Otic lesions and congenital hypothyroidism in the developing chick.

In an effort to elucidate the relation, if any, between thyroid abnormality and congenital deafness in Pendred's syndrome, an experiment was designed to study the effects of hypothyroidism on middle and inner ear hearing structures, including the auditory nerve and its central projection, in developing chick embryos. Propylthiouracil (PTU), 2 mg, was injected into the albumin of fertile chick eggs on the 10th incubation day. Single doses of L-thyroxine (range 1-100mug) were inoculated in a similar manner, either alone or with PTU. Control inocula included sterile saline or water. After hatching, each chick was examined for obvious malformations. The thyroid glands, middle and inner ear mechanisms, auditory nerve, and brainstem were studied grossly and with different histologic staining techniques. When compared to controls, chicks exposed to PTU on their 10th incubation day exhibited: increased mortality, delayed hatching, reduced size, incomplete yolk sac absorption, and death within 5 days unless exogenous thyroid hormone was provided in the first 24-48 hr after hatching. Specific, consistent, morphologic alterations were observed in their thyroid glands as well as in the sensory hair cells of the acoustic papilla and cells of the spiral ganglion of the cochlea. Our data also indicate that if 50-75 mug of L-thyroxine is given simultaneously with (or as long as 120 hr after) the PTU injection on the 10th incubation day, one cannot detect the gross defects, marked thyroid lesions, or abnormal histology in cells of the cochlea and its ganglion. A relationship between embryonic thyroid gland function and the hearing mechanism of the chick embryo is suggested.

Sudden infant death due to congenital adrenal hypoplasia.

Adrenocortical hypoplasia was found to be the cause of sudden death in a 9-month-old infant. Most sudden infant deaths in the first year of life are related to the sudden infant death syndrome, in which no specific pathologic changes are found at autopsy. Although specific causes for sudden death in infancy are well documented, adrenocortical hypoplasia is not a well-recognized cause of sudden infant death.

Adrenal scan in 17-alpha-hydroxylase deficiency: false indication of adrenal adenoma.

A patient who was thought to have testicular feminization syndrome and primary aldosteronism had an adrenal scan that suggested an adrenal adenoma. After later diagnosis of 17-alpha-hydroxylase deficiency, she was treated with glucocorticoids rather than surgery. Her clinical course and a repeat adrenal scan confirmed she did not have a tumor.

Larval brine shrimp (Nauplii): a potentially useful model to study cystic fibrosis.

One of the most consistent characteristics of cystic fibrosis is the abnormal handling of electrolytes by exocrine glands. The present study has examined the possibility that diminished respiratory energy formation is a primary biochemical error responsible for this abnormality. Using oxygen consumption of intact larval brine shrimp, quantitative differences have been observed from reaction of mixed mouth saliva between CF heterozygotes and CF homozygotes. In addition, information demonstrating a correlation between a biochemical abnormality and disease severity was observed. The differences observed in inhibition by saliva from both CF homozygotes and obligate heterozygotes may occur as the result of 1) interference with electron transfer from organic fuel molecules to molecular oxygen or 2) interference with the mechanism responsible for generating the biochemical reducing power necessary for multiple biosynthetic reactions.

Acetaminophen hepatotoxicity and malnutrition.

A patient with severe anorexia nervosa, who ingested 15 gm. of acetaminophen, was treated with oral N-acetylcysteine. Contrary to suggestions in the literature that malnutrition increases the susceptibility of patients to the hepatotoxic effects of acetaminophen this patient survived without evidence of liver damage. Changes in the metabolism of acetaminophen secondary to poor nutrition may explain the benign course in this and similar patients.

Absence of spermatogonia in the Prader-Willi syndrome.

Bilateral testicular biopsies in an 81/2 year old boy with the Prader-Willi syndrome showed total absence of spermatogonia. Similar findings in postpubertal cases (Wannarachue et al., 1975) suggest that testicular dysplasia is one of the reasons for hypogonadism in males with the Prader-Willi syndrome.

Anorexia Nervosa: the hospital's role in family treatment.

When an anorexia nervosa patient requires hospitalization for her medical condition the treatment team faces the problem of integrating the individual focus of inpatient care with the systems focus of family therapy. In this paper we propose a family-systems model of hospitalization, the aim of which is to facilitate such integration. The model draws on current theories of anorexia nervosa, as well as general concepts from psychodynamic, developmental, and family systems theories. The major hypothesis of the model is that all members of the anorexic family are developmentally arrested in the area of separation-individuation. On this assumption, we propose that the entire treatment team (including medical professionals and therapist) needs to function as "parents" to the anorexic family in much the same way that two cotherapists become parental figures in a family therapy. Specifically, the team needs to provide those parenting the responses that facilitate the family's individuation process.

Studies of malformation syndromes of man XLVII: disappearance of spermatogonia in the Fanconi anemia syndrome.

A 15 year old boy with the Fanconi malformation-aplastic anemia syndrome developed erythroleukemia and died of multiple arterial thromboses and hemorrhage. He was one of 10 siblings including 3 affected sisters. He was short of stature and had hypoplastic thumbs; his testes were small and secondary sexual characteristics were inadequately developed. At autopsy he was found to have very few spermatogonia, i.e., a histological picture compatible with the "Sertoli-cell-only" defect. Male hypogonadism in other chromosome breakage syndromes (the Bloom syndrome and ataxia telangiectasia) may have a similar pathogenesis.

Skeletal demineralization in Turner's syndrome.

The bone mineral status of 17 girls with Turner's syndrome was evaluated by single photon absorptiometry. Bone mineral content (BMC) was 25.4% below that predicted by normalization for age, sex, height, weight, and bone width. Only 25% of this demineralization could be attributed to delayed skeletal maturation. Bones of girls who received estrogen replacement therapy were less demineralized than those of the others. The bone mineral deficit became less pronounced with advancing age. It could not be determined if the apparent effect of estrogens was related to age or if the apparent improvement with age was really due to an effect of estrogen treatment. For 8 subjects followed longitudinally there was no significant change in the BMC deficit.

Bone mineral status in growth hormone deficiency.

Bone mineral status was monitored by photon absorptiometry in 18 children with growth hormone deficiency. Before exogenous growth hormone therapy, bone mineral content, bone width, and BMC/BW were below predicted values. Delayed maturation, as assessed by skeletal age, accounted for approximately 35% of the deficit for these values. Height velocity doubled during therapy, and BMC, BW, and BMC/BW increased commensurate with height and weight increases so that the relative deficit was unchanged. The pathogenesis of relative osteopenia in growth hormone deficiency was not determined.

Osteopenia in juvenile diabetes.

The bone mineral status of fifty-one children with diabetes mellitus was studied by single photon absorptiometry. The mean bone mineral content was 13% below values predicted by age, sex, height, and weight. Those children whose diabetes was one year or less in duration were as osteopenic as those whose diabetes was of longer duration. The demineralized children received a higher daily insulin dose than others. No association was noted between the degree of skeletal demineralization and sex, statural growth, renal function, and serum calcium and phosphorus. No significant changes in bone mineral content were noted longitudinally.