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Biomedical subjects

H Gautier

Publications and source records attributed to H Gautier.

At least 19 recordsLinked to original sources
PubMed1998

In vitro influence of apatite-granule-specific area on human growth hormone loading and release.

Although calcium phosphate biomaterials often are used as drug delivery systems (DDS) at bone sites, the conditions affecting the loading of the therapeutic agent (TA) have not been well documented. A human growth hormone (hGH) adsorption method was used in this study to investigate the influence of the formulated apatite (AP)-specific area on loading and release. AP powders were formulated with a 200-500 microm granulometry and various specific areas. Two milligrams of hGH in solution were deposited for 24 h at 37 degrees C on 100 mg of AP with different specific areas. The amount of hGH loaded was determined by immunoradiometric assay (IRMA) and eluted stain bioassay (ESTA) using Nb2 lymphoma rat cells. Although loading was not greatly influenced by a specific area between 3 and 25 m2/g, dependency was noted for higher specific areas. Human GH release was measured by IRMA and ESTA over a 33-day period, with half-time release between 25 and 79 h. Comparison of IRMA and ESTA measurements for the hGH amounts loaded showed that hGH biologic activity was conserved. Results indicate that it is feasible to control the quantity of TA loading on AP by modifying specific areas for in vivo applications.

Animals↗
PubMed1998

Neuromodulators and hypoxic hypothermia in the rat.

This study was designed to assess if opioids or adenosine are involved in the hypometabolism induced by hypoxia in the rat. Accordingly, antagonists such as naloxone (NLX) for opioids or theophylline (THEO) for adenosine were injected into conscious adult rats acutely exposed to either ambient hypoxia (AHx, FIO2: 12%) at ambient temperatures of 26 or 9 degrees C, or to CO hypoxia (COHx, FICO = 0.05%) at an ambient temperature (Ta) of 9 degrees C. Oxygen consumption, ventilation, colonic temperature and shivering were recorded. The results show that with NLX, the degree of hypoxic hypometabolism was reduced with AHx at 26 degrees C and slightly decreased with COHx at 9 degrees C. With THEO, hypoxic hypometabolism was slightly reduced with AHx and COHx at 9 degrees C. The ventilatory response to AHx and COHx was not consistently affected by either NLX or THEO. It is concluded that adenosine and opioids play a minor role, in mediating AHx or COHx hypothermia, especially during cold exposure.

Adenosine↗
PubMed1998

Exercise limitation in obstructive lung disease.

OBJECTIVE: To study the relationship of resting pulmonary function to maximal exercise power output (Wmax) in obstructive lung disease (OLD). SETTING: University Hospital Pulmonary Function Laboratory. SUBJECTS: Twenty-five patients with OLD (6 with asthma and 19 with COPD). METHODS: Measurement of pulmonary lung function, resting arterial blood gases, and maximal symptom-limited exercise on a cycle ergometer. RESULTS AND CONCLUSIONS: In OLD, the only significant contributor to Wmax was the inspiratory capacity (r2 = 0.66; p < 0.001).

Blood Gas Analysis↗
PubMed1997

Association of human growth hormone and calcium phosphate by dynamic compaction: in vitro biocompatibility and bioactivity.

The association of therapeutic agents with biomaterials has been achieved through various techniques, such as coating of the ceramic block surface or drug incorporation into ceramics. The dynamic compaction method recently was developed to consolidate drug-loaded calcium phosphate powder without a sintering step. In the present work, human recombinant growth hormone was loaded on biphasic calcium phosphate powder and consolidated by a specific process of cold sintering (dynamic compaction). Analyses of the biocompatibility of compacted pellets (mouse L929 fibroblastic cell culture) and the bioactivity of the drugs released by them (growth hormone bioassay) were performed. This report demonstrates the biocompatibility of the compacts prepared by dynamic compaction. L929 cell proliferation was maintained and the capacity to secrete fibronectin was conserved in the presence of compacted materials. Comparison of released growth hormone integrity, revealed by radioimmunoassay and eluted stain bioassay, has shown that the biological activity of growth hormone was totally preserved after dynamic compaction. However, 35% of loaded growth hormone was not released in our experimental conditions, probably because of the inaccessibility of growth hormone within the granulated compacts. Dynamic compaction shows good potential for the production of biomaterials capable of releasing therapeutic agents in situ.

Animals↗
PubMed1997

Ventilatory and metabolic responses to ambient hypoxia or hypercapnia in rats exposed to CO hypoxia.

We have investigated at ambient temperatures (Tam) of 25 and 5 degrees C the effects of ambient hypoxia (Hxam; fractional inspired O2 = 0.14) and hypercapnia (fractional inspired CO2 = 0.04) on ventilation (V), O2 uptake (VO2), and colonic temperature (Tc) in 12 conscious rats before and after carotid body denervation (CBD). The rats were concomitantly exposed to CO hypoxia (HxCO; fractional inspired CO = 0.03-0.05%), which decreases arterial O2 saturation by approximately 25-40%. The results demonstrate the following. 1) At Tam of 5 degrees C, in both intact and CBD rats, V/VO2 is larger when Hxam or CO2 is associated with HxCO than with normoxia. At Tam of 25 degrees C, this is also the case except for CO2 in CBD rats. 2) At Tam of 5 degrees C, the changes in VO2 and Tc seem to result from additive effects of the separate changes induced by Hxam, CO2, and HxCO. It is concluded that, in conscious rats, central hypoxia does not depress respiratory activity. On the contrary, particularly when VO2 is augmented during a cold stress, both V/VO2 during HxCO and the ventilatory responses to Hxam and CO2 are increased. The mechanisms involved in this relative hyperventilation are likely to involve diencephalic integrative structures.

Animals↗
PubMed1996

Interactions among metabolic rate, hypoxia, and control of breathing.

This review attempts to emphasize the fact that the interpretation of the ventilatory response to hypoxia may be complicated by the reduction in metabolic rate that is often associated with hypoxia. The hypoxic hypometabolism is more apparent when oxygen consumption is relatively high, either in small or young mammals at subnormal ambient temperatures or in larger mammals exposed to cold. This hypometabolism is not mediated by an activation of the arterial chemoreceptors and, furthermore, may result from a decrease in arterial oxygen content independent of the arterial PO2. Substantial experimental evidence supports the hypothesis of a lowering of the thermoregulatory set point during hypoxia through a direct action on central neural structures. The ventilatory response to hypoxia, which may appear blunted or depressed, especially in small animals exposed to cold, should in fact be reevaluated by taking into account the hypometabolism and hypothermia associated with hypoxia. Finally, it is emphasized that the mechanisms involved in control of body temperature and those that account for the interactions with hypoxia are located in the hypothalamus. This suggests that common integrative structures are probably involved in the metabolic and ventilatory responses to hypoxia.

Animals↗
PubMed1995

Ventilatory response to CO2 and hypoxia during cold exposure in awake rats.

Recently, we have described the effects of hypoxia and of hypercapnia on the metabolic (VO2) and ventilatory responses to cold in unanesthetized intact and carotid body-denervated (CBD) rats (Gautier et al., J. Appl. Physiol. 73: 847-854, 1992 and 75: 2570-2579, 1993). In the present paper, we have reanalyzed the above results for a more detailed study of the interactions of hypoxia (FIO2 = 0.12), hypercapnia (FICO2 = 0.04) and changes in VO2 with the ventilatory control. The results show that: (1) Compared to normoxia, in hypoxia increments in V and VT are proportional to VO2 whereas in hypercapnia increments in ventilation (V) and tidal volume (VT) are independent of VO2. In both hypoxia and hypercapnia, increases in respiratory frequency (fR) are independent of VO2; and (2) Interactions of hypoxia, hypercapnia and VO2 with control of V persist in CBD rats but, for a given VO2, V, VT and fR are lower than in intact rats. These interactions are essentially similar to those observed during muscular exercise performed in normoxia, hypoxia or hypercapnia. It is suggested that during cold exposure or muscular exercise, resulting both in increased VO2, there are common integrative structures probably located in the hypothalamus which are involved in the control of breathing.

Animals↗
PubMed1994

Ventilatory and metabolic responses to cold and CO-induced hypoxia in awake rats.

Experiments were carried out in awake rats to compare the effects of ambient and CO-induced hypoxia on thermoregulation and ventilatory control. Measurements of metabolic rate (VO2), ventilation (V), shivering (EMG) and colonic temperature (Tc) were made at fixed ambient temperature (Ta) of 25, 15 and 5 degrees C. Animals were exposed to ambient hypoxia (FIO2 of 21, 17, 14, 12 and 10%) or to CO hypoxia (FICO of 0.03% in air). The results show that: (1) Both ambient and CO-induced hypoxia provoked decreases in VO2 and Tc which were more marked at low Ta values; non-shivering thermogenesis was depressed with both types of hypoxia, whereas shivering was depressed only with ambient hypoxia; (2) Ventilatory response to ambient hypoxia was blunted at low Ta values and CO-induced hypoxia did not affect ventilation. It is concluded that: (1) hypoxia affects markedly the control of Tc by altering thermogenesis: inhibition of non-shivering thermogenesis seems to result from a decrease in CaO2 whereas inhibition of shivering seems to result from a decrease in PaO2; (2) during hypoxia, ventilation is controlled by the opposite stimulation from chemoreceptors and inhibition from hypometabolism. However, as revealed by CO-induced hypoxia, another stimulatory factor may also interact with the control of breathing.

Animals↗
PubMed1994

Lack of clinical benefit from subcutaneous tunnel insertion of central venous catheters in immunocompromised patients.

To assess the efficacy of subcutaneous tunneling, we randomly designated 212 central venous catheters for tunneling (107 catheters) or for standard insertion (105 catheters) in 169 immunocompromised patients. The patients who received tunneled catheters (TCs) and the patients who received nontunneled catheters (NTCs) were similar with respect to age, gender, underlying disease, incidence of leukopenic episodes, receipt of blood product transfusions or parenteral nutrition, and medical care and attendants. The life span of catheters was 112.5 +/- 9.5 days in the TC group and 119 +/- 9 days in the NTC group (P = .5). Clinically relevant bacteremia occurred in 26 cases in the TC group (0.22 episode per 100 catheter-days), a rate not significantly different from that in the NTC group (25 episodes; 0.20 episode per 100 catheter-days). Catheter-related bacteremia was documented in seven cases and non-catheter-related bacteremia in five cases. In most instances, the precise origin of the septic episode could not be determined. Cutaneous infection and bacteremia were associated with the same microorganism in two cases in each group. Since the present study failed to demonstrate any clinical benefit of subcutaneous tunneling, such a procedure is no longer performed in our hospital.

Adolescent↗
PubMed1994

Ventilatory strategy in hypoxic or hypercapnic newborns.

In conscious newborns, the ventilatory response to hypoxia is characterized by precocious hyperventilation followed by tardive hypoventilation, the latter disappearing with age. The hypoventilation could be mainly related to a weak peripheral drive and to the persistence of the diaphragmatic activity during expiration. Also, a decrease in metabolic rate and body temperature interferes with the response. The hyperventilation in response to hypercapnia increases as maturation proceeds and the maturation of the peripheral chemoreceptors contribute to this effect, as during hypoxia. The responses to both stimuli depend on many factors such as sleep state, anesthesia or ambient temperature.

Animals↗
PubMed1993

Ventilatory and metabolic responses to cold and CO2 in intact and carotid body-denervated awake rats.

We investigated in conscious rats the characteristics and modes of action of CO2 on thermoregulation and ventilatory control during cold stress. In a group of 10 rats studied intact and after carotid body denervation, measurements of metabolic rate (VO2), ventilation (V), shivering, and colonic temperature (Tc) were made at controlled ambient temperatures (Ta) of 25, 20, 15, 10, and 5 degrees C. Animals were exposed on different days to 1) normoxia, 2) normoxia and 4% CO2, 3) 12% hypoxia, or 4) 10.8% hypoxia and 4% CO2. The following results were obtained. 1) During CO2 exposure in normoxia or hypoxia, VO2 is increased at Ta of 25 degrees C and decreased for lower Ta. These effects are partly mediated by carotid body afferents. 2) Shivering and nonshivering thermogenesis and therefore Tc regulation are affected by CO2 exposure as shown by relationships between VO2-Tc and VO2-shivering intensity. 3) V is controlled by PO2 and PCO2 directly through their peripheral and central actions but also indirectly through their effects on VO2. Our conclusions are as follows. 1) Control of Tc is markedly dependent on PCO2 level. Carotid body afferents play a role, but direct central effects acting on the different sources of thermogenesis and possibly on thermolysis are most prominent. 2) As far as control of V is concerned, during hypercapnia in normoxia or hypoxia, several analogies may be formed between exposure to cold and muscular exercise, both of which increase VO2 and V, suggesting common integrative mechanisms at the central nervous system level.

Animals↗
PubMed1992

Control of metabolic and ventilatory responses to cold in anesthetized cats.

Interactions between the control of thermogenesis and ventilation were studied during normoxia, hyperoxia, and ambient or CO hypoxia in adult anesthetized intact or carotid-denervated cats. Shivering, metabolic and ventilatory responses to cold stress were studied. In addition, the effects of transient pharmacological stimulation (NaCN) or inhibition (Dopamine) of arterial chemoreceptor activity were studied under different levels of oxygenation. In intact animals, cold exposure provoked increases in VO2 and ventilation which were directly proportional to the intensity of shivering. During ambient or CO hypoxia, VO2 was less than in normoxia for all values of shivering intensity, suggesting that a non-shivering thermogenesis component may also be inhibited by hypoxia. The decrease in VO2 was associated with a smaller decrease in ventilation in ambient than in CO hypoxia because of the presence of the chemoreflex drive during ambient hypoxia. Pharmacological changes in chemoreceptor activity induced transient and opposite changes in ventilation and shivering intensity, confirming their role in the control of thermogenesis. After carotid denervation, when the drug effects were inconsistent or absent, changes in levels of oxygenation were still followed by changes in shivering activity and associated changes in VO2 and ventilation. We conclude that control of thermogenesis and ventilation and their interaction may be mediated by chemoreceptors as well as by direct effects upon central, possibly diencephalic structures.

Animals↗
PubMed1992

Diaphragmatic and ventilatory responses to alveolar hypoxia and hypercapnia in conscious kittens.

Ventilation and electromyographic (EMG) activity of the diaphragm were recorded in unanesthetized kittens 2 and 10 wk of age during normoxia, hypercapnia (2 and 4% CO2), and hypoxia (12 and 10% O2). We measured integrated diaphragmatic EMG activity at end inspiration (DIAI) and end expiration (DIAE); the difference (DIAI-E), which represents the phasic change of the diaphragmatic activity, was considered responsible for a given tidal volume (VT). During hypercapnia, the 2-wk-old kittens increased minute ventilation (V) by increases in both VT and respiratory frequency (f), whereas the 10-wk-old kittens increased V primarily by an increase in VT. At both ages, DIAI and DIAI-E increased during hypercapnia, whereas DIAE did not change significantly. During hypoxia, in the young kittens, V and VT decreased while f increased markedly; in the older kittens, V, VT, and f did not change significantly. In kittens of both ages, DIAI increased during hypoxia; because diaphragmatic activity persisted into expiration, DIAE also increased. DIAI-E, as well as VT, was decreased in the young kittens, whereas in the older ones DIAI-E was slightly increased despite an unchanged VT. Finally, the ventilatory and diaphragmatic response to hypoxia changes with maturation in contrast to the response to hypercapnia. It is concluded that 1) the hypoxia-induced reduction of VT may result from prolongation of diaphragmatic activity into expiration, inasmuch as it induces a reduction of the phasic change of the diaphragmatic activity, and 2) because DIAI-E indirectly reflects central inspiratory output, a central mechanism should be involved in the reduced VT and V in response to hypoxia in newborns.

Animals↗
PubMed1992

Ventilatory and metabolic responses to cold and hypoxia in intact and carotid body-denervated rats.

The effects of hypoxia on thermoregulation and ventilatory control were studied in conscious rats before and after carotid denervation (CD). Measurements of metabolic rate (VO2), ventilation (V), shivering intensity (SI), and colonic temperature (Tc) were made in groups of eight rats subjected to three protocols. In protocols 1 and 2, at ambient temperature (Ta) of 25 and 5 degrees C, respectively, rats were exposed to normoxia and hypoxia [inspired O2 fraction (FIO2) 0.13-0.11]. In protocol 3, Ta was decreased from 25 to 5 degrees C in 30-min steps of 5 degrees C. Recordings were made in normoxia and hypoxia (FIO2 0.12). The results show that in both intact and CD rats 1) in normoxia, cold exposure increased VO2, V, and SI, and these increases were proportional to the decrease in Ta; 2) hypoxia induced only a transient decrease in SI, and, for a given Ta, VO2 was reduced whereas V and SI were increased; and 3) in CD rats, V increased less during cold exposure in both normoxia and hypoxia; VO2 and Tc were more depressed during hypoxia. It is concluded that 1) the interaction between Ta and FIO2 in the control of V is partly dependent on the carotid body afferents, 2) shivering thermogenesis may be transiently affected by hypoxia independently of the carotid body afferents, and 3) nonshivering thermogenesis may be directly inhibited by hypoxia, especially during cold exposure.

Afferent Pathways↗