Unequal Day-Night Terbutaline I.V. Dosing in Acute Severe Asthma: Effect on Nocturnal Bronchial Patency, Heart Rate, and Arterial Pressure

Our study investigated the differential effects of continuous or unequal day-night terbutaline dosing on circadian bronchial patency, heart rate, and arterial pressure in severe acute asthma. Forty-five hospitalized asthmatic patients (19 women and 26 men, mean age 45.4 years, mean weight 63.5 kg) were included in this multicenter study. Three groups of patients (corresponding to three dosing schedules) were randomized; the three groups were comparable, since no statistically significant difference was detected in the age, weight, or peak expiratory flow values at the beginning of the study. In order to reach immediately the concentrations of terbutaline corresponding to the desired unequal day-night concentrations, a theoretical pharmacokinetic simulation was done to predict the outcome in terms of the plasma concentrations after the three dosing regimens; the results of this simulation allowed us to calculate the initial bolus dose to be given over 5 min to groups A, B, and C, i.e., 1.47, 2.94, and 4.41 Mg/kg, respectively. This bolus was given to all patients at 0700 h, the beginning of the study. The patients were randomly divided into three groups (A, B, C) receiving one of these treatments: 0.0111 mg/kg of terbutaline i.v. from 0700 to 1900 h at a constant rate delivered by an electrical pump and 0.0222 mg/kg of terbutaline i.v. from 1900 to 0700 h at a constant rate (A) (one third the total daily dose during the day and the remaining two thirds at night), 0.0166 mg/kg of terbutaline i.v. from 0700 to 1900 h at a constant rate and 0.0166 mg/kg of terbutaline i.v. from 1900 to 0700 h at a constant rate (B) (one half the total daily dose during the day and the remaining one half at night), or 0.0222 mg/kg of terbutaline i.v. from 0700 to 1900 h at a constant rate and 0.0111 mg/kg of terbutaline i.v. from 1900 to 0700 h at a constant rate (C) (two thirds the total daily dose during the day and the remaining one third at night). Since acute severe asthma could not be treated without steroids, a 40 mg dose of SoluMedrol was injected into all patients at 0700. Peak expiratory flow rate, heart rate, systolic arterial pressure, and possible side effects were recorded at different times during the 24-h scale: 0700, 1000, 1300, 1600, 1900, 2300, 0300, and 0700 h. Our results have shown a significant therapeutic effect of terbutaline i.v. dosing in severe acute asthma whatever the unequal daynight dosing, but did not demonstrate the efficacy of one of the three dosing schedules over the others.     

Unequal Day-Night Terbutaline I.V. Dosing in Acute Severe Asthma: Effect on Nocturnal Bronchial Patency,Heart Rate,and Arterial Pressure

Our study investigated the differential effects of continuous or unequal day-night terbutaline dosing on circadian bronchial patency, heart rate, and arterial pressure in severe acute asthma. Forty-five hospitalized asthmatic patients (19 women and 26 men, mean age 45.4 years, mean weight 63.5 kg) were included in this multicenter study. Three groups of patients (corresponding to three dosing schedules) were randomized; the three groups were comparable, since no statistically significant difference was detected in the age, weight, or peak expiratory flow values at the beginning of the study. In order to reach immediately the concentrations of terbutaline corresponding to the desired unequal day-night concentrations, a theoretical pharmacokinetic simulation was done to predict the outcome in terms of the plasma concentrations after the three dosing regimens; the results of this simulation allowed us to calculate the initial bolus dose to be given over 5 min to groups A, B, and C, i.e., 1.47, 2.94, and 4.41 Mg/kg, respectively. This bolus was given to all patients at 0700 h, the beginning of the study. The patients were randomly divided into three groups (A, B, C) receiving one of these treatments: 0.0111 mg/kg of terbutaline i.v. from 0700 to 1900 h at a constant rate delivered by an electrical pump and 0.0222 mg/kg of terbutaline i.v. from 1900 to 0700 h at a constant rate (A) (one third the total daily dose during the day and the remaining two thirds at night), 0.0166 mg/kg of terbutaline i.v. from 0700 to 1900 h at a constant rate and 0.0166 mg/kg of terbutaline i.v. from 1900 to 0700 h at a constant rate (B) (one half the total daily dose during the day and the remaining one half at night), or 0.0222 mg/kg of terbutaline i.v. from 0700 to 1900 h at a constant rate and 0.0111 mg/kg of terbutaline i.v. from 1900 to 0700 h at a constant rate (C) (two thirds the total daily dose during the day and the remaining one third at night). Since acute severe asthma could not be treated without steroids, a 40 mg dose of SoluMedrol was injected into all patients at 0700. Peak expiratory flow rate, heart rate, systolic arterial pressure, and possible side effects were recorded at different times during the 24-h scale: 0700, 1000, 1300, 1600, 1900, 2300, 0300, and 0700 h. Our results have shown a significant therapeutic effect of terbutaline i.v. dosing in severe acute asthma whatever the unequal daynight dosing, but did not demonstrate the efficacy of one of the three dosing schedules over the others.     

Influence of dosage and dietary sodium on the first-dose effects of prazosin.

The effects of the first dose of prazosin were assessed in hypertensive patients on different sodium intakes. Patients received 250, 100, or 30 mmol sodium per 24 hours for a week before taking 2 mg or 0-5 mg prazosin. The acute effects of prazosin on blood pressure and pulse rate were milder with a high sodium intake. On the 100-mmol intake symptomatic postural hypotension occurred in five out of seven patients given 2 mg prazosin and in two out of four given a 0-5-mg dose, whereas those taking 2 mg or 0-5 mg and a 250-mmol sodium intake experienced no postural symptoms. These findings indicate that particular care should be taken in starting prazosin treatment in sodium-depleted patients.     

Effects and mechanism of action of terbutaline on diaphragmatic contractility and fatigue

We studied the effects of intravenously administered terbutaline on diaphragmatic force and fatigue during electrical stimulation of the diaphragm in 17 anesthetized dogs. The diaphragm was stimulated indirectly through the phrenic nerves with electrodes placed around the fifth roots and directly with electrodes surgically implanted in the abdominal side of each hemidiaphragm. Transdiaphragmatic pressure (Pdi) during direct or indirect supramaximal 2-s stimulation applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. In seven dogs the administration of terbutaline (0.5 mg) had no effect on Pdi at any stimulation frequency applied directly or indirectly. The effect of terbutaline (0.5 mg) on diaphragmatic fatigue was then tested in 10 other dogs. Diaphragmatic fatigue was produced by continuous 20-Hz electrical supramaxial stimulation of the phrenic nerves during 30 min. At the end of the fatigue procedure Pdi decreased by 50 +/- 5 and 30 +/- 8% of control values at 10 and 100 Hz, respectively, for either direct or indirect stimulation. The decrease in Pdi for low frequencies of stimulation (10 and 20 Hz) lasted 100 +/- 18 min, whereas it lasted only 40 +/- 10 min for the high frequencies (50 and 100 Hz). When terbutaline (0.5 mg) was administered after the fatiguing procedure, Pdi increased within 15 min by 20 +/- 4% at 10 Hz and by 12 +/- 3% at 100 Hz for either direct or indirect stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of bioactive luteinizing hormone and testosterone by a progesterone antagonist ZK 98.734 in adult male common marmosets, Callithrix jacchus

The effects of a progesterone antagonist ZK 98.734 on release of bioactive luteinizing hormone (LH) and testosterone were studied in adult male common marmosets by using the following experimental protocols: (1) the blocking of the nocturnal rise in testosterone levels by ZK 98.734, (2) the pharmacodynamic effects of ZK 98.734 on testosterone and LH levels, (3) the reversal of ZK 98.734-induced decrease in testosterone by treatment with human chorionic gonadotropin (hCG), and (4) the blocking of estradiol-induced positive feedback release of LH by ZK 98.734. Sixteen adult male common marmosets were used for different experiments after resting them for at least 4 wk between experiments. Testosterone and bioactive LH levels were measured by specific radioimmunoassay and in vitro bioassay methods, respectively. Treatment (i.m.) of male common marmosets (n = 6/group) with ZK 98.734 (1 mg or 5 mg/day) at 1700 h for 3 consecutive days significantly (p less than 0.05) suppressed the nocturnal (2200 h) rise in testosterone levels. The effects of the two doses were not dose-related; however, the decrease on the first day of treatment was more pronounced with the 5-mg dose than with the 1-mg dose. Diurnal rhythms were restored during the post-treatment period. Similarly, treatment with ZK 98.734 (5 mg, n = 8/group) at 1000 h caused a decrease in testosterone and LH levels. The levels were significantly (p less than 0.05) lower at 3 and 6 h after treatment compared to pretreatment levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantification of terbutaline in urine by enzyme-linked immunosorbent assay and capillary electrophoresis after oral and inhaled administrations

The International Olympic Committee and World AntiDoping Agency restricts the use of beta2-agonists and only the inhaled administration of terbutaline, salbutamol, formoterol and salmeterol is permitted for therapeutic reasons. The aim of this study was to develop a test for the quantitation of terbutaline in urine and evaluate different parameters to distinguish between oral and inhaled administration of the drug. Urine samples were collected from asthmatic and non-asthmatic recreational swimmers who had received repeated doses of oral (3x2.5 mg plus 1x5 mg during 24 h) and inhaled (12x0.5 mg in 24 h with half of it being in the last 4 h) racemic terbutaline, and single oral (5 mg) or single inhaled doses (1 mg). Total terbutaline concentrations (free+conjugated) were determined by enzyme-linked immunosorbent assay. Results showed that after oral administrations urinary terbutaline concentrations were higher than those detected after inhalation. For confirmation purposes, a chiral capillary electrophoretic procedure was established and validated. A solid-phase extraction with Bond-Elut Certify cartridges was undertaken, separation performed using a 50 mM phosphate buffer (pH 2.5) containing 10 mM of (2-hydroxypropyl)-beta-cyclodextrin as running buffer and diode-array UV detection set at 204 nm. The proposed procedure is rapid, selective and sensitive allowing quantitation of free terbutaline enantiomers in urine. No statistical differences were found between total free terbutaline concentrations [S-(+)+R-(-)] in urine collected after oral and inhaled administrations of the drug. After oral doses enantiomeric [S-(+)]/[R-(-)] ratios lower than those obtained after inhalation were observed probably due to an enantioselective metabolism that take place in the intestine, but differences between both routes of administration were not statistically significant. Although different trends were observed after oral and inhaled doses in total terbutaline, total free terbutaline concentrations and in ratios between its enantiomers, differences observed were not sufficiently significant to establish cut-off values to clearly distinguish between both routes of administration.     

The effects of 5-bromo-2-thienyl-ethyl-ketone thiosenicarbazone on ovarian cyclicity and ovulation in the rat.

Pseudopregnant and cyclic rats were injected for 5 to 26 days with daily doses of 5 and/or 3 mg of 5-bromo-2-thienyl-ethyl-ketone thiosemicarbazone (70026) starting on Day 0 (the day of oestrus). The vaginal smear cytology, record of ovulation and ability to breed and conceive were compared with the results for corn oil-injected controls. Both doses of 70026 were found to cause a reappearance of pro-oestrous and/or oestrous vaginal smears within 4 to 6 days in the pseudopregnant rats, but ovulations did not occur. The 5-mg dose of 70026 inhibited ovulation and interrupted the oestrous cycle in cyclic rats, even though the daily 3-mg dose seemed to have little effect on ovulation, ovarian cyclicity, breeding or conception. In spite of the absence of an ovulation accompanying the induced pro-oestrous and/or oestrous vaginal smears in the pseudopregnant rats, the pattern of the vaginal smears suggested the occurrence of a 'delayed pseudopregnancy' in most of the pseudopregnant rats treated daily with 3 mg, but in few of those treated with 5 mg, 70026.     

小剂量米非司酮用于紧急避孕200例的临床观察

目的 比较米非司酮25mg和10mg用于紧急避孕的有效性、副反应、对月经周期的影响。方法 采用双盲随机比较试验方法,共接纳合格妇女200例1次无防护性交72小时内随机进入第一组和第二组,第一组一次性口服米非司酮25mg和安慰剂1片;第二组一次性口服米非司酮10mg。随访至月经来潮,了解避孕效果、副反应、月经周期的变化。结果两组分别有2例和1例妊娠,失败率分别为2％和1％,避孕有效率分别为82.21％和90.18％,p>0.05,无统计学意义;副反应很轻微,发生率很低;服药时间对月经周期有影响;两种药量对月经周期没影响。结论 小剂量米非司酮25mg和10mg用于紧急避孕同样有效,并且效果良好。     

Follicular deviation and acquisition of ovulatory capacity in bovine follicles.

Selection of dominant follicles in cattle is associated with a deviation in growth rate between the dominant and largest subordinate follicle of a wave (diameter deviation). To determine whether acquisition of ovulatory capacity is temporally associated with diameter deviation, cows were challenged with purified LH at known times after a GnRH-induced LH surge (experiment 1) or at known follicular diameters (experiments 2 and 3). A 4-mg dose of LH induced ovulation in all cows when the largest follicle was > or =12 mm (16 of 16), in 17% (1 of 6) when it was 11 mm, and no ovulation when it was < or =10 mm (0 of 19). To determine the effect of LH dose on ovulatory capacity, follicular dynamics were monitored every 12 h, and cows received either 4 or 24 mg of LH when the largest follicle first achieved 10 mm in diameter (experiment 2). The proportion of cows ovulating was greater (P < 0.05) for the 24-mg (9 of 13; 69.2%) compared with the 4-mg (1 of 13; 7.7%) LH dose. To determine the effect of a higher LH dose on follicles near diameter deviation, follicular dynamics were monitored every 8 h, and cows received 40 mg of LH when the largest follicle first achieved 7.0, 8.5, or 10.0 mm (experiment 3). No cows with a follicle of 7 mm (0 of 9) or 8.5 mm (0 of 9) ovulated, compared with 80% (8 of 10) of cows with 10-mm follicles. Thus, follicles acquired ovulatory capacity at about 10 mm, corresponding to about 1 day after the start of follicular deviation, but they required a greater LH dose to induce ovulation compared with larger follicles. We speculate that acquisition of ovulatory capacity may involve an increased expression of LH receptors on granulosa cells of the dominant follicle and that this change may also be important for further growth of the dominant follicle.     

The physiological effects of caffeine in women during treadmill walking

Although the effects of caffeine ingestion on athletic performance in men have been studied extensively, there is limited previous research examining caffeine's effects on women of average fitness levels participating in common modes of physical activity. The purpose of this study was to determine the effect of 2 levels of caffeine dosage on the metabolic and cardiorespiratory responses to treadmill walking in women. Subjects were 20 women (19-28 years of age) of average fitness, not habituated to caffeine. Each subject was assigned randomly a 3-mg x kg(-1) dose of caffeine, 6-mg x kg(-1) dose of caffeine, and placebo for 3 trials of moderate steady-state treadmill walking at 94 m x min(-1) (3.5 mph). Steady-state rating of perceived exertion (RPE), heart rate (HR), respiratory exchange ratio (RER), weight-relative VO2, %VO2max reserve (%VO2R), and rate of energy expenditure (REE) were measured during each trial. Repeated measures analysis of variance revealed that a 6-mg x kg(-1), but not a 3-mg x kg(-1) dose of caffeine increased VO2 (p = 0.04), REE (p = 0.03), and %VO2R (p = 0.03), when compared to the placebo. Caffeine had no effect on RPE, HR, or RER. No significant differences were observed between the placebo trials and the 3-mg x kg(-1) dose trials. Although a 6-mg x kg(-1) dose of caffeine significantly increased REE during exercise, the observed increase (approximately 0.23 kcal x min(-1)) would not noticeably affect weight loss. Because caffeine had no effect on RPE, it would not be prudent for a trainer to recommend caffeine in order to increase a woman's energy expenditure or to decrease perception of effort during mild exercise. These data also demonstrate that caffeine intake should not interfere with monitoring walking intensity by tracking exercise heart rate in women.     

Ameltolide. I: Developmental toxicology studies of a novel anticonvulsant

Ameltolide, a novel anticonvulsant agent, has been shown in animal models to be effective in controlling seizures. The developmental toxicity of ameltolide was evaluated in two species. Naturally mated rats and rabbits were dosed once daily by gavage on gestation days (GD) 6-17 and 6-18, respectively. Rats were given doses of 0, 10, 25, or 50 mg/kg; rabbits were given 0, 25, 50, or 100 mg/kg. Laparotomy was performed on rats on GD 20 and on rabbits on GD 28. In rats, maternal toxicity was indicated at the 25- and 50-mg/kg dose levels by depressed body weight gain. Fetal body weight was depressed at the 50-mg/kg dose level. Fetal viability and morphology were not affected. The no-observed effect levels (NOEL) for adult and developmental toxicity in the rat were 10 and 25 mg/kg, respectively. In rabbits, maternal toxicity was indicated by a net loss in body weight at the 50- and 100-mg/kg dose levels. Fetal viability and body weight were depressed at the 100 mg/kg dose level. Shortened digits occurred on the right forepaw of one fetus at the 50-mg/kg dose level (in conjunction with severe maternal toxicity) and on the hindpaws of two fetuses from separate litters at the 100-mg/kg dose level. Incomplete ossification of the phalanges occurred on the forepaws of nine fetuses from four litters at the 100-mg/kg dose level. Ameltolide was weakly teratogenic in the rabbit. The NOEL for adult and developmental toxicity in the rabbit was 25 mg/kg.     

Single intraamniotic injections of prostaglandin F-2-alpha as an abortifacient agent: size of effective dose and effect of parity

This report discusses the authors' experience with intraamniotic administration of single doses of the prostaglandin PGF2alpha as an abortifacient agent. 98 healthy women between the 12th and 26th week of pregnancy admitted to the Clinical Research Unit of the North Carolina Memorial Hospital were given a single intraamniotic dose of PGF2a administered through an indwelling polyethelene catheter inserted either transabdominally or transvaginally. The drug was given as Tham salt with the first 5 mg of any dose being given at the rate of 1 mg/minute for 5 minutes, followed by more rapid administration of the balance of the dose. Abortion which did not occur within 48 hours was considered a failure. Each patient received 1 of the following dosages: 25, 40, 50, and 75. 9 (64%) of 14 patients given 25 mg PGF2a aborted within the 48-hour period. The percentages of abortion in the doses 40, 50, and 75 mg were 88.9% (9 patients), 96.7% (60 patients) and 93.3% (15 patients) respectively. As these figures were almost similar, the 84 patients were combined as a single group (84 patients) relative to the injection-abortion time, effect of parity, and stage of gestation at which the abortion was carried out. Half of the patients in this combined group aborted in approximately 21 hours; more than 90% at the end of 32 hours; and 95% at the end of the 48 hours post-injection. For comparison, the cumulative abortion curve of 552 patients who had intraamniotic saline for abortion showed that 50% of the women aborted within 31 hours, 84% within 48 hours, and 97% within 72 hours. Prostaglandin induced abortions thus are shown to reach the 50% level 10 hours before the saline patients, and the 90% level about 21 hours before the saline patients. Significant side effects (presented elsewhere) were observed in all groups, with the incidence increasing at higher dosages. Mean induction-abortion time for nulliparas at all dosages was 17.4 hours; for multiparas, 20.4 hours. There was no clear relationship between gestational age and parity. The study shows that the effective dose for inducing abortion with PGF2a lies within the 40 to 50 mg dose range.     

Comparative Study to Determine the Optimal Melatonin Dosage form for the Alleviation of Jet Lag

To compare the impact of various dosage forms of melatonin and placebo on jet lag symptoms, 320 volunteers who had flights over 6 to 8 time zones were recruited for a double-blind, randomized, placebo-controlled study. The volunteers received either melatonin 0.5-mg fast-release (FR) formulation, melatonin 5-mg FR formulation, melatonin 2-mg controlled-release (CR) formulation, or placebo. The study medication was taken once daily at bedtime during 4 days after an eastward flight. The volunteers completed the Profile of Mood States (POMS), sleep log, and symptoms questionnaires once daily and the Karolinska Sleepiness Scale (KSS) three times daily prior to departure and during the 4 days of medication intake postflight. A total of 234 (73.1%) participants were compliant and completed the study. The FR melatonin formulations were more effective than the slow-release formulation. The 5-mg FR formulation significantly improved the self-rated sleep quality (p <. 05), shortened sleep latency (p <. 05), and reduced fatigue and daytime sleepiness (p <. 05) after intercontinental flight. The lower physiological dose of 0.5 mg was almost as effective as the pharmacological dose of 5.0 mg. Only the hypnotic properties of melatonin, sleep quality and sleep latency, were significantly greater with the 5.0-mg dose. (Chronobiology International, 15(6), 655-666, 1998)     

Treatment of nocturnal asthma: the role of sustained-release theophylline and oral beta-2-mimetics

In two double-blind, multiple-dose cross-over studies the therapeutic effects of SR theophylline preparations given once each night (mean 11.2 mg/kg per day) versus twice daily in equal doses (mean 10.3 mg/kg per day) (study I) and SR-terbutaline in equal doses (mean 0.25 mg/kg per day) versus SR theophylline in unequally divided daily doses (mean 5.3 mg/kg morning dose, 10.6 mg/kg evening dose) study II) were compared in 19 patients with nocturnal asthma. At the end of each treatment period drug serum concentrations and PEFR were measured every 2 hr over a 24-hr period. With the twice-daily, equally divided regimen, serum theophylline concentrations were lower at night than during the day (mean 9.4 +/- 0.9 versus 11.3 +/- 1.0 mg/l). With the single evening administration, serum theophylline concentrations were considerably higher at night (Cmax 16.3 +/- 1.4 mg/l) and the circadian variation of PEFR was significantly reduced. PEFR was higher during night and early morning (283 +/- 14 versus 217 +/- 11 l/min, P less than 0.005). During daytime in study II, PEFR values were slightly higher with theophylline than terbutaline. There was no significant difference in peak flow between either treatment during the night and early morning. However, additional use of inhaled beta-2-mimetics because of asthmatic attacks occurred more often during terbutaline (79 times in 8/10 patients) than theophylline treatment (29 times in 5/10 patients). Symptom scores, number of attacks and side-effects clearly favor the theophylline regimen. We conclude that for patients with nocturnal asthma a once-nightly dose of SR theophylline can be sufficient for stabilization of the airways.     

长春瑞滨联合顺铂治疗三阴性乳腺癌的临床观察

目的：观察长春瑞滨联合顺铂治疗三阴性乳腺癌临床疗效。方法：选择我院2007年5月～2011年8月期间收治经细胞学或病理学诊断并确诊TNBC患者85例,术后免疫学化疗证实ER、PR、HER-2均呈阴性,随机分组入试,长春瑞滨联合顺铂（NP组）45例,第1、8天予以静脉滴注长春瑞滨25 mg/m2,前3天辅以顺铂25 mg/m2滴注,21天为1个周期,治疗2个周期后观察临床疗效;紫杉醇联合顺铂（TP组）40例,第1天小剂量滴注紫杉醇135～175 mg/m2,,顺铂用量、用法及用药周期同上所示。对比观察病症缓释情况和毒副作用。结果：NP组总有效率（RR）48.89%,控制率（PD）为77.78%,TP组总有效率（RR）为37.50%,控制率（PD）55.56%,两组间有效率及控制率比较差异有统计学意义（P〈0.05）。两组常见毒副反应为骨髓抑制、消化道和胃肠道反应。NP组消化道反应和骨髓抑制微重于TP组,两组间比较有显著差异（P〈0.05）。结论：长春瑞滨联合顺铂（NP）新辅助化疗方案针对三阴性乳腺癌患者耐受性好、毒副反应较小、有效率高、不良反应可逆等优势,可作为临床推广药物。     

Safety,biodistribution, pharmacokinetics,and immunogenicity of <Superscript>99m</Superscript>Tc-labeled humanized monoclonal antibody BIWA 4 (bivatuzumab) in patients with squamous cell carcinoma of the head and neck

Previous studies have shown the potential of murine and chimeric anti-CD44v6 monoclonal antibodies (MAbs) for radioimmunotherapy (RIT) of head and neck squamous cell carcinoma (HNSCC). A limitation of these MAbs, however, appeared to be their immunogenicity. Therefore, humanized monoclonal antibody BIWA 4 (bivatuzumab), with an intermediate affinity for CD44v6, was recently selected. As a prelude to RIT, we evaluated the safety, tumor-targeting potential, pharmacokinetics, and immunogenicity of technetium-99m-labeled BIWA 4 in patients undergoing operations for primary HNSCC in this study. Ten patients were treated at BIWA 4 dose levels of 25 mg (n=3), 50 mg (n=4), and 100 mg (n=3). Patients received 2 mg of 750 MBq 99mTc-BIWA 4, together with 23-, 48-, and 98-mg unlabeled BIWA 4, respectively. Radioimmunoscintigraphy (RIS) was performed within 1 h and after 21 h, and patients underwent surgery at 48 h after injection. Biodistribution of 99mTc-BIWA 4 was evaluated by radioactivity measurements in blood, bone marrow, and in biopsies of a surgical specimen obtained 48 h after injection. BIWA 4 concentration in blood was assessed by ELISA and high performance liquid chromatography and related to soluble CD44v6 levels in serum samples. The development of human anti-human antibody (HAHA) responses was determined. Administration of 99mTc-BIWA 4 was well tolerated by all patients and no HAHA responses were observed. A mean t1/2 in plasma of 54.8 +/- 11.5 h, 76.1 +/- 21.8 h, and 68.5 +/- 21.2 h was found for the 25-, 50-, and 100-mg dose group, respectively. No complex formation of BIWA 4 with soluble CD44v6 in blood was observed. RIS showed targeting of primary tumors and lymph node metastases in 8 of 10 and 1 of 5 patients, respectively. The highest tumor uptake and tumor to nontumor ratios were observed for the 50-mg dose group. Tumor uptake was 12.9 +/- 5.9, 26.2 +/- 3.1, and 15.4 +/- 1.9% of the injected dose (ID)/kg for the 25-, 50-, and 100-mg dose group, respectively, while the tumor to bone marrow ratios for these groups were 1.7 +/- 0.5, 3.2 +/- 1.1, and 2.0 +/- 0.6, respectively. CONCLUSION: 99mTc-BIWA 4 can safely be administered to patients with HNSCC, with absence of detectable HAHA responses. The 50-mg dose level showed the highest tumor uptake and tumor to nontumor ratios. These findings support the use of BIWA 4 for RIT studies in patients with HNSCC.     

Induction of abortion by intra- and extra-amniotic prostaglandin F2 administration

PGF2 alpha was administered intrauterine in 115 patients during the 11th to 20th week of pregnancy for abortion induction. An intra-amniotic method was used in 61 cases, an extra-amniotic one in 54 cases. Average total dose administered was 35.1 (range 5 to 65 mg) in the amniotic group and 6358 mcg (range 1500 to 14000 mcg) in the extra-amniotic group. The intra-amniotic group had an abortion rate of 92% and a 74% rate of side effects, mainly gastrointestinal irritation. Corresponding figures for the extra-amniotic group were 72% and 54% respectively. In the extra-amniotic group, doses of 4750 mcg or more increased the abortion rate up to 80% and side effects up to 64%. There were no serious complications. The intra-amniotic approach of prostaglandin induction is suitable for second trimester therapeutic abortions. The extra-amniotic approach is useful in cases of fetus mortuus and hydatiform mole.     

Palliative effect of curcumin on doxorubicin‐induced testicular damage in male rats

This study aimed to investigate the effect of curcumin (CUR) on doxorubicin (DOX)‐induced testicular damage in male rats. Thirty‐five adult male Wistar rats were used. Control group was received saline for 7 days. CUR group received CUR for 7 days. DOX group received single dose DOX on the 5th day. DOX+ CUR‐100 group received 100 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX + CUR‐200 group received 200 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX treatment decreased in sperm motility rate, live sperm percentages, cellular antioxidants, and increased malondialdehyde (MDA) levels, necrosis, degenerations, and slimming in seminiferous tubules, and DNA damages in testes by inducing oxidative stress. CUR treatment mitigated significantly these side effects when compared with DOX group in a dose‐dependent manner. In conclusion, CUR treatment can be used in the mitigation of DOX‐induced testicular toxicity.     

降纤酶治疗急性脑梗死临床疗效观察

目的 为了观察降纤酶治疗急性脑梗死临床疗效及其安全性。方法 采用随机双盲对照方法,对４０例（治疗组２１例,对照组１９例）发病２￣２４ｈ的急性发编号随机用药（降纤酶或安慰剂）,首次１０ｕ,第３、５天５ｕ分别加入生理盐水２５０ｍｌ缓慢静滴,同时应用钙拮抗剂 血化瘀等。用药前后分别检测纤维蛋白原（Ｆｇ）,凝血酶原时间（ＰＴ）,凝血的活动度（ＰＡ）,其中１８例（治疗组１０例,对照组８例）还检测了优球蛋白酶     

Hormonal effects, tolerability, and preliminary kinetics in men of MK-906, a 5 alpha-reductase inhibitor.

The hormonal effects following the acute (single dose) administration of a 4-azasteroid inhibitor of 5 alpha-reductase (MK-906) were evaluated in 10 healthy male volunteers. Marked suppression of serum dihydrotestosterone (DHT) was observed after the administration of single doses as low as 12.5 mg. The mean percent decrease in DHT at 24 hours in the group treated with a single 25-mg dose was 56% +/- 10% compared with the baseline. The suppression of plasma DHT levels continued for up to 72 hours. This study demonstrates that administration of single oral doses (12.5 to 400 mg) of MK-906 results in a significant decrease in the conversion of testosterone to DHT.