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Introduction: The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV-V pancreaticoduodenal injuries., Methods: This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020. Included patients were ≥15 years of age with the American Association for the Surgery of Trauma grade IV-V duodenal and/or pancreatic injuries. The study compared operative repair strategy: PD versus non-PD., Results: The sample (n=95) was young (26 years), male (82%), with predominantly penetrating injuries (76%). There was no difference in demographics, hemodynamics, or blood product requirement on presentation between PD (n=32) vs non-PD (n=63). Anatomically, PD patients had more grade V duodenal, grade V pancreatic, ampullary, and pancreatic ductal injuries compared with non-PD patients (all p<0.05). 43% of all grade V duodenal injuries and 40% of all grade V pancreatic injuries were still managed with non-PD. One-third of non-PD duodenal injuries were managed with primary repair alone. PD patients had more gastrointestinal (GI)-related complications, longer intensive care unit length of stay (LOS), and longer hospital LOS compared with non-PD (all p<0.05). There was no difference in mortality or readmission. Multivariable logistic regression analysis determined PD to be associated with a 3.8-fold greater odds of GI complication (p=0.010) compared with non-PD. In a subanalysis of patients without ampullary injuries (n=60), PD patients had more anastomotic leaks compared with the non-PD group (3 (30%) vs 2 (4%), p = 0.028)., Conclusion: While PD patients did not have worse hemodynamics or blood product requirements on admission, they sustained more complex anatomic injuries and had more GI complications and longer LOS than non-PD patients. We suggest that the role of PD should be limited to cases of massive destruction of the pancreatic head and ampullary complex, given the likely procedure-related morbidity and adverse outcomes when compared with non-PD management., Level of Evidence: IV, Multicenter retrospective comparative study., Competing Interests: None declared., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hemorrhaging trauma patients may be disproportionately affected by choice of induction agent during rapid sequence intubation (RSI). Etomidate, ketamine, and propofol are safe in the trauma population-at-large but have not been assessed in patients with ongoing hemorrhage. We hypothesize that in hemorrhaging patients with penetrating injury, propofol deleteriously affects peri-induction hypotension compared to etomidate and ketamine., Methods: Retrospective cohort study. Primary outcome was the effect of induction agent on peri-induction systolic blood pressure. Secondary outcomes were the incidence of peri-induction vasopressor use and quantity of peri-induction blood transfusion requirements. Linear multivariate regression modeling assessed the effect of induction agent on the variables of interest., Results: 169 patients were included, 146 received propofol and 23 received etomidate or ketamine. Univariate analysis revealed no difference in peri-induction systolic blood pressure (P = .53), peri-induction vasopressor administration (P = .62), or transfusion requirements within the first hour after induction (PRBC P = .24, FFP P = .19, PLT P = .29). Choice of RSI agent did not independently predict peri-induction systolic blood pressure or blood product administration. Rather, only presenting shock index independently predicted peri-induction hypotension., Conclusions: This is the first study to directly assess the peri-induction effects of anesthetic induction agent choice in penetrating trauma patients undergoing emergent hemorrhage control surgery. Propofol does not appear to worsen peri-induction hypotension regardless of dose. Patient physiology is most predictive of peri-induction hypotension., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Rapid triage of blunt agonal trauma patients is necessary to maximize survival, but autopsy is uncommon, slow, and rarely informs resuscitation guidelines. Postmortem computed tomography (PMCT) can serve as an adjunct to autopsy in guiding blunt agonal trauma resuscitation., Methods: Retrospective cohort review of trauma decedents who died at or within 1 hour of arrival following blunt trauma and underwent noncontrasted PMCT. Primary outcome was the prevalence of mortal injury defined as potential exsanguination (e.g., cavitary injury, long bone and pelvic fractures), traumatic brain injury, and cervical spine injury. Secondary outcomes were potentially mortal injuries (e.g., pneumothorax) and misplacement airway devices. Patients were grouped by whether arrest occurred prehospital/in-hospital. Univariate analysis was used to identify differences in injury patterns including multiple-trauma injury patterns., Results: Over a 9-year period, 80 decedents were included. Average age was 48.9 ± 21.7 years, 68% male, and an average ISS of 42.3 ± 16.3. The most common mechanism was motor vehicle accidents (67.5%) followed by pedestrian struck (15%). Of all decedents, 62 (77.5%) had traumatic arrest prehospital while 18 (22.5%) arrived with pulse. Between groups there were no significant differences in demographics including ISS. The most common mortal injuries were traumatic brain injury (40%), long bone fractures (25%), moderate/large hemoperitoneum (22.5%), and cervical spine injury (25%). Secondary outcomes included moderate/large pneumothorax (18.8%) and esophageal intubation rate of 5%. There were no significant differences in mortal or potentially mortal injuries, and no differences in multiple-trauma injury patterns., Conclusion: Fatal blunt injury patterns do not vary between prehospital and in-hospital arrest decedents. High rates of pneumothorax and endotracheal tube misplacement should prompt mandatory chest decompression and confirmation of tube placement in all blunt arrest patients., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Duodenal leak is a feared complication of repair, and innovative complex repairs with adjunctive measures (CRAM) were developed to decrease both leak occurrence and severity when leaks occur. Data on the association of CRAM and duodenal leak are sparse, and its impact on duodenal leak outcomes is nonexistent. We hypothesized that primary repair alone (PRA) would be associated with decreased duodenal leak rates; however, CRAM would be associated with improved recovery and outcomes when leaks do occur., Methods: A retrospective, multicenter analysis from 35 Level 1 trauma centers included patients older than 14 years with operative, traumatic duodenal injuries (January 2010 to December 2020). The study sample compared duodenal operative repair strategy: PRA versus CRAM (any repair plus pyloric exclusion, gastrojejunostomy, triple tube drainage, duodenectomy)., Results: The sample (N = 861) was primarily young (33 years) men (84%) with penetrating injuries (77%); 523 underwent PRA and 338 underwent CRAM. Complex repairs with adjunctive measures were more critically injured than PRA and had higher leak rates (CRAM 21% vs. PRA 8%, p < 0.001). Adverse outcomes were more common after CRAM with more interventional radiology drains, prolonged nothing by mouth and length of stay, greater mortality, and more readmissions than PRA (all p < 0.05). Importantly, CRAM had no positive impact on leak recovery; there was no difference in number of operations, drain duration, nothing by mouth duration, need for interventional radiology drainage, hospital length of stay, or mortality between PRA leak versus CRAM leak patients (all p > 0.05). Furthermore, CRAM leaks had longer antibiotic duration, more gastrointestinal complications, and longer duration until leak resolution (all p < 0.05). Primary repair alone was associated with 60% lower odds of leak, whereas injury grades II to IV, damage control, and body mass index had higher odds of leak (all p < 0.05). There were no leaks among patients with grades IV and V injuries repaired by PRA., Conclusion: Complex repairs with adjunctive measures did not prevent duodenal leaks and, moreover, did not reduce adverse sequelae when leaks did occur. Our results suggest that CRAM is not a protective operative duodenal repair strategy, and PRA should be pursued for all injury grades when feasible., Level of Evidence: Therapeutic/Care Management; Level IV., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To define what sleep deprivation is, how it relates to the growing problem of burnout within surgeons, and what can be done to mitigate its effects., Recent Findings: There is a growing awareness that sleep deprivation, in both its acute and chronic manifestations, plays an immense role in burnout. The physical and mental manifestations of sleep deprivation are manifold, effecting nearly every physiologic system. Studies evaluating strategies at mitigating the effects of sleep deprivation are promising, including work done with napping, stimulant use, and service restructuring, but are fundamentally limited by generalizability, scale, and scope., Summary: The overwhelming majority of data published on sleep deprivation is limited by size, scope, and generalizability. Within acute care surgery, there is a dearth of studies that adequately define and describe sleep deprivation as it pertains to high-performance professions. Given the growing issue of burnout amongst surgeons paired with a growing patient population that is older and more complex, strategies to combat sleep deprivation are paramount for surgeon retention and wellbeing., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: To evaluate the percentage of misplaced medical support lines and tubes in deceased trauma patients using post-mortem computed tomography (PMCT)., Methods: Over a 9-year period, trauma patients who died at or soon after arrival in the emergency department were candidates for inclusion. Whole body CT was performed without contrast with support medical devices left in place. Injury severity score (ISS) was calculated by the trauma registrar based on the injuries identified on PMCT. The location of support medical devices was documented in the finalized radiology reports., Results: A total of 87 decedents underwent PMCT, of which 69% (n = 60) were male. For ten decedents, the age was unknown. For the remaining 77 decedents, the average age was 48.4 years (range 18-96). The average ISS for the cohort was 43.4. Each decedent had an average of 3.3 support devices (2.9-3.6, 95% CI), of which an average of 1 (31.3%, 0.8-1.2, 95% CI) was malpositioned. A total of 60 (69.0%) had at least one malpositioned medical support device. The most commonly malpositioned devices were decompressive needle thoracostomies (n = 25/32, 78.1%). The least malpositioned devices were intraosseous catheters (n = 7/69, 10.1%). Nearly one quarter (n = 19/82, 23.2%) of mechanical airways were malpositioned, including 4.9% with esophageal intubation., Conclusion: Malpositioned supportive medical devices are commonly identified on post-mortem computed tomography trauma decedents, seen in 69.0% of the cohort, including nearly one quarter with malpositioned mechanical airways. Post-mortem CT can serve as a useful adjunct in the quality improvement process by providing data for education of trauma and emergency physicians and first responders., (© 2022. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Background: The limitations of resuscitative thoracotomy (RT) after penetrating trauma have been well documented, but there is a paucity of data on the effect age has on mortality. This begs the question as to the utility of RT in an aging patient population. We investigate the significance of age as a predictor for failure to rescue after RT in penetrating trauma., Objective: We sought to identify whether chronologic age has a measurable effect on rates of failure to rescue after RT., Methods: We performed a retrospective cohort analysis using the Trauma Quality Improvement Program from 2011 to 2015 including all pulseless patients undergoing RT after penetrating injury. Our primary outcome was failure to rescue defined as death in the emergency department after RT. Multivariate analyses were performed to identify the relationship between age and morality controlling for injury severity., Results: One thousand one hundred twelve RTs were performed during the study period with an overall failure to rescue rate of 61.8% (n = 687) within the emergency department and an in-hospital mortality rate of 96.9%, which is in line with national data. On univariate analysis, there was no significant association between age and mortality (p = 0.44). On multivariate analysis examining the interaction between age and mortality adjusting for injury severity, we found that chronologic age was not an independent predictor of death after RT., Conclusions: Age does not appear to be an independent predictor of failure to rescue after RT in penetrating trauma and should not be a sole determinant in procedural decision making., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To assess a multimodal physician-to-physician communication initiative that is low in cost and impact to daily workflow to reduce blood product wastage., Background: Blood product stewardship is an important issue in all hospital systems. Previous studies have proposed low-cost interventions to reduce blood product wastage, but few have evaluated improvements in communication between the blood bank and providers. We undertook a prospective quality improvement project focusing on improving communication to reduce blood product wastage., Methods: We conducted a prospective quality improvement project over the first quarter of 2017, identifying patients with issued but unused blood products. Each service overseeing the care of patients identified on the unit status report was contacted through two possible methods: (i) phone or (ii) proprietary Health Insurance Portability and Accountability Act of 1996 compliant digital messaging application. Collected variables included reserved blood product type and participant time spent. Outcomes included the rate of blood product release and changes in wastage compared with historical data tracked by the blood bank., Results: Eight hundred and forty products were reserved during the study period, of which 436 (52%) were released. Average participant times ranged from 2 ± 1 min to 15 ± 4 min with no significant differences in time spent between participants (P = 0·194). Compared with the average product wastage 10 months prior to project initiation, there were significant reductions in the average wastage for platelets (5·3 ± 2·5 units vs 2·5 ± 1·5 units, P = 0·05), RBCs (6·1 ± 3·7 units vs 0 ± 0 units, P = 0·01) and overall wastage (58·3 ± 14·9 units vs 40 ± 15·7 units, P = 0·05)., Conclusion: Efforts focusing on improving provider-to-provider communication can reduce blood product wastage., (© 2019 British Blood Transfusion Society.)

Background and Purpose: Reversible cerebral vasoconstriction syndrome (RCVS) is a vascular headache disorder characterized by severe headaches with vasospasm of cerebral arteries. Transcranial Doppler ultrasonography (TCD) has been widely applied and validated in studying vasospasm of intracranial vessels, but the role of TCD in the diagnosis and monitoring of RCVS is less well established. We sought to determine the reliability of TCD for diagnosis and monitoring of RCVS., Methods: Patients admitted to an inpatient neurology service between 2011 and 2014 with a discharge diagnosis of RCVS were retrospectively analyzed for demographics, neuroimaging, and functional outcomes. Baseline and follow-up TCD flow velocities in the middle cerebral artery (Vmca) were compared relative to the final diagnosis., Results: The cohort consisted of fifteen patients (93% females; mean age 46.7 +/- 12.4 years); initial TCD evaluation was performed 10.9 +/- 6.6 (range 1-24) days after headache onset. Fourteen patients (93.3%) had increased flow velocities by initial TCD in at least one major cerebral blood vessel (MCA, ACA, PCA, vertebral, basilar). TCD flow velocities in the middle cerebral artery (Vmca) reached a mean peak of 163 cm/s three to four weeks after the onset of thunderclap headache., Conclusion: TCD is a non-invasive neuroimaging modality that may have potential for the initial diagnosis and subsequent monitoring of patients with suspected RCVS. Larger studies will be needed to establish its utility. [Full article available at http://rimed.org/rimedicaljournal-2016-09.asp, free with no login].

Background: Prescription opioid-acetaminophen products account for the majority of cases of acetaminophen-related acute liver failure in the United States. We sought to examine the frequency of opioid-acetaminophen overuse at the Providence VA Medical Center and improve the quality and safety of opioid-acetaminophen prescription practices in a system employing electronic health records and e-prescribing., Results: During fiscal year 2011, the Providence VA pharmacy dispensed a total of 19,841 acetaminophen prescriptions to a total of 4455 different patients. There were only 15 acetaminophen prescriptions dispensed in excess of 4g/day, and there were only 14 patients exposed to a potential maximum daily dose of acetaminophen greater than 4g., Conclusions: The Providence VAMC appears to have a low rate of prescription acetaminophen misuse, in contrast to rates seen in previous studies. The VHA electronic health record, accessible to all healthcare providers, appears to offer considerable benefit in reducing the overuse of acetaminophen containing opioid products.

Objective: Rheumatic diseases cause significant morbidity within American Indian populations. Clinical disease presentations, as well as historically associated autoantibodies, are not always useful in making a rapid diagnosis or assessing prognosis. The purpose of our study was to identify autoantibody associations among Oklahoma tribal populations with rheumatic disease., Methods: Oklahoma tribal members (110 patients with rheumatic disease and 110 controls) were enrolled at tribal-based clinics. Patients with rheumatic disease (suspected or confirmed diagnosis) were assessed by a rheumatologist for clinical features, disease criteria, and activity measures. Blood samples were collected and tested for common rheumatic disease autoantibodies [antinuclear antibody (ANA), anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), anti-Ro, anti-La, anti-Sm, anti-nRNP, anti-ribosomal P, anti-dsDNA, and anticardiolipins]., Results: In patients with suspected systemic rheumatic diseases, 72% satisfied American College of Rheumatology classification criteria: 40 (36%) had rheumatoid arthritis (RA), 16 (15%) systemic lupus erythematosus, 8 (7%) scleroderma, 8 (7%) osteoarthritis, 4 (4%) fibromyalgia, 2 (2%) seronegative spondyloarthropathy, 1 Sjögren's syndrome, and 1 sarcoidosis. Compared to controls, RA patient sera were more likely to contain anti-CCP (55% vs 2%; p < 0.001) or RF IgM antibodies (57% vs 10%; p < 0.001); however, the difference was greater for anti-CCP. Anti-CCP positivity conferred higher disease activity scores (DAS28 5.6 vs 4.45; p = 0.021) while RF positivity did not (DAS28 5.36 vs 4.64; p = 0.15). Anticardiolipin antibodies (25% of rheumatic disease patients vs 10% of controls; p = 0.0022) and ANA (63% vs 21%; p < 0.0001) were more common in rheumatic disease patients., Conclusion: Anti-CCP may serve as a more specific RA biomarker in American Indian patients, while the clinical significance of increased frequency of anticardiolipin antibodies needs further evaluation.

Background Context: The prospective, double-blind, randomized, placebo-controlled study design is essential in the interventional spine literature to truly evaluate whether or not a procedure is effective., Purpose: This article will critically evaluate the highest quality interventional spine literature with strict interpretation of the results of these trials., Study Design: Review article., Methods: Extensive Medline/Pubmed searches and searches of the large review articles on the major interventional spine topics were performed to find all prospective, double-blind, randomized placebo-controlled trials in the English language interventional spine literature., Results: Fluoroscopically-guided lumbosacral transforaminal epidural corticosteroid injections are effective in the treatment of acute/subacute lumbosacral radicular pain, and in preventing future surgeries. Injection of corticosteroid or Sarapin on the cervical or lumbar medical branch nerves is not effective. When done with proper technique, percutaneous radiofrequency lumbar and cervical medial branch neurotomy are both effective. Intraarticular sacroiliac joint corticosteroid injections are effective in patients with spondyloarthropathy. IDET is modestly effective in the treatment of lumbosacral discogenic pain in carefully selected patients. Percutaneous radio frequency neurotomy of the ramus communicans is effective in the treatment of lumbosacral discogenic pain. No firm conclusions can be drawn about cervical epidural corticosteroid injections, lumbosacral epidural corticosteroid injections for the treatment of chronic radicular pain, cervical or lumbosacral intraarticular zygapophysial joint corticosteroid injections for the treatment of degenerative zygapophysial joint pain, or intradiscal corticosteroid injections., Conclusions: The prospective, double-blind, randomized placebo-controlled trials in the interventional spine literature demonstrate efficacy from several different procedures when properly performed on appropriate patients. Other procedures have been shown to lack efficacy, while inconclusive evidence exists from multiple other interventional spine procedures. Further details are discussed in the text.

Introduction: Candida lusitaniae was originally described as a human pathogen in 1979 and typically affects immunocompromised patients., Case Presentation: We describe a case of prosthetic valve endocarditis with Candida lusitaniae in an immunocompetent 62-year-old woman following aortic valve replacement. In vitro testing demonstrated that our isolate was sensitive to amphotericin B, caspofungin and fluconazole., Conclusion: The infection was lethal despite aggressive medical and surgical management and sterilization of blood cultures. The outcome of our case illustrates the need to recognize Candida lusitaniae fungemia as a life-threatening infection in a patient with a prosthetic aortic valve.

The acronym PHACES is used to describe the association of posterior fossa malformations, hemangiomas, arterial anomalies (cardiovascular or cerebrovascular), coarctation of the aorta and cardiac defects, eye abnormalities, and sternal or ventral defects. We report a female patient with an uncommon variant of this neurocutaneous disorder who manifested a sternal cleft; supraumbilical raphe; hemangiomas of the face, chest, and extremities; micrognathia and cerebrovascular anomalies. A literature review of PHACES patients with both sternal cleft and supraumbilical raphe showed a marked female predilection. Taken together with cases of sternal cleft, supraumbilical raphe and facial hemangiomas tabulated by Gorlin et al. (1994), 91% (40/44) of patients are female. One affected male died shortly after birth. We hypothesized that the gender bias in PHACES results from mutation in an X-linked dominant gene often lethal in males, and performed X-inactivation analysis of the polymorphic androgen receptor locus in this family. We documented consistently skewed X-inactivation (80%/20% in two independent analyses) in the unaffected mother and consistently random X-inactivation (47:53 and 61:39 in independent analyses) in the proband. These findings are consistent with favorably skewed X-inactivation producing a normal maternal phenotype, a phenomenon documented in X-linked dominant Rett syndrome.

More controversial aspects of the administration of vaccines are discussed with particular emphasis on the uncertainties surrounding measurement and significance of immunological markers in predicting efficacy. New areas of vaccine development are highlighted, particularly the importance of greater understanding of the gut immune mechanisms which promise oral delivery routes for a variety of immunogens. Emphasis is laid on the requirement for expert administration of intradermal injection if protection is to be reliable. Several new vaccines have been introduced recently and relevant issues relating to typhoid, cholera and hepatitis A vaccines are discussed. New possibilities for immunisation against travellers diarrhoea are appraised. The required frequency of booster doses is discussed for several vaccines where it is found that long term protection has often not been well researched. This is nowhere better demonstrated than with hepatitis B. Finally less commonly used vaccines are discussed and the importance of assessing true risk before deciding on use is emphasized.

Objective: To determine if fluoroimmunoassay (FIA) of serum luteinizing hormone (LH) is more useful clinically than a conventional radioimmunoassay (RIA) because it has been suggested that FIA closely reflects biological activity., Design: Comparison of serum LH measurements by RIA and FIA during various perturbations in normal ovulatory women and in women with polycystic ovarian syndrome (PCOS)., Setting: Normal ovulatory subjects were healthy volunteers and women with PCOS were untreated and newly diagnosed outpatients in our Reproductive Endocrinology/Infertility Clinic, Women's Hospital, at the Los Angeles County+University of Southern California Medical Center., Participants: Fifty-three normal ovulatory women, ages 20 to 35, and 27 women with PCOS, ages 21 to 35. All were in good health and received no other medications during the study period., Results: Fluoroimmunoassay of serum LH reflected status of known altered bioactivity better than with a conventional RIA. This was most evident during conditions of gonadotropin suppression and in patients with PCOS. An excellent correlation was found between values of FIA and RIA., Conclusions: The measurement of LH by FIA is clinically useful, specifically when a change in biological activity of LH is sought.

Objective: To determine the production of the vasoactive prostaglandins (PGs), prostacyclin, and thromboxane (TX) in endometrial stromal cell cultures and their steroid modulation by sex steroids., Design: Primary stromal cell cultures with steroid modulation in tissues from the follicular and luteal phases of normal women., Setting: Laboratories of the Division of Reproductive Endocrinology and tissues obtained from normal patients at the Los Angeles County and University of Southern California Medical Center in Los Angeles, California., Measures: Stromal cell tissue culture for 14 days. Radioimmunoassay of 6-keto-PGF1 alpha, TXB2, and prolactin (PRL) as well as determination of protein content., Results: Estradiol stimulated 6-keto-PGF1 alpha production more than TXB2. This effect occurred after day 6 and was as much as 10-fold greater in luteal phase tissue. The effect was eliminated by progestins that alone had no effect. This modulatory response was greater in luteal endometrial tissue than in follicular phase tissue. As expected, in these tissues progestin stimulated PRL, an effect opposite to its negative influence on the vasoactive PGs., Conclusion: These data provide evidence for a steroid-related influence on the balance of vasoactive PGs in the stroma of the endometrium.

Objective: To assess gonadotropin alterations in adult-onset congenital adrenal hyperplasia (CAH) and to compare these findings with those of patients with polycystic ovary syndrome (PCOS) in an effort to better understand the pathophysiology of these abnormalities., Design: Prospective study of 9 newly diagnosed patients with CAH, 10 with PCOS, and 10 ovulatory controls., Interventions: Baseline measurements of serum androgens, progestins, estradiol (E2), estrone (E1), unbound E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Serum LH and FSH were measured after intravenous gonadotropin-releasing hormone (GnRH) and in 15-minute blood samples for 6 hours to determine LH pulsatility., Results: Serum androgens were elevated but comparable in the two patient groups. Serum LH was also elevated (P less than 0.05) but was higher in PCOS than CAH. Serum LH:FSH ratios were similar as were the responses to GnRH. Serum E1 was elevated only in PCOS, but unbound E2 was elevated to the same degree in both PCOS and CAH (P less than 0.05). Patients with PCOS had a decreased LH interpulse interval compared with controls and CAH (P less than 0.05), but LH pulse amplitude was increased in both PCOS and CAH (P less than 0.05). Serum E2 and unbound E2 correlated significantly with LH (P less than 0.05), LH responses to GnRH as well as to LH pulse amplitude in CAH (P less than 0.05). The LH interpulse interval did not correlate with estrogen in any group. None of the LH parameters correlated with serum progestin levels in CAH., Conclusions: The gonadotropin abnormalities of CAH appear to be intermediate between those of controls and PCOS. Although elevated estrogen may explain these abnormalities in CAH, additional factors may be operative in PCOS.

To determine if pregnanediol glucuronide (PG) excretion is useful in luteal phase assessment, we compared daily first morning urinary PG concentrations during the luteal phase in nine normal and nine deficient cycles. Total luteal pregnanediol excretion (44.1 +/- 11.3 versus 64.0 +/- 11.6 area units +/- SEM) was not different. However, significantly less pregnanediol was excreted by the abnormal group during the 1st 5 days of the luteal phase (12.7 +/- 1.2 versus 18.0 +/- 1.7 area units +/- SEM, respectively). Thus, delayed PG excretion may be characteristic of luteal phase defect and measurement of urinary PG may be useful only if daily samples during the early luteal phase are obtained.

Progestins stimulate prolactin production from endometrial stromal cells in culture. We compared the potencies of the synthetic progestins norethindrone and medroxyprogesterone acetate to natural progesterone in inducing stromal prolactin production. Modifications of the culture system provided an increase in stromal cell yield, thus permitting multiple comparisons from the treatment of cells from a common endometrial sample. The effects of high-dose estradiol also were evaluated in this system. The findings suggest relative potencies of 50:1 for medroxyprogesterone acetate and progesterone. Norethindrone gave intermediate and more variable responses. Estradiol potentiated prolactin production from only submaximal progestins doses. The differences between the progestin effects, in large measure, were due to differential culture growth as reflected by culture mass. Compared to controls and estradiol alone, all the progestins induced much greater prolactin production. Thus during decidualization, progestins probably promote both stromal growth and intracellular prolactin production. High-dose estradiol may not interfere with these events.

Eighteen hyperandrogenic, hirsute women received ovine corticotropin-releasing factor (CRF; 1 microgram/kg) as well as a dexamethasone (DEX) suppression test. Nine of the 18 hirsute women exhibited increased DEX sensitivity. Plasma adrenocorticotropic hormone (ACTH) responses after ovine CRF were significantly lower in the DEX-sensitive subgroup, but serum androstenedione was higher. Baseline serum androgen levels could not predict DEX responses. A significant negative correlation existed between the suppression of androgens after DEX and the increase in ACTH after ovine CRF. The suppression of androgen correlated with the ratio of the increase in androgen to the increase in ACTH after ovine CRF. We conclude that DEX sensitivity occurs frequently and cannot be predicted by levels of serum androgens. Blunted ACTH responses to ovine CRF may reflect enhanced adrenal sensitivity and altered feedback control.

A patient treated with mifepristone (RU 486), which successfully induced abortion of an intrauterine pregnancy, was discovered to have a heterotopic ovarian pregnancy resistant to this antiprogesterone. The ovarian pregnancy was removed with operative laparoscopy. This case demonstrates for the first time that an ovarian pregnancy may be resistant to treatment with RU 486 at a dose adequate to abort an intrauterine pregnancy.

Cessation of ovarian function is associated with a marked increased in morbidity and mortality secondary to ischemic heart disease. Estrogen replacement has been shown to impart protection against ischemic heart disease. We hypothesized that estrogen may influence vascular production of vasodilators such as prostacyclin. To investigate this relationship we have measured the production of 6-keto-prostaglandin F1 alpha, and thromboxane B2 by superfused uterine arteries from pre- and postmenopausal women. Arterial specimens from healthy normotensive premenopausal (n = 5) and postmenopausal women (n = 5) were superfused for 5 hours. Production of 6-keto-prostaglandin F1 alpha reached steady state levels by 120 minutes and remained linear for the length of the experiment. Indomethacin (4 x 10(-5) mol/L) added at 120 minutes significantly decreased prostanoid production. In subsequent experiments, 17 beta-estradiol in concentrations of 10, 100, 1000 ng/ml was added to the superfusion media at 120 minutes. Total production of 6-keto-prostaglandin F1 alpha by premenopausal arteries superfused with neat media during the steady state interval (3 hours) was significantly greater than that of postmenopausal specimens (1.25 versus 0.27 ng/mg dry tissue, p less than 0.05). Thromboxane B2 levels were undetectable in spent media. However, the addition of 17 beta-estradiol did not alter production of 6-keto-prostaglandin F1 alpha. These data suggest that arterial production of prostacyclin is significantly decreased in uterine arteries from postmenopausal women, but in this in vitro model system estrogens did not affect vascular prostanoid production.