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Biomedical subjects

P Franco

Publications and source records attributed to P Franco.

At least 37 records · Page 2Linked to original sources

Factors influencing the determination of arousal thresholds in infants - a review.

Objective: To review the major confounding factors that influence the determination of arousal thresholds in infants.Review of confounding factors: The determination of arousal thresholds in infants measures their arousability from sleep. The evaluation is influenced by various conditions. The infant's arousability is decreased by maternal factors, such as exposure to cigarette smoke, alcohol, illegal drugs or medications during gestation or breastfeeding. The levels of arousal thresholds also depend on the age of the infant and on experimental conditions, such as previous sleep deprivation, type of arousal challenges, time of administration of the arousal challenge, sleep stage, body position, room temperature, use of a pacifier, bed sharing, or type of feeding. In addition, spontaneous arousals can occur and modify the infant's response to external arousal challenges.Conclusions: Factors known to modify infants' arousability from sleep should be controlled during studies designed to determine arousal thresholds.

Journal Article↗

Frequency of obstructive and mixed sleep apneas in 1,023 infants.

STUDY OBJECTIVES: To collect normative data on the frequency of obstructive and mixed sleep apneas in healthy infants. STUDY DESIGN: 1100 infants were recorded during one night in a sleep laboratory. SETTING: the recordings were performed in an infant sleep laboratory. PATIENTS: The recordings of 1023 infants were used for analysis, the data of 77 infants being excluded because of poor recording quality. The infants were born full-term, were healthy at the time of study, had no history of apnea and were aged between 2 and 28 weeks. The polysomnographic recordings were analyzed visually and were subdivided according to the age of the subjects into 2-7 weeks, 8-11 weeks, 12-15 weeks, 16-19 weeks and 20-27 weeks of life. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: At 2-7 weeks of life, obstructive apneas (p=.013) and mixed apneas (p=.004) were significantly more frequent than at any other age group. At 8 to 11 weeks of life, obstructive apneas were significantly more frequent in boys than girls (p=.016). CONCLUSIONS: The present findings add to our knowledge of infants' respiratory characteristics during sleep.

Female↗

Influence of ambient temperature on sleep characteristics and autonomic nervous control in healthy infants.

OBJECTIVE: To evaluate the influence of ambient temperature on infant's sleep and cardiorespiratory parameters during sleep. PATIENTS AND METHOD: 20 healthy infants with a median age of 11.5 weeks (range 7 to 18 weeks) were recorded polygraphically for one night. They were exposed to 3 different ambient temperatures (20 degrees C-25 degrees C-30 degrees C). Ambient and core temperatures were measured throughout the procedure. RESULTS: Influence of ambient temperature was seen in: RESPIRATORY PARAMETERS: The frequency of central apneas increased significantly with increasing temperatures in REM sleep, but not in NREM sleep. HEART RATE (HR) PARAMETERS AND HR SPECTRAL ANALYSIS: Elevation of temperature was characterized by significantly higher basal HR, shorter RR intervals, and lower parasympathetic activity in REM and NREM sleep. SATURATION IN OXYGEN: During total sleep time, rise in temperature induced a decrease in basal oxygen saturation. During REM sleep, a greater frequency of oxygen saturation drops was associated with central apneas. CORE TEMPERATURE: With increasing ambient temperature, the rise of rectal temperature was mild. Despite this lack of significant increase, similar results were found when sleep and cardiorespiratory parameters were evaluated according to rectal temperatures. CONCLUSION: Changes in ambient temperatures associated with mild increases in body temperature significantly modified cardiorespiratory parameters and autonomic controls in healthy infants. The changes associated with increases in temperature were mainly seen during REM sleep.

Apnea↗

Coordinate up-regulation of Sp1 DNA-binding activity and urokinase receptor expression in breast carcinoma.

The regulatory mechanisms underlying the overexpression of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in highly invasive breast carcinomas remain poorly understood. In this study, we have simultaneously determined the level of uPAR and the activity of the transcription factor Sp1 in 14 breast carcinomas and 5 benign lesions. We found that uPAR levels and Sp1-binding activity are coordinately elevated in malignant tumors (r, 0.94; P < 0.001). On the contrary, undetectable or only barely detectable levels of uPAR and Sp1 activity were found in benign breast lesions. Finally, the engagement of uPAR by catalytically inactive uPA in the MDA-MB-231 breast carcinoma cell line results in a rapid up-regulation of Sp1-binding activity followed by an increase of uPAR protein. These results, taken together, suggest the existence of a uPA-dependent positive regulatory loop that may progressively enhance malignant breast cell invasiveness.

Adult↗

Novel cinchona alkaloid carbamate C9-dimers as chiral anion-exchange type selectors for high-performance liquid chromatography.

Nine new quinine (QN) carbamate C9-dimers (QN-X-QN), with different aliphatic and cyclic spacers (X), have been synthesized and immobilized onto porous silica gel for HPLC. The chiral discriminating behavior of these "dimeric" anion-exchange type chiral stationary phases (CSPs) has been investigated in detail, to elucidate the role of the presence of a second QN subunit on the chiral selector (SO), as well as the influence of the structure and length of the spacer, on the overall chiral recognition of a set of N-derivatized amino acids and other acidic drugs. The bulkiness of the intermediate spacer tuned the chiral recognition abilities of these SOs, with the 1,3-adamantylen-derived CSP being the one that led to the best separations. Shorter spacers reduced the chiral discrimination abilities of the "dimeric" selectors, with the n-hexylen bridge being the most favorable distance to allow a nearly independent interaction of the two QN subunits with the racemic analytes. The comparison to five "monomeric" CSPs showed that the "dimeric" ones usually retain the chiral analytes more strongly, though the enantioseparation is not improved. Nevertheless, the exceptional resolution abilities of dimeric SOs with a trans- 1,2-diaminocyclohexylen-bridge for the separation of DNP-derivatives of amino acids and certain acidic drugs of therapeutical interest (e.g., profens) seemed to be superior to most of the other CSPs.

Anion Exchange Resins↗

Influence of maternal smoking on autonomic nervous system in healthy infants.

To determine the influence of maternal smoking on autonomic nervous system in healthy infants, 36 infants were recorded polygraphically for one night. Their mothers were defined, according to their smoking frequency during pregnancy, as "nonsmokers" (no cigarettes smoked during pregnancy) or "smokers" (10 or more cigarettes per day). The infants had a median postnatal age of 10.5 wk (range 6 to 16 wk); 18 were born to nonsmokers, and 18 to smokers. During the whole night, spectral analyses of heart rate (HR) were evaluated as a function of sleep stages. Two major peaks were recognizable: a low-frequency component (LF) related to sympathetic and parasympathetic activities and a high-frequency component (HF) reflecting parasympathetic tonus. The ratio of LF/HF powers was calculated as an index of sympathovagal interaction. In REM sleep, "smokers" infants were characterized by significantly lower HF powers and normalized HF powers, and higher LF/HF ratios than "nonsmokers." The finding did not reach statistical significance in NREM sleep. In conclusion, maternal smoking induced changes in autonomic control and maturation in infants. These effects of cigarette smoke exposure can be added to those already reported and offer additional evidence for counseling mothers to stop smoking.

Adult↗

The influence of a pacifier on infants' arousals from sleep.

OBJECTIVE: The risk of sudden infant death during sleep was postulated to decrease with the use of a pacifier and by conditions facilitating arousals from sleep. We evaluated the influence of a pacifier on arousal from sleep in healthy infants. STUDY DESIGN: Fifty-six healthy infants were studied with polygraphy during 1 night; 36 infants used a pacifier regularly during sleep, and 20 never used a pacifier. Thumb users or occasional pacifier users were not included in the study. The infants were recorded at a median age of 10 weeks (range 6 to 19 weeks). To evaluate auditory arousal thresholds, the infants were exposed to white noise of increasing intensity during rapid eye movement sleep. RESULTS: Polygraphic arousals occurred at significantly lower auditory stimuli in pacifier users than in nonusers (P =.010). Compared with nonusers, pacifier users were more frequently bottle-fed than breast-fed (P =. 036). Among infants sleeping without a pacifier, breast-fed infants had lower auditory thresholds than bottle-fed infants (P =.049). CONCLUSIONS: Infants using pacifiers during sleep had lower auditory arousal thresholds than those who did not use a pacifier during sleep. Breast-feeding could be a further factor contributing to lower arousal thresholds. These findings could be relevant to the occurrence of sudden infant deaths during sleep.

Arousal↗

Urokinase receptor interacts with alpha(v)beta5 vitronectin receptor, promoting urokinase-dependent cell migration in breast cancer.

Perturbation of adhesive interactions at cell-substratum and cell-cell contact sites is a critical event in the multistep process of cancer invasion. Recent studies indicate that the urokinase receptor (uPAR) is associated in large molecular complexes with other molecules, such as integrins. To test the possibility that uPAR may physically and functionally interact with vitronectin (Vn) receptors, we determined the expression level of uPAR, alpha(v)beta3, and alpha(v)beta5 Vn receptors in 10 human breast carcinomas. Here, we show the ability of uPAR to physically associate with alpha(v)beta5 in the breast carcinomas examined. The functional effects of this interaction were studied using HT1080 human fibrosarcoma and MCF-7 human breast carcinoma cell lines, both exhibiting a urokinase-dependent physical association between uPAR and alpha(v)beta5. Both cell lines respond to urokinase or to its noncatalytic amino-terminal fragment by exhibiting remarkable cytoskeletal rearrangements that are mediated by alpha(v)beta5 and require protein kinase C activity. On the contrary, binding of Vn to alpha(v)beta5 results in the protein kinase C-independent formation of F-actin containing microspike-type structures. Furthermore, alpha(v)beta5 is required for urokinase-directed, receptor-dependent MCF-7 and HT1080 cell migration. These data show that uPAR association with alpha(v)beta5 leads to a functional interaction of these receptors and suggest that uPAR directs cytoskeletal rearrangements and cell migration by altering alpha(v)beta5 signaling specificity.

Adult↗

Prenatal exposure to cigarette smoking is associated with a decrease in arousal in infants.

OBJECTIVE: Sudden infant death syndrome has been related to both exposure to prenatal cigarette smoke and impaired arousability from sleep. We evaluated whether healthy infants born to mothers who smoked during pregnancy had higher auditory arousal thresholds than those born to mothers who did not smoke and whether the effects of smoking occurred before birth. STUDY DESIGN: Twenty-six newborns were studied with polygraphic recordings for 1 night: 13 were born to mothers who did not smoke, and 13 were born to mothers who smoked (>9 cigarettes per day). Other infants with a median postnatal age of 12 weeks were also studied, 21 born to nonsmoking mothers and 21 born to smoking mothers. White noise of increasing intensity was administered during rapid eye movement sleep to evaluate arousal and awakening thresholds. RESULTS: More intense auditory stimuli were needed to induce arousals in newborns (P =.002) and infants (P =. 044) of smokers than in infants of nonsmokers. Behavioral awakening occurred significantly less frequently in the newborns of smokers (P =.002) than of nonsmokers. CONCLUSIONS: Newborns and infants born to smoking mothers had higher arousal thresholds to auditory challenges than those born to nonsmoking mothers. The impact of exposure to cigarette smoke occurred before birth.

Arousal↗

Biomechanics of mandibular distractor orientation: an animal model analysis.

PURPOSE: Previous reports suggest that device orientation may be one of the most important parameters affecting the successful application of osteodistraction. However, only computer models or cadaver mandibles have been used to investigate the biomechanical effects of device orientation during mandibular distraction osteogenesis. Therefore, the purpose of this study was to compare two different device orientations during bilateral mandibular osteodistraction in an animal model. MATERIALS AND METHODS: Fifteen skeletally mature beagle dogs underwent 10 mm of bilateral mandibular lengthening by intraoral distraction osteogenesis. The dogs were divided into two groups based on the orientation of the distraction device relative to the mandible when viewed occlusally: either parallel to the body of the mandible (group I) or parallel to the axis of distraction (group II). The effects of device orientation during osteodistraction were then analyzed clinically, radiographically, and by dental cast measurements. RESULTS: Distractors oriented parallel to the body of the mandible caused an increase in the anterior width of the proximal mandibular segments. This lateral displacement of the proximal segments led to several clinical complications, including screw fixation failure and bone resorption under the fixation plates. These effects were minimized when the device was oriented parallel to the axis of distraction. CONCLUSIONS: Device orientation plays an important role when applying distraction osteogenesis in a clinical setting. Although other intrinsic and extrinsic factors affect the success of osteodistraction, the devices should be oriented parallel to the axis of distraction to minimize adverse biomechanical effects during bilateral mandibular lengthening.

Animals↗

Decreased autonomic responses to obstructive sleep events in future victims of sudden infant death syndrome.

To evaluate changes in autonomic nervous system controls in response to obstructive events in future victims of sudden infant death syndrome (SIDS), we studied the polysomnographic sleep recordings of 18 future SIDS infants and those of 36 matched control infants. A heart rate autoregressive power spectral analysis was performed preceding and after the obstructive apneas. The low-frequency to high-frequency power ratio was computed to evaluate sympathovagal balance. Future SIDS victims had significantly more obstructive apneas (p = 0.001) and mixed apneas (p = 0.005) than control infants. Obstructive events occurred mainly during rapid eye movement sleep in the two populations (84.5% in future SIDS victims and 95.8% in control infants; p = NS). Comparing heart rate power spectral analysis before and after obstructive apneas in rapid eye movement sleep, high-frequency power values were significantly lower and low-frequency to high-frequency power ratios higher in future SIDS victims than in control infants. Compared with preapnea values, low-frequency to high-frequency power ratios significantly decreased after obstructive apneas in control infants (p < 0.001) but not in the future SIDS victims. When the obstructive apneas were divided according to duration, the findings were seen mainly for long apneas. In conclusion, future SIDS victims were characterized by different autonomic status and responses to obstructive apneas during sleep. These findings could be relevant to mechanisms implicated in some cases of SIDS.

Apnea↗

Protein kinase C-dependent in vivo phosphorylation of prourokinase leads to the formation of a receptor competitive antagonist.

We recently reported that in vivo phosphorylation of urokinase-type plasminogen activator on Ser138/303 prevents its catalytic-independent ability to promote myelomonocytic cell adherence and motility. We now show that Ca2+ activated, phospholipid-dependent protein kinase C from rat brain phosphorylates in vitro a peptide corresponding to prourokinase residues 133-143 (DGKKPSSPPEE) and the full-length molecule on Ser138/139. The in vivo involvement of the protein kinase C isoenzyme family is supported by the finding that inhibition of kinase C activity prevents prourokinase phosphorylation on Ser138/303 in A431 human carcinoma cells. Conversely, a short treatment of A431 cells with phorbol myristate acetate increases the extent of phosphorylated prourokinase and, concomitantly, affects its function; under these conditions, the capability of prourokinase to up-regulate U937 monocyte-like cell adherence is severely impaired, although receptor binding is unaltered. By the aid of a "phosphorylation-like" variant (Ser138 to Glu) we show that modification of Ser138 is sufficient to confer to prourokinase the antagonistic properties observed following in vivo stimulation of protein kinase C activity. These observations provide the first evidence that protein kinase C directs the formation of a receptor competitive antagonist by regulating the in vivo phosphorylation state of prourokinase.

Amino Acid Sequence↗

Polysomnographic study of the autonomic nervous system in potential victims of sudden infant death syndrome.

To determine the influence of sleep stages and night-time distribution on cardiac autonomic activity, the polysomnographic recordings of 18 victims of sudden infant death syndrome (SIDS) and of 36 control infants were studied. Autoregressive spectral analyses of heart rate (HR), using both short-term and whole-night methods, were evaluated as a function of sleep stages. The two main peaks of normalized LF and HF were computed during the night and the sympathovagal balance (LF/HF) was determined. In both NREM and REM sleep, SIDS infants were characterized by significantly lower normalized HF powers and higher LF/HF ratios. This finding was observed in both short-term and whole-night HR spectral analyses. In addition, SIDS victims were characterized by the presence of a high desynchronized peak of sympathetic tonus in the late hours of the night, a finding not seen in the control subjects. This report adds further indirect evidence for a possible sleep-related impairment of autonomic controls in some infants who died of SIDS.

Autonomic Nervous System↗

Auditory arousal thresholds are higher when infants sleep in the prone position.

OBJECTIVE: To evaluate the possibility that infants sleeping in the prone position have higher arousal thresholds to auditory challenges than when sleeping in the supine position. STUDY DESIGN: Polygraphic recordings were performed for 1 night in 25 healthy infants with a median age of 9 weeks. The infants were exposed to white noises of increasing intensities while sleeping successively in the prone and supine positions, or vice versa. Arousal thresholds were defined by the auditory stimuli needed to induce polygraphic arousals. RESULTS: Three infants were excluded from the study because they awoke while their position was being changed. For the 22 infants included in the analysis, more intense auditory stimuli were needed to arouse the infants in the prone position than those in the supine body position (p = 0.011). Arousal thresholds were higher in the prone than in the supine position in 15 infants; unchanged in 4 infants; and lower in the prone position in 3 infants (p = 0.007). CONCLUSIONS: Infants show higher arousal thresholds to auditory challenges when sleeping in the prone position than when sleeping in the supine position. The finding could be relevant to mechanisms concerned with the reported association between sudden deaths and the prone sleeping position in infants.

Auditory Threshold↗