Sequential changes in oral dryness evaluated by a moisture-checking device in patients with oropharyngeal cancer during chemoradiotherapy: a pilot study.

PURPOSE: Although oral dryness is a predictor for oral mucositis caused by Chemoradiotherapy (CRT) for head and neck cancer, there have been few reports evaluating the sequential changes in oral dryness during therapy. Studies have determined the reliability and usefulness of a moisture-checking device for the evaluation of dry mouth. This study aimed to evaluate the oral moisture level in patients with Oropharyngeal Cancer (OPC) during CRT using a moisture-checking device. METHODS: Oral moisture level was measured with an oral moisture-checking device (Moisture Checker Mucus®) at the lingual and buccal mucosa before, at the midpoint, and at the end of CRT in patients with OPC. Sequential changes in oral dryness were evaluated. RESULTS: A significant decrease in oral moisture level at the lingual mucosa was found when comparing values before and at the end of CRT (P=0.017). Decreases in oral moisture level at the buccal mucosa were not significant. CONCLUSIONS: A moisture-checking device is considered a useful tool for determining the sequential changes in oral dryness during CRT for head and neck cancer. Our findings provide a basis for future larger long-term studies of oral moisture levels in OPC patients receiving CRT.

Levodopa challenge test and (123) I-metaiodobenzylguanidine scintigraphy for diagnosing Parkinson's disease.

OBJECTIVES: To explore the possibility of a generally applicable tool for the immediate diagnosis of Parkinson's disease (PD) in its early stage, we compared the sensitivity and specificity of an acute levodopa challenge test with that of (123) I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. MATERIALS AND METHODS: A consecutive series of 45 patients with extrapyramidal symptoms were recruited to the acute levodopa challenge and evaluated for improvement by use of the Unified Parkinson's Disease Rating Scale motor scores. Of these patients, 32 of them were also examined by MIBG scintigraphy. The patients were followed up for at least 24 months, and 22 patients were diagnosed as having clinically definite PD. RESULTS: The sensitivity and specificity of the acute levodopa challenge test to predict clinical diagnosis of PD were 81.8% and 81.8%, respectively, which were better than those obtained by MIBG scintigraphy (62.5% and 62.5%). In both early- and middle-stages of PD, the test gave better sensitivity than MIBG scintigraphy. CONCLUSIONS: Considering that the well-established and frequently referred clinical diagnostic criteria require longitudinal observation for at least 24 months, the acute levodopa challenge test can be used as an immediate diagnostic tool for PD with sensitivity and specificity comparable to those of MIBG.

Diagnostic and prognostic biomarkers in acute myocarditis. Interleukin-10.

Acute myocarditis is a major inflammatory heart disease with a variety of clinical courses from the acute to chronic phases represented by unexpected circulatory deterioration during hospitalization and progression to dilated cardiomyopathy. Predicting these disease courses is important for patient management. However, biomarkers have not been fully investigated. In addition, clinical profiles including symptoms, serological data, and electrocardiographic findings in acute myocarditis often mimic more common disorders such as coronary artery disease, which have reduced the diagnostic accuracy of acute myocarditis. These issues hamper the development of safer and earlier therapeutic interventions specific for acute myocarditis. Against this background, identifying simple prognostic and diagnostic biomarkers would contribute dramatically to the improvement in outcomes. Interleukin-10 may be a strong candidate for an excellent biomarker.

Sarcoidosis with Both Plaques and Subcutaneous Nodules Associated with Combination Therapy with Peginterferon α-2a and Ribavirin.

A 64-year-old woman with hepatitis C was treated using combination therapy with peginterferon α-2a and ribavirin. After 3 months, she presented with raised nodules on her knees and elbows. After 8 months, she developed painful subcutaneous nodules on her forearms. We diagnosed sarcoidosis with both plaques and subcutaneous nodules associated with combination therapy with peginterferon α-2a and ribavirin. Sarcoidosis with both plaques and subcutaneous nodules is very rare. The patient had a sustained Th2 response in the liver. And a sustained Th1 response occurred only in the skin. It is likely that, for this reason, sarcoidosis was localized to the skin, and the patient developed sarcoidosis with both plaques and subcutaneous nodules.

Efficacy and safety of sitagliptin monotherapy compared with voglibose in Japanese patients with type 2 diabetes: a randomized, double-blind trial.

OBJECTIVE: To compare the efficacy and safety of sitagliptin (a dipeptidyl peptidase-4 inhibitor) and voglibose (an alpha-glucosidase inhibitor) monotherapy in Japanese patients with type 2 diabetes who have inadequate glycaemic control (HbA1c > or =6.5% and <10.0%) on diet and exercise. METHODS: In a multi-center, randomized, double-blind, parallel-group study, 319 patients were randomized (1:1) to 12-week treatment with sitagliptin 50 mg once daily or voglibose 0.2 mg thrice daily before meals. The primary analysis assessed whether sitagliptin was non-inferior to voglibose in lowering HbA1c. RESULTS: After 12 weeks, sitagliptin was non-inferior to voglibose for HbA1c-lowering efficacy. Furthermore, sitagliptin was superior to voglibose, providing significantly greater reductions in HbA1c from baseline [least squares mean changes in HbA1c [95% confidence intervals (CI)] = -0.7% (-0.8 to -0.6) and -0.3% (-0.4 to -0.2), respectively; between-group difference = -0.4% (-0.5 to -0.3), p < 0.001]. Sitagliptin was also superior to voglibose on other key efficacy endpoints, including change from baseline in 2-h postmeal glucose (-2.8 mmol/l vs. -1.8 mmol/l, p < 0.001) and fasting plasma glucose (-1.1 mmol/l vs. -0.5 mmol/l, p < 0.001). After 12 weeks, the incidences of clinical adverse experiences (AEs), drug-related AEs and gastrointestinal AEs in the sitagliptin group (48.5, 10.4 and 18.4%, respectively) were significantly (p < 0.05) lower than those in the voglibose group (64.7, 26.3 and 34.6%, respectively). The incidences of hypoglycaemia, serious AEs and discontinuations due to AEs were low and similar in both groups. CONCLUSIONS: In Japanese patients with type 2 diabetes, once-daily sitagliptin monotherapy showed greater efficacy and better tolerability than thrice-daily voglibose over 12 weeks.

Estimation of plasma and saliva levels of coenzyme Q10 and influence of oral supplementation.

Coenzyme Q10 (CoQ(10)) levels in human saliva were measured by HPLC with a highly sensitive electrochemical detector (ECD) and a special concentration column. This HPLC system showed satisfactory analytical results within the standard range of 0.78-50 ng/ml. We also found a significant correlation between CoQ(10) levels in plasma and in saliva from parotid glands, while this correlation was lacking between plasma CoQ10 and CoQ10 in whole saliva. Unlike in plasma, there are some fluctuations of saliva CoQ(10) levels throughout the day. A good correlation was obtained by collecting parotid gland saliva at times between meals. The mean saliva CoQ(10) level for 55 healthy volunteers was 17.0 ng/ml (S.D. 6.8 ng/ml); approximately one fiftieth of that in plasma. Regarding the influence of oral supplementation, CoQ(10) was analyzed in plasma and parotid gland saliva from 20 healthy volunteers supplemented daily with 100 mg of CoQ(10) for the first week and 200 mg for the second. The plasma CoQ(10) levels of all volunteers increased to different extents in accordance with the CoQ(10) daily intake and the corresponding change in saliva showed almost the same trend.

ONO-8815Ly, an EP2 agonist that markedly inhibits uterine contractions in women.

OBJECTIVE: To determine the effect of ONO-8815Ly on uterine contractions. DESIGN: A randomised, double-blind, placebo-controlled, dose-ascending, cross-over study. SETTING: Department of Obstetrics and Gynaecology, University Hospital of Lund, Sweden. POPULATION: Seventeen, healthy, parous and permanently sterilised women. METHODS: Intrauterine pressure was recorded on days 1-3 of bleeding of two menstruations. Subjects were intravenously treated with 4 or 8 microg/minute of ONO-8815Ly or placebo for 130 minutes. Intravenous bolus injections of oxytocin, 50 pmol/kg body weight, were given 10 minutes before, during infusion after 60 and 120 minutes and 60 minutes after completion of infusion. The plasma concentrations of ONO-8815Ly were measured in samples obtained immediately before each oxytocin injection. MAIN OUTCOME MEASURE: Area under pressure recording curve (AUC) 10 minutes before and after each oxytocin injection. RESULTS: Twelve women, six in each dose group, completed both recordings. Of these, two women of each group were not included in efficacy analysis due to non-responsiveness to oxytocin or missing baseline value. The AUC over 10 minutes before oxytocin injection after 60 minutes of infusion of ONO-8815Ly at 4 and 8 microg/minute was reduced to 21% and 37% of that before infusion, respectively. The AUC after oxytocin at that time amounted to 21% and 19%, respectively, of that before infusion. The activity and responsiveness remained low after 120 minutes but started to return to baseline 60 minutes after stopping infusion. Placebo had no effect. CONCLUSIONS: ONO-8815Ly is a potent inhibitor of spontaneous uterine contractility in non-pregnant women and it reduces the uterine response to oxytocin injections.

Scleroderma renal crisis complicated by hemolytic uremic syndrome in a case of elderly onset systemic sclerosis.

We report a case of renal crisis in a patient with elderly onset systemic scleroderma (SSc). A sixty-one-year-old woman was diagnosed as having SSc with rapidly advancing generalized skin sclerosis. After experiencing an upper respiratory infection, she suddenly developed renal failure, hemolytic anemia and malignant hypertension. Laboratory examination revealed uremia with a significantly high plasma renin level. Ophthalmologic study revealed Keith-Wagner's retinopathy Grade IV. Combination therapy including captopril, systemic corticosteroid and prostaglandin E1 venous infusion for the hemolytic uremic syndrome was effective and saved her from the renal crisis. However, her renal function deteriorated and she needs permanent hemodialysis. Rapidly progressive skin sclerosis in SSc, especially in elderly onset cases, suggests a high risk for renal crisis and indicates the need for careful consideration of hypertension and renal function.

Isolation and characterization of [Pro2]somatostatin-14 and melanotropins from Russian sturgeon, Acipenser gueldenstaedti Brandt.

A new form of somatostatin (SRIH), along with melanotropins (MSHs), was isolated from pituitaries of the Russian sturgeon Acipenser gueldenstaedti Brandt by gel filtration, ion exchange, and reversed-phase HPLC following acid-acetone extraction. The sturgeon SRIH consists of 14 amino acid residues and differs from mammalian SRIH-14 by the substitution Pro for Gly at position 2. Synthetic [Pro2]SRIH-14 was as potent as mammalian SRIH-14 in inhibiting release of growth hormone into medium from the organ-cultured pituitary of rainbow trout. Sturgeon alpha-MSH has the same amino acid sequence as those found in mammals. Sturgeon beta-MSH is composed of 17 amino acid residues, and its amino acid sequence is identical to the N-terminal 15 residues of salmon beta-MSH I and to the C-terminal 2 residues of mammalian beta-MSH.

[Immunohistochemical study of PCNA, EGFR, c-erbB-2 and p53 in carcinomas of large intestine].

Immunohistochemical stainings for EGFR, c-erbB-2, p53 and PCNA were performed on 36 and 30 cases of intramucosal and advanced carcinomas of large intestine. Positive rate was 58.3%, 41.6%, 58.3% and 60.6% for EGFR, c-erbB-2, p53 and PCNA in the intramucosal cases, and 66.7%, 50%, 66.7% and 72.6% in the advanced ones, respectively. Relationship between EGFR and c-drbB-2 was more significant in the advanced carcinomas than that in the intramucosal ones. It seemed likely that relationship between p53 and c-erbB-2 was more significant than that between p53 and EGFR. Positive rate of PCNA was of intimate relationship among that of EGFR, c-erbB-2 and p53, and the positive rate increased in the advanced carcinomas.

Urinary bladder-selective action of the new antimuscarinic compound vamicamide.

1. The inhibitory action of vamicamide (FK176, (+/-)-(2R*,4R*)-4-dimethylamino-2-phenyl-2-(2-pyridyl)valeramide, CAS 132373-81-0) on the responses of various tissues to the cholinergic agonists, carbachol and McN-A-343 (4-[m-chlorophenylcarbamoyloxy]-2-butynyl-trimethylammonium chloride, CAS 55-45-8), was investigated in isolated tissue preparations. Vamicamide showed competitive antagonistic actions against all the preparations tested and its pA2 value for the urinary bladder was 6.82, which was higher than that for the atria (5.94) and almost the same as that for the vas deferens (6.90) and for the stomach (6.81). The pA2 values of oxybutynin hydrochloride (oxybutynin) and atropine sulfate monohydrate (atropine) were nearly the same in all the tissues tested. 2. Oral administration of vamicamide 0.1-1.0 mg/kg inhibited dose-dependently spontaneous bladder contractions caused by raising the intravesical volume in conscious rats. Inhibitory actions were also obtained with 0.32-3.2 mg/kg of oxybutynin or 0.0032-0.032 mg/kg of atropine, but the duration of action of oxybutynin was shorter than that of vamicamide or atropine. Vamicamide further inhibited bladder contractions in rats following intravesical administration of 0.05-0.5 mg/ml solution. 3. Vamicamide had no effect or only slightly inhibited spontaneous motility of the stomach and distal colon in conscious rats, as well as heart rate and salivary secretion in conscious dogs, after oral dosing with 3.2 mg/kg of the compound. Similar results were obtained with oxybutynin, excepting the occurrence of tachycardia.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of a homologous radioimmunoassay for coho salmon insulin-like growth factor-I.

A specific homologous radioimmunoassay (RIA) for measurement of insulin-like growth factor-I (IGF-I) in plasma of salmonid and a few non-salmonid fish species was developed using recombinant coho salmon IGF-I (rsIGF-I) as tracer and standard, and antiserum against this peptide raised in rabbits. The minimum detection level of IGF-I was 1.5 ng/ml and linearity was obtained in a range from 1.5 to 23 ng/ml. No cross-reaction was detected in the salmon IGF-I RIA with mammalian growth factors, salmon pituitary hormones, salmon or mammalian insulin, or any peptide in rat plasma. Although salmon IGF-I has high sequence similarity to mammalian IGF-I, it did not cross-react with anti-human IGF-I serum in human RIA and serial dilutions of plasma from salmon were not parallel to the human IGF-I standards in this assay system. In contrast, dilution curves for plasma of salmonids, such as coho (Oncorhynchus kisutch), Atlantic (Salmo salar), and sockeye (O. nerka) salmon, rainbow trout (O. mykiss), some other teleost fish, such as tilapia (Oreochromis mossabmica), carp (Cyprus carpio), eel (Anguilla rostrata), Atlantic halibut (Hippoglossus hippoglossus), and agnathan, the sea lamprey (Petromyzon marinus), assessed in salmon IGF-I RIA were parallel to the rsIGF-I standards. Acid-ethanol extraction of plasma samples altered the molecular weight, but not the quantity, of immunoreactive IGF-I, implying that IGF-I binding proteins in salmon plasma do not affect the performance of the salmon IGF-I RIA. Gel filtration of nonacidified plasma on a Sephadex G-75 superfine column produced two immunoreactive IGF-I peaks of molecular weights of approximately > 70 k and 7 kDa, whereas acidification of plasma increased the relative amount of the 7-kDa peak (IGF-I) and the > 70-kDa peak disappeared. The recoveries of rsIGF-I added to extracted or nonextracted plasma were 97.4 and 94.9%, respectively. Inter- and intraassay coefficients of variation were 3.6 and 3.3%, respectively. Plasma IGF-I levels in coho salmon smolts were 117.4 +/- 19.1 ng/ml as compared to IGF-I levels in parr (45.3 +/- 2.5 ng/ml) or in adult fish (45.2 +/- 5.4 ng/ml) measured in the same assay. Injection of salmon growth hormone, but not prolactin or somatolactin, caused a significant and dose-dependent elevation of plasma IGF-I levels, while either fasting or injection of streptozotocin led to a significant decline in systemic IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)

[Recent advances in imaging diagnosis of pancreatic neoplasma with special reference to early diagnosis of the cancer].

Recent advance in various diagnostic imagings has enabled the early diagnosis of pancreatic tumors. In pancreatic cancer, the tumor-demonstrability by US, CT, and MRI has reached 80% in the recent 6 years, which is superior to the rate in the past decade from 1978 and 1987. However, the prognosis of pancreatic cancer is still poor even if the cancer can be resected. To improve the outcome of surgical intervention, early detection of small cancers (< or = 2 cm in diameter) and appropriate intervention based on preoperative diagnosis of the tumor extension are proposed. The tumor detectability of small pancreatic cancer by US, CT, MRI was 67%, 25%, 20%, respectively, and thus US was the most valuable tool. In the prediction of tumor extension of serosal invasion (S factor), retroperitoneal invasion (Rp factor) and vessel invasion (PV factor), both US and CT were efficacious with an accuracy of more than 70%. In conclusion, recently-advanced imaging seems to be useful for detecting a small pancreatic cancer and evaluating the tumor extension, but it remains difficult to diagnose a carcinoma in situ; a truly early cancer.

Vasorelaxant mechanism of the new vasodilator, FK409.

To define the vasorelaxation mechanism of FK409, we examined the effect of the compound on vascular tension and cyclic nucleotide levels in isolated rat thoracic aorta contracted with norepinephrine, and on activities of guanylate cyclase and cyclic GMP phosphodiesterase prepared from rat or rabbit thoracic aorta. FK409 (1 x 10(-9) to 1 x 10(-6) M), like nitroglycerin (1 x 10(-9) to 1 x 10(-6) M), produced a potent vasorelaxant effect associated with an increase in cyclic GMP content of the tissue. There was no change in cyclic AMP levels. The vasorelaxant effect of FK409 was independent of the integrity of the endothelium, and was unaffected by L-NG-monomethylarginine (0.1 mM) or oxyhemoglobin (1 microM). On the other hand, FK409 (3.2 x 10(-7) M) activated soluble guanylate cyclase, and the activating effect was completely inhibited by oxyhemoglobin (10 nM). Cyclic GMP phosphodiesterase was unaffected by FK409 (1 x 10(-7) to 1 x 10(-5) M). Furthermore, in rat aortic soluble fraction FK409 (3 mM) was found to liberate nitric oxide (NO) which was evaluated spectrophotometrically after diazotization of sulfanilic acid and coupling with N-(1-naphthyl)-ethylenediamine. The liberation occurred even in the absence of L-cysteine (5 mM), in contrast to the case with nitroglycerin (3 mM). These results suggest that the vasorelaxant effect of FK409 is associated with an increase in intracellular cyclic GMP, and that the cyclic GMP accumulation is due to activation of soluble guanylate cyclase. The enzyme activation is probably due to NO released from the compound molecule in the vascular smooth muscle cells.

[Immunohistochemical study of growth factors and oncogenes in gastric carcinomas].

Immunohistochemical staining for EGF, EGFR, c-erbB-2, p53, K-ras and PCNA was performed on the formalin-fixed, paraffin embedded sections of resected gastric carcinomas. A relatively high positive rate was observed for EGFR and c-erbB-2 in the well-differentiated adenocarcinomas and p53 in the poorly-differentiated adenocarcinomas. The positive rate of these factor was higher in the advanced cases than in the early cases, and also in the deep invasive area than the superficial area. According to the PCNA staining, a relatively high positive rate was observed in the well-differentiated adenocarcinomas compared with the early cases of poorly-differentiated adenocarcinomas, but the positive rate was markedly higher in the advanced cases of the latter. Typical signet-ring cell carcinomas showed the lowest positivity rate compared with the other histological types of gastric carcinomas.

[Immunohistochemical study for growth factor and oncogene on atypical epithelium of the stomach].

Almost all atypical epithelial lesions of the stomach consist of atypical cells in the superficial part of the glands and nonatypical cells in the deeper portion of the glands. A transition zone was formed between the superficial atypical gland cells and the deeper nonatypical gland cells. Positive cells were widely demonstrated with immunohistochemical stains for PCNA in the superficial atypical glands and transition zone. The rate of PCNA positivity was 37.7%. However, a small number of positive cells for EGFR (8.5%), c-erbB-2(11.3%), p53(11.3%) and c-K-ras(1.7%) were found in ATP. The incidence of positivity for these factors was low compared with that for carcinomas. The percentages of positive cells for EGFR(1.5%) and c-erbB-2(4.5%) were very low in intestinal metaplasia.

[Immunohistochemical study of the lymph-follicles and lymphocytes in the gastric mucosa].

Immunohistochemical stainings according to ABC method (UCHL-1,L-26,MT-1,MB-1,IgG,IgA,IgD,IgM, kappa, lambda, LN-1 and LN-2) for the lymphocytes in the germinal center, mantle zone and infiltrative lymphocytes in the gastric mucosa of 30 cases of chronic gastritis and 10 cases of reactive lymphoreticular hyperplasia (RLH) were performed. Lymphocytes in the germinal center and mantle zone consisted usually of B-cells positively stained by L-26 and MB-1. However, in the interstitially infiltrative cells,T-cells positively stained by UCHL-1 and MT-1 were not infrequently contained. Immunoglobulin stainings revealed marked positivity for IgG,IgA,IgD,IgM, kappa and lambda in the interstitial lymphocytes and plasma cells. As to the RLH, small number of T-cells scattered in the germinal center and surrounding area of lymph follicles, and large number of T-cells were found among the follicles, where B-cells were more infrequently found than in the interstitial area of propria mucosae. Confusion of enlarged germinal centers and monotonous proliferation of lymphocytes among the lymph follicles showing monotonous positivity for the stains of heavy and light chains in the cases of RLH were suggestive of malignant change.

Purines. LII. Synthesis and biological evaluation of 8-methylguanine 7-oxide and its 9-arylmethyl derivatives.

The synthesis of 8-methylguanine 7-oxide (3) was accomplished via a "phenacylamine route", which started from condensation of alpha-(4-methoxybenzylamino)propiophenone (6), prepared by coupling of alpha-bromopropiophenone (4) and 4-methoxybenzylamine (5), with 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone (7) and proceeded through cyclization of the resulting phenacylaminopyrimidinone (8) and removal of the 4-methoxybenzyl group. The N-oxide 3 and its 9-arylmethyl derivatives 9 and 11 showed only very weak antileukemic activity and no antimicrobial activity.

A case of nephrotic syndrome and renal dysfunction in a pregnant woman with diabetes mellitus.

A 29-year-old diabetic woman who developed severe anaemia, nephrotic syndrome, and hypertension before the 28th week of gestation, had residual evidence of toxaemia and renal dysfunction more than 1 month following delivery. The histopathological findings of renal biopsy specimens were considered most consistent with toxaemia of pregnancy complicated by diabetic glomerulosclerosis. We consider that rapid acceleration of renal dysfunction may have been induced by: (1) poor control of diabetes before pregnancy; (2) glomerular hyperfiltration of the remnant nephrons throughout pregnancy; (3) hypercoagulopathy associated with pregnancy; (4) appearance of hypertension following these three conditions.

Heterotopic pancreas of the stomach. Histogenesis and immunohistochemistry.

Ordinary histological investigation has suggested that heterotopic pancreas of the stomach may have two types of histogenesis; one is development from immigrated fetal pancreas tissue, and the other is development from primitive gastric mucosal epithelium following penetration into the submucosa with subsequent erroneous differentiation into pancreas tissue. It is suspected that type-I lesions include the majority of cases caused by immigration from fetal pancreas, and that some type-II cases arise through erroneous differentiation of primitive gastric mucosal epithelium. With regard to immunohistochemical findings, cells positive for pancreatic polypeptide and amylase were much more numerous in the acini of type-I cases compared with type-II cases. Positive cells were found not infrequently in the acini of type-II cases after staining for pancreatic polypeptide, insulin, glucagon, somatostatin, serotonin, and gastrin. On the other hand, a small number of cells in islets were not infrequently positive for alpha 1-antitrypsin, alpha 1-antichymotrypsin, and amylase. It is considered that in the heterotopic pancreas, ductal cells have the potential to differentiate into acinar cells and islet cells, as is the cases in the orthotopic pancreas.