Treatment of irritable colon with the food additive Appital

Appital is a herbal medicine. The aim was to examine its effect in patients with irritable bowel syndrome (IBS). Other diseases were excluded by physical examination, rectoscopy, blood tests and in patients older than 35 years X-ray of the colon or colonoscopy. The study was designed as a double-blind placebo-controlled trial. The patients were randomized to either Appital or placebo. Following two weeks without medicine, the patient had Appital or placebo for eight weeks. Fifty-nine patients were randomized, 47 completed the study. The results were based on symptom scores registered by the patients. The symptom score was significantly reduced in patients treated with Appital (p = 0.002), but when compared to placebo, the difference was insignificant (p = 0.081). We concluded that Appital has no effect in relieving symptoms of IBS compared to placebo, although due to the possibility of type two error we cannot exclude a small, but hardly clinically relevant effect.     

Establishment of a highly differentiated thyroid cancer cell line of Hürthle cell origin

Hürthle cell carcinomas (HCC) of the thyroid are a variant of follicular thyroid tumors. In contrast to follicular thyroid carcinoma, HCC rarely take up radioiodine and frequently metastasize to the lymph nodes. Histologically they are indistinguishable from Hürthle cell adenomas except for evidence of invasion and metastasis. How these carcinomas develop and why they behave differently than other follicular tumors is not known. Although some differentiated thyroid cancer cell lines exist, none are from Hürthle cell tumors. We have established a well-differentiated thyroid cancer cell line from a metastasis of a HCC, designated XTC.UC1. In vitro, XTC cells display epitheloid morphology, grow with a population doubling time of 4.3 +/- 0.3 days, migrate, and invade through reconstituted basement membranes. The cells are immunoreactive for and release thyroglobulin, respond to thyrotropin (TSH) with increase of intracellular cyclic adenosine monophosphate (cAMP), proliferation, and invasion of reconstituted basement membrane, thus exhibiting characteristics of well-differentiated thyroid carcinoma. In vivo, xenografted XTC cells grow with a doubling time of 9.8 +/- 0.8 days. Tumors spontaneously metastasize to the lymph nodes and less frequently to the lungs and the liver. The cells retained their differentiated function in vivo as assessed by human thyroglobulin (hTG) secretion and immunohistochemistry. This is a first report of the establishment of a unique, highly differentiated thyroid carcinoma cell line derived from an HCC. Based on the ability to invade through reconstituted basement membrane in vitro and the potential to metastasize in vivo, this cell line may provide a unique model to study invasion and metastazation of well-differentiated thyroid cancer.     

In vitro evaluation of three-dimensional ultrasonography based on magnetic scanhead tracking

The objective of this study was to evaluate the accuracy and precision of a magnetic position sensor system for acquisition of three-dimensional (3D) ultrasound images in volume estimation of phantoms in vitro. Installation of either 0.9% solution of saline at 37 degrees C or distilled water at 20 degrees C to a condom was performed. Scanning was performed either by a continuous or stepwise acquisition. This 3D ultrasound system demonstrated good correlation (r = 0.99-1.0, n = 8) between estimated (EV) and true volumes (TV). The errors were in the range 1.3%+/-0.3% (SEM) to 1.9%+/-0.6%, independent of sound velocity. Scanning through a porcine abdominal wall positioned at the fluid surface yielded a systematic underestimation of the volume: mean (EV - TV) = -7.2+/-0.8 ml. Eight repeated scans of the same volume yielded a coefficient of variation of 1.1%. Interobserver error of the tracing procedure was 2.6%+/-0.9%. This 3D ultrasound system gave high accuracy and precision in volume estimation in vitro, and yielded low interobserver error. A change in ultrasound velocity of approximately 60 m/s did not influence the accuracy significantly. Scanning through an abdominal wall underestimated volumes slightly.     

Sustained activation of phospholipase D via adenosine A3 receptors is associated with enhancement of antigen- and Ca(2+)-ionophore-induced secretion in a rat mast cell line

The adenosine analog, N-ethylcarboxamidoadenosine (NECA), causes transient activation of phospholipase C and an enhancement of antigen-induced secretion in a rat mast cell (RBL-2H3) line via adenosine A3-receptors (Ramkumar et al., J. Biol. Chem. 268:16887, 1993) by a mechanism that is inhibited by bacterial toxins and potentiated by dexamethasone (Ali et al., J. Biol. Chem. 265:745-753, 1990). Here we show that NECA synergizes the secretory response to Ca(2+)-ionophore as well as to antigen. The ability of NECA to synergize the secretory responses persisted for 10 to 20 min, long after the early phospholipase C-mediated reactions to NECA had subsided. NECA caused, however, a dose-dependent sustained activation of phospholipase D, as indicated by the formation of [3H]phosphatidic acid, or in the presence of 0.3% ethanol, [3H]phosphatidylethanol. This activation was associated with a sustained increase in diglycerides, in protein kinase C activity and in the phosphorylation of myosin light chains by protein kinase C. The generation of diglycerides was enhanced in dexamethasone-treated cells and suppressed in cells that had been treated with cholera toxin or pertussis toxin. Collectively, the studies suggested that the generation of diglycerides via phospholipase D and the associated activation of protein kinase C were, by themselves, insufficient signals for secretion in RBL-2H3 cells, but that these reactions synergized responses to stimulants such as antigen or A23187 that caused substantial increases in [Ca2+]i.     

Molecular basis of Refsum disease: identification of new mutations in the phytanoyl-CoA hydroxylase cDNA

OBJECTIVE: This study aimed to review the management of cerebrospinal fluid (CSF) fistulae in the setting of developmental inner ear deformity. STUDY DESIGN: The study design was a case review, close examination of preoperative radiology, and corresponding intraoperative images. TECHNIQUE: A definitive method of CSF fistula closure is described using previously known techniques used commonly in skull base surgery. CONCLUSIONS: The use of a multiple-level, reinforced wound closure technique is necessary to definitively close CSF fistulae in extreme inner ear deformity and to prevent further episodes of CSF leak and meningitis.     

Postpericardiotomy syndrome in pediatric heart transplant recipients. Immunologic characteristics

Clinical features of postpericardiotomy syndrome (PPS) occur in pediatric heart transplant recipients despite immunosuppression, which raises questions about the mechanism of PPS. We studied the clinical and immunologic characteristics of 15 pediatric heart transplant patients, ages 1.1 to 17.8 years (mean, 7.5 years); 7 had clinical evidence of PPS (PPS+), and 8 were without clinical features of PPS (PPS-). Indicators of PPS included fever, irritability, pericardial friction rub, leukocytosis without other cause, and pericardial effusion. The onset of PPS was from 9 to 26 postoperative days (mean, 16 days). Immunosuppressive regimens were comparable up to the day of PPS diagnosis in PPS+ patients, and up to day 16 in PPS- patients (average onset of PPS in PPS+ patients). No differences were found between groups with respect to weight-adjusted dosages of cyclosporin A, azathioprine, or corticosteroids. Mean cyclosporin A levels in PPS+ and PPS- patients were 142 +/- 88 ng/mL (mean +/- standard deviation) and 265 +/- 122 ng/mL (p = 0.045), respectively. Echocardiographic data on 3 PPS+ patients within 1 day of PPS diagnosis revealed pericardial effusions ranging from 5 to 24 mm. No data were available on the remaining 4 PPS+ patients. Minimal pericardial effusions (< 10 mm) were seen in 4 PPS- patients during a comparable time period. One PPS- patient required pericardiocentesis. Endomyocardial biopsy rejection grade did not differ between groups. Means pretransplant soluble interleukin-2 receptor levels did not differ between PPS+ and PPS- patients (758 +/- 410 vs 653 +/- 270 IU/mL); nor did the PPS+ pretransplant levels differ from levels obtained 1 or 2 months postoperatively (700 +/- 437 and 751 +/- 367 IU/mL, respectively). Although pretransplant percentages of the standard T-cell (CD2, CD3, CD4, CD8) and B-cell (DR and CD19) markers differed from post-transplant values, the changes could be explained by the immunosuppressive regimen and did not differ between PPS+ and PPS- patients. In the PPS+ patients, however, there were significant increases in the proportion of activated helper T cells (CD4+/25+) and cytotoxic T cells (Leu-7+/CD8+) following heart transplantation in comparison with pretransplant levels. We speculate that these changes in activation marker in PPS+ patients suggest a possible role for cell-mediated immunity in the pathogenesis of PPS in this group of patients.