A case of euglyacemic diabetic ketoacidosis in a patient with gestational diabetes mellitus.

A 30-year old woman at 30 weeks gestation with insulin-controlled gestational diabetes was admitted with nausea and vomiting. Plasma glucose was 3.3 mmol/l with pH 7.23 and raised capillary ketones at 6.1 mmol/l. She was diagnosed with euglycaemic diabetic ketoacidosis. Cardiotocography showed good fetal movement and accelerations. She was given intramuscular betamethasone and started on intravenous dextrose, insulin and 0.9% saline with potassium chloride with resolution of ketosis. Euglycaemic diabetic ketoacidosis has been reported during pregnancy in patients with type 1 and type 2 diabetes. We believe that this is a report of such an occurrence in a patient with gestational diabetes.

A comparison of spontaneously conceived twins and twins conceived by artificial reproductive technologies.

Evidence on pregnancy outcomes of twins conceived by artificial reproductive technology (ART) compared with those naturally conceived (NC) is conflicting. We retrospectively audited outcomes of ART and NC twin births at Royal Maternity Hospital, Belfast from 01.01.2002-31.12.2003. Of 202 twins, 53 (26%) were ART and 149 (74%) were NC. ART group had increased maternal age (p < 0.001), more primiparous mothers (p < 0.001), used more peri-conceptual folic acid (p = 0.01), booked earlier for antenatal care (p < 0.05), delivered by caesarean section (p = 0.035) more often at a later gestation (p = 0.048) with a higher birth weight (p < 0.05). The NC group had increased congenital anomalies (p = 0.005) and babies requiring neonatal intensive care (p = 0.003). Of confirmed cases, ART twins were all dichorionic compared with 81.7% of NC (p = 0.002). Most neonatal outcome differences disappeared when NC dichorionic twins were compared with ART twins. ART twins have fewer complications than NC twins. Chorionicity accounts for most of these differences.

Evidence-based medicine: how do we find the evidence?

Applying evidence-based medicine in clinical practice is an important advance in the attempt to improve clinical care. However, if appropriate evidence is unobtainable, it obviously cannot be used. Several resources are available to find quality studies in our field, detailing successes as well as shortcomings with respect to many aspects of patient care. Databases such as MEDLINE and EMBASE are helpful, but they require specific strategies to maximize the efficiency and comprehensiveness of literature searches. In addition, they are incomplete and thus do not allow access to many good studies. In an attempt to remedy this dilemma, the Cochrane Library was created. This database contains systematic reviews on a large number of subjects as well as a controlled trial registry. It approaches the criteria of an ideal database, and has proved to be an invaluable tool in the practice of evidence-based medicine.

Immunohistochemical expression of inhibin/activin subunits in epithelial and granulosa cell tumours of the ovary.

Dimeric inhibin-A has been shown recently by a sensitive two-site ELISA assay to be a useful tumour marker in granulosa cell tumours of the ovary. It is also elevated in some patients with malignant epithelial ovarian tumours. To identify the precise subunits of inhibin expressed in ovarian tumours, three monoclonal antibodies, R1, E4, and INPRO (against the alpha C-, beta A-, and pro-alpha-subunits, respectively), were evaluated by immunohistochemistry on a panel of six granulosa cell and nine epithelial tumours. All granulosa cell tumours stained positively with E4 and R1, suggesting expression of dimeric inhibin-A; in two patients where serum levels were measured pre-operatively, they were elevated. The tumours also reacted weakly with INPRO, suggesting the presence of precursor forms of the alpha-subunit. Eight malignant epithelial ovarian tumours expressed the beta A-subunit only, as recognized by E4, while one tumour expressed both alpha- and beta A-subunits, which correlated with an elevated serum inhibin-A level. Thus, while granulosa cell tumours express inhibin, the majority of epithelial tumours probably express activin, a result which needs to be confirmed by serum measurements.

The genomic structure of discoidin receptor tyrosine kinase.

The discoidin domain receptor (DDR) is a new class of receptor tyrosine kinase that is distinguished by a unique extracellular domain homologous to the lectin Discoidin I found Dictyostelium discoideum. A cosmid was isolated from a human chromosome 6 cosmid library containing the DDR gene. A complete genomic contig of the DDR gene was constructed from seven subclones of the cosmid. The cosmid fragments were analyzed by PCR, sequencing, and comparison of genomic/cDNA sequence. The DDR gene is composed of 17 exons, ranging in size from 96 to 1014 bp, distributed along approximately 12 kb of genomic DNA. The extracellular domain is encoded by 8 exons of which three code for the discoidin domain. The transmembrane domain is encoded by 1 exon, the juxtamembrane by 3 exons, and the catalytic domain by 5 exons. The generation of the two splice variants of DDR, EDDR1 and EDDR2 are explained by the genomic structure. Exon 11 (111 bp in the juxtamembrane domain) is present in DDR and absent in the splice variant EDDR1. An inverted repeat of 20 bp was identified at the 3' exon-intron junction of exon 11, which results in a lariat loop-like secondary structure. EDDR2 is generated because of a cryptic splice acceptor site that results in an extra 18 bp (6 amino acids) inserted 5' of exon 14 in the catalytic domain. A polymorphic (GT)17 repeat was identified in intron 5 with a heterozygosity of 0.71. The exon-intron structure of the DDR gene will be helpful in further understanding of its function and explains the possible structural basis for the two splice variants.

Allele loss on chromosome arm 6q and fine mapping of the region at 6q27 in epithelial ovarian cancer.

Genetic changes have been shown to be important in determining the multistep progression of cancer. Allele loss studies and karyotypic analysis of epithelial ovarian tumours have indicated the presence of putative tumour suppressor genes on chromosomes 6, 11, 13, 17, 18, 22, and X. We have focused on chromosome arm 6q to identify the minimal region that may contain a putative tumour suppressor gene. Nineteen polymorphic microsatellite markers from 6q and one centromeric marker (D6S294) have been used to detect allele loss in 68 ovarian tumours (six benign, six borderline, and 56 with malignant histology). Allele loss was evaluated by separation of fluorescence labelled polymerase chain reaction-amplified products. Forty-six of fifty-six (82%) malignant tumours showed allele loss on 6q, whereas only four of 56 had lost all the markers tested. Forty-one of fifty-six (73%) malignant tumours showed allele loss at 6q26-27. The minimal region of allele loss was between markers D6S264 and D6S297 (3 cM), with maximal allele loss of 62% at D6S193 and 52% at D6S297. Three tumours showed loss of D6S193 only, while retaining flanking informative markers. Allele loss around 6q26-27 was observed in all histological types of epithelial ovarian cancer and did not correlate with any clinical factors. In addition, there was allele loss at ESR (56%) and D6S286 (47%), though a minimal region was not defined. Allele loss at 6q12-25 correlated significantly with endometrioid and mucinous ovarian malignant tumours (P = 0.01). The physical mapping of the region between D6S297 and D6S264 will allow the eventual identification of the putative tumour suppressor gene.

The influence of laparoscopy on infertility management.

In 1983, we reported on the role of laparoscopy in the Infertility Clinic at the Rotunda Hospital. We now present the current position and the effect of a laparoscopic investigation on subsequent patient management. At laparoscopy, 31% of patients had evidence of pelvic inflammatory disease and 5% had endometriosis. Management was altered in 39 (43%) patients. When reviewed, 14 (23%) patients had conceived, 5 patients without medical intervention and more patients with secondary infertility. The incidence of pelvic inflammatory disease is increased and of endometriosis is unchanged from the previous report.