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PubMedDate not supplied

[In vitro availability of a topical corticosteroid from various vehicles. Attempt at a correlation with an in vivo study].

The object of the study is to show the availability of a topical corticosteroïd (difluprednate) from pharmaceutical forms: the gel and cream forms in which the substance is solubilised, the greasy and emulsified forms in which the substance is dispersed. The bioavailability of these forms dosed to 0.025% was evaluated by a cutaneous vasoconstriction test. The results show that the cutaneous penetration of difluprednate is more favourable in the gel and cream forms. The "in vitro" availability of commercial dosage forms (0.05% of difluprednate) and the "in vivo" results are compared and commented.

Biological Availability↗

PubMed1981

Biological availability of sulfamethoxypyridazine and sulfisomidine polymers.

Dissolution rates and apparent solubilities of forms I, II and III of Sulfamethoxypyridazine (1) and forms I and II of sulfisomidine (2) were determined in water at 37 degrees C. The ratios of apparent solubilities of I:II:III for 1 forms and I:II for 2 forms were 1:1.18:1.25 and 1:1.32 respectively. Upon long contact of 2 with water the ratio of II:I decreased. This has been attributed to gradual transformation of 2 from form II to I. Gastrointestinal absorption of form III of 1, in human volunteers, was studied in comparison with the more stable form I. The same study was carried out on forms I and II of 2. Data were correlated and expressed in availability rate constants (K1), applying the one compartment open: model. This and other parameters show that form III of 1 is 1.4 times as much absorbed as form I, and that the availability of the metastable form II of 2 is 1.2 times as much absorbed as the stable form I.

Biological Availability↗

PubMed1981

Anemia of inflammatory disease in the dog: availability of storage iron in inflammatory disease.

The iron-chelating agent deferoxamine (DF) was administered as a single dose and also daily over a prolonged period to evaluate availability of storage iron in dogs with induced anemia of inflammatory disease. In a 6-hour period, total urinary ferrioxamine (measured as urinary iron) excretion in controls was 251.22 +/- 119.68 microgram (mean +/- 1 SD), a 5.32 +/- 2.64-fold increase over prechelation values. In anemia of inflammatory disease-affected dogs, excretion was diminished to 115.67 +/- 34.86 microgram, a 2.87 +/- 1.10-fold increase, indicating a restricted iron excretion and sequestration of iron in a less soluble, less chelatable form. During prolonged DF administration, a pattern of increasing total urinary iron excretion was observed. This pattern is consistent with iron being stored as an insoluble polynuclear hydroxide in protein of ferritin and hemosiderin. The increase in hemoglobin and serum iron concentrations during prolonged DF administration indicates that increased iron stores are present, but in a less labile form. During the process of chelation, iron is converted to a more readily utilized state, and the increased availability of iron promotes hemoglobin synthesis. Thus, storage iron in the form of hemosiderin and ferritin is released to the metabolizable pool.

Anemia↗

PubMed1980

Physical and dissolution characteristics and bio-availability of five brands of digoxin tablets.

Five brands of digoxin were investigated and compared for physical and dissolution characteristics and bio-availability. The dissolution characteristics, which are regarded as a measure of bio-availability in the case of digoxin, were investigated with a spectrofluorimeter. Significant differences were found among the five brands. Only one brand met all the various criteria that were investigated.

Biological Availability↗

PubMedDate not supplied

The availability and accessibility of the contraceptive implant from family planning agencies in the United States, 1991-1992.

During the first year and a half after the hormonal contraceptive implant became available in February 1991, an estimated 81,100 women obtained this method from family planning agencies in the United States. Nevertheless, according to a recent survey of family planning providers, implant availability through the family planning clinic system is still far from universal. By September 30, 1992, only 40% of all family planning agencies were offering implant services to their clients: That proportion ranged from 30% of health department family planning providers to 80% of Planned Parenthood affiliates. Some of the key reasons cited by agencies that do not yet provide implants include the special clinician training required to learn insertion and removal procedures, and the cost of the method. Furthermore, full accessibility of this method to low-income women attending family planning clinics has been limited primarily to those who receive Medicaid, which has paid for more than 60% of all hormonal implants inserted by family planning agencies.

Contraceptive Agents, Female↗

PubMedDate not supplied

[Modelling of the biological availability of 137Cs in soils subjected to contamination after the accident at the Chernobyl Atomic Electric Power Station].

Results of the application of the model describing behaviour of the radionuclide in meadow ecosystems for the analysis of the factors governing of the radionuclide availability in soils are presented. The estimation of characteristics of fuel particles in "near" zone of the Chernobyl NPP is given. It's shown that in the first period after the accident the main factors determining 137Cs availability in soil are property of soil and mat as well as fallout characteristics.

Biological Availability↗

PubMedDate not supplied

Increasing the availability of vasectomy in public-sector clinics.

A program designed to improve the availability of vasectomy in public-sector clinics trained physicians at 43 facilities in no-scalpel vasectomy between 1993 and 1995. Among the 38 clinics that responded to a follow-up survey in 1996, the number of clinics providing vasectomies rose from 23 to 32, an increase of almost 40%, while the number of vasectomies performed rose by 18%. Seventeen of the 32 clinics performed more vasectomies after the training; 10 of the 17 had not previously provided the procedure. In-depth interviews with staff from seven sites that experienced large caseload increases and from seven that experienced decreases identified three elements for the successful establishment or expansion of vasectomy services-sufficient numbers of trained providers, funds to subsidize vasectomies for men who cannot afford them and activities to raise awareness about the availability of low-cost or free vasectomy.

Ambulatory Care Facilities↗

PubMed1997

Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents. Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins.

Grapefruit juice increases the oral availability of a variety of CYP3A4 substrates. It has been shown that recurrent grapefruit juice ingestion results in a loss of CYP3A4 from the small bowel epithelium. We now show that the reduction in intestinal CYP3A4 concentration is rapid; a 47% decrease occurred in a healthy volunteer within 4 hr after consuming grapefruit juice. To identify the specific components of the juice responsible for this effect, we used a recently developed Caco-2 cell culture model of human intestinal epithelium that expresses catalytically active CYP3A4. We found that grapefruit oil and two furanocoumarin constituents (6', 7'-dihydroxybergamottin and a closely related dimer) caused a dose-dependent fall in CYP3A4 catalytic activity and immunoreactive CYP3A4 concentration. The effect was selective in that concentrations of CYP1A1 and CYP2D6 did not fall, consistent with previous results obtained in vivo. Assays of various juices confirmed that 6',7'-dihydroxybergamottin is the major furanocoumarin present and, although its concentration varies significantly among types and brands of grapefruit juice, it is consistently present in concentrations exceeding the IC50 (1 microM) for loss of midazolam 1'-hydroxylase activity determined in the Caco-2 cells. Studies with recombinant CYP3A4 revealed that 6', 7'-dihydroxybergamottin is a mechanism-based inactivator, which supports the idea that loss of CYP3A4 results from accelerated degradation of the enzyme. We conclude that the effect of grapefruit juice on oral availability of CYP3A4 substrates can be largely accounted for by the presence of 6',7'-dihydroxybergamottin although other furanocoumarins probably also contribute.

Biological Availability↗

PubMed1996

Diagnosis of pediatric human immunodeficiency virus infection by means of a commercially available polymerase chain reaction gene amplification.

OBJECTIVE: To assess the sensitivity and specificity of polymerase chain reaction (PCR) in infants and children at risk for human immunodeficiency virus (HIV) infection. DESIGN: A prospective, blinded study of 286 HIV-seropositive infants and children. Infection was diagnosed by antibody detection after 18 months of age, two positive direct tests (p24 antigen and HIV culture), or the presence of an illness that defines the acquired immunodeficiency syndrome. SETTING: University of South Florida and All Children's Hospital, St Petersburg, inpatient and outpatient centers. PARTICIPANTS: Two hundred eighty-six infants and children seropositive for HIV who were examined between July 1988 and September 1992. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive values of a commercially available PCR test. RESULTS: Five hundred sixty-seven PCR tests were performed on samples from 286 seropositive subjects followed up for a minimum of 16 months. Of the subjects, 105 were confirmed to be infected and 181 uninfected. Overall, 96 of 105 initial PCRs in infected subjects were positive (sensitivity, 91.4%; positive predictive value, 99%). If samples obtained during the first week of life are excluded, 95 to 100 samples were positive (sensitivity, 95%). Of 181 initial PCR tests from seropositive subjects who seroreverted, 180 were negative (specificity, 99.4%,; negative predictive value, 95.2%). The predictive value of a positive test was 90.9% and that of a negative test was 93.1% in the first month of life. All 145 initial samples obtained between 5 weeks and 12 months of age correctly predicted infection status (positive predictive value, 100%). CONCLUSIONS: Gene amplification by means of a commercially available PCR is useful in the diagnosis of HIV infection for infants born to seropositive mothers. Between day 7 through 1 year of age, HIV infection is accurately diagnosed by the PCR assay.

Age Factors↗

PubMed1989

Age of alcoholism onset. II. Relationship to susceptibility to serotonin precursor availability.

Alcoholics who start abusing alcohol early in life have been found to exhibit problems with mood and aggression control more frequently than patients with a later onset of alcoholism. Because alcohol preference and consumption, as well as mood and aggression regulation, are believed to be influenced by serotonin, relationships between tryptophan availability and mood and aggression regulation were explored in alcoholics. When studied in the entire population, the ratio of tryptophan over other amino acids competing for brain entry (which influences brain serotonin) was found to be lowest one day after cessation of drinking and to increase progressively over the following two to three weeks. When the population was divided into two groups of patients according to whether subjects started abusing alcohol before or after 20 years of age, associations between a low tryptophan ratio and depressive and aggressive tendencies were significant only in the subgroup of patients with an early onset of alcoholism. They were not significant in the rest of the population. Our data are compatible with the interpretation that patients with an early onset of alcoholism have a preexisting serotonin deficit that could manifest itself by an increased alcohol intake early in life and by an increased vulnerability to fluctuations in precursor availability.

Adult↗

PubMed2007

Long-term results of endovascular abdominal aortic aneurysm treatment with the first generation of commercially available stent grafts.

HYPOTHESIS: Little information about the long-term results of endovascular abdominal aortic aneurysm repair is available. This study was performed to evaluate the long-term data of patients treated with the first generation of commercially available stent grafts. DESIGN: Multicenter registry. SETTING: Sixty-two European centers that participated in the EUROSTAR (EUROpean collaborators on Stent-graft Techniques for abdominal aortic Aneurysm Repair) registry. PATIENTS: A total of 1190 patients with a follow-up of up to 8 years, who underwent endovascular abdominal aortic aneurysm repair with a stent graft (Stentor or Vanguard). INTERVENTION: Elective endovascular abdominal aortic aneurysm repair. MAIN OUTCOME MEASURES: The morbidity and mortality data of patients treated with the first-generation stent graft who enrolled in the EUROSTAR registry were analyzed. Incidence rates of complications were calculated to quantify annual risks. Life-table analyses and multivariate Cox proportional hazards models were used for the survival analysis. RESULTS: Conversion to open repair, aneurysm rupture, all-cause death, and aneurysm-related death occurred in 7.1%, 2.4%, 19.9%, and 3.0% of the patients, respectively. The cumulative percentage of the combined outcome event, conversion-free and rupture-free survival, after 8 years was 48.0%. Procedure-related complications that frequently occurred were endoleak (13.0 cases per 100 patient-years), stenosis/thrombosis (4.6 cases per 100 patient-years), and stent migration (4.3 cases per 100 patient-years). CONCLUSIONS: Patients treated with the first generation of stent grafts will need lifelong surveillance because of a considerable risk of late complications. How these findings translate to the outcome of newer-generation stent grafts is unknown. For this reason, vigilant surveillance remains indicated in all patients who undergo endovascular abdominal aortic aneurysm repair.

Adult↗

PubMed1993

High-technology cardiac procedures. The impact of service availability on service use in New York State.

OBJECTIVE: To study the impact of the in-hospital availability of three cardiac procedures (cardiac catheterization, bypass surgery, and angioplasty) on their use in patients during the period following acute myocardial infarction (AMI). DESIGN: Retrospective cohort study, based on a statewide hospital discharge abstract data set. PARTICIPANTS: Patients admitted with a principal diagnosis of AMI to New York State hospitals during March through June of 1986. MAIN OUTCOME MEASURES: The odds of utilizing each of the three services either during the initial admission for AMI or during the 6-month postdischarge interval. Odds ratios (ORs) were calculated comparing utilization in three groups of patients: those initially presenting to hospitals lacking all three services, those initially presenting to hospitals offering only cardiac catheterization, and those initially presenting to hospitals offering all three of the cardiac services. Odds were adjusted for age, sex, race, income, primary payer, severity of illness, and geographical distance to hospital. RESULTS: Relative to patients initially presenting to hospitals lacking all three services, patients initially presenting to hospitals offering only cardiac catheterization were more likely to undergo cardiac catheterization (OR, 3.57; 95% confidence interval [Cl], 3.03 to 4.22), but were not significantly more likely to undergo bypass surgery or angioplasty. Relative to patients initially presenting to hospitals lacking all three services, patients initially presenting to hospitals offering all three services were more likely to undergo cardiac catheterization (OR, 5.50; 95% Cl, 4.66 to 6.50), bypass surgery (OR, 2.52; 95% Cl, 1.95 to 3.24), and angioplasty (OR, 6.85; 95% Cl, 4.73 to 10.58). CONCLUSIONS: The availability of cardiac services in the hospital to which patients initially present strongly influences the likelihood of their use in the period following AMI.

Aged↗

PubMed2000

Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry.

CONTEXT: Since the introduction of combined antiretroviral therapy, mortality rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have decreased. However, little information is available outside the setting of controlled trials on survival of perinatally HIV-infected children treated with antiretroviral therapy. OBJECTIVE: To assess effect of availability of antiretroviral therapy on decreasing mortality in perinatally HIV-infected children. DESIGN: Population-based, multicenter longitudinal study involving data collected by the Italian Register for HIV Infection in Children. SETTING: A network of 106 pediatric clinical centers. SUBJECTS: A total of 1142 children born between November 1980 and December 1997 with perinatally acquired HIV infection with a median follow-up of 5.9 years. MAIN OUTCOME MEASURE: Time to HIV-related death calculated for birth cohort and calendar period and grouped by distribution of predominant type of antiretroviral therapy administered over time. RESULTS: Survival was longer in the 1996-1997 birth cohort (crude relative hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996-1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth cohort and calendar period 1980-1995, but not when adjusted for maternal antiretroviral treatment during pregnancy and clinical condition at time of delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI, 0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16, for calendar period). In a multivariate model with 1980-1995 as comparison, the 1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects of birth cohort, calendar period, and type of antiretroviral therapy were evaluated simultaneously in the same model, the RH of death was not significantly different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period 1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of death and use of combination therapy. The RH of death in children receiving monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55-1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs no antiretroviral therapy. CONCLUSION: Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197

Adolescent↗

PubMed1998

Distribution of the flocculation protein, flop, at the cell surface during yeast growth: the availability of flop determines the flocculation level.

The yeast FLO genes encode cell surface proteins which are expected to play a major role in the control of flocculation. We have assessed the availability of the Flo proteins at the cell surface during the growth of two flocculent strains, ABXL-1D (FLO1) and STX347-1D (FLO5) using immunological approaches, enzyme-linked immunosorbent assays and immunofluorescence. Our data show that they are not permanently present at the cell surface but that their amount increases during growth. With both strains the flocculation level is tightly correlated to the amount of Flop antigen detected, suggesting that it is the availability of the Flo proteins at the cell surface which determines the flocculation level. Our data are consistent with the idea that the Flo proteins correspond to the flocculation lectins. The differences of flocculation pattern among strains could originate from variations in the regulation of the expression of the FLO genes. Monitoring of the distribution of the Flo proteins during cellular development revealed that they are incorporated essentially in the cell wall of growing buds. Incorporation of the Flo proteins in the cell wall displays a highly polarized aspect, at the bud tip and at the mother-daughter neck junction, which can persist in mature cells. Such a localization could be relevant to constraints of the cell wall incorporation of the mannoproteins. Depending on the regulation of Flop expression and on the incorporation of the proteins in the cell wall, a yeast population can be highly heterogeneous in Flo protein equipment.

Cell Wall↗

PubMed1997

Surface-bound plasmin induces selective proteolysis of insulin-like-growth-factor (IGF)-binding protein-4 (IGFBP-4) and promotes autocrine IGF-II bio-availability in human colon-carcinoma cells.

Limited proteolysis of insulin-like-growth-factor (IGF)-binding proteins (IGFBPs) represents a key process to modulate IGF bio-availability at the cellular level. In human colon carcinomas, urokinase-type plasminogen activator (u-PA) produced by stroma cells can bind to cancer-cell-associated u-PA receptor (u-PAR), and then catalyze the conversion of plasminogen (Pg) into plasmin (Pm). We therefore investigated the interplay between the IGF and Pm systems in the HT29-D4 human colon-carcinoma-cell model. HT29-D4 cells secreted IGF-II totally complexed to IGFBP-2, IGFBP-4 and IGFBP-6. Approximately 15% of IGFBP-4 was associated with the extracellular matrix. HT29-D4 cells produced neither u-PA- nor IGFBP-specific proteases. However, activation of Pm at the HT29-D4 cell surface obtained by the sequential addition of exogenous u-PA and Pg to mimic the stromal complementation induced selective proteolysis targeted to IGFBP-4 only (>95%). IGFBP-2 and IGFBP-6, though sensitive to proteolysis by soluble Pm, were not altered by cell-bound Pm. IGFBP-4 proteolysis yielded 18- and 14-kDa immunoreactive fragments which were not detectable by Western ligand blotting, indicating that they bound IGF-II with poor affinity. Release of IGF-II from IGF-II-IGFBP complexes after IGFBP-4 proteolysis by cell-bound Pm was indicated by the observation that approximately 20% of the 125I-IGF-II initially associated with endogenous IGFBP in reconstituted complexes was transferred to HT29-D4 cell-surface IGF-I receptors. These results suggest that IGFBP-4 proteolysis by cell-bound Pm can promote autocrine/paracrine IGF-II bio-availability in colon-cancer cells. This may have important consequences on the behavior of cancer cells at the interface between stroma and malignant cells in carcinomas of the colon in vivo.

Adenocarcinoma↗

PubMed1998

Availability of epidemiologic data for chemicals known to cause cancer in animals: an update.

Between 1972 and 1996, the International Agency for Research on Cancer (IARC) identified 282 chemicals as having experimental evidence "sufficient" to conclude that the chemicals cause cancer in animals. Of the 282 IARC animal carcinogens, 7% (20) also had "sufficient" evidence from epidemiology studies. "Limited" human evidence was available for 5% (13) of the 282 IARC animal carcinogens. A 1996 IARC international compendium of cancer studies indicated that epidemiologic studies of chemicals determined by IARC to cause cancer in both humans and animals were considerably more common than studies of chemicals determined to cause cancer in animals but for which human data were inadequate or limited. Of the 1,101 studies reported to IARC by investigators, the IARC animal carcinogens, with the most ongoing studies were asbestos (50 studies) and benzene (26 studies). Both chemicals have sufficient evidence of carcinogenicity from studies of humans. There were epidemiologic studies ongoing for 65% (13/20) of the chemicals for which evidence of carcinogenicity was sufficient in both animals and humans. Epidemiologic studies were reported to IARC for 12% (30/247) of the IARC animal carcinogens for which human data were inadequate or for which no human data were available. Two factors appear critical in determining whether an IARC animal carcinogen becomes the subject of an epidemiologic study: the likelihood of overcoming methodological obstacles to carrying out successful epidemiologic studies, and the economic and/or regulatory interest in the chemical.

Animals↗

PubMed1996

Perceived availability of different types of social support among cynically hostile women.

One hundred and ninety six young women completed the Cook-Medley Hostility (Ho) scale and a measure of the perceived availability of social support. Results of partial correlations that adjusted for the confounding effects of neuroticism showed total hostility was most strongly associated with appraisal support (r = -.40, p < .001) and most weakly associated with esteem support (r = -.19, p < .01). These findings help contribute to a more precise understanding of the specific nature of the support deficits experienced by high hostile women. In addition, other findings suggest that different aspects of the Ho scale are differentially related to social support. Specifically, deficiencies in the perceived availability of support appear to be most strongly linked to cynicism.

Adult↗

PubMed1998

The timing of food availability affects growth in chicks.

Three experiments challenged the ability of domestic chicks to grow normally by differentially restricting when and for how long food was available. In Experiments 1 and 2, food was available for six 1-hr, three 2-hr, two 3-hr, or one 6-hr (a.m., p.m.) periods/day over the first 3 posthatch weeks. Control groups received continuous access to food. In Experiment 3, different amounts of light surrounded the 6-hr feeding period. In Experiments 2 and 3, chicks composed their own diets from separate sources high in protein or carbohydrate. Except for the single 6-hr meal preceding dark, large meals at other times of day impaired growth--primarily because chicks consumed insufficient dietary protein and ate less earlier in the light phase. We conclude that both the amount eaten and the proportion of the diet consumed as protein at given times of the day are phylogenetically acquired strategies that fit the omnivorous, diurnal chicken to its niche, independent of its momentary requirements, and appear early in development.

Analysis of Variance↗