Needed: Revolution Within by Arthur Naftalin, Spring Commencement: June 8, 1969

Text of speech delivered by Arthur Naftalin at the UND Spring Commencement on June 8, 1969. A North Dakota native, Naftalin was the mayor of Minneapolis from 1961 until 1969. He entitled his remarks: Needed: Revolution Within

Interactions of sodium pentobarbital with d-glucose and l-sorbose transport in human red cells

AbstractPentobarbital acts as a mixed inhibitor of net d-glucose exit, as monitored photometrically from human red cells. At 30°C the Ki of pentobarbital for inhibition of Vmax of zero-trans net glucose exit is 2.16±0.14 mM; the affinity of the external site of the transporter for d-glucose is also reduced to 50% of control by 1.66±0.06 mM pentobarbital. Pentobarbital reduces the temperature coefficient of d-glucose binding to the external site. Pentobarbital (4 mM) reduces the enthalpy of d-glucose interaction from 49.3±9.6 to 16.24±5.50 kJ/mol (P<0.05). Pentobarbital (8 mM) increases the activation energy of glucose exit from control 54.7±2.5 kJ/mol to 114±13 kJ/mol (P<0.01). Pentobarbital reduces the rate of l-sorbose exit from human red cells, in the temperature range 45°C–30°C (P<0.001). On cooling from 45°C to 30°C, in the presence of pentobarbital (4 mM), the Ki (sorbose, glucose) decreases from 30.6±7.8 mM to 14±1.9 mM; whereas in control cells, Ki (sorbose, glucose) increases from 6.8±1.3 mM at 45°C to 23.4±4.5 mM at 30°C (P<0.002). Thus, the glucose inhibition of sorbose exit is changed from an endothermic process (enthalpy change=+60.6±14.7 kJ/mol) to an exothermic process (enthalpy change=−43±6.2 7 kJ/mol) by pentobarbital (4 mM) (P<0.005). These findings indicate that pentobarbital acts by preventing glucose-induced conformational changes in glucose transporters by binding to ‘non-catalytic’ sites in the transporter

Ultrasound studies of the endometrial-myometrial junction for the diagnosis of adenomyosis and endometrial cancer

This thesis investigated the ultrasound assessment of the endometrial-myometrial junction (EMJ) and its clinical relevance to the uterine diseases, adenomyosis and endometrial cancer. The inter- and intraobserver variability in the classification of EMJ visualisation using three-dimensional ultrasound was assessed and a high level of agreement was found. Endometrial thickness and parity were found to be significantly associated with the quality of EMJ visualisation. Seven recognised ultrasound features of adenomyosis, including an irregular endometrial-myometrial junction, were investigated for their role in the ultrasound diagnosis of adenomyosis. The other features were an asymmetrically thickened myometrium, parallel shadowing, linear striations, myometrial cysts, hyperechoic lesions and adenomyomas. The presence of any of these features was considered diagnostic of adenomyosis. The inter- and intraobserver variability of ultrasound diagnosis of adenomyosis was also investigated and a good level of agreement was found. This was the case when real-time ultrasound assessments were compared with assessments made from stored uterine volumes, as well as when both assessments were made from stored volumes. Transvaginal ultrasound was used to assess the prevalence of adenomyosis in women attending a general gynaecology clinic in a large prospective observational study. Women were considered to have adenomyosis if one or more ultrasound feature of adenomyosis was found. Using this criterion, the prevalence was estimated to be 20.9% with 7.6% of women being excluded from the data analysis. It was also found that age, gravidity and pelvic endometriosis were all significantly associated with the presence of adenomyosis. Menorrhagia was evaluated in order to assess if it was associated with adenomyosis. Multivariable analysis revealed that while adenomyosis was not significantly associated with menorrhagia when assessed as a binary outcome, when severity of disease was taken into account, there was a significant association. A similar analysis found that adenomyosis was significantly associated with dysmenorrhoea. A second-stage ultrasound test that incorporated assessment of the EMJ was investigated for its use in the diagnosis of endometrial cancer in women presenting with post-menopausal bleeding. It was found to significantly increase the specificity of ultrasound in the diagnosis of endometrial cancer while having a minimal impact on sensitivity

The malady of boredom

Boredom or ennui is a subjective feeling that embodies a number of symptoms similar to those implied by the term "depression," and varies in degree of depth from what might be described as normal to several levels or pathology. When met with as a "normal" phenomenon, it is usually of transient duration and of little consequence, although Schopenhauer takes another view of the matter

An integrated care pathway for menorrhagia across the primary–secondary interface : patients' experience, clinical outcomes, and service utilisation

Background: ‘‘Referral’’ characterises a significant area of interaction between primary and secondary care. Despite advantages, it can be inflexible, and may lead to duplication. Objective: To examine the outcomes of an integrated model that lends weight to general practitioner (GP)-led evidence based care. Design: A prospective, non-random comparison of two services: women attending the new (Bridges) pathway compared with those attending a consultant-led one-stop menstrual clinic (OSMC). Patients’ views were examined using patient career diaries, health and clinical outcomes, and resource utilisation. Follow-up was for 8 months. Setting: A large teaching hospital and general practices within one primary care trust (PCT). Results: Between March 2002 and June 2004, 99 women in the Bridges pathway were compared with 94 women referred to the OSMC by GPs from non-participating PCTs. The patient career diary demonstrated a significant improvement in the Bridges group for patient information, fitting in at the point of arrangements made for the patient to attend hospital (ease of access) (p,0.001), choice of doctor (p = 0.020), waiting time for an appointment (p,0.001), and less ‘‘limbo’’ (patient experience of non-coordination between primary and secondary care) (p,0.001). At 8 months there were no significant differences between the two groups in surgical and medical treatment rates or in the use of GP clinic appointments. Significantly fewer (traditional) hospital outpatient appointments were made in the Bridges group than in the OSMC group (p,0.001). Conclusion: A general practice-led model of integrated care can significantly reduce outpatient attendance while improving patient experience, and maintaining the quality of care

A protocol for developing, disseminating, and implementing a core outcome set for adenomyosis research

BACKGROUND: Adenomyosis is a common benign gynaecological condition that has been associated with heavy and/or painful periods, subfertility and poor obstetric outcomes including miscarriage and preterm delivery. Studies evaluating treatments for adenomyosis have reported a wide range of outcomes and outcome measures. This variation in outcomes and outcome measures prevents effective data synthesis, thereby hampering the ability of meta-analyses to draw useful conclusions and inform clinical practice. OBJECTIVES: Our aim is to develop a minimum set of outcomes to be reported in all future studies that investigate any uterus-sparing intervention for treating uterine adenomyosis. Wide adoption of ‘core outcomes’ into research on adenomyosis would reduce the heterogeneity of studies and make data synthesis easier. This will ultimately lead to comparable, prioritised, and patient-centred conclusions from meta-analyses and guidelines. MATERIALS AND METHODS: Outcomes identified from a systematic review of the literature will form a long list, agreed by an international steering group representing key stakeholders, including healthcare professionals, researchers, and public research partners. Through a modified Delphi process, key stakeholders will score outcomes from the agreed long list on a nine-point Likert scale that ranges from 1 (not important) to 9 (critical). Following the Delphi process, the refined outcome set will be finalised by the steering group. Finally, the steering group will develop recommendations for high-quality measures for each outcome. The study was prospectively registered with Core Outcome Measures in Effectiveness Trials Initiative; number 1649. CONCLUSION: The implementation of the core outcome set for adenomyosis in future trials will enhance the availability of comparable data to facilitate more patient-centred evidence-based care. WHAT IS NEW? The core outcome set will facilitate the generation of clinically important and patient centred outcomes for studies evaluating treatments for adenomyosis

Imaging in gynecological disease: clinical and ultrasound characteristics of accessory cavitated uterine malformations

Objective: To describe the clinical and ultrasound characteristics of accessory cavitated uterine malformations (ACUMs). Methods: This was a single-center observational study of consecutive patients diagnosed with an ACUM, who had undergone an ultrasound examination by an experienced ultrasound examiner between January 2013 and May 2019, identified retrospectively from medical records. ACUM was diagnosed when a cavitated lesion with a myometrial mantle and echogenic contents was seen within the anterolateral wall of the myometrium beneath the insertion of the round ligament. In all women, presenting symptoms and clinical history were recorded along with detailed descriptions of the lesions and any concomitant pelvic abnormalities. Results: Twenty patients diagnosed with an ACUM were identified. Median age was 29.2 (interquartile range, 25.0–35.8) years. None of the women was premenarchal or postmenopausal. All of the women reported painful periods or pelvic pain and none of them reported subfertility. Twelve of the ACUMs were in the right anterolateral myometrium and eight were in the left anterolateral myometrium. Both a myometrial mantle and a fluid-filled cavity were considered to be defining features on ultrasound. The fluid contained within the cavity was either echogenic with a ground-glass appearance or hyperechoic. All of the lesions were spherical in shape. The Doppler flow seen in the outer rim was not markedly different from that of the surrounding myometrium, and the content of the cavity was avascular on Doppler examination. The mean outer cavity diameter of the ACUMs was 22.8 (95% CI, 20.9–24.8) mm and the mean internal cavity diameter was 14.1 (95% CI, 12.2–16.1) mm. Four women opted for transvaginal ultrasound-guided alcohol sclerotherapy. Surgical excision was carried out in eight cases, and the diagnosis was confirmed on histopathological examination in all of them. Conclusions: ACUMs are a uterine abnormality with a distinct ultrasound appearance, which are associated with dysmenorrhea and chronic pelvic pain. Knowledge of their typical appearance on ultrasound could facilitate early detection and treatment. There are several treatment options for ACUM, ranging from simple analgesia to complete excision. Further prospective and longitudinal studies are required to study the prevalence and natural history of this condition. © 2020 International Society of Ultrasound in Obstetrics and Gynecolog

Natural history of endometriosis in pregnancy: ultrasound study of morphology of deep endometriosis and ovarian endometrioma

Objective: To assess the morphological appearance of deep endometriosis and ovarian endometrioma in pregnancy using pelvic ultrasound examination. Methods: This was a prospective observational cohort study conducted over 3 years at University College London Hospital, which is a tertiary level referral unit for early pregnancy complications and an accredited endometriosis center. All women who participated provided written consent and were invited for surveillance ultrasound examination at the time of their routine scans in pregnancy. All scans were performed by a single operator to eliminate interobserver variability. The change in size of ovarian endometrioma and nodules was reported as change in their mean diameter. Ovarian endometrioma with irregular thick inner walls, hyperechoic papillary projections and/or high vascularity and hyperechoic nodules with moderate to high vascularity were reported as decidualized. Results: Sixty-five women with a live, normally sited pregnancy and concomitant ultrasound features of deep and/or ovarian endometriosis were included in the study. The median age of the study population was 34 (range, 23–44) years, and the median gestational age at presentation was 7 + 6 (range, 3 + 6 to 18 + 0) weeks. From the cohort, 47/65 (72%) were nulliparous, 48/65 (74%) had a previous diagnosis of endometriosis and 19/65 (29%) conceived via in-vitro fertilization. There were 10/65 (15% (95% CI, 7–24%)) women with ovarian endometrioma alone, 28/65 (43% (95% CI, 31–55%)) with endometriotic nodules alone and the remaining 27/65 (42% (95% CI, 30–54%)) had both. Of the women with ovarian endometrioma who underwent follow-up, 29/34 (85% (95% CI, 73–97%)) experienced cyst regression, 2/34 (6% (95% CI, 0–14%)) experienced cyst growth, and in 3/34 (9% (95% CI, 0.0–18%)) women, cyst size was unchanged. In 10/34 (29% (95% CI, 14–45%)), there was complete resolution of all cysts. Of the women with nodules who underwent follow-up, 43/51 (84% (95% CI, 74–94%)) experienced nodule regression, 2/51 (4% (95% CI, 0–9%)) experienced nodule growth and, in 6/51 (12% (95% CI, 3–21%)) women, nodule size was unchanged. In 4/51 (8% (95% CI, 0–15%)) women, there was complete resolution of all nodules. In 5/37 (14% (95% CI, 3–25%)) women who attended postnatal follow-up, complete resolution of all endometriotic lesions occurred during pregnancy. In 10/34 (29% (95% CI, 14–45%)) women with ovarian endometrioma and 27/51 (53% (95% CI, 39–67%)) women with nodules, a pattern of growth was observed in the first and second trimesters, followed by regression later in pregnancy. Features of decidualization were observed in 17/34 (50% (95% CI, 33–67%)) women with ovarian endometrioma, most commonly in the first trimester, and in 25/51 (49% (95% CI, 35–63%)) women with nodules, most commonly in the second trimester. Conclusions: For the majority of women, despite features of decidualization being common in the first and second trimesters, ovarian endometrioma and deep nodules regress during pregnancy. Morphological changes of endometriosis in pregnancy are difficult to differentiate from characteristics of malignant lesions. Better understanding of the appearance of endometriosis in pregnancy is vital to minimize intervention and help counsel women regarding their condition. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

Osmotic Water Transport with Glucose in GLUT2 and SGLT

Carrier-mediated water cotransport is currently a favored explanation for water movement against an osmotic gradient. The vestibule within the central pore of Na+-dependent cotransporters or GLUT2 provides the necessary precondition for an osmotic mechanism, explaining this phenomenon without carriers. Simulating equilibrative glucose inflow via the narrow external orifice of GLUT2 raises vestibular tonicity relative to the external solution. Vestibular hypertonicity causes osmotic water inflow, which raises vestibular hydrostatic pressure and forces water, salt, and glucose into the outer cytosolic layer via its wide endofacial exit. Glucose uptake via GLUT2 also raises oocyte tonicity. Glucose exit from preloaded cells depletes the vestibule of glucose, making it hypotonic and thereby inducing water efflux. Inhibiting glucose exit with phloretin reestablishes vestibular hypertonicity, as it reequilibrates with the cytosolic glucose and net water inflow recommences. Simulated Na+-glucose cotransport demonstrates that active glucose accumulation within the vestibule generates water flows simultaneously with the onset of glucose flow and before any flow external to the transporter caused by hypertonicity in the outer cytosolic layers. The molar ratio of water/glucose flow is seen now to relate to the ratio of hydraulic and glucose permeability rather than to water storage capacity of putative water carriers