Preliminary assessment of the safety and efficacy of tanezumab in Japanese patients with moderate to severe osteoarthritis of the knee: a randomized, double-blind, dose-escalation, placebo-controlled study.

OBJECTIVE: To investigate the use of tanezumab, a humanized monoclonal antibody that inhibits nerve growth factor, for the treatment of moderate to severe osteoarthritis in Japanese patients. DESIGN: Patients received tanezumab 10, 25, 50, 100, 200 µg/kg, or placebo and were followed for 92 or 120 days. Endpoints included the incidence of adverse events (AEs) and the change from baseline to week 8 in pain intensity and the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) subscales. RESULTS: Patients (n = 83) were 69% female, age 44-73 years, with a Kellgren-Lawrence X-ray grade of 2-4. At week 8, compared with placebo, tanezumab 25, 100, and 200 µg/kg improved index knee pain during walking (-18.5, -14.3, and -27.6, respectively), index knee pain in the past 24 h (-19.1, -14.6, and -24.2, respectively), current index knee pain (-16.5, -10.9, and -22.8, respectively), and the WOMAC pain (-11.5, -9.6, and -18.8, respectively), physical function (-8.7, -9.5, and -17.6, respectively), and stiffness (-20.4, -11.2, and -10.2, respectively) subscales. Overall, seven patients reported AEs of abnormal peripheral sensation: allodynia (two in the tanezumab 200 µg/kg group); paresthesia (two in the tanezumab 200 µg/kg group), dysesthesia (one in the tanezumab 200 µg/kg group); thermohypoesthesia (one in the tanezumab 100 µg/kg group), and decreased vibratory sense (one in the placebo group). All of these AEs were mild to moderate in severity and transient in nature. CONCLUSIONS: Tanezumab was safe and generally well tolerated and may improve pain symptoms in Japanese patients with moderate to severe osteoarthritis of the knee. CLINICALTRIALS.GOV IDENTIFIER: NCT00669409.

Association between maternal antibodies to the external envelope glycoprotein and vertical transmission of human T-lymphotropic virus type I. Maternal anti-env antibodies correlate with protection in non-breast-fed children.

Vertical transmission of human T-lymphotropic virus type I (HTLV-I) depends primarily on breast-feeding; substitution of bottle-feeding has reduced the transmission rate from 20% in breast-fed children to 3% among bottle-fed. To determine the correlates of transmission for long breast-feeding (> or = 6 mo), short breast-feeding (< 6 mo), and bottle-feeding mothers, the antibody titers of transmitter (T) mothers and non-transmitter (nT) mothers were analyzed by using synthetic and recombinant epitopes representing the immunodominant epitopes of gag (Gag1a, r24), env (Env1/5, MTA1, RE3), and tax (Tax8/22-24) proteins. Seroreactivity to gag and tax epitopes was not significantly different except for anti-r24 antibody titer, which was significantly higher among T-mothers (geometric mean 134) when compared with nT-mothers (62) in the long-feeding group (P < 0.001). Profiles of antibody titers against env epitopes were different. Within the long-feeding group, Env1/5, MTA1, and RE3 titers were significantly higher among T-mothers (258, 1,476, and 738, respectively) when compared with nT-mothers (106, 279, and 320, respectively) (P < 0.01 for all three epitopes). In contrast, within the bottle-feeding group, antibody titers to Env1/5 (269) and RE3 (418) among nT-mothers were significantly higher than those among T-mothers (80 and 113, respectively) (P < 0.01). These data confirm that high-titered anti-HTLV-I antibodies in the long-feeding group correlate with milk-borne transmission of HTLV-I and, more importantly, imply that maternal anti-env antibodies may reduce the risk of non-milkborne infection.

Primary prevention of HTLV-1 in Japan.

The Nagasaki Prefecture, Japan (population: 1.5 million), is one of the hot endemic foci of Human T-lymphotropic virus type 1 (HTLV-1). Prevalence of HTLV-1 carriers are approximately 10% in the age group over 40 years old (40,000 individuals), approximately 10 times of the national average. Annual registry of adult T-cell leukemia (ATL) in the Prefecture is approximately 60 cases (estimated incidence: 100 cases), or a half percent of total deaths. A effective measure to control the endemic cycle of HTLV-1 has been imperative, since practical ways to prevent or control ATL are not available. A prefecture wide intervention at Nagasaki by refrain from breast-feeding blocked approximately 80% of mother-to-child transmission of HTLV-1.

Intervention of maternal transmission of HTLV-1 in Nagasaki, Japan.

Seroepidemiological and laboratory virological evidences strongly suggested that endemicity of HTLV-1 in Nagasaki Japan depends on maternal infant infections via breast milk. The most obvious way to prove this concept was an intervention study with refraining from breast-feeding by carrier mothers. Most infected babies seroconverted by the age of 12 months, which made it possible to diagnose the infection at the age of 12 months for the statistical purpose. Serology and PCR on both adults and children were consistent each other, suggesting the absence of seronegative carriers. The intervention study revealed that approximately 80% of maternal infection was prevented by refraining from breast feeding by carrier mothers. The remaining fraction of infections in formula-fed babies suggested an alternative infection pathway. Although intrauterine infections has been suggested by others to explain the PCR-positive cord blood samples. However, groups of cord blood-positive children and seroconverted children were distinct each other. Therefore, the presence of HTLV-1 provirus in the cord blood can not be a marker of intrauterine infection. Mothers who infected a child has approximately 10 times higher risk of another infection for the next baby than those who did not.

Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial.

BACKGROUND: The AMPLIFY trial compared apixaban with enoxaparin followed by warfarin for the treatment of acute venous thromboembolism (VTE). OBJECTIVE: To perform a subgroup analysis to compare the efficacy and safety of apixaban and enoxaparin followed by warfarin for the treatment of VTE in patients with cancer enrolled in AMPLIFY. PATIENTS/METHODS: Patients with symptomatic VTE were randomized to a 6-month course of apixaban or enoxaparin followed by warfarin. The primary efficacy outcome and principal safety outcome were recurrent VTE or VTE-related death and major bleeding, respectively. RESULTS: Of the 5395 patients randomized, 169 (3.1%) had active cancer at baseline, and 365 (6.8%) had a history of cancer without active cancer at baseline. Among patients with active cancer, recurrent VTE occurred in 3.7% and 6.4% of evaluable patients in the apixaban and enoxaparin/warfarin groups, respectively (relative risk [RR] 0.56, 95% confidence interval [CI] 0.13-2.37); major bleeding occurred in 2.3% and 5.0% of evaluable patients, respectively (RR 0.45, 95% CI 0.08-2.46). Among patients with a history of cancer, recurrent VTE occurred in 1.1% and 6.3% of evaluable patients in the apixaban and enoxaparin/warfarin groups, respectively (RR 0.17, 95% CI 0.04-0.78); major bleeding occurred in 0.5% and 2.8% of treated patients, respectively (RR 0.20, 95% CI 0.02-1.65). CONCLUSIONS: The results of this subgroup analysis suggest that apixaban is a convenient option for cancer patients with VTE. However, additional studies are needed to confirm this concept and to compare apixaban with low molecular weight heparin in these patients.

Major histocompatibility complex class I expression on neurons in subacute sclerosing panencephalitis and experimental subacute measles encephalitis.

Lack of major histocompatibility class I antigens on neurons has been implicated as a possible mechanism for viral persistence in the brain since these antigens are required for cytotoxic T-lymphocyte recognition of infected cells. In subacute sclerosing panencephalitis (SSPE), measles virus (MV) persists in neurons, resulting in a fatal chronic infection. MHC class I mRNA expression was examined in formalin-fixed brain tissue from 6 SSPE patients by in situ hybridization. In addition MHC class I protein expression in MV-infected neurons was examined in experimental Subacute Measles Encephalitis (SME) by double immunohistochemistry. MHC class I mRNA expression was found to be upregulated in SSPE tissues studied, and in 5 out of 6 cases the expression was definitively seen on neurons. The percentage of neurons expressing MHC class I mRNA ranged between 20 to 84% in infected areas. There was no correlation between the degree of infection and expression of MHC class I molecules on neurons. Importantly, the number of neurons co-expressing MHC class I and MV antigens was markedly low, varying between 2 to 8%. Similar results were obtained in SME where 20 to 30% of the neurons expressed MHC class I but <8% co-expressed MHC class I and MV antigens. Perivascular infiltrating cells in the infected regions in SME expressed IFNgamma immunoreactivity. The results suggest that MV may not be directly involved in the induction of MHC class I on neurons and that cytokines such as IFNgamma may play an important role. Furthermore, the paucity of neurons co-expressing MHC class I and MV antigens in SSPE and SME suggests that such cells are either rapidly cleared by cytotoxic T lymphocytes (CTL), or, alternatively, lack of co-expression of MHC class I on MV infected neurons favors MV persistence in these cells by escaping CTL recognition.

Cytokine-gene expression in measles-infected adult human glial cells.

The expression of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF) alpha transcripts in cultured human glial cells was examined using reverse transcription followed by polymerase chain reaction (PCR) amplification and Southern blot quantitation. Microglial cultures derived from brain biopsy specimens from three different individuals expressed transcripts for the three cytokines under basal culture conditions. This expression was enhanced in response to measles virus (MV) infection (IL-1 beta, 2.2-8.8-fold; IL-6, 2.5-8.4-fold; TNF alpha, 2.2-3.2-fold). Neither IL-1 beta nor TNF alpha transcripts were detectable in undissociated brain tissue from two individuals, suggesting that the basal expression of these cytokines in culture may have been induced by tissue dissociation or by the culture conditions. Oligodendrocytes did not express cytokine transcripts under basal culture conditions, and IL-1 beta and IL-6 but not TNF alpha transcripts could be induced by MV. Similarly, meningeal fibroblasts expressed IL-1 beta and IL-6 but not TNF alpha in response to MV-infection, suggesting that the production of TNF alpha is more cell type-restricted than either IL-1 beta or IL-6. The results indicate that adult human microglia can participate in the inflammatory response to MV infection in the CNS by producing cytokines that contribute to inflammation and demyelination. In addition, besides their role in myelination, oligodendrocytes can potentially influence immunoreactivity in the CNS by producing IL-1 beta and IL-6.

Prevention of mother-to-child transmission of human T-lymphotropic virus type-I.

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic human retrovirus of adult T-cell leukemia/lymphoma (ATLL), causes approximately 60 new cases of ATLL each year in Nagasaki Prefecture; essentially all cases are fatal, and they account for approximately 0.5% of total deaths in the area. The estimated life risk for an HTLV-I carrier to develop ATLL is approximately 5%. The major transmission pathway of HTLV-I peculiarly endemic in the Nagasaki Prefecture was studied. The prevalence of HTLV-I infection in children of carrier mothers (21%) was significantly higher than that in children in the general population in the area (1%) and more than 85% of mothers of carrier children were carriers. The breast milk of carrier mothers contained HTLV-I-infected cells and was infectious for marmoset via oral administration. A retrospective survey of children of carrier mothers showed that the prevalence of carrier children of carrier mothers was 17 (39%) of 44 and 0 (0%) of 10 when they were given breast milk only or formula only, respectively. These data provide a powerful basis for devising an intervention measure to block the endemic cycle of HTLV-I, ie, if carrier mothers refrain from breast-feeding, the incidence of ATLL will be significantly reduced some 50 years later.

Left ventricular diastolic pressure-volume response immediately after successful percutaneous transvenous mitral commissurotomy.

The left ventricular (LV) diastolic pressure-volume response after percutaneous transvenous mitral commissurotomy (PTMC) was investigated to determine whether it was related to the baseline conditions of the left ventricle. Left ventriculography was performed, and the measurements of LV pressure were obtained in 32 patients before and after PTMC. Mitral valve area increased from 1.0 +/- 0.3 to 1.9 +/- 0.4 cm2 (p < 0.005) after PTMC, which caused a decrease in left atrial mean pressure (14.8 +/- 5.9 to 7.4 +/- 2.7 mm Hg; p < 0.005). LV end-diastolic pressure increased in all patients 5 minutes after PTMC. However, patients could be divided into 2 groups according to the following changes in LV end-diastolic pressure 20 minutes after PTMC: In 22 patients, LV end-diastolic pressure returned to the near-baseline level 20 minutes after PTMC (before 5.0 +/- 2.2, 5 minutes after 8.6 +/- 3.1, and 20 minutes after 6.3 +/- 2.5 mm Hg) with a significant increase in LV end-diastolic volume index (64 +/- 12 to 74 +/- 14 ml/m2; p < 0.001) and augmentation of LV stroke volume index (39 +/- 9 to 47 +/- 11 ml/m2; p < 0.001). However, in the remaining 10 patients with a larger LV volume (> 80 ml/m2) and reduced ejection fraction (< 50%) at baseline, LV end-diastolic pressure further increased 20 minutes after PTMC (before 5.5 +/- 2.8, 5 minutes after 7.8 +/- 2.7, and 20 minutes after 11.0 +/- 2.9 mm Hg) without significant changes in LV volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Direct participation of potassium ion in the catalysis of coenzyme B(12)-dependent diol dehydratase.

The direct ion-dipolar interactions between potassium ion (K(+)) and the two hydroxyl groups of the substrate are the most striking feature of the crystal structure of coenzyme B(12)-dependent diol dehydratase. We carried out density-functional-theory computations to determine whether K(+) can assist the 1,2-shift of the hydroxyl group in the substrate-derived radical. Between a stepwise abstraction/recombination reaction proceeding via a direct hydroxide abstraction by K(+) and a concerted hydroxyl group migration assisted by K(+), only a transition state for the latter concerted mechanism was found from our computations. The barrier height for the transition state from the complexed radical decreases by only 2.3 kcal/mol upon coordination of the migrating hydroxyl group to K(+), which corresponds to a 42-fold rate acceleration at 37 degrees C. The net binding energy upon replacement of the K(+)-bound water for substrate was calculated to be 10.7 kcal/mol. It can be considered that such a large binding energy is at least partly used for the substrate-induced conformational changes in the enzyme that trigger the homolytic cleavage of the Co-C bond of the coenzyme and the subsequent catalysis by a radical mechanism. We propose here a new mechanism for diol dehydratase in which K(+) plays a direct role in the catalysis.

Triplet state of Würster's blue-based di(cation radical).

[reaction: see text] N,N-bis[4-(dimethylamino)phenyl]-N,N'-dimethyl-1,3-benzenediamine was prepared in order to investigate the corresponding Würster blue-based di(cation radical). The generated diradical was found to be a ground-state triplet, and moreover, the observed ESR spectrum had no definite fine structure, suggesting a mixture of some conformers.

Hourly fetal urine production rate in the fasting and the postprandial state of normal and diabetic pregnant women.

OBJECTIVE: To examine whether maternal meal ingestion affects fetal urine production in normal and diabetic pregnancies and whether fetal urine production is increased in diabetic pregnancy. METHODS: The hourly fetal urine production rate was measured before and after breakfast in 17 fetuses of diabetic mothers and 14 of women with normal glucose tolerance. The rate was calculated by taking serial measurements of fetal bladder volume at 2-3-minute intervals by ultrasonography. RESULTS: In the control group, the hourly fetal urine production rate was significantly greater during the 2 hours after breakfast than that in the fasting state (P < .0005). In the diabetic group, the rate also tended to increase after breakfast (P = .07). In the postprandial state, the hourly fetal urine production rate was not significantly different between the groups. However, in the fasting state, it was significantly greater in the diabetic group than in the control group (P < .03). CONCLUSIONS: Maternal meal ingestion should increase fetal urine production. The increased fetal urine production in the fasting state in diabetics is assumed to be one cause of hydramnios.

Change in fetal urine production rate in growth-restricted fetuses after maternal meal ingestion.

OBJECTIVE: To determine if fetal urine production is affected by maternal meal ingestion in growth-restricted fetuses. METHODS: We studied 25 normal-growth fetuses in uncomplicated pregnancies and 15 growth-restricted fetuses, all after 30 weeks' gestation. Serial fetal bladder volume measurements were obtained at 2-3 minute intervals with ultrasonography 2 hours before and 2 hours after maternal breakfast. The hourly fetal urine production rate in each maternal state was calculated from the bladder volume measurements. The amniotic fluid index (AFI) and the pulsatility index of both umbilical and fetal middle cerebral arteries were also measured. RESULTS: Two of the 15 growth-restricted fetuses were excluded from analysis, one because it was anomalous and the other because it was not small for gestational age at birth. In the normal-growth fetuses, the hourly fetal urine production rate increased significantly after maternal breakfast (mean +/- standard deviation 30.2 +/- 11.7 versus 41.1 +/- 14.6 mL/hour, P < .001). In contrast, in the growth-restricted fetuses, the rate did not change after maternal breakfast (24.6 +/- 6.2 versus 24.9 +/- 5.7 mL/hour). Although the urine production rate before breakfast did not differ between groups, 2 hours after maternal breakfast it was significantly lower in the growth-restricted fetuses than in the control group (normal-growth) (P < .001). The AFI also was significantly lower in the growth-restricted fetuses than in the control group (15.0 +/- 3.5 versus 18.6 +/- 5.0 cm, P < .04). There were no significant differences in the pulsed Doppler studies. CONCLUSION: In contrast to normal-growth fetuses, maternal meal ingestion for growth-restricted fetuses does not increase fetal urine production. Decreased fetal urine production in the maternal fed state may lead to decreased amniotic fluid volume in growth-restricted fetuses without obvious hypoxia.

First observation of clusters for solvated tropylium ions.

We have first observed clusters for solvated tropylium ions (Tr+(ROH)n) which were isolated from ROH-CH3CN (1:1 by vol.; R = Me, Et, and Prn) solutions by using a specially designed mass spectrometer and found the clear-cut essential features concerning the solvation structure around Tr+.

Expression of estrogen and progesterone receptors in endometrium and peritoneal endometriosis: an immunohistochemical and in situ hybridization study.

OBJECTIVE: To clarify the role of ovarian steroids in the development and progression of endometriosis, estrogen receptors (ERs) and progesterone receptors (PRs) were localized by immunohistochemistry, and ER messenger RNA (mRNA) was detected by in situ hybridization in the uterine endometrium and in normal and altered pelvic peritoneum. DESIGN: Retrospective and prospective study. SETTING: Nagasaki University School of Medicine, Nagasaki, Japan. PATIENT(S): A retrospective study of 61 formalin-fixed uterine endometria and normal and altered pelvic peritonea from patients suffering from various gynecologic diseases was conducted. In addition, in 22 fresh frozen tissue specimens, ER mRNA expression was evaluated prospectively. MAIN OUTCOME MEASURE(S): In formalin-fixed tissues, ER and PR were localized immunohistochemically. The results of immunohistochemical staining were scored from 0 to 4, depending on the signal intensity and frequency of positive cells. In fresh frozen specimens, ER mRNA expression was assessed by nonradioactive in situ hybridization using thymine-thymine dimerized oligonucleotide probes. RESULTS: The highest score of ERs and PRs was observed in the epithelial and stromal cells of the normal uterine endometrium at the early proliferative phase of the menstrual cycle. The ER and PR scores declined throughout the secretory phase. In typical endometriotic lesions, the ER and PR scores were constantly high independent of the menstrual cycle. The expression pattern of ER mRNA was mostly in parallel with that of ERs. In typical endometriosis, ERs and PRs were found in both glandular epithelial cells and their surrounding stromal cells. Expression of ER mRNA was found in typical endometriotic peritonea and in pelvic peritoneum with columnar epithelial cells, but not in normal pelvic peritoneum (mesothelium). Estrogen receptors and PRs were negative in mesothelium, but were positive in the nuclei of fibroblasts in the connective tissue. CONCLUSION(S): We demonstrated the expression of ERs, ER mRNA, and PRs in the columnar cells in pelvic peritonea and typical endometriosis, but not in normal mesothelium. These results suggest that endometriosis may originate from the columnar cells with ERs and PRs in the pelvic peritoneal lining.

Effect of cilazapril on vascular restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: In experimental studies using cilazapril, the strongest inhibition of neointima formation was obtained when treatment was initiated 6 days before injury. The MERCATOR trial showed no reduction in restenosis with cilazapril given after percutaneous transluminal coronary angioplasty (PTCA). The purpose of this study is to determine whether previous administration of cilazapril could prevent restenosis. METHODS: A total of 167 patients were randomly and prospectively assigned to the cilazapril group or the control group. In the cilazapril group, 78 patients received a 2 mg dose of cilazparil daily, starting 7 days before PTCA and continuing for 6 months. Only 128 patients (cilazapril 56, control 72) completed the study because 39 dropped out. Coronary angiograms were evaluated by the quantitative coronary angiogram (QCA) system. RESULTS: There were no differences between the two groups of patients with regard to baseline clinical and angiographic characteristics. QCA analysis (cilazapril 66 lesions, control 101 lesions): the loss at follow-up in minimal lumen diameter was 0.36 +/- 0.57 mm in the cilazapril group and 0.57 +/- 0.75 mm in the control group (P < 0.05). Restenosis rate: in the cilazapril group, 16 of 56 patients (28.6%) had restenosis in contrast to 36 of 72 patients (50.0%) in the control group (P < 0.02). When vessel restenosis was evaluated, 16 of 63 vessels (25.4%) demonstrated restenosis in the cilazapril group, in contrast to 41 of 82 vessels (50.0%) in the control group (P < 0.01). CONCLUSIONS: Treatment using cilazapril 7 days before PTCA significantly reduced the rate of restenosis. These data suggest that previous administration of cilazapril might be important for preventing restenosis.

A comparison of the prevalence and risk factors of high blood pressure among Japanese living in Japan, Hawaii, and Los Angeles.

THE AUTHORS STUDIED THE PREVALENCE AND RISK FACTORS of hypertension in samples of 2053 Japanese ages 40 to 70 in Hiroshima, Hawaii, and Los Angeles. The prevalence of hypertension (systolic blood pressure greater than or equal to 140 mmHg, diastolic blood pressure greater than or equal to 90 mmHg, or receiving antihypertensive drug treatment) was higher in Hawaii and Los Angeles for both sexes and almost all ages than in Hiroshima. The age- and sex-adjusted prevalence of hypertension in Hawaii, Los Angeles, and Hiroshima was 42.6%, 37.2%, and 29.7%. Hypertension was associated with a significant elevation in serum glucose, insulin, triglyceride, and total cholesterol levels in the combined participant population of Hawaii, Los Angeles, and Hiroshima. Age- and sex-adjusted mean values of serum total cholesterol, triglyceride, and insulin were highest in Hawaii and lowest in Hiroshima. The mean body mass index and 2-hour serum glucose levels were greatest in Hawaii and equal in the two other cohorts. These results suggest that hyperinsulinemia and hyperlipidemia may explain the prevalence of hypertension in the research participants.

Needle aspiration biopsy of vulvar endometriosis. A case report.

Vulvar involvement by endometriosis is extremely rare. A patient presented with a vulvar tumor and was diagnosed on needle aspiration biopsy and subsequently on histopathology as having endometriosis of the vulva. The treatment offered was conservative, local excision of the tumor. The patient was well and free of complaints when last seen in the Outpatient Department, at six months of follow-up. Needle aspiration biopsy as a diagnostic tool in vulvar tumors and the histogenesis of the endometriosis are discussed.

[Clinical studies on ceftriaxone in the field of obstetrics and gynecology].

Clinical studies were made on ceftriaxone (CTRX, Ro 13-9904), a new long-acting cephalosporin antibiotic, with the following results. Following a single intravenous injection of 1 g, the transfer of CTRX to the internal genital organs was found to be good. The transfer of CTRX to exudate of the dead space of pelvis was also good. Elbow vein and uterine artery blood serum levels revealed marked increase immediately after administration, then followed by gradual reduction at very slow rate. CTRX was given to 3 patients of female genital infections. Efficacy was excellent in 1 case and good in 2 cases. As to side effect, 2 cases of diarrhea and 1 case of leukopenia were observed.

[Fundamental and clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology].

The following results were obtained during pharmacokinetic, bacteriological and clinical evaluation of the usefulness of the combination (1:1) of imipenem (MK-0787) and cilastatin sodium (MK-0791), an inhibitor of dehydropeptidase-I, in the treatment of patients with obstetric and gynecologic infections. Plasma concentrations of MK-0787 in antecubital vein and uterine artery were 18.2 micrograms/ml and 16.4 micrograms/ml, respectively, and of MK-0791 were 9.5 micrograms/ml and 10.3 micrograms/ml, respectively, at 1.28 hours after the end of a drip infusion of 0.5 g/0.5 g of MK-0787/MK-0791. Plasma concentrations of both MK-0787 and MK-0791 decreased slowly, and concentrations of the former in antecubital vein and uterine artery were 0.7 micrograms/ml and 1.0 micrograms/ml, respectively, and of the latter were 1.5 micrograms/ml and 1.9 micrograms/ml, respectively at 2.83 hours after the end of a drip infusion. Concentrations of the 2 agents in female genital tissues decreased with increasing time in a manner similar to concentrations in the plasma. Clinical responses in 10 patients were excellent in 2 and good in 8, and the efficacy rate was 100 percent. Organisms were isolated from all 10 patients before the treatment, but were eradicated in 9 patients by the treatment. No side effects were observed, but increase of eosinocytes was observed in 1 patient.