The potential hazards of dinitrochlorobenzene.
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Animals↗
Biomedical subjects
R Happle
Publications and source records attributed to R Happle.
[Teratogenic effects of etretinate in humans].
Etretinate (Tigason) is an orally administered retinoid which is used primarily for the treatment of severe keratinization disorders of the skin. The compound has been shown by animal studies to be teratogenic. Because of its lengthy period of storage in the body, the teratogenic risk in humans persisting even after cessation of therapy is an important problem. Despite insistent warnings, female patients have become pregnant in temporal relationship to etretinate therapy. According to observations reported to the manufacturers until February 1984, 19 women had taken etretinate during pregnancy; ten of these patients bore children with no recognizable teratogenic abnormalities. Three women bore children with skeletal defects which had to be attributed to etretinate. One woman had a spontaneous abortion in the 5th month; the fetus was found to have a meningomyelocele. Two fetuses which were aborted for medical reasons had marked cerebral abnormalities. A further 3 fetuses from interrupted pregnancies showed no defects. Among 18 women who became pregnant within two years after etretinate having been discontinued there was no case of teratogenic damage to the embryo. Even if, to date, no malformed infants have been born to woman conceiving after stopping etretinate therapy, the stipulated period of pregnancy prevention after withdrawal of etretinate must continue to be scrupulously respected, since etretinate is apparently teratogenic.
Abnormalities, Drug-Induced↗
[Monilethrix: exclusive involvement of body hair].
In a family suffering from monilethrix, at first sight only one generation seemed to be affected, suggesting a recessive mode of inheritance. A thorough examination of the scalp and body hair of all family members, however, revealed three other affected persons in two more generations proving autosomal dominant transmission. We consider this observation an additional argument against the existence of a recessive type of monilethrix which has been postulated in the past.
Adult↗
[Regression of plantar warts following treatment with diphencyprone].
Therapy-resistant plantar warts of 8 patients have been topically treated with diphencyprone, a new potent contact allergen. Three of the patients showed only one single aggregation of warts, which completely disappeared within two or three months after start of treatment. In the other five patients who had multilocular warts, a controlled trial was performed. In three of these patients only the treated warts resolved whereas the untreated ones persisted. In one case all warts disappeared already during the period of sensitization, and in the fifth patient the warts persisted without any change.
Administration, Topical↗
Intrabulbar and peribulbar accumulation of dendritic OKT 6-positive cells in alopecia areata.
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Alopecia Areata↗
The Tay syndrome (congenital ichthyosis with trichothiodystrophy).
We report a 5-year-old boy affected with the Tay syndrome, and give a review of 12 pertinent cases previously reported under various designations. The Tay syndrome is a distinct type of congenital ichthyosis characterized by a peculiar anomaly of hair growth which has been termed trichothiodystrophy. The hair shafts are extremely brittle, and they show alternating light and dark banding when examined microscopically between polarizing filters. Other features of this syndrome are low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections. The syndrome is inherited as an autosomal recessive trait. We delineate the criteria for distinguishing this gene defect from other types of congenital ichthyosis associated with disturbed hair growth, as well as from other types of trichothiodystrophy which are not associated with ichthyosis.
Growth Disorders↗
The inheritance of common baldness: two B or not two B?
So far, it is a widely accepted opinion that androgenetic alopecia is caused by an autosomal dominant gene with reduced penetrance in women. This view is essentially based on a family study performed by Osborn in 1916. She believed that balding men would be either heterozygous (Bb) or homozygous (BB), whereas balding women would be homozygous (BB). By contrast, we here present five arguments favoring a polygenic inheritance of the trait: (1) the high prevalence of the trait, (2) the distribution of balding patterns in the general population along a gaussian curve of variation, (3) the fact that the risk increases with the number of relatives already affected, (4) the slightly increased risk of relatives of severely affected women as compared to the relatives of mildly affected women, and (5) the fact that a predisposition inherited from an affected mother is of greater importance than that inherited from an affected father. In conclusion, the simple mendelian model of Bb and BB can no longer be upheld.
Adult↗
Ichthyosis vulgaris with hypogenitalism and hypogonadism: evidence for different genotypes by lipoprotein electrophoresis and steroid sulfatase testing.
We report two cases with ichthyosis vulgaris, hypogenitalism and hypogonadism. So far, little endocrinological information has been available on this association and the exact type of ichthyosis was unknown. Our first patient suffered from very severe hypergonadotropic hypogonadism, whereas the second patient showed normal levels of luteinizing hormone, but slightly elevated follicle stimulating hormone values. In lipoprotein electrophoresis we found fast moving beta-lipoproteins in the first patient and a normal electrophoretic mobility of pre- beta and beta-lipoproteins in the second patient. Correspondingly, steroid sulfatase (STS) testing revealed STS deficiency in the first patient and normal STS activity in the second patient, thus excluding X-linked recessive ichthyosis. These two different types in the association of ichthyosis with hypogenitalism and hypogonadism could not be discriminated by clinical, morphological and cytogenetic studies.
Abnormalities, Multiple↗
Autosomal dominant lamellar ichthyosis: a new skin disorder.
Lamellar ichthyosis (nonbullous congenital ichthyosis) has been explained as an autosomal recessive trait. We have found an autosomal dominant type of this disorder. Four patients, belonging to three consecutive generations of a family, were affected from birth. The disorder was characterized by large, dark brown scales covering the entire body including flexural folds, palms and soles. X-linked recessive ichthyosis was excluded by clinical appearance, pattern of transmission and normal electrophoretic mobility of beta-lipoproteins. Autosomal dominant ichthyosis vulgaris and bullous ichthyosiform erythroderma were excluded by the histological and ultrastructural features. In the absence of a positive family history, this skin disorder would have been taken for autosomal recessive lamellar ichthyosis. This new autosomal dominant type of ichthyosis should be considered for differential diagnosis, when genetic counselling is given in a sporadic case of lamellar ichthyosis.
Child↗
Immunohistochemical analysis of T-cell subsets in the peribulbar and intrabulbar infiltrates of alopecia areata.
In 11 patients with untreated alopecia areata in the progressive stage of the disease, an in situ analysis of the inflammatory infiltrate of the hair bulbs was performed by means of different monoclonal antibodies. Most of the peribulbar cells reacted with the pan T-cell antibodies OKT 3 and Lyt 3. Staining for T-cell subsets revealed that the proportion of OKT 4+ cells was about fourfold higher than that of OKT 8+ cells. Almost all of the T cells were OKIa1+, indicating that they were in an activated state. In four of the 11 cases, both subsets of T lymphocytes were also found to infiltrate the hair matrix itself. These results would appear to be consistent with the assumption that alopecia areata is caused by a T cell mediated autoimmune mechanism.
Alopecia Areata↗
Histologic and ultrastructural features of the ichthyotic skin in X-linked dominant chondrodysplasia punctata.
The ichthyotic skin in X-linked dominant chondrodysplasia punctata was investigated in a four-week-old baby and a fourteen-year-old girl. Histologically, the ichthyosiform erythroderma of the newborn and the ichthyosis of the older child presented as a retention hyperkeratosis with several distinctive features such as calcification of the keratotic follicular plugs, atrophy of the hair follicles and focal hyperpigmentation of the basal keratinocytes. On ultrastructural examination, small to medium sized vacuoles were regularly seen in the thinned granular layer. Some of these vacuoles contained needle-like calcium inclusions. The histologic and ultrastructural findings are therefore characteristic for this rare type of ichthyosis.
Adolescent↗
[How are the Blaschko lines arranged on the scalp?].
Linear inherited or nevoid skin lesions mostly follow a characteristic pattern which was delineated by Blaschko in 1901. The system of lines published by this author covered the entire human body, with the exception of the scalp because of lack of pertinent case reports regarding this area. We here report an observation which enables us to fill the blank area in the atlas of the lines of Blaschko. On the scalp of a girl affected with the oral-facial-digital syndrome, we observed an alopecia distributed in several spiral streaks. The pattern resembled that of the normal vertex, but the direction of the hairless streaks did not correspond completely to the direction of hair growth. As the oral-facial-digital syndrome is inherited as an X-linked dominant trait, the linear alopecia probably reflects functional X-chromosome mosaicism. Arguments are presented in favor of the assumption that the hairless streaks of this child follow the lines of Blaschko.
Abnormalities, Multiple↗
[Clinical course and pathomechanisms of chronic granulomatosis].
Chronic granulomatous disease (CGD) is characterized by frequent uncontrollable infections which often lead to death in early childhood. The first clinical signs may be confined to the skin and manifest themselves as abscesses, pyoderma, eczema or draining sinuses. Frequently, lymph nodes, spleen, lungs or liver are also involved. The basic defect is a failure of leukocytes to kill certain bacteria or fungi. The exact biochemical defect is however not yet known. The diagnosis of CGD is based on the clinical picture and on a defect of the granulocytes, as proven by bactericidal, NBT-reduction or chemiluminescence tests. In most and possibly in all of the cases, the disease is X-linked, and the CGD-gene has been regionally assigned to the X-chromosome. The existence of a second type of CGD with autosomal recessive inheritance has been assumed by several authors. In order to improve the prognosis of CGD, it is essential that the disease is diagnosed as early as possible so that prompt treatment can be given.
Adult↗
Sectorial cataract: a possible example of lyonisation.
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Adult↗
Homologous genes for X-linked chondrodysplasia punctata in man and mouse.
X-linked dominant chondrodysplasia punctata is a human gene defect characterized by punctate foci of epiphyseal calcification, cataracts, ichthyosis, and systematized atrophoderma. In a comparative study, the murine X-linked mutant 'bare patches' was found to display strikingly similar skeletal, ocular, and cutaneous anomalies. The human as well as the murine phenotypes occur exclusively in the female sex, apparently because the underlying mutations are lethal for male embryos. In both traits, the cutaneous lesions are arranged in a linear and blotchy pattern reflecting lyonization. The observed similarities constitute strong evidence that the two genes are homologous. The proposed homology is a further example of the evolutionary conservatism of the X-chromosome in mammals.
Animals↗
Clinical spectrum of steroid sulfatase deficiency: X-linked recessive ichthyosis, birth complications and cryptorchidism.
When boys affected with steroid sulfatase deficiency are delivered, the lack of the enzyme in the placenta may cause birth complications. In postnatal life this gene defect gives rise to X-linked recessive ichthyosis. In a series of 25 patients birth complications were reported in 9 cases. Of these boys, 4 displayed bilateral inguinal cryptorchidism and one was affected unilaterally. In a further boy we observed unilateral inguinal cryptorchidism without a history of birth complications. In one patient who had been delivered by forceps, abdominal bilateral cryptorchidism resulted in severe hypogenitalism. A review of the literature revealed 30 cases with X-linked recessive ichthyosis displaying hypogenitalism or cryptorchidism or both. In conclusion, cryptorchidism should be considered as a further clinical manifestation of steroid sulfatase deficiency.
Adolescent↗
Thalidomide in the treatment of sixty cases of chronic discoid lupus erythematosus.
The therapeutic effect of thalidomide in chronic discoid lupus erythematosus (CDLE) was studied in sixty patients who were followed up for 2 years. In fifty-four patients (90%) a complete or marked regression of the disease was observed, but when the thalidomide was stopped, thirty out of forty-one (71%) patients relapsed. Patients undergoing a second course of thalidomide treatment again responded well. Nine of the patients in whom the disease recurred after successful treatment with thalidomide and who had been unresponsive to intermittent treatment with antimalarials, showed a good response to a second or third course with thalidomide. Mild side-effects were common and 25% of patients complained of slight to moderate polyneuritic symptoms. Since electroneurological examinations had not been performed before the thalidomide therapy, the frequency of neurological side-effects cannot be accurately calculated but we recommend neurological examinations before and periodically during thalidomide treatment. Thalidomide is a very effective drug in CDLE, but in most cases it exerts its effect only whilst treatment is continued. Its use should be restricted to patients resistant to topical steroids and systemic antimalarials.
Chronic Disease↗
Diphencyprone in the treatment of alopecia areata.
27 patients suffering from either extensive alopecia areata (n = 5) or alopecia totalis (n = 22) were treated topically with diphencyprone, a new potent contact allergen. The duration of treatment ranged from 4 to 17 months. Unilateral induction of hair growth after unilateral treatment was observed in 23 patients. A continuous response after continuous treatment has been observed so far in 18 of these patients. Thus, diphencyprone was found to be as effective as DNCB or squaric acid dibutylester in the treatment of alopecia areata. Unlike DNCB, diphencyprone is not mutagenic in the Ames test. Compared with squaric acid dibutylester, diphencyprone is more stable and thus more suitable for storage when dissolved in acetone. Further investigative evaluation of diphencyprone may show whether this drug is suitable for a more general use in the treatment of severe forms of alopecia areata.
Adolescent↗