Kazuhiko Fujiki

Improvement in Atrophic Gastritis and Intestinal Metaplasia in Patients in Whom Helicobacter pylori Was Eradicated

Few long-term studies of chronic gastritis associated with Helicobacter pylori have been published. Kuipers (1) and Valle (2) and their colleagues showed that in about one third of infected patients, nonatrophic gastritis progressed to glandular atrophy and intestinal metaplasia before final follow-up (mean duration of follow-up, 11.5 years and 32 years, respectively). Two studies of 10 patients (3) and 35 patients (4) infected with H. pylori found long-term improvement in intestinal metaplasia after H. pylori eradication. However, in one study of more than 100 patients with H. pylori infection, glandular atrophy and intestinal metaplasia did not improve during long-term follow-up (5). We evaluated histologic changes 12 to 15 months after attempted eradication of H. pylori to explore whether glandular atrophy and intestinal metaplasia improve after eradication. Methods Patients We enrolled all consecutive patients with dyspepsia and H. pylori infection who were seen at our gastroenterology clinic in Tokyo, Japan, for diagnostic upper gastrointestinal endoscopy. The proportions of patients who were self-referred, were referred from within our hospital, and were referred from other hospitals were roughly equal. Patients with possible allergy to penicillin, amoxicillin, or proton-pump inhibitors and those with previous gastrectomy were excluded. Written informed consent was obtained from participants in accordance with the Declaration of Helsinki and its later revision. The protocol was approved by the institutional review board of Tokyo Medical and Dental University, Tokyo, Japan. Study Design At entry, patients underwent upper gastrointestinal endoscopy; gastric mucosa was histologically evaluated by performing biopsy. Helicobacter pylori status was assessed by using bacteriologic culture, histologic results, the rapid urease test, and the urea breath test. Eligible patients were treated for 1 week with a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and clarithromycin with or without a mucoprotective agent (ecabet sodium, rebamipide, or sofalcone). At 1 to 3 months (short-term follow-up) and at 12 to 15 months (long-term follow-up) after eradication therapy, patients again underwent upper gastrointestinal endoscopy and gastric biopsy specimens were examined histopathologically. H. pylori Assessment At each endoscopy, three biopsy specimens each were taken from the greater curvature of the antrum and the greater curvature of the corpus of the stomach. One sample from each site was cultured, one was used for the rapid urease test, and one was used for histologic examination. Cultures on modified Skirrow agar with 10% horse blood were incubated for 5 to 7 days at 37 C in a microaerobic atmosphere. We identified H. pylori by observing colony structure and performing biochemical tests for urease, catalase, and oxidase activities. Biopsy specimens for histologic examination were stained with Giemsa stain or hematoxylineosin. After an overnight fast, a [13C]urea breath test was done with 100 mg of [13C]urea per 100 mL of distilled H2O. The results were considered negative if the ratio of 13CO2 to 12CO2 in 15 minutes increased by less than 5 parts per million. The presence of H. pylori was investigated at each endoscopic examination. The bacterium was considered to be present if results of at least two of four tests (bacteriologic culture, histologic results, rapid urease test, and urea breath test) were positive. Helicobacter pylori was considered eradicated if results were negative for all four tests at both short-term and long-term follow-up. No patient had only one positive test result. Gastritis Scores The endoscopists were blinded to the results of treatment. For each patient, two pathologists who were blinded to the results of treatment made independent histologic diagnoses by examining one biopsy specimen each from the antrum and corpus. The pathologists disagreed on the diagnosis in 99 of the 978 specimens examined (49 specimens from the antrum and 50 specimens from the corpus; the final diagnoses were chronic inflammation in 24 specimens, neutrophil activity in 39, glandular atrophy in 27, and metaplasia in 9). Consensus was reached by re-examination and discussion. Severity of chronic inflammation, neutrophil activity, glandular atrophy, and intestinal metaplasia was graded from 0 (normal) to 3 (markedly abnormal) according to the visual analogue scales of the updated Sydney System (6). Specimens stained with Giemsa were evaluated for H. pylori by another investigator. Statistical Analysis We divided patients into two groups on the basis of the success or failure of H. pylori eradication. We examined background factors and histologic findings at baseline to identify pretreatment differences between the two groups. We used the unpaired t-test for age, the chi-square test for sex ratios in the two groups, both the chi-square test and the Fisher exact test for comorbid conditions, and the Wilcoxon rank-sum test for histologic findings. For the antrum and corpus, we performed the Wilcoxon signed-rank test to compare histologic findings at baseline with those at follow-up (1 to 3 months and 12 to 15 months after treatment). To evaluate differences in changes in the histologic findings during follow-up, we performed mixed-effects ordinal logistic regression by using the computer program MIXOR (7). This method prevents problems caused by regression to the mean. We used SAS software, version 6.12 (SAS Institute, Inc., Cary, North Carolina), to perform all other analyses. A P value less than 0.05 was considered statistically significant. Results We studied 207 consecutive patients with H. pylori infection and dyspepsia. Patients underwent endoscopy before treatment and at least once after treatment, at 1 to 3 months. In addition, 163 patients agreed to undergo another endoscopy at 12 to 15 months after treatment (mean, 14 months). Thirty-three patients declined to undergo a second follow-up examination, and 11 patients were untraceable because they had moved out of the area. Helicobacter pylori was eradicated without serious side effects in 115 of the 163 patients who had long-term follow-up. The 115 patients in whom H. pylori was eradicated were similar to the 48 who remained infected in terms of mean (SD) age (54 12 years vs. 59 10 years), sex distribution (84 men and 31 women vs. 30 men and 18 women), and diagnosis (47 and 18 patients with chronic gastritis, 30 and 15 with duodenal ulcers, 25 and 15 with gastric ulcer, and 13 and 0 with gastroduodenal ulcers). The Table shows histologic findings for the gastric mucosa before treatment and again at the two follow-up points. The two groups did not differ significantly in histologic findings before treatment. In patients with successful eradication, scores for chronic inflammation and neutrophil activity at both sites were lower at both follow-up points than before treatment, and scores for glandular atrophy in the corpus and intestinal metaplasia in the antrum were lower at 12 to 15 months than before treatment. Glandular atrophy in the corpus improved in 34 (89%) of the 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of the 46 patients with metaplasia before treatment. Table. Histologic Results before Treatment To Eradicate Helicobacter pylori and at Short- and Long-Term Follow-up In patients with unsuccessful eradication of H. pylori, no significant histologic changes were observed at follow-up, except for progression of chronic inflammation. Mixed-effects ordinal logistic regression showed statistically significant differences between groups in changes at follow-up for chronic inflammation and neutrophil activity at both sites and for intestinal metaplasia in the antrum (Table, Figure). Individual histologic changes were as follows (some percentages do not total 100 because of rounding). Among patients with successful eradication of H. pylori, glandular atrophy in the antrum decreased in 29% and 27% at short- and long-term follow-up, respectively, was unchanged in 40% and 30%, and increased in 31% and 43%; in the corpus, glandular atrophy decreased in 24% and 30%, was unchanged in 70% and 64%, and increased in 6% and 6%. Intestinal metaplasia in the antrum decreased in 16% and 25% of patients of these patients, was unchanged in 78% and 71%, and increased in 5% and 4%; intestinal metaplasia in the corpus decreased in 3% and 4%, was unchanged in 88% and 91%, and increased in 10% and 5%. Among patients without eradication of H. pylori, glandular atrophy in the antrum decreased in 23% and 38%, at short- and long-term follow-up, respectively, was unchanged in 44% and 29%, and increased in 33% and 33%; glandular atrophy in the corpus decreased in 25% and 19%, was unchanged in 46% and 65%, and increased in 29% and 17%. Intestinal metaplasia in the antrum decreased in 0% and 0%, was unchanged in 98% and 96%, and increased in 2% and 4%; intestinal metaplasia in the corpus decreased in 12% and 8%, was unchanged in 81% and 83%, and increased in 6% and 8%. Figure. Predicted curves obtained by mixed-effects ordinal logistic regression models for histologic changes in the gastric mucosa in patients in whom Helicobacter pylori infection was or was not successfully eradicated . H. pylori H. pylori P Discussion Tucci and colleagues (8) reported that atrophic gastritis of the corpus of the stomach had regressed by 12 months after discontinuation of treatment in 10 of 20 patients with fundic atrophic gastritis in whom H. pylori was successfully eradicated. In contrast, Witteman and colleagues (10) found no changes at 57 weeks in glandular atrophy of the antrum and corpus of patients in whom the bacterium was eradicated. In a prospective study with a mean follow-up of 1 year (range, 6 to 18 months), van der Hulst and colleagues (5) found that the degree of atrophy did not change; however, their grading of a

Disappearance of Hyperplastic Polyps in the Stomach after Eradication of Helicobacter pylori: A Randomized, Controlled Trial

Although the malignant potential of hyperplastic gastric polyps was originally denied, a low risk for carcinomatous conversion (1.5% to 3%) is now recognized [1, 2]. Patients with gastric polyps may present with bleeding of the upper gastrointestinal tract, abdominal pain, or gastric outlet obstruction [3]. Therefore, most endoscopists agree that large gastric polyps or polyps associated with complications should be removed endoscopically or surgically [4]. In a previous investigation of the relation of Helicobacter pylori infection to various gastric polyps [5], we found that H. pylori infection was closely associated with hyperplastic polyps and that H. pylori was present in 100% of hyperplastic polyps. This relation is supported by two case reports [6, 7] indicating that clearance and eradication of H. pylori led to the disappearance of hyperplastic polyps. We also reported that 15 polyps (8 to 26 mm in diameter) in a patient with hyperplastic polyps had disappeared by 12 months after eradication of H. pylori [8]. However, these observations were made in only a few patients. We conducted a randomized, controlled trial to see whether hyperplastic polyps would disappear after eradication of H. pylori. Methods Patients We enrolled 35 patients (19 men and 16 women; age range, 29 to 75 years) with H. pylori infection and hyperplastic polyps of the stomach diagnosed by endoscopic biopsy. These patients were randomly assigned to one of two groups and sequentially numbered. In the treatment group (n = 17), patients received a proton-pump inhibitor (omeprazole or lansoprazole), amoxicillin, and either clarithromycin or ecabet sodium; in the control group [n = 18], patients had endoscopic examination but did not receive treatment. Our criteria for hyperplastic gastric polyps were 1) hyperplasia of the foveolar epithelium on histologic examination and 2) infiltration of inflammatory cells into the stroma in biopsy specimens [9]. Polyps were diagnosed by two blinded pathologists. Two patients who had hyperplastic polyps 2 mm or less in diameter and 1 patient who did not have H. pylori infection were excluded. Written, informed consent was obtained from each study participant in accordance with the Declaration of Helsinki (1964) and revisions thereof. The protocol was planned according to the guidelines of the H. pylori eradication trial approved by the committee of the Japanese Society of Gastroenterology. If polyps progressed and were accompanied by malignant transformation, the study was stopped and the polyps were removed endoscopically. After our study was completed, treatment for controls and for patients in whom the first attempt at eradication had failed was proposed in the form of endoscopic removal of polyps or eradication of H. pylori. Data entry and data analyses were done by code so that treatment assignments remained concealed. Compliance with treatment was assessed by pill count. Endoscopy and Assessment of Eradication of Helicobacter pylori Patients in the treatment group underwent endoscopy 1 to 3, 7 to 9, and 12 to 15 months after the end of treatment. On each occasion, biopsy specimens were taken from the same areas (three from the antrum and three from the body, exclusive of polyps) for culture, rapid urease testing, and histologic examination. Controls underwent endoscopy 12 to 15 months after enrollment. The H. pylori cultures were done by using a modified Skirrow agar with 10% horse blood and were incubated for 5 to 7 days at 37C in a microaerobic atmosphere. We identified H. pylori by colony morphology and biochemical tests, such as urease, catalase, and oxidase activity tests. Rapid urease testing was done with the CLO test (Delta West Pty. Ltd., Bentley, Australia), and the result was considered positive if the color changed after 24 hours. Biopsy specimens for histologic examination were immediately placed in 10% neutral buffered formalin, embedded in paraffin wax, stained with hematoxylin and eosin and with Giemsa, and evaluated for the presence of H. pylori. After patients had fasted overnight, the 13C-urea breath test was done by using 100 mg of urea per 100 mL of 13C-urea solution. The test result was considered negative if the excess delta 13CO2/sup 12 CO2 after 15 minutes was less than 5 parts per million. The presence of H. pylori was determined at each endoscopic examination and was defined by positive results on at least two of four tests: culture, urease testing, histologic examination, and urea breath testing. Eradication of H. pylori was confirmed by negative results on all four tests 1 to 3 months after the end of treatment and at each endoscopic examination. Endoscopists were blinded to treatment assignments. The size and number of polyps were measured at each endoscopic examination by using biopsy forceps (FB-25K, Olympus, Tokyo, Japan) placed near the polyp (open size, 6 mm in diameter; closed size, 2 mm in diameter), and the endoscopic film data on the disappearance and regression of polyps were reviewed independently by two blinded endoscopists. Histologic Examination, Gastrin Levels, and Titer of IgG to Helicobacter pylori Histologic diagnosis of the biopsied mucosa of the antrum and body was made by two blinded pathologists. The severity of activity, inflammation, atrophy, and metaplasia was graded on a scale from 1 to 4 and expressed by using the histologic index according to the updated Sydney System [10]: 1 = normal, 2 = mild, 3 = moderate, and 4 = marked. The serum gastrin level for each patient in both study groups was measured under fasting conditions before the start of treatment and 1, 3, and 12 months after the end of treatment by using radioimmunoassay (GASTRIN-RIA KIT II, Dinabot Co. Ltd., Tokyo, Japan [normal range, 37 to 172 pg/mL]). The titer of IgG to H. pylori was measured by using an enzyme immunoassay kit (HEL-pTEST II, AMRAD Operations Pty. Ltd., Victoria, Australia [range indicating negativity, <30 U/mL]) in serum specimens obtained before treatment and 1, 3, and 12 months after the end of treatment. Laboratory analyses were done by code so that treatment assignments remained concealed. Statistical Analysis Pretreatment clinical and laboratory data were analyzed by using the unpaired t-test (for age), the Wilcoxon rank-sum test (for number and size of polyps, histologic findings, serum gastrin levels, and titer of IgG to H. pylori), and the Fisher exact test (for sex, coexisting disease, and distribution of polyps). Post-treatment data were analyzed by using the Fisher exact test (for rates of disappearance, regression of polyps, and eradication of H. pylori) and the Wilcoxon rank-sum test (for histologic and laboratory data). P values less than 0.05 were considered statistically significant. All statistical analyses were done by using STATVIEW software (version 4.02, Japanese edition, Nankodo, Inc., Tokyo, Japan). Results The treatment and control groups were similar with respect to number of patients; age; sex; coexisting disease; number, size, and distribution of polyps; histologic findings; serum gastrin levels; and titers of IgG to H. pylori (Table 1). All patients in both groups completed the entire study protocol and had coexisting chronic atrophic gastritis. Table 1. Baseline Characteristics of the Treatment and Control Groups* During the follow-up period in the control group, no hyperplastic polyps regressed or disappeared (Table 2). Polyps enlarged or increased in number in 3 of the 18 patients. However, no polyps in the control group were accompanied by malignant transformation. Table 2. Results of Analyses of the Treatment and Control Groups In the treatment group (Table 2), H. pylori was successfully eradicated without serious side effects in 15 of 17 patients (88% [95% CI, 64% to 98%]), and polyps disappeared in 12 of 17 patients (71% [CI, 44% to 89%]). In 12 of the 15 patients (80% [CI, 52% to 95%]) in whom eradication was successful, disappearance of the polyps and histologic confirmation of a reduction of the inflammatory cell infiltration in the gastric mucosa were seen. The polyps had disappeared in these 12 patients by 3 to 15 months (average, 7.1 1.2 months) after the end of treatment. Smaller polyps tended to disappear within a few months. However, in the 2 patients in whom H. pylori was not eradicated, no polyps showed regression at 12 to 15 months after the end of treatment and no diminution of the inflammatory cell infiltration in the gastric mucosa was seen. The rates of disappearance of polyps in the treatment group were significantly higher than those in the control group (P < 0.001). In patients who received eradication therapy, a significant decrease was seen in serum gastrin levels and titers of IgG to H. pylori compared with those in patients who did not receive eradication therapy (P < 0.001 for serum gastrin levels; P < 0.002 for titers of IgG to H. pylori) (Table 2). Discussion In our study, the disappearance of hyperplastic polyps with histologic confirmation of a reduction in the inflammatory cell infiltration in the gastric mucosa was seen in 12 of the 15 patients (80%) in whom eradication of H. pylori was successful. The polyps had disappeared in the 12 patients by 3 to 15 months (average, 7.1 1.2 months) after the end of treatment. However, none of the polyps in any of the controls or in either of the patients in whom H. pylori was not eradicated showed regression. These results strongly suggest that eradication of H. pylori leads to regression and disappearance of hyperplastic gastric polyps. The patients in both study groups had high serum gastrin levels (251 pg/mL in the treatment group and 299 pg/mL in the control group) at baseline. Bonilla and associates [11] also reported that patients with hyperplastic polyps had high serum gastrin levels. Because gastrin has a trophic effect on the enterochromaffin-like cells of the gastric mucosa [12] and colonic mucosa [13], an elevated plasma gastrin level is of intere

Endoscopic and histological comparison of nonulcer dyspepsia with and without Helicobacter pylori infection evaluated by the modified Sydney system

OBJECTIVE:Our aim was to identify endoscopic features associated with Helicobacter pylori (H. pylori) infection in patients with nonulcer dyspepsia.METHODS:A total of 50 infected patients with nonulcer dyspepsia who underwent endoscopy with antral and corporal biopsies and 50 patients matched for age and sex but with nonulcer dyspepsia without H. pylori were reviewed retrospectively by three endoscopists blinded to the H. pylori status and the patients history. The endoscopic findings of gastritis, classified by a modification of the Sydney system as present or absent, were evaluated, and the histological severity was graded by the updated Sydney system.RESULTS:For endoscopic features, the odds ratio was 53.1 (95% confidence interval, 6.8–414.9) for edema, 18.8 (5.8–60.5) for erythema with reddish streaks excluded, 0.0275 (0.0002–0.477) for reddish streaks, 17.4 (0.97–313.7) for friability, 14.2 (5.1–40.0) for exudate, 17.2 (2.2–137.6) for flat erosions, 2.54 (0.81–7.94) for raised erosions, 40.1 (2.3–694.5) for rugal hypertrophy, 19.1 (2.4–151.6) for rugal atrophy, 96.2 (23.4–395.9) for a vascular pattern, 0.125 (0.010–1.06) for bleeding spots, and 21.0 (2.6–166.5) for nodularity. The histological severity of inflammation, neutrophil activity, and atrophy in the antrum and corpus and of metaplasia in the antrum was greater in the infected patients than in the noninfected patients.CONCLUSIONS:Endoscopic features associated with H. pylori were a vascular pattern, edema, rugal hypertrophy, nodularity, rugal atrophy, erythema with reddish streaks excluded, flat erosions, and exudate. These endoscopic features were associated with the histological findings of inflammation, neutrophil activity, atrophy, and metaplasia.

Changes in serum pepsinogen, gastrin, and immunoglobulin G antibody titers in Helicobacter pylori-positive gastric ulcer after eradication of infection

There are no studies of changes in immunoglobulin G (IgG) titers to Helicobacter pylori, serum pepsinogen, and gastrin in patients with H. pylori-positive gastric ulcers. We investigated the effect of therapy for H. pylori-positive gastric ulcer on IgG titers to H. pylori, serum pepsinogen I and II, and gastrin. Thirty-six patients with H. pylori-positive gastric ulcer were treated with lansorazole and antibiotics for 2 weeks. Serum pepsinogen I and II concentrations, serum gastrin, and IgG titers to H. pylori were measured before treatment and then at 4 and 12 weeks after stopping the treatment. The presence or eradication of H. pylori was determined using the rapid urease test and by histologic H. pylori staining. For 19 patients in whom H. pylori had been successfully eradicated, the pepsinogen I/II ratio increased, pepsinogen II levels decreased, and the anti-H. pylori IgG decreased compared with the results from before therapy and with those from 4 and 12 weeks after therapy. Gastrin levels decreased compared with pretreatment results and those from 4 weeks after the end of treatment. In 17 patients in whom the therapy failed to eradicate H. pylori infection, there were no sequential significant changes in the pepsinogen I/II ratio or in the levels of pepsinogen I, pepsinogen II, anti-H. pylori IgG, and gastrin. A decrease in the serum levels of the IgG antibody to H. pylori and gastrin and also an increase in the pepsinogen I/II ratio could be used as predictors for the eradication of H. pylori infection in gastric ulcer.

IL-12 and IL-18 induction and subsequent NKT activation effects of the Japanese botanical medicine Juzentaihoto.

In this study, we first measured some cytokine concentrations in the serum of patients treated with Juzentaihoto (JTT). Of the cytokines measured interleukin (IL) -18 was the most prominently up-regulated cytokine in the serum of patients under long term JTT administration. We next evaluated the effects of JTT in mice, focusing especially on natural killer T (NKT) cell induction. Mice fed JTT were compared to control group ones. After sacrifice, the liver was fixed, embedded and stained. Transmission electron microscope (TEM) observations were performed. Although the mice receiving the herbal medicine had same appearance, their livers were infiltrated with massive mononuclear cells, some of which were aggregated to form clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of IL-12 and IL-18 in the liver of JTT treated mice. To clarify what the key molecules that induce immunological restoration with JTT might be, we next examined in vitro lymphocyte cultures. Mononuclear cells isolated and prepared from healthy volunteers were cultured with and without JTT. Within 24 hours, JTT induced the IL-12 and IL-18 production and later (72 hours) induction of interferon (IFN)-gamma. Oral administration of JTT may induce the expression of IL-12 in the early stage, and IL-18 in the chronic stage, followed by NKT induction. Their activation, following immunological restoration could contribute to anti-tumor effects.

Gastrointestinal autonomic nerve tumor with giant abscess : A case report and literature review

We report a gastrointestinal autonomic nerve tumor of the stomach with a giant abscess. The patient had fever and pain and was found to have anemia and an abdominal mass. X-ray and endoscopic examination showed a gastric submucosal tumor with a fistula to the gastric lumen. Partial gastrectomy was performed and no metastasis was found. On gross examination, the excised tumor was seen to be a submucosal solid tumor with a giant abscess. Alpha streptococci and anaerobic gram-negative rods were cultured from the pus of the abscess. The tumor resembled a gastric myogenic tumor composed of spindle cells, partly showing storiform and epithelioids. Tumor cells showed positive staining for vimentin and neuron-specific enolase but were negative for desmin, alpha-smooth muscle actin, and S-100 protein. Ultrastructural examination showed remarkable interdigitation of cytoplasmic processes with neurosecretory granules between the tumor cells. This lesion was similar to previously described gastrointestinal autonomic nerve tumors. Gastrointestinal autonomic nerve tumors are a rare, distinct subtype of gastrointestinal stromal tumors; although several cases of focally necrotic tumors have been reported, there has been only one report of the tumor with an abscess, as in our case.

Evaluation of the effects of esophageal varicosclerosants on local vascular occlusion and systemic blood coagulation

The efficacy and safety of the various sclerosants available for esophageal sclerotherapy have not been adequately investigated. In the present study, we experimentally evaluated the effects on local vascular occlusion and systemic blood coagulation of five sclerosants: 5% ethanolamine oleate, 99.5% ethanol, 2% aethoxysclerol, thrombin, and n-butyl-2-cyanoacrylate. The effects were tested after injection into the auricular vein of rabbits. Prothrombin time, activated partial thromboplastin time, plasma fibrinogen level, and peripheral blood platelet count were measured before injection and 5 minutes, 1 hour, 1 day, and 7 days later. Histologic examinations were then made of the auricular vein, lungs, liver, spleen, and kidneys. In the initial period after injection of ethanol or thrombin, fibrinogen level and platelet count were significantly reduced. Except for thrombin, none of the drugs affected prothrombin time or partial thromboplastin time. Local thrombosis took place after the injection of ethanolamine oleate, ethanol, and aethoxysclerol, whereas thrombin injection did not result in local thrombosis or vascular occlusion. Cyanoacrylate produced no local thrombus formation but caused vascular occlusion. Over-dosing of thrombin and ethanol led to sudden death of animals. These findings suggest that it is necessary to assess further the safety of intravascular use of thrombin, that the other drugs seem to be usable, and that careful consideration should be given to the excess use of ethanol in clinical settings. The present animal model may be useful for evaluating various sclerosants, although findings may not be applicable to humans because of differences in vascular size.

Losartan potassium/hydrochlorothiazide (Preminent®) and hyponatremia: case series of 40 patients.

The clinical course of losartan potassium/hydrochlorothiazide (Preminent®)-induced hyponatremia has not been described. We summarized 40 patients with Preminent-induced hyponatremia. The study involved 15 (37.5%) men and 25 (62.5%) women (mean age [SD], 76.4 [8.3] years; range, 55–95). Their sodium levels before Preminent administration were 139.5 (4.9) mEq/L (range, 131–145; reference range, 135–147). The duration from the day of Preminent administration to the day with the lowest sodium level was 59.3 (64.9) days (range, 2–207; median, 24). Most patients for whom this duration was <50 days exhibited progressive symptoms, whereas most of those for whom this duration was >50 days did not exhibit progressive symptoms but exhibited symptoms after fever or appetite loss. The lowest sodium value was 114.4 (8.2) mEq/L (range, 99–133). The duration from the time of Preminent discontinuation to (1) the time of early recovery and (2) the time of final recovery was 6.8 (5.5) days (range, 1–20; median, 5) and 11.6 (7.6) days (range, 2–29; median, 7.5), respectively. Of the 40 patients, 36 (90.0%) achieved full recovery, 1 (2.5%) suffered from after-effects due to central pontine myelinolysis, 1 (2.5%) died, and 2 (5.0%) were unknown. In the analysis of other adverse effects of Preminent and the same adverse effects of other three angiotensin II receptor blocker (ARB)/thiazide combinations, hyponatremia was observed as a primary adverse effect of all ARB/thiazide combinations. However, hyperesthesia dermatitis was reported as an adverse effect of Preminent only.

Glutest Neo Super--a new handheld blood glucose meter-corrects for the effects of the hematocrit values in both hematocrit-adjusted samples and samples obtained from anemic patients.

BACKGROUND Handheld blood glucose (BG) meters are convenient tools that are widely used to measure the BG levels. However, the hematocrit (Hct) value has been identified as a confounding factor for accurate BG measurement. Some BG meters are equipped with an Hct-correcting feature, whose effectiveness has been tested previously. Nevertheless, the measurements yielded by many BG meters are confounded by the Hct values. Recently, a new BG meter equipped with an Hct-correcting feature has been developed; however, its effectiveness has not yet been confirmed. STUDY DESIGN Venous blood samples were collected from two healthy volunteers, and the Hct values in the samples were adjusted to approximately 0%, 10%, 20%, 30%, 40%, 50%, and 60%. Further, venous blood samples were collected from 10 anemic patients (Hct <40%). The whole BG (WBG) levels in the samples were measured using two devices-the new BG meter (Glutest Neo Super [Sanwa Kagaku Kenkyusho Co. Ltd., Nagoya, Japan]) and a standard BG meter (OneTouch Ultra [Life Scan Inc., Milpitas, CA]). For reference, plasma glucose (PG) levels were measured using a machine at our hospital laboratory (GA08 [A&T Co., Kanagawa, Japan]). The bias in the measurements was calculated as follows: bias = ([WBG - PG]/PG) x 100. Further, the correlation between the Hct values and the bias was assessed by performing linear regression analysis. RESULTS In both the Hct-adjusted samples and the samples obtained from anemic patients, the WBG levels measured using Glutest Neo Super were minimally affected by the Hct values, while those measured using OneTouch Ultra were affected by the Hct values to a statistically significant extent. CONCLUSIONS The Hct-correcting feature of the new BG meter Glutest Neo Super was effective. The use of this new device for BG measurements may lead to more appropriate treatment selection.