Preventive Dental Treatment Workload/Costs to Mitigate Antiresorptive Bone Medication-related Osteonecrosis Risk.

PURPOSE: To determine the extent of dental disease and associated treatment costs designed to mitigate the risk of medication-related osteonecrosis of the jaws (MRONJ) among older, socially disadvantaged veterans prior to physician's administration of antiresorptive medication for osteoporosis or malignant bone disease. MATERIALS AND METHODS: This prospective study based on over seven years (2008-2015) of data describes the type and volume of disease, treatment, work-load measures, and costs using Veterans Affairs databases. RESULTS: One hundred fifty-two outpatients (94% male, mean age 69 ± 12 years) were referred by physicians for clinical/radiographic examination and treatment. Sixteen had a healthy dentition and 17 were completely edentulous with satisfactory prostheses. Three edentulous patients required prosthesis adjustment, 116 dentate individuals required restoration of carious teeth (mean 6.3 ± 5.7) and multiple quadrant (mean 3.1 ± 1.0) scaling/subgingival curettage. In the latter group, 75 required extractions (mean 6.0 teeth, range 1-23). Clinician's (dentist and dental assistant) costs for providing care and preventive education over the 7-year timespan came to almost $132,700. CONCLUSION: Older veterans requiring initiation of antiresorptive bone medication harbor extensive, untreated dental disease requiring immediate treatment. An appropriate physician-to-dentist referral network and provision of oral care and patient education prior to initiation of medication can potentially moderate the risk of jaw osteonecrosis.

Preoperative prediction for regaining ambulatory ability in paretic non-ambulatory patients with metastatic spinal cord compression.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To analyze the predictive factors for postoperative ambulatory recovery in paretic non-ambulatory patients with metastatic spinal cord compression (MSCC). SETTING: Japan. METHODS: Eighty-two consecutive patients (74.4% men; mean age, 66.2 years) who could not walk before surgery due to cervical or thoracic MSCC and underwent posterior decompressive surgery between 2003 and 2014 were included. Patients were divided into two groups according to ambulatory status at 6 weeks after surgery: recovery (group R) and non-recovery (group NR). To evaluate the speed of progression of motor deficits, we assessed the period from onset of neurological symptoms to gait inability (T1). RESULTS: Fifty patients (61.0%) regained the ability to walk (group R). The period of T1 demonstrated a positive correlation with probability of ambulatory recovery (P=0.00; Kendall's tau-b=0.38), and a receiver operating characteristic curve analysis showed that the cutoff value of T1 was 5 days (area under the curve=0.72; P=0.001). In multivariate analysis, <6 days of T1 was one of the independent risk factors for failing to regain ambulatory ability (odds ratio, 8.74; P=0.00). CONCLUSIONS: The speed of progression of motor deficits can independently and powerfully predict the chance of postoperative ambulatory recovery as well as previously identified predictors. Since information about the speed of progression can be obtained easily by interviewing patients or family members, even if the patient is in an urgent state, our results will be helpful in clinical decision-making.

Robb-Smith type malignant histiocytosis associated with a mediastinal germ cell tumor.

A 22-year-old Japanese man with a mediastinal germ cell tumor with mixed teratoma and hepatoid alpha-fetoprotein positive, and glandular yolk sac components, also demonstrated widely disseminated malignant histiocytosis involving the lungs, liver, pancreas, spleen, bone marrow and lymph nodes. Sensitivity to chemotherapy was acute and the patient died of disseminated intravascular coagulation syndrome within four months of his initial presentation.

[Cu, Zn-superoxide dismutase, glutathione peroxidase location in kidney of IgA nephropathy].

To study the role of reactive oxygen species (ROS) in chronic renal disease, we studied the localization of Cu, Zn-Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in glomeruli of patients with IgA nephropathy by immunohistochemical method. Thirty three kidney specimens were used consisting of 28 IgA nephropathy and, normal parts of the 5 resected kidneys with renal tumors as controls. To evaluate the change of renal function and renal histological grade, creatine clearance (Ccr) and histological grade were assessed at the time of biopsy. In normal kidney, Cu, Zn-SOD and GSH-Px was localized in tubular cells, and not in glomeruli. In the kidney with IgA nephropathy, Cu, Zn-SOD and GSH-Px were detected in epithelial side of the glomerular capillary wall in addition to the tubular cells. The positive correlation was observed between the glomerular localization of Cu, Zn-SOD and that of GSH-Px. As for the relation between the extent of localization of these enzymes and clinical findings at the time of biopsy, the following results was obtained. When Cu, Zn-SOD and GSH-Px was strongly stained in glomeruli, histological change of glomeruli was milder. These results suggest that Cu, Zn-SOD and GSH-Px have the beneficial actions for renal function as anti-oxidative factors.

Protection of gastric mucosa against ethanol-induced injury by intragastric bolus administration of epidermal growth factor combined with hydroxypropylcellulose.

Orally administered epidermal growth factor (EGF) has been shown to protect the gastric mucosa against injury induced by noxious agents. However, EGF administered by intragastric bolus appears to have less effect on the gastric mucosa because of its rapid excretion from the gastric lumen. In this study, mouse EGF given to rats by gastric intubation was confirmed to remain in the stomach at significantly high concentrations when given in combination with hydroxypropylcellulose (HPC), an agent that retards drug release. The residual mouse EGF levels in the gastric luminal content and tissue 3 h after administration of 50 micrograms/kg of EGF dissolved in 1 ml of 2% HPC were 30 and 60 times higher, respectively, than those obtained after EGF alone. Pretreatment with intragastric bolus administration of EGF and HPC at the same dose for 3 h attenuated significantly the development of gastric lesions induced by absolute ethanol compared to that with HPC alone, EGF alone, or saline (mean values of ulcer index: EGF + HPC, 14.3; HPC, 52.8; EGF, 50.7; and saline, 63.2 mm). There were no significant differences between the ulcer index in the HPC, EGF, and saline groups. The present study indicates that exogenous EGF given as an intragastric bolus protects the gastric mucosa against injury when combined with HPC, which can bind to EGF and prevent its rapid excretion from the gastric lumen.

Experimental and clinical studies on epidermal growth factor for gastric mucosal protection and healing of gastric ulcers.

In experimental studies, 0.6 N HCl-induced gastric mucosal injury was significantly severe in submandibularectomized rats (SMR rats) than that in either SMR rats receiving exogenous mouse EGF (SMR + EGF rats) or controls. This was also true in gastric injury induced by 0.4 N HCl under pretreatment with indomethacin to reduce gastric mucosal prostaglandins (PGs). Somatostatin (SLI), PGE2, and PAS-stained mucus in the corpus were significantly reduced in SMR rats in comparison to SMR + EGF and control rats. In clinical studies, salivary EGF secretion was much higher in peptic ulcer patients than healthy controls. beta-Urogastrone was effective in the treatment of gastric ulcers. On the basis of experimental studies, we conclude that the protective effect of EGF on the gastric mucosa is, in part, mediated indirectly by increases in SLI, PGE2, and mucus production. However, endogenous, as well as exogenous, EGF has an important direct, cytoprotective effect on the gastric mucosa. From the clinical studies, we also conclude that salivary EGF secretion in ulcer patients increases in a homeostatic response to the presence of an ulcer, facilitating ulcer healing. Furthermore, we believe that beta-urogastrone, human EGF, might prove to be an effective drug in the clinical treatment of gastric ulcers.

Immunoreactive epidermal growth factor in mouse digestive organs. Use of a sensitive enzyme immunoassay.

A sandwich enzyme immunoassay (ELISA) system for mouse epidermal growth factor (EGF), which has a high sensitivity (500 fg/tube), has been established. It makes it possible to measure minute amounts of immunoreactive EGF in various mouse tissue without pretreatment. The immunoreactive EGF concentrations in digestive tissues of adult mice were much lower than previously reported. A significant sex difference was detected not only in the submandibular gland, but also in the oesophagus and forestomach. Although sialoadenectomy decreased the immunoreactive EGF contents in the alimentary tract to 4.2-23.8% of the pre-operative levels, the duodenal immunoreactive EGF was unaffected. Positive immunostaining was observed in the submandibular and sublingual gland, but not in the other digestive tissues, including the duodenum. These data implied that most of the EGF in the digestive tissues was derived mainly from the saliva and that a small amount of endogenous EGF existed in the duodenum. The physiological role of exogenous salivary EGF in the alimentary tract and the origin of endogenous duodenal EGF are discussed.

Physiological concentrations of human epidermal growth factor in biological fluids: use of a sensitive enzyme immunoassay.

A sandwich enzyme immunoassay for epidermal growth factor (EGF) has been developed which measures EGF concentrations in serum, urine, saliva, gastric and pancreatic juices without pretreatment. Sensitivity for human EGF is 500 fg/tube. Serum EGF concentration in normal males and females is 780 and 604 pg/ml, respectively. Urinary human EGF is 51.3 ng/mg creatinine for males, and 68.3 ng/mg creatinine for females. The difference is not significant, and no correlation between serum and urinary concentrations exists, but serum concentration changes with age. The highest concentration is seen up to 9 years of age, suggesting that EGF promotes cell proliferation during growth.

Effects of cyclic nucleotides, betazole hydrochloride and acetylcholine on pepsinogen secretion from isolated rabbit gastric mucosa.

The effects of dibutyryl cyclic AMP (db-cAMP), dibutyryl cyclic GMP (db-cGMP), betazole hydrochloride (betazole) and acetylcholine (ach.) on pepsinogen secretion from isolated rabbit gastric mucosa were studied using an organ culture system. The 10(-3) M db-cAMP, but not db-cGMP of any concentration, produced a significant enhancement of pepsinogen secretion into the culture medium. In the presence of aminophylline (phosphodiesterase inhibitor), betazole stimulated pepsinogen secretion at concentrations of 10(-8), 10(-6) and 10(-4) M. The 10(-4) M betazole stimulated pepsinogen secretion most strongly (208% of control) and 10(-6) M betazole induced submaximal secretion (137% of control). Ach. stimulated pepsinogen secretion at 10(-8), 10(-6), 10(-4) and 10(-2) M. The peak secretion occurred at 10(-4) M ach. (303% of control). Betazole (with aminophylline) against a background of 10(-6) M ach. (submaximal stimulation dose), produced an intense stimulation of pepsinogen secretion at the concentrations of 10(-8), 10(-6) and 10(-4) M, and the secretion rate expressed as percent of control were 277, 350 and 329%, respectively. These responses were not considered the additive action by betazole and ach. but the potential interaction between the two agents in pepsinogen secretion. From these findings, we conclude that betazole-ach. interdependency exists in in vitro pepsinogen secretion.

Effects of betazole hydrochloride and cyclic AMP on the pepsinogen secretion by rabbit gastric mucosa in organ culture.

The effects of betazole hydrochloride, dibutyryl cyclic AMP (DB-cyclic AMP) and betazole hydrochloride plus aminophylline on pepsinogen secretion by rabbit gastric mucosa were studied in organ culture. Betazole hydrochloride alone did not stimulate pepsinogen secretion at the concentrations of 10(-8), 10(-6), 10(-5) and 10(-4) M. However, 10(-3) M DB-cyclic AMP produced a significant stimulation of pepsinogen secretion into the culture medium when compared with the control. In the presence of 3 x 10(-3) M aminophylline, betazole hydrochloride in the concentration of 10(-5) and 10(-4) M stimulated pepsinogen secretion into the culture medium, and the magnitude of this increase was 2.0- and 2.8-fold, respectively, compared with the control. Aminophylline alone could not change pepsinogen secretion into the culture medium. These results suggested that the pepsinogen secretion, stimulated by betazole hydrochloride, was mediated by cyclic AMP in the chief cells.