Early Radiographic Progression of Scleroderma: Lung Disease Predicts Long-term Mortality.

BACKGROUND: Radiographic end points commonly are included in therapeutic trials for systemic sclerosis (SSc)-interstitial lung disease (ILD); however, the relationship between these outcomes and long-term mortality is unclear. RESEARCH QUESTION: Do short-term changes in radiographic measures of ILD predict long-term survival in patients with SSc? STUDY DESIGN AND METHODS: The Scleroderma Lung Study (SLS) I and II evaluated the safety and efficacy of cyclophosphamide (in SLS I and II) and mycophenolate mofetil (in SLS II) for the treatment of SSc-ILD. Changes in the extent of ILD over time were assessed on high-resolution CT scans of the chest by quantitative image analysis, an approach that applies a computer-based algorithm to assess changes in the radiographic extent of ILD objectively. Participants subsequently were followed for up to 12 years (SLS I) and 8 years (SLS II). Cox proportional hazards models determined whether the change in the quantitative radiographic extent of ILD predicted survival, adjusting for other known predictors of survival. RESULTS: Among SLS I and II participants, 82 and 90 had follow-up imaging scans, respectively, and were included in the analysis. Participants in both trials who showed an increase in the total quantitative radiographic extent of ILD scores of ≥ 2% at 12 months (SLS I) or 24 months (SLS II) experienced significantly worse long-term survival than those with change scores of < 2% (P ≤ .01, log-rank test). In the multivariate Cox models, radiographic progression remained associated with worse long-term survival in SLS I (P = .089) and SLS II (P = .014). INTERPRETATION: Data from two independent clinical trial cohorts with extensive long-term follow-up demonstrated that radiographic progression of ILD over 12 to 24 months, in both treatment and placebo arms, can predict increased risk for long-term mortality in patients with SSc. These findings suggest that radiographic end points may serve as surrogates for mortality in SSc-ILD.

Cyclopia-synotia: an unusual presentation.

An infant showing an unusual combination of craniofacial abnormalities is described. Synotia, astomia, a rudimentary proboscis, and a central placode in the hairline were observed. Serial sections of the head were examined microscopically. The proboscis contained a mass of striated muscle, but no bony or nervous tissue. Cyclopia was suggested by the central placode, the latter consisting of a thin, stratified, squamous nonkeratinized epithelium attached to an incomplete orbit by a strand of connective tissue. The orbit consisted of a bony shelf with bundles of nerves, striated muscle, and degenerate retinal tissue. The central nervous system cranial to the hindbrain was poorly developed. The midbrain and diencephalon were rudimentary, and there was poor separation of the small cerebral hemispheres. The auditory system was well represented. The maxilla and mandible were present, but there was no evidence of tooth formation. The wide range of midline abnormalities and anodontia suggest that this is a case of cranial neural crest deficiency.

Raised maternal serum alpha-fetoprotein levels not associated with fetal malformations. A case report.

A pregnant black woman was found to have extremely high serum alpha-fetoprotein (AFP) concentrations on several occasions between 18 and 28 weeks of gestation; the amniotic fluid total AFP level was borderline at 22 weeks, and the concanavalin-A non-reactive fraction was below normal. At this stage termination of pregnancy was considered, but qualitative acetylcholinesterase electrophoresis was negative and repeated echographic examinations revealed no fetal defect. The pregnancy was allowed to continue, and a normal premature female infant was delivered at 36 weeks. Possible explanations and the potentially serious implications of the results of laboratory tests in a case such as this are discussed.

Maternal serum alpha-fetoprotein screening in Natal. Results of over 12 000 tests.

Mass screening of maternal serum alpha-fetoprotein levels for the prenatal detection of fetuses with neural tube defects (NTDs) was introduced in Natal during 1979. From then until 31 October 1982, 12318 pregnancies were monitored and 16 fetuses with NTDs identified. A further 7 abnormal fetuses, 3 with defects other than of the neural tube, were encountered. It is shown that the screening process is reliable and that it does not generate much additional work for ultrasonographers or other laboratories. Few problems related to the management of the screening programme were met; they are discussed with particular reference to the role of ultrasonography.

A 3-year cytogenetic survey of 9 661 patients in South Africa.

During the period 1 January 1977 - 31 December 1979, 9 661 patients underwent cytogenetic investigation at seven participating laboratories in South Africa. The chromosome data were coded using a standard protocol and the results tabulated, being listed according to the clinical signs which led to referral for investigation. Cytogenetic investigation was most commonly requested for prenatal studies, and 22% of the group's effort was directed towards this. One in 27 amniotic cell specimens was reported to have shown anomalous chromosomes, trisomy 21 being the most frequent abnormality. The majority of postnatal investigations were requested because congenital abnormalities suggested an underlying chromosomal defect. In 42,3% of 2 420 patients a chromosome defect was confirmed. Results of chromosome studies are tabulated by indication for referral and the findings summarized. This collaborative study gives an indication of the nature and frequency of chromosome disorders in South Africa.

Prenatal screening for neural tube defects in South Africa. An assessment.

Neural tube defects (NTDs) occur in at least 1 in every 1000 babies born in South Africa. The incidence is uncertain but appears to be highest in Whites and Coloureds and lowest in Blacks. Spina bifida is a particularly serious problem because many affected babies survive and require extensive, costly treatment and care. A high maternal serum alpha-fetoprotein (AFP) level may indicate that the fetus has an NTD. Enzyme-linked immunosorbent assay is well suited to mass screening of maternal sera. The Natal population is used as a model here, and it is calculated that of some 122000 pregnancies annually 38725 might be screened. Of 98 expected fetuses with an NTD, 32 (16 with anencephaly and 16 with spina bifida) should be detected. If the 16 fetuses with spina bifida were not detected and those pregnancies terminated, the cost of caring for the affected children through their first decade is conservatively estimated at R145660, an average of R9 100 per patient; 92% of this would be incurred in the first 3 years. The cost of screening, at R2,27 per subject, is calculated to be R87 825, equivalent to R2 744 per fetus with an NTD detected or R5 489 per fetus with spina bifida detected. Financially the introduction of mass screening of maternal serum AFP is justified, but before this can be done adequate ultrasound facilities must be provided and a permanent health visitor must be available to trace women at risk and arrange their further investigations. A public education campaign should also be introduced. Some ethical and legal implications of mass screening for NTDs are discussed briefly.

Prenatal detection of neural tube defects by maternal serum alphafetoprotein assay.

Mass screening for fetal neural tube defects using maternal serum alpha-fetoprotein assay as the initial test is financially justified in South Africa, despite the relatively low incidence of these defects in this country, using enzyme-linked immunosorbent assay. This technique is efficient and inexpensive and lends itself to mass screening. We report a pilot study in which 3153 maternal serum samples were received during a 4-month period. Of these 3102 were assayed and the outcome of pregnancy was recorded in 2069 cases. On the first assay 147 (4.7%) of the women had serum alpha-fetoprotein levels which were high for the gestational dates given, but in retrospect about half of these had been misinterpreted because of incorrect dates. Among the remainder, 6 women proved to be carrying twins, 4 aborted spontaneously, 10 delivered prematurely or had infants with intra-uterine growth retardation, and 4 had a fetus with a neural tube defect. Two affected fetuses were missed by screening, in both cases because serum was taken after 20 weeks gestation. In this sample the incidence in Indians (1/1000)and Coloureds (1/600) was as expected, but in Whites it was much higher (1/130), which probably reflects a sampling error and indicates that the epidemiology of neural tube defects in South Africa requires investigation.

Trisomy-12p syndrome: Family study and prenatal diagnosis.

A young unrelated Indian couple produced a baby who had an unusual facies, marked abdominal distension and muscular hypotonia. At 8 weeks cytogenetic investigation revealed what appeared to be trisomy-21. Because this did not agree with the clinical signs the parents were tested and the mother was found to have a balanced translocation between chromosomes 12 and 14; her karyotype was 46,XX,rcp(12; 14)(p11; q11) and it was realized that her son had inherited her translocation chromosome involving the short arms of chromosomes 12 and 14. He thus had trisomy-12p. The present case and 10 others reported in the literature confirm that trisomy-12p produces a recognizable syndrome. Parents carrying a balanced translocation have a 50:50 risk of producing an abnormal infant at every pregnancy because both the trisomic and monosomic conditions may be viable. Amniocentesis for fetal karyotyping must be recommended to the couples concerned.

Hereditary hypotrichosis. A previously undescribed syndrome.

A syndrome of hereditary hypotrichosis with an unusual natural history and clinical features was encountered in a Caucasian family of four generations with a total of twenty-four members of whom eleven were affected. The mode of inheritance was autosomal dominant with variable penetrance. The loss of hair involved the scalp, eyebrows, eyelashes and body hair, manifesting itself in the school years and progressing to almost complete baldness. There were no associated abnormalities and no sex limitation. Clinical, genetic, biochemical, mechanical, histological and immunological aspects were studied. Essential differences between this type of hereditary hypotrichosis and others previously recorded are stressed.

A cytogenetic study of a mentally retarded population in South Africa.

The entire population of the Umgeni Waterfall Institution for mentally retarded Whites was karyotyped using aceto-orcein and ASG banded preparations. Of the 512 subjects, 376 were males and 136 were females. Their ages ranged from 1 to 72 years and mental retardation ranged from borderline to profound. Altogether 11,1% had chromosome abnormalities, of which 8,2% had trisomy-21, 1,9% had other autosome abnormalities, and sex chromosome anomalies occurred in 1%. Normal variant chromosomes were seen in 4,5% of the population. Problems that arose in the course of the survey were mainly due to inadequate family histories and the high proportion of cases in which contact with the family had been lost, thus precluding proper follow-up studies.

Chromosome abnormalities in South African mental retardates.

Standard and differential staining techniques were employed in this cytogenetic study of mentally retarded Whites at the Umgeni Waterfall Institution. All of the 512 patients were karyotyped and 57 were found to have chromosome abnormalities. Of these, 42 had trisomy-21; there were 3 subjects with 5p deletion (cri-du-chat) syndrome, 3 had supernumerary small marker chromosomes, and 2 had complex structural rearrangements. Gonosomal aneuploidies were less common than the autosomal defects and only 2 poly-X males and 1 poly-X female were identified. Long Y chromosomes were found in 11 males and 4 others had deleted Y chromosomes. One abnormal chromosome, a deletion of the terminal region of 11q, was missed in unbanded karyotypes. Banding is essential to the identification of structurally abnormal chromosomes.

XYY karyotype, female phenotype and gonadal dysgenesis. A case report.

A rare association of female phenotype with the 47,XYY karyotype in a 14-year-old White girl is described. She was studied because of her short stature and proved to have gonadal dysgenesis. She showed no masculinization and there were no Turner stigmata. Her intelligence was normal, she was sociable and her outlook was feminine.

Concentrations of similar finger print patterns in four race groups.

Random samples from four races were examined to determine the frequency of subjects with none, or between 5 and 10 loops or whorls; with 2 or more radial loops, and with 3 or more simple arches. Inter-racial and sex differences occur and affect the description of various concentrations as being common or unusual.

A family with partial and total deficiency of complement C3.

A young White girl was found to have no detectable complement C3 or C1q. She suffered repeated attacks of pneumococcal meningitis and pneumococcal pneumonia. Her parents, and some of her siblings, had half the normal level of C3; other siblings were normal. She also had decreased IgG levels and increased IgM concentrations. These findings are correlated with a dysmorphic state of the germinal centres of the peripheral lymphoid tissues, seen after death.

Distribution of hypothenar radial arches.

A study of the frequency of the radial arch in the hypothenar area has confirmed that there are bimanual and sex differences, and has shown that racial differences in the frequency exist between Whites, Indians, Negros, and a Coloured (mixed racial origin) population. The pattern is not uncommon, and in about 25% of cases there is an associated marginal triradius.

Klinefelter's syndrome in South African Indians and blacks.

Poly-X syndromes are very uncommon in Indian and Black South Africans. Two affected males of each race group are described; the Indians are probably the first to be reported in this country, and there are now 8 case histories of Klinefelter's syndrome in Blacks. The possible reasons for the rarity of the poly-X syndromes in South Africa are discussed and it is suggested that these syndromes are less common here than in other countries.

Digital and palmar dermatoglyphs of South African Whites.

Digital and palmar dermatoglyphs in a random sample of normal Whites from Durban are described. The sample consisted of 200 males and 200 females. Features examined included frequency and distribution of finger patterns, digital and total ridge count, a-b score, and palmar topography. Data from this study are compared to similar data from South African Negroes, Indians, and Coloureds (mixed racial origin) and several outstanding racial characteristics are demonstrated in the dermatoglyphic profiles. It is suggested that the Indians' dermatoglyphic profile is dominant to those of Whites and Negroes.