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.

Neonatal intraventricular hemorrhage due to an intracranial arteriovenous malformation: a case report.

A full-term newborn infant with intraventricular hemorrhage due to a small arteriovenous malformation draining into the vein of Galen is presented. Other reported series are reviewed, and differences between this case and the usual pattern of morbidity are discussed. The use of computerized tomography is demonstrated.

Cerebral toxoplasmosis in an immunocompromised host. A precise and rapid diagnosis by electron microscopy.

In immunocompromised patients with cerebral toxoplasmosis, the tachyzoite forms rather than cystic and bradyzoite forms of the protozoon are commonly seen. These tachyzoites are minute, scattered among cellular debris, sometimes lodged inside macrophages and neutrophils, and difficult to visualize by light microscopy, even with special stains. Immunodiagnostic tests may be falsely negative due to inability of the host to produce appropriate antibodies. Isolation of the organism is dangerous because Toxoplasma gondii is highly infective. In this situation, transmission electron microscopy (EM) may be a diagnostic tool of choice. It demonstrates the fine definitive features of the protozoon and can be expedited to give results in five hours. Further evaluation of EM for diagnosing possible toxoplasmosis in immunocompromised patients is indicated.

MR of the diaphragma sellae.

The appearance of the diaphragma sellae is described in cryomicrotomic sections and on MR in patients with and without intra- and suprasellar masses. On MR, it appears as a thin band of negligible signal that is best shown when adjacent CSF or a mass has greater signal intensity. Its position or absence can be used to differentiate intrasellar masses with suprasellar components from suprasellar masses.

Magnetic resonance imaging of the jugular foramen.

The jugular foramen in normal volunteers was studied with 1.5 T magnetic resonance (MR) systems in 3-mm-thick head- and surface-coil images. Anatomic sections through cadaver heads were correlated with the MR images to identify the jugular bulb and the course of cranial nerves IX-XI. Sagittal images were more useful than coronal or axial to show the course of these nerves through the skull base. MR demonstrates the anatomic relations of the jugular foramen (except its osseous margins) such that its primary use in evaluating this region can be anticipated.

Facial nerve enhancement in MR imaging.

The significance of facial nerve enhancement after IV gadolinium administration has not been determined. We evaluated the MR appearance of facial nerves (nonenhanced and enhanced) in patients without and with masses involving the temporal bone, internal auditory canal, or cerebellopontine angle. In patients without such masses, no facial nerve enhancement was seen. In the other group, four of 11 patients showed facial nerve enhancement and geniculate ganglion masses. Three of these four patients had neurofibromatosis; one had surgical verification of a facial nerve neurofibroma. Enhanced MR facilitates identification of abnormal facial nerves.

Neuroepithelial cysts of the lateral ventricles: MR appearance.

The MR imaging appearance of neuroepithelial cysts in the lateral ventricle is reported. Two cases of proven and two of presumed intraventricular neuroepithelial cysts are presented. In one case, MR observations documented spontaneous regression of a large intraventricular cyst. Theories regarding the origin of neuroepithelial cysts are briefly reviewed. Standard T1- and T2-weighted spin-echo pulse sequences were used to study cysts in the lateral ventricles in axial, coronal, and sagittal planes. The cyst wall can be demonstrated reliably with MR images, eliminating the need for CT and/or contrast ventriculography. MR may also be useful in monitoring cyst size on serial examinations.

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.

Validation of a new technique for measurement of intracranial pressure with a scintillation counter.

Intracranial pressure sensors and subdural and subgaleal sensing tambours were used to measure the pressure difference between the intracranial and subgaleal spaces in two monkeys. The pressure differential was transmitted to fluid bathing a piston, to which an isotope source (145Pm) was attached. The radiation signal emanating through a fixed collimator was detected transcutaneously by a sodium iodide crystal contained within a photomultiplier tube connected to a scintillation counter. After in vitro testing of linearity, in vivo infusion studies were performed. Linearity between intracisternal pressure and radioactivity (r = 0.99; p less than 0.001) was established in the two experimental animals for an interval of 5 months and 1 year, respectively. Autopsy findings confirmed that the sensing tambours became encapsulated with a pseudomembrane that did not attenuate the pressure signal. The results of this investigation suggest that this method for measurement of intracranial pressure without transcutaneous connections may be suitable for long term monitoring of intracranial pressure.

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.

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.

Radiation therapy for incompletely resected meningiomas.

Twelve patients with incompletely resected meningiomas were treated with postoperative radiation therapy. Nine of these patients had previously undergone incomplete surgical resection, and three had suffered one or more postoperative recurrences. The median dose of irradiation was 5490 rads in 6 weeks (range 4800 to 6080 rads). All patients were followed with serial neurological examinations and computerized tomography (CT) scans. Median follow-up period was 54 1/2 months (range 20 to 120 months); 10 of the 12 patients were followed for longer than 42 months posttreatment. Nine patients had no clinical evidence of recurrent disease after radiation therapy, and CT scans confirmed lack of progression or a gradual decrease in tumor size. Three patients had tumor recurrences; two of these lesions appeared at 70 and 112 months after irradiation as extracranial extensions beyond the margin of the irradiation field, and one has exhibited recurrence within the field at 48 months. Three patients who were treated after prior recurrences have demonstrated prolonged progression-free intervals in comparison to the intervals between recurrences prior to irradiation. No significant complications attributable to treatment have been found in any of the patients. These results are discussed in relation to previous reports of the incidence of meningioma recurrence after incomplete resection.

Estrogen-receptor protein in intracranial meningiomas.

The increased frequency of meningiomas in women compared with men, and the rapidly progressive course of these tumors in pregnant patients suggest that hormones may be involved in this disease. Tumor tissue from six patients with meningiomas was analyzed for estrogen-receptor protein. Two patients had tumors with very high concentrations of this protein, approaching that found in hormonally sensitive breast carcinoma. The biochemical and possible clinical significance of these findings is discussed.

PIP: Because the epidemiology and clinical course of some meningiomas suggest that these tumors may be hormonally sensitive and that they may contain estrogen receptor protein, and because two-thirds of all intracranial meningiomas and 80% of all spinal meningiomas occur in women, the relationship between pregnancy (and its hormonal alterations) and development of these meningiomas was studied using tissue samples obtained from 6 patients with meningiomas. These samples were analyzed for estrogen receptor protein and were then correlated with preoperative and intraoperative observations. The 6 cases studies are presented, and the following results were apparent. Significant quantities of estrogen receptor protein were found in tissue from 4/6 patients (212 [ this patient was 10 weeks pregnant] , 62, 57, and 223 total receptors in fmol/gm.). Tumor tissue from 3/4 women and 1/2 men contained measurable estrogen receptor protein. The highest concentrations were found in 2 mid-30-year-old premenopausal women (1 of whom was 10 weeks pregnant). Common findings in these cases were premenopausal status, prominent tumor vascularity, and adjacent tissue invasion. The remaining female whose tissue sample showed estrogen receptor protein was classified as a perimenopausal woman based on a 6-month period of amenorrhea within the previous year. No significant estrogen-receptor activity was found in the cases of 1 man and 1 woman. The sedimentation coefficient of the estrogen receptor protein varied among the tissue samples. In 2 cases, the receptor protein was present in primarily the 4s fraction, whereas in the 2 other cases the concentration was greatest in the 8s sedimenting fraction.

Craniosynostosis in vitamin D-resistant rickets. A mouse model.

Craniosynostosis and associated craniofacial deformities, such as frontal bossing, often occur as symptoms of vitamin D-resistant rickets in children. Similar skull deformities develop in mice with X-linked dominant hypophosphatemia, the most common form of vitamin D-resistant rickets. These mice have a short, wide, high neurocranium, which suggested an inhibition of coronal suture growth. To study this question, we compared histologically the postnatal development of the coronal sutures in normal and hypophosphatemic mice between 1 and 13 weeks of age. Premature fusion of the coronal suture occurred in hypophosphatemic mice by 4 weeks of age. The proportion of the suture obliterated by bone varied among individual animals, but craniosynostosis was present in all animals studied at 4 weeks and older. Fusion of the coronal suture did not occur through 13 weeks of age in any of the normal mice studied. The x-linked hypophosphatemic mouse is an animal model that can be used to study the role of vitamin D-resistant rickets in the development of craniosynostosis, to relate craniosynostosis to the development of associated skull deformities, and to test new treatment procedures.

BSS Plus: a potential irrigating solution for neurosurgery.

BSS Plus is a pH-stable balanced salt solution similar to glutathione bicarbonate Ringer's solution. Extensively used in ophthalmology, it is of potential value in neurosurgery. In comparative tests of its effectiveness, 28 cats underwent bilateral irrigation of the surface of the cerebral cortex with normal saline on one side and BSS Plus on the other. After 2 hours, a marked decrease was seen in the surface pH of the hemisphere irrigated with normal saline but not of the hemisphere treated with BSS Plus. Blood-brain barrier changes (measured with Evans blue dye techniques) were more evident following saline irrigation. Somatosensory evoked potentials and cerebral blood flow were not significantly altered. Conventional light microscopy using three standard stains did not reveal a significant difference. Transmission electron microscopy studies were performed in 14 animals and scanning electron microscopy in six. In five animals both transmission and scanning electron microscopy studies were conducted after irrigation with both agents without a cottonoid cover and with immediate harvest of superficial layers from the living brain and immersion-fixation in glutaraldehyde. Tissue preservation was superior on the BSS Plus side in all studies. This agent may represent an improved irrigation solution for neurosurgery, but further studies are required.

Hemodynamic responses to acute quadriplegia with or without chest trauma.

This report describes the pathophysiology, as manifested by hemodynamic and blood volume determinations, in nine acutely quadriplegic patients studied in Vietnam. Four of the nine patients developed fulminating pulmonary edema while in the hospital and showed marked differences in the hemodynamic and blood volume data when compared with five patients who did not develop pulmonary edema. The unique hazard of excessive intravascular volume replacement in quadriplegic patients is documented, and effective diagnostic and therapeutic procedures are suggested. Related reports and physiological studies are discussed.

The role of photodynamic therapy in posterior fossa brain tumors. A preclinical study in a canine glioma model.

Photodynamic therapy was studied in dogs with and without posterior fossa glioblastomas. This mode of therapy consisted of intravenous administration of Photofrin-II at doses ranging from 0.75 to 4 mg/kg 24 hours prior to laser light irradiation in the posterior fossa. Tissue levels of Photofrin-II were four times greater in the tumor than in the surrounding normal brain. Irradiation was performed using 1 hour of 500 mW laser light at a wavelength of 630 nm delivered through a fiberoptic catheter directly into the tumor bed via a burr hole. All animals receiving a high dose (4 or 2 mg/kg) of Photofrin-II developed serious brain-stem neurotoxicity resulting in death or significant residual neurological deficits. A lower dose (0.75 mg/kg) of Photofrin-II produced tumor kill without significant permanent brain-stem toxicity in either the control animals or the animals with cerebellar brain tumors receiving photodynamic therapy.

Relationships between leaf age and the food quality of cottonwood foliage for the gypsy moth, Lymantria dispar.

The cottonwood tree, Populus deltoides, continues to produce leaves late into the growing season, exposing midseason herbivores to leaves of a wide range of maturity. Gypsy moth larvae preferred and grew best on the oldest cottonwood leaves and suffered higher mortality and 85% less growth when fed young, expanding leaves. Concentration of phenolics in the youngest leaves was 3 times that in the oldest leaves and was negatively correlated with caterpillar growth rate. The active phenolics were not identified; tannin was present but its concentration changed more with season than leaf age.