Relationship between multiple water swallows and gastroesophageal reflux in patients with normal esophageal motility.

Multiple water swallows (MWS) stimulates neural inhibition, resulting in abolition of contractions in the esophageal body and complete lower esophageal sphincter relaxation, which is followed by peristalsis and the lower esophageal sphincter contraction. We assessed the relationship between MWS and gastroesophageal reflux in patients with esophageal symptoms and with normal findings by high-resolution manometry (HRM). We retrospectively reviewed the clinical records of patients who underwent HRM and a 24-hour ambulatory impedance-pH study. Correlation between the findings of the impedance-pH study and abnormal MWS responses without motility disorders was evaluated. Independent t-tests were used for statistical analysis. Of 28 patients, 20 (71%) had abnormal MWS responses: four (20%) had abnormal responses during MWS, six (30%) had abnormal responses after MWS, and 10 (50%) had abnormal responses both during and after MWS. Total acid exposure times were significantly longer in patients with abnormal MWS responses than in patients with normal MWS responses. In particular, upright acid exposure time and all reflux percent times were significantly longer in patients with abnormal MWS responses. However, bolus clearance time and longest reflux episode were not different between the two groups. Abnormal MWS responses predicted increased acid exposure times in patients with normal findings of HRM by the Chicago classification.

The effect of water bolus temperature on esophageal motor function as measured by high-resolution manometry.

BACKGROUND: Ingestion of cold fluids may induce pain in patients with esophageal motility disorders. Hot fluids, on the other hand, may help to relieve pain. We studied changes in esophageal motility as a variable of water bolus temperature using high-resolution manometry (HRM) in healthy human. METHODS: Thirty-two healthy subjects were recruited at Kosin University Hospital. HRM was performed in a sitting position, with room temperature (RT, 25 °C), hot (45 °C), and cold (2 °C) water swallowed in that order. This exam included single swallowing (10 swallows of 5 mL water, 30 s intervals) and multiple water swallows (MWS; 100 mL water within 30 s). KEY RESULTS: In the single swallowing, hot water caused a decrease in lower esophageal sphincter (LES) residual pressure (5.87 ± 4.20 mmHg vs 7.45 ± 4.17 mmHg (RT), p = 0.001) and duration of esophageal body (EB) contraction (3.01 ± 0.80 s vs 3.15 ± 1.16 s (RT), p = 0.009). Cold water caused an increase in the duration of EB contraction (3.52 ± 0.87 s vs 3.15 ± 1.16 s (RT), p = 0.001) and a decrease in contractile front velocity (CFV) (4.43 ± 1.50 cm/s vs 4.90 ± 2.53 cm/s (RT), p = 0.007). Similarly, in the MWS, hot water caused a decrease in the duration of EB contraction (12.95 ± 5.02 s vs 16.33 ± 5.94 s (RT), p = 0.024) and an increase in the amplitude of EB contraction (114.27 ± 83.36 mmHg vs 82.70 ± 46.77 mmHg (RT), p = 0.007). Cold water caused an increase in the duration of EB contraction (27.38 ± 2.89 s vs 16.33 ± 5.94 s (RT), p = 0.03) and a decrease in the amplitude of EB contraction (51.68 ± 33.94 mmHg vs 82.70 ± 46.77 mmHg (RT), p = 0.001). CONCLUSIONS & INFERENCES: This study showed changes in esophageal motility to be dependent on water temperature. Especially, MWS showed clear changes in esophageal motility at different temperatures of water.

Is there a role of food allergy in irritable bowel syndrome and functional dyspepsia? A systematic review.

A significant proportion of adults believe they suffer from food allergy, and 20-65% of patients with irritable bowel syndrome (IBS) attribute their symptoms to something in food that activates an abnormal response. This systematic review evaluates the role of food allergy in aetiology and management of these disorders. Activation of gastrointestinal mucosal immune system may be one of the causative factors in the pathogenesis of functional dyspepsia and IBS. This activation may result from effects of bacterial infection or other luminal factors including commensal microbial flora and food antigens. Some studies have reported on the role of food allergy in IBS; only one epidemiological study on functional dyspepsia and food allergy has been published. The mechanism by which food activates mucosal immune system is uncertain, but food specific IgE and IgG4 appeared to mediate the hypersensitivity reaction in a subgroup of IBS patients. Exclusion diets based on skin prick test, RAST for IgE or IgG4, hypoallergic diet and clinical trials with oral disodium cromoglycate have been conducted, and some success has been reported in a subset of IBS patients. Further well-controlled studies are needed to establish whether food allergy plays a role in the pathophysiology of functional dyspepsia and IBS.

Effect of atilmotin on gastrointestinal transit in healthy subjects: a randomized, placebo-controlled study.

We studied effects of i.v. atilmotin (BAX-ACC-1638, a novel motilin agonist, circulating t(1/2) < 10 min) on gastrointestinal transit in humans using a randomized, parallel-group, dose-response double-blind study of i.v. atilmotin, 6, 30, 60 microg or vehicle (placebo) given 2 min after standardized breakfast, lunch and dinner. The breakfast meal contained (99m)Tc-eggs and (111)In-milk. Full gastrointestinal transit was measured by scintigraphy. Primary endpoints were % gastric emptying (GE) at 30 min, GE t(1/2), colonic filling (CF) at 6 h, and geometric centre of colonic transit at 24 h. Analysis included adjustment for age, gender and body mass index, with Bonferroni correction applied for multiple comparisons. A significant treatment effect of atilmotin was detected for GE (%) at 30 min for solids and liquids (P < 0.01 for both). There were no significant effects on CF or CT and no significant adverse clinical events. Thus, atilmotin accelerates GE of solids and liquids in healthy humans. These data suggest that, at the doses tested, atilmotin should be considered for treatment of stomach motility disorders.

Opioids and the gut: pharmacology and current clinical experience.

This article reviews the pharmacology and physiology of opiate receptors and the current and potential uses of opioid agonists and antagonists in clinical gastroenterology. Mu-receptors are involved in motor and sensory functions, and their modulation is established for treatment of diarrhea. Mu-antagonists have potential to reverse endogenous (e.g., postoperative ileus) or iatrogenic dysmotility (e.g., opioid bowel dysfunction). Modulation of the function of kappa-receptors may be a novel approach to control visceral pain in functional gut disorders. Results of formal testing of novel opioid modulators are keenly awaited.

Computerized analysis of fetal heart rate parameters by gestational age.

OBJECTIVE: The aim of this study is to define the reference ranges for fetal heart rate (FHR) parameters according to gestational age, by determining the relationship between the FHR and gestational age using a computerized FHR analysis system. METHODS: Using our own software developed by Hanyang University Hospital in Korea, non-stress tests were performed for 20 min. FHR parameters for 6455 subjects were analyzed for various gestational groups; <25 weeks, 25-28 weeks, 29-32 weeks, 33-36 weeks, 37-40 weeks, and >40 weeks. RESULTS: The FHR parameters were related to gestational age. The mean baseline FHR, signal loss, and fetal movements decreased significantly with gestation (P<0.0001). The variability and accelerations of FHR were highest for the 37-40 weeks gestational group (P<0.05). CONCLUSIONS: The results showed that overall, the differences in the FHR parameters between gestational groups were statistically significant, and the gestational age of the fetus should be considered when interpreting FHR patterns.

Genetic Alterations in Gastric Carcinomas and Adjacent Mucosa Detected by Comparative Genomic Hybridization (CGH).

PURPOSE: Comparative genomic hybridization (CGH) was used to detect any amplified or deleted chromosomal regions in tumors by mapping their locations on normal metaphase chromosomes. METERIALS AND METHODS: Twenty-six gastric carcinomas and their adjacent mucosa were screened for chromosomal aberrations using CGH. RESULTS: All carcinomas had chromosomal aberrations, and chromosomal material was more likely to be gained than lost. Ten out of 26 adjacent mucosa had chromosomal aberrations, and a gain was less frequently observed than a tumor (1.6/2.6). The most common gains were detected on 13q (58.3%), 8q (30.8%), 6q (27.0%), and 20p (19.2%), while the most frequent losses were detected on 17p (38.5%) and 16q (7.2%). The most commonchromosomal aberrations in the adjacent mucosa were a gain of 13q (11.5%) and a loss of 17q (11.5%). The tumors had more chromosomal gains of 2q, 3q, and 13q and more losses of 17p and 16q than the adjacent mucosa. CONCLUSION: S: The most common gain in the tumors was detected on 13q, 8q, 6q, and 20p, and the most frequent loss was on 17p and 16q. While CGH may be useful in predicting the prognosis or therapeutic decision of gastric carcinomas, further study of several candidate genes, such as DP1, FLT1, c-myb, AIB1, BTAK, is needed to clarify gastric carcinogenesis and its progression.

Chaotic and periodic heart rate dynamics in uncomplicated intrauterine growth restricted fetuses.

We studied how chaotic and periodic heart rate dynamics differ between normal fetuses (n = 192) and uncomplicated intrauterine growth restricted fetuses (n = 86), aged 31-42 weeks of gestation. We analyzed each fetal heart rate time series for 25 min. We quantified the chaotic dynamics of each fetal heart rate time series by correlation dimension. The periodic dynamics were analyzed by power spectral analysis. The correlation dimension and, therefore, the complexity, of the heart rate dynamics of the uncomplicated intrauterine growth restricted fetuses was significantly lower than that of the normal fetuses, which was marked at 38-42 weeks of gestation. The low-frequency (0.04-0.15 Hz) component and, therefore, the periodicity of the low-frequency range was significantly higher than that of the normal fetuses during all the gestational weeks. These results mean that, although the intrauterine growth restricted fetuses are not severely compromised, the overall integrity of their cardiovascular control is impaired, especially at term; and sympathetic modulation is increased, both of which may contribute to increased perinatal mortality.

Tissue and serum concentrations of amikacin after intramuscular and intrauterine administration to mares in estrus.

Concentrations of amikacin in endometrial tissue and plasma were studied in mares in estrus after intrauterine infusion of 1.0 or 2.0 g once a day for 3 consecutive d, and after 9.7 or 14.5 mg/kg body weight (BW) had been injected intramuscularly once a day for 3 consecutive d to determine concentrations of amikacin sulfate in plasma and endometrial tissues, and whether parenteral administration provides any advantages over intramuscular infusion. No amikacin was detected in serum at the 1.0 g dose. At the infusion dose of 2.0 g once a day, very low levels of serum amikacin were detected at 1 and 4 h postinfusion on the 1st treatment day. Amikacin was found to penetrate the endometrium after intramuscular injection; however, the levels attained were not as high as those achieved following intrauterine infusion. Based on the tissue and serum concentrations of amikacin, an intrauterine infusion at a dose of 4.4 mg/kg BW/d would appear to be an appropriate therapeutic regimen for the treatment of gram-negative endometritis.

Interpretation of blocking activity in maternal serum depends on the equation used for calculation of mixed lymphocyte culture results.

Immunosuppressive blocking factors in maternal serum are usually determined by inhibition of mixed lymphocyte cultures (MLC), but reports on the importance of these factors for successful pregnancy are conflicting. Here we measured serum blocking activity in men, non-pregnant nulliparous women, non-pregnant multiparous women, women with normal pregnancies, and in women who had had recurrent spontaneous abortions and were treated with leucocyte immunizations. Three different equations were used for calculation of blocking activity: blocking effect index (BEI); stimulation index (SI); and blocking index (BI). By all three methods of calculation, significantly lower levels of blocking activity were noted for men and women compared with pregnant women and multiparae. In the patients with a history of recurrent spontaneous abortions blocking activity as determined by BEI and BI increased into the positive range after treatment with infusions of third-party donor leucocytes in a statistically significant number of women (P less than 0.05). However, blocking activity as determined by BEI had a higher predictive value for successful pregnancy than did that determined by BI or SI. Our data suggest that the equation used for calculating BEI is superior to other methods for the determination of blocking activity when monitoring the response to leucocyte immunization in women with recurrent spontaneous abortion. However, these results also cast doubt on the importance of blocking antibodies in histories of recurrent abortion, since pregnancies occurred in the absence and spontaneous abortions occurred in the presence of blocking activity.

Histologic disappearance of locally advanced vaginal cancer after combination chemotherapy.

Clinically and histologically complete disappearance of local tumor and pelvic sidewall involvement was achieved in a patient with primary advanced squamous cell carcinoma of the vagina administered combination chemotherapy prior to operation. Radical hysterectomy, total vaginectomy, bilateral salpingo-oophorectomy, bilateral pelvic lymphadenectomy, and paraaortic lymph node biopsy were performed after seven courses of combination chemotherapy with vinblastine, bleomycin, and cis-platinum. This encouraging result warrants further investigation of combination chemotherapy in other patients.

Maternal and fetal survival following surgery and chemotherapy of endodermal sinus tumor of the ovary during pregnancy: a case report.

An ovarian endodermal sinus tumor was found in a patient with a 15-week intrauterine gestation. She received conservative surgery and six courses of combination chemotherapy from 16 weeks' gestation, and delivered a normal term infant at 37 weeks' gestation. Two other courses of combination chemotherapy including cisplatin were added. No residual tumor was found at subsequent exploration, and she is alive 33 months after the original diagnosis without any evidence of recurrence. We believe this is the first reported case of maternal survival past 2 years and the earliest chemotherapy done in the early second trimester of pregnancy without resulting in fetal abnormalities.

Successful treatment of cervical pregnancy by cervical evacuation after use of methotrexate.

A case is described with cervical pregnancy successfully treated by two 8-day courses of methotrexate and leucovorin rescue with cervical evacuation. The apparent beneficial outcome suggests that cervical evacuation after the use of methotrexate and leucovorin rescue will be considered for treatment of cervical pregnancy whenever uterine preservation is desirable.

The acoustic stimulation test in the anencephalus: preliminary results.

It is not yet clear whether the acoustic stimulus influences the fetus by auditory or vibrational pathways. The anencephalic fetus is an interesting model for the study of the pathway for receipt of acoustic stimulation because of the near absence of cerebral hemispheres. After the traditional nonstress test (NST), the response to acoustic stimulation was assessed in eight fetal heart rate (FHR) recordings of six anencephalic fetuses of gestational age between 18 and 39 weeks. Although four preterm fetuses demonstrated nonreactive results in the NST, two term fetuses revealed reactive NSTs. However, none of these six anencephalic fetuses responded to acoustic stimulation. These data suggest that the cerebral cortex is the origin or transmission route of the FHR response to acoustic stimulation. We hypothesize that the normal fetus might receive externally applied sounds via auditory pathways rather than vibratory pathways, at least in term pregnancy.

Comparative review of diagnostic accuracy in tubal pregnancy: a 14-year survey of 1040 cases.

This paper summarizes our experience from 1972-1985 with the changing tools used in the diagnosis of ectopic pregnancy. The study was divided into three time periods based on the diagnostic methods used in each. In the first period (1972-1975), diagnosis was by culdocentesis and the urine pregnancy test. In the second period (1976-1978), diagnostic laparoscopy was added. Finally, in the third period (1979-1985), serum beta-human chorionic gonadotropin (beta-hCG) assay and pelvic ultrasonography were added. A rising trend in diagnostic accuracy was observed from the first period to the third. The predictability and the negative predictive value of diagnostic tests in the third period were 96.3 and 94.9%, respectively--significantly higher than in the first and second periods. The incidence of unruptured tubal pregnancy increased significantly, from 27.6% in the first and the second periods to 42.5% in the third period. Laparoscopy, ultrasonography, and serum beta-hCG assay each revealed a positive rate of more than 90% in the diagnosis of tubal pregnancy. Laparoscopy had the highest positive predictive value as a single test in the third period. Among suspected cases, however, laparoscopy was found to have a low accuracy in discriminating between tubal pregnancy and infection. The combination of serum beta-hCG testing and ultrasonography produced a 99% positive predictive value, and revealed a higher degree of accuracy in the diagnosis of tubal pregnancy than any other single test or combination of tests.