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Published nonadherence rates in the adolescent oncology population range from 33 to 60% though little is known about the psychological factors that contribute to adherence and the relationship between outcome and nonadherence. Our study was designed to investigate psychological and family factors related to adherence and the relationship between adherence and survival in this population. We evaluated 44 (27 males, 17 females) patients with cancer (13–17 years) who were at least 6-months postdiagnosis. Adherence with trimethoprim/sulfamethoxazole (TMP/SMX) was determined at one point in time, using serum assay. Twelve of the patients (27%) had no detectable TMP/SMX. Patients without detectable drug had higher levels of depression, lower self-esteem, and higher levels of parent–child incongruence. Survival rates, 6 years after the initiation of the study, were lower in the group of participants categorized as nonadherent. These findings, if confirmed, have implications for the management of nonadherence and mood in this population.

OBJECTIVE: Cord blood pH, lactate, hypoxanthine, and erythropoietin levels has all been used as markers of either acute or chronic asphyxia. We sought to determine whether these index values were significantly different in infants with or without meconium-stained amniotic fluid. STUDY DESIGN: Fifty-six pregnant women in spontaneous labor at term were divided into two groups on the basis of the presence or absence of meconium-stained amniotic fluid. All meconium-stained fluid was centrifuged, and the volume percentage of particulate mater (i.e., meconium) was recorded. Umbilical artery blood and mixed arterial and venous cord blood were obtained at each delivery. Lactate, hypoxanthine, and erythropoietin levels were measured. Statistical analysis included Student t test and rank sum statistics where appropriate. Normal and Spearman correlation coefficients wer also used. RESULTS: There were no significant differences in mean umbilical artery pH 97.26 ± 0.06 vs 7.25 ± 0.10), lactate levels (32.8 ± 10 mg/dl vs 30.4 ± 14.2 mg/dl), and hypoxanthine levels (13.4 ± 6.7 μmol/L vs 14.0 ± 6.0 μmol/L) in newborns with meconium ( n = 28) compared with controls ( n = 26). Erythropoietin levels were significantly greater in newborns with meconium (median 39.5 mlU/ml vs 26.8 mlU/ml, p = 0.039). There was no correlation between the amount of particulate matter and any marker of asphyxia. CONCLUSIONS: There was no correlation between markers of acute asphyxia (i.e., umbilical artery blood pH, lactate, or hypoxanthine) and meconium. However, erythropoietin levels were significantly elevated in newborns with meconium-stained amniotic fluid. This latter marker may better correlate with chronic asphyxia.

Objective: The purpose of the present investigation was to analyze the effets of zidovudine on the postimplantation embryo and fetus.Methods: Pregnant Sprague-Dawley rats were given various doses (10 mg/kg, 30 mg/kg, 150 mg/kg) of zidovudine or saline by an endotracheal tube during the period of embryogenesis (days 6–8, 9–11, 6–11 postconception). The animals were sacrificed on days 18–19 of pregnancy, and their fetuses were removed by hysterotomy. Autopsies under low (15×) and high (40×) power light microscopy were performed on all fetuses.Results: There was no statistically significant difference among the groups with respect to maternal weight gain. There were more pregnancy resorptions in the group receiving high-dose zidovudine (150 mg/kg/day) throughout embryogenesis than in the control group (P = 0.001, respectively). Four major structural anomalies were noted among the 689 fetuses examined, but zidovudine was not associated with an increased frequency of congenital anomalies in rats when it was administered in doses similar to, 3-, and 15-fold higher than the regimen recommended for adult humans. The drug, however, was embryocidal in the high-dose group (P = 0.002).Conclusions: These findings are consistent with previous studies of preimplantation mouse embryos that demonstrated an embryocidal effect on preimplantation conceptuses. In summary, post-implantation embryonic zidovudine exposure was associated with significantly increased pregnancy losses (resorptions and intrauterine deaths).

The purpose of this study was to determine the ex vivo maternal-fetal placental transfer of 2',3'-didehydro-3'-deoxythymidine (d4T) and to compare it to the perfusion characteristics of 3'-azido-2',3-dideoxythymidine (AZT). This study used the single cotyledon perfusion system and antipyrine to determine the clearance index of this thymidine-containing anti-human immunodeficiency virus (HIV) compound. The endogenous base thymidine and the inhibitor dipyridamole were used to determine if this anti-HIV compound crossed the placenta by simple diffusion. The clearance index of d4T was 0.24 +/- 0.07 at 1.0 micrograms/ml and 0.235 +/- 0.045 at 10.0 micrograms/ml. These data suggest that the clearance index of d4T is 77-81% of AZT. The presence of high concentrations of dipyridamole and endogenous thymidine did not alter the clearance of d4T. In studies in which both the maternal and fetal circulations were closed, the accumulation in the fetal circulation was linear when the maternal concentration was in the range of 1-100 micrograms/ml. These data suggest that d4T crosses the human placenta by simple diffusion, and has similar perfusion characteristics to that of AZT.

OBJECTIVE: The purpose of this study was to determine the stability of oxytocin in lactated Ringer's solution and lactated Ringer's–dextrose 5% solution over a 24-hour period at 25°C and over a 7-day period at 5°C. STUDY DESIGN: Twenty units (2.1 μg equal 1 unit) of oxytocin were injected into 1000 mL of lactated Ringer's solution and lactated Ringer's–dextrose 5% solution. Samples for the analysis were drawn at specified times after storage at 5°C and 25°C. These samples were stored at −70°C for later analysis. Statistical analysis was done with 1-way analysis of variance and Tukey-Kramer multiple comparisons. RESULTS: Twenty units of oxytocin in 1000 mL of lactated Ringer's solution and lactated Ringer's–dextrose 5% solution was found to be stable for 7 days at 5°C and for 24 hours at 25°C. CONCLUSION: Premixed oxytocin solutions in lactated Ringer's solution and lactated Ringer's–dextrose 5% solution are stable in conditions commonly found in dispensing pharmacies and labor and delivery units. This finding could lead to the more efficient use of personnel during the mixing process, could provide solutions that are aseptically prepared, and could be a tool to reduce costs and improve patient care. (Am J Obstet Gynecol 2002;186:496-8.)

OBJECTIVES: In vitro perfusion of human placentas was used to quantify the net placental transfer of ticarcillin and clavulanic acid. STUDY DESIGN: Placentas were obtained from uncomplicated pregnancies at term. The maternal and fetal circulations were reestablished at flow rates of 17.5 ml/min and 5 ml/min, respectively. Open circulations were used to evaluate steady-state pharmacodynamics and transplacental gradient formation. Drug levels were measured by high-pressure liquid chromatography. RESULTS: The clearance index of ticarcillin was 0.037 ± 0.004. The fetal/maternal ratio was 0.91. Therapeutic concentrations of clavulanate (2 to 6 11g/ml) in the maternal media resulted in undetectable transfer to the fetal compartment. By using higher levels of clavulanate, a clearance index of 0.061 ± 0.001 (mean ± SEM) and 1 : 1 fetal/maternal gradient was obtained. CONCLUSIONS: These data correspond to relatively low transfer of ticarcillin with a cord/maternal ratio of \lt 1. Clavulanate transfer is slightly greater. Agents with similar acitvity and superior transfer would optimize intrauterine treatment. (AM J OBSTET GYNECOL 1992;167:1595-9.)

OBJECTIVE: The purpose of this study was to compare the maternal-fetal placental transfer of 2',3'-dideoxyinosine and 2',3'-dideoxycytidine with that of 3'-azido-2', 3-dideoxythymidine (azidothymidine). STUDY DESIGN: The perfusion system used carbon 14-labeled antipyrine as a reference compound to determine the clearance index of each compound. The inhibitor dipyridamole and the endogenous bases were used to determine if these anti-human immunodeficiency virus compounds crossed the placenta other than by simple diffusion. RESULTS: The clearance index of azidothymidine was 0.29 ± 0.04 at maternal concentrations of 1.0 to 10 µg/ml, and the clearance index of 2' ,3'-dideoxyinosine was 0.14 ± 0.05, which was 48% of the clearance index of azidothymidine. The clearance index of 2',3'-dideoxyinosine was essentially identical to azidothymidine in the range from 1 to 10 µg/ml. The results of the closed-closed studies suggest that at therapeutic peak concentrations of 1 to 2 µg/ml of these compounds in the maternal circulation therapeutic levels will be reached in the fetal circulation. CONCLUSION: These anti-human immunodeficiency virus inhibitors appear to cross the placenta rapidly by simple diffusion because (1) the transfer of the drugs to the fetal circulation was not saturable even at 100 µg/ml, (2) there was no change in clearance index with the addition of 300 µmol/L of thymidine, inosine, cytosine, or 30 µmol/L dipyridamole, and (3) there was no accumulation against the maternal fetal or fetal maternal concentration gradient. (AM J OBSTET GYNECOL 1992;167:1570-4.)

Although intrapartum antibiotics are beneficial to both the mother and newborn, there is no consensus as to the most efficacious antibiotic regimen in the treatment of intra-amnionic infection, especially with regard to anaerobic coverage. We randomized pregnant women with intra-amnionic infection to receive either dual agent therapy (ampicillin and gentamicin) or triple agent therapy (ampicillin, gentamicin, and clindamycin). The frequency of vaginal and cesarean delivery was similar in both groups. There was no significant difference in the incidence of endometritis between the two groups (10 of 69 versus 5 of 64; p = NS). There were no significant differences in either neonatal morbidity or mortality. The addition of clindamycin to provide anaerobic coverage for intra-amnionic infection does not significantly alter the incidence of endometritis in women delivered by cesarean section, although it may have an impact on women delivering vaginally.

Fibronectin (FN) has been postulated to prevent gram-negative bacillary (GNB) colonization of the oropharynx by covering epithelial cell GNB receptors. We investigated the distribution of FN along the luminal surface of oropharyngeal epithelium in animals and humans. Examination of buccal epithelial biopsies obtained from normal rats revealed no luminal surface FN by either immunofluorescent or immunoperoxidase staining. Extraction of epithelial surface proteins and quantitation of FN by rocket immunoelectrophoresis and electrophoretic transfer to nitrocellulose followed by immunologic detection also detected no FN from normal animals' oropharyngeal biopsies. Buccal epithelial biopsies from three normal humans were examined for FN using electrophoretic transfer to nitrocellulose followed by immunologic detection, and no FN was demonstrable. Our results suggest that FN is not present on the oral epithelial surface of healthy rodents or humans, and that FN may not be involved in the pathogenesis of bacillary colonization.

To assess placental metabolism of cocaine, placentas were obtained at the time of delivery and the microsomes were extracted by ultracentrifligation within 2 hours. Placental microsomes were cultured with cocaine at physiologic plasma concentrations similar to those of cocaine users (0.75 µg/ml). Two control groups were established. In the first group an anticholinesterase was added to the culture to suppress enzyme activity, and in the second cocaine was cultured alone without placental microsomes to obtain baseline spontaneous conversion of the drug. The results indicate that cocaine is biotransformed by the human placenta, presumably by cholinesterase activity. This suggests that the placenta may provide a moderate degree of protection from cocaine-induced morbidity, such as abruptio placentae and fetal growth retardation, by converting cocaine into less active metabolites. These results also have pharmacogenetic implications because cholinesterase activity varies among individuals. Hence placentas that cannot transform the drug may place the conceptus at greater risk of developmental abnormalities.

By using a high-pressure liquid chromatography assay, we investigated the ability of collagen shield therapeutic contact lenses to release amphotericin B and deliver it to the anterior segment of rabbit eyes. In vitro studies showed that presoaked collagen shields released most of the amphotericin B within the first hour of elution. We compared the corneal and aqueous humor amphotericin B levels produced by collagen shields soaked in amphotericin B and frequent-drop therapy at four time points over a six-hour period. The collagen shields soaked in amphotericin B produced corneal levels that were higher than those produced by frequent-drop therapy at one hour, equivalent to drop therapy at two and three hours, and lower than drop therapy at six hours. There were no differences in amphotericin B levels in aqueous humor at any time point between rabbits treated with collagen shield delivery and rabbits treated with frequent-drop delivery. The results of this study suggest that amphotericin B delivery to the cornea by collagen shields is comparable to frequent-drop delivery but has the potential benefit of added convenience and compliance.

Objective:The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in theex vivohuman placental model.Methods:Theex vivohuman placental model used C14antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by high pressure liquid chromatography.Results:The clearance index of abacavir was 0.47 ± 0.19 and 0.50 ± 0.07 at peak and trough concentrations, respectively. The clearance index of amprenavir was 0.38 ± 0.09 and 0.14 ± 0.08 at peak and trough concentrations, respectively. There was no unusual accumulation of either drug in the media or tissue when the perfusion system was closed.Conclusion:Abacavir is the first nueleoside compound studied in the perfusion system with a high clearance index. The transfer of the protease inhibitor amprenavir had a clearance index 2.75 times greater than the clearance index of ritonavir at peak concentration determined in a previous study. At trough concentration the clearance index was much less than at the peak concentration. A similar result was found with ritonavir.

The MHC class I-related receptor, neonatal Fc receptor (FcRn), plays a central role in regulating the transport andin vivopersistence of immunoglobulin G (IgG). IgG–FcRn interactions can be targeted for engineering to modulate thein vivolongevity and transport of an antibody, and this has implications for the successful application of therapeutic IgGs. Although mice are widely used to preclinically test antibodies, human and mouse FcRn have significant differences in binding specificity. Here we show that an engineered human IgG1 has disparate properties in murine and human systems. The mutant shows improved transport relative to wild-type human IgG1 in assays of human FcRn function but has shortin vivopersistence and competitively inhibits FcRn activity in mice. These studies indicate potential limitations of using mice as preclinical models for the analysis of engineered antibodies. Alternative assays are proposed that serve as indicators of the properties of IgGs in humans.

Background. The incidence of unilateral twin ectopic pregnancy is a rare condition. Several factors increase the risk of ectopic pregnancy, the most important of which is pelvic inflammatory disease, followed by operative trauma, congenital anomalies, tumors, and adhesions resulting in anatomically distorted fallopian tubes. We present a case of a woman with a history of four confirmed sexually transmitted infections (STIs) including Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus 2, and Treponema pallidum. The case illustrates the potential impact of sexually transmitted infections (STIs) on the risk of a twin ectopic pregnancy. Case. A 24-year-old primigravida, presented with an unknown last menstrual period, lower abdominal pain, watery vaginal discharge, and vaginal spotting. During this hospitalization, serumβ-HCG testing was 263 mIU/mL and transvaginal ultrasonographic examination suggested a nonviable unilateral twin ectopic pregnancy. At exploratory laparotomy, a 10 cm mass involving the right fallopian tube and ovary was excised. Pathological evaluation of the specimen identified a monochorionic, diamnionic twin ectopic pregnancy within the fallopian tube. Conclusions Patients with a history of multiple (STIs) are known to be at risk for the development of chronic pelvic infection and postinflammatory scarring. The resulting distortion of the normal tubal anatomy leads to an increased risk of an uncommon presentation of ectopic pregnancy.

Objective The objective of the study was to determine transplacental passage of rosiglitazone (Avandia) using the ex vivo human placental model. Study design Perfusion studies were performed on 10 placentas from term, uncomplicated deliveries. Concentrations typical for an 8-mg oral dose (216 to 692 ng/mL) as well as 2- to 3-fold increased concentrations were tested (734 to 1261 ng/mL). Transfer of rosiglitazone was assessed and accumulation was determined using the 14 C-antipyrine reference method. Results The clearance index for low and high concentrations were 0.14 ± 0.04 and 0.20 ± 0.08, suggesting that the drug passes through the placenta at a relatively low rate. Fetal accumulation occurred in only 1 of 5 placentas at 16.4 ng/mL (5%) for the 8-mg dose and in 2 of 5 placentas ranging from 0 to 74 ng/mL (5% to 8%) at higher concentrations. Conclusion There is minimal transfer and fetal accumulation of rosiglitazone according to the ex vivo human perfusion model.

Objective The purpose of this study was to determine whether the placental transfer of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) occurs. Methods Four normal-term placentas were perfused for maternal-fetal transfer of the cytokines, 2 placentas for fetal-maternal transfer, and 4 additional placentas were used for an endogenous control. The ex vivo isolated cotyledon human placental perfusion model was used. The reference compound antipyrine was used to determine the transport fraction and clearance index of the cytokines. The cytokines were added to either the maternal or fetal circulations, and samples were collected for 1 hour in a constant-flow open circulation. Cytokine levels were compared between the study and control placentas. Concentrations of the cytokines were measured by sandwich enzyme immunoassay. Results The clearance index for the maternal-fetal transfer of IL-1alpha and TNF-alpha was 0.001, suggesting minimal transfer to the fetal circulation. The clearance index for IL-6 was 0.30, indicating transfer to the fetal circulation. When the cytokines were added to the fetal circulation, the clearance index for IL-1alpha was 0.001, again indicating minimal transfer. The clearance index for TNF-alpha in the fetal-maternal study was not determined. IL-6 had a clearance index of 0.23, which was similar to that observed with maternal-fetal transfer. IL-6 concentrations in the study placentas were higher than the concentrations found in the controls. Conclusion There appears to be bidirectional transfer of IL-6 in the healthy-term human placental perfusion model. Level of evidence II-2

The object was to determine the placental transfer of ritonavir alone and in combination with zidovudine.Twelve placental perfusion studies were performed at trough (1-2 microg/mL) and peak (approximately 20 microg/mL) combinations of ritonavir and zidovudine. Accumulation of ritonavir was determined.Transfer of ritonavir at trough concentrations was undetectable (0.025 microg/mL). The clearance index of ritonavir at peak concentration was 0.085 +/- 0.05 and was unaffected by zidovudine. The fetal concentration of ritonavir was 0.0758 +/- 0.22 microg/mL at a maternal concentration of approximately 20 microg/mL and 25.5 +/- 6.9 microg/mL at a concentration of 100 microg/mL. There was no tissue accumulation of ritonavir either alone or with zidovudine.The clearance index of ritonavir at therapeutic levels was extremely low, with little accumulation in the fetal compartment and no accumulation in placental tissue. Zidovudine does not significantly affect the transfer or accumulation of ritonavir.

OBJECTIVE: Our purpose was to measure the transfer of lamivudine ([-]-2′-deoxy-3′-thiacytidine] across the human placenta both alone and in the presence of zidovudine. STUDY DESIGN: Nine placentas from term, elective cesarean deliveries were analyzed with use of the ex vivo single cotyledon perfusion system. Antipyrine was used as the reference compound to measure the clearance index values of lamivudine alone and in combination with zidovudine. Lamivudine concentrations in the perfusates and tissues were quantified by high-pressure liquid chromatography. RESULTS: The clearance index of lamivudine at a maternal concentration of 1.39 μg/ml was 0.23 ± 0.14. At a peak concentration of 14.68 μg/ml the clearance index was 0.14 ± 0.06. These index values did not significantly change in the presence of 1 or 10 μg/ml of zidovudine. In a closed recirculating system the fetal lamivudine concentration increased as more lamivudine was added to the maternal perfusate. The addition of zidovudine did not influence this transfer. CONCLUSION: Lamivudine appears to cross the placenta by simple diffusion and its transfer does not appear to be altered by zidovudine. (Am J Obstet Gynecol 1997;176:291-30.)

OBJECTIVE: Our purpose was to determine how rapidly bactericidal concentrations of ampicillin against group B streptococci are achieved in amniotic fluid and cord blood after a 2 gm maternal infusion. STUDY DESIGN: Ampicillin was administered at varying time intervals between 3 and 67 minutes before elective cesarean delivery in 40 women. Samples of amniotic fluid were obtained by amniocentesis just before the uterine incision was made. Umbilical and maternal blood were obtained at the time of delivery. Ampicillin concentrations were measured by high-pressure liquid chromatography. RESULTS: The mean concentrations of ampicillin measured in maternal and umbilical cord sera all exceeded the minimum bactericidal concentrations reported for group B streptococci (0.25 to 2.0 μg/ml) and were achieved as soon as 5 minutes after ampicillin infusion. Similarly, bactericidal levels of ampicillin in the amniotic fluid could be detected as early as 5 minutes. However, such concentrations of ampicillin in the amniotic fluid were achieved in only 85% of the pregnancies studied. CONCLUSIONS: Bactericidal levels of ampicillin against group B streptococci can usually be achieved rapidly in both fetal blood and amniotic fluid after a standard 2 gm intravenous dose given to the mother for neonatal prophylaxis. (Am J Obstet Gynecol 1996;175:974-6.)

OBJECTIVE: Our purpose was to determine whether human immunodeficiency virus-1 p24 antigen crosses the human placenta and, if so, to determine its clearance index relative to antipyrine. STUDY DESIGN: Eight term human placentas from uncomplicated vaginal or cesarean section deliveries were studied by ex vivo placental perfusion to determine the incidence and concentration required to obtain passage of p24 antigen into the fetal circulation. The concentration of p24 antigen was determined by antigen-capture enzyme immunoassay. RESULTS: The passage of p24 antigen into the fetal circulation was observed in three of five placentas studied when the p24 antigen concentration in the maternal circulation was 2942.8 ± 401 pg/ml. When the p24 concentration in the maternal circulation was raised approximately fourfold to 14506 ± 4124 pg/ml, p24 antigen passed to the fetal circulation in two of three placentas and in three of three placentas in the closed perfusion system. CONCLUSIONS: p24 antigen crossed the human placenta to the fetal circulation in what appears to be a concentration-dependent manner.

We compared serum levels and tolerability of oral amoxicillin in 30 healthy adults who each received 2.0 g of amoxicillin and, 1 week later, 3.0 g of the same preparation. Serum levels of amoxicillin were determined at 1, 2, 4, and 6 hours following its ingestion. Mean serum levels of amoxicillin were significantly higher after 3.0-g doses than after 2.0-g doses. Levels in females were higher than in males; this was a reflection of differences in body weights. Food intake had no effect on serum levels. The 2.0-g doses resulted in adequate serum levels; 6 hours after dosing levels were still substantially higher than the MICs for oral streptococci. Three individuals (10%) experienced mild gastrointestinal side effects after they received the 3.0-g doses; no side effects were noted after the 2.0-g doses. We propose that to prevent bacterial endocarditis in adults who are at risk, a single 2.0-g dose of oral amoxicillin may be adequate prophylaxis for dental, oral, or upper respiratory tract procedures.

OBJECTIVE:We studied whether the human placenta has the structural integrity to impede transplacental passage of cell-free human immunodeficiency virus (HIV)-1 or p24 antigen from the maternal to the fetal circulation.METHODS:Nine term human placentas from uncomplicated vaginal or cesarean section deliv eries were studied ex vivo with a placental perfusion apparatus to determine whether cell-free HIV-1 at 200-2000 tissue culture infectious dose (TCID50/mL) would pass to the fetal circu lation. Passage of virus or p24 was assessed by infectivity titration and/or p24 antigen capture enzyme immunoassay.RESULTS:Infectious HIV-1 was not detected in any of the fetal perfusate samples taken periodically during experiments. Low concentrations of HIV-1 p24 antigen, however, were detected in fetal perfusate samples from three placentas.CONCLUSIONS: The term human placenta effectively impedes passage of cell-free HIV-1 from the maternal to the fetal circulation. However, it may be permeable to passage of p24 anti ge...

The pharmacokinetics of cefoperazone 2 g combined with sulbactam 1 g after a single dose administered intravenously were evaluated in 24 subjects with normal and impaired renal function. Subjects were categorized into four groups based on endogenous creatinine clearance Clcr. Patients in groups 1, 2 and 3 had ClcrS of greater than 60, 31 to 60, and 10 to 30 mL/min/1.73 m2, respectively. Patients in group 4 required maintenance haemodialysis and were assumed to have Clcr less than 10 mL/min/1.73 m2. Pharmacokinetic parameters were determined by noncompartmental methods. No significant differences (P greater than 0.05) in mean peak serum cefoperazone-sulbactam concentrations for group 1 (208.4/29.0 mg/L), group 2 (199.0/34.1 mg/L), group 3 (163.2/35.0 mg/L), and group 4 (234.0/66.0 mg/L) were noted. Correlations between both total serum (r = 0.58) and renal (r = 0.35) clearance and creatinine clearances were negative for cefoperazone, although both were shown to decline with diminished renal function. Correlations between serum (r = 0.85) and renal (r = 0.72) clearances and creatinine clearance for sulbactam were, on the other hand, both positive and declined in a linear fashion. No significant differences in steady state volumes of distribution were noted for either cefoperazone (P = 0.53) or sulbactam (P = 0.85) amongst the four groups. After 24 h, urinary recovery was also comparable for both cefoperazone (P = 0.64) and sulbactam (P = 0.85) amongst the four groups. The concentrations of cefoperazone and sulbactam remained at or above the MICs (16/8 mg/L) for common bacterial pathogens for 2.5, 3, 7 and 14 h in groups 1, 2, 3 and 4, respectively.

The object of this randomized study was to compare the safety and efficacy of oral ofloxacin, 400 mg twice daily for 10 days, versus intramuscular cefoxitin, 2 gm, plus oral probenecid, 1 gm, followed by oral doxycycline, 100 mg twice daily for 10 days, in the outpatient treatment of uncomplicated acute salpingitis. Thirty-eight women (53%) had Neisseria gonorrhoeae from their pretreatment endocervical or endometrial cultures, and 18 had Chlamydia trachomatis (25%). Thirty-five of 37 women (95%) treated with the ofloxacin regimen were clinically cured, and 34 of 35 (97%) were cured with the cefoxitin-doxycycline regimen (p = 0.52). One clinical failure occurred in each group with N. gonorrhoeae infection, and one failure occurred in the ofloxacin group because of side effects. The bacteriologic response for N. gonorrhoeae in both groups was 100%. The eradication of C. trachomatis was 100% (10/10) for the cefoxitin/doxycycline group and 86% (6/7) for ofloxacin. The side effects were similar in both groups of subjects. In this study both regimens were effective for the outpatient treatment of uncomplicated acute salpingitis.

To our knowledge, placental transfer of pentamidine has not been previously studied in vivo. In the present study, the pharmacokinetics of pentamidine were analyzed in late gestation (18 days) among Sprague-Dawley rats. Pentamidine's kinetics were assessed in the following maternal compartments over a 12-hour period in 16 timed-pregnant rats: serum, liver, and kidney. Placentas were also analyzed for pentamidine concentration as were fetal brain, liver, and kidney tissues. Significant placental transfer of the drug was found, with pentamidine reaching all fetal compartments studied. Notably, by the twelfth hour fetal brain tissue achieved pentamidine concentrations that were not significantly different from those of maternal serum at the second hour of the experiment. This is an interesting observation because adult mouse and rat brains were found to be unexposed to the drug.

Utilizing the in vitro human placental model, we studied the placental transfer of trimethoprim and sulfamethoxazole. At trimethoprim concentrations of 7.2 micrograms/ml, only 1.4 micrograms/ml was transported across the placenta after 1 h, and at concentrations of 1.0 microgram/ml, one half the usual serum level, only 0.08 microgram/ml was transported across the placenta. Maternal concentrations of sulfamethoxazole of 29.6 and 127.7 micrograms/ml resulted in concentrations of 5.1 and 14.8 micrograms/ml on the fetal side, respectively. Thus, it would appear that trimethoprim is slowly transported across the placenta and in low concentrations whereas sulfamethoxazole readily crosses the placenta. The combination of these drugs is useful for treatment of bacteriuria. It may also prove to be especially useful for Pneumocystis carinii infections in pregnant women with AIDS. With a half-life of 13 h for trimethoprim and 6 h for sulfamethoxazole, the drugs are not likely to achieve toxic levels in the fetal compartment. Thus, it would appear that trimethoprim and sulfamethoxazole may be both efficacious and safe for the treatment of both these infections during pregnancy.

The effects of pentamidine isethionate on the developing embryo and fetus have not been previously published. Pregnant Sprague-Dawley rats were given various doses of pentamidine during the period of embryogenesis. Animals were killed on days 18 to 20 of pregnancy and their fetuses were removed by hysterectomy. Autopsies were performed on all fetuses. There were significant differences among groups with regard to maternal weight gain and pregnancy resorption. More pregnancy resorptions were noted in the group that received normal human doses (4 mg/kg/day) of pentamidine than in the control group (p less than 0.05). One structural anomaly consisting of unilateral renal agenesis was noted in the 711 fetuses examined. Skeletal survey of fetal rats was unremarkable. Pentamidine was without teratogenic effects in rats when administered in doses similar to those recommended for adult humans; however, it appears to have an embryocidal effect when given in those same doses during embryogenesis.

Although the administration of prophylactic antibodies for intrauterine transfusion is controversial, little information is available regarding placental transfer of antibiotics administered to the mother, or whether the presence of hydrops affects this placental transfer. Sixteen intravascular intrauterine transfusions were performed in 10 patients. Seven (10 procedures) patients were given 2 gm of cefazolin before the procedure and samples were obtained by fetal vascular access. Three patients (six procedures) were given 4 gm of piperacillin and samples were similarly obtained. Specimens were obtained for fetal serum, maternal serum, and amniotic fluid antibiotic concentration. The mean serum cefazolin concentration in hydropic fetuses was 18.04 +/- 3.37 micrograms/ml, and in nonhydropic fetuses the concentration was 21.02 +/- 17.8 micrograms/ml (p = 0.72). The mean fetal serum concentration of piperacillin was 22 +/- 12 micrograms/ml. The placental transfer of both drugs was similar. We conclude that the transplacental passage of these antibiotics is prompt and that the presence of hydrops does not significantly impair the passage of cefazolin.

Moxalactam is a newer beta-lactam antibiotic with increased activity and an extended antimicrobial spectrum. Three 1 gm doses were given to women scheduled for elective vaginal hysterectomy. This perioperative regimen was prospectively compared to identical doses of cefazolin, a first-generation cephalosporin of proved efficacy. The overall incidence of major postoperative infection in 193 women was less than 5% and there were no significant interregimen differences. The incidence of major infection was directly related to the type of procedure performed.

Uptake and incorporation of L-leucine-C14 and L-cystine-S35 was studied in the mycelial [MP] and yeastlike [YP] phases of the dimorphic fungal pathogen,Blastomyces dermatitidis. Both amino acids entered the cells of the two morphological forms ofB. dermatitidis by a permease-like system at low external concentrations of substrate. At high substrate levels, the amino acids entered the cells by a simple diffusion-like process in addition to the permease-like system. Michaelis-Menten constants [Km] for L-leucine was found to be 1.1×10−5 M and 4.4×10−5 M for the MP and YP phases, respectively. The Km for L-cystine was found to be 1.0×10−5 M for the MP and 0.5×10−5 M for the YP. A requirement for energy supplied by metabolic activity was demonstrated by the inhibition of uptake and incorporation of the amino acids by cells incubated with either 2,4-dinitrophenol or sodium azide. Amino acid uptake was broadly tolerant of hydrogen ion concentration, but definite optima were demonstrated at pH 7.0 to 7.5.

A method for the determination of methicillin, oxacillin, cloxacillin, dicloxacillin, and nafcillin in serum using high-pressure liquid chromatography (HPLC) is described. The drugs were extracted from serum using a two-step procedure employing acetonitrile followed by methylene chloride. The extraction procedure concentrated the antibiotics in a smaller volume which allows more accurate determinations of low serum levels. The treated sera were analyzed by HPLC on a reverse-phase column and detected by ultraviolet light absorption at 254 nm. Serum concentrations were measurable as low as 0.5 μg/ml. Recovery procedures showed less than 2.5% variation in peak heights when the antibiotics were extracted from different pools of serum. No interfering absorption was found in extracts of serum samples pooled from healthy volunteers, from a commercial source, or from two serum pools from patients receiving a variety of other drugs. Two spiked serum specimens prepared for each antibiotic were assayed four...

Two hundred fourteen women having vaginal or abdominal hysterectomy were entered into a prospective, randomized, blind clinical trial comparing a preoperative intravenous dose of piperacillin to three perioperative intravenous doses of cefoxitin given over an eight-hour period. Interregimen clinical, surgical, and outcome variables of the 207 evaluable subjects were statistically similar, but there were significant interprocedure differences in a variety of categories; many benefits exist when vaginal hysterectomy is possible. Efficacy of a single dose of piperacillin was similar to that of three cefoxitin doses. Seven women (3.4%) had major postoperative infection requiring parenteral antimicrobial therapy, two (1.9%) after vaginal hysterectomy and five (4.8%) after abdominal hysterectomy. Three of the latter five infections (60%) occurred after discharge from the hospital. Even with prophylaxis, postoperative anemia was associated with increased frequency of infection at the operative site after both procedures, and diabetes was associated with late infection of the abdominal incision after abdominal hysterectomy.

A total of 1140 aerobic and anaerobic isolates were recovered from cultures of specimens from the reproductive tracts of 435 uninfected patients who underwent elective hysterectomy. Standard minimum inhibitory concentration susceptibility studies were performed on these isolates to 13 newer penicillins, cephalosporins, and some traditional antimicrobial agents. These data were generated to evaluate the in vitro efficacy of these antibiotics for potential use in prophylaxis or as a single agent for treatment of polymicrobial infections of the female pelvis. The minimum inhibitory concentration data for each antibiotic against 16 genera of aerobic and nine genera of anaerobic bacteria were determined and were used to compare the in vitro antimicrobial activity of newer antibiotics to that of the more traditional antibiotics. Of the antimicrobial agents tested, piperacillin had the highest in vitro activity against these isolates of any antibiotic tested.

The pharmacokinetics of intravenous ampicillin and sulbactam, a beta-lactamase inhibitor, were evaluated in two different age groups. Twelve healthy elderly subjects (age 65-93 years) and 12 healthy young adult subjects (age 20-35 years) received both a dose of ampicillin 1 g plus sulbactam 0.5 g and a higher dose of ampicillin 2 g plus sulbactam 1 g after a one-week period between doses. A reverse-phase high-pressure liquid chromatography method was used for the quantitation of ampicillin and sulbactam in serum and urine. The pharmacokinetic parameters for both ampicillin and sulbactam were calculated by computer-based two-compartment nonlinear model. After a 30-min infusion, serum concentrations of both drugs declined in a biexponential manner for both doses. Elderly subjects demonstrated significantly lower total clearances (Clt) than young adult subjects of ampicillin 1 g (220.0 +/- 104.2 vs 360.0 +/- 95.8 ml/min/1.73 m2), ampicillin 2 g (72.6 +/- 36.6 vs 306.8 +/- 109.77 ml/min/1.73 m2), sulbactam 0.5 g (122.3 +/- 47.8 vs 263.9 +/- 93.7 ml/min/1.73 m2), and sulbactam 1 g (171.2 +/- 85.8 vs 391.7 +/- 70.8 ml/min/1.73 m2), respectively. Significance was defined as P less than 0.05. Renal clearance was also significantly reduced in the elderly subjects. Area under the curve was found to be significantly increased in the elderly subjects compared to the young subjects for both ampicillin and sulbactam as were the beta elimination half-lives. No significant difference in the apparent volume of distribution, when adjusted for body weight, was found for either sulbactam (P greater than 0.95) or ampicillin (P greater than 0.95) between the two groups. Linear regression analysis revealed that age was significantly correlated with the Clt of ampicillin 1 g (r = 0.85, P less than 0.001), ampicillin 2 g (r = 0.90, P less than 0.001), sulbactam 0.5 g (r = 0.80, P less than 0.001), and sulbactam 1 g (r = 0.93, P less than 0.001). A multivariate analysis showed a slight improvement in correlation when creatinine clearance was added to age and compared with Clt. Urinary recovery of both ampicillin and sulbactam was approximately 60% after 14 h.