Controversies in acute primary angle closure glaucoma in Chinese people.
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Acute Disease↗
Biomedical subjects
P Chew
Publications and source records attributed to P Chew.
Diagnosis and treatment of acute bacterial rhinosinusitis.
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Anti-Bacterial Agents↗
Evaluation of a weight-adjusted single-bolus plasminogen activator in patients with myocardial infarction: a double-blind, randomized angiographic trial of lanoteplase versus alteplase.
BACKGROUND: Lanoteplase (nPA) is a rationally designed variant of tissue plasminogen activator with greater fibrinolytic potency and slower plasma clearance than alteplase. METHODS AND RESULTS: InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early), a multicenter, double-blind, randomized, double-placebo angiographic trial, evaluated the dose-response relationship and safety of single-bolus, weight-adjusted lanoteplase. Patients (n=602) presenting within 6 hours of acute myocardial infarction were randomized and treated with either a single-bolus injection of lanoteplase (15, 30, 60, or 120 kU/kg) or accelerated alteplase. The primary objective was to determine TIMI grade flow at 60 minutes. Angiographic assessments were also performed at 90 minutes and on days 3 to 5. Follow-up was continued for 30 days. Lanoteplase achieved its primary objective, demonstrating a dose-response in TIMI grade 3 flow at 60 minutes (23.6% to 47.1% of subjects, P<0. 001). Similar results were observed at 90 minutes (26.1% to 57.1%, P<0.001). At 90 minutes, coronary patency (TIMI 2 or 3) increased across the dose range up to 83% of subjects at 120 kU/kg lanoteplase compared with 71.4% with alteplase. Thus, at this dose, lanoteplase was superior to alteplase in restoring coronary patency (difference, 12%; 95% CI, 1% to 23%). The early safety experience in this study suggests that lanoteplase was well tolerated at all doses with safety comparable to that of alteplase. CONCLUSIONS: Lanoteplase, a single-bolus, weight-adjusted agent, increased coronary patency at 60 and 90 minutes in a dose-dependent fashion. Coronary patency at 90 minutes was achieved more frequently with 120 kU/kg lanoteplase than alteplase. In this study, safety with lanoteplase and alteplase was comparable. InTIME-II, a worldwide mortality trial, will evaluate efficacy and safety with this promising new agent.
Adolescent↗
Trabeculectomy survival with and without intra-operative 5-fluorouracil application in an Asian population.
PURPOSE: To define and compare the trabeculectomy survival with regard to intra-ocular pressure (IOP) control without further surgery or anti-glaucoma medication n an Asian population. METHODS: A retrospective review of two consecutive groups of patients who had trabeculectomy surgery in a university eye department setting. The first group of patients (group A) did not receive any adjunctive 5-fluorouracil (5-FU), while the second group (group B) had intra-operative sponge application of 5-FU. Only the first trabeculectomy of patients who had bilateral trabeculectomy and the first trabeculectomy performed in patients who had repeated surgery was analysed. Combined procedures were excluded. Survival analysis was performed using the Kaplan-Meier product limit method. RESULTS: Eighty-nine patients (51 in group A and 38 in group B) were studied, with a mean follow up of 37.5 and 27.0 months, respectively (P = 0.014). There were no statistical differences in age, gender, mean pretreatment IOP, pre-operative medication, proportion of patients with previous ocular surgery, or proportion of primary compared with secondary glaucoma between the two groups. The probability of trabeculectomy survival (IOP < 22 mmHg without additional medication/surgery) at 12 and 36 months was 54.3 and 36.4%, respectively, in group A and 75.8 and 65.8%, respectively, in group B. The differences in survival were significant (P = 0.006, log rank test). CONCLUSIONS: Our experience with trabeculectomy survival in the Asian population showed poorer success when compared with Caucasian populations reported by other investigators. The survival of trabeculectomy surgery was improved significantly with intra-operative 5-FU. There may be justification for advocating a more liberal use of intra-operative 5-FU in such a population.
Administration, Topical↗
Somatostatin inhibits gastrin release and acid secretion by activating sst2 in dogs.
Somatostatin is a potent inhibitor of gastrin-stimulated acid secretion by activation of somatostatin receptor type 2 (sst2) in vivo, probably in part by blocking gastrin-stimulated histamine release from enterochromaffin-like cells expressing sst2. We propose that activation of sst2 may also regulate meal-stimulated acid secretion by blocking gastrin release from antral G cells. Using peptide analogs relatively selective for sst2 (NC-8-12), sst3 (BIM-23058), and sst5 (BIM-23052), we tested this hypothesis in two ways: first, in vivo by measuring plasma gastrin release during meal-stimulated acid secretion in dogs, and second, in vitro by measuring bombesin-stimulated gastrin release from an enriched culture of canine antral G cells. In vivo, a low dose (0.05 nmol.kg-1.h-1) of NC-8-12 inhibited acid secretion 56 +/- 16% without blocking gastrin release. A higher dose (1 nmol.kg-1.h-1) of NC-8-12 abolished acid secretion and inhibited gastrin release by 61 +/- 4%, whereas the highest dose (5 nmol.kg-1.h-1) inhibited gastrin release by 84 +/- 3%. Only the highest doses (5 nmol.kg-1.h-1) of BIM-23058 and BIM-23052 significantly inhibited gastrin release and acid secretion. In vitro, NC-8-12 (10(-9) M) reduced bombesin-stimulated gastrin release from antral G cells by 49 +/- 5%, whereas BIM-23058 and BIM-23052 were at least 100-fold less effective. These results indicate that somatostatin activation of sst2, but not sst3 or sst5, is the major pathway for somatostatin-induced inhibition of meal-stimulated gastrin release and acid secretion.
Animals↗
Evidence that CCK-58 has structure that influences its biological activity.
Many biologically active peptides exist in multiple molecular forms, but the functional significance of regions outside the region of bioactivity is unknown. The biological and immunological data presented in this study indicate that cholecystokinin-58 (CCK-58), unlike other forms of cholecystokinin, has structure that influences its bioactivity. CCK-58 was purified from acid extracts of canine intestinal mucosa until a single absorbance peak was obtained during reverse-phase chromatography. Amino acid analysis precisely determined the peptide concentrations of purified CCK-58 and synthetic CCK-8. Our hypothesis was that if the amino terminus of CCK-58 influences its bioactivity then its activity would be modified when this region was removed from the peptide. To evaluate the importance of the amino terminus of CCK-58 to influence its biological activity, the abilities of CCK-58 and CCK-8 to release amylase from pancreatic acini were compared before and after tryptic digestion. Tryptic digestion of CCK-58 decreased the half-maximal stimulation (EC50) for amylase release from 96 to 28 pM. The EC50 for digested CCK-58 was similar to that for CCK-8 (17 pM). These results suggest that CCK-58 has a structure that shields its bioactive carboxyl terminus. This is further supported by the finding that carboxyl fragments generated from CCK-58 by trypsin or by partial acid hydrolysis were greater than twofold more immunoreactive than the intact CCK-58. The diminished activity of CCK-58 SK shields the carboxyl terminus, which is important to its biological and immunological activities.
Acids↗
The effect of tecogalan sodium on the development of the collateral circulation after acute arterial occlusion.
The survival of tissues distal to major arterial occlusions is critically dependent on the development of collateral blood vessels. The biochemical events fundamental to their evolution remain undefined. To determine the role of endogenous basic fibroblast growth factor in the development of the collateral circulation we evaluated the dose response to Tecogalan Sodium (DS-4152) in a rat model of hind limb ischaemia. Treatment with DS-4152 inhibited the recovery following acute arterial occlusion and impaired limb viability. The inhibitory effects were more pronounced in the calf than in the adductor muscles and tended to be more marked in the groups treated with the higher dose regimens. The results provide further evidence that collateral development and tissue recovery following acute arterial occlusion are dependent on endogenous basic fibroblast growth factor and that this dependence is greater in the more ischaemic, distal tissues.
Acute Disease↗
Natural and synthetic CCK-58. Novel reagents for studying cholecystokinin physiology.
CCK-58 is a unique reagent for testing how segments of a peptide far removed from its active site can influence the expression of its biological activity. Indications of tertiary structure have come from studies with natural peptide purified from canine small intestine. These studies gave clear indications that tertiary structure affects CCK-58 bioactivity, but the small quantities of CCK-58 available made it impossible to characterize completely how tertiary structure influenced bioactivity. Canine CCK-58 was synthesized manually using a solid support and was purified by reverse phase high pressure liquid chromatography (HPLC). Synthetic CCK-58 was characterized by isocratic reverse phase and gradient HPLC, amino acid analysis, mass spectral analysis, sequence analysis, and three bioassays. Synthetic and natural canine CCK-58 had the same elution profiles, amino acid composition, sequence, and mass. The two peptides were equipotent for the stimulation of pancreatic secretion. Natural canine CCK-58 was equipotent to CCK-8 for CCK "B" receptor binding, a further indication of the purity of the natural peptide. However, natural CCK-58 was more potent than CCK-8 for CCK "A" receptor binding and less potent than CCK-8 for stimulation of pancreatic secretion. These data support the concept that CCK-58 has a stable tertiary structure. This structure does not affect its binding to CCK "B" receptors, enhances its binding to low affinity CCK "A" receptors, and decreases its activity expressed through binding to high affinity CCK "A" receptors. The concept of a stable tertiary structure is also supported by the fact that many antibodies directed towards the carboxyl terminus of cholecystokinin react better with CCK-8 than CCK-58. The availability of synthetic CCK-58 will allow analysis of its tertiary structure by physical and chemical methods as well as studies on how peptide tertiary structure can affect receptor binding, receptor activation, metabolism in blood, degradation in interstitial fluid, and inactivation at the receptor. Evaluating all of these systems will help investigators understand the regulation of cholecystokinin activity by its major endocrine form, CCK-58.
Amino Acid Sequence↗
Effects of prostaglandins on gastrin release from canine antral mucosal cells in primary culture.
Evidence in vivo indicates that endogenous and exogenous prostaglandins can alter gastrin secretion. We have used primary cultures containing canine antral G-cells to study the cellular actions of prostaglandins on gastrin secretion, comparing the effects of prostaglandin E2 (PGE2) and its synthetic analogue enprostil. Enprostil (10(-10)-10(-6) M) inhibited gastrin secretion in response to bombesin, carbachol, and forskolin, the latter a receptor-independent activator of adenylate cyclase. This inhibition by enprostil was reversed by treatment with pertussis toxin (200 ng/ml, 8 h). However, enprostil did not inhibit the postreceptor stimuli 8-bromoadenosine 3',5'-cyclic monophosphate (10(-3) M), calcium ionophore A-23187 (10(-7) M), or 4 beta-phorbol 12-myristate 13-acetate (10(-8) M). In contrast, whereas PGE2 inhibited forskolin-stimulated gastrin release, PGE2 did not inhibit the response to carbachol or bombesin in control cultures. However, in pertussis toxin-treated cultures, PGE2 inhibition was reversed and, in contrast, the responses to bombesin, carbachol, and possibly forskolin were augmented. Indomethacin at a dose of 10(-5) M did not alter basal or bombesin-stimulated gastrin secretion. However, the somatostatin antibody CURE-S6 enhanced the response to forskolin and enhanced inhibition by PGE2, suggesting that endogenous somatostatin produced an inhibitory tone in these cultures and excluding the possibility that PGE2 acted via release of endogenous somatostatin. Our data suggest that in cultured antral cells gastrin release is regulated by inhibitory and stimulatory prostaglandin mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenylate Cyclase Toxin↗
Laser iridoplasty in the treatment of severe acute angle closure glaucoma.
Twenty eyes of 19 patients presenting with acute angle closure glaucoma (AACG) which failed to respond to medical treatment were treated with laser iridoplasty. In all 20 eyes, laser peripheral iridectomy (PI) was prevented by a hazy cornea. In all cases, iridoplasty resulted in a rapid and significant reduction in intraocular pressure. Laser iridoplasty appears to have a useful role in the management of medically unresponsive AACG, particularly in those cases where laser peripheral iridotomy (PI) has failed or is not possible to perform.
Acute Disease↗
The prospect for non-surgical drainage procedures.
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Glaucoma↗
Characterization of canine intestinal cholecystokinin-58 lacking its carboxyl-terminal nonapeptide. Evidence for similar post-translational processing in brain and gut.
An antibody raised against a synthetic cholecystokinin (CCK) analog, (1-27)-(CCK)-33, corresponding to the midregion of CCK-58, detected immunoreactivity in intestinal extracts which eluted between the positions of CCK-33/39 and CCK-58 on high performance liquid chromatography. This peak, lacking carboxyl-terminal cholecystokinin immunoreactivity, was purified by reverse phase and cation-exchange chromatographies. Amino acid, mass spectral, and microsequence analysis established that it was the amino-terminal desnonapeptide fragment of cholecystokinin-58, (1-49)-CCK-58. It was demonstrated further that CCK-58 has less biological activity than CCK-8, suggesting that the amino terminus either sterically hindered the ability of CCK-58 to exert its biological activity or that its amino terminus acted at another site to inhibit release of amylase from rat pancreatic acini. The desnonapeptide of CCK-58 by itself had no biological activity, nor did it affect CCK-8-stimulated amylase release from isolated rat pancreatic acini, suggesting that the amino terminus shields the carboxyl terminus from expressing its biological activity. Its presence in intestine suggests that it is released into the circulation where it could be detected by midregion antibodies. The presence of high proportions of (1-49)-CCK-58 indicates that most CCK-8 is directly derived from CCK-58. Its occurrence in brain and intestine indicates similar processing for procholecystokinin in both tissues.
Amino Acid Sequence↗
Purification and structural characterization of progastrin-derived peptides from a human gastrinoma.
Several peptides derived from the gastrin-predicted preprohormone sequence were isolated from a human gastrinoma by gel permeation, anion exchange, and reverse phase chromatography. The peptides were identified and characterized structurally by a combination of radioimmunoassays, mass spectral analysis, and microsequence analysis. The largest peptide, progastrin-(1-35) (cryptagastrin), extends from the putative processing site for the signal peptidase to the double basic residues adjacent to the amino terminus of gastrin 34. A shorter form of this peptide, progastrin-(6-35) (cryptagastrin-(6-35), was also isolated in smaller amounts. In addition, sulfated and nonsulfated gastrin 17 amides (progastrin-(55-71)) and the glycine-extended nonsulfated gastrin 17 (progastrin-(55-72)) were identified by radioimmunoassay, and their structures were confirmed by mass spectral analysis. Isolation of cryptagastrin indicates that the signal peptide of human preprogastrin contains 21 amino acid residues, and progastrin, therefore, contains 80 amino acids. There is minimal processing of the cryptic peptide preceding the sequence of gastrin 34. An amidated gastrin form larger than gastrin 34 could contain 71 amino acids. No evidence was obtained for processing that would produce gastrins containing more than 34 but less than 71 amino acid residues.
Amino Acid Sequence↗
Characterization of the carboxyl terminal flanking peptide of rat progastrin.
A peptide identical in structure to the carboxyl-terminal flanking nonapeptide of rat progastrin, predicted by cDNA sequence, was synthesized. The synthetic peptide was used for production of a rabbit antiserum. This antiserum was used to develop a radioimmunoassay specific for rat carboxyl terminal flanking peptide. This assay was used to monitor the purification of immunoreactivity from rat antral extracts. Gel permeation, anion exchange and reverse phase chromatography steps resulted in a single absorbance peak associated with the carboxyl terminal flanking peptide immunoreactivity. The purified peptide eluted in the same position as the synthetic peptide during all three types of chromatography. This material was shown to be identical in mass to Ser-Ala-Glu-Glu-Glu-Asp-Gln-Tyr-Asn, the predicted sequence of the carboxyl terminal nonapeptide of rat progastrin.
Amino Acid Sequence↗
Prolonged inhibition of meal-stimulated acid secretion and gastrin release following single subcutaneous administration of octreotide (SMS 201-995) in man.
Single subcutaneous doses of the somatostatin analogue, SMS 201-995, were evaluated for the degree and duration of effects on acid secretion, serum gastrin levels, and gastric emptying in eight human male subjects (mean age 44 years) over an 8-h period. All the subjects received subcutaneous 50-micrograms and 100-micrograms doses of SMS 201-995 and placebo on three separate days in a double-blind random order. Drug or placebo was administered at time 0 followed by peptone meals at time 0, 2, 4, and 6-h. Peptone meals were evacuated at time 1, 3, 5 and 7-h to create 'basal' conditions between alternate hours. Gastric acid secretion was determined hourly beginning at time--1. Both the 50-micrograms and 100-micrograms doses of SMS 201-995 significantly inhibited 'basal' and peptone meal-stimulated gastric acid secretion throughout the 8-h measurement period. The minimum effective plasma concentration of SMS 201-995 for inhibition of peptone meal-stimulated gastric acid secretion was approximately 1000 pg/ml. Peptone meal-stimulated plasma gastrin concentrations were inhibited for 5 and 7 h after 50-micrograms and 100-micrograms doses of SMS 201-995, respectively, whereas 'basal' plasma gastrins were inhibited for 4 and 6 h, respectively. Gastric emptying determined by marker dilution was not significantly enhanced compared to placebo. These results indicate prolonged and potent effects of single subcutaneous doses of SMS 201-995 on peptone-meal stimulated acid secretion and gastrin release.
Adult↗
Idiopathic subretinal neovascularization.
Idiopathic subretinal neovascularization is a potentially blinding condition and often strikes patients in their prime of life. It appears to be seen in more females, at an earlier age than males. Treatment is possible by photoablation of the subretinal new vessel by Argon or Yag laser. There is a clinical impression that Argon laser is more effective than the Yag laser for this purpose.
Adult↗
Implantation and diabetes: analysis of 525 cases.
This is a retrospective study of 525 posterior chamber implants in diabetics performed by A S M Lim and B C Ang of Singapore. The patients were reviewed by visiting ophthalmologists--J E Kennedy (Sydney), M Ngui (East Malaysia) and P M Hart (Belfast). This study did not show any significant difference in the complication of post-operative visual acuity between diabetics and non-diabetics. 95% obtained 6/12 vision or better when pre-existing disease was excluded. It also showed that posterior chamber implants can be inserted in eyes with maculopathy or proliferative retinopathy if laser treatment was effectively done before or after surgery.
Adult↗
Effect of terbutaline, a beta 2-adrenoreceptor agonist, on gastric acid secretion and serum gastrin concentrations in humans.
Because beta-adrenoreceptor agonists inhibit gastrin-stimulated gastric acid secretion in animals, we postulated that the beta 2-adrenoreceptor agonist, terbutaline, would inhibit pentagastrin-stimulated acid secretion in humans. Moreover, we hypothesized that terbutaline might inhibit food-stimulated acid secretion, as gastrin is a major mediator of food-stimulated acid secretion. Subcutaneous terbutaline (0.25 mg) reduced acid secretion during intravenous infusion of a submaximal dose of pentagastrin by 30%-40% (p less than 0.005), even though terbutaline increased serum gastrin levels (p less than 0.05). Furthermore, subcutaneous (0.25 mg) or oral (5 mg) terbutaline, given before a homogenized steak meal was infused into the stomach, lowered mean food-stimulated acid secretion rates, despite enhanced postprandial serum gastrin concentrations. Terbutaline also increased serum gastrin concentrations in patients with Zollinger-Ellison syndrome and in vagotomized individuals. Thus, beta 2-adrenoreceptor agonists enhance gastrin release while at the same time inhibiting gastrin-stimulated acid secretion in humans.
Adult↗