Gastric emptying rate in subjects with malocclusion examined by [(13) C] breath test.

Masticatory function is significantly lower in individuals with malocclusion than in those with normal occlusion. Although several studies suggest that masticatory function influences gastrointestinal digestive function, the relationship between malocclusion and gastrointestinal symptoms has not been studied extensively. We hypothesised that insufficient masticatory function would increase the functional burden of the stomach and have some influence on the gastrointestinal system. The purpose of this study was to investigate masticatory function and gastric emptying rate in subjects with malocclusion. Eleven healthy dentate female volunteers and eleven female patients with maloc-clusion underwent a (13) C-acetate breath test with a liquid meal. Maximum (13) CO2 exhalation time (Tmax ) was compared statistically between both groups. Masticatory function was assessed by colour-changeable chewing gum. In addition, the frequency scale for the symptoms of gastroeso-phageal reflux disease (FSSG) and questionnaires on food intake were given to both groups. The mean Tmax of the malocclusion group was significantly longer than that of the normal occlusion group (P = 0·007). Masticatory performance, measured by colour-changeable gum and questionnaires, was significantly lower in the malocclusion group than in the normal occlusion group (P = 0·023, P = 0·003). There was no significant difference in the FSSG results between the two groups (P = 0·262). This study suggested that there was a correlation between malocclusion and gastric emptying function in women.

Genomics and proteomics approaches to the study of cancer-stroma interactions.

BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.

LHX6 is a sensitive methylation marker in head and neck carcinomas.

Head and neck cancer remains a morbid and often fatal disease and at the present time few effective molecular markers have been identified. The purpose of the present work was to identify new molecular markers for head and neck squamous cell carcinoma (HNSCC). We applied methylation-sensitive arbitrarily primed PCR (MS/AP-PCR) to isolate sequences differentially methylated in HNSCC. The most frequently hypermethylated fragment we found maps close to a cytosine guanine dinucleotide (CpG) island on chromosome 9q33.2, and hypermethylation of this CpG island was associated with transcriptional silencing of an alternative transcript of the LHX6 gene. Using combined bisulfite restriction analysis (COBRA), hypermethylation of this fragment was detected in 13 of 14 (92.8%) HNSCC cell lines studied and 21 of 32 (65.6%) primary tumors, whereas little or no methylation was seen in 10 normal oral mucosa samples. We extended this investigation to other cancer cell lines and methylation was found in those derived from colon, breast, leukemia and lung, and methylation was also found in 12/14 primary colon tumors. These findings suggest that differentially methylated (DIME)-6 hypermethylation is a good cancer marker in HNSCC as well as in other kinds of neoplasias and confirm the importance of searching for markers of epigenetic dysregulation in cancer.

[A case report of the patient at a terminal stage of stomach cancer, who had a visiting nurse].

We have started the visiting nurse system in our Kimitsu Central Hospital since September 1990, and have currently had 33 patients with 4 visiting nurses as of February 2001. Out of these 33 patients with the visiting nurse system, 9 patients are at a terminal stage of diseases. In the present study, we reported here a case of a 63 year-old female patient, who was at a terminal stage of stomach cancer and wished to have a regular home life, having a visiting nurse at home. The patient was not informed of her diagnosis as a cancer, but was convinced of her symptoms by her primary care physician that she was under a good care. Meanwhile, the patient showed less pain than that she was expected to have as a patient at the terminal stage of cancer. A daughter of the patient (actual caretaker) was first considering of hospitalization as an inpatient. However, since the patient strongly desired to stay and get care at home, the caretaker started a dual life of taking care of her mother at home and of raising children in parallel, in aware of a case of pronouncing death at home. While the patient's condition was relatively stable, the good quality of life (QOL) was maintained as she could make a trip of one-night stay. As the symptom progressed, however, the caretaker had a high anxiety with a pressure of accepting her own mother's death. On the other hand, a visiting nurse, who understood the patient's strong desire to stay at home and live her life as usual, also assisted in reducing the caretaker's high anxiety. Therefore, the visiting nurse basically assumed one possibility that the patient would die at home, but also prepared for the another possibility that the caretaker could choose to send her mother back to hospital whenever she felt her limit for being a caretaker. Moreover, the visiting nurse supported the patient and her family with an encouragement that they could live their favorable life till the end. As a result, the caretaker could continue to keep the patient at home, although she had a tremendous fear about taking care of her at home. When the patient's condition suddenly changed and got worsened, however, the caretaker desired to have her mother stay and get medicated in the hospital. Thus, the patient was sent to our hospital by ambulance. Although the caretaker did not have her mother die at home under her direct care, she recognized the great advantages in having a visiting nurse, who really assisted them well. Thus, it was confirmed that participation of a visiting nurse in the home healthcare could give the patient and her family a better, satisfactory life till the end. In general, although the patients or their family members wish to stay home and to have a home healthcare service, their desire or mind can be easily changed according to their situation. Especially in a case of the patient at a terminal stage, the family can be easily influenced by the condition of progression of the disease. One of the major roles of visiting nurses is always to understand the feelings of the patients and family and to prepare for the best as they can.

Changes in jaw-jerk on different levels of jaw closure and teeth-clenching in humans.

We investigated how the jaw-jerk in the human masseter muscle is modulated in relation to the level of jaw closure (JC) and teeth clenching. Electromyographic (EMG) activity was recorded with surface electrodes. Background EMG activity of the masseter muscle was kept at three low teeth clenching levels with visual feedback. The level of JC was changed in six steps along the habitual path of closure relative to the mean maximal jaw opening during gum chewing by inserting a bite block between the upper and lower molars. The jaw-jerk was evoked by applying mechanical stimulation of about 20 N with a hammer to the bite-fork placed on the lower molars on one side in each condition of combination of a level of JC with a level of teeth-clenching. At the resting condition the excitability of the jaw-jerk increased with JC, while at weak voluntary teeth clenching it then decreased and increased again as the jaw was progressively closed. It is suggested that the excitability of the jaw-jerk would increase toward the occlusal position, which in turn would contribute to smooth masticatory movements. In addition, the mode of modulation of the jaw-jerk was studied in a subject with skeletal malocclusion.

Development of a new device for recording condylar head movement.

Several excellent devices have recently been developed to precisely record mandibular movement. However, these devices are not always suitable for use under certain conditions, such as during sleep, because they incorporate a face bow unit. We report here a newly developed, easy and convenient recording device that does not require the use of an instrument within the mouth. Instead, a subminiature pressure transducer is inserted between the outer surface of a fixation device in the external auditory meatus and the anterior cutaneous surface of the external auditory meatus. The fixation device was made using silicone impression material in the shape of the inner external auditory meatus. Following moulding, the material was cut in half and the parts were reconnected using a coiled spring. This method is based on a routine clinical method for palpating the external auditory meatus to observe condylar head movement. By comparing the results obtained using this device with those obtained using CADIAX, we confirmed that it is useful for recording the movement of the condylar head in routine clinical examinations.

[Phase I study on DMDC].

Phase I study on antimetabolic carcinostatic DMDC was conducted at 16 medical institutions nationwide for patients with various types of malignant tumors. DMDC was administered by intravenous infusion as per the following three schedules: single administration, single repeated administration, and 5-consecutive-day administration. The safety of the compound was examined single administration in 16 patients, by the single repeated administration in 5 patients, and by the 5 consecutive-day administration in 7 patients, for a total of 28 patients. In the single administration trial, 200 mg/m2 (1 n) was given as an initial dose, then increased stepwise to 450 mg/m2 (2.25 n). The single repeated administration trial was conducted at a single dose of 300 mg/m2. One treatment course lasts until recovery from side effects and abnormalities in laboratory test values. As a general rule, the administration was repeated for 2 treatment courses or more. In the 5-consecutive-day administration trial, an initial dose was 30 mg/m2/day (1 n), and increased to 40 mg/m2/day (1.3 n). The dose-limiting factors for both the single and 5-consecutive-day administration trials were decreases in the numbers of leukocytes and neutrophils. The maximum tolerated dose for single administration trial was over 400 mg/m2 (2 n), and for the 5-consecutive-day administration trial 40 mg/m2 (1.3 n). The decrease in the number of leukocytes and neutrophils for both the single administration and 5-consecutive-day administration trial reached its nadir one to two weeks after administration, and recovered in about one week. In the single repeated administration trial, the administration interval for patients who had completed 2 courses was 2 approximately 3 weeks. The plasma half-life of DMDC in the final phase of elimination in the single administration trial was 5.2 approximately 6.3 hours, and no differences were seen among dose levels. The urinary excretion rate was between 32.0 approximately 61.5% until 48 hours after administration. No accumulation was seen in the 5-consecutive-day administration trial. There were no findings to suggest an antitumor effect in the present study. Given the recovery pattern for suppression of marrow, the above mentioned results led us to decide that an recommended method of administration and dosage in an early phase II trial would be 300 mg/m2 per administration by an intravenous infusion every 2 approximately 3 weeks.

Elevated plasma levels of matrix metalloproteinase-9 (92-kd type IV collagenase/gelatinase B) in hepatocellular carcinoma.

BACKGROUND: Matrix metalloproteinase 9 (MMP-9), a 92-kd gelatinase/type IV collagenase, has been implicated as playing an important role in cancer invasion and metastasis. A previous study showed that serum type IV collagenase activity correlated with metastasis by hepatocellular carcinoma (HCC). The aims of this study were to determine the plasma levels of immunoreactive MMP-9 in patients with HCC and to compare the levels with the clinical features including vascular invasion. PATIENTS AND METHODS: This study included 100 patients with HCC, 21 patients with chronic hepatitis (CH), 24 patients with liver cirrhosis (LC), and 138 healthy control subjects. Plasma MMP-9 levels were measured with a specific one-step sandwich enzyme immunoassay. RESULTS: Plasma MMP-9 levels in HCC (62 [33 to 130 ng/mL] median [25%, 75%], 13 to 660 ng/mL, minimum, maximum) were significantly elevated compared with those in normal controls (36 [25 to 45], range, 2.8-70 ng/mL), in CH (28 [18 to 30], 13 to 66 ng/mL) and in LC (35 [26 to 58], 16 to 86 ng/mL) (P < .0000001; P = .0000003; and P = .00205, respectively). When the cut-off level was defined as 60 ng/mL from a receiver operating characteristic curve, plasma MMP-9 concentrations had a sensitivity of 53% and a specificity of 89% for the detection of HCC from CH and LC. The levels were significantly higher in HCC patients with macroscopic portal venous invasion (79 [36 to 160], 15-660 ng/mL) than those without the invasion (44 [27 to 80], 13 to 210 ng/mL) (P = .00726). Plasma MMP-9 levels in patients with HCC were not correlated with tumor number, size, volume, or serum alpha-fetoprotein levels. CONCLUSIONS: The present data suggest that plasma MMP-9 levels can be a candidate for a novel marker for HCC. The levels appear to reflect its potential and ongoing activity of vascular invasion. A long-term follow-up of the patients will be necessary to determine whether increased plasma MMP-9 levels are predictive of more invasive and metastatic HCC.

[UFT + MMC and UFT + ACNU therapy in advanced gastric cancer].

The effects of UFT + MMC and UFT + ACNU therapy on advanced gastric cancer were compared by randomized controlled trial in 12 institutions. Unresectable and postoperatively recurrent patients were divided into PS 0-2 and 3-4 groups. After classification according to cancer spread, such as localized type, hepatic metastatic type, ascitic type and distant metastatic type, regimens of (A) UFT 375 mg/m2/day + MMC 5 mg/m2 for 1-2 W or (B) UFT + ACNU 60 mg/m2/W/x2 (with a 4-week interval) were administered for as long as possible. As a result, among a total of 104 cases, responses were recognized in 7 out of 32 cases (21.9%) treated with regimen A and in 5 out of 25 cases (20.0%) treated with regimen B, giving a total of 57 evaluable cases excluding 33 incompletely evaluated cases and 14 ineligible cases. This study therefore demonstrated no significant difference between the two regimens. The median survival of patients treated with regimen A was 120 days, and that of patients treated with regimen B, 155 days. There was no significant difference between the two regimens. As side effects, UGI symptoms were recognized in 35.4% of regimen A patients and in 37.1% of regimen B patients. Bone marrow suppression appeared in 39.6% of regimen A patients and in 54.3% of regimen B patients.