Glucose metabolism and oscillatory behavior of pancreatic islets.

A variety of oscillations are observed in pancreatic islets. We establish a model incorporating two oscillatory systems of different time scales: One is the well-known bursting model in pancreatic cells and the other is the glucose-insulin feedback model which considers direct and indirect feedback of secreted insulin. These two are coupled to interact with each other in the combined model, and two basic assumptions are made on the basis of biological observations: The conductance gK(ATP) for the ATP-dependent potassium current is a decreasing function of the glucose concentration whereas the insulin secretion rate is given by a function of the intracellular calcium concentration. Obtained via extensive numerical simulations are complex oscillations including clusters of bursts, slow and fast calcium oscillations, and so on. We also consider how the intracellular glucose concentration depends upon the extracellular glucose concentration, and examine the inhibitory effects of insulin.

Absorption, distribution, metabolism and excretion of telmesteine, a mucolitic agent, in rat.

1. The metabolism and disposition of telmesteine, a muco-active agent, have been investigated following single oral or intravenous administration of (14)C-telmesteine in the Sprague-Dawley rat. 2. (14)C-telmesteine was rapidly absorbed after oral dosing (20 and 50 mg kg(-1)) with an oral bioavailability of >90% both in male and female rats. The C(max) and area under the curve of the radioactivity in plasma increased proportionally to the administered dose and those values in female rats were 30% higher than in male rats. 3. Telmesteine was distributed over all organs except for brain and the tissue/plasma ratio of the radioactivity 30 min after dosing was relatively low with a range of 0.1-0.8 except for excretory organs. 4. Excretion of the radioactivity was 86% of the dose in the urine and 0.6% in the faeces up to 7 days after oral administration. Biliary excretion of the radioactivity in bile duct-cannulated rats was about 3% for the first 24 h. The unchanged compound mainly accounted for the radioactivity in the urine and plasma. 5. Telmesteine was hardly metabolized in microsomal incubations. A glucuronide conjugate was detected in the urine and bile, but the amount of glucuronide was less than 6% of excreted radioactivity.

Angiogenic therapy for the chronically ischemic lower limb in a rabbit model.

The purpose of this study was to evaluate the long-term effectiveness of basic fibroblast growth factor (bFGF) in achieving neovascularization following ischemia from arterial ligation and to determine an optimal dosage level. We used an Ameroid constrictor to produce progressive occlusion of the left femoral artery of rabbits. At 2 weeks, the rabbits were randomized to receive intravenous injection of vehicle (group A, n = 15); 3 microg/kg/day bFGF (group B, n = 12); 10 microg/kg/day bFGF (group C, n = 12); or 16 microg/kg/day bFGF (group D, n = 15) for 3 days. At 1 to 37 days after surgery, we assessed limb neovascularization by transcutaneous oximetry (TCPO(2)), angiography, heart rate, arterial pressure, peripheral vascular resistance (PRU), and muscle blood flow (MBF) during steady-state intra-arterial infusion of saline (basal), acetylcholine, papaverine, or serotonin under anesthesia and capillary density (cap/mm(2)) and capillary per muscle fiber ratio (cap/F). Groups B and C showed significantly greater change in TCPO(2) over time than groups A and D (P < 0.0001). Group D showed the lowest TCPO(2) values from days 14 to 37 and group C the highest. Groups B and C showed a higher number of vessels filled with contrast agent than groups A and D (P < 0.0001). Calf cap/mm(2) and cap/F were significantly higher in groups B and C than groups A and D (P < 0.0001). Calf basal MBF values were higher in groups B and C than in groups A and D, but were not statistically significant. Group D showed the highest level in basal PRU. There were no significant differences in heart rate or blood pressure among the groups. These results show (1) treatment with bFGF has no adverse hemodynamic effects, (2) bFGF enhances angiogenesis and circulation at moderate doses, and these effects persist at least several weeks, and (3) high doses of bFGF may inhibit angiogenesis and collateral circulation.

A prospective comparison of two expanded polytetrafluoroethylene grafts for linear forearm hemodialysis access: does the manufacturer matter?

BACKGROUND: The function and patency of standard 6-mm Goretex (W.L. Gore and Associates, Flagstaff, AZ) and Impra (Impra, Inc., Tempe, AZ) expanded polytetrafluoroethylene (e-PTFE) grafts for hemodialysis as radial-antecubital linear arteriovenous fistulae for dialysis are compared. STUDY DESIGN: A randomized clinical trial was conducted in two community dialysis centers and in one hospital-based center serviced by one vascular surgical practice, that performed the access surgery. Selection of linear forearm access, as opposed to other hemodialysis graft configurations, was at the discretion of the surgeon. Candidates for linear grafts had palpable radial pulses with a normal Allen test and normal digital Doppler flow in the hand. Linear grafts were placed using end-to-side anastomoses to the artery and vein, and the graft type was determined by randomization. Primary patency was determined by first episode of thrombosis, first revision, or angioplasty of the graft. Secondary patency after thrombectomy, revision, or angioplasty was determined when the graft was no longer clinically usable, and a new graft needed to be placed as a parallel conduit in the forearm or in another site. Statistical analysis was by actuarial life-table methods. RESULTS: There were 131 linear forearm grafts in 117 patients. The Impra and Goretex groups were equally matched for gender and major risk factors, except for smoking, which was more common in the Goretex group. Minimum followup was 24 months. Life table primary patencies at 1 year (Impra 43%, Goretex 47%) and at 2 years (Impra 30%, Goretex 26%) were not statistically different (p = 0.78); secondary patency was also equal at 1 year (Impra 49%, Goretex 69%) and at 2 years (Impra 33%, Goretex 41%) (p = 0.15). Discontinuance of use of a patent graft, complications, episodes of thrombosis, and the need to replace the original graft occurred in the two groups without a statistically significant difference. CONCLUSIONS: In the linear forearm position from the radial artery to an antecubital vein, there is no difference in the performance of 6-mm standard e-PTFE grafts on the basis of manufacturer, whether Goretex or Impra. On the basis of performance, linear forearm dialysis grafts are an acceptable method for hemodialysis access.

Feasibility and safety of 1-day postoperative hospitalization for carotid endarterectomy.

OBJECTIVE: To determine whether 1-day postoperative hospitalization after carotid endarterectomy is safe and the degree to which this can be achieved. DESIGN: Consecutive sample series of all carotid endarterectomies performed by a single surgical group. SETTING: A single tertiary-care hospital. PATIENTS: All who underwent carotid endarterectomy. Patients with procedures combined with coronary revascularization and patients undergoing the first part of a staged bilateral carotid endarterectomy performed in 1 hospitalization were excluded. INTERVENTION: In December 1993, a fast-track protocol was initiated, aiming for a 1-day stay after carotid endarterectomy without admission to an intensive care unit (ICU). Before this date, postoperative care included obligatory monitoring for at least 1 night in an ICU. MAIN OUTCOME MEASURES: Length of stay, admission to and stay in the ICU, complications, and hospital readmission rate. RESULTS: Over a 21-month period, 152 patients had 163 carotid endarterectomies. Of these, 124 were elective and 39 urgent (patients with a critical stenosis). Indications were stroke (n = 14 [8.6%]), transient ischemic attack (n = 50 [30.7%]), amaurosis fugax (n = 36 [22.1%]), and asymptomatic stenosis (n = 63 [38.7%]). General anesthesia was used for 159 procedures, cervical block for 4. Mean operation time was 2.6 hours. Postoperative stay was 1 day for 82 procedures (50%), 2 days for 49 procedures (30%), 3 days for 12 procedures (7%), and longer for 20 procedures (12%). In the last half of the study, 61% of patients (50/82) were discharged on postoperative day 1 and 87% (71/82) by postoperative day 2. One hundred three patients went to a surgical floor postoperatively. Overall, 60 patients went to the ICU, but only 18 (22%) of the last 82 procedures required ICU admission. The total stay averaged 3.8 days. Twenty-one patients (13%) experienced complications, including 3 deaths within 30 days and 5 neurological deficits. There were 14 early readmissions, but none was attributable to discharge on the first or second postoperative day. CONCLUSIONS: Early discharge home after carotid endarterectomy is safe and efficacious, and obligatory admission to an ICU is not necessary. At least 60% of patients who undergo carotid endarterectomy can have a postoperative stay of 1 day, and more than 80% can be discharged by postoperative day 2. A short postoperative stay is not associated with a significant risk of readmission for complications.

Superior oblique lengthening procedure with silicone expander in rabbits.

Using a rabbit model, we assessed the postoperative status and histopathologic findings of superior oblique tenotomy with silicone expander procedure. In the control group we marked and cut the superior oblique, and in the experimental group we inserted a silicone 240 retinal band 4 mm in length along the edges of incision. At the postoperative weeks 1,3,5 and 7, we randomly chose five rabbits and made a histopathologic examination after hematoxylin-eosin and Masson's trichrome stain. The distance between the incised edges was various in the control group, but constant in the experimental group. With time inflammation decreased and fibrosis of the superior oblique increased. Foreign body reaction occurred around the suture material in both groups., but not around the silicone expander. At 5 weeks atrophy of the superior oblique was observed in both groups. From the above results, we concluded that the superior oblique lengthening procedure using silicone expander is a useful surgical method for weakening the superior oblique muscle.

Enhanced angiogenesis and growth of collaterals by in vivo administration of recombinant basic fibroblast growth factor in a rabbit model of acute lower limb ischemia: dose-response effect of basic fibroblast growth factor.

The purpose of this study was to evaluate the effects of exogenous recombinant basic fibroblast growth factor (bFGF) on angiogenesis in severely ischemic tissue beds. We used a two-stage procedure to produce severe ischemia of the hindlimb of 34 New Zealand rabbits. The ischemic hindlimb received intramuscular injection of saline (group A), 1 microgram bFGF (group B), or 3 micrograms bFGF (group C), daily for 2 weeks. Tissue perfusion, skeletal muscle infarction, angiogenesis, and collateral growth were assessed by angiography, transcutaneous oximetry (TcPO2), quantitative spectrophotometric assay of triphenyltetrazolium chloride reduction in muscle, capillary density (capillaries per square millimeter), and capillary per muscle fiber ratio. There were no significant differences in baseline TcPO2 among the three groups for both thigh and calf measurements. Angiography revealed extensive perfusion of the left hindlimb in all the assessed bFGF treated animals. Both thigh and calf TcPO2 values showed a significant increase in all groups over the 14 days ischemia was induced (p less than 0.0001), but the two treatment groups exhibited a much more rapid rise in TcPO2 than the control group (p less than 0.0001). The capillaries per square millimeter and capillaries per muscle fiber ratios were significantly increased in all posttreatment measurements for all animals that received bFGF. The treatment groups with bFGF had a significant (p = 0.025) increase in thigh muscle viability compared with controls based on triphenyltetrazolium chloride reduction. Whereas there was evidence of muscle infarction in both the thighs of groups A and B, there was none in group C.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects on the surrounding tissues and morphological changes of components after implantation of PMMA and heparin surface modified PMMA intraocular lens in rabbit eyes.

The aim of this study was to evaluate the cellular response and morphological changes of cells on the intraocular lens(IOL) implanted over a course of time and to identify the basic mechanism of IOL adaptation to tissue reaction in the implanted eye by comparing polymethylmethacrylate (PMMA) IOL with heparin surface modified PMMA IOL. ECCE using Healon was done in 36 eyes of 36 rabbits. A heparin surface modified IOL was implanted in 18 eyes (Group I), while PMMA IOL was implanted into another 18 eyes (Group II). Corneal thickness and endothelial cell density were measured for 3 months. Postoperatively, the eyes were enucleated, and a cytopathologic examination of the cells on the surface of the IOL and their ultrastructural changes were observed with light and scanning microscope at various points of time. The findings of this present study suggested that heparin surface modified PMMA IOL reduced the degree of endothelial cell damage, postoperative tissue reaction, and pigment deposits on the surface of the IOL. These were statistically significant. The most important cell was considered to be the macrophage for the adaptation of IOL in the eye which gradually changed into a fibroblast-like cell, giant cell and finally disappeared after forming an acellular membrane on the IOL.

The effect of combined application of argon and Nd-YAG lasers on iridectomy in rabbits.

Recently iridectomy using an argon or Nd-YAG laser to treat narrow angle glaucoma has become popular, and is now the procedure of choice over the standard surgical technique. However, the shock wave of the Nd-YAG laser causes hemorrhage in almost all cases and the high energy level of the Nd-YAG laser, which is required for iridectomy, causes injury to the lens and cornea. Furthermore, there is a tendency toward closure of the iridectomy site after argon laser application. We performed iridectomies by a combined application of argon and Nd-YAG lasers in pigmented rabbits to improve iris bleeding, iridectomy patency, and lens and corneal damage. The iridectomy patency and the lens and corneal damage were examined with a scanning electron microscope. The rabbits that underwent laser iridectomies with only the Nd-YAG laser were used as a control group. Based on the results, it can be concluded that laser iridectomy by a combined application of argon and Nd-YAG lasers results in a lower rate of bleeding, a higher rate of patency, and less damage to the lens and cornea as compared with iridectomy performed by Nd-YAG laser only.

Carotid endarterectomy. Clinical results in a community-based teaching hospital.

Since 1971, 688 consecutive carotid endarterectomies were performed in 612 patients in a community-based teaching hospital by 16 surgeons; 82% of the procedures were performed in patients who had suffered a transient ischemic attack, amaurosis fugax, or a previous stroke. Seven patients (1%) died, five of perioperative stroke and two of myocardial infarction. Thirty-one patients suffered a perioperative stroke (4.5% of the 688 endarterectomies); 20 patients (2.9% of 688) were left with moderate to severe neurologic deficits. The combined mortality/major neurologic deficit morbidity rate (number of patients divided by number of endarterectomies) is 3.2%. Both operative mortality and morbidity have progressively declined in successive 5-year periods, with no deaths and a 2.7% stroke rate in 148 endarterectomies performed after 1984. Our results indicate that carotid endarterectomy as practiced in a community-based teaching hospital can be performed without excessive risk.