Cell domain-dependent changes in the glutamatergic and GABAergic drives during epileptogenesis in the rat CA1 region

An increased ratio of the glutamatergic drive to the overall glutamatergic/GABAergic drive characterizes the chronic stage of temporal lobe epilepsy (TLE), but it is unclear whether this modification is present during the latent period that often precedes the epileptic stage. Using the pilocarpine model of TLE in rats, we report that this ratio is decreased in hippocampal CA1 pyramidal cells during the early phase of the latent period (3–5 days post pilocarpine). It is, however, increased during the late phase of the latent period (7–10 days post pilocarpine), via cell domain-dependent alterations in synaptic current properties, concomitant with the occurrence of interictal-like activity in vivo . During the late latent period, the glutamatergic drive was increased in somata via an enhancement in EPSC decay time constant and in dendrites via an increase in EPSC frequency and amplitude. The GABAergic drive remained unchanged in the soma but was decreased in dendrites, since the drop off in IPSC frequency was more marked than the increase in IPSC kinetics. Theoretical considerations suggest that these modifications are sufficient to produce interictal-like activity. In epileptic animals, the ratio of the glutamatergic drive to the overall synaptic drive was not further modified, despite additional changes in synaptic current frequency and kinetics. These results show that the global changes to more glutamatergic and less GABAergic activities in the CA1 region precede the chronic stage of epilepsy, possibly facilitating the occurrence and/or the propagation of interictal activity.     

Acral myxoinflammatory fibroblastic sarcoma: a report of two cases

Acral myxoinflammatory fibroblastic sarcoma is a rare low-grade malignant soft tissue tumor, usually observed in the extremities of middle-aged adults. We report two cases which occurred in the thumb and knee of middle-aged women. Both tumors showed a multinodular architecture, with cellular areas, occasional foci of hyalinized fibrosis, and hypocellular areas with a myxoid background. Various neoplastic cells were identified including spindled or rounded epithelioid cells and occasional bizarre giant cells, morphologically mimicking Reed-Sternberg cells or ganglion cells. Tumor cells were strongly immunoreactive for vimentin, and variably positive for CD68 and CD34. Both tumors were completely resected and patients were free of disease without any further treatment after a mean follow-up of 14 months.     

The effect of target modality on visual and proprioceptive contributions to the control of movement distance

The goal of this study was to determine whether the sensory nature of a target influences the roles of vision and proprioception in the planning of movement distance. Two groups of subjects made rapid, elbow extension movements, either toward a visual target or toward the index fingertip of the unseen opposite hand. Visual feedback of the reaching index fingertip was only available before movement onset. Using a virtual reality display, we randomly introduced a discrepancy between actual and virtual (cursor) fingertip location. When subjects reached toward the visual target, movement distance varied with changes in visual information about initial hand position. For the proprioceptive target, movement distance varied mostly with changes in proprioceptive information about initial position. The effect of target modality was already present at the time of peak acceleration, indicating that this effect include feedforward processes. Our results suggest that the relative contributions of vision and proprioception to motor planning can change, depending on the modality in which task relevant information is represented.     

Determinants of maximal oxygen uptake in moderate acute hypoxia in endurance athletes

The factors determining maximal oxygen consumption were explored in eight endurance trained subjects (TS) and eight untrained subjects (US) exposed to moderate acute normobaric hypoxia. Subjects performed maximal incremental tests at sea level and simulated altitudes (1,000, 2,500, 4,500 m). Heart rate (HR), stroke volume (SV), cardiac output arterialized oxygen saturation oxygen uptake ventilation ( expressed in normobaric conditions) were measured. At maximal exercise, ventilatory equivalent transport and O₂ extraction (O₂ER_max) were calculated. In TS, remained unchanged despite a significant reduction in at 4,500 m. SV_max remained unchanged. decreased in TS at 4,500 m, was lower in TS and greater at 4,500 m vs. sea level in both groups. Sa′O_2max decreased at and above 1,000 m in TS and 2,500 m in US, O₂ER_max increased at 4,500 m in both groups. decreased with altitude and was greater in TS than US up to 2,500 m but not at 4,500 m. decreased with altitude but the decrement was larger in TS at 4,500 m. In both groups in moderate hypoxia was correlated with Several differences between the two groups are probably responsible for the greater in TS at 4,500 m : (1) the relative hypoventilation in TS as shown by the decrement in at 4,500 m (2) the greater decrement in TS due to a lower Sa′O_2max and unchanged 3) the smaller increase in O₂ER_max in TS, insufficient to compensate the decrease in      

How to Avoid Nontherapeutic Laparotomy in Patients With Multiple Organ Failure of Unknown Origin. The Role of CT Scan Revisited

Diagnosis of intra-abdominal diseases in critically ill patients remains a clinical challenge. Physical examination is unreliable whereas exploratory laparotomy may aggravate patient''s condition and delay further evaluation. Only a few studies have investigated the place of computed tomography (CT) on this hazardous situation. We aimed to evaluate the ability of CT to prevent unnecessary laparotomy during the management of critically ill patients. Charts of all consecutive patients who had undergone an emergency nontherapeutic laparotomy from 1996 to 2013 were retrospectively studied and patient''s demographic, clinical characteristics, and surgical findings were collected. During this period 59 patients had an unnecessary laparotomy. Fifty-one patients had at least one preoperative imaging and 36 had a CT scan. CT scans were interpreted to be normal (n = 12), with minor anomalies (n = 10), or major anomalies (pneumoperitoneum, portal venous gas/pneumatosis intestinalis, thickened gallbladder wall, and small bowel obstruction signs). Surgical exploration was performed through laparotomy (n = 55) or laparoscopy. Overall mortality was 37% with a median survival after surgery of 7 days. In univariate analysis, hospitalization in ICU before surgical exploration was the only factor related to death. In our series CT scans, objectively interpreted, helped avoid unnecessary surgical exploration in 61% of our patients.Key words: Laparotomy, Critical care, Abnormalities, Digestive system, CT scansEarly diagnosis of acute nontraumatic life-threatening intra-abdominal diseases remains a clinical challenge. In critically ill patients, pathologies such as mesenteric ischemia, intestinal perforation, pancreatitis and biliary diseases carry a high mortality rate ranging from 50% to 100%.^1,2 For these patients, physical examination can be unreliable due to deep sedation and absence of acute abdomen symptoms, and use of imaging studies may therefore be necessary to identify intra-abdominal pathologies and prevent delay in diagnosis. Also, imaging studies may help avoiding unnecessary laparotomy which can be associated with a morbidity rate up to 22%.³ Ultrasonography (US) can be performed at the bedside and is a good alternative for the diagnosis of biliary tract disease; however, it is highly operator dependent, made difficult by abdominal distension,⁴ and not effective for bowel perforation or ischemia.⁵ Computed tomography (CT) scans are increasingly used for emergency patients with acute nontraumatic abdominal pain and tenderness, however, misinterpretation or overinterpretation of CT findings are not rare.^6,7 Despite the large use of imaging procedures in the evaluation of intra-abdominal pathologies, few studies have attempted to assess their impact on the management of critically ill patients.^8,9 The aim of this observational work was to evaluate the results of preoperative imaging procedures, especially CT, in a consecutive series of nontraumatic critically ill patients who underwent nontherapeutic surgical abdominal exploration in a French university tertiary care hospital.     

Incidental colonic focal lesions detected by FDG PET/CT

OBJECTIVE: The aim of this study was to assess the performance of FDG PET/CT for the detection of colonic lesions, especially advanced neoplasms (villous or >10-mm adenomas, carcinomas). Because of 18F FDG accumulation in adenomatous polyps, PET using FDG can detect early premalignant colorectal lesions. MATERIALS AND METHODS: FDG PET/CT studies performed for a 1-year period in 1,716 consecutive patients with various malignant diseases, except colorectal cancer, were retrospectively reviewed. PET images obtained 1 hr after FDG injection and non-contrast CT images used for attenuation correction were fused for analysis. Of 45 patients showing intense focal colonic FDG uptake, 20 patients (with 21 foci) underwent a colonoscopic investigation, and, when necessary, polyp resection. The intensity of FDG uptake was quantified using the standardized uptake value (SUV(max)). RESULTS: The FDG colonic foci were associated with 18 colonoscopic abnormalities in 15 patients, with no colonic abnormality detected in five patients (false-positive [FP] results). Histopathologic findings revealed advanced neoplasms in 13 patients (13 villous adenomas and three carcinomas) and two cases of hyperplastic polyps. A difference in the mean SUV(max) was found between FP and true-positive colonic FDG foci but was not statistically significant (p = 0.14). CONCLUSION: Presence of a focal colonic FDG uptake incidental finding on a PET/CT scan justifies a colonoscopy to detect (pre-)malignant lesions. The fusion of PET and CT images allows an accurate localization of the lesions. PET/CT is a useful tool to differentiate pathologic from physiologic FDG uptake.     

Imaging of cerebellopontine angle lesions: an update. Part 1: enhancing extra-axial lesions

Computed tomography (CT) and magnetic resonance (MR) imaging reliably demonstrate typical features of vestibular schwannomas or meningiomas in the vast majority of mass lesions in the cerebellopontine angle (CPA). However, a large variety of unusual lesions can also be encountered in the CPA. Covering the entire spectrum of lesions potentially found in the CPA, these articles explain the pertinent neuroimaging features that radiologists need to know to make clinically relevant diagnoses in these cases, including data from diffusion and perfusion-weighted imaging or MR spectroscopy, when available. A diagnostic algorithm based on the lesion’s site of origin, shape and margins, density, signal intensity and contrast material uptake is also proposed. Part 1 describes the different enhancing extra-axial CPA masses primarily arising from the cerebellopontine cistern and its contents, including vestibular and non-vestibular schwannomas, meningioma, metastasis, aneurysm, tuberculosis and other miscellaneous meningeal lesions.     

Gastrointestinal bleeding and obstructive jaundice:Think of hepatic artery aneurysm

Hemobilia is an uncommon and potential life-threatening condition mainly due to hepato-biliary tree traumatic or iatrogenic injuries.Spontaneously ruptured aneurysm of the hepatic artery is seldom described.We report the case of an 89-year-old woman presenting with abdominal pain,jaundice and gastrointestinal bleeding,whose ultrasound and computed tomography revealed a non-traumatic,spontaneous aneurysm of the right hepatic artery.The oeso-gastro-duodenoscopy and colonoscopy did not reveal any bleeding at the ampulla of Vater,nor anywhere else.Selective angiography confirmed the diagnosis of hepatic artery aneurysm and revealed a full hepatic artery originating from the superior mesenteric artery.The patient was successfully treated by selective embolization of microcoils.We discuss the etiologies of hemobilia and its treatment with selective embolization,which remains favored over surgical treatment.Although aneurysm of the hepatic artery is rare,especially without trauma,a high index of suspicion is needed in order to ensure appropriate treatment.     

Survival and postoperative complication in daily practice after neoadjuvant therapy in resectable stage IIIA-N2 non-small cell lung cancer

Regarding persisting controversies about neoadjuvant treatment (NT), we studied the impact of neoadjuvant therapy in daily practice. Patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) resected after NT were eligible. Data on preoperative treatments, surgical procedure, postoperative complications and survival were collected. Overall, 71 (60 men, median age of 60 years) patients met inclusion criteria. All patients received a two-drug platinum-based regimen (median of 2.5 cycles [2-4 cycles]) and 15 (21%) had an associated radiotherapy (20-40 Gy). Nine complete and 27 partial responses were achieved. Surgical procedure principally was a lobectomy (44%), a left (15.5%) or a right (27%) pneumonectomy. Operative mortality was 4.2% while 21 patients (29%) experienced postoperative complications. Median survival was 17 months (95% CI, 13-21 months) with 3- and 5-year survival rates of 24 and 13%, respectively. Five-year survival was worse if postoperative complication occurred (18 versus 0%, p=0.09). Multivariate analysis showed male gender (RR=0.37, 95% CI, 0.16-0.81, p=0.013) and postoperative positive lymph node (RR=2.7, 95% CI, 1.4-5.2, p=0.002) to influence survival. In conclusion, achievement of a clinical and pathological response after NT for stage IIIA-N2 NSCLC patients enables a better survival. More efficient but also less toxic regimens of chemotherapy should be developed regarding its impact on long-term survival.     

Impact of Preoperative α-Fetoprotein Level on Disease-Free Survival After Liver Transplantation for Hepatocellular Carcinoma

Background

Preoperative α-fetoprotein (AFP) levels may have an influence on disease-free survival (DFS) of patients after liver transplantation for hepatocellular carcinoma (HCC) located on a cirrhotic liver.

Methods

Between 2000 and 2009, two groups were distinguished according to preoperative AFP level: normal-level group (<10?ng/ml) and increased-level group (>10?ng/ml). The increased-level group was further divided into three levels of preoperative AFP: 10–150, 150–500, and ≥500?ng/ml. DFS and recurrence rates were compared. All patients underwent transplantation using the preoperative 5/5 criteria.

Results

Of the 122 patients in this study, 63 had normal and 59 had increased preoperative AFP. There were no differences between the two groups concerning perioperative or pathologic data. Those with an increased preoperative AFP level had a significantly shorter 5-year DFS, and their recurrence rate was higher than that of the normal AFP group. The 5-year DFS and recurrence rates were 71 and 4?%, respectively, for those with normal AFP; 57 and 10?%, respectively, for those with AFP 10–150?ng/ml; 46 and 24?%, respectively, for those with AFP 150–500?ng/ml; and 28 and 62?%, respectively, for those with AFP ≥500?ng/ml.

Conclusions

This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.