840 .4nnotntions

isotope techniques call greatly simplif?, the measure- ment of renal clearances.

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REFERENCES

Smith, H. \jT.: The kidney-, New York, 1951, Oxford University Press. Thomas, S.: Solute excretion ill man during changing urine Bow occurring spontaneouslJ., and induced by vasopressin injection, J. Clill. Invest. 43:1, 1964. Miller, B. F., Leaf, A., llamby, A. K., and Miller, Z.: Validity of endogenous creatinine clearance as a measure of glomerular filtration rate in the diseased human kidney, J. Clin. Invest. 31:309, 1952. Berlyne, G. M., Nilwarangkur, S., Varley, H., and Hoerni, M.: Endogenous creatinine clenr- ante and glomerular filtration rate, I.ancet 2:874, 1964. Nelp, m’. B., L%-agner, H. N., and Kebn, Ii. C.: Renal excretion of vitamin Ble, and its use in the measurement of glomerular filtration rate in man, J. Lab. & Clin. Med. 63:480, 1964. Cutler, 1~. E., and Glatte, H.: Simultaneous measurement of glomerular filtration rate and effective renal plasma flow with 57Co-cyanoco- bnlamin, and ‘?SI-Hippurnn, J. Lab. & Clin. Med. 65:1041, 1965.

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14.

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16.

17.

Breckenridge, A., and hletcalfe-Gibson, A.: Method> of measuring glomerulx filtration rate: ;I conlparisoll of inulin, vitctmiri IS,,, x11(1 creatinine clearances, l.ancet 2: 65, 1965. ~lalamoh, B., I)oiitas, A. S., Koutras, I). .\., Marketos, S., Sfontouris, J. , and l’npanirolaou N.: The determination of glomerular filtration rate in clinical practice, Lnncet 1:913, 1966. Foley, T. H., Jones, N. F., and Clapham, Lt.. I-.: Renal clearance of 57Co-c\.a110cobalillllill; in- portance of plasma-protein binding, 1,;11lcrt 2:86, 1966. Miller, 0. N.: Determination of bound vitamin I<,:, Arch. B&hem. Bioph! 5. 68:155, 1957. Ekills, K. I’., Nashat, F. S., Portal, R. \\‘., and Sgherzi, A. A,1 .: Determination of glomenl- lar filtration rate, T,ancet 2:109, 1066. Gregory, H. E., and Holdsworth, E. 5.: .A study of protein binding in the metabolisnl of vitamin B,,, Biochem. J. 72:549, 1959. Gottlieb, C., 1m1. K. S.. \\~asserman, I*. Ii., and Herbert, C..: Rapid charcoal assay for intrinsic factor (IF), gastric juice unsaturated B,r binding capacity, antibod>- to IF, a1~1 serum unsaturated Bj2 binding capnrit~-, Blood 25S37.5, 1965. Slapak, hl.. and Hume, L). nI.: X new method of estimating glomerulnr filtration rate: I’se of diminishing blood concentration of labelled vltamln B,?, I<ancet 1:1095, 1965. A~lrell, 11.: Estimating glonier~~lar filtrxtior rate, Ialcet 2:188, 1965. Skins, R. P., Nashat, F. S., and Portal, Ii. \\‘.: Measurilig glomerular filtration rate, Lancet 1:364, 1966. Ik \,‘ries, I,. -A., and Goudsmit, I<.: Measuring glomerular filtratioil rate, Lancet 1:.195, 1966.

The nature of the increased vascular

resistance in chronic hypertension

There is much evidence that, although the blood pressure may be raised by a variety of mechanisms (renal, endocrine, nervous), hypertension in its fully developed state is maintained by a mechanism different from that which initiated it,l and that the various etiological types of hypertension end in a “final common pathway.‘12 Recently, there has been considerable support for the suggestion that this common pathway is due to the develop- ment of medial hypertrophy in the small muscular arteries.3a’

Hemodynamic studies in patients with chronic hypertension have shown that there is usually an increase in peripheral vascular resistance, that this increased resistance is distributed more or less uni-

formly throughout the body, and that it is situated in the small muscular arteries.” It is suggested that this accords well with the distribution of medial hypertrophy.

It may seem surprising to question the existence of medial hypertrophy in the small muscular ar- teries; but it is necessary to do so. What in fact is the evidence? The increased wall to lumen ratio in these vessels? This is not proof of medial hpper- trophy; it might equally well be due to arterial constriction.

The only way to ascertain whether there is an increase in the amount of tissue in the vessel wall is to measure its cross-sectional area. Only in the last few years has this been done in any systematic

~1 nm)lcitio~ls X41

wan-, and iii so far as the systemic circulation is concerned, the measurements have been limited to the superior mesenteric artery and its branches. Thr results are interesting and perhaps unexpected. 111 the live largest branches of the superior mesen- teric artery, the cross-sectional area of the walls xvas approsimately twice the normalfi; but in the mescnteric and arteriolar branches there was no increase in cross-sectional area, and in arteries of cert,lin sizes there was even a decrease.7

Ii the Ruperior mesenteric arterial territory is representative of the systemic circulation generally in c,hronic hypertension, it appears that there is 110 medial hypertroph!. iu the arterioles (the vessels in \vhich the main increase in vascular resistance is belie\-etl to reside), so that the increased wall to lume11 ratio ill these vessels must be due to con- IlXCtiOll.

‘l‘hk leads; to a further question. \\:hat is the nature of the arteriolar contraction? Is it a rapidly rcvcrsible \-asoc,ollstrictioll, a condition of “hyper- tolllls,” or i, it a more permanent contraction? 111 sonic of these studies,’ the arteries were distended as fully as possible by injecting a warm suspension of bismuth osychloride (or barium sulfatej and gelatin into the superior mesentcric artery at a prcasure of 150 to 250 mm.Hg. In the cases in which there had been hyperteusion during life, the injec- tion wxs made at :I higher pressure than in the controls; the pressure of injection roughly corrc- sponded to the systolic pressure during life. .\fter the injection, the arteries and arterioles in the intestinal wall all appeared to be fully distended, as judged by the fact that the internal elastic lamina \~a5 cx-erywherc quite smooth. However, when these distended arterioles from the hypertensive cases were compared with the corresponding ar- terioles from control cases, it xvas found that their (xliber \vas significantly reduced-in spite of the fact th<lt the)- had been iujected at a higher pres- sure. ‘l-he reduction in cxliber w-as found to be greatest cxer the range of 70 to 200~. (The corrc- >pc,nding tlianlcters in routine microscopic prep+

rations, w-here the arteries are collapsed, would lx approximately 4.5 to 120~.)

Thus, the increased wall to lumen ratio of the arterioles in chronic hypertension is due not tn hl.pertrophv but to contraction. ‘I‘hese x,essels, although siill capable of wide variation in caliber, are unable to ddate as fully as in the normal case. It is postulated8 that in the early stages of hyper- tension the arterioles are in a state of reversible “hypertonus,” but that, as the hypertension enters the chronic phase, a persistent shortening of some of the elements of the arteriolar wall takes place, leading to an intrinsic increase in peripheral V~WII- lar resistance. Hypertrophy develops in the Iar,q:cr arteries proximal to the zone of contraction.

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3 I .

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6.

7.

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Pickering, G.: High blood preh>tlrc, I.ondon, 1955, J. 8r .A. Churchill, Ltd. LVilson, C.: Control of vascular tone in hyper- tension, ix Harington, M., editor: Hypotensive drugs, London, 1956, Pergamon Press. Follow, B.: Structural. m\-ogeuic, humoral and nervous factors co11 trolljng peripheral rc- sistance, in Harington.? Pickering, G.: The nature of eshelltial hyper- tension, I-olldon, 1961, J. 91 A. Churchill, l.tti. Freis, E. D.: Haemodynamics of h!-pertensioll, I’hysiol. Rev. 40:27, 1960. Barrett, .A. XI.: Arterial measurements in the interpretation of cardiomegaly a~ nerropsl : cardiac hypertrophy and m!~ocnrdial infarction, J. Path. Bact. 86:9, 1963. Short, I). S.: JIorpholog>- of the intestinal arterioles in chronic human h!-pertension, Brit. Heart J. 28:181, 1966. Short, I ). S.: ‘The vascular fault in chronic hypertension. l*ancet 1:1302. 1966.

Antibiotic persistence

during renal failure and dialysis

Toxicity irom drugs retained CLmlulatively during ren,ll insufficienc~y can be prevented if the possibility is considered when dosage schedules are selected. At the same tinle, further modification of dosage sc,hedllles may be mcessary if concentrations are to be kept within therapeutic ranges when hemodialysis treatment is interposed. Information upon which to base these adjustments in dosage is seriously meager,

except for a considerable amount of meaningful study which has been concluded on antibiotics.

Vancomycin, kauamycili, Ileomycin. streptomy- cin, and colistin are currently used antibiotics that are now known to depend primarily upon glomerular filtration for clearance from the serum, thereby re- quiring a reduction in dosage during renal insuf- ficiency if cumulative toxicity is to be avoided. Inter-