Spontaneous intracranial meningioma bleeding: clinicopathological features and outcome

OBJECT: The aim of this study was to determine the clinicopathological features of patients with intracranial bleeding from unsuspected meningioma and to relate these data to surgery-related outcome. METHODS: The authors report on two cases in which hemorrhage of an unsuspected meningioma occurred in the tentorial ridge and in the falx, and they discuss the details of 143 cases described in the literature. A bleeding propensity index of the meningioma, related to the patient's age, sex, and the lesion's intracranial location and histological type was computed as a ratio between the frequencies of bleeding meningioma and all meningiomas. This was tested by independent samples t-test for proportions. A chi-square test was used to determine the correlations between several variables: location and type of bleeding; survival and type of bleeding; and consciousness and survival. Increased bleeding tendency was found to be associated with two age groups (< 30 years and > 70 years), convexity and intraventricular locations, and fibrous meningiomas. The overall mortality rate documented in cases of bleeding meningiomas was 21.1% (13.9% in the computerized tomography [CT] scanning era), and that in surgically treated cases was 9.5% (7.5% in the CT scanning era). The overall major morbidity rate was 36% (33.8% in the CT scanning era). Overall 96.2% of conscious patients survived after their meningiomas spontaneously hemorrhaged. In patients who were unconscious before surgery, overall mortality rate was 74.1%, and that in surgically treated cases was 46.2%. CONCLUSIONS: The mortality rate in preoperatively conscious patients (those in whom acute deterioration and irreversible brain damage were prevented by early diagnosis and definitive surgery) was similar (< 3% in the CT scanning era) to that documented in cases in which meningiomas did not bleed. In contrast, the associated morbidity rates were much higher. One-stage total removal of the hemorrhagic meningioma and hematoma is the treatment of choice in such patients.     

Isoflurane inhibits cardiac myocyte apoptosis during oxidative and inflammatory stress by activating Akt and enhancing Bcl-2 expression

BACKGROUND: Volatile anesthetics attenuate apoptosis. The underlying mechanisms remain undefined. The authors tested whether isoflurane reduces apoptosis in cardiomyocytes subjected to oxidative or inflammatory stress by enhancing Akt and B-cell lymphoma-2 (Bcl-2). METHODS: Adult and neonatal rat ventricular myocytes and atrial HL-1 myocytes were exposed to hypoxia, hydrogen peroxide, or neutrophils with or without isoflurane pretreatment. The authors assessed cell damage and investigated apoptosis using mitochondrial cytochrome c release, caspase activity, and TUNEL assay. They determined expression of phospho-Akt and Bcl-2 and tested their involvement by blocking phospho-Akt with wortmannin and Bcl-2 with HA14-1. RESULTS: Isoflurane significantly reduced the cell damage and apoptosis induced by hypoxia, H2O2, and neutrophils. Isoflurane reduced hypoxia-induced mitochondrial cytochrome c release in HL-1 cells by 45 +/- 12% and caspase activity by 28 +/- 4%; in neonatal cells, it reduced caspase activity by 43 +/- 5% and TUNEL-positive cells by 50 +/- 2%. Isoflurane attenuated H2O2-induced caspase activity in HL-1 cells by 48 +/- 16% and TUNEL-positive cells by 78 +/- 3%; in neonatal cells, it reduced caspase activity by 30 +/- 3% and TUNEL-positive cells by 32 +/- 7%. In adult cardiomyocytes exposed to neutrophils, isoflurane decreased both mitochondrial cytochrome c and caspase activity by 47 +/- 3% and TUNEL-positive cells by 25 +/- 4%. Isoflurane enhanced phospho-Akt and Bcl-2 expression. Wortmannin and HA14-1 prevented the action of isoflurane (53 +/- 8% and 54 +/- 7% apoptotic cells vs. 18 +/- 1% without blockers). CONCLUSIONS: Isoflurane protects cardiomyocytes against apoptosis induced by hypoxia, H2O2, or activated neutrophils through Akt activation and increased Bcl-2 expression. This suggests that a reduction in apoptosis contributes to the cardioprotective effects of isoflurane.     

Superoxide dismutase activity in colostrum, transitional and mature human milk

Colostrum and mature human milk are rich sources of nutrients and contain biologically active molecules that are essential for specific antioxidant functions. The aim of the present study was to determine the activity of copper, zinc superoxide dismutase (CuZnSOD) and manganese superoxide dismutase (MnSOD) activity in different phases of lactation. Specific enzyme activity was determined in colostral milk (3rd-5th days after delivery), and in mature milk in the third week (15-20 days), and the fourth and seventh months of lactation. In the third week of lactation, the activity of CuZnSOD and MnSOD was significantly higher in comparison to the colostral phase. In the fourth month of lactation, the activity of both enzymes was suppressed, while in the seventh month of lactation the MnSOD activity was increased, and the CuZnSOD activity was not significantly changed. These findings show that the activities of superoxide dismutases significantly change during different phases of lactation.     

TP53, Bcl-2 and growth hormone receptor expression in cutaneous squamous cell carcinoma

The incidence and prevalence of premalignant and malignant skin lesions including squamous cell carcinoma (SCC) of the skin are increasing worldwide. The aim of the study was to determine TP53, Bcl-2 and growth hormone receptor (GHR) expression in SCC and to investigate relative importance of these proto-oncogenes in its biological behavior. Expression of TP53, Bcl-2 and GHR was determined by immunohistochemistry in 27 SCC specimens and adjacent perilesional skin. The relative proportion of immunoreactive cells was counted with semiquantitative method. TP53 positivity was detected in 24 (89%), Bcl-2 in 18 (67%) and GHR in 25 (93%) of 27 SCC specimens investigated. In comparison with perilesional skin, TP53 and GHR positivity was significantly increased, and Bcl-2 positivity significantly decreased in SCC. Increased TP53 expression in SCC lesions implies that Tp53 mutation is an early and crucial event in its development. Increased GHR expression suggests a role of growth hormone in the development of SCC.     

Significance of transvaginal Doppler ultrasonography for detection of malignant gestational trophoblastic disease

Transvaginal Doppler ultrasonography has an important role in detecting and confirming the gestational trophoblastic disease (GTD). It can also be helpful in early detection of the malignant cases of GTD such as the invasion and protrusion of trophoblastic tissue into the uterine wall. Ultrasonographic picture of the malignant GTD is also specific for the presence of prominent zones of vasculavization in the peritrophoblastic tissue, as well as in the uterine tissue in which malignant GTD is developed. Resistance Index (RI) values were measured at the level of blood vessels of peritrophoblastic tissue and of suspected zones in the uterine tissue to detect neovascularization, which followed the malignant process. Theca luteal cysts were often detected by Transvaginal Doppler ultrasonography.     

Ethnic differences in the association of factor V Leiden mutation and the C677T methylenetetrahydrofolate reductase gene polymorphism with preeclampsia

OBJECTIVE: This case-control study evaluates the association of the factor V Leiden mutation with preeclampsia and potential synergistic effects of the MTHFR-677T and factor V Leiden mutations with regard to disease risk in two different ethnic populations. STUDY DESIGN: 198 women and their 143 newborns from Germany/Croatia and Indonesia with normal pregnancy or preeclampsia participated in the study. The factor V Leiden mutation was determined by direct sequencing and the MTHFR genotype by a PCR-based RFLP method. RESULTS: The factor V Leiden mutation is rare in Indonesians. In Germans/Croatians, the frequency of the mutation was significantly increased in mothers with preeclampsia compared to controls. No disease association was found for combined factor V Leiden/MTHFR-677T genotypes on the maternal and fetal level. CONCLUSIONS: Our results underline the need for a clear distinction of ethnicity in association studies of functional gene polymorphisms. They further support the concept of preeclampsia as a complex disease with variable contributions of disease genes in different ethnic groups.     

Differential regulation of basolateral Cl-/HCO3- exchangers SLC26A7 and AE1 in kidney outer medullary collecting duct

SLC26A7 is a recently identified Cl(-)/HCO(3)(-) exchanger that co-localizes with AE1 on the basolateral membrane of Alpha intercalated cells (A-IC) in outer medullary collecting duct (OMCD). The purpose of these studies was to determine whether AE1 and SLC26A7 are differentially regulated in OMCD in pathophysiologic states. Toward this end, the expression and regulation of AE1 and SLC26A7 was examined in water deprivation, a condition known to increase the osmolality of the medulla. Rats were subjected to 3 d of water deprivation while having free access to food. Northern hybridizations demonstrated that in the outer medulla, the mRNA expression of SLC26A7 increased by approximately 300% (P < 0.01 versus control; n = 3), whereas the expression of AE1 decreased by approximately 50% (P < 0.05 versus control, n = 3) in water-deprived rats. Immunoblot analysis studies demonstrated that in the outer medulla, SLC26A7 abundance increased by approximately 3.5-fold (P < 0.02 versus control; n = 3), whereas the AE1 abundance decreased by approximately 55% (P < 0.05 versus control) in water deprivation. The expression of SLC26A7 remained unchanged in the kidney cortex and stomach in water deprivation, indicating the specificity of SLC26A7 upregulation in outer medulla. In situ hybridization indicated the exclusive expression of SLC26A7 in the outer medulla and double immunofluorescence labeling confirmed the co-localization of AE1 and SLC26A7 on the basolateral membrane of A-IC cells in OMCD. It is concluded that AE1 and SLC26A7 are differentially regulated in OMCD in water deprivation. On the basis of these results and previous functional studies indicating the activation of SLC26A7 activity by high osmolality, it is proposed that SLC26A7 may play an important role in bicarbonate reabsorption and or cell volume regulation in OMCD (specifically under hypertonic conditions).     

Functional dissociation between serotonergic pathways in dorsal and ventral hippocampus in psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition in rats

Altered hippocampal function and brain serotonin activity are implicated in the development and symptoms of schizophrenia. We have previously shown that lesions of the median raphe nucleus, but not the dorsal raphe nucleus, produced a marked enhancement of locomotor hyperactivity induced by phencyclidine and disruption of prepulse inhibition. The dorsal and ventral hippocampus receive serotonin projections predominantly from the median raphe nucleus and dorsal raphe nucleus, respectively. Therefore, we investigated the effect of local lesions of serotonin projections into the dorsal and ventral hippocampus on psychotomimetic drug-induced locomotor hyperactivity and prepulse inhibition. Male Sprague-Dawley rats were anaesthetized with pentobarbitone and stereotaxically microinjected with 5 microg of the serotonergic neurotoxin 5,7-dihydroxytryptamine into either the dorsal or the ventral hippocampus. Two weeks after surgery, dorsal hippocampus-lesioned rats showed a 100% enhancement of the locomotor hyperactivity caused by phencyclidine treatment and a slight but significant reduction of the effect of amphetamine. Prepulse inhibition was significantly disrupted in lesioned rats and serotonin levels in the dorsal hippocampus were reduced by 80%. Rats with lesions of the ventral hippocampus showed 85% depletion of serotonin and partial disruption of prepulse inhibition, but no significant changes in the effect of phencyclidine or amphetamine. These results suggest that serotonin projections from the median raphe nucleus to the dorsal hippocampus play an important role in locomotor hyperactivity and prepulse inhibition in rats, animal models of aspects of schizophrenia. This suggests that these serotonin projections may be involved in the pathophysiology of schizophrenia symptomology.     

Muscle force and muscle torque in humans require different methods when adjusting for differences in body size

Different methods for adjusting muscle strength (S) to normalise for differences in various estimates of body size [such as body mass (m) or, infrequently, some other anthropometrical measurements] have been either proposed or applied when presenting the results of muscle function tests in various medical, ergonomic, and sport related studies. However, the fact that the relationship between S and body size may differ when muscle torque (measured using a standard isokinetic apparatus) and muscle force (measured using a dynamometer) are recorded has not been taken into account. To address this problem, we tested both muscle force and muscle torque under isometric conditions in six different muscle groups. The relationship assumed between S and m was S=k·m ^b and, according to a simple mechanical model based on geometrical similarity we developed, the exponential parameter b would be expected to equal 1.00 and 0.67 for torque and force, respectively. The experimentally obtained values for the parameter b were higher for muscle torque than for muscle force in five out of the six muscle groups tested (P=0.068; Wilcoxon matched pairs test). Despite a relatively wide scatter, the mean (SD) values were also close to those predicted, being b=0.67 (0.19) (corresponding to the allometric scaling method) and b=1.02 (0.34) (corresponding to the ratio standards method) for muscle force and for muscle torque, respectively. Therefore, we concluded that the ratio standards and allometric scaling should be employed to adjust S for body size when muscle torque and muscle force, respectively, are tested. Electronic Publication