Verification of the Usefulness of an Assessment and Risk Control Sheet that Promotes Management of Cancer Drug Therapy.

Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire. Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet's content and quality, respondents' satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale. Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet. Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.

Effects of lightwand (Trachlight) compared with direct laryngoscopy on circulatory responses to tracheal intubation.

We compared the effects of the lightwand technique on circulatory responses to tracheal intubation with those of direct-vision laryngoscopy. Forty adult patients received propofol and vecuronium, and their lungs were ventilated for 2 min via a mask with 5% sevoflurane in oxygen, after which the trachea was intubated orally using either the lightwand (Trachlight, n = 20) or the Macintosh laryngoscope (n = 20). Maximum mean arterial pressure changes did not differ between groups during (lightwand group, 25 (SD 21) mm Hg vs laryngoscopy group, 23 (19) mm Hg) and after (21 (24) mm Hg vs 21 (16) mm Hg) tracheal intubation. Maximum heart rate changes were similar for groups during (16 (14) beat min-1 vs 16 (15) beat min-1) and after (2 (11) beat min-1 vs 7 (19) beat min-1) tracheal intubation. There were no differences between the lightwand technique and direct-vision laryngoscopy in changes in mean arterial pressure and heart rate during and after tracheal intubation. We conclude that the effects of the lightwand technique on circulatory responses to tracheal intubation were similar to those of direct-vision laryngoscopy.

[Cesarean section in a morbidly obese parturient under epidural anesthesia].

A 26-yr-old morbidly obese parturient with a body mass index of 62 kg.m-2 underwent elective cesarean section for preeclampsia under epidural anesthesia. The distance between the skin and the epidural space was about 9 cm at the L3-4 interspace via mid approach. Epidural catheter was inserted 5 cm cephalad in the sitting position and a bolus of 17 ml of mepivacaine 1.5% was given in the supine position. The T5 level of analgesia was obtained 10 min later. Forty minutes after the start of the surgery, a female newborn weighing 3,206 g was delivered with an Apgar score 8 at 1 min and 9 at 5 min. Throughout the surgery, sufficient analgesia was obtained and any complications such as severe hypotension and respiratory depression did not develop. Postoperative pain was relieved sufficiently with a continuous epidural infusion of 0.25% bupivacaine at a rate of 0.5 ml.h-1 for two days. Both maternal and neonatal postpartum courses were uneventful. In conclusion, elective cesarean section in a morbidly obese parturient was successfully managed with epidural anesthesia. This indicates that an elective cesarean section under epidural anesthesia reduce the risk of perioperative complications in a morbidly obese parturient.

Spectral analysis of body weight, food and water consumption and spontaneous motor activity in male Sprague-Dawley rats.

Spectral analyses by maximum entropy method were performed on the time-series data of body weight, food and water consumption and spontaneous motor activity in Sprague-Dawley rats. These parameters were recorded by a monitoring system collected every 30 min for 10 days. All the parameters had circadian (24 +/- 4 hr) and ultradian (less than 20 hr) rhythms. From the logarithmic transformation of spectral frequencies and their power spectral densities, the characteristics of the spectrum of body weight showed 1/f fluctuation and those of food and water consumption were white noises. The spectrum of the spontaneous motor activity showed complex characters. The range of frequencies lower than 0.1 Hz showed white noise while the range of those higher than 0.1 Hz were 1/f or 1/f2 fluctuations, especially in the range between 0.5 and 1.0 Hz (1-2 hours cycle). The auto-correlation coefficients of body weight did not declined suggesting that 24 hours cycle is only periodic phenomenon in body weight changes. Though the auto-correlation coefficients of food and water consumption also did not declined, they had not enough auto-correlations. This was consistent with the appearance of white noise in spectral analyses. The auto-correlation coefficients of spontaneous motor activity declined remarkably, and this suggests that there are various periodic changes in spontaneous motor activity including one to two hours cycles. These results suggest that the possibility of further extension of research is expected by using rhythmicity. It is also indicated that the time of measurement of body weight must be taken into consideration in experiments because of the presence of the circadian rhythmic changes.

Correlation of body weight gain with food and water consumption and spontaneous activity in rats.

We developed a data acquisition system which measure the body weight, food and water consumption and spontaneous activity of a rat automatically. The correlation of body weight gain with other parameters obtained by this system were analysed. Each parameter showed rhythmic circadian changes. The multiple regression analysis with stepwise method brought the high coefficiency on the body weight gain with water consumption in the dark period, whereas only low correlation was observed among the body weight gain, food consumption and spontaneous activity in the light period. Since the body weight is affected by various factors, food and water consumption, spontaneous activity and/or other parameter(s) with body weight should be monitored simultaneously.

Automatic monitoring system for the measurement of body weight, food and water consumption and spontaneous activity of a mouse.

The simultaneous recording system for body weight, food and water consumption and behavior (spontaneous motor activity and drinking and feeding behavior) of a mouse was developed. The body weight and food consumption were measured by force transducers. Food and water consumption and drinking and feeding behavior were measured by an infrared luminous diode and a phototransistor. Spontaneous motor activity was measured by photosensors. The system control and data acquisition were performed by using a personal computer. Every parameter could be monitored with a desired time interval. All the data collected by this system revealed apparent circadian rhythm. In conclusion, this system would be a powerful tool for pharmacological and/or toxicological research.

Effects of intrastriatal injections of selective dopamine D-1 and D-2 agonists and antagonists on jaw movements of rats.

The effects of bilateral intrastriatal injections of the selective D-1 and D-2 antagonists, SCH23390 and sulpiride on apomorphine-induced jaw movements were studied in ketamine-anaesthetized rats after C1 spinal transection. A photo-transducer attached to the lower mandible automatically detected jaw movements. Apomorphine (0.2, 0.5 and 1.0 mg/kg i.v.) dose dependently increased jaw movements, an effect prevented by prior administration into the ventral striatum of either SCH23390 (0.1, 0.5 and 1 microgram) or sulpiride (125 ng). To be effective, SCH23390 had to be given less than 30 min before apomorphine whereas sulpiride had to be given earlier. Sulpiride injected into the dorsal striatum potentiated the effects of apomorphine, an action prevented by administering the sulpiride with SCH23390. Local application of the selective D-1 and D-2 agonists, SKF38393 (5 micrograms) and quinpirole (10 micrograms) into sites within the ventral striatum from which repeated jaw movements could be obtained by electrical stimulation, also evoked jaw movements; the effects of combining the two drugs were much greater than the effects of either drug alone.

Serum cortisol levels in pregnancy induced hypertension patients.

We measured the serum cortisol levels in 15 normal and 8 pregnancy induced hypertension (PIH) primigravidas. The normal pregnancy had a significant (p less than 0.05) higher cortisol level than that of PIH patient. Especially, 4 severe PIH patients had a significantly (p less than 0.05) lower cortisol level. The lower maternal cortisol level of PIH patients became more significant with the severity of clinical symptoms of PIH. After the onset of labor, the cortisol levels of PIH patients did not elevate compared with normal pregnancy. These data suggest that in the PIH patient the reactivity of the adrenal cortex to adrenocorticotropic hormone (ACTH) may be blunted or the cortisol production in the adrenal cortex may be decreased by the tissue circulation insufficiency due to PIH.

[Urinary kallikrein quantity and activity of normal pregnant women and toxemia patients in third trimester].

In this study, urinary kallikrein quantity and activity were measured by the kallikrein direct RIA and kininogenase activity with human low molecular weight kininogen in 32 non pregnant healthy women, 20 normal 3rd trimester pregnant women and 18 3rd trimester hypertension type toxemia patients. There was no significant difference in urinary kallikrein quantity between non pregnant women (n = 32, 64.0 +/- 6.3 micrograms/day, mean +/- SE) and normal pregnant women (n = 20, 68.1 +/- 10.1 micrograms/day). There was a significant difference (p less than 0.001) between non pregnant women and toxemia patients (n = 18, 22.5 +/- 3.3 micrograms/day). There was a significant difference (p less than 0.001) between toxemia patients and normal pregnant women. There was a significant difference (p less than 0.05) in urinary kallikrein activity between non pregnant women (n = 32, 496.2 +/- 57.2 micrograms kinin/day) and normal pregnant women (n = 20, 319.5 +/- 48.1 micrograms kinin/day). There was a significant difference (p less than 0.0001) between non pregnant women and toxemia patients (n = 18, 82.6 +/- 13.6 micrograms kinin/day). There was a significant difference (p less than 0.01) between normal pregnant women and toxemia patients. There were no correlation in both urinary kallikrein quantity and activity between severe type toxemia patients (systolic blood pressure greater than or equal to 160mmHg or diastolic blood pressure greater than or equal to 110mmHg) and mild type toxemia patients (160mmHg greater than systolic blood pressure greater than or equal to 140mmHg and 110mmHg greater than diastolic blood pressure greater than or equal to 90mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

[Urinary kallikrein quantity and activity in normal pregnant women in the third trimester].

In this study, urinary kallikrein quantity and activity were measured by the kallikrein direct RIA and kininogenase activity with human low molecular weight kininogen in 32 non pregnant healthy women and 20 normal 3rd trimester pregnant women. There was no significant difference in urinary kallikrein quantity between non pregnant healthy women (n=32, 64.0 +/- 6.3 micrograms/day, mean +/- S.E.) and normal pregnant women (n=20, 68.1 +/- 10.1 micrograms/day). There was a significant difference (p less than 0.05) in urinary kallikrein activity between non pregnant healthy women (n=32, 496.2 +/- 57.2 micrograms kinin/day) and normal pregnant women (n=20, 319.5 +/- 48.1 micrograms kinin/day). The reason for no significant difference in the urinary kallikrein quantity may be that neither non pregnant women nor normal pregnant women have renal damage. And, one of the reasons for significant low urinary kallikrein activity in normal pregnant women may be that the sensitivity of blood vessels to angiotensin II in normal pregnancy is less than in non pregnancy.

[Changes in active and inactive renin throughout pregnancy].

There have been few reports about the changes in active and inactive renin throughout pregnancy. In this study, the changes in total and active renin concentrations during pregnancy were measured and their physiological roles are discussed. The present method employed radioimmunoassay of angiotensin I generated during incubation of plasma in an excess of sheep renin substrate. For determination of total renin concentration, inactive renin was activated by exposing plasma to trypsin. Concurrent with the progress of pregnancy, active renin increased gradually and reached its maximum during the third trimester, then fell sharply to first trimester levels by the fifth day of the puerperium. Total renin levels during pregnancy were about twice as high as puerperal levels. We found no difference in total renin levels between trimesters but a marked difference in individual women was observed. In the first trimester of pregnancy, inactive renin in plasma rapidly increased (to 4 times the average concentration in plasma of puerperal women), then declined slowly throughout pregnancy, and fell quickly after delivery. These results suggest that in pregnancy total renin levels are consistently elevated, 67% of which is inactive renin in the first trimester and active renin increases gradually with advancing gestation. After delivery, both active and inactive renin fall to normal levels within a few days.

[Amniotic fluid 3,3',5'-triiodothyronine (reverse T3)].

RT3(3,3',5'-triiodothyronine) levels in amniotic fluid and T4(thyroxine), T3(triiodothyronine), rT3 and TSH(thyroid-stimulating hormone) levels in maternal and cord serum were determined simultaneously by RIA. We also determined the activities of the monodeiodination of thyroxine to rT3 in placentas. Amniotic fluid rT3 and cord serum rT3 levels decreased, but T4, T3 and TSH levels increased with advancing gestational age. The activities of the monodeiodination in placentas decreased rapidly from midgestation, preterm to term. In maternal hyperthyroidism, amniotic fluid rT3 levels were markedly elevated. Moreover, there were significant positive correlations between amniotic fluid rT3 and maternal serum rT3 (r = 0.756, p less than 0.001, n = 26) and T4(r = 0.509, p less than 0.01, n = 26) in the normal 3rd trimester. We found significant correlations between amniotic fluid rT3 and fetal thyroid function as well as the activity of the monodeiodination in placenta after 17 weeks' gestation. But we couldn't find any such correlations in the 3rd trimester. These data suggest that the amniotic fluid rT3 in the 3rd trimester was affected by maternal thyroid function as well as fetal thyroid function and the activity of the monodeiodination in placenta.

[Studies on the symptoms of EPH-gestosis patients one month after delivery].

We investigated 1805 puerperants, after the twenty-fourth-week of pregnancy, who delivered from January 1st, 1981 till December 31st, 1982 in our hospital. 271 pregnancies were diagnosed as EPH-gestosis according to the new diagnostic standard in Japan (prevalence 15%). The severer the type of EPH-gestosis that had been diagnosed during pregnancy, the more symptoms they showed and the more often complications were diagnosed one month after delivery. In mild type as well as in severe type EPH-gestosis patients, if they had more than one symptom one month after delivery, they were more frequently diagnosed as having complications in pregnancy. In addition, those who had one or more symptoms one month after delivery often had shown symptoms of EPH-gestosis earlier in pregnancy. There were no significant correlations between the symptoms one month after delivery and the age of the mother, or between these symptoms and the time of delivery. Furthermore there was no significant correlation between these symptoms and the frequency of neonatal asphyxia, or the frequency of intrauterine death. These data suggest that symptoms one month after delivery of EPH-gestosis have some relation to complications in pregnancy.

Effects of caffeine ingestion during pregnancy.

We studied the effects of caffeine ingestion during pregnancy. A total number of 9,921 healthy pregnant women with a gestational age after 24 weeks were subjected to the study. The women who drank more than 5 cups of coffee per day had a high incidence of impending abortion, premature labor, and fetuses small for gestational age. The heavy coffee drinkers among the pregnant women had high rates of spontaneous abortion, chromosomal abnormality and congenital multi-anomalies. However, we would like to stress that the multiple socioeconomic variables might be more important than any direct effect of caffeine.

Simultaneous and serial measurement of serum levels of human placental lactogen, beta-human chorionic gonadotropin and unconjugated estriol levels in pregnant women.

Serum levels of human placental lactogen (hPL), beta-human chorionic gonadotropin (beta-hCG) and unconjugated estriol (E3) were measured simultaneously and serially in regular menstrual late pregnant women (155 samples) by radioimmunoassay. The peak of beta-hCG level was shown at 37 weeks' gestation. After that, there was a moderate decline of the beta-hCG level. Serum hPL showed the peak at 30 weeks' gestation. The level of unconjugated E3 rose toward 41 weeks' gestation. In the 155 samples, there were significant positive correlations among these hormone levels. Also, there were highly significant positive correlations between placental weight and these three hormone levels. Only unconjugated E3 level which was obtained within a week before the onset of labor had a significant positive correlation with birth weight. These data suggest that even in late pregnancy, maternal beta-hCG makes a peak and may change parallel with hPL and unconjugated E3. Only the unconjugated E3 level may be affected by fetal growth.

Chemical synthesis of the 5'-terminal part bearing cap structure of messenger RNA of cytoplasmic polyhedrosis virus (CPV): m7G5'pppAmpG and m7G5'pppAmpGpU.

The 5'-terminal structures of mRNA bearing the so-called 'cap' from cytoplasmic polyhedrosis virus (CPV), m7G5' pppAmpG and m7G5' pppAmpGpU, were first chemically synthesized. S,S-Di(4-methoxyphenyl) N6-benzoyl-2'-O-methyladenosine 5'-phosphorodithioate ((ArS) 2pAbmz) was prepared by phosphorylation of the 5'-hydroxyl group of N6-benzoyl-2'-O-methyladenosine with S,S-di(4-methoxyphenyl) phosphorodithioate by TPS. By the triester approach using (ArS) 2pAbmz as starting material, the protected dinucleotide and trinucleotide bearing 5'-phosphate group were synthesized. The protective groups of the dinucleotide and trinucleotide were removed to obtain pAmpG and pAmpGpU, respectively. By the reaction of a capping agent ((PhS) ppm7G) with pAmpG and pAmpGpU in the presence of silver nitrate or iodine. The 5'-terminal structure of the messenger RNA strand of CPV which was labelled isotopically, was confirmed completely as m7G5' pppAmGpU by cochromatography with the materials chemically synthesized here.

Retrograde time-scale analysis of human placental lactogen, beta human chorionic gonadotropin, and unconjugated estriol levels in human maternal serum from the onset of spontaneous labor.

We analyzed on a retrograde time scale which calculated in maternal serum, from the onset of spontaneous labor, human placental lactogen (hPL), beta human chorionic gonadotropin (beta-hCG), unconjugated estriol (E3) levels, and the ratios among these hormones in the normal late pregnancy. Maternal serum hPL, beta-hCG, and unconjugated E3 levels were measured simultaneously and serially in regular menstrual sera from 27 women in late pregnancy (total 155 samples) by radioimmunoassay. The peak level of hPL was found at 2 weeks before labor, and the peak of beta-hCG was found during 2-4 weeks before the onset of spontaneous labor. On the other hand, the mean level of E3 rose slightly with advancing gestational age. The hormonal ratios of hPL to E3 and beta-hCG to E3 decreased gradually toward the onset of labor, but the ratios of hPL to beta-hCG did not change. From these data, it is possible to conclude that the onset of spontaneous labor can be predicted by measuring the levels of hPL and unconjugated E3 in maternal peripheral serum.

Clinical background of preeclampsia in Japanese women.

In Japan, the maternal mortality rate from preeclampsia is still high. In this study, we analyzed the clinical background of 70(1.5%) cases of severe preeclampsia in 4,633 deliveries in our clinic. The main family history was hypertension (34.2%). The medical complication of this pregnancy were nephritis (11.4%), hypertension (5.7%) and diabetes mellitus (4.3%). In previous obstetrical complication, preeclampsia was found very high frequency (44.4%). In this pregnancy, the cesarean section was done for 15 (21.4%) cases. There was a significant high frequency of low birth weight infant in preeclampsia (2,400 +/- 925 gr, mean +/- S.D.). The stillbirth was found in 12 (17.1%) cases. The perinatal mortality rate was 169/1,000 deliveries, this was a significantly higher than total rate (15/1,000 deliveries). These data suggest that it is important to control medical complications before to be pregnant to prevent preeclampsia.