TRANSFERRING THE COMATOSE HEAD-INJURED PATIENT

985 For patients with non-T ALL, the frequency of testicular involvement at diagnosis was 4 of 7 (57%) among patients with WBC counts greater than 25 000/1. Nesbit et al.’ have shown the strong contribution of the initial WBC count to the probability of testicular relapse. This suggests that the apparent resolution of leukaemic infiltrates after initial systemic chemotherapy does not ensure against isolated testicular recurrence and early death. Kim et al. state that "Only longitudinal studies of pre-induction and sequential post-treatment testicular biopsy specimens will deflne which set of patients are at risk for the development of testicular leukaemia and might profit from early gonadal irradiation." Since the incidence of initial testicular involvement and late testicular relapse are both associated with high initial WBC counts and massive organomegaly, we would argue that prophylactic irradiation of the testes represents an appropriate treatment in the selected group of patients at higher risk for testicular relapse. Since this group also experiences a higher incidence of bone marrow relapse, current studies may underestimate the true incidence of testicular sanctuary disease. If improvements in systemic chemotherapy result in prolonged bone marrow remissions, isolated testicular relapse may become a more significant source of leukaemic recurrence. While a longitudinal study such as that proposed by Kim et al. might identify early testicular relapse, there is no indication that early treatment of such a relapse will improve ultimate survival. There is a need for a prospective randomised study of prophylactic testicular irradiation in newly diagnosed boys with "poor prognosis" ALL. Department of Pediatrics, Memorial Sloan-Kettering

PAUL A. MEYERS MICHAEL SORELL

Cancer Center New York, N.Y. 10021, U.S.A.

RECURRENCE AND EARLY ACTIVITY AFTER GROIN HERNIA REPAIR

SIR,-The timing of return to work and full activity after groin hernia repair depends more on the advice from the surgical team than on that of the general practitioner.2Mr Bourke and his colleagues (Sept. 19, p. 623) encourage earlier return to work and hope to improve on inactivity periods of 48 (early) and 65 (control) days. The hernia series with fewest recurrences has been from the Shouldice Hospital with immediate return to mobility, office work after a few days, and even the heaviest work within a month.3 The recurrence rate depends on the surgical technique used and on the care taken by the surgeon. 70% of the final wound strength is present immediately when a non-absorbable monofilament material is used.It would seem logical to encourage early return to full activity so that the patients’ muscles support the repair. With absorbable sutures the repair becomes weaker before improving and the use of such material should be discouraged or abandoned. Since April, 1974, my surgical team has been using a simplified Shouldice technique for primary and recurrent groin herniae. A recurrence rate of 1 5% in 1400 cases (follow-up rate more than 95%) seems acceptable. Immediate mobility and return to normal activities was encouraged. Early return to work has been a little disappointing but contrasts with that achieved by Bourke et al. Of 321 employed men 175 (54%) were working in 35 days or less. The range for all 321 men was 3-112 days. 78 self-employed men, including farmers, carpenters, and plumbers provide a contrast. 27 (34%) returned in 7 days or less; 63 (80%) returned by 21 days. Perhaps they were better motivated and less restricted by the opinions of their lay advisors and general practitioners. 1 Nesbit ME, Robison LL, Ortega JA, Sather HN, Donaldson M, Hammond D. Testicular relapse in childhood lymphoblastic leukemia: Association with pretreatment patient characteristics and treatment: A report for Children’s Cancer Study Group Cancer 1980; 45: 2009-16. 2. Semmence A, Kynch J. Hernia repair and time off work in Oxford. J Roy Coll Gen Practit 1980; 30: 90-96. 3. Glasgow F. Surgical repair of inguinal and femoral hernias.Con Med Assoc J 1973; 108:

Self-employed

Employed

"

.

-

z

.

z_

..._

.,........

Weeks Time off work after hernia

repair

in 78

self-employed

and 321

employed men. Recurrences shown

by asterisk.

Many of the employed were very active at home-gardening or re-roofing their houses-before being allowed back to work. Early return to full activity can only benefit patients. It is up to the surgeon to ensure careful repair of tissues. He should also advise on the timing of return to work. The patient will decide when to go back to work, in conjunction with his general practitioner who has to sign his sickness absence certificates. At a time of high unemployment some patients are afraid to have their uncomfortable hernias repaired because they think that the expected long period off work will result in them losing their jobs. There is no evidence that lengthy rest reducess the chance of recurrence-indeed, the opposite is usually the case. even

Royal Cornwall Hospital (Treliske),

N.J. BARWELL

Truro, Cornwall TR1 3LJ

TRANSFERRING THE COMATOSE HEAD-INJURED PATIENT

SIR,-Dr Gentleman and Professor Jennett (Oct. 17, p. 853) discuss the management of unconscious head-injured patients during transport to a neurological centre, but no mention is made of controlled intermittent positive ventilation (IPPV) with- muscle relaxants and endotracheal intubation. In the district general hospitals in Reading we have since 1972 increasingly used controlled hyperventilation with muscle relaxants and endotracheal intubation in the early management of unconscious patients with head injury and have found far less hypoxaemia as a result of this change of policy. Previously there were many incidents of respiratory obstruction, inhaled vomitus, and unexpected cardiac and respiratory arrest; now these are rare, and we have had no difficulty in assessing neurological status on the Glasgow coma scale between intermittent relaxant dosage. The quiet condition of the patient with the absence of stertorous breathing and hypertonic spasms provides better conditions for the resolution of cerebral damage. It seems likely that the incidence of secondary cerebral damage will be reduced by these stable conditions. Intracranial pressure monitoring has been reported as showing a reduction in the surges in intracranial pressure that straining and extensor spasms produce. The general monitoring, routine for all IPPV patients leads to the early perception and correction of hypotension and early decisions

308-13. 4. Lichtenstein

IL, Herzikoff S, Shore JM, Gynecol Obstet 1970; 130: 685-90.

et

al. The

dynamics of wound healing. Surg

5. Ross APJ. Incidence 326-28.

of inguinal hernia recurrence. Ann Roy

CollSurg Engl 1975; 57:

986 for referral to the regional neurological unit in Oxford, 30 miles away. The transfer is routine, monitored and safe and conducted in the manner described by Ledingham, although not every case may have a central venous or arterial line in position. A nurse, doctor, and, usually, an intensive care unit technician accompany the patient. Not all the neurosurgeons are pleased to find our patients so controlled but we are quite convinced of the benfit and increased likelihood of avoiding hypoxia and some secondary brain damage. Our treatment was based on Emeric Gordon’s article (Acta Anaesth Scand 1971; 15: 193-208) where he concluded that the protection of the airway and adequate oxygenation provided by IPPV under muscle relaxants was probably more important in his team’s good results than was any theoretical effect on cerebral blood flow produced by hyperventilation. Without relaxants the airway is not well controlled by intubation in unconscious head injury

patients. Intensive Care Unit, Royal Berkshire Hospital, Reading, Berkshire RG1 5AN

D. G. PRICE

HETEROGENEITY OF MATURITY ONSET DIABETES AT YOUNG AGE (MODY)

SIR,-At the end of December, 1978, in the district of Erfurt,

centrally registered. With the support of the fourteen centres caring for these patients we collected all cases fulfilling the MODY (maturity onset diabetes at young age) criteria of Tattersall and Fajanswithin this closed diabetic population. 58 diabetics, diagnosed before the age of 25 years and treated successfully with diet (50) or oral drugs (8) for at least two years were found. Investigations of heredity were based on family history and on medical records of the diabetics. 145 living first-degree relatives of the propositi appeared to be unaffected. In 100 of them an oral glucose tolerance test (50 g) was done. For 75% of the MODY propositi the parents were already known to be diabetic or were identified as diabetic by the glucose tolerance test (table). Another argument for the suggested autosomal dominant trait2-4 would be the direct parent-to-child transmission through three generations in 17 cases (30%). In families with 40 927 diabetics

were

vertical transmission, all affected individuals had non-insulindependent diabetes mellitus (NIDDM). However, the ratio of affected to unaffected siblings and offspring was far below the expected value of 1:1, and in 10 cases diabetic relatives could not be found. The evidence of sporadic as well as a familial cases of MODY within a geographically defined population demonstrates the of NIDDM in early life. Mason type genetic diabetes5 seems to be a rare condition, at least in our population. Pedigrees with a strong aggregation of affected individuals we found only in 3 propositi. On the basis of family studies there seems to be no relation between MODY type and HLA system.6,7 Only in one MODY family has a common HLA haplotype (A3, Bwl55 in8 of 11 subjects) been described.8 The comparison of the A, B, and C antigen

heterogeneity

RB, Fajans SS. A difference between the inheritance of classical juveniletype diabetes in young people. Diabetes 1975; 24: 44-53. Tattersal RB. The inheritance of maturity-onset type diabetes in young people. In: Creutzfeld W, Köbberling J, Neel JV, eds. The genetics of diabetes mellitus. New York and Berlin: Springer, 1976: 88-94. Johansen K, Gregersen G. A family dominantly inherited mild juvenile diabetes. Acta Med Scand 1977; 201: 567-70. Fa)ans SS, Cloutier MC, Crowther RL. Clinical and etiological heterogeneity of idiopathic diabetes mellitus. Schwetz Med Wschr 1979; 109: 1774-85. Pyke DA. Diabetes: the genetic connections. Diabetologia 1979; 17: 333-43. Nelson PG, Pyke DA. Genetic diabetes not linked to the HLA locus. Br Med J 1976; i: 196-97. Faber OK, Thomsen M, Binder C, Platz P, Svejgaard A. HLA antigens in a family with maturity-onset type diabetes mellitus. Acta Andocrin 1978; 88: 329-38. Barbosa J, King R, Goetz FC, Noreen H, Yunis EJ HLA in maturity-onset type of hyperglycemia in the young Arch Intern Med 1978; 138: 90-93. Panzram G, Adolph W. Der Chlorpropamid-Alkohol-Flush-Test beim nicht-insulinabhängigen Diabetes mellitus im jungen Lebensalter (MODY-Typ) Endokrinologie

1. Tattersall onset

2.

3. 4. 5. 6. 7.

8 9.

(in press)

HEREDITY IN MODY PATIENTS

*1 patient excluded because of lack of data

on

family history.

frequencies in our MODY patients with those of 605 healthy individuals of the same population revealed no differencies when p values were corrected for the number of alleles tested. Our findings do not provide convincing evidence of gene association in MODY patients. Only 8 of the 40 MODY patients tested were chlorpropamide alcohol flush (CPAF) positive. Comparison of flushers and nonflushers with respect to genetic and clinical features, including HLA type and vascular complications, revealed no significant differences. Thus, we found no evidence of specifity of the CPAF for NIDDM in early life. Our findings, in cases from a closed diabetic population, suggest that MODY is a heterogeneous subgroup of diabetes. Outpatient Department of Internal Medicine, Medical Academy, Erfurt 5060, German Democratic Republic

GÜNTHER PANZRAM WERNER ADOLPH

CHOLECYSTECTOMY AND COLON CANCER

SIR,-The studies by Dr Linos and colleagues and Dr Vernick and Dr Kuller in the Aug. 22 issue of The Lancet provide tantalising evidence of a causal link between prior cholecystectomy and rightsided colon cancer (RSC). The studies, on two different populations and utilising two different study designs (cohort and case-control), each demonstrated a significantly increased risk, though this was limited to women in the first study. This risk was of a similar magnitude and was site-specific in both studies. Furthermore a plausible biological mechanism was provided. As alternatives to a causal interpretation, both papers discuss the possibility of an indirect biological association between cholecystectomy and colon cancer. Conspicuously absent from both, however, is the possibility of "ascertainment" bias, to wit, patients who have had gallbladder surgery are likely to remain under closer medical/surgical/radiological surveillance for investigation of future gastrointestinal symptoms, with perhaps particular attention to the right side of the abdomen. Under such circumstances, one might postulate that latent or slow-growing cancers of the right colon, notorious for becoming overtly symptomatic at a late stage of development, might be detected earlier and more frequently in the more medically and gastrointestinally attended patient than in others. The puzzling observation that a significant association was found only for women in the first study is compatible with the postulated ascertainment bias, given the generally recognised tendency for middle-aged women, particularly those who have received elective surgery, to receive closer medical scrutiny than their male counterparts. The possible role of medical surveillance or ascertainment bias (a variant of sorts on the Berksonian bias, which was dismissed in the Linos paper) has been pointed out in a number of other recent studies of postulated causal association between medical interventions and occurrence of malignant disease.1,2 As the cholecystectomy/RSC cancer hypothesis is further explored, this possibility needs to be accounted for. The University of Rochester, Medical Centre, School of Medicine and Dentistry, Rochester, New York 14642 1. Mack TM,

et

al

Reserpine and breast cancer

WILLIAM H. BARKER in

a retirement community. N Engl

J Med

1975; 292: 1366-71. 2 Horwitz

RI, Feinstein AR. Alternative analytic methods for case-control studies of estrogens and endometrial cancer. N Engl JMed 1978; 299: 1089-94