Erythrocytosis Associated with Multiple Cutaneous Leiomyomata: Report of a Case with Demonstration of Erythropoietic Activity in the Tumour

A patient with leiomyomata of the skin and erythrocytosis is reported. After surgical removal of the larger skin tumours there was remission of the haematologic abnormalities and the erythrocytosis and the red cell mass decreased to normal levels. The raised serum erythropoietin levels were reduced but remained slightly elevated and less than those recorded prior to surgery. Tumour extracts contained significant erythropoietic activity. This seems to be the first documented case of erythrocytosis associated with skin leiomyomata.     

PENILE SIZE AND GROWTH IN CHILDREN AND ADOLESCENTS WITH ISOLATED GONADOTROPHIN DEFIENCY (IGnD)

Penile length and circumference were measured in twenty boys with isolated gonadotrophin deficiency, before and during the administration of androgen therapy. Their age ranged between 3 and 20 years. Considering as normal, measurements above the tenth centile, in all the patients but four the penile length was below normal, and in two it was borderline. Penis circumference was normal in two, borderline in four and subnormal in sixteen. Regular administration of androgen therapy increased penile length in eleven out of fourteen patients with achievement of normal length in four. It is concluded that congenital lack of LH and testicular androgen activation causes small sized penises, even in the prepubertal period. Gonadotrophin deficiency should be looked for in patients with measurements below the tenth centile. Early diagnosis and institution of androgen therapy between 11 and 12 years is likely to increase penile size and prevent the psychological side effects of undersized genitals and delayed puberty.     

Topical mechlorethamine therapy for mycosis fungoides

Patients with limited skin involvement by mycosis fungoides were treated with daily topical mechlorethamine. Seven of thirteen patients had a complete remission of diseases. Six of these seven experienced a contact dermatitis and four underwent a successful topical desensitization programme. The possible beneficial therapeutic effects of developing a contact allergy are discussed.     

ADRENOCORTICAL FUNCTION IN CHILDREN WITH PRECOCIOUS SEXUAL DEVELOPMENT DURING TREATMENT WITH CYPROTERONE ACETATE

Adrenal function was studied in thirty-two children with precocious sexual development who were being treated with cyproterone acetate (CPA) at doses ranging from 68 to 175 mg. m2. day for periods lasting from 2 to 79 months. In eighteen children the adrenocortical function evaluation was made before and during CPA treatment. In these eighteen patients, the mean basal plasma cortisol level during the morning hours was 11.2 +/- 4.6 micrograms/dl (m +/- SD) before treatment and fell significantly to 7.2 +/- 4.1 micrograms/dl (P less than 0.02) during therapy. In fifteen patients tested during insulin hypoglycaemia the cortisol peak fell from 21.6 +/- 5.5 micrograms/dl before treatment to 16.7 +/- 6.8 micrograms/dl (P less than 0.05) during CPA therapy. There was a significant inverse correlation between this peak and the dose of CPA but no correlation was found between the cortisol response and duration of treatment. In eight of twenty patients tested, urinary free cortisol levels were undetectable during treatment. No change in basal plasma ACTH levels were demonstrated using standard radioimmunoassay techniques. In the patient receiving the highest dose of CPA and showing complete suppression of the adrenal axis, prolonged stimulation with ACTH-Depot demonstrated a responsive adrenal gland. Addition of a replacement dose of cortisol to the CPA treatment led to the rapid development of the typical signs of Cushing's syndrome. It was concluded that despite the evidence of adrenal suppression by CPA, cortisol supplementation is not necessary and may not even be contraindicated.     

Adenylate cyclase in the maturing human reticulocyte: selective loss of the catalytic unit, but not of the receptor-cyclase coupling protein

Hormone sensitive adenylate cyclase consists of at least three components; hormone receptor, a catalytic unit, and the N-protein, which couples the receptor to the catalytic unit. Human erythrocytes have very low adenylate cyclase activity, but do have N-protein activity. We have investigated the fate of the catalytic unit and the N protein during maturation of human reticulocytes. We compared red blood cell membranes derived from nine patients with reticulocytosis averaging 12% to erythrocyte membranes from eight normal subjects. The catalytic unit was assayed by stimulation of adenylate cyclase with forskolin, and the N-protein activity by an in vitro complementation assay. Forskolin stimulated adenylate cyclase activity was ten times higher in membranes derived from patients with reticulocytosis as compared with those of normal subjects. N-protein activity was only slightly (12%) and insignificantly (P = 0.08) higher in the reticulocytosis patients membranes. We conclude that during maturation of the human erythrocyte there is a differential loss of the catalytic unit of adenylate cyclase.     

ADDISON'S DISEASE ASSOCIATED WITH PRECOCIOUS SEXUAL DEVELOPMENT IN A BOY

ABSTRACT. Marilus, R., Dickerman, Z., Kaufman, H., Varsano, I. and Laron, Z. (Institute of Pediatric and Adolescent Endocrinology, Steroid Laboratory and Pediatric Department B, Beilinson Medical Center, Petah Tikva, Sackler School of Medicine, Tel Aviv University, Israel). Addison's disease associated with precocious sexual development in a boy. Acta Paediatr Scand, 70:587,.–An eleven-year-old boy was diagnosed to have Addison's disease with an ACTH level of over 4 500 pg/ml after a short episode of fever and dehydration. From the age of 6 years his skin and buccal mucosa had been hyperpigmented but there were no other subjective complaints. The clinical examination also revealed signs of advanced puberty for his age (3rd-4th stage according to Tanner's criteria), with advanced bone age (13 years). The elevated levels of plasma testosterone and gonadotropins and their response to LH-RH stimulation were appropriate for his clinical stage of puberty and supported the diagnosis of true precocious puberty. It is proposed that the concomitant appearance of Addison's disease and precocious puberty is due to a "drift" phenomenon of LH-RH and/or gonadotropins following the prolonged elevation of ACTH secretion.     

Carotid Sinus Hypersensitivity: Diagnosis of Vasodepressor Type in the Presence of Cardioinhibitory Type

The diagnosis of carotid sinus syncope may sometimes be difficult because its symptoms are not specific, especially in the older age group where carotid sinus hypersensitivity and syncope are not uncommon events. Of major diagnostic importance is the screening of the vasodepressor type of carotid sinus syncope in the presence of the cardioinhihitory type, as this diagnosis has important therapeutic applications. This work is based on the electrophysiological studies performed on seven men with a mean age of 61.9 years who had syncope of unknown cause and hypersensitive carotid sinus reflex. The studies revealed no evidence of sinus node dysfunction or high degree atrioventricular block that would explain the neurological symptoms. The studies also included carotid sinus stimulation with simultaneous interarterial pressure recordings with and without atrial or A-V sequential pacing. The pacing assured the maintenance of normal heart rate during carotid sinus stimulation. The results of these studies revealed that five patients suffered from cardioinhibitory type and two from a combined form of cardioinhibitory and vasodepressor type (mixed form) of carotid sinus syncope. A permanent cardiac pacemaker was implanted in the five patients with the isolated cardioinhibitory type and in one patient with the mixed type of carotid sinus syncope.     

Droperidol decreases the incidence and the severity of vomiting after tonsillectomy and adenoidectomy in children

We assessed the effect of intravenous droperidol on the incidence and the severity of postoperative vomiting in children undergoing tonsillectomy and adenoidectomy. Seventy-nine ASA physical status I or II children aged 1.5 to 18 years (mean 6.1 years) were randomized into two groups. Group I received droperidol 50 μg·kg^?1 i.v. (maximum 1.25 mg), while group II received saline placebo immediately following the induction of general anaesthesia. All episodes of vomiting were recorded from the time of extubation until discharge the next morning. Of the 35 assigned to group I only 16 (46%) had one or more episodes of emesis compared to 31 of 44 (71%) in group II (P < 0.05). Patients in group I who vomited, did so only 1.9 ± 1.2 times compared to 4.6 ± 3.8 times for the control patients (P < 0.01). The authors conclude that droperidol at a dose of 50 μg·kg^?1 given at the time of induction of anaesthesia to healthy children decreases the incidence and the severity of vomiting during the first postoperative day following tonsillectomy and adenoidectomy.;     

Synthesis of keto-methylene and dehydro-keto-methylene pseudo-dipeptides

A new synthetic pathway is proposed for the preparation of keto-methylene and dehydro-keto-methylene dipeptide isosteres bearing the general formulas (RS)XxxΨ(COCH₂)(RS)Yyy and (RS)XxxΨ(COCH₂)ΔYyy. The method involves the condensation of an oxazolone derived from an N-benzoyl amino acid ( 3a, b ) via a modified Dakin-West reaction with the appropriately α-substituted succinoyl chloride half ester ( 2a, b ). This last compound is obtained from a Stobbe condensation followed by reaction with oxalyl chloride. The fully protected pseudo-dehydro dipeptides ( 41, b ) thus obtained can then be catalytically hydrogenated to the desired pseudo-dipeptides ( 5a, b ). Acid hydrolysis of ( 4 ) and ( 5 ) gives the pure fully deblocked dipeptide surrogates which are then N-protected for coupling into the desired peptide analogs. For preparative applications, the prior isolation of intermediates is not required throughout the procedure up to the final products. In this manner, the following compounds were prepared: Boc-(RS)PheΨ(COCH₂)(E, Z)Δ Phe-OH ( 9 ), Boc-(RS)Pheψ(COCH₂)(RS)Phe-OH (7a), and Boc-Glyψ(COCH₂)(RS)Leu-OH ( 7b ). Characterization of isolated intermediates and final products was carried out.