Definitive radiotherapy in the management of paragangliomas arising in the head and neck: a 35-year experience.

BACKGROUND: An evaluation of the treatment results for 104 patients with 121 paragangliomas of the temporal bone, carotid body, and/or glomus vagale who were treated with radiation therapy (RT) at the University of Florida between 1968 and 2004. METHODS: Eighty-nine paragangliomas (86%) were treated with conventional megavoltage techniques, 15 (14%) patients with stereotactic fractionated radiation therapy, 6 (6%) patients with stereotactic radiosurgery (SRS), and 11 (11%) patients with intensity-modulated radiation therapy (IMRT). RESULTS: There were 6 local recurrences. One recurrence was salvaged with additional RT. The actuarial local control and cause-specific survival rates at 10 years were 94% and 95%. The overall local control rate for all 121 lesions was 95%; the ultimate local control rate was 96%. The incidence of treatment-related complications was low. CONCLUSION: Fractionated RT offers a high probability of tumor control with minimal risks for patients with paragangliomas of the temporal bone and neck.

Rat carotid body chemosensory discharge and glomus cell HIF-1 alpha expression in vitro: regulation by a common oxygen sensor.

Addition of Pco ( approximately 350 Torr) to a normoxic medium (Po(2) of approximately 130 Torr) was used to investigate the relationship between carotid body (CB) sensory discharge and expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) in glomus cells. Afferent electrical activity measured for in vitro-perfused rat CB increased rapidly (1-2 s) with addition of high CO (Pco of approximately 350 Torr; Po(2) of approximately 130 Torr), and this increase was fully reversed by white light. At submaximal light intensities, the extent of reversal was much greater for monochromatic light at 430 and 590 nm than for light at 450, 550, and 610 nm. This wavelength dependence is consistent with the action spectrum of the CO compound of mitochondrial cytochrome a(3). Interestingly, when isolated glomus cells cultured for 45 min in the presence of high CO (Pco of approximately 350 Torr; Po(2) of approximately 130 Torr) in the dark, the levels of HIF-1 alpha, which turn over slowly (many minutes), increased. This increase was not observed if the cells were illuminated with white light during the incubation. Monochromatic light at 430- and 590-nm light was much more effective than that at 450, 550, and 610 nm in blocking the CO-induced increase in HIF-1 alpha, as was the case for chemoreceptor discharge. Although the changes in HIF-1 alpha take minutes and those for CB neural activity occur in 1-2 s, the similar responses to CO and light suggest that the oxygen sensor is the same (mitochondrial cytochrome a(3)).

A common oxygen sensor regulates the sensory discharge and glomus cell HIF-1alpha in the rat carotid body.

The relationships between the chemosensory discharge and glomus cells HIF-1alpha (hypoxia inducible factor 1alpha) in the rat carotid body in vitro were investigated using CO as a tool. Both chemosensory discharge and HIF-1alpha were stimulated by CO, although the former took only a few seconds and the latter a few minutes to develop. These developments were suppressed by light. By using the monochromatic lights, the action spectra were prepared. Lights of 430 nm 590 nm were most effective in suppressing the responses. It is known that these lights are the signature markers for cytochrome oxidase, making identification of the entities. Thus, cytochrome oxidase serves as a common oxygen sensor for both.

Effects of prolonged hypobaric hypoxia on carotid nerve endings and glomus cells. Changes in intercellular coupling.

Carotid bodies were removed from anesthetized rats kept under normobaric (640 Torr) and hypobaric conditions (380 Torr for 2-3 weeks). Slices (100-150 microm) of the organ were viewed under an inverted microscope for simultaneous stimulation and recording of coupled glomus cells and carotid nerve endings. The latter were identified by their more negative Em, high input resistance (Ro) and time-dependent rectification in response to negative current pulses. Also, when nerve endings had an Em more negative than -40 mV showed spontaneous activity in the form of mini-receptor potentials (mrps). Glomus cells had less negative Em and lower Ro. Prolonged hypobaric hypoxia did not change the Em of nerve endings and glomus cells. However, in both structures, Ro increased. Also, the mrps became smaller and occurred less frequently. Intercellular coupling was recognized when currents applied to one cell spread to adjoining ones. In the case of glomus cells (GC/GC coupling), it was mostly resistive and bidirectional. Coupling between nerve endings and glomus cells was more complex, When a glomus cell was stimulated, current spread to the nerve ending (GC/NE coupling) was similar in magnitude (2-3%) to coupling between GCs. However, when NE was stimulated current spread to GC (NE/GC coupling) was minimal (less than 0.1%) and transient (capacitive). Nerve endings were also bidirectionally and capacitively coupled (NE/NE coupling) with a median of 2,8%. Intracellularly injected Lucifer Yellow or Alexa 488 diffused to neighboring structures. Prolonged hypobaric hypoxia significantly tightened coupling modes GC/NE, NE/GC, and NE/NE but reduced GC/GC coupling. Tighter coupling was accompanied by lower coupling resistance, and the opposite occurred when intercellular coupling decreased. Increased GC/NE and reduced GC/GC coupling during hypobaric hypoxia may be partly responsible for the increased reactivity of these receptors under this condition.

CO-induced K(+) currents in rat glomus cells are insensitive to light unlike carotid body neural discharge and Vo(O(2)).

The hypothesis that the light sensitive properties of CO-induced chemosensory nerve (CSN) discharge and oxygen consumption of the carotid body (CB) were shared by the pre-synaptic glomus cells was tested. The light effect on K(+) currents were measured before and during perfusion of the isolated rat glomus cells with high P(CO) of 550 Torr during nomoxia (P(O(2)approximately equal 100 Torr) at extra-cellular pH 7.0 and intracellular pH 6.8 with HEPES buffer. CO increased the K(+) currents with a left ward shift of the reversal potential, which showed no light effect. Thus the K(+) permeability of the glomus cell membrane were not shared by the light-sensitive CSN discharge of the CB and oxygen consumption in the presence of high P(CO.)

Carotid body O2 chemoreception: respiratory and nonrespiratory aspects.

The respiratory and nonrespiratory hypotheses of O2 chemoreception in arterial chemoreceptors have been compared to provide a perspective that both mechanisms can potentially coexist. The nonrespiratory membrane mechanism operates at a relatively higher level of PO2 and that respiratory metabolic mechanisms at a lower level. The two mechanisms may overlap in the intermediate range of PO2.