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Biomedical subjects

D Wong

Publications and source records attributed to D Wong.

At least 91 records · Page 5Linked to original sources

Stabilisation of diabetic retinopathy following simultaneous pancreas and kidney transplant.

BACKGROUND/AIMS: Simultaneous pancreas and kidney transplantation (SPK) has become an important option in selected IDDM patients with end stage renal disease (ESRD). Successful SPK transplants are associated with long term normoglycaemic control and improved quality of life. However, debate still continues on the benefit to patients in terms of stabilisation or amelioration of diabetic retinopathy. The progression of diabetic retinopathy (DR) in a cohort of 20 SPK transplant patients is reported. METHODS: All patients were reviewed postoperatively with corrected visual acuity, slit lamp examination, and fundal biomicroscopy. Preoperative data were collected retrospectively and DR was considered unstable if there had been a drop in Snellen acuity greater than three lines or a need for laser photocoagulation or vitrectomy in the 2 years preoperatively. RESULTS: 20 patients who received SPK transplants between March 1983 and April 1994 were reviewed (mean age 35.1 years; mean duration of IDDM = 24.6 years). 17 patients still had functioning grafts at a mean follow up of 5.1 years. Nine of these patients had unstable DR before transplantation. Of these, 89% (8/9) had stabilised DR following transplantation with only a single case requiring laser photocoagulation. Of the eight patients that had stable DR before transplantation all had stable DR following transplantation. 41% of cases (7/17) required cataract surgery during the follow up period. CONCLUSIONS: Advanced diabetic retinopathy is present in a high proportion of cases managed with SPK transplant as a consequence of the duration of IDDM and the presence of ESRD. More than 90% of cases have stable DR following transplant.

Adult↗

Pinacidil suppresses contractility and preserves energy but glibenclamide has no effect during muscle fatigue.

The effects of 10 microM glibenclamide, an ATP-sensitive K(+) (K(ATP)) channel blocker, and 100 microM pinacidil, a channel opener, were studied to determine how the K(ATP) channel affects mouse extensor digitorum longus (EDL) and soleus muscle during fatigue. Fatigue was elicited with 200-ms-long tetanic contractions every second. Glibenclamide did not affect rate and extent of fatigue, force recovery, or (86)Rb(+) fractional loss. The only effects of glibenclamide during fatigue were: an increase in resting tension (EDL and soleus), a depolarization of the cell membrane, a prolongation of the repolarization phase of action potential, and a greater ATP depletion in soleus. Pinacidil, on the other hand, increased the rate but not the extent of fatigue, abolished the normal increase in resting tension during fatigue, enhanced force recovery, and increased (86)Rb(+) fractional loss in both the EDL and soleus. During fatigue, the decreases in ATP and phosphocreatine of soleus muscle were less in the presence of pinacidil. The glibenclamide effects suggest that fatigue, elicited with intermittent contractions, activates few K(ATP) channels that affect resting tension and membrane potentials but not tetanic force, whereas opening the channel with pinacidil causes a faster decrease in tetanic force, improves force recovery, and helps in preserving energy.

Action Potentials↗

Effect of induced metabolic alkalosis on human skeletal muscle metabolism during exercise.

The purpose of the study was to examine the roles of active pyruvate dehydrogenase (PDH(a)), glycogen phosphorylase (Phos), and their regulators in lactate (Lac(-)) metabolism during incremental exercise after ingestion of 0.3 g/kg of either NaHCO(3) [metabolic alkalosis (ALK)] or CaCO(3) [control (CON)]. Subjects (n = 8) were studied at rest, rest postingestion, and during constant rate cycling at three stages (15 min each): 30, 60, 75% of maximal O(2) uptake (VO(2 max)). Radial artery and femoral venous blood samples, leg blood flow, and biopsies of the vastus lateralis were obtained during each power output. ALK resulted in significantly (P < 0.05) higher intramuscular Lac(-) concentration ([Lac(-)]; ALK 72.8 vs. CON 65.2 mmol/kg dry wt), arterial whole blood [Lac(-)] (ALK 8.7 vs. CON 7.0 mmol/l), and leg Lac(-) efflux (ALK 10.0 vs. CON 4.2 mmol/min) at 75% VO(2 max). The increased intramuscular [Lac(-)] resulted from increased pyruvate production due to stimulation of glycogenolysis at the level of Phos a and phosphofructokinase due to allosteric regulation mediated by increased free ADP (ADP(f)), free AMP (AMP(f)), and free P(i) concentrations. PDH(a) increased with ALK at 60% VO(2 max) but was similar to CON at 75% VO(2 max). The increased PDH(a) may have resulted from alterations in the acetyl-CoA, ADP(f), pyruvate, NADH, and H(+) concentrations leading to a lower relative activity of PDH kinase, whereas the similar values at 75% VO(2 max) may have reflected maximal activation. The results demonstrate that imposed metabolic alkalosis in skeletal muscle results in acceleration of glycogenolysis at the level of Phos relative to maximal PDH activation, resulting in a mismatch between the rates of pyruvate production and oxidation resulting in an increase in Lac(-) production.

Adenine Nucleotides↗

A crosslinguistic PET study of tone perception.

In studies of pitch processing, a fundamental question is whether shared neural mechanisms at higher cortical levels are engaged for pitch perception of linguistic and nonlinguistic auditory stimuli. Positron emission tomography (PET) was used in a crosslinguistic study to compare pitch processing in native speakers of two tone languages (that is, languages in which variations in pitch patterns are used to distinguish lexical meaning), Chinese and Thai, with those of English, a nontone language. Five subjects from each language group were scanned under three active tasks (tone, pitch, and consonant) that required focused-attention, speeded-response, auditory discrimination judgments, and one passive baseline as silence. Subjects were instructed to judge pitch patterns of Thai lexical tones in the tone condition; pitch patterns of nonspeech stimuli in the pitch condition; syllable-initial consonants in the consonant condition. Analysis was carried out by paired-image subtraction. When comparing the tone to the pitch task, only the Thai group showed significant activation in the left frontal operculum. Activation of the left frontal operculum in the Thai group suggests that phonological processing of suprasegmental as well as segmental units occurs in the vicinity of Broca's area. Baseline subtractions showed significant activation in the anterior insular region for the English and Chinese groups, but not Thai, providing further support for the existence of possibly two parallel, separate pathways projecting from the temporo-parietal to the frontal language area. More generally, these differential patterns of brain activation across language groups and tasks support the view that pitch patterns are processed at higher cortical levels in a top-down manner according to their linguistic function in a particular language.

Adult↗

Perfluorocarbons and semifluorinated alkanes.

The introduction of perfluorocarbons (PFCs) and, more recently, semifluorinated alkanes (SFAs) has greatly facilitated vitreoretinal surgery. A distinction is made between the use of these substances as intraoperative tools and internal tamponade agents. This article reviews the physical and chemical properties of PFCs and SFAs and discusses the indications, results, and complications. The effectiveness of these substances as internal tamponade agents is discussed with reference to the specific gravity, contact angle, viscosity and ability to fill model eye chambers and the vitreous cavity. The evidence for the toxicity in animal and human is examined.

Alkanes↗

Hypoglycaemia from islet cell hyperplasia and nesidioblastosis in a patient with type 2 diabetes mellitus--a case report.

INTRODUCTION: We report the first case of hypoglycaemia from beta cell hyperplasia with nesidioblastosis in an Asian adult with pre-existing type 2 diabetes. CLINICAL PICTURE: A 57-year-old Chinese woman presented with hyperinsulinaemic hypoglycaemia despite discontinuation of oral hypoglycaemic agents 4 months after diagnosis of type 2 diabetes. Preoperative portal venous sampling suggested regionalisation to the neck of the pancreas. Intraoperative ultrasound and palpation of the fully mobilised pancreas were non-localising. TREATMENT: A subtotal 85% pancreatectomy was performed with success. OUTCOME: Histology showed no evidence of tumour, but revealed islet hyperplasia and nesidioblastosis. Her diabetes was subsequently well controlled on metformin therapy. CONCLUSION: Endogenous hyperinsulinism from beta cell hyperplasia with nesidioblastosis may rarely occur in type 2 diabetics. However, this remains a diagnosis of exclusion that is confirmed only on surgical pathology. In affected individuals, preoperative portal venous sampling may be falsely localising, especially if selective sampling of the smaller peri-pancreatic veins is omitted. Definite treatment involves pancreatectomy, although the extent of surgical resection is not well established.

Diabetes Mellitus, Type 2↗

DNA bending by EcoRI DNA methyltransferase accelerates base flipping but compromises specificity.

EcoRI DNA methyltransferase was previously shown to bend its cognate DNA sequence by 52 degrees and stabilize the target adenine in an extrahelical orientation. We describe the characterization of an EcoRI DNA methyltransferase mutant in which histidine 235 was selectively replaced with asparagine. Steady-state kinetic and thermodynamic parameters for the H235N mutant revealed only minor functional consequences: DNA binding affinity (KDDNA) was reduced 10-fold, and kcat was decreased 30%. However, in direct contrast to the wild type enzyme, DNA bending within the mutant enzyme-DNA complexes was not observed by scanning force microscopy. The bending-deficient mutant showed enhanced discrimination against the methylation at nontarget sequence DNA. This enhancement of enzyme discrimination was accompanied by a change in the rate-limiting catalytic step. No presteady-state burst of product formation was observed, indicating that the chemistry step (or prior event) had become rate-limiting for methylation. Direct observation of the base flipping transition showed that the lack of burst kinetics was entirely due to slower base flipping. The combined data show that DNA bending contributes to the correct assembly of the enzyme-DNA complex to accelerate base flipping and that slowing the rate of this precatalytic isomerization can enhance specificity.

Amino Acid Sequence↗

The influence of explants on the physical efficiency of tamponade agents.

BACKGROUND: The effectiveness of tamponade agents depends on the interfacial energies of the surfaces involved, the buoyancy of the tamponade agent and its volume. The ability of gas or silicone oil to tamponade retinal breaks may also depend on the shape of the vitreous cavity, and this in turn may be altered by the application of surgical explants or encircling bands. METHOD: We have constructed a model eye chamber (using surface-modified polymethylmethacrylate) to study the influence of indentations on the overall tamponade effect. RESULTS: We show that in the case of silicone oil, the presence of indentations may enhance the tamponade to specific areas of the model eye cavity, namely inferiorly and posteriorly, and may diminish the tamponade to areas immediately adjacent to the indentations. This modification of the tamponade effect is not observed when air is used. CONCLUSION: The position of explants is critical to the efficiency of tamponade agents.

Humans↗

Impact of red cell salvage on transfusion requirements during elective abdominal aortic aneurysm repair.

Elective abdominal aortic aneurysm (AAA) surgery may result in substantial blood loss. Concerns regarding the safety, availability, and acceptability of homologous blood have led to initiatives toward reducing transfusion requirements at the time of aneurysm repair. This study was designed to determine if the routine use of intraoperative red cell salvage and autotransfusion resulted in a reduction in homologous transfusion at our institution. A retrospective review of elective AAA repairs in the years 1987, 1992, and 1997 was carried out. Demographic data, operative details, blood loss, hemoglobin levels, red cell salvage and return volumes, and transfusion requirements were recorded and compared across the study years. From this study we conclude that routine use of red cell salvage and autotransfusion is an effective means for reducing transfusion requirements in elective AAA repair.

Aged↗

Systemic findings associated with central serous chorioretinopathy.

PURPOSE: To determine systemic factors associated with central serous chorioretinopathy. METHODS: In a retrospective study, 230 consecutive patients with central serous chorioretinopathy examined in a referral setting were compared with a historical gender-matched and age-matched control group of 230 patients with ocular findings who were examined in the same referral setting. RESULTS: The median age of the patients was 49.8 years, and of the control subjects, 50.0 years. The male-female ratio for both groups was 2.7:1. Patients with central serous chorioretinopathy were more likely to use psychopharmacologic medications (odds ratio = 2.6; 95% confidence interval = 1.30 to 5.19; P = .0049) and corticosteroids (odds ratio = 3.17; 95% confidence interval = 1.30 to 7.70; P = .0067) and were more likely to have hypertension (odds ratio = 2.25; 95% confidence interval = 1.39 to 3.63; P = .0008) than were the control subjects. CONCLUSIONS: This study identified psychopharmacologic medication use, corticosteroid use, and hypertension as factors associated with central serous chorioretinopathy. These findings reinforce the concept that stress and adaptations to stress play a role in this disorder. The findings of possible associations between central serous chorioretinopathy and both hypertension and corticosteroid usage suggest that these modifiable factors may influence morbidity of central serous chorioretinopathy.

Adult↗

PET imaging of cochlear-implant and normal-hearing subjects listening to speech and nonspeech.

Functional neuroimaging with positron emission tomography (PET) was used to compare the brain activation patterns of normal-hearing (NH) with postlingually deaf, cochlear-implant (CI) subjects listening to speech and nonspeech signals. The speech stimuli were derived from test batteries for assessing speech-perception performance of hearing-impaired subjects with different sensory aids. Subjects were scanned while passively listening to monaural (right ear) stimuli in five conditions: Silent Baseline, Word, Sentence, Time-reversed Sentence, and Multitalker Babble. Both groups showed bilateral activation in superior and middle temporal gyri to speech and backward speech. However, group differences were observed in the Sentence compared to Silence condition. CI subjects showed more activated foci in right temporal regions, where lateralized mechanisms for prosodic (pitch) processing have been well established; NH subjects showed a focus in the left inferior frontal gyrus (Brodmann's area 47), where semantic processing has been implicated. Multitalker Babble activated auditory temporal regions in the CI group only. Whereas NH listeners probably habituated to this multitalker babble, the CI listeners may be using a perceptual strategy that emphasizes 'coarse' coding to perceive this stimulus globally as speechlike. The group differences provide the first neuroimaging evidence suggesting that postlingually deaf CI and NH subjects may engage differing perceptual processing strategies under certain speech conditions.

Adult↗

Hereditary progressive mucinous histiocytosis.

We describe a 61-year-old woman who presented with multiple small, firm, shiny, skin-coloured papules in a symmetrical pattern on the dorsum of the hands, sides of the fingers and extensor aspect of the forearms. These had slowly increased in number over a period of 40 years, and were asymptomatic. Both laboratory results and systemic review were unremarkable. Histological examination of six papules revealed well-circumscribed but unencapsulated dermal nodules composed of epithelioid histiocytes and abundant alcian blue-positive mucin separating broad bundles of collagen. Histiocytes within the nodule stained positively with vimentin, and were focally positive for alpha1-antitrypsin and lysozyme. The interstitium was positive for tenascin. On electron microscopy, the histiocytes showed numerous circular, osmophilic myelin bodies and zebra bodies reminiscent of those seen in lysosomal storage diseases. Our patient's clinical, histological and ultrastructural features have been previously described as hereditary progressive mucinous histiocytosis, a rare familial form of eruptive histiocytoma characterized by multiple persistent papules with prominent mucinosis.

Disease Progression↗