Aplasia ras homologous member I gene and development of glial tumors.

The ARHI (aplasia Ras homologue member I, also known as DIRAS3) gene shows 60.0% sequence homology to the Ras proto-oncogene and was the first mater-nally-imprinted tumor suppressor gene identified in the Ras family. It is constitutively expressed from the paternal allele in normal breast, ovary, heart, liver, pancreas, thyroid and brain tissues, and is lost or markedly down-regulated primarily in breast, ovarian, pancreas and thyroid tumor tissues. We have investigated the expression, LOH (loss of heterozygosity) and methylation status of this gene in glial tumors and peripheral blood samples of 21 patients, and in seven normal brain tissue samples. Gene expression by real time reverse transcriptase polymerase chain reaction (RT-PCR) was found to be increased in 14 and decreased in seven of the 21 tumors. The LOH was detected by fragment analysis, using five labeled polymorphic markers specific for the 1p31 region, in two of the tumors. Methylation status of the CpG island I, II and III was evaluated using COBRA (combined bisulfite restriction analysis) and RFLP (restriction fragment length polymorphism) in 21 tumors and also a hypermethylated healthy volunteer as a positive control, revealed that only two tumors had hypermethylation in CpG island I (of which one also had LOH). These results suggest that LOH and hypermethylation may be one mechanism of silencing the ARHI gene expression and development of glial tumor development.

The effects of environmental light--dark changes on experimental mild traumatic brain injury.

OBJECTIVES: The aim of this study was to investigate the effects of environmental light-dark changes on the outcome of mild traumatic brain injury (MTBI) using an experimental rodent model. The functions of endogenous and exogenous melatonin on the outcome of injury were also investigated METHODS: Mild traumatic brain injury was experimentally induced in 56 male Sprague-Dawley rats using a weight-drop device. Animals were divided into four groups of 14 each as follows: (i) sham-operated (trauma only, normal day-night cycle), (ii) treated with melatonin (trauma+melatonin, normal day-night cycle), (iii) darkness-induced (trauma+48 h constant dark), and (iv) treated with melatonin and darkness-induced (trauma+48 h constant dark+melatonin). Melatonin (50 mg/kg) was administered, intraperitoneally, immediately after trauma. EEG recordings were taken at three time periods (pretrauma, immediately after trauma, and 48 h after trauma). Motor functions were tested pretrauma, 24 and 48 h post-trauma. Serum melatonin levels were determined pretrauma and 48 h post-trauma. Tissue samples from right frontal area were taken 48 h after trauma for light and electron microscopic examinations. CONCLUSION: Following MTBI light deprivation alone and light deprivation in combination with exogenously administered melatonin indicated significant neuroprotective effects. Although there may be other important pathways, darkness-induced elevation in endogenous melatonin secretion appears to play an important role in this neuroprotective outcome.

Primary primitive neuro-ectodermal tumor of cauda equina with intracranial seeding.

Primitive neuro-ectodermal tumor (PNET) of the cauda equina is a rare entity. 18 cases have been reported in the literature so far, including 4 cases with intracranial seeding. Moreover parenchymal involvement of brain has never been reported as a form of intracranial seeding from PNET of the cauda equina. A 31 year-old female patient, with PNET of cauda equina showing intracranial seeding 6 months after surgery, is presented in this report. To our knowledge, this is the first adult case of spinal cord PNET with parenchymal involvement of brain. The histopathological, clinical and radiological findings as well as treatment of the patient were evaluated.

Prognostic importance of transferrin receptor expression and correlation with K1-67 labelling indices in intracranial meningiomas.

Meningiomas are variously benign, atypical or anaplastic neoplasms and can be treated by surgical removal. However, recurrence can be seen even after complete surgical resection in benign meningiomas and some are histologically aggressive. As predictors of recurrence or malignant proliferation some immunohistochemical markers have been used. In this study, we postoperatively identified TfR (transferrin receptor) staining and Ki-67 proliferative index in patients with intracranial meningiomas and evaluated the correlation between these parameters and the recurrence or malignant proliferation. Immunohistochemical techniques (streptavidin-biotin complex) were used to assess the TfR expression and Ki-67 labelling index in 50 surgically removed intracranial meningiomas. Significantly high TfR expression was observed in all types of meningiomas, eight of which recurred. Four cases died because of primary intracranial pathology and one died from uncontrollable epileptic seizures. Ki-67 levels were high in the cases which showed recurrence and showed atypical features. Based on our observations and the results presented above, meningioma patients with TfR score of 3 or higher and high Ki-67 labelling index must be carefully followed up for recurrence, as well as for malignant transformation. Thus, we suggest that TfR and Ki-67 immunostains should be applied routinely in patients with meningiomas.

Geographic differences in the distribution of intestinal metaplasia in duodenal ulcer patients.

OBJECTIVE: A strong correlation exists between atrophic gastritis and the intestinal type of gastric carcinoma. Duodenal ulcer disease characteristically has an antral predominant gastritis and a lower risk for gastric cancer. The aim of this study was to investigate the extent and distribution of intestinal metaplasia in duodenal ulcer in countries differing in gastric cancer incidence. METHODS: Topographically mapped gastric biopsy specimens (median 11) were obtained from patients with duodenal ulcer in four countries (Korea, Colombia, USA, and South Africa). Sections were stained with a triple stain and evaluated for Helicobacter pylori (H. pylori), active inflammation, and intestinal metaplasia. RESULTS: One hundred and sixty-five patients with duodenal ulcer were examined (29 from Korea, 52 from Colombia, 62 from the USA, and 22 from South Africa). The percentage of biopsies with intestinal metaplasia was significantly greater in Korean patients (86%) compared with that in other countries (50%) (p = 0.0004). Intestinal metaplasia was most prevalent in the antrum lesser curve and greater curve, and the body lesser curve. Intestinal metaplasia was present in the gastric corpus of 38% of duodenal ulcer patients from Korea compared with an average of 10% elsewhere (p = 0.018). No differences were observed in the density or distribution of H. pylori infection or in the degree of active gastritis between countries. CONCLUSIONS: Although antral predominant gastritis is the prevalent pattern of gastritis in duodenal ulcer, intestinal metaplasia in the gastric corpus may be found with geographic differences. These findings suggest that duodenal ulcer and gastric cancer are not mutually exclusive diseases but are rather ends of the spectrum of H. pylori infection.

The utilization of immunohistochemical prognostic factor in endometrial adenocarcinoma: is it cost effective?

This study investigated the relation between immunohistochemical prognostic factors and clinical stage and histopathological grade in endometrial adenocarcinoma. Twenty-seven patients with a mean age of 61 (38-74), who underwent radical surgery due to endometrial adenocarcinoma in our hospital between 1983-1998, were re-evaluated. For clinical staging FIGO criteria were used. Histopathological differentiation of the tumor was graded as good (grade 1), moderate (grade 2), and poor (grade 3). Estrogen and progesterone receptors, c-erb B2, UEA 1, Ki-67, PCNA and p53 were studied as immunohistochemical prognostic factors. There were no patients in stages IA and IIIB. Among the prognostic factors, PCNA was the most significantly stained marker, followed by c-erb B2, estrogen and progesterone receptors, regardless of the clinical stage and histopathological grade of the tumor. The least positivity was achieved with Ki-67. There was no significant difference when each prognostic factor was analysed with respect to clinical stage and histopathological grade. In our study no significant relation was found between the prognostic factors and the clinical stage and histopathological differentiation of the tumor. Therefore the cost effectiveness of the utilization of these factors should be reconsidered.

Effect of Helicobacter pylori eradication on peptic ulcer disease complicated with outlet obstruction.

BACKGROUND: At present, the prevalence of Helicobacter pylori (H. pylori) in complicated peptic ulcer and the effect of H. pylori eradication on complicated peptic ulcer have not been fully established. In this study, we report the prevalence of H. pylori in peptic ulcer patients complicated with gastric outlet obstruction, effectiveness of oral eradication therapy on these patients, and their long-term follow up. PATIENTS AND METHODS: Ten consecutive patients presenting with clinically and endoscopically significant obstructed peptic ulcers were included in this study. During each endoscopy, seven gastric biopsy specimens were obtained and analyzed for H. pylori colonization. RESULTS: The antral mucosal biopsy specimens were positive for H. pylori in nine patients. H. pylori infection was eradicated and complete ulcer healing was observed in all patients. The mean follow-up period was 14 (7-24) months. One patient had duodenal perforation and underwent surgical intervention following medical treatment, despite the eradication of H. pylori. Ulcer recurrence was noted in two (22.2%) of nine patients, and in one of them the recurrent ulcer was complicated with obstruction (11. 1%). The mean time to ulcer recurrence was 17 months (range, 10-24 months). The biopsies and CLOtests were H. pylori negative at the time of ulcer or erosion recurrence in two patients. CONCLUSION: We suggest that H. pylori eradication may improve the resolution in obstructive ulcer cases with colonization.

Influence of endoscopic biopsy forceps characteristics on tissue specimens: results of a prospective randomized study.

BACKGROUND: A large variety of endoscopic biopsy forceps are commercially available. However, little is known regarding the influence of forceps characteristics such as disposability, size, shape, and presence of a needle on the adequacy of the specimens for histologic diagnosis. Our aim was to analyze in a prospective, randomized, pathologist-blinded study the performance of different biopsy forceps. METHODS: Twelve biopsy forceps were tested, 6 each at upper endoscopy and colonoscopy. Two biopsy specimens were obtained with each forceps, for a total of 12 specimens per patient. The tissue samples were examined for the following parameters: weight (mg), size (mm3), depth, crush artifact, sheering effect, and adequacy of the specimens for histologic information (0 = inadequate, 1 = suboptimal, and 2 = adequate). RESULTS: Fifty-five patients undergoing routine upper or lower gastrointestinal endoscopy were included in the study, and a total of 624 tissue samples were available for analysis. Overall, disposable forceps provided specimens of greater size and depth. At upper endoscopy, alligator-shaped forceps improved the depth of the sample as did the absence of a needle within the cup. These factors, however, had no impact on the specimens obtained at colonoscopy. When the adequacy of the specimens was assessed for histologic diagnosis, no significant difference was noted between any of the individual forceps, although collectively oval-shaped forceps were superior to alligator-shaped forceps at colonoscopy. CONCLUSIONS: The biopsy forceps currently available in the market are equally efficient in providing histologic diagnosis. The primary consideration when selecting an endoscopic biopsy forceps, therefore, should be the cost and ease of use and not any perceived advantage in performance.

Successful low-dose amoxycillin, metronidazole and omeprazole combination therapy in a population with a high frequency of metronidazole-resistant Helicobacter pylori.

AIM: Effective anti-Helicobacter pylori therapies with few side-effects are needed. We studied the effectiveness of a low-dose combination of metronidazole, amoxycillin and omeprazole for treatment of ulcer patients in Seoul, Korea. METHODS: Patients with gastric or duodenal ulcer received metronidazole (125 mg b.d.), amoxycillin (500 mg b.d.) and omeprazole (20 mg at bedtime) for 2 weeks. Endoscopic examinations were performed before treatment and at least 6 weeks after completion of antimicrobial therapy. H. pylori status was confirmed by histological examination of two gastric biopsies using the Genta stain. RESULTS: Seventy-nine patients (64 men, 15 women, mean age 46 years) with peptic ulcer were enrolled. H. pylori infection was cured in 56 (71%) 95% CI: 60-81%). The cure rate in non-smokers was significantly higher than in smokers (88% vs. 65%, P = 0.035). Twelve pre-treatment isolates were available and metronidazole resistance was noted in all; H. pylori infection was cured in 10. Thirty-six patients cured of H. pylori have been followed for 1 year (mean of 361 days) and 2 cases became reinfected (5.5%, 95% CI: 1-18%). CONCLUSIONS: The low-dose combination of metronidazole, amoxycillin and omeprazole was effective even the in face of metronidazole resistance. Recurrence of H. pylori infection is infrequent even in countries with a high prevalence of H. pylori infection.

Adherence of Helicobacter pylori to areas of incomplete intestinal metaplasia in the gastric mucosa.

BACKGROUND & AIMS: Helicobacter pylori is not usually found in areas of intestinal metaplasia. Thus, the development of intestinal metaplasia has been viewed as a mechanism by which the stomach eliminates H. pylori. The aim of this study was to evaluate the frequency of H. pylori adherence to intestinal metaplasia in different populations. METHODS: Mapped gastric biopsy specimens from 378 H. pylori-positive subjects from various geographical regions were examined. Intestinal metaplasia was typed by staining with periodic acid-Schiff/alcian blue and high-iron diamine/alcian blue. RESULTS: In 32 patients, H. pylori was found in intimate contact with intestinal metaplasia. This was documented by electron microscopy. All areas of intestinal metaplasia showing adherence contained sulfomucins and had no brush border. Posttreatment biopsy specimens from 4 patients whose infection was not cured showed persistence of H. pylori in intestinal metaplasia. CONCLUSIONS: These patients may have a strain of H. pylori with unusual adhesion characteristics, or their type of intestinal metaplasia may have biochemical properties that make it hospitable for H. pylori. The exclusive association of H. pylori adherence with incomplete intestinal metaplasia (a putative precursor of carcinoma) and its greater frequency in Koreans (a population at risk for gastric cancer) suggest that this phenomenon may play a role in the hypothetical sequence metaplasia > dysplasia > carcinoma.

Bilateral inflammatory linear verrucous epidermal nevus associated with psoriasis.

Inflammatory linear verrucous epidermal nevus is a benign hyperplasia of the epidermis. Bilateral distribution of inflammatory linear verrucous epidermal nevus is an extremely rare presentation. Although inflammatory linear verrucous epidermal nevus is generally accepted as a distinct entity, it has similar clinical and histopathologic features to psoriasis, or they occasionally may overlap. We report the case of an 8-year-old boy with bilateral inflammatory linear verrucous epidermal nevus who also had psoriasis.

Geographical pathology of Helicobacter pylori infection: is there more than one gastritis?

Helicobacter pylori is the aetiological agent of chronic gastritis and a major causative factor in duodenal and gastric peptic ulcer disease; a strong association also exists with gastric cancer and primary gastric lymphoma. The prevalence of infection in adults ranges from less than 15% in developed countries to virtually 100% in less developed areas. If H. pylori infection alone was responsible for the development of gastritis, peptic ulcer disease, gastric carcinoma and primary gastric lymphoma, one would expect the frequency of all these conditions to parallel closely the prevalence of H. pylori infection. This is clearly not the case: therefore, genetic, environmental and cultural factors must act in concert with H. pylori to induce different outcomes of the infection. This paper outlines the geographic approach to the study of disease and discusses the possible application of this methodology to the inquiry into the relationship between H. pylori, atrophic gastritis and gastric cancer. Preliminary results of a study showing great variation in the prevalence of intestinal metaplasia in duodenal ulcer patients from different geographic origin are presented and briefly discussed.