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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
PubMed2001

Group I metabotropic glutamate receptors elicit epileptiform discharges in the hippocampus through PLCbeta1 signaling.

Activation of metabotropic glutamate receptors (mGluRs) produces multiple effects in cortical neurons, resulting in the emergence of network activities including epileptiform discharges. The cellular mechanisms underlying such network responses are largely unknown. We examined the properties of group I mGluR-mediated cellular responses in CA3 neurons and attempted to determine their role in the generation of the network activities. Group I mGluR stimulation causes depolarization of hippocampal neurons. This depolarization is primarily mediated by two sets of conductance change: the opening of a voltage-dependent cationic conductance (mediating I(mGluR(V))) and the closing of a voltage-independent (background) K(+) conductance. I(mGluR(V)) was no longer elicited by group I mGluR agonists in the presence of U73122, a phospholipase C (PLC) blocker. Also, the current could not be activated in hippocampal CA3 neurons from PLCbeta1 knock-out mice. In contrast, suppression of PLC signaling did not affect the group I mGluR-mediated suppression of background K(+) conductance. Thus, the suppression of the background K(+) conductance occurred upstream to PLC activation, whereas the generation of I(mGluR(V)) occurred downstream to PLC activation. Group I mGluR agonists normally elicited rhythmic single cell and population burst responses in the CA3 neurons. In the absence of an I(mGluR(V)) response, CA3 neurons in slices prepared from PLCbeta1-/- mutant mice could no longer generate these responses. The results suggest that I(mGluR(V)) expression in CA3 hippocampal neuron is PLCbeta1-dependent and that I(mGluR(V)) plays a necessary role in the generation of rhythmic single cell bursts and synchronized epileptiform discharges in the CA3 region of the hippocampus.

Animals↗
PubMed2001

Historical perspective of achalasia.

This article provides an overview of the historic background of achalasia. It describes how achalasia was first chronicled in the 17th century. Prevalent theories of etiology from the original description to present day constructs are examined. Important individuals and their contributions to the concepts of achalasia are reviewed and various nonsurgical and surgical therapeutic techniques from antiquity to today are presented.

Dilatation↗
PubMed2001

Pneumatic balloon dilation for esophageal achalasia.

Pneumatic balloon dilation remains the medical treatment of choice for patients with achalasia. It is superior to other medical therapies including intrasphincteric botulinum toxin injection. The overall efficacy rate for long-term excellent or good result is 80 to 85%. It is extremely important that the endoscopist be quite experienced in the technique of pneumatic dilation and develop a standard protocol to minimize the complications. The technique of graded balloon dilation starting with 3.0-cm Rigiflex balloon as the initial dilator and progressing to 3.5-cm and 4.0-cm balloon in absence of response to previous balloon size offers the safest approach. Patients not responding to three serial dilations should be offered surgery, although some patients may prefer repeat dilations to surgery. The overall complication rate for Rigiflex dilation is about 3% and for Witzel dilation is about 6%. Some patients will develop GER when measured by 24-hour esophageal pH monitoring, but most patients remain asymptomatic.

Botulinum Toxins, Type A↗
PubMed2001

Risk and surveillance intervals for squamous cell carcinoma in achalasia.

This article discusses the risk of esophageal squamous cell carcinoma in patients with achalasia. A broad review of the literature is provided with incidence and prevalence data. Clinical features, pathophysiologic, diagnostic, and prognostic aspects are discussed. Information is also provided on how different treatment methods impact this disease. Finally, recommendations on surveillance intervals are made, based on an evidence-based approach.

Aftercare↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗