A randomized, double-blind, placebo-controlled trial of the effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on rectal polyps in familial adenomatous polyposis patients.

PURPOSE: The aim of this study was to examine the effect of a specific cyclooxygenase-2 inhibitor, rofecoxib, on rectal polyps in familial adenomatous polyposis patients. EXPERIMENTAL DESIGN: This was a randomized, double-blind, placebo-controlled study of the efficacy and safety of rofecoxib in the rectum. Initially, 21 patients were assigned randomly in a 1:1 ratio to receive either 25 mg rofecoxib once a day or a placebo p.o. for 9 months. Patients underwent endoscopy at the beginning of the study and then every 3 months thereafter. We reviewed the videotapes to measure the number and size of polyps in the same area throughout the study period in each individual patient. RESULTS: The polyp number, measured as the percentage of change from the baseline values, was significantly decreased in the rofecoxib group at 3, 6, and 9 months. At 9 months, the polyp number in the rofecoxib group decreased by 6.8% from the baseline values, whereas that in the placebo group increased by 3.1%. The 9.9% difference between the rofecoxib and placebo groups was statistically significant (P = 0.004). At 9 months, the rofecoxib group showed a significant reduction from the baseline in polyp size as compared with the placebo group (-16.2% versus 1.5%; P < 0.001). There was no statistically significant increase in the incidence of any adverse events in treatment with rofecoxib compared with placebo (P = 0.922). CONCLUSIONS: In this study, once-daily treatment with 25 mg rofecoxib, a cyclooxygenase 2-specific inhibitor, significantly decreased the number and size of rectal polyps in familial adenomatous polyposis patients.     

Induction of Squamous Cell Carcinomas in the Salivary Glands of Rats by Potassium Iodide

In a 2-year carcinogenicity study of potassium iodide (KI) in F344/DuCrj rats, squamous cell carcinomas (SCCs) were observed in the salivary glands of 4/40 males and 3/40 females receiving 1000 ppm KI in the drinking water. Ductular proliferation with lobular atrophy was observed at high incidence in the submandibular glands of the high-dose animals, and squamous metaplasia was frequently evident within the proliferative ductules and the larger interlobular ducts. A transition from metaplasia to SCC was apparent. The results suggest that squamous metaplasia in proliferative ductules, occurring secondarily to lobular impairment induced by KI, may develop into SCCs via a non-genotoxic, proliferation-dependent mechanism.     

Age-specific effects of noradrenergic alpha-2 agonist clonidine on the development of amygdaloid kindling in developing rats

The effects of clonidine on the development of amygdaloid kindling were studied in rats of various ages (14, 21, 28 and 70 postnatal days). Administration of clonidine (0.2, 0.5 mg/kg i.p.) caused a significant retardation of kindling development in the 28-day-old rats as well as in the adult rats, whereas, in the 14-day-old rats, the development of kindling was significantly facilitated by clonidine. No significant effect of clonidine was observed in the 21-day-old rats. These results indicate that in rats the effects of clonidine on the development of amygdaloid kindling vary during development.     

Simultaneous treatment with citrate prevents nephropathy induced by FYX-051, a xanthine oxidoreductase inhibitor, in rats.

The possible mechanism of the underlying nephropathy found in the rat toxicity study of FYX-051, a xanthine oxidoreductase inhibitor, was investigated. Rats received oral treatment of either 1 or 3 mg/kg of FYX-051, with and without citrate for four weeks to elucidate whether nephropathy could be caused by materials deposited in the kidney. Furthermore, analysis of the renal deposits in rats was also performed. Consequently, interstitial nephritis comprising interstitial inflammatory cell infiltration, dilatation, basophilia and epithelial necrosis of renal tubules and collecting ducts, deposits in renal tubules and collecting ducts, and so forth was seen in six of the eight rats and in all eight rats in the 1 and 3 mg/kg FYX-051 alone groups, respectively, with the intensity in the 3 mg/kg group being moderate to severe. In the simultaneous treatment with citrate group, however, no alterations were observed in the kidney, except for minimal interstitial nephritis in one instance in the 3 mg/kg FYX-051 + citrate group along with an increased urinary pH, leading to an increase in xanthine solubility. Analysis of intrarenal deposits showed that the entity would be composed of xanthine crystals. The present study, therefore, showed that nephropathy in rats occurring after the administration of FYX-051 was a secondary change caused by xanthine crystals being deposited in the kidney, and no other causes could be implicated in this kidney lesion.     

Fatigue-induced changes in longitudinal relaxation time determined by magnetic resonance imaging

Longitudinal relaxation time (T₁) determined by 3.0-T magnetic resonance imaging of the tibialis anterior and extensor digitorum longus muscles increased gradually with muscle fatigue caused by three 120-s periods of repeated ankle dorsiflexion separated by 5-min rest periods. T₁ values decreased in the recovery period, although they remained higher than the preexercise values. T₁ values for the soleus muscle were unchanged throughout the experiment. Results suggest that muscle T₁ values increase with increasing muscle fatigue.     

Age‐ and sex‐associated morphological variations of metatarsal torsional patterns in humans

It has been demonstrated that the torsional patterns of the metatarsal heads are associated with the presence or absence of the medial longitudinal arch in hominoid feet. The relatively untwisted second metatarsal is unique in humans, but that of the African apes is much more inverted, suggesting that the torsion of the second metatarsal might represent the overall shape and flatness of the foot. Some clinical studies have recently argued that the onset of foot pathologies such as hallux valgus might be related to the torsional pattern of the metatarsals. However, to date, no studies have systematically investigated the morphological variations of the torsional patterns of human metatarsals. In this study, therefore, the aim was to clarify the age‐ and sex‐associated variations in the torsional patterns of human metatarsals using three‐dimensional computed tomography. The torsion angles of the five metatarsals were calculated by defining the dorsopalmar vector of the metatarsal base and the vector corresponding to the rotational axis of the metatarsal head. The present result demonstrated that the second metatarsals of females were significantly more inverted with increasing age. Flat foot is known to be most common in elderly women. Whether there is a cause–effect relationship between second metatarsal torsion and flattening of the medial longitudinal arch has yet to be answered, but this study suggested that torsion of the second metatarsal might possibly be used as an indicator for the early diagnosis of flat foot and associated foot pathologies. Clin. Anat. 30:1058–1063, 2017. © 2017 Wiley Periodicals, Inc.     

Reliability of the skin blotting method when used on the elderly

The aim of this study was to compare protein secretion on intact skin of extremities and verify the relationship between the marker proteins on abdominal skin and systemic factors using skin blotting. A cross‐sectional study was conducted among elderly patients aged 65 years and older (N = 73) at a long‐term medical facility in Japan. Skin blotting was performed on the right and left forearms, right and left lower legs, and abdomen. Pearson's correlations and Bland–Altman plots were utilised for comparing the protein secretion from the skin between the right or left forearms or lower legs. Multiple regression analysis was applied to determine the relationship between intensity levels of 3 proteins on the abdominal skin and the systemic factors. Bland–Altman plots demonstrated that there was no significant difference between right and left secretion levels on the forearms and lower legs among 3 proteins. Multiple regression analysis showed that age and antiplatelet use was positively associated with decreased collagen type IV and increased matrix metalloproteinase 2 levels, respectively. Our findings suggested that collecting samples from either the right or the left skin would be sufficient if skin properties between arms and legs are evaluated using skin blotting.