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Summary Reasons for performing study: Sex chromosome aberrations are often associated with clinical signs that affect equine health and reproduction. However, abnormal manifestation with sex chromosome aberration usually appears at maturity and potential disorders may be suspected infrequently. A reliable survey at an early stage is therefore required. Objectives: To detect and characterise sex chromosome aberrations in newborn foals by the parentage test and analysis using X- and Y-linked markers. Methods: We conducted a genetic diagnosis combined with a parentage test by microsatellite DNA and analysis of X- and Y-linked genetic markers in newborn light-breed foals (n = 17, 471). The minimum incidence of sex chromosome aberration in horses was estimated in the context of available population data. Results: Eighteen cases with aberrations involving 63,XO, 65,XXY and 65,XXX were found. The XO, XXY (pure 65,XXY and/or mosaics/chimaeras) and XXX were found in 0.15, 0.02 and 0.01% of the population, respectively, based solely on detection of abnormal segregation of a single X chromosome marker, LEX003. Conclusions and potential relevance: Detection at an early age and understanding of the prevalence of sex chromosome aberrations should assist in the diagnosis and managment of horses kept for breeding. Further, the parental origin of the X chromosome of each disorder could be proved by the results of genetic analysis, thereby contributing to cytogenetic characterisation.

Background & Aims: Adenocarcinoma of the esophagus and esophagogastric junction (EGJ) is increasing, the earliest lesion being specialized intestinal metaplasia (SIM). This study determined the prevalence and demographic features of patients with SIM, dysplasia, and cancer in the esophagus and EGJ. Methods: Two antegrade biopsy specimens were taken distal to the squamocolumnar junction (SCJ) and any tongues of pink mucosa proximal to the SCJ. Patients were categorized endoscopically and histologically as having long-segment (LSBE) or short-segment Barrett's esophagus (SSBE), EGJ-SIM, or a normal EGJ. Results: Of 889 patients studied, 56 were undergoing esophagoduodenoscopy screening or surveillance and were not included in the prevalence calculation. The overall prevalence of SIM was 13.2%, with 1.6% LSBE, 6.0% SSBE, and 5.6% EGJ-SIM. Dysplasia or cancer was noted in 31% of LSBE, 10% of SSBE, and 6.4% of EGJ-SIM patients ( P ≤ 0.043). Two cancers were associated with LSBE, 1 with SSBE, and 1 with EGJ-SIM. Patients with LSBE and SSBE were predominantly white ( P ≤ 0.001), male ( P ≤ 0.009), and smokers ( P ≤ 0.004), with LSBE patients having a longer history of heartburn ( P ≤ 0.009). In contrast, patients with EGJ-SIM were similar in gender and ethnicity to the reference group, tended to be older ( P ≤ 0.05), drank less alcohol ( P ≤ 0.02), and had a higher prevalence of Helicobacter pylori infection ( P ≤ 0.05). Conclusions: The prevalence of SSBE and EGJ-SIM is similar, but each entity is 3.5 times more prevalent than LSBE. However, the prevalence of dysplasia in LSBE is 2 times greater than in SSBE and 4 times greater than in EGJ-SIM. Demographically, EGJ-SIM patients are different from patients with Barrett's esophagus and have a higher prevalence of H.pylori infection. These data help to explain the increasing incidence of adenocarcinoma of the distal esophagus and EGJ. GASTROENTEROLOGY 1999;116:277-285

As ketamine has local anaesthetic actions and local anaesthetics are known to have anti-inflammatory effects, ketamine could be expected to be an anti-inflammatory agent. Here we sought to determine whether ketamine is indeed anti-inflammatory in chemical peritonitis induced by HCl in rats.Peritonitis was elicited by applying 0.02 M HCl on the surface of the cecum or appendix and quantified by measuring the extravasation of intravenously injected Evan's Blue bound to albumin extracted from those tissues. Three experimental sets were performed. In the first set, four groups of 10 rats each received: 1%, 2%, and 4% ketamine and 1% lidocaine. In the same animal, before induction of peritonitis one area was topically pre-treated with 0.9% saline (control site) and another area was topically pre-treated with 1%, 2% or 4% ketamine or 1% lidocaine (experimental site). In the second set, two groups of 10 rats each received: 2% ketamine or 1% lidocaine. Ten min after the induction of peritonitis, the control site was topically treated with 0.9% saline, while the experimental site was treated with 2% ketamine or 1% lidocaine. In the third set 20 rats, divided into two groups, were pre-treated either with 2% S(+)ketamine or 2% R(-)ketamine before the induction of peritonitis instead of the previously employed racemic version of the drug.Treatment of the cecum or appendix areas with ketamine or lidocaine before the induction of peritonitis decreased the extravasation of Evan's Blue-albumin from 5.7 +/- 0.7 micrograms/100 mg tissue to 4.5 +/- 0.8, N.S. with 1% ketamine; from 5.9 +/- 0.8 to 4.1 +/- 0.7, P0.01 with 2% ketamine; from 4.8 +/- 0.7 to 3.5 +/- 0.6, P0.05 with 4% ketamine and from 5.9 +/- 0.6 to 3.6 +/- 0.8, P0.01 with 1% lidocaine. Treatment of the areas of peritonitis with 2% ketamine or 1% lidocaine decreased the extravasation of Evan's Blue-albumin from 5.6 +/- 0.5 micrograms/100 mg tissue to 4.4 +/- 0.6, P0.05 and from 6.0 +/- 0.8 to 5.0 +/- 0.7, P0.01. Administration of the isomer S(+)ketamine to colonic areas before the induction of peritonitis reduced the extravasation of Evan's Blue-albumin from 6.5 +/- 0.7 micrograms/100 mg tissue to 4.1 +/- 0.6, P0.01; while the isomer R(-)ketamine was inactive.These results indicate that topically applied ketamine inhibited the development of chemical peritonitis. This action of racemic ketamine was due to the isomer S(+)ketamine.

This study evaluated the differences between linear and non-linear modelled heritability estimates of racing performance based on lifetime earnings (LE) and lifetime ranking (LR) in Japanese Thoroughbred racehorses. The heritability estimate (h(2) = 0.25) obtained from a non-linear model based on formal Japan Racing Association ranking was much higher than that obtained from a linear model based on the original trait phenotype (h(2) = 0.11). The linear models showed slightly higher heritability estimates under the trait categorizations than under the original phenotypes, while the non-linear categorical trait models showed much higher heritability estimates than the linear models, especially for binary trait categorizations (h(2) = 0.34) with non-winning and winning horses. The binary trait categorizations were consistent with the case and control classifications in the previous genome-wide association study (GWAS), which identified possible sequence variants on ECA18 that affect racing performance in Japanese Thoroughbred racehorses. Those findings suggested that the different heritability estimates obtained from several trait categorizations would reflect the possible presence of susceptibility gene segregations in the analyzed population, indicating that heritability estimates from non-linear models are useful for the selection of case and control populations in GWAS.

Using 1710 Thoroughbred racehorses in Japan, a cohort study was performed to evaluate the influence of genotypes at four single nucleotide polymorphisms (SNPs) on equine chromosome 18 (ECA18), which were associated in a previous genome-wide association study for racing performance with lifetime earnings and performance rank. In males, both g.65809482TC and g.65868604GT were related to performance rank (P= 0.005). In females, g.65809482TC (P = 1.76E-6), g.65868604GT (P=6.81E-6) and g.66493737CT (P=4.42E-5) were strongly related to performance rank and also to lifetime earnings (P 0.05). When win-race distance (WRD) among all winning racehorses and best race distance (BRD) among elite racehorses were considered as the phenotypes, significant associations (P0.001) were observed for all four SNPs. The favourable race distance of both elite (BRD) and novice racehorses (WRD) was also associated with genotypes in the ECA18 region, indicating the presence of a gene in this region influencing optimum race distance in Thoroughbred racehorses. Therefore, the association with performance rank is likely due to the bias in the race distances. The location of the SNPs within and proximal to the gene encoding myostatin (MSTN) strongly suggests that regulation of the MSTN gene affects racing performance. In particular, the g.65809482TC, g.65868604GT and g.66493737CT SNPs, or their combinations, may be genetic diagnostic markers for racing performance indicators such as WRD and BRD.

Synthetic oligonucleotide primers were used in the polymerase chain reaction (PCR) to amplify a sequence of the spaP gene, which encodes the surface protein antigen I/II of Streptococcus mutans. A DNA fragment of c. 192 bp was amplified from lysed S. mutans cells or isolated DNA. With S. mutans cells, the lower limit of detection was 4-40 cfu. With these primers, 13 reference and 50 clinical strains of S. mutans were identified. Amplification of the 192-bp product was not demonstrated when 41 strains of other streptococcal and non-streptococcal species were tested. The spaP gene PCR has potential for the rapid diagnosis of S. mutans infections.

Background Central noradrenergic neurones have a role in alertness, analgesia, and thermoregulation; these neurones are also involved in the mechanism of anaesthesia. Locus coeruleus neurones innervate various central nervous regions including the cerebral cortex and hippocampus, and are responsible for wakefulness and analgesia. We hypothesized that these neurones are also involved in both activation of the γ-aminobutyric acid type A (GABAA) receptor and inhibition of N-methyl- d -aspartate (NMDA) receptor-mediated anaesthesia. Methods Forty-seven male rats were used to compare duration of anaesthesia before and 10 days after noradrenergic neurone depletion after intraperitoneal (i.p.) administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4; 0, 5, and 50 mg kg−1). The animals received i.p. thiopental (GABA anaesthetic, 45 mg kg−1) or ketamine (NMDA anaesthetic, 100 mg kg−1). We also tested the effects of coerulean noradrenergic neurone depletion on i.p. ketamine analgesia (15 mg kg−1) using the hot-plate test in a further 21 male rats. At the end of each experiment, norepinephrine contents in the cerebral cortex and hippocampus were measured. Results I.P. DSP-4 5 and 50 mg kg−1 significantly decreased ketamine anaesthesia duration by 12.7% and 22.4%, increased thiopental anaesthesia duration by 10.8% and 24.5%, and reduced ketamine-increased hot-plate latency by 55.2% and 68.1%, respectively. In addition, i.p. DSP-4 5 and 50 mg kg−1 significantly reduced norepinephrine contents in coerulean brain regions by ∼20% and ∼75%, respectively. There were significant correlations between norepinephrine contents in coerulean brain regions and anaesthesia durations and ketamine analgesia. Conclusions The present data indicate that coerulean noradrenergic neurones may be responsible for both GABA- and NMDA-mediated anaesthetic actions.

Objectives: To investigate whether daily systemic and/or topical medication contributes to the development of oral lichen planus (OLP) lesions. Study Design: The study involved 110 OLP patients and 76 control subjects, matched by age, race and sex. The analyzed data included medical records, drug intake and topical medication. Criteria for analysis of drug intake included: (1) ATC-code drug classification; (2) number of different drugs used daily in the categories of monopharmacy (1 drug), minor polypharmacy (2 4 drugs), and major polypharmacy (> 5 drugs); and (3) drugs implicated in lichenoid reactions (DILRs). Results: Sixty (54.5%) of the 110 OLP patients reported daily medication (prior to the appearance of the OLP lesion) compared to 52 (68.4%) of the 76 control subjects. No statistical difference was found between the two groups in terms of systemic diseases, number of medicated individuals in the categories of mono- and polypharmacy, nor use of DILRs (P > 0.05). Regarding the clinical forms and site of involvement, a statistically significant difference was only found for the clinical erosive form of OLP, seen more frequently in non-DILR (P = 0.04) and nonmedicated OLP patients (P = 0.02) than in DILR OLP patients. Daily use of topical oral medication was reported by 2 (1.8%) OLP patients and 1 (1.3%) control subject. Conclusions: It seems that the use of systemic medication does not lead to a significant increase in the incidence of OLP lesions. For their part, lichenoid drug reactions are likely to occur only in a very low percentage of patients. © Medicina Oral S. L.

Phosphodiesterase (PDE) III exists in airway smooth muscles. In addition, PDEIII inhibitors have been suggested to relax airway smooth muscle by increasing intracellular cAMP concentrations. We report a successful use of olprinone, a PDEIII inhibitor, for treatment of an asthmatic attack. A 15-year-old male patient treated with oral theophylline 400 mg x d(-1) was anesthetized with propofol, fentanyl and ketamine for knee joint surgery. Immediately after tracheal intubation, an asthma attack occurred with peak airway pressure (Paw)>40 cmH2O. Thus, propofol 20 mg was additionally given to increase anesthetic depth, and Paw gradually decreased to 30 cmH2O. In addition, we started monitoring bronchial cross-sectional area using a superfine fiberoptic bronchoscopic method previously reported. However, as Paw did not further decrease for 30 min, olprinone was intravenously infused (10 microg x kg(-1) x 10 min(-1) + 0.3 microg x kg(-1) x min(-1), total 5 mg). Olprinone infusion rapidly decreased peak Paw from 30 cmH2O to 24 cmH2O and increased bronchial cross-sectional area by 50%. These findings suggest that olprinone produced bronchodilation.

Arbaclofen placarbil (AP), previously designated as XP19986, is an investigational prodrug of the active R-isomer of baclofen, a gamma-aminobutyric acid agonist reflux inhibitor. The aim of this study was to assess the efficacy and safety of AP for decreasing meal-induced reflux episodes in patients with gastroesophageal reflux disease (GERD).We conducted a multicenter, randomized, double-blind, crossover study comparing single doses of AP with placebo. Different patients were enrolled at each of four escalating AP doses: 10, 20, 40, and 60 mg. Enrolled patients had GERD symptoms at least three times a week and 20 reflux episodes on impedance/pH monitoring over a period of 2 h. During study visits separated by periods of 3-7 days, patients received single doses of AP or placebo, followed by high-fat meals 2 and 6 h after treatment. The primary end point was the number of reflux episodes over 12 h after treatment.A total of 50 patients were treated; efficacy analysis included 44 patients who received both AP and placebo and had technically satisfactory impedance/pH data. For the combined data from all dose cohorts, there was a statistically significant (P=0.01) decrease in reflux episodes over 12 h after treatment with AP compared with placebo. The mean (s.d.) number of reflux episodes over 12 h after AP treatment was 50.5 (27.2), with a mean reduction of 10.4 (23.9) episodes (17%) compared with placebo, for which a mean (s.d.) number of 60.9 (35.3) episodes was observed. Heartburn events associated with reflux were reduced during treatment with AP compared with placebo. AP seemed to be the most efficacious in the 60-mg dose group, and was well tolerated at all dose levels.AP decreased reflux and associated symptoms with good tolerability in patients with GERD.

PURPOSE: This study aimed to evaluate the efficacy of the systemic drugs thalidomide, dapsone, colchicine, and pentoxifylline in the treatment of severe manifestations of RAS. METHODS: An open, 4-year clinical trial was carried out for 21 consecutive patients with severe RAS. Initially, patients were given a 2-week course of prednisone to bring them to a baseline status. Simultaneously, one of the four test drugs was assigned to each patient to be taken for a period of 6 months. During the course of the trial, patients were switched to one of the other three drugs whenever side effects or a lack of satisfactory results occurred, and the 6-month limit of the treatment was then reset. RESULTS: The most efficient and best-tolerated drug was thalidomide, which was administered to a total of eight patients and resulted in complete remission in seven (87.5%). Dapsone was prescribed for a total of nine patients, of whom eight (89%) showed improvement in their symptoms, while five showed complete remission. Colchicine was administered to a total of ten patients, with benefits observed in nine (90%), of whom four showed complete remission. Pentoxyfilline was administered to a total of five patients, with benefits observed in three (60%), of whom one patient showed complete remission. CONCLUSION: The therapeutic methods used in this trial provided significant symptom relief. Patients experienced relapses of the lesions; however, this occurred after withdrawal of their medication during the follow-up period.

We report the case of an 8-year-old boy who presented with a 2-month history of headaches and mild visual impairment and was found to have a medulloblastoma with primary leptomeningeal involvement. No mass lesion was found on imaging studies, during subsequent intraoperative surgical inspection or at autopsy. The pathologic findings were first documented on cerebrospinal fluid cytologic examination and biopsy of the cerebellum and were later confirmed at necropsy. To our knowledge, this is the third reported case of medulloblastoma identified with primary leptomeningeal involvement without a cerebellar mass and the first such case with documented autopsy findings.

This study was aimed to test if the frequency of oral lesions bears statistical correlation or not with the condition of cutaneous psoriasis.Two groups were examined, one made up of 166 patients with skin psoriasis and the other with the same number of individuals with a negative history of skin diseases (control group), matched by age, race, and sex. Patients with psoriasis were grouped according to their having localized or generalized forms of the disease. The oral mucosa was thoroughly examined in both groups. Data were analyzed using chi-square test, Fisher's test, the odds ratio (OR) with a 95% confidence interval (CI), and the Ryan-Holm step-down Bonferroni procedure. The overall significance was set at Por = 0.05.The oral lesions significantly associated with psoriasis were fissured tongue (FT, OR = 2.7; 95% CI: 1.3-5.6), and geographic tongue (GT, OR = 5.0; 95% CI: 1.5-16.8). Other factors analyzed, such as topical and/or systemic medication for treatment of psoriasis versus nontreated patients, and localized versus generalized forms of psoriasis presented no statistical association with the frequency of FT or GT lesions (p0.05).Patients with psoriasis presented no specific oral lesion different from those seen in the control group. Although further investigation is warranted to establish whether or not either FT or GT can be characterized as an oral expression of psoriasis, the present investigation did find for both these types of lesions that the frequency of each bore a statistically significant relation with the presence of cutaneous psoriasis.

The aim of this study was to investigate risk factors and clinical aspects associated with oral squamous cell carcinoma (OSCC) in young patients as compared to older ones. STUDY DESIGN. Data was obtained by retrospective analysis of files of patients with OSCC, who were categorised into two groups: the young group (or =40 years old) and the older group (40 years old). Clinical data, including habits, familial antecedents, medical records and occupation were collected.One hundred and twenty-one patients were found to have OSCC; 13 (10.7%) were young individuals and 108 (89.3%) older ones. Consumption of tobacco and/or alcohol was reported by 7 (53.8%) young patients and by 81 (75.0%) older patients, this difference not being statistically significant (P = 0.18). However, only 1 young patient (12.5%) was a heavy consumer of tobacco and alcohol as opposed to 49 (60.5%) of the older patients. Familial antecedents of malignant neoplasm were reported by 11 (84.6%) young patients and 32 (29.6%) older ones respectively, this difference being statistically significant (P = 0.0001). Medical records and patient's occupation did not show correlation with the aetiology of OSCC.Although the young and older patients share a similar habit for the consumption of tobacco and/or alcohol, the pattern of consumption and time of exposure to these two risk factors suggested that these etiologic factors are less clearly implicated in the development of oral cancer in the young patients than in older ones. Thus, for young patients with OSCC, the search for predisposing factors should assign greater weight to familial antecedents of malignant neoplasm.

Attention has focused on whether normalization, regression, and development of dysplasia and cancer in specialized intestinal metaplasia (SIM) differ among long-segment Barrett's esophagus (LSBE), short-segment BE (SSBE), and esophagogastric junction SIM (EGJSIM). We prospectively followed a cohort of SIM patients receiving long-term antisecretory medications to determine: (a) histologic normalization (no evidence of SIM on biopsy), (b) change in SIM length, (c) incidence of dysplasia and cancer, and (d) factors associated with normalization.One hundred forty-eight patients with SIM were identified in our original cohort. Of these, 60.5% (23/38) LSBE, 69.8% (44/63) SSBE, and 72.3% (34/47) EGJSIM patients underwent repeat surveillance over a mean 44.4 +/- 9.7 months. Demographic, clinical, and endoscopic data were obtained.(a) With long-term, antisecretory therapy, normalization occurred in 0/23 LSBE, 30% (13/44) of SSBE, and 68% (23/34) of EGJSIM (P0.001). (b) Normalization was more likely with EGJSIM (odds ratio [OR] 6.7, CI 2.3-19.3, P= 0.005), female gender (OR 7.3, CI 2.3-23.1, P= 0.001), or absence of hiatal hernia (OR 2.9, CI 1.02-8.06, P= 0.002). (c) A significant decrease in mean SIM length was noted for the entire population (2.5 +/- 0.3 to 2.13 +/- 0.3 cm, P= 0.004). (d) Follow-up incidence of dysplasia and cancer was 26.1% (3 indefinite, 2 low-grade dysplasia [LGD], 1 cancer) for LSBE, 6.8% (2 indefinite, 1 LGD) for SSBE, and none for EGJSIM (P0.004).(a) Normalization of SIM occurs most frequently in EGJSIMSSBELSBE. (b) Factors associated with normalization favor less severe GER and shorter segments of SIM. (c) Surveillance of LSBE results in the greatest yield for identifying dysplasia and cancer.

Acute ipsilateral pulmonary oedema is a well documented complication of the treatment of lung collapse secondary to pneumothorax, pleural effusion and atelectasis. We present a case of bilateral re-expansion pulmonary oedema following removal of an intrathoracic haematoma. High protein concentration of the oedema fluid suggests increased pulmonary vascular permeability as a cause of this pulmonary oedema.

The U.S. Army administers the hepatitis A virus (HAV) vaccination for prophylaxis against HAV infection. There is little comparative data as to whether prescreening for previous HAV infection before immunization is less costly than universal vaccination. We designed a study to determine the prevalence of previous HAV infection in U.S. Army recruits and then perform a cost analysis. The cost analysis compared selective vaccination versus universal vaccination. Basic demographic information, including age, gender, geographic origin, and ethnicity, were collected after which patients were tested for HAV antibodies. A total of 1,332 individuals was prospectively enrolled with 183 individuals (13.74%) having evidence of previous HAV infection. Minority recruits were found to have a higher prevalence than Caucasian recruits (p = 0.0451. The cost analysis demonstrates that vaccination without prescreening was the least costly of two vaccination strategies for this cohort. To achieve current vaccination goals, all U.S. military recruits should be vaccinated without evaluation for previous HAV immunity.

There are few prospective studies estimating the prevalence of hepatitis A in chronic liver disease patients. Furthermore, there are minimal cost-comparative data as to whether or not screening for hepatitis A exposure before immunization is an effective fiscal strategy. The objectives of this study were to determine the prevalence of prior hepatitis A infection and to perform a prospective cost analysis for hepatitis A immunization in patients with chronic liver disease.This is a prospective cohort study of 100 patients with chronic liver diseases. Patients were screened for potential risk factors for hepatitis A including history of jaundice, socioeconomic status, birth origin, and ethnic background. Each patient underwent testing for evidence of prior infection using an ELISA. Seronegative patients then went on to receive an immunization series. Cost analysis of vaccination without prescreening (universal strategy) was compared to cost analysis of prescreening and selective immunization of those without prior infection (selective strategy).Fifty-three patients (53%) had serological evidence of prior hepatitis A infection (95% CI = 43-63%). Of the risk factors assessed, foreign birth was associated with prior hepatitis A exposure (p = 0.0002). Cost analysis revealed that prescreening for hepatitis A before vaccination was cost saving given the current prevalence.The seroprevalence of hepatitis A in those with chronic liver diseases was 53%. Cost analysis revealed that screening for hepatitis A before immunization is cost saving, and this strategy should be applied to follow current vaccination guidelines.

The purpose of this study was to examine the effect of diltiazem on cardiac function and neurohumoral factors (BNP, epinephrine, norepinephrine) after reperfused myocardial infarction without congestive heart failure (Killip class I). On the first day after myocardial infarction following reperfusion therapy patients were randomly assigned to diltiazem treatment (group 1, n=33) or no treatment (group 2, n=39). We then performed echocardiographic examinations on the patients and measured heart rate, mean blood pressure and neurohormones (BNP, epinephrine and norepinephrine). Follow-up evaluations of echocardiography were performed at 4 and 12 weeks and of neurohormones at 1 and 4 weeks after acute myocardial infarction. The highest peaks of plasma BNP, epinephrine, and norepinephrine levels were observed before treatment and decreased with time in both groups. After 4 weeks the level of plasma BNP in the diltiazem treatment group was lower than in the no treatment group [55+/-3 pg/mL vs 85+/-5 pg/mL (P0.05)]. Other neurohormones did not differ between groups. Fractional shortening (FS) and ejection fraction (EF)improved after myocardial infarction in both groups, but significantly more in the diltiazem group (P0.05) after 12 weeks of treatment. Changes in BNP correlated significantly with changes in left ventricular end systolic volumes, FS and EF. In this study, diltiazem significantly improved systolic function and reduced the level of plasma BNP after myocardial infarction, which suggest that diltiazem may have a beneficial effect on myocardial infarction without congestive heart failure.

The role of the voltage-sensitive Ca2+ channel (VSCC) as a target for anaesthetic action remains controversial. In this study we characterized the VSCC subtypes involved in K+-evoked norepinephrine and dopamine release from rat striatal slices and used this model system to examine the effects of a range of i.v. anaesthetics on release. Nifedipine (L-channel-selective), omega-conotoxin GVI(A) (N-channel-selective), omega-agatoxin IV(A) (P-channel-selective), omega-conotoxin MVIIc (P/Q-channel-selective) and Cd2+ (non-selective), along with alphaxalone, propofol and ketamine, were used in various combinations. Omega-Agatoxin IV(A), omega-conotoxin MVIIc and Cd2+ fully (100%) inhibited norepinephrine and dopamine release. Clinically achievable concentrations of alphaxalone inhibited norepinephrine and dopamine release, with concentrations producing 25 and 50% inhibition (IC25 and IC50) of the maximum of 2.1 and 7.8 microM respectively for norepinephrine and 2.9 and 7.2 microM for dopamine. The effects of propofol were observed at the top of the clinical range and those of ketamine exceeded this range. In addition, IC50 values for alphaxalone in the presence and absence of nifedipine and omega-conotoxin GVI(A) did not differ from the control. Our data suggest that clinically achievable concentrations of alphaxalone and propofol inhibit norepinephrine and dopamine release, which is mediated predominantly through P/Q-type VSCCs, suggesting a role for these channels in anaesthetic action.

1. Orexin A and B, recently identified in the rat hypothalamus are endogenous neuropeptide agonists for the G-protein coupled orexin-1 (OX1) and orexin-2 (OX2) receptors. 2. In the present study, we have examined the effects of orexin A, B and raised extracellular K(+) on noradrenaline release from the rat cerebrocortical slice. We have compared this with other sleep-wake-related (excitatory) neurotransmitters; dopamine, glutamate, serotonin and histamine. 3. Neurotransmitter release studies were performed in rat cerebrocortical slices incubated in modified Krebs buffer (with and without Ca(2+)+EGTA 1 mM) with various concentrations of orexin A, B and K(+) for various times. 4. Orexin A and B-evoked (10(-7) M) noradrenaline release was time-dependent reaching a maximum some 10 min after stimulation. K(+) (40 mM) evoked release was also time dependent but reached a maximum after 6 min. Orexin A, B and K(+) stimulation of release was concentration dependent with pEC(50) and E(max) (% of basal) values of 8.74+/-0.32 (1.8 nM) and 263+/-14% and 8.61+/-0.38 (2.4 nM) and 173+/-7% and 1.43+/-0.02 (37 mM) and 1430+/-70%, respectively. Orexin-evoked release was partially extracellular Ca(2+) dependent. 5. Of the other transmitters studied there was a weak orexin A and B stimulation of glutamate release. In contrast K(+) evoked dopamine, glutamate, histamine and serotonin release with pEC(50) and E(max) (% of basal) values of 1.47+/-0.05 (34 mM) and 3430+/-410%, 1.38+/-0.04 (42 mM) and 1240+/-50%, 1.47+/-0.02 (34 mM) and 480+/-10% and 1.40+/-0.05 (40 mM) and 560+/-60% respectively. 6. We conclude that the neuropeptides orexin A and B evoke noradrenaline release from rat cerebrocortical slices.

A 65-year-old man experienced anorexia and abdominal enlargement and died suddenly 45 days after admission. Multiple necrotic and hemorrhagic tumors were present in the liver (6 kg). The fragile tumor ruptured and a large amount of blood accumulated in the peritoneal cavity. The tumor was composed of cytotrophoblast and syncytiotrophoblast cells. Neoplastic cells were positive for human chorionic gonadotropin and negative for alpha-fetoprotein and carcinoembryonic antigen. The huge tumor directly invaded the entire antrum of stomach. Neoplastic trophoblastic cells proliferated mainly in the serosa and propria muscular layer of the stomach, and tiny cancer nests were observed in many vessels of the submucosa and propria mucosa. The serum alpha and beta human chorionic gonadotropin subunits showed a very high level; 51 ng/mL and 820 ng/mL, respectively. No tumor, cyst or scar was observed in the testes, mediastinum and retroperitoneum, macroscopically and microscopically. Based on these autopsy findings, we diagnosed this patient as having primary hepatic choriocarcinoma.

We report a patient in whom hypoxia developed during percutaneous cardiopulmonary bypass (PCPS) and was detected with the lowering of the bispectral index (BIS) values. A 7-yr-old boy was managed with PCPS for the treatment of cardiogenic shock after cardiac surgery. His circulation was dependent on PCPS and pulse pressure was nearly zero. Signals by pulse oxymetry were undetectable and periodical blood gas analysis was performed to confirm proper oxygenation. BIS was monitored, and a gradual decrease in the value was observed. Careful observation also revealed darkening of the blood in the PCPS circuit and blood gas analysis showed severe hypoxia. Oxygen concentration of the gas to a PCPS oxygenator was increased immediately and new PCPS circuit was prepared. It took almost two minutes to exchange the circuit. Near circulatory arrest might have occurred during the procedure and BIS and suppression ratio (SR) became below 10 and above 90, respectively. Both returned to the previous values 30 min after the replacement of the circuit. Severe hypoxia, otherwise overlooked, was detected with BIS monitoring and BIS reflected the circulatory status of the patient, especially of the brain. This monitoring is useful to confirm proper oxygenation during PCPS.

A 41-year-old male patient with well-controlled hypertension underwent a partial nephrectomy under total intravenous anesthesia with propofol, fentanyl and ketamine. To avoid allogeneic blood transfusion, preoperative autologous blood donation (400 g) a week before the surgery and acute normovolemic hemodilution (800 g) after induction of anesthesia were performed. As surgical blood loss was more than 4000 g, blood hemoglobin (Hb) level decreased to 6.4 g.dl-1. However, as intraoperative hemodynamics was relatively stable with no ischemic changes in ECG and arterial blood gas analysis did not show metabolic acidosis, autologous blood transfusion was withheld till hemostasis had been done. After returning the autologous blood, Hb increased to 9.4 g.dl-1. On the 2nd postoperative day, Hb decreased to 7.6 g.dl-1. As the patient's vital signs did not show any severe complications, blood transfusion was not performed. Then, the Hb level increased gradually to 13.9 g.dl-1, 3 month later without allogenic blood transfusion. In addition, any postoperative complications by low Hb level were not recognized so far. This case suggests that combination of autologous transfusion techniques may be effective to avoid allogeneic blood transfusion even against massive hemorrhage. However, to avoid disadvantage of these technique, we should always evaluate preoperative patient conditions.

This study was designed to compare prebypass haemodynamics under total intravenous anaesthesia (TIVA) using midazolam-fentanyl (group M) and propofol-fentanyl (group P) combinations. Sixteen adult patients undergoing CABG were studied with patients in group M and P (n = 8 each) given intravenous midazolam 0.1 mg.kg-1.h-1 and propofol 4 mg.kg-1.h-1 with fentanyl 25 micrograms.kg-1 until sternotomy, respectively. Following induction of anaesthesia, cardiac index and heart rate decreased significantly (30% and 20% in both groups, p0.05) these variables returned to baseline on completion of sternotomy. In addition, in group P mean arterial pressure decreased significantly (about 15%) following induction and there were no ischaemic signs. Overall for MAP there was no significant difference between the two groups. LVSWI and RVSWI were reduced by around 25% in both groups. Only the change in LVSWI reached statistical significance (p0.05). This reduction may have exert a caridioprotectant action by decreasing myocardial oxygen consumption. We conclude that both TIVA techniques represent an acceptable anaesthetic regimen for use in cardiac anaesthesia.

Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50-94% of patients withor =2 x 10(4) copies/ml (competitive RT-PCR) or100 x 10(3) copies/ml (Amplicor monitor) of HCV RNA by 468-1206 MU of IFN, but response was only 0-25% of the patients withor =2 x 10(5.5) copies/ml (competitive RT-PCR) or200 x 10(3) copies/ml (Amplicor monitor), even with 468-1206 MU of IFN. A high sustained rate was demonstrated in patients with 100-200 x 10(3) copies/ml of HCV RNA by 901-1206 MU of IFN, in comparison to that withor =900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100-200 x 10(3) copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000-227,000 for one person-viral eradication in the patients with100, 100-200, and200 x 10(3) copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with200 x 10(3) copies/ml of HCV RNA.

This report describes a 58-year-old man who exhibited the clinical features of amyotrophic lateral sclerosis (ALS) at autopsy, 1 year after clinical onset of the disease. Neuropathologically, in addition to degeneration of the upper and lower motor neurons, marked degeneration of the substantia nigra with the appearance of Lewy body-like inclusions (LBI) and skein-like inclusions (SLI) were observed in the remaining pigmented neurons. An immunohistochemical study revealed that both LBI and SLI were immunopositive for ubiquitin. Ultrastructurally, LBI in the substantia nigra were composed of randomly arranged 15 nm thick tubular structures associated with ribosome-like granules, similar to those of LBI in the lower motor neurons. SLI in the substantia nigra were composed of curved bundles of 5 nm thick filaments (thinner than those comprising the SLI in the lower motor neurons). We believe that degeneration of the substantia nigra could be one of the degenerative processes involved in ALS.

Infusion rate of propofol during anaesthesia is usually based on total body weight. In this study, we have determined the relationship between total body weight and plasma propofol levels when the infusion rate was based on total body weight.Sixty patients undergoing elective surgery were studied. Anaesthesia was induced with propofol 1 mg x kg(-1), ketamine 1 mg x kg(-1) and fentanyl 2 microg x kg(-1), and maintained with propofol 5 mg x kg(-1) x h(-1), ketamine 0.5-1 mg x kg(1) x h(-1) and fentanyl 5-15 microg x kg(-1). Propofol infusion rate did not change during anaesthesia, and infusion was terminated at the end of surgery. Immediately prior to termination of the propofol infusion, arterial blood (5 ml) was collected to measure plasma level of propofol by a high-performance liquid chromatography equipped with electrochemical detection.There was a significant correlation between plasma propofol and total body weight (r=0.646, P0.001). Plasma propofol concentration also correlated with infusion rate, corrected to lean body mass (r=0.527, P0.001).During a fixed infusion rate, plasma propofol concentration may be dependent on total body weight.

The prevention of nausea, vomiting and appetite loss induced by remission induction chemotherapy for acute myeloid leukemia was compared by randomization between granisetron alone and combination with granisetron plus methylprednisolone. Granisetron was administered at 40 micrograms/kg during chemotherapy, and methylprednisolone was administered concomitantly at 125 mg/body for 3 days or more in the combination group. The single and combination groups comprised 14 and 13 patients, respectively, and there was no significant difference between the background of both groups. To evaluate the effect they were scored according to 4 grades, and evaluated every 24 hours from the start of chemotherapy to 5 days after its completion. The complete inhibition rate of vomiting was as high as 71.4% and 92.3% in the single and combination groups, respectively, showing no significant difference. The grade of vomiting was mild in both groups. Nausea was noted in 71.4% and 46.2%, respectively, and the inhibitory effect tended to be higher in the combination group. Appetite loss developed in 92.9% and 41.7%, respectively, and the prevention effect was clearly higher in the combination group. The prevention effects on nausea 7, 8 and 10 days after the start of chemotherapy, on appetite loss 2-10 days after it, and 2-5 days after its completion, were higher in the combination group. Granisetron revealed an excellent inhibitory effect on vomiting induced by remission induction chemotherapy for acute myeloid leukemia, but combination with granisetron and methylprednisolone was considered useful for nausea in the latter half of the treatment period and for appetite loss during the whole period.

We examined the relationships among the activity of daily living (ADL), oral cavity care, and the number of oral cavity microorganisms in 40 patients with cerebrovascular diseases (CVD). The CVD patients were classified into 4 groups, I, II, III and IV based on their ADL and the method used for oral cavity care. The ADL was highest in group I and lowest in group III. Only the patients of only group III could not eat by themselves and were receiving naso-esophageal feeding. Oral cavity care was performed by the patients themselves in groups I and IV, but was performed by caregivers in groups II and III. The group IV patients had no teeth, but could eat by themselves using full dentures. The numbers of microorganisms in the pharyngeal swabs from the 4 groups were measured and expressed as colony-forming units (cfu). The numbers of both Staphylococci spp. and Candida spp. were significantly higher in group III than in the other groups. Moreover, Pseudomonas aeruginosa was isolated only from patients of group III (in about 66%). The oral cavity care by caregivers was almost the same in groups II and III, but the numbers of oral cavity microorganisms were significantly higher in group III than in group II. These results indicated that microorganisms grow more easily in the oral cavities of CVD patients with low ADL compared with CVD patients with higher ADL, and that eating is thought to be important for the prevention of an increase of microorganisms in the oral cavity.

Background: Histamine is most densely distributed in the hypothalamus and has an important effect on consciousness or wakefulness. It has been little considered whether general anesthetics could exert their effects on hypothalamic histamine metabolism. The present study was conducted to investigate the effects of isoflurane and sevoflurane anesthesia on hypothalamic histamine metabolism. Methods: Sixty male Wistar rats were divided equally into isoflurane and sevoflurane anesthesia groups. Each group was divided into three equal sub-groups: the control, anesthesia and recovery groups. The rats of the anesthesia and recovery groups were exposed to either 2% isoflurane or 3% sevoflurane for 30 min. The recovery group was kept in air for 30 min after anesthesia. The rats were decapitated to dissect out hypothalamus which was divided into the fore and rear portion. The contents of histamine and 1-methylhistamine, which is a main histamine metabolite, were determined by high-performance liquid chromatography. The obtained data were analyzed by one-way analysis of variance followed by Bonferoni's test. Results: Histamine contents of the anterior and posterior hypothalamus in both isoflurane and sevoflurane groups increased significantly during the anesthesia and 1-methylhistamine contents of the anterior and posterior hypothalamus in sevoflurane group increased remarkably after anesthesia. The increases of histamine contents supposedly reflected inhibited histamine metabolism and the increases of 1-methylhistamine would be caused by acceleration of histamine degradation. Conclusions: Histamine metabolism was inhibited during both isoflurane and sevoflurane anesthesia and accelerated only in the posterior hypothalamus during the emergence from these anesthetics.

We report two cases of self-induced water intoxication with rhabdomyolysis. They had been diagnosed as chronic schizophrenia, and admitted to mental hospitals. The patients were transferred to our emergency room because of sudden loss of consciousness and generalized convulsions. Laboratory findings revealed marked hyponatremia (case 1; 109 mEq/L and case 2; 104 mEq/L). CT scans showed the effacement of interhemispheric and bilateral sylvian fissures and sulci of the cerebral hemisphere due to diffuse brain edema. 10% glycerol and saline were intravenously injected to the patients. They recovered from hyponatremia after excreting a large amount of urine. Their disturbed consciousness recovered to the normal level in parallel with the normalization of their serum sodium concentration. Soon after the normalization of their consciousness level, their serum creatine kinase (CK) was markedly elevated (case 1; 13086 IU/L and case 2; 41832 IU/L), and their serum myoglobin level was also significantly elevated (case 1; 2670 ng/ml and case 2; 1420 ng/ml). A sufficient amount of transfusion was performed for avoiding the acute renal failure. The two patients recovered from rhabdomyolysis without any severe complication. We conclude that brain CT is useful for the diagnosis of brain edema, and monitoring of CK is also important to anticipate renal damage secondary to rhabdomyolysis.

We have studied the influence of fluid replacement on serum magnesium (Mg2+) concentrations, and studied proper Mg2+ supplementation during general anesthesia. Thirty eight patients undergoing elective surgery randomly received: Mg(2+)-free acetated Ringer solution (Group I, n = 15), acetated Ringer solution containing 0.5 mmol.l-1 of Mg2+ (Group II, n = 6), 1.0 mmol.l-1 of Mg2+ (Group III, n = 7), 2.0 mmol.l-1 of Mg2+ (Group IV, n = 6), or 4.0 mmol.l-1 of Mg2+ (Group V, n = 4). Measurements were made on serum and urine Mg2+ concentrations during anesthesia. In Group I, the serum Mg2+ concentrations decreased in correspondence with the water balance. It is suggested that dilution due to the fluid replacement induced the reduction in serum Mg2+ concentrations since the observed urine Mg2+ concentrations were negligible. In Group II-V, the reduction in serum Mg2+ concentrations was inhibited by Mg2+ supplementation, and the serum Mg2+ concentrations remained unchanged in Group IV. We conclude the Mg2+ supplementation is required during anesthesia when a large amount of fluid is infused.

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin (TRX). ADF/TRX is a conserved multifunctional reductant presumably associated with redox regulation of the cellular environment; it works in vitro as a cytokine, free radical scavenger, activator of transcription factors, and substrate for several enzymes. In the present series of experiments, we studied the expression and intracellular localization of ADF/TRX in mouse kidney from two different renal tubular injury models: a free radical-associated model with ferric nitrilotriacetate (Fe-NTA) and a free radical-independent model with HgCl2. Markers of oxidative damage, such as 8-hydroxy-2'-deoxyguanosine, thiobarbituric acid-reactive substances, and 4-hydroxy-2-nonenal-modified proteins, were significantly increased in kidney from male C57B/6 mice 1 hour after a single intraperitoneal injection of Fe-NTA (5 mg iron/kg). However, in kidney from mice given a subcutaneous injection of HgCl2 (5 mg Hg/kg), none of these markers were increased, despite tubular necrosis with sulfhydryl depletion. In the Fe-NTA model only, Northern and Western blot analyses of the kidney revealed induction of ADF/TRX (2.5-fold) after 16 hours and translocation of ADF/TRX from the cytoplasmic to nuclear fraction (3.5-fold) after 24 hours. Immunohistochemistry showed a patchy distribution of ADF/TRX in the normal renal proximal tubules. In ex vivo experiments using serial normal kidney frozen sections, it was found that renal proximal tubules with low expression of ADF/TRX were more vulnerable to oxidative stress mediated by Fe-NTA. Collectively, these data suggest that: (a) ADF/TRX is induced and translocated to nuclei by oxidative damage mediated by Fe-NTA in the renal proximal tubules; (b) induction of ADF/TRX is independent of tubular necrosis or sulfhydryl depletion; and (c) ADF/TRX is involved in the cellular defense mechanisms in vivo against oxidative damage.

We report a 39-year-old man with seven-year history of adult onset Still's disease (AOSD) who developed left abducens palsy and ataxic gait. T2-weighted MRI demonstrated high-intensities in the left side of the lower pons, including nucleus abducens and the inferior cerebellar peduncle, and in the right anteromedial portion of the thalamus corresponding to his neurological abnormalities. He responded favorably to corticosteroid treatment, and the high-intensities in the T2-weighted MRI diminished subsequently. Previously, he had developed bilateral sensorineural hearing loss which had responded to corticosteroid treatment during an exacerbation of the disease. There was no evidence of multiple sclerosis or other systemic diseases affecting the central nervous system (CNS) in the laboratory findings. Although the precise reason for the MRI lesions was unclear, we thought they were CNS manifestations of Still's disease. We suggest that AOSD is one of the causes of focal CNS involvement in young adults, particularly who has a history of fever of unknown origin.

It has been suggested that volatile anaesthetics enhance synaptic inhibition via gamma-aminobutyric acid (GABA) in the central nervous system. We have examined the effects of sevoflurane on GABAA and GABAB receptors in rat hippocampus in vitro. Extracellular recordings were used to record field potentials in rat CA1 pyramidal neurones of transverse hippocampal slices, stimulated electrically via stratum radiatum input. Sevoflurane 0.4-5.0 vol% decreased the amplitudes of population spikes (PS) of CA1 neurones in a concentration-dependent (calculated ED50 = 6.31 vol%) and reversible manner. The GABAA antagonist, bicuculline methiodide 5 x 10(-5) mol litre-1, induced oscillations (multiple spikes) and blocked the inhibitory actions of sevoflurane in the initial component (up to 24.8 ms) of the oscillation. The latter portion of the oscillation (greater than 24.8 ms) was depressed by sevoflurane. The GABAB antagonist, phaclofen 5 x 10(-4) mol litre-1 partially blocked the effects of sevoflurane on the latter portion of the bicuculline-induced oscillation. Sevoflurane 2.0 vol% significantly enhanced paired-pulse (PS2/PS1) facilitation (from 128.4% to 155.5% at an inter-stimulus interval of 37.9 ms); this enhancement was blocked by phaclofen. Stimulus-response relationships revealed that 2.0 vol% sevoflurane increased the intensity of threshold for PS generation to 109.8% of control. Both the GABAA agonist, muscimol 2 x 10(-5) mol litre-1 and the GABAB agonist, (+/-)-baclofen 10(-5) mol litre-1, potentiated the effects of sevoflurane. Sevoflurane enhanced thresholds by 137.1% and 138.5% of control in the presence of muscimol and (+/-)-baclofen, respectively. The results demonstrate that sevoflurane at clinical concentrations activated both GABAA- and GABAB-mediated inhibitions in area CA1 of the hippocampus, and that sevoflurane and GABA agonists (muscimol and baclofen) acted on different domains on the GABAA and GABAB receptors, respectively.

Non-Fukuyama type congenital muscular dystrophy (n-FCMD), a subtype of progressive muscular dystrophy (PMD), is a very rare autosomal recessive disorder. N-FCMD is characterized by severe and progressive motor weakness and atrophies of proximal muscles during the infant period. A 9-year-old boy with n-FCMD underwent elective surgery for muscle release around the hip joints bilaterally. As many perioperative complications related with volatile anesthetics and muscle relaxants had been reported in the anesthetic management of PMD, these drugs were thought to be contraindicated in patients with n-FCMD. Because n-FCMD seemed to have very similar pathogenesis with PMD, caudal epidural block was chosen, supplemented with the administration of diazepam, pentazocine and nitrous oxide. The operation and anesthesia were conducted uneventfully. No complications occurred postoperatively.

This paper describes rapid bone resorption in the peri-implantitis of HA implants based on both our clinical observations of and histological research on extracted dense hydroxyapatite (HA) implants. The surfaces of extracted HA implants were rough, although they were smooth at fixture placement. Plaque formed on the necks of the implants, whereas little plaque was seen on the bottoms. The plaque consisted of cocci and rods, including filamentous bacteria. Few spirochetes were observed. Although surrounding bone was formed rapidly around the HA implant, bone thickness gradually decreased compared with the titanium implant. These facts suggest that the rigid biointegration of HA with the thin surrounding bone--that is, the overstressing of the bone--causes rapid bone resorption rather than plaque accumulation on HA.

Whole-saliva samples were collected from 45 asymptomatic carriers, 18 patients with AIDS-related complex (ARC) or AIDS, and 76 medical students by simple spitting with no stimulation and tested by an ultrasensitive enzyme immunoassay (immune complex transfer enzyme immunoassay) for anti-HIV-1 IgG using recombinant reverse transcriptase as antigen and beta-D-galactosidase as label. With as little as 1 microliter of whole saliva, the lowest signals among the 45 asymptomatic carriers, 8 patients with ARC, and 10 patients with AIDS were 38-, 78-, and 3-fold, respectively, higher than the highest signal among the medical students. When the volume of whole saliva for test was increased up to 100 microliters, no significant effect was observed on signals for seropositive cases and signals for the medical students increased only very slightly. Therefore, whole-saliva samples containing extremely low levels of anti-HIV-1 IgG, even 2,000-fold lower than the lowest level among the 45 asymptomatic carriers tested, were considered to be discriminated from those of seronegative individuals. Thus, the sensitivity and specificity were expected to be both 100% with whole saliva even for a larger number of samples, although the number of samples tested was limited.

During the inflammatory response, tissues release histamine (H), substance P, serotonin (5-HT), prostaglandins and kinins, agents that mediate manifestations of inflammation such as pain, vasodilation, increased capillary permeability and smooth muscle contraction. In this study we investigated whether racemic (R[+]) ketamine (K) and its isomers are spasmolytic on intestinal smooth muscle contracted by inflammatory mediators, and whether the spasmolytic effect of K is related to changes in calcium influx through the L-type calcium channel or to an interaction of K with opioid receptors. We measured the contractions of guinea-pig ileum mounted in an organ bath containing Tyrode's solution gassed with 95% O2/5% CO2 at 37 degrees C. In the first protocol we determined the effect of K and its isomers on contractions induced by five mediators: 10(-7) M H, 10(-8) M substance P, 10(-8) M neurokinin A, 5 x 10(-9) M bradykinin and 5 x 10(-7) M 5-HT. For each of these mediators, we plotted concentration-response curves for the inhibitory effect of K, and from regression fitting of these curves, we calculated the IC50 concentration of K that inhibited the contraction by 50%). In the second protocol we measured the contraction induced by the calcium ionophore A23187 (5.0 x 10(-6) M), both alone and after 1.8-7.2 x 10(-4) M R(+/-)K. Then we examined how the inhibition caused by R(+/-)K was affected by increases in the concentration of extracellular calcium by adding calcium (1.8-7.2 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)

We anesthetized 34 sumo wrestlers. All patients were male. Average age was 21.1. Their height was 181.9 +/- 4.5 (mean +/- SD) cm, and they weighted 135.2 +/- 16.9 kg. Anesthetic methods used were spinal anesthesia alone in 17 patients, general anesthesia alone in 9, general anesthesia + epidural anesthesia/or spinal anesthesia/or axillary block in 8. The preoperative data showed findings common to obese patients; liver dysfunction, abnormal blood sugar, and abnormal ECG such as ST depression or left ventricular hypertrophy. For intubation, fiberscopy was required in one patient, and almost all patients required high FIO2, otherwise SaO2 decreased. For spinal anesthesia or epidural anesthesia, we needed long needles of 8 to 15 cm.

Effect of pirenzepine alone or the combination of pirenzepine and famotidine on gastric secretion during anesthesia and surgery was evaluated in 52 elective surgical patients ranged in age from 17 to 68 years. These patients of each group were divided into two subgroups according to their age either 40 years and under or over. The patients underwent orthopedic, ophthalmic, ENT, plastic or non-abdominal general surgery under neuroleptanesthesia except 5 patients who had enflurane or isoflurane anesthesia. They received either pirenzepine 10 mg or the combination of pirenzepine 10 mg and famotidine 20 mg intravenously just before the induction of anesthesia. Volume and acidity of gastric juice were measured for 3 hours after the administration of these agents. Decrease in volume and acidity of gastric juice continued for more than 3 hours after the administration of pirenzepine alone or the combination of pirenzepine and famotidine, and it was more prominent in the combination group than in the pirenzepine group. There was no statistical difference in volume of gastric juice between the patients of 40 years and under in age and those over 40 years in each group. However, the intragastric pH tended to be lower in patients of 40 years and under in age than that in those over 40 years. A percentage of patients who had intragastric pH below 2.5 was larger in the pirenzepine administered patients of 40 years and under in age than that of the remaining patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of ursodeoxycholic acid on liver function tests and on bile acid metabolism was investigated in a multi-center randomized controlled dose study for chronic hepatitis C. Twenty, 18 and 19 patients were administered 150, 600 and 900 mg/day, respectively of ursodeoxycholic acid every day for 16 wk. Serum liver parameters and bile acid composition in the treatment groups were compared with 17 control patients. A similarly significant decrease of serum alanine aminotransferase and serum gamma-glutamyltransferase was observed in patients administered 600 and 900 mg of ursodeoxycholic acid. Serum bile acid composition was determined by high-performance liquid chromatography. At entry, the relative proportions of major bile acids were similar to those observed in normal individuals. Maximal concentrations of total ursodeoxycholic acid were 0.30 mumol/L, 5.59 mumol/L, 21.42 mumol/L and 14.73 mumol/L in the control, 150, 600 and 900 mg/day groups, respectively. The fraction of the total ursodeoxycholic acid increased in a dose-dependent manner, and it was significantly higher than in controls (p0.001). The hydrophobicity index of bile acids was calculated by the method of Heuman, and its correlation with serum parameter levels was analyzed. In the 600 and 900 mg/day dose groups, serum alanine aminotransferase decreased in the cases in which hydrophobicity index significantly decreased during treatment. The same correlation was observed between the hydrophobicity index and serum gamma = glutamyltransferase in these two groups. There was no correlation between these parameters in the control and 150-mg groups. There was no correlation between reduction rate of serum alanine aminotransferase and initial liver histology.(ABSTRACT TRUNCATED AT 250 WORDS)