SiR,—Icannot accept the existence of non-renin-mediated as a new syndrome on the evidence Dr Marks and his colleagues (March 19, p. 615). Far more substantiation is required because if this syndrome does not exist, the clinical value of divided renal-vein-renin determinations will have been needlessly questioned. Saralasin will consistently lower the blood-pressure only when plasma-renin is raised, irrespective of whether this high renin is brought about by renovascular hypertension or by sodium depletion.1,2 The subnormal renin in the two patients of Marks et al. would preclude a blood-pressure-lowering effect of saralasin2 but not an initiation of renovascular hypertension I by the renin angiotensin system.3 More important, the renal-vein-renin studies cannot exclude renin-mediated renovascular hypertension in their two patients. The low peripheral renin concentrations suggest that the renin-angiotensin system had already fulfilled the perfusion needs of the stenotic kidney by raising the blood-pressure sufficiently, and a left/right difference in renin secretion at this late stage3 of renovascular hypertension would not be expected. Instead of measuring renal-vein renins under "slight

renovascular hypertension

provided by

Supine 4.01




return to


blood-pressure after operation




expected. Renal-vein-renin studies should be done during acute reduction of blood-pressure to normal. This would simulate preoperatively the expected postoperative fall in blood-pressure and thereby unmask the perfusion needs of the stenotic and contralateral kidney. Hydrallazine6 or diazoxide7 may provide a less elaborate means than nitroprusside4,1 for doing these studies. This work was supported by the Fonds schaftlichen Forschung, Austria.


Forderung der

Medizinische Universitätsklinik, A-6020 Innsbruck, Austria




SIR,-Extensive measurements have been made of the total loads borne by human synovial joints.’ Progress in understanding the failure of articular cartilage in osteoarthrosis has been hampered, however, by lack of information about the distribution of pressures upon joint surfaces, the extent of the deformation of articular cartilage that occurs in the intact joint under load, and the relation between the degree of deformation under measured loads and age. We have developed a radiographic technique that permits measurement of the deformation under load of human articu-


Stenotic kidney

Contralateral kidney

Renal-vein-renin studies in seven patients with unilateral renovascular hypertension done when the patient was supine and after nitroprusside-induced normotension.

Results are expressed as venous/arterial ratio of plasma-renin action both sides. A factor greater than 1 indicates renin secretion. Plasma-renin activity was measured by the method of Boyd et al.8 which ensures the exclusive measurement of active renin. Renal arterial renin peripheral venous renin.’ Patients 6 and 7 are indicated


I-Distribution of deformation of femoral-head cartilage for load of five times body-weight. Lateromedial projection.




Left, female, 32

sodium depletion", as Marks et al. did, it would seem more rational to use a test which strains the baroreceptors of the ischsemic and contralateral kidney. During the past three years we have investigated seven patients with renovascular hypertension similar to the two described by Marks et al. All were cured by surgery. The figure shows that in all of them we got false-negative results when the renal-vein was sampled with the patient supine. Only after reduction of blood-pressure to normal by sodium nitroprusside infusiondid we find a selective increase in renin secretion on the stenotic side; contralateral renin secretion remained suppressed. In our experience’ stimulation of renin secretion in both kidneys indicates hypertensive damage in the contralateral kidney and permanent 1. Brunner,


R., Gavras, H., Laragh, J. H., Keenan,

1045. 2.Streeten, D. H. P.,


G. H.


right, female,

80 years.

in specimens of whole hip joints obtained post Phosphotungstic acid added to propyliodine (’Dionosil’ oily) was selected as a radio-opaque contrast medium. Injected into the joint spaces this medium provided excellent lar



definition of the acetabular/femoral-head interface in the intact joint. The joints were subjected to loads of five times bodyweight for the 35s required to make a radiograph. From the X-ray films, the thickness of the femoral-head cartilage was determined to an accuracy of 1%. Measurements were made every 200 around the femoral-head circumference.2 Comparison of cartilage thickness before and during loading provided an accurate assessment of the cartilage deformation profile. Twenty-eight whole hip joints from people aged 26-83 years were


Lancet, 1973, ii,

Jr., Dalakos, T. G. Am. J. Med. 1976,

60, 817. 3.Brown, J.J., and others, Lancet, 1976, i, 1219. 4.Kaneko, Y., Ikeda, T., Takeda, T., Ueda, H. J. clin. Invest. 1967, 46, 705. 5. Skrabal, F., Margreiter, R., Stampfel, G. O., Rössler, R., Hammerer, I., Spielberger, M., Flora, G., Dittrich, P. Nier-Hochdruckkrankheit. 1976,



6. Mannick, J. A., Huvos, A., Hollander, W. E. Ann.Surg. 1969, 170, 409. 7. Stokes, G. S., Weber, M. A., Gain, J., Scott, A. J., Roberts, B. A., Sheil, A. G. R. Aust. N.Z. Jl. Med. 1976, 6, 26. 8. Boyd, G. W., Adamson, A. R., Fitz, A. E., Peart, W. S. Lancet, 1969, i, 213. 9. Stockigt, J. R., Collins, R. D., Noakes, C. A., Schambelan, M., Biglieri, E. G. ibid. 1972, i, 1194. 1. Paul, J. P. Proc.R.Soc.B, 1976, 192, 163. 2. Armstrong, C. G., Gardner, D. L. Ann. rheum. Dis. 1977, 36, (in the press).


damaging mechanisms, further increasing cartilage compliance and precipitating mechanical failure. other

Department of Mechanical Engineering, Queen’s University of Belfast Department of Histopathology, University of Manchester, Manchester M13 9PT



SIR,-Endocrine dysfunction can cause severe psychological disturbances, but the prevalence of endocrine disorder among has not been determined. Psychological abnormalities are associated with thyroid-gland dysfunction" and also with Cushing’s syndrome,4.s Addison’s disease,6 and hypopituitarism.’ The long-term psychological impact in females with adrenal hyperproduction of 17-ketosteroids (17-K.s.) with resulting secondary amenorrhaea, obesity, and hirsutism8 has not been fully elucidated. No specific psychological profile has been correlated with any endocrine disorder, so there may be no way to distinguish psychiatric problems caused by purely emotional disturbances .from those caused or aggravated by underlying endocrine disease. We report here the results of a routine endocrine screen for thyroid and adrenal dysfunction among psychiatric patients not on drugs, Fifty patients (thirty-eight females) aged 18-62 have been screened since July, 1976. These were patients who were admitted to the general psychiatric service at the Upstate Medical Center and who could be safely kept off medications, apart from aspirin for headache and flurazepam for sleep. This restriction was necessary because barbiturates, antidepressants, chloral hydrate, phenothiazines, and chlordiazepoxide interfere with Porter-Silber analysis of urinary 17-hydroxycorticosteroids (17-OHc.s.).9 We also wished to control for any direct effect these drugs could have on thyroid or adrenal function, After a 5-day adaptation period to avoid spurious results secondary to the stress of admission,1O 24 h urines were collected for analysis of 17-OHc.s. as Porter-Silber chromagens.11 Blood was drawn for serum-thyroxine (T4) by radioimmunoassay and free thyroxine (FT4) analysis by Bio-Science Laboratories (Van Nuys, California). Urinary collections were repeated 2 weeks later on patients with abnormal 17-OHc.s. values (normal range 2-0-6-5mg/g creatinine/24 h). Patients known to have adrenal or thyroid dysfunction were excluded. Three patients had serum-thyroid-hormone levels outside the normal range. Further tests excluded the "sick euthyroid" as the cause of these increases in T and FT4. The first patient was a female admitted for psychosis, with agitation, tachycardia, diffuse sweating, and restlessness, These symptoms had been attributed to her psychiatric disease. After a month of treatment with 60 mg daily of methimazole her psychosis and clinical symptoms resolved. All psychological and physical symptoms disappeared in 2 months as her FT4 and T4 levels fell to normal. The second patient was a 28-year-old male admitted for

psychiatric patients




between compliance of femoral-head and age, measured in intact hip joint.

Fig. 2-Relation


Compliance = -0.0059 + 0.00032 (age) (r=0.846,0 <0.001.) The distribution of deformation in the lateromedial projection was a double-peaked curve approximately symmetrical about the load axis (fig. 1). Experiments indicated a similar distribution over the rest of the contact area. The distribution of deformation over the whole contact area could consequently be inferred from measurements made in a single plane. The average compliance over each whole hip-contact area was determined by dividing the integrated deformation over the contact area by the total force applied to the joint. Compliance increased with the age of the specimen (fig. 2). In young specimens (fig. 1) the cartilage was almost incompressible but in old specimens (fig. 1) reductions in cartilage thickness of 15% were common.

This increase in cartilage compliance implies mechanical or biochemical changes3 in the cartilage microstructure with age. These changes are likely to influence the mode of failure of cartilage as a bearing material. The resistance of normal cartilage to deformation is due to the elasticity of the tissue and to resistance to the flow of interstitial fluid in the matrix. The elastic stiffness of the tissue may be affected by a number of factors. Resistance to deformation by a small indentor is dependent on the proteoglycan content of the tissue.4 A reduction in the degree of aggregation or polymerisation of these large molecules has been observed in osteoarthrosis.’ Fracture of the collagen fibres constraining the proteoglycans and their aggregates has also been suggested as a mechanism for failure.6 The flow of interstitial fluid is dependent on the permeability of the cartilage and the porosity of the surface.’ This investigation demonstrates that older cartilage becomes

increasingly compliant.

A load


to an




deformation than the same load applied to young joint. These large deformations could accentuate

cause a



Elliott, R. J., Gardner, D. L. Unpublished. Kempson, G. E., Muir, H., Freeman, M. A. R., Swanson, S. A. V. Biochim. biophys. Acta, 1970, 215, 70. 5. Brandt, K. D., Palmoski, M. Arthr. Rheum. 1976, 19, 209. 6. Freeman, M. A. R. Acta orthop. scand. 1975, 46, 323. 7. Torgill, P. A., Mow, V. C. J. Biomech. 1976, 9, 193.

3. 4.


1. 2. 3.

Johnson, W. O. J. nerv. ment. Dis. 1928, 67, 558. Asher, R. Br. med. J. 1949, ii, 555. Whybrow, P. C., Prange, A. J., Treadway, C. R. Archs. gen. Psychiat. 1961, 20, 48. 4. Freedman, A. M., Kaplan, H. I., Sadock, B. J. Comprehensive Textbook of Psychiatry: Modern Synopsis; p. 467. New York, 1975. 5. Michael, R. P., Gibbons, J. L. Int. Rev. Neurobiol. 1963, 5, 243. 6. Cleghorn, R. A. Can. med. Ass. J. 1951, 65, 449. 7. Dissanayake, S. A. W., Leiberman, D. M. J. Neurol. Neurosurg. Psychiat. 1969, 32, 233. 8. Bolinger, R. E. Endocrinology: New Directions in Therapy; p. 164. New York, 1977. 9. Alsever, R. N., Gotlin, R. W. Handbook of Endocrine Tests; p. 40. New York, 1967. 10. Sachar, E. J. Archs. gen. Psychiat. 1967, 17, 544. 11. Porter, C. C., Silber, R. H. J. biol. Chem. 1950, 85, 201. 12. Carter, J. N., Corcoran, J. M., Eastman, C. J., Lazarus, L. Lancet, 1974, ii, 971.