[Carcinoma of the thyroid gland].

[Carcinoma of the thyroid gland]. A series of 172 surgical cases of thyroid carcinoma accumulated in apprximately 21 years have been classified according to their microscopical patterns as follows: papillary carcinoma, follicular carcinoma, medullary carcinoma with amyloid and anaplastic carcinoma. The author briefly mentions the significance of scintigraphy and of the so-called cold nodules as well as the interrelationship between thyroiditis and thyroid carcinoma. Attention is drawn to the sequelae of cervical irradiation, particularly in young individuals with respect to the possibility of development of thyroid carcinoma within this region.


Inactivation of bacteriophages with cis-platinum(II) diamminedichloride. The ability of the cis-plantinum(II) diamminedichloride and its hydrolytic products to inactive DNA bacteriophages was examined on the models T2, T4, T4BO1, T3, and lambda. The inactivation of all bacteriophages under study increases gradually during the first 40-90 min of the action of neutral cis-Pt(II) and later passes into an exponential phase. The extent of the region of slower inactviation is larger for osmotically sensitive strains T2 and T4. Inactivation with the hydrolytic products for cis-Pt(II) proceeds exponentially starting from the very beginning and their inactivating effect is higher by 40-80 times than for a comparable concentration of the original complex. The extent of inactivation is not affected with the HCR marker of the host bacteria. The sensitivity to cis-Pt(II) is higher for bacteriophages with a head permeable to salts. An additional inactivation ("after-effect") was observed after dilution of the complex; it can be removed by adding S-aminoisothiuronium dihydrobromide (AET). The results obtained are in good accord with the assumption that inactivation is due to the hydrolytic products arising in the head of bacteriophage.


Acute biochemical and morphological effects of N-nitrosomorpholine in comparison to dimethyl- and diethylnitrosamine. Some biochemical and ultrastructural changes induced in the livers of rats treated with N-nitrosomorpholine are described and compared with parallel observations in rats given dimethyl- or diethylnitrosamine. Hepatotoxic doses of the nitrosamines caused inhibition of incorporation of [14C]leucine into hepatic proteins, accompanied by progressive disaggregation of polysomes which paralleled the known time course of metabolism of each compound. Dimethylnitrosamine (DMN) and N-nitrosomorpholine (NM) inhibited incorporation of [14C]orotate into liver RNA but diethylnitrosamine (DEN) caused a slight stimulation of orotate incorporation. Electron microscopy revealed similar hepatic cytoplasmic changed induced by each nitrosamine, including dilation and degranulation of the rough surfaced endoplasmic reticulum and subsequent increase of the smooth endoplasmic reticulum. Nuclear changes differed with each compound, N-nitrosomorpholine having more marked effects than either dialkyl compound. The results are discussed with particular reference to the metabolism of N-nitrosomorpholine in the liver.


fMet-tRNA F Met binding and peptidyl transferase function in free and bound ribosomes from normal and puromycin aminonucleoside-treated rats. Treatment of rats with the aminonucleoside of puromycin, which increases the incorporation of labelled phenylalanyl-tRNA into polypeptide chains in liver ribosome preparations studied in vitro, did not change the factor-dependent binding of fMet-tRNA f Met to ribosomes nor the peptidyl transferase function of the ribosomes. Peptidyl transferase function, as measured by fMet-tRNA f Met-puromycin formation, was comparable in the free and bound ribosome preparations. Similarly, the factor-dependent binding of fMet-tRNA f Met to ribosomes was the same in free ribosome preparations obtained from rat liver as it was in bound ribosome preparations that had been freed of membranes by puromycin incubation and high salt wash.


The use of high pressure liquid chromatography to study chemically induced alterations in the pattern of benzo[a]pyrene metabolism. The metabolism of radiolabeled benzo[a]pyrene (BP) by control, 3-methyl-cholanthrene (3-MC) induced, and 1,1,1-trichloropropene-2,3-oxide (TCPO)-inhibited rat liver microsomes was measured using fluorescence, radiometric, and high-pressure liquid chromatographic (HPLC) assays. Significant differences in the total measurable metabolism of BP by the three microsomal enzyme incubations resulted from the use of the three assay procedures. Appreciable differences in the concentration of the metabolite fractions after 3-MC induction and TCPO inhibition are clearly demonstrated. NMR analysis revealed that while the 3-hydroxy-BP fraction is greater than 90% pure, the 9-hydroxy fraction contains a number of metabolites having essentially identical retention times.


Inhibition of hepatic aryl hydrocarbon hydroxylase by 3-methylcholanthrene, 7,8-benzoflavone and other inducers added in vitro. A close correlation has been observed between the ability of aromatic polycyclic hydrocarbons and 7,8-benzoflavone (7,8-BF) to induce hepatic aryl hydrocarbon hydroxylase (AHH) in vivo and to inhibit the induced enzyme system in vitro. The activity of this mono-oxygenase was measured by the conversion of 14C-labeled dimethylbenz(a)anthracene (DMBA) or benzo(a)pyrene (BP) to water-soluble products by rat liver preparations (8000 X g supernatant). DMBA as substrate had the advantage over BP in giving a wider range of ethyl acetate-soluble metabolites and allowing the observation of changes in the pattern of these products following injection or addition of the inducing agents. This property was used to detect low concentration (0.1 muM) of polycyclic hydrocarbons which are strong AHH inducers and which may also be carcinogenic. The liver preparation was active for several months when stored at --20 degrees. A possible mechanism of action for the in vitro behaviour of polycyclic hydrocarbons and 7,8-BF towards AHH is proposed.


Interaction of sequential stimuli applied during the relative refractory period in relation to determination of fibrillation threshold in the canine ventricle. An ineffective stimulus applied to cardiac tissue within the relative refractory period can alter the response to an immediately subsequent stimulus. We observed three response patterns that can coexist at different sites of stimulation in the same heart. In the first pattern, a stimulus of two to ten times diastolic threshold, applied too early to elicit a propagated response, becomes effective when a stimulus of equal strength is delivered 10 msec earlier. In the second pattern, a stimulus applied just late enough to evoke a response fails to do so when a stimulus of equal strenght precedes it by as much as 30 msec. Finally, in the third pattern, two stimuli, separated by 10 msec, both of which are late enough to be effective when they are given alone, fail to yield a propagated response when they are applied together. These results have a bearing on the use of trains of stimuli to assess the ventricular fibrillation threshold. Possible interpretations are based on the temporal dispersion of recovery from the refractory state.


Acetylcholine-induced reversal of canine and feline atrial myocardial depression during stretch, cardiac failure, and drug toxicity. Microelectrode and isometric recording techniques were used to evaluate the effects of acetycholine (ACh) on depressed isolated preparations of dog and cat atrial muscle. Atrial muscles were maintained at 36-37 degrees C with warmed Tyrode's solution and were stimulated at frequencies of 30 or 60/min. Depolarization to resting potentials of approximately -50 mv was noted (1) after excessive stretch was applied, (2) in muscles obtained from cats in overt right heart failure, and (3) during exposure of the muscles to excessive concentrations of acetylstrophanthidin or lidocaine. Depolarized muscles demonstrated action potentials of smaller amplitude and rate of rise. Exposure to ACh (2.7 X 10(-6)M) had a minimal effect on resting potential in normal dog and cat atrial muscle and was accompanied by significant negative inotropic actions. The same concentration of ACh markedly increased resting potential and action potential amplitude and induced positive inotropic effects in depolarized muscles; these effects also occurred during beta-adrenergic blockade. We suggest that the positive inotropic effect of ACh in depressed muscles may result from (1) a more synchronous contraction of cells within each muscle, (2) recruitment of previously quiescent cells in contraction, (3) possibly increased calcium inflow in individual cells during depolarizations of greater magnitude, and (4) an increase in the number of interacting sites between actin and myosin after resting potential is improved.


Pathogenesis of acute renal failure following temporary renal ischemia in the rat. In this study, we characterized the sequence of several intrarenal events and evaluated their relative importance in the pathogenesis of unilateral oliguric acute renal failure induced experimentally in rats by complete occlusion of a renal artery for 1 hour. Kidneys were studied prior to occlusion and 1-3 hours and 22-26 hours after release of the temporary occlusion. Renal blood flow measured by an electromagnetic flow transducer was reduced to 40-50% of control during both postocclusion periods. Flow of tubular fluid was markedly reduced, and the damaged kidneys were oliguric. Proximal and distal convolutions were filled with fluid and dilated 1-3 hours after occlusion; their pressures were greatly heterogeneous and were elevated, on the average, to 31 and 16 mm Hg, respectively. Glomerular capillary pressure at this time was normal or slightly increased. Histological sections showed extensive tubular obstruction. We conclude that initially the oliguria is primarily due to intraluminal obstruction in the absence of predominant increases in preglomerular vascular resistance. Observations at 22-26 hours after occlusion indicated acute tubular necrosis. Moreover, the combined involvement of preglomerular vasoconstriction, presisting tubular obstruction, and passive backflow of tubular fluid appeared to be important in the maintenance of the oliguria. Glomerular capillary, proximal intratubular, and peritubular capillary hydrostatic pressures were reduced below control values. After acute volume expansion, the reduced pressures and renal blood flow were reversed, yet the experimental kidneys remained oliguric. Thus, it is clear that tubular obstruction is a significant factor responsible for both the genesis and the maintenance of oliguria in this experimental model of ischemia-induced acute renal failure.


Central and peripheral adrenergic mechanisms in the development of deoxycorticosterone-saline hypertension in rats. The role of the sympathetic nervous system in the development of deoxycorticosterone-sodium chloride (DOCA-saline) hypertension was investigated by measuring plasma levels of norepinephrine, total catecholamines, and dopamine-beta-hydroxylase activity at intervals after the initiation of the DOCA-saline regimen. Plasma norepinephrine was significantly higher in DOCA-saline-treated rats at 4 and 7 weeks and in rats treated with saline alone at 4 weeks compared with that in untreated controls. Total plasma catecholamine levels (epinephrine and norepinephrine) and dopamine-beta-hydroxylase activity were similar in hypertensive rats, untreated controls, and rats that received either DOCA or saline alone. The increases in plasma norepinephrine levels may have resulted from centrally mediated increases in peripheral sympathetic neuronal activity, since the destruction of central catecholaminergic neurons with intracerebroventricularly administered 6-hydroxydopamine (6-OHDA) prevented both the DOCA-saline-induced rise in blood pressure and the increases in plasma norepinephrine. Rats treated with 6-OHDA consistently drank less water or saline than did vehicle-treated controls. The actions of centrally administered 6-OHDA on blood pressure and plasma norepinephrine levels were not secondary to a reduction in salt intake, however, since intact rats given a similar reduced saline intake became hypertensive and demonstrated elevated plasma norepinephrine concentrations. Chronic salt loading may cause a centrally mediated increase in peripheral sympathetic neuronal activity with raised plasma concentrations of norepinephrine. The increased adrenergic activity in the presence of mineralocorticoid-induced sodium retention leads to the development of hypertension.


Active and passive immunization against angiotensin II in the rat and rabbit. Evidence for a normal regulation of the renin-angiotensin system. Active or passive immunization has been used repeatedly as a tool in studies on the role of the renin-angiotensin system in the control of blood pressure and kidney function. The results are not consistent among each other, and they are also at variance with other studies using different approaches. To evaluate the possible causes of these discrepancies, the biological characteristics of angiotensin antibodies were studied in rats. Following the intravenous injection of angiotensin II antibodies (purified by affinity chromatography), the plasma concentration of the antibodies declined in a two-exponential curve with half times of 11 hours and 7 days, which probably reflect distribution in the extracellular space and elimination, respectively. Plasma angiotensin II levels rose from preinjection levels of 100 pg/ml to 12,000 pg/ml within 10 minutes and then declined concomitantly with the decline in antibody concentration. We calculated that only a samll fraction of the circulating antibody was occupied by angiotensin II. Plasma renin concentrations were initially elevated both in controls and in antibody-injected rats, but they returned to the control level after 30 minutes and remained at that level throughout the rest of the experiment (10 days). This fact indicates that feedback mechanisms which control renin secretion, such as free plasma angiotensin II concentrations, are in the normal range. We therefore concluded that the renin-angiotensin system in antibody-injected rats was regulated at a normal level. Similar conditions seemed to exist in rabbits actively immunized against angiotensin II; these animals exhibited high concentrations of total immunoreactive angiotensin II (up to 200,000 pg/ml) and a small increase in plasma aldosterone and corticosterone concentrations.


Abnormalities of renal perfusion and the renal pressor system in dogs with chronic aortic coarctation. To clarify the role of the renin-angiotensin system in coarctation hypertension, 2-year-old inbred dogs with chronic neonatally induced thoracic aortic coarctation were subjected to 6 days of rigorous salt restriction. The following parameters were then measured: glomerular filtration rate, renal plasma flow, plasma renin activity, plasma renin concentration, renin reactivity, and renin substrate concentration. Glomerular filtration rate and renal plasma flow were significantly lower in salt-restricted coarcted dogs: 3.0 +/- 0.2 and 9.0 +/- 1.5 ml/min kg-1, respectively, compared with values of 4.0 +/- 0.2 (P less than 0.005) and 13.2 +/- 0.6 (P less than 0.025) ml/min kg-1 in salt-restricted controls. Plasma renin activity was abnormally high in experimental dogs: 13.5 +/- 2.5 vs. 4.5 +/- 1.5 ng angiotensin I/ml hour-1 in controls (P less than 0.005). In addition, a significant elevation of renin reactivity (indicating a relative increase in circulating accelerators or a relative decrease in inhibitors of the renin reaction) was apparent in the plasma of coarcted dogs. Plasma renin concentration was elevated but to an insignificant degree in coarcted dogs, and renin substrate concentration was comparable with that of controls. The impaired renal perfusion and abnormal elevation of plasma renin activity during salt restriction is analogous to clinical and experimental observations in hypertensive states associated with total renal underperfusion and supports a major role for the renal pressor system in the pathogenesis of coarctation hypertension. The insignificant elevation of plasma renin concentration is not incompatible with this view. The demonstration of increased renin reactivity in coarctation hypertension provides additional evidence that acceleration of the renin reaction is common to all hypertensive states.


Influence of potassium ions and osmolality on the resting membrane potential of rabbit ventricular papillary muscle with estimation of the activity and the activity coefficient of internal potassium. Resting membrane potentials of rabbit right ventricular papillary muscles were measured in modified Tyrode's solutions that were isotonic (1.0 X T), hypertonic (1.58 X T), or hypotonic (0.76 X T) at eight different concentrations of external potassium, [K]o, ranging from 0.78 to 100 mM. The amount of hyperpolarization produced by exposure to the hypertonic solutions was relatively constant with an average of 4.6 mv at all levels of [K]o except 0.78 and 1.56 mM. This potential change is much less than the 10.6 mv which would be predicted if the papillary muscles behaved as nearly perfect osmometers and the activity coefficient of intracellular potassium (K) remained constant. The amount of depolarization produced by exposure to the 0.76 X T hypotonic solutions averaged 6.8 mv at all levels of [K]o except 0.78 mM; this value is close to the predicted value of 6.9 mv. Variations in the activity and the activity coefficient of intracellular K were introduced to explain these discrepancies. We estimated that the activity of intracellular K in 1.58 X T hypertonic solution was increased 15-23% compared with that in isotonic solution. This change is much less than the 58% that would be predicted if the papillary muscle behaved as a nearly perfect osmometer. We also estimated that the activity of intracellular K in 0.76 X T hypotonic solution fell 22-26%, which is very close to the predicted value of 24%. The activity coefficient of intracellular K appeared to fall in 1.58 X T hypertonic solution to about 0.76 of its value in isotonic solution. This decline in the estimated activity coefficient of intracellular K could not be attributed to an increase in Coulombic attractive and repulsive forces as predicted by the Debye-Hückel equation for a univalent electrolyte.


Effect of lidocaine on the early inward transient current in sheep cardiac Purkinje fibers. We used two experimental techniques to study the effect of lidocaine hydrochloride on the early inward transient (sodium) current as it is reflected by the maximum rate of change of action potential phase 0 (Vmax). We assessed the effect of lidocaine on Vmax as Purkinje fibers were slowly depolarized by increasing the extracellular potassium concentration from 4.0 to 16.0 mM; these voltage-dependent effects were compared with lidocaine's effect on membrane responsiveness (which measures both the time and the voltage dependence of Vmax). We also used a voltage clamp technique to establish the effect of lidocaine on the voltage dependence of Vmax by measuring Vmax 800-1000 msec after transmembrane voltage (Vm) had been changed in small steps. We studied the effect of lidocaine on the time course of early inward transient current reactivation by depolarizing the membrane to -25 +/- 5 mv for 100 msec to inactivate this current, clamping Vm to a repolarized test voltage for various periods, and then measuring phase 0 Vmax of action potentials elicited immediately after termination of the voltage clamp. We showed that lidocaine at 5 mg/liter, but not a 1 mg/liter, shifted the steady-state Vmax- Vm relationship to a more negative position on its voltage axis by about 5 mv and markedly slowed the reactivation of the measure early inward transient current.


Effect of the angiotensin II blocker 1-Sar-8-Ala-angiotensin II on renal artery clip hypertension in the rat. Twenty-four conscious male Wistar rats with hypertension induced by left renal artery clipping (two-kidney hypertension) were infused intravenously with 1-Sar-8-Ala-angiotensin II a competitive angiotensin II antagonist. The spectrum of responses was wide, ranging from a mild elevation in blood pressure to a marked fall in blood pressure, despite effective and specific angiotensin blockade in all cases. The change in blood pressure during 1-Sar-8-Ala-AII infusion activity showed a significant correlation with the level of plasma renin prevailing immediately before the infusion (r = - 0.78, P less than 0.01) but not with the prevailing blood urea level (r = 0.27, 0.1 greater than P greater than 0.05), the drgree of hypertension (r = 0.42, 0.1 greater than P greater than 0.05), or the time since clipping (r = 0.02, P greater than 0.05). There was no significant correlation between the degree of hypertension and the plasma renin activity (r = 0.42, 0.1 greater than P greater than 0.05). In rats with blood pressure drops greater than 20 mm Hg in response to 1-Sar-8-Ala-AII, the final blood pressure level was still above the normotensive range. Excision of the clipped kidney reduced blood pressure to normal or to near normal within 24 hours in all of the rats tested. It is concluded that the degree of dependence of renal hypertension on the renin-angiotensin system is directly related to the increase in circulating angiotensin itself and not to an increase in sensitivity to angiotensin. Other factors appear to be involved in renal clip hypertension in addition to circulating renin and angiotensin, especially when the measured activity of plasma renin is normal.


Increased sheep lung vascular permeability caused by histamine. To see whether histamine increases lung vascular permeability to protein, we compared the effects of steady-state histamine infusions on lung vascular pressures, lung lymph flow, and lung lymph protein content with the effects of mechanically elevated lung vascular pressures on these variables in the same unanesthetized sheep. We surgically implanted catheters in the pulmonary artery, the left atrium, the superior vena cava, and a main lung lymphatic. After the sheep had recovered from surgery, we carried out steady-state experiments without anesthesia. Histamine induced a dose-related, quickly reversible increase in lung lymph flow without affecting pulmonary artery pressure, and it caused left atrial pressure to fall. During 4-hour intravenous 4-mug/kg min-1 histamine infusions, lymph flow and lymph protein clearance (lymph flow X lymph-plasma protein concentration ratio) increased more than they did with mechanically elevated pressure even though vascular pressures fell. Lymph-plasma protein ratios decreased linearly with increasing lymph flow during increased pressure experiments, but during histamine infusions the ratios did not decrease even though lymph flow increased 2-6-fold. Lymph clearance and permeability-surface area products (PS) for eight protein fractions with molecular radii ranging from 36 to 100 A decreased with increasing molecular size in base-line, increased pressure, and histamine studies. PS values for all eight fractions were significantly higher than base line in histamine experiments but not in increased pressure experiments. Four-hour intravenous histamine infusions caused moderate increases in lung water content. Left atrial infusions had less effect on lymph flow than did intravenous infusions. We conclude that histamine causes pulmonary vascular permeability to protein to increase but that the effects on exchanging vessel porosity are more modest than those suggested for systemic microvessels. Histamine should be considered a possible mediator of increased lung vascular permeability.


Dissociation constant of the norepinephrine-receptor complex in normotensive and hypertensive rats. Previous reports have suggested that smooth muscle obtained from the thoracic aorta of spontaneously hypertensive rats is less responsive to vasoconstrictive agents than that obtained from normotensive rats. The present study was undertaken to determine whether the responsiveness of aortic muscles from normotensive and spontaneously hypertensive rats correlates with a difference in the affinity of the adrenergic receptors for norepinephrine and whether antihypertensive therapy alters the affinity of the adrenergic receptors for norepinephrine. The affinity of the adrenergic receptors for norepinephrine was determined by computing the dissociation constant of the norepinephrine-receptor complex (KDR). The values computed for KDR in aortic muscles from normotensive and spontaneously hypertensive rats that had received no antihypertensive therapy were 1.07 X 10(-7)M and 1.17 X 10(-7)M, respectively. The values computed for KDR in aortic muscles from normotensive and spontaneously hypertensive rats that had received antihypertensive therapy were 1.38 X 10(-7)M and 1.29 X 10(-7)M, respectively. The differences in these values for KDR are not significant. These results indicate that the difference in the contractility of aortic muscles from normotensive and spontaneously hypertensive rats is not related to an alteration in the affinity of the adrenergic receptors for norepinephrine and that the affinity of the adrenergic receptors for norepinephrine is not altered by antihypertensive therapy. Thus, it appears that the etiology of hypertension cannot be directly correlated with a difference in the affinity of the adrenergic receptors for norepinephrine.


Membrane currents and tension in cat ventricular muscle treated with cardiac glycosides. The effect of cardiac glycosides on membrane currents and tension in cat ventricular muscle was studied using the single sucrose gap voltage clamp method. Complete tension-voltage and current-voltage relations were obtained in five preparations before and during treatment with dihydro-ouabain (DHO, 1.7 X 10(-5)M). After 1-2 minutes of DHO, the developed tension was 15% greater than control, but there was no change in either the slow inward (calcium) current (Ica) or the level of the outward current flowing at the end of a 300-msec depolarization (Iout). After 6-8 minutes of DHO, there was a 60% increase in developed tension, a noticeable increase in resting tension, a 20% decrease in Ica, and a smaller increase in Iout. It seems possible that the reduction of Ica was due to a reduced driving force. In preparations treated with ouabain (5 X 10(-7)M, 3-5 minutes), developed tension was 45-150% greater than control with no change in Ica or Iout between -45 and + 15 mv. We conclude that the inotropic action of these cardiac glycosides is not mediated by an increase in Ica.


Role of prostaglandins in the reversal of one-kidney hypertension in the rabbit. Hypertensive rabbits with a clip on the renal artery of their solitary remaining kidney show an abrupt decrease in blood pressure after the arterial constriction is released. Although the mechanism underlying this phenomenon remains controversial, some experimental evidence suggests that it could be humorally mediated. The involvement of prostaglandins was investigated by examining the effect of the release of the arterial constriction on blood pressure, renal blood flow, glomerular filtration rate, and urinary output in five conscious single-kidney hypertensive rabbits in which prostaglandin synthesis was blocked with indomethacin (priming intravenous injection of 9 mg/kg followed by a constant infusion of 1 mg/kg hour-1). The results were compared with those obtained in another group of five single-kidney hypertensive rabbits submitted to the same protocol but not treated with indomethacin. The blockade of prostaglandin synthesis with indomethacin prevented the increments in renal blood flow and glomerular filtration rate seen in the control rabbits after unclipping a significantly retarded the appearance of diuresis and the fall in blood pressure. Despite these observations, the results do not indicate a major participation of prostaglandins in the reversal of single-kidney hypertension, because the decrease in blood pressure 9 hours after the removal of the arterial constriction was similar in both groups.


Chronic one-kidney hypertension in rabbits. I. Treatment with kidney extracts. An investigation into the mechanism that sustains the blood pressure in chronic one-kidney hypertension in rabbits was made using passive and active immunization with hog kidney extracts containing renin and with angiotensin antagonists. Seven hypertensive rabbits were passively immunized for extended periods with antiserum prepared in other rabbits. Antirenin levels were in the range of 1-3 units/ml. Control experiments demonstrated that antirenin concentrations of 1.0 unit/ml or more eliminated more than 99% of the pressor response to renin. There was no lowering of blood pressure that could be attributed to the antibodies. No decrease in blood pressure was observed in 13 experiments in 7 rabbits given the angiotensin II antagonist 1-Sar-8-Ile-angiotensin II; infusion rates of 0.09-87 mug/min kg-1 were used for periods of a few hours up to 3 days. A reduction in blood pressure occurred in 16 of 19 rabbits immunized directly with extracts containing renin with specific activities of 9.6-757 GU/mg. Plasma antirenin titers correlated poorly with reductions in blood pressure. The blood pressure of 22 rabbits given equal amounts of protein without renin was unaffected. It is concluded that the elevation of blood pressure in rabbits with chronic one-kidney hypertension is not dependent on ciculating renin or angiotensin; rather, it results from the presence of renin in an extravascular location or from an unknown pressor substance.


Expansion of extracellular space in the nonischemic zone of the infarcted heart and concomitant changes in tissue electrolyte contents in the rat. The alterations in electrolyte content that occur in an infarcted zone of the heart have also been reported to occur in a similar manner, although to a far less degree, in the distant, apparently normal zones of the heart. These alterations in the nonischemic myocardium have usually been tabulated without comment, presumably because their magnitudes approach values of statistical dispersion. Our measurements of electrolyte content in the normal zone of the infarcted rat heart confirmed that all of the electrolyte contents were slightly modified. There was a rise in sodium, calcium, and chloride and a decline in potassium and magnesium. In addition, the extracellular space ([14C]sucrose) in this zone was elevated by nearly 15%. We have postulated a mechanism for this elevation based on an increase in the net filtration rate through myocardial capillaries. The expansion of the extracellular space can account for all of the electrolyte changes in the normal zone with the exception of the alteration in calcium. Therefore, there is no basis for assuming that these myocardial alterations reflect general movements of electrolytes down their electrochemical gradients. We suggest that the increment in the nominal concentration of cellular calcium is related to a compensatory mechanism that allows the reduced mass of functional myocardium to contract more vigorously.


Analysis of coronary flow fields in thoracotomized dogs. A nonlinear theory of pulsatile flow was used to investigate the detailed flow field in the left circumflex coronary artery of anesthetized open-chest dogs. Studies were carried out under a wide range of blood pressures and flow rates induced by intravenous infusions of dipyridamole. The results indicated that (1) the flow profiles, although less blunt than those in the descending aorta, are still nonparabolic, (2) the wall shear in the coronary arteries maintains a high value through diastole, and (3) during intravenous infusions of dipyridamole both coronary flow and wall shear increase. The peak value of the shear stress during these infusions, which reached 360 dynes/cm2, can approach the yield stress value of 400 dynes/cm2 reported by Fry for endothelial cells.


Baroreceptor reflex control of arterial hemodynamics in the dog. The regional differentiation of carotid sinus control of arterial pressure-flow relationships was studied in chloralose-anesthetized dogs. Simulatneous pressure-flow measurements were made in the ascending aorta, the celiac artery, the cranial mesenteric artery, the renal artery, and the femoral artery. The carotid sinuses were bilaterally isolated and perfused with pulsatile pressure. The open-loop reflex gain was not symmetrical about and was maximum at pressures below the closed loop operating point pressure. Changes in both peripheral resistance and cardiac output contributed significantly to the open-loop gain with the former predominating. Aortic impedance for frequencies above 3 Hz was at a minimum at the closed-loop operating point and increased for both higher and lower values of carotid sinus pressure. For the frequency range from 3 to 9 Hz, regional impedance in all of the beds varied inversely with carotid sinus pressure. The sensitivity of the various beds to changes in carotid sinus pressure around the operating point increased in the order celiac less than mesenteric less than renal less than femoral. Following vagotomy, operating point values of regional resistance and sensitivity were significantly increased. This fact suggests that the aortic arch receptors exert a significant influence on regional vascular impedance at operating point pressures. The fraction of cardiac output in the celiac, mesenteric, and renal beds was nearly independent of carotid sinus pressure before and after vagotomy, but that in the femoral bed increased with carotid sinus pressure. These results demonstrate the nonuniform nature of carotid sinus and aortic arch baroreceptor control of regional blood flow.


Muscle stiffness determined from canine left ventricular pressure-volume curves. We measured pressure-volume curves in nine excised dog ventricles and stress-strain curves in two to five muscle specimens from each ventricle to verify a derived formula that relates muscle stiffness to the ventricular pressure-volume curve. The assumptions underlying this formula are: (1) the ventricle is a uniform spherical shell, (2) all muscle fibers carry average stress and deform as if they were at the midwall, (3) static equilibrium exists, (4) internal pressure induces the only load, and (5) the muscles exhibit an exponential stress-strain curve given by the equation sigma(epsilon) = alpha(ebeta epsilon - 1), where sigma = stress, epsilon = strain, and alpha and beta are constants. There was no significant difference between the stiffness constant, beta, inferred from the left ventricle pressure-volume curves (14+/-4.3[SD]) and that measured directly from the muscle stress-strain curves (16+/-2.8).


Hypotensive effect of clonidine during sodium depletion in the rat. Clonidine was nonhypotensive in conscious unrestrained rats maintained on a normal sodium intake. In contradistinction, clonidine caused a dose-related hypotension in conscious unrestrained rats subjected to sodium depletion via furosemide. The plasma renin activity of normal and sodium-depleted rats was reduced after the administration of clonidine (100 mug/kg, iv) by 22.8% and 34.4%, respectively. Intravenous infusion of an angiotensin II antagonist, 1-Sar-8-Ala-angiotensin II, caused a significant reduction of arterial blood pressure in sodium-depleted rats but not in normal rats. Similarly, bilateral nephrectomy reduced arterial blood pressure and completely abolished the hypotensive effect of clonidine in sodium-depleted rats. Subcutaneous administration of chlorisondamine caused a significantly greater reduction of arterial blood pressure in sodium-depleted rats than it did in normal rats. Treatment of normal and sodium-depleted rats with 6-hydroxydopamine reduced the arterial blood pressure of both groups to approximately 85 mm Hg and completely abolished the hypotensive effect of clonidine in the sodium-depleted rats. The data presented in this paper are consistent with the conclusion that clonidine acts at some site in the sympathetic nervous system of sodium-depleted rats to inhibit renal nerve activity with a resultant suppression of renin secretion and a reduction of the angiotensin II-maintained arterial blood pressure. A similar sequence of events occurring in normal rats would not result in hypotension because their arterial blood pressure is not maintained by angiotensin II.


Hormone interactions in the isolated rabbit heart. Synthesis and coronary vasomotor effects of prostaglandins, angiotensin, and bradykinin. In the present study, the synthesis and degradation of several potent vasoactive substances influencing coronary resistance were characterized in the isolated perfused rabbit heart. Prostaglandin synthetase activity, angiotensin converting enzyme activity, and bradykininase activity (without angiotensinase) were observed. A prostaglandin E2-like substance appeared to be the ednogenous mediator of the coronary vasodilation produced by bradykinin and angiotensin II (AII). (1) The concentration of this prostaglandinlike substance in the coronary venous effluent was directly proportional to the concentration of the coronary vasocilator stimulus (bradykinin or AII). (2) The prostaglandinlike substance released and the coronary dilation produced by the agonists correlated temporally and quantitatively. (3). Abolition of cardiac biosynthesis of the prostaglandinlike substance by indomethacin also abolished the decrease in coronary resistance produced by the agonists. AII, the most potent naturally occurring vasoconstrictor substance, produced a paradoxical coronary vasodilation because it stimulated cardiac prostaglandin biosynthesis, but the direct coronary vasoconstrictor action of AII could be readily unmasked by indomethacin, which blocks prostaglandin synthesis. The nonapeptide SQ-20881 blocked cardiac biosynthesis of AII (from angiotensin I) and enhanced the coronary vascular effects of bradykinin by interfering with bradykininase activity. Similarly, the AII-receptor antagonist, 1-Sar-8-Ile-AII, blocked the coronary vascular effect of AII.


Pressure-flow and pressure-volume relations in the entire pulmonary vascular bed of the dog determined by two-port analysis. To quantify the resistance and particularly the capacitance properties of the entire pulmonary vascular bed, isolated perfused lungs of nine dogs were studied. In each dog, with a fixed endotracheal pressure of 5 mm Hg, the arterial pressure-flow and pressure-volume relations were determined while venous pressure was fixed at constant values of 2, 5, and 8 mm Hg. In the same dogs, the venous pressure-flow and pressure-volume relations were also obtained when arterial pressure was fixed at constant values of 15 and 20 mm Hg. The arterial and venous pressure-flow relations could be regarded as linear around the physiological ranges of arterial and venous pressures; however, at very low pressures, these relations became nonlinear. The arterial and venous pressure-volume relations were also approximately linear within the physiological pressure ranges. The mean arterial compliance was 0.1798 ml/mm Hg kg-1 and was independent of venous pressures. The venous compliance values were 0.1236 and 0.0955 ml/mm Hg kg-1 for arterial pressures of 15 and 20 mm Hg, respectively. The sums of the arterial and venous compliances were 0.3034 and 0.2753 ml/mm Hg kg-1 for arterial pressures of 15 and 20 mm Hg, respectively. These values were nearly identical to the mean total compliance, 0.3265 ml/mm Hg kg-1, measured in a separate series of experiments in the same dogs. Therefore, the data obtained in these experiments using two-port analysis techniques represent the compliances and the resistance of the entire pulmonary vascular bed around the normal operating pressures and flows.


Glomerular filtration response to elevated ureteral pressure in both the hydropenic and the plasma-expanded rat. The factors affecting glomerular ultrafiltration with elevated ureteral pressure were examined in both plasma-expanded (2.5% body weight) and hydropenic Munich-Wistar rats. Elevated ureteral pressure (20 mm Hg) alternated as the initial condition in both groups. Glomerular capillary hydrostatic pressure (PG) and Bowman's space pressure (Pt) were measured directly in surface glomeruli with a servonulling device (deltaP = PG - PT), systemic (piA) and efferent (piE) peritubular capillary oncotic pressures were estimated by microprotein methods, and single-nephron glomerular filtration rates (sngfr) were determined by micropuncture techniques under control ureteral pressure and after increased ureteral pressure in both experimental groups. All data were then applied to equations describing the process of glomerular ultrafiltration to define the profile of effective filtration pressure (EFP = deltaP - pi) and the glomerular permeability coefficient (LpA), where sngfr = LpA-EFP. In plasma-expanded rats, sngfr fell from 44.8 +/- 2.2 to 38.5 +/- 1.5 nilters/min g-1 kidney weight (P less than 0.025) with elevated ureteral pressure entirely as a result of a decrease in the hydrostatic pressure gradient (deltaP), since PG did not rise and nephron plasma flow remained constant. In hydropenic rats, sngfr fell from 34.7 +/- 1.6 to 27.3 +/- 1.6 nliters/min g-1 kidney weight with increased ureteral pressure. PG rose 8.7 mm Hg (P less than 0.001) due to an increase in vascular resistance between the peritubular capillaries and the renal vein which prevented the reduction in deltaP. The reduction in sngfr appeared to result from a reduction in LpA resulting in disequilibration of EFP. Nephron plasma flow was not changed. The filtration response to elevated ureteral pressure was modified by the prior state of volume expansion and was not associated with changes in either nephron blood flow or afferent arteriolar resistance.


Anaylsis of ventricular activation and repolarization from intramural and epicardial potential distributions for ectopic beats in the intact dog. Ventricular activation and repolarization were examined by measuring intramural and epicardial potential distributions during ectopic sequences in intact dogs. Potential distributions were used because they provided a direct measure of all of repolarization. Ectopic sequences produced almost unidirectional excitation across the heart along with repolarization events that were different from normal. During ectopic repolarization, positive potentials occurred over a broad area surrounding the ectopic focus, and negative potentials occurred over a large area on the opposite side of the heart where excitation terminated. The potentials in the walls of both ventricles were more positive in the outer layers and more negative in the inner layers, a gradient similar to normal. A maximum initially was at the ectopic site with a magnitude greater than that of the minimum, but the maximum subsequently decreased in magnitude and shifted toward the minimum while the minimum increased in magnitude. The steepest gradients were initially around the maximum, and they then shifted toward the minimum. The results show that ventricular repolatization potential distributions during ectopic beats are predominantly influenced by gradients from one side of the heart to the other (transventricular gradients) in  contrast to normal repolatization distributions which are predominantly influenced by gradients across the wall (transmural gradients).


Electrophysiological actions of disopyramide phosphate on canine ventricular muscle and purkinje fibers. Disopyramide phosphate is a new antiarrhythmic drug that has been shown to possess significant antiarrhythmic effects in animals and man. In the present investigation, the effects of 2, 5, and 10 mug/ml of disopyramide phosphate were studied on the electrophysiological properties of canine Purkinje fibers and ventricular muscle superfused in vitro. Transmembrane action potentials were recorded from Purkinje fibers in the region of maximum action potential duration (gate), from Purkinje fibers proximal and distal to the gate, and from ventricular muscle. Disopyramide phosphate produced a concentration-dependent decrease in the slope of phase 4 diastolic depolarization of spontaneously beating Purkinje fibers. In all electrically stimulated fibers, the drug decreased the amplitude and the maximum upstroke velocity of the action potential. This depression of phase 0 characteristics was accompanied by a decrease in conduction velocity. In Purkinje fibers located at the gate, a concentration-dependent parallel shift to the right and a depression of the maximum of the membrane responsiveness curve occurred. Effects on action potential duration were variable. Repolarization was altered so that action potentials with dissimilar durations recorded from sites proximal to, at, and distal to the gate became equal. The total action potential duration and the effective refractory period of gate Purkinje fibers were prolonged, but the change in action potential duration was always greater than the change in effective refractory period so that the ratio of the change in duration to the change in refractory period was always greater than one.


Norepinephrine turnover in the heart and spleen of the cardiomyopathic Syrian hamster. Although a reduction in myocardial norepinephrine stores in cardiac hypertrophy and congestive failure is well documented, norepinephrine turnover has been inadequately studied in such hearts. We compared norepinephrine turnover in control and cardiomyopathic hamsters by following the decline in specific activity of myocardial norepinephrine after labelling with an intraperitoneal tracer dose of 3H-norepinephrine. Adult myocardial norepinephrine concentrations were not attained until 4 weeks of age in both strains. There was no difference in the rate of constant (K) for myocardial norepinephrine turnover (0.107+/-0.004 hours-1 vs. 0.100+/-0.005 hours-1) in the two strains of hamsters during the neonatal period. In young control hamsters, K fell to 0.064+/-0.004 hours-1, but that for age-matched hamsters with mild cardiac hypertrophy was 0.102+/-0.001 hours-1 (P less than 0.001). There was little change in K as control hamsters aged. With the development of more severe hypertrophy in cardiomyopathic hamsters, cardiac norepinephrine decreased and resting K rapidly increased to approach the value obtained when hamsters were subjected to immobilization stress (0.302+/-0.013 hours-1). The maximum achievable K remained the same for both control and dystrophic hamsters even during terminal disease. Prolonged immobilization led to a reduction in cardiac norepinephrine in both strains. Ganglionic blockade of failing hamsters completely restored the levels of both cardiac norepinephrine and K to control values. Splenic noradrenergic nerves showed no change in K, norepinephrine content, or maximum K during cardiac decompensation. We conclude that, in the late stages of hamster cardiomyopathy, there is a progressive and possibly specific increase in cardiac sympathetic tone which leads to a concomitant decrease in cardiac norepinephrine. With the loss of sympathetic reserve, congestive failure supervenes.


Current concepts of "normal values," "reference values," and "discrimination values," in clinical chemistry. The term "normal values" is seriously afflicted by sylleptic ambiguities and conceptual problems, and it is gradually being discarded from the lexicon of clinical chemistry. The neutral term "reference values" preferable on semantic and scientific grounds, and its use in clinical chemistry is rapidly gaining acceptance. The term "discrimination value" has been added to the lexicon of clinical chemistry. Use of the "discrimination value" for the results of a laboratory test in a specified clinical situation provides the optimal discrimination between the "healthy" and the "diseased," or between "those who need not be investigated further" and "those who do."


Radioimmunoassay of methaqualone and its monohydroxy metabolites in urine. A commercial radioimmunoassay kit was evaluated for efficacy in detecting methaqualone or its metabolites in urine of persons receiving this drug. The drug and its unconjugated 3'- and 4'-monohydroxy metabolites could be detected equally well. The unconjugated alpha-monohydroxy metabolite was about 80% as reactive and the unconjugated 6-monohydroxy metabolite reacted only very weakly. Quantitation of the conjugated metabolites was less sensitive than of unconjugated. Nineteen urine specimens which reacted positively to radioimmunoassay and which thin-layer chromatography had shown to contain methaqualone and its metabolites were also examined by gas-liquid chromatography. Those specimens that reacted strongly to radioimmunoassay contained high concentrations of the drug or its metabolites. In the specimens examined by gas-liquid chromatography, the apparent concentrations of the metabolites were generally higher than those of the drug itself. Methaqualone in combination with its unconjugated metabolites reacted additively with the radioimmunoassay, resembling the same concentration of parent drug alone. Detection limits were between 10-200 mug/liter.


Separation of synthetic mixtures of sugars and of sugars in body fluids with a high-resolution carbohydrate analyzer. With use of a specially designed gradient-generating system, of anion-exchange resins of 10-20 mum particle diameter, and of an orcinol solution in concentrated sulfuric acid (1 g/liter) as detection reagent, a mixture of 16 carbohydrates can be separated in less than 4 h. The limit of detection for most sugars is in the 0.1--2.0 nanomole range. The detection reagent is stable for months and does not become colored. The reagent mixes with the column effluent in an exothermic reaction and allows use of relatively short mixing coils. The analyzer is appropriate for investigating body fluids rapidly and with high sensitivity.


Gas-chromatographic/mass-spectrometric identification and quantitation of tetronic and deoxytetronic acids in urine from normal adults and neonates. Gas chromatographic/mass spectrometric/computer analyses of trimethylsilyl derivatives of urine extracts, prepared by an anion-exchange procedure, reveal the presence of several tetronic and deoxytetronic acids. Identifications were confirmed by comparing gas-chromatographic methylene unit values and mass spectrometric characteristics with those of chemically synthesized samples. In addition, several 1,4-lactones corresponding to the acids were detected in small amounts. The acids were measured in groups of adults and neonates by gas chromatographic/computer determination of peak areas and the use of calculated response factors. In urines from adults, 4-deoxythreonic, threonic, and erythronic acids were present in relatively large amounts. 4-Deoxyerythronic and 2-deoxytetronic acids were present in small to moderate amounts; 3-deoxytetronic and 2-methylglyceric acids were only trace constituents. These latter two acids, in addition to 4-deoxyerythronic, were also trace constituents of several urines from neonates but could not be detected in others. Expressed in terms of creatinine excretion, both groups excreted similar amounts of 4-deoxythreonic acid and neonates excreted significantly more 2-deoxytetronic, erythronic, and threonic acids.


Factors influencing evaporation from sample cups and assessment of their effect on analytical error. We studied sample evaporation and its effect on analytical error. Several factors influencing evaporative loss have been identified and measured: environmental, instrumental, and operational factors, and the chemical and physical properties of the sample and its container. Such losses from several different types of sample cups have been measured, either chemically or gravimetrically, and compared with those calculated by using a model that allows evaporative loss from a cup of known geometry to be predicted under various environmental conditions. We discuss some steps that may be taken to minimize evaporative loss and give an example to demonstrate that analytical error from this source can be decreased to a routine 1--2% or less by selecting a  particular cup design.


Gas-chromatographic analysis for cocaine in human plasma, with use of a nitrogen detector. We describe a procedure for measuring the concentration of cocaine in plasma by gas chromatography, with use of a nitrogen detector. The procedure was tested on patients receiving intranasal cocaine for topical anesthesia. The propyl ester of benzoylecgonine is used as an internal standard. The lower limit of sensitivity of the procedure is 5--10 mug of cocaine per liter of plasma. The coefficients of variation are 5.3% and 3.0% for concentrations of 50 and 100 mug/liter, respectively.


Comparison of commercial kits for radioimmunoassay: III. Radioassay of serum folate. We evaluated six commercial radioassay kits in which tritium or iodine tracers are used to measure serum folate. We assessed the adequacy of the literature supplied with the kits, within-run precision, reagent stability, analytical recovery of added pteroylglutamic acid and N-methyltetrahydrofolic acid, results of analysis of patients' samples, and minimum detection limits. There were serious discrepancies among manufacturers' kits in each of these respects. Such discrepancies could affect interpretation of results and of data on like samples derived from different laboratories that are using different kits. Laboratories are urged to assess carefully the materials and method supplied by a manufacturer before putting a kit to clinical use.


Relative efficacy of separation of "free" and "bound" (3',5'-3H) pteroylglutamate by charcoal coated with various materials. We studied the effectiveness with which various charcoal preparations separate free [3H]pteroylglutamate from that complexed with milk folate binder. We tested, in various concentrations, uncoated charcoals and charcoals coated with dextrans of various molecular weights, or with albumin, hemoglubin, or polyvinylpyrrolidone with an average molecular weight of 40 000. Althouth there was some distinction between the "bound" and "free" fractions with all charcoals, those treated with dextrans of average molecular weights of 43 500 or 70 000, or with polyvinylpyrrolidone gave the best separation over a greater range of charcoal concentration. Uncoated charcoal and charcoals coated with albumin, hemoglobin, or dextran T10 (average molecular weight, 10 500) were least effective.


Accurate estimation of standard deviations for quantitative methods used in clinical chemistry. Although the standard deviation is the most widely used measure of the precision of quantitative methods, there is a need to re-examine the conditions necessary to obtain a meaningful estimate of this quantity. The importance of the material to be sampled, the sample size, the calculation of confidence intervals, and the segregation of outliers are discussed.


A systematic approach to enzyme assay optimization illustrated by aminotransferase assays. We have developed a systematic approach to optimization of reagent concentrations for assays of alanine aminotransferase and aspartate aminotransferase: (a) Michaelis constants describing the initial-velocity kinetics of the coupled enzyme reactions were evaluated by a nonlinear least-squares fit of the appropriate equation to measured enzyme activities. Activities of more than 50 normal and pathological sera were measured at 30 degrees C. (b) These kinetic equations are used to calculate the set of reagent amino- and keto-acid concentrations that all yield a selected fraction of the theoretical maximum enzyme velocity. An optimal pair is determined by defining an additional criterion, such as minimal reagent cost or minimal concentration to Km ratio. (c) The optimum amounts of reagent NADH and coupling enzyme, being a function of desired pre-incubation and measurement intervals, maximum aminotransferase activity to be measured, and endogenous keto-acid concentration, are determined by computer simulation. An approximate relationship and an exact method for computing assay lag time are presented, along with experimentally measured endogenous keto-acid concentrations in serum. All procedures may be applied to other enzyme assays if appropriately modified.


Identification of human hemoglobins by use of isoelectric focusing in gel. Newly-developed gel isoelectric focusing techniques provide for rapid and correct identification of human hemoblobins. With this technique, we examined samples previously identified by the National Hemoglobinopathy Standardization Laboratory of the Center for Disease Control. A wide variety of both normal and abnormal hemoglobins was included in the 134 different specimens examined. The isoelectric points (pl's) were precisely determined; no discrepancies with results by standard techniques of identification were found. The method is accurate and precise. It is proposed as a powerful adjunct to other laboratory methods suitable for use in a hemoglobinopathy reference laboratory or specialized hematology service laboratory.


Gas-chromatographic measurement of codeine and norcodeine in human plasma. A gas-chromatographic method is described for determination of codeine and norcodeine in human plasma. The method is specific, sensitive, and precise. It was developed for use in bioavailability studies of therapeutic doses of codeine sulfate. After ingestion of a 60-mg codeine sulfate tablet, mean peak codeine concentration in plasma was 107 mug/liter at 1.0 hour. No measurable concentration of norcodeine was found in the plasma by this method.


Temporal intrapersonal physiological variability of cholinesterase activity in human plasma and erythrocytes. Erythrocyte and plasma cholinesterase activities were measured biweekly in one group of 22 subjects for a year and daily for three weeks in another group of nine men. The average range [i.e., (range/mean) X 100] of activity of erythrocyte cholinesterase in men during a year was 8% and during three weeks was 5%. For plasma, the corresponding values were 25% and 12%. The average ranges for erythrocyte and plasma cholinesterase activity in women during a year were 12% and 24%. Erythrocyte cholinesterase activity varies less than do hematocrit, hemoglobin, or erythrocyte count.


5-Decynedioic acid, an acetylenic compound in human urine. An acetylenic dicarboxylic acid, 5-decynedioic acid, has been isolated from human urine. The structure was determined by mass spectrometry of several derivatives, and by infrared spectroscopy. On osmium tetroxide oxidation, a vic-diketone was formed, the mass spectrum of which established the position of the triple bond between carbon atoms 5 and 6. Mass spectrometric evidence for the presence of a small amount of the isomeric 4-decynedioic acid was also obtained. The 24-h excretion of these acids is 0.01-0.1 mmol for healthy adults on a regular diet.


Sex-related patterns in the profiles of human urinary amino acids. The urinary amino acid profiles of 79 young women and 72 young men were studied with an automated highpressure amino acid analyzer. A nonparametric statistical analysis was applied for detecting profile differences related to sex and other variables. A strong sex-related pattern was confirmed and its power for sex determination was evaluated. For the women, profile differences related to the use of oral contraceptives were also discovered and evaluated. No correlation with the menstrual cycle was detected.


Fluorometric screening method for detecting benzodiazepines in blood and urine. We report a fluorometric method for detecting diazepam, chlordiazepoxide, oxazepam, chlorazepate, and (or) their major metabolites in blood, urine, or gastric contents at low therapeutic concentrations. The drugs are first hydrolyzed to their respective benzophenones and converted to highly fluorescent 9-acridanones. Total benzodiazepines (parent plus metabolites) in blood and gastric contents are semiquantitatively evaluated and compared to results of gas-chromatographic determinations.


Faster enzymatic procedure for serum triglycerides. We describe a single-reagent, enzymatic procedure for triglycerides in serum, which may be performed in 5 min per sample with use of an Abbott ABA-100 analyzer system. This procedure is compared to the semi-automated enzymatic procedure with the ABA-100, which requires 30 min per sample.


Use of the carbon rod atomizer for analysis of lead in blood: three methods compared. Measurement of lead in whole blood by use of the carbon rod atomizer and atomic absorption spectrophotometry was investigated for three methods: (a) a simple dilution (one volume of whole blood to two volumes of surfactant solution; (b) direct analysis of whole blood (no sample preparation); and (c) a standard chelation extraction procedure in which sodium diethyldithiocarbamate and methyl isobutyl ketone (isopropylacetone) are used. Within-run precision data for normal and above-normal pools favored the Triton dilution method, for which coefficients of variation were less than 5%. Recoveries of added lead ranged from 94-107% for all three methods. We saw no change in the standard curves for any of the procedures on addition of ethylenediaminetetraacetate to samples. The method of additions was necessary to prepare standards of a matrix composition identical to that of the unknowns.


Rapid, simplified diagnosis of cystinosis in conjunctival biopsies. Assessment of the markedly elevated concentration of free cystine in conjunctival tissue from patients with cystinosis permits a rapid, simple, and unequivocal diagnosis of this disorder of amino acid metabolism.


Distinction between fibrinogen and fibrin degradation products in plasma. Polyacrylamide (PA) gel electrophoresis in sodium dodecyl sulphate (SDS) has been shown to distinguish between the major components in the plasmin induced lysates of purified crosslinked fibrin and fibrinogen. The D dimer fragment from crosslinked fibrin separated on SDS-PA gels from the fibrinogen fragments X, Y, Dg and E. Follwing immuno-absorption of plasmin induced lysates of plasma clots, plasma fibrinogen, and mixtures of both, the major fragments of fibrinogen and fibrin were capable of being discriminated by SDS-PA gel electrophoresis. The presence of D dimer in patient plasma suggested the efficacy of heparin in the management of haemorrhage associated with amniotic fluid embolism.


The effect of heparin in vitro on human plasm post-heparin lipolytic activity. Human plasma post-heparin lipolytic activity was reduced when collected in tubes containing lithium heparin as compared with samples collected in lithium sequestrene. The addition of heparin in vitro to samples abolished the inhibitory effect of protamine sulphate on plasma post-heparin lipolytic activity. It is suggested that heparin should not be used as an anticoagulant for the collection of samples for assay of post-heparin lipolytic activity.


A new fat-dependent time-modified relationship between basal plasma glucose levels and the early glucose response to oral glucose loading in normal human subjects. Plasma glucose responses to 50 g oral glucose loads were measured in 17 young healthy males during the morning and the afternoon after 4-h and 12-h fasts. After 4-h fasts certain glucose response values correlated significantly with the basal glucose values (P less than 0.014) in both the morning and the afternoon tests, and are described as "fast-dependent" relationships. No significant correlations were found after 12 -h fasts either in the morning or the afternoon. The "fast-dependent" relationships are also "time-modified", as demonstrated by markedly different morning and afternoon regression equations.


Evaluation of a radioassay for serum folate and the effects of ascorbate and methotrexate. In this study a competitive binding assay for serum folate is evaluated with special attention to storage conditions of the serum samples and the effect of methotrexate on the assay results. Average serum folate levels were 31 nmol/1 +/- 8 (S.D.) in 59 nromal sera and 19 nmol/1 +/- 12 (S.D.) in 354 sera from hospitalized patients of which 43 values were lower than 9 nmol/1. Serum folate appeared to be stable at - 20 degrees C for at least 5 weeks. The addition of ascorbate, which is said to stabilize serum folate, caused a non-specific increase of the measured folate. Methotrexate acted competitively with the tracer folate in the assay sytem when added  in vitro and elevated the folate readings. The same occurred in the serum of a patient after intravenous methotrexate.


Glyoxalase enzyme system in human muscular dystrophy. Glyoxalase I and glyoxalase II activities were determined in skeletal muscle of control subjects and of patients with Duchenne dystrophy, other major forms of muscular dystrophies and certain neuromuscular disorders. The glyoxalase I activity was normal in all diseases examined except in Duchenne and limb girdle types of muscular dystrophy, where it showed a significant moderate decrease. The glyoxalase II activity in normal human muscle was very low, and the activity was unaltered in muscle of patients with Duchenne and other major forms of muscular dystrophies and spinal muscular atrophy. The selective decrease of glyoxalase I activity in recessively inherited muscular dystrophies may have some relevance to some phases of these disease processes.


An automated, direct method for measuring adipocyte cell size. Current methods for direct determination of fat cell size are optical and non-automated. They are thus tedious, but have the advantage of providing estimates of the variance of a cell size distribution, as well as a measure of the mean cell size. An indirect method based on counting the number of osmium-fixed fat cells derived from a known wet weight of adipose tissue is also available. This method is automated and thus rapid, but does not provide information about the variance of the cell size distribution. In the present paper we describe a direct, automated method of fat cell sizing that provides estimates for both mean cell size and the variance of the cell size distribution. The correlation between our method and in indirect method based on counting osmium-fixed cells was 0.96. Transformation of the volume distribution to diameters indicated that cell diameters appeared to be normally distributed, confirming the observations of others.


Serum alkaline phosphatase isoenzymes linked to immunoglobulin G. An unusual isoenzyme pattern of serum alkaline phosphatase was found in a patient with skeletal abnormalities due to multiple epiphyseal dysplasia and it was demonstrated that the abnormal pattern was caused by complex formation between serum alkaline phosphatase and immunoglobulin G of the lambda class. Physicochemical studies of the patient's serum alkaline phosphatase showed the properties of an osseous enzyme. Evidence was obtained indicating that the complexing occurred in vitro and that the patient's immunoglobulin G had the ability to bind the hepatic and osseous isoenzymes selectively but not to bile, placental and intestinal isoenzymes. No abnormality was detected in the leucocyte isoenzyme pattern. The relationship between the occurrence of complex formation and the patient's bone disease was not established.


Lecithin:cholesterol acyltransferase initial fractional rates of esterification in human and rat serum during development. The initial fractional rates of cholesterol esterification were measured in human cord serum, in a group of apparently healthy "young adults" (mean age +/- S.D. 32 +/- 5 years), in a group of "middle aged" adults (51 +/- 8 years) with normal coronary angiograms and in newborn, 10-, 20-, 45-, 180- and 365-day-old rats. The initial fractional rate of esterification was inversely related to serum cholesterol levels in humans and, with the exception of newborns, also in rats. A theory of lecithin:cholesterol acyltransferase participation in cholesterol metabolism is discussed.


The effect of long-distance running on some biochemical variables. Biochemical variables have been measured in a group of volunteers during and after a long-distance run. Plasma glucose levels remained relatively constant and a significant decrease in plasma bicarbonate was noted. Plasma sodium, chloride, total protein, albumin and calcium showed significant increased of an order compatible with water losses occurring during the run. Plasma potassium, urea, creatinine, uric acid, phosphate and bilirubin all show much more marked and variable increases. The plasma enzymes alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase and creatine kinase likewise increased significantly throughout the run. Whilst most constituents showed a tendency to return to normal at 20-30 hours after the run, gross increases were observed for aspartate aminotransferase and creatine kinase.


Fluid balance, renal function, and blood pressure. After many detours in the search for the basic mechanism of hypertension, evidence now seems to corroborate the earliest concept that developed in the 1800's, namely, that hypertension almost always results from a tendency of the kidneys to retain water and salt. Animal studies show that the amount of excess body water and salt required to cause hypertension is exceedingly small, and that the hypertensive effect of the excess water and salt may not develop for days or weeks. When vascular constriciton occurs simultaneously, as occurs in the presence of large quantities of angiotensin, the blood volume may be less than normal, but even in these circumstances the fluid volume is relatively increased and is responsible for the hypertension because the vascular constrictont has decreased the capacity of the circulation to a greater extent than the decrease in blood volume.


Renal control of interstitial space compliance: a physiological mechanism which may play a part in the etiology of hypertension. "Overloading" with salt and water, i.e., increasing extracellular fluid, can, if maintained for a period, lead to hypertension in which the main hemodynamic abnormality is increased peripheral resistance. There is evidence that salt and water overload is the chief factor in the hypertension of the majority of patients suffering from chronic renal failure. "Overloading" occurs not only when the contents of a container are increased, but also when the capacity of a container is decreased. Reduction of the compliance of the interstitial space would reduce its capacity to hold fluid without increase in pressure. Evidence is presented that the presence of the kidney affects interstitial space compliance; bilateral nephrectomy decreases interstitial space compliance four fold. Hypertension induced by renal artery partial constriction and removal of the other kidney is also associated with reduction of interstitial space compliance; a sudden rise in interstitial space compliance may be the primary factor in the course of events that leads to the rapid fall in blood pressure which occurs when the constriction is removed from the renal artery. It is suggested that the kidney secretes a hormone which increases interstitial space compliance and that this represents a physiological mechanism which enables animals to store water in the interstitial space without undue rise in interstitial tissue pressure. The role of this mechanism in hypertension and in chronic renal failure is discussed.


Management of Candida peritonitis by prolonged peritoneal lavage containing 5-fluorocytosine. A 55 year old woman on chronic maintenance peritoneal dialysis developed Candida albicans peritonitis. This was successfully treated by continous five day peritoneal lavage containing 5-fluorocytosine. By this technique stable serum levels of the drug (58 mug/ml +/- 3.2 SEM) could be maintained. The peritoneal clearance of 5-fluorocytosine was found to be 7.5 ml/min (for peritoneal dialysis flow rate 1.2 1/hr) and the serum half-life 34 hours. The use of this drug in renal failure and its kinetics are reviewed.


Pathogenesis of malignant hypertension: experimental evidence from the renal hypertensive rat. In rats with unilateral renal artery stenosis, the malignant phase of hypertension is characterized by: systolic blood pressure above 180-190 mm Hg; sodium and water loss; polyuria and polydipsia; markedly activated renin-angiotensin-aldosterone system; impairment of renal function and malignant nephrosclerosis in the contralateral kidney; some rats exhibit signs of cerebral hemorrhage, heart failure, acute renal failure, and some rats die. After such a phase of malignant hypertension, a period of remission may occur, which is followed by another malignant phase, etc. When malignant hypertensive rats are offered, in addition to water, saline as drinking fluid, they compulsively drink the saline, BP falls transiently, and all signs of malignant hypertension nearly or completely disappear. These observations indicate that, at a critically high BP level, it is salt and water loss which, by activating the renin-angiotensin system, trigger the vicious circle of malignant renal hypertension in rats.


General and regional hemodynamics in hypertension in chronic renal disease. Cardiac output, total peripheral vascular resistance, renal, extrarenal, forearm muscle and skin hemodynamics and an indicator of the splanchic vascular resistance were estimated in 20 subjects with chronic renal disease without signs of chronic renal failure and without anemia. The data were compared with a group of subjects with essential hypertension. The high blood pressure of chronic renal disease of mild or moderate severity was maintained in the first place by a high cardiac output, this being due to a rise of the stroke volume, while the heart rate was only slightly increased. The total peripheral vascular resistance was within the normal range in most of the subjects. The vascular resistance in the skin was slightly raised, that in the splanchnic area and muscle unchanged in renal hypertension. The possible pathogenic mechanisms are considered.


Overhydratation and renin in hypertensive patients with terminal renal failure: a hemodynamic study. Twenty-nine patients with terminal renal failure were treated by periodic hemodialysis for 2 to 18 months. Serial determinations of blood pressure, blood volume, cardiac output, exchangeable sodium and plasma renin activity were performed. Bilateral nephrectomy was performed in 17 patients and followed by a fall in blood pressure. Cardiac index was elevated in all patients but the blood pressure changes were mainly related to resistance changes. In non-nephrectomized patients, mean arterial pressure was directly correlated to plasma volume (P less than 0.0001), exchangeable sodium  (P less than 0.01) and plasma renin activity (P less than 0.001). In anephric patients, mean arterial pressure was only directly correlated to plasma volume (P less than o.005). The slope of the curve relating arterial pressure to plasma volume was significantly shallower in nephrectomized than in non-nephrectomized patients, indicating a lower sensitivity of pressure to volume changes. The study provides evidence that, in hypertensive patients with chronic renal failure, the positive pressure-volume relationship is the fundamental cause of the high blood pressure and that the renin-angiotensin system acts mainly by changing the sensitivity of this mechanism.


The clinical picture of renal hypertension. Renal hypertension can usually be recognized only by examining all the features of the hypertensive illness. On the other hand, the investigation of a case of hypertension whose genesis was previously unclear can lead to the diagnosis of a hitherto unrecognized renal disease. The blood pressure values found in patients with renal hypertension are of widely differing degrees of severity. Slight rises in blood pressure (e.g. 140/90 mm Hg), can be a sign of renal disease in adolescent patients. 10-15% of the cases of chronic renal hypertension develop into malignant hypertension. High diastolic values above 120 mm Hg without renal symptomatology and without reduced renal function speak against a primary renal cause of the rise in blood pressure. The finding of hypertension developing during the course of renal disease is, with respect to the hypertensive cardiovascular complications, just as important as in the case of essential hypertension. Complications which can occur during renal hypertension include cardiac insufficiency, hypertensive encephalopathy, retinopathy, hypertensive crises and acceleration of the renal disease.


Membranous glomerulonephropathy with crescents. A case is reported in which typical histological features of idiopathic membranous glomerulonephropathy co-existed with atypical glomeruli showing cellular epithelial crescents in addition to diffuse basement-membrane thickening. These features were seen in a renal biopsy specimen taken during rapidly progressive deterioration of renal function in a patient previously known to have mild ankle edema for four years.


Acute renal failure secondary to ureteral fungus ball obstruction in a patient with reversible deficient cell-mediated immunity. A patient with a single functioning kidney and anuria due to ureteropelvic obstruction by a Candida fungus ball is described. During treatment with amphotericin B administered via a nephrostomy tube the drug was not detected in the serum, indicating that absorption from urothelium was not significant. Immunological studies demonstrated a lack of cell-mediated immunity which was probably brought about by a long course of prednisone and later restored when this drug was discontinued. This immunosuppression was evident even with a relatively small dosage of prednisone (5 mg daily). The literature concerning renal candidiasis and predisposing factors is reviewed.


Spinal cord injury in children.

Spinal cord injury in children. The spinal injured child has speical needs owing to the processes of physical, mental and social growth. Goals of physical treatment programs include prevention of: genitourinary complications; contractures; pressure sores; long bone fractures, hip subluxation and dislocation; spinal deformity. Nonoperative treatment of spinal deformity employing external support should be initiated when the potential for spinal deformity exists. External support delays the development of spinal deformity, improves sitting balance and allows free upper extremity use. The overall treatment programs must consider altered body proportions, immaturity of strength and coordination. Case examples of children with spinal injury are presented above to illustrate specific problems stemming from immaturity of physical, cognitive, and social development. Spinal surgery can be a conservative measure in the growing child when there is radiologic evidence of progressive spinal deformity. Posterior spinal fusion with Harrington instrumentation and external support permits immediate return to vertical activity.


Spinal cord injury as a complication of elective anterior cervical fusion. The true incidence of spinal cord injury as a complication of elective anterior discectomy and interbody fusion is not known. It would appear that the risk of encountering this complication increases if the surgical procedure includes instrumentation within the spinal canal. In 5 of the cases reported herein the cause for spinal cord injury was identifiable; in the remaining 5, the mechanism of injury is either obscure or not reported. All 10 patients reported had their surgery performed using the drill and dowel technique. The role of the posterior osteophyte in spondylosis and the rationale for routinely entering the spinal canal in order to decompress the spinal cord and nerve roots are examined. Since the majority of refractory disk problems that require surgery can be satisfactorily managed by discectomy and interbody fusion alone, routine instrumentation within the spinal canal may be an avoidable hazard in the majority of instances. The pathogenesis and prognosis of the anterior cord syndrome is reviewed, a possible etiology is suggested, and the anatomy, the autonomy and the importance of the anterior spinal artery system are noted. Its vulnerability in the treatment of degenerative disk disease and a possible mechanism for its occult impairment is mentioned.


Dynamic spine alloplasty (spring-loading corrective devices) after fracture and spinal cord injury. Dynamic alloplasty in spine fractures is a method of stabilization of the fracture site of the injured spine by obtaining a steady, gradual correction of the spine in accordance with Guttman's method. Gait training may begin within 2 weeks after surgery. The method shortens the rehabilitation time of paraplegics to approximately 3 months, as compared with the conventionally treated group. Dynamic spine fitting not only enables the patient to accept his disability, take interest in vocational and social rehabilitation sooner than conventional methods, but also prevents the typical psychological and physiological complications, such as depression, neurasthenic status, urological complications and bedsores. There is no need for prolonged muscle reconditioning because the patients are immobilized only for the essential postoperative period. Following our research on "Amputations with Immediate Prosthetic Fitting," we sould like to propose the term "Immediate Functional Paraplegic Fitting" for this technique.


Biomechanical analysis of structural stability of internal fixation in fractures of the thoracolumbar spine. Three different methods of internal fixation for the flexion-rotation thoracolumbar spinal fractures were tested biomechanically in a cadaver model for strength, mode of failure and ease of application. The compression rod system was clearly superior in strength and rotational stability to the spring device, but it was more difficult to apply than springs. The distraction rod system exhibited an intermediate level of strength with adequate rotational stability. Technically, the method is exacting and requires a clear understanding of its principle of 3 point fixation.


Rate of wear in total hip replacement.

Rate of wear in total hip replacement. The wear of high molecular weight polyethylene sockets was measured on radiographs, over a period of 9 to 10 years, in a group of patients whose ages averaged 73.3 years at the end of the period. The average rate of wear was 0.15 mm/year and 68 per cent of patients followed this pattern. Wear more than 2.5 mm in 10 years occurred in 15 per cent. There was a diminution in the rate of wear with the passage of time; in the second 5 years the rate of wear was approximately 40 per cent less than in the first 5 years. Body weight and physical activity did not appear to have any relationship to the final amount of wear. In a second series of very disabled subjects under 30 years of age (33 patients, 59 hips, followed only for an average of 38.4 months) the wear was rather more than in the previous series. Most remarkable was the performance of 4 patients, below the age of 50, who were considered completely normal for their age (category A); three of these wore less than the average for the main series.


Results of low friction arthroplasty in patients thirty years of age or younger. The results of total hip replacement in 39 patients 30 years old or younger were evaluated including 67 Charnley low-friction arthroplasties and one McKee total hip arthroplasty. The average age was 25.9 years with an average follow-up of 39 months, the longest being 8 years, 3 months. The diagnoses included rheumatoid arthritis, ankylosing spondylitis, CDH, Still's disease, and a miscellaneous group. Over-all function did not improve as greatly as in the 9 to 10 year series, but this was due to a higher proportion of patients with severely disabling rheumatoid polyarthritis, hemiplegia, severe obesity, or cardiovascular disease. Wear did not seem to be any greater in this younger age group as compared to previous studies in older patients.


Physiologic emboli changes observed during total hip replacement arthroplasty. A clinical prospective study. Fat embolism does occur with introduction of femoral components during total hip replacement arthroplasty. If massive, abrupt severe irreversible interruption of pulmonary oxygen exchange or profusion can occur. Adequate intramedullary femoral canal venting can significantly reduce the amount or dosage of fat embolism and thereby reduce and prevent primary or superimposing secondary injury of the capillary-alveolar gas exchange area within the lungs. The occurrence of fat embolism supports the mechanical theory. It also demonstrates that a patient surviving the effects of the acute mechanical pulmonary insult may still have to survive the more common and typical clinical picture of the metabolic pulmonary disease result of fat embolism that likewise can be irreversible. To prevent the occurrence of fat embolism during femoral component insertion with total hip replacement arthroplasty, the following techniques are imperative: (1) adequate femoral intramedullary canal venting; (2) maintenance of pulmonary arterial oxygen tension; (3) maintenance of blood volume.


Total hip replacement: a comparison between the transtrochanteric and posterior surgical approaches. It can be argued with good justification, that the trochanteric complications which stimulated this study could have been avoided by strict adherence to Charnley's technique regarding trochanteric advancement and re-attachment. Should trochanteric reattachment be required, it should be done with strict attention to the details outlined by Charnley, or by use of some other device such as the Volz bolt. Trochanteric removal is usually unnecessary. The transtrochanteric approach to total hip replacement has inherent technical problems that increase the potential for complications. These problems include: painful trochanteric bursitis, displacement of trochanter, non-union of trochanter, broken wires and, an increase in dislocation rate (12% as compared to 4%). The posterior approach reduces operative time, blood loss, hospitalization, and shortens the period of time to unprotected weight bearing. Should certain conditions such as external rotation contracture, acetabular protrusion, or relative lengthening of the operated limb indicate trochanteric osteotomy, it can be accomplished readily by way of the posterior exposure.


Unicompartmental polycentric knee arthroplasty: description and preliminary results. Unicompartmental polycentric knee arthoplasty is a procedure that we have performed in relatively few patients whose disease has not been suitable for conventional reconstruction or for total knee replacement. Preoperative and postoperative evaluations and operative technique differ little from that previously published for total knee arthroplasty. One-year follow-up of 14 knees (13 patients) reveals no major complications. These early results encourage further trial of the procedure in selected patients. Unicompartmental arthroplasty is reserved for conditions affecting predominantly one side of the joint. More specific indications are clearly defined and pertain to patients who have osteoarthritis unsuitable for valgus upper tibial osteotomy, condylar fracture and necrosis, and failure of osteotomy and tibial plateau prosthesis.


Displaced fractures of the major pelvis: a method of management. Fractures of the bony pelvis occur with such violence that associated non-musculo-skeletal injury is common. The patients require an aggressive team approach if they are to leave the hospital alive. After the visceral injuries are treated, the bony pelvis should be aligned to minimize secondary sacroiliac arthritis. Following initial pelvic sling management, the reduction of these fractures is accomplished by using the Keim-Surcingle table coupled with a pantaloon spica cast to maintain the reduction. The patient is then managed by bedrest at home until 12 weeks post-injury at which time the plaster is removed and ambulation is progressed as tolerated. The pubic diastasis may increase if plaster immobilization is discontinued too early. We hope that an aggressive initial evaluation and team approach coupled with this method of reduction and immobilization will decrease significantly the mortality and morbidity associated with displaces fractures of the major pelvis.


Iatrogenic subcapital fracture of the hip: a new complication of intertrochanteric fractures. A recently recognized complication of intertrochanteric fracture is a subcapital fracture occurring at the tip of the blade of an intertrochanteric fracture fixation blade plate. Histological examination reveals that this is not a fatigue fracture but is the result of stress concentration effects of a stiff metalic device. This fracture may be prevented by using a blade plate with a long blade which is well seated in the head, and by removing the metallic device as soon as it is safe to do so. Ultimate prevention lies in using a more compatible material for the internal fixation of fractures.


Rationale and indications for the "hanging hip" procudure: a clinical and experimental study. A series of 71 patients treated by "hanging hip" procedures was followed for up to 12 years. The procedure provided a satisfactory result in patients even with severe hip joint degeneration as long as the congruity of the joint is preserved and there was no concentration of stress. When these conditions are not fulfilled the results are poor. An experimental study was carried out to try and ascertain the physiological rationale for the "healing" seen in patients with good preoperative indications. The articular cartilage of one hip in cats was denuded with a curette. This was accompanied in half the animals with a "hanging hip" procedure. The hips of the animals with "hanging hip" went onto fibrocartilaginous and chondroid healing of their articular surfaces and clinically did well. The hips of the animals who did not have multiple tenotomies developed osteoarthrosis. Full thickness cartilage defects in weight-bearing areas in adult animals are capable of functional healing if the mechanical stress on the joint is sufficiently decreased. The "hanging hip" operation should no longer be considered a salvage procedure. A physiological rationale exists for it in properly selected patients and represents a reasonable alternative to total hip replacement.


Knee morphology as a guide to knee replacement. The complexity of knee geometry requires correct prosthesis design and size selection for the recipient. This study analyzes the morphological relationships within the knee; 16 linear anatomical parameters were measured on 30 cadaveric knees. The marginal femoral condylar contour was geometrically described by two tangent radii. Standardized radiographic techniques were developed to obtain a modified tunnel and true lateral view of the knee. Subsequently, X-rays were taken from 11 cadaver knees to achieve reproducible magnification factors. From X-rays of 53 normal subjects, 11 comparable linear dimensions were measured. The linear dimensions and condylar contour measurements were analyzed for their interrelationships by computer techniques. The width of the femur was found to be dimensionally related (correlation coefficient significant at the one per cent level) to the measured parameters with the exception of the intercondylar notch and interspinous widths. Using regression analysis, nomograms were developed to predict the linear and marginal femoral contour dimensions from the femur width. The resulting standard deviations were low, ranging from 1.0 mm for ascertaining the tibial width to 3.5 mm for determination of the femoral width at the level of the intercondylar notch. The nomograms we developed will aid the surgeon in a more precise, preoperative, morphological evaluation and may be used as a guide for future knee prosthesis design.


A jig for pin insertion in the performance of high tibial osteotomy. The crucial step in high tibial osteotomy is to translate the computed angle of correction into a bone wedge outlined by 2 Kisrchner wires to guide the surgery. The wedge can be excised with precision in 2 planes. A jig facilitates accurate placement of the pins to correspond exactly to the predetermined angles.


Keyhole tenodesis of biceps origin at the shoulder. A simple but efficient way to secure the biceps tendon after it has been detached at its upper end by either trauma, attrition or surgical interference is the use of the keyhole in the upper humerus. A tied or rolled knot of tendon inserted into a keyhole shaped opening in the bicipital groove permits firm attachment of the tendon to bone permitting immediate shoulder and elbow motion. Immediate postoperative joint motion avoids aggravation of coexisting shoulder disease and permits early return to work or sports. Use of this procedure in 11 patients with good to excellent results in all confirns its merit.


Epidemiology of fracture of the upper end of the humerus. The age and sex specific indicence was calculated in 729 cases of fracture of the upper end of the humerus. The prevalence of other fractures and conditions in these patients was investigated. The age and sex specific incidence is as that of femoral neck fracture with a rapid increase with age, twice as fast in women as in men. Only fractures which include evulsion of the greater tuberosity deviate somewhat from that pattern. The more displaced fractures have a tendency to occur later in life. The prevalence of other fractures is about doubled in patients with fracture of the proximal end of the humerus as compared to age and sex matched controls. This is true for fracture of the distal end of the forearm and fracture of the upper end of the femur but also for other fractures. The prevalence of severe alcoholism was significantly greater than in controls. A history of gastric resection was in these patients about three times as frequent as in a control sample. We conclude that fracture of the upper end of the humerus must be assigned a prominent place in the category of bone fragility fractures.


Fractures of the humeral shaft: a retrospective study of 240 adult fractures. Of 240 humeral fractures, 60 per cent occurred in patients under 35 years old, 39 per cent of fractures being in the middle third of the shaft, 28 per cent were open with an infection rate of 4 per cent. Radial nerve palsy was present in 18 per cent; midshaft fractures accounting for 69 per cent, with 60 per cent of radial nerves recovering spontaneously; 24 per cent after 12 weeks post injury. One hundred and eleven fractures had documentation greater than 3 months. Closed treatment in 100 patients resulted in 5 non-unions and 15 delayed unions; 11 primary internal fixations resulted in 3 non-unions and 2 delayed unions. Subsequent operative procedures reduced the total non-union rate to 5 per cent with 1 per cent delayed union and 4 per cent unknown. Fractures of the humeral shaft that have not begun to unite at 6 to 10 weeks probably will go on to non-union unless the treatment plan is changed. Closed methods of immobilization, other than the sling and swathe, should be used in chronic brain syndrome patients to avoid compounding their fractures. Sixty-three patients with 64 fractures were evaluated in follow-up using Cave's AEF system (92% excellent and satisfactory results) and a modification of Neer's protocol for proximal humeral fractures, (87% excellent and satisfactory results). A functional evaluation on the Cybex machine, (torque through range of motion) gave a useful graphic end result.


Treatment of thoracolumbar dislocation and fractures with paraplegia. Ninety per cent of fractures of the dorsal lumbar spine with paraparesis or paraplegia can be best treated and reduced by closed methods when satisfactory alignment can be obtained. The pathology of the corc can thus be allowed to regress and recover if it will do so. Strict posturing techniques are the most important part of medical and nursing care. Approximately 10 per cent of the cases can be treated by gentle, active surgical techniques such as manipulation under general anesthesia or open reduction. The use of spinal rods and clamps is rarely indicated. Surgical techniques may be advisable later for treatment of non-union with spinal stenosis and failure to improve.


Lysozyme in calcifying tissues.

Lysozyme in calcifying tissues. Lysozyme, present in several connective tissues, is synthesized in cartilage by chondrocytes and immediately secreted into the extracellular matrix, where it is bound in the territorial (lacunar) matrix and along collagen fibers. In the epiphyseal growth plate, lysozyme levels increase toward the cartilage-bone junction, but cartilage lysozyme seems to be bound or inactivated by an inhibitor. Parathyroid extract injections decrease bone lysozyme levels. Cartilage lysozyme levels are low in rickets, while vitamin D increases it in both cartilage and aorta, suggesting an association between lysozyme and the calcification process. Although it is cationic and forms salt-like complexes with cartilage proteoglycans and chondroitin sulfate in vitro, lysozyme does not seem to be bound to proteoglycans in the native tissue. Proteoglycans in cartilage exist in a monomeric and aggregated form. Aggregation occurs by an interaction of monomers with hyaluronic acid and spedific link proteins. Aggregated proteoglycans inhibit mineral accretion in vitro. Mammalian cartilage lysozyme but not hen egg white lysozyme seems to inactivate this inhibitory capacity of aggregated proteoglycans, which is probably due to an interaction with hyaluronic acid resulting in a disaggregation. Therefore, we hypothesize that cartilage lysozyme plays an important role in the regulation and initiation of cartilage calcification.