Field size consistency of nominally matched linacs.

Given that there is increasing recognition of the effect that sub-millimetre changes in collimator position can have on radiotherapy beam dosimetry, this study aimed to evaluate the potential variability in small field collimation that may exist between otherwise matched linacs. Field sizes and field output factors were measured using radiochromic film and an electron diode, for jaw- and MLC-collimated fields produced by eight dosimetrically matched Varian iX linacs (Varian Medical Systems, Palo Alto, USA). This study used nominal sizes from 0.6 × 0.6 to 10 × 10 cm(2), for jaw-collimated fields, and from 1 × 1 to 10 × 10 cm(2) for MLC-collimated fields, delivered from a zero (head up, beam directed vertically downward) gantry angle. Differences between the field sizes measured for the eight linacs exceeded the uncertainty of the film measurements and the repositioning uncertainty of the jaws and MLCs on one linac. The dimensions of fields defined by MLC leaves were more consistent between linacs, while also differing more from their nominal values than fields defined by orthogonal jaws. The field output factors measured for the different linacs generally increased with increasing measured field size for the nominal 0.6 × 0.6 to 1 × 1 cm(2) fields, and became consistent between linacs for nominal field sizes of 2 × 2 cm(2) and larger. The inclusion in radiotherapy treatment planning system beam data of small field output factors acquired in fields collimated by jaws (rather than the more-reproducible MLCs), associated with either the nominal or the measured field sizes, should be viewed with caution. The size and reproducibility of the fields (especially the small fields) used to acquire treatment planning data should be investigated thoroughly as part of the linac or planning system commissioning process. Further investigation of these issues, using different linac models, collimation systems and beam orientations, is recommended.

Modulation of T lymphocyte function by neuropeptides. Evidence for their role as local immunoregulatory elements.

In mucosa-bearing organs with inherent lymphoid populations, classical modes for control of the immune response may be augmented by products of extrinsic sensory afferent nerve endings which arborize through the lamina propria compartment containing large numbers of T and B lymphocytes. Therefore, we sought to determine the role of neuropeptides (substance P, vasoactive intestinal peptide, and somatostatin) in immune response regulation by using a homogeneous line of T lymphocytes (AO40.1 hybrid), whose activation is driven by a specific Ag (OVA) and where the end point (IL-2 release) could not be contributed to by accessory or other cells. IL-2 was quantitated by the rate of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) metabolism with the use of a murine CD4+ IL-2-dependent T lymphocyte line, and dose-response effects of each neuropeptide were examined over a broad concentration range (10(-14)-10(-6) M) encompassing that regarded as physiologic. Vasoactive intestinal peptide stimulated IL-2 release at low concentrations with a marked effect at 10(-14) M that gradually returned to control levels by 10(-7) M. Somatostatin was associated with a substantial augmentation of AO40.1 T lymphocyte IL-2 release at 10(-10) to 10(-8) M concentrations, whereas substance P demonstrated a stimulatory effect only at high concentrations (10(-9) to 10(-6) M). Concomitant [3H]thymidine uptake studies suggested that changes in cell proliferation or viability did not account for neuropeptide-induced effects in our system. With several exceptions, similar results were found with mitogen (Con A)-stimulated AO40.1 cells and human colonic lamina propria mononuclear cells. It was concluded that the three study neuropeptides, over a broad range of concentrations, have profound stimulatory (and occasionally inhibitory) effects upon the function of a cloned T lymphocyte hybrid cell responding to specific Ag and that these events may reflect those of Ag-driven mucosal T lymphocytes exposed to neuropeptides in vivo.

Cycloheximide potentiation of prostaglandin E1- and cholera toxin-stimulated cyclic AMP accumulation in NG108-CC15 neuroblastoma-glioma hybrid cells.

Previous studies have demonstrated that catecholamine responsiveness in a variety of cells can be altered by inhibitors of RNA and protein synthesis. The neuroblastoma-glioma hybrid, NG108-CC15, which lacks catecholamine-stimulated accumulation of cyclic AMP, was investigated to determine if the responsiveness to prostaglandin E1 (PGE1) could be modified by inhibitors of protein synthesis. Cycloheximide in a time-dependent manner potentiated the ability of prostaglandin E1 to stimulate accumulation of intracellular cyclic AMP. However, the alpha-adrenergic inhibition of the prostaglandin response was not affected by cycloheximide. Withdrawal of norepinephrine following a long-term incubation resulted in a potentiation of subsequent PGE1-stimulated cyclic AMP accumulation. Cycloheximide enhanced this norepinephrine withdrawal effect. Our previous studies have shown that cholera toxin induces refractoriness to beta-adrenergic agonists in C6-2B rat astrocytoma cells and that cycloheximide blocked this action of cholera toxin. In an analogous manner cholera toxin caused refractoriness to subsequent prostaglandin-stimulated cyclic AMP production in NG108-CC15 cells, and cycloheximide reduced cholera toxin-induced prostaglandin refractoriness. Thus cycloheximide potentiates the prostaglandin stimulatory effect, has no effect on the ability of alpha-agonists to inhibit the prostaglandin response, increases the stimulatory effect of PGE1 after norepinephrine withdrawal, and reduces cholera toxin-induced PGE1 refractoriness. these observations suggest that PGE1-stimulated cyclic AMP accumulation in NG108-CC15 cells contains components which are regulated by de novo protein synthesis.

Effect of adenosine on adrenergic neurotransmission in the superfused rat portal vein.

This study examined the effect of exogenously applied adenosine on the release of 3H-norepinephrine from the field-stimulated, superfused rat portal vein. Adenosine was found to inhibit the field-stimulated release of 3H-norepinephrine in a dose-dependent manner in 50- to 1,000-microM concentrations. The effect was reversed when adenosine was washed out. The inhibitory effects of adenosine were antagonized by theophylline (10-4 M) which by itself showed a slight enhancement of stimulated 3H-norepinephrine release. ATP was found to inhibit 3H-norepinephrine release at the same concentration as adenosine while inosine was inactive. When adenosine was tested in the presence of the muscarinic and alpha-adrenergic blocking agents atropine and phenoxybenzamine along with indomethacin, a prostaglandin synthesis inhibitor, its inhibotory effect on the stimulated release of 3H-norepinephrine persisted. It is concluded that adenosine and/or ATP can modulate the nerve-stimulated induced release of norepinephrine presumably by an action on the adrenergic nerve terminals.

Metastatic infection secondary to genitourinary tract sepsis.

Metastatic infections arising from sepsis in the genitourinary tract are reviewed in 175 cases, including five in which we treated the patients. The skeleton was the most common site of metastasis (59 per cent). The endocardium was next most frequently involved (28 per cent). Gram-negative organisms were implicated in less than two-thirds of the cases (59 per cent). Impaired host defense mechanisms were noted in 25 per cent of the patients experiencing metastatic infections. The lower urinary tract was the source of metastasis in 75 per cent of the patients, particularly after urologic manipulation in men. Women were more likely to experience metastatic infection from the upper urinary tract. Anatomic and pathologic considerations explaining these sex differences are presented.