Dying to give birth: the Pakistan Liaison Committee's strategies to improve maternal health in Pakistan.

Pakistan has one of the worst maternal mortality ratios worldwide: 260-490 women die for every 100,000 live births in Pakistan. The Pakistan Liaison Group (PLG) was formed to work with and through the international office of the Royal College of Obstetricians and Gynaecologists (RCOG). It works with the RCOG representative committee in Pakistan to improve the health of women. It aims to contribute to improving maternal morbidity and mortality through strategies directed at improving the education and training of health professionals. In addition, the PLG aims to promote changes in the legislature to allow for the notification of maternal deaths so that accurate figures can be obtained, and so that health parameters can be accurately assessed and, in the long term, a confidential enquiry into maternal deaths can be initiated.

Improving essential obstetric and newborn care in resource-poor countries.

Skilled birth attendance (SBA) and essential obstetric care (EOC) are key strategies for reducing maternal and newborn mortality and morbidity globally. Lack of adequately trained competent staff is a key barrier to achieving this. We assessed the effectiveness of a new package of 'Life Saving Skills - Essential Obstetric and Newborn Care Training' (LSS-EOC and NC) designed specifically around the UN signal functions in seven countries in sub-Saharan Africa. Among 600 healthcare providers (nurse-midwives, doctors, clinical officers and specialists), knowledge about the diagnosis and management of complications of pregnancy and childbirth as well as newborn care significantly increased (p < 0.001). There was measurable improvement in skills (p < 0.001), and participants expressed a high level of satisfaction with the training. The training package was found to meet the needs of healthcare providers, increased awareness of the need for evidence-based care and encouraged teamwork.

Impact of a regional training program in fetal echocardiography for sonographers on the antenatal detection of major congenital heart disease.

OBJECTIVES: The aims of this study were to ascertain the effect of a regional training program in fetal echocardiography for obstetric radiographers on the antenatal detection of major congenital heart disease (CHD) and to document short-term outcomes for major CHD. METHODS: All 87 obstetric radiographers in Northern Ireland were invited to attend 2.5 days of training during a 1-year period. Data were collected before and after the training, over a 5-year study period, to assess the effect of training on the antenatal detection of CHD in the population. RESULTS: The antenatal detection of major CHD rose significantly, from 28% (72/262) pretraining to 43% (36/84) in the year of training (P = 0.008). Antenatal diagnosis of four-chamber-view defects rose significantly (from 38% to 54%; P = 0.04), as did detection of outflow-tract-view defects (from 8% to 21%; P = 0.05). Twelve per cent (13/108) of cases died spontaneously in utero and 8% (9/108) were terminated. Only 78% (67/86) of live-born cases in which CHD had been diagnosed antenatally survived the neonatal period, compared to 93% (221/238) with a postnatal diagnosis of CHD (P < 0.001). CONCLUSIONS: Even with a relatively simple training program, significant improvements can be made in the antenatal detection of CHD. With training, obstetric sonographers can successfully assess outflow tracts. Antenatally diagnosed cases have more complex CHD and this probably contributes to poor neonatal survival.

Admission to neonatal intensive care with respiratory morbidity following 'term' elective caesarean section.

Delaying the timing of elective caesarean section (ELCS) from 37/38 weeks to 39/40 weeks reduces the risk of respiratory morbidity in otherwise healthy neonates. The aims of this study were to clarify the number and clinical details of term infants delivered by ELCS who were admitted to neonatal intensive care (NIC) from 1st April 2001 to 31st March 2002 in Northern Ireland, to record the level of care required by these infants and to identify infants who were diagnosed with transient tachypnoea of the newborn (TTN) and/or Respiratory Distress Syndrome (RDS). Two hundred and ten (8%) of babies born by ELCS were admitted to NIC. Term infants delivered by ELCS used 343 days of level 1 & 2 care with 230 (68%) of these days being used by infants with RDS/TTN (n=105) the majority of whom were delivered at 37/38 weeks. Definitions of 'term' and clinical indications for ELCS urgently need to be debated to avoid unnecessary morbidity following ELCS in so called 'term' infants.

Techniques and materials for skin closure in caesarean section.

BACKGROUND: Caesarean section is a common operation with no agreed standard on operative techniques and materials to use. The skin layer can be repaired by sub cuticular stitch immediately below the skin layer, an interrupted stitch or with skin staples. A great variety of materials and techniques are used for skin closure after caesarean section and there is a need to identify which provide the best outcomes for women. OBJECTIVES: To compare the effects of skin closure techniques and materials on maternal outcomes and time taken to perform a caesarean section. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (August 2002). SELECTION CRITERIA: All randomised comparisons of skin closure techniques in caesarean section. DATA COLLECTION AND ANALYSIS: Three papers were identified from the search. Data were extracted independently by two reviewers. On further inspection two were not considered to be randomised controlled trials. MAIN RESULTS: Only one small randomised controlled trial, involving 66 women, was included in the review. Frishman et al compared staples with absorbable sub-cuticular suture for closure following caesarean section. While operating time was significantly shorter when using staples, the use of absorbable sub cuticular suture resulted in less postoperative pain and yielded a better cosmetic result at the post-operative visit. REVIEWER'S CONCLUSIONS: There is no conclusive evidence about how the skin should be closed after caesarean section. Questions regarding the best closure technique and material and the outcomes associated with each remain unanswered. The appearance and strength of the scar following caesarean section is important to women and the choice of technique and materials should be made by women in consultation with their obstetrician based on the limited information currently available.

A randomized trial investigating an iron-rich natural mineral water as a prophylaxis against iron deficiency in pregnancy.

Spatone Iron-Plus is a naturally occurring mineral water from Trefriw Wells Spa in Conwy County, North Wales, UK. It contains approximately 0.20 mg of iron per millilitre as ferrous sulphate and has been shown to provide iron in a highly bio-available form. A 24 ml sachet contains approximately 5 mg of iron. Iron deficiency is common in the obstetric population. However, compliance with traditional iron supplements is poor because of gastrointestinal side-effects. We designed a randomized, double-blind, placebo-controlled trial. A total of 102 low-risk antenatal patients, who were noncompliant with routinely prescribed ferrous sulphate tablets, were randomized to receive 48 ml of Spatone water or placebo. The study was conducted between 22 and 28 weeks gestation. Primary outcome measures were compliance, gastrointestinal side-effects and changes in ferritin levels during the trial period. Compliance in the intervention group was 57% compared with 67% in the control group, P = 0.22. Dyspepsia scores, as determined by a recognized and well-validated questionnaire, did not differ between the two groups. During the trial period, mean ferritin levels fell by 24% in the Spatone Iron-Plus group compared with a mean fall of 51% in ferritin levels among the control group, P = 0.016.

Acarbose in the treatment of elderly patients with type 2 diabetes.

AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.

Crystallization and preliminary X-ray analysis of ocr, the product of gene 0.3 of bacteriophage T7.

Ocr, the product of gene 0.3 of bacteriophage T7, prevents the action of restriction endonucleases of the host bacteria. The amino-acid sequence of ocr has less than 20% similarity to any protein of known three-dimensional structure. Ocr has been crystallized in a number of different crystal forms and X-ray data for the seleno-L-methionine-substituted form has been collected to a resolution of 1.8 A. The presence of caesium was found to be required for good crystal growth. Anomalous X-ray data was used to identify possible positions for Se and Cs atoms in the unit cell.

Two structures of cyclophilin 40: folding and fidelity in the TPR domains.

BACKGROUND: The "large immunophilin" family consists of domains of cyclophilin or FK506 binding protein linked to a tetratricopeptide (TPR) domain. They are intimately associated with steroid receptor complexes and bind to the C-terminal domain of Hsp90 via the TPR domain. The competitive binding of specific large immunophilins and other TPR-Hsp90 proteins provides a regulatory mechanism for Hsp90 chaperone activity. RESULTS: We have solved the X-ray structures of monoclinic and tetragonal forms of Cyp40. In the monoclinic form, the TPR domain consists of seven helices of variable length incorporating three TPR motifs, which provide a convincing binding surface for the Hsp90 C-terminal MEEVD sequence. The C-terminal residues of Cyp40 protrude out beyond the body of the TPR domain to form a charged helix-the putative calmodulin binding site. However, in the tetragonal form, two of the TPR helices have straightened out to form one extended helix, providing a dramatically different conformation of the molecule. CONCLUSIONS: The X-ray structures are consistent with the role of Cyclophilin 40 as a multifunctional signaling protein involved in a variety of protein-protein interactions. The intermolecular helix-helix interactions in the tetragonal form mimic the intramolecular interactions found in the fully folded monoclinic form. These conserved intra- and intermolecular TPR-TPR interactions are illustrative of a high-fidelity recognition mechanism. The two structures also open up the possibility that partially folded forms of TPR may be important in domain swapping and protein recognition.

Biochemical and structural characterization of a divergent loop cyclophilin from Caenorhabditis elegans.

Cyclophilin 3 (CYP-3) is one of the most abundantly expressed cyclophilin isoforms in the free living nematode Caenorhabditis elegans. The detailed post-embryonic expression pattern of the cyp-3 transcript is unusual, peaking during early larval development. The spatial expression pattern was examined via reporter gene analysis demonstrating that the cyp-3 transcript is exclusively expressed in the single anterior excretory cell. Recombinant cyclophilin 3 has been purified, crystallized and solved to a resolution of 1.8 A. The peptidyl-prolyl isomerase activity of CYP-3 has been characterized against the substrate N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, and gives a k(cat)/K(m) value of 2.4 x 10(6) M(-1) s(-1). The immunosuppressive drug cyclosporin A binds and inhibits CYP-3 with an IC(50) value of 16 nM, comparable with the range of values found for human cyclophilin A. The x-ray structure shows that the overall fold and active site geometry is similar to other cyclophilin structures. There are however a number of distinctive features, and we use this structure and amino acid sequence alignment analysis to identify a subgroup of "divergent-loop cyclophilins". This subgroup has a number of uniquely conserved features: an additional loop between residues 48 and 54 (KSGKPLH); two cysteine residues (Cys(40) and Cys(168)) that are in close proximity but remain in the unoxidized form, and two other conserved residues, His(54) and Glu(83). We suggest that these features are functionally important for the role played by this class of cyclophilins during cellular responses to stress caused by changes in the redox environment or by up-regulation of cellular activity. This study represents a detailed biological, biochemical, and structural characterization of a single cyclophilin isoform in the model organism Caenorhabditis elegans.

Incidence and risk factors for ventricular septal defect in "low risk" neonates.

AIMS: To quantify the incidence of ventricular septal defect in "low-risk" neonates; and to define any associated risk factors. METHODS: One hundred and seventy three patients with ventricular septal defects from a scanned population of 3971 clinically normal neonates were compared with scanned controls, considered to be clinically normal. A subset of the group with defects was compared with normal infants delivered over the same period, to identify any seasonal variation. RESULTS: Ventricular septal defects were detected in 4.36 % of the "scanned" group (173 out of 3971). Ten had perimembranous defects and the remainder apical or muscular lesions. Eleven neonates had multiple defects. The incidence of ventricular septal defect was independent of most tested risk factors. There were significantly more girls in the group with defects compared with the controls (p = 0.004). The defects group also contained fewer infants born during summer months (p = 0.04). CONCLUSIONS: The incidence of ventricular septal defects was much higher than might be expected, given that "high risk infants" were excluded. The observations that gender and season of birth affect the rate suggest that both genetic and environmental factors may be involved in the aetiology.

Purification, characterization and crystallization in two crystal forms of bovine cyclophilin 40.

The purification and crystallization of two different crystal forms of the two-domain protein bovine cyclophilin 40 is reported. Tetragonal crystals grown in methyl pentanediol belong to space group P4222 with unit-cell parameters a = 94.5, c = 118.3 A. Long thin needles grown from PEG belong to space group C2 with unit-cell parameters a = 125.71, b = 47.3, c = 74.6 A, beta = 93.90 degrees. The N-terminal 170 amino acids have significant homology with the well characterized human cyclophilin A. The C-terminal domain is largely made up of three copies of the tetratricopeptide repeat motif thought to be involved in mediating protein-protein interactions. Cyclophilins are frequently found as domains in larger multidomain proteins. To date, only X-ray structures of single-domain cyclophilins have been reported, and this work provides the first example of the purification and crystallization of a larger protein containing a cyclophilin domain.

Early amniocentesis: effect of removing a reduced volume of amniotic fluid on pregnancy outcome.

In mid-trimester amniocentesis (MTA), 12-15 ml of amniotic fluid is aspirated for cytogenetic analysis. When a similar volume of amniotic fluid is removed by early amniocentesis (EA), it represents a significant proportion of the total amniotic fluid volume in the first trimester. The fluid depletion, which may persist for 7 to 10 days, is considered to impair development of fetal lungs and extremities and, possibly, contribute towards procedure-related congenital abnormalities and miscarriages. By only removing 7 ml of amniotic fluid, we have demonstrated a total miscarriage rate (3.8 per cent) comparable with previous large studies (Table V), a low incidence of respiratory difficulties at birth (2.7 per cent) and a low incidence of fixed flexion deformities (1.6 per cent), at the expense of a small increase in the incidence of culture failure (2.2 per cent).