Methylene Blue inhibits the inflammatory process of the acetic acid-induced colitis in the rat colonic mucosa.

Inflammatory bowel disease is a serious health problem. Although it has been widely investigated, treatment of inflammatory bowel diseases currently remains as a challenging clinical problem. Over production of nitric oxide has been demonstrated to cause tissue damage and inflammation. In this study, the effect of methylene blue (MB), a well-known inhibitor of nitric oxide synthesis, was investigated in acetic acid (AA)-induced colitis model in Sprague-Dawley rats. Eighty male rats randomized into 4 groups (control, control MB, colitis, colitis + MB). AA was applied to groups 3 and 4. MB was added into group 2 and 4. Three days later, animals were sacrificed and 8 cm distal colonic segment resected and the specimens are examined using macroscopical, histological, and biochemical methods. The results of the macroscopic and microscopic examination showed that in group 4 the mucosal damage and inflammation score significantly lower than group 3. Increased intestinal permeability in acetic acid-administered group was significantly reversed by MB application. Myeloperoxidase activity and malondialdehyde levels increased significantly, while superoxide dismutase and catalase activities were suppressed after AA-administration. These biochemical parameters were reversed in MB-treated group. Administration of acetic acid resulted in increased levels of tumor necrosis factor-α, interleukin-1ß, interleukin-6, total nitrite/nitrate levels and nitric oxide synthase activity. These biochemical alterations were significantly reversed by MB application also. In conclusion, our results indicate that MB decreases the level of nitric oxide and decreases inflammation in acetic acid-induced colitis.

Effect of ß-glucan on drain fluid and amount of drainage following modified radical mastectomy.

INTRODUCTION: To reduce the seroma formation following mastectomy and axillary dissection, many different techniques and drugs have been investigated. The aim of this study is to evaluate the effects of oral ß-glucan on drain fluid and efficacy of daily drainage and drain removal day in mastectomy patients. METHODS: One hundred and thirty breast cancer patients of Ankara Oncology Training and Research Hospital were divided into 2 groups by consecutive randomization (n = 65 each). ß-glucan 10 mg capsules were administered to Group 1 twice a day for 10 days. Group 2 took placebos in the same manner. Age, menarche age, menopause, parity, history of oral contraceptives, comorbidities, postoperative daily drainage volumes and drain removal days were recorded and compared. Seroma samples during the first and second day of drainage were taken for analysis of Interleukin-6 (IL-6) and Tumor Necrosis Factor (TNF-α). RESULTS: There was no difference between groups in terms of age, menarche age, menopause period, parity, oral contraceptive use and comorbidities. Group 1 showed significantly lower daily drainage volumes between days 2 and 8. Mean drain removal day was 7.16 ± 1.72 in Group 1 and 8.59 ± 2.27 in Group 2. The difference was significant (p < 0.001). TNF-α and IL-6 levels on days 1 and 2 in Group 1 were significantly lower (p < 0.001). In addition, ß-glucan significantly shortened the number of days required for the drain removal in patients who have comorbidities (p = 0.018). The earliest removal was in patients without comorbidity and who received ß-glucan (p = 0.002). CONCLUSION: ß-glucan decreased drain discharges after mastectomy. The drains were removed earlier in ß-glucan administered patients.

Malign cylindroma of the scalp with multiple cervical lymph node metastasis-A case report.

INTRODUCTION: Cylindromas are usually benign tumors as small, solitary, slow-growing nodules of the scalp, face and trunk. Multiple cylindromas may form a "turban tumors" in the autosomal dominant Brooke-Spiegler syndrome. Malignant dermal cylindromas are very rare. There are few cases of malignant transformation of dermal cylindromas in the literature. We present an unusual case of malign cylindroma of the scalp with multiple metastasis to cervical lymph nodules and also this case is the only case that has the most lymph node metastasis. PRESENTATION OF CASE: A 52-year-old man initially presented to our clinic with hyperemic plaque located on his scalp. Measures of the plaque was 20cm×10cm with bilateral, multiple palpable submandibulary lymph nodes. Entire scalp was removed reaching in depth the periostal level and bilateral modified radical neck dissection was performed. The histopathological examination of the scalp specimen was malignant skin ecrine tumor, cylindroma and on the neck dissection specimen, 55 lymph nodes were reported as metastatic out of 79. The patient was treated with chemotherapy and radiotherapy. No recurrence or metastasis was observed during a 5 year follow-up period. DISCUSSION: Malign cylindroma of the scalp rarely presents with multiple cervical lymph node metastasis, however it is important to be aware of this possibility. CONCLUSION: The case reported below is outstanding in literature for being the only case that has the most lymph node metastasis. Although malign transformation of dermal cylindromas is rare, aggressive surgery should be considered with locoregional metastasis of the tumor.

Temporal variation in the recovery from impairment in adriamycin-induced wound healing in rats.

BACKGROUND: An adriamycin-induced impairment of wound healing has been demonstrated experimentally in rats. The purpose of this study is to investigate a possible temporal variation in recovery from the impairment of wound healing caused by adriamycin administration. METHODS: The subjects were 120 female Spraque-Dawley rats. They were divided into eight groups, undergoing adriamycin administration (8 mg/kg, i.v.) at 9 a.m. or 9 p.m. on day 0 and laparotomy on day 0, 7, 14 or 21. Blast pressures were recorded after the incision line had been opened, and tissue samples were kept at -30 degrees C for later measurement of hydroxyproline levels. RESULTS: Adriamycin treatment in rats at 9 p.m. resulted in significantly lower blast pressure levels than treatment at 9 a.m. between days 7 and 21, indicating a lag effect of healing time in wounded tissues. However the decreased hydroxyproline levels were not changed at these days and sessions. CONCLUSION: It is concluded that adriamycin-induced impairment of wound healing in adult female rats exhibits nycthemeral variation.

Long term administration of granulocyte-macrophage colony stimulating factor decreases development of 1-2 dimethylhydrazine-induced colon cancer in rats.

BACKGROUND AND OBJECTIVES: The antitumoral activities of granulocyte-macrophage colony stimulating factor (GM-CSF) were shown earlier. In this study, the effects of GM-CSF were investigated on colon cancer induced by 18 weeks of 1-2 dimethylhydrazine (DMH) administration in rats. METHODS: Four groups received subcutaneous saline (n = 20), 15 mg/kg DMH (n = 30), DMH +6 microg/kg GM-CSF (n = 30), and DMH +12 microg/kg (n = 30) GM-CSF. RESULTS: The average number of tumors (2.8 vs. 1.5) and mean tumor volume (179 +/- 36 vs. 27 +/- 9 mm(3); means +/- SEM) were reduced in DMH + GM-CSF groups as compared to the DMH group (n = 30, P < 0.01). DMH-induced enhancement of free radicals and lipid peroxidation were decreased in DMH + GM-CSF group (n = 8-12, P < 0.05). The magnitude of DMH-induced alterations in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities was lowered in the DMH + GM-CSF group (n = 12-16, P < 0.05). DMH-induced increases in the total nitrite/nitrate levels and the nitric oxide synthase (NOS) activity (n = 10-12, P < 0.05) were also reduced in the DMH + GM-CSF group (n = 8-9, P < 0.05). CONCLUSIONS: The results indicate that GM-CSF inhibits the development of DMH-induced colon cancer in rats and suggest that inhibition of oxidative stress and NO pathway are involved in the observed antitumoral effects.

Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing.

OBJECTIVES: Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. METHODS: We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. RESULTS: During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. CONCLUSION: MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient inhibitory effect on the nitric oxide pathway.

The incidence of hyperthyroidism in patients with thyroid cancer in an area of iodine deficiency.

BACKGROUND: The incidence of hyperthyroidism among thyroid malignancy varies greatly depending on the geographical area and iodine intake. The aim of the study was to evaluate the association of hyperthyroidism and thyroid cancer (TC) in an iodine deficient area. PATIENTS AND METHODS: Medical records of 422 patients who underwent operation for TC between 1992 and 2000 in Ankara Oncology Hospital were reviewed. The characteristics of TC patients with hyperthyroidism were analyzed in respect to gender, age, histopathological type, thyroid function status, tumor size, extrathyroidal invasion, local recurrences, distant metastasis, AMES and MACIS scoring. RESULTS: In the present patient series, among 422 patients with TC, hyperthyroidism was found in 12 patients (2.8%). None of the patients had Graves' disease. Of 12 patients with hyperthyroidism, 9 patients had papillary carcinoma, 1 patient had follicular carcinoma and 2 patients had follicular variant of papillary carcinoma. The tumor was in the active nodule in 5 patients. CONCLUSION: The existence of hyperthyroidism among patients with differentiated TC is a clinical entity. Patients with hyperthyroidism and nodules require a careful approach in order to establish or exclude the possibility of TC especially in formerly iodine deficient areas.

Local granulocyte-macrophage colony-stimulating factor improves incisional wound healing in adriamycin-treated rats.

PURPOSE: Neoadjuvant treatment is often given for locally advanced malignancies; however, clinical and experimental studies have shown that some chemotherapeutic agents impair wound healing. It has been reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) applied locally improves dermal wound healing. Thus, we investigated the effects of locally injected GM-CSF on abdominal wounds impaired by adriamycin, a widely used chemotherapeutic agent. METHODS: We divided 120 female Sprague-Dawley rats into five treatment groups of 24 rats. Group 1 received saline 8 mg/kg intravenously (i.v.) + laparotomy 14 days later (control); group 2 received 8 mg/kg i.v. adriamycin + laparotomy 14 days later; group 3 received adriamycin 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; group 4 received saline 8 mg/kg i.v. + laparotomy + local GM-CSF 50 microg 14 days later; and group 5 received adriamycin 8 mg/kg i.v. + laparotomy + systemic GM-CSF 50 microg 14 days later. Sutures were removed on postoperative day (POD) 7 in all five groups, and the abdominal bursting pressures were measured and recorded. Tissue samples were taken from the incision line for histopathological evaluation and hydroxyproline content measurement. RESULTS: The bursting pressure was significantly lower in groups 2 and 5 than in groups 1, 3, and 4. The hydroxyproline content and histopathological findings supported this result. CONCLUSION: The local injection of GM-CSF improved impaired wound healing in adriamycin-treated rats.

Efficacy of granulocyte-macrophage colony-stimulating factor on the survival of ischaemic skin flaps in rats.

Our objective was to find out whether granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the survival of skin flaps in rats. Random skin flaps were raised in 30 male Sprague-Dawley rats, and recombinant GM-CSF 50 microg in 0.5 ml saline solution (n=15) or 0.5 ml saline solution alone (n=15) was injected intradermally into the area of the flap after it had been raised. Surviving areas were measured after seven days, and the median area surviving in the group treated with GM-CSF was greater than that in the control group (728 mm2 (range 565-1120) compared with 985 mm2 (range 636-1368), p=0.005). These results suggest that in this model, GM-CSF given postoperatively improves the viability of ischaemic skin flaps.

Locally applied molgramostim improves wound healing at colonic anastomoses in rats after ligation of the common bile duct.

BACKGROUND: Several systemic factors, including jaundice, long-term corticosteroid therapy, diabetes and malnutrition, increase the risk of anastomotic dehiscence. The local application of molgramostim (recombinant human granulocyte-macrophage colony stimulating factor) has been reported to improve impaired dermal wound healing. Since jaundice, one of the systemic risk factors for anastomotic dehiscence, causes significant impairment of anastomotic healing, we hypothesized that locally injected molgramostim could improve the healing of bowel anastomoses in bile-duct-ligated rats used as an experimental model for jaundice. METHODS: Eighty-six Sprague-Dawley rats were randomized into 4 groups of 20-22 animals each as follows: group 1--colonic anastomosis only; group 2--laparotomy followed 7 days later by colonic anastomosis; group 3--common-bile-duct ligation (CBDL) followed 7 days later by colonic anastomosis (control group); group 4--CBDL followed by colonic anastomosis with locally applied molgramostim. Laparotomy was performed under anesthesia in group 2 rats. In groups 3 and 4, laparotomy was followed by ligation and dissection of the common bile duct. After 7 days, colonic anastomosis was performed; in group 4 rats, molgramostim (50 microg) was injected into the perianastomotic area. On postoperative day 3, rats were killed, and the bursting pressures and hydroxyproline levels measured. Two rats from each group were selected for histopathological examination. RESULTS: The mean bursting pressure in group 4 was significantly higher than that in group 3 (37.8 v. 30.5 mm Hg [p < 0.01]). The mean hydroxyproline level in group 3 was significantly lower than that of the other groups (2.7 v. 3.1-3.5 mg/g tissue [p < 0.01]). On histopathological examination, specimens from group 4 rats showed an increased mononuclear cell population and a smaller gap on the anastomotic line than those from group 3. CONCLUSION: The local injection of molgramostim improves healing of the impaired wound in rats subjected to CBDL.

Granulocyte macrophage-colony stimulating factor improves impaired anastomotic wound healing in rats treated with intraperitoneal mitomycin-C.

PURPOSE: Intraperitoneal chemotherapy (IPCT) delivers higher local concentrations of cytotoxic drugs than intravenous (i.v.) chemotherapy, but it can adversely affect the healing of intestinal anastomoses if given in the early postoperative period. Intestinal anastomotic leakage is a serious surgical complication. Experimental and clinical studies have shown that the local administration of granulocyte macrophage-colony stimulating factor (GM-CSF) improves would healing. Therefore, we evaluated the effects of locally applied GM-CSF on anastomotic wound healing in rats treated with intraperitoneal mitomycin-C immediately after surgery. METHODS: We performed colon anastomoses in albino rats, which were then divided into three treatment groups. Group A was a control group that received no treatment, Group B was given intraperitoneal mitomycin-C postoperatively, and Group C was given intraperitoneal mitomycin-C with a local injection of GM-CSF postoperatively. We measured bursting pressures and hydroxyproline content, and histologically examined the resected anastomoses on postoperative day (POD) 3. RESULTS: Anastomotic healing was impaired after intraperitoneal mitomycin-C, but this was overcome by the injection of GM-CSF into the perianastomotic area. CONCLUSION: Local GM-CSF administration counteracts the detrimental effects of intraperitoneal mitomycin-C treatment on intestinal anastomoses in rats.

Optimal timing for surgery after adriamycin treatment in rats.

PURPOSE: To determine the optimal timing of surgery after adriamycin treatment, we investigated the time-related effect of adriamycin on wound healing over a long period. METHODS: We divided 119 female Sprague-Dawley rats into seven treatment groups. Group 1 was subjected to laparatomy only. All the other groups were given 8 mg/kg adriamycin intravenously followed by laparotomy on the same day (group 2), 7 days later (group 3), 14 days later (group 4), 21 days later (group 5), 28 days later (group 6), or 35 days later (group 7). On postoperative day 7, the sutures were removed, abdominal bursting pressure was measured, and tissue samples were taken for histopathological evaluation and analysis of hydroxyproline content. RESULTS: Bursting pressures were significantly lower in groups 3, 4, 5, and 6 than in group 1. The hydroxyproline content and histopathological evaluation supported these findings. CONCLUSIONS: Our results showed that the optimal timing for surgery after adriamycin treatment is before the 7th day or after the 35th day. If surgery is performed between these days, there is a high risk of impaired wound healing.

Prognostic significance of apex axillary invasion for locoregional recurrence and effect of postmastectomy radiotherapy on overall survival in node-positive breast cancer patients.

Postmastectomy irradiation substantially reduces the risk of locoregional recurrences (LRR) of breast carcinoma. However, debates continue on the prognostic factors for radiotherapy and the effect of radiotherapy on overall survival. The present study was undertaken to investigate the prognostic significance of level III positive nodes, along with the other factors for LRR, and to evaluate the effect of postmastectomy radiotherapy on overall survival among node-positive breast carcinoma treated systemically. Data from 549 consecutive node-positive breast cancer patients who underwent modified radical mastectomy and received adjuvant systemic therapy were studied retrospectively. Prognostic factors for LRR and the effect of postmastectomy radiotherapy on overall survival were analyzed. Survival curves were generated by the Kaplan-Meier method, and multivariate analysis was performed by the Cox proportional hazard model. The 5-year locoregional recurrence rate is 7%. Apical invasion was found to be an independent prognostic factor for LRR (HR 2.6, CI 1.29-5.35) along with a finding of 4 or more positive nodes and T3 tumor. Adjuvant radiotherapy decreased LRR and improved survival significantly. Apical invasion, 4 or more positive axillary lymph nodes, and T3 tumor are the predictors of LRR, and patients with these adverse factors are candidates for adjuvant radiotherapy. Postmastectomy radiotherapy improves overall survival.

Effects of intraperitoneal chemotherapy and GM-CSF on anastomotic healing: an experimental study in rats.

BACKGROUND: Intraperitoneal chemotherapy (IPCT) is an alternative local adjuvant treatment for patients with resectable colonic and gastric cancers. This is the simplest and safest method for systemic toxicity, but it can affect the healing of colonic anastomoses. Granulocyte macrophage-colony stimulating factor (GM-CSF) may be used to prevent this side effect by means of macrophage activity stimulation. METHODS: In this experimental study the effects of early postoperative intraperitoneal 5-fluorouracil (5-FU) and local administration of recombinant human GM-CSF (rGM-CSF) were studied on rats. The anastomotic bursting pressures, hydroxyproline contents of tissues, and histological appearance were assessed. RESULTS: It was found that anastomotic healing of colon was impaired after intraperitoneal 5-FU administration, but when rGM-CSF was injected to the both sides of the anastomoses locally, this side effect could be prevented. CONCLUSIONS: IPCT may diminish the activity of macrophages and impair the wound healing; locally applied rGM-CSF enhanced wound healing on colonic anastomoses.

Locally applied granulocyte-macrophage colony-stimulating factor improves the impaired bowel anastomoses in rats with long-term corticosteroid treatment.

Inflammation is an essential component of the first phase of anastomotic wound healing, and it is suppressed by corticosteroids. The anti-inflammatory effect of corticosteroids is largely responsible for the impairment of wound healing in bowel anastomosis. It has been reported that local application of granulocyte-macrophage colony-stimulating factor (GM-CSF) improves the healing process in dermal wounds. In the present study, we investigated the effects of locally injected GM-CSF on anastomotic wound healing in long-term corticosteroid treated rats. Eighty male Sprague-Dawley rats were randomized into four groups. (1) control, (2) steroid, (3) steroid + local GM-CSF, (4) steroid + systemic GM-CSF. In groups 2, 3, and 4, methylprednisolone (5 mg/kg) was injected IM daily for 14 days. After 14 days, following anesthesia and laparotomy, colonic anastomosis was performed 3 cm away from the peritoneal reflection. In group 3, 50 mg GM-CSF was injected into the perianastomotic area. In group 4, 50 mg GM-CSF was applied subcutaneously. On postoperative day 3, repeat laparotomies were performed and bursting pressures, hydroxyproline levels, and histopathology examinations were studied. The mean values of bursting pressures and hydroxyproline levels in group 3, treated with steroid + local GM-CSF, were significantly higher than that of the group 2 and group 4 values. In the histopathology examination, the mean score of group 3 was significantly higher than that of groups 2 and 4. Our study indicates that local application of GM-CSF significantly improves the impaired anastomotic wound healing in rats treated with long-term corticosteroid.

Risk factors for breast cancer in Turkish women with early pregnancies and long-lasting lactation--a case-control study.

A hospital-based case-control study was carried out among 504 women with breast cancer and 610 controls to analyse the risk factors for breast cancer in Turkey. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor were obtained from logistic regression analysis. Risk factors for breast cancer were found to be long-term lactation (> or = 5 years versus never OR 0.31, 95% CI 0.12-0.79), young age at menarche (< 15 years versus > or = 15 OR 1.72, 95% CI 1.30-2.28), late age at first full-term pregnancy (> or = 30 versus < 20 OR 2.86, 95% CI 1.32-6.21), oral contraceptive use (ever versus never OR 1.51, 95% CI 1.10-2.08), positive family history (positive versus negative OR 2.81, 95% CI 1.35-5.82), and menstrual irregularity (yes versus no OR 1.61, 95% CI 1.05-2.49). The results of the present study will lead to a better understanding of the risk factors for breast cancer in a developing country.