Evans Pr

GONADAL FUNCTION IN BOYS WITH STEROID-RESPONSIVE NEPHROTIC SYNDROME TREATED WITH CYCLOPHOSPHAMIDE FOR SHORT PERIODS

Semen analysis was undertaken in 19 men over the age of 18 years who had been treated during childhood for steroid-responsive nephrotic syndrome with a single course of cyclophosphamide 3 mg/kg bodyweight for 8 weeks. A further 4 men who received two such courses of treatment were also studied. Plasma total androgens and gonadotropins were also determined. A comparison group consisted of medical students investigated as potential donors for artificial insemination. Lower ejaculate volumes and sperm densities with a higher percentage of immotile and abnormal forms were detected in patients who had received cyclophosphamide. However, the abnormalities were not severe enough to suggest infertility. Plasma total androgens were lower in the patients, but there were no differences in gonadotropic hormones. The data suggest that a course of treatment with cyclophosphamide known to influence the natural history of the nephrotic syndrome is not necessarily followed by a severe abnormality of sperm production; nevertheless, great caution is still required in the use of the drug.

Nuclear Agenesis: Möbius' Syndrome: The Congenital Facial Diplegia Syndrome

Thus Harlan (1881) described the appearance of a patient with bilateral congenital facial and external rectus paralysis. Chisholms account (1882) was equally clear. The collation of cases of congenital facial palsy combined with other cranial muscle weakness by Mobius (1892) led to more general recognition of nuclear degeneration (as he termed it), or agenesis, and to eponymous fame. More recently Henderson (1939) and Danis (1945) have fully reviewed the condition. Paralysis may be total or partial, unilateral or bilateral. The face is practically always involved, the external rectus muscles rather commonly, those supplied by the twelfth, third and fifth nerves, and the palate, may be affected. The weakness or paralysis is assumed to be due to aplasia of the appropriate nuclei, but the pathological evidence is hard to interpret, and until it becomes decisive, ideas about the nature of the condition must depend partly on consideration of how the various cranial paralyses come to be associated. Further weight must be attached to the circumstantial evidence provided by other congenital anomalies found in these patients. Most of them have been seen and recorded in adolescence and adult life, but patients seen in early childhood may show additional features, for example, mandibular hypoplasia and laryngeal stridor, which do not appear in other lists such as Wilsons (1940): epicanthus, absence of lacrymal caruncles, microphthalmia, deformed ears, syndactyly, micromely, localized muscle defects and club foot. The following account includes all the cases that I have seen. Those with solitary unilateral facial paralysis are omitted, for in them the common presence of deformity of the face and external ear suggests that simple pressure by the shoulder may have produced the deformation ofadjacent structures during intra-uterine life (Browne, 1936). Case 1. Unilateral Extel Recta and Facial Pals C.P., a boy, was born in 1948. He was the second child of healthy parents not related by blood: there was no illnss during pregnancy; he was born by normal labour, at term, and weighed 6 lb. Right facial weakness was noticed at once: he could not suck well but was breast fed for two months. Because gain in weight was slow he was brought to hospital at 3 months. Weakness of the right external rectus muscle was noted. At 5 months there was slight hypoplasia of the right side of the face, which was completely paralysed. At 9 months there was a right convergent squint, which was treated operatively when he was 23 months old.

Antecedents of Infantile Cerebral Palsy

The causes of infantile cerebral palsies, and especially of diplegia, have been much argued. Colliers (1924) able discussion of diplegia shows the incontlusiveness of many of the arguments. Before studying particular features, it seemed reasonable to survey the histories antecedent to the development of palsy obtained in a series of cases. The term infantile cerebral palsy includes several syndromes, and these different conditions may have different causes. The series has, therefore, been grouped into sets of cases with similar clinical pictures. Only two of these, the spastic and the athetoid, form large enough groups for statistical study, and this paper is concerned mainly with them. Owing to the different methods of classification used by various observers (Evans, 1948) only patients examined personally are included. Furthermore, children whose mothers were not questioned are excluded; fathers rarely have precise knowledge about the birth of their children. Information was also sought by written questionnaire from doctors or midwives in attendance at childbirth, or from hospitals or nursing homes where the patients were bor. Replies were received from 80 per cent. of those questioned. The history was thus usually compiled from two sources. They were rarely contradictory. Where they were, the case was judged on the apparent merits of the two stories. The medical record was often more precise about pregnancy and labour, while the mother was almost always more circumstantial in her account of the condition of the newly born child. About half the patients were seen in hospital and private practice, and the rest at the preliminary examination of children whose admission to a school for children with cerebral palsy was sought. The mothers of fifty children not suffering from disease ofthe central nervous system, seen in hospital and private practice, were questioned similarly. There may have been differences in social class between the children in the control group and the patients, as no control for the children seen at the school was devised. This should be taken into account in considering such factors as parental age, size of family, and use of obstetric analgesia. The groups were balanced as to age, and all were seen within the same period of about fifteen months. Their ages varied from 1 to 13 years (average 6-4 years, standard deviation 3-1). The total number of patients was 122. In eight the mother was not interviewed, and only the remaining 114 are considered here. Chssification Tbe clinical condition may be classified by reference to the distribution of the palsy and to its functional type. The distribution is expressed in terms of the limbs affected as monoplegia, hemiplegia, paraplegia, triplegia, and tetraplegia. The last term is preferred to diplegia because this is sometimes unfortunately used in the same sense as paraplegia . On the functional side there have also been ambiguities, but there must be few cases which cannot be described as spastic, athetoid, flaccid, choreic, or ataxic. The terms may be combined, theoretically in any combination, but in practice as spastic or flaccid paraplegia or tetraplegia. Athetosis, chorea and ataxia are usually generalized and only exceptionally need topical qualification. Hemiplegia is almost always spastic. Double hemiplegia may be a useful concept, and indeed two cases classified in this series as mixed type, spastic legs and athetoid arms were probably double hemiplegias. Some of the athetoid patients might also be given the same label. For reasons indicated elsewhere (Evans, 1948) I have not considered extensor plantar responses as a criterion for taking these children out of the athetoid group. It is often difficult to distinguish between paraplegia and mild tetraplegia. I have therefore included paraplegias and tetraplegias in the same group. The classffication of the 114 patients in this series is shown in table 1. Nearly two-fifths were cases of spastic paraor tetraplegia and will be referred to simply as spastic; a similar number of cases of athetoid tetraplegia or double athetosis will be referred to as athetoid. Phelpss (1941) generalization that 40 per cent. ofcases are spastic, 40 per cent. athetoid, and 30 per cent. ataxic is borne out only as far as the two major groups are concerned. 213

Histoplasmin sensitivity in Uganda.

and it is necessary in order to help to assess the significance of radiological changes found in the chest or bones. As in everything else, experience of the relative advantages of different methods is required. The test gives a positive result four to six weeks after primary infection, and thereafter a positive reaction means simply that a child has undergone primary infection. It does not mean that any particular illness is tuberculous in origin, but it emphasizes the possibility, or indeed with a young child the probability, that it is so. A negative reaction is important, for the presence of tuberculosis is practically dismissed unless the child is very ill, when other physical signs are almost certainly present. Two tests are in general use-the percutaneous (jelly) and intradermal (Mantoux). In the jelly test the skin is carefully cleaned with acetone or ether, and a petroleum jelly ointment containing Old Tuberculin is placed on the skin; usually the childs initial or a v mark is outlined with the jelly, to the length of about 1 in. (2.5 cm.). This is covered with a piece of strapping without any intervening lint. After 48 hours the strapping is removed and the skin examined 72 hours later-that is, after five days. This interval allows any strapping reaction to fade and gives a delayed tuberculin reaction time to appear. The result is not often in doubt. There is either no reaction whatsoever or, if positive, a reddish-brown slightly raised area; or sometimes a line of papules, not indurated or oedematous, will show on the skin in contact with the jelly. It is best to regard any reaction as positive until proved otherwise, but sometimes if only two or three papules are present the intradermal test will be necessary. We do not recommend the use of flourpaper (very fine sandpaper) in testing children under 5 years of age. The jelly test is roughly equivalent to 0.1 ml. of 1: 1,000 Old Tuberculin by intradermal injection. It is most useful in clinic work where repeated tests are necessary and time is not important. Avoiding a prick. the doctor retains the childs confidence. But it takes five days, and occasionally an intradermal tuberculin test is necessary afterwards. So if there is any urgency, if the child is ill and tuberculosis seems likely, an intradermal (Mantoux) test should be used. The intradermal test consists of the intradermal injection of 0.1 ml. of 1: 1,000 Old Tuberculin; 48 hours later a weal or area of induration more than 5 mm. in diameter indicates a positive reaction. Redness without induration is ignored, and redness surrounding a weal is not included in measurement. The reactions of the tests are therefore very different and should not be compared. That of the jelly is on the skina series of small spots, papules, or vesicles which sometimes coalesce ; that of the intradermal test is oedema in the skin at the site of injection. Every child with a positive reaction should be known to his family doctor, and it is most important that the results of tuberculin tests done in clinics or elsewhere should be communicated to him. It is also important that he should recognize the significance of the information and its value if the child becomes ill.

Deformity of vertebral bodies in cretinism

Summary 1. Of thirteen cretins, one had anormal spine, five had minor abnormalities, and seven showed deformity of the bodies of the twelfth thoracic or first or second lumbar vertebrae. (The high incidence of abnormality is due partly to a special interest in the subject, which was responsible for the inclusion of two abnormal cases.) 2. Kyphosis with subsequent bony abnormality developed between the ages of 6 months and 2 ½ years. Bony abnormality without kyphosis was seen in two hitherto undiagnosed cases examined at 4 ½ years. 3. The deformity may disappear under treatment with thyroid. 4. Similar deformities are seen in other diseases in which there is chondrodystrophy. 5. The affected vertebrae are thosemost subject to trauma, and the abnormality is probably caused by the stress of flexion acting on chondrodystrophic vertebral bodies.

An Epidemic of Hepatitis

to the front and to hospitals in the rear. During twelve months of war literally hundreds of tons of blood have been thus applied to wounded men in all stages of evacuation, and with truly tremendous success. Narkomzdrav regularly sends out groups of experienced specialists-scientific collaborators from the institutes and stations-who give practical assistance in ensuring the adequate supply of conserved blood at the front. Thus, thanks to timely blood transfusion, we can indeed say that hundreds of thousands of human lives have been saved.

Generalized Cutaneous Vaccinia.

Generalized cutaneous vaccinia is a rare disease: Chalke6 and Ellis quote figures showing an incidence of from 1 case in 10,000 to 1 in 100,000 vaccinations. It may follow auto-inoculation, the integrity of the skin in these patients being usually impaired by some other skin disease, for example, eczema-231 or seborrhoeic dermatitis21: in others the virus is inoculated by scratching37. When there is no pre-existing skin disease and lesions appear without scratching, implantation must be secondary to generalization in the blood. The notes which follow refer to this type.

CLINICAL DIAGNOSIS OF WHOOPING-COUGH WITHOUT THE WHOOP

more children in this country than scarlet fever and diphtheria together. Its diagnosis, like that of pregnancy, is difficult in the early stages, and obvious to the household in the late. It is made obvious by the onset of whoop;ng. Earlier diagnosis is important, affecting as it does the treatment of the child, the prevention of yet further spread of the infection, and the reputation of the practitioner. Two laboratory methods may be of great help in early diagnosis: (1) an absolute and relative lymphocytosis is usually present (Kolmer,2 Crombie3), and (2) the bacillus of Bordet and Gengou may be isolated in the catarrhal stage of the malady. The former takes too much time in

Hereditary disease and its control.

Waren Tay was born in 1843; he qualified in medicine at the London Hospital and was appointed to it as a surgeon. He was also on the staff of the Royal London Ophthalmic Hospital at Moorfields and City Road, and the North East Hospital for Children, which became Queen Elizabeth Hospital, Hackney Road. A versatile man, he was also dermatologist to the Hospital for Diseases of the Skin. In 1881 he reported his findings in the eyes of a 1-year-old child with severe muscular weakness. Six years later, in 1887, Bernard Sachs gave a detailed clinical and pathological account of the disease and gave the name cherry red spot to the macular changes. He recognized that the condition was hereditary and occurred in Jewish babies and called it amaurotic family idiocy. He was born in Baltimore in 1858 to German immigrant parents and after studying at Harvard and Strasburg he became a leading neurologist in New York, and in 1905 wrote the first American book on paediatric neurology. He lived on into the penicillin era and died in 1944. Tay-Sachs disease is characteristically commoner among