Review of clinical studies on the nocebo effect.

Objective: To review clinical studies on the nocebo effect. PubMed was searched for relevant clinical studies as well as studies on the relationship between the nocebo effect and genes. Data sources: A total of 35 clinical studies on the nocebo effect and one study on its relationship with genes were selected for review. All were conducted outside Japan. Results and conclusion: An increasing number of clinical studies on the nocebo effect are being published. The 36 studies selected for review were grouped into the following five categories: (1) studies of how differences in participant characteristics such as personality affect susceptibility to the nocebo effect, (2) studies of how differences in provision of information about side effects affect susceptibility to the nocebo effect, (3) studies of how nocebo conditioning affects susceptibility to the nocebo effect, (4) studies of nocebo response mechanisms, and (5) studies of the nocebo effect and genetic polymorphisms. The first four categories comprised 5, 19, 8, and 3 studies, respectively, and the fifth comprised 1 study. Most of the studies investigated how differences in the provision of information affect susceptibility to the nocebo effect. Few studies investigated individual differences in the nocebo effect (differences between responders and non-responders) or mechanisms of the nocebo effect.

Invasive colorectal cancer within 5 years of negative colonoscopy in a Japanese population.

AIM: Colonoscopy provides imperfect protection against colorectal cancer (CRC). In an attempt to improve cancer detection we evaluated the clinical features of invasive CRC detected within 5 years of a negative colonoscopy. METHOD: The details of colonoscopies performed in a rural hospital in Japan were prospectively recorded at the time of the examination. The patients were followed over 5 years for the subsequent occurrence of cancer. RESULTS: In a 5-year period, 10148 patients underwent colonoscopy and 202 without previous colonoscopy were diagnosed with invasive CRC. Of 3212 patients with a colonoscopy negative for cancer, nine developed invasive cancer within 5 years. The ratios for invasive CRC detected without/with previous colonoscopy were 60:1 in the rectum, 54:1 in the sigmoid colon, 15:1 in the descending colon, 28:0 in the transverse colon, 31:5 in the ascending colon and 14:1 in the caecum (P=0.041). The ratio between left- and right-sided colonic cancer was also significantly different (129:3 and 45:6, P=0.0078). Six (67%) of the invasive CRCs were in the ascending colon or caecum. Five of six patients with invasive CRC in the ascending colon and caecum had right-sided small adenomas at prior colonoscopy. CONCLUSION: The majority of early/missed CRCs were right-sided and associated with prior right-sided colonic adenomas. Repeated colonoscopy of patients with right-sided adenomas at a shorter surveillance interval deserves consideration.

Endoscopic decompression of benign large bowel obstruction using a transanal drainage tube.

AIM: Endoscopic decompression of malignant colorectal obstruction is often dealt with using expandable metallic stents. Endoscopic decompression of benign large bowel obstruction is more difficult. We report the technique and outcome of transanal endoscopic decompression for benign large bowel obstruction. METHOD: From January 2001 to June 2010, endoscopic decompression using a transanal drainage tube placement was attempted in consecutive patients with benign large bowel obstruction. The clinical features, technical success, complications, treatment after the tube placement and clinical success were retrospectively evaluated. RESULTS: There were 13 patients (seven males, age 47-87, mean 69 years). The sites of obstruction were transverse colon [5 (38%)], sigmoid colon [3 (23%)], ileocecal valve [2 (15%)], splenic flexure [1 (8%)], descending colon [1 (8%)] and rectum [1 (8%)]. The most common cause of obstruction was anastomotic stricture [9 (69%)]. In 12 (92%) patients transanal decompression was technically successful with one perforation. An overtube, the reinsertion of colonoscope along the decompression tube, or the use of a small-diameter endoscope was required for the tube placement in seven (54%). In seven (54%) patients tube placement alone resulted in relief of bowel obstruction without operation. CONCLUSION: Endoscopic decompression using a transanal drainage tube is effective for the management of benign large bowel obstruction.

Colonoscopic enema as rescue for inadequate bowel preparation before colonoscopy: a prospective, observational study.

AIM: Colonoscopy may need to be rescheduled because of inadequate bowel preparation. We evaluated the effectiveness of colonoscopic enema as rescue for an inadequate 1-day bowel preparation before colonoscopy. METHOD: Patients referred for afternoon colonoscopy were prospectively enrolled in the study during a 1-year period. Patients took bowel preparation (polyethylene glycol) solution on the morning of the endoscopy. If during colonoscopy the bowel preparation was poor, an enema of polyethylene glycol solution (500 ml) was instilled into the colon at the level of the hepatic flexure via the biopsy channel of the colonoscope which was then removed. The patient was allowed to recover from the propofol sedation and used the bathroom to evacuate the enema. The colonoscope was then introduced and the examination continued. RESULTS: Of 504 patients undergoing colonoscopy, 26 (4.9%) received an enema. The median age was 59 (29-79) years and 19 (73%) were female. A subsequent successful colonoscopy was achieved in 25/26 (96%). There were no complications. The mean time spent for the entire colonoscopy from the initial preparation to the end of the examination including the enema was 7.6± 1.1h (5.4 h preparation, 0.2h first colonoscopy+enema, 0.66h waiting in the lavatory, 0.33h second colonoscopy and 1 h for recovery). CONCLUSION: Colonoscopic enema was highly successful as rescue for patients with inadequate bowel preparation and avoided postponement of the procedure.

Pedunculated colorectal polyps with heads ≤ 1 cm in diameter can be resected using cold snare polypectomy.

BACKGROUND AND STUDY AIMS: Cold snare polypectomy (CSP) is not recommended for the resection of pedunculated colorectal polyp. The aim of this study was to examine the adequacy of CSP compared to hot snare polypectomy (HSP) for the complete resection of pedunculated polyps with heads ≤ 1 cm in diameter. PATIENTS AND METHODS: This was a retrospective study of a cohort of consecutive outpatients who had resection of pedunculated polyps with heads 6-10 mm in diameter using either dedicated CSP or HSP from 2014 through 2019. The primary outcome measure was occurrence of delayed bleeding. Secondary outcome measures included total procedure time, en bloc resection rate, immediate bleeding, and number of clips used. RESULTS: 415 patients with 444 eligible polyps were enrolled; the CSP group (363 patients; 386 polyps) and HSP group (52 patients; 58 polyps). Patient characteristics, polyp characteristics and en bloc resection rate were similar between groups. The mean total procedure time and mean number (range) of hemostatic clips/ patient used were significantly lower with CSP than with HSP (18± 8 min vs. 25± 9 min, P<0.001; 1.1 ± 0.6 (1-3) vs.3.1 ± 1.6 (1-5), respectively, P<0.001). Delayed bleeding occurred significantly less frequently in the CSP, 0% (0/363 vs.3.8% (2/52) in the HSP group (P<0.001), although immediate bleeding was significantly higher in CSP than HSP (84% (325/386) vs. 12% (7/58), P<0.001). CONCLUSION: Pedunculated colorectal polyps with heads ≤ 1 cm can be removed using CSP, which has several advantages over HSP.

Suppression of mid-infrared light absorption in undoped congruent lithium niobate crystals.

Absorption measurements on 5 mol. % MgO-doped and undoped congruent lithium niobate (LiNbO(3)) crystals revealed absorption bands in the wavelength range of 2500-2800 nm, caused by incorporated hydrogen ions. High-temperature annealing was applied to the congruent LiNbO(3) (CLN) crystals, which decreased the absorption significantly. Then the annealed CLN crystals were periodically poled. As an application of the low-loss annealed CLN crystal, the operation of a 1550 nm pumped singly resonant CW optical parametric oscillator, resonant around 2600 nm, using a periodically poled crystal was demonstrated.

Prospective randomized trial comparing the direct method using a 24 Fr bumper-button-type device with the pull method for percutaneous endoscopic gastrostomy.

BACKGROUND AND STUDY AIMS: Percutaneous endoscopic gastrostomy (PEG) is the preferred route for long-term enteral feeding. The aim of this study was to compare a direct, modified introducer method using a bumper-button-type device with the standard pull method for PEG. PATIENTS AND METHODS: Between October 2005 and January 2007 consecutive patients with dysphagia were randomly assigned to PEG using either the direct method or the pull method. The direct method directly placed a 24 Fr bumper-button-type device assisted by dual gastropexy. The primary outcome measure was the rate of peristomal infections. Secondary measures included success rates, procedure times, and other complications. The long-term outcome measure was the need for catheter change within 180 days of the PEG procedure. RESULTS: Of the 140 patients enrolled, 68 were assigned to the direct method and 72 to the pull method. There were no significant differences between the two groups with respect to clinical baseline parameters. The occurrence of peristomal infection within 30 days was significantly lower following the direct method (0 vs. 6, P = 0.028). The success rates and duration of both methods were similar (100% vs. 100%; 10.5 vs. 9.6 minutes, P = 0.48). The catheters used in the direct method required replacement significantly less often than those placed using the pull method (no catheter change in 180 days: 75% vs. 45.2%, P = 0.0019). CONCLUSIONS: The direct method using a 24 Fr bumper-button-type device was associated with reduced peristomal infections in the early phase and reduced catheter changes compared with a 20 Fr catheter placed using the standard pull method.

Effectiveness and safety of a new regimen of polyethylene glycol plus ascorbic acid for same-day bowel cleansing in constipated patients.

BACKGROUND AND STUDY AIMS: In an exploratory study we compared a new regimen of low-volume polyethylene glycol plus ascorbic acid (PEG-Asc) with the standard regimen for same-day bowel cleansing in constipated patients. PATIENTS AND METHODS: Between January and June 2015 we studied consecutive patients with constipation (Rome III constipation criteria) scheduled for colonoscopy. The initial group received the standard regimen of PEG-Asc. The subsequent group received the new regimen. The new regimen involved ingestion of 10 mL of sodium picosulfate and 50g of magnesium citrate dissolved in 0.2 L of water followed by 0.2 L of PEG-Asc +0.2 L of water given 6 or 7 times over 3 hours. Bowel cleansing was prospectively evaluated using the Boston bowel preparation scale (BBPS). Bowel cleansing, adenoma detection rates and adverse events were reviewed using electronic medical records and endoscopic filing system. RESULTS: Sixty-two patients used the standard regimen and sixty used the new regimen. The basic characteristics of the two groups were similar. The mean volume of PEG-Asc and total liquid intake was less with the new regimen compared to the standard regimen (1.3 L vs. 2.0 L, P<0.001; 2.6 L vs. 3.0 L, P<0.001). The proportion of patients with a BBPS score ≥ 6 was significantly greater with the new than the standard regimen (93% vs. 76%, P=0.008). Nausea and/or vomiting was also significantly less frequent than with the standard regimen (5% vs. 16%, P=0.046). CONCLUSIONS: The new regimen of PEG-Asc gave improved same-day bowel cleansing for colonoscopy in constipated patients.

Superoxide dismutase in various tissues from rabbits bearing the Vx-2 carcinoma in the maxillary sinus.

Distribution profiles of superoxide dismutase isoenzymes in various tissues of rabbits with the Vx-2 carcinoma in the maxillary sinus were compared with those of control rabbits. Copper- and zinc-containing superoxide dismutase (Cu,Zn-SOD) activity in the liver of rabbits decreased significantly 3 weeks after transplantation. Manganese-containing superoxide dismutase (Mn-SOD) activity did not decrease significantly within 5 weeks after transplantation. In other tissues from the tumor-bearing rabbits, Cu,Zn-SOD and Mn-SOD activities were not changed within 5 weeks. No Mn-SOD activity and low Cu,Zn-SOD activity were detected in the Vx-2 carcinoma. These results suggest that the Vx-2 carcinoma has lost most of its ability to defend against oxygen toxicity and this ability decreased only in the liver of rabbits bearing the Vx-2 carcinoma in the maxillary sinus.

Hydrated ionic liquids as a liquid chaperon for refolding of aggregated recombinant protein expressed in Escherichia coli.

We have succeeded in refolding of aggregated recombinant protein from Escherichia coli in hydrated ionic liquids. In cholinium dihydrogen phosphate containing a limited amount of water molecules, aggregated solid cellulase was dissolved and refolding was successfully carried out without further processing.

The Perrault syndrome: clinical report and review.

We report on two Japanese sisters with Perrault syndrome, i.e., autosomal recessive ovarian dysgenesis associated with sensorineural deafness. They also had ataxic gait, pes equinovarus, nystagmus, limited extraocular movements, and short stature. One older affected sister had partial growth hormone deficiency. Our review included 21 patients from 8 families, including our patients; 16 are women with ovarian dysgenesis and deafness, 3 deaf males without gonadal defect, one a woman with ovarian dysgenesis without deafness, and one a girl with deafness in whom ovarian function was not evaluated. Perrault syndrome may not be uncommon; some cases may have gone unrecognized, especially when a single child in a family is affected.

Changes in blood pressure and heart rate variability during dental surgery.

The objective of the present study was to determine the changes in blood pressure, pulse rate, and heart rate variability during dental surgery. The study included 40 patients, 19 to 74 years of age (mean age: 42.7+/-3.0 years), who underwent tooth extraction at our hospital. Holter electrocardiographic monitoring was used to determine the power spectrum of R-R variability before and during dental surgery. The low frequency (LF: 0.041 to 0.140 Hz), high frequency (HF: 0.140 to 0.500 Hz), and total spectral powers (TF; 0.000 to 4.000 Hz) were calculated, and the ratio of LF to HF and percentage of HF relative to TF (%HF: HF/TF x 100) were used as indices of sympathetic and parasympathetic activities, respectively. The baseline blood pressure and pulse rate were 121+/-3/70+/-2 mm Hg and 70+/-1 beats/min, respectively. After the administration of local anesthetic (2% lidocaine) containing 1:80,000 epinephrine, both the blood pressure and pulse rate increased. During dental surgery, blood pressure increased further to 132+/-3/73+/-2 mm Hg. The increase in blood pressure was greater in middle-aged and older patients (> or =40 years old). In young patients (<40 years old), the %HF decreased and the LF/HF increased during local anesthesia. In contrast, in middle-aged and older patients, the LF/HF decreased during local anesthesia. These results suggest 1) that middle-aged and older patients have a greater increase in blood pressure during dental surgery than younger patients, and 2) that the regulation of the autonomic nervous system during dental surgery differs between younger and older patients.

Blood pressure response during dental surgery.

To investigate blood pressure and pulse rate responses to dental surgery, 21 patients 18 to 73 years of age (mean age, 42 +/- 4 years) who visited our hospital for tooth extraction were studied. Before dental treatment, the patients underwent a mental arithmetic stress test, electrocardiography, and an anxiety evaluation with the State-Trait Anxiety Inventory. Baseline blood pressure and pulse rate were 118 +/- 4/70 +/- 3 mmHg and 69 +/- 2 beats/min, respectively. Blood pressure rose by 24 +/- 3/17 +/- 2 mmHg during the mental stress test, and the magnitude of the rise in systolic blood pressure was significantly correlated with age (r = 0.81, p < 0.001) and baseline blood pressure (r = 0.56, p < 0.01). After the topical injection of local anesthetic containing 1: 80,000 epinephrine, a transient increase in systolic blood pressure was observed. The maximum blood pressure and pulse rate increases during dental surgery were 24 +/- 4/13 +/- 2 mmHg and 17 +/- 3 beats/min, respectively. Similarly, the rate pressure product increased from 8,196 +/- 486 to 11,802 +/- 682. The magnitude of the blood pressure increase during dental surgery was not correlated with age, sex, family history of hypertension, baseline blood pressure, anxiety score, or response to mental stress. On the other hand, when the subjects were divided into two subgroups according to the blood pressure response during dental surgery, the larger response group (increase in mean blood pressure greater than 15 mmHg, n = 9) required a significantly larger dose of local anesthetic than did the smaller response group. The number of cases of pericoronitis of the third molar tended to be greater in the larger response group. These results indicate that an increase in blood pressure during dental surgery cannot be predicted on the basis of baseline blood pressure or the response to mental stress, but is related to the cause of tooth extraction and the volume of local anesthetics required to control the pain.

Suppression of cardiac sympathetic nervous system during dental surgery in hypertensive patients.

We determined the changes in blood pressure, pulse rate, and heart rate variability during dental surgery in hypertensive patients. The study included 18 essential hypertensives and 18 age and sex matched normotensive controls who underwent tooth extraction at our hospital. Holter electrocardiographic monitoring was used to determine the power spectrum of R-R variability before and during dental surgery. The low frequency (LF: 0.041 to 0.140 Hz), high frequency (HF: 0.140 to 0.500 Hz), and total spectral powers (TF: 0.000 to 4.000 Hz) were calculated, and the ratio of LF to HF and the percentage of HF relative to TF (%HF: HF/TF x 100) were used as indexes of sympathetic and parasympathetic activities, respectively. The baseline blood pressure for hypertensive patients (149 +/- 4/85 +/- 2 mmHg) was significantly higher than that for normotensive patients (119 +/- 3/71 +/- 2 mmHg). The baseline pulse rates were similar between the two groups. Blood pressure increased during tooth extraction in both groups; however, changes in blood pressure did not differ between them. Administration of local anesthetic significantly decreased the %HF in normotensive patients (before vs. after anesthesia; 22.3 +/- 2.4 vs. 13.8 +/- 2.7%, p < 0.05). In contrast, the LF/HF significantly decreased during the local anesthesia and tooth extraction in hypertensive patients. These results suggest that pressor response induced by tooth extraction did not differ between normotensive and hypertensive patients, and that suppression of the cardiac sympathetic nervous system during dental surgery might attenuate the pressor response in patients with hypertension.

Copper concentration in hyperintense hepatocellular carcinomas of Long-Evans cinnamon rats on T1-weighted images.

The Long-Evans Cinnamon (LEC) rat has abnormal intrahepatic copper accumulation and spontaneously develops hepatocellular carcinomas following hereditary hepatitis. The hepatocellular carcinomas are very similar to human well-differentiated hepatocellular carcinoma in histopathological features and on MR images. Copper is believed to be one of the causes of hyperintensity of hepatocellular carcinomas compared to surrounding non-cancerous tissues on T1-weighted MR image. Eight LEC rats were studied by MR imaging. We measured copper concentrations from the hepatocellular carcinomas and surrounding non-cancerous liver tissues. Signal intensity of hepatocellular carcinomas without cystic areas was iso- to slightly hyperintense relative to surrounding non-cancerous tissues on T1-weighted images. Histopathologically, most of the tumors resembled human highly or well-differentiated hepatocellular carcinomas. Copper concentrations of the hepatocellular carcinomas were lower than the surrounding non-cancerous liver tissues. Copper may not be the cause of increased signal intensity typically observed on T1-weighted images of hepatocellular carcinomas.

Successful zonisamide treatment for infants with hypsarrhythmia.

We determined that zonisamide was effective in three epileptic infants with hypsarrhythmia. Two patients had the electroencephalographic pattern of hypsarrhythmia associated with developmental delay but lacked the characteristic tonic spasms. A third patient exhibited the typical triad of infantile spasms but had a poor general condition requiring controlled ventilation. We therefore chose zonisamide instead of adrenocorticotropin for these patients. Our data suggest that zonisamide may be a useful treatment in patients falling short of the diagnostic triad of infantile spasms or complicated by a poor overall medical condition.

Quantitative analyses of correlations of signal intensity on T1-weighted images and T1 relaxation time with copper concentration in the rat liver.

RATIONALE AND OBJECTIVES: To evaluate the effects of intrahepatic copper on magnetic resonance (MR) images, we studied the signal intensity (SI) of T1-weighted images and the T1 relaxation time of Long-Evans Cinnamon (LEC) rats, which have abnormal copper metabolism, and compared them with those of Sprague-Dawley (SD) rats. METHODS: We imaged the livers of four LEC rats before they developed hepatitis and four SD rats. The SI ratio of the liver to a phantom of polyvinyl alcohol gel was measured on T1-weighted images, and the T1 relaxation time was obtained from calculated T1 images. Copper concentration was measured by atomic absorption spectrophotometry. RESULTS: The mean copper concentrations in the liver of LEC rats were approximately 20-fold and statistically higher than in SD rats. There was no significant difference in the SI ratio and the T1 relaxation time between the LEC and SD rats. CONCLUSION: Intrahepatic copper does not significantly influence either the SI of T1-weighted MR images or the T1 relaxation time of the rat liver.

Magnetic resonance imaging of Long-Evans cinnamon rats as a new model of hepatocellular carcinoma.

RATIONALE AND OBJECTIVES: Following hereditary hepatitis, Long-Evans Cinnamon (LEC) rats spontaneously develop hepatocellular carcinomas (HCC) histopathologically similar to human well-differentiated HCC. We demonstrated that LEC rats are an appropriate model of evaluating magnetic resonance (MR) imaging of well-differentiated liver tumors. METHODS: Six 23-25-month-old LEC rats were studied using liver MR imaging and histologic observation. RESULTS: Signal intensity of HCCs without cystic areas was normal or slightly high on T1-weighted images and slightly high on T2-weighted images. Histopathologically, most tumors resembled human highly or well-differentiated HCCs. CONCLUSION: The LEC rat is a good model of investigating MR imaging of well-differentiated HCC.

Evaluation of tumor markers in patients with squamous cell carcinoma in the oral cavity.

Serum levels of six tumor markers (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCA), immunosuppressive acidic protein (IAP), alpha-fetoprotein (AFP), ferritin (FER), and carbohydrate antigen 19-9 (CA 19-9)) were simultaneously measured in 29 patients with primary squamous cell carcinoma (SCC) of the oral cavity to determine their significance. The positive rates were 34.5% for CEA, 41.4% for SCCA, 51.7% for IAP, 0% for AFP, 10.3% for FER, and 6.9% for CA 19-9 in patients with oral SCC. Therefore, CEA, SCCA, and IAP levels, of which the positive rates were significantly different (P < 0.01) from those of control patients without oral cancer, were considered to be of diagnostic value. The sensitivity (69.0%) and accuracy (90.3%) of the combination assay with these three tumor markers proved to be higher than those obtained with individual markers. A combination assay with CEA, SCCA, and IAP could be useful for the screening of patients with oral cancer.

Hepatitis G virus infection in a high-risk subgroup of hospitalized dental patients.

OBJECTIVE: The prevalence of hepatitis G virus infection was evaluated in dental patients whose clinical laboratory test results were positive for hepatitis C virus antibody, hepatitis B virus surface antigen, or elevated serum alanine transaminase concentrations. STUDY DESIGN: Frozen serum samples from patients with hepatitis C virus antibody (n = 63), hepatitis B virus surface antigen (n = 20), or alanine transaminase concentrations greater than 100 IU (n = 14) were assessed for GB virus C (GBV-C)/hepatitis G virus RNA by a reverse transcriptase-polymerase chain reaction. RESULTS: Six of 63 patients with hepatitis C virus antibodies had serum hepatitis G virus RNA (9.5%), and 2 of 20 subjects with hepatitis B virus surface antigen had hepatitis G virus RNA (10.0%). None of 14 patients whose alanine transaminase concentration was greater than 100 IU/L had hepatitis G virus RNA. Of 4 subjects with both hepatitis C virus antibody and hepatitis B virus surface antigen, 2 had hepatitis G virus RNA (50%). In the total study population (N = 92), 6 subjects (6.5%) had hepatitis G virus RNA. All hepatitis G virus-infected patients also had hepatitis C virus antibody. Neither serum alanine transaminase nor aspartate transaminase concentrations were different between subjects with and subjects without hepatitis G virus RNA. The lack of a relationship between hepatitis G virus infection and elevation of alanine transaminase and aspartate transaminase might suggest that this virus is not truly a hepatitis virus. CONCLUSIONS: Hospitalized dental patients are infected with hepatitis G virus at a prevalence similar to or slightly higher than that seen in the general population. Dentists should pay close attention to infection control with respect to the potential new hepatitis virus known as hepatitis G virus.