Monotherapy of topical tacrolimus 0.03% in the treatment of vernal keratoconjunctivitis in the pediatric population.

PURPOSE: To report the results of treating children with vernal keratoconjunctivitis (VKC) using a monotherapy of topical tacrolimus 0.03%. METHODS: This was a prospective, nonrandomized observational study of children newly diagnosed with VKC. The severity of the disease was graded on a 4-point scale of symptoms and signs. Patients were treated with tacrolimus 0.03% ointment and were followed for 8 months according to a schedule based on the severity of the disease. The primary measure of treatment efficacy was the change in the score of objective signs. The incidence and severity of adverse events, if any, were recorded. RESULTS: A total of 45 children aged 5-15 years were enrolled. The mean composite symptom score was 6.84 ± 2.26 at baseline and 0.71 ± 1.62 at 8 months, a statistically significant reduction (P < 0.001). The mean composite sign score was 9.6 ± 3.14 at baseline and 1.16 ± 1.28 at 8 months, also a statistically significant reduction (P < 0.001). Four patients had to be started on steroids within the first month of treatment and were considered treatment failures. Thus, 89% of patients showed significant improvement. No participant experienced adverse effects, although some reported a transient stinging sensation. CONCLUSIONS: In our study cohort topical tacrolimus ointment 0.03% as a monotherapy for VKC was successful in the majority of subjects, and there was no adverse effect.

Optic nerve aplasia: A case series.

Optic nerve aplasia (ONA) is a congenital optic nerve anomaly characterized by the absence of optic nerve head, retinal blood vessels, retinal ganglion cells, and optic nerve fibers in a malformed eye. Clinically, the condition presents with the absence of perception of light, afferent pupillary defect and a fundus appearance of absent optic nerve head, and retinal vessels with associated ocular and nonocular abnormalities. Systemic anomalies have been reported with bilateral ONA, whereas unilateral ONA is seen in otherwise healthy individuals. We report three cases of ONA with varied clinical presentations.

Optic disk contractility in morning glory disk anomaly.

Morning glory disk anomaly is a nonhereditary, congenital optic disk dysplasia characterized by conical excavation of the posterior fundus with a central glial tuft and radial retinal vessels. We report the case of a 4-year-old girl who presented with esotropia, enophthalmos, no light perception, and afferent pupillary defect in her left eye; fundus examination revealed morning glory disk anomaly. Ultrasound B-scan showed axial length increasing in the left eye on consensual light exposure. Magnetic resonance imaging/angiogram of the brain and orbits were within normal limits except for globe elongation posteriorly in the left eye. On examination under anesthesia with video indirect ophthalmoscopy, the left optic disk showed contraction and expansion when stimulated by strong light to the fellow eye and no spontaneous contraction on direct light stimulation. Morning glory disk contractility with increasing axial length on consensual light exposure in a child has not been reported previously.

Transcriptional regulation of fibronectin by p21-activated kinase-1 modulates pancreatic tumorigenesis.

Pancreatic ductal adenocarcinoma (PDAC) is the eighth largest cause of cancer-related mortality across the world, with a median 5-year survival rate of less than 3.5%. This is partly because the molecules and the molecular mechanisms that contribute to PDAC are not well understood. Our goal is to understand the role of p21-activated kinase 1 (Pak1) signaling axis in the progression of PDAC. Pak1, a serine/threonine kinase, is a well-known regulator of cytoskeletal remodeling, cell motility, cell proliferation and cell survival. Recent reports suggest that Pak1 by itself can have an oncogenic role in a wide variety of cancers. In this study, we analyzed the expression of Pak1 in human pancreatic cancer tissues and found that Pak1 levels are significantly upregulated in PDAC samples as compared with adjacent normals. Further, to study the functional role of Pak1 in pancreatic cancer model systems, we developed stable overexpression and lentiviral short hairpin RNA-mediated knockdown (KD) clones of Pak1 and studied the changes in transforming properties of the cells. We also observed that Pak1 KD clones failed to form tumors in nude mice. By adopting a quantitative PCR array-based approach, we identified fibronectin, a component of the extracellular matrix and a mesenchymal marker, as a transcriptional target of Pak1 signaling. The underlying molecular mechanism of Pak1-mediated transformation includes its nuclear import and recruitment to the fibronectin promoter via interaction with nuclear factor-κB (NF-κB)-p65 complex. To our knowledge, this is the first study illustrating Pak1-NF-κB-p65-mediated fibronectin regulation as a potent tumor-promoting mechanism in KRAS intact model.

Nonlinear analysis of EEG signals at different mental states.

BACKGROUND: The EEG (Electroencephalogram) is a representative signal containing information about the condition of the brain. The shape of the wave may contain useful information about the state of the brain. However, the human observer can not directly monitor these subtle details. Besides, since bio-signals are highly subjective, the symptoms may appear at random in the time scale. Therefore, the EEG signal parameters, extracted and analyzed using computers, are highly useful in diagnostics. This work discusses the effect on the EEG signal due to music and reflexological stimulation. METHODS: In this work, nonlinear parameters like Correlation Dimension (CD), Largest Lyapunov Exponent (LLE), Hurst Exponent (H) and Approximate Entropy (ApEn) are evaluated from the EEG signals under different mental states. RESULTS: The results obtained show that EEG to become less complex relative to the normal state with a confidence level of more than 85% due to stimulation. CONCLUSIONS: It is found that the measures are significantly lower when the subjects are under sound or reflexologic stimulation as compared to the normal state. The dimension increases with the degree of the cognitive activity. This suggests that when the subjects are under sound or reflexologic stimuli, the number of parallel functional processes active in the brain is less and the brain goes to a more relaxed state

Mechanical stability of thoracolumbar pedicle screw fixation. The effect of crosslinks.

STUDY DESIGN: Pedicle screw fixation for unstable thoracolumbar spine injuries is relatively new. The effect of one or two crosslinks on rotational and lateral bending stiffness was studied. OBJECTIVE: To determine the rotational and bending stiffness values of thoracolumbar fractures fixed by the AO's internal fixation system with zero, one, or two crosslinks. METHODS: Eight embalmed thoracolumbar spine segments. (T12-L2) were instrumented at T12 and L2 with a pedicle screw-rod system. Rotational stiffness was determined for 10 cycles to 2.5 degrees, 3.5 degrees, and 5 degrees of rotation, with and without one or two crosslinks, and lateral bending stiffness for 10 cycles to 0.25, 0.40, and 0.50 inch. The results showed a clear trend toward increased stiffness with crosslinks. RESULTS: The stiffness values of the two-crosslink construct at 2.5 degrees and 3.5 degrees of rotation were significantly higher than those of the zero-crosslink system. Also, the bending stiffness of the two-crosslink construct was significantly higher than that of no-crosslink system at all of the displacements. CONCLUSIONS: Rotational stiffness values of the two-crosslink construct were significantly higher than those of the zero-crosslink system, at 2.5 degrees and 3.5 degrees of rotation. Lateral bending stiffness of the two-crosslink system was higher than that of the zero-crosslink system at all levels of displacement.

Apoptosis is coordinately regulated with osteoblast formation during bone healing.

The ultimate fate of the expanded pool of osteoblasts formed following a typical bone injury is unclear. Since necrosis has not been described in the latter stages of bone healing, there must be some other mechanism by which obsolete osteoblasts are cleared from an injury site. We therefore evaluated the possibility that their removal is pre-programmed, by investigating the occurrence of apoptosis in rats that received a standardized bone injury. Histological evidence identical to that found in tissues known to exhibit apoptosis was obtained, thereby showing that programmed cell death was a normal concomitant of fracture healing. The concentration of apoptotic bodies reached its maximum after the differentiative response had peaked, suggesting that the two processes were coordinated. The same result was found in a second group of rats that received the same bone injury plus a simultaneous standardized soft-tissue injury. The combined injuries resulted in more osteoblasts and more apoptotic bodies, but an identical temporal relationship between the peak responses in the two parameters. The results suggested that osteoblasts were removed from the injury site via apoptosis, and that the process was coordinately regulated with differentiation. Since the number of apoptotic bodies per osteoblast varied during healing, it is likely that apoptosis was associated with healing and not merely with osteoblast concentration.

Open dislocation of the knee.

Traumatic open dislocation of the knee is an infrequent, severe injury associated with extensive ligamentous damage and a high incidence of vascular and neurologic involvement. Eighteen patients with 19 open knee dislocations were treated at the affiliated hospitals of the University of Pennsylvania and Louisiana State University Medical Center during an 18-year period. Final results included three above-knee amputations, one knee fusion, and one total knee arthroplasty. The 14 knees salvaged had only fair to poor function according to the Hospital for Special Surgery Knee Injury Score at an average follow-up of 36 months after the injury (average score = 29, range - 17 to 37). Nine patients (47%) had concomitant neurologic or vascular injury, and eight patients (42%) had wound healing difficulties. Five complete disruptions of the popliteal artery or posterior tibial artery underwent emergent revascularization, successful in three of the extremities, with the remaining two extremities requiring above-knee amputations. These massive injuries are often limb-threatening despite prompt surgical intervention and early antibiotic therapy. There is a very high incidence of infection and neurologic injury with a guarded prognosis for limb survival and satisfactory function.

Biomechanical study of atlantoaxial arthrodesis: transarticular screw fixation versus modified Brooks posterior wiring.

OBJECTIVE: The purpose of the present study was to compare the biomechanical stability of C1 and C2 vertebrae after treatment of ligamentous instability by either modified Brooks posterior wiring (MB) or transarticular screw (TAS) techniques. We hypothesized that the TAS technique would be more stable because of direct fixation through the facet joints. STUDY DESIGN: We studied the in vitro stability (arthrodesis) of TAS fixation of C1 and C2 versus that of MB. TAS fixation involves placing screws across the facets from posteriorly at C2 to the anterior surface of C1, plus a bone graft and posterior wiring of C1 and C2. METHODS: Cervical spines from nine individuals with an average age of sixty-two years (range 51 to 71 years) were harvested from cadavers (six male, three female). C1 and the segment from C2 to C5 were potted to allow motion only at the C1-C2 articulation. The specimens were destabilized by cutting the transverse ligament on both sides of the odontoid and the tectorial membrane between C1 and C2. The MB and TAS techniques were performed by methods similar to those described in the literature. The stiffness of the C1-C2 articulation of each specimen was tested under rotation, lateral bending, flexion, and anterior translation in random order. Intact and destabilized specimens fixed with either MB or TAS were tested in sequence. RESULTS: Significantly higher stiffness values in the elastic zone were obtained with the TAS technique than with the MB technique for all modes of testing (p < 0.002, t test). Values for the neutral zone (the region where minimal loads produce displacement) were not significantly different between the MB and TAS techniques (p > 0.1, t test). CONCLUSION: We conclude that stability is significantly enhanced by use of the TAS construct for treatment of ligamentous instability at the atlantoaxial joint for all motions tested in the present study.

Regulation of osteoblast levels during bone healing.

OBJECTIVE: To confirm the occurrence of programmed cell death of osteoblasts during bone healing and to evaluate the role of interleukin-1beta (IL-1beta) in regulating osteoblast concentration. STUDY DESIGN: Electron microscopic study of the response of rats to a controlled bone injury, and a randomized controlled study of the effect of IL-1beta administered continuously for three days. METHODS: A standardized defect (1.1 millimeter in diameter, 0.5 millimeter deep) was created unilaterally on the anteromedial surface of the tibia. In some animals, the injury site was recovered five days after operation and processed for ultrastructural evaluation of osteoblasts in the callus. In another group, IL-1beta was delivered to the bone defect using micro-osmotic pumps (0.5 nanograms/hour); control rats received vehicle only. The bones were recovered one to fourteen days after injury, and concentrations of proliferating cells, osteoblasts, and apoptotic bodies were determined. The amount of callus that formed in the defect was measured. RESULTS: Osteoblasts in the callus exhibited ultrastructural changes characteristic of cells undergoing apoptosis, including condensation of chromatin, membrane blebbing, formation of apoptotic bodies, and phagocytosis by nearby osteoblasts. Addition of IL-1beta significantly increased the number of osteoblasts at the injury site and significantly decreased the number of apoptotic bodies in relation to the number of osteoblasts. The amount of callus in the bone defect was not affected by IL-1beta treatment. CONCLUSION: The role of programmed cell death of osteoblasts as a normal concomitant of bone healing was confirmed. Evidence was found suggesting that IL-1beta mediated the appearance and disappearance of osteoblasts, possibly by affecting the rates of differentiation and apoptosis, respectively. Understanding these mechanisms conceivably could lead to the ability to control osteoblast levels at an injury site.

Tibial plateau fractures: standardized evaluation of operative results.

Twenty patients with fractures of the tibial plateau were treated operatively by a single surgeon experienced in the techniques advocated by the Association for the Study of Internal Fixation (AO/ASIF). Patients were reviewed an average of 27.4 months postoperatively. Results are reported and evaluated according to standardized criteria recommended in the literature. In addition, subjective and objective evaluation parameters were integrated into a 100-point knee rating score. Thirteen patients had good or excellent results. Poor results were attributed to the severity of the fractures, associated soft tissue injuries, and postoperative complications. Results of patients treated in a similar manner and reported in the literature are reviewed. The recent emphasis on operative treatment of displaced tibial plateau fractures requires detailed uniform reporting and evaluation of results to allow comparison between series and to improve outcome.

Anatomic variations of the blood supply of the soleus muscle.

A total of 36 cadaver and fresh amputation specimens were studied by dissection. Two vascular patterns were identified--a segmental posterior tibial artery (Type 1) and a proximally dominant posterior tibial artery (Type 2). Type 1 was seen in 77.8% of cases, and Type 2 in 22.2%. Injection studies in five fresh specimens demonstrated numerous cross-connections between the two halves of the muscle. A distally based hemisoleus flap should not be performed when a Type 2 vascular pattern is encountered. Also, vascular cross-connections between the two halves of the soleus muscle should be preserved, when possible.

Analysis of mechanical factors affecting fixation of olecranon fractures.

Fractures of the most distal part of the olecranon process differ from more proximal fractures because a plane of instability exists between the humerus and the radial head. Thus, the fixation of these fractures must resist the deforming forces of the forearm flexor muscles. The investigators fixed 10 paired cadaver ulnae with either the tension-band wire technique or a one-third tubular plate, and tested the specimens to simulate the effect of the biceps and brachialis muscles. The average maximum fixation stiffness for specimens fixed with the one-third tubular plate was found to be 163 N/mm compared with 53 N/mm for the tension-band wire group. This study indicates that for fractures of the distal part of the olecranon, fixation with screws and a one-third tubular plate affords better resistance to the forces applied by the brachialis and the biceps brachii than the tension-band wire technique.

Elman neural networks for dynamic modeling of epileptic EEG.

In this paper, autoregressive modeling technique and neural network based modeling techniques are used to model and simulate electroencephalogram (EEG) signals. EEG signal modeling is used as a tool to identify pathophysiological EEG changes potentially useful in clinical diagnosis. The normal, background and epileptic EEG signals are modeled and the dynamical properties of the actual and modeled signals are compared. Chaotic invariants like correlation dimension (D(2)), largest Lyapunov exponent (lambda(1), Hurst exponent (H) and Kolmogorov entropy (K) are used to characterize the dynamical properties of the actual and modeled signals. Our study showed that the dynamical properties of the EEG signal modeled using neural network (NN) techniques are very similar to that of the signal.

Prophylactic and therapeutic fixation of weight-bearing long bones with metastatic cancer.

BACKGROUND: We retrospectively studied the duration of operations and the hospitalizations for impending and manifest fractures of weight-bearing long bones with metastatic disease, which has rarely been done. METHODS: The duration of operative fixation and the hospital stay in patients with an impending (n = 7) or actual (n = 15) fracture in a weight-bearing long bone with metastatic tumor were assessed, including symptomatic response, posttreatment mobility, and survival rate. RESULTS: Most patients had significant relief of pain. More than half of patients with impending fracture and 80% with actual fracture were ambulatory after therapy; 3-year survival rates were 29% and 13%, respectively. Corresponding mean durations for the operations were 175 minutes and 185 minutes, respectively; mean durations of hospitalization were 22 days and 16 days, respectively. CONCLUSION: Surgical fixation of fractures in weight-bearing long bones with metastatic cancer does not require excessive operative time as compared with that of impending fractures, does not extend hospitalization, and has an acceptable risk-reward ratio.

The natural history of cervical spondylotic myelopathy.

This is a retrospective study of twenty-two patients with cervical spondylotic myelopathy who were admitted to the hospital for surgical treatment of their neurological condition. The purpose of the study was to evaluate the presenting symptoms, factors affecting the diagnosis and the course of the disease prior to surgical intervention. The earliest consistent symptom in all of our patients was a gait abnormality. The course of the disease was one of progressive deterioration. Spontaneous regression did not occur in any of the cases. The vagueness of the initial complaints led to considerable delay in the diagnosis (average of 6.3 years). Magnetic Resonance Imaging (MRI) was the most useful test in confirming the diagnosis.

The fate of intraarticular loose bodies of meniscus origin in canine species.

A potential risk of arthroscopic meniscectomy is the retention of debris of meniscus origin in the knee joint. This prospective study analyzes the fate of loose bodies of meniscus origin placed into the canine knee joint. At 12 weeks, 16.7% of the free fragments were completely degraded, 16.7% were absorbed by the synovium, and 66.6% were loose, located between synovial folds. At 12 weeks, 93.3% of the fragments had disappeared, and the remaining fragments had decreased 70% in length and 50% in width. A focus of calcification was present in one fragment at 12 weeks. By three weeks, all loose bodies had a pseudocapsule composed of cells with intense fibroblastic activity, occasional mitoses, and a loss of connective tissue matrix at the periphery. A mononuclear leucocytic response was present in the synovium at 12 weeks in four of the five dogs. Free fragments of meniscus origin are most commonly degraded completely by 12 weeks. Enzymatic digestion, mechanical abrasion, and synovial phagocytosis are processes that may contribute to this phenomenon.

Effect of femoral fracture and intramedullary fixation on lung capillary leak.

BACKGROUND: Pulmonary injury is an important complication in the trauma patient with long-bone fractures. The purpose of this study was to determine the effect of femoral fracture or fracture and intramedullary fixation on lung capillary leak. The contribution of leukocytes to lung injury in this model was also determined. METHODS: The pulmonary capillary filtration coefficient was determined in lungs of rats after femur fracture or fracture and reamed or unreamed intramedullary fixation. Pulmonary arterial vascular resistance and lung neutrophil content were also determined. RESULTS: Fracture alone did not cause lung injury, whereas fracture and intramedullary fixation elicited lung capillary leak. Fracture alone and intramedullary fixation increased pulmonary vascular resistance, whereas unreamed intramedullary fixation caused lung leukosequestration. CONCLUSION: Femoral fracture alone does not cause an increase in pulmonary microvascular permeability. Femoral fracture and intramedullary fixation causes lung capillary leak, which is not increased by reaming the femoral canal.

Meniscal abnormalities of the knee: 3DFT fast-scan GRASS MR imaging.

The ability to use fast-scan techniques to obtain MR images without sacrificing diagnostic accuracy is a desirable goal in MR imaging. We describe a series of patients in whom fast-scan MR imaging was found to be equal to conventional spin-echo imaging in the detection and characterization of meniscal abnormalities. Thirty-five patients with suspected meniscal tears were studied with fast-scan imaging (3DFT-GRASS), and the results were compared with those of conventional spin-echo imaging. Three-millimeter contiguous sections through the entire knee were obtained in 5 min by using the 3DFT-GRASS technique. 3DFT-GRASS and spin-echo images agreed in all cases regarding the presence or absence of an abnormality and its degree of severity. We conclude that fast-scan 3DFT-GRASS MR imaging is useful when screening the knee for the presence of meniscal abnormalities.