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Healthcare students are key resources after nuclear disasters. Healthcare students at Fukushima Medical University volunteered after the Great East Japan Earthquake and Fukushima nuclear accident. At the time of the disaster, healthcare students, who were in a position between medical and non-medical people, listened to the various concerns and worries of victims. Specifically, they established the Fukushima WILL – a disaster medical club. These activities have continued for about 10 years after the Fukushima disaster. In this paper, we introduce lessons from and perspectives for healthcare student volunteer activities during disasters. When volunteering, healthcare students needed to acquire sufficient medical knowledge and skills as well as display effective communication skills considering the background of the affected people. In addition, to respond to potential future disasters, healthcare students need to proactively, independently, and repeatedly learn about diseases that are likely to occur in shelters and how to prevent them. Seminars and workshops should be implemented to ensure students are taught these lessons and provided daily training on disaster response.

Medications used to treat the symptoms of psychosis and mental retardation often cause side effects that involve the extrapyramidal motor system, and result in twitching and related involuntary motions. To counteract these adverse effects, anticholinergic drugs, which suppress the transmission of nerve signals, are often prescribed along with antipsychotic drugs. However, in addition to possessing side effects themselves, anticholinergics such as biperiden and piroheptine have another undesirable effect, in that they bring about a decrease in the blood levels of the antipsychotic drugs, leading to a loss of efficacy in controlling psychotic symptoms. The effects of anticholinergic drugs on the bioavailability of a new antipsychotic, zotepine, were studied in 21 schizophrenic or mentally retarded patients. Zotepine, a tranquilizer with effects similar to the more commonly prescribed chlorpromazine, has been found to be effective in the treatment of schizophrenia. After two weeks of taking a constant dose of zotepine, the patients were also given biperiden in 6 milligrams (mg) daily doses for another two weeks. Following that sequence, zotepine was again taken alone for two weeks, after which 12 mg per day of piroheptine was added for two more weeks. Blood levels of zotepine were measured at appropriate points, and psychotic symptoms of the 15 schizophrenic patients were evaluated. Blood levels zotepine were not affected by either of the anticholinergics, which produced only mild side effects in a few cases. The results demonstrate that biperiden and piroheptine are appropriate anticholinergics to reduce the extrapyramidal side effects caused by zotepine and other antipsychotic drugs. (Consumer Summary produced by Reliance Medical Information, Inc.)

Sound velocity of laser-irradiated iron foils was measured with side-on x-ray radiograph technique. Iron foils were irradiated with two-stepped laser pulse to reach earth's core condition. We measured not only the sound velocity but also temperature, pressure, shock velocity, compressibility, and particle velocity. The experimental parameters of temperature and pressure were very close to the earth's core condition. The experimental results on the sound velocity are in good agreements with previous experimental results and one-dimensional simulation results.

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce cytokines, including tumor necrosis factor-α and interleukins (ILs), in the small intestine via a Toll-like receptor 4 (TLR4)-dependent pathway, leading to intestinal ulceration. Activation of the inflammasome promotes pro-caspase-1 cleavage, leading to pro-IL-1β maturation. We examined the role of NLRP3 inflammasome in NSAID-induced enteropathy. Small intestinal damage developed 3 h after indomethacin administration, accompanied by increases in IL-1β and NLRP3 mRNA expression and mature caspase-1 and IL-1β levels. In vivoblocking of IL-1β using neutralizing antibodies attenuated indomethacin-induced damage, whereas exogenous IL-1β aggravated it. NLRP3−/−and caspase-1−/−mice exhibited resistance to the damage with reduction of mature IL-1β production. This resistance was abolished by exogenous IL-1β. TLR4 deficiency prevented intestinal damage and inhibited upregulation of NLRP3 and IL-1β mRNAs and maturation of pro-caspase-1 and pro-IL-1β, whereas TLR4 activation by its agonists exerted opposite effects. Apyrase, an adenosine triphosphate (ATP) scavenger, or Brilliant Blue G, a purinergic P2X7receptor antagonist, inhibited the damage as well as caspase-1 activation and IL-1β processing, despite there being sufficient amounts of pro-IL-1β and NLRP3. These results suggest that NLRP3 inflammasome-derived IL-1β plays a crucial role in NSAID-induced enteropathy and that both TLR4- and P2X7-dependent pathways are required for NLRP3 inflammasome activation.

Small intestinal injury caused by non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin is an epoch making topic in clinical field with the aid of new devices, capsule endoscopy and double balloon enteroscopy to look at small intestine directly. However, the injury has been reported in animals since more than 40 years ago. Proposed mechanisms are impairment of mucosal defense through inhibition of cyclooxygenase (COX) resulting in deficiency of prostaglandins, and mitochondrial disorder. Possible aggressive factors are NSAIDs/aspirin themselves, bile, and enterobacteria. Translocation of enterobacteria through the mucosa impaired integrity may be the first step of the injury. Bacterial lipopolysaccharides stimulate toll-like receptor-4 in macrophages, which increases proinflammatory cytokines through MyD88 signaling pathway. Finally neutrophils are activated and the small intestinal mucosa is injured with the attacks of NSAIDs/aspirin themselves, bile, and proteolytic enzymes and active oxygen species released by neutrophils. Candidates of treatment tools are prostaglandin derivatives, mucoprotective drugs, probiotics, and mitochondrial protective drugs such as metronidazole and cyclosporin A. Further clinical studies are needed to elucidate the effect in humans.

Background: The quantitative assessment of myocardial blood flow using real-time myocardial contrast echocardiography is based on a replenishment of bubble density after bubble destruction by high-power ultrasound exposure (burst). However, all microbubbles in the myocardial vessels are not necessarily completely destroyed, which results in unreliable data of the replenishment curve analysis. Objective: The aim of this study was to propose a corrected equation for the replenishment curve analysis based on the hypothesis in which the initial intensity just after burst should be equivalent to the baseline intensity before contrast infusion, and to examine whether the regional difference of myocardial perfusion parameters could be minimized by the use of corrected equation of replenishment curve. Methods: Myocardial opacification of the left ventricular short-axis view was observed using low mechanical index during infusion of Definity in open-chest dogs. Bubble destruction was set in two ways, either high (0 dB) or low (-11 dB) power burst. The videointensity (VI) of baseline before contrast infusion (f-value) was assumed as an initial intensity after complete bubble destruction. Changes of the VI after burst were fitted to both exponential functions: y = a (1 - e^-^@b^t) + c (conventional equation) and y = a (1 - e^-^@b^(^t^ ^-^ ^d^)) + f (corrected equation). The c-value was the measured VI just after burst. The d-value was the hypothetical time of onset of the replenishment curve if all bubbles were completely destroyed. The plateau VI was defined as the A-value, which was the sum of a- and c-values or a- and f-values, respectively. The maximal difference of @b-value among myocardial regions was calculated by either equation. Results: The A-value was almost identical in either equation regardless of the acoustic power of burst. The @b-value by the conventional equation was higher after the incomplete burst than that after complete burst (0.45 +/- 0.12 vs 0.54 +/- 0.16). By contrast, the @b-value calculated by the corrected equation was almost identical despite complete or incomplete bursts (0.46 +/- 0.13 vs 0.48 +/- 0.15). The maximal difference of @b-value was significantly reduced by the use of corrected equation (conventional 0.24 +/- 0.14 vs corrected 0.18 +/- 0.10). Conclusions: Variation of @b-value because of the incomplete bubble destruction can be minimized by using the corrected equation: y = a (1 - e^-^@b^(^t^ ^-^ ^d^)) + f. Further, the corrected equation can improve the regional variation of @b-value.

Background: The severity of the coronary flow reduction that corresponds to myocardial perfusion and functional abnormalities remains unclear. We estimated the impact of various severities of flow-limiting coronary stenosis at rest on myocardial perfusion and functional indices from myocardial contrast echocardiography and tissue strain imaging and characterized the relationship between both the indices. Methods: Four levels of flow-limiting stenoses (slight, mild, moderate, severe) of the left circumflex coronary artery were examined in 10 open-chest dogs. In the left circumflex coronary artery area, plateau videointensity and time to plateau (TP) of the replenishment curve from myocardial contrast echocardiography were calculated for perfusion analysis, and peak systolic strain and postsystolic strain index (PSI) from tissue strain imaging were measured for functional analysis. Results: Plateau videointensity and peak systolic strain tended to decrease with increased severity of stenosis, although these differences did not reach the level of statistical significance. TP and PSI were significantly increased in the context of moderate (>=30-<50%) and severe (>=50%) flow reduction when compared to baseline values (TP, moderate 1.69 +/- 0.20 and severe 1.77 +/- 0.25 vs baseline 0.93 +/- 0.17, P < .01, respectively; PSI, moderate 0.96 +/- 0.15 and severe 1.28 +/- 0.32 vs baseline 0.59 +/- 0.18, P < .05 and P < .01, respectively). Further, TP and PSI were positively correlated with flow reduction (r = 0.81 and r = 0.84, P < .0001, respectively), and PSI was positively correlated with TP (r = 0.72, P < .0001). Conclusions: In contrast to conventional indices, such as plateau videointensity and peak systolic strain, novel indices, such as TP and PSI, were both able to detect 30% or greater coronary flow reduction at rest.

Background & Aims: Alcohol consumption exacerbates liver injury in chronic hepatitis C, and enhanced mitochondrial oxidative stress is one possible mechanism. The aim of this study was to determine whether hepatitis C virus core protein and alcohol-inducible cytochrome P450 2E1 contribute to reactive oxygen species production and cytotoxicity in human hepatoma cells. Methods: Huh-7 cells expressing core protein, cytochrome P450 2E1, or both were exposed to 0.1 mmol/L tertiary butyl hydroperoxide, tumor necrosis factor @a, and/or 25 mmol/L ethanol. Cytotoxicity, reactive oxygen species production, glutathione content, and mitochondrial membrane potential were measured. Results: Expression of core/cytochrome P450 2E1 synergistically enhanced cell death induced by either tertiary butyl hydroperoxide or tumor necrosis factor @a. After tertiary butyl hydroperoxide treatment, total reactive oxygen species production was increased more than 3-fold compared with cells that did not express core and cytochrome P450 2E1. Mitochondrial depolarization and reduced glutathione depletion occurred as well, and cell death was prevented by inhibition of mitochondrial permeability transition or caspase activity. Confocal microscopy showed that the mitochondria themselves were the origin of the reactive oxygen species. In the absence of core/cytochrome P450 2E1 expression, mitochondrial changes and cell death did not occur. Ethanol treatment further decreased mitochondrial reduced glutathione content and exacerbated mitochondrial reactive oxygen species production, depolarization, and cell death. All these effects were prevented by the antioxidant N-acetylcysteine. Conclusions: Mitochondrial reactive oxygen species production is induced by hepatitis C virus core and cytochrome P450 2E1, resulting in a reduction of mitochondrial antioxidant capacity and sensitivity to oxidants and tumor necrosis factor @a. Alcohol further depletes mitochondrial reduced glutathione, which exacerbates depolarization and cell death. Sensitization of mitochondria to oxidative insults is thus a potential mechanism for alcohol-related exacerbation of liver injury in chronic hepatitis C.

Background: Although stress myocardial contrast echocardiography (MCE) can be used to detect coronary stenosis, its efficacy relative to other methods, such as detection of wall-motion abnormalities, remains unknown. Thus, the goal of this study was to compare the sensitivity of MCE versus wall-motion abnormality detection in the assessment of coronary artery stenosis. Method: Nine dogs with severe but nonflow limiting stenosis in the circumflex coronary artery underwent evaluation with real-time MCE along the short-axis view during infusion of Optison. The equation of y = a (1 - e^-^@b^t) + c, which fits the replenishment curve of MCE, was calculated in the midseptum (normal region) and in the lateral wall (ischemic region) before and during adenosine triphosphate infusion. Wall-motion abnormalities were also evaluated by visual assessment and by measurement of wall thickening. Results: Area under the receiver operating characteristic curve in @b- and A x @b-value, and percent wall thickening, was 0.963, 0.963, and 0.889, respectively, indicating that the diagnostic accuracy for detecting the coronary artery stenosis by real-time MCE was higher than that by the wall-motion assessment. Conclusion: Real-time MCE has higher sensitivity in detecting coronary stenosis during adenosine triphosphate stress test when compared with wall-motion assessment.

Transitional vertebrae (TV) may be one of the risk factors for lumbar disc herniation. It is not clear, however, whether the presence of TV can affect the development of nerve-root symptoms. Our aim was to clarify this relationship. A total of 501 patients with lumbar degenerative disease and nerve-root symptoms was studied in respect of their level and the presence of TV. As a control group, 508 patients without low back pain or nerve-root symptoms were studied to establish the incidence of TV. In patients with disc herniation, the incidence was statistically higher and the mean age lower in patients with TV than in those without. In most patients, the symptomatic disc level was just above the TV. Similarly, in those with stenosis of the spinal canal without spondylolisthesis, the symptomatic disc level was most commonly just above the TV.

The effects of diclofenac and ketoprofen on nerve conduction velocity in experimental nerve root compression were evaluated in a setup using an established pig model.

Four patients of delusional disorder, somatic type, were treated with clomipramine 60–120 mg/day. All patients showed marked clinical improvement after 27–57 days of clomipramine treatment. In one case, previous treatments by various antipsychotic drugs including pimozide had been unsuccessful. This report suggests that clomipramine is effective at least for some patients with delusional disorder, somatic type, including pimozide-resistant cases. It is also suggested that there is some association between delusional disorder, somatic type, and serotonergic dysfunction. Int Clin Psychopharmacol 14:181–183 © 1999 Lippincott Williams & Wilkins

The effects of repeated ingestion of grapefruit juice, an inhibitor of cytochrome P4503A4 (CYP3A4), on the steady-state plasma concentrations of haloperidol and reduced haloperidol were examined. Twelve schizophrenic inpatients receiving haloperidol 12 mg/day, ingested grapefruit juice 600 ml/day for 7 days. Blood samples were collected before and during grapefruit juice coadministration and 1 week after its discontinuation together with an assessment of clinical status. Plasma drug concentrations were measured using high-performance liquid chromatography. Clinical status for each patient was assessed by the Brief Psychiatric Rating Scale (BPRS) and the UKU side-effect rating scale (UKU). Plasma concentrations of haloperidol and reduced haloperidol during grapefruit juice coadministration (9.0 ± 3.0 and 2.6 ± 1.4 ng/ml, respectively) were not significantly different from those before grapefruit juice coadministration (9.1 ± 2.8 and 2.6 ± 1.5 ng/ml) or those 1 week after its discontinuation (8.8 ± 2.7 and 2.6 ± 1.3 ng/ml). There was no change in the scores of BPRS or UKU during the study period. The present results shows that grapefruit juice does not affect the plasma concentrations of haloperidol and reduced haloperidol or clinical status in patients receiving haloperidol.

A case of the SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome in a 35-year-old woman is presented. Ignorance of this entity on the part of the physicians treating the patient may have contributed to her having repeated diagnostic procedures and treatment, some of which may have been unnecessary. Dentists are encouraged to suspect the SAPHO syndrome when they encounter a patient with mandibular osteomyelitis together with symptoms involving other bones and skin lesions such as pustulosis or psoriasis.

Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP) were studied in six depressed patients treated with trazodone. The daily dose of trazodone was 150 mg in three cases and 300 mg in three cases. Carbamazepine, 400 mg/day, was coadministered for 4 weeks, and blood samples were taken before carbamazepine addition and at weekly intervals after the addition. Carbamazepine significantly (p< 0.01) decreased plasma concentrations of not only trazodone but also m-CPP at each week. On the average, plasma concentrations of trazodone and m-CPP at 4 weeks were 24 and 40% of the corresponding precarbamazepine values. This study thus suggests that carbamazepine coadministration decreases plasma concentrations of trazodone and m-CPP by inducing the metabolism of these compounds.

Twenty-seven patients with severe tuberculous kyphosis have been treated at the National Murayama Hospital between 1966 and 1977.

Effects of various factors on steady state plasma concentrations of trazodone and its active metabolitemchlorophenylpiperazine mCPP were studied in 43 depressed patients 19 males, 24 females receiving trazodone 150 mg at bedtime for 13 weeks. Sixteen cases were smokers, and 19 cases were also receiving various benzodiazepines. The means and ranges of plasma concentrations of trazodone and mCPP, and the mCPPtrazodone ratio were 619 2511059 ngml, 59 32139 ngml and 0.100 0.0440.219, respectively. Smokers had significantly p< 0.05 lower plasma concentrations of trazodone and higher mCPPtrazodone ratios than nonsmokers. Age, sex and coadministration of benzodiazepines did not affect any plasma concentrations or the mCPPtrazodone ratio. In 11 cases where the dose was increased to 300 mg, neither plasma concentrationdose ratios nor the mCPPtrazodone ratio changed significantly. The present study thus suggests that 1 there is a large interindividual variation in the metabolism of trazodone 2 smoking enhances the metabolism, but age, sex and coadministration of benzodiazepines do not affect it 3 trazodone and mCPP have linear kinetics.

m-Chlorophenylpiperazine (m-CPP), which is a metabolite of trazodone, is a serotonin agonist. To examine for the possibility that m-CPP is involved in biochemical effects during treatment with the parent compound, prolactin response to trazodone treatment (150 mg at bedtime for 3 weeks) was studied in 12 depressed patients. The means ± S.D. of plasma prolactin concentrations before treatment, 12 h. and 1,2 and 3 weeks after initiation of treatment were 9.1 ± 5.6, 14.7 ± 9.1, 15.3 ± 8.5, 13.2 ± 7.0 and 13.0 ± 7.0 ng/ml, respectively. The mean prolactin concentrations at 12 h(p < 0.01), 1 week(p < 0.001) and 2 weeks (p < 0.05) were significantly higher than that before treatment. The present study thus shows that trazodone treatment increases prolactin concentrations, suggesting that m-CPP is involved in biochemical effects during treatment with the parent compound.

Tecto-thalamic projections in the hereditary bilaterally microphthalmic rat were studied by means of WGA-HRP injection into the dorsal lateral geniculate nucleus (LGNd) and the lateroposterior thalamic nucleus (LP). Histological study in the mutant rats showed that whereas LGNd and superficial layers of the superior colliculus (SC) suffered from a remarkable reduction in size, LP had no histological changes as compared to the normal animals. Unilateral injection of the tracer into the microphthalmic LGNd showed that WGA-HRP positive neurons were present mostly in the ipsilateral str. griseum superficiale (SGS) of the SC. However, the number of labeled SGS neurons of the microphthalmic animals was about 3% of the normal. Although cell bodies of the normal tecto-LGNd neurons in the SGS were spindle-form in shape and issued one or two proximal dendrites from each pole, the microphthalmic tecto-LGNd neurons showed an irregular contour and their dendrites were not so intensively labeled. Unilateral injections of WGA-HRP into the LP revealed that the tecto-LP neurons were mainly distributed in the ipsilateral str. opticum of the colliculus. (SO) in both normal and microphthalmic animals. However, the number of labeled SO cells in the microphthalmic rat was about one-half of the normal. Furthermore, the size of labeled tecto-LP neurons was smaller than that of the normal ones, and they showed irregular round to oval cell bodies with equivocally labeled dendrites, in contrast to the normal tecto-LP neurons with polygonal cell bodies extending three or more dendrites in a radial fashion. These results indicate that there exist the tecto-LGNd and -LP projection neurons in the microphthalmic rat and that their laminally segregated projection is fundamentally preserved. However, the number of the tecto-thalamic projection neurons, especially of the tecto-LGNd cells, was markedly diminished in the mutant tectum compared to normals.

The relationship between oral signs and osteoporosis was investigated to assess the possibility of using this as an indicator of postmenopausal osteoporosis. Sixty-four women between the ages of 50 and 70 years were evaluated. Osteoporotic signs consisted of thoracic spine fracture as demonstrated on lateral chest radiographs. Oral signs were the number of teeth present, mandibular cortical width, alveolar bone resorption, and the morphologic classification of the inferior cortex on panoramic radiographs. The number of teeth present (N) was highly related to the probability of thoracic spine fracture and was used to derive the probability equation for the presence of thoracic spine fracture: probability value =1/(1+e^-^z), Z=18.68-0.29 age -0.27N. A probability value higher than 0.5 suggests the possibility of thoracic spine fracture. It was concluded that this equation could serve as a simple and useful tool for dentists to assess the possibility of latent osteoporosis.

Abstract: Objective: The interaction between carbamazepine and bromperidol was studied in 13 schizophrenic inpatients. Methods: Before carbamazepine addition, the subjects were taking bromperidol 12–24 mg  day−1 for 1–20 weeks. Carbamazepine 400 mg  day−1 was coadministered for 4 weeks, and blood samplings were performed before carbamazepine addition and at weekly intervals after the addition. Plasma concentrations of bromperidol and its reduced metabolite were measured by high-performance liquid chromatography. Results: Carbamazepine significantly decreased plasma concentrations of both bromperidol and reduced bromperidol for all weeks. On average, the plasma concentrations of bromperidol and reduced bromperidol at 4 weeks were 37% and 23% of the corresponding precarbamazepine values. Despite these decreases in plasma concentration, the Clinical Global Impression scores decreased slightly but significantly after carbamazepine addition. Conclusion: The present study suggests that carbamazepine decreases plasma concentrations of bromperidol and its reduced metabolite by inducing the metabolism of these compounds. Nevertheless, adjunctive carbamazepine may be useful for schizophrenic patients treated with bromperidol.

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. Twenty–one FCMD families, 13 of them with consanguineous marriages, were analysed by genetic linkage analyses with polymorphic microsatellite markers to map the FCMD gene. Significant lod scores were obtained with the markers D9S58 (Zmax=5.81 at θ=0.06), D9S58 (Zmax=4.33 at θ=0.02), and HXB (Zmax=3.28 at θ=0.09) on chromosome 9q31–33. Multipoint analysis placed FCMD between D9S58 and D9S58, with a maximum lod score of 16.93. These markers will be useful for presymptomatic, prenatal and carrier diagnosis of family members carrying FCMD, and they represent important resources for the identification of a gene responsible for FCMD.

Participation of the autonomic nerve in tonsillar focal infection was investigated by measuring neurotransmitters, receptors and microvibration. In focal infection patients, the volume of norepinephrine in the tonsil increased significantly and the number of α-adrenergic receptors decreased. These findings suggest that the focally infected tonsil exhibits a high degree of sympathetic nerve activity. The ratio of N-type in microvibration decreased systematically, which indicates some imbalance or immaturity of the autonomic nervous system in focal infection patients. Based on this data, the production mechanism of tonsillar focal infection was speculated from the point of view of the autonomic nerve.

Summary. One hundred and thirty-four patients with idiopathic scoliosis were treated between 1973 and 1993 in our hospital, and 53 were followed for a minimum of 10 years in a retrospective study. Forty-five were female and 8 male with an average age of 32 years at follow up. Dwyer instrumentation was used in 17 and Zielke in 36. The curve was thoracic in 16, thoracolumbar in 27 and lumbar in 10. The average preoperative Cobb angle was 64°. The average angle at follow up was 21° with 62% of the average correction maintained (61% in the Dwyer and 65% in the Zielke). Most patients were satisfied subjectively and we recommend this type of operation.:

Seven psychiatric inpatients receiving carbamazepine 600 mg/day were coadministered clarithromycin 400 mg/day for 5 days to treat atypical pneumonia. Blood samples were taken after clarithromycin coadministration and at 1 and 4 weeks after its discontinuation. Plasma concentrations of carbamazepine and carhamazepine-10,11-epoxide were measured using high-performance liquid chromatography. During clarithromycin coadministration. four out of the seven patients developed moderate-to-severe toxic symptoms of carbamazepine. such as drowsiness, dizziness and ataxia, which resolved within 5 days after clarithromycin discontinuation. In these four patients, plasma carbamazepine concentrations alter clarithromycin coadministration were approximately twice as high as those after its discontinuation. In the seven patients, the mean plasma concentration of carbamazepine, but not of carbamazepine-10,11-epoxide, after elarithromycin coadministration was significantly (p < 0.01) higher than those at 1 and 4 weeks after its discontinuation. The present report suggests that clarithromycin coadministration induces increased plasma carbamazepine concentrations, which may result in carbamazepine toxicity. Therefore, care should be given to prescribing clarithromycin for patients receiving carbamazepine.

The relationship between the single oral dose pharmacokinetics of alprazolam and triazolam was studied in 10 healthy male volunteers. Each subject took single oral doses of alprazolam 0.8 mg and triazolam 0.5 mg with at least a 2 week interval between each dose. Blood samplings were performed up to 48 h after alprazolam dosing and up to 12 h after triazolam dosing. Plasma concentrations of both drugs were measured by high-performance liquid chromatography. The means ± standard deviation of the peak plasma concentration, the total area under the plasma concentration-time curve and the elimination half-life of alprazolam were 11.3 ± 3.1 ng/ml, 232.4 ± 59.2 ng/h/ml and 16.5 ± 4.6 h, respectively, and those of triazolam were 3.2 ± 1.0 ng/ml, 11.8 ± 5.2 ng/h/ml and 2.5 ± 1.1 h, respectively. There was no significant correlation between the two drugs in any pharmacokinetic parameters (r = 0.35, 0.25 and 0.50). The present study thus suggests that the single oral dose pharmacokinetics of alprazolam and triazolam and triazolam do not correlate well in individuals.

The carbohydrate-deficient glycoprotein (CDG) syndromes are a newly recognized group of inherited metabolic diseases. We report a Japanese brother and sister with a CDG syndrome. Both patients showed decreased activities of blood coagulation Factor XI and of the coagulation inhibitor protein C. In one of them there was also a somewhat decreased activity of Factor IX and of antithrombin III. Isoelectric focusing of antithrombin III revealed a decrease of negatively charged fractions and an increase of more cathodal bands. Furthermore, there was a discrepancy between activity and antigen level of Factor VIII and protein C. The patients had an incidental deficiency of factor XII. This is the first detailed report on blood coagulation systems in the CDG syndromes. These blood coagulation abnormalities may explain at least in part the thrombotic or haemorrhagic complications of the CDG syndromes.

Six healthy male subjects were randomly given nortriptyline (NT) (25 and 50 mg) and placebo in a double-blind, crossover study. An NT dose of 50 mg (but not 25 mg) clearly reduced saliva flow (P < 0.05) and was therefore used for comparison with the major and active metabolite of NT, E-10-hydroxynortriptyline (E-10-OH-NT). Equimolar doses of both compounds (and placebo) were randomly given to eight healthy male subjects in another double-blind, crossover study aimed to assess the reduction of saliva flow. NT significantly depressed saliva flow compared with both placebo (P < 0.01) and E-10-OH-NT (P < 0.05). By contrast, there was no difference between E-10-OH-NT and placebo. This study confirms previous indications that the anticholinergic effect of E-10-OH-NT is considerably less than that of the parent drug NT.Clinical Pharmacology and Therapeutics (1987) 41, 97–102; doi:10.1038/clpt.1987.16

Bromperidol is a close structural analog of haloperidol. The authors studied the effects of levomepromazine and thioridazine, which are frequently added to other neuroleptics as sedatives, on plasma concentrations of bromperidol and its reduced metabolite. The subjects were 26 inpatients with schizophrenia receiving bromperidol, 12 to 24 mg/day, for 1 to 19 weeks. In 10 cases, 50 mg levomepromazine per day and in nine cases, 50 mg thioridazine per day were coadministered for 1 week. In seven cases, both drugs were coadministered with ≥2-week intervals. Plasma concentrations of bromperidol and reduced bromperidol were measured by a high-performance liquid chromatographic method. Levomepromazine (n= 17) significantly (p< 0.001) increased plasma concentrations of bromperidol (7.3 ± 4.1 versus 10.2 ± 4.8 ng/ml) and reduced bromperidol (1.8 ± 1.4 versus 4.5 ± 3.3 ng/ml). Thioridazine (n= 16) did not significantly change plasma concentrations of bromperidol (9.1 ± 5.7 versus 8.6 ± 5.5 ng/ml), while those of reduced bromperidol could not be measured because of interfering peaks. The current study suggests that levomepromazine, but not thioridazine, increases plasma concentrations of bromperidol and reduced bromperidol by inhibiting the metabolism of these compounds.