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Surgical culture has shifted to recognize the importance of resident well-being. This is the first study to longitudinally track regional surgical resident well-being over 5 years.An anonymous cross-sectional, multi-institutional survey of New England general surgery residents using novel and published instruments to create three domains: health maintenance, burnout, and work environment.Overall, 75% (15 of 20) of programs participated. The response rate was 44% (250 of 570), and 53% (133 of 250) were women, 94% (234 of 250) were 25 to 34 years old, and 71% (178 of 250) were in a relationship. For health maintenance, 57% (143 of 250) reported having a primary care provider, 26% (64 of 250) had not seen a primary care provider in 2 years, and 59% (147 of 250) endorsed being up to date with age-appropriate health screening, but only 44% (109 of 250) were found to actually be up to date. Only 14% (35 of 250) reported exercising more than 150 minutes/week. The burnout rate was 19% (47 of 250), with 32% (81 of 250) and 25% (63 of 250) reporting high levels of emotional exhaustion and depersonalization, respectively. For program directors and attendings, 90% of residents reported that they cared about resident well-being. Eighty-seven percent of residents believed that it was acceptable to take time off during the workday for a personal appointment, but only 49% reported that they would personally take the time.The personal health maintenance of general surgery residents has changed little over the past five years, despite an overwhelming majority of residents reporting that attendings and program directors care about their well-being. Further study is needed to understand the barriers to improvement of resident wellbeing.

The brain’s ability to associate different stimuli is vital to long-term memory, but how neural ensembles encode associative memories is unknown. Here we studied how cell ensembles in the basal and lateral amygdala (BLA) encode associations between conditioned and unconditioned stimuli (CS, US). Using a miniature fluorescence microscope, we tracked BLA ensemble neural Ca2+ dynamics during fear learning and extinction over six days in behaving mice. Fear conditioning induced both up- and down-regulation of individual cells’ CS-evoked responses. This bi-directional plasticity mainly occurred after conditioning and reshaped the CS ensemble neural representation to gain similarity to the US-representation. During extinction training with repetitive CS presentations, the CS-representation became more distinctive without reverting to its original form. Throughout, the strength of the ensemble-encoded CS-US association predicted each mouse’s level of behavioral conditioning. These findings support a supervised learning model in which activation of the US-representation guides the transformation of the CS-representation.

Cognitive faculties such as imagination, planning, and decision-making entail the ability to represent hypothetical experience. Crucially, animal behavior in natural settings implies that the brain can represent hypothetical future experience not only quickly but also constantly over time, as external events continually unfold. To determine how this is possible, we recorded neural activity in the hippocampus of rats navigating a maze with multiple spatial paths. We found neural activity encoding two possible future scenarios (two upcoming maze paths) in constant alternation at 8Hz: one scenario per ∼125-ms cycle. Further, we found that the underlying dynamics of cycling (both inter- and intra-cycle dynamics) generalized across qualitatively different representational correlates (location and direction). Notably, cycling occurred across moving behaviors, including during running. These findings identify a general dynamic process capable of quickly and continually representing hypothetical experience, including that of multiple possible futures.

Background Antenatal detection of fetal growth restriction (FGR) prompts antepartum surveillance to reduce perinatal mortality, yet most cases of FGR are undetected. Objective This study aims to compare rates of adverse neonatal outcomes when FGR is detected versus undetected. Study Design Small-for-gestational-age (SGA) newborns (birth weight Results Out of 29,885 neonates, 2,475 (8.3%) were SGA. Out of the 826 (33%) SGA neonates who underwent growth ultrasound, 185 (22%) were considered FGR. In the SGA-no US group, the adjusted odds ratio (aOR) for Apgar Conclusion Fetal growth ultrasound effectively stratifies risk amongst SGA neonates.

SummaryFollowing skeletal muscle injury, muscle stem cells (satellite cells) are activated, proliferate, and differentiate to form myofibers. We show that mRNA-decay protein AUF1 regulates satellite cell function through targeted degradation of specific mRNAs containing 3′ AU-rich elements (AREs). auf1−/− mice undergo accelerated skeletal muscle wasting with age and impaired skeletal muscle repair following injury. Satellite cell mRNA analysis and regeneration studies demonstrate that auf1−/− satellite cell self-renewal is impaired due to increased stability and overexpression of ARE-mRNAs, including cell-autonomous overexpression of matrix metalloprotease MMP9. Secreted MMP9 degrades the skeletal muscle matrix, preventing satellite-cell-mediated regeneration and return to quiescence. Blocking MMP9 activity in auf1−/− mice restores skeletal muscle repair and maintenance of the satellite cell population. Control of ARE-mRNA decay by AUF1 represents a mechanism for adult stem cell regulation and is implicated in human skeletal muscle wasting diseases.

How does an animal know where it is when it stops moving? Hippocampal place cells fire at discrete locations as subjects traverse space, thereby providing an explicit neural code for current location during locomotion. In contrast, during awake immobility, the hippocampus is thought to be dominated by neural firing representing past and possible future experience. The question of whether and how the hippocampus constructs a representation of current location in the absence of locomotion has stood unresolved. Here we report that a distinct population of hippocampal neurons, located in the CA2 subregion, signals current location during immobility, and furthermore does so in association with a previously unidentified hippocampus-wide network pattern. In addition, signaling of location persists into brief periods of desynchronization prevalent in slow-wave sleep. The hippocampus thus generates a distinct representation of current location during immobility, pointing to mnemonic processing specific to experience occurring in the absence of locomotion.

Acquired progressive lymphangioma (benign lymphangioendothelioma) is a rare lymphatic anomaly of unclear pathogenesis. Excision is generally advised for local disease, although other therapies have been tried. This report describes a unique case of extensive acquired progressive lymphangioma involving the abdomen, genitalia, and lower extremity of a 1-year-old boy. Rapid progression and multisite involvement required exploration of nonsurgical options for management.

Objective This study aims to determine the risk of adverse outcomes associated with the current diagnostic criteria for fetal macrosomia. Study Design We evaluated three techniques for characterizing birth weight as a predictor of shoulder dystocia or third- or fourth-degree laceration in 79,879 vaginal deliveries. First, we compared deliveries with birth weights above or below 4,500 g. We then performed logistic regression using birth weight as a continuous predictor, both with and without fractional polynomial transformation. Finally, we calculated the number of cesarean sections required to prevent one incident of the interrogated outcomes (number needed to treat [NNT]). Results Rates of adverse intrapartum outcomes increase incrementally with increasing birth weight and are predicted most accurately with logistic regression following fractional polynomial transformation. The NNT for third- or fourth-degree laceration dropped from 14.3 (95% confidence interval [CI], 13.9–14.7) at a birth weight of 3,500 g to 6.4 (95% CI, 6.1–6.8) at 4,500 g and, for shoulder dystocia, from 54.9 (95% CI, 51.5–58.6) at 3,500 g to 5.6 (95% CI, 5.2–6.0) at 4,500 g. Conclusion The conventional distinction between “normal” and “macrosomic” does not reflect the incremental effect of increasing birth weight on the risk of obstetric morbidity. Outcomes analysis can inform fetal growth standards to better reflect relevant thresholds of risk.

While ongoing experience proceeds continuously, memories of past experience are often recalled as episodes with defined beginnings and ends. The neural mechanisms that lead to the formation of discrete episodes from the stream of neural activity patterns representing ongoing experience are unknown. To investigate these mechanisms, we recorded neural activity in the rat hippocampus and prefrontal cortex, structures critical for memory processes. We show that during spatial navigation, hippocampal CA1 place cells maintain a continuous spatial representation across different states of motion (movement and immobility). In contrast, during sharp-wave ripples (SWRs), when representations of experience are transiently reactivated from memory, movement- and immobility-associated activity patterns are most often reactivated separately. Concurrently, distinct hippocampal reactivations of movement- or immobility-associated representations are accompanied by distinct modulation patterns in prefrontal cortex. These findings demonstrate a continuous representation of ongoing experience can be separated into independently reactivated memory representations.

Intrauterine mammalian development depends on the preservation of placental function. The expression of the protein N-myc downstream–regulated gene 1 (NDRG1) is increased in placentas of human pregnancies affected by fetal growth restriction and in hypoxic primary human trophoblasts, where NDRG1 attenuates cell injury. We sought to assess the function of placental NDRG1 in vivo and tested the hypothesis that NDRG1 deficiency in the mouse embryo impairs placental function and consequently intrauterine growth. We found that Ndrg1 knock-out embryos were growth restricted in comparison to wild-type or heterozygous counterparts. Furthermore, hypoxia reduced the survival of female, but not male, knock-out embryos. Ndrg1 deletion caused significant alterations in placental gene expression, with a marked reduction in transcription of several lipoproteins in the placental labyrinth. These transcriptional changes were associated with reduced fetal:maternal serum cholesterol ratio exclusively in hypoxic female embryos. Collectively, our findings indicate that NDRG1 promotes fetal growth and regulates the metabolic response to intrauterine hypoxic injury in a sexually dichotomous manner.

Objective We assessed the effect of an open vascular simulation course on the surgical skill of junior surgical residents in performing a vascular end-to-side anastomosis and determined the course length required for effectiveness. We hypothesized that a 6-week course would significantly increase the surgical skill of junior residents in performing an end-to-side anastomosis, while a 3-week course would not. Methods We randomized 37 junior residents (postgraduate year 1 to 3) to a course consisting of three (short course, n=18) or six (long course, n=19) consecutive weekly 1-hour teaching sessions. Content focused on instrument recognition and performance of an end-to-side vascular anastomosis using a simulation model. A standardized 50-point vascular skills assessment (SVSA) measured knowledge and technical proficiency. Senior residents (postgraduate year 4 to 5) were tested at baseline. Junior residents were tested at baseline and at 1 and 16 weeks after course completion, and their scores were compared with baseline and senior resident scores. Residents and faculty completed a standardized anonymous evaluation of the course. Results Baseline scores between short-course and long-course participants were not different. At baseline, junior residents had significantly lower SVSA scores than senior residents (36 ± 7 vs 41.4 ± 2.5; P = .002). One week after course completion, SVSA scores for short-course (43.5 ± 2.9 vs 34.2 ± 7.5; P = .008) and long-course (43.9 ± 5.6 vs 38.3 ± 5.9; P = .006) participants were significantly improved from baseline. SVSA scores decreased slightly at 16 weeks but remained above baseline in short-course (39 ± 6.2 vs 34.2 ± 7.5; P = .03) and long-course (40 ± 4.5 vs 38.3 ± 5.9; P = .08) participants. Long vs short course length didnot affect improvement in SVSA scores at 1 or 16 weeks. In short-course and long-course participants, SVSA scores at 1 and 16 weeks were not significantly different from senior resident scores. Course ratings were high, and 95% of residents indicated the course "made them a better surgeon." Residents and faculty felt the educational benefit of the course merited the investment of resources. Conclusions An open vascular simulation course consisting of three weekly 1-hour sessions increased the surgical skill of junior residents in performing a vascular end-to-side anastomosis to that of senior residents on a standardized assessment. A 6-week course provided no additional benefit. This study supports the use of an open vascular simulation course to teach vascular surgical skills to junior residents. A course consisting of three 1-hour sessions is an effective and efficient component of a simulation program for junior surgical residents in a busy surgical center.

ObjectivesWe sought to determine the level of procedural justice experienced by individuals at the time of involuntary admission and whether this influenced future engagement with the mental health services.MethodsOver a 15-month period, individuals admitted involuntarily were interviewed prior to discharge and at one-year follow-up.ResultsEighty-one people participated in the study and 81% were interviewed at one-year follow-up. At the time of involuntary admission, over half of individuals experienced at least one form of physical coercion and it was found that the level of procedural justice experienced was unrelated to the use of physical coercive measures. A total of 20% of participants intended not to voluntarily engage with the mental health services upon discharge and they were more likely to have experienced lower levels of procedural justice at the time of admission. At one year following discharge, 65% of participants were adherent with outpatient appointments and 18% had been readmitted involuntarily. Insight was associated with future engagement with the mental health services; however, the level of procedural justice experienced at admission did not influence engagement.ConclusionsThis study demonstrates that the use of physical coercive measures is a separate entity from procedural justice and perceived pressures.

Adrenalectomy remains the definitive therapy for most adrenal neoplasms. Introduced in the 1990s, laparoscopic adrenalectomy is reported to have lower associated morbidity and mortality. This study aimed to evaluate national adrenalectomy trends, including major postoperative complications and perioperative mortality. The Nationwide Inpatient Sample was queried to identify all adrenalectomies performed during 1998–2006. Univariate and multivariate logistic regression were performed, with adjustments for patient age, sex, comorbidities, indication, year of surgery, laparoscopy, hospital teaching status, and hospital volume. Annual incidence, major in-hospital postoperative complications, and in-hospital mortality were evaluated. Using weighted national estimate, 40,363 patients with a mean age of 54 years were identified. Men made up 40% of these patients, and 77% of the patients were white. The majority of adrenalectomies (83%) were performed for benign disease. The annual volume of adrenalectomies increased from 3,241 in 1998 to 5,323 in 2006 (p

Unconventional gas drilling (UGD) has enabled extraordinarily rapid growth in the extraction of natural gas. Despite frequently expressed public concern, human health studies have not kept pace. We investigated the association of proximity to UGD in the Marcellus Shale formation and perinatal outcomes in a retrospective cohort study of 15,451 live births in Southwest Pennsylvania from 2007–2010. Mothers were categorized into exposure quartiles based on inverse distance weighted (IDW) well count; least exposed mothers (first quartile) had an IDW well count less than 0.87 wells per mile, while the most exposed (fourth quartile) had 6.00 wells or greater per mile. Multivariate linear (birth weight) or logistical (small for gestational age (SGA) and prematurity) regression analyses, accounting for differences in maternal and child risk factors, were performed. There was no significant association of proximity and density of UGD with prematurity. Comparison of the most to least exposed, however, revealed lower birth weight (3323 ± 558 vs 3344 ± 544 g) and a higher incidence of SGA (6.5 vs 4.8%, respectively; odds ratio: 1.34; 95% confidence interval: 1.10–1.63). While the clinical significance of the differences in birth weight among the exposure groups is unclear, the present findings further emphasize the need for larger studies, in regio-specific fashion, with more precise characterization of exposure over an extended period of time to evaluate the potential public health significance of UGD.

We evaluated six D-dimer methods to determine their sensitivity, specificity, and negative predictive values (NPV) in symptomatic patients suspected of deep vein thrombosis (DVT). In patients suspected of DVT a whole blood D-dimer test (SimpliRED, Agen) was performed, and then tested using enzyme-linked immunosorbent assay (VIDAS D-Dimer, BioMerieux; Asserachrome D-Di, Stago International; Dimertest Gold, Agen) and automated immunoturbidometric methods (Advanced D-Dimer, Dade Behring; MiniQuant, Biopool). Each D-dimer method was independently compared with radiographic results to determine sensitivity and NPV. There were 151 patients enrolled in the study. Thirty-five (23.2%) patients had a positive Doppler ultrasound, with 26 proximal, eight distal, and one patient with both proximal and distal thrombus. Two patients (1.3%) had inconclusive studies and were excluded from the analyses. For all patients, the sensitivities for the rapid D-dimer methods were: SimpliRED, 82.3% [95% confidence interval (CI), 80.3-84.3%]; VIDAS D-Dimer, 91.4% (95% CI, 89.9-92.9%); MiniQuant D-Dimer, 96.3% (95% CI, 95.1-97.5%); and Advanced D-Dimer, 97.1% (95% CI, 96.3-97.9%). The sensitivity improved for SimpliRED (86.4%; 95% CI, 83.3-89.4%), VIDAS D-Dimer (95.5%; 95% CI, 85.0-100%), MiniQuant D-Dimer (100%; 95% CI, 96.9-100%) and Advanced D-Dimer (100%; 95% CI, 98.9-100%) in the inpatient population. The automated immunoturbidometric methods, the MiniQuant D-Dimer and Advanced D-Dimer, demonstrated comparable sensitivities and NPV with the VIDAS D-Dimer method in symptomatic patients suspected of DVT, which would suggest that these newer D-dimer methods could be used as part of the diagnostic algorithm for patients suspected of DVT.

Hypothesis: Children who undergo cardiopulmonary bypass (CPB) are proportionally more hemodiluted than adults who undergo CPB. Current methods of monitoring high-dose heparin sulfate anticoagulation are dependent on fibrinogen level. Because of the decreased fibrinogen levels in children, current methods of monitoring heparin anticoagulation overestimate their level of anticoagulation. Design: Prospective controlled trial. Main Outcome Measure: Production of thrombin (adequacy of anticoagulation). Methods: Children and adults undergoing cardiac surgery who received CPB were anticoagulated in the standard fashion as directed by activated clotting time (ACT) results. Each subject had blood sampled at baseline; heparinization; start of the CPB; CPB at 30, 60, and 90 minutes; and at termination of CPB. Samples were used to assess anticoagulation with the Heparin Management Test (less dependent on fibrinogen level than ACT). We also assessed 2 subclinical markers of thrombosis, thrombin-antithrombin complexes and prothrombin fragment F1.2; a marker of procoagulant reserve, fibrinogen; the natural antithrombotic, anti-thrombin; and heparin concentration. Results: Ten children and 10 adults completed the study. Children had lower fibrinogen levels than adults throughout CPB (P

Background The whole blood D-dimer assay has gained recognition as a noninvasive test to rule out pulmonary embolism (PE) in medical patients. Methods We performed a whole blood D-dimer assay in medical and surgical patients undergoing either pulmonary angiogram or pulmonary ventilation perfusion scan for suspected PE or duplex Doppler or venogram for suspected deep venous thrombosis (DVT). Results A total of 483 patients were enrolled; 16 were excluded because of an equivocal pulmonary ventilation perfusion scan. The 467 remaining patients had a mean age of 56 +/- 27 years. There were 258 women and 209 men. A total of 353 patients were admitted to a medical service and 114 to surgery/ trauma. A total of 82 patients (18%) developed thromboembolism: 20 had PE, and 62 had DVT. Conclusion No surgical patient with PE or DVT (n = 27) had a negative D-dimer. A negative D-dimer result in a stable surgical patient should be considered conclusive evidence to rule out thromboembolism and, thus, negate the need for further diagnostic studies. In our surgical patients suspected of DVT or PE, had D-dimer been used, one third of the patients would have avoided an expensive or invasive diagnostic test.

BackgroundIt was hypothesised that schizophrenic patients with tardive dyskinesia show an excess of neurodevelopmental disturbance, particularly minor physical anomalies, in association with cognitive dysfunction and abnormalities of cerebral structure.MethodForty-seven out-patients with a DSM–III diagnosis of schizophrenia were examined for tardive dyskinesia using the Abnormal Involuntary Movement Scale; they were examined also for minor physical anomalies and neuropsychological test performance. Cortical atrophy, signal hyperintensities and lateral ventricular volume were determined on magnetic resonance imaging.ResultsPatients with and without tardive dyskinesia could not be distinguished by age, gender distribution or a number of clinical measures; however, patients with tardive dyskinesia sorted fewer categories on the Wisconsin Card Sorting Test (P = 0.04). Cerebral structure in patients with and without tardive dyskinesia could not be distinguished on magnetic resonance imaging but those with dyskinesia, all of whom showed involvement of the orofacial region, showed more evident minor physical anomalies of the head relative to those of the periphery (P = 0.02).ConclusionsTardive orofacial dyskinesia in schizophrenia appears to be associated particularly with poorer frontal lobe function, while predominance of craniofacial dysmorphogenesis may constitute a vulnerability factor that is related to the early origins of the disease process.

Background This study examines the development and implementation of a pilot human factors curriculum during a 2-year period. It is one component of a comprehensive 5-year human factors curriculum spanning core competencies of interpersonal and communication skills, systems-based practice, and professionalism and using low-and high-fidelity simulation techniques. Study Design Members of the Department of Surgery and the Center for Clinical Communication and Performance Outcomes jointly constructed a curriculum for PGY1 and PGY2 residents on topics ranging from challenging communication to time and stress management. Video demonstrations, triggers, and simulated scenarios involving acting patients were created by surgeons and medical educators. Pre- and postintervention measures were obtained for communication skills, perceived stress level, and teamwork. Communication skills were evaluated using a series of video vignettes. The validated Perceived Stress Scale and Teamwork and Patient Safety Attitudes survey were used. Residents' perceptions of the program were also measured. Results Twenty-seven PGY1 residents and 15 PGY2 residents participated during 2 years. Analyses of video vignette tests indicated significant improvement in empathic communication for PGY1 ( t = 3.62, p=0.001) and PGY2 ( t = 5.00, p=0.004). There were no significant changes to teamwork attitudes. Perceived levels of stress became considerably higher. PGY1 residents reported trying 1 to 3 strategies taught in the time management session, with 60% to 75% reporting improvement post-training. Conclusions This unique and comprehensive human factors curriculum is shown to be effective in building communication competency for junior-level residents in the human and emotional aspects of surgical training and practice. Continued refinement and ongoing data acquisition and analyses are underway.

Adverse effects observed in alcoholic rats are often attributed to alcohol per se. Alcoholic liver damage, however, can be avoided by modulating nutritional factors despite high blood alcohol concentrations. Hence, we examined the effect of blood alcohol concentration on pancreatic enzyme activity and release. Three liquid diets containing 36 and 18% of total energy derived from alcohol and protein, respectively, were fed. Each alcohol diet contained 11, 21 or 31% of energy from carbohydrate, and the fat concentration was appropriately adjusted. The control groups of rats (fed an isoenergetic liquid diet without alcohol) and the alcoholic groups of rats were maintained for 2 wk. The three groups of alcoholic rats consumed 13.3 +/- 2.3, 13.3 +/- 2.2 and 13.2 +/- 1.9 g/kg of alcohol daily, and their corresponding blood alcohol levels were 41.5 +/- 4.3, 55.4 +/- 8.9 and 44.6 +/- 2.2 mmol/L. Pancreatic acinar amylase activity in alcoholic rats was proportional to carbohydrate ingested, despite high blood alcohol concentrations; chymotrypsin and trypsin activities were unchanged. Acinar enzyme activities in control rats were similar. Furthermore, cholecystokinin-octapeptide-stimulated amylase release in alcoholic rats corresponded with the amylase concentration in acini, whereas stimulated trypsin output was unaltered in both control and alcoholic rats. These results demonstrate that neither alcohol ingestion nor high blood alcohol concentration affects the activities of pancreatic proteases and that the changes in the activity and release of amylase are related to the intake of carbohydrate.

Non-Hodgkin's lymphoma (NHL) occurring as a synchronous malignancy with chronic myelogenous leukemia (CML) is rare. To our knowledge, this is the first case reported of a patient who developed mantle cell lymphoma (MCL) after therapy with imatinib mesylate for CML. After a 3-year history of CML, the patient developed a lymphocytosis associated with diarrhea, anorexia, and weight loss. Imaging studies revealed abdominal adenopathy and extensive lymphomatous infiltration of the liver, stomach, pancreas, and kidneys. Flow cytometric and cytogenetic studies were consistent with MCL. Fluorescence in situ hybridization (FISH) of the bone marrow revealed a genetically distinct lymphoid neoplasm rather than an extramedullary blast crisis of CML. The development of lung cancer, prostate cancer, CML and MCL in this patient suggests a genetic predisposition, although other factors, including environmental exposures and therapy with imatinib mesylate could have had a contributory or synergistic role in the development of MCL.

Background and Objectives Platelet function abnormalities have been reported in blood donors who have not consumed aspirin. Our objective was to identify factors other than aspirin that may contribute to impaired platelet function in qualified volunteer blood donors. Materials and Methods Blood samples were obtained from 24 donors following routine blood donation. Donors completed a study questionnaire that included questions about recent food consumption, medication and medical history. Platelet activation was measured using monoclonal antibodies and flow cytometry. CD62P expression and PAC-1 binding on platelets were used as indicators of platelet activation. Platelet function was measured on a platelet function analyser (PFA-100®) using both collagen/epinephrine (cEPI) and collagen/ADP (cADP) cartridges. Results Fifty-four per cent of donors (13 of 24) had normal platelet function. Thirty-eight per cent (nine of 24) had prolonged cEPI closure times, of whom four (17%) had no cEPI closure (> 300 seconds). No closure was associated with aspirin use (two donors) or chocolate consumption (two donors) before donation. Two donors (8%) had either a shortened cEPI or cADP closure time. Conclusions Platelet dysfunction in qualified blood donors is underestimated. Platelet function screening can identify donors with diet-related platelet dysfunction or with poor recollection of aspirin use.

The objective of our study was to evaluate the performance characteristics of a new automated d-dimer, the Advanced D-Dimer (Dade Behring Inc., Deerfield, IL) for use in the diagnosis of venous thromboembolism (VTE). To do this we compared the Advanced D-Dimer to existing d-dimer methods using established target cut-off values in patients suspected of VTE who were to undergo definitive radiographic studies for VTE. We studied hospitalized patients and outpatients who were suspected of having VTE and who had whole blood d-dimer performed. The patients who underwent a diagnostic study for VTE had their D-dimer results used to determine sensitivity, specificity and negative predictive values. There was relatively poor correlation between the Advanced D-Dimer and D-Dimer Gold (r = 0.63; t-test: P < 0.005) and Asserachrome D-Di (r = 0.58; t-test: P < 0.005). The Advanced D-Dimer target cutoff values for excluding VTE in hospitalized and outpatients were < or = 1800 microg/L and < or = 1500 microg/l respectively. There were 139 patients suspected with pulmonary embolism (PE) and 328 evaluated for deep vein thrombosis (DVT). There were 24 patients with PE, and 43 with DVT. The Advanced D-Dimer had comparable sensitivity, specificity and negative predictive values (96, 43, 98% for PE and 96, 48, 99% for DVT respectively) to other d-dimer methods used for that purpose. We conclude that the Advanced D-Dimer correlates relatively poorly with enzyme-linked immunosorbent assay methods. This poor correlation is likely due to incorrect reporting units and concentration. When these factors are corrected correlations improved. Compared to existing d-dimer methods used for VTE exclusion, the high sensitivity and negative predictive value would suggest that this method can be used as part of a diagnostic algorithm for the exclusion of PE and DVT.

Three patients with schizophrenia-like psychosis and two with schizoaffective-like psychosis who experienced cerebral trauma before the onset of their illness underwent clinical and magnetic resonance imaging evaluation. Each patient with a schizophrenia-like psychosis, but neither of those with a schizoaffective-like psychosis, showed abnormalities confined to or including the left temporal lobe. These observations complement recent findings in schizophrenia.

Background: We have advocated the use of a D-dimer assay to exclude the diagnosis of pulmonary embolism (PE) and deep venous thrombosis (DVT) in surgical and trauma patients suspected of having these diagnoses. Injury is known to increase D-dimer levels independent of thromboembolism. The purpose of this study was to assess the period after injury over which the D-dimer assay remains positive because of injury exclusive of thromboembolism. Methods: We prospectively sampled the plasma of severely injured patients for D-dimer using an enzyme-linked immunosorbent assay method at admission; at hours 8, 16, 24, and 48; and at days 3, 4, 5, and 6. Patients were then screened for DVT with a routine duplex Doppler at day 7. Patients were followed for PE, adult respiratory distress syndrome, and disseminated intravascular coagulation. Results: One hundred fifty-four patients (mean Injury Severity Score of 23) underwent a total of 1,230 D-dimer assays. Twenty-six (17%) had thromboembolism. Nine (6%) patients developed DVT, 2 (1%) developed PE, 13 (8%) developed disseminated intravascular coagulation, and 11 (7%) developed severe adult respiratory distress syndrome. None of the trauma patients with thromboembolism had a (false) negative D-dimer at or after the time of their thromboembolic complication. True-negative D-dimer results as a function of time from injury are: 0 hours, 18%; 8 hours, 16%; 16 hours, 17%; 24 hours, 22%; 48 hours, 37%; day 3, 34%; day 4, 32%; day 5, 30%; and day 6, 30%. The negative predictive value of the assay was 100%. D-dimer levels were significantly higher in those who developed a thromboembolic complication than in those who did not (independent of Injury severity Score). Conclusion: These data serve to validate D-dimer as a means of excluding thromboembolism, specifically in patients with severe injury (100% negative predictive value). Before 48 hours after injury, however, the vast majority of these patients without thromboembolism had positive D-dimer assays. Because of the high false-positive rate early after severe injury, the D-dimer assay may be of little value before postinjury hour 48.

Background. Although it is well recognized that individuals with schizophrenia display evidence of subtle neurological impairment, its aetiopathological and clinical significance continues to be unclear.Methods. Patients presenting with a first episode of schizophrenia or schizophreniform psychosis (DSM-IV criteria) were examined using two previously validated neurological examinations. The majority (N = 35) were examined prior to their ‘first ever’ dose of neuroleptic while the remaining patients (N = 21) had been medicated for less than one month. The manner in which neurological functioning is influenced by symptomatology and handedness was ascertained.Results. The majority of patients who were examined neuroleptic-naive displayed evidence of neurodysfunction. A combination of relative hand preference and symptomatology explained a significant proportion of the variance in neurological functioning. Mixed handedness among adults at the time of first presentation with schizophrenia was associated with more severe neurological impairment and a history of poorer scholastic attainment and pre-morbid social adjustment.Conclusions. Neurological soft signs are an intrinsic part of schizophrenia rather than a direct consequence of treatment. Early developmental processes are associated with the level of subsequent neurological impairment in first episode schizophrenia. However, symptomatology appears to have an influence on the apparent severity of neurological impairment.

To estimate the prevalence, and identify the clinical correlates of comorbid substance misuse (abuse or dependence) among readmissions with schizophrenia, particularly to establish whether comorbid substance misuse is associated with higher rates of depressive symptoms and suicidal ideation.Over 12 months, consecutive readmissions from a catchment area psychiatric service with DSM-IV schizophrenia/schizoaffective disorder were assessed using clinical assessments of symptomatology including depression, insight and compliance. Comorbid substance misuse was diagnosed using DSM-IV criteria.Of 102 readmissions 40% had lifetime, while 20% had current comorbid substance misuse and were predominately young males. Comorbid substance misuse had no statistically significant impact on positive, negative or depressive symptomatology. However, those currently misusing substances reported more suicidal ideation compared with past or non-substance misusers.Readmissions with comorbid substance misuse were more likely to report suicidal ideation, and may represent a group of individuals who are at higher risk of suicide.

The somatostatin analogue octreotide (Sandostatin, Novartis, Basie) significantly improves the syndromes suffered by most patients with neuroendocrine tumours (NETs). The use of [111In-DTPA-D-Phe1]-octreotide scintigraphy ([111In]-pentetreotide) to predict the response to octreotide treatment has been described. Short-term hormone inhibition by a single injection of octreotide has also been reported. This study aimed to compare the effects of the suppression test with the response to long-term somatostatin analogue treatment, and to seek a correlation between the short-term suppression test, [11In]-pentetreotide observations and long-term somatostatin analogue treatment.Short octreotide suppression test and octreotide scintigraphy. Blood samples were collected before (0900, 0930 h), at (1000 h), and after (1030, 1100, 1200, 1300 h) the injection of 50 micrograms octreotide subcutaneously. Plasma hormones relevant to the syndrome were analysed by radioimmunoassay. The short suppression effects, the [111In]-pentetreotide observations and the response to long-term treatment with somatostatin analogue were evaluated and compared.Twenty-six patients with metastatic NETs were evaluated, including 14 carcinoid tumours, 10 pancreatic endocrine tumours and 2 medullary carcinomas of thyroid (MCTs). Twelve patients had received octreotide treatment before the study, another 4 patients were treated subsequently with somatostatin analogue.During the short suppression test, hormones relevant to the syndromes were suppressed in 24 patients (those with carcinoids and pancreatic endocrine tumours). There was no suppression in the 2 patients with MCT. [111In]-pentetreotide observations closely correlated with the short suppression response to octreotide. Fourteen patients were treated with somatostatin analogue, and responded clinically; they had a positive short inhibition test and positive tumour uptake. Two patients with MCT did not respond to the treatment and had a negative suppression test and a negative [111In]-pentetreotide.Our results suggest that a consistent relationship exists between the short suppression test and the response to somatostatin analogue treatment in the majority of the patients with neuroendocrine tumours. The octreotide suppression test and octreotide scintigraphy together will be helpful in selecting appropriate patients for clinical treatment with somatostatin analogues.

We document the occurrence of a solitary extramedullary plasmacytoma (SEP) in a cardiac transplant patient. The diagnosis of plasma cell malignancy was confirmed by histopathologic and immunohistochemical examination of a nodular skin lesion. A complete systemic evaluation showed no evidence of metastatic disease. The patient was treated locally with radiation therapy (RT), but disseminated multiple myeloma developed 4 months after diagnosis. A variety of tumors have been reported to develop in the cardiac or renal transplant recipient, although plasma cell malignancies are rare. To our knowledge, this is the first reported case of an SEP in an organ transplant recipient.

Background. Evidence suggests that schizophrenia may be a disorder with origins in early intrauterine mal-development. We have constructed a comprehensive anthropometric scale for the evaluation of dysmorphic features as an index of the nature and timing of developmental disturbance.Method. A detailed set of craniofacial and bodily measures was compiled and applied to 174 patients with schizophrenia and 80 matched control subjects.Results. Patients had significantly higher scores on this scale and displayed multiple anomalies of the craniofacial region with an overall narrowing and elongation of the mid-face and lower face. Twelve craniofacial anomalies independently distinguished patients from controls and these variables correctly classified 95% of patients and 80% of control subjects.Conclusions. This new scale, while procedurally more exacting than the Waldrop scale, more clearly defines the topography of anomalies previously suspected in individuals with schizophrenia. These findings constitute direct evidence for disturbed craniofacial development in schizophrenia and indicate origins in the foetal period during which the characteristic human facial pattern evolves in close association with brain differentiation.

This study was designed to evaluate dosimetric, pharmacokinetic, and other treatment-related parameters as predictors of outcome in patients with advanced B-lymphocytic malignancies. Fifty-seven patients were treated with radiolabeled Lym-1 antibody in early phase trials between 1985 and 1994. Logistic regression and proportional hazards models were used to evaluate treatment parameters for their ability to predict outcome, taking into account patient risk group based on Karnofsky performance status and serum lactic dehydrogenase. The occurrence of a partial or complete response (31 of 57 patients) and development of human antimouse antibody (HAMA) predicted improved survival using a time-dependent proportional hazards model. The final multivariate model for survival with parameters significant at P/= 0.05 included overall response and pretreatment risk group. Although some of the dosimetric and pharmacokinetic parameters were predictive in univariate analyses, only longer half-time of radionuclide in the blood showed any indication of improved prediction beyond that provided by the lactic dehydrogenase/Karnofsky performance status-based risk groups. Splenic volume, splenectomy, and malignant tissue Lym-1 reactivity were not contributory. In this patient group, the effect of radiolabeled Lym-1 treatment as indicated by measurable tumor response was associated with improved survival. Development of HAMA was also associated with improved survival, indicating that concern about HAMA should not preclude exploration of radioimmunotherapy. Although dosimetry has a role in determining safety based on dose to normal organs, when adjusted for baseline clinical features, dosimetric and pharmacokinetic parameters showed limited ability to improve outcome prediction.

The Ann Arbor staging classification has proven less useful in nonHodgkin's lymphoma, because this malignancy is inherently a multifocal disorder. Since 1985, 57 adult patients with advanced B-lymphocytic malignancies that progressed despite standard therapy entered into one of three different therapy trials using radiolabeled Lym-1 antibody. Tumor regression in 31 (54%) of these patients fulfilled conventional requirements for an oncological response to the therapy. To define the role of radioimmunotherapy in B-lymphocytic malignancies better and to find opportunities for improving its therapeutic efficacy, the records of these patients were reviewed to assess the significance of various parameters as prognostic indicators. Twenty-one pretherapy characteristics were evaluated, including age at diagnosis, age at study entry, sex, Karnofsky performance status, prior chemotherapy and radiation therapy, interval since diagnosis, histology, constitutional B symptoms, extranodal malignancy (excluding marrow), bone marrow malignancy, tumor bulk, and circulating malignant cells; blood tests included lymphocyte, granulocyte, platelet, hematocrit, serum lactate dehydrogenase (LDH), interleukin 2 receptor, and human antimouse antibody levels. In the multivariate analysis, LDH and Karnofsky performance status were the parameters that best predicted survival, complete and partial remission, and time to progression; interleukin 2 receptor and LDH best predicted complete remission. These prognostic factors for radioimmunotherapy outcome are consistent with the pretherapy characteristics observed to be significant for chemotherapy.

Two groups of rats were fed liquid diets containing 35% of energy as fat and either 36 or 26% of energy as alcohol to examine the effect of fat and energy intake on alcoholic fatty liver production. After 4 wk, five rats in each group were killed for analysis of liver triglyceride concentration, and then the alcohol diets fed to remaining rats were switched. All remaining rats were killed for hepatic triglyceride determination after another 4 wk. Rats initially fed the 36% alcohol diet or those switched to this diet ingested less energy, exhibited alcoholemia and slow growth, and developed fatty livers. Rats initially fed the 26% alcohol diet or those switched to this diet ingested significantly more energy, high amounts of alcohol and fat, exhibited low alcoholemia and faster growth than when they were fed the 36% alcohol diet. Fatty liver was absent in rats fed the 26% alcohol diet but was induced when they were fed the 36% alcohol diet. Fatty liver in rats initially fed the 36% alcohol diet regressed completely when the rats were switched to the 26% alcohol diet. Additional studies employing 36% alcohol diets containing 35% of energy as fat, derived from either corn oil or olive oil, revealed that unsaturated fat and not specifically linoleate plays a role in the induction of fatty liver. Thus, nutritional factors regulate the induction or regression of fatty liver and alcoholemia in alcoholic rats.

Objective The purpose of this study was to determine whether a customized standard of large-for-gestational age (LGA) identifies pregnancies with increased perinatal risk. Study Design We evaluated 7510 estimates of fetal weight to generate a fetal growth curve. Next, we analyzed the gestational age at delivery, physiologic and pathological variables from 5072 pregnancies to predict birthweight, and calculated a customized ideal birthweight and cutoff for LGA. In a separate analysis of 32,271 pregnancies, rates of macrosomia-related adverse outcomes were compared in pregnancies that had been identified as LGA by a customized standard (LGA cust ) and those pregnancies that had been identified as LGA or macrosomic by conventional standards. Results LGA cust pregnancies carried increased risk of shoulder dystocia, third- or fourth-degree laceration, and cephalopelvic disproportion. LGA cust pregnancies that did not meet conventional criteria for LGA/macrosomia were at increased risk of all measured outcomes. Conclusion A customized standard of LGA identifies a previously unrecognized population that is at increased risk of perinatal morbidity.

The literature on the putative association between cognitive dysfunction in schizophrenia and the presence of tardive dyskinesia is critically reviewed, focusing on potential artifacts and specific relationships to a particular topography of involuntary movements. These issues are exemplified via a study of cognitive function in 64 schizophrenic patients, in which impaired cognitive flexibility was identified as the primary measure distinguishing those with tardive orofacial dyskinesia. The significance of such an association with cognitive dysfunction is considered in relation to competing hypotheses of organic vulnerability to vs. state marker for this movement disorder.

Hypothesis: Early introduction of a full-day human factors training experience into the surgical clerkship curriculum will teach effective communication skills and strategies to gain professional satisfaction from a career in surgery. Design: In pilot 1, which took place between July 1, 2007, and December 31, 2008, 50 students received training and 50 did not; all received testing at the end of the rotation for comparison of control vs intervention group performance. In pilot 2, a total of 50 students were trained and received testing before and after rotation to examine individual change over time. Setting: University of Massachusetts Medical School. Participants: A total of 148 third-year medical students in required 12-week surgical clerkship rotations. Interventions: Full-day training with lecture and small-group exercises, cotaught by surgeons and educators, with focus on empathetic communication, time management, and teamwork skills. Main Outcome Measures: Empathetic communication skill, teamwork, and patient safety attitudes and self-reported use of time management strategies. Results: Empathy scores were not higher for trained vs untrained groups in pilot 1 but improved from 2.32 to 3.45 on a 5-point scale (P < .001) in pilot 2. Students also were more likely to ask for the nurse's perspective and to seek agreement on an action plan after team communication training (pilot 1, f=7.52, P=.007; pilot 2, t= 2.65, P=.01). Results were mixed for work-life balance, with some trained groups scoring significantly lower than untrained groups in pilot 1 and no significant improvement shown in pilot 2. Conclusions: The significant increase in student-patient communication scores suggests that a brief focused presentation followed by simulation of difficult patient encounters can be successful. A video demonstration can improve interdisciplinary teamwork.

A susceptibility locus for schizophrenia in the ‘pseudo-autosomal’ region has been proposed on the basis of the reported excess of sex-chromosome aneuploidies (e.g. XXY and XXX) among patients with schizophrenia and the finding that schizophrenic sib-pairs are more often of the same than of the opposite sex. This hypothesis has been tested in 83 sibships with two or more siblings fulfilling Research Diagnostic Criteria for schizophrenia or schizoaffective disorder. Alleles at the pseudo-autosomal telomeric locus DXYS14, which is unlinked with sex, were analysed using the method of affected sib-pairs. Affected sibs shared alleles at DXYS14 more frequently than expected by random Mendelian assortment, supporting genetic linkage between DXYS14 and schizophrenia.

SYNOPSISThe significance of the excess of obstetric complications which appears to characterize the histories of schizophrenic patients is critically dependent on the validity of the source of obstetric information, especially when this is obtained by maternal recall. Twenty-one biological mothers of 17 schizophrenic and four other patients were interviewed for their recollections of individual events characterizing the pregnancy and delivery relating to each patient. These were then compared with those events documented in maternity hospital records. Only in two of the 21 instances (9·5%) were inconsistencies of detail apparent which would have affected the designation of the relevant patient as having, or as not having, experienced major obstetric complication(s). It is concluded that maternal recall can be a surprisingly accurate source of obstetric information in relation to research on schizophrenia.

Earlier studies showed that the fatty liver, caused by feeding rats the Lieber-DeCarli alcohol diet for four weeks, was prevented if the diet was supplemented with dihydroxyacetone (22 g/l), pyruvate (22 g/l) and riboflavin (2.2 g/l). In the present study, we observed that fatty liver was prevented if the alcohol diet was supplemented with glycerol and lactate (22 g/l each) and riboflavin (2.2 g/l). Hence, the prevention of alcoholic fatty liver by the dietary supplementation with dihydroxyacetone and pyruvate may not be related to their capacity to serve as hydrogen acceptors and to oxidize NADH produced during ethanol metabolism. When rats were fed the alcohol diet supplemented with either glycerol or pyruvate, the hepatic triglyceride (TG) levels were similar to those in rats pair-fed a Lieber-DeCarli control diet in which alcohol was replaced with an isocaloric amount of dextrins. Therefore, the prevention of fatty liver does not require the simultaneous presence of several supplements. Dietary dihydroxyacetone or riboflavin did not reduce alcoholic fatty liver. Supplementation of the ethanol diet with isocaloric amounts of lactate or glucose, instead of pyruvate, did not abolish the development of fatty liver but caused a marked reduction in the hepatic TG levels. Animals fed the alcohol diet consumed only small amounts of carbohydrate for long periods of time. Since the inclusion of glucose or its metabolites in the alcohol diet fed to rats caused a marked decrease in the liver TG content, it is likely that the production or prevention of fatty liver is related to carbohydrate metabolism.

Male Sprague-Dawley rats were fed for 8 weeks a corn oil (CO) diet or a hydrogenated coconut oil (HCNO) diet. These diets were fed in the absence or presence of eicosa-5,8,11,14-tetraynoic acid (TYA). The inclusion of TYA in the HCNO diet reduced the levels of 12:0 and 14:0 in the total fatty acids of livers and plasma. With either diet, the presence of TYA caused an alteration in the fatty acid composition of these tissues so as to reduce the values of the ratios: 16:1/16:0, 18:1/18:0. and 20:4/18:2. These results suggest that dietary TYA can influence the hepatic metabolism of medium chain fatty acids and that it may inhibit the desaturase enzyme involved in the synthesis of not only 20:4 but also of monoenoic fatty acids.

An iron-deficient diet containing no fat (FF-Fe) or containing either 14% hydrogenated coconut oil (HCNO-Fe) or 14% corn oil (CO-Fe) was fed to separate groups of rats for 10 weeks. In the control group, the corresponding iron-supplemented diets were fed FF+Fe, HCNO+Fe, CO+Fe. When rats were fed iron-deficient diets, their plasma lecithin cholesterol acyl transferase (LCAT) activity was significantly reduced as compared to controls. Their plasma also contained releatively more cholesteryl esters (CE) than free cholesterol (CH). In rats fed FF+Fe and CO+Fe diets, plasma contained similar levels of CE and CH. In those fed HCNO+Fe diet, plasma had 40% less Ce than CH. Red cell CH content was significantly greater in the CO-Fe group. Iron deficiency, as indicated by low blood hemoglobin (Hb) and hematocrit (Hct) values, was also observed only in this group. The triglyceride and phospholipid contents of plasma in rats fed iron-deficient diets were significantly lower than of those in the control groups. Thus, changes in LCAT activity and CE/CH ratio in plasma showed the effect of iron-deficient diet consumption even before the blood Hb and Hct levels were reduced.

Blood alcohol levels (BAL) were maintained at high levels (overall mean +/- S.D. achieved in 14 alcoholic rats was 216.0 +/- 120.1 mg%) in male Wistar rats for 15 to 85 days by continuous intragastric infusion of ethanol and nutritionally defined low fat liquid diet. The ethanol intake was progressively increased from 32% of total calories up to 41.4% in order to maintain high BAL. Pair-fed animals received isocaloric glucose solution and the liquid diet. Despite the low level of dietary fat (4.9% of total calories), histopathological evaluation of the liver revealed severe and progressive fatty infiltration in the alcoholic rats. In addition, following 30 days of intoxication, one third of the animals showed focal necrosis with mononuclear cell infiltration in centrilobular areas of the livers. This was correlated with the markedly elevated levels of SGOT and SGPT in these animals. Pair-fed controls showed no abnormality in the morphology of liver or blood chemistry. Chemical quantitation of liver triglycerides confirmed the histological observation, with triglyceride levels of 61.51 +/- 16.45 and 89.61 +/- 5.94 mg per gm at 30 and 85 days, respectively. Most importantly, the degree of steatosis was tightly and significantly correlated with the mean BAL achieved (r = 0.80, p less than 0.001). These data represent the first confirmation of the hypothesis that continuously high BAL correlate with the severity of alcohol-induced liver pathology.

Male Sprague-Dawley rats were fed, ad libitum for 30 days, a fat-free (FF) liquid diet containing 34% of the calories as ethanol or a control FF diet in which alcohol was replaced by an isocaloric amount of dextrins. The cytosolic fatty acid synthetase and the microsomal stearoyl-CoA desaturase activities in the livers of rats fed the alcohol diet were about half of those observed in the livers of control rats. The conclusion is that chronic ethanol consumption depresses the activities of these lipogenic enzymes in the liver.

Carbohydrate consumption regulates pancreatic amylase synthesis in rats. The Lieber-DeCarli 36% alcohol diet employed in chronic alcohol studies and the isocaloric control diet contain 11 and 47% of total calories from carbohydrates, respectively. Young rats fed ad libitum the 36% ethanol diet for 2 weeks obtained 1.2 g/day of carbohydrate, whereas those pair-fed with control diet received 5.8 g/day. Rats fed the 36% ethanol diet and given an intramuscular injection of a solution of 1.5 g of glucose daily for 2 weeks received twofold greater amounts of carbohydrate than saline-injected controls (2.7 versus 1.2 g). These changes in carbohydrate intake produced proportionate changes in pancreatic amylase levels. The secretory responses to cholecystokinin-octapeptide (CCK8) of acini from control and glucose-injected rats were significantly higher compared with those in the saline-injected or noninjected alcohol groups. The blood alcohol levels in glucose-injected rats were markedly reduced compared with other alcohol groups (71.7 versus 274.9 mg/dl) despite similar amounts of ethanol ingestion daily (2.4 g) in the three groups. In vitro experiments with acini from rats fed a nutritionally optimal diet revealed that high pharmacologic concentrations of ethanol, while inducing basal secretion, inhibited CCK8-stimulated amylase secretion. These results indicate that: (a) the amount of alcohol consumption does not correlate with either the levels of blood alcohol or of pancreatic amylase; (b) the carbohydrate availability in rats regulates pancreatic amylase levels despite significant levels of alcohol in blood; (c) blood alcohol levels observed in vivo may not affect synthetic and secretory processes of amylase in pancreatic acini.