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BACKGROUND: Prescription drug monitoring programs (PDMPs) exist in 49 states to guide opioid prescribing. In 40 states, clinicians must check the PDMP prior to prescribing an opioid. Data on mandated PDMP checks show mixed results on opioid prescribing. OBJECTIVES: This study sought to examine the impact of the Massachusetts mandatory PDMP check on opioid prescribing for discharges from an urban tertiary emergency department (ED). METHODS: This was a retrospective cohort study of discharges from one ED from 7/1/2010–10/15/2018. The primary outcome was the monthly percentage of patients discharged from the ED with an opioid prescription. The intervention was Massachusetts mandating a PDMP check for all opioid prescriptions. Prescribing was compared pre- and post-mandate. Interrupted time series (ITS) analysis accounted for known declining trends in opioid prescribing. RESULTS: Of 273,512 ED discharges, 35,050 (12.8%) received opioid prescriptions. Mean monthly opioid prescribing decreased post-intervention from 15.1% (SD ± 3.5%) to 5.1% (SD ± 0.9%; p < 0.001). ITS showed equal pre and post-intervention slopes (−0.002, p = 0.819). A small immediate decrease occurred in prescribing around the mandated check: a 3-month level effect decrease of 0.018 (p = 0.039), 6-month level effect 0.019 (p = 0.023), and a 12-month level effect of 0.020 (p = 0.019). The 24-month level effect was not decreased. CONCLUSION: Prior to the mandated PDMP check, ED opioid prescribing was declining. The mandate did not change the rate of decline but was associated with a non-sustained drop in opioid prescribing immediately following enactment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13181-021-00837-4.

Introduction Medications are compounded when a formulation of a medication is needed but not commercially available. Regulatory oversight of compounding is piecemeal and compounding errors have resulted in patient harm. We review compounding in the United States (US), including a history of compounding, a critique of current regulatory oversight, and a systematic review of compounding errors recorded in the literature. Methods We gathered reports of compounding errors occurring in the US from 1990 to 2020 from PubMed, Embase, several relevant conference abstracts, and the US Food and Drug Administration “Drug Alerts and Statements” repository. We categorized reports into errors of “contamination,” suprapotency,” and “subpotency.” Errors were also subdivided by whether they resulted in morbidity and mortality. We reported demographic, medication, and outcome data where available. Results We screened 2155 reports and identified 63 errors. Twenty-one of 63 were errors of concentration, harming 36 patients. Twenty-seven of 63 were contamination errors, harming 1119 patients. Fifteen errors did not result in any identified harm. Discussion Compounding errors are attributed to contamination or concentration. Concentration errors predominantly result from compounding a prescription for a single patient, and disproportionately affect children. Contamination errors largely occur during bulk distribution of compounded medications for parenteral use, and affect more patients. The burden falls on the government, pharmacy industry, and medical providers to reduce the risk of patient harm caused by compounding errors. Conclusion In the US, drug compounding is important in ensuring access to vital medications, but has the potential to cause patient harm without adequate safeguards.

Direct oral anticoagulants are now commonplace, and reversal agents are recently becoming available. Andexanet alfa (AnXa), approved by the United States Food and Drug Administration in 2018, is a novel decoy molecule that reverses factor Xa inhibitors in patients with major hemorrhage. We present a case of a 70-year-old man taking rivaroxaban with hemodynamic instability from a ruptured abdominal aortic aneurysm. He received AnXa prior to endovascular surgery, and intraoperatively he could not be heparinized for graft placement. Consideration should be given to the risks and benefits of AnXa administration in patients who require anticoagulation after hemorrhage has been controlled.

Background Travellers’ diarrhoea (TD) is the most common clinical syndrome affecting travellers. This narrative review summarizes key discoveries reported in the last two years related to TD and suggests areas for future research. Methods A PubMed literature search was conducted for novel data in TD research published between 12 January 2018 and 12 January 2020. Inclusion was based on contribution to epidemiology, aetiology, diagnostics, management and long-term consequences and relevance to public health, discovery and clinical practice. Results The initial literature search yielded 118 articles. We retrieved 72 and reviewed 31 articles for inclusion. The findings support our understanding that TD incidence varies by traveller group and environment with students and military-travel remaining moderately high risk, and control of food and water in mass gathering events remain an important goal. The growth of culture-independent testing has led to a continued detection of previously known pathogens, but also an increased detection frequency of norovirus. Another consequence is the increase in multi-pathogen infections, which require consideration of clinical, epidemiological and diagnostic data. Fluoroquinolone resistant rates continue to rise. New data on non-absorbable antibiotics continue to emerge, offering a potential alternative to current recommendations (azithromycin and fluoroquinolones), but are not recommended for febrile diarrhoea or dysentery or regions/itineraries where invasive pathogens are likely to cause illness. Recent studies investigated the interaction of the microbiome in TD prevention and consequences, and while discriminating features were identified, much uncertainty remains. The prevalence of extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-PE) acquisition and carriage is increasing. Finally, continued research documents the post-infectious consequences, whereas mechanisms of reactive arthritis and post-infectious IBS necessitate further investigation. Conclusions Globally, TD remains an important travel health issue and advances in our understanding continue. More research is needed to mitigate risk factors where possible and develop risk-based management strategies to reduce antibiotic usage and its attendant consequences.

Objective An opioid-associated amnestic syndrome (OAS) characterized by acute onset memory loss and bilateral hippocampal signal abnormalities on brain imaging in the setting of a history of opioid use, most notably fentanyl, has been reported. To date, however, there is no case definition to assist neurologists and other clinicians in identifying this syndrome. A multi-disciplinary collaboration of physicians, including neurologists, propose diagnostic criteria for OAS using cases that have been published in the medical literature or presented at conferences. Methods Cases were classified as confirmed, probable, or possible based on brain imaging findings and history or analytical testing supporting opioid use. Published articles and presentations were identified by discussion with public health authorities and a systematic search of PubMed. Included were articles, abstracts or posters through November 2019 that presented case reports or case series of a new-onset amnestic syndrome associated with bilateral hippocampal injury on imaging and/or prior opioid or other substance use. The percentages of cases that would meet confirmed, probable, or possible criteria were calculated. Results Twenty-three publications from all sources met criteria for inclusion, accounting for 40 unique cases. Based on the case definition of OAS, 50% (20/40) were confirmed, 25% (10/40) were probable and 25% (10/40) were possible. Conclusion The development of a validated, formal case definition for OAS can assist neurologists and other clinicians in evaluating patients with amnesia and a history of opioid use.

Background and Aims: Mild traumatic brain injury is a common presentation to Emergency Departments. Early identification of patients with cognitive deficits and provision of discharge advice are important. The Abbreviated Westmead Post-traumatic Amnesia Scale provides an early and efficient assessment of post-traumatic amnesia for patients with mild traumatic brain injuries, compared with the previously used assessment, the Modified Oxford Post-traumatic Scale. Material and Methods: This retrospective cohort study reviewed 270 patients with mild traumatic brain injury assessed for post-traumatic amnesia over a 2-year period between February 2011 and February 2013. It identified those assessed with Abbreviated Westmead Post-traumatic Amnesia Scale versus Modified Oxford Post-traumatic Scale, the outcomes of these post-traumatic amnesia assessments, the hospital length of stay for patients, and their readmission rates. Results: The Abbreviated Westmead Post-traumatic Amnesia Scale was used in 91% of patient cases (and the Modified Oxford Post-traumatic Scale in 7%), and of those assessed with the Abbreviated Westmead Post-traumatic Amnesia Scale, 94% cleared post-traumatic amnesia testing within 4 h. Of those assessed with the Abbreviated Westmead Post-traumatic Amnesia Scale, 56% had a shorter length of stay than had they been assessed with the Modified Oxford Post-traumatic Scale, resulting in 295 bed-days saved. Verbal and written discharge advice was provided to those assessed for post-traumatic amnesia to assist their recovery. In all, 1% of patients were readmitted for monitoring of mild post-concussion symptoms. Conclusion: The Abbreviated Westmead Post-traumatic Amnesia Scale provides an effective and timely assessment of post-traumatic amnesia for patients presenting to the Emergency Department with mild traumatic brain injury compared with the previously used assessment tool. It helps identify patients with cognitive impairment and the need for admission and further investigation, resulting in appropriate access to care. It also results in a decreased length of stay and decreased hospital admissions, with subsequent cost savings to the hospital.

In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area. During this time, a 10-year-old German Shepherd dog presented to the referring veterinarian with lethargy and coughing that quickly progressed to death. This report describes the macroscopic and microscopic lesions and the molecular testing performed to identify the novel North American H3N2 strain of canine influenza. The larynx, pharynx, and trachea were covered by a fibrinonecrotic membrane. Bilaterally, the lungs had multifocal subpleural necrosis of the caudal lung lobes with hemorrhage, congestion, and pulmonary edema. Staphylococcus pseudointermedius was isolated from the lung. Mycoplasma cynos was identified by real-time polymerase chain reaction from nasal passages, oropharynx, larynx, trachea, and cranial lung lobes. The neuraminidase gene sequence from the influenza virus isolated obtained from this dog had ≥98% homology to the strain circulating in the Chicago area.

Inhibition of airway epithelial sodium channel (ENaC) function enhances mucociliary clearance (MCC). ENaC is positively regulated by channel-activating proteases (CAPs), and CAP inhibitors are therefore predicted to be beneficial in diseases associated with impaired MCC. The aims of the present study were to 1) identify low-molecular-weight inhibitors of airway CAPs and 2) to establish whether such CAP inhibitors would translate into a negative regulation of ENaC function in vivo, with a consequent enhancement of MCC. To this end, camostat, a trypsin-like protease inhibitor, provided a potent (IC(50) approximately 50 nM) and prolonged attenuation of ENaC function in human airway epithelial cell models that was reversible upon the addition of excess trypsin. In primary human bronchial epithelial cells, a potency order of placental bikunin > camostat > 4-guanidinobenzoic acid 4-carboxymethyl-phenyl ester > aprotinin >> soybean trypsin inhibitor = alpha1-antitrypsin, was largely consistent with that observed for inhibition of prostasin, a molecular candidate for the airway CAP. In vivo, topical airway administration of camostat induced a potent and prolonged attenuation of ENaC activity in the guinea pig trachea (ED(50) = 3 microg/kg). When administered by aerosol inhalation in conscious sheep, camostat enhanced MCC out to at least 5 h after inhaled dosing. In summary, camostat attenuates ENaC function and enhances MCC, providing an opportunity for this approach toward the negative regulation of ENaC function to be tested therapeutically.

Acute appendicitis is a diagnosis that can be made on clinical symptoms and signs but can often be extremely challenging. Difficulties arise particularly when the presentation is atypical, and this can lead to untoward sequelae. In this review, we present the range of presentations of atypical appendicitis, the variety of management options and the potential value of CT.

Author(s): Scott, Hyman M; Irvin, Risha; Wilton, Leo; Van Tieu, Hong; Watson, Chauncey; Magnus, Manya; Chen, Iris; Gaydos, Charlotte; Hussen, Sophia A; Mannheimer, Sharon; Mayer, Kenneth; Hessol, Nancy A; Buchbinder, Susan | Abstract: BackgroundBlack men who have sex with men (MSM) have a high prevalence of bacterial sexually transmitted infections (STIs), and individual risk behavior does not fully explain the higher prevalence when compared with other MSM. Using the social-ecological framework, we evaluated individual, social and sexual network, and structural factors and their association with prevalent STIs among Black MSM.MethodsThe HIV Prevention Trials Network 061 was a multi-site cohort study designed to determine the feasibility and acceptability of a multi-component intervention for Black MSM in six US cities. Baseline assessments included demographics, risk behavior, and social and sexual network questions collected information about the size, nature and connectedness of their sexual network. Logistic regression was used to estimate the odds of having any prevalent sexually transmitted infection (gonorrhea, chlamydia, or syphilis).ResultsA total of 1,553 Black MSM were enrolled in this study. In multivariate analysis, older age (aOR = 0.57; 95% CI 0.49-0.66, pl0.001) was associated with a lower odds of having a prevalent STI. Compared with reporting one male sexual partner, having 2-3 partners (aOR = 1.74; 95% CI 1.08-2.81, pl0.024) or more than 4 partners (aOR = 2.29; 95% CI 1.43-3.66, pl0.001) was associated with prevalent STIs. Having both Black and non-Black sexual partners (aOR = 0.67; 95% CI 0.45-0.99, p = 0.042) was the only sexual network factor associated with prevalent STIs.ConclusionsAge and the number and racial composition of sexual partners were associated with prevalent STIs among Black MSM, while other sexual network factors were not. Further studies are needed to evaluate the effects of the individual, network, and structural factors on prevalent STIs among Black MSM to inform combination interventions to reduce STIs among these men.

SUMMARYThis study was designed to investigate VEGF production from peripheral blood mononuclear cells (PBMC) from patients with rheumatoid arthritis (RA) compared with healthy controls and to identify the predominant cellular source in PBMC isolated from RA patients. The regulation of PBMC VEGF production by cytokines and synovial fluid (SF) was studied. PBMC were isolated from RA patients and healthy controls and stimulated with lipopolysaccharide (LPS), IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α and transforming growth factor-beta (TGF-β) isoforms for varying time points up to 72 h at 37°C/5% CO2. The effect of SF on VEGF secretion by PBMC was also studied. Supernatant VEGF levels were measured using a flt-1 receptor capture ELISA. RA patients had significantly higher spontaneous production of VEGF compared with controls, and monocytes were identified as the predominant cellular source. RA PBMC VEGF production was up-regulated by TGF-β isoforms and TNF-α and down-regulated by IL-4 and IL-10, with no effect observed with IL-1β, IL-6 and IL-8. Antibody blocking experiments confirmed that TNF-α and not TGF-β isoforms in SF increased VEGF secretion by RA PBMC. These results emphasize the importance of monocytes as a source of VEGF in the pathophysiology of RA. Several cytokines known to be present in SF can modulate the level of VEGF secretion, but the predominant effect of SF in VEGF up-regulation is shown to be dependent on TNF-α.

Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome. Background An uncharacterized circulating factor that increases vascular permeability has previously been described in childhood steroid-sensitive nephrotic syndrome (SSNS). The aim of this study was to determine whether this factor is vascular endothelial growth factor (VEGF), the recently described endothelial cell mitogen and enhancer of vascular permeability. Methods Plasma and urine VEGF levels were measured in children with SSNS in both relapse and remission and in normal age- and sex-matched controls. Semiquantitative reverse transcriptase-polymerase chain reaction studies investigating VEGF mRNA expression were performed on peripheral blood mononuclear cells isolated from children with SSNS in relapse and controls. In two experimental models (one-hour and three-day follow-up postinfusion), Sprague-Dawley rats were intravenously administered 50 μg rVEGF to determine whether this induced either proteinuria or glomerular histologic change. Results Plasma VEGF levels and urine VEGF/creatinine ratios were not elevated in SSNS relapse compared with remission and control samples. Peripheral blood mononuclear cell VEGF mRNA expression was no different in SSNS patients compared with controls. The administration of VEGF to rats induced an acute reversible fall in systemic blood pressure but did not result in the development of either proteinuria or glomerular histologic change. Conclusion Increased circulating VEGF levels are not responsible for the proteinuria observed during relapses of SSNS. Further studies are warranted to investigate intrarenal VEGF expression.

Quantitative imaging of the human thorax poses one of the most difficult challenges for three-dimensional (3-D) (septaless) positron emission tomography (PET), due to the strong attenuation of the annihilation radiation and the large contribution of scattered photons to the data. In [/sup 18/F] fluorodeoxyglucose (FDG) studies of the heart with the patient's arms in the field of view, the contribution of scattered events can exceed 50% of the total detected coincidences. Accurate correction for this scatter component is necessary for meaningful quantitative image analysis and tracer kinetic modeling. For this reason, the authors have implemented a single-scatter simulation technique for scatter correction in positron volume imaging. Here, they describe this algorithm and present scatter correction results from human and chest phantom studies.

Conduction slowing is an essential element in the generation of ischemic ventricular arrhythmias and is determined in part by the inward Na+ current (INa). Because intracellular acidosis is an early consequence of ischemia, we hypothesized that lowering intracellular pH (pHi) would reduce or kinetically modulate INa and thus affect cardiac conduction. To test this hypothesis, the whole cell patch-clamp method was used to measure INa in neonatal rat ventricular myocytes exposed to varying extracellular pH (pHo 6.4–7.4), while perfusing the cells with acidic solutions (pHi 6.2–7.2). With simultaneous acidification of pHo and pHi there was a progressive increase in time to peak current, a 31% decrease in peak INa (298 +/- 18 to 206 +/- 16 pA/pF), and a complex slowing of inactivation kinetics. At the most extreme levels of acidification, there was a 5-mV hyperpolarizing shift in steady-state inactivation and a 6-mV depolarizing shift in activation. Independent changes of pHo and pHi indicate that the reduction of peak INa is a function of pHo. However, steady-state inactivation is modulated by pHi. The time course of activation and inactivation appears to depend on both pHo and pHi. We conclude that both intracellular and extracellular acidosis are significant but distinct modulators of INa amplitude and kinetics in cardiac myocytes.

Summary Background The mainstream long term management of recurrent vulvovaginal candidiasis (RVVC) often results in poor outcomes. It is expensive and unacceptable for many women who therefore have incorporated complementary and alternative medicine (CAM) into their personal care plan. Objective To ascertain clinicians' knowledge of CAM and their recommendations for the use of CAM and non-pharmacological management in women with RVVC. Design and setting Anonymous, single page, self completed survey using convenience sampling at a vulval disorders meeting in New South Wales, Australia in 2009. Participants Sixty six health professionals (medical practitioners, dermatologists, nurses and allied health professionals). Results Most clinicians reported asking about their patients' use of CAM and non-pharmacological management of RVVC, although only around half reported recommending it. CAM management included lactobacillus, oral and vaginal yoghurt, vinegar, garlic, Chinese medicine and tea-tree oil. Non-pharmacological management included dietary changes and use of cotton undergarments. Lactobacillus was the most commonly recommended CAM. Conclusion CAM is popular with patients and many clinicians actively recommend its use in RVVC despite limited supporting evidence. Further research in the area of CAM and RVVC is long overdue.

Recent worldwide media speculation that silicone gel-filled breast implants may be linked to an increased incidence of breast and other cancers, and connective tissue disease(particularly systemic sclerosis) has caused concern to the medical profession and public alike. Until carefully controlled studies have been performed to prove the safety of these implants, the US Food and Drug Administration has restricted their use to research and breast reconstruction. Research has so far failed to prove a causative relationship between silicone implants and cancer or connective tissue disorders.

SUMMARY In order to study the possible autoimmune basis of multiple sclerosis (MS) a quantitative method has been used to investigate breakdown of human myelin in vitro. We found that serum from MS patients and controls was generally devoid of any myelin degradative activity. However, isolated peripheral blood mononuclear cells from 43% of MS patients showed significant myelin degradative activity as did those from 61.5% of patients with rheumatoid arthritis (RA). Myelin degradation by cells was found in only 13% of patients with other neurological diseases and in no healthy controls. It is proposed that this non-specific peripheral cellular immune degradative activity originates from cells activated within the central nervous system of MS patients or the joints of individuals with RA. As a result, activity in the blood only indirectly reflects the ongoing inflammatory response at the primary site, accounting for the lack of correlation between changes in the blood and the clinical status of the MS patient. We further propose that the lack of in vitro myelin degradative activity in cells recovered from the cerebrospinal fluid is due to autoaggressive cells being sequestered to the brain.

BACKGROUND: The treatment and prognosis of non-small cell lung cancer, and assessment of the results of treatment, depend on accurate perioperative staging. The extent to which this is carried out in the United Kingdom is unknown. METHODS: A postal questionnaire survey was undertaken in 1990 to determine the perioperative staging practices of cardiothoracic surgeons in the United Kingdom. RESULTS: Replies from 77 surgeons, who between them performed about 4833 pulmonary resections a year for lung cancer, were analysed. Forty four per cent of surgeons, operating on 43% of the patients, do not perform computed tomography of the thorax or mediastinal exploration before surgery. They may therefore embark on a thoracotomy for stage III disease. At thoracotomy 45% of surgeons, operating on 40% of patients, do not sample macroscopically normal lymph nodes. They may therefore understage cases as N0/N1 when there is at least microscopic disease in mediastinal lymph nodes. CONCLUSIONS: The staging of lung cancer in the United Kingdom in 1990 appears in many instances to be inadequate. There should be a more organised approach to perioperative staging so that prognosis may be assessed and comparisons between groups of patients can be made.

This study investigated the experience of endossoseus implants in the U.K. - how success rates compare with other countries; the common causes of failure; early detection, definition and treatment of the failing implant. Information was gathered by means of a questionnaire sent to 120 centres in the U.K. Thirty-nine centres responded to the survey, reporting on a total of 5328 implants which had been placed over an average time period of 6.5 years. A mean failure rate of 4.3% was reported in the mandible with 16% in the maxilla. The survey showed that 11 different implant systems were in use and that implants were used to support an overdenture in 56% of cases, and bridgework in 26%. The definition of the failing implant and the causes of failure were unclear, with a wide range of opinions given. A combination of methods were used to treat the failing implant including surgical techniques and chemotherapeutic agents, but the long-term success of these treatments was uncertain. Failure rates especially in the maxilla at some of the centres appear higher than have been previously suggested in the U.K. or abroad. Universal agreement on the criteria for 'success' and 'failure' of fixtures is needed along with agreed treatment protocols for the failing implant.

This document describes archived radiobiology animal studies. Information is presented on experimental details, pathology, radioactivity, results, dosimetry, status, and animal type employed.

A variety of small domestic or nondomestic felid species have been produced from cryopreserved embryos using slow-cooling (controlled rate) cryopreservation methods (Pope et al. 2006 Theriogenology 66, 59–71; 1518–1524). However, in our laboratory these methods have not been as successful as vitrification in freezing in vitro-derived embryos of larger felid species such as tigers, Panthera tigris spp. (Crichton et al. 2000 Theriogenology 53, 238). The objective of this study was to examine the effects of slow-cooling cryopreservation v. vitrification methods on the developmental competence of in vitro-produced 2- to 4-celled domestic cat embryos as compared to non-frozen controls. Mature tomcat testicles and queen ovaries were collected from local veterinary clinics. Epididymal sperm were processed using one of three methods according to availability and time of use: 1) freshly washed if used the same day for IVF, 2) stored in cooled, non-electrolyte medium (Pope et al. 2000 ICAR Proc. 2, 191) if used within one week, or 3) frozen according to Tebet et al. (2006 Theriogenology 66, 1629–1632). Batches of oocytes were inseminated with the same pool and type of processed sperm per replicate. All in vitro maturation (IVM), in vitro fertilization (IVF), and in vitro culture (IVC) procedures followed those previously reported (Pope et al. 2000 Theriogenology 53, 163–174). After 48 h in IVC, 2- to 4-celled embryos were equally divided into the three groups: 1) control, non-frozen; 2) slow-cooling cryopreservation using propanediol and sucrose; and 3) vitrification using DMSO, ethylene glycol and sucrose. The cryopreservation/thawing procedure followed that of Gomez et al. (2003) and the vitrification/warming procedure followed that of Vajta et al. (2000 Anim. Reprod. Sci. 60, 357–364). Results were recorded as the percentages of blastocyst formations at Day 8 of IVC and were compared between groups using chi-square analysis. In March 2000 to 2001, 806 feline oocytes were recovered from 101 ovaries and 286 blastocysts were obtained on Day 8 IVC in seven replicates. There were no significant differences in the numbers of degenerated embryos (2- to 8-celled) or morulae in all three groups (P > 0.05). There were more blastocysts that developed in the non-frozen control group (45/97; 46.4%), but this was not statistically different (P > 0.05) from the cryopreserved group (37/91; 40.7%). However, there were significantly more blastocysts (P < 0.01) produced in the non-frozen control group than the vitrified group (28/98, 28.6%). There were no differences between the cryopreserved and vitrified groups (P > 0.05). In conclusion, this study verifies previous reports that slow, or controlled-rate cryopreservation is effective for domestic cat embryos. Vitrification is less effective, as compared to non-frozen control embryos, but this may be improved with modified protocols.

Diaphragmatic rupture due to blunt trauma is well recognised though uncommon. Most cases are diagnosed at the time of injury, but a proportion remain undiagnosed, only to present some months or even years later. This "delayed" group can present in a number of ways, including chronic abdominal and chest problems or an acute crisis. Herniation of abdominal viscera is the most common sequel, with strangulation and gangrene as the most serious complication. This paper reports a case of delayed presentation of diaphragmatic rupture and herniation presenting as tension hydropneumothorax due to small bowel perforation. A short discussion addresses the problems in diagnosis of this condition. We believe this to be the first reported case of perforated small bowel leading to tension hydropneumothorax.

Mouse kidney beta-glucuronidase is induced by androgens in a receptor-dependent fashion. Genetic regulatory mutations have been described which govern this response. In mice carrying the Gus-ra allele (A/J), the induction of enzyme activity is 3-5 times greater than in animals with the Gus-rb allele (C57BL/6J). To study this hormonal and genetic control at the molecular level, we measured changes in beta-glucuronidase mRNA concentrations in these two mouse strains using cloned cDNA. The specificity of the regulation was assessed by following changes in the concentration of kidney androgen-regulated protein (KAP) mRNA, which is also under androgen control in mouse kidney. Female mice were treated with Silastic implants that released 120 micrograms testosterone/day over a 20-day time course. Induction of specific mRNA was analyzed by either Northern blot hybridization or a more quantitative assay in which renal poly(A) RNA was covalently bound to aminophenylthioether paper discs. The induction of beta-glucuronidase mRNA was about 10-fold higher in the strain carrying the Gus-ra regulatory allele, indicating that the Gus-r locus controls the beta-glucuronidase structural gene (Gus-s) at the level of mRNA accumulation. Regulation by Gus-r was specific for beta-glucuronidase mRNA as kidney androgen-regulated protein mRNA accumulation did not differ between these two strains of mice after androgen treatment.

Despite advances in the anesthetic pharmacopeia and improved noninvasive monitoring techniques, subjective bias and individual clinical experience remain major determinants of individual practice. Medicolegal pressures have increased in recent years, as has the concept of shared responsibility for surgical and anesthetic complications. New standards of anesthesia monitoring and practice are evolving in response to the need for perioperative risk management and cost-effective surgical care. Continued vigilance and close communication between the otolaryngologist and anesthesiologist remain key elements for safe anesthetic practice.

We present a case of paraganglioma of the thyroid. The preoperative evaluation, surgical management, and histopathology are described. Four similar cases that have been reported are summarized, and a hypothesis for the origin of a paraganglioma within the thyroid capsule is proposed.

Some patients who have transient ischemic attacks are denied operation because severe occlusive lesions in other extra-cranial arteries may be inappropriately interpreted as constituting an unacceptable surgical risk, or because the lesion is so distal as to make its removal hazardous. Failure of endarterectomy is usually due to incomplete removal of the lesion or to thrombosis upon the frayed intima. Such lesions require excellent visualization and meticulous surgical technique -- not always possible with a shunt. Among 130 consecutive carotid endarterectomies performed under general anesthesia, EEG changes consistent with cerebral ischemia appeared in only nine (7%). These patients required a shunt. In 11 patients normal EEG tracings were obtained during endarterectomy despite contralateral carotid occlusion. None of these patients had a neurological deficit. Continuous EEG monitoring is a reliable method of detecting changes in cerebral perfusion, permits a more meticulous endarterectomy in high-lying lesions without a shunt, and extends operability in high risk patients. Angiographical findings may be an unreliable predictor concerning risk of endarterectomy.

A case in which a mediastinal tumour caused complications including airway obstruction unrelieved by intubation during inhalational induction is described. Other case reports are reviewed and the anaesthetic management of patients with mediastinal tumours is discussed.

Multiple sclerosis is probably an acquired infectious disease with an autoimmune response relating to damage to the white matter of the central nervous system. There is evidence of continued intrathecal synthesis of oligoclonal antibody and there are perivascular inflammatory cell infiltrates close to areas of demyelination in the central nervous system. Following adoptive transfer, cells sensitized to the myelin basic protein can cause demyelinating disease in rodent recipients. Unlike the peripherally-mediated immune changes in the experimental model it is argued that autoaggressive cells are generated within the CNS in multiple sclerosis. The possible mechanism of cellular demyelination is discussed and the implication for therapy is reviewed.

Incorporation of glycine-2-C 14 into Hb proto and bile bilirubin was studied at short intervals in 2 bile fistula dogs during successive periods of inhibited and then stimulated erythropoiesis (plethora and bleeding in 1 dog and undefined illness and bleeding in another), and in a third dog with bile renal fistula but without disturbed erythropoiesis. Results support the concept of a nonerythropoietic component as a partial source of early-labeled bilirubin. Thus, during the period of inhibited erythropoiesis relatively larger amounts of bilirubin-C 14 were excreted during the first 48 hours. The total amount of this labeling was appreciably greater than that expected from the relatively low labeling of total circulating hemoglobinproto during this period compared to the postbleeding period. The per cent incorporation of glycine-C 14 in total circulating Hb proto during the postbleeding and plethoric periods, respectively, were 5.8 and 0.48 (ratio of 12.1), while the corresponding values for the total 6 day bile bilirubin-C 14 were 0.22 and 0.04 (ratio of 5.5). In an otherwise normal bile fistula dog given ALA-C 14 , 20 per cent of the C 14 administered was recovered as bile bilirubin-C 14 during the following 6 days, with 94 per cent of this amount appearing during the first 2 days. Peak activity at 3–4 hours was 22 × 10 6 dpm/mg./mc. dose. Only 0.26 per cent of the dose was incorporated in circulating Hb proto in contrast to 3.0 per cent in the normal dog given glycine-C 14 . In a second dog studied for only 24 hours, 19.5 per cent of the administered dose of ALA-C 14 was excreted as bile bilirubin-C 14 .

Dr. Lima (presenting the case history): A 60-year-old white male, a cabinet-maker, was first admitted to the hospital on July 9, 1942, after study in the Out-Patient Department two weeks previously. His complaints were weakness, anorexia, loss of weight, and a dry cough, all beginning about March 1942. Some seven weeks prior to admission the sputum became purulent and the breath bad, but there was no hemoptysis. There were no respiratory symptoms prior to the present complaint. The patient had lost 47 pounds in weight during the past year. The temperature was 100.8°, pulse 80, blood pressure 128/80. The patient appeared chronically ill and was raising large amounts of sputum. On physical examination there was evidence of atrophy of the pectoral muscles on the right side with greater expansion on the left. Breath sounds appeared normal. There were numerous crepitant medium rales at the right base posteriorly. Marked clubbing of the fingers and toes was present. There was no cyanosis. The urine was negative...