High-affinity biomolecular interactions are modulated by low-affinity binders.

The strength of molecular interactions is characterized by their dissociation constants (KD). Only high-affinity interactions (KD ≤ 10-8 M) are extensively investigated and support binary on/off switches. However, such analyses have discounted the presence of low-affinity binders (KD > 10-5 M) in the cellular environment. We assess the potential influence of low-affinity binders on high-affinity interactions. By employing Gillespie stochastic simulations and continuous methods, we demonstrate that the presence of low-affinity binders can alter the kinetics and the steady state of high-affinity interactions. We refer to this effect as 'herd regulation' and have evaluated its possible impact in two different contexts including sex determination in Drosophila melanogaster and in signalling systems that employ molecular thresholds. We have also suggested experiments to validate herd regulation in vitro. We speculate that low-affinity binders are prevalent in biological contexts where the outcomes depend on molecular thresholds impacting homoeostatic regulation.

Early postoperative imaging and image-guided procedures on patients with face transplants.

Face transplantation is being performed with increasing frequency. Facial edema, fluid collections, and lymphadenopathy are common postoperative findings and may be due to various etiologies, some of which are particular to face transplantation. The purpose of this study was to demonstrate how postoperative imaging and image-guided minimally invasive procedures can assist in diagnosing and treating complications arising from face transplantation. Retrospective evaluation of 6 consecutive cases of face transplantation performed at Brigham and Women's Hospital between April 2009 and March 2014 was performed with assessment of postoperative imaging and image-guided procedures, including aspiration of postoperative fluid collection, lymph node biopsy, and treatment of salivary gland leak. Through these cases, we demonstrate that early postoperative imaging and image-guided procedures are key components for the management of complications following face transplantation.

Zuckerkandl tubercle of the thyroid: a common imaging finding that may mimic pathology.

BACKGROUND AND PURPOSE: The posterior thyroid tubercle, also known as ZT, is an important surgical landmark due to its close proximity to the recurrent laryngeal nerve. A recent case of ZT with a nodular configuration caused clinical concern but was shown on biopsy to be normal thyroid tissue. The purpose of this study was to review a series of CT neck studies to identify how often ZT-specifically, a nodular subtype-was present. MATERIALS AND METHODS: A total of 96 neck CTs from sequential patients were retrospectively identified from January 2010 to July 2010. ZT was defined on imaging as a thyroid lobe extending posterior to the tracheoesophageal groove. A nodular subtype was defined as having a narrowed neck at the level of the tracheoesophageal groove. RESULTS: There were 31 women and 45 men (mean age of 56.1 years, range 22-100 years) who met inclusion criteria. Sixty-seven patients had thyroid glands that extended posterior to the tracheoesophageal groove at CT imaging; this finding was bilateral in 43 patients, more commonly on the right (60 versus 49). Thirty-two of these patients (42.1%; 16 male, 16 female) had a nodular subtype. CONCLUSIONS: ZT is an important surgical landmark of the thyroid that has important radiologic variations. It has a nodular shape in over a third of CT neck studies in our series. Recognition of this feature of the thyroid gland at CT imaging can obviate the need for biopsy and avoid potential recurrent laryngeal nerve injury.

[Facial allograft transplantation: fiction or reality? Surgical techniques in a fresh human cadaver model]. / Allogene Gesichtstransplantation: Fiktion oder Realität? : Darstellung chirurgischer Techniken am Leichenmodel.

BACKGROUND: The aim of this study was to describe two methods of face-harvesting techniques -- a skin and soft tissue flap and a combined osteocutaneous flap -- and to demonstrate the compatibility between donor and recipient in a human fresh cadaver model. METHODS: In fresh human cadavers the skin and soft tissue of the face (type 1) and a combined osteocutaneous flap (including a le Fort III segment, type 2) were harvested. The faces were subsequently exchanged among the donor crania, simulating full-face transplantation. RESULTS: Both flaps are based on the external blood supply of the faciotemporal vessels and the external jugular vein. The end branches of the trigeminal nerve could potentially be used for restoration of sensation (type 1 flap). With type 2 flaps the facial expression may be restored with the inclusion of the facial nerve. Four morphological parameters determine the donor/recipient compatibility: skin color and texture, anthropometric head dimensions, specific soft tissue components (nose, lip, cheek, and eyebrow), and gender. CONCLUSION: Apart from ethical considerations, long-term immunosuppression will remain the limiting factor of full facial transplantation in the near future.

Ganglioneuroma of the neck.

Ganglioneuroma (GN) has a neuroectodermic origin and is localized along the sympathetic trunk. GN of the neck is a rare tumour and due to proximity to the thyroid gland, clinically and radiologically, these lesions can be mistaken as thyroid swellings. Definite diagnosis only can be suspected after surgical exploration and complete surgical excision is the treatment of choice, as it will ensure thorough sampling of the tumour and cure.

A clinically applicable reporting system for the diagnosis of facial fractures.

A clinically applicable, comprehensive reporting system for the diagnosis of facial fractures was developed with three guiding principles: (1) preservation of classical anatomical terminology and nomenclature, (2) facilitation of uniform interpretation of radiographs between radiologists and (3) non-redundant diagnostic descriptions of complex fractures, in a manner that correlates with treatment modality. Twenty-two fracture types (17 simple fracture types and 5 complex fracture types) are included in the system. Each patient's fracture pattern is described by listing the component fractures present. A short narrative (modifying description) is provided after each fracture listed. Simple fractures that help to comprise more complex fractures are not listed separately, but are described within the modifying description of the complex fracture they help to comprise. When components of multiple complex fractures are present, a hierarchy of complex fractures dictates which fracture is described first. Additional complex fractures are only described separately when they do not share common components. In all other cases, the second (lower order) complex fracture is best described by simply listing the component (simple or complex) fractures that are not accounted for in the higher order complex fracture. Adoption of this reporting system should improve communication between emergency medicine physicians, radiologists and surgeons.

High-resolution vascular imaging of the rat spine using liposomal blood pool MR agent.

BACKGROUND AND PURPOSE: High-resolution, vascular MR imaging of the spine region in small animals poses several challenges. The small anatomic features, extravascular diffusion, and low signal-to-noise ratio limit the use of conventional contrast agents. We hypothesize that a long-circulating, intravascular liposomal-encapsulated MR contrast agent (liposomal-Gd) would facilitate visualization of small anatomic features of the perispinal vasculature not visible with conventional contrast agent (gadolinium-diethylene-triaminepentaacetic acid [Gd-DTPA]). METHODS: In this study, high-resolution MR angiography of the spine region was performed in a rat model using a liposomal-Gd, which is known to remain within the blood pool for an extended period. The imaging characteristics of this agent were compared with those of a conventional contrast agent, Gd-DTPA. RESULTS: The liposomal-Gd enabled acquisition of high quality angiograms with high signal-to-noise ratio. Several important vascular features, such as radicular arteries, posterior spinal vein, and epidural venous plexus were visualized in the angiograms obtained with the liposomal agent. The MR angiograms obtained with conventional Gd-DTPA did not demonstrate these vessels clearly because of marked extravascular soft-tissue enhancement that obscured the vasculature. CONCLUSIONS: This study demonstrates the potential benefit of long-circulating liposomal-Gd as a MR contrast agent for high-resolution vascular imaging applications.

Central nervous system extraosseous Ewing sarcoma: radiologic manifestations of this newly defined pathologic entity.

Although these entities are histologically similar, recent advances in molecular genetics have allowed the distinction of central nervous system extraosseous Ewing sarcoma (CNS-EES) from central primitive neuroectodermal tumors (c-PNET) including medulloblastoma and supratentorial PNET. We present 2 cases of pathologically confirmed CNS-EES. Knowledge of CNS-EES as a distinct entity enables the neuroradiologist to suggest the proper diagnosis and the need for special immuno-histochemical and molecular studies to confirm the diagnosis. Because treatment and prognosis are vastly different, the proper diagnosis of CNS-EES versus c-PNET is critical.

Direct antithrombin agents ameliorate disseminated intravascular coagulation in suspected heparin-induced thrombocytopenia thrombosis syndrome.

This is a case series of 5 patients who were treated with the direct antithrombin agents (lepirudin or argatroban) for known or suspected heparin-induced thrombocytopenia thrombosis syndrome (HITTs). Coincidentally all had evidence of disseminated intravascular coagulation (DIC). The DIC parameters improved with treatment and each patient was successfully discharged from the hospital. These observations provide evidence that the direct antithrombin inhibitors, lepirudin and argatroban, can improve DIC. Moreover the presence of DIC in a patient with suspected HlTTs should not mitigate against the use of these agents.

Diffusion-weighted MR imaging of the normal human spinal cord in vivo.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging is a robust technique for evaluation of a variety of neurologic diseases affecting the brain, and might also have applications in the spinal cord. The purpose of this study was to determine the feasibility of obtaining in vivo diffusion-weighted images of the human spinal cord, to calculate normal apparent diffusion coefficient (ADC) values, and to assess cord anisotropy. METHODS: Fifteen healthy volunteers were imaged using a multi-shot, navigator-corrected, spin-echo, echo-planar pulse sequence. Axial images of the cervical spinal cord were obtained with diffusion gradients applied along three orthogonal axes (6 b values each), and ADC values were calculated for white and gray matter. RESULTS: With the diffusion gradients perpendicular to the orientation of the white matter tracts, spinal cord white matter was hyperintense to central gray matter at all b values. This was also the case at low b values with the diffusion gradients parallel to the white matter tracts; however, at higher b values, the relative signal intensity of gray and white matter reversed. With the diffusion gradients perpendicular to spinal cord, mean ADC values ranged from 0.40 to 0.57 x 10(-3) mm2/s for white and gray matter. With the diffusion gradients parallel to the white matter tracts, calculated ADC values were significantly higher. There was a statistically significant difference between the ADCs of white versus gray matter with all three gradient directions. Strong diffusional anisotropy was observed in spinal cord white matter. CONCLUSION: Small field-of-view diffusion-weighted images of the human spinal cord can be acquired in vivo with reasonable scan times. Diffusion within spinal cord white matter is highly anisotropic.

External validation of the Ottawa knee rules in an urban trauma center in the United States.

OBJECTIVE: We evaluated the Ottawa knee rules in a high-volume teaching hospital in the United States to determine whether the rules could be safely used to decide whether patients with acute blunt knee trauma should undergo radiography. SUBJECTS AND METHODS: During a 13-month period, 378 patients with acute blunt knee trauma were prospectively examined using the Ottawa knee rules. Data collected included the presence or absence of fracture predictors and the results of radiography. RESULTS: A fracture was seen in 43 (11%) of the 378 patients who met inclusion criteria. The knee rules predicted 42 of the 43 fractures; sensitivity was 98%, and specificity was 19%. Radiography of 65 patients (17%) who had no predictors for fracture could have been avoided if the knee rules had been used to screen for radiography. CONCLUSION: The Ottawa knee rules are highly sensitive for fracture in this setting and may safely be used to decide whether patients with acute blunt knee trauma should undergo radiography.

Experience with low-dose aspirin as thromboprophylaxis for the Tissuemed porcine aortic bioprosthesis: a survey of five years' experience.

BACKGROUND AND AIMS OF THE STUDY: In patients in sinus rhythm following aortic valve replacement (AVR) with bioprosthetic valves, aspirin prophylaxis generally keeps bleeding complications to a minimum without increasing the risks of thromboembolic events. To study the efficacy of aspirin prophylaxis in patients receiving the recently introduced Tissuemed porcine bioprosthetic implant in the aortic position we reviewed our database of 145 patients who underwent AVR between 1991 and 1996. METHODS: Mean patient age was 73.5 years (range: 56 to 94 years); 85 were males and 60 females. Preoperatively, 70% of the patients were in NYHA functional class III or IV. Concomitant procedures were performed in 26% of patients. Following AVR, low-dose aspirin prophylaxis (75 mg/day) was commenced in all patients in sinus rhythm. The bioprosthesis was evaluated using standard Society of Thoracic Surgery guidelines. RESULTS: Follow up was 100% complete (total cumulative follow up 253.7 patient-years (pt-yr)). There were three minor thromboembolic episodes, all occurring at least one year after surgery; there were no major thromboembolic complications and bleeding events. Valve-related complication rates (expressed as %/pt-yr and number of events) were thromboembolism 0.7%/yr (three episodes), hemorrhage 0.4%/yr (one) and bacterial endocarditis 0.4%/yr (one). The reoperation rate was 0.4%/yr (one). At five years, actuarial freedom from thromboembolism was 95 +/- 3.6% (SE); hemorrhage 99.2 +/- 0.75%; endocarditis 98.4 +/- 1.5); non-structural valve failure 100%; structural valve dysfunction 100% and reoperation 98.4 +/- 1.5%. The 30-day mortality rate in this elderly population, influenced by clinical status (NYHA class III and IV; p = 0.005), was 9.6% (95% CI, 4.8 to 14.4), with no early valve-related deaths. Patient survival at five years was 78.5 +/- 3.7%. At follow up, 94.8% of the patients were in NYHA functional class I or II. CONCLUSIONS: Early clinical evaluation showed that, following AVR, bleeding complications were minimal with no increase in thromboembolic events in the first three months and on long-term follow up, when low-dose aspirin prophylaxis was started in patients in sinus rhythm. There was overall improvement in patient symptoms while valve-related complications were minimal with no episode of structural deterioration or non-structural failure.

The use of the diagnostic radionuclide ascites scan to facilitate treatment decisions for hepatic hydrothorax.

A 44-year-old man had an intractable right-sided pleural effusion due to cirrhosis, despite the absence of abdominal ascites. Instillation of Tc-99m macroaggregated serum albumin under CT guidance into the peritoneal space demonstrated transdiaphragmatic communication. This finding indicated the necessity for decompressing the portal system to treat the hydrothorax. The diagnostic radionuclide ascites scan may play an important role in the treatment approach to such patients.

Early clinical experience with the Tissuemed porcine bioprosthesis.

BACKGROUND: Tissuemed (Leeds, England) porcine bioprostheses are freshly mounted and dilated for correct functional sizing and commissural alignment, then fixed under low pressure. These valves closely approximate the natural leaflet geometry, reduce opening commissural bending stresses, and may provide a solution to structural valve failure from calcification and tears. To evaluate the performance of the bioprosthesis 207 Tissuemed bioprostheses were implanted in 203 patients, 114 men and 89 women (mean age 73 years; range 56 to 94 years), between 1991 and 1996. Preoperatively 66% of the patients were in New York Heart Association functional class III or IV. There were 175 aortic, 22 mitral, 2 tricuspid, and 4 multiple replacements. Concomitant procedures were performed in 26.1% (53 of 203) of patients. Follow-up was 99.5% (total cumulative follow-up 447.5 patient-years). RESULTS: The 30 day mortality, influenced by age and valve position, was 11.8% with no early valve-related deaths. Patient survival at 5 years was 76% (standard error 3.3%). Valve-related complication rates (expressed as percent per patient-year and number of events) were thromboembolism 1.1% (5), hemorrhage 0.7% (3), bacterial endocarditis 0.2% (1), nonstructural valve failure 0.2% (1), and reoperation 0.5% (2). At 5 years freedom from valve-related events were as follows: thromboembolism 92.9% (standard error 2.7%), hemorrhage 96.1% (standard error 1.9%), endocarditis 98.1% (standard error 1.8%), nonstructural valve failure 99.2% (standard error 0.7%), structural valve dysfunction 100% (standard error 0.0%), and reoperation 98.1% (standard error 1.8%). At follow-up 73.8% of the patients were in New York Heart Association functional class I or II. CONCLUSIONS: There were no early valve-related deaths, no episodes of structural valve failure, and valve-related complications compared favorably with other porcine series. There was overall clinical improvement in patient symptoms. Our experience suggests that the Tissuemed porcine bioprosthesis is a safe and reliable heart valve providing good clinical improvement in patient symptoms. Long-term clinical follow-up is, however, essential to complete the evaluation.

Improved measurement of pressure gradients in aortic coarctation by magnetic resonance imaging.

OBJECTIVES: This study evaluated whether magnetic resonance imaging (MRI) and magnetic resonance (MR) phase velocity mapping could provide accurate estimates of stenosis severity and pressure gradients in aortic coarctation. BACKGROUND: Clinical management of aortic coarctation requires determination of lesion location and severity and quantification of the pressure gradient across the constricted area. METHODS: Using a series of anatomically accurate models of aortic coarctation, the laboratory portion of this study found that the loss coefficient (K), commonly taken to be 4.0 in the simplified Bernoulli equation delta P = KV2, was a function of stenosis severity. The values of the loss coefficient ranged from 2.8 for a 50% stenosis to 4.9 for a 90% stenosis. Magnetic resonance imaging and MR phase velocity mapping were then used to determine coarctation severity and pressure gradient in 32 patients. RESULTS: Application of the new severity-dependent loss coefficients found that pressure gradients deviated from 1 to 17 mm Hg compared with calculations made with the commonly used value of 4.0. Comparison of MR estimates of pressure gradient with Doppler ultrasound estimates (in 22 of 32 patients) and with catheter pressure measurements (in 6 of 32 patients) supports the conclusion that the severity-based loss coefficient provides improved estimates of pressure gradients. CONCLUSIONS: This study suggests that MRI could be used as a complete diagnostic tool for accurate evaluation of aortic coarctation, by determining stenosis location and severity and by accurately estimating pressure gradients.

Two-dimensional coronary MR angiography without breath holding.

PURPOSE: To determine whether breath holding can be eliminated in two-dimensional magnetic resonance (MR) imaging of the coronary arteries by using real-time respiratory gating. MATERIALS AND METHODS: Thirty-one subjects (20 healthy volunteers, 11 patients) underwent MR imaging. In 13 subjects, a respiratory monitoring belt was used, and in 18 subjects, a navigator echo was used. MR imaging was performed with breath holding, respiratory gating, and respiratory gating with two signals acquired. Three reviewers conducted a blinded review of the images, and overall image quality was rated on a scale from 1 (poor) to 5 (excellent). RESULTS: Respiratory gating with two signals acquired provided image quality superior to that with breath-hold imaging (3.7 vs 3.0, respectively; P < .05). Measurements of signal-to-noise ratio (14.5 for respiratory gating with two signals acquired and 11.9 for breath holding) supported the results of the image review. Navigator-echo gating provided better image quality than the monitoring belt (3.7 vs 3.1, respectively; P < .05). CONCLUSION: Breath holding may be eliminated by gating image acquisition to a real-time monitor of respiratory position. Respiratory gating enables improved resolution by means of acquisition of multiple signals, provides aligned sections of coronary arteries, and improves patient tolerance.

Determination of wall shear stress in the aorta with the use of MR phase velocity mapping.

MR phase velocity mapping was used to calculate wall shear stress (WSS) in the suprarenal and infrarenal abdominal aorta, two sites with very different proclivities for development of a atherosclerosis. For the eight subjects studied, the average value of the mean (time averaged over the cardiac cycle) WSS in the suprarenal aorta was 10.4 dynes/cm2 at the posterior wall and 8.6 at the anterior wall. In the infrarenal aorta, WSS values were 4.7 at the posterior wall and 6.1 at the anterior wall. Peak WSS over the cardiac cycle was 48 and 54 at the anterior and posterior walls of the suprarenal aorta, respectively, and 33 and 30 at the anterior and posterior walls of the infrarenal aorta, respectively. Wide variation was found in both mean and peak WSS values among subjects. However, for 28 of 32 locations examined, mean and peak WSS were higher in the suprarenal aorta than in the infrarenal aorta. Because atherosclerosis is more likely to form in the infrarenal aorta than in the suprarenal aorta, this study supports the hypothesis that low WSS is a localizing factor for atherosclerosis, and high WSS may act as a deterrent against formation of atherosclerosis.

MR detection of leakage from silicone breast implants: value of a silicone-selective pulse sequence.

OBJECTIVE: The purpose of this study was to determine the value of MR imaging with a silicone-selective pulse sequence for detecting leakage from silicone breast implants. SUBJECTS AND METHODS: Women with silicone breast implants were referred for this study on the basis of clinical or imaging findings suggestive of implant rupture. Twenty-eight patients with 38 implants were examined with silicone-selective MR imaging and also underwent surgical removal of the studied implant. All but four also had mammography before MR imaging. Results of silicone-selective MR imaging for the detection of silicone leakage were compared with mammographic and surgical findings. Surgical proof was considered the gold standard. RESULTS: Silicone-selective MR imaging showed an apparently intact implant in 21 cases; 20 of these were found to be intact at surgery. Silicone-selective MR imaging showed evidence of leakage in 17 implants, all of which showed leakage at surgery. The sensitivity for detection of leakage was 94%; the specificity was 100%. The findings of silicone-selective MR imaging and mammography were in agreement in 30 of 34 cases in which both studies were performed. In the four cases of disagreement, surgical findings agreed with MR findings in three and with mammographic findings in one. When the findings of mammography and silicone-selective MR imaging were combined, the correct status (leakage or no leakage) of all implants examined was determinable. CONCLUSION: Silicone-selective MR imaging is highly effective for detecting leakage from silicone breast implants. Accuracy is improved when mammographic and MR findings are considered together.

Vi-specific latex agglutination for early and rapid detection of Salmonella serotype typhi in blood cultures.

Latex particles coated with rabbit antisera against Salmonella serotype typhi (S. typhi) Vi and O (STO) antigens were used in slide agglutination tests for the rapid identification of S. typhi in blood culture broths as soon as Gram-negative bacilli (GNB) were detected in them. Among 231 consecutive blood cultures showing GNB tested for Vi, and a subset of 163 tested for STO, by latex agglutination (LA), 125 and 32, respectively, were positive. The GNB in 127 blood cultures were confirmed by conventional methods as S. typhi, 125 (98.4%) of which had been identified by the Vi LA test. In the subset of 163, 81 grew S. typhi, of which only 32 (39.5%) had been identified by the STO LA tests. Thus, the sensitivity of the Vi and STO LA tests was 98.4% and 39.5%, respectively, whereas the specificity was 100% for both tests. Of the S. typhi isolates, 38 (30.4%) were detected by the Vi LA test on day 2 and 73 (58.4%) on day 3, day 1 being the date of inoculation of the blood culture broths. Thus, the Vi LA test is suitable for the early and rapid confirmation of S. typhi in blood culture.