The effect of topically administered carbonic anhydrase inhibitors on aqueous humor dynamics in rabbits

Repeated topical administration of 2.5% trifluormethazolamide, a halogenated derivative of methazolamide, resulted in a unilateral decrease in intraocular pressure in rabbits. Mean (+/- S.E.M.) baseline intraocular pressure (19.8 +/- 2.1 mm Hg) was significantly (P less than .05) decreased 30 minutes (16.1 +/- 2.2 mm Hg) and 60 minutes (15.8 +/- 2.7 mm Hg) after drug administration. Trifluormethazolamide did not alter outflow facility. Aqueous humor flow calculated from the tonographic data was reduced 44% and flow measured by fluorophotometry was reduced 29%. Topical delivery of trifluormethazolamide decreased the level of carbon dioxide in the aqueous humor in the treated eye in a manner similar to that observed after systemic administration of carbonic anhydrase inhibitors. Topical administration of 10% acetazolamide did not decrease intraocular pressure. However, topical administration of either trifluormethazolamide or acetazolamide before oral administration of water resulted in a blunting of the water-induced ocular hypertensive response.     

The effect of hyperthermia on aqueous humor dynamics in rabbits

Hyperthermia increased intraocular pressure (Po) by approximately 5 mm Hg in rabbit eyes. This increase was not associated with changes in plasma osmolarity, blood lactate, or pH. Episcleral venous pressure (Pv) decreased from a baseline of 11 +/- 1 mm Hg(mean +/- SEM) to 8 +/- 1 mm Hg after one hour of hyperthermia. Outflow facility (c) as measured by tonography remained unchanged. Aqueous humor flow [c(Po - Pv)] as estimated by tonography increased by about 126%. The elevation of intraocular pressure was not prevented by aspirin pretreatment nor altered by unilateral optic nerve transection.     

Determination of the facility of aqueous humor outflow in the dog, comparing in vivo and in vitro tonographic and constant pressure perfusion techniques

The gross facility of aqueous humor outflow (C) was estimated in the normal in vivo and in vitro dog eye, using tonography and constant pressure perfusion. Tonographic C value for 36 normal eyes, with the dog anesthetized with ketamine hydrochloride and acetylpromazine maleate, was 0.21 (+/- 0.14, SD); the mean tonographic value in 35 eyes with the patient anesthetized with sodium pentobarbital was 0.15 (+/- 0.09). Constant pressure perfusion of the in vivo normal dog eyes at 20 mm of Hg intraocular pressure yielded a mean C value of 0.13 (+/- 0.07) and at 30 mm of Hg 0.18 (+/- 0.13). As intraocular pressure increased from 10 to 50 mm of Hg, the rate of outflow, as determined by constant pressure perfusion, increased. The C values from in vitro constant pressure perfusion were greater than those in the in vivo eyes and deceased in most eyes as intraocular pressure was increased as compared with the in vivo preparation.     

Effect of intravenous fenoldopam on intraocular pressure in ocular hypertension

Intravenous fenoldopam, a selective dopamine-1 receptor agonist, was compared with placebo in this randomized, double-blind, two-period crossover study to evaluate its effects on intraocular pressure, aqueous dynamics, and macular blood flow in patients with elevated intraocular pressure or primary open-angle glaucoma. Doses of fenoldopam were titrated up to a maximum of 0.5 microgram/kg/min. Intraocular pressure, measured by pneumotonometry, was the primary outcome variable. Other outcomes included macular blood flow assessed by blue field examination, visual field examined by automated perimetry, aqueous outflow facility measured by tonography, and aqueous humor production determined by fluorophotometry. During infusions of fenoldopam, intraocular pressure increased from a mean baseline level of 29.2 mmHg to a mean maximum level of 35.7 mmHg. During the placebo infusions, pressure increased from a mean baseline of 28.4 mmHg to a mean of 29.0 mmHg at the time point that corresponded to the mean maximum intraocular pressure on the day intravenous fenoldopam was administered, to yield a mean difference in pressure between study days of 6.7 mmHg (P < 0.05). There were no apparent changes in macular blood flow, visual fields, or production or outflow of aqueous humor associated with fenoldopam infusion. The increase in intraocular pressure seen in this population of patients with ocular hypertension during infusions of fenoldopam is consistent with fenoldopam-associated increases in intraocular pressure reported in previous studies of healthy volunteers and of patients with accelerated systemic hypertension. These results further suggest that dopamine-1 receptors play a role in the regulation of intraocular pressure.     

Comparison of the efficacy of apraclonidine and brimonidine as aqueous suppressants in humans

OBJECTIVE: To measure and compare the effect of apraclonidine hydrochloride and brimonidine tartrate on the rate of aqueous humor flow in human subjects. SUBJECTS AND METHODS: Forty normal human subjects were given apraclonidine or brimonidine by topical instillation. Aqueous humor flow was measured by the rate of disappearance of topically applied fluorescein. Intraocular pressure was measured by applanation tonometry. RESULTS: Apraclonidine suppressed aqueous humor flow between 39% and 44% and lowered intraocular pressure between 20% and 23%. Brimonidine suppressed aqueous humor flow between 44% and 48% and lowered intraocular pressure between 19% and 22%. CONCLUSION: No statistically significant differences were found between the effects of the 2 drugs on aqueous humor dynamics in normal subjects.     

NaCl-preferring NZB/B1NJ mice and NaCl-avoiding CBA/J mice have similar amiloride inhibition of chorda tympani responses to NaCl

After intracameral injection calcitonin gene-related peptide has been demonstrated to break the blood aqueous barrier and increase intraocular pressure in rabbits. However in cats, calcitonin gene-related peptide decreases intraocular pressure by increasing the outflow facility of aqueous humor. In the present study, the effect of intracameral injection of calcitonin gene-related peptide on the outflow facility in rabbits has been investigated and the intraocular pressure and outflow facility were measured following intravitreal administration of calcitonin gene-related peptide. The results demonstrate that in spite of the apparent pseudofacility component caused by a breakdown of the blood aqueous barrier also the true trabecular outflow is probably increased in the rabbit eye after intracameral injection of calcitonin gene-related peptide. The intravitreal administration of calcitonin gene-related peptide leaves the blood aqueous barrier intact and causes an increase in the outflow facility of aqueous humor with a concomitant long-lasting decrease in intraocular pressure.     

Effects of Al3+ and Be2+ ions combined with NaF on ciliary process adenylyl cyclase activity and aqueous humor dynamics in the rabbit eye

PURPOSE: The activity of Al3+, Ga3+, and Be2+ ions in the presence of NaF to directly activate G-proteins was investigated by their potentiative effect on forskolin (FSK)-activated adenylyl cyclase in rabbit ciliary process membranes and their effects on aqueous humor dynamics in vivo. METHODS: Adenylyl cyclase (AC) was determined by radiometric conversion of ATP to cAMP by the particulate fraction of rabbit ciliary processes. Intravitreal injections of sterile solutions of analytical grade salts were made into the center of the vitreous in a volume of 20 microliters. Intraocular pressure, aqueous humor flow, and uveoscleral outflow measurements were made by pneumatonometry, fluorophotometry, and fluorescein-dextran method, respectively. Outflow facility was determined by tonography in the intact eyes and by two-level constant pressure perfusion in cannulated eyes. RESULTS: Both Al3+ (EC50, 40 mumol/l) and Be2+ (EC50, 11 mumol/l) in the presence of 0.5-2 mM NaF activated the stimulatory G-protein Gs. Ga3+ was ineffective and did not antagonize the activation by Al3+. Intravitreal injections of Al3+ (1 mumol/eye) or Be2+ (0.5 or 1 mumol/eye) had no significant intraocular pressure (IOP) effect, nor did 1.5 or 3 mumol/eye of NaF, but when either cation was injected together with NaF, IOP decreased by up to 40% for up to 140 hr. At the time of maximum IOP effect (72 hr) aqueous humor flow determined by fluorophotometry was decreased in BeCl2+ NaF-treated eyes by 40% relative to BeCl2-treated eyes; however, tonographic facility of outflow was unaffected. Uveoscleral flow was also decreased by 38% in BeCl2+ NaF treated eyes. CONCLUSIONS: These findings support the hypothesis that Gs activation of ciliary process adenylyl cyclase decreases aqueous humor formation rate in rabbit eyes, and that activation of G-proteins mediates contraction of ciliary muscles causing a decrease of aqueous humor outflow via the uveoscleral route. The results suggest that G-proteins putatively involved in trabecular facility changes are less sensitive to activation by BeF3- than are other parameters of aqueous humor dynamics.     

Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease

BACKGROUND: Variation of the arterial carbon dioxide partial pressure (PaCO2) is not uncommon in anesthetic practice. However, little is known about the myocardial consequences of respiratory alkalosis and acidosis, particularly in patients with coronary artery disease. The aim of the current study was to investigate the effects of variation in PaCO2 on myocardial blood flow (MBF), metabolism, and systemic hemodynamics in patients before elective coronary artery bypass graft surgery. METHODS: In 10 male anesthetized patients, measurements of MBF, myocardial contractility, metabolism, and systemic hemodynamics were made in a randomized sequence at PaCO2 levels of 30, 40, and 50 mmHg, respectively. The MBF was measured using the Kety-Schmidt technique with argon as a tracer. End-diastolic left ventricular pressure and the maximal increase of left ventricular pressure were assessed using a manometer-tipped catheter. RESULTS: The cardiac index significantly changed with varying PaCO2 levels (hypocapnia, - 9%; hypercapnia, 13%). This reaction was associated with inverse changes in systemic vascular resistance index levels. The MBF significantly increased by 15% during hypercapnia, whereas no change was found during hypocapnia. Myocardial oxygen and glucose uptake and the maximal increase of left ventricular pressure were not affected by varying PaCO2 levels. CONCLUSIONS: In anesthetized patients with coronary artery disease, short-term variations in PaCO2 have significant effects on MBF but do not influence global myocardial oxygen and glucose uptake. Changes in systemic hemodynamics associated with respiratory alkalosis and acidosis are caused by changes in systemic vascular resistance rather than by alterations in myocardial contractility.     

Relationship between sympathetic nervous system activity, baroreflex and cardiovascular effects after acute nitric oxide synthesis inhibition in humans

OBJECTIVE: To examine the cardiovascular effects of acute systemic nitric oxide synthesis inhibition in humans in relation to the possible involvement of changes in sympathetic nervous system activity or in the baroreceptor reflex. DESIGN: Placebo or NG-monomethyl-L-arginine (250 mg by intravenous infusion for 5 min) was administered to seven healthy male volunteers according to a random, double-blind sequence. METHODS: Blood pressure and heart rate were measured non-invasively using a Finapres device from 20 min before to 80 min after starting infusion; beat-to-beat variability of blood pressure, pulse interval and systolic blood pressure and pulse interval covariation were assessed by means of spectral and sequence analysis methods. Under basal conditions and 15 min and 60 min after infusion, we measured stroke volume and indices of cardiac systolic and diastolic function by echocardiography, forearm blood flow by strain-gauge venous occlusion plethysmography, and plasma catecholamine levels. RESULTS: Compared with placebo, administration of NG-monomethyl-L-arginine caused a transient increase in blood pressure and reduction in heart rate. Stroke volume and indices of cardiac function did not change significantly, whereas cardiac index and forearm blood flow were significantly reduced after 15 min. Spectral analysis of blood pressure and pulse interval showed a significant reduction of power spectral density in the low frequencies (0.03-0.15 Hz) that persisted 60 min after infusion. The plasma noradrenaline level was significantly reduced after 15 min. No change in baroreflex engagement or sensitivity was detected by the cross-spectral or the sequence method. CONCLUSIONS: Acute systemic nitric oxide synthesis inhibition transiently increases blood pressure and reduces heart rate and cardiac index. The acute hypertensive response to NG-monomethyl-L-arginine is dependent neither on sympathetic nervous system activity, which is probably reduced as a consequence of baroreceptor reflex activation, nor on baroreceptor reflex sensitivity, which is not impaired.     

Functional morphology of the trabecular meshwork in primate eyes

The trabecular meshwork forms most of the resistance to aqueous humor outflow needed for maintenance of a pressure gradient between intraocular pressure of approximately 17 mmHg and venous pressure of approximately 10 mmHg. The composition of the extracellular material in the subendothelial or cribriform layer seems to be mainly responsible for outflow resistance. The aqueous humor pathways through the subendothelial layer can be influenced by ciliary muscle contraction and presumably also by contractile elements recently found both in trabecular meshwork and scleral spur. Pharmacologically induced disconnection of inner wall and cribriform cells leads to wash out of extracellular material through breaks of the endothelial lining of Schlemm's canal and to increase of outflow facility. In glaucomatous eyes the resistance to aqueous humor outflow is increased due to an increase in different forms of extracellular material deposited within the cribriform layer. The amount of this newly developed extracellular material is correlated with loss of axons in the optic nerve, indicating that a common factor is responsible for both changes. To investigate the effect of various factors on the biology of trabecular cells monolayer cultures derived from cribriform and corneoscleral trabecular meshwork have been established. The two cell lines can be differentiated because cribriform cells in vivo as in vitro stain for alphabeta-crystallin whereas the corneoscleral cells remain unstained. The effect of TGFbeta, a growth factor increased in aqueous humor of glaucomatous eyes and glycocorticoids on trabecular meshwork cells show typical changes in formation of extracellular matrix components and of stress proteins. Dexamethasone and oxidative damage also lead to increase of trabecular meshwork inducible glucocorticoid response (TIGR) protein. A mutation of the TIGR-gene family has recently been found in families with juvenile and chronic simple glaucoma. Future research has to clarify the significance of these genetic factors for the pathophysiology of glaucoma and the role of trabecular cell activity in this respect.     

Pharmacologic atrial natriuretic peptide reduces human leg capillary filtration

Atrial natriuretic peptide (ANP) is produced and secreted by atrial cells. We measured calf capillary filtration rate with prolonged venous-occlusion plethysmography of supine healthy male subjects during pharmacologic infusion of ANP (48 pmol/kg/min for 15 min; n = 6) and during placebo infusion (n = 7). Results during infusions were compared to prior control measurements. ANP infusion increased plasma [ANP] from 30 +/- 4 to 2,568 +/- 595 pmol/l. Systemic hemoconcentration occurred during ANP infusion: mean hematocrit and plasma colloid osmotic pressure increased 4.6 and 11.3%, respectively, relative to preinfusion baseline values (p < 0.05). Mean calf filtration, however, was significantly reduced from 0.15 to 0.08 ml/100 ml/min with ANP. Heart rate increased 20% with ANP infusion, whereas blood pressure was unchanged. Calf conductance (blood flow/arterial pressure) and venous compliance were unaffected by ANP infusion. Placebo infusion had no effect relative to prior baseline control measurements. Although ANP induced systemic capillary filtration, in the calf, filtration was reduced with ANP. Therefore, pharmacologic ANP infusion enhances capillary filtration from the systemic circulation, perhaps at upper body or splanchnic sites or both, while having the opposite effect in the leg.     

Does aqueous humor secretion decrease with age?

Aqueous humor flow was calculated during day-time in 148 healthy volunteers and 75 older patients using the Fluorotron Master II anterior chamber protocol (Coherent, Palo Alto, USA). Healthy volunteers as well as patients had no history of ocular pathology, surgery or laser treatment. Slitlamp examination revealed no ocular pathology. Hypertension, diabetes, local and systemic drug therapy, neoplasia, kidney or liver disease, contact lens and ocular trauma were excluded. Mean age of volunteers was 26.5 +/- 3.8 years; age of patients: 65.5 +/- 10.5 years. Aqueous humor flow during day-time in healthy volunteers in the OD: (mean +/- s.d.) 2.26 +/- 1.0 microliters/min, in the OS: 2.17 +/- 1.0 microliters/min, OS: 1.86 +/- 1.1 Ml/min. Correlation coefficient: r = 0.8. The mean aqueous humor flow in the older patients during day-time: OD: 1.91 +/- 1.1 microliters/min. Correlation coefficient: r = 0.54. The Mann-Whitney-U-test revealed a significant difference when comparing the right eyes of healthy volunteers with the right eyes of patients (p < 0.01). When comparing all left eyes the difference is also significant (p = 0.01). The results of the study underline, that the mean aqueous humor secretion does significantly decrease with age. However, the data show that there is only a slight decrease of flow of approximately 2.5% per decade. From the clinical point of view it should be concluded, that although the aqueous humor secretion does decrease with age, this is not of clinical importance, even in cases of glaucoma surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aqueous humor induces transforming growth factor-beta (TGF-beta)-producing regulatory T-cells

PURPOSE: The intraocular microenvironment is an immune-privileged site where immunogenic inflammation is suppressed. Suppression of immunogenic inflammation has been associated with immunosuppressive factors found in aqueous humor produced by ocular tissues. To further understand the mechanisms suppressing immunogenic inflammation in the eye, we have examined the production of lymphokines by primed T-cells activated in the presence of aqueous humor. METHODS: Enriched in vivo primed T-cells were T-cell receptor-stimulated in the presence of fresh aqueous humor. The culture supernatant was assayed for IFN-gamma and IL-4 by sandwich ELISA. TGF-beta production by T-cells stimulated in the presence of aqueous humor was assayed by a TGF-beta bioassay of the culture supernatant and by quantitative RT-PCR for TGF-beta 1 mRNA expression. Aqueous humor-treated T-cells were assayed for their capacity to suppress IFN-gamma production by stimulated, primed T-cells. RESULTS: Aqueous humor-enhanced proliferation but irreversibly suppressed production of both IFN-gamma and IL-4 by in vitro-activated, in vivo-primed T-cells. Aqueous humor induced in vivo primed T-cells to produce TGF-beta in vitro, and these TGF-beta-producing T-cells suppressed IFN-gamma production by other T-cells activated in co-cultures. CONCLUSIONS: Aqueous humor alters the functional program of TCR-ligand-activated, primed T-cells, converting the cells to TGF-beta-producing regulatory cells.     

Effect of mitomycin C on aqueous humor flow, flare and intraocular pressure in eyes with glaucoma 2 years after trabeculectomy

BACKGROUND: The purpose of this study was to determine the intraocular pressure (IOP), aqueous humor flow, flare and ocular side effects in eyes with a history of hypotony after trabeculectomy with adjunctive mitomycin C (MMC). METHODS: Thirty-six eyes with primary or secondary open-angle glaucoma and IOP < or = 8 mmHg during the postoperative period were studied 745 +/- 315 days after surgery. MMC (0.2 or 0.5 mg/ml) was applied to the episclera with a cellular sponge. Flare was studied with the Kowa Laser Flare Meter 500. Aqueous humor flow was measured in the afternoon (Fluorotron Master II). IOP, visual fields and best corrected visual acuity were also examined. Twenty-two contralateral eyes without surgical intervention served as controls. RESULTS: The mean age of patients was 44.5 +/- 16.8 years. The mean IOP was significantly lower in the MMC group than in the control group: 9.6 +/- 6.4 mmHg vs 18.0 +/- 13.6 mmHg at 2 years (P < 0.001). Aqueous flow was significantly lower in subjects treated with MMC than in controls (P < 0.001). The flare values were significantly higher in the MMC-treated group, with a mean of 12.0 +/- 7.7 photon counts/ms, than in the control group, mean 7.9 +/- 4.6 photon counts/ms (P < 0.019). CONCLUSION: Our data suggest that MMC is a useful ocular hypotensive agent which seems to participate in a change in aqueous humor dynamics when applied topically as an aqueous solution.     

The effect of melatonin on aqueous humor flow in humans during the day

BACKGROUND: Aqueous humor flow through the anterior chamber of the eye undergoes a circadian cycle. The rate of flow during the day is twice as high as the rate of flow at night. The pineal hormone, melatonin, also undergoes a circadian cycle. Melatonin levels are high at night, whereas aqueous humor flow is low. The authors studied the effect of oral melatonin on aqueous humor flow in humans. METHODS: The effect of melatonin on aqueous humor flow was evaluated in 19 healthy human volunteers in a randomized, masked crossover study with a placebo control. The hormone or placebo was administered orally during the day when endogenous levels of melatonin are low. Aqueous flow was measured by fluorophotometry for 8 hours. RESULTS: The mean rate of flow during melatonin treatment was 2.71 +/- 0.64 microliters/minute (+/- standard deviation). The rate of flow during placebo treatment was 2.80 +/- 0.66 microliters/minute. There is no statistically significant difference between these two rates (P = 0.4). With a sample size of 19, the study has a power of 92% to detect at least a 15% difference in the rate of flow under the two conditions. Measurement of plasma concentration of melatonin in five subjects confirmed that concentrations after oral dosage reached peaks comparable with the normal endogenous nocturnal peaks. CONCLUSIONS: The authors conclude that melatonin concentrations during the day, comparable with plasma concentrations that occur spontaneously during sleep, do not suppress aqueous humor formation. The authors find no support for the idea that plasma melatonin, per se, can suppress aqueous formation or that the circadian rhythm of plasma melatonin is primarily responsible for the circadian rhythm of aqueous humor flow.     

An experimental study of cytology in the aqueous humor of rabbit eyes after intraocular lens implantation

OBJECTIVE: The study was designed to count the number of white blood cells and observe their subset distribution in the aqueous humor after extracapsular lens extraction and intraocular lens (IOL) implantation in capsular bag in rabbits and to discuss the mechanism of postoperative intraocular inflammatory response. METHODS: 27 adult pigmented rabbits were divided into three groups: (1) The IOL was placed in the capsular bag after extracapsular lens extraction; (2) The extracapsular lens extraction; and (3) The control group without any surgical intervention. Aqueous humor samples were aspirated on the postoperative 1, 3, 7 and 14 days, and the total number of white blood cells in the aqueous humor and their subset distribution were counted. The data were analyzed by using analysis of variance of SAS software. RESULTS: There was a significantly higher number of inflammatory cells in the IOL implanted eyes than that in the eyes with only extracapsular lens extraction. CONCLUSIONS: In the early postoperative stage, there was a marked increase in the number of white blood cells and polymorphonuclear leukocytes in the IOL group, that is probably related to the mechanical ocular tissue damage and the breakdown of the blood-aqueous barrier induced by the operative procedures. There were a significant increase in the macrophages, eosinophiles, and lymphocytes in the IOL group, that suggests that an active immune response exist in the anterior ocular inflammation after IOL implantation.     

Social isolation induces preference for odours of oestrous females in sexually naive male staggerer mutant mice

PURPOSE: To evaluate Sturge-Weber-associated glaucoma using ultrasound biomicroscopy. METHOD: Case report. Clinical examination combined with ultrasound biomicroscopy was performed in a patient with Sturge-Weber-associated glaucoma. RESULTS: In the patient's left eye, which had Sturge-Weber-associated glaucoma, a 360-degree supraciliary effusion, dilated superficial and intrascleral vessels, and an open angle were detected by ultrasound biomicroscopy. CONCLUSION: The presence of dilated intrascleral vessels and supraciliary fluid support the hypothesis of increased episcleral venous pressure as the cause of elevated intraocular pressure in this syndrome.     

Measuring sexual harassment: development and validation of the Sexual Harassment Inventory

Recent studies have suggested that intravenous infusion of fenoldopam, a selective dopamine-1 receptor agonist, elevates intraocular pressure (IOP) in man. This study evaluated the effect of intravenous fenoldopam on IOP, aqueous humor outflow facility and gonioscopy in 12 healthy human subjects. Three doses (0.2, 0.5 and 1.0 microg/kg/min) were infused for 120 minutes in a double masked, placebo controlled, four-way crossover design. IOP was measured every 20 minutes in the supine position and every 40 minutes while sitting during the drug and placebo infusions. Tonography and gonioscopy were performed at baseline and after 120 minutes of infusion. Compared to placebo, IOP increased by 3.5 mm Hg (32%) for the lowest dose, 5.8 mm Hg (46%) for the intermediate dose, and 6.9 mm Hg (55%) for the highest dose (p<0.05 for all three doses). IOP returned to baseline within 30 minutes of stopping the infusion. The outflow facility decreased from baseline by 26% after 120 minutes of infusion for all drug doses. In contrast, outflow facility increased from baseline by 11% during placebo infusion. Compared to placebo, the fenoldopam induced changes in outflow were statistically significant (p<0.05). There was no change in the gonioscopic appearance of the anterior chamber angle during the infusion. This study shows that systemic administration of a selective dopamine-1 receptor agonist causes a significant dose-dependent increase in IOP that can be explained in part by diminished outflow facility. These results support a role for the dopamine-1 receptor in the modulation of IOP in general and suggest modulation of aqueous humor outflow by dopaminergic receptors.     

Glucagon and insulin metabolism in cirrhotic patients

BACKGROUND/AIMS: The aim of this study was to investigate glucagon and insulin metabolism in order to clarify the mechanisms that lead to hyperglucagonemia and hyperinsulinemia in cirrhosis. METHODOLOGY: Splanchnic output and metabolic clearance rates were studied in 16 cirrhotic patients and 5 non-cirrhotic controls. Splanchnic glucagon and insulin output into the portal circulation were calculated by the difference between portal venous and systemic arterial concentration multiplied by portal plasma flow. The metabolic clearance rate was calculated as the ratio of output to systemic arterial concentration. Portal blood flow was measured by continuous local thermodilution. RESULTS: Arterial glucagon levels were higher in cirrhotics than in controls. Glucagon output was triple of that found in controls (52.4 +/- 7.0 vs 17.7 +/- 2.9 ng/min, p < 0.05). Both groups exhibited similar metabolic clearance rates of glucagon. Systemic arterial insulin values were higher in cirrhotics than in non-cirrhotics. Insulin output was not significantly different between the two groups. However, metabolic clearance of insulin in cirrhotics was reduced to one half of the rate found in controls (237.0 +/- 39.8 vs. 450.5 +/- 17.5 mL/min, p < 0.05). CONCLUSIONS: Hyperglucagonemia in cirrhotic patients results from increased pancreatic output, while hyperinsulinemia results from decreased insulin clearance.     

Endoscopic pancreaticobiliary procedures in patients with a Billroth II resection: a 10-year follow-up study

PURPOSE: To report uveitis associated with human immunodeficiency virus (HIV) infection and to suggest guidelines for treatment. METHODS: Six HIV-seropositive patients (10 eyes) with anterior or posterior uveitis or both were evaluated. After ineffective prolonged treatment with systemic and topical corticosteroids, specific systemic antiretroviral therapy with zidovudine was initiated in all patients. Aqueous humor was cultured in three eyes of three patients, and vitreous humor was cultured in one eye of one patient. RESULTS: In all 10 eyes of six patients, there was resolution of inflammation in 10 to 42 days after commencement of treatment with zidovudine (600 to 800 mg/day), despite no or minimal response to corticosteroids. Cultures of aqueous humor from three eyes of three patients and culture of vitreous humor from one eye of one patient were positive for HIV; no other organism was isolated. Systemic evaluation disclosed no other identifiable cause for the uveitis in any patient. CONCLUSIONS: Infection with HIV appears to be a cause of uveitis. A trial of zidovudine may be warranted in HIV-seropositive patients with uveitis that is poorly responsive to corticosteroid treatment when no other cause is identified. The efficacy of other retroviral agents was not determined.