Evaluation of the efficacy of adjuvant chemotherapy in patients with high-risk stage II colon cancer.

PURPOSE: This study aimed at comparing the disease-free survival (DFS) in high-risk TNM stage II colon cancer patients who had been subjected to adjuvant chemotherapy and TNM low-risk stage II patients who did not receive chemotherapy. METHODS: We retrospectively reviewed the medical records of stage II colon cancer patients between January 2006 and December 2011. High-risk patients were defined those with any colonic obstruction/perforation, mucinous histology, inadequate lymph node sampling, T4 disease, lymphatic/ vascular or perineural invasion, preoperatively elevated carcinoembryonic antigen (CEA) and high-grade tumor. All patients with high-risk features received adjuvant chemotherapy. RESULTS: There were 42 patients in the high-risk treatment group and 21 patients in the non-treatment (observation) group. There were no significant differences in terms of gender, tumor size, tumor localization, or the number of excised lymph nodes between the groups. The median follow- up time was 33.9 months in the treatment group and 29.3 months in the non-treatment group. Recurrence developed in 4 patients (6.3%), 3 of which were in the treatment group. DFS in both groups was statistically similar. CONCLUSION: Adjuvant chemotherapy in the high-risk patients resulted in similar DFS as that in the low-risk patients. Although the role of adjuvant chemotherapy for stage II colon cancer is unclear, it is rational to offer adjuvant chemotherapy to patients with high-risk stage II colon cancer.

Is there any relationship between imatinib mesylate medication and hypothalamic-pituitary-adrenal axis dysfunction?

BACKGROUND: Imatinib mesylate [tyrosine kinase (TK) inhibitor] is a novel medication in the treatment of chronic myelogenous leukaemia (CML). TK is also essential in hypothalamo-pituitary-adrenal (HPA) axis. PURPOSE: The aim of this study was to evaluate HPA axis in patients treated with imatinib. Twenty-five patients were included in this study. METHODS: Glucagon stimulation test (GST) and low-dose (1 microg) adrenocorticotropin test (LDSST) were used to assess the HPA gland axis. RESULTS: Seventeen (68%) subjects had impaired peak response when a cortisol cut-off value is accepted as 500 nmol/L. Twelve (48%) out of 17 subjects also failed to show a response to LDSST. Therefore, 12 patients (48%) were defined as HPA deficient. Only two of these 25 patients had morning serum cortisol < 200 nmol/l (7.22 microg/dl), and failed the GST and/or LDSST, indicating that the majority had partial glucocorticoid deficiency. If the cut-off presume for LDSST is from 500 to 600 nmol/l, 16 patients (64%) would have failed both the GST and LDSST. CONCLUSION: Our results indicate an increased prevalence of subclinical glucocorticoid deficiency in patients receiving imatinib mesylate for CML. Therefore under stressed conditions, such as intercurrent illness state, overt and untreated partial glucocorticoid deficiency in CML patients become life threatening.

Does imatinib mesylate therapy cause growth hormone deficiency?

OBJECTIVE: The purpose of this study was to determine whether or not imatinib mesylate therapy induces growth hormone deficiency (GHD). SUBJECTS AND METHODS: Seventeen patients with chronic myloid leukemia (CML) were enrolled in the study. The glucagon stimulation test (GST), and standard deviation scores (SDSs) of insulin-like growth fac- tor 1 (IGF-I) and insulin-like growth factor binding protein (IGFBP-3) were used to determine GHD. The L-dopa test was performed on those with IGF-I SDSs above the -1.8 cut-off level. RESULTS: Of the 17 patients in the study, 12 (70%) had severe GHD (serum GH level <3 microg/l after GST). IGF-I SDSs and IGFBP-3 SDSs were below -1.8 in 12 patients (70%) and below -0.9 in 10 subjects (58%). Four of the 5 remaining subjects with IGF-I SDS >-1.8 showed insufficient GH response to L-dopa stimulation. Nine subjects (52%) had both severe GHD based on GST response and IGF-I SDS below -1.8. If an IGF-I SDS cut-off value l<-3 were used,5 out of 17 subjects (30%) would be classified as GH deficient. These same patients also showed severe GHD based on GST response. CONCLUSIONS: The data showed that a large number of patients on imatinib mesylate therapy had GH deficiency. A study involving a larger number of patients with a matched control group is needed to confirm the present observations.

Psychopharmacology of pediatric obsessive-compulsive disorder: three case reports.

We present the treatment of three very young preschool patients (four- to five-year old) with obsessive-compulsive disorder (OCD). Two of the patients had severe ego-dystonic obsessions with sexual, aggressive, religious themes and forbidden thoughts, while the other one had contamination obsession and cleaning compulsions. Physical and neurological examination and laboratory work-up did not reveal any abnormalities. The symptoms resolved after sertaline monotherapy up to 50 mg/day and sertraline plus risperidone 0.5 mg/day (two cases) treatment. There is very limited data on the treatment of such young pediatric population of patients with OCD and, especially, the safety of using such psychotropic drugs in this special population.

Circulating ghrelin levels in obese women: a possible association with hypertension.

OBJECTIVE: The orexigenic hormone ghrelin induces weight gain by stimulating food intake. Ghrelin has been shown to modulate sympathetic activity, to exert vasodilative effects and to counterreact with leptin on both food intake and blood pressure. Of these two hormones, ghrelin levels are decreased in obesity, whereas leptin levels are increased. In this cross-sectional study, differences in serum ghrelin and leptin levels were examined in normotensive and hypertensive obese women. MATERIAL AND METHODS: Sixty-one normotensive and hypertensive women were classified according to the body mass indices as follows: (a) 18 healthy subjects with BMI 21.5-27.5 kg/m(2); (b) 22 normotensive subjects with BMI 30-47 kg/m(2); (c) 21 hypertensive obese subjects (BMI 30-48 kg/m(2)) with systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg. Anthropometric measurements including height, weight, BMI, waist and hip circumferences and blood pressure were recorded. The levels of ghrelin and leptin were determined in sera using the commercial ELISA kits. RESULTS: In normotensive obese subjects, ghrelin levels were significantly lower than in controls (0.21+/-0.13 vs 0.60+/-0.3 ng/mL), whereas hypertensive obese women had elevated ghrelin levels (0.64+/-0.36 ng/mL). Ghrelin concentration was decreased despite the presence of hypertension in the patients who had BMIs above 35 kg/m(2). Leptin levels were significantly higher in both normotensive and hypertensive obese groups (19.54+/-11.19 and 21.61+/-12.7 ng/mL, respectively) than in controls (7.61+/-3.3 ng/mL), and were not affected by the presence of hypertension in obese subjects. CONCLUSION: Ghrelin was positively associated with hypertension in obese women and this association was inversely influenced by the increase of BMI.

Advanced oxidation protein products in obese women: its relation to insulin resistance and resistin.

Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus (T2DM). Resistin, an adipocyte-secreted hormone, is thought to take a part in the development of insulin resistance and T2DM. The aim of this study was to characterise the changes in circulating levels of resistin and proinflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6 in diabetic and prediabetic obese patients and to explore their relationship to insulin resistance. Attempts were also made to see whether resistin levels are related to the degree of oxidative stress, as determined by the measurement of advanced oxidation protein products (AOPPs). The study groups consisted of obese diabetic (BMI: 30-42 kg/m(2), n=28) and prediabetic (BMI: 29-41 kg/m(2), n=23) women. Fourteen healthy women, with BMI in the range 21.5-25.5 kg/m(2), were taken as controls. Serum levels of TNF-a, IL-6, resistin, glucose, insulin and AOPPs were measured. Insulin resistance was calculated by the homeostasis model assessment (HOMA-IR). Diabetic and prediabetic obese patients had increases in serum resistin and TNF-alpha levels (P<0.01 and P<0.001, respectively). IL-6 levels in diabetic patients were significantly higher than in prediabetics (P<0.05). AOPP levels were also significantly higher in diabetics than prediabetics and controls (P<0.05 and P<0.001, respectively); and positively correlated with blood glucose. Insulin was significantly associated with circulating resistin and TNF-alpha. The development of insulin resistance may contribute to the elevation of circulating resistin or vice versa. Determination of AOPPs may be helpful for monitoring the impaired glucose metabolism in obesity.

Psychotic disorder in a case with Hallervorden-Spatz disease.

OBJECTIVE: Hallervorden-Spatz disease is a rare autosomal recessive condition, with early onset of predominantly extrapyramidal dysfunction. The symptoms of the disease are dystonia, rigidity, choreoathetosis, pyramidal signs, and intellectual decline. Recent genetic studies mapped the disease to chromosome 20p12.3-p13, and identified mutations in the pantothenate kinase gene. This report describes a childhood onset case of Hallervorden-Spatz disease with schizophreniform psychotic symptoms. Former reports about the psychiatric comorbidity generally included depressive disorder. METHOD: A single case report. RESULTS: A 14-year-old boy with Hallervorden-Spatz disease presented a psychotic episode with prominent auditory hallucinations. Symptoms were relieved after neuroleptic treatment. CONCLUSION: To the authors' knowledge, this is the first published report of the disease with psychotic symptoms. The contribution of basal ganglia, with their wide projections, to the emergence of psychotic symptoms was discussed.

Effect of exogenous melatonin on ethanol-induced changes in Na(+),K(+)- and Ca(2+)-ATPase activities in rat synaptosomes.

In the present study, the effects of acute ethanol (EtOH) toxicity and of exogenous melatonin (MLT) on this toxicity were examined by measuring membrane-bound ATPases and acetylcholinesterase activities in rat synaptosomal membranes. The concentrations of plasma alpha-tocopherol and adrenal ascorbic acid (AA) were also measured. Synaptosomal Na(+),K(+)-ATPase and Ca(2+)-ATPase activities were significantly depressed in acute EtOH-intoxicated rats compared with controls, while acetylcholinesterase activity remained unaltered. Pretreatment with MLT (10 mg/kg) prior to acute EtOH administration prevented EtOH-induced inhibition of ATPases. Adrenal AA and plasma alpha-tocopherol levels were also depressed regardless of MLT pretreatment. MLT treatment alone affected neither membrane-bound enzyme activities nor tissue and blood levels of vitamins C and E. It is concluded that acute EtOH intoxication disturbs neural transport functions through the membrane-bound ATPase activity depression. Reduced AA and alpha-tocopherol levels may contribute to the neurodegenerative effects of EtOH. However, pretreatment with a high dose of MLT before EtOH administration may be beneficial to prevent EtOH-induced toxicity on ATPase-mediated neural transport functions.

The effects of acute melatonin and ethanol treatment on antioxidant enzyme activities in rat testes.

The pineal hormone melatonin (N -acetyl, 5-methoxytryptamine) was recently accepted to act as an antioxidant under both in vivo and in vitro conditions. In this study, we examined the possible preventive effect of melatonin on ethanol-induced lipid peroxidation in rat testes. Thirty-seven male Wistar albino rats, 5.5--6 months old, were randomly divided into four groups (9--10 animals in each). The first group (control animals) received 4% ethanol at similar intervals to the experimental groups to equalize the stress effect. The second group received only melatonin i.p. 7 mg kg(-1)bw three times over 1.5 h intervals. The third group received only 30% alcohol 3 g kg(-1)bw twice daily. The fourth group were treated with melatonin and ethanol according to the above protocol, melatonin injections preceding ethanol treatments. The product of lipid peroxidation, malondialdehyde (MDA) and antioxidant enzymes, superoxide dismutase (Cu--Zn SOD), glutathione peroxidase (GPx) and catalase (CAT) were measured in the post-mitochondrial fraction of the testes. MDA levels were significantly increased due to acute ethanol intoxication. GPx activity was higher in the three experimental groups than the control levels. The activity of CAT was increased significantly in the melatonin plus ethanol-treated group but the other groups appeared not to be influenced by acute ethanol treatment. Cu--Zn SOD activity remained unaltered. These results suggest that antioxidants may be a protective agent for the testicular injury caused by ethanol consumption.

Evaluation of leukocyte arylsulfatase-A activity in patients with breast cancer and benign breast disease.

This study was planned to evaluate the feasibility of using the assay of leukocyte arylsulfatase-A (AS-A) activity as a non-invasive diagnostic tool in patients with benign and malignant breast disease. The leukocyte AS-A activity of a total of 81 women was analyzed, including 28 healthy women, 29 women with benign breast disease (BBD) and 24 patients with primary breast cancer (BC). The mean leukocyte AS-A activity in patients with BBD was slightly higher (14.3%) that observed in the healthy subjects, but the difference was not statistically significant. In patients with BC the enzyme activity was significantly higher than in the healthy subjects (60.3%, P<0.05) and in the benign group (40.2%, P<0.05). In addition, since no significant differences have been observed between premenopausal patients and their controls, it is suggested that the measurement of leukocyte AS-A activity may not be a reliable test for differential diagnosis of benign and malignant proliferation in mammary glands due to the possible interfering effect of gonadal hormones on AS-A activity. In contrast, since peri- and postmenopausal BC patients have negligible or no gonadal activity function, the elevation in the activity of leukocyte AS-A in these age groups of patients may only be expected to originate from malignant proliferation. Based on our results, it is concluded that in patients in whom high leukocyte AS-A activities were observed the possibility of the presence of malignancy might also be high. Therefore, this test might be valuable as a non-invasive biochemical technique in combination with other established markers for the identification of masses in the breast.

Sex-dependent changes in blood-brain barrier permeability and brain NA(+),K(+) ATPase activity in rats following acute water intoxication.

To understand the increased susceptibility of the development of serious complications to hypoosmotic hyponatremia in young females, we examined the resistance of blood brain barrier (BBB) permeability to water along with the synaptosomal Na(+),K(+)ATPase activity in both sexes of rats during acute water intoxication. Four groups of rats were used: Group I and II were normal female and male rats injected with only Evans-blue. Group III and IV were water intoxicated female and male rats respectively. BBB permeability in female rats was found to be increased following acute water intoxication. In contrast, synaptosomal Na(+),K(+)ATPase activities in both water intoxicated male and female rats were found significantly lower than those in control rats. But inhibition in enzyme activity in synaptosomes from water intoxicated female rats was more pronounced than those of corresponding male rats. Our results concluded that female sex steroids may be responsible for the highly significant decrease in synaptosomal Na(+),K(+)ATPase activity and increased BBB permeability in female rats following water intoxication.

Effects of streptozotocin-induced diabetes and pentylenetetrazol-induced seizure on brain cortex (Ca2+)ATPase activity in rats.

The aim of the present study was to obtain information about the effects of pentylenetetrazol-induced status epilepticus (SE) and streptozotocin-induced diabetes on brain cortex Ca(2+)ATPase activity. Treatment with pentylenetetrazol (PTZ) and streptozotocin (STZ) to rats resulted in significant decrease in brain cortex Ca(2+)ATPase activity as compared with controls. However, PTZ-treated diabetic rats had a slight but non-significant decrease in enzyme activity. Treatment with PTZ caused a more pronounced effect in inhibiting enzyme activity than that of treatment with STZ. Our results concluded that reduced brain cortex Ca(2+)ATPase activity following PTZ and STZ treatments to rats, may be an initial biochemical lesion which triggers a sequence of events which may culminate in cell death.

Evaluation of the effect of low-dose oral theophylline therapy on some bone turnover markers and serum prolidase I activity in mild asthmatics.

Hypercalcemia and hypercalciuria observed both in humans and in animals who were on long-term theophylline therapy, prompted us to investigate whether oral theophylline treatment at optimal doses causes any adverse side effects on bone metabolism in mild asthmatics. Therefore, serum osteocalcin (BGP) and total alkaline phosphatase (TALP, EC 3.1.3.1) as bone formation markers, serum prolidase I (EC 3.4.13.9) activity as a marker for collagen metabolism, urinary deoxypyridinoline (Dpd), hydroxyproline (Hyp) and fasting urinary calcium as bone resorption markers, were measured in 18 mild asthmatics who had been treated with theophylline over 1-10 years. Among measured bone turnover markers, BGP, TALP, and Hyp levels were found to be increased in mild asthmatics; and BGP showed the greatest percent mean increase (98%) over the healthy subjects. However, these increments did not exceed the upper reference limits. Serum prolidase I activity was also increased in mild asthmatics receiving theophylline. Our results indicate that theophylline therapy at optimal doses may not exert adverse side effects on bone homeostasis, but patients receiving supratherapeutic doses of theophylline should be under close examination in order to predict future bone mass status.

Brain cortex Na(+)-K+ ATPase activities in streptozotocin-diabetic and pentylenetetrazol-epileptic rats.

The aim of this study was to investigate the brain cortex Na(+)-K+ ATPase activity in rats made diabetic by streptozotocin and epileptic by pentylenetetrazol. Streptozotocin diabetic rats showed a significant decrease in brain cortex Na(+)-K+ ATPase activity whereas the pentylenetetrazol treatment caused no significant change in enzyme activity. On the other hand, no brain cortex Na(+)-K+ ATPase activity could be detected in all the diabetic rats treated with pentylenetetrazol. Our results concluded that reduced Na(+)-K+ ATPase activity in streptozotocin diabetic rats may contribute to the pathogenesis of metabolic complications of the central nervous system, and that the undetectable enzyme activity in diabetic convulsing rats may result from considerable damage or necrosis of brain tissue during pentylenetetrazol seizures.

Evaluation of the changes in serum lipid profile and ferritin concentrations in relation to body ascorbic acid status in healthy pre- and postmenopausal women.

The aim of this work was to study the relationship between body ascorbic acid (AA) status and serum lipid profile and ferritin concentrations in healthy pre- and postmenopausal women. The mean leukocyte and plasma ascorbate values in postmenopausal women were found to be significantly low but within acceptable ranges as compared to premenopausal women. According to these results, plasma and leukocyte AA concentrations decreased after the cessation of ovarian hormone production. In addition, significant increases in total cholesterol, triglyceride and LDL-cholesterol but a significant decrease in HDL-cholesterol were observed in postmenopausal women as compared to premenopausal women. A close positive relationship was found between plasma and leukocyte AA and body iron status in postmenopausal women. The findings were prominent especially in the subgroup of postmenopausal women with low body AA status. Thus, it is concluded that women having low body AA concentrations might have a predisposition for iron depletion.

Relationship of some endogenous sex steroid hormones to leukocyte arylsulphatase A activities in pre- and postmenopausal healthy women.

This study was planned to investigate whether the physiological variations in endogenous gonadal steroid hormones during fertile period to menopause might affect the Arylsulphatase A (ARS-A) activities in leukocytes in healthy women. In premenopausal women, means of the leukocyte ARS-A activity were significantly highest at ovulatory phase, and lowest at early follicular phase. In contrast, the mean leukocyte ARS-A activity in postmenopausal women was approximately equivalent to the mean leukocyte enzyme in cycling women at early follicular phase in whom the lowest enzymatic activity was observed. The results of our study, therefore, concluded that gonadal steroid released physiologically into the bloodstream might be expected to stimulate the lysosomal system thereby leading to an enhancement in leukocyte ARS-A activity.

Comparative effects of chronic administration of some psychotropic drugs on rat brain cortex acetylcholinesterase activity.

The response of central cholinergic neurotransmission to the chronic administration of some psychotropic drugs to rats was investigated using brain acetylcholinesterase activity as a neurochemical marker for cholinergic neurons. Rats were divided into four groups. Three experimental groups were given chlorpromazine, amitriptyline, or diazepam respectively, for a period of 30 days; and the control group received physiological saline only. Long-term treatment of chlorpromazine and amitriptyline resulted in significant increases in rat brain cortex enzyme activity, whereas only a slight increase was observed in the diazepam-treated group. These results indicate that the chronic treatment with some psychotropic drugs causes changes in central cholinergic transmission.

Leukocyte arylsulphatase A activity in acute leukemia.

Lysosomal arylsulphatase A of peripheral leukocytes from patients with acute lymphoblastic and myeloblastic leukemia and from healthy subjects, were studied. Arylsulphatase A activity of both types of leukemic cells was significantly higher than those of cells from healthy subjects. From our present observations, it can be concluded that estimation of lysosomal arylsulphatase A of leukocytes, may be of value clinically as a biochemical assay which can serve to demonstrate the presence of malignancy.