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Biomedical subjects

R K Wong

Publications and source records attributed to R K Wong.

At least 37 records · Page 2Linked to original sources

Reflux laryngitis: pathophysiology, diagnosis, and management.

Gastroesophageal reflux disease is felt to be associated with a variety of laryngeal conditions and symptoms of which "reflux laryngitis" is perhaps the most common. The most likely mechanism for laryngeal injury and symptoms is secondary to direct acid and pepsin contact, although studies concerning the cause and effect between gastroesophageal reflux disease and laryngeal disorders are conflicting. Likewise, the most effective method to diagnose such patients is unclear. Empiric treatment of patients with reflux laryngitis has been shown to be effective though none of the studies are controlled.

Gastroesophageal Reflux↗

Cadherin-5 redistribution at sites of TNF-alpha and IFN-gamma-induced permeability in mesenteric venules.

The response of the endothelial permeability barrier in microvascular networks of the rat mesentery to perfused immune inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was examined. TNF-alpha (12.5 U/ml) treatment did not change albumin permeability, but in combination with IFN-gamma (20 U/ml), there was a marked increase in the number of sites of extravascular albumin in postcapillary venules. Endothelial integrity was characterized by cadherin-5 immunoreactivity, which was localized to the continuous intercellular junctions of endothelium in arterioles, capillaries, and venules. Perfusion with the combined cytokines showed that the increased albumin permeability was dose dependent and correlated with the focal disorganization of cadherin-5 at intercellular junctions of venular endothelium. No correlation was found between the increase in albumin permeability and the localization of intravascular leukocytes or extravascular mast cells. These results show that the combination of TNF-alpha and IFN-gamma induces an endothelial phenotype with focal loss of cadherin-5 intercellular adhesion, which, in part, facilitates passage of blood macromolecules and cells to the interstitium.

Actins↗

Group I mGluR activation causes voltage-dependent and -independent Ca2+ rises in hippocampal pyramidal cells.

Application of the metabotropic glutamate receptor (mGluR) agonist (1S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) or the selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) depolarized both CA3 and CA1 pyramidal cells in guinea pig hippocampal slices. Simultaneous recordings of voltage and intracellular Ca2+ levels revealed that the depolarization was accompanied by a biphasic elevation of intracellular Ca2+ concentration ([Ca2+]i): a transient calcium rise followed by a delayed, sustained elevation. The transient [Ca2+]i rise was independent of the membrane potential and was blocked when caffeine was added to the perfusing solution. The sustained [Ca2+]i rise appeared when membrane depolarization reached threshold for voltage-gated Ca2+ influx and was suppressed by membrane hyperpolarization. The depolarization was associated with an increased input resistance and persisted when either the transient or sustained [Ca2+]i responses was blocked. mGluR-mediated voltage and [Ca2+]i responses were blocked by (+)-alpha-methyl-4-carboxyphenylglycine (MCPG) or (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG). These data suggest that in both CA3 and CA1 hippocampal cells, activation of group I mGluRs produced a biphasic accumulation of [Ca2+]i via two paths: a transient release from intracellular stores, and subsequently, by influx through voltage-gated Ca2+ channels. The concurrent mGluR-induced membrane depolarization was not caused by the [Ca2+]i rise.

Animals↗

Role of metabotropic glutamate receptors in epilepsy.

Considerable information is available regarding the role of ionotropic glutamate receptors in the generation of interictal spikes. Progress in the study of metabotropic glutamate receptors (mGluRs) makes clear that activation of these receptors can contribute greatly to seizure discharges and epileptogenesis. The effects of activation of the different mGluR subgroups on neuronal hypersynchrony and the initiation and propagation of seizure discharges in hippocampal slices are discussed herein. To help one understand the mechanisms that underlie these effects, information regarding the action of mGluRs on cellular and synaptic properties is summarized. The data bring to the forefront the critical role of mGluRs in epilepsy and emphasize the anticonvulsant effects of group II and III mGluR activation as opposed to the convulsant action of group 1, which elicits seizure discharges and epileptogenesis in experimental models.

Action Potentials↗

The value of screening for psychiatric disorders prior to upper endoscopy.

Gastrointestinal (GI) complaints are among the most common symptoms in primary care yet are frequently unexplained and often lead to costly diagnostic testing. We sought to determine the prevalence of psychiatric disorders in patients with unexplained GI complaints undergoing upper endoscopy, and the likelihood of endoscopic abnormalities in patients with and without psychiatric diagnoses. We prospectively evaluated 116 adult patients who were undergoing upper endoscopy to evaluate GI complaints. All subjects received a structured psychiatric interview prior to endoscopy using PRIME-MD, and endoscopists were blinded to the PRIME-MD results. Psychiatric disorders were detected in 70 (60%) patients. Overall, there were 113 diagnoses (some patients had multiple disorders) with the most common being somatoform (44%), depressive (29%), and anxiety (19%) disorders. Only 29 patients had major endoscopic abnormalities, including esophageal disease (14), peptic ulcer (9), severe gastritis (4), gastric cancer (1), and esophageal cancer (1). There was a much higher prevalence of psychiatric disorders in patients without major endoscopic abnormalities (74% vs. 21%, p < 0.0001). Psychiatric disease was strongly predictive of endoscopic findings (OR for major abnormality = 0.11 in women, and 0.40 in men), especially if somatoform disorder was present (OR = 0.15). We conclude that, with a simple questionnaire, psychiatric disorders can be diagnosed in a large proportion of patients with unexplained GI complaints who are referred for upper endoscopy. The presence of a psychiatric disorder, particularly if somatoform, makes it unlikely that endoscopy will reveal significant GI disease.

Adult↗

Esophageal manometry and ambulatory 24-hour pH monitoring in patients with short and long segment Barrett's esophagus.

OBJECTIVE: Short segment Barrett's esophagus (SSBE) is defined as the presence of specialized intestinal metaplasia (SIM) in the distal 2-3 cm of the esophagus. Although gastroesophageal reflux and heartburn is very common in these patients, the pathophysiology of the development of a short segment of SIM versus a longer segment of Barrett's epithelium is not clear. The aim of this study was to assess the extent of gastroesophageal reflux in short versus long segments of SIM. METHODS: Of 203 consecutive patients undergoing endoscopy with two biopsies performed just distal to the squamocolumnar junction, 28 patients were identified as having SSBE as evidenced by SIM on biopsy. Twenty-two SSBE patients underwent esophageal manometry and 24-h dual pH monitoring, and the results were compared with 18 long segment Barrett's esophagus (LSBE) patients and 15 patients with normal 24-h pH studies. RESULTS: SSBE and LSBE patients were significantly older than normal subjects (p < 0.0001). Also, lower esophageal sphincter pressure was significantly greater in SSBE patients compared with LSBE patients (12.3 +/- 1.6 vs 5.2 +/- 1.0 mm Hg,p < 0.0008). LSBE patients had a significantly lower distal esophageal peristaltic amplitude as compared with normals (p < 0.012). At 5 cm proximal to the LES, SSBE patients had significantly lower total 24-h pH scores, percent upright and percent supine reflux as compared with LSBE patients. Similarly, when measured at the proximal LES (0 cm), SSBE patients had significantly lower 24-h pH scores when compared with LSBE patients (p < 0.03), whereas percent upright and percent supine reflux were not significantly different. Both LSBE and SSBE patients had a greater degree of GER measured at 5 cm above and just proximal to the LES when compared with normals. CONCLUSION: As a group, SSBE patients have more competent LES sphincters and less gastroesophageal reflux at 0 and 5 cm above the LES as compared with patients with LSBE. These data indicate that the degree and length of acid exposure in the esophagus are important factors in the pathogenesis of SIM involvement of the esophagus.

Barrett Esophagus↗

Esophagogastric fistula: a complication of Crohn's disease--case report and review of the literature.

Esophagogastric fistula formation as a complication of esophageal Crohn's has been reported in only one case in the literature. In addition, only eight cases of esophageal fistulae of any type have been reported in the setting of Crohn's disease. Unlike the more often described superficial, aphthous disease of the esophagus, response of fistulae to medical therapy has been disappointing, and recurrence and progression are likely. Surgery remains the primary modality for refractory disease. The roles of salicylates, antibiotics, immunosuppressive agents, sealants, and intralesional steroid injections have not been well defined. We present a case of severe, refractory Crohn's disease with fistula formation between the esophagus and stomach, and concomitant involvement of the oropharynx, duodenum, terminal ileum, and cecum.

Adult↗

Zn2+ blocks the NMDA- and Ca2+ -triggered postexposure current ipe in hippocampal pyramidal cells.

Whole cell voltage-clamp recordings from acutely isolated hippocampal CA1 pyramidal cells from adult guinea pigs were used to evaluate divalent cations as possible blockers of the postexposure current (Ipe). Ipe is a cation current that is triggered by the rise in intracellular Ca2+ concentration that occurs after the application of a toxic level of N-methyl-D-aspartate (NMDA). Once triggered, Ipe continues to grow until death of the neuron occurs. Ipe may be a critical link between transient NMDA exposure and cell death. Ipe was blocked by micromolar concentrations of Zn2+. The Zn2+ effect had an IC50 of 64 microM and saturated at 500 microM. Prolonged Zn2+ block of Ipe revealed that the maintenance of a steady Ipe is not dependent on Ipe-mediated Ca2+ influx but that the continuous growth in Ipe is dependent on Ipe-mediated Ca2+ influx. The availability of an effective blocker of Ipe should facilitate the investigation of the intracellular activation pathway of Ipe and the role of Ipe in neuronal death.

Action Potentials↗

Requirement of protein synthesis for group I mGluR-mediated induction of epileptiform discharges.

Picrotoxin (50 microM) elicited rhythmic synchronized bursting in CA3 pyramidal cells in guinea pig hippocampal slices. Addition of the selective group I metabotropic glutamate receptor (mGluR) agonist (S)-3,5-dihydroxyphenylglycine (25 microM) elicited an increase in burst frequency. This was soon followed by a slowly progressive increase in burst duration (BD), converting the brief 250-520 ms picrotoxin-induced synchronized bursts into prolonged discharges of 1-5 s in duration. BD was significantly increased within 60 min and reached a maximum after 2-2.5 h of agonist exposure. The protein synthesis inhibitors anisomycin (15 microM) or cycloheximide (25 microM) significantly impeded the mGluR-mediated development of the prolonged bursts; 90-120 min of agonist application failed to elicit the expected burst prolongation. By contrast, the mGluR-mediated enhancement of burst frequency progressed unimpeded. Furthermore, protein synthesis inhibitors had no significant effect on the frequency or duration of fully developed mGluR-induced prolonged discharges. These results suggest that the group I mGluR-mediated prolongation of synchronized bursts has a protein synthesis-dependent mechanism.

Action Potentials↗

Heterogeneity of polarographic oxygen tension measurements in cervix cancer: an evaluation of within and between tumor variability, probe position, and track depth.

PURPOSE: To evaluate the heterogeneity of cervix cancer oxygenation as measured using the Eppendorf polarographic electrode and define the optimal number of measurements required to adequately sample a cervix cancer. METHODS AND MATERIALS: Two to 6 tracks with 20-30 measurements per track were obtained in each of the 44 patients evaluated. One hundred sixty-eight tracks and 4719 measurements formed the basis of this analysis. Median pO2 and hypoxic proportion (HP5), defined as the percentage of pO2 values <5 mmHg, were calculated for each track and for each tumor. Within-tumor (W) and between-tumor (B) variability in oxygenation was evaluated using a variance component analysis. The standard error of the measured HP5 with each additional track in each patient was analysed as a function of the total number of tracks. RESULTS: The ratio W/W + B was 0.67 and 0.76 for median pO2 and HP5, respectively, indicating that multiple measurements are needed to adequately sample a tumor. The median value of the standard error of the HP5 decreased from 7.0 to 4.0% from the first to the fifth track, respectively. It was estimated that adding the sixth track would only result in a small change (<0.3%) in the standard error. There was no significant difference in oxygen tension measurements as a function of the location of the measurements around the circumference of the cervix or the depth along the measurement tracks. CONCLUSIONS: There is significant within tumor variability in oxygen tension in cervix cancer. Five tracks with 20-30 measurements per track is optimal to sample the oxygenation status of a cervix cancer. The present data does not suggest that there is a significant difference related to the position in the tumor at which the pO2 measurements were taken.

Adult↗

Secondary activation of a cation conductance is responsible for NMDA toxicity in acutely isolated hippocampal neurons.

One of the key questions concerning glutamate toxicity is how a transient NMDA exposure can lead to a delayed death of neurons. To address this issue, we performed whole-cell recording on acutely isolated hippocampal CA1 neurons to monitor the membrane response after NMDA exposure. Transient NMDA exposure (100 microM, 10 min) induced an inward current (postexposure current; Ipe) which was associated with a Ca2+- and Na+-permeable cation conductance. Ipe continuously increased (in the absence of NMDA) until death of the neuron occurred. Application of NMDA in the absence of extracellular calcium failed to trigger Ipe and neuronal death. Postexposure suppression of Ipe protected against NMDA toxicity. These results indicate that a cation current, which is induced by an increase in intracellular calcium concentration ([Ca2+]i) and is itself partly carried by Ca2+, links the initial NMDA exposure to neuronal death.

Animals↗

Role of group I metabotropic glutamate receptors in the patterning of epileptiform activities in vitro.

In guinea pig hippocampal slices, picrotoxin elicited spontaneous epileptiform bursts 300-550 ms in duration. Additional application of (R,S)-3,5-dihydroxyphenylglycine or (S)-3-hydroxyphenylglycine, agonists specific for group I metabotropic glutamate receptors (mGluRs), or (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, a broad-spectrum mGluR agonist, converted picrotoxin-induced interictal bursts into prolonged discharges measured on the order of seconds. The prolonged discharges induced by selective group I mGluR agonist continued to be produced for hours after agonist removal. The antagonists (S)-4-carboxyphenylglycine and (+)-alpha-methyl-4-carboxyphenylglycine had no effect on the duration of picrotoxin-induced interictal bursts. However, after agonist exposure, the persistent prolonged discharges occurring in the absence of agonist were reversibly suppressed by the antagonists, suggesting that the activity is maintained via endogenous activation of group I mGluRs by synaptically released glutamate. Our results suggest that, under some conditions, activation of group I mGluRs produces long-lasting enhancement of synaptic responses, mediated at least in part by autopotentiation of the group I mGluR response itself, which may result in the production of seizure discharges and contribute to epileptogenesis.

Animals↗

A new probable increasing cause of esophageal ulceration: alendronate.

We present a case of esophageal ulcerations caused by alendronate (Fosamax), a recently marketed medication. The patient presented with a chief complaint of retrosternal pain and severe odynophagia of 5 days duration. She was taking prednisone 10 mg and azathioprine 100 mg p.o. q.d. for systemic lupus erythematosus. To prevent osteoporosis, she was started on alendronate 10 mg q.d. 2 wk before her symptoms started. Endoscopy of the upper GI tract revealed two deep, large ulcers at the gastroesophageal junction. Multiple biopsy specimens revealed necroinflammatory debris and acute esophagitis. However, no organisms were identified, and the result of her HIV test (ELISA) was negative. Alendronate was discontinued, and her symptoms resolved completely in 1 wk. Follow-up endoscopy performed 4 wk later revealed complete healing of the ulcers.

Adult↗

Analysis of gunshot residues on human tissues and clothing by X-ray microfluorescence.

The analysis of gunshot residues on human tissues and clothing in suicide, homicide, suspicious death, or attempted murder events, permits the forensic scientist to confirm the possibility of an entry wound caused by a gunshot bullet from a pistol, revolver, rifle, etc. The residues to be detected are lead (Pb), antimony (Sb), barium (Ba) usually from the primer, copper (Cu) and zinc (Zn) usually from the metal jacket bullet and iron (Fe) possibly from the barrel of the gun used. The presence or absence of these elements and their relative concentrations can help in the interpretation of the event.

Clothing↗

The depolarizing GABA response.

In some situations the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) elicits a hyperpolarizing response (H response) followed by a depolarizing response (D response) on cortical neurons. It has recently been established that the D response on hippocampal pyramidal cells is largely carried by bicarbonate ions (HCO3-). However, there is still controversy over whether the hyperpolarizing and depolarizing responses to GABA are mediated by the same receptor channel. A relatively new single receptor channel model proposes that the D response appears because chloride (Cl-) accumulates as a results of the Cl(-)-HCO3- conductance mediating the GABA response, dissipating the Cl- driving force and unmasking a net inward HCO3- current. This chloride accumulation model has gained favor because it provides an explanation for why higher concentrations of GABA are required to elicit the D response and why the D response generally follows an H response. On the other hand, there are some data that are best explained if there are two separate types of receptor channels mediating the H and D responses. This paper presents evidence for and against both the chloride accumulation hypothesis and the two different receptor channels hypothesis in the hope that investigators will recognize that this key problem concerning the generation of the D response remains unsolved.

Bicarbonates↗

Extracellular Mg2+ modulates intracellular Ca2+ in acutely isolated hippocampal CA1 pyramidal cells of the guinea-pig.

Using digital imaging microscopy and fluorescent probes, isolated hippocampal CA1 pyramidal neurons of the guinea-pig were used to examine the roles of [Mg2+]o in regulation of [Ca2+]i and [Mg2+]i. Low extracellular Mg ([Mg2+]o) (0.3 mM) significantly increased [Ca2+]i compared to 1.2 and 4.8 mM [Mg2+]o. In contrast, [Mg2+]i levels remained relatively constant, irrespective of alterations of [Mg2+]o. The sustained rise in [Ca2+]i induced by low [Mg2+]o was reduced 70% by 1 microM verapamil and 42% by 1 mM Ni2+, and completely abolished by 5 mM Ni2+. The data suggest that [Mg2+]o regulates [Ca2+]i in hippocampal neurons, probably by modulating Ca2+ entry via voltage-sensitive Ca2+ channels, which may play important roles in epileptogenesis, memory, learning and brain trauma. Furthermore, the results demonstrate that intracellular Mg2+ concentration does not follow passively the concentration of Mg2+ in the extracellular solution.

Animals↗

Selective expression of transient outward currents in different types of acutely isolated hippocampal interneurons.

1. Voltage-dependent outward currents in CA1 interneurons were studied with the use of whole cell voltage-clamp techniques. Tissue slices containing strata lacunosum-moleculare and radiatum (L-M-R regions) of the hippocampal CA1 region were prepared. Neurons were then isolated from these tissue slices with the use of an acute dissociation procedure. The morphologies of the isolated neurons were distinct from those of pyramidal cells and correlated with those of interneurons identified in the L-M-R regions after immunohistochemical stainings. 2. Total outward currents were elicited from the isolated cells by depolarization steps applied after a 300-ms hyperpolarization prepulse to 100 mV from a holding potential of 50 mV. Delayed outward currents were obtained by intercalating a 120-ms step at 55 mV between the hyperpolarizing prepulse and the depolarization. The intercalating step served to inactivate transient outward currents. Transient outward current were isolated by subtracting the delayed outward currents from the total outward currents. 3. Interneurons were subgrouped on the basis of their ability to produce transient outward current in response to the above protocol. 4. The two groups of interneurons possessed distinct morphological features. Cells producing transient outward currents had polygonal-shaped somata with thick primary processes that gave rise to smaller secondary processes at a short distance from the soma. Interneurons without activatable transient outward currents had somata that were not polygonal and they had more slender primary dendritic processes. 5. These results suggest that interneurons in the L-M-R regions can be divided into two groups on the basis of the presence or absence of voltage-dependent transient outward currents. The two groups of cells differentiated on this basis also have distinguishable morphological traits. The difference in the properties of the outward current may be a factor contributing to the variation in the firing pattern of recorded interneurons reported in previous studies.

Animals↗

Ionic basis of the postsynaptic depolarizing GABA response in hippocampal pyramidal cells.

1. Whole cell voltage-clamp recording with recording pipette solutions of differing ionic composition was used to determine the ionic basis of the depolarizing gamma-aminobutyric acid (GABA) response. In the presence of 4-aminopyridine and excitatory amino acid receptor blockers, giant GABA-mediated postsynaptic currents (GPSCs) were recorded from CA3 pyramidal neurons in hippocampal slices from adult guinea pigs. With the GABAB component blocked, the GPSC was composed of an initial outward current (GABAA component) that peaked at 115 ms followed by a late inward current (GABAD component) that peaked at 400-600 ms. 2. Reduction of the intracellular concentration of potassium ([K+]i)resulted in no significant change in the reversal potential of the GABAD component of the GPSC, indicating that it is not a nonspecific cation current. 3. The HCO3- permeability of the channel mediating the GABAD response was assessed by using recording pipette solutions containing three different concentrations of bicarbonate ([HCO3-], 19, 49, and 102 mM). The reversal potential of the GABAD response shifted in the depolarizing direction as the HCO3- equilibrium potential was shifted in the depolarizing direction, indicating that the channel mediating the GABAD response is permeable to HCO3-. The reversal potential of the GABAD response was more sensitive to changes in recording pipette [HCO3-] than the reversal potential of the GABAA response, indicating that the GABAD response is carried by HCO3- to a greater extent than the GABAA response. 4. The outward current-inward current sequence of the biphasic GPSC was reversed to an inward current-outward current sequence by using a high [Cl-]/low [HCO3-] recording pipette solution (40 mM Cl-/6 mM HCO3-), indicating that the GABAA component is more sensitive to changes in [Cl-]i, and the GABAD component is more sensitive to changes in [HCO3-]i. 5. These data indicate that the GABAD component of the GPSC is predominantly carried by HCO3-. While this result supports the recently propsed chloride accumulation model, the model in its present form cannot explain the inward current-outward current polarity sequence of the GPSC recorded with the high [Cl-]/low [HCO3-] intracellular solution. The data obtained using that solution reveal the need for a more expansive chloride accumulation/ depletion model or for a model utilizing two distinct ionotropic GABA channels with different anion permeability ratios to account for the biphasic nature of the GPSC.

Animals↗