Effective connectivity in temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: We hypothesized that temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS) showed differences in their limbic networks. This study aimed to evaluate the role of the thalamus in TLE patients with HS. MATERIALS AND METHODS: Twenty-nine TLE patients with HS and 30 controls were enrolled in this study. In addition, we included eight TLE patients without HS as a disease control group. Using whole-brain T1-weighted MRIs, we analyzed the volumes of the limbic structures, including the hippocampus, thalamus, and total cortex, with FreeSurfer 5.1. We also investigated the effective connectivity among these structures using SPSS Amos 21 based on these volumetric measures. Moreover, we quantified correlations between epilepsy duration and the volumes of these structures. RESULTS: There was a statistically significant effective connectivity from the hippocampus to the thalamus in TLE patients with HS. Moreover, the volumes of the left and right thalamus were negatively correlated with epilepsy duration (r=-.42, P=.0315 and r=-.52, P=.0062, respectively). However, neither TLE patients without HS nor normal controls had a significant effective connectivity from the hippocampus to the thalamus. CONCLUSIONS: The limbic networks of TLE patients with and without HS could be different, and the thalamus might play a critical role in TLE patients with HS.

Impact of guideline adherence on patient outcomes in early-stage epithelial ovarian cancer.

AIM: The aim of this study was to evaluate the effects of adherence to National Comprehensive Cancer Network (NCCN) guidelines on survival outcomes in patients with early-stage epithelial ovarian cancer. METHODS: Our institutional cancer registry data on 266 patients with Stage I epithelial ovarian cancer was reviewed retrospectively and compliance with treatment guidelines for surgery and adjuvant treatment was determined. Patients were categorized according to adherence or non-adherence. The primary endpoints were recurrence-free survival and disease-specific survival. Hazard ratios (HRs) for survival were estimated with a Cox proportional hazards model. RESULTS: Of the 266 patients, 71 (26.7%) underwent adequate surgical staging in accordance with the guidelines. The guidelines for adjuvant chemotherapy were followed adequately in all 71 patients that were adherent to surgical staging and in 163 of the 195 patients with non-adherence to surgical staging (83.6%). Multivariate analysis, adjusted for prognostic factors, identified higher recurrence-free survival (HR, 0.36; 95% CI, 0.15-0.88) and disease-specific survival (HR, 0.42; 95% CI, 0.16-1.12) among patients whose treatment adhered to both surgical and chemotherapy guidelines, although disease-specific survival was not statistically significant. When excluding clear cell histology from the cohort, the guideline-adherent group had significantly better disease-specific survival than the non-adherent group (HR, 0.13; 95% CI, 0.02-0.94). CONCLUSION: The results of this study suggest that adherence to NCCN guidelines may improve survival outcomes in patients with early-stage epithelial ovarian cancer, particularly in cases other than clear cell histology.

Differences in omega-3 and fatty acid profiles between patients with endometriosis and those with a functional ovarian cyst.

Endometriosis is a chronic inflammatory gynaecological disease. Problems associated with endometriosis include dysmenorrhoea, dyspareunia and infertility. We evaluated the omega-3 and fatty acid profiles in erythrocytes and tissues in patients with endometriosis (n = 10) or a functional ovarian cyst (n = 12), using a food frequency questionnaire that included questions about 117 food items typical of Korean meals. Erythrocyte levels of 20:5n3 and 22:6n3, the omega-3 index, and n-3 PUFA were significantly higher, and the n-6:n-3 ratio was significantly lower in the endometriosis group than in the functional ovarian cyst group. The functional ovarian cyst group consumed significantly more fruit than the group with endometriosis.

A multicenter, randomized, controlled trial testing the effects of acupuncture on allergic rhinitis.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of acupuncture in the treatment for allergic rhinitis. METHODS: This study was a multicenter, randomized, parallel-controlled study. Participants were randomized to either the active acupuncture, sham acupuncture, or waitlist groups. The active and sham acupuncture groups received acupuncture treatment three times per week for 4 weeks. In the sham group, minimal acupuncture at nonacupuncture points was used. The waitlist group did not receive any acupuncture treatment. RESULTS: Of the 238 participants, 97, 94, and 47 individuals were assigned to the active acupuncture, sham acupuncture, and waitlist group, respectively. After the treatment, the difference in the total nasal symptom score (TNSS) was significantly reduced in the active acupuncture group compared with the sham acupuncture (difference: -1.03, 95% confidence interval [CI]: -1.96, -0.09, P = 0.03) and waitlist (difference: -2.49, 95% CI: -3.68, -1.29, P < 0.0001). The active acupuncture group exhibited a significant change in the total non-nasal symptom score (TNNSS) compared with the waitlist (difference: -0.78, 95% CI: -1.22, -0.34, P = 0.0002), but not the sham acupuncture group (difference; 0.15, 95% CI: -0.21, 0.5, P = 0.56). Both active and sham acupuncture treatments resulted in significant improvements in TNSS and TNNSS compared to baseline. CONCLUSION: Active acupuncture showed a significantly greater effect on symptoms of allergic rhinitis than either sham acupuncture or no active treatment. The symptoms of allergic rhinitis decreased significantly after treatment in the both acupuncture and sham acupuncture groups. Acupuncture appears to be an effective and safe treatment for allergic rhinitis.

Pre-operative chemo-radiotherapy improves the sphincter preservation rate in patients with rectal cancer located within 3 cm of the anal verge.

AIMS: To evaluate whether pre-operative chemo-radiotherapy (CRT) improves the sphincter preservation rate for distal rectal cancers within 3 cm of the anal verge. METHODS: Between January 2001 and December 2004, 49 patients underwent surgery with or without pre-operative CRT for primary rectal adenocarcinoma within 3 cm of the anal verge. Clinical data were retrospectively reviewed, including stage workups, surgical records and pathology records to determine sphincter preservation rate and the factors influencing sphincter preservation. RESULTS: Of 49 patients with rectal tumours within 3 cm of the anal verge, 31 underwent pre-operative CRT followed by surgery (CRT group), and 18 underwent surgery alone (non-CRT group). Sphincter preservation was possible in 11 of 31 CRT patients, and only one of 18 non-CRT patients (p=0.036). The factors most influencing sphincter preservation were reduction in tumour size (p=0.005) and downstaging (p=0.001) following pre-operative CRT. CONCLUSION: We could observe that sphincter preservation was improved in CRT group with statistical significance when compared to non-CRT group in our study patients with rectal cancer within 3 cm of the anal verge.

Modular domain structure of Arabidopsis COP1. Reconstitution of activity by fragment complementation and mutational analysis of a nuclear localization signal in planta.

The Arabidopsis COP1 protein functions as a developmental regulator, in part by repressing photomorphogenesis in darkness. Using complementation of a cop1 loss-of-function allele with transgenes expressing fusions of cop1 mutant proteins and beta-glucuronidase, it was confirmed that COP1 consists of two modules, an amino terminal module conferring a basal function during development and a carboxyl terminal module conferring repression of photomorphogenesis. The amino-terminal zinc-binding domain of COP1 was indispensable for COP1 function. In contrast, the debilitating effects of site-directed mutations in the single nuclear localization signal of COP1 were partially compensated by high-level transgene expression. The carboxyl-terminal module of COP1, though unable to substantially ameliorate a cop1 loss-of-function allele on its own, was sufficient for conferring a light-quality-dependent hyperetiolation phenotype in the presence of wild-type COP1. Moreover, partial COP1 activity could be reconstituted in vivo from two non-covalently linked, complementary polypeptides that represent the two functional modules of COP1. Evidence is presented for efficient association of the two sub-fragments of the split COP1 protein in Arabidopsis and in a yeast two-hybrid assay.

Adaptive response is differently induced depending on the sensitivity to radiation-induced cell death in mouse epidermal cells.

We investigated the relationship between induction of radio-adaptive response and cell death in mouse normal and neoplastic epidermal cells. Mouse normal primary keratinocytes (PK), cancer-prone cells [v-rasHa-transfected mouse keratinocytes (ras-PK), and line 308 cells (mouse skin papilloma cells which have activated rasHa gene with A-to-T transversion at codon 61) were primed with a low dose of gamma-rays (0.01 Gy), and were challenged with a high dose (4 Gy) after a 4 or 7 h interval. The induction of cell death in PK was 2-10 times higher and was also more rapid in PK than in ras-PK or 308 cells. Low-dose pretreatment with a 4 h interval decreased cell death, and this adaptive response was prominent in PK, whereas it was less obvious in the cases of ras-PK and 308 cells. The response of each protein kinase C (PKC) isozymes to high-dose radiation, especially PKCalpha, PKCdelta, PKCepsilon, and PKCeta, were different between the normal and ras oncogene-activated neoplastic keratinocytes; translocation of these isozymes to membrane occurred more rapidly in normal than in neoplastic cells. Furthermore, low-dose pretreatment did not induce the translocation of PKCdelta in PK significantly more than in ras-PK and 308. Thus, the difference in the induction of radio-adaptive responses between mouse normal and neoplastic epidermal cells reflects difference in the rapidity of cell death, and responsiveness of PKC may affect this adaptive response.

alpha-Glucosidase inhibitors from Commelina communis.

A methanolic extract of Commelina communis showed potent inhibitory activity against alpha-glucosidase. One pyrrolidine alkaloid, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP, 1) and four piperidine alkaloids, 1-deoxymannojirimycin (2), 1-deoxynojirimycin (3), alpha-homonojirimycin (4) and 7-O-beta-D-glucopyranosyl alpha-homonojirimycin (5) were isolated by bioassay-directed fractionation and separation. These compounds have been identified for the first time from Commelina communis, supporting the pharmacological basis of this plant that has been used as a traditional herbal medicine for the treatment of diabetes.

Burkitt's lymphoma presenting as ileocaecal intussusception in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) are reported to have an increased risk of malignancy, especially lymphoproliferative disorders. We decribe the occurrence of ileocaecal intussusception secondary to Burkitt's lymphoma in a patient with SLE. A 23-year-old woman, who had been diagnosed with SLE 2 years ago, developed intermittent abdominal pain with a palpable mass. Computed tomography and a double-contrast barium enema showed a lobulated mass with intussusception at the ileocaecal junction. Right hemicolectomy and splenectomy was performed after histopathological examinations on colonoscopic biopsy revealed Burkitt's lymphoma. Fourteen months after chemotherapy, there is no evidence of recurrence of the Burkitt's lymphoma. When a patient with SLE has abdominal complaints, besides serositis, lupus enteritis such as peptic ulcer disease, mesenteric vasculitis with or without complications and pancreatitis, we have to consider intussusception secondary to gastrointestinal lymphoma as one of the differential diagnoses. Therefore, we should thoroughly investigate patients with SLE presenting with abdominal pain and not simply consider it afeature of lupus enteritis until other causes have been ruled out.

Panax ginseng prevents apoptosis in hair follicles and accelerates recovery of hair medullary cells in irradiated mice.

We studied the effect of the water fraction of Panax ginseng, one of traditional oriental medicine herbs on apoptosis and the formation of medullary cell in the hair follicles of irradiated mice. The hair follicle or its differentiated product, the hair, which represents a linear historical record of follicular proliferative activity, could provide a biological indicator of the effect of radioprotective drugs. Adult N:GP(s) mice with hair follicles synchronously in the middle of the hair growth cycle received whole-body doses of gamma-radiation. The hair follicles were analysed either 12 hours after irradiation with 2 Gy in the experiment on the apoptosis, or 3 days after irradiation with 3 Gy in the experiment on the forming medulla. The number of medullary cells per unit length (100 microns) were measured by H and E staining. Apoptosis was detected by a nonisotopic in situ DNA end-labeling (ISEL) technique and H and E stain applied to the serial histologic sections. Ginseng administration before irradiation resulted in a suppression of apoptosis, as shown by a reduced number of cells stained with ISEL for fragmented DNA, both i.p. (0.3 mg/head, p < 0.05) and p.o. (2 mg/ml of drinking water, p < 0.05) treatment. In addition, ginseng treatment was associated with an increase in the number of medullary cell per unit length as compared with the vehicle treated mice (p < 0.001, i.p.; p < 0.05, p.o.). These results indicate that the water fraction of ginseng can exert a potent effect on the recovery of the hair follicles by its combined effects on proliferation and apoptosis of the cells in the hair follicle.

Appendicitis: usefulness of color Doppler US.

PURPOSE: To assess whether color Doppler ultrasonography (US) can help diagnose early acute appendicitis in appendices of equivocal size at gray-scale US. MATERIALS AND METHODS: In a retrospective study, color Doppler US findings were evaluated in 20 individuals with proved normal appendix at barium enema examination and in 50 patients in whom pathologic findings confirmed acute appendicitis. In a prospective study, the diagnostic value of hyperemia in the wall of the appendix in differentiating a normal from an inflamed appendix was evaluated in 26 patients with appendices of equivocal size (5-7 mm in maximal outer diameter) at grayscale US. RESULTS: In the retrospective study, 44 of the 50 patients had hyperemia at color Doppler US. The remaining six patients had no hyperemia, and pathologic findings confirmed gangrenous appendices. The 20 patients with proved normal appendix at barium enema examination had no detectable blood flow in the wall. In the prospective study, 10 of 26 patients had hyperemia at color Doppler US, and pathologic findings confirmed early acute appendicitis. Results of barium enema examination (n = 12) or clinical follow-up (n = 4) confirmed no appendicitis in the remaining 16 patients. CONCLUSION: Hyperemia in the wall of the appendix at color Doppler US is a sensitive indicator for inflammation. A simple additional color Doppler US examination may be helpful in the diagnosis of early acute appendicitis when an appendix is well depicted and is equivocal in size at gray-scale US.

Protective effect of ginseng on radiation-induced DNA double strand breaks and repair in murine lymphocytes.

We have examined the effects of ginseng on the induction and repair of gamma-ray-induced DNA double strand breaks (dsb) using neutral filter elution technique at pH 9.6 in cultured murine spleen lymphocytes. Ginseng water extract 500 micrograms/ml was added to the culture medium either for 48 hours prior to irradiation. Ginseng extract showed protective effect against the formation of dsb when it was treated for 48 hours before 100 Gy gamma-ray-irradiation. While repair was almost completed until 220.2 minutes after irradiation, DNA repair of irradiated cells in the presence of ginseng extract was did not return to the corresponding control levels even after 621.8 minutes. From these data, it could be calculated that ginseng reduced the relative strand scission factor (RSSF) by about 2. Therefore, it could be concluded that ginseng has radioprotective effect against gamma-ray induced DNA dsb and repair in cultured mouse lymphocytes.

Protective effects of potato extracts and 16,16-dimethyl prostaglandin E2 on the induction of hepatic foci by cotreatment of gamma radiation and diethylnitrosamine.

We investigated the effect of potato extracts and 16,16-dimethyl prostaglandin E2 (DiPGE2) on the induction of glutathione S-transferase P-positive (GST-P+) altered hepatic foci in newborn Sprague-Dawley rats given single treatment with 60Co gamma irradiation and diethylnitrosamine (DEN) alone or in sequential combination. Intraperitoneal injection of 0.15 mumol/g body weight of DEN 1 hour after gamma radiation significantly increased the frequencies of GST-P+ hepatic foci compared to DEN or gamma radiation alone and DEN injection 1 hour before irradiation (p < 0.001). Potato extract was given at a dose of 2 mg/ml in drinking water for 3 weeks and DiPGE2 given at a dose of 10 micrograms/mouse 30 minutes before irradiation. Potato extracts and DiPGE2 decreased significantly the number (p < 0.001), area (p < 0.001) and Dmax (p < 0.05) of GST-P+ hepatic foci compared to the corresponding control. These results suggest that potato extracts and DiPGE2 have radio-protective potential and further studies for underlying mechanisms will be necessary.

Sonography of inflammatory bowel disease: findings and value in differential diagnosis.

OBJECTIVE: Inflammatory bowel diseases produce segmental or diffuse mural thickening of the intestine that can be detected and evaluated by using sonography. The purpose of this study was to evaluate the sonographic findings and determine their diagnostic value in patients with inflammatory bowel diseases. MATERIALS AND METHODS: We reviewed sonograms of 81 patients with inflammatory bowel diseases. The findings were compared with those of barium study, colonoscopy, and surgery. Forty-five patients had tuberculous enterocolitis, 13 had ulcerative colitis, eight had Crohn's disease, five had ischemic colitis, two had Behçet's syndrome, and eight had unspecified colitis. Diagnosis was based on surgical and pathologic findings in 23; results of barium study and endoscopic biopsy in 20; and results of barium study, colonoscopic findings, and clinical findings in 38. RESULTS: Seventy-two patients (89%) had sonograms that showed segmental or diffuse mural thickening and a paucity of luminal content in the involved bowel. Involved areas were the ileocecal region in the cases of tuberculous enterocolitis and Behçet's syndrome, the left side of the colon in ulcerative colitis, and the colon and terminal part of the ileum in Crohn's disease. In ischemic colitis, the distribution of involved bowel was nonspecific. Sonographic findings correlated well with the findings of barium enema or colonoscopy in terms of the involved segments of the bowel. Mesenteric lymphadenitis, omental thickening, and ascites were frequently observed in cases of tuberculous enterocolitis. CONCLUSION: Sonographic evidence of mural thickening of the bowel with a paucity of luminal content may be helpful in the detection of inflammatory bowel diseases. However, the findings are nonspecific, and the differential diagnosis must be related to the specific segment of the bowel involved.

In vivo radioprotective activity of Panax ginseng and diethyldithiocarbamate.

Studies were performed to determine whether the water fraction and the alkaloid fraction of Panax ginseng protect against radiation damage to jejunal crypts of N:GP(s) mice and induction of micronuclei (MN) in cytokinesis-blocked (CB) lymphocytes of C57BL/6 mice after in vivo irradiation with 60Co gamma-rays. The radioprotective effect of ginseng was compared with the effect of diethyldithiocarbamate (DDC). Jejunum was protected by the water fraction (2 mg/ml of drinking water) (P < 0.001) and the alkaloid fraction (5.4 mg/day, P.O.) (P < 0.005), both pre-and post-treatment, and by DDC (1000 mg/kg B.W., single I.P., 30 minutes before 15 Gy irradiation) (P < 0.001). The frequency of radiation (3 Gy)-induced micronuclei in spleen lymphocytes was also reduced by pretreatment of water fraction, alkaloid fraction of ginseng (P < 0.025) and DDC (P < 0.001). The data suggested that the water fraction and alkaloid fraction of Panax ginseng may reduce cell damage caused by gamma-rays, especially damage to DNA molecules, and play a role in the repair or regeneration process of damaged cells.

Adjuvant chemotherapy for advanced nasopharyngeal carcinoma in childhood.

Seven children with advanced nasopharyngeal carcinoma younger than 20 years of age diagnosed between 1975 and 1986 (inclusive) were treated with a uniform adjuvant chemotherapy regimen, which consisted of vincristine (1.5 mg/m2; day 1), doxorubicin (45 mg/m2; day 1), 5-fluorouracil (8 mg/kg; days 1 through 5), and cyclophosphamide (7 mg/kg; days 1 through 5). This combination chemotherapy was given for 12 to 24 months after completion of radiation therapy. The radiation doses to the primary sites ranged from 6000 cGy to a maximum of 6800 cGy. The radiation doses for neck prophylaxis ranged from 4500 cGy to a total of 5000 cGy. Involved sites were irradiated to at least an additional boost of 1000 cGy. One patient had an external dose 6000 cGy to the primary site boosted with brachytherapy of 3000 cGy at the surface of an ovoid. After chemotherapy myelosuppression occurred in all patients and was tolerable. All seven patients are surviving, six disease-free, for 22 months to 12 years (median, 4 years). This study suggests that the combination of radiation therapy and chemotherapy as used here has acceptable toxicity and is effective and further suggests that children with nasopharyngeal carcinoma, even in its advanced stage at diagnosis, may be curable.

Changes in acidity of mouse tumor by hyperthermia.

The intratissue pH of SCK tumor and leg muscle of unanesthetized mice were determined before, during and after hyperthermia with the use of bulb type pH microelectrodes having pH-sensitive hemisphere 20-40 micron in outer radius. Intratumor pH was heterogeneous throughout tumor (range, 6.60-7.38; average, 6.96), and was more acidic than the intramuscle pH of mouse leg (average, 7.46). Hyperthermia at 43.5 degrees C for 30 min induced a further increase in acidity (decrease in pH of about 0.2 units) in tumor but not in muscle. The heat-induced acidity in tumor lasted for 12 hr following hyperthermia and then recovered to almost control pH value 24 hr after heating. The cause of the increase in acidity in the heated tumors is not clear, but it appears to result from an increase in the contents of acidic metabolites and a sluggish drainage of them due to induced vascular damage. The increased acidity in the heated tumors may inhibit the repair of thermal damage and sensitizes the tumor cells to subsequent heating.

Thyroid dysfunction among long-term survivors of bone marrow transplantation.

Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.