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Biomedical subjects

D Wong

Publications and source records attributed to D Wong.

At least 127 records · Page 7Linked to original sources

Intravitreal penetration of teicoplanin.

Teicoplanin is a glycopeptide antibiotic, similar to vancomycin, but safer and better tolerated. The purpose of this study was to evaluate the penetration of teicoplanin into the vitreous when administered topically and intravenously. Twenty-five patients undergoing routine vitrectomy were recruited. Twenty were given intravenous teicoplanin: five 1 h pre-operatively, five 12 h pre-operatively, five 24 h pre-operatively and five 24 h as well as 48 h pre-operatively. Five received teicoplanin drops half-hourly for the 6 h immediately preceding vitrectomy. Undiluted vitreous specimens were obtained at the beginning of each vitrectomy procedure. Teicoplanin levels were measured using a biological assay with Staphylococcus aureus as the indicator organism. Teicoplanin activity was detected in 8 of the 20 specimens from those patients receiving the intravenous antibiotic. Teicoplanin did not penetrate readily into the vitreous cavities in these eyes despite the blood-ocular barrier being compromised in some patients, although there was evidence of accumulation with time. No activity was detected in the vitreous of those patients who received topical teicoplanin.

Adolescent↗

Local anaesthesia for vitreoretinal surgery: a case-control study of 200 cases.

PURPOSE: In the United Kingdom the majority of vitreoretinal (VR) surgery is performed under general anaesthesia (GA). The aim of this study was to demonstrate the scope of local anaesthesia (LA) for VR surgery, to measure the acceptance of LA to patients and surgeons and to compare the surgical outcomes, complication rates and duration of the surgical procedures under LA and GA. METHODS: A case-control study was undertaken to compare 100 cases performed under LA with 100 matched cases performed under GA. The matching of cases was based on multiple criteria such as configuration and complexity of retinal detachment, the involvement of the macula, the number and site of retinal tears, presence and severity of proliferative vitreoretinopathy, experience of the surgeon and the type of the surgical procedure. A clinical audit was also carried out on 65 successive patients using a questionnaire to determine the acceptability of LA to patients and surgeons. RESULTS: Anatomical and visual success rates, and intra-operative and post-operative complications, were similar in cases carried out under LA and GA. The mean duration of the surgery (excluding anaesthetic time) was significantly shorter for LA than GA procedures (p < 0.001). The acceptance for LA was high for both patients and the operating surgeons. CONCLUSIONS: We found that VR surgery can be safely and efficiently performed under LA. Adoption of LA has increased our throughput.

Anesthesia, General↗

Optimization of sustained-release diltiazem formulations in man by use of an in-vitro/in-vivo correlation.

In-vitro/in-vivo correlations (IVIVC) are useful for predicting in-vivo results from in-vitro data. An IVIVC has been used to optimize a hydrocolloidal-based matrix tablet designed to be bioequivalent to an existing once-daily diltiazem HC1 product (Dilacor XR 240mg; Rhone-Poulenc Rorer). Data from a preliminary formulation dosed to fasted and fed subjects were used to establish the IVIVC. The correlation was then used during reformulation of the dosage forms to predict changes in the maximum plasma concentration (Cmax) and the area under the plasma-concentration-time curve (AUC) for fasted and fed subjects using in-vitro dissolution data. The IVIVC adequately predicted plasma profiles of two optimized formulations in studies with fasted and fed subjects.

Cardiovascular Agents↗

Endoresection of choroidal melanoma.

AIMS: The results of 52 endoresections for choroidal melanoma are reported. METHODS: The current technique involves vitrectomy, retinal incision over or peripheral to the tumour, haemostasis by raising intraocular pressure and by moderate hypotensive anaesthesia, choroidal incision around tumour, endoresection with vitrector, endodiathermy to bleeding points and residual tumour, fluid-air exchange to reattach retina, endolaser to achieve retinal adhesion around the coloboma and destroy residual tumour in the sclera, silicone oil injection with removal after 12 weeks, cryotherapy to the sclerotomies, and adjunctive ruthenium plaque radiotherapy in selected cases. RESULTS: Patients receiving primary endoresection had a mean age of 53 years, a mean largest basal tumour diameter of 8.2 mm, and a mean tumour thickness of 3.9 mm. 40 tumours extended to within 2 disc diameters of the optic disc, with 17 involving disc. Follow up ranged from 40 days to 7 years (median 20 months). At the last visit, 90% of eyes were retained, with vision of 6/6-6/12 (two), 6/18-6/36 (three), 6/60 to counting fingers (18), hand movements (nine), and light perception (four). The main complications were retinal detachment in 16 and cataract in 25. Secondary endoresection (11) was performed after plaque radiotherapy (four), photocoagulation (four), trans-scleral local resection (two), and proton beam radiotherapy (one), with retention of the eye in nine cases. By the close of the study, no patients developed definite local tumour recurrence but one died of metastatic disease 41 months postoperatively. CONCLUSION: Depending on tumour location, endoresection may conserve central vision or temporal field when radiotherapy would be expected to cause optic neuropathy. Longer follow up is necessary to establish the efficacy of tumour control.

Adult↗

Effects of increased fat availability on fat-carbohydrate interaction during prolonged exercise in men.

The study examined the existence and regulation of fat-carbohydrate interaction during low- and moderate-intensity exercise. Eight males cycled for 10 min at 40% and 60 min at 65% maximal O2 uptake (VO2max) while infused with either Intralipid and heparin (Int) or saline (Con). Before exercise, plasma arterial free fatty acid (FFA) was 0.69 +/- 0.04 mM (Int) vs. 0.25 +/- 0.04 mM (Con). Muscle biopsies were taken at rest and at 10, 20, and 70 min of exercise. Arterial and femoral venous blood samples and expired gases were collected simultaneously throughout exercise, and blood flow was estimated from pulmonary O2 uptake and the leg arterial-venous O2 difference. Respiratory exchange ratio was higher in Con (0.94 +/- 0.01) compared with Int (0.91 +/- 0.01). Mean net leg FFA uptake was higher in Int (0.16 +/- 0.03 vs. 0.04 +/- 0.01 mmol/min), and net lactate efflux was reduced (Int, 1.55 +/- 0.36 vs. Con, 3.07 +/- 0.47 mmol/min). Leg net glucose uptake was unaffected by Int. Muscle glycogen degradation was 23% lower in Int [230 +/- 29 vs. 297 +/- 36 mmol glucosyl units/kg dry muscle (dm)]. Pyruvate dehydrogenase activity in the a form (PDHa) was lower during Int (1.61 +/- 0.17 vs. 2.22 +/- 0.24 mmol.min-1.kg wet muscle-1), and muscle citrate was higher (0.59 +/- 0.04 vs. 0.48 +/- 0.04 mmol/kg dm). Muscle lactate, phosphocreatine, ATP, acetyl-CoA, acetyl-carnitine, and P(i) were unaffected by Int. Calculated free AMP was significantly lower in Int compared with Con at 70 min of exercise (3.3 +/- 0.8 vs. 1.5 +/- 0.3 mumol/kg dm). The high FFA-induced reduction in glycogenolysis and carbohydrate oxidation at 65% VO2max appears to be due to regulation at several sites. The reduced flux through phosphorylase and phosphofructokinase during Int may have been due to reduced free AMP accumulation and increased cytoplasmic citrate. The mechanism for reduced PDH transformation to the a form is unknown but suggests reduced flux through PDH.

Adult↗

Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway.

Mutagenic abasic (AP) sites are generated directly by DNA-damaging agents or by DNA glycosylases acting in base excision repair. AP sites are corrected via incision by AP endonucleases, removal of deoxyribose 5-phosphate, repair synthesis, and ligation. Mammalian DNA polymerase beta (Polbeta) carries out most base excision repair synthesis and also can excise deoxyribose 5-phosphate after AP endonuclease incision. Yeast two-hybrid analysis now indicates protein-protein contact between Polbeta and human AP endonuclease (Ape protein). In vitro, binding of Ape protein to uncleaved AP sites loads Polbeta into a ternary complex with Ape and the AP-DNA. After incision by Ape, only Polbeta exhibits stable DNA binding. Kinetic experiments indicated that Ape accelerates the excision of 5'-terminal deoxyribose 5-phosphate by Polbeta. Thus, the two central players of the base excision repair pathway are coordinated in sequential reactions.

DNA Polymerase I↗

Protein binding and signaling properties of RIN1 suggest a unique effector function.

Human RIN1 was first characterized as a RAS binding protein based on the properties of its carboxyl-terminal domain. We now show that full-length RIN1 interacts with activated RAS in mammalian cells and defines a minimum region of 434 aa required for efficient RAS binding. RIN1 interacts with the "effector domain" of RAS and employs some RAS determinants that are common to, and others that are distinct from, those required for the binding of RAF1, a known RAS effector. The same domain of RIN1 that binds RAS also interacts with 14-3-3 proteins, extending the similarity between RIN1 and other RAS effectors. When expressed in mammalian cells, the RAS binding domain of RIN1 can act as a dominant negative signal transduction blocker. The amino-terminal domain of RIN1 contains a proline-rich sequence similar to consensus Src homology 3 (SH3) binding regions. This RIN1 sequence shows preferential binding to the ABL-SH3 domain in vitro. Moreover, the amino-terminal domain of RIN1 directly associates with, and is tyrosine phosphorylated by, c-ABL. In addition, RIN1 encodes a functional SH2 domain that has the potential to activate downstream signals. These data suggest that RIN1 is able to mediate multiple signals. A differential pattern of expression and alternate splicing indicate several levels of RIN1 regulation.

3T3 Cells↗

The effect of anaesthesia on the intraocular volume of the C3F8 gas bubble.

Long-acting intraocular gas bubbles are frequently used during vitrectomy to tamponade retinal breaks. The aim of this study was to determine the effect of nitrous oxide anaesthesia on the size and effectiveness of the post-vitrectomy gas bubble. Twenty vitrectomy procedures with injection of 12% perfluoropropane (C3F8) gas were performed. For 10 of the cases routine anaesthesia with nitrous oxide was used and for 10 cases non-nitrous anaesthesia with propofol was used. The volume of the intraocular gas bubble was estimated 24 hours post-operatively using A-scan biometry. At 24 hours the gas bubble occupied a mean of 65.1% of the eye in anaesthesia with nitrous oxide and a mean of 66.1% in anaesthesia with intravenous propofol. The wide range of values of gas-fill recorded at 24 hours makes comparison of the two groups inappropriate. Several factors may account for this spread of values, but in our opinion it is the uncontrolled leakage from the sclerostomies which is the most likely. This study suggests that anaesthesia using nitrous oxide does not adversely affect the size of the C3F8 gas bubble at 24 hours post-vitrectomy when compared with anaesthesia without nitrous oxide.

Adult↗

Removal of lens fragments from the vitreous cavity.

Between March 1993 and September 1994 we treated 25 cases of lenses in the vitreous cavity. Nineteen of the 25 were the result of dislocation during phacoemulsification. During this time, we adopted a single surgical algorithm involving vitrectomy, heavy liquids and ultrasound fragmentation. The aims of this retrospective study were to test the validity of our surgical algorithm and to report on outcomes and complications. The indications for vitreous surgery were raised intraocular pressure, uveitis and poor vision. Vitreous surgery was carried out at a mean of 29 days following phacoemulsification. Six patients required heavy liquids and 5 needed ultrasound fragmentation. Vitreous surgery undertaken less than 17 days after phacoemulsification had an increased likelihood of requiring heavy liquids and/or fragmentation (p < 0.02). The greatest threat to a favourable visual outcome was retinal detachment, which was significantly associated with fragmentation and use of heavy liquids (p < 0.02). The presence of an intraocular lens (IOL) reduced the surgical options for removal of the lens fragments, and IOL should not be inserted where lens matter dislocates. The study suggests that we should avoid fragmentation and, provided the intraocular pressure and uveitis can be controlled, that vitreous surgery should be deferred for 2-3 weeks following phacoemulsification.

Adult↗

Colonic delivery of dexamethasone: a pharmacoscintigraphic evaluation.

BACKGROUND: Colonic delivery of corticosteroids may reduce the side-effects commonly associated with their use. Therefore, we tested the ability of the naturally occurring polysaccharide guar gum to deliver a corticosteroid, dexamethasone, to the colon using pharmacoscintigraphy. Guar gum is metabolized in the colon by resident bacterial enzymes to trigger drug release. MATERIALS: Each subject (eight per group, parallel study design) was administered one of four dexamethasone (9 mg) tablet formulations, radiolabelled with 153Sm using neutron activation, under fasted conditions. One formulation was designed to release drug rapidly following ingestion while the other three formulations were designed to delay release of dexamethasone to varying degrees. Progression of the formulations down the gastrointestinal tract was followed by gamma scintigraphy. Serum concentrations were measured over time to relate disintegration profiles of the tablets with pharmacokinetic observations. RESULTS: The immediate release formulation disintegrated in the stomach, on average, within 20 min of dosing. One of the three delayed release preparations (CD1) began to disintegrate in the small intestine 1.7 +/- 1.0 h after dosing. The second and third delayed release preparations (CD2 and CD3) did not begin to disintegrate until 5.8 +/- 2.3 and 3.6 +/- 1.6 h after dosing, respectively. All three colonic delivery preparations completely disintegrated in the colon ranging from 7.8 +/- 2.7 h (CD1) to 12.4 +/- 3.2 h (CD2) following oral administration. Pharmacoscintigraphic data indicated that 72-82% of the dexamethasone was delivered into the colon although not all the dexamethasone delivered into the colon was absorbed. CONCLUSIONS: Simple guar gum formulations are capable of delivering the corticosteroid dexamethasone to the colon of normal subjects. Locally delivered corticosteroids may be useful in the treatment of ulcerative colitis and Crohn's disease. Pharmacoscintigraphic evaluation is a useful method to discriminate between the in vivo behaviour of colonic delivery systems.

Adult↗

Upper airway edema after carotid endarterectomy: the effect of steroid administration.

The objective of this study was to evaluate the effect of preoperative steroid administration on the site and extent of upper airway edema after carotid endarterectomy. The design was a randomized, prospective, double-blind controlled trial. Thirty-eight patients undergoing elective carotid endarterectomy (17 patients were in the steroid-treated group and 21 in the control group) were administered either 16 mg of dexamethasone or saline placebo prior to surgery. Computed tomograms (CT) scans of the neck were performed on the patients preoperatively and 24 h postoperatively. Measurements were taken from the CT scans of the airway transverse and anterior-posterior diameters at the levels of the hyoid bone, arytenoid cartilage, and cricoid cartilage. No postoperative neck hematomas were seen on the CT scans. Although neck edema was observed postoperatively, the upper airway dimensions were not statistically significantly different between the steroid and the control groups. We conclude that steroid administration immediately preoperatively has no clinical effect in reducing edema formation in the upper airway postcarotid endarterectomy.

Aged↗

Predictive factors in global and anesthesia satisfaction in ambulatory surgical patients.

BACKGROUND: Patient satisfaction is one of the variables that affect the outcome of health care and the use of health-care services. As more procedures are performed on an ambulatory basis, the role of the anesthesiologist becomes more important. To improve the delivery of care, the predictors of dissatisfaction with the entire process (global dissatisfaction) of ambulatory surgery and with anesthesia itself must be identified. The authors conducted a hypothesis-generating study to identify predictors; specifically, they hypothesized that satisfaction with anesthesia was a predictor of global satisfaction with ambulatory surgery and that 24-h postoperative symptoms were a predictor of satisfaction with anesthesia. METHODS: The authors prospectively studied 5,228 consecutive patients having surgery in the ambulatory setting during a 1-yr period. Preoperative, intraoperative, and postoperative variables were gathered and patient satisfaction was assessed using a postoperative telephone questionnaire administered 24 h after operation in 2,730 respondents. Significant univariate variables and clinically important variables were entered into multiple logistic regression models. Qualitative data on dissatisfaction were obtained by asking patients' reasons for dissatisfaction. RESULTS: Sixty-eight of the 2,730 respondents (2.5%) had global dissatisfaction with ambulatory surgery. Nine of these patients were dissatisfied with anesthesia. Dissatisfaction with anesthesia was associated with a 12-fold increase in global dissatisfaction (P = 0.0001). Thirty-one of the 2,730 respondents (1.1%) were dissatisfied with anesthesia. An increasing number of symptoms occurring 24 h after operation was associated with an exp(0.28 x N)-fold increase in dissatisfaction with anesthesia for N number of symptoms (P = 0.0001). Qualitative data showed that the most common reason for global dissatisfaction with ambulatory surgery was personal preference for inpatient care (26%), whereas intraoperative and postoperative adverse outcomes were the major causes of dissatisfaction with anesthesia (88%). CONCLUSIONS: Dissatisfaction with anesthesia is a predictor of global dissatisfaction with ambulatory surgery. An increasing number of symptoms 24 h after operation is a predictor of dissatisfaction with anesthesia. The rate of global dissatisfaction and anesthesia dissatisfaction is very low. The predictors from this model need to be validated by a second data set from either this or another center. Given the low rate of dissatisfaction, a focused study testing specific interventions to improve patient satisfaction would be difficult.

Adult↗

Effects of varying levels of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure.

OBJECTIVE: To determine the influence of positive end-expiratory pressure (PEEP) on intracranial pressure and cerebral perfusion pressure. DESIGN: Neurosurgical intensive care patients requiring intracranial pressure monitoring and mechanical ventilation were studied in a randomized, controlled study. SETTING: Tertiary care, neurosurgical intensive care unit. PATIENTS: Eighteen patients were enrolled in the study. Patients had posttraumatic head injuries (n = 9), subarachnoid hemorrhage (n = 7), obstructive hydrocephalus (n = 1), and intracerebral hemorrhage of unknown cause (n = 1). INTERVENTIONS: Patients had PEEP levels of 5, 10, and 15 cm H2O applied to their lungs. MEASUREMENTS AND MAIN RESULTS: Changes in intracranial pressure, mean arterial pressure, and cerebral perfusion pressure were measured. The results were analyzed separately for patients with normal and increased intracranial pressure (> 15 mm Hg). PEEP at 5 cm H2O had no effect on intracranial pressure in the group with normal intracranial pressure. However, PEEP at 10 and 15 cm H2O produced a significant (p < .05) increase in intracranial pressure (1.9 and 1.5 mm Hg, respectively). In the group with increased intracranial pressure, no significant change in intracranial pressure occurred at any of the PEEP levels used. In both groups, cerebral perfusion pressure was unchanged throughout. CONCLUSIONS: In patients with normal intracranial pressure, PEEP at 5 cm H2O did not significantly alter intracranial pressure. The clinical relevance of the intracranial pressure increase at PEEP levels of 10 and 15 cm H2O is questionable because cerebral perfusion pressure did not change and remained > 60 mm Hg. In patients with increased intracranial pressure, higher levels of PEEP did not significantly change intracranial pressure or cerebral perfusion pressure.

Adult↗

Does cryotherapy before drainage increase the risk of intraocular haemorrhage and affect outcome? A prospective, randomised, controlled study using a needle drainage technique and sustained ocular compression.

AIMS/BACKGROUND: A prospective, randomised, controlled clinical trial was conducted to investigate the effect of performing cryotherapy before drainage of subretinal fluid (SRF) on the incidence of intraocular haemorrhage (IOH) in the management of retinal detachment. METHODS: Eighty eyes of 80 patients with rhegmatogenous retinal detachment requiring SRF drainage were recruited. Thirty four cases were randomised to receive drainage before cryotherapy (drainage, air injection, cryotherapy, and explant = DACE group) while 46 cases had drainage after cryotherapy (cryotherapy, drainage, air injection, and explant = CDAE group). All cases had trans-scleral drainage of SRF using a 27 gauge hypodermic needle combined with prolonged, intraocular hypertension. RESULTS: There was a low incidence of IOH associated with drainage in both groups with no statistically significant difference between the groups (DACE group = 2.9%; CDAE group = 4.3%; p = 0.43). There was no significant difference between the groups in the rate of anatomical success with a single operation (DACE group = 82.4%; CDAE group = 86.9%; p = 0.38). There was no significant difference between the groups in the visual outcome. An improvement of two Snellen lines or more occurred in 52.9% of the DACE group and in 56.5% of the CDAE group (p = 0.93). CONCLUSION: It was concluded that the surgical sequence of applying cryotherapy before drainage of SRF can be safely and effectively performed. The sequences CDAE and CDE, when air injection is not required, along with DACE should all be part of the surgical repertoire for the management of retinal detachments.

Adolescent↗