Interobserver agreement on classifying endoscopic diagnoses of nonerosive esophagitis.

BACKGROUND AND STUDY AIMS: The majority of patients with gastroesophageal reflux disease in Japan have low-grade esophagitis, including minimal changes. A modified Los Angeles classification of esophagitis, consisting of erosive esophagitis (grades A - D) and nonerosive esophagitis (grades M and N) has been proposed and is in clinical use in Japan. However, it is unclear whether nonerosive esophagitis with only undemarcated mucosal discoloration (grade M) is clinically significant, since interobserver variations in classification have not been investigated. The aim of the present study was therefore to evaluate interobserver variance and diagnostic agreement in the diagnosis of nonerosive esophagitis (grades M and N). MATERIALS AND METHODS: A total of 84 endoscopists were enrolled to assess the grade of esophagitis in 30 patients by viewing endoscopic images of the gastroesophageal junction. The images were projected onto a screen, and all of the endoscopists reviewed them concurrently. The diagnosis was selected from the following three categories in the modified Los Angeles classification: grades N, M, or A. The endoscopists were grouped according to their experience, whether they had a board license, and whether they had received specialist training in esophagitis. The kappa coefficient of reliability was calculated. RESULTS: The kappa coefficient of reliability for all the endoscopists in the diagnosis of cases of grade M and N nonerosive esophagitis was unacceptably low at 0.22 (95 % CI, 0.21 - 0.24). Endoscopists with a board license and those who had completed a special esophagitis diagnostic course had slightly higher kappa values (0.26; 95 % CI, 0.23 - 0.30 and 0.29; 95 % CI, 0.26 - 0.32), respectively. CONCLUSIONS: Interobserver agreement on the endoscopic diagnosis of nonerosive esophagitis (grades M and N) is too low to be of clinical value.

A comparative study of intragastric acidity during post-breakfast and pre-dinner administration of low-dose proton pump inhibitors: a randomized three-way crossover study.

BACKGROUND: The absorption and bioavailability of proton pump inhibitors is influenced by food intake. Proton pump inhibitors bind to the parietal cell active proton pump, which is maximally stimulated after dinner: usually the largest meal of the day. However, it has not been fully clarified whether the efficacy of proton pump inhibitors differs between post-breakfast and pre-dinner dosing. AIM: To perform a pH-monitoring study to clarify this issue for two low-dose proton pump inhibitors. SUBJECTS AND METHODS: The subjects were 20 healthy male volunteers (seven Helicobacter pylori-positive and 13 H. pylori-negative), who were divided into two groups of 10 and administered 15 mg lansoprazole or 10 mg rabeprazole, respectively. All subjects underwent ambulatory intragastric 24-h pH- monitoring under three conditions allocated randomly: (i) without medication, (ii) seventh day of post-breakfast administration and (iii) eighth day of pre-dinner administration of each drug. RESULTS: There was no significant difference in the percentage time during which pH > or =4.0 in the 24-h period between post-breakfast and pre-dinner administration of both drugs (56.6% vs. 55.8%; P = 0.557), although intragastric acidity during administration of both drugs was significantly lower than that without medication. CONCLUSIONS: The timing of drug administration does not significantly influence the efficacy of low-dose proton pump inhibitors.

A prospective randomized comparative study on the safety and tolerability of transnasal esophagogastroduodenoscopy.

BACKGROUND AND STUDY AIM: Transnasal esophagogastroduodenoscopy (EGD) with a small-caliber endoscope is well tolerated by patients. However, the effect of this procedure on cardiopulmonary function has not been fully investigated. The aim of this prospective, randomized study was to investigate the effect of transnasal EGD in comparison with transoral EGD on cardiopulmonary function. PATIENTS AND METHODS: The study involved 450 patients referred for diagnostic EGD. Patients were randomly assigned to one of three types of unsedated EGD (150 patients per group): transnasal EGD using a small-caliber endoscope (the "XP-N" group), transoral EGD using the same small-caliber endoscope ("XP-O" group), and transoral EGD using a conventional endoscope ("XQ" group). Systolic and diastolic blood pressure, pulse rate, and arterial oxygen saturation were monitored before, and 2, 4 and 6 minutes after intubation, and just after endoscope extubation. Gagging episodes were also counted, to determine tolerance. RESULTS: It was not possible to perform transnasal EGD in 12 patients (8.0%). A small amount of epistaxis was observed in eight (5.8%) of 138 patients who were examined successfully by transnasal EGD. Systolic and diastolic blood pressure, pulse rate, rate-pressure product (pulse rate x systolic blood pressure/100), and the drop in arterial oxygen saturation in the XQ group were significantly greater than in the XP-N and XP-O groups at each time point. In the XP-N group, these parameters were significantly lower than those in the XP-O group at 2 minutes after intubation. Of the tree groups the number of gagging episodes was significantly lower in the XP-N group. CONCLUSION: Transnasal EGD is safer than transoral EGD as it is associated with fewer adverse effects on cardiopulmonary function and is better tolerated by patients.

Helicobacter pylori infection prevents the occurrence of the tolerance phenomenon of histamine H2 receptor antagonists.

BACKGROUND: The attenuated anti-secretory activity of H2 receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. However, it is not clarified whether Helicobacter pylori infection affects the occurrence of tolerance to H2RA. It is also not clarified whether the tolerance phenomenon occurs to a new H2RA, lafutidine. AIM: To investigate the occurrence of the tolerance phenomenon in subjects with and without H. pylori infection during the continuous administration of lafutidine and famotidine. SUBJECTS AND METHODS: Subjects were 20 healthy male volunteers (seven H. pylori positive and 13 H. pylori negative cases). All subjects were examined by ambulatory intragastric pH monitoring five times without medication, on the first and 15th day of the administration of 20 mg b.d. famotidine and 10 mg b.d. lafutidine in a cross-over fashion. RESULTS: The tolerance phenomenon was not observed in H. pylori-positive subjects during the 15-day-long administration of both H2RAs. In contrast, the tolerance phenomenon was observed in H. pylori negative subjects, which has been previously reported. CONCLUSIONS: This study demonstrated that H. pylori infection affects the tolerance phenomenon during continuous administration of H2RAs.

The significance of bivariate cytokeratin and DNA flow cytometry in paraffin-embedded specimens of non-small cell lung cancer.

BACKGROUND: The presence of non-tumor cells inside cancer tissue is one of the causes of errors in cell cycle analysis by DNA flow cytometry. The recent establishment of bivariate cytokeratin and DNA flow cytometry has made feasible the accurate assessment of tumor proliferative activity. METHODS: Bivariate flow cytometry and immunohistochemistry examinations of paraffin-embedded specimens were performed in 92 patients with non-small cell lung cancer (NSCLC). Determination of the S-phase fraction by flow cytometry, with cytokeratin gating (CK-gated SPF) and without gating (ungated SPF), and the expression of proliferating cell nuclear antigen by immunohistochemistry (PCNA labeling index), were used to assess cancer cell proliferation. RESULTS: Two tumors had DNA histograms with a coefficient of variation of more than 8.0% and were excluded from the flow cytometric analysis. In DNA diploid tumors (n = 25), the ungated SPFs (8.7 +/- 3.6%) showed a lower distribution than the CK-gated SPFs (14.3 +/- 4.7%) (P < 0.0001). In DNA aneuploid tumors (n = 65), there was no difference in distribution between the ungated SPFs (15.0 +/- 8.3%) and the CK-gated SPFs (15.1 +/- 7.1%) (P = 0.94). The CK-gated SPF and the PCNA labeling index of an individual tumor had a good correlation (P < 0.0001), and this agreed with the result showing that DNA diploid and aneuploid tumors had equal proliferative activity (P = 0.64 and P = 0.63, respectively). CONCLUSION: The technique using CK-gating markedly improved the SPF measurement in DNA diploid tumors. This assessment showed no difference in proliferative activity between DNA diploid and aneuploid tumors in NSCLC. Bivariate cytokeratin and DNA flow cytometry is an accurate and objective method for cancer-specific analysis, and will surely be informative in clinical oncology.

Aging effects on auditory middle latency responses.

Age-related effects on auditory middle latency responses (MLR) were studied in 51 normal subjects. The linear relationship between the amplitude of Na-Pa and Pa-Nb components and aging was observed, although there was no correlation between aging and the latencies of Na, Pa and Nb. The increases in the amplitudes of Na-Pa and Pa-Nb components might reflect the age-related change of auditory responses.

Auditory middle latency responses in patients with epilepsy.

Middle latency auditory responses (MLRs) were studied in 55 normal subjects and 49 epileptic patients. We evaluated the function of the auditory system and of the temporal lobe in epileptic patients using MLRs. (1) The patients with epilepsy had significantly prolonged Pa and Nb latencies and the significantly increased amplitude of Pa-Nb component. (2) The prolongation and the increase of MLR components in latency and amplitude were more obvious in patients with intractable epilepsy than patients without intractable epilepsy. (3) The difference between left and right sides was larger in epileptic patients than normal subjects. (4) Epileptic patients with polypharmacy had reduced amplitude of Pa-Nb component and prolonged latency of Pa component than patients with monotherapy. Antiepileptic drugs (AEDs) appeared to decrease the amplitude of Pa-Nb component. It was supposed that the enhancement of amplitude of Pa-Nb component represented the abnormality of central nerve system in epileptic patients, in part.

Limitation of detection and evaluation of coronary arterial stenosis by densitometry.

In coronary cineangiography, both X-ray absorption and light scatter in the image intensifier tend to degrade image quality, and so affect the accuracy of densitometric measurement of vessel diameter. To investigate this problem, we compared the accuracy and precision of the densitometric method and the edge detection method in the automated detection of stenosis in both vessel phantom and clinical studies. In the phantom study, the X-ray penetration was varied by altering the thickness of the model, and the change in the measured diameter obtained by each of the two methods was evaluated simultaneously. A difference of 5 mm in the thickness of the model was found to alter significantly (P < 0.01) measurement of the diameter obtained using the densitometric method, but not that obtained by the edge detection method. In the clinical part of the study, the accuracy of each method in the automated detection of coronary stenosis was evaluated. With respect to the detection of stenosis, the level of disagreement between the assessment of the 3 observers and what was detected by densitometry (22.8%) was 2.9 times higher than the disagreement between the observers' assessment and what was detected using the edge detection method (7.9%). When the background density of the coronary cineangiogram along the axis of the vessel was uneven, many vessel segments which had been evaluated as normal when edge-detection was used were evaluated as stenosed when densitometry was used. This study, then, demonstrates that the Lambert-Beer law does not apply in cases where the thickness of the subject varies in different locations along the axis of the same vessel. We therefore conclude that densitometry is not a reliable means of assessing coronary stenosis in such cases, due to veiling-glare and scatter, and recommend that it not be routinely used in the automated detection of coronary arterial stenosis.

Exteroceptive suppression of the trapezius muscle produced by mental nerve stimulation in normal subjects.

The purpose of the present study was to evaluate the similarities and differences in exteroceptive suppression produced by mental nerve stimulation between the masseter and trapezius muscles. Six normal subjects were studied using various intensities of stimulation. Although the duration and degree of exteroceptive suppression were increased with stimulus intensity in the masseter muscle, they did not correlate with stimulus intensity in the trapezius muscle. The latency and duration in the trapezius muscle were almost the same as those in the masseter muscle. The degrees in the masseter muscle were significantly larger than those in the trapezius muscle. Exteroceptive suppression of the trapezius muscle might have a similar mechanism as that of the masseter muscle, but it may be mediated by the separate interneurons. The projection from the trigeminal afferent to the trapezius motoneuron might be smaller than that to the masseter motoneuron.

Effects of cisapride on gastrointestinal motor activity and gastric emptying of disopyramide.

The effects of cisapride on the gastrointestinal contractile activity and pharmacokinetics of disopyramide were determined in beagle dogs and patients with arrhythmia. In the animal experiments, the gastric motor index was significantly decreased by i.v. administration of disopyramide in a dose-dependent fashion. The peak decrease of the motor index was observed within 5 min after i.v. injection of disopyramide; the motor index then recovered gradually to the level present prior to drug administration. I.v. administration of cisapride (0.5 mg/kg) markedly increased gastrointestinal contractile activity following the decrease induced by disopyramide pretreatment (5 mg/kg, i.v.). In the clinical studies, the gastric emptying test was performed using the acetaminophen method. A significant correlation between plasma concentrations of disopyramide and gastric emptying time has been found (p < 0.001). The combination of disopyramide (100 mg t.i.d.) and cisapride (2.5 mg t.i.d.) significantly increased gastric emptying compared with that induced by disopyramide alone. The peak plasma concentration of disopyramide in association with cisapride oral administration was significantly higher, and the apparent absorption rate constant and lag time of disopyramide were about 2-fold higher and 2-fold shorter, respectively, than for disopyramide alone. Cisapride, acting as a cholinergic agonist, may counteract the anticholinergic effect of disopyramide on gastric motility. As a factor influencing drug absorption, gastric emptying is of importance, as it determines the rate of drug delivery to the small intestine. Therefore, the oral administration of disopyramide with cisapride may be useful for patients with delayed gastric emptying.

Computer-aided interpretation of coronary cineangiograms. Accuracy of automatic detection of stenotic lesions.

To accurately diagnose stenotic lesions on coronary cineangiograms, an automatic detection method using computer image processing was developed. We evaluated its accuracy by comparing the results of computer-aided interpretation (CAI) with those obtained independently by 3 observers. Evaluation was performed on 129 segments from 27 arteries visualized on angiograms obtained in 18 patients. The detection rates of stenosis of the 3 observers by pure visual interpretation were 7.0%, 27.9%, and 17.1%, and using CAI 40.0%, 42.6%, and 47.3%. By computer recognition alone, a detection rate of 51.9% was achieved. The agreement by at least 2 observers (consensus) on the sites with lesions was 41.1% while the consensus of computer recognition regarding the sites with lesion was 40.3%. Therefore, our findings indicated that computer recognition of cineangiograms is likely to result in overdetection of lesions. However, all 3 observers detected stenotic lesions better with CAI than with pure visual interpretation. Accordingly, CAI may improve the reliability of cineangiographic diagnosis.

Purification and structural characterization of progastrin-derived peptides from a human gastrinoma.

Several peptides derived from the gastrin-predicted preprohormone sequence were isolated from a human gastrinoma by gel permeation, anion exchange, and reverse phase chromatography. The peptides were identified and characterized structurally by a combination of radioimmunoassays, mass spectral analysis, and microsequence analysis. The largest peptide, progastrin-(1-35) (cryptagastrin), extends from the putative processing site for the signal peptidase to the double basic residues adjacent to the amino terminus of gastrin 34. A shorter form of this peptide, progastrin-(6-35) (cryptagastrin-(6-35), was also isolated in smaller amounts. In addition, sulfated and nonsulfated gastrin 17 amides (progastrin-(55-71)) and the glycine-extended nonsulfated gastrin 17 (progastrin-(55-72)) were identified by radioimmunoassay, and their structures were confirmed by mass spectral analysis. Isolation of cryptagastrin indicates that the signal peptide of human preprogastrin contains 21 amino acid residues, and progastrin, therefore, contains 80 amino acids. There is minimal processing of the cryptic peptide preceding the sequence of gastrin 34. An amidated gastrin form larger than gastrin 34 could contain 71 amino acids. No evidence was obtained for processing that would produce gastrins containing more than 34 but less than 71 amino acid residues.

Exteroceptive suppression of the masseter and temporalis muscles produced by electrical stimulation of the mental nerve in patients with Parkinson's disease.

Exteroceptive suppression of the masseter and temporalis muscles, produced by electrical stimulation of the mental nerve, was studied in 23 cases of Parkinson's disease (PD) and 20 age-matched control subjects. Two components were usually observed: early (ES1) and late (ES2). ES2 was estimated in this study. The background electromyographic activity prior to the stimulation showed no difference between normal subjects and patients with PD. The latency of suppression in patients with PD was not different from that in normal subjects. The duration and the degree of suppression were lower in patients with PD when compared with the normal subjects. The reduction of exteroceptive suppression might, at least in part, play a role in the failure of motor control of the face in PD.

[Exteroceptive suppression after mental nerve stimulation in patients with chronic headache].

In 18 normal subjects and 36 patients with chronic headache (3 cluster headache, 18 maigraine and 15 muscle contraction headache), exteroceptive suppression in the temporalis, masseter and trapezius muscles was examined. In the temporalis and masseter muscles, early and late phases (ES1 and ES2) were observed. In the present study, late response (ES2) was examined. Patients with muscle contraction headache showed an obvious decrease of exteroceptive suppression in duration and degree. Patients with common migraine showed slight reduction of exteroceptive suppression in duration and amount, when compared with normal subjects. Patients with classic migraine or cluster headache elicited almost normal exteroceptive suppression. Exteroceptive suppression in the trapezius muscle consisted of one or two suppressive phase(s). Early phase was small and unstable. In the present study, late response with latency of about 45 ms was examined. In the trapezius muscle, migraine and patients with muscle contraction headache elicited the reduction of the exteroceptive suppression in degree. There might be the failure of the inhibitory interneuron mediating the pathway of exteroceptive suppression not only in patients with muscle contraction headache, but also in patients with migraine, especially in patients with common migraine.

[A case of lupus pneumonia treated by pulse therapies and plasma exchange therapy].

A case of interstitial pneumonia accompanying SLE (lupus pneumonia) was reported. Shortness of breath in this patient was aggravating very rapidly even during methyl prednisolone pulse therapy, but the patient was relieved from this symptom soon after double filtration plasma exchange was carried out. We concluded that some cases which are resistant to pulse therapy and whose prognosis is very poor might be saved by plasma exchange.

Measurement of distensibility of blood vessels using cineangiograms.

We developed a new, cineangiographic method to accurately measure the dynamic changes in the internal diameter of human arteries in vivo. Cine films were digitized at a spatial resolution of 4 microns/pixel, using a line image sensor. The vessel edges, with a Gaussian fit to a unilateral profile curve of the vessel, were determined with the aid of a computer program. We measured contrast-filled cylinder vessel models (2 to 7 mm in diameter) and evaluated precision, accuracy and linearity of the diameter measurement. A pulsatile vessel model of about 3.9 mm in internal diameter was used to examine the reliability of our method for detecting arterial wall motion. If the coefficient of variation of the vessel diameter determined cineangiographically was less than 2.2% we considered the cineangiograms sufficiently accurate to determine the internal vessel diameter and evaluate arterial distensibility.

Electromyographic responses in leg muscles after electrical stimulation in myelopathy patients with tonic seizures.

The electromyographic (EMG) responses in leg muscles after electrical stimulation of the peripheral nerves were examined in patients with myelopathy. The stimuli were delivered to the tibial nerve at the ankle joint. The EMG responses were recorded from the anterior tibial muscle at the latencies of 80-280 ms. In myelopathy patients with tonic seizures in the extremities, the EMG responses evoked both by single and repeated stimulation were frequently observed. Electrical stimulation also provoked the following tonic seizures in the legs. Stimulation of the back of the big toe or of the sural nerve, also produced the EMG responses in the anterior tibial muscle, and tonic seizure in the leg. There was no difference in the appearance of the EMG responses between patients with and without pain sensation during the seizure. A kind of flexor reflex might be related to tonic seizures in patients with myelopathy, at least in part.