissue fragments failed to reveal any significant difference in any specific population of fucose-labeled glycoproteins. It is concluded that, as a whole, many different labeled molecules are released in response to cholinergic stimulation. Taken together, these results suggest that the mucous membrane of the porcine bronchus is a useful in vitro model for studying respiratory mucus secretion.

Animals↗

[Intestinal occlusion and enterocolitis caused by Gelopectose].

A case of intestinal obstruction and enterocolitis, probably as a consequence of inappropriate use of thickened feedings, is reported. Products which thicken feedings take an important part in the treatment of gastro-oesophageal reflux in infants. In order to thicken feedings, pectin and silicium have been added to milk. However, they may lead to an obstructive medication bezoar. Thus, it is necessary to limit their use to 3-5% of feeding and to clearly explain their potential hazards to the family.

Enterocolitis↗

[Standardisation of the in vitro chemosensitivity test for Plasmodium falciparum ].

Reliable in vitro tests are needed to study the epidemiology, pharmacology, genetics and the treatment of Falciparum malaria. We have studied the reproducible nature of an in vitro method using either patients blood or a continuous strain with which we did 254 chemosensitivity tests with chloroquine, mefloquine and quinine. The method is based on ED50 determination which is done by assessing the plasmodial maturation on thin blood film after 24-48 hours incubation. This method is simple to carryout but long to interpret. It has proved reliable and sensitive enough to be used for the proposed studies. The blood group, the limited variations of erythrocyte concentrations, of the composition and volume of the culture medium, of the atmosphere and of the incubation time had little influence on the ED50. It was considered that 47 p. cent of the tests could be interpreted and that this percentage could be improved with a better understanding of the in vitro behaviour of P. falciparum.

Antimalarials↗

Modulation of fertilization in vitro by peptides released during hamster sperm-zona pellucida interaction.

The penetration of the zona-pellucida by hamster sperm in vitro (assay drops) was inhibited by aliquots of ultrafiltrates obtained from another set of drops (experimental drops) in which capacitated sperm had interacted with the surface of the zona pellucida. This inhibition was inversely related to the concentration of sperm in the assay drop, and it was noted that the inhibitory response declined when the gametes in the assay drop were incubated together beyond the standard 90-min period. Thus, inhibition was not irreversible. A number of criteria suggest that the inhibitory activity resides in at least some of the peptides (S1 factors) released at four different times after contact between the surfaces of the sperm and zona pellucida. Like the S1 factors, the substances responsible for the inhibitory activity of the supernatants, collected at 2 and 50 min after gamete combination, traversed ultrafilters with Mr cutoffs of 5000 and 2000, respectively, and were inactivated by subtilisin. In addition, the quantity of inhibitory material recovered in the ultrafiltrates from experimental drops containing various numbers of eggs was well correlated with the amount of 2- and 50-min S1 factors from similar experimental drops. These results suggest that the S1 factors are peptide modulators of the penetration process and it is speculated that one of their functions may be to prevent or at least to discourage polyspermic penetration of the hamster zona pellucida.

Animals↗

Effects of pentoxifylline on cerebral ultrastructure of normal and ischemic gerbils.

Normal gerbils and those made ischemic for 15 to 60 minutes by bilateral common carotid artery occlusion were studied ultrastructurally after administration of the vasoactive drug pentoxifylline. In both groups, hypertrophy of neuronal mitochondria was found in the hippocampus and cerebral cortex. Planimetry of electron micrographs revealed a statistically significant increase in average mitochondrial size of drug-treated animals compared with untreated ischemic gerbils and normal controls; the treated ischemic group showed the greatest increase. Incubated cortical slices from normal gerbils that were given the drug 5 hours before they were killed showed a significant increase in oxygen consumption compared with controls.

Animals↗

Surface interactions between mammalian sperm and egg: variation of spermatozoa concentration as a probe for the study of binding in vitro.

The pre-penetration binding interactions between gametes of the golden hamster were investigated in vitro. Binding between capacitated spermatozoa and the surface of eggs, that is the zonae pellucidae with intact vitelli, as a function of the concentration of spermatozoa, followed a sigmoidal curve. This was in sharp contrast to the linear binding obtained with mechanically isolated zonae pellucidae (zonae lacking vitelli). Penetration of eggs as a function of the concentration of spermatozoa paralleled the binding curve that occurred between gametes. The binding curve obtained with uncapacitated spermatozoa and eggs was not sigmoidal but was linear after a slight lag and parallel to the curve obtained with uncapacitated spermatozoa and isolated zonae pellucidae. Taken together these results support previous work which implicated a vitelline factor in the binding reaction between the surfaces of eggs and capacitated spermatozoa. By scoring binding at one minute intervals it was possible to relate the rapid uninterrupted binding that occurs between capacitated spermatozoa and isolated zonae pellucidae with the equally rapid but transient and vitellus-influenced binding that occurs between gametes. It was concluded that the vitelline factor acts by preventing most of the early type of binding that occurs between spermatozoa and isolated zonae pellucidae and not by terminating the early, rapid, initial binding as previously postulated. Thus, this early binding never occurs between most of the gametes that finally bind 30 to 40 minutes later and, therefore, does not play a role in the establishment of the late binding step which leads to penetration.

Animals↗

Experimental acute lead encephalopathy in the juvenile rhesus monkey.

Lead subacetate (0.5g) and 1000 units of vitamin D were given three times a week to four newly-weaned rhesus monkeys. In addition, two animals received only the vitamin D. The poisoned animals had an increase in the urinary excretion of delta-aminolevulinic acid, an elevated content of lead in the blood, and a fall in hemoglobin concentration. Between 6 and 18 weeks the animals suddenly developed ataxia, nystagmus, generalized weakness, and convulsions. At this time the animals were killed by perfusion of fixative and the brain prepared for light and electron microscopic studies. Definite morphological evidence of disease was confined to the central nervous system, except for one animal which showed the characteristic renal inclusions of lead poisoning. All animals showed PAS-positive globules associated with blood vessels and an exudative edema involving the white matter of the cerebral hemispheres and cerebellum. Ultra-structurally, this appeared as a granular precipitate within an expanded extracellular space. Alterations of nerve fibers were not seen in the white matter but axonal swelling was observed in the cerebral cortex. The perikaryon and neuropil appeared normal. The control animals showed no significant cerebral changes.

Acute Disease↗