Concomitant occurrence of genetically distinct Hodgkin lymphoma and primary mediastinal lymphoma

Synchronous Hodgkin Lymphoma and Primary Mediastinal B‐cell Lymphoma is possible, with molecular analyses proving the absence of clonal filiation between both entities. This suggests a common etiology but the existence of two divergent clones.     

Successful Weight Loss Surgery Improves Eating Control and Energy Metabolism: A Review of the Evidence

Eating behavior is determined by a balance of memories in terms of reward and punishment to satisfy the urge to consume food. Refilling empty energy stores and hedonistic motivation are rewarding aspects of eating. Overfeeding, associated adverse GI effects, and obesity implicate punishment. In the current review, evidence is given for the hypothesis that bariatric surgery affects control over eating behavior.Moreover, any caloric overload will reduce the feeling of satiety. Durable weight loss after bariatric surgery is probably the result of a new equilibrium between reward and punishment, together with a better signaling of satiation due to beneficial metabolic changes.We propose to introduce three main treatment goals for bariatric surgery: 1) acceptable weight loss, 2) improvement of eating control, and 3) metabolic benefit. To achieve this goal, loss of 50% to 70% of excess weight will be appropriate (i.e. 30% to 40% loss of initial weight), depending on the degree of obesity prior to operation.     

Interaction of benzylidene-anabaseine analogues with agonist and allosteric sites on muscle nicotinic acetylcholine receptors

Background and purpose

Benzylidene-anabaseines (BAs) are partial agonists of the α7 nicotinic acetylcholine receptor (nAChR) but their mechanism(s) of action are unknown. Our study explores several possibilities, including direct interactions of BAs with the nAChR channel.

Experimental approach

Functional and radioligand-binding assays were used to examine the interaction of two BA analogues, 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA) and its primary metabolite 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine (4OH-DMXBA) with both agonist and non-competitive antagonist (NCA)-binding sites on muscle-type nAChRs.

Key results

Both BAs non-competitively inhibited ACh activation of human fetal muscle nAChRs and sterically inhibited the specific binding of the NCAs [piperidyl-3,4-3H(N)]-(N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([³H]TCP) and [³H]dizocilpine to Torpedo nAChRs in the desensitized state. These compounds modulated [³H]tetracaine, [¹⁴C]amobarbital and [³H]TCP binding to resting nAChRs by allosteric mechanisms. Both BAs enhanced [³H]TCP binding when the nAChR was initially in the resting but activatable state, suggesting that both compounds desensitized the Torpedo nAChR. Although DMXBA failed to activate human fetal muscle nAChRs, 4OH-DMXBA was found to be a partial agonist. [³H]Nicotine competition-binding experiments confirmed that 4OH-DMXBA has higher affinity than DMXBA for the agonist sites, and that DMXBA is also a competitive antagonist.

Conclusions and implications

3-(4-hydroxy-2-methoxybenzylidene)-anabaseine is a partial agonist for human fetal muscle nAChRs, whereas DMXBA only has competitive and NCA activities. The NCA-binding site for BAs overlaps both the phencyclidine-and dizocilpine-binding sites in the desensitized Torpedo nAChR ion channel. The desensitizing property of BAs suggests another possible mode of non-competitive inhibition in addition to direct channel-blocking mechanisms.     

Development and validation of the Food Allergy Quality of Life Questionnaire – Adult Form

Background: Health‐related quality of life (HRQL) may be affected by food allergy. Presently, no disease‐specific HRQL questionnaire exists for food allergic adults. Therefore, we developed and validated the Food Allergy Quality of Life Questionnaire – Adult Form (FAQLQ‐AF) in the Dutch language. Methods: Twenty‐two food allergic patients (≥18 years) were interviewed and generated 180 HRQL items. The most important items were identified by 54 food allergic patients using the clinical impact method resulting in the FAQLQ‐AF containing 29 items (score range 1 ‘not troubled’ to 7 ‘extremely troubled’). The FAQLQ‐AF, the Food Allergy Independent Measure (FAIM) and a generic HRQL questionnaire (RAND‐36) were sent to 100 other food allergic adults for cross‐sectional validation of the FAQLQ‐AF. Results: Cross‐sectional validity was assessed by the correlation between FAQLQ‐AF and FAIM (ρ = 0.76, P < 0.001). The FAQLQ‐AF had excellent internal consistency (Cronbach’s α = 0.97). The FAQLQ‐AF discriminated between patients who differ in severity of symptoms (anaphylaxis vs no anaphylaxis, total FAQLQ‐AF score 4.9 vs 4.1; P = 0.041) and number of food allergies (>3 food allergies vs≤3 food allergies, total FAQLQ‐AF score 5.2 vs 4.2; P = 0.008). The total FAQLQ‐AF score was correlated with one RAND‐36 scale (convergent/discriminant validity). Conclusions: The FAQLQ‐AF is the first disease‐specific HRQL questionnaire for food allergic adults and reflects the most important issues that food allergic patients have to face. The questionnaire is valid, reliable and discriminates between patients with different disease characteristics. The FAQLQ‐AF is short and easy to use and may therefore be a useful tool in clinical research.     

Bacterial contamination of donor blood at the Tamale Teaching Hospital,Ghana

Background

Transfusion of bacterially contaminated blood can result in sepsis and will constitute a substantial health burden to the patient.

Objective

To assess the level of transfusion related sepsis and the bacterial types responsible for the contamination at the Tamale Teaching Hospital in Ghana.

Method

We sampled 80 refrigerated donor blood at the blood bank and cultured them for bacteria. The antimicrobial sensitivities of the isolates were also determined.

Results

14 blood bags representing 17.5% grew isolates of various bacteria. Ten (10) of the 14 isolates were Gram positive cocci representing 71.42% making it the commonest contaminant. 50% of the gram positive cocci were identified to be coagulase negative staphylococci and 21.42% were Staphylococcus aureus. There were 14.28% isolates which were Gram positive rods, and were identified to be Corynebacterium diphtheroids. There were two isolates which were Gram negative rods; one was identified as Escherichia coli and the other one Klebsiella pneumoniae. Sensitivity among the organisms were varied; as all the 14 (100%) of the organisms isolated were sensitive to amikacin, only 14.28% of the coagulase negative staphylococci were sensitive to co-trimoxazole, 28.5% were sensitive to ampicillin, 42.8% were sensitive to cefuroxime and 71.4% were sensitive to ciprofloxacin. Sensitivity to gentamicin was observed to be 85.7% and 28.5% were sensitive to Tetracycline. Only the 10 Gram positive cocci were tested against erythromycin and Cloxacillin; where 70.00% were sensitive to cloxacillin and 90% were sensitive to erythromycin.

Conclusion

All the Staphylococcus aureus isolated were resistant to both ampicillin and cotrimoxazole. Potential dangers and consequences of transfusing multidrug resistance bacteria have been discussed.     

Digital holographic microscopy for the three-dimensional dynamic analysis of in vitro cancer cell migration

Cancer cell motility and invasion are critical targets for anticancer therapeutics. Whereas in vitro models could be designed for rapid screening with a view to investigate these targets, careful consideration must be given to the construction of appropriate model systems. Most investigations focus on two-dimensional (2-D) assays despite the fact that increasing evidence suggests that migration across rigid and planar substrates fails to recapitulate in vivo behavior. In contrast, few systems enable three-dimensional (3-D) cell migration to be quantitatively analyzed. We previously developed a digital holographic microscope (DHM) working in transmission with a partially spatial coherence source. This configuration avoids the noise artifacts of laser illumination and makes possible the direct recording of information on the 3-D structure of samples consisting of multiple objects embedded in scattering media, such as cell cultures in matrix gels. The software driving our DHM system is equipped with a time-lapse ability that enables the 3-D trajectories of living cells to be reconstituted and quantitatively analyzed.     

Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis but can reacquire sensitivity upon additional loss of the p21Cip1 gene

The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable for skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to p21(Cip1), which is induced in tumors by the activated Ras-ERK pathway but repressed by c-Myc. Acute elimination of c-Myc in established tumors leads to the up-regulation of p21(Cip1), and epidermis lacking both p21(Cip1) and c-Myc reacquires normal sensitivity to DMBA/TPA-induced tumorigenesis. This identifies c-Myc-mediated repression of p21(Cip1) as a key step for Ras-driven epidermal tumorigenesis.     

Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study

OBJECTIVE: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients. DESIGN:: Prospective, controlled, randomized study. SETTING: Thirty-one-bed, mixed medicosurgical department of intensive care. PATIENTS: All adult patients with a serum albumin concentration < or =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload. INTERVENTIONS: The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group). MEASUREMENTS AND MAIN RESULTS: The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 +/- 1156 vs. 658 +/- 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05). CONCLUSIONS: Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.