Surgical management of massive cerebellar infarction.

Massive cerebellar infarction accounts for less than 2% of strokes. Unlike massive hemispherical infarctions, in pure cerebellar infarctions, the prognosis is better. This case report discusses, a 61 year old lady who presented with atrial fibrillation and a massive cerebellar infarction. Timely surgical intervention reversed the deterioration in neurological status. The indications for surgical management, based on review of the literature, is presented.     

Changes in selected biochemical parameters in the kidney and blood of the fish,Tilapia mossambica (Peters), exposed to heptachlor

Bulletin of Environmental Contamination and Toxicology -     

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in colorectal cancer.

Endoglin (CD105) has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor expression as possible prognostic markers in colorectal cancer. Surgical specimens from 150 patients with resected colorectal carcinomas were immunostained for endoglin, CD31 and vascular endothelial growth factor. Colorectal carcinoma cases consisted of 50 cases without lymph node metastases, 50 cases with only lymph node metastases and 50 cases with liver metastases (38 cases also had positive lymph nodes). Positively stained microvessels were counted in densely vascular foci (hot spots) at x 400 fields in each specimen. For vascular endothelial growth factor, intensity of staining was scored on a three-tiered scale. Results were correlated with other prognostic parameters. Endoglin demonstrated significantly more proliferating neoplastic microvessels than CD31 (31+/-10 vs 19+/-8/0.15 mm2 field, P<0.001). Low vascular endothelial growth factor expression within tumor cells was seen in 49 (33%) and high expression in 101 cases (67%). There was a positive correlation of endoglin, CD31 counts and vascular endothelial growth factor overexpression with the presence of angiolymphatic invasion and lymph node metastases (P<0.05). Only endoglin counts correlated significantly with liver metastases and positive vascular pedicle lymph nodes (P<0.05), while vascular endothelial growth factor showed significant correlation with the depth of invasion (P<0.01). Endoglin, by staining higher numbers of the proliferating vessels in colon carcinoma, is a more specific and sensitive marker for tumor angiogenesis than the commonly used panendothelial markers. Endoglin staining also showed prognostic significance with positive correlation with angiolymphatic invasion and metastases to lymph nodes and liver.     

In vitro combination treatment with perifosine and UCN-01 demonstrates synergism against prostate (PC-3) and lung (A549) epithelial adenocarcinoma cell lines.

PURPOSE: Antineoplastic agents often achieve antitumor activity at the expense of close to unacceptable toxicity. One potential avenue to improve therapeutic index might combine agents targeting distinct components of the same growth regulatory pathway. This might lead to more complete modulation of the target pathway at concentrations lower than those associated with limiting adventitious toxicities from either agent alone. The protein kinase antagonist UCN-01 is currently used in Phase I/II trials and has recently been demonstrated to inhibit potently PDK1. We have recently documented that the alkylphospholipid perifosine potently also inhibits Akt kinase (PKB) activation by interfering with membrane localization of Akt. This leads to the hypothesis that these two agents might act synergistically through distinct mechanisms in the PI3K/Akt proliferation and survival-related signaling pathway. EXPERIMENTAL DESIGN: The synergistic effects of UCN-01 and perifosine, on two cell lines (A-549 and PC-3), were examined using various long-term in vitro assays for cell growth, cell cycle distribution, clonogenicity, survival morphology, and apoptosis. Along with Western blotting experiments were performed to determine whether this synergistic combination of two drugs has significant effect on their downstream targets and on biochemical markers of apoptosis. RESULTS: After 72 h, perifosine at concentrations of 1.5 and 10 microM UCN-01 at 40 and 250 nM did not significantly affect the growth of PC-3 and A459 cells, respectively. However, in combination at the same respective individual concentrations (1.5 microM and 40 nM of perifosine and UCN-01, respectively, in PC-3 cells and 10 microM perifosine and 0.25 microM UCN-01 in the somewhat more resistant A549 cells), virtually complete growth inhibition of both the cell lines resulted. Supra-additive inhibition of growth was also demonstrated in independent clonogenic assays. Mechanistic studies in cell culture models suggest enhanced depletion of the S-phase population in cells treated by the combination. This correlated with enhanced inactivation of Akt along with activation of caspases 3 and 9 and poly(ADP-ribose) polymerase cleavage. Evidence of synergy was formally demonstrated and occurred across a wide range of drug concentrations and was largely independent of the order or sequence of drug addition. CONCLUSIONS: As the concentrations of UCN-01 and perifosine causing synergistic inhibition of cell growth are clinically achievable without prominent toxicity, these data support the development of clinical studies with this combination.     

SYNTHESIS OF THE RIGID ANALOGUES OF AN SSRI BENZENEPROPANAMINE

Several 1-(substituted phenoxy)-3-{[4-(4-trifluoromethyl) phenoxy] piperidin-1-yl} propan-2-ols (str.II) were prepared in a six-step reaction sequence starting from methylamine and ethyl acrylate and evaluated for antidepressant activity. The compounds were fully characterized by spectral and elemental analyses, and were tested for their effect on gross behavior, antireserpine and anorexigenic activity. No effect was observed on gross behavior and some of them showed fluoxetine like antireserpine and anorexigenic activity.     

Effect of Punarnavine,an Alkaloid from Boerhaavia diffusa,on Cell-Mediated Immune Responses and TIMP-1 in B16F-10 Metastatic Melanoma-Bearing Mice

Effect of Punarnavine on the cell-mediated immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of Punarnavine enhanced Natural Killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared to the metastatic tumor-bearing control. Production of cytokines such as IL-2 and IFN-γ were significantly enhanced by the administration of Punarnavine compared to the untreated metastatic tumor-bearing control. Peaks of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α were significantly lowered by Punarnavine administration compared to metastatic control. The level and expression of TIMP-1 was also enhanced by the administration of Punarnavine compared to metastatic tumor bearing control. These results indicate Punarnavine could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice.     

The effect of transport on the physiologic stability of neonates with ductal-dependent single-ventricle lesions

Objective: To compare the status of infants with hypoplastic left heart syndrome (HLHS) or pulmonary atresia-hypoplastic right heart (PA-HRH) before and following transport using the validated Transport Risk Index of Physiologic Stability (TRIPS) score.

Methods: In this retrospective review of infants with HLHS or PA-HRH transported to a Children’s Hospital by a pediatric transport team, an increase in TRIPS score (temperature, blood pressure, respiratory status, and response to stimuli) following transport was defined as deterioration. Statistical analyses included t-test (paired and independent), χ², and McNemar’s tests for comparisons between groups with and without deterioration and before and after transport.

Results: Our cohort [n?=?64; 39 (61%) HLHS and 25 (39%) PA-HRH] was predominantly female (61%), black (56%), and diagnosed antenatally (78%). Median transport time was 20 (10–30) min and age was?<12?h in 48 (75%) infants. TRIPS scores worsened after transport in 24 (37.5%) infants, due to temperature (n?=?10) or respiratory (n?=?7) dysregulation. Infants who deteriorated during transport had HLH more often (83 versus 48%) and lower pH [7.27 (0.12) versus 7.33 (0.07)]. HLH was significantly predictive of deterioration during transport [OR 5.60 (95% C.I. 1.18–26.62)].

Conclusions: The physiologic deterioration in a third of infants with single ventricle following short transports is intriguing and may have implications on their optimal place of birth.