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Biomedical subjects

H Gautier

Publications and source records attributed to H Gautier.

At least 19 recordsLinked to original sources

Developing a free supportive care program for cancer patients within an integrative medicine clinic.

The cancer patient's journey not only includes a threat to one's life, but the need to face many medical and emotional challenges. The free Cancer Supportive Care Program (CSCP) within the Center for Integrative Medicine Clinic at Stanford University Hospital and Clinics has been identified as a successful model for helping patients to deal with these challenges. Its programs include informational lectures, support groups, chair massages, exercise, alternative modality classes, a Life Tapes Project, an informational website, and a bimonthly newsletter available free to anybody touched by cancer. Now in its third year, this program benefits from a blending of leadership resources, availability of space, institutional agreement on patient need and funds from private and corporate donations. By presenting the basic premises of the Cancer Supportive Care program and outlining specifics about the program, institutions in various national and international demographic regions may implement similar programs according to their resources and the needs of patients. It is our hope that the CSCP can become a model for the development of similar programs in various parts of the United States and abroad.

Adult↗

Compactibility study of calcium phosphate biomaterials.

This study investigated the micromechanism responsible for the densification and consolidation of powders during dynamic compaction, an experimental process in which ceramic is formed without heating. Three calcium-deficient apatites (CDA: two powders and a fibrous compound) and a biphasic calcium phosphate (BCP) were studied to determine their aptitude (rheological and physical properties) for compactibility under various dynamic compaction pressures. Powders were investigated for their physicochemistry, particle size, and flow time, and compacts for their compaction rate, density, specific area, mechanical characteristics, and disintegration time. Powder particles showed different morphological features depending on the synthesis protocol used, specific area and rheological behaviour. Compacts were not obtained with BCP, regardless of the gas pressure used, whereas CDA produced compacts with good mechanical properties (high hardness and compression stress), particularly for the fibrous compound. The poor compressibility and compactibility of BCP powders were confirmed, whereas fibrous CDA powders showed good compactibility conducive to high-quality filling of biomaterials.

Biocompatible Materials↗

NO and the hypometabolic and hypothermic responses to hypoxia in the rat.

Nitric oxide (NO) has been identified as a possible mediator of the thermoregulatory and respiratory responses to hypoxia. The present study was designed to assess the effects of an NO donor (S-nitroso-N-acetylpenicillamine, SNAP) injected systemically (0.5-2.0 mg/kg) in unanesthetized adult rats studied at ambient temperatures (Ta) of 26, 24, and 15 degrees C. The metabolic rate (VO2), ventilation (V), and colonic temperature (Tc) were recorded while the animals were exposed to normoxia or to hypoxia (FI(O2)=0.11). During normoxia, at all values of Ta, SNAP increased VO2 and V and the decrease in Tc observed following saline injection was prevented or attenuated. However, SNAP did not modify the hypometabolic, hypothermic, and hyperventilatory responses to hypoxia. We concluded that, confirming previous studies, NO may play a role in the control of VO2 and V in normoxia. The failure to observe any effect following the systemic NO donor injection during hypoxia may indicate opposing actions of the drug at different sites resulting in no net changes in ventilatory and metabolic responses to hypoxia.

Animals↗

Association of vancomycin and calcium phosphate by dynamic compaction: in vitro characterization and microbiological activity.

Dynamic compaction has rarely been used to produce drug-delivery devices in granule form. This report considered four processes associating vancomycin and compared dynamic compaction with wet granulation, a classical method. In the wet granulation study, vancomycin was associated with biphasic calcium-phosphate (BCP) granules either by adsorption or incorporation with a new granulation. In the dynamic compaction study, BCP powder was compacted at 1.1, 1.5 and 1.9 MPa. The compacts obtained were crushed and sieved (200-500 microm), and the vancomycin solution was adsorbed on the resulting granules. After crushing and sieving, the compaction of BCP and vancomycin powders produced vancomycin-loaded granules. In each study, 4.76% of vancomycin was associated with BCP. Granules were characterized in terms of porosity, vancomycin release and vancomycin biological activity. Physicochemical studies of BCP and vancomycin showed their structural integrity after dynamic compaction, which prolonged vancomycin release time from 1 to 6 days. However, a microbiological assay indicated that vancomycin had been altered since only 27.7% was found to be active.

Anti-Bacterial Agents↗

Vitamin B intake and status in healthy Havanan men, 2 years after the Cuban neuropathy epidemic.

A prospective epidemiological study was carried out over 1 year to evaluate vitamin B complex dietary intake and status in Cuba, 2 years after the Cuban neuropathy epidemic of 1993. Of the 199 healthy middle-aged men selected, 141 completed the study. Volunteers were followed up every 3 months for 1 year. Dietary intake and status of thiamin, riboflavin, vitamin B6, folate and vitamin B12 were assessed each time. The dietary intake of vitamin B complex was low, particularly in June and July (folate), and October (thiamin). A deficient status was observed for vitamin B complex, except for vitamin B6. Vitamin B complex intake and status varied over the year. However, dietary intake and status were poorly related. The results prove that healthy Cuban men represent a vulnerable population in terms of vitamin B complex status and stress the necessity to both promote preventive multivitamin supplementation and produce local food rich in vitamin B complex.

Adult↗

Body temperature regulation in the rat.

In loosely-restrained adult conscious rats exposed to stepwise changes in ambient temperature (T(a)) from 25 to 5 degrees C or from 20 to 35 degrees C, we have recorded body and tail temperatures, metabolic rate (VO(2)), shivering and ventilation (V). It was found that VO(2) and V vary with T(a) and show a nadir for a T(a) of 30 degrees C whereas shivering starts at 20 degrees C and increases progressively with cold exposure. T(tail) follows changes in T(a) whereas T(body) decreases slightly in cold and increases markedly in warm exposure. These results suggest that the control of T(body) interacts with the control of breathing in order to increase VO(2) during cold exposure and to facilitate evaporative respiratory heat dissipation during warm exposure.

Journal Article↗

Influence of isostatic compression on the stability of vancomycin loaded with a calcium phosphate-implantable drug delivery device.

It is essential to prevent microbial infections after osteoarticular trauma or prosthesis implantation. As an alternative to antibiotic parenteral administration, antibiotic-loaded biomaterials allow high concentrations to be obtained in situ without systemic toxicity. Although the formulation of biphasic calcium-phosphate (BCP)-vancomycin granules by isostatic compression has recently been used to produce drug-delivery devices, the stability of vancomycin needs to be proven. In this study, vancomycin was associated with BCP powders by isostatic compression at 100, 140, or 200 MPa and then extracted or released by a rotating paddle system for 24 h. Vancomycin assays were performed by spectrophotometric and microbiological methods. The results show that all vancomycin associated with the material was recovered after extraction without degradation. Thus, vancomycin was not denaturated after application of 100, 140, or 200 MPa of isostatic compression. The results for vancomycin released from granules compressed at the three pressures were not significantly different (p =.01) whether assays were performed microbiologically or spectrophotometrically, indicating a good correlation between the two methods. This process involving high pressure appears to be a good means of developing drug delivery devices loaded with therapeutic agents without denaturating the components.

Anti-Bacterial Agents↗

Isostatic compression, a new process for incorporating vancomycin into biphasic calcium phosphate: comparison with a classical method.

Isostatic compression has rarely been used to load calcium-phosphate biomaterials with therapeutic agents. This report, concerning four processes associating vancomycin, compares isostatic compression with wet granulation, a classical method. In the wet granulation study, vancomycin was associated with biphasic calcium-phosphate (BCP) granules either by adsorption or incorporation with a new granulation. In the isostatic compression study, BCP powder was compressed at 100, 140 and 200 MPa. The blocks obtained were crushed and 200-500 microm, sieved; thus, the vancomycin solution was absorbed on these granules. Compaction of BCP and vancomycin powders gave, after crushing and sieving, granules loaded with vancomycin. In each study, 5% vancomycin was associated with BCP. Vancomycin release profiles were assessed by an in vitro culture chamber dissolution test. Physicochemical studies of BCP and vancomycin showed their structural integrity after isostatic compression. Isostatic compression prolonged vancomycin release time from 3 to 7 days and the release time became greater as isostatic pressure increased, probably because of the porosity decrease of the granules during compression.

Calcium Phosphates↗

Intracellular pH determination of pristinamycin-producing Streptomyces pristinaespiralis by image analysis.

Intracellular pH (pH(i)) is an essential parameter in the regulation of intracellular processes. Thus, its measurement might provide clues regarding the physiological state of cells cultivated in vitro. pH(i) of the filamentous, pristinamycin-producing Streptomyces pristinaespiralis was determined by epifluorescence microscopy and image analysis using the pH-sensitive fluorescent probe BCECF-AM [2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, acetoxymethyl ester]. Staining cell culture samples (OD(660)=1) of S. pristinaespiralis with 20 microM BCECF at 28 degrees C for 30 min yielded a green/red fluorescence ratio (R:(527/600)) that correlated with the pH(i) of the cells for values ranging from 6.5 to 8.5. When S. pristinaespiralis was cultivated in pristinamycin-producing conditions (in batch mode, with a constant external pH of 6.8), the measured pH(i) varied between 6.3 and 8.7. In fact, pH(i) correlated with the excretion of pristinamycins and glucose consumption during the production process.

Anti-Bacterial Agents↗

Role of nitric oxide in hypoxic hypometabolism in rats.

Because it has been recently suggested that nitric oxide (NO) may mediate the effects of hypoxia on body temperature and ventilation, the present study was designed to assess more completely the effects of a neuronal NO synthase inhibitor (7-nitroindazole, 25 mg/kg ip), at ambient temperature of 26 and 15 degrees C, on the ventilatory (V), metabolic (O(2) consumption), and thermal changes (colonic and tail temperatures) induced by ambient hypoxia (fractional inspired O(2) of 11%) or CO hypoxia (fractional inspired CO of 0.07%) in intact, unanesthetized adult rats. At both ambient temperatures, 7-nitroindazole decreased oxygen consumption, colonic temperature, and V in normoxia. The drug reduced ambient or CO hypoxia-induced hypometabolism and ventilatory response, but the hypothermia persisted. It is concluded that NO arising from neural NO synthase plays an important role in the control of metabolism and V in normoxia. As well, it mediates, in part, the hypometabolic and the ventilatory response to hypoxia. The results are consistent with the notion that central nervous system hypoxia resets the thermoregulatory set point by decreasing brain NO.

Animals↗

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↗

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↗

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↗

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↗

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↗

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↗