Vocal Vibration Opening Onset Position Abnormality in Patients With Adductor Spasmodic Dystonia by Using High-Speed Endoscopy.

OBJECTIVE: To analyze vocal fold vibration onset in patients with adductor laryngeal dystonia (ADLD) by analyzing vocal vibration opening onset position (VVOOP). STUDY DESIGN: Case-control study SETTING: A voice center. METHODS: Eleven patients with ADLD diagnosed in our voice center were enrolled in the ADLD group. Eleven healthy subjects matched by exact age and gender to the ADLD patients were selected as the control group. All subjects underwent laryngeal high-speed video endoscopy. VVOOP and its change were assessed by two otolaryngologists. The multiline video kymography was used to analyze the open quotient (OQ) and standard deviation of OQ. RESULTS: VVOOP had more than one position in 54.6% (6/11) of the patients with ADLD, which was higher than the control group (P < 0.05). VVOOP appeared in the front of the vocal fold in 54.6% (6/11) of patients with ADLD and in the back of the vocal fold in 81.8% (9/11) of patients with ADLD. VVOOP can be abnormal in 90.9% (10/11) of patients with ADLD, and the rate of VVOOP abnormality was higher than that of the control group (P < 0.05). Of 11, 6 (54.6%) patients with ADLD had a variable VVOOP; the variability rate of VVOOP was higher than that in the control group (P < 0.05). OQ and OQ standard deviation in the ADLD group were significantly greater than in the control group (P < 0.05). CONCLUSIONS: In patients with ADLD, vocal fold vibration was irregular, and VVOOP was abnormal and had a variable position and could reflect variability of the vocal vibration. LEVEL OF EVIDENCE: Level 4.

Adenoid Cystic Carcinoma of Salivary Glands: A Ten-Year Review and an Assessment of the Current Management, Surgery, Radiotherapy, and Chemotherapy.

Adenoid cystic carcinoma (ACC) is a rare cancer that arises from the salivary glands and other sites in the body, such as the lung and breast. Although the tumor accounts for 10% of all salivary gland malignancies, it only accounts for 1% of head and neck malignancies. It can affect both major and minor salivary glands; here, it is called salivary gland adenoid cystic carcinoma or SACC, with a slight predilection to the latter, and commonly manifests between the 6th and 7th decades of life. The disease also shows a slight female predilection, with a reported female to male ratio of 3 : 2. Lesions of SACC are often insidious and slow-growing, and symptoms such as pain and altered sensation are frequently associated with advanced stages of the disease. Salivary adenoid cystic carcinoma is characterized by perineural invasion (PNI), a distinctive feature that potentially plays a significant role in the tumor's relapse and recurrence, which is approximately 50%. The disease is not prevalent, and its etiopathogenesis is poorly understood, although several genetic patterns and biomarkers have been linked to its initiation and/or progression. The discovery of these mutations and biomarkers has encouraged several clinical studies to use therapeutic agents to target the specific receptors on the cancer cells to potentially prevent further proliferation of the tumor cells and metastasis of the disease. Diagnosis of SACC is often challenging and frequently requires a combination of clinical examination, imaging, and histopathology. Management of SACC is primarily surgical excision, while radiotherapy has shown to be effective in improving local control in cases with microscopic residual disease. However, treatment of recurrent or metastatic tumors by radiotherapy with or without chemotherapy has so far shown limited success. The aim of this thesis is to provide an update of literature on SACC with a particular focus on the latest management approaches and future trends.

Exploring the Clinical Characteristics of Superior Laryngeal Nerve Injury.

OBJECTIVES: To observe the cases of superior laryngeal nerve injury along with summarizing and analyzing its clinical characteristics. METHODS: A total of 14 patients with unilateral superior laryngeal nerve injury (SLN) diagnosed by laryngeal electromyography (LEMG) in our department from 2018 to 2020 were collected as SLN injury group. A total of 14 healthy subjects with normal laryngeal electromyography were recruited as normal group matched by age and sex. The etiology and LEMG of the SLN injury group were analyzed, and the video stroboscopic manifestations of SLN injury group and normal group were compared to see the characteristic video stroboscopic manifestations of SLN injury. RESULTS: The most common causes of SLN injury were surgery and idiopathic etiology. Compared with normal group, the most frequent video stroboscopic manifestations of SLN injury group were vocal fold dyskinesia. Abnormal video stroboscopic manifestations occurred in normal group except larynx deviation, epiglottic petiole deviation, and dyskinesia. There was a significant difference between the two groups in various abnormal video stroboscopic manifestations (P < 0.05). Time limit widening was the most common manifestation of LEMG. CONCLUSIONS: Vocal fold dyskinesia was a prominent finding in SLN injury, laryngeal deviation and epiglottic petiole deviation were relative specific signs of SLN injury. Vocal fold bowing combined with shortening will contribute to the diagnosis of SLN injury. There were no specific diagnostic signs for SLN injury, clinicians need further LEMG for a firm diagnosis.

Maternal and perinatal outcome of eclampsia over a decade at a tertiary hospital in Kuwait.

AIMS: To determine maternal and perinatal outcome of eclampsia patients over a decade. METHODS: Analysis of case records of all eclampsia cases from January 2005 to December 2014. RESULTS: There were 30 cases of eclampsia. The most significant risk factors for developing pre-eclampsia are unbooked cases (97%), nulliparity, young age, marriage ≤4 months, history of pre-eclampsia in previous pregnancy, remarriage, preexisting diabetes mellitus, interval between pregnancies ≥10 years, positive family history. The incidence of eclampsia was 0.05%, antepartum eclampsia 15 (50%), intrapartum 6 (20%) and postpartum 9 (30%) with no maternal deaths, and 1 perinatal death. Perinatal mortality was 33.3/1000. 22 (73%) patients received magnesium sulphate (MgSO4) and 8 patients (27%) received Diazepam, of which 1 had recurrence of convulsions. All 15 antepartum cases were delivered by cesarean section as were 2 intrapartum. 13 (43%) of women delivered vaginally. Only 6 (20%) patients were of low socio-economic status and were primary school educated. Severe maternal complications occurred in 8 (27%), with abruptio placentae being the most common 3 (38%). CONCLUSIONS: Incidence of eclampsia was low, with no maternal deaths. MgSO4 was found to be highly effective. Lack of antenatal care is a major risk factor.

Is membrane sweeping beneficial at the initiation of labor induction?

OBJECTIVE: To determine whether cervical membrane sweeping during labor induction is beneficial. METHODS: Outcomes of labor after induction in pregnant women at term were compared in a randomized trial. Women were assigned to having their membranes "swept" or "not swept" at the initiation of labor induction. RESULTS: We recruited a total of 870 women of which 70 were excluded. There were 400 nullipara (Group A) [198 "swept", 202 "not swept"] and 400 multiparas (Group B) (201 "swept" and 199 "not swept"]. Among group A who received intravaginal prostaglandin (PG) E2, those who had simultaneous sweeping had significantly shorter mean induction-labor interval (12.9 ± 1.3 versus 16.2 ± 1.1 hours, p = 0.046), lower mean dose of oxytocin (6.6 ± 0.6 versus 10.11 ± 1.4 mU/minute, p = 0.01), and increased normal delivery rates (vaginal delivery 82.8% versus 58.6%, p = 0.01). Sweeping also had a favorable effect on nulliparas who had ARM and received oxytocin alone (mean induction-labor interval 5.9 ± 2.9 versus 10.9 ± 2.6 hours p = 0.04, mean maximum dose of oxytocin 9.8 ± 1.1 versus 15.2 ± 1.1 mU/min, p = 0.01). These results were restricted to women with unfavorable cervix in Group A those who had membrane sweeping. CONCLUSION: Membrane sweeping, has beneficial effects on labor and delivery, which is limited to nulliparas with unfavorable cervix requiring PGE2 or Oxytocin alone.

Induction of labor in grand multiparous women with previous cesarean delivery: how safe is this?

OBJECTIVE: To compare the outcome of induced and spontaneous labor in grand multiparous women with one previous lower segment cesarean section (CS), so that the safety of labor induction could be assessed. METHODS: In 102 women (study group), labor was induced and the outcome was compared with 280 women (control group) who went into spontaneous labor. All 382 women were grand multiparous and had one previous CS. RESULTS: There were no significant difference in oxytocin augmentation, CS, scar dehiscence, fetal birth weight or apgar scores between groups. There was one neonatal death, two still births, one early neonatal death and one congenital malformation in the study group and this was not significant. There was no significant difference in vaginal birth in the study (80.9%) and the control group (83.8%). CONCLUSION: In this moderate-sized study, induction of labor may be a safe option in grand multiparous women, if there is no absolute induction for repeating CS.

Motor-vehicle injury in pregnancy and subsequent feto-maternal outcomes: of grave concern.

OBJECTIVES: (1) To evaluate maternal and fetal outcome after motor-vehicle injury during pregnancy. (2) To determine if there was prenatal care provider counseling for seat belt use. METHODS: Retrospective chart analysis of materno-fetal outcome following motor vehicle injury in 728 pregnant women between 2009 and 2012. Women attending antenatal clinics over these years were asked if they were counseled regarding correct seat belt use by prenatal health care providers during their antenatal visits. RESULTS: In these pregnant women, 80 (11%) sustained minor injuries/sprains. 648 women (89%) had severe adverse materno-fetal pregnancy outcomes. Important causes being: (1) placental abruption 58.8%; (2) preterm labor (40%); and (3) uterine rupture (1.6%). There were 100 (13.7%) maternal and 78 (10.7%) fetal deaths. 91 (12.5%) perimortem cesarean deliveries were performed and 74 (81%) fetus survived, as did 31 women. Prenatal care provider counseling for seat belt use occurred in 44.8% of prenatal visit. Only 125 (21%) were using seat belt during the accident. CONCLUSION: Important causes of adverse pregnancy outcome were: abruptio placenta, preterm labor and uterine rupture. There were 100 maternal and 78 fetal deaths with 97 preterm births. Counseling occurred in 44.8% of women. Those using seat belts during the accidents sustained minor injuries.

Phylogenetic analysis of partial L1 gene of 10 human papillomavirus types isolated most commonly from women with normal and abnormal cervical cytology in Kuwait.

This study was undertaken to evaluate the presence of human papillomavirus (HPV) variants in cervical samples. L1 genetic variable region was studied in 10 HPV types: HPV 11, 16, 18, 33, 53, 54, 56, 61, 66 and 81. A total of 116 isolates were examined, including 47 HPVs isolated from women with normal cytology and 69 with abnormal cytology of different grades. HPV sequences were detected using MY09/MY11 consensus primers. Fifty silent and 65 missense mutations were detected. Two missense mutations were detected in HPV18, 3 in HPV56 and 17 in HPV61. The number of missense mutations per isolate ranged from 1 to 3, except in HPV54 and HPV61, where 7 and 11 missense mutations were found, respectively. Most of the isolates (52.3 %) with missense mutations were isolated from women with abnormal cervical samples. Low-grade squamous intraepithelial lesion cytology diagnosis dominated all cervical abnormalities. This study is the first on the identification of molecular variants in the Middle East and suggests the circulation of new HPV subtypes and variants in Kuwait, which needs to be confirmed by further analysis of the complete HPV genome.

Viral load of human papillomavirus in women with normal and abnormal cervical cytology in Kuwait.

INTRODUCTION: Human papillomaviruses (HPV) are the most commonly known sexually transmitted agents. Almost all cases of cervical cancer are caused by persistent infection. This study was conducted to ascertain whether there is a difference in HPV load in cervical samples with normal and abnormal cervical cytology reports in Kuwait. METHODOLOGY: HPV-positive abnormal ThinPrep samples (n = 206) and normal ThinPrep samples (n = 120) were taken from women attending gynecology clinics. Real-time PCR was used to measure the viral load for all HPV genotypes. RESULTS: The median normalized viral load in samples with normal and abnormal cytology reports was 0.86 × 10-7 and 4.66 × 10-7, respectively (p = 0.001). Median normalized viral load of high-risk (HR), intermediate-risk (IR) and low-risk (LR) HPV was 4.04 × 10-7, 0.71 × 10-7 and 2.38 × 10-7, respectively, (p = 0.002). CONCLUSIONS: The findings suggest that, in the absence of a proper screening programme in Kuwait, quantification of HPV viral load could be considered as a surrogate virology test to identify women with abnormal cytology. Further population-based prospective studies are needed to include more women with high-grade and invasive carcinoma reports.

Trends in maternal mortality over 29 years in a Kuwait Tertiary Teaching Hospital: signs of progress?

UNLABELLED: This study aims at (1) Assessing trends in maternal mortality in kuwait (2) Define strategies for prevention. METHODS: Retrospective analysis of maternal deaths that occurred among, 55,979 live births at a tertiary hospital, between 1980 and 2009. RESULTS: There were 14 maternal deaths, and 55,979 live births, giving a maternal mortality rate of 25 per 100,000 live birth. In terms of decades maternal mortality declined from 54.8 in 1980-90 to 28.4 in 1990-2000 and continued to decline to 12.2 in 2000-2009. Thromboembolism (28.6%), Obstetric haemorrhage (21.5%) and Eclampsia (14.3%) were the leading causes of direct deaths. Cardiac disease is the most common cause of indirect deaths (14.3%) followed by H1N1 pneumonia 7.1%. Eclampsia contributed to 40% of deaths, only in the 1980s. Thromboembolism caused 28.6% of deaths, 50% of which were in the last 9 years. Indirect deaths from cardiomyopathies (66.7%) gained prominence in the 1990s. No deaths from puerperal sepsis were reported after the 1980s (14.3%). CONCLUSIONS: Maternal mortality rates are decreasing significantly (p<0.01) at our institution over the last 29 years. Obstetric haemorrhage and thromboembolism remain important causes of maternal mortality. Substandard care was identified in 70% of Direct and 55% of indirect deaths.

A 26-year review of emergency peripartum hysterectomy in a tertiary teaching hospital in Kuwait - years 1983-2011.

OBJECTIVE: To identify the risk factors and study the incidence, indications and complications of emergency peripartum hysterectomy (EPH). MATERIALS AND METHODS: This was a retrospective case-control study. The cases consisted of all women who underwent EPH between January 1983 and January 2011. Two controls per case were randomly selected from the remaining deliveries by using a random number table. Case records were retrieved from the medical records. RESULTS: Among 150,993 deliveries, there were 59 EPHs (cases), giving a rate of 0.390 per 1,000. Of the 59 cases, only 56 were analysed because 3 files were unavailable. These women were older (mean age 36 ± 5.7 vs. 22 ± 5.3 years, p < 0.01) and had delivered more than 1 child (p = 0.02). Thirty-seven (66%) cases had had previous caesarean sections (CSs) and the number of CSs in this group was greater than in the controls (21%, p < 0.01). More index cases had a history of atonic postpartum haemorrhage (46 vs. 4%, p < 0.001) and placenta praevia (34 vs. 4%, p < 0.01). More cases than controls were delivered by CS (73 vs. 29%; p = 0.003). The leading indications for EPH were haemorrhage due to uterine atony and placenta praevia. Independent risk factors were older age, multiparity, history of one or more CSs and placenta praevia. There were 2 maternal deaths from coagulopathy following massive obstetric haemorrhage. The main complications of EPH were febrile morbidity: 12 (21%), wound infection: 8 (14%) and bladder or ureteric injury: 8 (14%). CONCLUSIONS: CSs, especially repeat CSs in women with placenta praevia and persistent uterine atony, significantly increased the risks of peripartum hysterectomy.

Influence of coconut oil administration on some hematologic and metabolic parameters in pregnant rats.

OBJECTIVE: Data on the effect of coconut oil intake on various hematologic and metabolic parameters in pregnant women or animals are scanty. Hence we attempted to assess the effect of oral administration of graded doses of this edible oil during pregnancy, on various hematologic and metabolic parameters in rats. METHODS: Groups of pregnant Sprague Dawley rats were given oral doses of 1 ml, 2 ml, and 4 ml coconut oil twice per day, respectively. Control group of rats were given tap water. Oral feeding of oil was done continuously for a period of 20 days and at the end of the study period the animals were lightly anaesthetized with ether and sacrificed to collect blood samples for analysis. Various hematologic parameters such as red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin (Hg), platelets, lymphocytes, and mean corpuscular hemoglobin concentration (MCHC) were analyzed by a hematology blood analyzer, while metabolic parameters such as cholesterol, triglycerides, urea, uric acid, creatinine, and protein were analyzed by specific analytical kits. Activities of antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant activity (TAO) were assessed by specific analytical kits. Statistical analysis of data was performed using a SPSS data analytical package. RESULTS: Oral administration of coconut oil for 20 continuous days of pregnancy did not significantly alter any of the hematologic parameters studied, compared to control group even when the oil was administered at a relatively massive dose of 4 ml/day. Administration of coconut oil appeared to decrease WBC, Hg, platelet, and lymphocyte blood concentrations in treated rats, but the difference, however, was not statistically significant (ANOVA test; p > 0.05). However, platelet concentration was significantly lower (p < 0.05) in rats receiving 1 ml/day of coconut oil compared to control group rats. Administration of coconut oil did not alter the concentrations of protein, cholesterol, urea, triglycerides, uric acid, and creatinine in treated groups of rats significantly (Student's t-test, p > 0.05) compared to those of control rats. SOD, GPX, and TAO levels in control and treated groups were not significantly different (ANOVA test, p > 0.05) than controls. CONCLUSIONS: We conclude that oral administration of coconut oil during pregnancy in rats, even in massive doses, does not cause any significant alterations in hematologic and metabolic parameters. More detailed studies, however, are warranted before extrapolating these results to human situations.

Female circumcision: obstetrical and psychological sequelae continues unabated in the 21st century.

OBJECTIVES: To assess the incidence of female circumcision/female genital cutting (FGC) among pregnant women and describe the obstetrical and psychological sequelae of female circumcision. METHOD: Four thousand eight hundred pregnant women over a 4-year period were assessed for female circumcision. Odd ration (OR) and 95% confidence interval (CI) were calculated to measure association between female circumcision, maternal morbidity, and birth outcome. Variables included prolonged maternal hospitalization, low birth weight, prolonged labor, obstructed labor, cesarean section, and fetal outcome. Assessment measures to determine cognitive and emotional effects included the Mini international Neuro-psychiatric interview and Rey memory test. RESULTS: The prevalence of female circumcision was 38%; women who were circumcised were more likely have extended hospital stay. There was a positive association between such women and prolonged labor, cesarean section, post-partum hemorrhage, early neonatal death, and hepatitis C infection. Psychiatric sequelae included: 80% continued to have flashbacks to the FGC event; 58% had a psychiatric disorder (affective disorder); 38% had other anxiety disorders, and 30% had post-traumatic stress disorder. CONCLUSION: Female circumcision is associated with adverse materno-fetal outcome and psychiatric sequelae. Many will need psychiatric as well as gynecological care.

Uterine rupture and subsequent pregnancy outcome--how safe is it? A 25-year study.

OBJECTIVES: (a) To review the cases of ruptured uterus over the last 25 years and analyze the causative factors with a view to its prevention (b) To analyze subsequent pregnancy outcome with a view to its safety. METHOD: The case notes were reviewed for all patients with ruptured uterus over a period of 25 years from January 1982 to January 2007. Relevant dates relating to the characteristics of labor, delivery, maternal, perinatal, and subsequent pregnancy outcomes were assessed. RESULTS: The incidence of ruptured uteri was calculated to be 0.03%. Total deliveries included in the study were 152,426. There were 46 cases of ruptured uteri and 44 were available for study. Twenty-two (52%) ruptured uteri occurred in patients with previous caesarean scars, of which 10 occurred in women with previous four or more caesarean sections. In 12 cases (27%), uterine rupture occurred due to oxytocin; PGE2 and oxytocin were used in 3 of these 12 cases. Two (4.5%) ruptures occurred due to non-removal of cervical cerclage during labor. Two (4.5%) primigravidae ruptured their uterus following road traffic accident, resulting in maternal and fetal deaths. Malpresentation in labor resulted in eight (18%) ruptures. Rupture occurred at the fundus in 10 cases and in the lower segment in the remaining 34. Fetal heart abnormalities were observed in all cases in which the uterus ruptured during labor. Abdominal hysterectomy was performed in 20 cases (45%) of which 13 were subtotal and 7 (10%) were total. Of the remaining 24 (55%) patients, 10 had suture repair and in addition 14 patients underwent hypogastric artery ligation. Later, 22/24 (92%) women became pregnant. Twenty (91%) were delivered by planned caesarean section. There were no maternal or fetal complications. The remaining two women had previous classical scar, undetected malpresentation, and sparse antenatal care. Their uteri ruptured spontaneously at 32 and 35 weeks at home. They died intra-operatively due to intractable hemorrhage along with their fetus. CONCLUSION: In the previous caesarean section, the indiscriminate use of oxytocin and malpresentation are the risk factors for uterine rupture. Child birth after uterine rupture is not to be recommended routinely. Most women with a previous uterine rupture with meticulous tertiary level antenatal care had a favorable outcome in subsequent pregnancies.

Actions needed to improve maternal health.

The health of mothers and their children is of critical importance, both as a reflection of the current health status of a large segment of the world's population and as a predictor of the health of the next generation. A range of indicators of maternal and neonatal health exist-those primarily affecting pregnant and postpartum women, and those affecting the health and survival of infants. Pregnancy outcome may be affected by toxicant exposure, maternal habits, occupational hazards, psychosocial factors, socioeconomic status, racial disparity, chronic stress, and infections. An increase in obstetric pathologies related to lifestyle, environment, aging, and diet has been seen in Western countries. Large segments of the population are obese and this factor is associated with a great number of adverse reproductive health outcomes. In other countries, the most important objective is to reduce the incidence of infectious diseases and their transmission from mother to fetus. AIDS remains the leading cause of death of children worldwide.

Transport kinetics of cisplatin in the perfused human placental lobule in vitro.

OBJECTIVE: Platinum-containing drugs are used extensively in the treatment of various malignancies in humans. Data are scarce on the maternal-fetal transport characteristics in humans of one such widely used drug, cisplatin, and this prompted us to study its transport characteristics in the human placenta in vitro. METHODS: Placentae from normal pregnancies were collected after delivery. Cisplatin, along with antipyrine as an internal reference marker, was injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution, was used as the perfusate. The concentration of cisplatin in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was quantified by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. RESULTS: The differential transport rate of cisplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.49 +/- 0.02, 1.23 +/- 0.03, 2.41 +/- 0.04, 3.67 +/- 0.03, and 4.48 +/- 0.07 minutes in 12 perfusions, while corresponding rates for antipyrine, for above mentioned efflux fractions averaged 0.51 +/- 0.01, 1.26 +/- 0.05, 2.52 +/- 0.01, 3.78 +/- 0.01, and 4.52 +/- 0.01 minutes, respectively. Cisplatin transport rates averaged 0.97, 0.97, 0.96, 0.97, and 0.99 times the antipyrine reference value. Analysis of variance (ANOVA) did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of cisplatin, expressed as a fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.6 +/- 2.01% of injected bolus dose, representing 13.10% of reference marker value. The Student's t-test showed cisplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, and elimination rate of study and reference substances also varied significantly (p < 0.05). CONCLUSIONS: We report for the first time that cisplatin transport is negligible in the human placenta at term. It is reasonable to assume that the risk for the neonate from cisplatin use in pregnancy is minimal when it is used in emergency clinical situations.

Maternal-fetal transport kinetics of carboplatin in the perfused human placental lobule: in vitro study.

OBJECTIVE: Platinum-containing drugs are widely used in the treatment of various malignancies in humans. There is a paucity of data on maternal-fetal transport characteristics of one such widely used drug, carboplatin, and this prompted us to study its permeation characteristics in the human placenta in vitro. METHODS: Placentae from uncomplicated, normal pregnancies were collected postpartum. Carboplatin, along with antipyrine as internal reference marker were injected as a single bolus (100 ul) into the maternal arterial circulation of isolated perfused placental lobules and perfusate samples collected from both maternal and fetal circulations over a period of 5 minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Carboplatin concentration in various samples was determined by atomic absorption spectrophotometry, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using appropriate parameters. RESULTS: The differential transport rate of carboplatin for 10, 25, 50, 75, and 90% efflux fractions in fetal venous effluent averaged 0.60, 1.35, 2.52, 3.72, and 4.49 minutes in 12 perfusions, representing 1.16 +/- 0.10, 1.06 +/- 0.06, 1.00 +/- 0.02, 0.98 +/- 0.01, and 0.99 +/- 0.01, respectively, times the antipyrine reference value. Student's t-test did not show any significant difference (p > 0.05) between the control and study group data. The transport fraction (TF) of carboplatin, expressed as the fraction of the drug appearing in the fetal vein during a study period of 5 minutes, averaged 9.00 +/- 0.52% of bolus dose, while antipyrine TF averaged 68.60 +/- 2.01% of injected bolus dose, representing 13.1% of reference marker value. Student's t-test showed carboplatin and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, and absorption and elimination rates of study and reference substances showed varying differences. CONCLUSIONS: We report for the first time that carboplatin transport from the maternal to the fetal circulation is relatively small in the human placenta at term. It is reasonable to assume that the risk for the neonate from carboplatin use in pregnancy is minimal when used in emergency clinical situations.

Maternal-fetal transport kinetics of methotrexate in perfused human placenta: in vitro study.

OBJECTIVE: Folate antagonists are widely used in the treatment of diverse cancerous states. A paucity of data on transport characteristics of one such widely used drug, methotrexate, in the human placenta, prompted us to study its permeation characteristics in vitro. METHODS: Placentas from normal pregnancies were collected post-partum. Methotrexate, along with antipyrine as reference marker were injected as a single bolus (100 microL) into the maternal arterial circulation of isolated perfused placental lobules; perfusate samples were collected from both maternal and fetal circulations over a study period of five minutes. National Culture and Tissue Collection medium, diluted with Earle's buffered salt solution was used as the perfusate. The concentration of methotrexate in various samples was determined by high performance liquid chromatography, while antipyrine concentration was assayed by spectrophotometry. Transport and pharmacokinetic data of study and reference substances were computed using standard parameters. RESULTS: Differential transport rate of methotrexate for 10, 25, 50, 75 and 90% efflux fractions in fetal venous effluent averaged 0.52, 1.30, 2.37, 3.57 and 4.43 minutes in 12 perfusions, representing 1.01 + 0.08, 1.03 + 0.06, 0.95 + 0.03, 0.93 + 0.03, 0.93 + 0.03 respectively times antipyrine reference value. Student's t-test showed varying differences between the control and study group data. Transport Fraction (TF) of methotrexate, expressed as fraction of the drug appearing in fetal vein, during study period of 5 minutes averaged 24.00 + 2.50% of bolus dose while antipyrine TF averaged 68.73 + 2.01% of injected bolus dose, representing 24.00 percent of reference marker value. Student's t-test showed methotrexate and reference marker TF values to be significantly different (p < 0.05). Pharmacokinetic parameters such as area under the curve, clearance, time for maximum response, absorption and elimination rates of study and reference substances showed varying differences. CONCLUSIONS: We report for the first time that the transport of methotrexate from maternal to fetal circulation is not negligible in human placenta at term. It is reasonable to assume that a direct risk for the fetus from methotrexate use in pregnancy cannot be excluded, and caution is warranted when it is used in emergency clinical situations.

Maternal-fetal status of copper, iron, molybdenum, selenium, and zinc in obese pregnant women in late gestation.

Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Further, obese women are more prone to have babies born with congenital abnormalities. Paucity of data on maternal-fetal disposition of essential trace elements in obese pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous samples were collected from obese patients (body mass index >30) and control pregnant women (body mass index <25) at time of spontaneous delivery or cesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se, and Zn determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase, glutathione peroxidase, and total antioxidant activity in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-fetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se, and Zn in the serum of control pregnant women at time of delivery averaged 2232.6, 2398.1, 10.9, 108.9, and 661.9 microg/L respectively, whereas in the obese group, the values of the above elements averaged 2150.3, 2446.8, 12.6, 96.8, and 838.9 microg/L respectively. Umbilical vein/maternal vein ratios of Cu, Fe, Mo, Se, and Zn in the control group averaged 0.29, 1.93, 1.06, 0.76, and 1.12, respectively, whereas in the obese group, their fetal-maternal ratios averaged 0.32, 2.23, 1.06, 0.78, and 1.53, respectively. The Cu : Zn ratio in the maternal vein of the obese group (3.60 +/- 0.20) was significantly lower (Student's t-test; p < 0.05) than that of the controls (2.50 +/- 0.19); however, Cu : Fe ratio (1.04 +/- 0.08 vs 1.02 +/- 0.09) was not significantly different (Student's t-test; p > 0.05) in the two groups. Varying differences were noted in the case of antioxidant enzyme activities between the control and study groups. We conclude that obesity is associated with alterations in maternal-fetal disposition of some essential trace elements and antioxidant enzyme status and that these alterations could pose a potential health risk for the mother as well as the fetus.