A new immune-competent animal model of mucosally derived squamous cell carcinoma.

OBJECTIVES: To develop an immune-competent animal model for mucosally derived squamous cell carcinoma (SCCA). STUDY DESIGN: Fifteen Fischer 344 rats were inoculated with 1, 2, 5, 10, or 20 x 10(6) FAT7 cells in their flanks. The animals were observed for tumor growth and metastasis. RESULTS: All animals developed tumors that grew exponentially. Pulmonary metastases developed in all animals and 13% developed lymph node metastases. CONCLUSION: The FAT7 flank tumor in Fischer 344 rats is a new animal model that closely resembles the behavior of human mucosal head and neck cancer. SIGNIFICANCE: The existence of an immune-competent, mucosally derived, and reliable animal model of SCCA that somewhat resembles human head and neck SCCA gives the opportunity to perform immune-modulating experiments on head and neck cancer in these animals. EBM rating: B-3.     

Mundgesundheitskompetenz von Menschen mit Migrationshintergrund – Erste Auswertungen der MuMi-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Erste Studien heben den Migrationshintergrund von Menschen in Deutschland als eigenständigen Risikofaktor für eine...     

Mathematical model of volume kinetics and renal function after burn injury and resuscitation

This paper presents a mathematical model of blood volume kinetics and renal function in response to burn injury and resuscitation, which is applicable to the development and non-clinical testing of burn resuscitation protocols and algorithms. Prior mathematical models of burn injury and resuscitation are not ideally suited to such applications due to their limited credibility in predicting blood volume and urinary output observed in wide-ranging burn patients as well as in incorporating contemporary knowledge of burn pathophysiology. Our mathematical model consists of an established multi-compartmental model of blood volume kinetics, a hybrid mechanistic-phenomenological model of renal function, and novel lumped-parameter models of burn-induced perturbations in volume kinetics and renal function equipped with contemporary knowledge on burn-related physiology and pathophysiology. Using the dataset collected from 16 sheep, we showed that our mathematical model can be characterized with physiologically plausible parameter values to accurately predict blood volume kinetic and renal function responses to burn injury and resuscitation on an individual basis against a wide range of pathophysiological variability. Pending validation in humans, our mathematical model may serve as an effective basis for in-depth understanding of complex burn-induced volume kinetic and renal function responses as well as development and non-clinical testing of burn resuscitation protocols and algorithms.     

Differential pharmacology between the guinea-pig and the gorilla 5-HT1D receptor as probed with isochromans (5-HT1D-selective ligands).

1. Both the 5-HT1D and 5-HT1B receptors are implicated in migraine pathophysiology. Recently isochromans have been discovered to bind primate 5-HT1D receptors with much higher affinity than 5-HT1B receptors. In the guinea-pig, a primary animal model for anti-migraine drug testing, however, isochromans bound the 5-HT1D receptor with lower affinity than the gorilla receptor. 2. This species-specific pharmacology was investigated, using site-directed mutagenesis on cloned guinea-pig receptors heterologously expressed in human embryonic kidney 293 cells. Mutations of threonine 100 and arginine 102 at the extracellular side of transmembrane II of the guinea-pig 5-HT1D receptor to the corresponding primate residues, isoleucine and histidine, respectively, enhanced its affinity for isochromans to that of the gorilla receptor, with little effects on its affinities for serotonin, sumatriptan and metergoline. Free energy change from the R102H mutation was about twice as much as that from the T100I mutation. 3. For G protein-coupling, serotonin marginally enhanced GTPgamma35S binding in membranes expressing the guinea-pig 5-HT1D receptor and its mutants, but robustly in membranes expressing the gorilla receptor. Sumatriptan enhanced GTPgamma35S binding in the latter nearly as much as serotonin, and several isochromans by 30-60% of serotonin. 4. We discovered key differences in the function and binding properties of guinea-pig and gorilla 5-HT1D receptors, and identified contributions of I100 and H102 of primate 5-HT1D receptors to isochroman binding. Among common experimental animals, only the rabbit shares I100 and H102 with primates, and could be useful for studying isochroman actions in vivo.     

Intraoperative small bowel length measurements and analysis of demographic predictors of increased length

Few studies have measured small bowel length (SBL) in live humans and many textbooks base their “normal” SBL values on cadaver data. Here, we present a series of intraoperative SBL measurements and analyze predictors of increased length. SBL from ligament of Treitz to ileocecal valve was measured in patients undergoing laparotomy for colorectal resection. Patients with Crohn's disease and those who had undergone prior bowel resections were excluded. In the 240 patients studied, mean SBL was 506 ± 105 (285–845) cm. Height was positively associated with increased SBL (P < 0.001) and men had longer SBL than women (533 vs. 482 cm, P < 0.001). A multivariate linear regression model using patient sex, age, height and weight was significant (P = 0.001) and the predictors explained 8% of the variance in SBL. In this model, only height was independently predictive of increased SBL (P = 0.03). Correlation results differed between sexes. In men, height correlated with increased SBL (r = 0.20; P = 0.03), whereas in women it did not. In men, age had a positive correlation with SBL at a trend level (r = 0.17; P = 0.08), whereas in women age had a negative correlation with SBL (r = ?0.18; P = 0.04). The mean SBL was 506 cm in live patients, as compared with the 600–700 cm range derived from prior cadaver studies. Male sex and height had positive correlations with SBL. SBL may decrease with age in women but not in men. Clin. Anat. 26:827–832, 2013. © 2013 Wiley Periodicals, Inc.     

Superior calcium bioavailability of effervescent potassium calcium citrate over tablet formulation of calcium citrate after Roux-en-Y gastric bypass

BackgroundCalcium supplementation is commonly recommended for patients after Roux-en-Y gastric bypass to avert bone loss. To test the hypothesis that effervescent (liquid) potassium-calcium-citrate (PCC) might be more bioavailable than a tablet formulation of calcium citrate (Citracal Petite), the present study compared a single dose response of the 2 compounds. The present study was conducted at the University of Texas Southwestern Medical School at Dallas.MethodsA total of 15 patients who had undergone Roux-en-Y gastric bypass were included in a 2-phase, crossover, randomized study comparing the single-dose bioavailability of PCC versus Citracal Petite. After following a restricted diet for 1 week, the participants ingested either a single dose of 400 mg elemental calcium as PCC or Citracal Petite. Sequential serum and urine samples were collected for a 6-hour period after the dose and analyzed for calcium, parathyroid hormone, and acid-base parameters.ResultsCompared with citracal petite, PCC significantly increased the serum calcium concentrations at 2, 3, and 4 hours after the oral load. The peak to baseline variation and increment in serum calcium (area under the curve) were significantly greater after PCC (P = .015 and P = .002, respectively). Concurrently, the baseline to nadir variation and decrement in serum parathyroid hormone (area over the curve) were significantly greater after PCC (P = .004 and P = .005, respectively). Moreover, compared with Citracal Petite, PCC caused a significantly greater increment in urinary citrate (P < .0001) and potassium (P = .0004) and a significantly lower increase in urinary ammonium (P = .045).ConclusionIn patients who have undergone Roux-en-Y gastric bypass, PCC was superior to Citracal Petite in conferring bioavailable calcium and suppressing parathyroid hormone secretion. PCC also provided an alkali load.     

Endovenous laser ablation of the great saphenous vein versus high ligation: long-term results

Endovenous laser therapy (EVLT) for greater saphenous vein (GSV) insufficiency is a relatively new method of treatment only recently made available in Iran. This is the first long-term randomized trial comparing EVLT with high ligation of saphenous vein (HLS) in the Iranian population. Sixty-five patients met the inclusion criteria and were divided into homogenous treatment groups of EVLT (n?=?30) or HLS (n?=?35). Clinical severity, etiology, anatomy, pathophysiology (CEAP) classification and Aberdeen Varicose Vein Symptom Severity Scores (AVSS) were used to determine disease severity and symptoms before and after the procedure in both groups. Outcome was measured by the rate of recurrence as shown in Doppler ultrasonography evaluation. Follow-up was conducted 1 week and 3, 6, 12, and 18 months after the intervention. The occlusion rate of GSV was similar in both groups (93.6 % for EVLT, 88.3 for HLS) at 18 months of follow-up. The median CEAP score showed a dramatic decrease in both groups after 1 week which was sustained for the rest of the study. The Aberdeen Varicose Vein Symptom Severity score was significantly lower in the EVLT group at 12 and 18 months of follow-up. There was no significant difference in patient satisfaction in both groups. Our findings show that EVLT may offer a better long-term relief of symptoms. This, alongside its better cosmetic outcome, and less invasive anesthesia requirements may make it the favorable choice for treatment of GSV insufficiency.