Can diffusion tensor metrics help in preoperative grading of diffusely infiltrating astrocytomas? A retrospective study of 36 cases

Introduction  

Diffusion weighted imaging and diffusion tensor imaging (DTI) give information about the amount and directionality of water diffusion occurring in a given tissue. Here we study the role of diffusion tensor metrics including fractional anisotropy (FA) and spherical anisotropy (CS) in preoperative grading of diffusely infiltrating astrocytomas.     

Neuronal vs. Glial Fate of Embryonic Stem Cell-Derived Neural Progenitors (ES-NPs) is Determined by FGF2/EGF During Proliferation

Fate-specific differentiation of neural progenitors attracts keen interest in modern medicine due to its application in cell replacement therapy. Though various signaling pathways are involved in maintenance and differentiation of neural progenitors, the mechanism of development of lineage-restricted progenitors from embryonic stem (ES) cells is not clearly understood. Here, we have demonstrated that neuronal vs. glial differentiation potential of ES cell-derived neural progenitors (ES-NPs) are governed by the growth factors, exposed during their proliferation/expansion phase and cannot be significantly altered during differentiation phase. Exposure of ES-NPs to fibroblast growth factor-2 (FGF2) during proliferation triggered the expression of pro-neural genes that are required for neuronal lineage commitment, and upon differentiation, predominantly generated neurons. On the other hand, epidermal growth factor (EGF)-exposed ES-NPs are not committed to neuronal fate due to decreased expression of pro-neural genes. These ES-NPs further generate more glial cells due to expression of glial-restricted factors. Exposure of ES-NPs to the same growth factors during proliferation/expansion and differentiation phase augments the robust differentiation of neurons or glial subtypes. We also demonstrate that, during differentiation, exposure to growth factors other than that in which the ES-NPs were expanded does not significantly alter the fate of ES-NPs. Thus, we conclude that FGF2 and EGF determine the neural vs. glial fate of ES-NPs during proliferation and augment it during differentiation. Further modification of these protocols would help in generating fate-specified neurons for various regenerative therapies.     

The surgical management of patients who achieve a complete pathological response after primary chemotherapy for locally advanced breast cancer.

AIMS: Our aim was to investigate the role of minimal surgery in patients with locally advanced breast cancer (LABC) who achieve a complete pathological (pCR) response to primary chemotherapy (PC) and evaluate subsequent local recurrence (LRR), disease free survival (DFS) and overall survival (OS). METHODS: Between January 2000 and April 2005, 101 patients with operable LABC (T2, T3, N0 or N1, M0) who were not suitable for conservation surgery were treated with PC. Patients were treated with doxorubicin and cyclophosphamide for four cycles (100 patients) then four cycles with paclitaxel (91 patients). Post-PC surgery consisted of multiple core biopsies and axillary clearance for patients with a complete clinical and radiological response. If a pCR was confirmed no further breast surgery was performed. The remaining patients were treated with breast conserving surgery or mastectomy and axillary clearance as appropriate. Adjuvant radiotherapy was given to all patients. RESULTS: Breast conservation was possible in 60% of patients. Overall, 20 patients achieved a pCR of which 16 were confirmed on core biopsies alone. All patients were followed-up for a mean of 33.5 months (95% CI, 30.3-36.7). There were 10 local recurrences, four following mastectomy, four after wide excision and two after core biopsies. There was no difference in DFS (chi square=0.18; p=0.67) or OS (chi square=0.67; p=0.41) between patients achieving a pCR and the remainder. CONCLUSIONS: The local recurrence rate of these poor prognosis patients is similar to other reported series but higher than in our previously reported series of patients managed according to the same protocol. Our current management therefore now includes pre-treatment marking and subsequent surgical excision.     

Effects of the restriction of food and water intake on the distribution and retention of radioiodine in mice

The effects of the restriction of food and water intakes on gastrointestinal absorption, distribution to organs and excretion of 131I were investigated in C3H/He mice. The animals were divided into four groups and administered orally 37 kBq carrier-free Na 131I in 0.25 ml normal saline. One group of animals was given food and water ad libitum throughout the experimental period. Food and water to the remaining groups were restricted before and/or after the administration of 131I. The animals in each group were sacrificed 4 h and 24 h after administration, and the activity of 131I in thyroid, blood, liver, kidney, gastrointestinal tract, urine, feces, and carcass was measured. There was a significant increase in the retention of 131I in the thyroid and the concentration of 131I in the blood due to the restriction of food and water after the administration of 131I. In contrast, a significant decrease in the urinary excretion was observed in these animals. In those animals, which fasted before administration only, the retention of 131I in the thyroid and other organs were decreased. Therefore, for an accurate diagnosis and effective therapy with radioiodine as well as effective radiation protection, the intake of food and water should be taken into account.     

Cyclospora cayetanensis--an emerging coccidian parasite

Over the last decade increasing number of enteritis cases have been attributed to infection with a new coccidian sp that was named Cyclospora cayetanensis in 1993. Diarrhoea caused by this agent is clinically indistinguishable from cryptosporidiasis, isosporiasis and microsporidiasis but cyclospora infection are often very prolonged (upto 15 weeks) and may cause severe weight loss. Diagnosis is important because unlike diarrhoea caused by cryptosporidium and microsporidium, treatment with co-trimoxazole is effective. We report here a case of cyclosporiasis, to increase awareness of possibility of cyclospora infection in patients with prolonged diarrhoea. It should be considered in assessment of patients with unexplained prolonged diarrhoeal illness.     

Utilization of virtual reality for endotracheal intubation training

Tracheal intubation is performed for urgent airway control in injured patients. Current methods of training include working on cadavers and manikins, which lack the realism of a living human being. Work in this field has been limited due to the complex nature of simulating in real-time, the interactive forces and deformations which occur during an actual patient intubation. This study addressed the issue of intubation training in an attempt to bridge the gap between actual and virtual patient scenarios. The haptic device along with the real-time performance of the simulator give it both visual and physical realism. The three-dimensional viewing and interaction available through virtual reality make it possible for physicians, pre-hospital personnel and students to practice many endotracheal intubations without ever touching a patient. The ability for a medical professional to practice a procedure multiple times prior to performing it on a patient will both enhance the skill of the individual while reducing the risk to the patient.     

Calcified neurocysticercosis lesions and hippocampal sclerosis: Potential dual pathology?

In areas where cysticercosis is endemic, calcified neurocysticercosis lesion(s) (CNL) and hippocampal sclerosis (HS) commonly coexist in patients with localization-related epilepsies. To understand the pathogenesis of HS associated with CNL, we compared the characteristics of three groups of patients with antiepileptic drug-resistant epilepsies: CNL with HS, CNL without HS (CNL alone), and HS without CNL (HS alone). In comparison to patients with CNL alone, those with CNL with HS had CNL more frequently located in the ipsilateral temporal lobe. Those with CNL with HS had a lower incidence of febrile seizures, older age at initial precipitating injury and at onset of habitual complex partial seizures, and more frequent clustering of seizures and extratemporal/bitemporal interictal epileptiform discharges as compared to patients with HS alone. Our study illustrates that HS associated with CNL might have a different pathophysiologic basis as compared to classical HS.     

Variability in cimetidine absorption and plasma double peaks following oral administration in the fasted state in humans: correlation with antral gastric motility.

The role of gastrointestinal motility and pH in determining cimetidine bioavailability as well as double peaks in plasma profiles following oral administration, in the quiescent or active phase of antral motility, to humans in the fasted state was examined. Plasma cimetidine-time curves did not show the presence of double peaks in any subject following intravenous administration. The incidence of double peaks was 73% following oral administration and was independent of antral migrating motility complex phase. Further, it was found that oral administration of cimetidine in the quiescent phase resulted in significantly higher bioavailability and in other pharmacokinetic parameters compared to that obtained following administration in the active phase. Excellent linearity in plots of motility peaks vs. plasma peaks with slopes close to unity were evident for both quiescent (r(2)=0.93) and active phase (r(2)=0.97) administration. A total of 14 peaks out of 22 (10 subjects, 64%) and 20 out of 27 peaks (11 subjects, 74%), were accounted for in quiescent and active phase oral administration, respectively. The proximal occurrence of plasma peaks to antral motility peaks typical of phase III contractions strongly implies that motility patterns may be responsible for secondary maxima following oral cimetidine administration in the fasted state.     

A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan

Orally administered, immediate-release (IR) drug products in the top 200 drug product lists from the United States (US), Great Britain (GB), Spain (ES), and Japan (JP) were provisionally classified based on the Biopharmaceutics Classification System (BCS). The provisional classification is based on the aqueous solubility of the drugs reported in readily available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. Oral IR drug products constituted more that 50% of the top 200 drug products on all four lists, and ranged from 102 to 113 in number. Drugs with dose numbers less than or equal to unity are defined as high-solubility drugs. More than 50% of the oral IR drug products on each list were determined to be high-solubility drugs (55-59%). The provisional classification of permeability is based on correlations of the human intestinal permeabilities of 29 reference drugs with the calculated Log P or CLogP lipophilicity values for the uncharged chemical form. The Log P and CLogP estimates were linearly correlated (r2 = 0.79) for 187 drugs. Metoprolol was chosen as the reference compound for permeability and Log P or CLogP. A total of 62-69.0% and 56-60% of the drugs on the four lists exhibited CLogP and Log P estimates, respectively, greater than or equal to the corresponding metoprolol value and are provisionally classified as high-permeability drugs. We have compared the BCS classification in this study with the recently proposed BDDCS classification based on fraction dose metabolism. Although the two approaches are based on different in vivo processes, fraction dose metabolized and fraction dose absorbed are highly correlated and, while depending on the choice of reference drug for permeability classification, e.g., metoprolol vs cimetidine or atenolol, show excellent agreement in drug classification. In summary, more than 55% of the drug products were classified as high-solubility (Class 1 and Class 3) drugs in the four lists, suggesting that in vivo bioequivalence (BE) may be assured with a less expensive and more easily implemented in vitro dissolution test.     

Changing concepts in lipid nutrition in health and disease

Fat remains a hot topic because of concerns over associations between consumption of fats and the incidence of some chronic conditions including coronary artery disease, diabetes, cancer and obesity. Dietary fats serve multiple purposes. The effects of dietary fats generally reflect the collective influences of multiple fatty acids in the diet or food. This presentation highlights some recent developments on the role of dietary fats and oils in health and disease. Debate continues over the role of dietary modification in coronary prevention by lipid lowering. The degree to which a recommended diet will result in health benefits for an individual is difficult to predict, because the outcome will depend on the influence of other factors such as a person's genetic constitution, level of physical activity and total diet composition. There can now be little doubt about the importance of genetic factors in the etiology of cardiovascular disease, diabetes, obesity and cancer. The importance of antioxidant status in the prevention of cardiovascular disease as well as many cancers is being increasingly recognised. It is now evident that not all saturated fatty acids are equally cholesterolemic. Recent accounts evaluating palm oil's effects on blood lipids and lipoproteins suggest that diets incorporating palm oil as the major dietary fat do not raise plasma total and LDL cholesterol levels to the extent expected from its fatty acid composition. Palm oil is endowed with a good mixture of natural antioxidants and together with its balanced composition of the different classes of fatty acids, makes it a safe, stable and versatile edible oil with many positive health and nutritional attributes. In recent times, adverse health concerns from the consumption of trans fatty acids arising from hydrogenation of oils and fats have been the subject of much discussion and controversy. Trans fatty acids when compared with cis fatty acids or unhydrogenated fats have been shown to lower serum HDL cholesterol, raise serum LDL cholesterol and when substituted for saturated fatty acids, increase lipoprotein Lp (a) level, an independent risk factor for the development of coronary heart disease. The idea of which foods, nutrients and supplements are "healthy" is often being amended as new scientific data is presented and then simplified for the consumers. What was once perceived as a healthy diet is often no longer considered as such and vice versa. Dietary recommendations have to change with time and the evidence available. Nutritional recommendations should encourage eating a great variety of nutrient sources within our food supply in moderation. Various lifestyle options to improve health should also be promoted.