Diagnosis of superficial endometriosis on transvaginal ultrasound by visualization of peritoneum of pouch of Douglas.

OBJECTIVE: Around 80% of women with endometriosis have superficial endometriosis (SE) rather than ovarian or deep endometriosis (DE). However, to date, advances in non-invasive, imaging-based diagnosis have been limited to DE or ovarian disease. The objective of this study was to determine whether we can detect SE on transvaginal ultrasound scan (TVS) by assessing the peritoneum of the pouch of Douglas (POD). METHODS: This was a retrospective diagnostic test study following a change in practice to include POD peritoneum assessment for SE during TVS at a tertiary London hospital. Eligible patients underwent TVS by a single clinician trained in endometriosis scanning and a subsequent surgical procedure (laparoscopy) between April 2018 and September 2021. Participants formed a consecutive series. The TVS findings were compared with those of laparoscopy as the gold standard. Comparison of TVS findings with intraoperative findings was performed by calculating the diagnostic test performance measures (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive and negative likelihood ratios). RESULTS: The study included a total of 100 patients. We found that 43/100 (43.0%) patients had no endometriosis, 33/100 (33.0%) had SE and 24/100 (24.0%) had DE on laparoscopy. SE was correctly detected on TVS in 17/33 patients, with a sensitivity of 51.5% (95% CI, 33.5-69.2%), specificity of 94.0% (95% CI, 85.4-98.4%), PPV of 81.0% (95% CI, 60.8-92.1%) and NPV of 79.7% (95% CI, 73.4-84.9%). DE was correctly diagnosed in 20/24 cases, including all ovarian cases, with a sensitivity of 83.3% (95% CI, 62.3-95.3%), specificity of 97.4% (95% CI, 90.8-99.7%), PPV of 90.9% (95% CI, 71.6-97.5%) and NPV of 94.9% (95% CI, 88.3-97.8%). The detection of SE on TVS was most accurate in the POD (sensitivity, 50.0%; specificity, 96.4%; PPV, 76.9%; NPV, 88.9%). CONCLUSIONS: This study shows that the detection of SE in the POD is possible using routine TVS. While negative TVS does not reliably confirm the absence of disease or replace diagnostic laparoscopy, positive TVS facilitates non-invasive diagnosis for a much larger group of women than was previously possible. This should help to reduce the time from the onset of symptoms to diagnosis and enable initiation of medical treatment without the risk, cost and delay associated with a surgical diagnosis. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The risk of miscarriage following surgical treatment of heterotopic extrauterine pregnancies.

STUDY QUESTION: What is the risk of loss of a live normally sited (eutopic) pregnancy following surgical treatment of the concomitant extrauterine ectopic pregnancy? SUMMARY ANSWER: In women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine ectopic pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. WHAT IS KNOWN ALREADY: Previous studies have indicated that surgical treatment of the concomitant ectopic pregnancy in women with live eutopic pregnancies could be associated with an increased risk of miscarriage. The findings of our study did not confirm that. STUDY DESIGN SIZE DURATION: A retrospective observational case-control study of 52 women diagnosed with live eutopic and concomitant extrauterine pregnancies matched to 156 women with live normally sited singleton pregnancies. The study was carried out in three London early pregnancy units (EPUs) covering a 20-year period between April 2000 and November 2019. PARTICIPANTS/MATERIALS SETTING METHODS: All women attended EPUs because of suspected early pregnancy complications. The diagnosis of heterotopic pregnancy was made on ultrasound scan and women were subsequently offered surgical or expectant management.There were three controls per each case who were randomly selected from our clinical database and were matched for maternal age, mode of conception and gestational age at presentation. MAIN RESULTS AND THE ROLE OF CHANCE: In the study group 49/52 (94%) women had surgery and 3/52 (6%) were managed expectantly. There were 9/52 (17%, 95% CI 8.2-30.3) miscarriages <12 weeks' gestation and 9/49 (18%, 95% CI 8.7-32) miscarriages in those treated surgically. In the control group, there were 28/156 (18%, 95% CI 12.2-24.8) miscarriages <12 weeks' gestation, which was not significantly different from heterotopic pregnancies who were treated surgically [odds ratio (OR) 1.03 95% CI 0.44-2.36]. There was a further second trimester miscarriage in the study group and one in the control group. The live birth rate in the study group was 41/51 (80%, 95% CI 66.9-90.2) and 38/48 (79%, 95% CI 65-89.5) for those who were treated surgically. These results were similar to 127/156 (81%, 95% CI 74.4-87.2) live births in the control group (OR 0.87, 95% CI 0.39-1.94). LIMITATIONS REASONS FOR CAUTION: This study is retrospective, and the number of patients is relatively small, which reflects the rarity of heterotopic pregnancies. Heterotopic pregnancies without a known outcome were excluded from analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that in women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. This finding will be helpful to women and their clinicians when discussing the options for treating heterotopic pregnancies. STUDY FUNDING/COMPETING INTERESTS: This work did not receive any funding. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Research Registry: researchregistry6430.

The impact of the Covid-19 pandemic on care of women with ectopic pregnancy in a tertiary London hospital.

BACKGROUND: In response to the COVID-19 pandemic, a central London tertiary referral hospital's nurse-led Early Pregnancy & Acute Gynaecology Unit (EPAGU) suspended its walk-in service in favour of a telephone triage system with scheduled appointments. OBJECTIVE: To assess if the pandemic and this adaptation to clinical services had an impact on the presentation, management and complication rate of ectopic pregnancies. MATERIALS AND METHODS: A retrospective review was performed of ectopic pregnancies diagnosed in the EPAGU between 5th of March 2020 - 15th of July 2020 (pandemic) and 5th of March 2019 - 15th of July 2019 (pre-pandemic). MAIN OUTCOME MEASURES: Ultrasound findings, patient demographics, serum hCG concentrations, operative findings and complications. RESULTS: There was a 36% reduction in attendances to the unit during the pandemic. Allowing for this, there was no significant difference in the diagnosis rate between the two periods. There was no significant difference in the gestation at diagnosis, serum hCG concentration or volume of mass at presentation. There was also no significant difference in rate of surgical intervention or complications including rupture of fallopian tube, haemoperitoneum or need for blood transfusion. CONCLUSION: This study suggests this is a safe means of caring for women with ectopic pregnancies which does not limit management options nor lead to higher complication rates. WHAT IS NEW: Other EPAGUs may choose to adopt a telephone triage system with reassurance of its safety.

The Saccharomyces cerevisiae SRK1 gene, a suppressor of bcy1 and ins1, may be involved in protein phosphatase function.

The Saccharomyces cerevisiae SRK1 gene, when expressed on a low-copy shuttle vector, partially suppresses the phenotype associated with elevated levels of cyclic AMP-dependent protein kinase activity and suppresses the temperature-sensitive cell cycle arrest of the ins1 mutant. SRK1 is located on chromosome IV, 3 centimorgans from gcn2. A mutant carrying a deletion mutation in srk1 is viable. SRK1 encodes a 140-kDa protein with homology to the dis3+ protein from Schizosaccharomyces pombe. The ability of SRK1 to alleviate partially the defects caused by high levels of cyclic AMP-dependent protein kinase and the similarity of its encoded protein to dis3+ suggest that SRK1 may have a role in protein phosphatase function.

Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway.

We have isolated a snf1/ccr1 mutant of Saccharomyces cerevisiae which loses viability upon starvation and fails to accumulate glycogen in response to abrupt depletion of phosphate or glucose. A snf1 null mutant is sensitive to heat stress and starvation and fails to accumulate glycogen during growth in rich medium. The phenotypes of the snf1 mutants are those commonly associated with an overactivation of the adenylate cyclase pathway. Mutations in adenylate cyclase or RAS2 which decrease the level of cAMP in the cell moderate the snf1 phenotype. In contrast, a mutation in RAS2 (RAS2val19) which increases the level of cAMP or a mutation in the regulatory subunit (BCY1) of cAMP-dependent protein kinase which results in unregulated cAMP-dependent protein kinase activity accentuates the snf1 phenotype. However, the action of SNF1 in the stress response appears at least partly independent of cAMP-dependent protein kinase because a snf1 phenotype is observed in a strain that lacks all three of the genes that encode the catalytic subunits of cAMP-dependent protein kinase. SNF1 therefore acts at least in part through a cAMP-independent pathway.

Cell wall active antifungal compounds produced by the marine fungus Hypoxylon oceanicum LL-15G256. III. Biological properties of 15G256 gamma.

15G256 gamma is a cyclic lipopeptide antifungal agent discovered in a mechanism of action screen for cell wall acting antifungal agents. The compound shows moderate activity in both greenhouse tests against plant disease caused by pathogenic fungi and in in vitro tests against human fungal pathogens. Microscopic examination of treated fungi suggests that the compound acts by the inhibition of cell wall biosynthesis. However, in vitro inhibition of Neurospora crassa glucan and chitin synthase were only observed at high drug concentrations suggesting that 15G256 gamma may act on a novel cell wall target.

Routine staging laparoscopy has no place in the management of colorectal liver metastases.

AIMS: Staging laparoscopy has been recommended in the management of patients with colorectal liver metastases prior to hepatectomy in order to reduce the incidence and associated morbidity of futile laparotomies. The utility of staging laparoscopy has not been assessed in patients undergoing CT, PET-CT and MRI as standard preoperative staging. METHODS: All patients undergoing attempted open hepatectomy for colorectal liver metastases between 1/4/2008 and 31/3/2012 were identified from a prospectively maintained research database. All patients who underwent futile laparotomy were identified, with demographics and operative notes subsequently analysed. RESULTS: A total of 274 patients underwent attempted open hepatectomy during the study period. At laparotomy 12 (4.4%) patients were found to have irresectable disease. There were no unifying demographic factors within the patients undergoing futile laparotomy. CONCLUSIONS: With modern imaging, the potential yield of staging laparoscopy is low. Staging laparoscopy should not be used routinely, but may have a role in the case of specific clinical concerns.

Borderline and schizophrenic patients. A comparative study of defensive structure.

Historically unresolved diagnostic questions regarding the borderline diagnosis and its relationship to schizophrenia are explored. Is the borderline syndrome a subvariant of schizophrenia or does it constitute a distinct diagnostic entity in its own right with specific, common, and identifiable features which set this group of patients off from others? Based on recent developments in psychoanalytic object relations theory, a Rorschach scoring manual designed to assess the primitive defenses that are conceptualized to underlie as well as organize the borderline patient was applied to independently selected samples of hospitalized borderline (DSM-III criteria) and schizophrenic (Research Diagnostic Criteria) adolescent and young patients. Consistent and significant differences were found between groups on the basis of defensive functioning. Borderline patients were found to use test measures of splitting, primitive devaluation, idealization, denial, and projective identification significantly more than schizophrenic patients. The levels of inter-rater reliability and the direction of the results in discriminating borderline from schizophrenic patients on the basis of defensive functioning indicate that the Rorschach Scoring System is a reliable and valid instrument. The implications of the results in terms of the differential diagnostic issues, the nature of borderline defenses, and the utilization of the Rorschach as a research instrument are considered.

Multiple copies of PBS2, MHP1 or LRE1 produce glucanase resistance and other cell wall effects in Saccharomyces cerevisiae.

Five sequences were isolated by selection for multiple copy plasmids that conferred resistance to laminarinase, an enzyme that specifically degrades cell wall beta(1-3) glucan linkages. Strains carrying three of these plasmids showed alterations in cell wall glucan labelling. One of these plasmids carried PBS2, a previously identified, non-essential gene which produces a variety of phenotypes and encodes a mitogen-activated protein kinase kinase analogue (Boguslawski and Polazzi, 1987). Cells carrying PBS2 at multiple copy show a small decrease in cell wall beta(1-6) glucans. Measurements of beta(1-3) glucan synthase activity in multi-copy PBS2 cells showed an approximate 30-45% increase in enzyme specific activity while a pbs2 delta disruption strain showed a decrease in glucan synthase activity of approximately 45% relative to control. A pbs2 delta disruption strain was laminarinase super-sensitive and supersensitive to K1 killer toxin while a strain carrying PBS2 at multiple copy was resistant to killer toxin. A second plasmid carried a portion of the MHP1 gene which has been reported to encode a microtubule-interacting protein (Irminger-Finger et al., 1996). The MHP1 gene product is a predicted 1398 amino acid protein and only approximately 80% of the amino portion of this protein is required for laminarinase resistance. Cells carrying the amino portion of MHP1 at multiple copy show a decrease in high molecular weight cell wall beta(1-6) glucans and were killer toxin resistant while a disruption strain was viable and killer toxin super-sensitive. Cells carrying this plasmid showed decreased levels of high molecular weight beta(1-6) glucans and increased glucan synthase activity. The laminarinase resistance conferred by the third plasmid mapped to the previously uncharacterized YCL051W open reading frame and this gene was therefore named LRE1 (laminarinase resistance). The LRE1 gene encodes a non-essential 604 amino acid hydrophilic protein. Unexpectedly, cells carrying LRE1 at multiple copy show no alteration in cell wall glucans or glucan synthase activity. Subcloning experiments demonstrated that the production of these cell wall effects requires the presence of both LRE1 and YCL052C (PBN1), a second open reading frame present on the original plasmid. Cells carrying multiple copies of PBN1 alone show no significant alterations in cell wall glucans or glucan synthase activity, indicating that these effects require the presence of multiple copies of both genes.

Nikkomycin Z is a specific inhibitor of Saccharomyces cerevisiae chitin synthase isozyme Chs3 in vitro and in vivo.

Nikkomycin Z inhibits chitin synthase in vitro but does not exhibit antifungal activity against many pathogens. Assays of chitin synthase isozymes and growth assays with isozyme mutants were used to demonstrate that nikkomycin Z is a selective inhibitor of chitin synthase 3. The resistance of chitin synthase 2 to nikkomycin Z in vitro is likely responsible for the poor activity of this antibiotic against Saccharomyces cerevisiae.