Biomedical subjects
Publications and source records attributed to J Preston.
This research paper documents the current performance of an advanced CAD/CAM system. Patients with CAD/CAM Empress glass-ceramic or Aristeé composite machined complete crowns were retrospectively evaluated using U. S. Public Health Service criteria at least two years after placement. The composite restorations had unacceptable wear and surface loss. Development continues.
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Aldose reductase (aldehyde reductase 2) catalyses the conversion of glucose to sorbitol, and methylglyoxal to acetol. Treatment with aldose reductase inhibitors (ARIs) is a potential approach to decrease the development of diabetic complications. The sulphonylnitromethanes are a recently discovered class of aldose reductase inhibitors, first exemplified by ICI215918. We now describe enzyme kinetic characterization of a second sulphonylnitromethane, 3',5'-dimethyl-4'-nitromethylsulphonyl-2-(2-tolyl)acetanilide (ZD5522), which is at least 10-fold more potent against bovine lens aldose reductase in vitro and which also has a greater efficacy for reduction of rat nerve sorbitol levels in vivo (ED95 = 2.8 mg kg-1 for ZD5522 and 20 mg kg-1 for ICI 215918). ZD5522 follows pure noncompetitive kinetics against bovine lens aldose reductase when either glucose or methylglyoxal is varied (K(is) = K(ii) = 7.2 and 4.3 nM, respectively). This contrasts with ICI 215918 which is an uncompetitive inhibitor (K(ii) = 100 nM) of bovine lens aldose reductase when glucose is varied. Against human recombinant aldose reductase, ZD5522 displays mixed noncompetitive kinetics with respect to both substrates (K(is) = 41 nM, K(ii) = 8 nM with glucose and K(is) = 52 nM, K(ii) = 3.8 nM with methylglyoxal). This is the first report of the effects of a sulphonylnitromethane on either human aldose reductase or utilization of methylglyoxal. These results are discussed with reference to a Di Iso Ordered Bi Bi mechanism for aldose reductase, where the inhibitors compete with binding of both the aldehyde substrate and alcohol product. This model may explain why aldose reductase inhibitors follow noncompetitive or uncompetitive kinetics with respect to aldehyde substrates, and X-ray crystallography paradoxically locates an ARI within the substrate binding site. Aldehyde reductase (aldehyde reductase 1) is closely related to aldose reductase. Inhibition of bovine kidney aldehyde reductase by ZD5522 follows uncompetitive kinetics with respect to glucuronate (K(ii) = 39 nM), indicating a selectivity greater than 5-fold for bovine aldose reductase relative to aldehyde reductase.
OBJECTIVE: The purpose of this research was to investigate viability factors in the implementation of telemedicine systems. The Texas Telemedicine Project examined the viability of a rural network where multiple facilities shared a switchable long-distance network rather than using fixed point-to-point connections. METHODS: During Phase I, conducted in 1989, staff at participating institutions analyzed applications for the proposed network and developed methodologies for data collection. The capital costs and potential savings of a telemedicine network linking institutions in Austin and Giddings, Texas, were estimated. In April of 1991, Phase II of the system was implemented, and the first year's actual capital expenditures and savings (e.g., trips avoided, salaries of traveling specialists saved, reduced mileage and patient transport expenses, redundant tests avoided, reduced long distance telephone charges) attributed to the network were calculated. RESULTS: On the basis of the data collected in Phase I, it was projected that each $1.00 applied toward installation and operation of the network should yield $1.50 in benefits, with return on investment (break-even) within 1 year. In practice, there was a net deficit during the first year, although linear extrapolation predicted return on investment in 2.7 years. CONCLUSION: Linking multiple users over a shared infrastructure has the benefit of distributing cost among the participants and achieving an economy of scale for telecommunications services. The chief barriers to greater savings were the failure of five of the six network sites to design mission-oriented telemedicine policies and the absence of Medicare reimbursement.
Renal handling of 2',3'-dideoxycytidine (ddC), a new anti-HIV dideoxynucleoside which undergoes renal and non-renal clearance, was determined in CF-1 male mice. Since calmodulin inhibitors (CIs) and calcium channel blockers (CCBs) have been shown to influence the flux of pyrimidine nucleosides across mammalian membranes and since the plasma concentration (and hence the efficacy) of therapeutic nucleosides is usually affected by the rate of renal elimination, we decided to determine the impact of the CIs loperamide (LOP) and trifluoperazine (TFP) as well as the CCB verapamil (VER) on the renal excretion of ddC. The ratio of ddC clearance to inulin clearance suggests that ddC undergoes secretion into renal tubules. Pre-exposure of mice to the calmodulin inhibitors loperamide (LOP) and trifluoperazine (TFP) resulted in a decrease in ddC renal secretion while pre-treatment with the calcium channel blocker verapamil increased ddC secretion.
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The renal handling of two anticancer (a-Ca) pyrimidines 5-fluorodeoxyuridine (FUdR) and 5-fluorouracil (5-FU) was investigated in clearance experiments in CF-1 mice using specific inhibitors of classical renal transport systems. The 5-FU was derived from the metabolism of FUdR. Based on the FUdR:inulin clearance ratio and 5-FU:inulin clearance ratio, it was determined that FUdR was secreted into renal tubules while 5-FU underwent reabsorption. The secretion of FUdR was inhibited by cimetidine and dipyridamole but not by probenecid or phloridzin. While the clearance ratio of 5-FU:inulin was significantly reduced by phloridzin, it (i.e., the ratio) was not affected by cimetidine, dipyridamole, or probenecid. The impact of two calcium channel blockers, diltiazem (DZM) and verapamil (VER), on the renal handling of FUdR and 5-FU was also examined. VER increased the secretion of FUdR without affecting the reabsorption of 5-FU while DZM slightly decreased the secretion of FUdR and prevented the reabsorption of 5-FU. These data suggest that the organic cation carrier and a dipyridamole-sensitive nucleoside transporter are involved in the renal excretion of FUdR; that the renal transport of both FUdR and 5-FU is associated with the calcium channel; and that 5-FU utilizes, at least in part, the glucose transporter for its reabsorption.
To explore the novel concept of intrinsic brain regulation of the choroid plexus (CP), we studied the function of the CP exposed to increased intracranial pressure (ICP). The function of the CP was evaluated by in vitro chloride (Cl-) efflux from isolated CP 21 days after kaolin induced hydrocephalus. The Cl- efflux was significantly decreased in animals with elevated intracranial pressure (rate constant, K = 0.024 +/- 0.001 s-1) and enlarged ventricles (K = 0.023 +/- 0.001 s-1) compared to sham animals (K = 0.031 +/- 0.001 s-1). In contrast, the Cl- efflux of CP from animals with normal ICP and ventricular size did not differ from sham animals. These results illustrate the first demonstration of regulation of the CP epithelial function with elevated ICP; they also suggest a brain-CP regulatory mechanism that alters CP function.
Aldose reductase (aldehyde reductase 2, ALR2) is often isolated as a mixture of two forms which are sensitive (ALR2S), or insensitive (ALR2I), to inhibitors. We show that ICI 215918 ((2-6-dimethylphenylsulphonyl)-nitromethane) follows either noncompetitive, or uncompetitive kinetics with respect to aldehyde for ALR2S, or the closely related enzyme, aldehyde reductase (aldehyde reductase 1, ALR1). Similar behaviour is exhibited by two other structural types of aldose reductase inhibitor (ARI), spirohydantoins and acetic acids, when either aldehyde, or NADPH is varied. For ALR2S, we have demonstrated kinetic competition between a sulphonylnitromethane, an acetic acid and a spirohydantoin. Thus, different ARIs probably have overlapping binding sites. Published studies imply that ALR2 follows an ordered mechanism where coenzyme binds first and induces a reversible conformation change (E.NADPH-->E*.NADPH). Reduction of aldehyde appears rate-limited by the step E*.NADP+-->E.NADP+. Spontaneous activation converts ALR2S into ALR2I and increases kcat. This must be associated with acceleration of the rate-determining step. We now propose the following hypothesis to explain characteristics of ARIs. (1) Inhibitors preferentially bind to the E* conformation. (2) The ARI binding site contains residues in common with that for aldehyde substrates. When aldehyde is varied, uncompetitive inhibition arises from association at the site for alcohol product in the E*.NADP+ complex which has little affinity for the substrate. Any competitive inhibition arises from use of the aldehyde site in the E*.NADPH complex. (3) Acceleration of the E*.NADP+-->E.NADP+ step upon activation of ALR2 reduces steady state levels of E* and so decreases sensitivity to ARIs.
Success, as it is usually defined for osseointegrated implants, may leave much to be desired in terms of esthetics, phonetics, and function. Optimal occlusal function demands that the implant-supported restoration be placed in a position that will permit the desired cusp-fossae relations with axial loading. In the partially edentulous patient, the implant-supported restoration also should blend into the arch form of the adjacent and opposing teeth. From a phonetic viewpoint, the natural contour and position of the anterior teeth must be maintained. To achieve these goals, it may be necessary to restore the hard and soft tissue anatomy vertically and horizontally and to augment or reconstruct the sinus. Depending on the circumstances, these measures may be carried out before, during, or after implant placement. In this paper, the considerations involved in diagnosis and selection of reconstructive technique are outlined.
Many users consider telemedicine a partial solution to problems of delivering health care to remote areas or areas underserved by clinicians. Current telemedical technology benefits from recent developments such as the decreased cost and improved quality of the coder-decoder (codec) equipment used in interactive digital video systems and the expansion of fiber-optic cable networks. The authors outline some pioneering telemedicine programs of the 1960s and 1970s and describe two recently activated systems in Texas. One network, serving the western two-fifths of the state, links faculty members from four campuses of Texas Tech University Health Sciences Center with almost 40 rural communities. The other connects the state hospital and three other facilities in Austin with four health care sites in the town of Giddings, 65 miles away. Besides serving patients, the systems provide continuing medical education and support to reduce the isolation of rural health care professionals. Primary goals include evaluation and certification of telemedical training and analysis of the cost feasibility of telemedical services.
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Many of the complications of diabetes seem to be due to aldose reductase (aldehyde reductase 2, ALR2) catalysing the increased conversion of glucose to sorbitol. Therapy with aldose reductase inhibitors (ARIs) could, therefore, decrease the development of diabetic complications. (2,6-Dimethylphenylsulphonyl)nitromethane (ICI 215918) is an example from a newly discovered class of ARIs, and we here describe its kinetic properties. Preparations of bovine lens ALR2 exhibit biphasic kinetics with respect to glucose and various inhibitors including ICI 215918. The inhibitor sensitive form (ALR2S) has a higher affinity for glucose than does the inhibitor insensitive form (ALR2I). Only ALR2S was characterized in detail because ALR2I activity is very low at physiological levels of glucose and is difficult to measure with accuracy. Aldehyde reductase (ALR1) is the most closely related enzyme to ALR2. Inhibition of ALR1 was, therefore, investigated in order to assess the specificity of ICI 215918. The values of Ki and Kies (dissociation constants for inhibitor from enzyme-inhibitor and enzyme-inhibitor-substrate complexes, respectively) for ICI 215918 with bovine kidney ALR1 and bovine lens ALR2S have been determined. When glucose is varied, the compound is an uncompetitive inhibitor of ALR2S (Kies = 0.10 microM and Ki is much greater than Kies), indicating that ICI 215918 associates with an allosteric site on the enzyme. These kinetic characteristics would cause a decrease in the concentration required to give 50% inhibition when glucose levels rise during hyperglycaemia. ICI 215918 is a mixed noncompetitive inhibitor of ALR1 (Ki = 10 microM and Kies = 1.8 microM) when glucuronate is varied. Thus, the compound has up to 100-fold specificity in favour of ALR2S relative to ALR1. Therapeutic interest has now centred upon at least three distinct structural types of ARIs: spirohydantoins, acetic acids and sulphonylnitromethanes. Using one representative of each type, we have demonstrated kinetic competition for inhibition of ALR2S. This observation strongly suggests that the different inhibitors use overlapping binding sites.
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BACKGROUND AND METHODS: Although it is useful in certain clinical situations for manual resuscitator units to be used with spontaneously ventilating patients, there are few data regarding their performance in these settings. We measured the percent-delivered oxygen from 13 adult manual resuscitator units during simulated spontaneous ventilation in the range of respiratory frequency, tidal volume, and oxygen supply in which manual resuscitator units might be used with patients. We also measured the resistive pressure developed during simulated ventilation and at constant inspiratory flow of 50 L/min. RESULTS: Oxygen supply, tidal volume, minute ventilation, and reservoir volume all influenced percent-delivered oxygen, but the most important determinant of percent-delivered oxygen was valve design. Valves incorporating a "disc" element to prevent air entrainment from the expiratory port gave the most efficient oxygen delivery, while "duck-bill" valves did not reliably prevent air entrainment. Only two of the manual resuscitator units tested developed high resistive pressure. CONCLUSION: Reliable administration of high percent-delivered oxygen to spontaneously ventilating patients, while retaining the capability to manually ventilate them, is best achieved by a manual resuscitator unit with a valve of low resistance, incorporating a disc to prevent air entrainment. We recommend that manufacturers indicate on the product information sheet the degree (and confidence limits) to which their manual resuscitator unit presents resistance and delivers oxygen to a spontaneously ventilating subject.
OBJECTIVE: Because of rising costs in the Medicare program, the elderly have been encouraged to enroll in health maintenance organizations (HMOs). To evaluate the quality of care in these HMOs, detailed criteria on the treatment of elderly diabetics were established by an expert panel. DESIGN: Approximately 20 months of care for elderly diabetics was reviewed by medical record abstractions with a historical cohort design. SETTING: The care of elderly diabetics in eight HMOs was compared with the care received in fee-for-service (FFS) settings located in similar geographic areas. PATIENTS: Elderly diabetics enrolled in HMOs (n = 158) were compared with similar diabetics (n = 134) in FFS settings. RESULTS: Diabetic HMO enrollees were more likely to have funduscopic examinations (48% in HMOs vs 30% FFS) and urinalyses (89% in HMOs vs 74% FFS) performed. Enrollees with poor diabetic control were also more likely than FFS diabetics to be referred to an ophthalmologist (45% in HMOs vs 11% FFS). However, influenza vaccinations were administered to diabetics more often in FFS settings than to diabetic enrollees (19% in HMOs vs 62% FFS). One fifth of diabetics in both groups were treated with insulin and two thirds were treated with oral hypoglycemic agents, though HMO enrollees were more likely to have medication changes. CONCLUSION: We conclude that most aspects of the quality of diabetic care were similar in HMO and FFS settings and were unaffected by this effort at cost containment.
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