A B S T R A C T We investigated the relationship of the kallikrein-kinin system and the renin-angiotensin system in the regulation of blood pressure, salt and water excretion, and renal blood flow. Normotensive and hypertensive black and white men were studied during unrestricted sodium intake as well as on a 10-meq/day sodium intake; potassium intake was held constant throughout the study (80 meq/day).During unrestricted sodium intake, urinary kallikrein activity was greater in white normotensives than white hypertensives or black normotensives. There was no difference (P > 0.05) between white and black hypertensives or between black normotensives and black hypertensives. All groups had greater urinary kallikrein activity on low sodium vs. unrestricted sodium intake, but the increase in black hypertensives was small, and they excreted significantly less kallikrein than the other groups on the low sodium diet. Plasma renin activity showed similar increments after sodium restriction in all groups. Urinary kallikrein activity correlated with renal blood flow in all groups except the black normotensives on low sodium intake. Renal blood flow could be correlated uniformly with log (urinary kallikrein activity/supine plasma renin activity) in all groups on either diet. Urinary sodium and potassium excretion and urine volume were not different among the groups. We concluide: (a) support the concept that the kallikrein-kinin system and the renin-angiotensin system contribute to the regulation of renal blood flow and may account for racial differences in renal vascular resistance. INTRODUCTIONKallikrein is an enzyme that catalyzes the formation of the vasodilator hormones, lysyl-bradykinin (kallidin) and bradykinin, from a plasma alpha-2 globulin substrate, kininogen (1). Urinary kallikrein appears to be derived from the kidney and differs from the enzyme that circulates in plasma (2). It has been proposed that kallikrein exists in the renal cortex and may occupy a location that is juxtaposed to the enzyme renin (3). Although a physiologic function for lysyl-bradykinin, the enzymatic product, has not been established, pharmacologic infusion studies have shown that the peptide is a natriuretic and vasodilatory compound (4).A number of studies in humans and experimental animals have attempted to determine the relationship between urinary kallikrein activity and blood pressure regulation (5-9). Although most investigators feel that kallikreins could influence blood pressure, the meaning of these findings is controversial. Based on provocative preliminary observations (10) and the aforementioned studies, it seemed appropriate to examine the simultaneous influence of race and blood pressture on urinary kallikrein activity. In addition, we have examined the association between kallikrein in uirine and factors that have been related to blood pressure regulation including urinary volume, soditum excretion, plasma renin activity, and renal blood flow. These latter studies were designed to determine a possible physiologic role ...

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A B S T R A C T Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine 8-hydroxylase (D3H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 1"I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D#3H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in AR-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients.These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma Dj8H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals.

Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks. SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute risks are very low, large relative risks become less meaningful. A calculated relative radiation-induced second cancer risk benefit from SABR and FFF techniques was theoretically predicted, although absolute radiation-induced second cancer risks were low for all techniques, and absolute differences between techniques were small.

Observed advantages of autoplanning were clinically relevant and larger than reported in the literature. The latter is likely related to the multi-criterial nature of the applied autoplanning algorithm, with for each center a dedicated configuration that aims at plan improvements relative to its (clinical) training plans. Large variations among patients in differences between manVMAT and autoVMAT point at inconsistencies in manual planning.

For previously irradiated patients with recurrent pelvic disease, SABR re-irradiation could be a feasible intervention for those who otherwise have limited options. Evidence to support this technique is limited but shows initial promise. Based on the available literature, suggestions for a more formal SABR re-irradiation pathway are proposed. Prospective studies and a multidisciplinary approach are required to optimise future treatment.

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The choice of DIR algorithm was limited to those available in the RayStation 9B Treatment Planning System. However, these algorithms are representative of the range of approaches available commercially, encompassing grey-scale driven (correlation and mutual information), biomechanical and contour-driven methods. The Anaconda algorithm is capable of combining greyscale and contour registration and, herein, we have additionally combined biomechanical registration with Anaconda.Whilst many other DIR software platforms and algorithms exist, these do not fundamentally differ from the algorithms used here. Our focus was to explore the potential for combinations of existing DIR methods to overcome challenges in the case of extreme pelvic anatomical changes, so we have not attempted an algorithmic comparison. However, we would expect our findings to apply to any combination of similar grey-scale and biomechanical DIR algorithms in other contexts and systems, given an appropriate workflow as outlined below. 2 and Figure 3 and 4): DIR results (see also Supplementary Table Jacobian analysis:Clinical significance for reRT was assessed by overlaying the negative element mask onto the reRT CT image and combined dose distribution. In two cases the folding was <1 grid voxel (2.5 mm) and clinically insignificant. In one case, folding ~20 mm was observed, along the bladder-rectal interface. This case fell >3 s.d. from the mean for bladder DSC (0.