Effects of clonidine preemptive analgesia on acute postoperative pain in abdominal surgery.

Preemptive analgesia refers to blockade of afferent nerve fibers before a painful stimulus, which prevents or reduces subsequent pain even beyond the effect of the block. The aim of the study was to compare the effect of clonidine used before and at the end of operation on pain control in abdominal surgery. A total of 77 patients admitted for colorectal surgery were randomly classified into three groups: epidural clonidine before operation, epidural clonidine at the end of operation, and control group. After the operation on patient demand, analgesia with boluses of epidural morphine was instituted. The parameters of postoperative pain level using VAS score (visual analog scale), sedation and analgesics consumption were determined as outcome measures at 1, 2, 6, and 24 h of the operation. Clonidine administered before operation provided lowest pain scores at 6 and 24 h (p < 0.05). Clonidine administered at the end of operation had low pain scores at 1 and 2 h, with a significant pain breakthrough thereafter (6.93 +/- 1.66 at 6 h and 4.04 +/- 2.39 at 24 h) compared with the group administered clonidine before operation (3.60 +/- 2.94 and 3.71 +/- 1.82). Clonidine administered before operation provided less sedation (p < 0.05) and a significantly lower use of analgesics (p < 0.05). Blockade of nociceptive stimulus using the centrally acting alpha2-adrenergic agonist clonidine before the onset of pain stimulus resulted in reduced pain levels, sedation and analgesic requirement.

The consequences of insulin-like growth factors/receptors dysfunction in lung cancer.

The aim of this study was to investigate the consequences of insulin-like growth factors (IGF) and IGF receptor dysfunction in lung carcinomas. A correlation between increased expression (at mRNA and protein levels) for IGF-1 and IGF-1R and decreased apoptosis were found in large-cell carcinomas and adenocarcinomas. In 40% of informative adenocarcinomas expressing the highest values of IGF-2 and Ki-67 proteins, M6P/IGF-2R gene had LOH at one allele and a mutation in another allele. All four squamous cell carcinoma samples expressed LOH/mutation in the M6P/IGF-2R gene. The alphaIR3 strongly diminished proliferation and increased apoptosis in cultures established from squamous cell carcinomas overexpressing IGF-2 and IGF-1R. Telomerase activity was assessed in four squamous cell carcinomas. Cell treatment with IGF-1 increased telomerase activity. The opposite was observed when the cells were treated with alphaIR3, which inhibits the activity of IGF-1 receptors. Our findings suggest that disruption of the IGF/IGF receptors axis is involved in lung cancer formation.

Changes in the tissue expression of the C-erbB-2 oncogen in the oral lichen ruber.

The aim of this study was to determine the expression intensity of c-erbB-2 antigen in oral lichen planus and erosive form of oral lichen in 30 patients, and to compare the obtained results with the inflammation intensity i.e. hyperkeratosis. The examination of expression intensity of c-erbB-2 antigen was conducted through immunohistochemical analysis by APAAP method. Obtained reaction of examined tissue antigen was positive in individual or in group cells of spinous epithelium layer and mosaically expressed. The reaction was negative in basal cell epithelium layer. Strong intensity reaction was observed in intercellular bridges of spinous cells layer. In control group, the reaction was of uniform strong intensity in all epithelium layers. The reaction was not dependent on the inflammation intensity in lesions but it was positively correlated with their degree of hyperkeratosis. Changed expression of c-erbB-2 antigen in OLR lesions reveals the possibility of potential malignant transformation of these lesions.

Effects of war aggression in Croatia on some forms and manifestations of breast cancer.

The aim of this study was to determine the differences in epidemiological and clinical manifestations of breast cancer in time of war in Croatia and in peacetime before and after the war, in the defined population of Pozesko-Slavonska County. The methods used in this study were the evaluation of relative predictive value of variables by means of chi 2-test and the analysis of variance, while the survival studies were tested by Long Rank test according to Kaplan-Meier analysis of survival. This work encompasses 660 patients who had breast cancer. The differences between three time periods were evaluated: the war period (1991-1995), and two control periods: before the war (1981-1990) and after the war (1996-2000). The patients were grouped by age, localization of tumor and survival. During the war period the patients were, on the average, 4.2 years younger than those who acquired the disease in control periods, and the mean age of patients was between 50 and 59 years (36.5% of patients). Although the difference in tumor distribution by sides (left or right breast) and quadrants was statistically significant (war period vs. control periods; p < 0.001), there was no statistically significant difference in the survival of patients according to the results of Kaplan-Meier analysis of localization of tumor (p > 0.05). The length of survival in terms of age of patients in time of surgical procedure was significantly different (p < 0.001). This study confirms the effects of war on some epidemiological and clinical manifestation of breast cancer in the defined population of Pozesko-Slavonska County.

Anthropological and clinical characteristics in adolescent women with dysmenorrhea.

The aim of this study was to examine the prevalence of dysmenorrhea in female adolescents and the influence of anthropological characteristics and lifestyle factors on menstrual pain. Two hundred and ninety seven girls from several elementary and secondary schools were interviewed about the presence of the menstrual pain, their age, height and weight, menarcheal age, menstrual cycles quality, smoking and sexual activity. There were 164 (55%) subjects with and one hundred and thirty three (45%) without dysmenorrhea. The adolescents with dysmenorrhea answered the questions about missing activities and taking pills for pain. No difference was observed between the girls with and the girls without dysmenorrhea in their chronological age, height, weight, menarcheal age, menstrual cycles quality, cigarette smoking and sexual activity. In the group of dysmenorrheic adolescents there was infrequent missing activities and bedrest, but missing school was observed in 22 percent and taking pills for pain was observed in 96 percent of the subjects. Young girls who experienced menstrual pain are good candidates for a prophylactic therapy, such as hormonal contraception. A replication of this study is needed for public health services in the future to improve the quality of life of the dysmenorrheic young women.

Insulin-like growth factor family and combined antisense approach in therapy of lung carcinoma.

BACKGROUND: Perturbation in a level of any peptide from insulin-like growth factor (IGF) family (ligands, receptors, and binding proteins) seems to be implicated in lung cancer formation; IGF ligands and IGF-I receptor through their mitogenic and anti-apoptotic action, and the mannose 6-phosphate/insulin-like growth factor II receptor (M6-P/IGF-IIR) possibly as a tumor suppressor. MATERIALS AND METHODS: To determine the identity, role, and mutual relationship of IGFs in lung cancer growth and maintenance, we examined IGF's gene (by RT-PCR) and protein (by immunohistochemistry) expression in 69 human lung carcinoma tissues. We also examined IGF-I receptor numbers (Scatchard analysis) and IGF-II production and release (by Western blot) in IGF-II/IGF-IR mRNA positive and negative lung carcinomas. Finally, the potential role of IGF-IR and IGF-II as growth promoting factors in lung cancer was studied using antisense oligodeoxynucleotides that specifically inhibit IGF-IR and IGF-II mRNA. RESULTS: Thirty-two tumors were positive for IGF-I, 39 for IGF-II, 48 for IGF-IR, and 35 for IGFBP-4 mRNA. Seventeen tumors were concomitantly positive for all four IGFs, whereas 34 were positive for IGF-II, IGF-IR, and IGFBP-4 mRNA. An elevated amount of IGF-II peptide was secreted into the growth medium of cell cultures established from five different IGF-II/IGF-IR mRNA positive lung cancer tissues. The cells also expressed elevated numbers of IGF-IR. Nine IGF-II-negative and 19 IGF-II-positive lung cancers of different stages were selected, and M6-P/ IGF-II receptor was determined immunohistochemically. Most of the IGF-II-negative tumors were strongly positive for M6-P/IGF-IIR. IGF-II-positive tumors were mostly negative for M6-P/IGF-II receptors. Antisense oligodeoxynucleotides to IGF-II significantly inhibited, by 25-60%, the in vitro growth of all six lung cancer cell lines. However, the best results (growth inhibition of up to 80%) were achieved with concomitant antisense treatment (to IGF-IR and IGF-II). CONCLUSION: Our data suggest that lung cancer cells produce IGF-IR and IGF-II, which in turn stimulates their proliferation by autocrine mechanism. Cancer cell proliferation can be abrogated or alleviated by blocking the mRNA activity of these genes indicating that an antisense approach may represent an effective and practical cancer gene therapy strategy.