Showing papers by "David Spiegel published in 2013"

A systematic review of PTSD prevalence and trajectories in DSM-5 defined trauma exposed populations: intentional and non-intentional traumatic events.

Abstract: Objective We conducted a systematic review of the literature to explore the longitudinal course of PTSD in DSM-5-defined trauma exposed populations to identify the course of illness and recovery for individuals and populations experiencing PTSD. Methods We reviewed the published literature from January 1, 1998 to December 31, 2010 for longitudinal studies of directly exposed trauma populations in order to: (1) review rates of PTSD in the first year after a traumatic event; (2) examine potential types of proposed DSM-5 direct trauma exposure (intentional and non-intentional); and (3) identify the clinical course of PTSD (early onset, later onset, chronicity, remission, and resilience). Of the 2537 identified articles, 58 articles representing 35 unique subject populations met the proposed DSM-5 criteria for experiencing a traumatic event, and assessed PTSD at two or more time points within 12 months of the traumatic event. Results The mean prevalence of PTSD across all studies decreases from 28.8% (range = 3.1–87.5%) at 1 month to 17.0% (range = 0.6–43.8%) at 12 months. However, when traumatic events are classified into intentional and non-intentional, the median prevalences trend down for the non-intentional trauma exposed populations, while the median prevalences in the intentional trauma category steadily increase from 11.8% to 23.3%. Across five studies with sufficient data, 37.1% of those exposed to intentional trauma develop PTSD. Among those with PTSD, about one third (34.8%) remit after 3 months. Nearly 40% of those with PTSD (39.1%) have a chronic course, and only a very small fraction (3.5%) of new PTSD cases appears after three months. Conclusions Understanding the trajectories of PTSD over time, and how it may vary by type of traumatic event (intentional vs. non-intentional) will assist public health planning and treatment.

A comprehensive mathematical model for three-body binding equilibria.

Abstract: Three-component systems are often more complex than their two-component counterparts. Although the reversible association of three components in solution is critical for a vast array of chemical and biological processes, no general physical picture of such systems has emerged. Here we have developed a general, comprehensive framework for understanding ternary complex equilibria, which relates directly to familiar concepts such as EC50 and IC50 from simpler (binary complex) equilibria. Importantly, application of our model to data from the published literature has enabled us to achieve new insights into complex systems ranging from coagulation to therapeutic dosing regimens for monoclonal antibodies. We also provide an Excel spreadsheet to assist readers in both conceptualizing and applying our models. Overall, our analysis has the potential to render complex three-component systems—which have previously been characterized as “analytically intractable”—readily comprehensible to theoreticians and experiment...

Diurnal cortisol rhythm as a predictor of lung cancer survival

Abstract: Background Poorly coordinated diurnal cortisol and circadian rest-activity rhythms predict earlier mortality in metastatic breast and colorectal cancer, respectively. We examined the prognostic value of the diurnal cortisol rhythm in lung cancer. Methods Lung cancer patients (n = 62, 34 female) were within 5 years of diagnosis and had primarily non small-cell lung cancer, with disease stage ranging from early to advanced. Saliva collected over two days allowed calculation of the diurnal cortisol slope and the cortisol awakening response (CAR). Lymphocyte numbers and subsets were measured by flow cytometry. Survival data were obtained for 57 patients. Cox Proportional Hazards analyses were used to test the prognostic value of the diurnal cortisol rhythm on survival calculated both from study entry and from initial diagnosis. Results The diurnal cortisol slope predicted subsequent survival over three years. Early mortality occurred among patients with higher slopes, or relatively “flat” rhythms indicating lack of normal diurnal variation (Cox Proportional Hazards p = .009). Cortisol slope also predicted survival time from initial diagnosis (p = .012). Flattened profiles were linked with male gender (t = 2.04, df = 59, p = .046) and low total and cytotoxic T cell lymphocyte counts (r = −.39 and −.30, p = .004 and .035, respectively). After adjustment for possible confounding factors, diurnal slope remained a significant, independent predictor of survival. Conclusions Flattening of the diurnal cortisol rhythm predicts early lung cancer death. Data contribute to growing evidence that circadian disruption accelerates tumor progression.

A “Turn-On” Fluorescent Sensor for Methylglyoxal

Abstract: Methylglyoxal (MGO), a dicarbonyl metabolite produced by all living cells, has been associated with a number of human diseases. However, studies of the role(s) MGO plays biologically have been handicapped by a lack of direct methods for its monitoring and detection. To address this limitation, we have developed a fluorescent sensor (methyl diaminobenzene-BODIPY, or "MBo") that can detect MGO under physiological conditions. We show that MBo is selective for MGO over other biologically relevant dicarbonyls and is suitable for detecting MGO in complex environments, including that of living cells. In addition, we demonstrate MBo's utility in estimating plasma concentrations of MGO. The results reported herein have the potential to advance both clinical and basic science research and practice.

Dissociative disorders in DSM-5.

Abstract: The rationale, research literature, and proposed changes to the dissociative disorders and conversion disorder in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) are presented. Dissociative identity disorder will include reference to possession as well as identity fragmentation, to make the disorder more applicable to culturally diverse situations. Dissociative amnesia will include dissociative fugue as a subtype, since fugue is a rare disorder that always involves amnesia but does not always include confused wandering or loss of personality identity. Depersonalization disorder will include derealization as well, since the two often co-occur. A dissociative subtype of posttraumatic stress disorder (PTSD), defined by the presence of depersonalization or derealization in addition to other PTSD symptoms, is being recommended, based upon new epidemiological and neuroimaging evidence linking it to an early life history of adversity and a combination of frontal activation and limbic inhibition. Conversion disorder (functional neurological symptom disorder) will likely remain with the somatic symptom disorders, despite considerable dissociative comorbidity.

Adjunctive vancomycin powder in pediatric spine surgery is safe.

Abstract: STUDY DESIGN Therapeutic level II cohort study. OBJECTIVE To evaluate the safety of adjunctive local application of vancomycin powder (VP) for infection prophylaxis in posterior instrumented thoracic and lumbar spine wounds in pediatric patients weighing more than 25 kg. SUMMARY OF BACKGROUND DATA Spine surgeons have largely turned to vancomycin prophylaxis in an attempt to decrease the incidence of late surgical site infection and acute surgical site infection from methicillin-resistant Staphylococcus aureus. In adult patients, the adjunctive local application of VP with an intravenous cephalosporin has been shown to decrease postsurgical wound infection rates significantly; however, the safety of VP as an adjunct in pediatric spine surgery has not been reported. METHODS We reviewed data collected under a systematic protocol specifically designed to monitor the safety profile of VP. We measured changes in creatinine and systemic vancomycin levels after intrawound application of 500 mg of unreconstituted VP during spine deformity correction surgery in patients weighing more than 25 kg (patients also received routine intravenous cephalosporin prophylaxis). Laboratory values were measured preoperatively and on postoperative days 1 and 4. Any adverse reactions and infections through available follow-up (2-8 mo) were recorded. RESULTS Eighty-seven consecutive pediatric patients with spinal deformity weighing more than 25 kg who received intraoperative VP during a 9-month period were identified. Sixty-three percent of the patients in this series had adolescent idiopathic scoliosis, 15% congenital scoliosis, 15% neuromuscular scoliosis, and 5% spondylolisthesis. The average change in creatinine levels between the preoperative and postoperative day 1 draw was -0.03 and between the preoperative and postoperative day 4 draw was -0.075. The postoperative systemic vancomycin levels remained undetectable. None of the patients experienced nephrotoxicity or red man syndrome. Three of the 87 patients developed a surgical site infection. CONCLUSION In this cohort there were no clinically significant changes in creatinine level or systemic vancomycin level caused by use of intraoperative VP. LEVEL OF EVIDENCE 2.

Using the Science of Psychosocial Care to Implement the New American College of Surgeons Commission on Cancer Distress Screening Standard

Abstract: The American College of Surgeons (ACoS) Commission on Cancer (CoC) has advanced a new patient-centered accreditation standard requiring programs to implement psychosocial distress screening and referral for psychosocial care. The field of psychosocial oncology has advocated for routine distress screening as an integral component of quality cancer care since the NCCN Distress Management Panel first recommended this practice in 1999. Accreditation standards have a significant impact on practice patterns and quality of care. The new ACoS CoC Psychosocial Distress Screening Standard provides a unique opportunity to integrate the science of psychosocial care into clinical practice. National organizations, including the American Psychosocial Oncology Society, the Association of Oncology Social Work, the Cancer Support Community, and LIVESTRONG, can offer valuable guidance and resources. This article reviews ACoS CoC requirements, highlighting key research findings and providing practical considerations to guide programs with implementation. Although screening for distress encompasses many domains, this article reviews the evidence linking depression-one aspect of distress-and cancer outcomes to highlight the profound influence psychosocial care delivery can have on promoting medical outcomes and quality cancer survivorship. The authors describe distress screening program accomplishments at Northwestern University, including the electronic administration of NIH Patient Reported Outcomes Measurement Information System computerized adaptive testing item banks. Electronic medical record integration facilitates real-time scoring, interpretation, provider notification, and triage for psychosocial care. Roughly one-third of patients have requested assistance with psychosocial needs. As ACoS CoC programs implement psychosocial distress screening and management, the emerging field of implementation science can guide future clinical program developments and research priorities.

Vancomycin Prophylaxis of Surgical Site Infection in Clean Orthopedic Surgery

Abstract: Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as a public health concern since the mid-1990s. Because of the increase in reports of this pathogen, it has become increasingly tempting for clinicians to provide prophylaxis against this entity using antibiotics known to be effective against MRSA. The goal of this study was to assess the use of MRSA prophylaxis to determine whether it is safe and effective. A systematic search of the literature was performed to identify articles that examined the use of vancomycin in clean orthopedic surgery. Infection rates and adverse events were extracted, and the data were aggregated and analyzed using a DerSimonian and Laird random effects model. Publication bias and study quality were also assessed. No benefit of parenteral administration of vancomycin was identified. Local, vancomycin-impregnated cement and powder are associated with lower infection rates. Few adverse events occurred, and most of those that occurred involved infusion rate.Cost, resistance, and side effects are concerns in using vancomycin therapy in addition to standard antibiotic prophylaxis. Given the lack of efficacy of intravenous vancomycin, the authors do not recommend its routine use in clean orthopedic surgery. However, local administration appears to be safe and effective. The data are most compelling in orthopedic spine surgery in which a patient without prophylaxis is more than 4 times as likely to have a deep postoperative wound infection compared with a patient who received local vancomycin. The authors recommend the use of local antibiotics when possible in clean orthopedic surgery.

Exploring Binding and Effector Functions of Natural Human Antibodies Using Synthetic Immunomodulators

Abstract: The ability to profile the prevalence and functional activity of endogenous antibodies is of vast clinical and diagnostic importance. Serum antibodies are an important class of biomarkers and are also crucial elements of immune responses elicited by natural disease-causing agents as well as vaccines. In particular, materials for manipulating and/or enhancing immune responses toward disease-causing cells or viruses have exhibited significant promise for therapeutic applications. Antibody-recruiting molecules (ARMs), bifunctional organic molecules that redirect endogenous antibodies to pathological targets, thereby increasing their recognition and clearance by the immune system, have proven particularly interesting. Notably, although ARMs capable of hijacking antibodies against oligosaccharides and electron-poor aromatics have proven efficacious, systematic comparisons of the prevalence and effectiveness of natural anti-hapten antibody populations have not appeared in the literature. Herein we report head-t...

Do oblique views add value in the diagnosis of spondylolysis in adolescents

Abstract: Background: Anteroposterior, lateral, and right and left oblique lumbar spine radiographs are often a standard part of the evaluation of children who are clinically suspected of having spondylolysis. Recent concerns regarding radiation exposure and costs have brought the value of oblique radiographs into question. The purpose of the present study was to determine the diagnostic value of oblique views in the diagnosis of spondylolysis. Methods: Radiographs of fifty adolescents with L5 spondylolysis without spondylolisthesis and fifty controls were retrospectively reviewed. All controls were confirmed not to have spondylolysis on the basis of computed tomographic scanning, magnetic resonance imaging, or bone scanning. Anteroposterior, lateral, and right and left oblique radiographs of the lumbar spine were arranged into two sets of slides: one showing four views (anteroposterior, lateral, right oblique, and left oblique) and one showing two views (anteroposterior and lateral only). The slides were randomly presented to four pediatric spine surgeons for diagnosis, with four-view slides being presented first, followed by two-view slides. The slides for twenty random patients were later reanalyzed in order to calculate of intra-rater agreement. A power analysis demonstrated that this study was adequately powered. Inter-rater and intra-rater agreement were assessed on the basis of the percentage of overall agreement and intraclass correlation coefficients (ICCs). PCXMC software was used to generate effective radiation doses. Study charges were determined from radiology billing data. Results: There was no significant difference in sensitivity and specificity between four-view and two-view radiographs in the diagnosis of spondylolysis. The sensitivity was 0.59 for two-view studies and 0.53 for four-view studies (p = 0.33). The specificity was 0.96 for two-view studies and 0.94 for four-view studies (p = 0.60). Inter-rater agreement, intra-rater agreement, and agreement with gold-standard ICC values were in the moderate range and also demonstrated no significant differences. Percent overall agreement was 78% for four-view studies and 82% for two-view studies. The radiation effective dose was 1.26 mSv for four-view studies and 0.72 mSv for two-view studies (difference, 0.54 mSv). The charge for four-view studies was $145 more than that for two-view studies. Conclusions: There is no difference in sensitivity and specificity between four-view and two-view studies. Although oblique views have long been considered standard practice by some, our data could not identify a diagnostic benefit that might outweigh the additional cost and radiation exposure. Level of Evidence: Diagnostic Level I. See Instructions for Authors for a complete description of levels of evidence.

The Ponseti method in the treatment of children with idiopathic clubfoot presenting between five and ten years of age

Abstract: Our goal was to evaluate the use of Ponseti's method, with minor adaptations, in the treatment of idiopathic clubfeet presenting in children between five and ten years of age. A retrospective review was performed in 36 children (55 feet) with a mean age of 7.4 years (5 to 10), supplemented by digital images and video recordings of gait. There were 19 males and 17 females. The mean follow-up was 31.5 months (24 to 40). The mean number of casts was 9.5 (6 to 11), and all children required surgery, including a percutaneous tenotomy or open tendo Achillis lengthening (49%), posterior release (34.5%), posterior medial soft-tissue release (14.5%), or soft-tissue release combined with an osteotomy (2%). The mean dorsiflexion of the ankle was 9° (0° to 15°). Forefoot alignment was neutral in 28 feet (51%) or adducted ( 10° in seven feet (13%). Hindfoot alignment was neutral or mild valgus in 26 feet (47%), mild varus ( 10°) in ten feet (18%). Heel-toe gait was present in 38 feet (86%), and 12 (28%) exhibited weight-bearing on the lateral border (out of a total of 44 feet with gait videos available for analysis). Overt relapse was identified in nine feet (16%, six children). The parents of 27 children (75%) were completely satisfied. A plantigrade foot was achieved in 46 feet (84%) without an extensive soft-tissue release or bony procedure, although under-correction was common, and longer-term follow-up will be required to assess the outcome.

Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer.

Abstract: BACKGROUND: Chemotherapy-induced neutropenia has been associated with prolonged survival selectively in patients on a conventional schedule (combined 5-fluorouracil, leucovorin, and oxaliplatin [FOLFOX2]) but not on a chronomodulated schedule of the same drugs administered at specific circadian times (chronoFLO4). The authors hypothesized that the early occurrence of chemotherapyinduced symptoms correlated with circadian disruption would selectively hinder the efficacy of chronotherapy. METHODS: Fatigue and weight loss (FWL) were considered to be associated with circadian disruption based on previous data. Patients with metastatic colorectal cancer (n 5543) from an international phase 3 trial comparing FOLFOX2 with chronoFLO4 were categorized into 4 subgroups according to the occurrence of FWL or other clinically relevant toxicities during the initial 2 courses of chemotherapy. Multivariate Cox models were used to assess the role of toxicity on the time to progression (TTP) and overall survival (OS). RESULTS: The proportions of patients in the 4 subgroups were comparable in both treatment arms (P 5.77). No toxicity was associated with TTP or OS on FOLFOX2. The median OS on FOLFOX2 ranged from 16.4 (95% confidence limits [CL], 7.2-25.6 months) to 19.8 months (95% CL, 17.722.0 months) according to toxicity subgroup (P 5.45). Conversely, FWL, but no other toxicity, independently predicted for significantly shorter TTP (P <.0001) and OS (P 5.001) on chronoFLO4. The median OS on chronoFLO4 was 13.8 months (95% CL, 10.4-17.2 months) or 21.1 months (95% CL, 19.0-23.1 months) according to presence or absence of chemotherapy-induced FWL, respectively. CONCLUSIONS: Early onset chemotherapy-induced FWL was an independent predictor of poor TTP and OS only on chronotherapy. Dynamic monitoring to detect early chemotherapy-induced circadian disruption could allow the optimization of rapid chronotherapy and concomitant improvements in safety and efficacy. Cancer 2013;119:2564-73. V C 2013 American Cancer Society.

Tranceformations: hypnosis in brain and body

Abstract: In this review, the role of hypnosis and related psychotherapeutic techniques are discussed in relation to the anxiety disorders. In particular, anxiety is addressed as a special form of mind/body problem involving reverberating interaction between mental and physical distress. The history of hypnosis as a therapeutic discipline is reviewed, after which neurobiological evidence of the effect of hypnosis on modulation of perception in the brain. Specific brain regions involved in hypnosis are reviewed, notably the dorsal anterior cingulate gyrus and the dorsolateral prefrontal cortex. The importance of hypnotizability as a trait, stable variability in hypnotic responsiveness, is discussed. Analogies between the hypnotic state and dissociative reactions to trauma are presented, and the uses of hypnosis in treating posttraumatic stress disorder, stressful situations, and phobias as well as outcome data are reviewed. Effects of hypnosis on control of somatic processes are discussed, and then effects of psychosocial support involving Supportive-Expressive Group Therapy and hypnosis on survival time for cancer patients are evaluated. The evidence indicates an important role for hypnosis in managing anxiety disorders and anxiety related to medical illness.

Risk factors and complications in hip reconstruction for nonambulatory patients with cerebral palsy

Abstract: Background Hip dysplasia is prevalent in nonambulatory children with cerebral palsy, and may contribute to a decreased quality of life (Lonstein in J Pediatr Orthop 6:521–526, 1). Reconstructive procedures such as a femoral varus derotation osteotomy with or without a pelvic osteotomy are commonly employed with the goal of achieving and maintaining well reduced hips.

Tlr-agonist-conjugated antibody recruiting molecules (tlr-arms)

Abstract: The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) and Toll-like receptor agonist (TLR) through a linker and a multifunctional connector group or molecule.

Childhood cancer survivors exposed to total body irradiation are at significant risk for slipped capital femoral epiphysis during recombinant growth hormone therapy.

Abstract: Background Childhood cancer survivors treated with cranial or total body irradiation (TBI) are at risk for growth hormone deficiency (GHD). Recombinant growth hormone (rhGH) therapy is associated with slipped capital femoral epiphysis (SCFE). We compared the incidence of SCFE after TBI versus cranial irradiation (CI) in childhood cancer survivors treated with rhGH. Procedure Retrospective cohort study (1980–2010) of 119 survivors treated with rhGH for irradiation-induced GHD (56 TBI; 63 CI). SCFE incidence rates were compared in CI and TBI recipients, and compared with national registry SCFE rates in children treated with rhGH for idiopathic GHD. Results Median survivor follow-up since rhGH initiation was 4.8 (range 0.2–18.3) years. SCFE was diagnosed in 10 subjects post-TBI and none after CI (P < 0.001). All 10 subjects had atypical valgus SCFE, and 7 were bilateral at presentation. Within TBI recipients, age at cancer diagnosis, sex, race, underlying malignancy, age at radiation, and age at initiation of rhGH did not differ significantly between those with versus without SCFE. The mean (SD) age at SCFE diagnosis was 12.3 (2.7) years and median duration of rhGH therapy to SCFE was 1.8 years. The SCFE incidence rate after TBI exposure was 35.9 per 1,000 person years, representing a 211-fold greater rate than reported in children treated with rhGH for idiopathic GH deficiency. Conclusions The markedly greater SCFE incidence rate in childhood cancer survivors with TBI-associated GHD, compared with rates in children with idiopathic GHD, suggests that cancer treatment effects to the proximal femoral physis may contribute to SCFE. Pediatr Blood Cancer 2013;60:1766–1771. © 2013 Wiley Periodicals, Inc.

The unique reactivity of N-phenacyl-derived thiazolium salts toward α-dicarbonyl compounds

Abstract: Advanced glycation end products (AGEs), a heterogeneous mixture of compounds formed by non-enzymatic chemical reactions between sugars and the nucleophilic residues of proteins, have been implicated in the pathogenesis of a number of diseases. ALT-711 is an N-phenacyl-derived thiazolium carbene developed as a therapeutic agent for cardiovascular diseases that is proposed to function through cleaving preformed AGE-protein crosslinks. However, despite promising results in animal models and clinical trials, its mechanism of action still remains controversial. Herein, we report the first systematic investigations into dicarbonyl cleavage by ALT-711. We demonstrate that it is capable of cleaving α-diketones more efficiently and likely via a distinct mechanism compared with other N-heterocyclic carbene precursors. We also show that ALT-711 reacts rapidly with α-keto aldehydes to form cyclic diol products, and it can efficiently scavenge methylglyoxal under physiological conditions to protect Escherichia coli from lethal concentrations of this reactive α-keto aldehyde. This work suggests ALT-711 may be especially suited for α-dicarbonyl clearance in vivo and supports a mode of action similar to that originally proposed. To this end, our findings may provide insights into the development of next-generation crosslink breakers.

Toward the synthesis of phomoidride D.

Abstract: An efficient and highly stereoselective approach toward the phomoidride family of natural products is described. The carbocyclic core structure was assembled using a tandem phenolic oxidation/Diels–Alder cycloaddition and a tandem 5-exo-trig/5-exo-trig radical cyclization to deliver an isotwistane intermediate that, upon a late-stage xanthate-initiated Grob fragmentation, furnishes the requisite bicyclo[4.3.1]decene.

Disinformation about dissociation: Dr Joel Paris's notions about dissociative identity disorder.

Abstract: To the EditorWe write to record our objections to both the form and the content of Dr Joel Paris’s recent article entitled The Rise and Fall of Dissociative Identity Disorder (Paris, 2012). His claim that dissociative identity disorder (DID) is a “medical fad” is simply wrong, and he provides no sub

Synthetic antibody mimetic compounds (syams) targeting cancer, especially prostate cancer

Abstract: The present invention relates to compounds which function as antibody mimetic compounds. These compounds are bifunctional/multifunctional compounds which contain at least one cancer cell binding moiety which selectively binds to prostate specific membrane antigen (PSMA) and a FC receptor binding moiety which modulates an FC immune receptor, preferably a FcγRI receptor. Compounds according to the present invention bind selectively to cancer cells which upregulate PSMA and through that interaction, place the Fc receptor binding moiety of the compound in proximity to a Fc receptor, preferably a FcγRI receptor, which can modulate (preferably, upregulate) a humoral response in a patient to cancer cells. Through this biological action of the compounds according to the present invention, cancer cells, including metastatic cancer cells, especially prostate cancer cells can be immune regulated, resulting in the favorable therapy of cancer in a patient. Methods of using these compounds to treat cancer and/or reduce the likelihood of metastatis of cancer are additional aspects of the present invention.

An eye for an I: a 35-year-old woman with fluctuating oculomotor deficits and dissociative identity disorder.

Abstract: Physiologic changes, including neurological or pseudo-neurological symptoms, occur across identity states in dissociative identity disorder (DID) and can be objectively measured. The idea that dissociative phenomena might be associated with changes in brain function is consistent with research on the brain effects of hypnosis. The authors report a case of psycho-physiologic differences among 4 alter personalities manifested by a 35-year-old woman with DID. Differences in visual acuity, frequency of pendular nystagmus, and handedness were observed in this patient both when the alter personalities appeared spontaneously and when elicited under hypnosis. The authors consider several diagnostic possibilities for these findings and discuss whether prevailing treatment recommendations for DID patients could possibly be modified to ameliorate such visual and neurologic symptoms.

Cytotoxic-drug delivering molecules targeting hiv (cdm-hs), cytotoxic activity against the human immunodeficiency virus and methods of use

Abstract: The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as CDM-Hs, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by introducing cytotoxic moieties to gp120-expressing cells, thereby causing cell death and preventing cell infection and spread of HIV. It is shown that CDM-Hs bind to gp120 and gp-120 expressing cells competitively with CD4, and these compounds cause cell death of HIV-infected cells, thereby decreasing viral infectivity. Compounds and methods are described herein.

A call to ARMs: the promise of immunomodulatory small molecules.

Abstract: Small molecules possessing the properties of biologics hold promise for a wide range of therapeutic applications. Antibody-recruiting molecules (ARMs) – ‘bifunctional’ (two-headed) agents that can ...

Do Routine Radiographs Within the First Two Years Following Pediatric Posterior Spinal Fusion Prompt Revision Surgery

Abstract: Study Design. This is a retrospective review of 265 consecutive patients with scoliosis treated by posterior spinal fusion (PSF) and 2990 postoperative radiographs at a single institution. Objective. To document implant-related complications on postoperative radiographs within the first 2 years after PSF and determine if these led to additional surgical procedures. Summary of Background Data. To date, there is an absence of studies investing the utility of radiographs after pediatric PSF surgery. Methods. The patient's average age was 14.9 years (8.2–21.8 yr). Positive radiographical findings included implant loosening, fracture, migration, or loss of fixation. We also noted which patients’ required additional surgery for a radiographical finding and/or clinical finding (neurological deficit, intractable back pain, fever, and elevated erythrocyte sedimentation rate, c-reactive protein, or while blood cell count). Results. At an average follow-up of 16.3 months (12–24), only 18 (0.60%) radiographs demonstrated a positive finding. Of these, only 5 (0.17%) radiographs (along with clinical presentation) prompted revision. No patient returned to the operating room purely from a radiographical finding. The remaining 13 (0.37%) abnormal plain images were not associated with a clinical abnormality and were managed nonoperatively. The timing of the second operation was in the range from 1 day to 23 months (average, 11 mo). Postoperative plain radiographs had a sensitivity of 26.5%, a specificity of 99.5%, and a positive predictive value of 25%. Conclusion. Only 0.60% of postoperative images (18/2990) demonstrated an implant-related complication, and in the absence of clinical indications, none of these patients required surgical intervention. Isolated postoperative radiographs did not lead to any change in management, and consideration should be given to reviewing current protocols for plain radiographs as a monitoring tool after PSF. Conclusion. Level of Evidence: 4

Patients with DID are found and researched more widely than Boysen and VanBergen recognized.

Abstract: Sar V, O¨ztu¨rk E (2013) Stimulus deprivation and over-stimulation as dissociogenic agents in postmodernoppressive societies. J Trauma Dissociation .Spanos NP (1994) Multiple identity enactments andmultiple personality disorder: A sociocognitive per-spective. Psychol Bull. 116:145Y165.Tutkun H, Sar V, Yargi0 LI, O¨zpulat T, Yanik M,Kiziltan E (1998) Frequency of dissociative disordersamong psychiatric inpatients in a Turkish universityclinic. Am J Psychiatry. 155:800Y805.