Surgical approaches for condylar fractures related to facial nerve injury: deep versus superficial dissection.

The aim of this study was to investigate the probability of facial nerve injury (FNI) in the treatment of condylar neck and subcondylar fractures (CN/SCFs) with percutaneous approaches and to identify factors predicting FNI. The data of 80 patients with 87 CN/SCFs were evaluated retrospectively. The primary outcome was FNI occurrence. The predictor variables were age, sex, aetiology, alcohol consumption, fracture site and pattern (dislocation or not), concomitant fractures, time interval to surgery, surgeon experience, plate type, and the dual classification of percutaneous approaches. The approaches were classified based on whether subcutaneous dissection traversed the marginal mandibular branch (MMB) deeply (deep group: submandibular and retroparotid approaches) or superficially (superficial group: transparotid, transmasseteric anteroparotid (TMAP), and high cervical-TMAP approaches). Twenty-two patients (27.5%) suffered FNI, of whom two in the deep group had permanent paralysis of the MMB. In the multivariate logistic regression model, deeply traversing surgery approaches (odds ratio 12.4, P=0.025) and the presence of a dislocated fracture (odds ratio 6.66, P=0.012) were associated with an increased risk of FNI. These results suggest that percutaneous approaches in the superficial group should be recommended for the treatment of CN/SCFs to reduce the risk of FNI.

Phase II study of a novel oral formation of 5-fluorouracil in combination with low-dose cisplatin as preoperative chemotherapy of oral squamous cell carcinoma.

TS-1 is a novel oral 5-fluorouracil containing tegaful (prodrug of 5-FU) and two biochemical modulators. These modulators feature effect-enhancing and adverse reaction-reducing activity. We investigated the histological response and toxicities of combination chemotherapy with TS- 1 and low-dose cisplatin and evaluated its usefulness as preoperative chemotherapy Forty-four newly diagnosed patients with stage Il-IV oral squamous cell carcinoma were enrolled in this study from February 2002 to April 2004. Patients were administered TS-1 80 mg/m2/day (days 1-14) and cisplatin 5 mg/m2/day (days 1-5 and 8-12) followed by radical surgery within 2 weeks. The histopathological effect of chemotherapy, which was a surrogate endpoint of this trial, was evaluated with surgical or biopsy specimens. The rate of histological antitumor effect was as follows: complete response (CR) 36.4%, partial response (PR) 25.0%, minor response (MR) 18.1% and no change (NC) 20.5%. The rate of histological response (CR + PR) was 61.4%. The CR rate of effective cases was 59.3%. The main toxicities occurred in bone marrow and the digestive tract. The incidence of severe toxicity such as grade 3 or 4 was 4.5% in anemia, 9% in leukocytopenia, 11.4% in neutropenia, 4.5% in thrombocytopenia and 2.3% in anorexia, diarrhea and urticaria. Most patients showed no toxicity or mild toxicities. TS- 1 with low-dose cisplatin has highly effective antitumor activity and mild toxicities. In particular, the CR rate was very high. It is suggested that this regimen is suitable for neoadjuvant chemotherapy. We expect that this chemotherapy will contribute to avoidance of surgery for small tumors (stages I and II) and will enable function-preserving surgery for advanced tumors.

Fluorous oligosaccharide synthesis using a novel fluorous protective group.

The Bfp (bisfluorous chain type propanoyl) group, a novel fluorous protecting reagent, was able to be prepared easily. The Bfp group was readily introduced to carbohydrate, was removed in high yield, and was recyclable after cleavage. Use of the Bfp group made it possible to synthesize a tetrasaccharide by minimal column chromatography purification. Each synthetic intermediate was able to be easily purified by using only simple fluorous-organic solvent extraction and was monitored by NMR, mass spectroscopy, and TLC. [structure: see text]

A clinical and histological evaluation of titanium mini-implants as anchors for orthodontic intrusion in the beagle dog.

The aim of this study was to determine the anchorage potential of the titanium mini-implant for orthodontic intrusion of the mandibular posterior teeth. Six mini-implants were surgically placed around the mandibular third premolars on each side in 3 adult male beagle dogs. On the buccal site, three mini-implants were placed distal to the apex of the distal root of the third premolar, at the interradicular septa of the third premolar, and mesial to the apex of the mesial root of the third premolar, as linearly as possible. The same procedure was performed at the lingual site on both sides of the mandibular third premolars in each dog. Bilateral interradicular mini-implants on both the buccal and the lingual sites were used as the anchorage for the intrusion of the third premolars (loaded implants) and the other mini-implants were used as control (unloaded) implants. In 6 weeks, an intrusive force (150 g) was applied between the interradicular implants on the buccal and the lingual sites by closed coil springs run across the crowns of the third premolars. After 12 to 18 weeks of orthodontic intrusion, the animals were killed and their mandibles were dissected and prepared for histologic and fluorescent observation. The results indicated that the mandibular third premolars intruded 4.5 mm, on average, after 12 to 18 weeks of orthodontic force application, with mild root resorption at the furcation area as well as the root apex. All the mini-implants remained stable during orthodontic tooth movement without any mobility or displacement. The morphometrical findings indicated that the calcification of the peri-implant bone on the loaded implants was equal to or slightly greater than those of the controls. In addition, 6 of the 36 mini-implants were removed after tooth movement, and all of them were easily removed with a screwdriver. These findings suggest that mini-implants are effective tools for the anchorage of orthodontic intrusion in beagle dogs.

Synthetic glycogels for affinity electrophoresis: a facile and efficient method for investigating sugar-lectin interaction.

A novel and efficient method for analyzing sugar-lectin interaction using affinity electrophoresis (AEP) is described. Polyacrylamide gels covalently conjugated with 2-acetamido-2-deoxy-D-glucopyranose (GlcNAc) residues were successfully prepared by radical copolymerization of highly reactive 3-(N-acryloylamino)propyl 2-acetamido-2-deoxy-beta-D-glucopyranoside with acrylamide in the presence of N,N'-methylenebisacrylamide (BIS). When the glycogels carrying various densities of GlcNAc branches were employed for polyacrylamide gel electrophoresis (PAGE) of lectins, the mobilities of wheat germ agglutinin (WGA) were specifically reduced by increasing the concentrations of the GlcNAc residues in gels, although concanavalin A (Con A) showed no significant change in the mobility. It was also demonstrated that the association constant of WGA with immobilized GlcNAc residue can be determined by combined use of this stable glycogel and an automated gel-scanning system associated with fluorometric spectroscopy. The association constant of WGA with the GlcNAc moiety was estimated to be 1.24 x 10(4) M-1.

The Saccharomyces cerevisiae GAM2/SIN3 protein plays a role in both activation and repression of transcription.

We have cloned GAM2, which is required for transcription of STA1, a gene encoding an extracellular glucoamylase in Saccharomyces cerevisiae var. diastaticus. DNA sequence analysis revealed that GAM2 is the same gene as SIN3, known to be a general negative regulator of yeast genes. RNA blot analysis indicated that GAM2/SIN3 also acts as a positive regulator of GAM3/ADR6, which in turn is required for transcription of STA1 and ADH2. These results suggest that GAM2 regulates STA1 expression through transcriptional activation of GAM3 and indicate that GAM2/SIN3 protein is a transcriptional regulator that can play a role in both activation and repression of transcription.

Frequency of the hypercalcemia-leukocytosis syndrome in oral malignancies.

There have been a number of reports over the last 15 years of patients with cancer who develop both leukocytosis and hypercalcemia, particularly in patients with cancers of the oral cavity. In this study, the authors report the frequency of hypercalcemia and leukocytosis in 225 patients with oral malignancies. Ten patients (4.4%) had hypercalcemia, 11 patients (4.9%) had leukocytosis, and five (2.2%) had both hypercalcemia and leukocytosis. The occurrence of these two distinct paraneoplastic syndromes in the same patients was greater than could have been expected from chance alone (chi-square = 45.8, P less than 0.0001). This study demonstrates that although hypercalcemia and leukocytosis are relatively uncommon in oral cancers, when they do occur they are frequently associated. To the knowledge of the authors, this is the first report in which the frequency of the association hypercalcemia and leukocytosis is studied in detail in large numbers of patients with oral cancer.

[Multiple malignant tumors combined with oral cancer from annual of the pathological autopsy cases in Japan, 1984-1988].

During the 5-year period from 1984 to 1988, a total of 944 cases had been presented multiple (3 or more) primary malignant tumors in annual of the pathological autopsy cases in Japan. Forty-one cases (4.3%) had lip and oral cancer. Of this group, triple were described 36 cases, quadruple 3 cases and more discrete multiple 2 cases, respectively. It is more frequent in men than in women, the ratio being 12.7:1. The age range is from 34 to 86 years with a mean of 66.9 years. In these cases with oral cancer, the another primary site is almost always found in digestive system (90.2%), e.g. esophagus (36.6%), stomach (34.1%) and colon and rectum (34.1%).

Mechanism and kinetics of secretion degradation in aqueous solutions.

In order to clarify the mechanism of secretin degradation in aqueous solutions, the formation of degradation products from secretin, aspartoyl3 secretin and beta-aspartyl3 secretin was investigated; the stabilities of these three peptides were investigated as well. Aspartoyl3 secretion and beta-aspartyl3 secretin, degradation peptides produced during the storage of secretin in aqueous solutions, were isolated by preparative reversed-phase HPLC (RP-HPLC). The amounts of secretin and its two degradation peptides resulting from storage of secretin in various buffer solutions (pH 2.3 to 10.0, mu = 0.5 M, 60 degrees C) were determined by analytical RP-HPLC. Secretin and the isolated degradation peptides were stored separately in various aqueous buffer solutions resulting in the degradation of each peptide. A mixture of secretin and its degradation or cleavage peptides was formed in each solution. The observed degradation rates for each peptide approximately followed first-order kinetics. The pH-rate profiles for conversion of secretin and beta-aspartyl3 secretin were similar, while that for aspartoyl3 secretin was different from these two. Aspartoyl3 secretin was more stable than the others at pH 2.3 to 4.0, but it was easily degraded between pH 5.0 and 10.0. Investigation of aspartoyl3 secretin degradation showed that its degradation was related to the pH value of the solution, and that hydroxide ion catalyzes the ring opening of the aspartoyl peptide. Secretin was most stable in pH 7.0 buffer solution and more stable in acidic solutions than in alkaline solutions. Secretion was mainly degraded through the following pathways: cleavage peptides reversible secretin in equilibrium aspartoyl peptide in equilibrium beta-aspartyl peptide vector cleavage peptides.

Degradation peptides of secretin after storage in acid and neutral aqueous solutions.

During the storage of secretin in acid and neutral aqueous solutions, five degradation peptides (A1, A2, A3, A4, A5) and one degradation peptide (N1) were produced, respectively. They were isolated in pure form by HPLC, and the intramolecular structures were studied by a combination of amino acid analysis, enzymatic digestions, HPLC, and Fab-mass spectroscopy. Although the degradation peptides are composed of the same amino acids as secretin after acid hydrolysis (except A1 and A4 which are cleavage products S16-27 and S4-27, respectively), reversed-phase HPLC analysis of their digestive fragments with trypsin and alpha-chymotrypsin are different from those of secretin. By Fab-mass spectroscopy, the m/z values for the S1-6 fragments obtained from secretin, A2, and A3 were 663, 663, and 645, respectively. When S1-6 from A2 was treated with aminopeptidase M, a fragment obtained was identical with the synthetic beta-aspartyl3 S3-6, as determined by HPLC. The A2 and N1 peptides are completely the same based on various chemical analyses. The A3 peptide can also be rapidly degraded to secretin and beta-aspartyl3 secretin. Consequently, A1 and A4 are concluded to be the cleavage peptides of secretin, S16-27 and S4-27, respectively, A2 and N1 are concluded to be beta-aspartyl3 secretin, and A3 is concluded to be aspartoyl3 secretin.

Identification of secretin diastereoisomers produced during synthesis.

The byproducts P-1 and P-2, which were produced during the synthesis of porcine secretin, were isolated in pure form from the crude secretin by HPLC. These were identified by a combination of amino acid analysis, enzymatic digestion, and isocratic or linear gradient reversed-phase (RP)-HPLC. The amino acid compositions of P1 and P2, determined by amino acid analysis after acid hydrolysis, were found to be the same as those of porcine secretin without distinction between L-and D-amino acids. But, HPLC of their digestive fragments with trypsin and alpha-chymotrypsin differed from that of secretin. The fragments, S7-12 of P-1 and S13-21 of P-2 were determined to be different from the corresponding fragments obtained from secretin by HPLC analysis of their digestive fragments. The amino acid composition of each acid hydrolysate, following digestion with D-amino acid oxidase, was found to have less leucine or alanine content than secretin. The HPLC analysis of the fragments from P-1 and P-2 by tryptic and alpha-chymotryptic digestion showed that they are the same as those from synthetic D-Leu10 secretin or D-Ala17 secretin, respectively. Consequently, P-1 and P-2 are concluded to be the secretin diastereoisomers, D-Leu10 and D-Ala17 secretin, respectively.

Biphasic effects of alcohol drinking on methamphetamine metabolism in man.

In methamphetamine (MAP) addicts, long-term ethanol ingestion 3-4 times per week induced an increased rate of p-hydroxylation of MAP and amphetamine (AMP). Simultaneous ingestion of ethanol and MAP inhibited both p-hydroxylation of MAP and AMP and N-demethylation of MAP in inebriated addicts. The p-hydroxylation of MAP and AMP was also significantly inhibited in daily drinkers despite the almost total absence of urinary ethanol. This suggests that the intensity of MAP-induced behavioral and psychological effects in MAP addicts may, in part, depend upon their drinking habits.

Spontaneous resolution of a dissection of the descending aorta after medical treatment with a beta blocker and a calcium antagonist.

A 58 year old man experienced an attack of squeezing chest pain. A contrast enhanced computed tomographic scan showed acute dissection of the descending aorta. Treatment with metoprolol and nicardipine kept his blood pressure below 130/90 mm Hg while he was supine at rest and after walking. Serial contrast enhanced computed tomographic scans showed opacification of the false lumen (which was not opacified initially) on the 42nd day; moderate regression of the false lumen on the 67th day, and resolution of the false lumen on the 266th day. This is the first in vivo demonstration of spontaneous resolution of aortic dissection detected by serial contrast enhanced computed tomographic scans.

Effect of diltiazem hydrochloride in essential hypertension.

A number of studies have shown short term hemodynamic and symptomatic improvement in patients with essential hypertension under treatment with diltiazem. The long-term efficacy of the oral calcium antagonist, diltiazem, remain to be established in patient studies. We evaluated this drug in 70 patients with WHO classification 1-3 hypertension. Diltiazem was tested alone in 25 patients, in combination with diuretics in 14 patients and other drugs in 31 patients with essential hypertension. The fall in blood pressure after oral diltiazem was maximum with 24 weeks and then the fall continued steadily with significant improvement as judged by subjective patients impression in each group. The efficacy ratio of diltiazem was 57.1% in remarkably effective cases, 22.9% in effective, 10% in moderately effective and 10% in not effective cases. And this efficacy ratio was most prominent in other drugs concomitant group, followed by the diltiazem monotherapy group and in the diuretic concomitant use group. We concluded the oral calcium antagonist, diltiazem, is effective in patients with essential hypertension, providing significant blood pressure and symptomatic benefit with long-term treatment.

Electrocardiographic findings in experimental myocarditis in DBA/2 mice: complete atrioventricular block in the acute stage, low voltage of the QRS complex in the subacute stage and arrhythmias in the chronic stage.

To determine whether arrhythmias persist in the chronic stage of myocarditis, serial electrocardiograms were studied in DBA/2 mice with experimentally induced myocarditis. After baseline electrocardiograms with standard limb and two precordial leads were recorded, 52 mice were inoculated intraperitoneally with 0.1 ml of the myocardiotropic variant of encephalomyocarditis in a viral suspension containing 10(2) TCD50 (50% tissue culture infective dose). Electrocardiograms were recorded every day on days 3 to 18 and, thereafter, once every 10 to 20 days until day 220. The cumulative incidence rate of myocarditis was 90.4% (47 of 52). No arrhythmias were found on baseline electrocardiograms. Serial electrocardiograms showed atrial and ventricular premature complexes and complete atrioventricular (AV) block, respectively, in 6 (12.8%), 8 (17.0%) and 25 (53.2%) of 47 mice with myocarditis. Myocardial lesions were found in the heart of mice with these ectopic complexes. Mononuclear cell infiltrations into the His bundle were noted in the conduction system of mice with complete AV block. Heart rate began to increase after day 11 (638 +/- 105 beats/min, n = 16 versus control rate 557 +/- 57 beats/min, n = 47, mean +/- standard deviation, p less than 0.01) and reached a maximum on day 15 (40 +/- 22 beats/min, n = 8, p less than 0.01). The sum of QRS voltage in eight leads began to decrease after day 6 (62.1 +/- 18.8 mm, n = 24 versus control value 80.0 +/- 14.7 mm, n = 47, p less than 0.01) and reached a minimum on day 13 (32.5 +/- 7.5 mm, n = 8, p less than 0.01) when myocardial necrosis and congestion of the lungs and liver were most prominent.(ABSTRACT TRUNCATED AT 250 WORDS)