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Biomedical subjects

R Marion

Publications and source records attributed to R Marion.

At least 19 recordsLinked to original sources

Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut.

BACKGROUND & AIMS: Balance between pro-and anti-inflammatory mediators plays a key role in the pathogenesis and treatment of inflammatory bowel disease. Glutamine can modulate cytokine production by intestinal mucosa in healthy subjects, but studies in inflammatory states are still limited. The aim of this work was to evaluate the effects of glutamine on IL-1beta-induced cytokine production by human gut. METHODS: Duodenal biopsies from healthy volunteers were stimulated in vitro by IL-1beta in the presence of increasing glutamine concentrations. Cytokine production was assessed in culture media by ELISA and cytokine mRNA expression in biopsies by RT-PCR. Results, in pg/mg of tissue, (median [range]), were compared by non-parametric paired tests. RESULTS: IL-1beta stimulation increased IL-6 and IL-8, but did not affect IL-4 and IL-10 production. IL-8 and IL-6 production from stimulated biopsies significantly decreased with increasing glutamine concentration from 0.5 to 10mM, (2543 [828-3634] to 1499 [282-2617] for IL-8, 62 [22-117] to 24 [12-99] for IL-6, both P<0.05), whereas IL-10 production was increased (0.7 [0.2-1.6] to 1.2 [2.6-0.5],P<0.05). Glutamine also increased IL-10 mRNA level in biopsies (P<0.05). IL-4 production was not affected by glutamine. CONCLUSIONS: Glutamine was shown in human intestinal mucosa to reduce the production of the pro-inflammatory cytokines IL-6 and IL-8, and enhance the production of the anti-inflammatory cytokine, IL-10.

Adult↗

Cytokine-stimulated nitric oxide production and inducible NO-synthase mRNA level in human intestinal cells: lack of modulation by glutamine.

BACKGROUND & AIMS: Excess NO production has been reported during intestinal inflammation. Modulation of the inflammatory response with nutrients in critically ill patients has gained increasing interest. Glutamine has beneficial effects on gut mucosa but its effects on human intestinal NO production during an inflammatory response are not known. METHODS: Caco-2/TC7 and HCT-8 cells were stimulated with a cytokine mixture (IL-1 beta, TNF alpha, IFN gamma) and duodenal biopsies from human healthy volunteers in organ culture were stimulated with IL-1 beta. All cultures were performed in the presence of 2-10 mmol/l glutamine. NO release in culture supernatant and iNOS mRNA level in cultured cells or biopsies were assessed by nitrate reduction and Griess assay and RT-PCR, respectively. RESULTS: In Caco-2, HCT-8 cells and duodenal biopsies, cytokine stimulation increased iNOS mRNA level 1.2-fold (ns), 3.8-fold (P=0.02), 4.7-fold (P=0.03) and NO production 1.4-fold (ns), 9.1 (P=0.01) and 1.7-fold (P=0.01), respectively. Increasing glutamine concentration had no significant effect on NO production and iNOS mRNA in any type of culture, stimulated or not by cytokines. In various models of human intestinal cells, glutamine does not further increase NO production induced by pro-inflammatory cytokines.

Adult↗

[Neuronal expression of foreign genes with recombinant rabies virus variants].

Rabies virus variants obtained by recombinant DNA techniques enabled us to use the high neurotropism of rabies virus to express foreign genes (e.g: Chloramphenicol Acetyl Transferase gene) in neuronal cell cultures as well as in rodent brain. The foreign gene was inserted in the viral pseudogene region; this insertion did not affect the neurotropism of rabies virus, as shown by infection of neuronal cell cultures without any major cytopathic effects for several days. Stereotaxic inoculation of these rabies virus variants into rat striatum indicated that insertion of the foreign gene did not alter the viral axonal transport and the subsequent widespread brain infection. These data allow to consider rabies virus as a vector for the selective expression of foreign genes in neurons.

Animals↗

Beta-adrenergic receptor blockade as a therapeutic approach for suppressing the renin-angiotensin-aldosterone system in normotensive and hypertensive subjects.

Although beta-adrenergic-blocking drugs suppress the renin system (RAAS), plasma angiotensin II (Ang II) responses during beta-blockade have not been defined. This study quantifies the effects of beta-blockade on the RAAS and examines its impact on prorenin processing by measuring changes in the ratio of plasma renin activity (PRA) to total renin. In normotensive (N = 14) and hypertensive (N = 16) subjects, blood pressure (BP), heart rate, PRA, plasma prorenin, plasma total renin (prorenin + PRA), ratio of PRA to total renin (%PRA), plasma Ang II, and urinary aldosterone were measured before and after 1 week of beta-blockade. Plasma renin activity, Ang II, and urinary aldosterone levels were similar for normotensive and hypertensive subjects. Plasma renin activity correlated with Ang II. Total renin, which is proportional to (pro)renin gene expression, was lower in hypertensive subjects and was inversely related to BP. Beta-blockade decreased BP and heart rate in both groups, with medium- and high-renin hypertensive subjects responding more frequently than those with low renin. Beta-blockade consistently suppressed PRA, Ang II, and aldosterone. Total renin was unchanged, thus, %PRA fell. These results indicate that beta-blockers suppress plasma angiotensin II levels, in parallel with the marked reductions in PRA and urinary aldosterone levels in normotensive and hypertensive subjects. The suppression of Ang II levels was comparable to that produced during angiotensin converting enzyme (ACE) inhibition. However, by reducing prorenin processing to renin, beta-blockers do not stimulate renin secretion, unlike ACE inhibitors and Ang II receptor antagonists. This unique action of beta-blockers has important implications for the treatment of cardiovascular disease.

Adrenergic beta-Antagonists↗

White-coat hypertension and sex.

OBJECTIVES: To compare, by sex, selected behavioral and biologic characteristics among normotensive, white-coat hypertensive, and essential hypertensive patients, and to assess the similarities and differences in these characteristics between men and women diagnosed as having white-coat hypertension. METHODS: The subjects of this study were 764 men (80 normotensives, 112 white-coat hypertensives, and 572 essential hypertensives) and 442 women (53 normotensives, 81 white-coat hypertensives and 308 essential hypertensives) who were a nonrandom subset of a larger cohort of patients being assessed to determine the prognostic significance of ambulatory blood pressure measurements. Physician-measured technician-measured and ambulatory (average awake and asleep) blood pressures, daytime blood pressure variability, the difference between awake and sleeping blood pressures, cholesterol levels, plasma renin activity (PRA) and anthropometric and demographic characteristics were compared across the patient classifications within each sex group and between male and female white-coat hypertensives using one-way analysis of variance. Student's t tests and chi squared analysis. RESULTS: Among men, cholesterol levels of normotensives were significantly lower than those of either white-coat or essential hypertensives (P < 0.05 and P < 0.01, respectively). White-coat hypertensives were significantly younger than the essential hypertensives. The ambulatory and technician-measured blood pressures of the white-coat hypertensives were similar to those of the normotensives, as were most measures of variability of blood pressure. Among women, there were no differences in cholesterol level; however, white-coat hypertensives had lower PRA than did the essential hypertensives (P < 0.01) In contrast to the men, women with white-coat hypertension were similar in age to those with essential hypertension, and 10 years older than normotensives (P < 0.01). The ambulatory blood pressures of white-coat hypertensives were similar to those of normotensives, but their technician-measured blood pressures were intermediate between those of the normotensive and essential hypertensive groups. The daily variability of diastolic blood pressure among the white-coat-hypertensive women was greater than that of the normotensive women and similar to that of the essential hypertensive women. For all other measures of variability, data for white-coat-hypertensive women were similar to those for the normotensive women. There was no anthropometric or demographic difference among the patients either for men or for women. White-coat-hypertensive women were older than white-coat-hypertensive men and had higher systolic blood pressures and variabilities of blood pressure (P < 0.05). They also had lower PRA. CONCLUSIONS: These results are consistent with the ideas that the phenomenon of white-coat hypertension is similar for the two sexes, women may exhibit white-coat hypertension at a greater age than do men, and women with white-coat hypertension may further exhibit a broader white-coat effect, reflected in blood pressures measured by other medical personnel.

Journal Article↗

Ambulatory blood pressure variation and plasma renin activity in hypertensive women.

OBJECTIVE: To examine and compare the relationships between the level of plasma renin activity (PRA) and ambulatory blood pressure variability for hypertensive women aged under 45 years (n = 72, aged 36 +/- 6 years) and for women aged over 50 years (n = 175, aged 61 +/- 8 years). METHODS: The 247 white women studied were a nonrandom subset of a larger cohort of patients being assessed to determine the prognostic significance of ambulatory blood pressure measurements. The average awake ambulatory blood pressures (a minimum of 30 readings during at least 8 h), their SD and the coefficient of variation of the awake ambulatory blood pressures (awake SD/average awake blood pressure) of the women were examined by age group and three levels of PRA (less than 1.0, 1.0-4.0, and greater than 4.0 ng/ml per h) using two-way analysis of variance. The PRA was determined at the time of ambulatory monitoring. RESULTS: For the women aged 50 years and older, the average awake diastolic blood pressure was higher among women who had PRA greater than 4.0 ng/ml per h than it was among women who had PRA less than 1.0 ng/ml per h (P < 0.05). The average awake systolic blood pressure and systolic blood pressure variability were greater among women aged over 50 years than they were among women aged 45 years (P < 0.05). There were no significant relationships between the ambulatory blood pressure variability and the PRA, although the systolic blood pressure variability tended to be associated with the PRA among women aged under 45 years. These results contrasted sharply to previously reported findings among men, for whom there was an inverse relationship between the blood pressure and the PRA, particularly among those aged over 45 years, and a powerful positive association between measures of the awake ambulatory diastolic pressure variability and the PRA, again among older men. CONCLUSION: There seems to be a sex difference between hypertensive men and women in the relationship between the PRA and the ambulatory blood pressure variability. This difference might be related to factors associated with the menstrual cycle of women, although other biologic and behavioral influences may also play a role.

Journal Article↗

Spectrophotometry of amniotic fluid: a simple and rapid method for distinguishing between gestational sacs in second-trimester amniocentesis of twin pregnancies.

OBJECTIVE: To evaluate the use of an alternative and simple spectrophotometric method that could replace the intraamniotic injection of dye in the second-trimester amniocentesis of twins. METHODS: Optical densities (OD) of amniotic fluid (AF) obtained at second-trimester genetic amniocentesis were measured at 360 nm. Comparison was made between 36 twin pregnancies and 60 singleton controls. RESULTS: The mean difference in OD between two samples taken from the same sac of singleton pregnancies was very small (mean 0.004, standard deviation [SD] 0.003). However, samples drawn from each of the twin pairs' amniotic sacs varied widely (raw mean 0.176, SD 0.223; median 0.096, range 0.011-0.943). The difference between the groups was highly significant statistically (P < .001). CONCLUSION: Our preliminary experience with spectrophotometry of AF in twin amniocentesis suggests that this simple test may be useful in ascertaining that the AF samples were obtained from each of the two gestational sacs.

Amniocentesis↗

Nasal pyriform aperture stenosis and the holoprosencephaly spectrum.

Recent reports have described congenital nasal pyriform aperture stenosis, but do not address its etiology in detail. We describe a child with nasal pyriform aperture stenosis, submucus cleft palate, and hypoplastic maxillary sinuses. Chromosome analysis revealed a ring chromosome 18. Awareness of the association of midline facial defects with midline brain defects allowed us to predict that features of the holoprosencephaly sequence would be found. Subsequent evaluation revealed growth hormone deficit. Eventually the child manifested a single central incisor. We review the association between midline facial defects and holoprosencephaly to remind the otolaryngologist of the need to look at the whole patient as he treats specific upper airway problems.

Chromosomes, Human, Pair 18↗

Intracellular ionic consequences of dietary salt loading in essential hypertension. Relation to blood pressure and effects of calcium channel blockade.

To study the ionic basis of salt sensitivity in hypertension, 19F-, 13P-, and 23Na-nuclear magnetic resonance techniques were used to measure cytosolic free calcium (Cai), pH (pHi), free magnesium (Mgi), and sodium (Nai) in erythrocytes of essential hypertensive subjects (n = 19). Individuals were studied for 2 mo each on low- (UNaV < 50 meq/d) and high- (UNaV > 200 meq/d) salt diets, with the concomitant administration of nifedipine (10 mg t.i.d.) or placebo tablets for 1 mo of each diet. Salt loading elevated Cai and Nai while suppressing Mgi and pHi; these changes occurred predominantly in salt-sensitive subjects (n = 9). Nifedipine blunted the pressor response to salt loading > 50% (delta diastolic BP [high-low salt vs placebo] = 5 +/- 2 vs 14 +/- 2 mmHg, P < 0.05) and reversed salt-induced ionic changes, lowering Cai and elevating Mgi and pHi. Regardless of the definition of salt sensitivity, continuous relationships were observed between the pressure response to salt loading, the levels of Cai (r = 0.726, P < 0.001), Nai (r = 0.747, P < 0.001), and pHi (r = -0.754, P < 0.001), and the salt-induced change in Mgi (r = -0.757, P < 0.001). Altogether, these results emphasize the reciprocal and coordinate nature of intracellular ionic changes in response to dietary salt loading and calcium channel blockade in essential hypertension. They suggest that salt sensitivity is mediated by cellular calcium accumulation from the extracellular space, in association with magnesium depletion and acidification. Lastly, interpretation of intracellular ion measurements in the future will require concurrent assessment of dietary salt intake.

Analysis of Variance↗

Progressively intractable seizures, focal alopecia, and hemimegalencephaly.

We report a 3-year-old boy with the neurocutaneous combination of unilateral alopecia, ipsilateral hemimegalencephaly, and intractable seizures. He was born with an asymmetric hair pattern consisting of absent patches of hair, a small left eyebrow, and less eyelashes on the left eye; he had normal development until age 17 months, when he experienced right focal seizures with fever. Two months later, fever triggered new seizures characterized by flurries of head and body flexion and adduction of the right arm. He had left hand preference and language regression. EEG manifested left hemihypsarrhythmia, and MRI showed left hemimegalencephaly with marked enlargement of the temporal lobe with ventriculomegaly. Seizures were refractory to treatment with phenobarbital, adrenocorticotropic hormone, pyridoxine, sodium valproate, clonazepam, carbamazepine, phenytoin, and felbamate. This may represent a previously undescribed neurocutaneous syndrome.

Alopecia↗

Craniofacial, limb, and abdominal anomalies in a distinct syndrome: relation to the spectrum of Pfeiffer syndrome type 3.

Presented are 2 patients with abnormal craniofacial region, limbs, and abdomen, features that may be consistent with Pfeiffer syndrome, type 3. Both patients had bicoronal and bisphenoidal synostosis, extreme exophthalmic midface hypoplasia, and hydrocephalus. The limbs had a fixed flexion deformity of the elbows with broad thumbs which were radiopalmarly deviated; the toes were broad with a varus deformity and syndactyly toes 2-5. Both patients developed bowel obstruction secondary to midgut malrotation, and one of the patients had prune belly syndrome. Review of the literature disclosed an additional patient who, in retrospect, had Pfeiffer syndrome type 3 and midgut malrotation. These patients suggest that intestinal malrotation with or without prune belly syndrome may be a common component of this entity.

Abdomen↗

Velo-cardio-facial syndrome: a review of 120 patients.

A series of earlier reports has described the velo-cardio-facial syndrome (VCFS), a syndrome of multiple anomalies including cleft palate, heart malformations, facial characteristics, and learning disabilities. The patients reported previously were primarily ascertained from a craniofacial program at a large tertiary medical center. Recent reports, including a companion paper in this issue, suggest that this common syndrome of clefting is also a common syndrome of congenital heart defect (CHD) which is expressed as familial examples of DiGeorge sequence. Appreciation of more severely affected cases of VCFS and the detection of mild expressions have led to a broadening of the phenotypic spectrum of the syndrome. The purpose of this report is to describe the full spectrum of VCFS, including several new manifestations and to compare the VCFS phenotype with published cases of "familial DiGeorge sequence" which are now thought to represent examples of VCFS.

Abnormalities, Multiple↗

Variable phenotypes in velocardiofacial syndrome with chromosomal deletion.

Velocardiofacial syndrome (VCF) has overlapping features with DiGeorge sequence; both result from a developmental field defect and probably represent contiguous gene deletion syndromes. The association of chromosome 22q11 deletion with DiGeorge sequence led us to do molecular analysis of chromosome 22 in 18 patients with VCF, who ranged in age from 6 to 42 years. All 18 patients had monosomy for the chromosome region 22q11. Retrospectively, we correlated the presence of the deletion with various clinical findings: 100% had cleft palate, 67% the facial phenotype, 83% cardiac disease, 94% learning disabilities, 70% ophthalmologic findings, 50% short stature, 22% psychiatric disorders, and 17% hypocalcemia. Both severely phenotypically affected and mildly affected patients had the deletion. These findings stress the importance of continued surveillance of all patients with VCF for the many medical problems that may not be present at initial diagnosis. We conclude that the presence of the gene deletion does not predict the phenotypic expression in VCF. Further studies to characterize the size of the gene deletion may facilitate better prediction of the phenotype.

Abnormalities, Multiple↗

Duodenal atresia presenting as hematemesis in a premature infant with Down syndrome. Case report and review of the literature.

Congenital duodenal obstruction, a common complication of Down syndrome, most often presents as neonatal bilious vomiting. We report the first premature infant with Down syndrome whose duodenal atresia presented with a massive hematemesis secondary to duodenitis. Since a plain radiograph of the abdomen is diagnostic in the case of duodenal obstruction, it should be included in the diagnostic workup of hematemesis in newborn infants.

Down Syndrome↗

Voluntary control of submaximal grip strength.

Stokes (J Occup Med; 1983;25:683-684) proposed that feigned weak hand grip can be distinguished from sincere efforts by examining force measurements for the different handle positions of the Jamar hand dynamometer. Sincere efforts yield a curvilinear relationship between grip force and handle position; feigned efforts yield a horizontal, linear relationship. The purpose of the present set of three experiments was to investigate the degree of control normal subjects have over submaximal effort and their ability to feign weakened grip. In Experiment 1 we found that subjects instructed to exert a specific amount of submaximal effort (50%) did not produce a response pattern of grip force consistent with Stokes' hypothesis. In Experiment 2 we found a linear relationship between the degree of submaximal effort and grip force for efforts of 30, 50, 70, and 90% of maximal effort. In Experiment 3 we found that subjects, with proper instruction as to the amount of effort to exert, can produce feigned submaximal efforts similar to the sincere, maximal efforts of injured people. Simple maximal grip force measurements are insensitive to the different motor strategies used in maximal and submaximal efforts and may provide little evidence for the detection of feigning.

Adult↗

Pregnancy termination after detection of fetal chromosomal or metabolic abnormalities.

In 3400 midtrimester amniocenteses, 68 fetuses had abnormal findings. Three women elected to continue their pregnancies and the remainder chose terminations. Of these, 29 were cared for in our hospitals. Pregnancy termination was carried out in gestations averaging 21.6 +/- 2.3 weeks and fetal weights averaging 531 +/- 351 g. Three prostaglandins techniques were used, two of which proved to be effective. Dosages employed were comparable to those used in early second trimester pregnancy terminations. Side effects were similar; one retained placenta occurred. We have used a multidisciplinary counseling approach for these couples and have restricted ourselves to the medical aspects of their problems. Techniques are described for the psychologic support of the couple during this stressful period.

Abortion, Induced↗