Important Factors for Retrograde Nailing Through Total Knee Arthroplasty: A Cadaveric Study.

OBJECTIVES: Evaluate how total knee arthroplasty (TKA) implant design, femoral component size, and preoperative knee range of motion affect retrograde femoral nailing. METHODS: Cadaveric specimens were prepared for TKA with a single radius (SR) or medial pivot (MP) design and tested with cruciate retaining (CR), cruciate substituting (CS), and posterior stabilizing (PS) 9-mm liners. Knee extension identified the minimum flexion required to pass an opening reamer without impinging on TKA components. The angle between the reamer path and the femoral shaft was calculated from lateral fluoroscopic images. RESULTS: In SR TKA, the average flexion required was 70, 71, and 82 degrees for CR, CS, and PS, respectively. The required flexion in PS was significantly greater (P = 0.03). In MP TKA, the average flexion required was 74, 84, and 123 degrees for CR, CS, and PS, respectively. The required flexion was significantly greater in CS and PS designs (P < 0.0001). Femoral component size did not affect the minimum flexion required. The entry reamer resulted in 9.2 (SR) and 12.5 (MP) degrees of apex anterior deviation. CONCLUSIONS: When performing retrograde nailing through either of these TKA designs with a 12-mm opening reamer, at least 70 degrees of knee flexion is required to avoid damage to the polyethylene liner or femoral component. PS implants require significantly more flexion with both TKA designs. Femoral component size did not affect the flexion requirement. Approximately a 10-degree deviation exists between the reamer path and femoral shaft.

Impaired capillary-to-arteriolar electrical signaling after traumatic brain injury.

Traumatic brain injury (TBI) acutely impairs dynamic regulation of local cerebral blood flow, but long-term (>72 h) effects on functional hyperemia are unknown. Functional hyperemia depends on capillary endothelial cell inward rectifier potassium channels (Kir2.1) responding to potassium (K+) released during neuronal activity to produce a regenerative, hyperpolarizing electrical signal that propagates from capillaries to dilate upstream penetrating arterioles. We hypothesized that TBI causes widespread disruption of electrical signaling from capillaries-to-arterioles through impairment of Kir2.1 channel function. We randomized mice to TBI or control groups and allowed them to recover for 4 to 7 days post-injury. We measured in vivo cerebral hemodynamics and arteriolar responses to local stimulation of capillaries with 10 mM K+ using multiphoton laser scanning microscopy through a cranial window under urethane and α-chloralose anesthesia. Capillary angio-architecture was not significantly affected following injury. However, K+-induced hyperemia was significantly impaired. Electrophysiology recordings in freshly isolated capillary endothelial cells revealed diminished Ba2+-sensitive Kir2.1 currents, consistent with a reduction in channel function. In pressurized cerebral arteries isolated from TBI mice, K+ failed to elicit the vasodilation seen in controls. We conclude that disruption of endothelial Kir2.1 channel function impairs capillary-to-arteriole electrical signaling, contributing to altered cerebral hemodynamics after TBI.

Predictors of Outcome of Acute Partial Hospitalization: An Exploratory Study.

To identify predictors of outcome of acute partial hospital (PH) treatment, patients admitted during a 15-month period were studied. Outcomes were change in the Behavior and Symptom Identification Scale and readmission within 30 days. Predictors were clinical and demographic variables obtained on all patients. Most patients (92%) improved during acute PH treatment, only 5% were readmitted, and average changes were moderate to large. However, many patients still had significant symptoms and behavioral problems at discharge, 56.5% missed at least 1 day, and 16.5% dropped out. Less acute improvement was associated with greater long-term impairment, worse treatment attendance, more previous treatment episodes, and fewer medication changes. Readmission was associated with less acute improvement and its predictors, and with nonattendance. In summary, acute outcome in PH was predicted by functioning more generally. Factors that affect patients' acute PH responses may also affect functioning in other areas. These findings suggest possible modifications of PH practices and programs.

Traumatic brain injury impairs sensorimotor function in mice.

INTRODUCTION: Understanding the extent to which murine models of traumatic brain injury (TBI) replicate clinically relevant neurologic outcomes is critical for mechanistic and therapeutic studies. We determined sensorimotor outcomes in a mouse model of TBI and validated the use of a standardized neurologic examination scoring system to quantify the extent of injury. MATERIALS AND METHODS: We used a lateral fluid percussion injury model of TBI and compared TBI animals to those that underwent sham surgery. We measured neurobehavioral deficits using a standardized 12-point neurologic examination, magnetic resonance imaging, a rotating rod test, and longitudinal acoustic startle testing. RESULTS: TBI animals had a significantly decreased ability to balance on a rotating rod and a marked reduction in the amplitude of acoustic startle response. The neurologic examination had a high inter-rater reliability (87% agreement) and correlated with latency to fall on a rotating rod (Rs = -0.809). CONCLUSIONS: TBI impairs sensorimotor function in mice, and the extent of impairment can be predicted by a standardized neurologic examination.

Weight Loss Decreases Inherent and Allergic Methacholine Hyperresponsiveness in Mouse Models of Diet-Induced Obese Asthma.

Obese asthma presents with inherent hyperresponsiveness to methacholine or augmented allergen-driven allergic asthma, with an even greater magnitude of methacholine hyperresponsiveness. These physiologic parameters and accompanying obese asthma symptoms can be reduced by successful weight loss, yet the underlying mechanisms remain incompletely understood. We implemented mouse models of diet-induced obesity, dietary and surgical weight loss, and environmental allergen exposure to examine the mechanisms and mediators of inherent and allergic obese asthma. We report that the methacholine hyperresponsiveness in these models of inherent obese asthma and obese allergic asthma manifests in distinct anatomical compartments but that both are amenable to interventions that induce substantial weight loss. The inherent obese asthma phenotype, with characteristic increases in distal airspace tissue resistance and tissue elastance, is associated with elevated proinflammatory cytokines that are reduced with dietary weight loss. Surprisingly, bariatric surgery-induced weight loss further elevates these cytokines while reducing methacholine responsiveness to levels similar to those in lean mice or in formerly obese mice rendered lean through dietary intervention. In contrast, the obese allergic asthma phenotype, with characteristic increases in central airway resistance, is not associated with increased adaptive immune responses, yet diet-induced weight loss reduces methacholine hyperresponsiveness without altering immunological variables. Diet-induced weight loss is effective in models of both inherent and allergic obese asthma, and our examination of the fecal microbiome revealed that the obesogenic Firmicutes/Bacteroidetes ratio was normalized after diet-induced weight loss. Our results suggest that structural, immunological, and microbiological factors contribute to the manifold presentations of obese asthma.

Actinic keratoses, actinic field change and associations with squamous cell carcinoma in renal transplant recipients in Manchester, UK.

While actinic keratoses (AKs) have a known association with cutaneous squamous cell carcinoma (SCC), the relation of actinic field change to SCC has not been quantified. This study investigated the presence of field change and AKs in renal transplant recipients (RTRs) and estimated SCC risk. In May 2010 to October 2011, a dermatologist examined 452 white RTRs (mean age 53 years) at two hospitals in Manchester, UK, counting AKs and recording field change presence by body site and SCCs arising during the study period. Of the participants 130 (29%) had AKs at examination. In 60 (13%) RTR patients with AKs but no field change, 4 (7%) developed SCCs, compared with 15 (21%) of the 70 (15%) with AKs and field change. SCCs developed directly within field change areas in 11/15 (73%) RTRs. This study confirms that RTRs with widespread confluent actinic skin damage are at very high risk of SCC and should be monitored closely.

Subarachnoid Hemorrhage Induces Gliosis and Increased Expression of the Pro-inflammatory Cytokine High Mobility Group Box 1 Protein.

Subarachnoid hemorrhage (SAH) following cerebral aneurysm rupture is associated with high rates of morbidity and mortality. Surviving SAH patients often suffer from neurological impairment, yet little is currently known regarding the influence of subarachnoid blood on brain parenchyma. The objective of the present study was to examine the impact of subarachnoid blood on glial cells using a rabbit SAH model. The astrocyte-specific proteins, glial fibrillary acidic protein (GFAP) and S100B, were up-regulated in brainstem from SAH model rabbits, consistent with the development of reactive astrogliosis. In addition to reactive astrogliosis, cytosolic expression of the pro-inflammatory cytokine, high-mobility group box 1 protein (HMGB1) was increased in brain from SAH animals. We found that greater than 90% of cells expressing cytosolic HMGB1 immunostained positively for Iba1, a specific marker for microglia and macrophages. Further, the number of Iba1-positive cells was similar in brain from control and SAH animals, suggesting the majority of these cells were likely resident microglial cells rather than infiltrating macrophages. These observations demonstrate SAH impacts brain parenchyma by activating astrocytes and microglia, triggering up-regulation of the pro-inflammatory cytokine HMGB1.

Multidisciplinary insights into optimizing adherence after solid organ transplantation.

BACKGROUND: Nonadherence to medical treatment in transplant recipients is a major risk factor for graft rejection episodes, and it has significant financial implications. Despite its importance, there is a lack of common understanding across the disciplines involved of the key issues driving nonadherence. METHODS: A qualitative study, comprising a multidisciplinary workshop, followed by a consultation exercise to validate its outcomes, was initiated to gain further insight into nonadherence behavior and to identify priorities for optimizing adherence to posttransplantation regimens. RESULTS: Eight statements relating to actions necessary to maximize adherence to posttransplantation medication were developed and offered for validation. All but one of these attracted a median score of 9 on an agreement scale of 1 to 10, where 10 was the highest level of agreement. CONCLUSION: The outcomes generate a structure that will facilitate communication and understanding and informing clinical practice and future research.

A novel model of blunt thoracic aortic injury: a mechanism confirmed?

BACKGROUND: There is no consensus on the mechanism of traumatic injury to the thoracic aorta and no reproducible animal model. Advances in injury scene analysis suggest that lateral and oblique force vectors cause aortic injury. We hypothesized that the spectrum of aortic injury could be reproduced in an animal model by application of an obliquely directed load to the pressurized aorta. METHODS: Graded air impulses of 80, 100, 110, and 120 pounds per square inch (PSI) were delivered to the descending thoracic aorta of 19 swine with a novel pneumatic device. Aortic isthmus strain was recorded with microminiature probes. Gross and microscopic injury was recorded with digital photography. RESULTS: The spectrum of human aortic injury was reproduced in this model. Deep injuries to the aortic media were common. The majority of injuries occurred within the region of the isthmus. Impulse pressure of 120 PSI caused transections, whereas lower impulse pressure resulted in less severe injuries. Aortic isthmus strain was greater in the animals exposed to 120 PSI than those receiving lower PSI (19.6 +/- 4.9% vs. 8.7 +/- 2.5%, p = 0.067). CONCLUSIONS: Direct loading of the pressurized descending thoracic aorta causes isthmus injury secondary to aortic wall strain. Deep medial lesions are common and could propagate soon after injury to form pseudoaneurysms. A critical load is required to cause complete uncontained transection with exsanguination, which may have relevance to injury scene death.

Emergence of a R-type Ca2+ channel (CaV 2.3) contributes to cerebral artery constriction after subarachnoid hemorrhage.

Cerebral aneurysm rupture and subarachnoid hemorrhage (SAH) inflict disability and death on thousands of individuals each year. In addition to vasospasm in large diameter arteries, enhanced constriction of resistance arteries within the cerebral vasculature may contribute to decreased cerebral blood flow and the development of delayed neurological deficits after SAH. In this study, we provide novel evidence that SAH leads to enhanced Ca2+ entry in myocytes of small diameter cerebral arteries through the emergence of R-type voltage-dependent Ca2+ channels (VDCCs) encoded by the gene CaV 2.3. Using in vitro diameter measurements and patch clamp electrophysiology, we have found that L-type VDCC antagonists abolish cerebral artery constriction and block VDCC currents in cerebral artery myocytes from healthy animals. However, 5 days after the intracisternal injection of blood into rabbits to mimic SAH, cerebral artery constriction and VDCC currents were enhanced and partially resistant to L-type VDCC blockers. Further, SNX-482, a blocker of R-type Ca2+ channels, reduced constriction and membrane currents in cerebral arteries from SAH animals, but was without effect on cerebral arteries of healthy animals. Consistent with our biophysical and functional data, cerebral arteries from healthy animals were found to express only L-type VDCCs (CaV 1.2), whereas after SAH, cerebral arteries were found to express both CaV 1.2 and CaV 2.3. We propose that R-type VDCCs may contribute to enhanced cerebral artery constriction after SAH and may represent a novel therapeutic target in the treatment of neurological deficits after SAH.

Enhanced myogenic tone in cerebral arteries from a rabbit model of subarachnoid hemorrhage.

Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Currently, little is known regarding the impact of SAH on small diameter (100-200 microm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. With the use of a rabbit SAH model and in vitro video microscopy, cerebral artery diameter was measured in response to elevations in intravascular pressure. Cerebral arteries from SAH animals constricted more (approximately twofold) to pressure within the physiological range of 60-100 mmHg compared with control or sham-operated animals. Pressure-induced constriction (myogenic tone) was also enhanced in arteries from control animals organ cultured in the presence of oxyhemoglobin, an effect independent of the vascular endothelium or nitric oxide synthesis. Finally, arteries from both control and SAH animals dilated as intravascular pressure was elevated above 140 mmHg. This study provides evidence for a role of oxyhemoglobin in impaired autoregulation (i.e., enhanced myogenic tone) in small diameter cerebral arteries during SAH. Furthermore, therapeutic strategies that improve clinical outcome in SAH patients (e.g., supraphysiological intravascular pressure) are effective in dilating small diameter cerebral arteries isolated from SAH animals.

Multiple head injuries in rats: effects on behavior.

BACKGROUND: Evidence suggests that mild head injuries in humans can result in cumulative damage. No investigation to date has considered the effects of multiple subacute mild head injuries in an animal model. METHODS: Forty-one male Long-Evans hooded rats were trained in a Morris water maze. All animals were fitted with a hollow intracranial screw. Concussions were generated using a fluid percussion device. Animals were then evaluated in the water maze until performance returned to baseline. Control animals received no concussions. The remaining animals were randomized to receive one, two, or three concussions. Animals were allowed to return to baseline after each concussion and were then killed. Motor performance was evaluated on a balance beam both before and after concussions. RESULTS: After one concussion, 85% of animals showed performance deviation from baseline as measured by time to reach the platform, returning to baseline within a mean of 14.0 trials. After two concussions, 48% of animals showed deviation, with a mean return to baseline of 6.8 trials. After three concussions, 25% of animals showed deviation, with a mean return to baseline of 2.3 trials. Of postconcussive animals, 42% developed new inconsistent baseline levels of performance. Balance beam performance was unaffected. CONCLUSION: Multiple concussions cause immediate transient impairment in spatial recognition and have extended effects on baseline performance in rats. Motor performance is not affected.