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Biomedical subjects

C Simon

Publications and source records attributed to C Simon.

At least 127 records · Page 7Linked to original sources

[The interleukin-1 system during human implantation].

Although the immune and reproductive systems have been considered independent of each other, the cooperation of both systems are now known to be crucial for the initiation and maintenance of mammalian pregnancy. Nowadays cytokines and growth factors have became increasingly implicated in embryonic implantation. Endometrial functions, embryonic secretions and embryo-endometrial interactions require a continuous dialogue and synchronism between both partners (endometrium and embryo). The present review focuses on the Interleukin-1 system as an example of local regulator in embryonic implantation. Evidence demonstrating its presence and relevance on human endometrium physiology and human preimplantation embryonic development are presented. Furthermore, we described data suggesting the possible role of this cytokine in human implantation.

Embryo Implantation↗

Results of antibiotic treatment of Hickman-catheter-related infections in oncological patients.

A group of 330 oncological patients were supported throughout a 7-year period with central venous catheters (Broviac/Hickman catheters) and underwent standard oncological chemotherapy, because of hematological malignancies or solid tumors (156 children), or a myeloablative conditioning regimen followed by bone marrow transplantation because of leukemia or lymphoma (174 patients: 110 adults, 64 children). Of these, 17 patients (8 after bone marrow transplantation) developed a catheter-related bacteremia and were treated by at least two antibiotics according to the sensitivity of the bacteria. In 1 patient the catheter (infected by Bacillus cereus) was removed on day 25 of antibiotic treatment because of persistent high fever and further positive blood cultures. After bone marrow transplantation, 2 other patients, with a Pseudomonas or a Staphylococcus infection respectively, did not respond to the combined antibiotic treatment and died 1 week and 7 weeks later, respectively, from transplant-related severe graft-versus-host disease. In the other 14 patients antibiotic treatment was successful and removal of the central-vein catheter could be avoided.

Adult↗

Prevalence of aneuploidy, overexpressed ER, and overexpressed EGFR in random breast aspirates of women at high and low risk for breast cancer.

Breast tissue biomarkers which accurately predict breast cancer development within a 10 year period in high risk women are needed but currently not available. We initiated this study to determine 1) the prevalence of one or more breast tissue abnormalities in a group of women at high risk for breast cancer, and 2) if the prevalence of biomarker abnormalities is greater in high risk than in low risk women. Eligible high risk women were those with a first degree relative with breast cancer, prior breast cancer, or precancerous mastopathy. Low risk women were those without these or other major identifiable risk factors. Ductal cells were obtained via random fine needle aspirations and cytologically classified. Biomarkers included DNA ploidy, estrogen receptor (ER), and epidermal growth factor receptor (EGFR). The prevalence of DNA aneuploidy was 30%, overexpression of ER 10%, and overexpression of EGFR 35%, in the 206 high risk women whose median 10 year Gail risk (projected probability) of developing breast cancer was 4.5%. The prevalence of aneuploidy and overexpressed EGFR was significantly higher in the high risk women than in the 25 low risk controls (p < 0.002), whose median 10 year Gail risk was 0.7%. The difference in the prevalence of ER overexpression between high and low risk groups was not statistically significant (p = 0.095). This may be due to the low prevalence of overexpressed ER and the small number of controls. A significant difference was noted in the prevalence of one or more abnormal biomarkers between the high risk and low risk women (p < 0.001). A large prospective trial is needed to determine if one or more of these biomarkers, is predictive of breast cancer development.

Adult↗

Eating behaviour and depression before and after antidepressant treatment: a prospective, naturalistic study.

Eating behaviour of severely depressed patients was assessed before (n = 56), after acute (n = 46) and during maintenance (n = 35) treatment and compared to matched normal controls in order to investigate the behavioural mechanisms underlying the weight gain induced by antidepressants. Assessments included food intake, appetite and food preferences. Before treatment, there was a decrease in appetite and in food intake with a relative excess of carbohydrates and a preference for sweets. Maintenance treatment was associated with substantial weight gain. All differences in eating behaviour between patients and controls disappeared, with the exception of a decrease in appetite in a subgroup of less-improved patients. These results suggest that antidepressant treatment induces weight gain by mechanisms that are largely independent of their action on mood.

Adult↗

Prolactin secretion and sleep.

To clarify the relationship between prolactin (PRL) secretion and sleep, three experimental procedures were employed and secretory rates were estimated from plasma levels using a deconvolution procedure. Eight healthy young men participated in two 24-hour studies, one using normal night sleep and one using delayed sleep, to determine the influence of sleep as a whole on the PRL rhythm. Another group of 24 subjects underwent a 1-night study to investigate the relationship between PRL secretion and the internal sleep structure. The influence of sleep quality was studied in two more groups of eight subjects. Secretory rates were calculated by deconvolution from plasma PRL measured at 10-minute intervals. Sleep was recorded polygraphically in all experiments. PRL secretory pulses occurred throughout the 24-hour cycle without significant variation in frequency, but with enhanced pulse amplitude for both night and day sleep periods. Sleep onset was rapidly followed by an increase in secretion, and awakenings coincided with an immediate offset of active secretion. Analyzing the association between secretory pulses and sleep stages demonstrated that PRL secretory rate is low at the time of rapid eye movement sleep onset. Sleep quality appeared not to affect the PRL secretory profile. These results confirmed that PRL secretion is enhanced during the whole sleep period, as inferred from plasma levels. Considering secretory pulses provides a precise determination of the temporal relations between PRL and sleep structure and demonstrates that occasionally poor sleep does not influence PRL secretion in normal humans.

Adult↗

Slow oscillations of plasma glucose and insulin secretion rate are amplified during sleep in humans under continuous enteral nutrition.

Concomitant oscillations of plasma glucose and insulin secretion rate with a periodicity of about 80 minutes have been identified in normal humans. To determine whether these slow oscillations are influenced by sleep, peripheral levels of glucose and C-peptide were measured at 10-minute intervals over 24 hours in seven subjects, once with a normal nocturnal sleep from 2300 to 0700 hours, and once with a shifted daytime sleep from 0700 to 1500 hours. The subjects received continuous enteral nutrition and remained supine for the 8 hours preceding blood sampling and throughout the whole experiment. Insulin secretion rate was estimated by deconvoluting peripheral C-peptide levels using an open two-compartment model. The amplitude of glucose and insulin secretion rate oscillations increased by 160% during the 8-hour sleep periods, at whatever time they occurred, whereas the influence of the time of day was not significant. Glucose and insulin secretion rate mean levels were also significantly increased during normal nocturnal sleep compared to the remaining 8-hour waking periods, but this effect did not persist when sleep was shifted to the daytime. The number of oscillations was similar in both experimental series and was not affected by sleep. No systematic concordance was found between glucose and insulin secretion rate oscillations and the rapid eye movement-nonrapid eye movement sleep cycles, despite them having similar periodicities. This study demonstrates that increased amplitude of glucose and insulin secretion rate oscillations is related to sleep rather than to the time of day, without any associated frequency variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Renin as a biological marker of the NREM-REM sleep cycle: effect of REM sleep suppression.

We have previously described that, in normal man, the nocturnal oscillations of plasma renin activity (PRA) exactly reflect the rapid eye movement (REM)-non(N)REM sleep cycles, with increasing PRA levels during NREM sleep and decreasing levels during REM sleep. This study was carried out to determine whether REM sleep suppression affects nocturnal renin profiles and to define which sleep stage is essential for renin release. In a first experimental series, REM sleep was suppressed by using clomipramine, a tricyclic antidepressant. Seven healthy young men were studied once during a night when a placebo was given and once during a night following a single dose of 50 mg clomipramine. Blood was collected every 10 min from 23.00 hours to 07.00 hours. PRA was measured by radio-immunoassay and the nocturnal profiles were analysed using the pulse detection program ULTRA. Clomipramine suppressed REM sleep in all subjects but one, but did not affect the number of SWS episodes nor their duration. Similar PRA profiles were observed in both experimental conditions. Neither the mean levels, nor the number and the amplitude of the oscillations were modified and the normal relationship between slow wave sleep and increasing PRA levels was preserved. In a second experimental series, REM sleep was prevented by rapidly awakening the subjects as soon as they fell into REM sleep. The four subjects studied attempted several times to go into REM sleep, but only when PRA levels were decreasing. The interruption of REM sleep by short waking periods did not disturb PRA for which the oscillations remained unaffected. Again, the relationship between SWS and increasing PRA levels was preserved. These results provide evidence that mechanisms increasing slow-wave activity are principally involved in increasing PRA levels and that replacing REM sleep by waking periods and light sleep does not modify nocturnal PRA oscillations.

Journal Article↗

White matter lesions and cognitive deficits: relevance of lesion pattern?

Magnetic resonance imaging (MRI) permits efficient visualization of white matter lesions (WML). A growing body of literature deals with the correlation of WML and cognitive dysfunction with conflicting results. We studied the influence of lesion pattern as well as size by analyzing MRI and psychometric test performance in 2 patient collectives with different WML patterns. 22 patients with myotonic dystrophy (MD) and mainly subcortical WML were compared with 39 patients with multiple sclerosis (MS) and mainly periventricular lesions. 73% of MD patients had WML, the extent of which correlated with cognitive deficits. Severely impaired patients had psychometric findings compatible with "subcortical" dementia. In MS the extent of WML alone did not correlate significantly with cognitive deficits. Significant cognitive dysfunction was observed with extension of WML to areas of white matter immediately underlying cortex, but not with exclusively periventricular lesions. Cerebral atrophy had less impact. Comparison of MD and MS indicates that WML immediately subjacent to cortex are likely to cause significant cognitive deficits, whereas extensive periventricular demyelination may cause no major dysfunction. This may relate to early disturbance of associative fibers by subcortical lesions. Our results emphasize the significance of pattern as well as total extent of WML. Myotonic dystrophy is a useful model to study the effect of subcortical lesions, due to a typical lesion pattern unusual in other conditions.

Adolescent↗

Effect of pentoxifylline on the inhibition of surfactant synthesis induced by TNF-alpha in human type II pneumocytes.

Tumor necrosis factor alpha (TNF-alpha) seems to play an important role in the pathogenesis of the adult respiratory distress syndrome (ARDS). This study was designed to determine the effect of TNF-alpha and pentoxifylline (PTXF) on surfactant synthesis by isolated human type II pneumocytes. In order to isolate the pneumocytes, lungs obtained from both previously healthy multiple organ donors (n = 11) and patients who underwent surgical excision for lung cancer (n = 8) were used. Surfactant synthesis was measured by the incorporation of labeled glucose into the two most important phospholipid components of surfactant: phosphatidylcholine (PC) and phosphatidylglycerol (PGL). The pneumocytes of the donor group showed a greater degree of PC synthesis than those from the cancer group (3.44 +/- 0.19 versus 2.15 +/- 01.5 pmol/micrograms protein, p < 0.001). The synthesis of PC by pneumocytes in both the donor (1.13 +/- 0.19 versus 3.44 +/- 0.19 pmol/micrograms protein, p < 0.01) and cancer (0.99 +/- 0.11 versus 2.15 +/- 0.15 pmol/micrograms protein, p < 0.01) groups was decreased by TNF-alpha (100 ng/ml). This effect was blocked by PTXF (100 micrograms/ml), a substance that also increased PC production in the control-group pneumocytes from cancer patients, the final PC levels being similar to those of the donors in the absence of TNF-alpha. These results suggest that one of the mechanisms of TNF-alpha participation in the pathophysiology of ARDS is inhibition of surfactant synthesis, and support the hypothesis of in vivo production of TNF-alpha in lung-cancer patients, with subsequent chronic exposure of the lung epithelial cells to this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The relation between cardiac index and oxygen extraction in acutely ill patients.

The relation between cardiac index and oxygen extraction (O2ER) can represent a useful basis for the interpretation of hemodynamic parameters in the acutely ill patient. We prospectively collected cardiac index and paired arterial and mixed venous blood gas values in 79 acutely ill patients who were successively monitored invasively during their ICU course. For each patient, the degree of cardiac failure score and sepsis was scored at time of each measurement. A total of 122 observations were reported on a cardiac index/O2ER diagram, on which, based on physiologic data obtained during physical exercise, a line of reference was included representing equal increases in cardiac index and O2ER from normal values at rest. Patients with established heart failure fell below the line of reference. However, patients without cardiac failure or with compensated cardiac failure during adrenergic therapy fell close to the line of reference. Sepsis was associated with elevated oxygen delivery (Do2) and oxygen consumption (Vo2). Although O2ER was lower in the presence than in the absence of septic shock, patients with sepsis fell close to the line of reference. Among these patients with sepsis, O2ER was greater in patients with established heart failure than without heart failure (37.6 +/- 11.7 percent vs 21.5 +/- 4.4 percent, p < 0.01). The relationship between cardiac index and O2ER is much simpler than the relationship between Vo2 and Do2 and it avoids problems of mathematical coupling. It also allows us to refer to physiologic adaptation to changes in oxygen demand. This diagram may be useful at the bedside to facilitate the interpretation of cardiac index and to guide therapy.

Cardiac Output↗

Twenty-four-hour profiles of plasma renin activity in relation to the sleep-wake cycle.

OBJECTIVE: To evaluate the relative contribution of sleep and the endogenous circadian rhythmicity in producing the 24-h variations in the plasma renin activity. METHODS: Ten normal young men were studied, under basal conditions with normal nocturnal sleep from 2300-0700 h and once after a night of total sleep deprivation followed by 8 h daytime sleep from 0700 to 1500 h. Plasma renin activity was measured every 10 min for 24 h and the profiles were analysed using the pulse detection program ULTRA. RESULTS: During the 8 h night-time sleep a significant increase in the mean plasma renin activity levels occurred compared with the subsequent 8-h waking periods. After the shift in the sleep period, a sleep-associated increase was clearly apparent during the daytime hours. The number of the amplitude of the oscillations, linked to the non-rapid eye movement-rapid eye movement sleep cycles, increased during sleep (at whatever time it occurred), and were dependent on the regularity and the length of the sleep cycles. In awake subjects the plasma renin activity generally fluctuated in a more damped and irregular manner, but occasionally the plasma renin activity oscillated at a regular periodicity with two dominant peaks centred around 100 and 50 min. CONCLUSION: These results demonstrate that the 24-h plasma renin activity variations are not circadian in nature but are related to sleep processes, which create the nycthemeral rhythm by increasing both the frequency and the amplitude of the oscillations.

Adult↗

Biomarker and cytologic abnormalities in women at high and low risk for breast cancer.

Fine needle aspirates (FNA) from 106 high-risk women and 25 low-risk women were evaluated for overexpression of estrogen receptor (ER), epidermal growth factor receptor (EGFR), mutant p53, and HER-2/neu by immunocytochemistry, and for aneuploidy by image analysis. Aspirates were also classified cytologically as normal, apocrine metaplasia, epithelial hyperplasia (EH), or dysplasia. High-risk women were those with a first-degree relative with breast cancer (76%), precancerous breast disease (26%), prior cancer of the contralateral breast (9%), or multiple abnormalities (11%). Low-risk women had none of the above risk factors, nor a prior breast biopsy or clinical evidence of fibrocystic disease. The median 10-year Gail risk for the high-risk group was 4%, compared to 0.7% for the low-risk group. There were significant differences (p < 0.01) between high- and low-risk women in the prevalences of hyperplasia (55% versus 12%), dysplasia (19% versus 0%), aneuploidy (32% versus 0%), overexpressed EGFR (32% versus 4%), and overexpressed p53 (29% versus 4%). The prevalence of multiple biomarker abnormalities was also greater in high-risk than in low-risk women (28% versus 0%; p < 0.01). Four percent (4%) of FNAs from high-risk women with normal cytology, 29% of aspirates with hyperplastic cytology, and 60% of those with dysplasia were associated with two or more biomarker abnormalities. The differences in the prevalence of multiple biomarker abnormalities among various cytologic categories were statistically significant (p = 0.02, normal versus EH; p = 0.02, EH versus dysplasia; p < 0.01, normal versus dysplasia).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

Continuous positive airway pressure treatment. Effects on growth hormone, insulin and glucose profiles in obstructive sleep apnea patients.

The principal nocturnal GH peak normally coincides with the first episode of slow wave sleep (SWS). Obstructive sleep apnea (OSA) patients have low nocturnal GH levels which may be explained by their poor quality fragmented sleep but other factors are possibly involved. Obesity is frequently associated with OSA, and obese patients also manifest reduced GH secretion. The mechanisms reducing GH levels in obese subjects are not understood, but hyperinsulinaemia is a suggested factor. In this study nocturnal plasma and secretory GH profiles of OSA patients were examined in relation to the quality and quantity of sleep, together with plasma glucose and insulin levels. Eight OSA patients, (BMI 32.7 +/- 2.3 kg/m2), underwent 2 night studies. For one night no treatment was given and for the other continuous positive airway pressure (CPAP) treatment was administered for the first time. Blood was collected continuously throughout each night and plasma GH, insulin and glucose profiles established in 10 min interval samples. From the plasma data a deconvolution model was used to calculate GH secretion rates. Sleep was recorded during the studies. For the non-treatment night GH levels were low and increased significantly with treatment, p = 0.008 for plasma levels and p = 0.02 for secretion rates. Treatment significantly decreased the cumulative apnea duration and increased the quantity of SWS and Rapid Eye Movement (REM) sleep (p = 0.008), but the mean insulin and glucose profiles did not differ between the two nights. Individual GH plasma and secretion rates, on treatment, showed a tendency to correlate with the amount of SWS (p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of hematocrit on tissue O2 extraction capabilities during acute hemorrhage.

This study was performed to test the hypothesis that tissue O2 extraction capabilities during hemorrhage may be greater when hematocrit (Hct) is initially reduced. Twenty-four anesthetized and splenectomized dogs were randomly assigned in three groups of eight dogs each: group 1 (Hct 40), 40-45% Hct; group 2 (Hct 30), 30-35% Hct; and group 3 (Hct 20), 20-25% Hct. In each animal, the desired Hct was obtained by normovolemic hemodilution using hydroxyethyl starch 450/0.7 and maintained throughout the experiment. O2 delivery (DO2) was progressively reduced by hemorrhage. At each step, DO2 and O2 consumption (VO2) were measured separately. Critical DO2 obtained from a plot of VO2 vs. DO2 was lower in the Hct 30 and Hct 20 groups than in the Hct 40 group [(in ml.min-1.kg-1) Hct 30, 7.9 +/- 2.2; Hct 20, 7.8 +/- 1.0; Hct 40, 10.4 +/- 1.1; P < 0.05]. Critical DO2 obtained from blood lactate levels was also significantly lower in the Hct 30 and Hct20 groups than in the Hct 40 group. Critical O2 extraction ratio was also greater in the Hct 30 and Hct 20 groups than in the Hct 40 group (Hct 30, 73.0 +/- 13.9%; Hct 20, 70.1 +/- 9.6%; Hct 40, 57.1 +/- 11.5%; P < 0.05). In the conditions of our study, moderate hemodilution was associated with an improvement of the O2 extraction capabilities of the body, probably related to the reduction in blood viscosity.

Acute Disease↗

Hemorrhagic transformation in cardioembolic cerebral infarction.

BACKGROUND AND PURPOSE: Because the frequency of hemorrhagic transformation of cerebral infarcts is still a matter of controversy, we performed a prospective magnetic resonance imaging study in a series of consecutive patients with cardioembolic stroke. SUMMARY OF REVIEW: Among 200 consecutive patients with transient ischemic attack or ischemic stroke, 41 were identified with a computed tomographically proven supratentorial infarct due to cardiogenic embolism. Magnetic resonance imaging (T1-weighted) was performed 3 weeks after the stroke in 35 of these 41 patients. Eight patients received anticoagulants. Magnetic resonance images showed hemorrhagic transformation in 68.6% (24) of the 35 infarcts, always without clinical deterioration. In a stepwise forward logistic regression analysis only the volume of infarction edema on the initial computed tomogram was linked significantly with the risk of hemorrhagic transformation (p = 0.037). Hemorrhages were a regular finding on magnetic resonance images of infarcts exceeding a volume of 10 cm3 (94.4%, 17 of 18). CONCLUSIONS: Hemorrhagic transformation is a regular finding in medium-sized and large cardioembolic infarcts. Thus, in therapeutic and preventive studies of acute stroke the severity, not the frequency, of hemorrhages into brain infarcts should be the matter of interest.

Adult↗

Fatty liver hemorrhagic syndrome in hens overfed a purified diet. Selected enzyme activities and liver histology in relation to liver hemorrhage and reproductive performance.

A nutritionally adequate, purified diet was developed and used in studies to characterize selected aspects of laying hens in which fatty liver hemorrhagic syndrome (FLHS) was induced by overfeeding. Hens consuming the diet ad libitum or intubated with the diet in quantities equivalent to usual daily energy intake maintained normal rates of lay, did not become obese, and did not develop liver hemorrhage. Overfed hens had a 33% incidence of FLHS, as indicated by the presence of severe liver hemorrhage score, and displayed the full range of symptoms associated with spontaneous outbreaks of FLHS, including definitive lesions of hepatic reticulin. Among four groups of hens clinically classified according to rates of liver hemorrhage and egg production, there were no differences noted in total liver fat, liver fat concentration, or final body weight. Liver hemorrhage was associated with the degree of induction of liver lipogenic accessory enzymes. Serum enzyme activities indicate that overfed hens, unlike the overfed goose, retain hepatocellular membrane integrity. Overfeeding caused altered reproductive performance in 72% of hens. Alterations included erratic laying, increased incidence of double ovulations, shell defects, follicular collapse, and oviduct involution. Pattern of lay preceding necropsy seemed to influence follicle weight at necropsy. The data presented re-emphasize the interdependence among liver, ovary, and oviduct function in the etiology of FLHS.

Animal Feed↗