PubMed Health⌕ Search

Biomedical subjects

J F Molinari

Publications and source records attributed to J F Molinari.

At least 19 recordsLinked to original sources
PubMed1999

Molecular-weight-dependent effects of nonanticoagulant heparins on allergic airway responses.

We have hypothesized that antiallergic activity of inhaled heparin is molecular weight dependent and mediated by "nonanticoagulant fractions" (NAF-heparin). Therefore, we studied comparative effects of high-, medium-, and ultralow-molecular-weight (HMW, MMW, and ULMW, respectively) NAF-heparins on acute bronchoconstrictor response (ABR) and airway hyperresponsiveness (AHR) in allergic sheep. Specific lung resistance was measured in 23 allergic sheep, before and immediately after challenge with Ascaris suum antigen, without and after pretreatment with inhaled NAF-heparins. Airway responsiveness was estimated before and 2 h postantigen as the cumulative provocating dose of carbachol in breath units, which increased specific lung resistance by 400%. NAF-heparins attenuated ABR and AHR in a molecular-weight-dependent fashion. HMW NAF-heparin (n = 8) was the least effective agent: it attenuated ABR [inhibitory dose causing 50% protection (ID50) = 4 mg/kg] but had no effect on AHR. MMW NAF-heparin (n = 8) showed intermediate efficacy (ABR ID50 = 0.8 mg/kg, AHR ID50 = 1.4 mg/kg), whereas ULMW NAF-heparin (n = 7) was the most effective agent (ABR ID50 = 0.4 mg/kg, AHR ID50 = 0.2 mg/kg). ULMW NAF-heparin was 3.5 times more potent in attenuating antigen-induced AHR when administered "after" antigen challenge and failed to inhibit the bronchoconstrictor response to carbachol and histamine. In 15 additional sheep, segmental antigen challenge caused a marked increase in histamine in bronchoalveolar lavage fluid that was not prevented by any of the inhaled NAF-heparins. These data indicate that antiallergic activity of inhaled heparin is independent of its anticoagulant action and resides in the <2,500 ULMW chains. The antiallergic activity of NAF-heparins is mediated by an unknown biological action and may have therapeutic potential.

Animals↗
PubMed1998

Inhibition of antigen-induced airway hyperresponsiveness by ultralow molecular-weight heparin.

Unfractionated heparin (UF-heparin) has been shown to prevent antigen-induced airway hyperresponsiveness (AHR), but it is ineffective when administered after the antigen challenge. We hypothesized that the failure of UF-heparin to modify postantigen AHR might depend on molecular weight. We therefore studied the effects of UF-heparin and three low-molecular-weight heparin fractions (medium-molecular-weight heparin [MMWH]; low-molecular-weight heparin [LMWH]; and ultralow-molecular-weight heparin [ULMWH]) on antigen-induced AHR and histamine release in bronchoalveolar lavage fluid (BALF). Specific lung resistance (SRL) was measured in 20 allergic sheep before, immediately after, and up to 2 h after challenge with Ascaris suum antigen. Airway responsiveness was expressed as the cumulative provocative dose of carbachol, in breath units, that increased SRL by 400% (PD400). PD400 was determined before and 2 h after antigen, both without and after treatment with aerosolized UF-heparin (1,000 U/kg) and various heparin fractions (0.04 mg/kg to 5 mg/kg) administered after the antigen challenge. Inhaled UF-heparin (n = 4), MMWH (n = 4), and LMWH (n = 6) failed to modify postantigen AHR when administered after the challenge. Only ULMWH (n = 6) inhibited postantigen AHR in a dose-dependent manner (percent protection ranged from 31% to 139%). In eight additional sheep, histamine in BALF was measured with a radioimmunoassay (RIA) before and after the segmental antigen challenge, without and after pretreatment with inhaled UF-heparin, LMWH, or ULMWH. Inhaled UF-heparin and LMWH inhibited antigen-induced histamine release as measured in BALF by 81% and 75%, respectively; whereas ULMWH was ineffective in this respect. We conclude that: (1) modification of antigen-induced AHR by fractionated heparins is molecular-weight dependent; and (2) only ULMWH attenuates AHR when administered after antigen challenge, via an unknown mast-cell-independent action.

Administration, Inhalation↗
PubMed1997

Inhibition of antigen-induced acute bronchoconstriction, airway hyperresponsiveness, and mast cell degranulation by a nonanticoagulant heparin: comparison with a low molecular weight heparin.

Inhaled heparin prevents antigen-induced bronchoconstriction and inhibits anti-IgE-mediated mast-cell degranulation. We hypothesized that the antiallergic action of heparin may be dependent on molecular weight and related to its nonanticoagulant properties. Therefore, in the present investigation we studied the effects of a nonanticoagulant fraction of heparin (LA-heparin) on antigen-induced bronchoconstriction, airway hyperresponsiveness (AHR), and mast-cell degranulation, and compared its antiallergic activity with that of a low molecular weight heparin (LMW-heparin, fragmin). Specific lung resistance (SRL) was measured in 15 sheep before, immediately after, and serially for as long as 2 h after airway challenge with Ascaris suum antigen, without and after pretreatment with inhaled fractionated heparins at doses of 2.5 and 5 mg/kg. Airway responsiveness was estimated before, and 2 h after antigen as the cumulative provocating dose (PD400) of carbachol in breath units, which increased SRL by 400% (one breath unit was defined as one breath of 1% carbachol solution). LA-heparin caused a dose-dependent inhibition of antigen-induced bronchoconstriction, and a 5-mg/kg nebulized dose caused a 67% inhibition of allergic bronchoconstriction, whereas a 2.5-mg/kg dose was ineffective (20% inhibition). Inhaled fragmin was more potent than LA-heparin, as shown by 84% (2.5 mg/kg) and 82% (5 mg/kg) inhibition of allergic bronchoconstriction. Fragmin (5 mg/kg) also attenuated the postantigen AHR, whereas LA-heparin was ineffective. In vitro, preincubation with both LA-heparin and fragmin inhibited the anti-IgE-induced degranulation of rat peritoneal mast-cells in a dose-dependent fashion. LA-heparin was fourfold more potent than fragmin, with IC50 of 80 and 320 microg/ml, respectively. These data suggest that: (1) fractionated heparins attenuate antigen-induced acute bronchoconstriction, (2) nonanticoagulant fractions mediate the antiallergic activity of inhaled heparin, and (3) antiallergic activity of nonanticoagulant heparin and LMW-heparin may be related to prevention of mast-cell degranulation.

Acute Disease↗
PubMed1996

Inhaled tryptase causes bronchoconstriction in sheep via histamine release.

Allergen-induced bronchoconstriction involves mast cell activation. Tryptase is a mast cell serine protease that is released during this process, but little is known about the action of tryptase in the airway. The purpose of this study was to determine: (1) if aerosolized tryptase causes bronchoconstriction, and (2) the mechanism by which this occurs. We measured mean pulmonary flow resistance (RL) in five allergic sheep before and after consecutive inhalations of 100 and 500 ng tryptase (in 2 ml total volume). Inhaled tryptase at 100 and 500 ng increased RL (mean +/- SE) by 33 +/- 12 and 122 +/- 8% (p < 0.05) over baseline. The response was reproducible upon repeat challenges. These studies were repeated in the same animals after pretreatment with aerosolized APC 366 (9 mg/3 ml), a specific tryptase inhibitor. In APC-366-treated sheep, tryptase increased RL by 10 +/- 3 and 6 +/- 2% (p < 0.05 versus control values) at 100 and 500 ng, respectively. The response to tryptase was also blocked by pretreating the sheep intravenously with the histamine H1-antagonist chlorpheniramine (2 mg/kg), in which RL increased only 5 +/- 4 and 7 +/- 6% after 100 and 500 ng tryptase. APC 366, however, did not block histamine-induced bronchoconstriction. Consistent with these findings was the observation that segmental bronchial challenge with tryptase (1 microgram) resulted in a significant increase in histamine levels in bronchoalveolar lavage. Inhaled tryptase (500 ng) also caused airway hyperresponsiveness to aerosolized carbachol 2 h after tryptase challenge. This tryptase-induced airway hyperresponsiveness could be blocked either by pretreating the sheep with APC 366 (30 min before challenge) or by treating the sheep 30 min after challenge. These results indicate that inhaled tryptase causes bronchoconstriction and airway hyperresponsiveness in allergic sheep by an event that may involve mast cell activation.

Administration, Inhalation↗
PubMed1995

Dapiprazole's effect upon accommodative recovery: is it due entirely to changes in depth of field?

We conducted a study to evaluate the ability of dapiprazole 0.5% ophthalmic solution to reverse accommodative loss brought about by mydriatic drugs having mild cycloplegic effects. To accomplish this, we analyzed data from several earlier randomized, masked clinical studies. Our composite data include over 90 subjects dilated with tropicamide. Tropicamide was used alone in 1% concentration, as well as in combination with phenylephrine, 2.5% and in the proprietary preparation, Paremyd (Allergan Pharmaceuticals). Accommodative amplitude and pupillary diameter were measured before instilling dilating drops and then again one-half hour later, immediately before instilling either dapiprazole or a placebo. Accommodative amplitude and pupil diameter measurements were then repeated four more times, on both the treatment and control eyes and at 30, 60, 120, and 180 min after instillation of the last drop of dapiprazole or placebo. We found accelerated "accommodative" recovery with dapiprazole for each of the three tropicamide-containing drugs used in our study. This is not surprising because some recovery of accommodative amplitude after dapiprazole's administration is expected. This is because dapiprazole accelerates pupillary recovery and a narrowing of the pupil gives rise to an increase in ocular depth of field. Rate of accommodative recovery with dapiprazole was found not to be significantly different for all three tropicamide-containing preparations tested (p > 0.05). Does dapiprazole produce improvement in amplitude of accommodation beyond that attributable to increased depth of field?(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1995

Role of tryptase in immediate cutaneous responses in allergic sheep.

In this study, we used a specific tryptase inhibitor, APC-366 [N-(1-hydroxy-2-napthoyl)-L-arginyl-L- prolinamide hydrochloride] to investigate the effect of intradermally administered tryptase and tryptase released by antigen challenge on the immediate cutaneous reaction (ICR) in allergic sheep. The surface areas of cutaneous wheals produced by intradermal injections (0.05 ml) of 1 and 10 ng tryptase alone, tryptase combined with 3 U heparin (tryptase-heparin), or Ascaris suum antigen (10(-5) dilution) with or without pretreatment with APC-366 (1 mg/ml) were measured at 20 and 60 min after challenge. Intradermal injections of 1 and 10 ng tryptase alone (n = 7) produced an ICR of < or = 20% of that obtained after injection of histamine (5% wt/vol). Intradermal injection of tryptase-heparin (n = 7), however, resulted in 50 (1 ng) and 82% (10 ng) of the ICR to histamine (both, P < 0.05 vs. tryptase alone). APC-366 inhibited (P < 0.05) the ICR to 1 and 10 ng tryptase-heparin by > or = 70% at all times (n = 8) but had no effect on the histamine-induced ICR (n = 3). A combination of the histamine H1 antagonist chlorpheniramine (2 mg/kg iv) and the H2 antagonist metiamide (3 mg/kg iv) given 40 min before challenge (n = 8) inhibited the response to 1 and 10 ng tryptase-heparin by 42 and 62% at 20 min and by 96 and 86% at 60 min, respectively (all, P < 0.05). APC-366 also blocked the ICR to A. suum antigen by 68% (P < 0.05) in nine sheep. These results indicate that intradermal injection of tryptase-heparin can induce an ICR. This ICR can be inhibited by APC-366 or a combination of the histamine H1 and H2 antagonists, suggesting that the tryptase response is mediated by histamine. APC-366 also blocks the mast cell-mediated ICR to intradermally injected A. suum antigen. Collectively, these results suggest that tryptase may modulate mast cell histamine release.

Animals↗
PubMed1994

Dapiprazole clinical efficiency for counteracting tropicamide 1%.

We evaluated the clinical usefulness of dapiprazole in reversing the effects of tropicamide 1.0%. Our study was random, masked with placebo, and used one eye of each subject as a control. Thirty subjects were given dapiprazole as directed by the manufacturer 30 min after being dilated by one drop each of proparacaine 0.5%, tropicamide 1.0%, and then 5 min later another drop of tropicamide 1.0%. Pupil diameter, amplitude of accommodation, conjunctival injection, and intraocular pressure were evaluated. Each of these variables was measured: (1) before instillation of the diagnostic agents; (2) before the instillation of dapiprazole; and (3) at 30, 60, 120, and 180 min after the final instillation of dapiprazole. The average pupillary recovery time for dapiprazole-treated eyes was significantly less than for nontreated eyes. Accommodation also showed faster recovery. Comfortable reading ability returned after approximately 43 min with dapiprazole vs. 66 min without dapiprazole. All of our subjects exhibited conjunctival hyperemia after the administration of dapiprazole. This persisted throughout the 180 min observation period after its administration.

Accommodation, Ocular↗
PubMed1994

The Council on Clinical Optometric Care (CCOC): The American Optometric Association's Institutional-Practice Reviewer 1967-1993.

BACKGROUND: For 26 years the CCOC served professional optometry as its institutional-practice reviewer. METHODS: The council used nine standards for accrediting clinical institutions. RESULTS: The benefits of the accreditation process were many, with improved patient care as its cornerstone. CONCLUSION: During its 26 year existence, the Council on Clinical Optometric Care (CCOC) had a major influence on the quality of optometric care.

Accreditation↗
PubMed1993

Efficacy of dapiprazole.

A study was performed to evaluate the clinical usefulness of dapiprazole in a private clinical setting. This study was unmasked, but used one eye of each subject as a control. Thirty consecutive subjects were given dapiprazole as directed by the manufacturer. The administration of dapiprazole followed bilateral dilation for routine fundus examination. Subjects were dilated using one drop each of proparacaine 0.5%, tropicamide 1.0%, and phenylephrine 2.5%. Pupil diameter, amplitude of accommodation, and conjunctival injection were evaluated. Each of these three variables was measured (1) before instillation of the diagnostic agents, (2) before the instillation of diapiprazole, and (3) at 30, 60, 120, and 180 min after the final instillation of dapiprazole. The average pupillary recovery time for dapiprazole-treated eyes was similar to previously published data. Accommodation also showed significant recovery, with comfortable reading ability returning after approximately 30 min. The design of our study did not permit us to determine what portion of accommodation recovery was attributable to alpha ciliary muscle effect and what portion resulted from the increased depth of field that was due to the pupillary constriction. All of our subjects exhibited conjunctival hyperemia after the administration of dapiprazole. This side effect persisted through the entire 180-min observation period that followed dapiprazole administration.

Accommodation, Ocular↗
PubMed1993

Efficacy of dapiprazole with hydroxyamphetamine hydrobromide and tropicamide.

BACKGROUND: Clinical interest in ophthalmic agents to reverse pharmacologically induced mydriasis safely has been attempted for over fifty years. These agents may aid practitioners in assisting the younger patient to regain unable near visual function. METHODS: We evaluated the usefulness of dapiprazole in a private clinical setting. Our study was doubled masked, randomized and used one eye of each subject as a control. Twenty-six consecutive subjects were given dapiprazole as directed by its manufacturer. This administration of dapiprazole followed bilateral pupil dilation with proparacaine 0.5%, hydroxyamphetamine 1.0% and tropicamide 0.25%. Pupil diameter, amplitude of accommodation, intraocular pressure and conjunctival injection were each evaluated prior to instillation of the diagnostic agents, immediately before the instillation of dapiprazole and at 30, 60, 120, and 180 minutes after the final instillation of dapiprazole. RESULTS: The average pupillary recovery time for dapiprazole-treated eyes was similar to previously published data. Accommodation also showed significant recovery, with comfortable reading ability returning by approximately 45 minutes. CONCLUSION: The design of our study did not permit us to determine what portion of accommodation recovery if any was attributable to a ciliary muscle effect and what portion may have resulted from the increased depth of field attending pupillary constriction.

Accommodation, Ocular↗
PubMed1991

Extended-wear contact lenses: a philosophy for fitting and management.

The fitting and management of extended-wear contact lenses requires a conservative philosophy of patient selection and a structured program of care. Because of the increased risk of serious complications, informed consent must be obtained before fitting patients with lenses. Fitting philosophies favor hydrogel lenses of medium thickness and water content that provide adequate movement. Initial lens care is best provided by peroxide care systems. Patients are usually fitted in the morning, reevaluated in the afternoon, and allowed to wear lenses overnight if there are no contraindications. After reexamination the next morning, planned follow-up is usually provided at 3 days, 1 week, 1 month, and 3 months. If no adverse findings are encountered, patients are seen at 3- to 6-month intervals thereafter.

Contact Lenses, Extended-Wear↗
PubMed1990

Variability of ultrasonic pachometry.

We evaluated the intraobserver, interobserver, and intersession variability of the Humphrey model 580 ultrasonic pachometer. Twenty eyes (10 subjects) were measured in the intraobserver study. Forty-two eyes (21 subjects) were measured in the interobserver and intersession studies. Multiple analysis of variance revealed no statistical differences between observers or between right and left eyes. A marginally significant time (intersession) effect was found, with greater corneal thicknesses measured in the afternoon. The intraobserver variability averaged 6 microns, whereas the interobserver and intersession variabilities were approximately 11 microns and 14 microns, respectively. The relative simplicity, objectivity, and repeatability of ultrasonic pachometry should enable corneal thickness changes to be monitored in clinical practice on a more routine basis.

Adult↗
PubMed1988

Rigid gas permeable contact lenses in hyperbaric environments.

We studied the wearing of hard gas permeable contact lenses during decompression in a hyperbaric environment. Twenty-four exposures of three different lens materials were carried out in a hyperbaric chamber. The dry air dive profiles were: 45.72 m (150 ft) for 30 min and 15 min; 22.86 m (75 ft) for 15 min; and 11.43 m (37.5 ft) for 15 min. Bubbles occurred under all lens types; they were seen at simulated depths as shallow as 1.98 m (6.5 ft) after the least stressful exposure. Due to the tissue offgassing half-time of the eye, it is unlikely that the bubbles are a result of nitrogen from the eye. They probably arise from the tear layer.

Atmospheric Pressure↗
PubMed1987

Clinical evaluation of a custom toric hydrogel contact lens.

Eleven astigmatic patients seen in a private practice were fit with the Hydron-T custom toric soft lens. The fitting mechanics are described along with the results which illustrate the potential utilization of this lens in the management of patients with high astigmatic errors.

Adult↗
PubMed1986

High degrees of astigmatism: are hydrogels the answer?

A bilateral compound hyperopic astigmat, with-the-rule, with incipient presbyopia and refractive amblyopia fitted with toric (custom) soft lenses in a monofit mode is described. Shortly after wearing the hydrogel toric lenses the patient developed a severe allergic reaction from a thimerosal based saline, which eventually resolved.

Adult↗