Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Administration, Inhalation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed2005

The treatment of osteoporosis in patients with rheumatoid arthritis receiving glucocorticoids: a comparison of alendronate and intranasal salmon calcitonin.

OBJECTIVE: The purpose of this study was to assess the effects of alendronate and intranasal salmon calcitonin (sCT) treatments on bone mineral density and bone turnover in postmenopausal osteoporotic women with rheumatoid arthritis (RA) receiving low-dose glucocorticoids. METHODS: Fifty osteoporotic postmenopausal women with RA, who had been treated with low-dose corticosteroids for at least 6 months, were randomized to receive alendronate 10 mg/day or sCT 200 IU/day for a period of 24 months. All patients received calcium supplementation 1,000 mg and vitamin D 400 IU daily. Bone mineral density (BMD) of the lumbar spine, femoral neck, and trochanter was measured annually using dual-energy X-ray absorptiometry. Bone metabolism measurements included urinary deoxypyridinoline (DPD), serum bone alkaline phosphatase (BAP), and serum osteocalcin (OC). RESULTS: Over 2 years, the lumbar spine (4.34%, P < 0.001), femoral neck (2.52%, P < 0.05), and trochanteric (1.29%, P < 0.05) BMD in the alendronate group increased significantly. The sCT treatment increased lumbar spine BMD (1.75%, P < 0.05), whereas a significant bone loss occurred at the femoral neck at month 24 (-3.76%, P < 0.01). A nonsignificant decrease in the trochanteric region was observed in the sCT group (-0.81%). The difference between the groups with respect to the femoral neck and trochanteric BMD was statistically significant ( P < 0.001 and P < 0.05, respectively). The decreases in urinary DPD (-21.87%, P < 0.001), serum BAP (-10.60%, P < 0.01), and OC (-19.59%, P < 0.05) values were statistically significant in the alendronate group, whereas nonsignificant decreases were observed in the sCT group (-5.77%, -1.96%, and -4.31%, respectively). A significant difference was found in the DPD and BAP levels between the two treatment groups in favor of the alendronate group at all time points ( P = 0.001 and P < 0.05, respectively). CONCLUSION: The results of this study demonstrated that alendronate treatment produced significantly greater increases in the femoral neck BMD and greater decreases in bone turnover than intranasal sCT in RA patients receiving low dose glucocorticoids.

Absorptiometry, Photon↗
PubMed2005

Comparison of cyclic and continuous calcitonin regimens in the treatment of postmenopausal osteoporosis.

We aimed to compare and evaluate the efficacies of a continuous regimen of intranasal salmon calcitonin (SCT) and two cyclic regimens (different cyclic regimens from previous studies) based on alternating 15 days or on 10 days consecutively per month for 1 year in the treatment of postmenopausal osteoporosis. We performed an open-label, prospective, randomized clinical trial. A total of 120 postmenopausal osteoporotic participants between 50 and 65 years old were randomly assigned to one of three treatment groups. Patients in group 1 (n = 40) received continuously SCT nasal spray at a dose of 200 IU/day, plus continuously 500 mg/day elementary calcium and 0.25 microg/day 1-alpha hydroxyvitamin D3, for 1 year. Patients in group 2 (n = 40) received cyclically SCT nasal spray at a dose of 200 IU/day on alternating 15 days per month, plus continuously 500 mg/day elementary calcium and 0.25 microg/day 1-alpha hydroxyvitamin D3, for 1 year. Patients in group 3 (n = 40) received cyclically SCT nasal spray on 10 days consecutively per month (20 days/month rest), plus continuously 500 mg/day elementary calcium and 0.25 microg/day 1-alpha hydroxyvitamin D3, for 1 year. Data was evaluated by repeated analysis of variance (ANOVA). In addition, statistical differences between groups were assessed by the two-tailed Student's t test. After 1 year of the study, seven patients from group 1, eight patients from group 2 and five patients from group 3 withdrew from the study. No patient discontinued the study because of adverse drug effects. There was a statistically-significant improvement in pain intensity VAS scores at the end of the year to baseline scores in all three groups (p < 0.001). There was no significant difference in pain intensity VAS scores between groups at the end of the year (p > 0.05). Lumbar and femur neck BMD scores improved significantly at the end of treatment in all three groups (p < 0.05). There was no statistically-significant difference in BMD scores between groups at final (p > 0.05). Urinary DPD/Cre levels decreased significantly in all three groups by the end of the year (p < 0.05). There was no statistically-significant difference in urinary DPD/Cre final levels between groups (p > 0.05). According to the results of the present study, consecutive 10 days therapy with SCT, which is the first in the literature to our knowledge, is as effective as the other two regimens in the treatment of osteoporosis. Both cyclic regimens in our study (alternating 15 days and 10 consecutive days each month for 1 year) do appear to offer some advantages, especially economically and clinically, as compared to continuous treatment.

Administration, Inhalation↗
PubMed1999

Treatment with a gonadotropin-releasing-hormone analog and attainment of full height potential in a male monozygotic twin with gonadotropin-releasing hormone-dependent precocious puberty.

UNLABELLED: We report on a pair of male monozygotic twins, one unaffected and the other affected with gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, and discuss the role of treatment with a GnRH analog in the attainment of full height potential in GnRH-dependent precocious puberty. At 1.6 years of age, the affected twin was studied for tall stature (+3.8 SD), and was diagnosed as having GnRH-dependent precocious puberty due to a hypothalamic hamartoma of the tuber cinereum. He was treated with oral cyproterone acetate (110-170 mg/m(2) daily) from 1.8 through 5. 0 years of age, with oral cyproterone acetate and intranasal buserelin acetate (700-900 microg/m(2) daily) from 5.0 through 7.5 years, and with intranasal buserelin acetate alone (1100- 1400 microg/m(2) daily) from 7.5 through 12.6 years. He attained a final height of 171.0 cm at 14.9 years of age (+0.10 SD) and his twin 170. 0 cm at 15.3 years of age (-0.10 SD), with their target height being 174.5 +/- 9.0 cm. CONCLUSION: This study indicates that GnRH analog treatment may preserve near full height potential in some patients with GnRH-dependent precocious puberty.

Administration, Inhalation↗
PubMed2006

Anesthetic management of a pediatric patient on a ketogenic diet.

There are several specific considerations regarding seizure control during the perioperative period in patients who have been placed on a ketogenic diet (KD). A KD is high in fat and low in protein and carbohydrates and has a long history of use for the treatment of intractable seizures in children. Maintaining therapeutic ketosis and modifying the acid-base balance are particularly important for preventing seizures in patients on a KD. We report changes in the biochemical parameters of a patient with double cortex syndrome who was on a KD and who had been scheduled for the treatment of dental caries under sevoflurane anesthesia and acetate Ringer administration. Inhalation induction with a high concentration of sevoflurane should be reconsidered in view of recent reports describing the epileptogenic potential of sevoflurane.

Anesthesia↗
PubMed2002

Insulin analogues: new therapies for type 2 diabetes mellitus.

Insulin therapy is ultimately necessary for the control of blood glucose in a majority of patients with type 2 diabetes mellitus. Unfortunately, the pharmacokinetic characteristics of previously available rapid-, intermediate-, and long-acting preparations make sustained normoglycemia almost impossible. Advances in molecular genetic engineering have made possible the development of insulin analogues with pharmacokinetics that more closely mimic the needs of patients with type 2 diabetes. In the following article, we explore the insulin analogues currently available for clinical use, their pharmacokinetics, and the rationale for their use in the treatment of type 2 diabetes, and follow-up with a brief examination of future developments.

Administration, Inhalation↗
PubMed1987

A controlled trial of nebulized aminoglycoside and oral flucloxacillin versus placebo in the outpatient management of children with cystic fibrosis.

Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract, completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo. The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo.

Administration, Inhalation↗
PubMed1994

Effect of dexamethasone on A23187-induced airway responses in the guinea pig.

We examined the effect of dexamethasone on A23187-induced bronchospasm, pulmonary inflammation and airway responses to substance P. Guinea pigs, dosed orally once a day for 4 days with dexamethasone (3.0, 10.0 or 30.0 mg/kg) or saline, were exposed to an aerosol of A23187 for 12 min or until labored breathing began. Postmortem pulmonary gas trapping was used as an indicator of in vivo airway obstruction and changes in bronchial responses. Dexamethasone did not alter airway obstruction or inflammation 1 h after A23187 exposure. However, dexamethasone reduced the enhanced airway responses to substance P and bronchiolar/peribronchiolar inflammation 24 h post-A23187. It is possible that glucocorticosteroid suppression of A23187-induced pulmonary inflammation was important in reducing the increased airway responses to substance P.

Administration, Inhalation↗
PubMed1985

Relationship between the pharmacological effects and the biodisposition of [3H]diisopropylfluorophosphate in mice after inhalation.

The biodisposition of [3H]diisopropylfluorophosphate (DFP) and its metabolites was studied in mice after inhalation administration. In addition, the time course of DFP-induced cholinesterase inhibition in selected tissues, hypothermia, and motor coordination were studied to determine a possible correlation with [3H]DFP, or its metabolites. The time course of tissue concentrations of [3H]DFP showed that [3H]DFP rapidly penetrated all tissues and was quickly hydrolyzed to [3H]diisopropylphosphoric acid (free [3H]DIP) or was covalently bound to tissue (bound [3H]DIP). By 1 hr, the greater portion of the radioactivity was in the form of bound [3H]DIP. Cholinesterase inhibition in brain, lung, diaphragm, and plasma was temporally related to concentrations of bound [3H]DIP between 5 min and 1 day, except at early time points for the lung. Motor incoordination (rotarod test) produced by DFP exposure had a rapid onset, with complete recovery by 10 hr. DFP-induced hypothermia (rectal temperature) had a very similar time-course profile to that of motor incoordination. The time course of hypothermia and motor incoordination was correlated with neither free [3H]DFP nor bound [3H]DIP concentrations in the brain, nor with cholinesterase inhibition in brain. These findings suggest that non-cholinesterase bound [3H]DIP may contribute to the depression of these centrally mediated effects.

Aerosols↗
PubMed1990

Estimating the risk of liver cancer associated with human exposures to chloroform using physiologically based pharmacokinetic modeling.

A physiologically based pharmacokinetic (PB-PK) model for CHCl3 has been used to prepare estimates of the probability that human populations exposed to low levels of CHCl3 will develop liver tumors similar to those seen in rodent bioassays. The PB-PK model for CHCl3 was based on a model reported earlier by Corley et al. (1990), but this model differed from that of Corley et al. in that it was also capable of describing a pharmacodynamic endpoint: induction of cytotoxicity in the liver of CHCl3-exposed animals produced by reactive metabolites of CHCl3. Pharmacodynamic descriptions in this model were derived from experimental measurements of cell replication ([3H]thymidine incorporation) as well as from quantitative histopathology in the liver of rats and mice. Two different approaches were used for hazard evaluation: (1) a "Safety Factor" approach based on no observed effect levels for liver tumors. and (2) calculation of lower confidence limits on risk-specific doses with the GLOBAL83 computer program. In each case, cytotoxicity produced by reactive CHCl3 metabolites was used as the measure of "dose" to the liver. The Safety Factor approach suggested that continuous exposure of human populations to concentrations of CHCl3 less than 2840 ppb in air or 13,900 ppb in water would not be likely to significantly increase the risk of developing liver tumors. The second approach suggested a "plausible upper 95% confidence limit" of 1 x 10(-5) for lifetime excess cancer risk for human populations continuously exposed to 2200 or 13,100 ppb CHCl3 in air or water, respectively.

Administration, Inhalation↗
PubMed1991

PB-PK derived metabolic constants, hepatotoxicity, and lethality of BrCCl3 in rats pretreated with chlordecone, phenobarbital, or mirex.

Pharmacokinetic modeling has been very useful in examining the complex relationships between exposure concentration and target tissue dose. This study utilizes a physiologically based pharmacokinetic (PB-PK) modeling approach for assessing the metabolism of BrCCl3 and to investigate its relationship with hepatotoxicity and lethality. Male Sprague-Dawley rats maintained for 15 days on normal diet (control), or on diets containing either chlordecone (CD, 10 ppm), phenobarbital (PB, 225 ppm) or mirex (M, 10 ppm), were used in gas uptake studies to determine the kinetic constants of BrCCl3 metabolism. Four initial concentrations of BrCCl3 at approximately 30, 200, 700, and 3000 ppm were used for each group. The uptake data were analyzed by computer simulation using a PB-PK model containing relevant tissue solubilities and physiological parameters as well as an equation describing the behavior of BrCCl3 in the closed chamber atmosphere. Liver injury was assessed by serum enzyme elevations (alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase) and histopathological examination, at 24 hr after the exposure to BrCCl3. Another group of similarly pretreated rats was exposed to BrCCl3 and observed over a 14-day period for mortality. Dietary exposures resulted in increased Vmaxc value for BrCCl3 metabolism as compared to control (3.55 +/- 0.14 mg/hr/kg) for PB (8.52 +/- 0.28 mg/hr/kg) and M (5.06 +/- 0.19 mg/hr/kg) but not for CD (3.92 +/- 0.19 mg/hr/kg). Kfc, the first-order rate constant for BrCCl3 metabolism, was decreased after PB (12.9 +/- 0.5 hr-1/kg) and increased after M (17.6 +/- 0.5 hr-1/kg), but unchanged after CD (15.5 +/- 0.6 hr-1/kg) exposure as compared to control (15.0 +/- 0.3 hr-1/kg). The total amount of BrCCl3 metabolism at any initial concentration employed remained unchanged in all the pretreated groups as compared to control. However, the amount of BrCCl3 metabolized through saturable pathway only, at higher initial concentrations, was increased in the PB and M pretreated groups, but not in the CD pretreated group. It is concluded that the rates of metabolism of BrCCl3 were unchanged after CD pretreatment as compared to control, while PB and M pretreatment alter both the saturable and first-order rates. Serum enzymes were significantly increased in all the groups after exposure to BrCCl3 at 200 and 700 ppm concentrations. The increase was more pronounced in PB and M pretreated groups as compared to control and CD pretreated groups. Similarly, histopathological examination of liver showed alterations in the lobular architecture, the extent of alterations being dependent on the dose of BrCCl3 and the pretreatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMed1980

Bronchial response to methacholine and histamine in monkeys with beta adrenergic blockade.

The possibility has been investigated that propranolol administration could alter bronchial reactivity to methacholine and histamine in monkeys (Macaca fuscata and Macaca fascicularis). The impedance of the total respiratory system was measured by the forced 3-HZ oscillation method through an endotracheal tube. Methacholine and histamine dose-dependently increased the impedance in monkeys irrespective of the route of administration (inhalation of aerosol or intravenous injection). Propranolol treatment increased the bronchial response to intravenously injected methacholine and caused no significant change in the bronchial response to aerosolized methacholine. No marked difference was observed in the bronchial response to histamine due to treatment with propranolol regardless of whether administered by intravenous injection or aerosol challenge.

Adrenergic beta-Antagonists↗
PubMed1993

Intranasal flunisolide spray as an adjunct to oral antibiotic therapy for sinusitis.

BACKGROUND: The diagnosis of sinusitis is difficult and there are few controlled studies of customary therapies. In particular, the possible role of topical intranasal steroid as an adjunct to antibiotic treatment has not been evaluated. METHODS: The study was a multicenter, double-blind, randomized, parallel trial in which patients aged 14 years or older were recruited from allergy practices. All patients had maxillary sinusitis documented by radiographs. Treatment consisted of amoxicillin/clavulanate potassium 500 mg combined with nasal spray of either 100 micrograms flunisolide or placebo to each nostril three times a day for 3 weeks (phase I) followed by administration of flunisolide or placebo nasal spray alone three times a day for 4 weeks (phase II). RESULTS: Clinical symptoms and signs decreased significantly in both treatment groups during phase I (p < 0.01). There was a trend to greater improvement in the patients treated with flunisolide, but only the decrease in turbinate swelling/obstruction was statistically significant at the end of phase I when compared with placebo (p = 0.041). Patients' global assessment of overall effectiveness of treatment was higher for flunisolide than placebo after phase I (p = 0.007) and after phase II (p = 0.08). Maxillary sinus radiographs showed improvement in both treatment groups during phase I (p < 0.004) with somewhat greater regression of abnormal findings in patients treated with flunisolide after phase II (p = 0.066). However, 80% of radiographs were still abnormal at the end of phase I. All types of inflammatory cells were significantly decreased in nasal cytograms in patients treated with flunisolide in comparison with those treated with placebo. Flare-up of sinusitis during phase II occurred in 26% of with those treated with placebo. Flare-up of sinusitis during phase II occurred in 26% of patients treated with flunisolide and 35% of those treated with placebo and tended to be more severe in the latter, although these differences were not statistically significant. Adverse events, mainly gastrointestinal symptoms and headache, were similar in both groups and more frequent in phase I than in phase II, (42 vs 15 patients); these side effects were probably due to the antibiotic. CONCLUSION: The addition of flunisolide topical nasal spray as an adjunct to antibiotic therapy was most effective in global evaluations, tended to improve symptoms, to decrease inflammatory cells in nasal cytograms, to normalize ultrasound scans, and to aid regression of radiographic abnormalities compared with placebo spray.

Administration, Inhalation↗
PubMed1981

Issues relevant to the assessment of chemically induced chromosome damage in vivo and their relationship to chemical mutagenesis.

Rats have been exposed by different routes of administration (inhalation, orally and intraperitoneally) to known mutagens and their bone-marrow cells sampled at different times to determine the extent of chromosome damage. The mutagens investigated were ethyl methanesulphonate, mitomycin C, trimethylphosphate, benzene and vinyl chloride, at single and/or multiple doses (5 consecutive daily). Various categories of chromosome damage were observed in all cases. However, the extent of damage due to chromosome and chromatid gaps was greater than, and generally increased in parallel with, other categories of damage. It has been suggested tht chromosome and chromatid gaps are indicative of toxic phenomena but this study suggests that such aberrations could be useful and sensitive indicators of chemically induced genetic damage. In addition the study has also confirmed that single exposure is as effective as multiple exposure in producing chromosome damage and that the correct sampling time is necessary to detect this damage. Therefore for screening purposes a time course sampling after a single treatment regime would be suitable for detecting the mutagenic potential of a chemical.

Animals↗
PubMed1991

Comparison of intranasal and aerosol infection of mice in assessment of immunity to influenza virus infection.

A comparison was made of intranasal and aerosol routes of infection with X-31 influenza A virus in Balb/c mice. Mice were first infected with 100 MID50 by either route then challenged 42 days later with the same virus given by the same or alternative route. Three days following each infection, pulmonary virus was measured by inoculation of chick embryos. Mice initially infected under ether anesthesia by intranasal inoculation experienced higher initial mortality but proved most resistant to subsequent challenge by either method. In contrast, mice first infected by aerosol were least resistant to intranasal challenge, as indicated by increased rate of infection and pulmonary virus titers, but, like mice previously infected intranasally, were not reinfected by the aerosol route. Thus, intranasal infection appears to be more effective both in inducing and challenging immunity from infection. These results should be considered in the design of experiments utilizing influenza virus infection of mice as a model system.

Administration, Inhalation↗
PubMed1995

Radiotherapy with carbogen breathing and nicotinamide in head and neck cancer: feasibility and toxicity.

The feasibility and early toxicity of radiotherapy with carbogen breathing and nicotinamide was tested in 74 head and neck cancer patients. Forty patients with laryngeal and hypopharyngeal tumors were treated with an accelerated schedule combined with carbogen alone (16) or with carbogen and nicotinamide (24). Thirty-four patients with far advanced unresectable tumors of the oral cavity and oropharynx received conventional radiotherapy with carbogen [16] or with carbogen and nicotinamide (18). Some enhancement of skin reaction was observed with nicotinamide but this remained well within limits of tolerance. With the accelerated regimen there was increased severity of mucosal damage expressed as confluent mucositis in 95% of patients which required healing times of 3-4 months in four patients. Eventually restoration of the mucosal lining was complete in all cases. Nausea and vomiting are the most frequent side effects of nicotinamide and were reported by 60% and 36% of the subjects, respectively. In 26% this was reason to discontinue drug intake. Severe renal dysfunction was associated with nicotinamide intake in two patients of this study and in one other patient who presented later. It is our conclusion that radiotherapy combined with carbogen and nicotinamide is a safe treatment with manageable side effects. We recommend not to give nicotinamide concomitantly with nephrotoxic medication or to patients who have impaired renal function. Preliminary tumor control rates are encouraging and clinical testing will be continued.

Administration, Inhalation↗
PubMed1996

Tolerance of nicotinamide and carbogen with radiation therapy for glioblastoma.

Nineteen patients with glioblastoma were treated with nicotinamide and carbogen and radiotherapy. Eight patients did not complete the protocol because of hepatic toxicity from phenytoin/nicotinamide drug interactions, persistent nausea or vomiting with nicotinamide, intolerance of the carbogen breathing apparatus, or other reason. In addition, early radiation neurotoxicity appeared increased.

Administration, Inhalation↗
PubMed1994

Microcomputer programs for physiologically-based pharmacokinetic (PB-PK) modeling.

Physiologically-based pharmacokinetic (PB-PK) models are each defined as a set of mathematical equations offering a fairly comprehensive time course of a chemical's disposition in several pre-selected anatomical compartments. Each of these compartments has its characteristic blood flow, volume, tissue-blood partition coefficient, and metabolic or clearance rate constants that together are deemed responsible for a chemical's disposition in that region. Numerous investigators have used these models to predict tissue dose in the animal or human body in recent years. This simulation technique, if proven effective, will eventually reduce the large number of animals that are required in the costly classic, in vivo studies to be conducted for chemical disposition or metabolism. This communication offers 2 affordable micro-computer programs which can be used as a practical simulation tool in further exploring the application of PB-PK modeling in chemical risk assessment. These 2 programs are written especially for investigators who prefer to have some appreciation of the required computer simulation first before committing themselves to using more advanced, expensive simulation software packages that are commercially available.

Administration, Cutaneous↗
PubMed1993

Oral immunization with recombinant BCG induces cellular and humoral immune responses against the foreign antigen.

It has been shown recently that BCG can be used as a live recombinant vaccine to stimulate immune responses. Proliferative or cytotoxic T-cell responses against several viral proteins such as HIV Gag, Env or Nef were obtained after parenteral immunization with BCG expressing these proteins. Antibody responses were also obtained after immunization of mice with recombinant BCG strain which expressed lac Z under the control of a promoter sequence isolated from Mycobacterium paratuberculosis. We have used this recombinant vaccine in guinea-pigs to investigate the influence of various routes of immunization on the immunogenicity of a foreign antigen expressed by recombinant BCG. Guinea-pigs were immunized by oral, respiratory or intradermal routes and proliferative responses, delayed-type hypersensitivity and antibody responses specific for beta-galactosidase were followed for 16 weeks. Results demonstrated that humoral and cellular immune responses specific for beta-galactosidase can be produced in all groups of guinea-pigs. However, the respiratory and especially the oral route of administration induced higher local and systemic immune responses than the intradermal route of immunization. Moreover, the oral immunization of mice with this recombinant BCG induced IgA responses which could be detected in both sera and intestinal secretions. Therefore, this study demonstrates for the first time that oral immunization with recombinant BCG can induce strong cellular and humoral immune responses.

Administration, Inhalation↗