Endothelial cell CD36 regulates membrane ceramide formation, exosome fatty acid transfer and circulating fatty acid levels.

Endothelial cell (EC) CD36 controls tissue fatty acid (FA) uptake. Here we examine how ECs transfer FAs. FA interaction with apical membrane CD36 induces Src phosphorylation of caveolin-1 tyrosine-14 (Cav-1Y14) and ceramide generation in caveolae. Ensuing fission of caveolae yields vesicles containing FAs, CD36 and ceramide that are secreted basolaterally as small (80-100 nm) exosome-like extracellular vesicles (sEVs). We visualize in transwells EC transfer of FAs in sEVs to underlying myotubes. In mice with EC-expression of the exosome marker emeraldGFP-CD63, muscle fibers accumulate circulating FAs in emGFP-labeled puncta. The FA-sEV pathway is mapped through its suppression by CD36 depletion, blocking actin-remodeling, Src inhibition, Cav-1Y14 mutation, and neutral sphingomyelinase 2 inhibition. Suppression of sEV formation in mice reduces muscle FA uptake, raises circulating FAs, which remain in blood vessels, and lowers glucose, mimicking prominent Cd36-/- mice phenotypes. The findings show that FA uptake influences membrane ceramide, endocytosis, and EC communication with parenchymal cells.

A nonlinear model of passive muscle viscosity.

The material properties of passive skeletal muscle are critical to proper function and are frequently a target for therapeutic and interventional strategies. Investigations into the passive viscoelasticity of muscle have primarily focused on characterizing the elastic behavior, largely neglecting the viscous component. However, viscosity is a sizeable contributor to muscle stress and extensibility during passive stretch and thus there is a need for characterization of the viscous as well as the elastic components of muscle viscoelasticity. Single mouse muscle fibers were subjected to incremental stress relaxation tests to characterize the dependence of passive muscle stress on time, strain and strain rate. A model was then developed to describe fiber viscoelasticity incorporating the observed nonlinearities. The results of this model were compared with two commonly used linear viscoelastic models in their ability to represent fiber stress relaxation and strain rate sensitivity. The viscous component of mouse muscle fiber stress was not linear as is typically assumed, but rather a more complex function of time, strain and strain rate. The model developed here, which incorporates these nonlinearities, was better able to represent the stress relaxation behavior of fibers under the conditions tested than commonly used models with linear viscosity. It presents a new tool to investigate the changes in muscle viscous stresses with age, injury and disuse.

Sentinel node staging in colon carcinoma: value of sentinel lymph node biopsy with radiocolloid and blue staining.

BACKGROUND: Nodal staging accuracy is important in the prognosis and selection of patients for chemotherapy. This prospective study aims to assess the feasibility and accuracy of the sentinel lymph node procedure (SNP) using radiocolloid and blue dye in colon carcinoma. METHODS: In 56 patients, lymphatic mapping was accomplished by means of intraoperatively injecting patent blue and nanocoll subserosally around the tumour. Sentinel nodes (SNs) were harvested ex-vivo. Nodes were stained with H&E. If lymph nodes were interpreted as negative for metastatic tumour, serial sectioning and immunohistochemical staining were performed. RESULTS: At least one SN was detected in 49 of 53 patients (92.5%). Three patients were excluded because of preoperatively detected metastases. Overall, 121 SN were harvested with a mean of 2.2 SN/patients. Eighteen patients had tumour positive nodes. In four patients, pathological nodes were palpable during operation and were excluded. The SN was histologically negative in 2 of 14 patients with positive nodes (false-negative rate 14.3%). In 5 of 14 patients with positive nodes, the SN was the exclusive site of regional nodal metastasis. Four patients were upstaged by immunohistochemical staining (28.6%). The negative predictive value was 93.9% and the overall accuracy 95.6%. Scintigraphy was done in 17 patients. In three patients the SN was detected only by this modality. DISCUSSION: The SN biopsy with the combined technique proved a feasible technique with a steep learning curve. It can change the initial staging from stage II to stage III colon carcinoma. Scintigraphy can improve the success rate of the technique.

Effects of intravenous lidocaine overdose on cardiac electrical activity and blood pressure in the horse.

This study aimed to identify blood serum lidocaine concentrations in the horse which resulted in clinical signs of intoxication, and to document the effects of toxic levels on the cardiovascular and cardiopulmonary systems. Nineteen clinically normal mature horses of mixed breed, age and sex were observed. Lidocaine administration was initiated in each subject with an i.v. loading dose of 1.5 mg/kg bwt and followed by continuous infusion of 0.3 mg/kg bwt/min until clinical signs of intoxication were observed. Intoxication was defined as the development of skeletal muscle tremors. Prior to administration of lidocaine, blood samples for lidocaine analysis, heart rate, mean arterial blood pressure, systolic blood pressure, diastolic blood pressure, respiratory rate and electrocardiographic (ECG) data were collected. After recording baseline data, repeat data were collected at 5 min intervals until signs of intoxication were observed. The range of serum lidocaine concentrations at which the clinical signs of intoxication were observed was 1.85-4.53 microg/ml (mean +/- s.d. 3.24 +/- 0.74 microg/ml). Statistically significant changes in P wave duration, P-R interval, R-R interval and Q-T interval were observed in comparison to control values, as a result of lidocaine administration. These changes in ECG values did not fall outside published normal values and were not clinically significant. Heart rate, blood pressures and respiratory rates were unchanged from control values. This study establishes toxic serum lidocaine levels in the horse, and demonstrates that there were no clinically significant cardiovascular effects with serum lidocaine concentrations less than those required to produce signs of toxicity.

Adjunctive use of endoscopy during posterior fossa surgery to treat cranial neuropathies.

OBJECTIVE: The objective of this study was to determine the utility and safety of rigid endoscopy as an adjunct during posterior fossa surgery to treat cranial neuropathies. METHODS: A suboccipital craniotomy was performed for 19 patients with non-neoplastic processes involving the Vth, VIIth, and/or VIIIth cranial nerves. Ten patients with trigeminal neuralgia (n = 8), hemifacial spasm (n = 1), or intractable tinnitus (n = 1) underwent primarily microvascular decompression procedures. One patient with geniculate neuralgia underwent nervus intermedius sectioning combined with microvascular decompression. Eight patients underwent unilateral vestibular nerve neurectomies for treatment of Meniere's disease. A 0- or 30-degree rigid endoscope was used in conjunction with the standard microscopic approach for all procedures. RESULTS: All patients experienced resolution or significant improvement of their preoperative symptoms after posterior fossa surgery. The endoscope allowed improved definition of anatomic neurovascular relationships without the need for significant cerebellar or brainstem retraction. Cleavage planes between the cochlear and vestibular nerves entering the internal auditory canal and sites of vascular compression could not be microscopically observed for several patients; however, endoscopic identification was possible for all patients. There were no complications related to the use of the endoscope. CONCLUSION: The rigid endoscope can be used safely during posterior fossa surgery to treat cranial neuropathies, and it allows improved observation of the cranial nerves, nerve cleavage planes, and vascular anatomic features without significant cerebellar or brainstem retraction.

Pseudallescheria boydii infection of the nasal cavity of a horse.

An 18-year-old 454-kg (1,000-lb) American Quarter Horse gelding was evaluated because of chronic intermittent malodorous right-sided nasal discharge. Endoscopy revealed a mycotic plaque in the nasal cavity adjacent to the nasomaxillary opening of the right caudal maxillary sinus. The nasomaxillary opening appeared to be larger than normal. Fungal culture of specimens of the mycotic plaque yielded Pseudallescheria boydii. The horse was treated with 2% miconazole intranasally, sodium iodide i.v., and potassium iodide p.o. Thirty and 60 days after treatment was initiated, the nasal cavity was found to be free of infection.

The effect of oxytocin on contractility of the equine oesophagus: a potential treatment for oesophageal obstruction.

This study was performed to determine the effect of administration of i.v. oxytocin on the contractility of the musculature associated with the equine oesophagus. Nine clinically normal horses were fitted with a nasogastric tube modified with inflatable latex cuffs. These cuffs were connected to piezoelectric pressure recording devices. Oxytocin in 3 different doses or saline controls were administered i.v. in a randomised block pattern. Systolic blood pressure, ECG, heart rate and nasogastric tube cuff pressures were then measured for 60 min. Administration of oxytocin i.v. at 0.11 and 0.22 iu/kg bwt, resulted in a short-term statistically significant relaxation of the musculature of the equine oesophagus. When oxytocin was administered at 0.11, 0.22 and 0.44 iu/kg bwt, no clinically significant cardiovascular changes were seen. In approximately 5% of the oxytocin administrations, signs of mild short-term abdominal discomfort were observed. In clinical cases of noncomplicated oesophageal obstruction, it is suggested that reduction in tone of oesophageal musculature may result in passage of oesophageal obstructions with reduced risk of oesophageal injury when compared to other traditional treatments.

Identification of a novel signal sequence that targets transmembrane proteins to the nuclear envelope inner membrane.

Herpesvirus maturation requires translocation of glycoprotein B homologue from the endoplasmic reticulum to the inner nuclear membrane. Glycoprotein B of human cytomegalovirus was used in this context as a model protein. To identify a specific signal sequence within human cytomegalovirus glycoprotein B acting in a modular fashion, coding sequences were recombined with reporter proteins. Immunofluorescence and cell fractionation demonstrated that a short sequence element within the cytoplasmic tail of human cytomegalovirus glycoprotein B was sufficient to translocate the membrane protein CD8 to the inner nuclear membrane. This carboxyl-terminal sequence had no detectable nuclear localization signal activity for soluble beta-Galactosidase and could not be substituted by the nuclear localization signal of SV40 T antigen. For glycoprotein B of herpes simplex virus, a carboxyl-terminal element with comparable properties was found. Further experiments showed that the amino acid sequence DRLRHR of human cytomegalovirus glycoprotein B (amino acids 885-890) was sufficient for nuclear envelope translocation. Single residue mutations revealed that the arginine residues in positions 4 and 6 of the DRLRHR sequence were essential for its function. These results support the view that transmembrane protein transport to the inner nuclear membrane is controlled by a mechanism different from that of soluble proteins.

Preclinical evaluation of benzoporphyrin derivative combined with a light-emitting diode array for photodynamic therapy of brain tumors.

OBJECTIVE: The aim of this study was to investigate the second-generation photosensitizer benzoporphyrin derivative (BPD) and a novel light source applicator based on light-emitting diode (LED) technology for photodynamic therapy (PDT) of brain tumors. METHODS: We used a canine model to investigate normal brain stem toxicity. Twenty-one canines underwent posterior fossa craniectomies followed by PDT with BPD. These animals were compared to light only and BPD control. In addition, we investigated the ability of BPD and LED to cause inhibition of cell growth in canine glioma and human glioma cell lines, in vitro. The biodistribution of BPD labeled with 111In-BPD in mice with subcutaneous and intracerebral gliomas and canines with brain tumors was studied. RESULTS: The in vivo canine study resulted in a maximal tolerated dose of 0.75 mg/kg of BPD and 100 J/cm(2) of LED light for normal brain tissue. The in vitro study demonstrated 50% growth inhibition for canine and human glioma cell lines of 10 and 4 ng/ml, respectively. The mucine study using 111In-BPD showed a tumor to normal tissue ratio of 12:1 for intracerebral tumors and 3.3:1 for subcutaneous tumors. Nuclear scans of canines with brain tumors showed uptake into tumors to be maximal from 3 to 5 h. CONCLUSION: Our study supports that BPD and LED light sources when used at appropriate drug and light doses limit normal brain tissue toxicity at doses that can cause significant glioma cell toxicity in vitro. In addition, there is higher BPD uptake in brain tumors as compared to normal brain in a mouse glioma model. These findings make BPD a potential new-generation photosensitizer for the treatment of childhood posterior fossa tumors as well as other malignant cerebral pathology.

Adjunctive use of endoscopy during acoustic neuroma surgery.

OBJECTIVE/HYPOTHESIS: In specific clinical situations, endoscopes offer better visualization than the microscope during acoustic neuroma (vestibular schwannoma) surgery and can therefore decrease the incidence of the postoperative complications of cerebrospinal fluid (CSF) leakage and recurrence of tumor. This study was undertaken to determine if the use of adjunctive endoscopy provides complementary information to the operating surgeon during surgery for acoustic neuromas. METHOD: Seventy-eight patients with acoustic neuromas underwent tumor excision by two neurotologists (PAW., D.S.P.), together with their respective neurosurgical partners, via a retrosigmoid (suboccipital) approach (n = 68), translabyrinthine approach (n = 7), or middle cranial fossa approach (n = 3). Endoscopy with a rigid glass lens endoscope was used during tumor removal to examine posterior fossa neurovascular structures, and after tumor excision to inspect the internal auditory canal (IAC), inner ear, and middle ear, depending on the approach used. One of the authors (D.S.P.) has not used adjunctive endoscopy during resections via the translabyrinthine and middle cranial fossa approaches, and therefore, these cases were excluded from the data collection and analysis. RESULTS: Complete tumor excision was achieved in 73 patients. Endoscopy allowed improved identification of tumor and adjacent neurovascular relationships in all cases. In addition, residual tumor at the fundus of the IAC (n = 11) and exposed air cells (n = 24) not seen with the microscope during retrosigmoid approaches were identified endoscopically. In one of the translabyrinthine cases, the endoscope allowed identification of open air cells not visualized with the microscope. None of the 78 patients developed CSF rhinorrhea. Incorporating the endoscope did not significantly increase operative time. CONCLUSIONS: Endoscopy can be performed safely during surgery to remove acoustic neuromas. The adjunctive use of endoscopy may offer some advantages including improved visualization, more complete tumor removal, and a lowered risk of CSF leakage.

Single-voxel proton MR spectroscopy of nonneoplastic brain lesions suggestive of a neoplasm.

BACKGROUND AND PURPOSE: MR spectroscopy is used to characterize biochemical components of normal and abnormal brain tissue. We sought to evaluate common histologic findings in a diverse group of nonneoplastic diseases in patients with in vivo MR spectroscopic profiles suggestive of a CNS neoplasm. METHODS: During a 2-year period, 241 patients with suspected neoplastic CNS lesions detected on MR images were studied with MR spectroscopy. Of these, five patients with a nonneoplastic diagnosis were identified retrospectively; a sixth patient without tissue diagnosis was added. MR spectroscopic findings consistent with a neoplasm included elevated choline and decreased N-acetylaspartate and creatine, with or without detectable mobile lipid and lactate peaks. RESULTS: The histologic specimens in all five patients for whom tissue diagnoses were available showed significant WBC infiltrates, with both interstitial and perivascular accumulations of lymphocytes, macrophages, histiocytes, and (in one case) plasma cells. Reactive astrogliosis was also prominent in most tissue samples. This cellular immune response was an integral component of the underlying disorder in these patients, including fulminant demyelination in two patients, human herpesvirus 6 encephalitis in one patient, organizing hematoma from a small arteriovenous malformation in one patient, and inflammatory pseudotumor in one patient. Although no histologic data were available in the sixth patient, neoplasm was considered unlikely on the basis of ongoing clinical and neuroradiologic improvement without specific therapy. CONCLUSION: Nonneoplastic disease processes in the CNS may elicit a reactive proliferation of cellular elements of the immune system and of glial tissue that is associated with MR spectroscopic profiles indistinguishable from CNS neoplasms with current in vivo MR spectroscopic techniques. Such false-positive findings substantiate the need for histologic examination of tissue as the standard of reference for the diagnosis of intracranial mass lesions.

Absence of the fragile X CGG trinucleotide repeat expansion in girls diagnosed with a pervasive developmental disorder.

The purpose of this study was to determine the prevalence of the fragile X (FRAX) CGG trinucleotide expansion in a population of young girls (n = 45) diagnosed with pervasive developmental disorder (PDD). Their mean age was 43.7 months (range, 25 to 132 months). Diagnoses included autistic disorder (n = 20), PDD (n = 23), and Asperger's syndrome (n = 2). Molecular FRAX testing was performed on all patients by using the Southern gene blot technique. Genomic DNA was digested with both EcoRI and EagI, fractionated on agarose gel, and blotted and probed with the radiolabeled StB12.3 FMR-1 probe. None of the subjects were found to have an expansion of CGG in either the 2.8 kb or 5.2 kb fragments. A 95% CI, for the prevalence of the FRAX mutation in female subjects with PDD, has an upper bound of 2.9%. We conclude that the prevalence of FRAX positivity in girls with PDD is lower than previously reported. This raises the question of whether any association between FRAX and PDD in female subjects is specific to PDD or is related rather to the presence of mental retardation.

Surgical exposure of the fundus of the internal auditory canal: anatomic limits of the middle fossa versus the retrosigmoid transcanal approach.

OBJECTIVE: To define the anatomic limitations and advantages of the middle cranial fossa and the retrosigmoid transcanal approaches in the exposure of the fundus of the internal auditory canal (IAC). STUDY DESIGN: A series of 15 cadaver temporal bone specimens were dissected and the measurements of the lateral recess of the IAC were made with a millimeter rule and rounded to the nearest quarter millimeter. METHODS: Retrospective case review, surgical observation, review, and measurements recorded from magnetic resonance scans. Surgical observations and measurements recorded from cadaver specimens. RESULTS: These results were compared with historical studies of the retrosigmoid transcanal approach. The results utilizing a combination of these approaches to remove acoustic neuromas at a tertiary referral center during the preceding 11 years are also presented. Previous studies have shown that for the retrosigmoid transcanal approach, it is impossible to expose 3 to 4 mm of the lateral recess of the IAC without violating the vestibule and/or the endolymphatic duct. This has led some authors to advocate the middle cranial fossa approach to the IAC when hearing preservation is a consideration. The current study shows that the falciform crest obscures the inferior half of the fundus. This creates a pocket that cannot be visualized, which on average is 1.82 x 2.33 mm. CONCLUSION: The fundus of the IAC cannot be completely exposed without violating the labyrinth through either the posterior fossa or middle fossa approach. The clinical implications of these studies are unknown at this time. Low recurrence rates are achieved with both approaches. The anatomic limitations of both approaches must still be considered when planning or performing these approaches, to minimize the risk of recurrence.

Presentation of nursing diagnosis content in fundamentals of nursing textbooks.

The technique and rationale for the use of nursing diagnosis generally are introduced early in the undergraduate curriculum. The three purposes of this descriptive study were to describe the general characteristics and presentation of content on nursing diagnosis in fundamentals of nursing textbooks; describe how the content from the theoretical chapter(s) in nursing diagnosis is carried through in the clinical chapters; and describe how content on diagnostic errors is presented. Although most of the textbooks presented content on nursing diagnosis in a similar fashion, the clinical chapters of the books did not follow the same pattern. Content on diagnostic errors was inconsistent. Educators may find this an effective methodology for reviewing textbooks.

Cirsoid aneurysm treatment by percutaneous injection of sodium tetradecyl sulfate.

BACKGROUND: Cirsoid aneurysms are uncommon arteriovenous fistulas of the scalp. Surgery for these lesions can be difficult; transarterial embolization is rarely curative, while embolization of the venous pouch with permanent agents usually necessitates subsequent surgical removal of the embolic material. The ideal embolic agent would be one that is safe and effective, commercially available, and would not require subsequent removal. METHODS: We treated an arteriovenous fistula of the scalp with direct puncture and injection of sodium tetradecyl sulfate, a commercially available sclerosing agent. RESULTS: Control angiography immediately following percutaneous injection of sotradecol into the fistula showed decreased flow but not complete closure of the lesion. However, within several days of the embolization, the patient's scalp pain and mass resolved. Four months after embolization, MRA demonstrated no evidence of residual or recurrent fistula. Color doppler flow imaging demonstrated only slightly decreased vascular resistance in the distal superficial temporal artery, possibly indirect evidence of persistent micro-fistulae. Twenty-three months after the procedure, the patient continued to be asymptomatic and had no palpable lesion. CONCLUSIONS: Percutaneous injection of sotradecol can be considered as one of the treatment options for arteriovenous fistula of the scalp. Further experience is needed to compare the safety and effectiveness of sotradecol with other agents currently used in the treatment of scalp arteriovenous fistulae.

Light-emitting diodes as a light source for intraoperative photodynamic therapy.

The development of more cost-effective light sources for photodynamic therapy of brain tumors would be of benefit for both research and clinical applications. In this study, the use of light-emitting diode arrays for photodynamic therapy of brain tumors with Photofrin porfimer sodium was investigated. An inflatable balloon device with a light-emitting diode (LED) tip was constructed. These LEDs are based on the new semiconductor aluminum gallium arsenide. They can emit broad-spectrum red light at high power levels with a peak wavelength of 677 nm and a bandwidth of 25 nm. The balloon was inflated with 0.1% intralipid, which served as a light-scattering medium. Measurements of light flux at several points showed a high degree of light dispersion. The spectral emission of this probe was then compared with the absorption spectrum of Photofrin. This analysis showed that the light absorbed by Photofrin with the use of the LED source was 27.5% of that absorbed with the use of the monochromatic 630-nm light. Thus, to achieve an energy light dose equivalent to that of a laser light source, the LED light output must be increased by a factor of 3.63. This need for additional energy is the difference between a 630- and 677-nm absorption of Photofrin. Using the LED probe and the laser balloon adapter, a comparison of brain stem toxicity in canines was conducted. LED and laser light showed the same signs of toxicity at equivalent light energy and Photofrin doses. The maximal tolerated dose of Photofrin was 1.6 mg/kg, using 100 J/cm2 of light energy administered by laser or LED. This study concludes that LEDs are a suitable light source for photodynamic therapy of brain tumors with Photofrin. In addition, LEDs have the potential to be highly efficient light sources for second-generation photosensitizers with absorption wavelengths closer to the LED peak emission.

Association of pulmonary artery size on chest radiograph with residence at elevated altitudes.

Mean pulmonary artery pressure (PAP) has been demonstrated to correlate with measures of pulmonary artery size. We tested the hypothesis that residence at elevated altitudes, a determinant of mean PAP, can be associated with increases in pulmonary artery size on chest radiographs from healthy adults. The study population consisted of three groups of asymptomatic, nonsmoking adults without hazardous respiratory exposures living at altitudes approximating 0 m (group 1, n = 197), 1,400 m (group 2, n = 145), and 2,600 m above sea level (group 3, n = 196). The width of the right descending pulmonary artery (RDPA) was measured at its widest diameter before bifurcation. In a multivariate regression model, significant associations were detected between RDPA width and residence at elevated altitudes (F = 13.84, p = 0.0002), age (F = 32.49, p < 0.0001), and gender (F = 56.10, p < 0.0001), with 36% of the variability of the measure determined by these three variables (r2 = 0.36). Mean RDPA width increased as altitude at residence increased. Larger mean values were noted among older individuals and males. We conclude that residence at altitudes of 1,400 and 2,600 m above sea level is associated with increases in pulmonary artery size on chest radiograph.

Moraxella (Branhamella) catarrhalis bacteremia in children. A report of two patients and review of the literature.

We report two cases of Moraxella catarrhalis (M. catarrhalis) bacteremia in apparently healthy children. One patient had bilateral otitis media and the other had pharyngitis and sinusitis; both patients had uncomplicated clinical courses. A literature review revealed 22 reported cases of M. catarrhalis bacteremia in children, 14 (63%) of which occurred in patients who had no identified underlying condition. Eight (36%) cases were seen in children who were immunocompromised. Nine (40%) patients presented with either purpura, petechia, or a maculopapular rash. M. catarrhalis is well known as a respiratory pathogen, but it has not been recognized as a common cause of unsuspected bacteremia in children.

Cervical carcinoma: determination of recurrent tumor extent versus radiation changes with MR imaging.

PURPOSE: To evaluate the effectiveness of magnetic resonance (MR) imaging for assessment of the present and extent of tumor recurrence as determined with pathologic and surgical findings. MATERIALS AND METHODS: MR findings were retrospectively examined in 37 patients with a history of cervical carcinoma. Inter- and intraobserver variability was analyzed. Surgical or pathologic results were acquired in 34 of these patients; the remaining three patients were clinically followed up for at least 4 years. RESULTS: MR imaging allowed correct detection of recurrent tumor in 18 of 21 patients who had histologically documented recurrence. It helped correctly exclude recurrent disease in 15 of 16 patients. Sensitivity and specificity for detection of recurrence was 86% and 94%, respectively. Good intra- and interobserver agreement was demonstrated. CONCLUSION: MR imaging is a useful modality for differentiation of recurrent cervical carcinoma from radiation changes. Determination of the extent of recurrence with MR imaging may offer clinical assistance in the selection of optimal therapy.