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Biomedical subjects

D Charles

Publications and source records attributed to D Charles.

At least 37 records · Page 2Linked to original sources

Accumulation of pepstatin in cultured endothelial cells and its effect on endothelial processing.

Aspartic acid proteases have been implicated in the processing of ET-1(1-39) to ET-1(1-21). To further understand the role of this class of enzymes in ET-1 synthesis, cultured vascular endothelial cells were incubated with pepstatin, and the accumulation of the inhibitor and its effect on the processing of ET-1(1-39) was examined. Pepstatin accumulated in the cells in a time-dependent manner, to a concentration (greater than 10(-7) M) sufficient to inhibit aspartic acid proteases. Pepstatin did not alter the ratio of ET-1(1-21) to ET-1(1-39), nor did it affect the rate of secretion of either peptide. When endothelial cells were incubated with phosphoramidon under identical conditions, the secretion of ET-1(1-21) was significantly reduced with a concomitant increase in the secretion of ET-1(1-39). These results suggest that the processing of ET-1(1-39) does not involve a pepstatin-sensitive aspartic acid protease, and that the enzyme responsible for generating ET-1(1-21) is sensitive to phosphoramidon.

Amino Acid Sequence↗

[Tumor-like focal nodular hyperplasia. Apropos of 3 cases observed at the Dakar Central Hospital from 1986 to 1989].

Authors report three observations of Focal Nodular Hyperplasia, Tumor-like on two: senegalese female patients, 16 years and 37 years old, and a young senegalese man, 24 Years old. The mean age is about 25.5 years and oestro progestative intake has bean noted once. Diagnosis of Focal Nodular Hyperplasia was difficult and has been done twice after surgical intervention for chronic cholecystitis and blood peritonitis. The only complication reported, has been a rupture of nodular, causing the death of a patient. This benign tumor that never degenerates, does not need any particular treatment unless a stopping of oral contraception.

Adolescent↗

Comparisons of the clinical and radiological features and surgical management of posterior fossa meningiomas and acoustic neuromas.

Next to acoustic neuromas, meningiomas are the most common benign tumour of the posterior fossa. This paper reviews the personal experience of one of the authors with the management of 26 posterior fossa meningiomas and 212 acoustic neuromas. The aim was to compare the clinical and radiological features of these two types of posterior fossa tumours to determine whether they can be differentiated preoperatively. The study also aimed at analysing the surgical treatment of posterior fossa meningiomas. The results showed that posterior fossa meningiomas can usually be differentiated from acoustic neuromas on the basis of clinical and radiological features. Preoperative differentiation aids surgical management, especially for selection of surgical approach. In most instances, posterior fossa meningiomas can be totally resected with minimal morbidity and mortality.

Adult↗

[Diagnostic suspicion. Clinical, epidemiological, radiological, and endoscopic aspects of bronchopulmonary cancer in Senegal. Apropos of 700 endoscopies performed at the Hôpital Principal de Dakar from 1987 to 1990].

700 bronchial fiber endoscopies were performed at Dakar Main Hospital over a period of 3 consecutive years. 40 broncho-pulmonary cancers were identified (34 epidermoids, 4 adeno-cancers, 2 small cell cancers) among the 80 suspect cases. Comparison of clinical, radiological and endoscopic data revealed the following information: 1. most frequently radiology showed retractile, pulmonary condensation syndrome (40 cases); 2. a large predominance of close, bulging tumours (45 times) in relation to endoscopic bronchial stenosis (22 times); 3. almost exclusive identification of bronchial epidermoid cancer in this series (34 times); 4. the masculine sex and use of tobacco remain 2 unavoidable elements in this pathology. Bronchial endoscopy, a simple, indispensible examination, allows the lesion to be visualized, and a biopsy, on its own or associated with endoscopic cysto-brushing and alveolus washing, can then furnish conclusive histological proof.

Adult↗

Rat vascular tissue contains a neutral endopeptidase capable of degrading atrial natriuretic peptide.

Neutral endopeptidase (NEP, EC 3.4.24.11), purified from renal brush border, cleaves the Cys7-Phe8 amide bond of rat atrial natriuretic peptide (ANP), to generate the inactive metabolite (ANP cleaved at the Cys7-Phe8 bond; x-ANP). To determine if NEP contributes to the inactivation of circulating ANP, we investigated the degradation of rat ANP (rANP, 1-28) in the vasculature. Formation of x-ANP from exogenous ANP was studied in a mesenteric arterial preparation by perfusion in a single pass system in the presence and absence of the NEP inhibitors, thiorphan or phosphoramidon. In addition, a purified membrane fraction was prepared from mesenteric arterial homogenate and compared with an equivalent renal membrane fraction. Formation of x-ANP was quantified by a specific immunoassay (ELISA). Renal and vascular membranes shared the same pH optima for x-ANP formation (pH 7.5), although x-ANP generation was considerably greater in renal vs. vascular membranes (31.6 and 0.4 nmol min-1 mg-1 of protein, respectively). Both preparations were inhibited in a similar, dose-dependent manner by phosphoramidon, thiorphan or a polyclonal antibody to NEP. In perfused mesenteric arteries, 1.6 +/- 0.8 pmol of x-ANP were generated from 1 microgram of ANP; this formation was inhibited 51% by 10 microM phosphoramidon or thiorphan. Plasma levels of x-ANP after bolus i.v. administration of rANP in rats, were inhibited (70-80%) by thiorphan at comparable doses to those used in perfused mesenteric arteries. These studies indicate that ANP is degraded in the vasculature by NEP or an "NEP-like" enzyme(s).

Animals↗

Myopic and nonmyopic aphakic retinal detachment: time interval and location of breaks.

Of 471 retinal detachments occurring in aphakic patients after undergoing intracapsular cataract extraction, we reviewed 318 eyes with uncomplicated aphakia (no vitreous loss). Myopic eyes had equatorial breaks 38% of the time versus 19% for nonmyopic eyes. The time interval between aphakia and detachment was shorter for myopic than for nonmyopic eyes. Our results showed a significant incidence of: (1) equatorial breaks in myopic eyes versus nonmyopic eyes (P less than 0.005), and (2) earlier detachments for myopic eyes versus nonmyopic eyes (P less than 0.005). The presence of equatorial breaks seemed to be associated with earlier retinal detachments.

Aphakia, Postcataract↗

Electrophysiological monitoring during acoustic neuroma and other posterior fossa surgery.

Techniques used to monitor the function of the seventh and eighth cranial nerves during acoustic neuroma and other posterior fossa surgery are reviewed. The auditory brainstem response (ABR), electrocochleogram (ECochG) and direct recording from the auditory nerve (CNAP) were compared. The best technique is the ECochG, although in many cases, the CNAP should be used as a back-up technique. The CNAP is especially useful for the identification of the auditory nerve. Both can provide real-time feedback on the physiological integrity of the auditory nerve. The ABR may be helpful in monitoring brainstem function. For some procedures, optimal monitoring requires the combined recording of all three techniques. Monopolar constant-voltage intracranial stimulation of the facial nerve is helpful for the identification and preservation of the facial nerve. Audio monitoring of spontaneous electromyographic activity provides real-time feedback on the effect of surgical manipulation of the nerve. Monitoring of ephaptic transmission in the facial nerve during microvascular decompression for hemifacial spasm aids in the identification of the offending vessel.

Action Potentials↗

The effects of human insulin on antibody formation in pregnant diabetics and their newborns.

We studied the immunogenicity of human insulin in 11 diabetic mothers and their newborns. Serum antibody formation was assayed by two different methods. Upon switching four patients from beef/pork insulin to human insulin, we found that elevated baseline antibody levels in three women decreased, in two to undetectable levels at term. The fourth patient had undetectable antibody levels at baseline and borderline levels at term. Only one of their four newborns had antibodies. Upon initiation of insulin treatment in another five diabetics without detectable antibodies at baseline, only two developed antibodies, and only one of their newborns developed antibodies. Two other patients, initially not on insulin, had baseline elevations of antibody that decreased with administration of human insulin; both of their newborns had antibodies. Overt diabetes evolved subsequently in both mothers after pregnancy. We conclude the following: 1) Upon transfer from beef/pork insulin to human insulin, mothers and their newborns show a decrease in insulin antibodies; 2) new patients initiated on insulin develop low levels of antibodies, if any, and their newborns also have low levels of antibodies if any; and 3) the decreased or absent immunogenicity of human insulin supports its use in pregnant diabetics.

Adolescent↗

Rehabilitation of musicians with upper limb amputations.

Three saxophone players with upper limb amputations have been successfully rehabilitated to play their musical instruments using skin-conductivity touch control. Each attained a standard of musicianship sufficient to perform the standard repertoire of the instrument in a concert setting. The mechanical and electrical modifications to the saxophone are described, as well as the principles of operation of the skin-conductivity touch control module. The touch control module is commercially available for prosthetists who wish to fit musicians or others with upper extremity amputations who require rapid accurate control of a number of channels of powered prosthetic function.

Amputation, Surgical↗

Effect on birth weight of erythromycin treatment of pregnant women.

To test the hypothesis that treatment with antibiotics prevents low birth weight, pregnant women whose vaginal cultures contained Ureaplasma urealyticum or Mycoplasma hominis (or both) and who gave written informed consent were treated with one of the following: identical looking capsules containing 250 mg of either erythromycin estolate or stearate (active against U urealyticum), or 150 mg of clindamycin hydrochloride (active against M hominis), or placebo, four times daily for six weeks in a randomized double-blind study. Treatment with clindamycin had no effect. Treatment with erythromycin initiated during the second trimester had no effect on mean birth weight or on the frequency of low-birth-weight infants. In contrast, women whose treatment with erythromycin was initiated in the third trimester gave birth to infants with a heavier mean birth weight (3331 g) than infants born to placebo-treated women (3187 g) (P = .042). Similarly, in women whose erythromycin was begun during the third trimester, the birth rate of infants weighing 2500 g or less was 3%, whereas in women treated with placebo, the birth rate for low-birth-weight infants was 12% (P = .047). These data suggest that treatment with erythromycin during the third trimester prevents low birth weight in mycoplasma-colonized pregnant women. Whether the effect is due solely to the action of erythromycin on U urealyticum is uncertain.

Birth Weight↗

Pharmacokinetics of cefotaxime, moxalactam, and cefoperazone in the early puerperium.

Twelve parturient women volunteered to receive 1 g of cefotaxime on the second or third day postpartum by intravenous infusion over 3 min. Blood was taken from the antecubital vein of the contralateral arm at 0.25, 0.5, 0.75, 1, 2, 4, and 6 h. The concentration of cefotaxime in serum was assayed by agar diffusion, with Sarcina lutea ATCC 9341 as the indicator strain. The same 12 women received an identical dose of antibiotic 4 months after the first dose, and blood was taken at the same time intervals as in the first study to measure antibiotic levels. An additional 24 women participated in identical studies with either moxalactam or cefoperazone. Cefoperazone afforded the highest concentration in serum of the three drugs, followed by moxalactam. These differences in the concentration in serum were seen both early postpartum and 4 months later. However, the concentration in serum of all three drugs was diminished 2 and 3 days postpartum compared with 4 months postpartum. Most pharmacokinetic parameters were also significantly altered early in the puerperium relative to those obtained 4 months later. The altered pharmacokinetic behavior of antibiotics associated with pregnancy appears to persist into the early puerperium.

Adult↗

Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes.

The objective of this paper is to review the extent and mechanisms of lipoprotein alterations in pregnancy, present new data relating to placental lipid transport in normal humans and diabetic animals and consider possible effects on fetal growth and development in normal and diabetic pregnancy. The concentration of all lipoprotein fractions increases during pregnancy. VLDL cholesterol and triglyceride increase 2.5-fold over prepregnancy levels and LDL cholesterol increases 1.6-fold, all with peak levels at term. HDL cholesterol is maximally increased in midgestation by 1.45-fold and subsequently declines to 1.15-fold at term. The mechanisms of these lipoprotein changes have not been studied in humans but the hypertriglyceridemia in animal models is related to enhanced VLDL entry into the circulation. In addition, diminished adipose tissue lipoprotein lipase (LPL) activity in late gestation may cause a rerouting of triglyceride fatty acids to other tissues such as muscle and uterus for oxidation, rather than storage, since triglyceride transport is not reduced in pregnancy. All of these changes appear to be sex hormone mediated. In diabetic pregnancies, the available data indicate that triglyceride concentrations are increased and HDL cholesterol concentrations are decreased with reference to lipoproteins in nondiabetic pregnant women. Previously unpublished data show that a transplacental FFA gradient exists across the umbilical circulation in the direction of the fetus and is proportional to the maternal FFA concentration. No gradient is seen for triglyceride or total plasma cholesterol. However, transport of unmeasured amounts of triglyceride fatty acids may still occur via placental LPL and be exaggerated in diabetes where LPL declines in adipose tissue but not in placenta. The mechanism of transplacental cholesterol transport remains to be defined. Preliminary studies suggest that it depends on HDL as well as LDL since both can provide cholesterol for placental progesterone synthesis. In addition, fetal weight and length are associated with maternal apoproteins A-I and A-II, both major apoproteins of HDL. By lowering HDL in pregnancy, diabetes mellitus could negatively affect these relationships. In conclusion, sex hormone mediated modifications of lipoprotein physiology are described in pregnancy which may enhance triglyceride fatty acid transport to muscle for oxidation and LDL and HDL cholesterol delivery to growing maternal and fetal tissues, a process that diabetes could globally disrupt.

Animals↗