growth hormone

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1341 7 firm applications for commissions and 17 for medical cadetships. In the House of Commons on June 6, the Secretary of State for Air, Mr. Julian Amery, was asked about the response as seen in the R.A.F. medical and dental branches. He said it had been " distinctly encouraging ": there had been 650 inquiries and over 60 firm applications, com- pared with 12 inquiries and 2 applications in the same period of last year. THE SURGICAL KNOT THE first thing the budding surgeon does to prepare himself for his life’s work is to retire into a comer and tie bits of string round a button in his white coat. He is learning to tie knots speedily, scorning the " granny " and adopting the " reef ", and he is also recapitulating the historical development of his art. For the objective-the staunching of blood-must be one of the most ancient of surgical rites. This time-consuming, tedious, and sometimes difficult surgical manoeuvre has changed little since earliest days. From time to time accounts of finicky little instruments, designed hopefully to mechanise a hand-made job, appear in surgical journals. But the prototypes find their way to dusty cupboards reserved for discarded instruments. Some surgeons dispense almost entirely with ligatures and use diathermy-a modem variation of cauterisation with boiling oil. But large vessels cannot safely be dealt with by this method, and many surgeons dislike it because it tends to favour the collection of serum in the wounds. Metallic clips, which are popular with neurosurgeons (and which also date from the remote past), have a limited use- fulness. On the whole most surgeons seem content to rely on manual dexterity achieved with practice. Willis Potts 1 describes a method whereby the surgeon holds the haemostatic forceps vertically by its middle, the assistant loops the ligature around its tip, and the surgeon lets the forceps drop on its side, whereupon the assistant ties the knot. Obviously this manoeuvre is not easily applied in the depths of a wound. But for incisional wounds it seems simple and easy to learn. A good knot depends on the ligature material. This, too, has changed little over the years, except for the introduction of nonabsorbable synthetic substances. Catgut (universally popular) is slippery and not so easy to handle as silk or linen thread which produce less tissue reaction and give firm and non-yielding knots. Some surgeons swear at (and less often by) the material of their choice; but so long as patients bleed when tissues are severed there will be a need for surgical knots and some- one to tie them, whether it is the surgeon or his assistant. No machine seems likely to displace them. SCINTILLATION RADIODIAGNOSIS Two technical developments in the diagnostic use of radioactive tracers were reported by Brownell and Sweet 3 in 1953. The first was the detection of positrons by scintillators placed on opposite sides of the head and recording only when stimulated simultaneously (within narrow limits). The second was a method of detecting gamma rays and of recording only the difference between 1. Potts, J. W. J. Amer. med. Ass. 1962, 180, 494. 2. See Lancet, 1961, ii, 416. 3. Brownell, G. L., Sweet, W. H. Nucleonics, 1953, 11, 41. counting-rates on the two sides of the head. Botterell et al. have now described their use of these methods over four years; they employed the same technique throughout and used ’4as in the form of sodium arsenate. Tumours with the greatest cellularity seemed to retain the isotope in greatest concentration. The highest values were in meningiomas, followed in order by glioblastomas, meta- static carcinomas, and astrocytomas. Unlike radioactive iodinated human serum-albumin 5 6 the isotope did not become concentrated to any detectable degree in subdural haematomas or arteriovenous malformations. In the detection of meningiomas this method contrasted with electroencephalography: the latter might fail to reveal this extrinsic tumour but nearly always indicated an intrinsic tumour. Angiography may also fail to outline positively a sphenoidal wing meningioma, and, because of obstruction at the opposite foramen of Monro, ventriculography in this condition can be highly dangerous. Had the scintil- lation method no other justification, this alone would recommend its provision in appropriate centres. One of the most important tasks in neurosurgery is to detect, as far as possible, every benign tumour at an early enough stage to ensure complete recovery of the patient. This can now be more nearly achieved if clinical acumen is exer- cised properly and neurosurgical facilities are ample. Neither of these requirements has been met in the past.8 9 GROWTH HORMONE THE species specificity of preparations of growth hor- mone from different animals formed a stumbling-block to study of the action of this hormone in man. Eventually it was shown that only primate growth hormone was active in man; and since then much work has been done on its metabolic effects.1o Growth hormone is not concerned solely with somatic growth: it is produced by the pituitary throughout life, and is a general metabolic hormone. It causes synthesis of protein, which is reflected in retention of nitrogen in the body, and along with this a proportionate retention of the mainly intracellular electrolytes-potassium and phosphorus. It also causes retention of sodium and chloride, largely extracellular, and hence expansion of extracellular-fluid volume. These changes seem to be independent of the secretion of aldosterone, and growth hormone has no immediate effect on blood-pressure. It might be expected to cause consistently a retention of cal- cium in the skeleton, but changes in calcium balance have been variable and the serum-alkaline-phosphatase is usually unaffected. Growth hormone also has an important effect on carbo- hydrate metabolism by impairing glucose tolerance and increasing resistance to insulin: under its influence dia- betics rapidly develop gross glycosuria. It has a direct action on fat metabolism in the normal (and particularly in the fasting) individual, mobilising non-esterified fatty acids and ketones; and in the diabetic it rapidly causes gross ketosis. 4. Botterell, E. H., Lougheed, W. M., Morley, T. P., Tasker, R. R., Paul, W. Canad. med. Ass. J. 1961, 85, 1321. 5. Chiro, G. di. Acta radiol., Stockh. 1961, suppl. 201. 6. Lancet, 1961, ii, 1186. 7. ibid. 1961, i, 1388. 8. Segelov, J. N., Davis, R. Med. J. Aust. 1961, ii, 1. 9. McKissock, W. J. Neurol. Psychiat. 1961, 24, 296. 10. See Finkel, M. J. Amer. J. Med. 1962, 32, 588.

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Page 1: GROWTH HORMONE

1341

7 firm applications for commissions and 17 for medicalcadetships.

In the House of Commons on June 6, the Secretary ofState for Air, Mr. Julian Amery, was asked about theresponse as seen in the R.A.F. medical and dental branches.He said it had been " distinctly encouraging ": there hadbeen 650 inquiries and over 60 firm applications, com-pared with 12 inquiries and 2 applications in the sameperiod of last year.

THE SURGICAL KNOT

THE first thing the budding surgeon does to preparehimself for his life’s work is to retire into a comer and tiebits of string round a button in his white coat. He islearning to tie knots speedily, scorning the " granny " andadopting the

" reef ", and he is also recapitulating thehistorical development of his art. For the objective-thestaunching of blood-must be one of the most ancient ofsurgical rites.This time-consuming, tedious, and sometimes difficult

surgical manoeuvre has changed little since earliest days.From time to time accounts of finicky little instruments,designed hopefully to mechanise a hand-made job, appearin surgical journals. But the prototypes find their way todusty cupboards reserved for discarded instruments.Some surgeons dispense almost entirely with ligatures anduse diathermy-a modem variation of cauterisation withboiling oil. But large vessels cannot safely be dealt withby this method, and many surgeons dislike it because ittends to favour the collection of serum in the wounds.Metallic clips, which are popular with neurosurgeons (andwhich also date from the remote past), have a limited use-fulness. On the whole most surgeons seem content to relyon manual dexterity achieved with practice.

Willis Potts 1 describes a method whereby the surgeonholds the haemostatic forceps vertically by its middle,the assistant loops the ligature around its tip, and thesurgeon lets the forceps drop on its side, whereupon theassistant ties the knot. Obviously this manoeuvre is noteasily applied in the depths of a wound. But for incisionalwounds it seems simple and easy to learn.A good knot depends on the ligature material. This,

too, has changed little over the years, except for theintroduction of nonabsorbable synthetic substances.

Catgut (universally popular) is slippery and not so easy tohandle as silk or linen thread which produce less tissuereaction and give firm and non-yielding knots. Some

surgeons swear at (and less often by) the material of theirchoice; but so long as patients bleed when tissues aresevered there will be a need for surgical knots and some-one to tie them, whether it is the surgeon or his assistant.No machine seems likely to displace them.

SCINTILLATION RADIODIAGNOSIS

Two technical developments in the diagnostic use ofradioactive tracers were reported by Brownell and Sweet 3in 1953. The first was the detection of positrons byscintillators placed on opposite sides of the head andrecording only when stimulated simultaneously (withinnarrow limits). The second was a method of detectinggamma rays and of recording only the difference between

1. Potts, J. W. J. Amer. med. Ass. 1962, 180, 494.2. See Lancet, 1961, ii, 416.3. Brownell, G. L., Sweet, W. H. Nucleonics, 1953, 11, 41.

counting-rates on the two sides of the head. Botterellet al. have now described their use of these methods overfour years; they employed the same technique throughoutand used ’4as in the form of sodium arsenate. Tumourswith the greatest cellularity seemed to retain the isotopein greatest concentration. The highest values were inmeningiomas, followed in order by glioblastomas, meta-static carcinomas, and astrocytomas. Unlike radioactiveiodinated human serum-albumin 5 6 the isotope did notbecome concentrated to any detectable degree in subduralhaematomas or arteriovenous malformations. In thedetection of meningiomas this method contrasted withelectroencephalography: the latter might fail to reveal thisextrinsic tumour but nearly always indicated an intrinsictumour.

Angiography may also fail to outline positively a

sphenoidal wing meningioma, and, because of obstructionat the opposite foramen of Monro, ventriculography inthis condition can be highly dangerous. Had the scintil-lation method no other justification, this alone wouldrecommend its provision in appropriate centres. One ofthe most important tasks in neurosurgery is to detect, asfar as possible, every benign tumour at an early enoughstage to ensure complete recovery of the patient. This cannow be more nearly achieved if clinical acumen is exer-cised properly and neurosurgical facilities are ample.Neither of these requirements has been met in the

past.8 9

GROWTH HORMONE

THE species specificity of preparations of growth hor-mone from different animals formed a stumbling-blockto study of the action of this hormone in man. Eventuallyit was shown that only primate growth hormone wasactive in man; and since then much work has been doneon its metabolic effects.1o

Growth hormone is not concerned solely with somaticgrowth: it is produced by the pituitary throughout life,and is a general metabolic hormone. It causes synthesisof protein, which is reflected in retention of nitrogen inthe body, and along with this a proportionate retention ofthe mainly intracellular electrolytes-potassium and

phosphorus. It also causes retention of sodium andchloride, largely extracellular, and hence expansion ofextracellular-fluid volume. These changes seem to beindependent of the secretion of aldosterone, and growthhormone has no immediate effect on blood-pressure. It

might be expected to cause consistently a retention of cal-cium in the skeleton, but changes in calcium balance havebeen variable and the serum-alkaline-phosphatase is

usually unaffected.Growth hormone also has an important effect on carbo-

hydrate metabolism by impairing glucose tolerance andincreasing resistance to insulin: under its influence dia-betics rapidly develop gross glycosuria. It has a directaction on fat metabolism in the normal (and particularlyin the fasting) individual, mobilising non-esterified fattyacids and ketones; and in the diabetic it rapidly causesgross ketosis.

4. Botterell, E. H., Lougheed, W. M., Morley, T. P., Tasker, R. R., Paul, W.Canad. med. Ass. J. 1961, 85, 1321.

5. Chiro, G. di. Acta radiol., Stockh. 1961, suppl. 201.6. Lancet, 1961, ii, 1186.7. ibid. 1961, i, 1388.8. Segelov, J. N., Davis, R. Med. J. Aust. 1961, ii, 1.9. McKissock, W. J. Neurol. Psychiat. 1961, 24, 296.10. See Finkel, M. J. Amer. J. Med. 1962, 32, 588.

Page 2: GROWTH HORMONE

1342

There are still relatively few reports on long-termtreatment with growth hormone; but pituitary dwarfsgrow at an increased rate, whereas patients with dwarfismfrom other causes apparently may not, and it has beensuggested that this is due to " end-organ unresponsive-ness ". The dosage has varied from 6 to 35 mg. weekly,for several months, of a material claimed to be pure pro-tein human growth hormone. In hypopituitary dwarfs,the rate of growth is said to have increased by a factor of1-5 to 5-0 over the rate before treatment, while the bone

age has not altered materially. The side-effects of treat-ment have generally been mild but have included nausea,anorexia, a feeling of satiety, nervousness, headache,tachycardia, and sweating; and, with very high doses ofmonkey growth hormone, oliguria and anuria haveoccurred.

In rabbits the so-called pure hormone has been foundto evoke antibodies which inhibit the effect of the hormonein the standard assay (this depends on the growth of car-tilage in the tibial epiphysis of the hypophysectomisedrat), and the haemagglutination-inhibition method hasbeen used to assay the antigen in serum.

IDIOPATHIC PULMONARY HÆMOSIDEROSIS

VIRCHOW first described the lesions of pulmonaryhaemosiderosis,1 and Ceelen described the idiopathicform of the disease in 1931; but little progress has beenmade in explaining its cause. Over 100 cases have nowbeen reported, including some with associated neph-ritis.3-6 This strange and often fatal syndrome has beenwell reviewed by Saltzman et al.7 The cause of the intra-alveolar haemorrhage 8 which leads to pulmonaryhoemosiderosis remains as much of a mystery as the

nephritis occasionally accompanying it.

Soergel and Sommers, besides reviewing earlier

reports,9 have examined the histological changes in thelungs of 17 patients.10 The only consistent abnormalitieswhich they found were degeneration, excessive shedding,and hyperplasia of the alveolar epithelium, together withcytoplasmic vacuolation. These they regard as the"common characteristic pathogenic pulmonary lesion ofidiopathic pulmonary haemosiderosis ". They believethat by these changes a histological diagnosis can be madefrom lung tissue, which macroscopically may appearnormal. They admit that no factor is yet known which willcause these alveolar epithelial alterations, and they believethat the primary pathogenic mechanism is an abnormalityof alveolar epithelial growth and function.

Soergel and Sommers excluded cases in which neph-ritis was also present, since they regard this combination asa separate syndrome. Many may agree with Rusby andWilson,5 however, that lung purpura with nephritis,and idiopathic pulmonary hasmosiderosis, differ only inthe presence and severity of the renal lesion. Perhaps therelation between the two will only be clarified when

1. Virchow, R. Die Cellularpathologie in ihrer Begrundung auf physio-logische und pathologische Gewebelehre; p. 330. Berlin, 1858.

2. Ceelen, W. in Handbuch der speziellen pathologischen Anatomie undHistologie (edited by F. Henke and O. Lubarsch); vol. III, part 3, p. 26.Berlin, 1931.

3. Goodpasture, E. W. Amer. J. med. Sci. 1919, 158, 863.4. Heptinstall, R. H., Salmon, M. U. J. Clin. Path. 1959, 12, 272.5. Rusby, N. L., Wilson, C. Quart. J. Med. 1960, 29, 501.6. Cruickshank, J. G., Parker, R. A. Thorax, 1961, 16, 22.7. Saltzman, P. W., West, M., Chomet, B. Ann. intern. Med. 1962, 56, 449.8. See Lancet, 1958, i, 520.9. Soergel, K. H., Sommers, S. C. Amer. J. Med. 1962, 32, 499.

10. Soergel, K. H., Sommers, S. C. Amer. Rev. resp. Dis. 1962, 85, 540.

detailed biochemical study of the lungs receives as

much attention as that of the kidneys. Meanwhile

idiopathic pulmonary hsemosiderosis remains an obscureand unpleasant disease which responds poorly to anyform of treatment.

THREADWORM INFESTATION

EVEN in temperate climates tapeworm and roundworminfestation, including toxacariasis, can give rise to seriousdisturbance both within and remote from the gut. Thehumble threadworm or pinworm (Enterobius vermicularis),although it may cause distressing perineal itching andvulvovaginitis, is no longer regarded as the notorious andversatile villain known to physicians of a generation ortwo ago; but Litter, in a personal series of over 2000cases of oxyuriasis, finds that it can still give rise to dis-turbances in almost every system. Thus Litter finds thatit may cause protracted bleeding from the nose or thebreached skin; and he believes it to be the commonestcause of bleeding from the rectum in children. It may be

responsible, he says, for choked discs, migraine, spasmusnutans,

" pseudo-brain tumour ", and intestinal " pseudo-obstruction ". The faecal impaction which it may producecauses iliopsoas spasm with consequent limping to whicha toxic neuropathy may contribute. It is a cause of

onanism; and in the female its manifestations range fromvaginitis through nymphomania, menorrhagia, and

sterility to serious emotional disturbances.This article may seem to have about it something of the

" all dogs have tails, so all tails must be on dogs " logic,which comes as a sharp change from the cold double-blind controlled trials. But it is usefully provocative, andit may remind us that roundworms (toxacara) from thefamily’s pet dog or cat are probably even more likely tocause trouble, ranging from abdominal pain to hepaticgranuloma, visual disturbance, and possibly eosinophilicgranuloma of bone. Once threadworm infestation hasbeen discovered, it should be treated without fuss. AsEllis 2 says, the disgust with which unsympathetic orobsessional parents may view such infestation can be amore potent source of nervous symptoms in their childthan the worm itself.

HYPOTHESIS" DON’T think: why not try the experiment?" was a

sound injunction for its time. But if John Hunter werestill alive he might sometimes now exclaim as usefully" Don’t experiment: why not think? " For experimentsseldom solve a problem unless they test some sensiblehypothesis.

This week we make an editorial innovation; andwhether it will prove progressive or retrogressive we donot yet know. (We are trying the experiment.) For yearsour practice has been to refuse speculative articles unlesstheir speculation was supported by fresh evidence; butthis discouragement of nascent ideas has always beenreluctant and often perhaps it has been wrong. For a time,therefore, we propose to publish a selection of purelyspeculative articles-in the first half of the journal, butafter the Preliminary Communications-under the headingof Hypothesis. We are glad to be able to begin the seriesthis week with a distinguished example.

1. Litter, L. Arch. Pediat. 1961, 78, 455.2. Ellis, R. W. B. Disease in Infancy and Childhood, Edinburgh, 1960.