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| Sunday 05 September 2010 |
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| The effectiveness of laparoscopic sterilisation ‘versus’ the hysteroscopic permanent contraception techniques... What is the right decision for the patient? |
| Author: Femcare–Nikomed Limited |
| Molecular tests for human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae in liquid-based cytology specimen |
| Author: Sin Hang Lee, Veronica S Vigliotti and Suri Pappu Department of Pathology, Milford Hospital, Milford, Connecticut, USA BMC Women’s Health 2009, 9:8doi:10.1186/1472-6874-9-8 © 2009 Lee et al; licensee BioMed Central Ltd. |
| Obstetric anaesthesia matters |
| Author: Dr Neville Robinson FRCA, Consultant Anaesthetist, Northwick Park Hospital, Harrow, Middlesex, HA1 3UJ. e-mail: pnrfmt@msn.com |
| Chlamydia and pregnancy |
| Authors: Mr. A. Hakeem-Habeeb, MBBS, FRCOG, Consultant in Obstetrics and Gynaecology Dr Susan Young MBChB, FRCPI, FRCP, Consultant in Genitourinary Medicine Sherwood Forest Hospitals, Notts. |
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The effectiveness of laparoscopic sterilisation ‘versus’ the hysteroscopic permanent contraception techniques... What is the right decision for the patient?
There is currently a huge variety of contraceptive methods to choose from, all have the same aim - the prevention of pregnancy. The objective of this article is aimed at dispelling some of the myths associated with laparoscopic ‘versus’ hysteroscopic sterilisation. The method which is most suitable for an individual will depend on a number of factors such as age, sexual lifestyle, current relationship, family status and medical history.
Author: Femcare–Nikomed Limited  The Filshie Clip is considered the most effective and simple means of female laparoscopic sterilisation. With over 27 years of clinical use, a proven success rate of 99.76% and in the region of 10 million Filshie Clips having been successfully applied worldwide, the Filshie Clip’s strong clinical pedigree is recognised by leading surgeons around the world as the ‘number one’ choice for female surgical contraception / sterilisation. With an extremely low failure rate of 0.24%, the Filshie Clip System also has the lowest incidence of ectopic pregnancy: 4% of the 0.24%, in other words 0.001% of failures result in an ectopic pregnancy.
Filshie Clip tubal ligation is usually performed by laparoscopic surgery. The procedure is carried out by either single or dual incision laparoscopy, or via a laparotomy incision following caesarean section delivery. Once the surgeon has identified the Fallopian tube the Filshie Clip is applied to the Isthmic portion by fully encapsulating the tube causing complete occlusion. This is then repeated for the second Fallopian tube. The procedure is usually performed using general anaesthesia and patients may go home a few hours after an outpatient procedure, it can also be performed successfully under local anaesthesia.
No woman should consider any method of sterilisation unless she is certain that she does not wish to become pregnant in the future. However, relationship circumstances can and do change and it is a real possibility that a sterilised woman may want a reversal of the procedure in the future in order to conceive. Although the Filshie Clip procedure should be considered as a permanent form of surgical contraception / sterilisation, another of its key benefits is that the Filshie Clip destroys less than 4mm of the Fallopian tube, therefore, the procedure can be reversed following re-anastomosis of the Fallopian tubes, with over a 90% success rate. Hysteroscopic sterilisation, on the other hand, must be regarded as totally permanent, as reversibility is not possible.
 The Filshie Clip is extremely effective for larger tubes (postpartum) and is used extensively in the USA for postpartum sterilisation. There is no contraindication to the application of the Filshie Clip immediately following childbirth; conversely this is contraindicated for hysteroscopic methods of sterilisation. Unusual uterine shape or pathology does not affect the application of the Filshie Clip for surgical sterilisation. However, hysteroscopic sterilisation is contraindicated where uterine pathology or an unusual shaped uterus are present.
In essence, outside of the very small risk associated with anaesthesia, there are very few complications associated with the Filshie Clip.
However whilst hysteroscopic sterilisation is recommended in an outpatient setting, it is not without complication, some of these being noted below:-
 Another key clinical advantage of the Filshie Clip is that in-vitro fertilisation (IVF) is NOT contraindicated following the application of Filshie Clips. However, with hysteroscopic sterilisation, it is not well known whether the device affects the success of IVF, and if the patient were to fall pregnant following such a procedure whether the micro-inserts would harm the patient’s health or the health of the foetus.
Consideration should also be given to pre-menopausal women with heavy menstrual bleeding that may be considering endometrial ablation. Given that the Filshie Clip occludes the Fallopian tubes from the outside rather than blocks the tubes from the inside, the Filshie Clip System is compatible with ALL endometrial ablation techniques and can be used in conjunction with any such procedure.
In summary...Filshie is a globally recognised product that is... Beautifully Simple and Simply Beautiful !!
Stuart Court, Spursholt Place, Salisbury Road, Romsey, Hampshire SO51 6DJ, UK Tel: +44 (0)1794 525100 Fax: +44 (0)1794 525101 Web: www.femcare-nikomed.co.uk Email: customerservice@femcare-nikomed.co.uk Molecular tests for human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae in liquid-based cytology specimen
AbstractAuthor: Sin Hang Lee, Veronica S Vigliotti and Suri Pappu Department of Pathology, Milford Hospital, Milford, Connecticut, USA BMC Women’s Health 2009, 9:8doi:10.1186/1472-6874-9-8 © 2009 Lee et al; licensee BioMed Central Ltd. Background Laboratory detection of Human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae in liquid-based cervicovaginal cytology specimens is now based on identification of the DNA sequences unique to these infectious agents. However, current commercial test kits rely on nucleotide probe hybridization to determine DNA sequences, which may lead to diagnostic errors due to cross-reactivity. The aim of this study was to find a practical approach to perform automated Sanger DNA sequencing in clinical laboratories for validation of the DNA tests for these three infectious agents. Methods A crude proteinase K digestate of 5% of the cells collected in a liquid-based cervicovaginal cytology specimen was used for the detection of DNA molecules specific for HPV, C trachomatis and N gonorrhoeae, and for preparation of materials suitable for direct automated DNA sequencing. Several sets of commercially available polymerase chain reaction (PCR) primers were used to prepare nested PCR amplicons for direct DNA sequencing. Results Some variants of HPV-16 and HPV-31 were found to share an at least 34-base long sequence homology downstream of the GP5+ binding site, and all HPV-6 and HPV-11 variants shared an upstream 34-base sequence including part of the GP5+ primer. Accurate HPV genotyping frequently required more than 34-bases for sequence alignments to distinguish some of the HPV genotype variants with closely related sequences in this L1 gene hypervariable region. Using the automated Sanger DNA sequencing method for parallel comparative studies on split samples and to retest the residues of samples previously tested positive for C trachomatis and/or for N gonorrhoeae, we also found false-negative and false-positive results as reported by two commercial nucleic acid test kits. Conclusion Identification of a signature DNA sequence by the automated Sanger method is useful for validation of HPV genotyping and for molecular testing of C trachomatis and N gonorrhoeae in liquid-based cervicovaginal Papanicolaou (Pap) cytology specimens for clinical laboratories with experience in molecular biology to increase the specificity of these DNA-based tests. However, even a highly specific test for high-risk HPV genotyping may have unacceptably low positive predictive values for precancer lesion in populations with a low cervical cancer prevalence rate. Background Human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae are the causative agents for the three most common sexually transmitted infections in women. Newly introduced laboratory diagnostic procedures for these infectious agents are mostly nucleic acid-based, relying on detection and identification of a DNA sequence specific for the infectious agent with or without DNA replication (amplification) by polymerase chain reaction (PCR). The tests incorporating PCR amplification in the procedure, often referred to as nucleic acid amplification (NAA) tests, are extremely sensitive, capable of detecting a single copy of target DNA. The result of a DNA-based test may be validated by identifying a signature sequence of the target DNA and used for accurate genotyping if HPV DNA is the target1-8. The commercial NAA tests for C trachomatis and N gonorrhoeae, all relying on probe hybridization for DNA sequence determination, are claimed to have a sensitivity of 85% and a specificity of 97–99%, depending on the evaluating method chosen for comparison9. These tests tend to generate unacceptably low positive predictive value (PPV)10 in low prevalence populations. As a result, the Centers for Disease Control and Prevention (CDC) has issued recommendations that an additional test with different method or with the same method be performed to confirm a positive NAA test for C trachomatis and N gonorrhoeae to reduce the possibility of false-positive results that may have adverse medical, social and psychological impacts on the patient, but also cautions that such a supplementary test result might itself be falsely negative9. Clinical laboratories often find these tests are associated with 5.3% of initially C trachomatis-positive results and 10.7% of initially N gonorrhoeae-positive results that cannot be confirmed by repeated testing of the original sample11. In the past few years the cost of performing automated DNA sequencing has decreased considerably. This article gives a brief summary on the experience of applying this research tool in HPV genotyping and in the identification of C trachomatis and N gonorrhoeae DNA in liquid-based Pap cytology specimens to serve the physicians who want unequivocal evidence to validate each test result. Methods Clinical Materials The clinical samples used for the HPV study were 2,020 alcohol-preserved liquid-based cervicovaginal Pap cytology specimens (ThinPrep or Surepath) routinely submitted by 2 private gynecologists who provided general obstetric and gynecologic care to local residents in Milford, Connecticut. Milford has a rural and suburban population of 50,000+, in which 93.6% of the residents are non-Hispanic whites according to the latest available census12. The incidence of cervical cancer in the 2,020 patients selected for this study was considered to be representative of or below that in the state of Connecticut in which the cervical cancer rate is 6.8 per 100,000 women13. Publication of the laboratory data with blinded patient identities was approved by the Milford Hospital IRB. The cervicovaginal specimens were collected from women below age 30 who had a Pap cytology finding of atypical squamous cells of undetermined significance (ASCUS) or more severe, and from women 30 years and older in conjunction with Pap cytology screening when the clinical specimens were submitted for HPV testing with or without concomitant request for C trachomatis or N gonorrhoeae testing (Figure 1). The Pap cytology slides were screened by a commercial cytology laboratory and all abnormal slides reviewed by the 2 author pathologists for final classification.
The cellular debris derived from 5% of a liquid-based Pap cytology collection was pelleted for primary and nested PCR amplification of HPV, C trachomatis or N gonorrhoeae DNA without DNA extraction or purification, as previously described15-17. The residues of 26 endocervical samples which had been tested positive by the BD Probe Tec™ ET Chlamydia trachomatis and Neisseria gonorrhoeae Amplified DNA Assays (Becton, Dickinson, Sparks, MD) were retested by DNA sequencing for comparison16. All positive nested PCR products were validated by on-line Basic Local Alignment Search Tool (BLAST) algorithms for final validation of the signature sequence. The numbers of cases analyzed did not include 38 cases which were considered inadequate for failed PCR amplification of a human‚-globin genomic DNA in the samples. Results For the samples in which there was a single HPV genotype in the specimen, genotyping was readily determined with direct automated DNA sequencing by on-line BLAST sequence alignment algorithms. An exclusive 100% “identities” match between the “query” sequence and the “subject” sequence was required for accurate genotyping. A 34-base sequence downstream of the GP5+ primer site excised from the electropherogram of the sample, which is fully matched with a standard HPV signature sequence stored in the GenBank validated the HPV genotype, except for some variants of HPV-16, HPV-31 and HPV-33, for which BLAST algorithms of a 46–50 base sequence in this region were needed for unequivocal genotyping (Fig. 2). When the GP6/MY11 or the HiFi nested PCR primer pair (catalog #3002, HiFi DNA Tech, LLC, Trumbull, CT) was used to replace the GP5+/GP6+ primers to prepare a 190–200 bp nested PCR amplicon for DNA sequencing, an upstream 30- to 34-base long segment including 11 bases of the GP5+ primer site, was found to be sufficient to differentiate these variants. However, all variants of HPV-6 and HPV-11 share one DNA sequence homology in this region for 34 bases. Differentiation between these latter two HPV genotypes depended on finding the four isolated distinguishing bases further upstream of this sequence homology (Fig. 3).
Unlike the traditional methods based on bacterial culture, the highly sensitive commercial NAA tests for detecting C trachomatis and N gonorrhoeae lack a 100% analytical specificity9. No commercial test kits available in the USA for specific genotyping of the 13 generally recognized high-risk HPV genotypes. Several probe-based test kits for HPV genotyping have been evaluated19,20 for information on accurate HPV genotyping may play an important role in following persistent HPV infections21-24. However, when the GP5+/GP6+ PCR products with a hypervariable DNA sequence are targeted for developing genotyping methods, the DNA probe designed for one HPV type may cross-react with other non-target types despite the presence of four base mismatches in each pair25. Cross-reaction is a major challenge in distinguishing some of the individual genotypes of HPV based on the hybridization technology26. As we have demonstrated in this report, certain variants of HPV-16 and HPV-31 share a sequence homology of at least 34 bases downstream of the GP5+ site (Fig. 2). All variants of HPV-6 and HPV-11 share a sequence homology of 34 bases upstream of this region (Fig. 3). Increasing the specificity of the currently available HPV test has been suggested as a potential approach to reduce the number of excessive colposcopic procedures in the USA27. Using a modified automated Sanger DNA sequencing for HPV genotyping after nested PCR amplification, we found a 9.9% HPV positive rate in the specimens collected from 2 private gynecology offices primarily serving the local residents with a population 50,000+ in the rural and suburban United States. The true HPV positive rate in this general women population is probably lower because all patients under 30 who had a much higher HPV infection rate were pre-selected with an abnormal Pap cytology before being accepted for HPV testing. In this population, HPV-16 is the most prevalent single genotype found, constituting 19.0% of the HPV isolates, followed by HPV-52, -18 and -59 in decreasing order. Of the 2,020 cervicovaginal specimens, 5.9% (119 cases) contained at least 1 “high-risk” HPV genotype while only 0.2% (4 cases) showed an HSIL in cytology (Additional file 1, Table 1). Of the 4 HSIL cases, 2 were associated with an HPV-16, 1 with an HPV-39 and 1 with an HPV-69. HPV-69 is not included in the Digene HC2 “high risk” group, but has been shown to be of high risk in HIV-infected patients28. No invasive cancer was detected. If HSIL cytology were used as the endpoint for clinical evaluation, the clinical specificity for HSIL of one-occasion “high-risk” HPV positivity by the DNA sequencing method would be (2020-119)/(2020-4) = 94%; the clinical sensitivity would be 4/4 = 100%; the negative predictive value (2020-119)/(2020-119 + 0) = 100%; and the positive predictive value (ppv) would be 4/(4+115) = 3.4%. This extremely low ppv of an HPV DNA sequencing assay, even with a high 94% clinical specificity, emphasizes the reality that using one-occasion HPV testing to formulate guidelines for management triage is bound to generate excessive colposcopic procedures27 in populations with a low cervical cancer prevalence. In this series, even the most “high-risk” HPV-16 infection is rarely associated with cellular dysplasia. Of the 38 specimens positive for HPV-16 DNA, 2 cases (5.3%) show a HSIL as mentioned above, 2 a LSIL and 5 an ASCUS cytology. The remaining 29 HPV-16 isolates (76.3%) were associated with a reactive or a normal Pap cytology (Additional file 1, Table 1). It seems to be more appropriate to use this virology test for referring patients with an ambiguous Pap cytology result and persistent high-risk HPV infection to colposcopy29. Since the introduction of the liquid-based Pap cytology testing into clinical practice, there has been an increasing demand for performing Pap cytology, HPV detection, HPV genotyping, and the detection of C trachomatis and N gonorrhoeae with one specimen collected in a single container. In clinical practice, most of the cervicovaginal samples from patients presenting with symptomatic or acute gonococcal infections are collected by swabs which are usually submitted for bacteriological culture and Gram staining. NAA tests for N gonorrhoeae in liquid-based Pap cytology specimens are usually requested when the patients present with subclinical or asymptomatic gonococcal infections. Because the traditional cell culture method for C trachomatis detection is no longer readily available, requests for C trachomatis nucleic acid tests in the liquid-based specimens are often for both symptomatic and asymptomatic patients. As a result, we have seen mostly “low-positive” results for N gonorrhoeae opa gene DNA in the liquid-based Pap cytology specimens with a positive rate of 2.0%, but both “low-positive” and “high positive” cases for C trachomatis cryptic plasmid DNA in the same period with a positive rate of 1.4%. There seems to be more asymptomatic N gonorrhoeae than asymptomatic C trachomatis infections in this community. However, since the present series is small and the patients studied are highly selective, these numbers do no represent infection rates in women living in this population. Accurate nucleic acid detection of C trachomatis and N gonorrhoeae in clinical specimens is challenging. Most commercial NAA tests target a DNA segment of the cryptic plasmid DNA for C trachomatis detection and the sensitivity of the tests has been high. However, recently a variant of C trachomatis with a 377-bp deletion in the cryptic plasmid (GenBank accession no. EF 121757) has emerged, causing probe failures for certain commercial kits which target this deleted segment for their real time PCR assays30,31. In our procedure, we choose a species-specific sequence about 3000 bases downstream of the 377-bp deletion site for amplification to avoid the potential failure caused by the 377-bp deletion. Nucleic acid detection of N gonorrhoeae is more complex. All commercial gonococcal NAA tests, including those targeting the cppB, opa and 16S genes and the porA pseudogene for amplification32-38, are associated with a less than desirable degree of sensitivity and specificity. The great capacity of N gonorrhoeae for genetic variation and recombination is the major cause of this technical complexity. Members of the Neisseria species are capable of taking up exogenous DNA throughout their entire life cycle, causing gonococci acquiring commensal Neisseria DNA sequences, and vice versa39,40. Genetic recombination between gonococci can take place in vitro and in vivo41, turning any given DNA segment into a potential moving target for detection. The cppB-based PCR assays are known to have generated false-negative results in populations infected by gonococci lacking the cppB gene (non-PAU- subtype)42,43. For our procedure, we have chosen a DNA strand of 40 bases in the promoter region of the gonococcal opa genes for target amplification and as the signature sequence. This short DNA sequence appears to be highly conserved and constant for distinguishing itself from those of other non-gonococcal neisserial opa genes, including those of Neisseria meningitidis16. Conclusion DNA sequencing can be used for accurate HPV genotyping and accurate molecular identification of C trachomatis and N gonorrhoeae in clinical laboratories with molecular biology experience to increase the specificity of these microbiology tests. However, an HPV test even with a high virology specificity may still have a very low positive predictive value if a precancer lesion is used as the endpoint for evaluation in a population with low cervical cancer prevalence. Competing interests The corresponding author, Dr. S. H. Lee, declares that he is a shareholder and the president of HiFi DNA Tech, LLC, a company that developed the low temperature PCR technology. The other co-authors declare that they have no competing interests. Authors’ contributions SHL conceived the study and participated in acquisition, analysis and interpretation of data and in drafting the manuscript. SP participated in direction of the study, reviewing of the abnormal Pap slides, and analysis of the data with its potential clinical application. VSV participated in organization of the study, performing the nested PCR, performing the automated DNA sequencing, analyzing the sequencing data and alignment of the computer-generated DNA sequences with those stored in the GenBank to achieve the final DNA identification. All authors have read and approved the revised version of the manuscript. References
Obstetric anaesthesia matters
Obstetric anaesthesia and analgesia is always full of interest and challenge. As medically sicker patients becoming pregnant newer challenges have arisen. Some of these are discussed in the following article.
Pre-operative assessmentAuthor: Dr Neville Robinson FRCA, Consultant Anaesthetist, Northwick Park Hospital, Harrow, Middlesex, HA1 3UJ. e-mail: pnrfmt@msn.com Early identification and planning of obstetric care by multidisciplinary teams was emphasised in the last CEMACH report1. To this end all maternity units should now have obstetric anaesthetic antenatal clinics dealing with relevant anaesthetic problems, and obstetric or medical illnesses that need anaesthetic input. The problems of the obese patient from both a regional and a general anaesthetic point of view need special consideration. Anaesthetists are suggested to review patients who are morbidly obese (BMI > 35). Apart from predicting problems these clinics allow planning for more complicated parturient management. All elective caesarean section patients should now be seen in pre-assessment clinics by anaesthetists. Classification of caesarean section The degree of urgency of caesarean section has long been a source of tribulation between obstetricians and anaesthetists. Communication about the need of immediacy of caesarean section by obstetricians has often been subjective with a variety of results. The terms ‘crash section,’ emergency, semi-emergency, semi-elective and elective were used but meant different things to different members of the team. A ‘30 minute’ rule was used for emergency surgery but this is also subjective in terms of the potential emergency nature of the surgery. NICE guidelines and the Royal Colleges of both Obstetricians and Anaesthetists now recommend that classification2 be carried out on every case according to the following schedule: Category 1: immediate threat to the life of the mother or fetus Category 2: maternal or fetal compromise which is not immediately life threatening Category 3: needing early delivery but no maternal or fetal compromise Category 4: at a time to suit the woman and maternity team. All maternity units should now have obstetric anaesthetic antenatal clinics dealing with relevant anaesthetic problems, and obstetric or medical illnesses that need anaesthetic input Epidural equipment is standardised in the main with 16 or 18 gauge needles being in common practice. Newer refinements may occur soon with smaller and stronger epidural needles being manufactured. Newer advances in catheter material may allow for smaller atraumatic catheters to be manufactured. Safer loss of resistance devices which allow for two handed advancement of the needle and thus a potentially lower dural puncture rate have also been developed and the Epidrum® is one such example. This device has a small one ml priming pump attached to it which collapses once the epidural space is located. Newer equipment that is often deemed necessary in the delivery suite include a thromboelastograph for instantaneous clotting profiles, haemoglobin measurement from oximetry, oesophageal Doppler cardiac output monitoring, a Level 1 tranfusor device to assist in major haemorrhage and major patient transfer equipment for the transfer of the critically ill patient to the Intensive Care Unit. Maternity High Dependency Units of a Level 2 standard are now becoming an integral part of maternity units. Staffing of these areas is traditionally done by midwives. There are now several units with trained High Dependency Unit nurses assisting in the care of the ill parturient. Medical care can be delivered by these experienced staff and maternity care by midwives. More midwives are now trained in managing and understanding the sick mother. Nerve injuries after neuraxial anaesthesia Anaesthetists are often aware of obstetric palsies as regional anaesthesia is often blamed for them. However, the most common palsies are intrinsic and have a reported incidence of 0.6 to 92 per 10,000 deliveries. Stretch or compression injury to the lumbosacral plexus or lower extremity peripheral nerves in childhood is blamed for them but compression of the nerve vascular supply mechanism is another possibility. Nullparity, a prolonged second stage of labour, cephalo-pelvic disproportion, non-vertex presentation and forceps deliveries are associated with palsies. The most common is a lateral femoral neuropathy known as meralgia paresthetica. The nerve arises from the lateral border of the psoas muscle medial to the anterior superior iliac spine and then passes under or through the inguinal ligament and is vulnerable to compression. It is sensory to the lateral thigh and is also easily injured in caesarean section. Other nerves likely to be injured in childbirth include the femoral, obturator, sciatic and the common peroneal nerves3. Anaesthetic related nerve damage does exist but is rare. Estimates in obstetric anaesthesia range from 1.2 – 0.3 per 100,000 procedures. Damage caused can include spinal haematoma, epidural abscess, traumatic spinal cord injury (from the needle), intracranial subdural haematoma, abducens nerve palsy and the development of Horner’s syndrome. Direct spinal cord trauma is most worrying as it can lead to permanent spinal cord injury and is most likely to arise from spinal or combined spinal epidural anaesthesia. Recommendations for minimising this complication include choosing a lumbar puncture site below L3, halting needle advancement if the patient perceives pain or paraesthesia and injecting anaesthetic solutions only if all pain and paraesthesia has disappeared4. Magnesium Magnesium is a critical physiological cation and its deficiency in pregnant women may contribute to the development of pre-eclampsia, impaired neonatal development and to metabolic problems extending into adult life. Neurologically the inhibition of calcium channels and antagonism of the NMDA receptor raises the potential of neuronal protection and magnesium administration to prematurely labouring mothers may reduce the incidence of neonatal cerebral palsy. In the management of eclampsia magnesium has been shown to terminate convulsions and prevent further convulsions. It is also the agent of choice for the prevention of convulsions but the argument as to which pre-eclamptic mother should receive magnesium is unresolved. Magnesium therapy has potential complications in its own right and it is usually received for patients with severe disease5. Effects of labour analgesia on the foetus Labour pain and stress are associated with a progressive foetal acidosis. In terms of analgesia nitrous oxide relieves labour pain more effectively than pethidine and it is worth noting that if Entonox is found to be ineffective it is useless to offer pethidine. Pethidine is not recommended but is available for labour analgesia. It causes neonatal respiratory depression which is most severe if pethidine is given 3-5 hours prior to delivery but the depression is only slight if pethidine is given within an hour of delivery. Epidural analgesia in labour, whilst it has some short-term maternal side effects, when compared to systemic analgesia is shown to be consistently beneficial in terms of not only Apgar score but also of acid-base status and is less likely to impair breast feeding. Epidural analgesia is associated with maternal pyrexia but this does not appear to be of any consequence to the neonate because if it were there would be an increased incidence of fetal acidosis after epidural analgesia in labour whereas in reality the reverse is true6. Coagulation in pregnancy Pregnancy is associated with physiological changes that include an increase in the majority of clotting factors and a decrease in natural anticoagulants and a reduction in fibrinolytic activity. The mother becomes hypercoagulable and risks thromboembolism. The changes reverse to normal about 4 weeks post-partum. Pregnancy can induce changes in platelet numbers and function which can complicate the provision of regional analgesia and anaesthesia. Most practitioners will perform regional anaesthesia if the platelet count is above 80 x 109/l if the trend of platelet function is stable7. The use of low dose heparin is becoming more common and often decisions about the provision of regional anaesthesia are difficult. Normally the following rules are utilised:
Pharmacogenetics is the study of the variability in drug response due to genetic variability. The first observation of this influence was made in the 1950s when the genetic influence of the metabolism of suxamethonium was noted. It has been highlighted recently because of the variability of vasopressor requirement during spinal anaesthesia for caesarean section seems to have a genetically affected response distribution. This response is clearly affected by the ‚2AR genotype and it has been noted that women who are Gly16 homozygous and those who are heterozygous or homozygous for the Glu27 variant require significantly less vasopressors (ephedrine) for the treatment of hypotension during spinal anaesthesia. These 2 haploids appear to ‘protect’ women from requiring higher doses of vasopressors and these haploids are more likely to occur in Caucasian patients. These differences in the population may explain why a simple recipe approach to treating hypotension after regional anaesthesia is unsuccessful. Genetic differences may also explain why some ethnic groups respond better or are more resistant to blood pressure control in pre-eclampsia8. Genetic differences may also explain why some ethnic groups respond better or are more resistant to blood pressure control in pre-eclampsia World-wide, haemorrhage is the biggest cause of maternal death. It is variably defined and loss is always difficult to assess. In England and Wales the Health Care Commission defined ‘significant’ haemorrhage as > 1000 ml and ‘major’ loss as > 2500 ml. The Scottish Confidential Audit of Severe Maternal Morbidity (SCASMM) considered major haemorrhage as a loss of > 2500 ml or a transfusion of 5 or more units or treatment for coagulopathy. It is stating the obvious but obstetric haemorrhage is notoriously difficult to estimate and is normally under-estimated. Recent thinking in the treatment of major haemorrhage of relevance to anaesthetists is to increase the ratio of clotting factors to packed cells to a ratio of 1:2 or even 1:1 to prevent the onset of coagulopathy. Attempts should be made to avoid further precipitant factors which increase disseminated intravascular coagulation such as shock, acidosis and hypothermia. Adjuncts to treatment with surgery and drugs include the use of cell salvage. A cell saver cuts down on donor blood usage and is cost effective but it must be emphasised that salvaged blood has no coagulation factors. Concerns about amniotic fluid embolism and rhesus immunisation problems have been unfounded. Interventional radiology services are now nationally recommended to be available for the use in the management of placenta accrete and praevia and the use of such facilities has proven to be life saving10. References
Chlamydia and pregnancy
Authors: Mr. A. Hakeem-Habeeb, MBBS, FRCOG, Consultant in Obstetrics and Gynaecology Dr Susan Young MBChB, FRCPI, FRCP, Consultant in Genitourinary Medicine Sherwood Forest Hospitals, Notts. Background
Chlamydia trachomatis (Chlamydia) is the commonest bacterial sexually transmitted infection in the UK. It is an obligate intracellular parasite and can only survive by a replicative cycle that results in death of the infected host cells. Up to 10% of sexually active women aged less than twenty four years and men aged between twenty to twenty-four years may be currently infected with Chlamydia. Chlamydia prevalence is generally greater in women with ectropion than in those without (the organisms require columnar type epithelial cells in which replicate and such cells are more readily exposed to infection in the presence of ectropion) which may drive the infection in young females. From the Health Protection Agency statistics In the UK in 2008 over 79% of diagnosed Chlamydia infection in females attending genitourinary medicine clinics in the UK was in those under twenty five years of age. Chlamydia is thus likely to be a very relevant consideration in many pregnant women! Complications of Chlamydia infection in the female genital tract are responsible for significant morbidity but this article addresses Chlamydia in women who have already achieved a pregnancy. Chlamydia may be a coincidental, often asymptomatic, finding in pregnancy (a risk of pregnancy means a risk of acquiring sexually transmitted infections has occurred!) or it may be implicated in pregnancy- related complications. Symptoms and signs The majority of Chlamydia-infected pregnant and non-pregnant women are asymptomatic. A proportion of women may present with very mild or non-specific symptoms such as increased/altered vaginal discharge, dysuria, abdominal pain, arthritis, post coital bleeding or pregnancy related complications Vaginal discharge Chlamydia cervicitis may cause increased/altered vaginal discharge and post coital or intermenstrual bleeding, although the majority of infected females are totally asymptomatic. Cervicitis may be apparent in up to 30% of infected women. Examination of the ectocervix may show mucopurulent discharge, oedema, inflammation and contact bleeding may be elicited. Visual examination alone cannot exclude a diagnosis of Chlamydia. A cervical cytology smear is not a test for Chlamydia, although Chlamydia may cause inflammatory or other cytological changes. Urethral symptoms Most of the women attending clinics for sexually transmitted infections, who have Chlamydia, have no urethral symptoms. Studies in clinics suggest that for females tested for Chlamydia from both the cervix and urethra, the majority of the positive women yield Chlamydia from both sites while a significant number may test positive from either site alone. The diagnosis should be considered in women presenting with urethral symptoms where dysuria is present for more than a week, especially if there is lack of suprapubic tenderness and absence of haematuria. Non-genital symptom s Conjunctivitis, urethritis, sero-negative reactive arthritis (rare in females) and perihepatitis (occurring in about 10 per cent of laparoscopically diagnosed pelvic inflammatory disease) are all possible presenting complications of Chlamydia infection. They are in the context of this article, primarily important, as markers of probable concomitant genital infection. Pregnant women are at risk of pelvic inflammatory disease, ectopic pregnancy in the first trimester, miscarriage, premature rupture of membranes and pre-term labour as well as post-partum or post miscarriage endometritis. Lower abdominal pain Chlamydia-associated salpingitis or PID in early pregnancy rarely causes mild to severe, acute or chronic pelvic pain and deep dyspareunia, abnormal vaginal discharge, bleeding, systemic upset or pyrexia. Invasive gynaecological procedures such as suction termination of pregnancy, increases the risk of Chlamydia causing PID. An ultrasound scan of the pelvis may help confirm a clinical suspicion of PID. An obstetrician should always be involved if there is a clinical suspicion of PID in pregnancy. Some other possible complication A substantial number of studies suggest that Chlamydia trachomatis infection in pregnancy is associated with premature delivery. So far, there appears to be no proven link between Chlamydia and chorioamnionitis. DNA amplification has however found Chlamydia trachomatis in the amniotic fluid of 6.7 per cent of women with pre-labour rupture of membranes. Laboratory diagnosis Nucleic Acid Amplification tests (NAAT) are the tests of choice for urethral and endo-cervical or self-taken vaginal sampling in women in the UK because of their high level of sensitivity (around 90 to 95%) and specificity and should be available to all clinicians. The old enzyme immunoassay (EIA) tests were much less sensitive and specific for Chlamydia. Culture is not generally available. No test is 100% sensitive or specific and NAAT, Culture or EIA tests from the cervix can be negative in endometritis. Specific kits for obtaining samples should be available for your local laboratory. The attending physician considering the possibility of Chlamydia infection in a baby, or non genital sites in an adult, should discuss with the laboratory what test samples to obtain to exclude or make a diagnosis. Neonatal infection If Chlamydia is diagnosed in a neonate then it is essential that the mother and her partner(s) are also tested and treated for Chlamydia. Indeed, this may be the first indication of a missed or un-suspected maternal infection! Conjunctivitis occurs in about 20-50 per cent of neonates whose mother had Chlamydia at the time of delivery. Although the infection is derived from the mother’s genital tract at birth, there have been cases reports where neonatal Chlamydia trachomatis infection was found in infants delivered by caesarean section in the presence of intact membranes, suggesting the possibility of trans-placental or trans-membranous infection. Neonatal Chlamydia conjunctivitis has an incubation period of 10-12 days and therefore presents after midwifery involvement has generally been withdrawn. The eyelids are usually swollen, and there may be a sticky discharge which is purulent with conjunctival injection. The infection may be severe in pre-term babies. The cause of the relatively late presentation of this type of opthalmia neonatorum may be missed if it is not actively considered. The standard treatment for conjunctivitis will not clear the infection. The onset of the atypical Chlamydia pneumonia is often insidious, becoming apparent at some 3 to 12 weeks of age. The infants may become very unwell or develop a chronic cough with no clinical signs except possible tachypnoea with or without marked chest X-ray changes. In order to make the diagnosis and treat the baby with effective antibiotics, it helps if the Neonatal Physician is furnished with the mother’s profile which indicates the possibility of Chlamydial pneumonia. Management An integrated approach to care management following diagnosis begins with taking a sexual history, a history of reproductive health, past STIs and clinical assessment. The four C’s approach encapsulates the factors required to ensure effective care management (Contact tracing (to reduce the risk of re-infection), Compliance (with medication), Condoms (to use after completion of therapy and partner treatment to prevent re-infection) and Counselling.) Other sexually transmitted infections should be excluded. Rarely in pregnancy, PID is associated with an increase in both maternal morbidity and an obstetrician should be involved in management. The advice of a Genito-Urinary Medicine Consultant, as well as a Consultant Microbiologist, is important. The early diagnosis and treatment of Chlamydial infection of the female genital tract is essential to protect the reproductive health of women. Antibiotic therapy is the cornerstone of management. The optimal antibiotic treatment for Chlamydia (UK British Association for Sexual Health and HIV (BASHH) National Guideline) is that treatment should be effective with a microbiological cure rate of more than 95 per cent, easy to take (not more than twice daily) with a low side effect profile and cause minimal interference with daily life. Azithromycin 1gm stat in pregnancy is recommended by the World Health Organisation but unlicensed in the UK. However, it is suggested in the British National Formulary only if no alternative is available. Erythromycin is thought to have a high rate of intolerance manifested by gastrointestinal upset, although this side effect has not been universally demonstrated. There are no trials of erythromycin 500mg twice a day for 14 days, which is generally better tolerated than four times a day, but it probably has good efficacy. Azithromycin, although chemically related to erythromycin, has unique pharmacokinetics. The drug is rapidly absorbed from the gastrointestinal tract and widely distributed to body tissues, the safety of azithromycin in pregnancy and lactating mothers has not been fully assessed, although available data indicate that it is safe. Its efficacy in pregnancy has not been studied (although it has probably has less than 95% efficacy in pregnancy). Amoxicillin has similar cure rate to Erythromycin and a better side effect profile, although it may induce bacterial latency and possible re-emergence of infection at a later date, causing some concerns about its regular use in pregnancy.
Test of cure A test of cure is essential in all pregnant women, including those treated with Azithromycin. It must be performed at least 5 weeks after the end of treatment (6 weeks if Azithromycin is used) or the NAAT may give a false positive result. References
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