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Biomedical subjects

R K Wong

Publications and source records attributed to R K Wong.

At least 19 recordsLinked to original sources

Simultaneous intracellular recording and calcium imaging in single neurons of hippocampal slices.

Fluorescent Ca2+ indicator dyes can be introduced into cells through the same microelectrode used for intracellular voltage recording. Simultaneous measurement of cell membrane potential and intracellular Ca2+ concentration can be very helpful in interpreting the mechanisms of Ca2+ increases. This chapter describes fluorescence image acquisition using a CCD camera and a computer program that also records a synchronized membrane potential trace. The same program allows for preliminary data analysis. More elaborate analyses can be accomplished with commercial programs. We also describe quantitative evaluations of sources of error in the use of the statistic deltaF/F as an indicator of Ca2+ concentration. Especially important errors to minimize are changes in background fluorescence and inappropriate autofluorescence corrections. Some improvement of fluorescence images of cells deep within slices may be accomplished by masking. One method is described for making a mask based on the raw fluorescence image. With another method, highly detailed cell morphologies may be conveyed by using masks based on neurobiotin injections and camera lucida drawings.

Animals↗

ENT manifestations of gastroesophageal reflux.

Reflux laryngitis is a common disease and is probably only one of several laryngeal manifestations associated with GERD. The hypothesis that GER causes laryngeal symptoms and conditions remains to be definitively proved. In many patients, the cause of laryngeal symptoms may well be multifactorial, and to identify definitively those patients in which GER may be playing a role remains a challenge. Documentation of GER using 24-h pH monitoring may assist in identifying such patients. Pharyngeal pH probe monitoring, although not without limitations, may be the optimal method to evaluate such patients in terms of documenting the presence of EPR. A suggested algorithm based on the available data in evaluating and treating patients with suspected reflux laryngitis is shown in Figure 5. First, rule out other causes of hoarseness and laryngitis. An ENT consultation is appropriate for hoarseness present >4 wk. Second, empirically treat with PPIs b.i.d. for 2-3 months, as esophageal and pharyngeal pH monitoring is costly, not readily available, time consuming, and not sensitive in making the diagnosis of GERD related laryngitis. If the patient improves after 2-3 months, therapy should be stopped and the patient observed. If symptoms recur, reinstitution of the PPI at the lowest possible dose or with use of an H2RA to maintain remission should be initiated. Third, if no improvement is noted, the patient should undergo 24-h pH monitoring with an esophageal and, if possible, a pharyngeal probe if the diagnoses of GERD and EPR are still in question. In patients in whom there is a high suspicion for GERD, pH monitoring should be performed on PPI therapy to determine whether acid suppression is adequate. A pH probe should be placed in the stomach if the question to be answered is whether 1) the PPI regimen is maintaining a pH of >4, or 2) if the addition of a bedtime H2RA maintains nocturnal intragastric pH of >4 (52-56). Patients with a completely normal pH study who are on no medications should be referred back to the ENT physician for further evaluation, as other risk factors for chronic laryngitis such as voice overuse may benefit from concomitant voice therapy. If upright reflux is the predominant reflux pattern, increasing the b.i.d. PPI dose is reasonable; but if nighttime supine reflux is predominant, recent literature suggests that the addition of a bedtime H2RA will suppress nocturnal acid breakthrough. There are, however, no long-term studies with the PPI plus H2RA regimen that document persistent nocturnal acid suppression and that show clinically significant differences in patients with nocturnal acid breakthrough. Surgery should be cautiously considered for patients who are unresponsive to PPI therapy and who have documented or undocumented evidence of GERD or EPR. The body of experience concerning GERD and the extraesophageal manifestations of GERD suggests that patients who do not respond to adequate PPI acid suppression will do poorly after antireflux surgery.

Diagnosis, Differential↗

Characterization of esophageal striated muscle in patients with achalasia.

Many studies have been conducted analyzing the manometric properties of patients with achalasia, but the striated portion of the esophagus has never been analyzed and is often overlooked. We retrospectively reviewed 120 manometric tracings (20 achalasia, 100 controls) performed between 1994 and 1997 and excluded tracings from patients with chronic cough and nutcracker esophagus. The data were assessed for age, sex, symptoms, duration of symptoms, lower esophageal sphincter pressure, gastroesophageal gradient, upper esophageal sphincter pressure, smooth muscle contraction amplitude and duration, striated muscle contraction amplitude and duration, length from upper esophageal sphincter to maximal striated muscle contraction, and esophageal length. The maximum striated muscle contraction amplitude was significantly decreased in achalasia patients with a median amplitude of 45 mm Hg (range 12-95) vs 76 mm Hg (range 30-210) in the control group (P = 0.002). Although the wave forms were similar, the maximum striated muscle contraction duration and the distance from the upper esophageal sphincter in achalasia patients was not significantly different from controls. The length of the esophagus was significantly longer in achalasia patients with a median value of 25 cm (range 21-30) vs 21 cm (range 17-26) in the control group (P < 0.001). Patients with achalasia have significantly lower maximum striated muscle contraction amplitudes and longer esophagi, but the duration of the contractions and the configuration of the wave forms are not different.

Adult↗

Group I mGluR activation turns on a voltage-gated inward current in hippocampal pyramidal cells.

A unique property of the group I metabotropic glutamate receptor (mGluR)-induced depolarization in hippocampal cells is that the amplitude of the depolarization is larger when the response is elicited at more depolarized membrane potentials. Our understanding of the conductance mechanism underlying this voltage-dependent response is incomplete. Through the use of current-clamp and single-electrode voltage-clamp recordings in guinea pig hippocampal slices, we examined the group I mGluR-induced depolarization in CA3 pyramidal cells. The group I mGluR agonists (S)-3-hydroxyphenylglycine and (S)-3,5-dihydroxyphenylglycine turned on a voltage-gated inward current (I(mGluR(V))), which was pharmacologically distinct from the voltage-gated sodium and calcium currents intrinsic to the cells. I(mGluR(V)) was a slowly activating, noninactivating current with a threshold at about -75 mV. In addition to the activation of I(mGluR(V)), group I mGluR stimulation also produced a voltage-independent decrease in the K(+) conductance. Our results suggest that the depolarization induced by group I mGluR activation is generated by two ionic mechanisms-a heretofore unrecognized voltage-gated inward current (I(mGluR(V))) that is turned on by depolarization and a voltage-insensitive inward current that results from a turn-off of the K(+) conductance. The low-threshold and noninactivating properties of I(mGluR(V)) allow the current to play a significant role in setting the resting potential and firing pattern of CA3 pyramidal cells.

Animals↗

A case of isolated ACTH deficiency presenting with hypercalcaemia.

A 76-year-old man presented with a subacute history of weight loss, malaise and anorexia. Laboratory investigations revealed serially increasing hypercalcaemia, correlating with deterioration in his clinical status. He was subsequently shown to have hypocortisolaemia, which improved with the administration of intravenous steroids. Subsequent biochemical testing revealed the endocrinological defect to be one of isolated ACTH deficiency, which, unlike Addison's disease, does not classically include hypercalcaemia in its presentation.

Adrenal Cortex Diseases↗

Specialized intestinal metaplasia, dysplasia, and cancer of the esophagus and esophagogastric junction: prevalence and clinical data.

BACKGROUND & AIMS: Adenocarcinoma of the esophagus and esophagogastric junction (EGJ) is increasing, the earliest lesion being specialized intestinal metaplasia (SIM). This study determined the prevalence and demographic features of patients with SIM, dysplasia, and cancer in the esophagus and EGJ. METHODS: Two antegrade biopsy specimens were taken distal to the squamocolumnar junction (SCJ) and any tongues of pink mucosa proximal to the SCJ. Patients were categorized endoscopically and histologically as having long-segment (LSBE) or short-segment Barrett's esophagus (SSBE), EGJ-SIM, or a normal EGJ. RESULTS: Of 889 patients studied, 56 were undergoing esophagoduodenoscopy screening or surveillance and were not included in the prevalence calculation. The overall prevalence of SIM was 13.2%, with 1.6% LSBE, 6.0% SSBE, and 5.6% EGJ-SIM. Dysplasia or cancer was noted in 31% of LSBE, 10% of SSBE, and 6.4% of EGJ-SIM patients (P </= 0.043). Two cancers were associated with LSBE, 1 with SSBE, and 1 with EGJ-SIM. Patients with LSBE and SSBE were predominantly white (P </= 0.001), male (P </= 0. 009), and smokers (P </= 0.004), with LSBE patients having a longer history of heartburn (P </= 0.009). In contrast, patients with EGJ-SIM were similar in gender and ethnicity to the reference group, tended to be older (P </= 0.05), drank less alcohol (P </= 0.02), and had a higher prevalence of Helicobacter pylori infection (P </= 0.05). CONCLUSIONS: The prevalence of SSBE and EGJ-SIM is similar, but each entity is 3.5 times more prevalent than LSBE. However, the prevalence of dysplasia in LSBE is 2 times greater than in SSBE and 4 times greater than in EGJ-SIM. Demographically, EGJ-SIM patients are different from patients with Barrett's esophagus and have a higher prevalence of H. pylori infection. These data help to explain the increasing incidence of adenocarcinoma of the distal esophagus and EGJ.

Adenocarcinoma↗

The effect of oral decontamination with clindamycin palmitate on the incidence of bacteremia after esophageal dilation: a prospective trial.

BACKGROUND: Antibiotic prophylaxis to prevent bacterial endocarditis is recommended in high-risk patients undergoing esophageal dilation, a high-risk procedure. Some studies suggest that the oropharynx is the source of bacteremia. A topical antibiotic mouthwash, which reduces bacterial colonization of the oral flora, might decrease bacteremia rates and would be an attractive alternative to systemic administration of antibiotics. METHODS: Adults undergoing outpatient bougienage for a benign or malignant esophageal stricture were randomized in a clinician-blinded fashion to either pre-procedure clindamycin mouthwash or no treatment. Subjects were stratified by type of dilator used. Blood cultures were obtained immediately after the first esophageal dilation and 5 minutes after the last dilation. RESULTS: Fifty-nine patients were enrolled: 30 in the treatment arm and 29 in the no-treatment arm. There were 7 positive blood cultures: 5 in the treatment arm and 2 in the no-treatment arm. The identified organisms were Streptococcus viridans (2), Staphylococcus mucilaginous (2), Lactobacillus (2), and Actinomyces odontolyticus (1). Patients with bacteremia reported greater subjective difficulty with dysphagia (p = 0.01) irrespective of stricture diameter, procurement of biopsies, or dilator type. CONCLUSIONS: The percentage of cases with bacteremia for all dilations performed in this manner was 12% (95% CI [5.3, 23.6]), much lower than previously cited. All organisms in this study were oral commensals. There appears to be no effect of a clindamycin mouthwash on reducing bacteremia after esophageal dilation.

Aged↗

Lectin binding to human colonocytes is predictive of colonic neoplasia.

OBJECTIVE: The aim of this study was to determine whether lectin binding to exfoliated human colonocytes could be used as a noninvasive test for colorectal polyps or cancer. METHODS: Colonocytes were harvested from 31 patients (10 controls, 10 with adenomatous polyps, and 11 with cancer), incubated with a panel of fluorescent-labeled lectins, and assayed by flow cytometry. RESULTS: The lectins jacalin (JAC) and wheat germ agglutinin (WGA) were useful in predicting the presence of a colorectal neoplasm (p = 0.0018 for JAC and p = 0.0099 for WGA). For JAC, sensitivity reached 81% with a specificity of 80%, and for WGA the sensitivity and specificity were both 75%. CONCLUSIONS: Lectin binding to human colonocytes can predict the presence of malignant and premalignant lesions of the colon, and has potential as a noninvasive screening tool for colorectal neoplasms.

Adenomatous Polyps↗

A comparison of bowel preparations for flexible sigmoidoscopy: oral magnesium citrate combined with oral bisacodyl, one hypertonic phosphate enema, or two hypertonic phosphate enemas.

OBJECTIVE: Magnesium citrate with hypertonic enemas or oral bisacodyl provides superior preparation quality for sigmoidoscopy over enemas alone. We compared three magnesium citrate sigmoidoscopy preparations in a randomized, single-blind, controlled trial. METHODS: Two hundred and ninety-one adults scheduled for routine sigmoidoscopy were randomly assigned to receive one of three preparations containing oral magnesium citrate (296 cc) taken the night before the procedure in combination with the following: 1) oral bisacodyl (10 mg), given with the magnesium citrate the night before the procedure; 2) one hypertonic phosphate enema 1 h before the procedure; or 3) two hypertonic phosphate enemas, given singly at 2 and 1 h before the procedure. Endoscopists rated preparation quality, procedure duration, and depth of endoscopic insertion. Patients assessed preparation comfort and overall satisfaction. RESULTS: Preparation quality was rated as excellent or good for 80.6% in the bisacodyl group, 88.7% in the one-enema group, and 85.1% in the two-enema group (p = 0.30). Patients reported the oral bisacodyl regimen was better tolerated (p = 0.032). Although the three regimens were comparable in most side effects, the bisacodyl preparation was associated with more diarrhea (p = 0.0003). Mean procedure duration, mean insertion depth, and prevalence of diverticula and polyps were similar in all groups. Fewer than 4% of patients required repeat procedures due to poor preparation quality. CONCLUSIONS: There was no statistical difference between the quality of the three bowel preparations. Patients considered an oral bisacodyl and magnesium citrate regimen more easily tolerated, though it was associated with more diarrhea.

Administration, Oral↗

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↗