Sonographic markers of fetal adiposity and risk of Cesarean delivery.

OBJECTIVE: Increased fetal size is associated with shoulder dystocia during labor and subsequent need for assisted delivery. We sought to investigate if increased fetal adiposity diagnosed sonographically in late pregnancy is associated with increased risk of operative delivery. METHODS: This secondary analysis of the Genesis Study recruited 2392 nulliparous women with singleton pregnancy in cephalic presentation, in a prospective, multicenter study, to examine prenatal and intrapartum predictors of Cesarean delivery. Participants underwent ultrasound and clinical evaluation between 39 + 0 and 40 + 6 weeks' gestation. Data on fetal biometry were not revealed to patients or to their managing clinicians. A fetal adiposity composite of fetal thigh adiposity and fetal abdominal wall thickness was compiled for each infant in order to determine whether fetal adiposity > 90th centile was associated with an increased risk of Cesarean or operative vaginal delivery. RESULTS: After exclusions, data were available for 2330 patients. Patients with a fetal adiposity composite > 90th centile had a higher maternal body mass index (BMI) (25 ± 5 kg/m2 vs 24 ± 4 kg/m2 ; P = 0.005), birth weight (3872 ± 417 g vs 3585 ± 401 g; P < 0.0001) and rate of induction of labor (47% (108/232) vs 40% (834/2098); P = 0.048) than did those with an adiposity composite ≤ 90th centile. Fetuses with adiposity composite > 90th centile were more likely to require Cesarean delivery than were those with adiposity composite ≤ 90th centile (P < 0.0001). After adjusting for birth weight, maternal BMI and need for induction of labor, fetal adiposity > 90th centile remained a risk factor for Cesarean delivery (P < 0.0001). A fetal adiposity composite > 90th centile was more predictive of the need for unplanned Cesarean delivery than was an estimated fetal weight > 90th centile (odds ratio, 2.20 (95% CI, 1.65-2.94; P < 0.001) vs 1.74 (95% CI, 1.29-2.35; P < 0.001). Having an adiposity composite > 90th centile was not associated with an increased likelihood of operative vaginal delivery when compared with having an adiposity composite ≤ 90th centile (P = 0.37). CONCLUSIONS: Fetuses with increased adipose deposition are more likely to require Cesarean delivery than are those without increased adiposity. Consideration should, therefore, be given to adding fetal thigh adiposity and abdominal wall thickness to fetal sonographic assessment in late pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Are women having a vaginal birth after a previous caesarean delivery at increased risk of anal sphincter injury?

OBJECTIVE: To examine the incidence of obstetric anal sphincter injury in women who had a successful vaginal birth after a previous caesarean delivery (VBAC). DESIGN: Retrospective analysis of prospectively gathered data. SETTING: A tertiary referral university institution. POPULATION: All secundiparous women with a previous caesarean delivery who had a VBAC from 2001 to 2011. METHODS: Details of maternal demographics, intrapartum characteristics and outcomes were examined in cases of VBAC with accompanying anal sphincter injury. MAIN OUTCOME MEASURES: Rates of obstetric anal sphincter injury and associated risk factors. RESULTS: During the study period there were 3071 trials of labour in secundiparous women with a previous caesarean delivery; 65% (1981/3071) of these had a successful VBAC. Women having a VBAC were at greater risk of anal sphincter injury than nulliparous women having a vaginal delivery over the same period (5% [98/1981] versus 3.5% [1216/34,496], P = 0.001, odds ratio 1.4, 95% CI 1.15-1.75). The rate of instrumental delivery in woman having a VBAC was 39% (771/1981). On multiple logistic regression analysis an increased rate of instrumental delivery was a strong predictor of sphincter injury (P = 0.03, odds ratio 1.15, 95% CI 1.01-1.3). When the first labours of women with sphincter injury in the VBAC group were examined, 70% (60/86) had been in labour before undergoing their caesarean delivery. CONCLUSION: The incidence of anal sphincter injury in women undergoing VBAC is 5% and birthweight is the strongest predictor of this. The rate of instrumental delivery in this group was also increased.

A retrospective observational study of labour ward work Intensity: The challenge of maternity staffing.

BACKGROUND: The UK and Ireland are facing significant challenges in the recruitment and retention of midwifery staff. Deficiencies in staffing, training and leadership have been cited as contributory factors to substandard care in both regional and global independent maternity safety reports. Locally, workforce planning is critical to maintaining 'one to one' care for all women in labor and to meet the peaks of daily birthing suite activity. OBJECTIVES: Analyze the variation in work intensity, defined by the mean number and range of births per midwifery working hours. METHODS: Retrospective observational study of birthing suite activity between 2017 and 2020. 30,550 singleton births were reported during the study period; however, 6529 elective Cesarean sections were excluded as these were performed during normal working hours by a separate operating theatre team. The times of 24,021 singleton births were organized into five proposed midwifery working rosters lasting eight or 12 h; A (00.00-07.59), B (08.00-15.59), C (16.00-23.59), D (20.00-0.759) and E (0.800-19.59). RESULTS: The number of births was comparable between the eight-hour and 12-hour work periods with a mean of five to six babies born per roster (range zero to 15). Work periods D and E lasting 12-hours both recorded a mean of eight births (range zero to 18). Hourly births ranged from a minimum of zero to a maximum of five births per hour (greater than seven times the mean), a number that was achieved 14 times during the study period. CONCLUSIONS: The mean number of births is consistent between normal working hours and unsociable 'on-call' periods, however there is an extreme range of activity within each midwifery roster. Prompt escalation plans remain essential for maternity services to manage unexpected increases in demand and complexity. WHAT IS ALREADY KNOWN ON THIS TOPIC: Shortfalls in staffing and inadequate workforce planning have been frequently cited in recent maternity safety reports as barriers to sustainable and safe maternity care. WHAT THIS STUDY ADDS: Our study shows that the mean number of births in a large tertiary center are consistent across day and night rosters. However, there are large fluctuations in activity during which births can exceed the number of available midwives. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: Our study reflects the sentiments of the Ockenden review and APPG report on safe maternity staffing. Investment in services and the workforce to aid recruitment and reduce attrition is essential to establish robust escalation plans, including the deployment of additional staff in the event of extreme service pressures.

Effect of very high-dose thymidine infusions on leukemia and lymphoma patients.

The physiological pyrimidine nucleoside thymidine (dThd) is cytotoxic to normal and neoplastic cells in culture that are exposed to concentrations in excess of 1 mM for prolonged periods. In order to explore the antileukemic potential of the compound, we have treated six patients with relapsed leukemia or lymphoma with marrow and blood involvement, by prolonged infusions of dThd, at dosages of 90 to 240 g/sq m/day for 14 to 29 days. Mean plasma dThd concentration ranged from 3.8 to 5.5 mM. Cerebrospinal fluid levels were measured on three occasions and ranged from 2 to 23.5% of simultaneous plasma levels. Diarrhea was dose limiting in one patient. The other side effects included nausea and vomiting in all patients, hepatotoxicity in two patients, electrolyte imbalance in one, progression of a pericardial effusion to tamponade in one, and mild central nervous system toxicity in five. In all cases, this therapy produced bone marrow aplasia. One patient with acute lymphoblastic leukemia, refractory to prior treatment, achieved a complete remission which lasted for 16 weeks. Another patient with lymphoblastic lymphoma had a greater than 50% reduction in his mediastinal mass which lasted for less than 1 month. At multiple points during therapy, the bone marrow S-phase fraction was measured by flow cytometry and autoradiography. In five patients, the proportion of cells in S phase increased during the first few days of the infusion but then returned to base line, concomitant with an overall reduction in the number of bone marrow blasts. Cytoreduction was evaluated by the technique of W. Hiddemann, B. D. Clarkson, T. Buchener, M. R. Melamed, and M. Andreeff (Blood, 59: 216-225, 1982). The magnitude of tumor cell kill ranged from 0.7 to 3.6 logs of blasts/cu mm of bone marrow. The data demonstrate that dThd is able to induce a complete remission in a patient with acute leukemia previously refractory to treatment. However, because of the very large drug quantities, fluid volumes, and the prolonged course required to produce the necessary tumor cell kill, this treatment approach is too impractical to be used extensively.

Does anal sphincter injury preclude subsequent vaginal delivery?

OBJECTIVE: To assess continence and anal sphincter integrity during a subsequent pregnancy and delivery in women known to have a previous anal sphincter injury. DESIGN: Prospective observational study. SETTING: The National Maternity Hospital, Dublin, Ireland. POPULATION: Antenatal patients with a documented obstetric anal sphincter injury at a previous delivery. METHODS: Women underwent symptom scoring, endoanal ultrasound and manometry. MAIN OUTCOME MEASURES: Recommended and actual mode of delivery, continence scores and endoanal ultrasound findings after index delivery. RESULTS: 557 women were studied. 293 (53%) had no symptoms of faecal incontinence, 189 (34%) had mild symptoms and 75 (13%) moderate or severe symptoms. 408 (73%) had an endoanal ultrasound. 383(94%) had a normal or small (<1 quadrant) defect in the internal anal sphincter and 390 (96%) had a scar or small (<1e quadrant) defect in the external anal sphincter. 393 (70%) delivered vaginally. 164 (30%) were delivered by caesarean section. 197/557 (35%) returned for follow-up. There was no significant change in continence following either vaginal or caesarean delivery. 20 (5.1%) women had a recognised second anal sphincter tear during vaginal delivery. CONCLUSIONS: The majority of women who sustain a third degree tear have minimal or no symptoms of faecal incontinence when assessed antenatally in a subsequent pregnancy. 70% go on to have a vaginal delivery, with little impact on faecal continence. These findings provide reassurance for patients and clinicians about the safety of vaginal delivery following anal sphincter injury in appropriately selected patients.

Characterization of heterodimeric alkaline phosphatases from Escherichia coli: an investigation of intragenic complementation.

Escherichia coli alkaline phosphatase (EC 3.1.3.1) belongs to a rare group of enzymes that exhibit intragenic complementation. When certain mutant versions of alkaline phosphatase are combined, the resulting heterodimeric enzymes exhibit a higher level of activity than would be expected based upon the relative activities of the parental enzymes. Nine previously identified alkaline phosphatase complementation mutants were re-examined in this work in order to determine a molecular explanation of intragenic complementation in this experimental system. The locations of these mutations were determined by DNA sequence analysis after PCR amplification of the phosphatase-negative phoA gene. Most of the mutations involved ligands to metal-binding sites. Each of the mutant enzymes was re-created by site-specific mutagenesis, expressed, purified, and kinetically characterized. To investigate cooperativity between the two subunits, we analyzed heterodimeric forms of some of the site-specific mutant enzymes. To enable the isolation of the heterodimeric alkaline phosphatase in pure form, the overall charge of one subunit was altered by replacing the C-terminal Lys residue with three Asp residues. This modification had no effect on the kinetic properties of the enzyme. Heterodimeric alkaline phosphatases were created using two methods: (1) in vitro formation by dissociation at acid pH followed by reassociation at slightly alkaline pH conditions in the presence of zinc and magnesium ions; and (2) in vivo expression from a plasmid carrying two different phoA genes. Increases in k(cat), as well as a large reduction in the p-nitrophenyl phosphate K(m) were observed for certain combinations of mutant enzymes. These results suggest that the structural assembly of E. coli alkaline phosphatase into the dimer induces cooperative interactions between the monomers necessary for the formation of the functional form of the holoenzyme.

Kinetic and X-ray structural studies of three mutant E. coli alkaline phosphatases: insights into the catalytic mechanism without the nucleophile Ser102.

Escherichia coli alkaline phosphatase (EC 3.1.3.1) is a non-specific phosphomonoesterase that catalyzes the hydrolysis reaction via a phosphoseryl intermediate to produce inorganic phosphate and the corresponding alcohol. We investigated the nature of the primary nucleophile, fulfilled by the deprotonated Ser102, in the catalytic mechanism by mutating this residue to glycine, alanine and cysteine. The efficiencies of the S102G, S102A and S102C enzymes were 6 x 10(5)-fold, 10(5)-fold and 10(4)-fold lower than the wild-type enzyme, respectively, as measured by the kcat/Km ratio, still substantially higher than the non-catalyzed reaction. In order to investigate the structural details of the altered active site, the enzymes were crystallized and their structures determined. The enzymes crystallized in a new crystal form corresponding to the space group P6322. Each structure has phosphate at each active site and shows little departure from the wild-type model. For the S102G and S102A enzymes, the phosphate occupies the same position as in the wild-type enzyme, while in the S102C enzyme it is displaced by 2.5 A. This kinetic and structural study suggests an explanation for differences in catalytic efficiency of the mutant enzymes and provides a means to study the nature and strength of different nucleophiles in the same environment. The analysis of these results provides insight into the mechanisms of other classes of phosphatases that do not utilize a serine nucleophile.

Renal carcinoma with staghorn calculus, perinephric abscess, and xanthogranulomatous pyelonephritis in same kidney. Subcutaneous abscess of thigh as initial presentation.

A case is reported of the simultaneous occurrence of renal carcinoma with staghorn calculus, perinephric abscess, and xanthogranulomatous pyelonephritis in the same kidney, with subcutaneous abscess of the thigh as the initial presentation. The coexistence of these diseases in the same kidney would seem to be important since they are frequently confused with each other.

Transitional cell carcinoma of upper urinary tract: some prognostic indicators.

Thirty cases of transitional cell carcinoma were reviewed over a twenty-year period. The incidence of bladder tumor recurrence was no different in those who had complete or incomplete nephroureterectomy. Grade and stage correlated well with survival. Intravenous urogram findings at presentation were important prognostic indicators.

Predicted and actual change in serum PSA following prostatectomy for BPH.

OBJECTIVE: To determine the relationship between prostatic adenoma volume and serum prostate-specific antigen (PSA) levels in patients with benign prostatic hyperplasia (BPH), and to compare the predicted change in serum PSA following prostatectomy with the actual change observed. METHODS: Transrectal ultrasound (TRUS) estimation of prostatic adenoma (transition zone) and total gland volumes were calculated in 96 patients prior to prostatectomy. BPH was confirmed histologically following transurethral prostatectomy (in 86) and open prostatectomy (in 10). Serum PSA was measured preoperatively in all patients and post-operatively in 87 patients. RESULTS: Correlation coefficients of 0.607 and 0.614 were observed between PSA and adenoma and total gland volumes, respectively. The geometric mean ratio of PSA to adenoma volume was 0.120 micrograms/L/cc with 95% CI (0.104, 0.139) and to total gland volume was 0.068 micrograms/L/cc with 95% CI (0.058, 0.078). TRUS-determined adenoma and total gland volumes correlated well (r = 0.915), as did TRUS-determined adenoma volume and resected weight (r = 0.878). The mean ratio of change in PSA to resected weight was -0.096 micrograms/L/g with 95% CI (-0.128, -0.064). Neither total gland volume nor operation type affected the relationship between change in serum PSA and resected weight. CONCLUSIONS: The adenoma should be the main determinant of serum PSA levels in patients with BPH. TRUS adenoma volume measurement is therefore the most appropriate preoperative measure when one is interpreting elevated levels of serum PSA in men thought clinically to have BPH.

Applications of glucocorticosteroids. The effects of twice-daily vs once-every-other-day applications on mouse epidermal cell DNA synthesis.

To determine a schedule for continuous suppression of epidermal cell DNA synthesis, 0.05% fluocinonide ointment was applied either twice daily or once on alternate days to hairless mouse skin for 174 hours. Suppression occurred similarly for both regimens for 78 hours followed by an increase in DNA synthesis despite continued application of fluocinonide. The systemic effect was less marked with the alternate-day schedule. The effect of a single application of the fluocinonide ointment was also studied over 174 hours. Substantial inhibition of DNA synthesis occurred but for a shorter period followed by an increase and then return to normal values. Experiments were performed where second applications were made at various time intervals after the first. These did not appear to affect events until 192 hours had elapsed, when a second application caused profound inhibition of DNA synthesis once more.

Anthralin-corticosteroid combination therapy in the treatment of chronic plaque psoriasis.

A prospective randomized trial of anthralin in Lassar's paste compared with anthralin in 0.0125% clobetasol propionate in the treatment of chronic plaque psoriasis was undertaken. The psoriatic skin of patients treated with the corticosteroid-anthralin combination cleared significantly more quickly than those treated with anthralin alone, with a mean time to clearance of 14.9 days compared with 18.5 days, and with lower concentrations of anthralin. No significant difference was found in the rate of relapse of the two treatment groups, with relapse occurring in over 80% of patients within one year. Anthralin in 0.0125% clobetasol propionate was found to be an effective agent in the treatment of chronic plaque psoriasis, and one that was cosmetically acceptable to patients and nursing staff. An important disadvantage, however, was the development of a staphylococcal folliculitis in four of the 35 patients in which it was used. Because of this, anthralin in Lassar's paste remains our standard inpatient therapy, although the ease of use and cosmetic acceptability of anthralin in clobetasol propionate make it a useful remedy for outpatient use.

Myofibroblastoma of the breast.

Myofibroblastoma of the breast is an uncommon stromal tumor most often found in older men. It usually presents as a solitary well-circumscribed breast lesion consisting of slender bipolar spindle cells and broad bands of hyalinised collagen. This is the first documented case of myofibroblastoma of the breast in Australia. Found in a 71-year-old man, this case demonstrates many of the typical features of this entity. A history of previous trauma to the chest wall was present in this case, a finding only rarely associated with this lesion.

Reproducibility and observer variability of transrectal ultrasound measurements of prostatic volume.

Transrectal ultrasound (TRUS) is an established investigation in benign and malignant prostatic disease though the level of reproducibility of TRUS volume measurements is not known. A group of observers in the UK and the USA who were participating in linked prospective studies of benign prostatic hyperplasia each carried out measurements during real-time scanning and on a series of static TRUS images. Results demonstrated good reproducibility for measurements of antero-posterior, transverse, and longitudinal dimensions of the prostate by an experienced UK urologist; only a minor degree of interobserver variation occurred in measurements made between experienced UK and USA observers. Using static images, USA observers obtained results that were in good agreement, whereas the UK observers, only two of whom used TRUS regularly, were in poor agreement with each other. This study demonstrates a high level of reproducibility for TRUS volume measurements performed by experienced observers.

Phase II trial of 10-Edam in patients with advanced colorectal carcinoma.

10-Edam (10-ethyl-10-deaza-aminopterin), an antifolate derivative, was administered to 14 chemotherapy-naive patients with advanced colorectal carcinoma. The drug was given weekly by intravenous route at an initial dose of 80 mg/m2, with escalation or attenuation according to tolerance. Mucositis was dose limiting and occurred in 11 of 14 patients (78.6%). Removal from the study was required in one patient due to progressive pulmonary fibrosis that was histologically identical to methotrexate-induced lung damage. Toxicity was otherwise mild to moderate and included diarrhea, constipation, abdominal discomfort, anorexia, nausea/vomiting, rash, and fatigue. There were no responses to 10-Edam in this study, 95% confidence interval (0-0.23). Stable disease was achieved in four patients; the remaining 10 patients demonstrated progression within 9 weeks of initiating systemic therapy. 10-Edam employed at this dosage and schedule was not effective as a treatment against advanced colorectal carcinoma.

General practitioners miss disability and anxiety as well as depression in their patients with osteoarthritis.

BACKGROUND: General practitioners (GPs) integrate physical, psychological, and social factors when assessing patients, particularly those with chronic diseases. Recently, the emphasis has been on assessment of depression but not of other factors. AIM: To determine functional disability, psychological morbidity, social situation, and use of health and social services in patients with osteoarthritis and examine GP knowledge of these factors. METHOD: Two hundred patients completed a validated postal questionnaire about functional disability (Health Assessment Questionnaire [HAQ]), mood (Hospital Anxiety and Depression Scale [HAD]), employment status, who they lived with, welfare benefits received, and use of health and social services. A similar questionnaire was completed by the patient's GP, including a HAQ. However, a three-point scale was used to assess depression and anxiety. RESULTS: Forty-seven per cent of patients were moderately or severely disabled (HAQ > 1). GPs underestimated functional disability: mean patient HAQ = 1.04 (95% confidence interval [CI] = 0.92-1.16), mean GP HAQ = 0.74 (95% CI = 0.65-0.83), and there was low correlation between patient and GP scores (kappa = 0.24). There was moderate prevalence of depression and high prevalence of anxiety, which the GP often did not recognise: patient depression = 8.3% (95% CI = 4.1%-12.8%), GP depression = 6.0% (95% CI = 2.4%-9.6%), kappa = 0.11; patient anxiety = 24.4% (95% CI = 17.8%-31.0%), GP anxiety = 11.9% (95% CI = 6.9%-16.9%), kappa = 0.19. Only 46% of severely disabled patients (HAQ > 2) were receiving disability welfare benefits. GPs were often unaware of welfare benefits received or the involvement of other professionals. CONCLUSION: GPs frequently lack knowledge about functional disability, social factors, and anxiety as well as depression in their patients with osteoarthritis.

Impact of previously unrecognized benign prostatic hyperplasia on the daily activities of middle-aged and elderly men.

To assess the importance of benign prostatic hyperplasia on activities of daily living, a cross-sectional survey of 1627 men aged 40-79 years (representing a 65% response rate) registered with two health centres in central Scotland was carried out, using a urinary symptom questionnaire and uroflowmetry to identify men more likely to have benign prostatic hyperplasia. The condition was defined as a prostate gland of more than 20 g in the presence of symptoms of urinary dysfunction and/or a peak flow rate of less than 15 ml s-1, without evidence of malignancy. Transrectal ultrasonography was used to measure the volume (and by inference weight) of prostate glands. A total of 410 men satisfied the criteria for benign prostatic hyperplasia. Overall, 51% of men with benign prostatic hyperplasia reported interference with at least one of a number of selected activities of daily living as a result of urinary dysfunction, compared with 28% of men who did not have this condition. In 17% of men of working age (40-64 years) with benign prostatic hyperplasia, this interference occurred most or all of the time for at least one activity of daily living compared with only 3% of men in the same age group who did not have this condition. If the criteria of unmet need for treatment of benign prostatic hyperplasia constitutes interference by urinary dysfunction most or all of the time in at least one activity of daily living, then the findings of this survey suggest that a substantial number of middle aged and elderly men living in the United Kingdom may be in need of assessment and treatment for this condition.

Cholangio carcinoma treated by liver split and resection.

A case of cholangiocarcinoma at the liver hilum presenting with jaundice is described. Pre-operative transhepatic cholangiography, hepatic arteriography and splenoportography led to liver split, with successful resection of tumour and triple hepatico-jejunostomy. Despite tumour recurrence eight months of palliation were achieved. Current methods of treating the condition are discussed.

Hospital readmissions. We'll meet again.

A 12-month study of emergency medical admissions at one trust suggests most readmissions could not be avoided. The re-admission rate within 28 days was 10 per cent, of which 5 per cent were found to be preventable. Readmissions were higher among smokers, men and people living in hostels. The study found no evidence of increased readmissions in winter.