Isoniazid tumorigenicity in mice under different experimental conditions

Tumorigenicity of isoniazid in Swiss and A strain mice was studied with three different doses (0.55, 1.1 and 2.2 mg/mouse/day). Mice were fed isoniazid by gastric intubation and killed when they appeared weak. Incidence of tumour ranged from 32 to 100%. Subsequently sex-specificity in isoniazid tumorigenicity was also studied as well as the effect of vitamin B complex or protein deficiency, and of transplacental exposure of Swiss strain embryos to isoniazid. It was observed that protein deficiency and transplacental exposure stimulated tumour incidence in mice treated with 0.55 mg of isoniazid. No sex specificity was observed in isoniazid tumorigenesis.     

Significance of CA 125 serum level in discrimination between benign and malignant masses in the pelvis

Aim Our aim was to confirm that preoperative CA 125 serum level can be useful for discrimination between benign and malignant masses in the pelvis.Methods Preoperative CA 125 serum level was analyzed retrospectively in 121 patients who had surgery because of a malignant ovarian tumor and in 91 patients with benign masses in the pelvis. The cutoff serum level CA 125 between benign and malignant masses in the pelvis was 35 and 65 IU/ml.Results Of those patients with a malignant ovarian tumor, 65.3% had menopause whereas only 31.5% of those with a benign tumor did so. The average age of the patients with a malignant tumor was 54.2 years and of those with a benign tumor 46.8 years. The preoperative CA 125 serum level was higher than 35 IU/ml in 80.2% and higher than 65 IU/ml in 72.7% of all analyzed patients with a malignant tumor, whereas it was 23.9% and 9.8% respectively in patients with a benign mass. In early stage ovarian cancer disease (borderline stage, I/II) the preoperative CA 125 serum level was higher than 35 IU/ml in 67.8% and in 52.5% higher than 65 IU/ml. In advanced stages (III/IV), it was higher than 35 and 65 IU/ml in 96.1%. After therapy the CA 125 serum level dropped below 35 IU/ml in 70.8% and after three chemotherapy courses in 78.1%. A CA 125 level less than 35 IU/ml was achieved by therapy in 84.2% patients with an early stage disease (I/II) and in 62.1% in advanced stages (III/IV). The calculated sensitivity was 80.2% and negative 74.5% (CA 125 higher than 35 IU/ml) and 72.7%, 90.2%, 90.7%, 71.6% respectively (CA 125 higher than 65 IU/ml).Conclusion Preoperative determination of CA 125 is a very useful method to discriminate between benign and malignant masses in the pelvis.     

Evaluation of DNA damage in mice topically exposed to total particulate matter from mainstream and sidestream smoke from cigarettes and bidis

The genotoxic potential of total particulate matter (TPM) from mainstream smoke (MS) and sidestream smoke (SS) of Indian smoking products, namely cigarettes and bidis, as well as a brand of US cigarettes, was studied by determining the levels of bulky aromatic DNA adducts in mouse tissues. TPM from MS or SS of various smoking products [equal weights (2.5 mg) or the amount derived from equal (0.25) cigarette/bidi] was applied topically to mouse skin once a day for four consecutive days and adduct levels were determined in DNA from skin and lung by (32)P-post-labelling analysis. Relatively higher levels of bulky aromatic DNA adducts were noted in mouse skin treated with MS from a single Indian non-filter (INF) cigarette when compared with MS of a single bidi (with about half the product weight and one-quarter the tobacco compared with a cigarette), while comparable adduct levels were noted with SS from these two products. Considering the differences in the yields of constituents of tobacco smoke from the different products analyzed, the genotoxic potential of INF, Indian filter king (IFK) and American filter (AF) cigarettes as well as bidis was determined by topically applying an equal amount of TPM (rather than equal product-derived TPM). SS-derived TPM from all the products showed relatively higher levels of total polycyclic aromatic hydrocarbons and induced relatively higher levels of bulky aromatic DNA adducts than those derived from MS. The data indicate that TPM (MS + SS) from cigarettes appears to be more genotoxic than that from bidis and the contribution of tendu leaf (a non-tobacco bidi wrapper) to the generation of bulky aromatic DNA adducts appears to be significant, particularly in SS of bidis. Topical pretreatment with curcumin decreased the levels of TPM-derived adducts while pretreatment with dietary turmeric failed to show such protection.     

In vivo study of different ointments for drug delivery into oral mucosa by EPR oximetry

The aim of the present study was to determine the rate of transport and long-term effect of a drug applied to the oral mucosa in different ointments. Three ointments with bioadhesive properties: Orabase, Carbopol 935P, and polymethyl methacrylate (PMM) and the ointment Miglyol without such properties were used. Benzyl nicotinate (BN) was used as an active ingredient that causes hyperemia. The kinetics of drug action was measured by electron paramagnetic resonance (EPR) oximetry in vivo using the paramagnetic probe (Lithium phthalocyanine) implanted beneath the epithelium of the buccal mucosa in rats. EPR spectra line-width was proportional to local changes of partial pressure of oxygen (pO₂) in tissue and was monitored for 90 min after the application of ointments mixed with BN. The greatest increase in pO₂ and the highest efficiency of drug action was observed after the application of 2% BN in PMM (P<0.01). Additionally in PMM the drug effect increased linearly with BN concentration up to 3%, at higher concentrations (3.5 and 4% BN) no further effect was observed. The results demonstrated that the greatest and the longest effect caused by a hyperemic drug in PMM. By increasing the concentration of the drug in PMM higher pO₂ in the oral mucosa can be established but only until the saturation is reached.     

The clinicopathological characteristics in renal cell carcinoma with end-stage renal disease

OBJECTIVES: The influence and the interdependence of pathological and clinical factors on prognostic differences between renal cell carcinoma (RCC) with end-stage renal disease (ESRD) and RCC without ESRD after nephrectomy has remained unclear. We compare the clinicopathological features between RCC with and without ESRD. MATERIALS AND METHODS: From June 1993 to May 2000, 150 RCC patients who underwent nephrectomy were pathologically defined to have pT1 to pT3NXM0. The patients were followed for 1 to 84 months (median 30 months) after the surgery. Total of 16 patients with ESRD and 134 patients without ESRD were studied, and the differences of clinicopathological features between two groups were statistically compared. RESULTS: We compare the clinicopathological features between RCC with and without ESRD. Patients' age, tumor size, rate of incidental cancer, pathological T stage, and grade were not significantly different between two groups. The 5-year recurrence-free probability rate was significantly higher in patients without ESRD than in patients with ESRD (log-rank test: p = 0.04). The status of ESRD, patients age and pathological T stage were significant predictors of recurrence when analyzed by Cox proportional hazards analysis (p = 0.01, p = 0.03 and p = 0.02, respectively). CONCLUSIONS: This study demonstrated that the ESRD is an independent prognostic factor in RCC patients after surgery. These results reflect that the patients with ESRD have higher risk of tumor progression. Therefore, early detection of tumors is particularly important in these patients by regular abdominal ultrasound or CT screening.     

Intraoperative and conformal external-beam radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic carcinoma

BACKGROUND: Chemoradiotherapy is widely used for patients with locally advanced pancreatic carcinoma. The purpose of this study was to clarify the efficacy and feasibility of chemoradiotherapy with more intensive radiotherapy in these patients, using a combination of intraoperative radiotherapy (IORT), conformal external-beam radiaotherapy (EBRT), and protracted 5-fluorouracil (5-FU). METHODS: Thirty patients with unresectable locally advanced pancreatic carcinoma were enrolled in this Phase II study. The treatment consisted of IORT (25 grays [Gy]), followed by EBRT (40 Gy in 20 fractions, 5 times per week), and concurrent protracted 5-FU infusion (200 mg/m(2)), beginning 2-4 weeks after IORT. The authors evaluated the efficacy and adverse effects of this treatment by following up patients for 12.0-28.1 months. Survival from the date of IORT was calculated using the Kaplan-Meier method. RESULTS: In 11 of the 30 patients, metastatic spread was detected in the abdominal cavity at laparotomy. The full EBRT dose was administered in 28 of the 30 patients. Of the remaining 2 patients, EBRT was terminated at 8 Gy due to progression of brain metastasis and another patient did not receive EBRT or chemotherapy due to massive ascites after IORT. The overall response rate for primary pancreatic tumor on dynamic computed tomography scan was 23.3% (7 partial responses). Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria) was observed in 15 of the 28 patients who received the full irradiation dose (53.6%). These included anorexia, nausea, emesis, fatigue, leukopenia, and/or elevation of transaminase levels. There were no directly treatment-related deaths, but 1 patient died of hepatic failure related to late effects of irradiation after 25.6 months. The median survival time of the 30 patients was 7.8 months and the 2-year survival rate was 8.1%. The median survival time of the 19 patients without metastatic spread in the abdominal cavity was 12.9 months and that of the 11 patients with metastatic spread was 5.8 months. CONCLUSIONS: The present regimen of chemoradiotherapy is not superior to conventional chemoradiotherapy (EBRT and 5-FU) for patients with locally advanced pancreatic carcinoma.     

Influence of the wars in Croatia and Bosnia and Herzegovina on the incidence and outcome of singleton premature births in the Split University Hospital

To investigate the influence of the wars in Croatia and Bosnia and Herzegovina on incidence and perinatal outcome of singleton preterm births at the Department of Gynecology and Obstetrics in the Split University Hospital. Data were collected by reviewing patients’ files at the Department of Gynecology and Obstetrics from three periods: the three years before the war (1988–1990), during the war (1992–1994), and after the war (1996–1998). A total of 2,358 patients’ files of singleton preterm delivery were analyzed. Singleton preterm delivery rate decreased during the war (5.02%) and post-war period (4.74%) compared to the pre-war period (6.19%). Stillbirth and early neonatal mortality rates of singleton premature babies significantly increased during the war to 226%, compared to 193% before the war and 134% after the war. Early neonatal mortality rate was 215% during the war, 209% in the pre-war period, and 156% after the war. Despite the continuous decrease in singleton preterm birth rate throughout the observed periods, the increase in stillbirth rate and early neonatal mortality rate during the war might have been caused by the war. This may be due to primary gynecological care being inadequate for many pregnant women.