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Four patients with stenoses of an internal carotid artery and 6 with moyamoya disease were studied. H(2)(15)O was continuously infused, and data were recorded in 1-min frames. After equilibration of H(2)(15)O, 5 min of baseline data were acquired, and then 1 g of ACZ was administered intravenously and data collection continued for 10-22 min. Arterial blood was continuously drawn for absolute quantification of CBF.
To present the case of a 28-year-old man with acetazolamide-induced bilateral choroidal effusion after uneventful surgery of the second eye in delayed sequential bilateral insertion of an implantable collamer lens for hyperopia.
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Pseudotumor cerebri in children is rare. When present, PTC in children often manifests different characteristics than adults. First, no clear sexual predilection exists for PTC in children. Second, the role of associated illnesses and medications is stronger in children than in adults. Third, the extent of neurologic deficit present in children with PTC is broader than in adults. All children with swollen optic disks warrant a thorough diagnostic evaluation. In the absence of obvious neuropathology, knowledge of the differences between adult and pediatric PTC can help avoid a diagnostic dilemma.
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We examined whether acetazolamide (ACZ), a carbonic anhydrase inhibitor, would alter post-hypoxic ventilatory behavior and periodic breathing in the C57BL/6J (B6) mouse. Experiments were performed with unanaesthetized, awake adult male B6 mice (n = 5, 2.5 months old, 21.3 +/- 1.5 g, mean +/- SD) and ventilatory behavior was measured using a flow through body plethysmography. Mice were given an intraperitoneal injection of either vehicle or ACZ (40 mg/kg) and one hour later exposed to 1 min of 8% O2-balance N2 (poikilocapnic hypoxia) or 12%-O2, 3% CO2-balance N2 (non-poikilocapnic hypoxia) followed by rapid reoxygenation (100% O2) of 5 minutes. One minute after reoxygenation, ACZ-treated animals exhibited post-hypoxic frequency decline (p < 0.05), a lower coefficient of variability for frequency (p < 0.001) and no tendency towards periodic breathing (p < 0.05), as compared to vehicle-treated animals. ACZ improves unstable breathing in the B6 model of periodic breathing, despite producing post-hypoxic frequency decline. Our speculation is that periodic breathing occurs through pathways independent of the A5 pontine area.
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This paper reports intraocular pressure findings in 676 eyes that received penetrating keratoplasties. There were four groups: 1. keratoconus without preoperative glaucoma (75 cases); 2. Fuchs' dystrophy and cataract (triple procedure) without glaucoma (260 cases); 3. aphakic eyes with or without intraocular lenses (204 cases); and 4. pseudophakic eyes with or without intraocular lens removal (137 cases). The last two groups had a significant number of glaucoma cases. All were controlled before surgery. There were no early or late glaucoma cases in the first group. A few cases with triple procedures had mild early intraocular pressure elevation. Thirty percent of aphakic eyes and 52% of pseudophakic eyes had early glaucoma. Twenty percent and 25% of these two groups had persistent glaucoma. Preoperative glaucoma eyes were included in these long-standing glaucoma cases.
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BCS class IV drugs (e.g., amphotericin B, furosemide, acetazolamide, ritonavir, paclitaxel) exhibit many characteristics that are problematic for effective oral and per oral delivery. Some of the problems associated include low aqueous solubility, poor permeability, erratic and poor absorption, inter and intra subject variability and significant positive food effect which leads to low and variable bioavailability. Also, most of the class IV drugs are substrate for P-glycoprotein (low permeability) and substrate for CYP3A4 (extensive pre systemic metabolism) which further potentiates the problem of poor therapeutic potential of these drugs. A decade back, extreme examples of class IV compounds were an exception rather than the rule, yet today many drug candidates under development pipeline fall into this category. Formulation and development of an efficacious delivery system for BCS class IV drugs are herculean tasks for any formulator. The inherent hurdles posed by these drugs hamper their translation to actual market. The importance of the formulation composition and design to successful drug development is especially illustrated by the BCS class IV case. To be clinically effective these drugs require the development of a proper delivery system for both oral and per oral delivery. Ideal oral dosage forms should produce both a reasonably high bioavailability and low inter and intra subject variability in absorption. Also, ideal systems for BCS class IV should produce a therapeutic concentration of the drug at reasonable dose volumes for intravenous administration. This article highlights the various techniques and upcoming strategies which can be employed for the development of highly notorious BCS class IV drugs. Some of the techniques employed are lipid based delivery systems, polymer based nanocarriers, crystal engineering (nanocrystals and co-crystals), liquisolid technology, self-emulsifying solid dispersions and miscellaneous techniques addressing the P-gp efflux problem. The review also focuses on the roadblocks in the clinical development of the aforementioned strategies such as problems in scale up, manufacturing under cGMP guidelines, appropriate quality control tests, validation of various processes and variable therein etc. It also brings to forefront the current lack of regulatory guidelines which poses difficulties during preclinical and clinical testing for submission of NDA and subsequent marketing. Today, the pharmaceutical industry has as its disposal a series of reliable and scalable formulation strategies for BCS Class IV drugs. However, due to lack of understanding of the basic physical chemistry behind these strategies formulation development is still driven by trial and error.
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The diameter of optico-ciliary shunt vessels may be an indicator of the pressure within the optic nerve sheath.
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Despite the advent and increasingly wide availability of antiretroviral therapy, cryptococcal meningitis (CM) remains a significant cause of mortality and morbidity amongst individuals with HIV infection in resource-limited settings. The ideal management of CM remains unclear. The aim of this review is to assess the evidence for deciding on which antifungal regimen to use as well as other modalities of management to utilise especially resource poor settings in order to achieve the best possible outcome and enable an individual with CM to survive their acute illness and benefit from antiretroviral therapy.
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Topical application of acetazolamide has no known effect on intraocular pressure (IOP). We tried to detect the hypotensive effect on IOP of acetazolamide soaked onto soft contact lenses (CL). We applied CLs soaked in either 1%, 3%, or 5% acetazolamide solution onto one eye of 29 rabbits while the contralateral eye served as a control. There was an average 32% reduction of IOP amongst all acetazolamide applied eyes, and an average 19% reduction of IOP amongst all control eyes. Amongst the 1% acetazolamide-CL applied eyes there was a mean 37% reduction of IOP, amongst the 3% acetazolamide-CL applied eyes a mean 36% reduction, amongst the 5% acetazolamide-CL applied a mean 30% reduction, and a mean 19% reduction in control eyes. The longest period of IOP reduction followed the application of 1% acetazolamide-CLs, probably owing to improved drug corneal penetration at this concentration. Our results reveal that the application of acetazolamide soaked soft CLs has a significant hypotensive effect on IOP in both the applied and contralateral control eyes of rabbits.
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The cerebral hemodynamics remain normal in 80% of cases of CPH patients. The presence of CPH does not interfere with the clinical evolution. The initial and late clinical scores were not different compared to those of patients without hyperperfusion. The clinical outcome of the CPH patients cannot be accurately predicted by the interhemispheric asymmetry.
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Bicomponent fibers of two semi-crystalline (co)polymers, poly(varepsilon-caprolactone), and poly(oxyethylene-b-oxypropylene-b-oxyethylene), were obtained by electrospinning. Acetazolamide and timolol maleate were loaded in the fibers in different concentrations (below and above the drug solubility limit in polymer) in order to determine the effect of drug solubility in polymer, drug state, drug loading and fiber composition on fiber morphology, drug distribution and release kinetics. The high loadings fibers (with drug in crystalline form) showed higher burst and faster release than low drug content fibers, indicating the release was more sustained when the drug was encapsulated inside the fibers, in amorphous form. Moreover, timolol maleate was released faster than acetazolamide, indicating that drug solubility in polymer influences the partition of drug between polymer and elution medium, while fiber composition also controlled drug release. At low loadings, total release was not achieved (cumulative release percentages smaller than 100%), suggesting that drug remained trapped in the fibers. The modeling of release data implied a three stage release mechanism: a dissolution stage, a desorption and subsequent diffusion through water-filled pores, followed by polymer degradation control.