J. H. Edwards

Hypersensitivity pneumonitis after exposure to isocyanates.

Four patients exposed to isocyanate vapour developed dyspnoea associated with restriction and reduced gas transfer as well as moderate airways obstruction on lung function testing. In one patient bilateral radiographic shadowing was present and an open lung biopsy was performed. The microscopic appearances ranged from acute inflammation to end-stage fibrosis but the centribular accentuation of disease and the presence of areas resembling bronchopulmonary aspergillosis suggested that the process was a hypersensitivity response to inhaled allergen. Challenge tests with albumin and toluene diisocyanate-albumin were carried out in sensitized and control rabbits. The sensitized animals developed extensive lung damage of the type associated with an Arthus reaction. It is suggested that patients exposed to isocyanates may occasionally develop a hypersensitivity pneumonitis rather than the more usual asthmatic syndrome.

Precipitin test negative farmer's lung—activation of the alternative pathway of complement by mouldy hay dusts

Respirable fractions of mouldy hay and grain dusts were incubated with fresh human serum, Immunoelectrophoresis against rabbit anti C3 activator serum showed a conversion of C3 proactivator to C3 activator indicating that these respirable dust fractions are capable of operating the C3 by‐pass mechanism (alternative pathway). It is suggested that this, or other mechanisms, may contribute towards a disease essentially the same as classical immune complex farmers lung where exposure is sufficiently heavy.

Sex-linked Hydrocephalus Report of a Family with 15 Affected Members

Congenital hydrocephalus is a common cause of stillbirth and infant death [in Birmingham (Record and McKeown, 1950), Rhode Island (MacMahon, Pugh and Ingalls, 1953), and in Scotland (Edwards, 1958)], the incidence lying between one and two per thousand births, in each area the incidence being lower than that of either anencephalus or spina bifida. When the heterogeneous assembly of cases so designated is analysed intact it seems clear that genetic syndromes related to recessive or sex-linked recessive inheritance are rare as the incidence in siblings of propositi is very low. Penrose (1946) found no case in 84 sibs born after the propositus; Record and McKeown (1950) only one case in 61 sibs born after the propositus; and MacMahon et al. (1953) no case in 55 sibs born after propositus; the overall incidence in these three series is one case in 200 siblings. Further analysis of the Birmingham data (Record, 1959) showed no affected male sibling of 50 male propositi. When grouped together the cases resulting in stillbirth show a marked increase in risk with primogeniture and with maternal age, and also some increase with reduced social class of the father (Edwards, 1958), showing that a substantial proportion of cases are related to various environmental agencies. In 1949 Bickers and Adams described a family in which all of the three sons and four of the six brothers of a healthy woman died at birth with hydrocephalus, none of the three sisters or two daughters being affected (Fig. 1). An autopsy on one case showed evidence of aqueductal stenosis. Bickers and Adams commented that, although the numbers were too small to attach much weight to their observations, the pattern of inheritance was entirely consistent with a sex-linked recessive mechanism. The purpose of this paper is to present a further case of hereditary hydrocephalus pathologically similar to that described by Bickers and Adams, and showing, on far larger numbers, a pattern of inheritance entirely consistent with a sex-linked recessive mechanism. That is to say the syndrome appears to be the result of an abnormal gene carried on an X chromosome, the morbid influence of which is completely eclipsed in the presence of another X chromosome lacking this genetic aberration.

The Oxford Grid.

The ‘Oxford Grid’ is a term used to denote a method of displaying homologous loci from two species. It may also be used as a basis for historical inferences relating to co‐ancestry. These uses are discussed with special reference to man and mouse. It is inferred that as few as 30 reciprocal translocations are sufficient to explain the differences defined by the present grid and that the telocentric karyotype, through which the mouse differs from both man and many closely related rodents, including the rat, must have evolved mainly through the formation and suppression of centromeres rather than through pericentric inversions. Mouse and man share the widest distribution of any mammal and their success appears to be related to being omnivorous with behavioural modifications allowing a wide range of habitat.

A quantitative study on the activation of the alternative pathway of complement by mouldy hay dust and thermophilic actinomycetes

Materials associated with the induction of farmers lung were incubated with fresh normal human serum in the presence of magnesium ethylene glycol tetra‐acetic acid (MgEGTA) or ethylene diamine tetra‐acetic acid (EDTA) and results compared with material known to activate the alternative pathway of complement—zymosan. Results show that Micropolyspora faeni organisms are as active as zymosan in reducing complement (C) levels in the presence of MgEGTA, with a 50% reduction in CH50 at approximately 140 μg/ml. Thermoactinomyces vulgaris organisms produced a 50% CH50 reduction at approximately 1.25 mg/ml and two samples of respirable mouldy hay dust (MHD) at approximately 5.6 mg/ml whereas extracts of M. faeni and T. vulgaris reduced the CH50 titre by 17% and 39% respectively at 16 mg/ml in the presence of MgEGTA. Organisms and extracts did not reduce the CH50 titre in the presence of EDTA even at the maximum concentration quoted by more than 3%, thus it is considered that alternative pathway activation was responsible for C utilization in the presence of MgEGTA.

Pulmonary responses to particulate materials capable of activating the alternative pathway of complement

The cellular sequence of events evoked by the intratracheal injection of both respirable mouldy hay dust and zymosan in unsensitized rats and rabbits was markedly similar and contained many features seen in lung biopsies from farmers lung cases.

Respiratory disease due to sulphasalazine

A patient is described who developed a pulmonary hypersensiiivity reaction to sulphasalatzine used in the treatment of his ulcerative colitis. Challenge testing demonstrated that the patient was sensitive to the sulphapyridine component of the drug. The pulmonary response consisted of an immediate bronchial obstructive reaction and a late parenchymal reaction with fall in gas transfer factor. Detailed immunological testing failed to define the mechanisms of drug toxicity.

Allergy to inhaled egg material

The use of a spray system to coat meat rolls with egg solution resulted in the development of asthmatic type symptoms in eight of thirteen workers exposed to the spray. Symptoms were severe in five workers, less severe in two, and one worker experienced vague symptoms. Even though precipitins were present in nine of the workers there were no pyrexial episodes nor influenza‐like symptoms occurring some hours after inhaling the egg material to suggest extrinsic allergic alveolitis.

Patau's syndrome with D1 duplication‐deficiency derived from a maternal D group pericentric inversion

Pericentric inversions are detectable in somatic cells only if they result in a shift in centromere position which substantially alters the chromosome morphology so that the inverted chromosome can be distinguished from the other members of the group. For this reason, large-scale surveys are bound to give an underestimate of the extent of chromosome inversions in man. The population studies available suggest that detectable inversions are relatively infrequent and may show no adverse effect in individual carriers or their offspring (Court Brown et al. 1966; Jacobs et al. 1967). Inversions have also been ascertained through a wide variety of phenotypically abnormal individuals, but few of these have been causally implemented in the original disorders. They include two cases of an inversion in chromosome no. 1 (Lele, Dent & Delhanty, 1965), four involving chromosome no. 2 (Carr, 1962; De Grouchy et al. 1963; Miller, 1966; Breg, 1966), one involving a group-B chromosome (Morishima, Liu & Grumbach, 1964), four separate families with inverted C-group chromosomes (Jacobs et al. 1967 ; Ferguson-Smith, 1966) and two with D-group inversions (Cohen, Capraro & Takagi, 1967 ; Crandall & Sparkes, 1970). Other morphologically abnormal autosomes have been described which might represent either pericentric inversions or small duplications (De Grouchy et al. 1965; Prats & Moragas, 1967; Chandra & Hungerford, 1963; Gray, Mutton & Ashby, 1962; Ellis, Marshall & Penrose, 1962). The family presented here represents one of the few instances where a maternal autosomal pericentric inversion is thought to have given rise to duplication-deletion gametes resulting in congenitally malformed offspring.

Inhalation challenge in humidifier fever

When exposed to an amount of contaminated humidifier water roughly equivalent to that inhaled over an 8‐hour period at their work place, four out of six subjects developed symptoms of humidifier fever. Two non‐exposed subjects failed to react to the same challenge.