Although bladder function is thought to be unaffected in Duchenne muscular dystrophy, 46/88 boys interviewed had urinary problems. Nine underwent video urodynamics, showing in eight a small capacity, hyperreflexic bladder, and in the ninth (post spinal surgery) hyperreflexia and detrusor sphincter dyssynergia. Urinary dysfunction is a treatable feature of DMD.T he main clinical phenotype in Duchenne muscular dystrophy (DMD) is of progressive weakness of limb and trunk musculature, a degree of cognitive impairment, and later, cardiomyopathy. There is no recognised association between bladder dysfunction and DMD. As a number of patients admitted to urinary problems when asked, we decided to investigate in detail urinary symptoms in DMD. METHODSEighty eight males with DMD (aged 3-31 years), attending the neuromuscular clinic, were included in the study. A questionnaire was sent to them or their carers and followed up by telephone.Those who reported urinary symptoms were interviewed and examined to exclude other causes of urinary dysfunction.Renal and bladder ultrasound pre and post micturition, and video urodynamics were then offered to define the pattern of lower urinary tract dysfunction. RESULTSEighty four per cent (74/88) replied, of whom 46/74 (62%) were concerned about urinary problems; these are summarised in table 1. All 22 boys with daytime urinary incontinence had been continent at some stage and the problem had become apparent later. Twelve with nocturnal incontinence had been previously dry at night. Twenty used continence aids but only eight had been referred to a continence advisor. Of the 50 who were no longer able to walk independently, only 38 had some adaptation to their bathroom. Although 38 boys had learning difficulties, in only four were they severe enough to affect acquisition of continence.Urinary problems occurred in young, ambulant boys as well as wheelchair dependent patients, with a mean age of 10.8 years (range 3-25years). In all but one patient, who suffered hesitancy post spinal surgery, the problem had not been brought to medical attention previously. Day and night time incontinence, nocturia, urinary frequency, urgency and stress incontinence were found at a mean age of 10.3 years (range 3-25 years). Urinary hesitancy affected an older group with a mean age of 16.7 years (range 11-22 years).

Five patients with severe spinal muscular atrophy (SMA) type I, all of whom presented with reduced fetal movements in utero, severe weakness at birth, and short survival time were assessed to attempt to determine whether their phenotype could be explained by their genotype. The diagnosis was confirmed by clinical, electrophysiological and histopathological features. Polymerase chain reaction assays were used to define the molecular diagnosis. A genedosage assay was used to assess the quantity of centromeric survival motor neuron gene (SMNc) present. In all cases the telomeric survival motor neuron gene (SMNt) was absent. The SMNc gene was present but in reduced copy number compared with a control group of children with less severe type I SMA, so may be important in determining severity. In the differential diagnosis of reduced fetal movements, SMA should be considered. The clinical classification may in future be clarified by molecular genetic findings.

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Summary.-The effects of one large single dose of 5-fluorouracil (FU) have been compared to the same amount given in divided doses daily over a 3-or 5-day period.Comparison of the effects of single vs fractionated dosage was made on 2 types of experimental solid tumour with different growth, cell kinetic, histological and metastasizing properties. The tumour response was essentially the same for both the single and fractionated dose schedules.There were marked increases in animal mortality from drug toxicity following fractionated doses of FU compared to one large single dose. Mortality in animals with Tumour 3924A increased from 10% following one large single dose to 600/ for animals given daily fractionated doses for 3 days, and 80o/ for animals given daily fractionated doses for 5 days. Total marrow reserve was measured by the total DNA content of tibial marrow. The nadir of 6 days for loss of total tibial marrow DNA following one large dose of FU was increased to 9 days for both fractionated schedules of FU. The 3-day delay in recovery of the marrow prevented recovery within the time frame necessary for animal survival. The inference from these experimental cancertreatment studies is that daily fractions of chemotherapeutic agents such as FU result in increased morbidity and mortality, without benefit in the control of the solid tumour. The results question the advisability of the clinical practice of initially giving small daily "loading doses" of proliferation-dependent agents such as FU.These results emphasize the need for more precise information on the temporal relationship between the response and recovery of the host and the response and recovery of the solid tumour. They also emphasize the need for a better clinical understanding of the time sequence of solid-tumour recovery in relation to the time sequence of marrow recovery."ALTHOUGH 5-fluorouracil (FU) has been used clinically since 1957, there presently exists a wide divergence in opinion among individual investigators, institutions, and-cooperative groups about the optimal dosage regimen" (Ansfield et al., 1977). Initial "loading doses" of FU and other proliferation-dependent cancerchemotherapeutic agents are given daily or on alternate days and pushed to the point of mild toxicity. This approach to the clinical management of cancer patients uses, in most instances, host toxicity as the primary guide for the scheduling of the proliferation-dependent chemotherapy agents such as FU. Quantitative assessment of tumour response is often difficult or impossible. It is evident that more precise information on the temporal relationship between the response and recovery of the host and the response and recovery of the tumour is needed for a more rational design of clinical protocols.Studies on the effects of FU on experimental solid tumours have been carried out, to determnine quantitatively the effect of increasing doses of FU on tumour growth, animal morbidity and mortality. The ability to evaluate quantitatively the effects of different schedules of F...

Summary.-The effects of adriamycin (Adr) on the solid-tumour model, hepatoma 3924A, and on critical organs of the host, were determined at intervals after single injections of 60 mg/M2 of the agent. A reduced rate of tumour growth was evident 4 days after treatment, continued to Day 11, and then returned to rates comparable to control values. On Day 11 tumour volumes of treated animals were 38% of control.During the period of reduced growth, 3H-TdR incorporation into tumour DNA and percentage labelled tumour cells were less than control values. DNA concentration in tumour was not affected by drug treatment, which differs from observations made in other studies employing 5-fluorouracil (FU). No evidence of significantly increased necrosis or fibrosis of the tumour was found after Adr. The Adr treatment caused loss of 60% of the tibial marrow by Day 4, as measured by total DNA content.Marrow DNA recovered to control levels between Days 7 and 11. Incorporation of 3H-TdR into heart DNA was reduced more than 400/o during the first week after Adr treatment; enhanced incorporation was observed on Day 11, and control levels were attained by Day 17. No significant pathological evidence of cardiac toxicity was found 2-21 days after Adr but degeneration of myocardial cells and oedema was prominent at 14 weeks.