371

might easily be all that Nature required for this function,so little was the force called for.

Fig. 1 shows a dog’s stomach prepared as describedabove, filled with water, and inverted. No water is

escaping from the cardia. Fig. 2 shows the same preparationa few moments later. The stump of the oesophagus is nowbeing pulled on, and water is escaping. The amount oflongitudinal tension required was found to be a shadeover 1 g. weight.

It was suggested in the monograph that elevation of thecardia, which always accompanies opening, is an essentialelement of opening, and explanations of why this shouldbe so and how it might be effected were offered.

H. DAINTREE JOHNSON.

GONADOTROPHINS AND TESTOSTERONE

IN THE XYY SYNDROME

SIR,-Reports on the testicular status of males with anXYY chromosomal pattern have presented conflicting data.For example, Papanicolaou et al.,’ using a bioassay, foundraised urinary luteinising hormone (L.H.) excretion titres inthe three men they studied. Parker 2also reported uniformlyincreased L.H. levels in seven’XYY males. He measuredL.H. titres by radioimmunoassay. Further examination ofpituitary/Leydig-cell function was done by Hudson,3 whofound that plasma testosterone and L.H. levels were uni-formly normal in five XYY males. Price detected normaltestosterone titres in an additional seventeen XYY males.Evaluation of follicle-stimulating hormone (F.S.H.) hasreceived little attention. Papanicolaou 1 found normalurinary F.s.H. values in two men and intermittently raisedlevels in a third with the XYY pattern. Since much of thework discussed above was done on prison inmates, Shapiro 5has stressed the necessity of using control subjects froma similar population.

Six patients with the XYY syndrome were detected byscreening prison inmates and patients attending a derma-tology clinic with severe pustular acne. An additional

patient was studied after being diagnosed during a routineinfertility evaluation in a metropolitan hospital. Serum L.H.and F.S.H. levels were determined by radioimmunoassay 6,7and plasma-testosterone by a modification of the competitiveprotein-binding method described by Mayes and Nugent. 8

Serum-gonadotrophin levels were determined in normalmen to serve as control values. The mean serum-L.H. levelin 42 male prison inmates between 19 and 45 years of agewas 10.5 mi.u. per ml. (range 4-4-23). These values,whether for institutionalised or non-institutionalised men,did not differ significantly from the mean L.H. level (10-7) inour total control group of 112 normal men. The mean serum-F.S.H. titre in 62 men with normal sperm-counts was365 ng. per ml. LER-907 (range 150-610) and the meantestosterone in 60 normal males aged 20-45 years was0.67 g. per 100 ml. (range 0-28-1-44). The results in

patients with the XYY syndrome were as follows:

1. Papanicolaou, A. D., Kirkham, K. E., Loraine, J. A. Lancet, 1968,ii, 608.

2. Parker, C. E. ibid. 1969, i, 1101.3. Hudson, B., Burger, H., Weiner, S., Sutherland, G., Bartholo-

mew, A. A. ibid. 1969, ii, 699.4. Price, W. H., Van der Molen, H. J. J. Endocr. 1970, 47, 117.5. Shapiro, L. R. Lancet, 1970, i, 623.6. Paulsen, C. A., Gordon, D. L., Carpenter, R. W., Gandy, H. M.,

Drucker, W. D. Rec. Prog. Horm. Res. 1968, 24, 321.7. Midgley, A. R., Jr. J. clin. Endocr. Metab. 1967, 27, 295.8. Mayes, D., Nugent, C. A. ibid. 1968, 28, 1169.

All men with the XYY syndrome had normal plasma-testosterone levels. Six of seven had normal serum F.s.H.and L.H. levels. One male (case 1) with clinical evidence ofandrogen deficiency and a normal plasma-testosterone of0-48 fLg. per 100 ml. had raised F.S.H. (700 ng. per ml.) andL.H. (52 mi.u. per ml.) levels. Similar findings have beenreported from this laboratory in patients with Kline-felter’s (XXY) syndrome.’ While 50% of our Klinefelter’ssyndrome patients with clinical evidence of androgendeficiency had normal plasma-testosterone levels, all butone had raised L.H. levels. This combination of findingssuggests an alteration of the pituitary/ Leydig-cell axis in

response to gonadal disease, and may suggest that higher-than-normal levels of L.H. are necessary to promote testicu-lar steroidogenesis.The man who presented at an infertility clinic (case 7)

had azoospermia. A testicular-biopsy specimen revealed thefollowing: (1) absence of germ-cells; (2) no tubular-membrane hyalinisation; and (3) normal-appearing Sertoliand Leydig cells. The " Sertoli-cell only

"

syndrome hasnot been previously reported in association with the XYYchromosomal configuration. Most patients studied in ourlaboratory with the Sertoli-cell-only syndrome have hadraised F.S.H. levels. The normal F.S.H. values encountered inthis patient emphasise the lack of basic information aboutF.S.H. feedback mechanisms. F.S.H. levels, similarly, arenormal in many oligospermic patients with adult semini-ferous-tubule failure. 9

Apparently most patients with the XYY syndrome havenormal levels of serum L.H., F.S.H., and testosterone whenmeasured by specific methods and compared with suitablecontrols. This implies normal gonadal status, includingspermatogenesis, although in this study germ-cell matura-tion was not studied directly. On the other hand, a smallpercentage of patients with this syndrome have testiculardisease 10 and raised gonadotrophins.

This work was supported by N.I.H. grants AM 05436 andAM 05161.

University of Washington,Seattle.

RICHARD J. SANTENDAVID M. DEKRETSERC. ALVIN PAULSEN.

University of Michigan,Ann Arbor. JOHN VORHEES.

SEVERE CHILDHOOD HYPERTENSION

FOLLOWING CENTRAL-NERVOUS-SYSTEM

INFECTION

SIR,-Sustained arterial hypertension following polio-myelitis has been reported by several workers,ll,12 and otherviral infections of the nervous system may have a similareffect. 13 The following case-report describes malignanthypertension in a child who had had a non-paralyticinfection of the central nervous system at the age of 2.

Case-reportA 12-year-old schoolgirl was referred for further manage-

ment of her hypertension, having become too old for theChildren’s Hospital. There was no family history of hyper-tension or renal disease. At the age of 2 she had beenadmitted to a hospital with a febrile illness causing con-vulsions, coma, and head retraction. She had recoveredand had been discharged after 10 days; no paralysis hadbeen detected. No clinical details of this illness are avail-able, but there is an index card showing a diagnosis of9. Leonard, J. M., Leach, R. B., Paulsen, C. A. Clin. Res. 1970, 18,

169.10. Balodimos, M. C., Lisco, H., Irwin, I., Merrill, W., Dingman, J. F.

J. clin. Endocr. Metab. 1966, 26, 443.11. Lancet, 1959, ii, 120.12. Ostfeld, A. M. Archs intern. Med. 1961, 107, 551.13. Zimanyi, I., Prohaszka, M., Szondy, M., Ormai, S. Acta med.

scand. 1959, 164, 497.

372

meningitis. The mother was with the child during mostof the period in hospital and is sure that no antibiotics weregiven. The child first complained of headaches at the age of5, and at age 11 she was found to have a blood-pressure of185/140 mm. Hg, with retinal changes of arterial narrowing,haemorrhages, exudates, and papillcedema. Early urinespecimens contained blood and albumin, but these clearedwhen the blood-pressure was controlled. Many estimationsof blood-count, blood-urea, serum-electrolytes, blood-sugar, endogenous-creatinine clearance, and urine culturehave given normal results. Cystoscopy and bilateral retro-grade catheterisation were normal, and specimens fromboth ureters were normal. Urinary sp. gr. varied between1-000 and 1022. The adrenals had been explored when shewas aged 11, and had been macroscopically normal; theright adrenal had been removed but this did not changethe blood-pressure. At the age of 12, 24-hour urinarypressor amines were still normal, the kidneys were macro-scopically normal with normal vasculature, and a wedge-biopsy from the right kidney showed 1 hyalinised glomeru-lus but no evidence of pyelonephritis or other renal disease.Muscle-biopsy specimens from two different sites showedno evidence of a vascular lesion, and a bone-biopsy specimenfrom the 12th rib had a normal content of lead.She had originally been treated with oral pentolinium,

up to 900 mg. per day, and oral reserpine up to 1-0 mg. perday. This combination had caused disappearance of thepapillredema, leaving arterial narrowing and exudates, butpostural hypotension was a problem and morning headachesprevented the patient from attending school. At the timeof transfer to the adult hospital, the dose of oral pento-linium was 640 mg. per day, and resting blood-pressurewas approximately 180/120 mm. Hg. The patient wastherefore treated instead with mecamylamine alone, in anoral dose of 2’5 mg. 3 times daily. Blood-pressure fellto around 140/110 mm. Hg, but later rose to about160/120 mm. Hg. Oral reserpine was again added in a doseof 0-25 mg. 3 times daily and the blood-pressure wasstabilised at about 150/100 mm. Hg. The patient felt verywell, and was able to return to school, take part in normalsports and pass the State examination.

DiscussionThe description of the illness at the age of 2 suggests a

viral illness rather than a bacterial meningitis. Althoughthe encephalitic form of poliomyelitis can cause coma andconvulsions, there was apparently no paralysis and norespiratory failure. The hypertension following polio-myelitis has usually shown a correlation with the severityof the paralysis 2,3 and Ostfeld 2 has suggested that themuscle wasting is the cause of the sustained hypertension.It therefore seems reasonable in this case to suspect somevirus other than poliomyelitis.The apparent resistance of the hypertension to pento-

linium, and the ease of control by mecamylamine plusreserpine, is of interest in view of the finding that patientswho had required high doses of pentolinium also neededhigh doses of mecamylamine when their therapy waschanged.l4 It has been suggested that mecamylamine differsfrom pentolinium because of its ability to pass the blood-brain barrier .15

Since essential hypertension is very rare in children," andsince no other cause of hypertension was found, we postu-late that the intracranial infection was the cause of the

hypertension.. The differential response to an agent whichcan act on the nervous system appears to support this view.

Princess Alexandra Hospital,Woolloongabba,

Queensland, Australia. KEVIN J. MURPHY.

14. Freis, E. D., Wilson, I. M. Archs intern. Med. 1956, 97, 551.15. Bennett, G., Tyler, C., Zaimis, E. Lancet, 1957, ii, 218.16. Oliver, W. J., Talner, N. S., Stern, A. M. J. Mich. med. Soc. 1960,

59, 82.

FREE-CYANIDE LEVELS IN TROPICAL ATAXICNEUROPATHY

SiR,-Chronic cyanide intoxication is the most importantfactor in the aetiology of tropical ataxic neuropathy in

Nigerians. 1-6 The evidence includes raised levels of thio-cyanate (detoxication product of cyanide) and cyanide inplasma, increased 24-hour urinary excretion of thiocyanate,reduced levels of sulphur-containing aminoacids in the

plasma, and quantitative changes in the components ofvitamin B112 in the serum. In the earlier studies, the methodof estimation of plasma-cyanide 7 probably measured onlythe bound cyanide. The purpose of this investigation wasto estimate the free cyanide in the blood of Nigerian patientswith tropical ataxic neuropathy.

Heparinised blood was obtained from 37 Nigerianpatients with tropical ataxic neuropathy and from 30 normalNigerians (members of staff of U.C.H., Ibadan). Nonesmoked cigarettes. The normal Nigerians did not eat cassavameals more than 2 or 3 times a week. The patients atecassava meals 3 or more times a day (of necessity).

Glassware was cleaned in chromic acid, washed in tap-water, and rinsed 3 times with glass-distilled ion-free water.About 20 ml. of blood obtained from the subjects wasdivided into 2 equal portions.

Free cyanide.-Free cyanide was measured by a modificationof the method of Boxer and Rickards. To a measured amount ofwhole blood, 4 mmole of p-chloromercuribenzoic acid, an

enzyme inhibitor, and 1 ml. of 5% sodium hypophosphite wereadded, to prevent formation of cyanide from thiocyanate (by theenzyme thiocyanate-oxidase present in red blood-cells and freeoxidation of thiocyanate to cyanide). The blood was then aeratedby a cyanide-free-nitrogen stream of 1000 ml. per minute for90 minutes and the cyanide liberated was trapped or collected intwo tubes in series, each containing 1 ml. of freshly preparedsodium hydroxide (0-1 N). Aeration of whole-blood was com-menced within 10 minutes of collection. It was found necessaryto introduce a thin film of silicon oil to the aeration tube contain-ing the blood to prevent overflowing.Bound cyanide.-Plasma from the second aliquot of blood was

deproteinised with 10% trichloroacetic acid. 4 mmole of p-chloro-mercuribenzoic acid and 1 ml. of 5% sodium hypophosphatewere added. The solution was then aerated as described above.

Deproteinised plasma was immediately stored at - 20°C untilready for aeration, which was commenced within 3 hours ofcollection.

The results are shown below (expressed in mmole per100 ml. -{-S.B.).

Free cyanide Bound cyanide,

in blood in plasmaPatients (37) .... 0.051 +0’003 0-108+0-003Controls (30) .... 0 031 +0 003 0 071 +0 008

The difference in the concentrations of free cyanide andbound cyanide between patients and controls are statisticallysignificant (P < 001).

In man, there is dynamic equilibrium between cyanideand thiocyanate, the concentration of cyanide in the bodybeing of the order of 0-25-0-5% that of thiocyanate.8 Thecyanide ion is very reactive chemically and biologically, andhas great affinity for metal-containing enzymes and haemo-globin. This study shows that, in Nigerian patients withtropical ataxic neuropathy, the concentrations of freecyanide in whole-blood were significantly higher than innormal controls, and provides further evidence of the

important role of chronic cyanide intoxication in the

aetiology of tropical ataxic neuropathy in Nigerians.1. Monekosso, G. L., Wilson, J. Lancet, 1966, i, 1062.2. Osuntokun, B. O. Brain, 1968, 91, 215.3. Osuntokun, B. O., Durowoju, H. E. O., MacFarlane, H., Wilson, J.

Br. med. J. 1968, iii, 647.4. Osuntokun, B. O., Monekosso, G. L., Wilson, J. ibid. 1969, i, 547.5. Osuntokun, B. O. PH.D. thesis, University of Ibadan, 1969.6. Lancet, 1969, ii, 942.7. Boxer, G. E., Rickards, J. C. Archs Biochem. 1950, 30, 372.8. Boxer, G. E., Rickards, J. C. ibid. 1952, 39, 287.