Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treated by total laryngectomy

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in laryngeal squamous cell carcinomas. Ki-67 labeling was quantified in 63 laryngeal squamous cell carcinomas by counting at least 1,000 tumor cells in the most immunoreactive area in each sample, and the Ki-67 labeling index was calculated as a percentage. The antigen expression was compared with clinical factors, histopathological grading and prognosis. The Ki-67 mean proliferation index for all patients was 25.44% ( range, 2–75%). A significant correlation was found between Ki-67 mean proliferation index and patient age (P<0.05), T-stage (P<0.05), nodal metastasis (P=0.001) and recurrence (P<0.001). There was no significant association between the Ki-67 mean proliferation index and tumor site or histologic grade. A univariate analysis showed that the Ki-67 labeling index >21% (P<0.001), T-stage (P<0.001) and nodal metastasis (P=0.001) are determinants of recurrence. In the multivariate analysis, the Ki-67 labeling index >21% (P<0.001), T-stage (P<0.001) and nodal metastasis (P<0.05) were independent predictors of recurrence. Kaplan-Meier plots of survival in patients with Ki-67 values above and below the median (21%) of the general study population showed that a high Ki-67 labeling index correlated with a shorter disease-free survival (P<0.0001). The analysis of the Ki-67 labeling index at the time of initial surgery may be a powerful prognostic marker for patients with laryngeal squamous cell carcinoma and may be useful for selecting subgroups of patients who should be treated with more aggressive therapies.     

Cord blood cardiac troponin I as an early predictor of short-term outcome in perinatal hypoxia

BACKGROUND: In most perinatal-hypoxia survivors, myocardial dysfunction can be reversed with appropriate inotropic support and oxygenation. The main problem related to outcome is cerebral damage. OBJECTIVE: We tested the hypothesis that cardiac troponin I (cTnI), a known marker of myocardial injury, is also an early predictor of severity of cerebral damage and mortality in intrauterine hypoxia. METHODS: Venous and arterial cord blood samples were collected at delivery from 54 consecutive newborns with hypoxic-ischemic encephalopathy and from 50 consecutive healthy controls. Arterial blood gas analysis was performed and levels of cTnI, creatine kinase and creatine kinase-MB in venous cord blood were measured. The same serum parameters were also measured on the 3rd and 7th day of life. RESULTS: Infants with hypoxia had a significantly higher cord blood cTnI levels than controls (p < 0.0001). Cord blood and 3rd and 7th day serum cTnI values showed a significant increase with severity of HIE (p < 0.0001). In non-survivors cord blood cTnI levels were significantly higher than the survivors (5.9 ng/ml, range 2.1-12.8, and 1.6 ng/ml, range 0.4-5.8, respectively; p < 0.0001). Receiver-operator curve analysis revealed cord cTnI as the most sensitive factor for predicting early death (area under curve = 0.956; SE: 0.028; 95% CI: 0.9-1.01). Cord blood cTnI of 4.6 ng/ml was identified as the optimal cut-off level for predicting serious risk of early mortality. CONCLUSION: The results suggest that significant elevation of cord cTnI is an excellent early predictor of severity of hypoxic-ischemic encephalopathy and mortality in term infants.     

Serum insulin-like growth factor 1 and growth hormone levels of hypoxic-ischemic newborns

A number of growth factors, their binding proteins, and their receptors have been shown to be induced in the hypoxic-ischemic (HI) brain. In this prospective study, we aimed at determining the levels of insulin-like growth factor 1 (IGF-1), growth hormone (GH), and cortisol in HI babies and at identifying whether they differ from the levels of control infants. The serum IGF-1 levels were measured after the first 12-24 h of life, and the measurements were repeated on the 5th and 10th days of life for babies with HI encephalopathy (n = 18) and on the 10th day of life for controls (n = 19). Blood samples for measurement of cortisol and GH from both HI and control groups were collected after the first 12-24 h of life. There were 11 babies in the mild-to-moderate (stages I and II) group and 7 babies in the severe (stage III) group according to Sarnat and Sarnat. The IGF-1 levels of the HI group measured after 12-24 h [78.5 +/- 27.9 (range 9-123.4) ng/ml] and on the 10th day [72.2 +/- 36.8 (range 29.7-159.2) ng/ml] of life were statistically significantly lower than the IGF-1 levels of the control group [121.5 +/- 50.4 (range 74.4-280.5) ng/ml and 133.1 +/- 34.4 (range 65.9-202) ng/ml, respectively] (p = 0.002 and p = 0.001, respectively). But there was no statistically significant difference between mild-to-moderate HI group and severe HI group in terms of IGF-1 levels after 12-24 h and 5 and 10 days of life (p > 0.05). Also there was no statistically significant difference in IGF-1 values after the first 12-24 h and after 10 days of life between HI subjects who died or survived (p > 0.05). The GH levels of the HI group after the first 12-24 h of life [34.6 +/- 32.3 (range 0.1-120) mIU/l] were statistically significantly higher than those in the control group [10.4 +/- 4.5 (range 3.7-16.9) mIU/l] (p = 0.005). There was no statistically significant difference in the serum cortisol levels between HI and control groups after the first 12-24 h of life [18.7 +/- 17.0 (range 1.6-65.1) microg/dl vs. 10.8 +/- 5.4 (range 3.0-23.2) microg/dl] (p > 0.05). No statistically significant correlation was found between IGF-1 levels and GH and cortisol levels of the HI encephalopathy group [r = -0.113 (p > 0.05) and r = 0.108 (p > 0.05), respectively]. In conclusion, this study showed decreased levels of serum IGF-1 and increased levels of GH which may be secondary to serum IGF-1 influx from the circulation to the brain as a protective mechanism or may be due to some cytokines which alter the GH/IGF axis, inhibit the action of IGF-1, and stimulate IGF-binding protein 1.     

Effect of fludarabine on leukocyte functions

BACKGROUND: Fludarabine induces leukemic cell apoptosis and is highly efficient in chronic lymphocytic leukemia. However, fludarabine therapy causes severe leukopenia. Leukocyte myeloperoxidase (MPO) catalyzes the formation of HOCl, and this is the main microbicidal function in phagocytes. The aim of our study was to evaluate the effect of fludarabine on leukocytes, i.e. their degranulation capacity, MPO activity and HOCl production. METHODS: Peripheral blood leukocytes were incubated for 48 h with fludarabine. Degranulation was measured using a flow-cytometric method. MPO activity and HOCl production were measured spectrophotometrically. RESULTS: The degranulation capacity of fludarabine-treated leukocytes was significantly elevated compared to untreated controls. MPO activity and HOCl production were also increased in parallel. A possible direct activating effect of fludarabine was tested on the MPO activity of HL60 cells. Fludarabine did not affect MPO activity at concentrations ranging from 10 microM to 2 mM. CONCLUSION: Fludarabine had no inhibitory effect on the microbial killing of leukocytes.     

Doppler sonographic indices in diagnosing the nutcracker phenomenon in a hematuric adolescent

Compression of the left renal vein between the aorta and the superior mesenteric artery, known as the nutcracker phenomenon, may cause gross or microscopic hematuria, pain in the flank, proteinuria, or a combination of these symptoms. We report the case of a hematuric adolescent diagnosed with a high index of suspicion by noninvasive Doppler sonography using the diagnostic indices of Doppler sonography established for adults with hematuria. Compression of the patient's left renal vein at the aortomesenteric portion and dilatation at the hilar portion were visualized by magnetic resonance angiography, which verified the diagnosis.     

Effects of venlafaxine on ethanol withdrawal syndrome in rats

The present study was designed to investigate the effects of venlafaxine, a serotonin and noradrenaline reuptake inhibitor (SNRI), on ethanol withdrawal syndrome in rats. Adult male Wistar rats (187-319 g) were used for the study. Ethanol (7.2%, v/v) was given to rats by a liquid diet for 21 days. Control rats were pair-fed an isocaloric liquid diet containing sucrose as a caloric substitute to ethanol. Venlafaxine (5, 10, 20 and 40 mg/kg) and saline were injected to rats intraperitoneally just before ethanol withdrawal. After the 2nd, 4th and 6th hour of ethanol withdrawal, rats were observed for 5 min, and withdrawal signs that included locomotor hyperactivity, agitation, stereotyped behaviour and wet dog shakes were recorded or rated. A second series of injections was given at the 6th hour after the first one, and rats were then tested for audiogenic seizures. Venlafaxine produced some inhibitory effects on locomotor hyperactivity, stereotypic behaviours and wet dog shakes. However, a two-way anova of the data did not indicate any significant effect. It reduced the incidence of the audiogenic seizures at the 6th hour of ethanol withdrawal. Venlafaxine (20 mg/kg) also prolonged the latency of the seizures significantly. Our results suggest that acute venlafaxine treatment has limited beneficial effects on ethanol withdrawal syndrome in rats.     

Intracranial venous thrombosis after hypoxic-ischemic brain insult in two newborns: could low serum carnitine levels have contributed?

Sinovenous thrombosis is a definite cause of mortality or morbidity in newborns. Perinatal hypoxia is one of the well known risk factors. Two term newborns were diagnosed to have cerebral venous thrombosis after a hypoxic-ischemic insult. They were later found to have carnitine deficiency. Both of the patients died. Carnitine was previously shown to have inhibitory effects on thrombogenesis in experimental studies. The possible contribution of carnitine in thrombogenesis was discussed.