Effects of EMD in combination with bone swaging and calcium phosphate bone cement on periodontal regeneration in one-wall intrabony defects in dogs.

BACKGROUND AND OBJECTIVE: Although the application of EMD is a widely accepted periodontal-regenerative therapy, its effects on noncontained intrabony defects are unpredictable because of the lack of a space-making property. The combined use of EMD and autogenous bone grafts reportedly stimulates significant periodontal regeneration in intrabony defects. The aim of the present study was to evaluate the effects of EMD in combination with bone swaging (BS) and injectable calcium phosphate bone cement (CPC), which was placed into the spaces between the grafted swaged bone and the proximal host bone, on periodontal healing in one-wall intrabony defects in dogs. MATERIAL AND METHODS: One-wall intrabony defects (3 mm wide and 5 mm deep) were surgically created on the mesial and distal sides of the bilateral mandibular premolars in four dogs. The 16 defects were assigned to one of the following treatments: EMD only, BS only, EMD with BS (EMD + BS), or EMD with BS and CPC (EMD + BS + CPC). The animals were killed 8 wk after surgery for histologic evaluation. RESULTS: The height of newly formed bone was significantly greater in the EMD + BS + CPC group (3.73 ± 0.30 mm) than in the BS-only (2.74 ± 0.33 mm; p < 0.05) and EMD + BS (2.88 ± 0.98 mm; p < 0.05) groups. The area of newly formed bone was significantly larger in the EMD + BS + CPC group (5.68 ± 1.66 mm(2)) than in the EMD-only (3.68 ± 0.33 mm(2); p < 0.05), BS-only (3.48 ± 1.26 mm(2); p < 0.05) and EMD + BS (3.38 ± 1.37 mm(2); p < 0.05) groups. The EMD-only (4.63 ± 0.42 mm), EMD + BS (4.67 ± 0.30 mm) and EMD + BS + CPC (4.78 ± 0.54 mm) groups showed significantly greater cementum formation than did the BS-only group (3.93 ± 0.56 mm; p < 0.05). CONCLUSION: These results indicate that treatment with EMD + BS + CPC promotes favorable periodontal healing in one-wall intrabony defects in dogs.

Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease.

A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.

Ghrelin enhances gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurones in rats.

BACKGROUND: Ghrelin may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not yet been clearly defined. The present study was designed to investigate whether ghrelin accelerates gastric emptying via capsaicin-sensitive afferent neurones and directly affects the enteric neuromuscular function. METHODS: Gastric emptying of nutrient solids was assessed after intravenous administration of saline or ghrelin in conscious rats. The effects of ghrelin on gastric emptying were also examined in rats pretreated with capsaicin. Gastric emptying and intestinal transit of non-caloric liquids were evaluated using 51Cr solution. The effects of ghrelin on spontaneous contractile activities of isolated strips from stomach and jejunum were also investigated and the influence of ghrelin on motor responses to carbachol and electrical field stimulation was examined. RESULTS: Ghrelin significantly accelerated gastric emptying of both nutrient solids and non-caloric liquids in conscious rats. The intestinal transit of non-caloric liquids was also enhanced by ghrelin. Pretreatment with capsaicin prevented the ghrelin-induced acceleration of gastric emptying of nutrient solids. Ghrelin did not modulate spontaneous and carbachol-induced contractions of strips of gastric body, gastric antrum and jejunum. However, electrical field stimulation-induced contractions were significantly enhanced by ghrelin in the gastric body. CONCLUSIONS: The results suggest that the stimulatory effects of ghrelin on gastric motility are mediated by direct stimulation of the enteric neural pathway and capsaicin-sensitive afferent neurones.

Helicobacter pylori infection and the development of gastric cancer.

BACKGROUND: Although many studies have found an association between Helicobacter pylori infection and the development of gastric cancer, many aspects of this relation remain uncertain. METHODS: We prospectively studied 1526 Japanese patients who had duodenal ulcers, gastric ulcers, gastric hyperplasia, or nonulcer dyspepsia at the time of enrollment; 1246 had H. pylori infection and 280 did not. The mean follow-up was 7.8 years (range, 1.0 to 10.6). Patients underwent endoscopy with biopsy at enrollment and then between one and three years after enrollment. H. pylori infection was assessed by histologic examination, serologic testing, and rapid urease tests and was defined by a positive result on any of these tests. RESULTS: Gastric cancers developed in 36 (2.9 percent) of the infected and none of the uninfected patients. There were 23 intestinal-type and 13 diffuse-type cancers. Among the patients with H. pylori infection, those with severe gastric atrophy, corpus-predominant gastritis, and intestinal metaplasia were at significantly higher risk for gastric cancer. We detected gastric cancers in 21 (4.7 percent) of the 445 patients with nonulcer dyspepsia, 10 (3.4 percent) of the 297 with gastric ulcers, 5 (2.2 percent) of the 229 with gastric hyperplastic polyps, and none of the 275 with duodenal ulcers. CONCLUSIONS: Gastric cancer develops in persons infected with H. pylori but not in uninfected persons. Those with histologic findings of severe gastric atrophy, corpus-predominant gastritis, or intestinal metaplasia are at increased risk. Persons with H. pylori infection and nonulcer dyspepsia, gastric ulcers, or gastric hyperplastic polyps are also at risk, but those with duodenal ulcers are not.

PTEN expression is maintained in sporadic colorectal tumours.

Loss of PTEN (phosphatase and tensin homologue deleted from chromosome 10) function has been implicated in the progression of several types of cancer. Allele loss close to the PTEN locus occurs in sporadic colon cancer and germline PTEN mutations cause Cowden disease, an inherited cancer syndrome characterized by an increased incidence of gastrointestinal tract lesions that can progress to colorectal carcinoma. However, although PTEN is a good candidate for involvement in the pathogenesis of sporadic colon cancer, previous analyses have not revealed a high frequency of somatic mutations in colorectal tumours. Alternative mechanisms which could lead to a loss of PTEN expression in colon cancer have not been investigated. This study monitored PTEN mRNA and protein levels in a panel of 50 tumour tissues obtained from 35 patients with sporadic colon cancer. RT-PCR and immunohistochemistry were used to evaluate the expression of mRNA and protein, respectively, in normal, adenoma and adenocarcinoma colorectal tissues as well as in metastatic lesions. To overcome the problem of heterogeneity and normal stromal cell contamination in homogenized tissue specimens, specific cell types were isolated by microdissection prior to PCR analysis. No loss of PTEN expression was evident in any of the colon tissues examined. PTEN protein was localized exclusively in the cytoplasm of normal and tumour cells and no correlation of immunostaining intensity and tumour stage or grade was revealed. As with previous deletion and mutation analyses, the present study suggests that loss of PTEN expression is not prevalent in sporadic colon cancer.

Telepathology for the biopsy specimens from human allografted kidney: effectiveness and pitfalls.

This study was conducted to examine the validity and accuracy of telepathology for biopsy specimens from allografted kidney. The still video images of paraffin sections were transmitted via a two-way telephone by use of a digitized telephone network, ISDN. The quality of the transmitted images was sufficient for the diagnosis, especially at higher magnification. A total of 37 needle biopsy specimens from the 31 allografted kidneys were presented for consultation and diagnosed by an expert pathologist at Tottori University, until July 2000. The average number of transmitted images was 7.1 (range 3-12). Of the 37 specimens, diagnoses by telepathology agreed well with those made through direct microscopy in the 30 specimens. Insufficient or improper diagnosis was made in four specimens, in which proper and pathognomonic still images were not transmitted. Three cases were not diagnosed by telepathology because of the difficulty in making differential diagnosis. From these results, we concluded that telepathology is useful for transplantation pathology, in spite of limitations in some cases.

Changes in Helicobacter pylori-induced gastritis in the antrum and corpus during long-term acid-suppressive treatment in Japan.

BACKGROUND: Several studies have shown that acid-suppressive therapy aggravates corpus gastritis in patients with Helicobacter pylori infection, promoting the development of atrophic gastritis. AIM: To study the effects of long-term use of antisecretory agents on the H. pylori-positive gastric mucosa in Japan, a country with a high incidence of gastric cancer. METHODS: A total of 141 H. pylori-positive patients who had peptic ulcers or reflux oesophagitis were treated for 3 years with either omeprazole (20 mg/day) alone (n=7) or with omeprazole for primary therapy (8 weeks), followed by famotidine (40 mg/day) for maintenance therapy (n=134). Endoscopy was performed before, during, and after treatment. Biopsy specimens were taken from the greater curvature of the antrum and corpus and were examined histologically. RESULTS: The long-term use of famotidine after 8 weeks of treatment with omeprazole distinctly decreased H. pylori density and neutrophil infiltration in the antrum, but did not change H. pylori density in the corpus. The gastritis score increased in patients who had no, or only mild corpus gastritis before treatment (n=74), and significantly decreased in those who had moderate or severe gastritis before treatment (n=60). In four of the seven patients who received long-term treatment with omeprazole alone, neutrophil infiltration and H. pylori density decreased not only in the antrum but also in the corpus. There was no increase in intestinal metaplasia or mucosal atrophy as assessed endoscopically during follow-up. CONCLUSION: Changes in corpus gastritis in response to acid-suppressive therapy depend on the severity of gastritis before treatment. Long-term use of acid-suppressive therapy apparently does not accelerate the development of atrophy or intestinal metaplasia in Japanese patients.

Two distinct inactivation processes related to phosphorylation in cardiac L-type Ca(2+) channel currents.

We investigated the inactivation process of macroscopic cardiac L-type Ca(2+) channel currents using the whole cell patch-clamp technique with Na(+) as the current carrier. The inactivation process of the inward currents carried by Na(+) through the channel consisted of two components >0 mV. The time constant of the faster inactivating component (30.6 +/- 2.2 ms at 0 mV) decreased with depolarization, but the time constant of the slower inactivating component (489 +/- 21 ms at 0 mV) was not significantly influenced by the membrane potential. The inactivation process in the presence of isoproterenol (100 nM) consisted of a single component (538 +/- 60 ms at 0 mV). A protein kinase inhibitor, H-89, decreased the currents and attenuated the effects of isoproterenol. In the presence of cAMP (500 microM), the inactivation process consisted of a single slow component. We propose that the faster inactivating component represents a kinetic of the dephosphorylated or partially phosphorylated channel, and phosphorylation converts the kinetics into one with a different voltage dependency.

Lung cancer associated with pulmonary bulla. case report and review of literature.

A few reports have suggested the possible association between lung cancer and bullous disease. We report a surgical case of lung adenocarcinoma located in close proximity to pulmonary bullae. A 48-year-old nonsmoker, asymptomatic male was found to have a pulmonary tumor mass and giant bulla in the right lung. Thoracotomy identified a tumor arising from a firm, scarred and contracted area close to the bulla wall. Based on this report and review of other cases in the literature, we emphasize the need for physicians to be aware of the potential development of lung cancer in patients with pulmonary bulla.

[High-dose chemotherapy with autologous peripheral blood stem cell transplantation support in a patient with breast cancer metastasis to bone marrow: immunocytochemical monitoring of cancer-cell contamination].

A 32-year-old woman who 1 year earlier underwent a right mastectomy for stage II breast cancer with the histology of invasive ductal carcinoma (scirrhus type) was admitted due to recurrent, metastatic breast cancer in January 1997. She presented multiple metastatic lesions in the skin, lymph nodes, bone, lungs, liver, and spleen, and her bone marrow was replaced almost entirely by tumor cells. The patient was sequentially treated with 5 courses of cyclophosphamide (CPA) and adriamycin (ADM) (CA); 2 courses of CPA, ADM, and 5-fluorouracil; 5 caurses of docetaxel hydrate; and 1 course of CA. After recovery of the normal bone marrow by standard-dose chemotherapies, peripheral blood stem cells (PBSC) were then collected after mobilization with G-CSF. The number of breast cancer cells in bone marrow and PBSC samples was determined by immunocytochemical staining with an anti-cytokeratin monoclonal antibody. The number of tumor cells in PBSC sample was within the level for non-metastatic breast cancer. Complete remission was obtained with high-dose chemotherapy consisting of CPA and Thio-TEPA, and supported by autologous PBSC transplantation.

Primary anorectal malignant melanoma: report of a case.

Primary anorectal malignant melanoma is a fairly uncommon but highly malignant disease. This disease is sometimes mistaken for such benign conditions as either a hemorrhoid or rectal polyp. We herein describe a case of early primary malignant melanoma of the anal canal. In this case, magnetic resonance (MR) imaging was found to be useful for diagnosing the melanotic melanoma. We especially emphasize the usefulness of a fat-saturation MR image in distinguishing melanotic melanoma from other rectal tumors.

Benign asbestos pleural effusion associated with pulmonary aspergilloma.

A rare case of benign asbestos pleural effusion associated with aspergilloma is reported. A chest radiograph of a 75-year-old Japanese man who was admitted with right chest pain showed a right pleural effusion and nodular shadows in the right apex and left middle lung field. Thoracocentesis revealed an exudate with atypical mesothelial cells. An open lung biopsy showed aspergilloma in the right S2 area and no evidence of malignancy. Many reactive mesothelial cells were found in the pleura. A quantitative asbestos digestion study of the lung tissue biopsy showed high-grade asbestos exposure.

Solitary bronchioloalveolar adenoma of the lung.

A case of an unusual pulmonary neoplasia, called bronchioloalveolar adenoma of the lung, is reported. The neoplasm presented as a solitary peripheral lesion of the left lung on computed tomography. Examination of the tumor revealed a focal proliferating lesion consisting of cuboidal or peg-shaped epithelial cells with slight nuclear atypia. Immunohistochemical study with anti-carcinoembryonic antigen antibody, anti-surfactant apoprotein antibody, and anti-Clara cell antibody suggested that this neoplasia has the characteristics of a type II pneumocyte. It is likely that more of these small peripheral lesions, which have potential for evolution to carcinoma, will now be encountered due to the introduction of helical CT of the chest.

Two familial mesothelioma cases with high concentrations of soluble cytokeratin 19 fragment in pleural fluid.

We report two cases of diffuse malignant pleural mesothelioma occurring almost simultaneously in one family. Patient 1 was a 42-year-old Japanese man who had worked as an electrical engineer for 25 years. Patient 2, his mother, was 69 years old. She lived for 10 years with patient 1 after he started his work, and also worked at a shipyard herself for 6 years. The concentrations of cytokeratin subunit 19 fragment (CYFRA 21-1) in pleural fluid of the two patients were 1,500 ng/ml, and 1,200 ng/ml, respectively. Measurement of CYFRA 21-1 concentration in the pleural fluid may be a useful tool for a diagnosis of malignant mesothelioma.

The usefulness of CYFRA 21-1 in diagnosing and monitoring malignant pleural mesothelioma.

Five patients with malignant pleural mesothelioma (MPM) were studied to determine whether CYFRA 21-1 is useful for diagnosis of this disease. In pleural effusions, the median concentration of CYFRA 21-1 from 4 patients with MPM was significantly higher than for 34 patients with benign diseases. The sensitivity of serum CYFRA 21-1 for diagnosis of MPM was 40% and its concentration changed in proportion to disease activity in all cases. Immunohistochemically, anticytokeratin 19 antibody revealed strong staining in both epithelial and sarcomatous MPM tissues. Based on these results, we conclude that measurement of CYFRA 21-1 in pleural effusions and serum may be useful for diagnosing and monitoring MPM.

Fatal hepatic failure caused by miliary tuberculosis in a hemodialysis patient: case report.

A 57 year-old male dialysis patient died soon after the onset of high fever, hypoglycemia, and disturbance of consciousness. Autopsy revealed granulomatous lesions associated with caseous necrosis mainly found in the liver, despite the absence of pulmonary changes on chest radiographs performed during the patients illness. It appears that tubercle bacilli were hematogenously disseminated mainly to the liver causing miliary tuberculosis without producing typical diffuse lesions in the lungs. Since tuberculosis is a common complication in hemodialysis patients, the potential development of atypical miliary tuberculosis should always be borne in mind.

Function of the rat calcitonin receptors, C1a and C1b, expressed in Xenopus oocytes.

The function of the cloned rat calcitonin receptors, C1a and C1b, was studied in Xenopus oocytes using the two-electrode voltage clamp method. In oocytes expressing the C1a receptors and the cystic fibrosis transmembrane conductance regulator (CFTR), C1a/ CFTR, application (30 sec) of either salmon calcitonin (sCT) or human calcitonin (hCT) activated currents through CFTR. In C1b/CFTR, sCT activated the currents, whereas hCT failed to elicit a response. The sCT induced currents in C1a/CFTR were similar in size to those in C1b/CFTR. Both the activation and the deactivation of sCT-induced currents were slower in C1a/ CFTR. In oocytes expressing C1a or C1b alone, application of relatively high concentrations of sCT induced small oscillatory inward currents. Application of hCT induced small inward currents in C1a alone, but failed to activate currents in C1b alone. These results demonstrate new insights into the signal transduction of calcitonin receptors.

Spontaneous regression of malignant lymphoma of the stomach.

We report a case of complete and spontaneous regression of malignant lymphoma of the stomach. A submucosal tumor with central ulceration was detected on the greater curvature of the stomach in a 63-year-old woman. The tumor was diagnosed histopathologically as a diffuse large B-cell lymphoma (REAL classification). The tumor disappeared 18 days later without chemotherapy. Examination at that stage showed Helicobacter pylori (H. pylori), which was later treated with antibiotics. There was no evidence of recurrence of the malignant lymphoma at the last follow-up conducted at the time of preparation of this report, 13 months after the initial diagnosis. Spontaneous regression of an intermediate and high-grade non-Hodgkin's lymphoma is uncommon. We discuss the possible role of H. pylori in the regression of gastric malignant lymphomas.

Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer.

Although epidemiological studies strongly suggest an association between gastric cancer and Helicobacter pylori infection, there has been no clinical report indicating that cure of the infection prevents cancer. We conducted a nonrandomized H. pylori eradication trial in patients whose gastric cancer was removed by endoscopic resection (ER). We investigated the effect of treatment on the histopathology of the gastric mucosa, as well as on the incidence of metachronous gastric cancer during the long-term clinical and endoscopic follow-up. One hundred and thirty-two patients with early gastric cancer underwent ER and had H. pylori infection. Sixty-five (group A) were treated with omeprazole and antibiotics to eradicate the infection, and 67 (group B) were not. All patients were followed for 2 years post ER. After eradication treatment in group A, the disappearance of neutrophil infiltration in the antrum and body of the stomach was observed as was a decrease of the severity of intestinal metaplasia. Endoscopy after ER detected no new gastric cancers in these patients. After 3 years of follow-up, 6 (9%) of the 67 patients in group B had a new early-stage, intestinal-type gastric cancer endoscopically diagnosed. The above results suggest that H. pylori eradication may improve neutrophil infiltration and intestinal metaplasia in the gastric mucosa and inhibit the development of new carcinomas. This finding should be confirmed in a randomized, controlled trial.