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Biomedical subjects

Sabaratnam Arulkumaran

Publications and source records attributed to Sabaratnam Arulkumaran.

At least 19 recordsLinked to original sources

Postpartum hemorrhage.

Postpartum hemorrhage (PPH) is the most important single cause of maternal death in both developing and developed countries. It arises from abnormalities in one of four basic processes, with uterine atony being the most common. A multidisciplinary approach to management is important. The value of oxytocin and prostaglandins, including misoprostol, in treatment is discussed. Recently developed, less invasive treatment options, namely uterine tamponade and compression sutures, are fast becoming valuable alternatives to the traditional options of pelvic devascularization and hysterectomy. With a stark contrast in maternal mortality from PPH between the developing and developed countries, public health strategies and medical interventions intended to minimize this are further discussed.

Embolization, Therapeutic↗

Head injuries after instrumental vaginal deliveries.

PURPOSE OF REVIEW: The types, mechanisms and clinical manifestations of head injuries (extracranial, cranial and intracranial) after instrumental delivery are described along with current evidence of their prevention and management. RECENT FINDINGS: Asymptomatic subdural hematomas can occur in up to 6.1% of uncomplicated vaginal deliveries. Maternal nulliparity, incorrect placement of vacuum extraction cup and failed vacuum extraction are predisposing factors to subgaleal hemorrhage. Injuries associated with the vacuum devices may be minimized if the recommended limits for a safe traction force are not exceeded. There is no difference in the incidence of scalp trauma between vacuum deliveries by a rigid plastic cup (Omnicup) and the standard, silastic cup. The use of a metal cup may increase the occurrence of head injuries. Protective covers over forceps reduce the rates of neonatal facial abrasions and skin bruises. There is no difference in the incidence of cephalhematoma comparing a sequential operative vaginal delivery and a caesarean section following a failed vacuum delivery. SUMMARY: Instrumental vaginal deliveries carry substantial risks. Only practitioners who are adequately trained or are under supervision should undertake instrumental delivery. The mode of intervention needs to be individualized after consideration of the operator's skills and experience and the clinical circumstances.

Birth Injuries↗

Progesterone enhances the tocolytic effect of ritodrine in isolated pregnant human myometrium.

OBJECTIVE: To evaluate the effect of natural progesterone on the relaxant effect of ritodrine on pregnant human oxytocin-induced myometrial contractility. STUDY DESIGN: Isometric tension recordings were performed under physiologic conditions on isolated myometrial strips taken from low-risk term pregnant women undergoing elective cesarean section. Cumulative effects of natural progesterone (10 (-11) to 10 (-5) mol/L) on oxytocin-induced myometrial contractility were evaluated. Contractile activity following ritodrine exposure was also investigated in myometrium pretreated with natural progesterone. RESULTS: Natural progesterone alone exerted a concentration-dependent relaxant effect on myometrial contractions. The concentration-response curve for ritodrine from natural progesterone pretreated myometrium was shifted to the left with a significant reduction ( P < .01) of 50% of the maximal response, contraction amplitude ( P < .05), and frequency ( P < .05). However, there was no significant difference in the mean maximal inhibition achieved ( P = .95). CONCLUSION: Natural progesterone increased the relaxant effect of ritodrine by reducing 50% of the maximal response, amplitude, and frequency of myometrial contraction, most likely through nongenomic actions. These results suggest that natural progesterone may be beneficial for preventing preterm birth in a low-risk population.

Adrenergic beta-Agonists↗

Acute tocolysis.

PURPOSE OF REVIEW: Emergency uterine relaxation may decrease the morbidity and mortality of the mother and her fetus. Obstetricians need to be aware of the indications, pharmacological methods, efficacy and complications of acute tocolysis. RECENT FINDINGS: A variety of pharmacological agents are used to suppress uterine contractions. Newer agents like cyclo-oxygenase-2 inhibitors (Celecoxib) and oxytocin antagonists (atosiban) have been introduced into clinical practice with the hope of reducing the complications of betasympathomimetic drugs. Calcium-channel blockers are used but there are recent case reports of acute pulmonary oedema with the use of these agents. Most of the trials on tocolytics have been for suppression of preterm labour. Nitroglycerin has been used successfully as an acute tocolytic during Caesarean sections and manual removal of placenta. A recent randomized trial has suggested that atosiban may be an option for acute intrapartum tocolysis. This article will review the recent literature on the use of pharmacological agents used to suppress uterine contractions in emergency obstetric situations. SUMMARY: Acute tocolysis may be indicated in antepartum, intrapartum and postpartum periods for a variety of indications. It may help reduce maternal and fetal morbidity and mortality. The ideal tocolytic is yet to be developed. Research is needed to develop a drug which has a greater uterospecificity with no effect on other organs with a rapid onset and a short duration of action.

Emergency Medical Services↗

Does the route of administration of misoprostol make a difference? The uterotonic effect and side effects of misoprostol given by different routes after vaginal delivery.

OBJECTIVE: To compare the postpartum uterotonic effect and side effects of misoprostol administered by different routes. STUDY DESIGN: Fifty women were given misoprostol 400 microg either by the oral solution, oral tablet, rectal or vaginal route, or intramuscular syntometrine 1 ml after spontaneous vaginal delivery. Pre- and post-treatment uterine activity were measured with intrauterine pressure catheters. RESULTS: Uterine activity produced by oral solution misoprostol 400 microg was significantly higher than that of oral tablet, rectal and vaginal misoprostol (P = 0.004, 0.002, respectively). Onset of action after oral solution misoprostol was faster than by the oral tablet (P = 0.01), rectal (P < 0.001) and vaginal (P< 0.001) routes. Shivering and pyrexia were most common with oral solution misoprostol. Maximum body temperature recorded was significantly higher with oral solution misoprostol than with oral tablet, rectal and vaginal misoprostol (P = 0.009, 0.001, respectively). CONCLUSION: Different routes of administering misoprostol greatly influence the effects achieved. Oral solution misoprostol produces the fastest and strongest uterotonic effect, with the most side effects.

Administration, Intravaginal↗

Relaxant action of sildenafil citrate (Viagra) on human myometrium of pregnancy.

OBJECTIVE: The purpose of this study was to investigate the effect of the cyclic guanosine monophosphate phosphodiesterase 5-specific inhibitor, sildenafil citrate, on the contractions of isolated pregnant human myometrium. STUDY DESIGN: Myometrial samples were obtained from women who underwent elective cesarean delivery. Myometrial contractions that were recorded in response to sildenafil in the absence and presence of the potassium channel blocker, tetraethylammonium or the guanylate cyclase inhibitor, methylene blue (10 micromol/L) were studied. One-way analysis of variance with post-hoc analysis was used to test differences among groups. RESULTS: Sildenafil caused relaxation of myometrium in a concentration-dependent manner. The log(10) EC(50) value for this relaxation in the presence of 20 mmol/L tetraethylammonium was significantly different (P<.01) than values that were obtained with sildenafil alone or sildenafil in the presence of either methylene blue or 5 and 10 mmol/L tetraethylammonium. CONCLUSION: Myometrial relaxation that is evoked by the direct application of sildenafil occurs independently of cyclic guanosine monophosphate. Potassium channels appear to be the likely candidates in mediating this response.

Cyclic GMP↗

Current strategies for the prevention of postpartum haemorrhage in the third stage of labour.

PURPOSE OF REVIEW: Despite evidence that active management of the third stage of labour reduces the incidence of postpartum haemorrhage, expectant management is still widely practised. Factors accounting for this situation include the desire for a more natural experience of childbirth, the philosophy that active management is unnecessary in low-risk women, and avoidance of the adverse effects of conventional uterotonic agents. This review will evaluate the various strategies currently used for the prevention of primary postpartum haemorrhage. RECENT FINDINGS: Since publication of the first systematic review comparing active with expectant management in 1988, active management of the third stage using oxytocics has become increasingly adopted. Recent surveys, however, show that there are still wide variations in practice around the world. Recent interest has focused on the use of misoprostol for the prevention of postpartum haemorrhage. Carbetocin, an oxytocin receptor agonist, shows promise but has not been evaluated for use after vaginal births. SUMMARY: Active management of the third stage of labour is superior to expectant management in terms of blood loss, postpartum haemorrhage and other serious complications, but is associated with unpleasant side effects and hypertension when ergometrine is included. Intramuscular oxytocin results in fewer side effects. Oral and rectal misoprostol has been extensively assessed and found to be less effective than conventional oxytocics with more side effects. Until alternative regimes of misoprostol are studied in large controlled trials, misoprostol is not recommended for routine use in the third stage of labour. Of the remaining uterotonic agents evaluated, intramuscular carbetocin appears the most promising.

Delivery, Obstetric↗

Misoprostol: a quarter century of use, abuse, and creative misuse.

Misoprostol is a prostaglandin E1 analog originally intended for use to prevent NSAID-induced gastric ulcers. However, because of its cervical ripening and uterotonic property, misoprostol has become one of the most useful drugs in obstetrics and gynecology. Misoprostol has proven to be a very convenient and flexible drug because of its formulation as a tablet that is stable and that can be administered orally, rectally, vaginally and by the sublingual route. Beginning with its abuse for illegal abortion in the late 1980s, misoprostol has quickly become established as one of the most effective drugs for terminating pregnancies in the first and second trimesters, as well as for inducing labor in the third trimester. Its use for routine prevention of postpartum hemorrhage has not been so successful, partly as the high doses required for this indication often result in troublesome side effects. Despite the large body of medical evidence about its efficacy and relative safety, the use of misoprostol in pregnant women remained off-label until the spring of 2002.

Abortifacient Agents, Nonsteroidal↗

Fetal scalp pH and ST analysis of the fetal ECG as an adjunct to CTG. A multi-center, observational study.

OBJECTIVE: To evaluate the relationships between scalp-pH and CTG plus ST waveform analysis of the fetal ECG (STAN) clinical guidelines as indicators of intrapartum hypoxia in term fetuses born with cord artery acidemia. STUDY DESIGN: Data from 6999 term deliveries monitored by the STAN (R) S 21 as part of an EU multi-center study on clinical implementation of the STAN methodology for intrapartum fetal surveillance were analyzed. We identified 911 cases where a scalp-pH was obtained, including 53 cases with cord artery acidemia (pH < 7.06). Lag times between ST events and scalp-pH and time to delivery were related to cord artery metabolic and respiratory acidosis and neonatal outcome. RESULTS: 43 fetuses were identified by CTG plus ST as being in need of intervention 31 (25-46) minutes before delivery (median, 95% Cl). In five, no indications were given and in another five there were inadequate data. Fifteen cases with metabolic acidosis required special neonatal care, all 14 cases adequately monitored on STAN had indications to intervene for 19 minutes or more. In 30 adequately recorded cases, fetal blood sampling (FBS) was obtained within the last hour of labor. In 22 cases, FBS was obtained 13 (7-24) minutes after STAN guidelines had indicated abnormality and in eight no ST changes had occurred at time of FBS. The corresponding FBS data were pH 7.10 (7.01-7.15) and pH 7.21 (7.08-7.31), respectively, P = 0.01. In cases of metabolic acidosis, scalp-pH fell 0.01 units per minute after a baseline T/QRS rise was recorded during the second stage of labor. Apart from one newborn that died at 2 h from E. Coli septicemia, none of the neonates were affected neurologically. CONCLUSION: Cardiotocography plus ST analysis provides accurate information about intrapartum hypoxia similar to that obtained by scalp-pH.

Acidosis↗

Comparison of potassium currents in human decidua before and after the onset of labor.

The human decidua plays a prominent role in the signaling between maternal and fetal tissues. It also secretes a plethora of molecules that modulate uterine function. Ion-channel activity underpins many cellular functions; however, the channels in human decidua have not been characterized in any detail. We have used the whole-cell recording mode of the patch-clamp technique to carry out current-clamp and voltage-clamp recordings of membrane properties and whole-cell potassium (K+) currents of freshly isolated decidual stromal cells. Decidual tissue was obtained from women after spontaneous vaginal delivery (SVD) or elective cesarean section (CS). Cells from both groups generated action potentials, the overshoots and durations of which were dependent on extracellular calcium levels, inhibited by cobalt and enhanced by barium. Potassium current (IK) density was higher in the CS than in the SVD group. Outwardly directed currents were heterogeneous with respect to their activation/inactivation profiles and exhibited outward rectification. The main difference between the SVD and CS group was the presence of a sustained current component in CS cells that is tetraethylammonium chloride-resistant and appears to be unaffected by E-4031. No evidence for the activation of any calcium-activated K+ currents was obtained. We propose that human parturition is associated with subtle changes in K+ channel remodeling, reflecting the transition from uterine quiescence to activation and stimulation. An understanding of the signal transduction events underlying these process may eventually lead to novel approaches to prevent preterm labor via decidual rather than myometrial intervention.

4-Aminopyridine↗

Medical and conservative surgical management of postpartum hemorrhage.

Massive postpartum hemorrhage (PPH) is a major cause of maternal mortality in the United Kingdom and worldwide. Life-threatening PPH occurs with a frequency of 1 in 1000 deliveries in the developed world. In the latest triennial Why Mothers Die: Confidential Enquiries into Maternal Deaths in the United Kingdom (1997-1999), PPH was the fifth most common cause of maternal mortality. In this review, we discuss the role of medical management in primary PPH and the use of the "tamponade test" when such management fails. The less radical surgical options discussed include uterine compression sutures, uterine or internal iliac artery ligation, and arterial embolization, all of which have the advantage of potentially preserving reproductive function. Radical surgical options, including subtotal or total hysterectomy, are not discussed in this review. A systematic or algorithmic method of tackling the problem is described. The suggested management approach is likely to reduce maternal morbidity from bleeding, hysterectomies, and maternal deaths.

Arteries↗

Pituitary and adrenal disorders complicating pregnancy.

PURPOSE OF REVIEW: Confidential enquiries of maternal deaths in the UK for 1997-1999 revealed that the number of indirect deaths from medical conditions exacerbated by pregnancy was greater than deaths from conditions directly caused by pregnancy. Indirect maternal deaths accounted for 36% of all deaths. Although neoplastic disorders of the pituitary and adrenal glands are very rare during pregnancy, they can be potentially fatal. The rarity of these disorders may pose difficulty in formulating an optimum plan of management. Biochemical tests that can be performed in the non-pregnant state may be of little value during pregnancy. The presence of a fetus may also influence the type and timing of intervention. RECENT FINDINGS: A few case reports have been reported in the literature, but unfortunately no large series to develop guidelines or protocols. However, endoscopic surgical procedures have recently been used in their management with good outcomes. New drugs such as octreotide and lanreotide are increasingly being used during pregnancy. Although too soon to assess the safety of these new treatments, results so far have been very encouraging. SUMMARY: Awareness of these potentially fatal neoplastic disorders of the pituitary and adrenal glands, coupled with early diagnosis and appropriate treatment, may help improve maternal and fetal outcomes. Advances in imaging techniques and endoscopic procedures are also likely to change clinical practice. Various new treatment options are being reported in the literature, but they are not supported by randomized, controlled trials. Further research is needed to determine their safety and efficacy during pregnancy.

Adrenal Gland Neoplasms↗

Neonatal subgaleal hemorrhage and its relationship to delivery by vacuum extraction.

Subgaleal hemorrhage is a rare condition of the neonate often associated with instrumental delivery. It is a potentially fatal condition that is often underreported and underdiagnosed. The vacuum extractor is being advocated as the instrument of first choice for assisted vaginal delivery, but appears to be associated with an increased incidence of subgaleal hemorrhage. It is widely believed that the vacuum cup will dislodge before causing serious fetal trauma. Because of the ease of application, vacuum extractors could be used potentially in circumstances in which forceps would not be attempted, allowing an operator of average experience to perform rotational deliveries. The worrisome increase in the incidence of subgaleal hemorrhage associated with vacuum extraction leads to the issuance of warnings from governmental authorities in Canada and the United States. This review discusses the anatomy of this lesion, etiology, clinical presentation, management, and possible prevention.

Birth Injuries↗

Reduced expression of immunoreactive beta2-adrenergic receptor protein in human myometrium with labor.

A considerable body of evidence exists suggesting that the beta(2)-adrenergic receptor (beta(2)-AR) mediates uterine relaxation. However, little information exists on the localization, distribution, or expression of beta(2)-ARs in the human myometrium during the nonpregnant to labor transition. We have used immunochemical methods to investigate beta(2)-AR localization and expression in the nonpregnant, term pregnant, and term parturient uterus. Myometrial biopsies were obtained from 1) nonpregnant, menstruating women undergoing hysterectomy; 2) singleton term pregnant women undergoing elective cesarean section before the onset of labor; or 3) singleton term pregnant women undergoing emergency cesarean section after spontaneous labor. Tissues were processed for immunohistochemistry, immunofluorescence, and Western blotting and a primary polyclonal antibody specific to the human beta(2)-AR to identify immunoreactive myometrial beta(2)-AR. Protein levels were subsequently quantified by densitometry relative to rat brain protein. Immunohistochemistry and immunofluorescence demonstrated the presence of beta(2)-AR predominantly at the plasma membrane and also in the cytosol of myometrial cells. A 2-fold decrease in protein levels of the beta(2)-AR was apparent in the myometrium of labor compared with that of nonpregnant and pregnant nonlaboring women (P < 0.05). These results demonstrate that down-regulation of beta(2)-AR protein with labor may constitute a contributory mechanism by which uterine quiescence is removed at term.

Antibodies↗

Infrared spectral features of exfoliated cervical cells, cervical adenocarcinoma tissue, and an adenocarcinoma cell line (SiSo).

OBJECTIVE: The objective of the present study is to evaluate and compare the infrared spectral features of normal and malignant exfoliated cervical cells, cells from malignant tissue, and the SiSo cell line. METHODS: Infrared spectra of cervical adenocarcinoma (CA) tissue, normal and malignant exfoliated cervical cells, and a uterine cervical adenocarcinoma cell line (SiSo) were obtained. Spectral qualities in terms of band intensity ratio and band position, which reflect configurational changes in the functional groups of the above samples, were measured. RESULTS: Spectral bands of CA tissue, exfoliated cells from CA, and the cell line were similar but markedly different from that of exfoliated normal cervical cells. Significant changes in bands at 1025 cm(-1) (glycogen), 1080 cm(-1) (glycogen and nucleic acids), 1155 cm(-1) (C-OH groups of serine, threonine, and tyrosine of cell proteins, and C-O groups of carbohydrates), 1240 cm(-1) (PO(2) groups of nucleic acids), 1400 cm(-1) (methyl group of lipids and proteins), and 1450 cm(-1) (methylene group of lipids and proteins) were noted in the CA tissue, exfoliated CA cells, and adenocarcinoma cell line compared with exfoliated normal cells. Marked shifts in band positions from 1080 to 1086 cm(-1), 1153 to 1160 cm(-1), and 935 to 970 cm(-1) in CA tissue, exfoliated CA cells, and the adenocarcinoma cell line were noted. CONCLUSION: Spectral bands of the adenocarcinoma cell line matched very well with those of cervical CA tissue and exfoliated CA cells in terms of position. In contrast, spectral bands of the SiSo cell line differed greatly from those of normal exfoliated cells.

Adenocarcinoma↗