Androgen Receptor CAG Repeat Length in Relation to Phenotype Among Females with Nonclassical 21-Hydroxylase Deficiency.

Nonclassical 21-hydroxylase deficiency (NC21OHD) manifests with various degrees of post natal virilization. The length of CAG repeats of the androgen receptor gene (AR) is inversely correlated to activity of the human androgen receptor (AR) and affects phenotype of several androgen-dependent disorders. The aim of the study was to investigate the associations between CAG repeat length and the phenotype of females with NC21OHD. CAG repeat length and AR inactivation were assessed in females with NC21OHD, and related to their clinical presentation. CAG repeat length and AR inactivation were assessed in 119 females with NC21OHD. Biallelic mean (BAM) of the CAG repeat length and the weighted BAM (WBAM) were related to various clinical parameters. Age at diagnosis and age of menarche positively correlated with BAM (r=0.22, p=0.02, and r=0.23, p=0.01, respectively). A shorter (<25) BAM was associated with younger age at diagnosis (14.8 vs. 21.4 years, p<0.01), at adrenarche (8.1 vs. 10.2 years, p<0.01) and gonadarche (9.9 vs. 11.2 years, p<0.01), and higher corrected height standard deviation score at diagnosis (0.77 vs. 0.15, p=0.01). Precocious pubarche and precocious puberty were more frequent in these with the shorter BAM. Results of WBAM were similar. The CAG repeat length of the AR gene contributes to the clinical diversity of the phenotype in females with NC21OHD.

Behcet disease: long-term follow-up of three children and review of the literature.

Behcet disease is rare in children. There are only two reports of Behcet disease in childhood, describing seven patients. Three pediatric patients are described, in whom the age of onset ranged from 6 to 11 years. Aphthous stomatitis and arthritis were present in all of the patients; genital ulcers, iridocylitis, erythema nodosum, and CNS involvement were present in two patients. Other manifestations included Stevens-Johnson-like eruption, fever of unknown origin, and testicular involvement. All of the patients responded to glucocorticoids; two were also treated with colchicine and one was treated with chlorambucil. In two patients, follow-up of more than 10 years was done, with complete cure in one patient and benign course of illness in the other. Because of the rarity of the disease in childhood and the difficulty in making the diagnosis, there is not enough awareness by pediatricians concerning this disease.

Can exaggerated response to a GH provocative test identify patients with partial GH insensitivity syndrome?

OBJECTIVES: In the majority of children with short stature, the etiology is unknown. Mutations of the GH receptor (GHR) have been reported in a few children with apparent idiopathic short stature (ISS). These patients had low IGF-I, IGF-binding protein-3 (IGFBP-3) and GH-binding protein (GHBP), but a normal or exaggerated GH response to provocative stimuli, suggestive of partial GH insensitivity (GHI). We attempted to identify children with partial GHI syndrome, based on their response to GH provocative stimuli and other parameters of the GH-IGF-I axis. SUBJECTS AND METHODS: One hundred and sixty-four pre-pubertal children (97 boys, 67 girls) aged 7.2 (0.5-16.75) years were studied. All had short stature with height <3rd centile. The weight, bone age (BA) and body mass index (BMI) of the subjects, as well as the parents' heights and mid parental height (MPH) were assessed. Basal blood samples were taken for IGF-I, IGFBP-3 and GHBP. All subjects underwent a GH provocative test with either clonidine, arginine or insulin. The subjects were divided into three groups: (A) patients with peak GH concentration <18 mIU/l in two different provocative tests (GH deficiency - GHD, n=33); (B) patients with peak GH between 18.2 and 39.8 mIU/l (normal response, n=78); (C) patients with peak GH >40 mIU/l (exaggerated GH response, n=53). RESULTS: No significant differences were found in age, height (standard deviation score (SDS)), parental height (SDS) and the difference between chronological age and bone age (DeltaBA) between the groups. Patients with GHD were heavier (P=0.039) and had significantly higher BMI (SDS) (P=0.001) than the other groups. MPH (SDS) was lower in the group of exaggerated responders (P=0.04) compared with the other groups. No significant differences were found between the groups for the biochemical parameters when expressed nominally or in SDS, except for IGFBP-3 (SDS), which was lower in the GHD group (P=0.005). The GHBP levels were not lower in the group of exaggerated GH response to provocative stimuli. Height (SDS) correlated negatively with basal GH values in pooled data of all the subjects (r=-0.358, P<0.0001), in normal responders (r=-0.45, P<0.0001) and in the exaggerated responders (r=-0.341, P<0.0001), but not in the GHD group. CONCLUSION: Exaggerated GH response to provocative tests alone does not appear to be useful in identifying children with GHI.

Laparoscopic subtotal hysterectomy and bilateral adnexectomy in a child with congenital adrenal hyperplasia.

OBJECTIVE: To report the results of a subtotal hysterectomy and bilateral adnexectomy in a child with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. DESIGN: Case report. SETTING: Gynecology department, Afula, Israel. PATIENT(S): An 11-year-old child with a female genotype and saltwasting type congenital adrenal hyperplasia who was being raised as a boy. INTERVENTION(S): Laparoscopic subtotal hysterectomy and bilateral salpingo-oophorectomy were performed. MAIN OUTCOME MEASURE(S): Surgical efficiency, operating time, recovery, and aesthetic result. RESULT(S): The procedure was performed without complications in 26 minutes, and the child was dismissed the following day. Three 5-mL abdominal incisions were required. CONCLUSION(S): Laparoscopic subtotal hysterectomy and bilateral adnexectomy can be safely performed in children and is the procedure of choice in the rare cases in which it is indicated.

Juvenile Behçet's disease in Israel. The Pediatric Rheumatology Study Group of Israel.

OBJECTIVE: Behçet's disease (BD) is a vasculitis mainly observed in young adult males. Juvenile BD is rare and only small series of pediatric cases have been reported. The objective of this study was to define the epidemiology and clinical features of BD among Israeli children. METHODS: A questionnaire was sent to 8 pediatric rheumatology units in Israel and 30 cases of BD diagnosed before the age of 16 years were identified. RESULTS: Fifteen patients fulfilled the International Study Group Criteria for BD, while 15 had an incomplete form of BD. Among the patients with complete BD, stomatitis and skin involvement were the most common manifestations. Other symptoms included genital ulcers, uveitis, CNS involvement, arthritis, and gastrointestinal involvement. A positive family history was elicited in 3 patients. HLA B5 was found in 7 of 12 patients (58%). The 15 patients with incomplete BD all had recurrent stomatitis; other manifestations included uveitis, arthritis, and genital ulcers. HLA B5 was found in 94% of this group. CONCLUSION: Juvenile BD in Israel is not uncommon, and is frequently associated with HLA B5 positivity. This could indicate a genetic susceptibility in our region. Half of the patients in our series had an incomplete form of BD, which may represent a less severe variant of the disease. In any case, careful follow-up is required, since their condition could eventually evolve into complete BD.

Comparison between four immunoassays for growth hormone (GH) measurement as guides to clinical decisions following GH provocative tests.

OBJECTIVE: To compare four assays for the measurement of GH following provocative tests and to assess the projected clinical decisions, which would have been based on their respective results. DESIGN: Multiple assays of serum samples obtained during provocative tests for GH response. SUBJECTS: Forty-seven children with short stature, who underwent clinical evaluation and GH provocative tests. METHODS: All samples were measured by the immunoassay Sorin-RIA (A), which is routinely used in our laboratory. Basal and peak samples were analyzed by three other immunoassays: Sorin-IRMA (B), DPC-RIA (C) and Wallac-DELFIA (D). Results were classified as low, partial and normal GH response, corresponding to <10, 10-17.9 and >18 microIU/ml peak serum GH levels. RESULTS: High correlation was found between individual results by the four kits (r=0.92-0.94). However, the mean peak GH values were significantly different (p<0.0001). Further analysis using paired t-test has shown highly significant differences between the assays (p<0.0001) apart from assays A and B that were not significantly different. Clinical grouping by the four tests was profoundly different: by assay A, 14.9% were judged low response and 57.4% normal; by assay D, 36.2% were low and only 21.3% normal. Kappa statistics measurement demonstrated poor agreement between assays A and D and between B and D. CONCLUSION: As the criteria for the diagnosis of GH deficiency and the indications for GH therapy are based on laboratory GH results, more must be done to ensure uniformity and comparability of the GH assays.

The risk of postoperative haemorrhage in tonsillectomy as an outpatient procedure in children.

The safety of performing tonsillectomy as an outpatient procedure is still questionable. This study determined whether there was an increased risk of postoperative bleeding by performing tonsillectomy as an outpatient procedure. A six years' retrospective chart review was made of 363 children who underwent tonsillectomy. Out of 363 children, 43 had been selected as an inpatient group before the operation, 264 patients were discharged home 6 h after the operation and were the outpatient group, and 56 children had to be kept overnight because of complications that had occurred. We compared the haemorrhage rate in the outpatient and the inpatient groups. We found no increase in the postoperative haemorrhage rate in the outpatient group. No statistically significant correlations were found between the children's ages, indication for surgery, type of operation or intra-operative complications and the risk of postoperative haemorrhage. Only children who had haemorrhage in the recovery room were identified as a high risk subgroup for recurrent bleeding. On the basis of our findings we believe that tonsillectomy can be performed as an outpatient procedure regardless of age, indication for surgery, or type of procedure, as long as good recovery room supervision exists for 4 to 6 h.

Comparison of the incidence of cholesteatoma surgery before and after using ventilation tubes for secretory otitis media.

Inserting ventilation tubes has become, probably, the most common surgical operation performed on children in the free world. In our study, we attempted to examine whether the widely used procedure of inserting ventilation tubes in children with secretory otitis media is indeed justified in the long term. For this purpose, we have studied the influence of the procedure on the formation of cholesteatoma by comparing the incidence of cholesteatoma surgery before and after using ventilation tubes in our department. The data were divided into two periods. The first period included the number of operations in the 10 years (1961-1970) before ventilation tubes were used as a routine treatment for secretory otitis media in our department. The second period included the number of operations in the last 10 years (1989-1998) following the usage of ventilation tubes over 30 years. We found that the number of cholesteatoma operations has decreased, from 413 operations in the 10 years before ventilation tubes were used to 228 operations over the last 10 years. The number of operations per 10000 of the entire population has decreased from 20 operations to 6.6 operations after using ventilation tubes (P=0.0000001). We have shown that the incidence of surgery for cholesteatoma has been declining. Having analyzed the options that might cause this decline, we believe that using ventilation tubes in secretory otitis media might help to reduce the incidence of cholesteatoma surgery in the long term.

A comparison of partial inferior turbinectomy and cryosurgery for hypertrophic inferior turbinates.

A variety of surgical procedures are performed for treatment of hypertrophic inferior turbinates, but there is no completely effective therapy. We evaluated subjectively and objectively 52 patients who underwent one of two procedures: partial inferior turbinectomy (PIT) or cryosurgery of the inferior turbinates (CS). The results of PIT showed good functional results in 77 per cent of cases for long-term effectiveness. The results of CS showed that effectiveness was reduced from a 62 per cent success rate after one year to 35 per cent later, but CS was a simple procedure which was performed on an outpatient basis with no post-operative morbidity.

Acute bilateral total deafness complicating mumps.

While it is well known that mumps is a potential cause of deafness, it is not generally appreciated that it can produce total deafness. The damage is usually unilateral but bilateral disease has been recorded. A case is presented of severe bilateral hearing loss during a mumps epidemic in which, in spite of intensive conventional as well as lesser known therapy, no improvement occurred. In the absence of a successful therapeutic regime it is clearly advisable to intensify immunization in non-developed countries.

Hemifacial spasm associated with external carotid artery compression of the facial nerve.

We report a unique case of hemifacial spasm due to compression of the facial nerve by the main trunk of the external carotid artery within the parotid space. Decompression of the facial nerve as well as partial section of the proximal trunk of the nerve, caused the hemifacial spasm to disappear. Our case gives support to the theory that hemifacial spasm can be caused by pressure on the facial nerve along all its course and not only in its intra-cranial portion.

Comparison of the proteins of middle ear effusion with human mast cell proteins.

In order to clarify the role of mast cells in the aetiology of secretory otitis media (SOM), we compared the protein components of middle ear effusion (MEE) with human mast cells using acrylamide gradient gel electrophoresis and electrofocusing methods. This first direct comparison between the proteins of MEE and human mast cells has been made possible by a method developed in our laboratory for cultivation of human mast cells in tissue culture. On electrophoresis, we found that out of 12 bands of MEE proteins that were different from the serum, seven (58 per cent) had a similar electrophoretic migration rate (Rx) to mast cells. On electrofocusing, three of the four bands of MEE had a similar Rx to the mast cells. We have shown that proteins of mast cells and MEE had similar Rxs. Therefore, our study supports previous studies which suggests that mast cells play an important role in the aetiology of SOM.

Isolated extramedullary plasmacytoma of the true vocal fold.

We report a rare case of isolated extramedullary plasmacytoma (EMP) of the right true vocal fold in a 38-year-old male with a one-year history of hoarseness. Immunohistochemical staining of plasma cells in the tumour, showed over 90 per cent of them to be positive for kappa light chains. After two attempts at local surgical excision and recurrence within 10 months, the tumour was irradiated. Only seven reported cases of isolated EMP of the true vocal fold are reported in the literature. The therapeutic options are discussed.

Duration of antibacterial effectiveness of gentamicin ear drops in external otitis.

The recommendation of Anderson and Steele, for the use of ear drops four times a day, has not been changed since 1948. In order to re-evaluate the frequency of using ear drops, we examined the duration of the effectiveness of the antibacterial activity of gentamicin ear drops in external otitis. Seventeen patients (25 ears) with external otitis were studied. We took 18 samples from each ear at 0, 1, 2, 3, 6, 8, 10, 12 and 14 hours and measured the concentration of gentamicin on the wick and in the ear canal. We found that the concentration of gentamicin began to decrease only after 12 hours and a more significant decrease was detected after 14 hours of treatment. We have shown that the antibiotic used on the wick is effective for 12 hours. In conclusion, we recommend using ear drops twice a day on a wick as routine therapy for external otitis.

[Thyroid function disturbances in an infant following maternal topical use of polydine].

A male infant who had symptoms of transient sinus tachycardia and increased concentrations of blood total and free T4 is reported. The mother had used Polydine (P; povidone iodine) for vaginal douching during pregnancy and during the first few weeks after delivery, during which time the infant was fed mother's milk only. Follow-up showed transient elevation of TSH levels in the infant, but with no signs of hypothyroidism. 2 months after the mother stopped using P, the infant's functions had become normal. P should not be used in the perinatal period.

[Congenital hypothyroidism in the Jezreel Valley].

39 patients in the Jezreel Valley area with congenital hypothyroidism were studied during the years 1978-1991. The incidence of the disease was 1:3.085 births. The most common subgroup was peroxidase deficiency which was found in 12 (30.7%) of them, as compared to the 6% reported in the literature. The average age at diagnosis was 30 days, and the average age at the start of 1-thyroxin replacement therapy 48 days. 80% had clinical signs of hypothyroidism at the time of diagnosis. Average height was at the 25th centile, as compared to midparental height at the 40th centile. 15 (38%) of the children had psychomotor delay. This study reveals that despite the national thyroid function screening program which shortens the time to diagnosis and improves the clinical course of congenital hypothyroidism, 38% of these children have irreversible damage.

[Microalbuminuria and ischemic heart disease in noninsulin-dependent diabetes].

Prospective studies showed that hypersecretion of albumin in the urine of patients with type 2 diabetes mellitus is associated with high morbidity and mortality from cardiovascular disease and nephropathy. 65 type 2 diabetes from 6 family medicine practices were studied. Microalbuminuria was found in 37% and was significantly more common in men than in women (53% and 23%, respectively; p < 0.02). Uncontrolled blood glucose levels were also more common in men (p < 0.03). Using logistic regression with microalbuminuria as the dependent variable, a significant correlation was found with male gender, fasting blood glucose 155 mg/dl or more, and systolic blood pressure 159 mm Hg or higher. Among those with microalbuminuria, ischemic heart disease was significantly more common in those 65 years or older than in those younger (p = 0.02). This study strengthens the assumption that type 2 diabetics with microalbuminuria might be at greater risk for developing ischemic heart disease. Strict detection and control are recommended.

[Thyroid dysfunction and goiter among immigrants from Ethiopia].

1131 immigrants from Gonder, Ethiopia were surveyed a year after arrival in Israel. The overall prevalence of goiter was 46.1%; the lowest rates (6.7%) were in infants (aged 1-2 years) and the peak prevalence in males was 56.7% (in those aged 12-14 years) and in females, 77.7% (in those aged 35-40). A significant decrease in goiter prevalence was observed after the age of 60 for both men (7.2%) and women (35%). The prevalence of hypothyroidism was 1.1%, 2% in children and 0.2% in adults. That of hyperthyroidism was 1.7%, 0.8% in children and 2.4% in adults. The high prevalence of goiter and hyperthyroidism with low prevalence of hypothyroidism probably resulted from the combined effects of food goitrogens and iodine deficiency in Ethiopia, with the latter playing only a minor role. Neither factor was in effect after arrival in Israel. Genetic and hormonal factors may contribute to the low prevalence of both goiter and hypothyroidism in the adult males. In view of the high prevalence of hyperthyroidism, iodine enrichment is not recommended for Ethiopian immigrants.