Final height of Japanese patients with X-linked hypophosphatemic rickets: effect of vitamin D and phosphate therapy.

X-linked hypophosphatemic rickets (XLH) is one of the most common causes of rickets in infancy and childhood. Combination therapy of vitamin D and phosphate is generally used for patients with XLH. Effect of treatment of vitamin D and phosphate during childhood on final height of XLH has to be elucidated in Japanese. There have been only three Caucasian studies on final height of XLH with treatment since childhood. Purpose of this study is to report adult height and therapeutic effect of 22 Japanese participants (5 males, 17 females) with XLH who were treated with phosphate (33-200 mg/kg/day as phosphorus divided into 3 or 4 doses) and vitamin D (vitamin D2 or 1alpha-hydroxyvitamin D3) for more than five years and evaluate effect of the treatment on the final height retrospectively. Final height (FHt) for all participants was -1.69+/-11.11 SD. FHt (-1.69+/-1.11 SD) was significantly higher than height at the initiation of treatment (-2.38+/-0.88 SD) for all participants (P<0.01). In conclusion, combination therapy of vitamin D and phosphate improved final height of Japanese patients with XLH as is similar to previous Caucasian studies.

Use of bone turnover marker, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer.

BACKGROUND: We investigated whether a new marker of bone turnover, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis. METHODS: In all, 58 patients with prostate cancer (25 with bone metastasis and 33 without bone metastasis) and 52 patients with benign prostate hypertrophy who were treated between June 1994-August 1997 were included in this study. All patients were newly diagnosed. RESULTS: Serum ICTP levels in patients with prostate cancer with bone metastasis were significantly higher than those in patients with prostate cancer without bone metastasis (P<0.0001) or with benign prostate hypertrophy (P<0.0001). No significant differences were observed in serum ICTP levels between patients with prostate cancer without bone metastasis and those with benign prostate hypertrophy. Serum ICTP levels correlated significantly with Soloway's grading system for bone scans. Serum ICTP levels in patients with bone metastasis showed a significant downward trend in response to hormonal treatment. CONCLUSIONS: The determination of serum ICTP levels is useful in the assessment of bone metastasis and in monitoring the response of bone metastasis to treatment to prostate cancer.

High ratios of free to total insulin-like growth factor-I in early infancy.

Insulin-like growth factor-I (IGF-I) is a major effector of somatic growth and metabolism. In normal, nonpregnant plasma, most of the IGF-I is complexed to specific IGF-binding proteins (IGFBPs), particularly IGFBP-3; only a minor fraction of plasma IGF-I exists in a free form. Recently, we have reported that free IGF-I levels, as measured using a new immunoradiometric assay, are relatively high in maternal plasma during pregnancy because of increased IGFBP-3 proteolytic activity. These high free IGF-I levels are physiologically important for the growth of maternal tissues such as uterus and placenta, which are related to the fetal growth. Growth during early infancy may be a continuation of fetal growth. In the present study, we have analyzed free and total plasma IGF-I and IGFBP-3 proteolytic activity in early infancy. Although the levels of free and total IGF-I were not significantly different in early infancy as compared with prepubertal periods, the ratio of free to total IGF-I (mean = 2.04%) was relatively increased and was similar to the ratio in pregnancy plasma (1.86%). However, unlike in maternal plasma, the high ratios were not totally caused by increased IGFBP-3 proteolytic activity. Our results suggest that there may be an increased conversion of plasma IGF-I to a free form in early infancy. The resultant increase in IGF-I bioavailability could contribute to the rapid somatic growth in early infancy.

HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia) associated with del(10)(p13).

A combination of hypoparathyroidism, sensorineural deafness, and renal dysplasia has been considered to be a new syndrome inherited in an autosomal dominant fashion; we name the condition "HDR syndrome." We describe a Japanese girl who has HDR syndrome associated with de novo del(10)(p13). The chromosome deletion suggests that the putative gene(s) responsible for HDR syndrome is located at a 10pter-->p13 region.

Incomplete androgen insensitivity associated with a thermolabile androgen receptor.

One infant and a cousin with incomplete androgen insensitivity syndrome were reported. The familial pedigree showed that the disorder was inherited in three generations in X-linked recessive fashion. An androgen binding study of cultured genital skin fibroblast from patients showed normal maximum binding capacity and a normal apparent dissociation constant. Heat stability assay showed binding decreased to less than 30% at 41 degrees C compared with the amount at 30 degrees C, indicating that the androgen receptor was thermolabile.

Japanese type of spondylo-metaphyseal dysplasia.

Five members of a Japanese family with a new form of spondylo-metaphyseal dysplasia (SMD) are reported. Another member was also probably affected. The disease was characterised by severe coxa vara, moderately severe metaphyseal changes of the long bones of the lower limbs, mild changes in the long bones of the upper limbs and grossly normal short tubular bones. Platyspondyly, present in the boys, was less marked in their father, whereas two affected aunts had normally shaped vertebral bodies.

Malignant thymoma in a patient with growth hormone deficiency during growth hormone therapy.

Malignant thymoma was found in an 8-year-old Japanese boy with growth hormone (GH) deficiency who had received GH therapy for 3 years and 5 months. There may be a possible relationship between the occurrence of malignant thymoma and GH therapy.

Unmasking of latent hypoparathyroidism in a child with partial DiGeorge syndrome by ethylenediaminetetraacetic acid infusion.

DiGeorge syndrome is a rare congenital anomaly with a wide range of clinical manifestations. This syndrome is usually associated with hypocalcaemia resulting from primary hypoparathyroidism. We report here a case of an 8-year-old boy with partial DiGeorge syndrome who presented initially with neonatal hypocalcaemia, but was subsequently normocalcaemic. Latent hypoparathyroidism was unmasked by a diagnostic EDTA infusion resulting in hypocalcaemia without a parathyroid hormone response. We propose that EDTA infusions can be useful in the diagnosis of latent hypoparathyroidism in children.

Spontaneous growth hormone secretion in healthy prepubertal children of normal stature.

To evaluate the dynamics of growth hormone (GH) secretion in healthy prepubertal children of normal stature, we determined spontaneous GH secretion by measuring GH every 30 min in 21 Japanese subjects, age: 5.4 +/- 2.3 (1.6-10.6) years; height: -1.4 +/- 1.1 (-1.98-1.77) SD. The 24-h mean GH concentration was 4.8 +/- 1.5 ng/ml. The 24-h mean GH was similar in boys and girls (mean +/- SD: 4.8 +/- 1.7 vs 4.7 +/- 1.1 ng/ml). No correlation was found between chronological age and the 24-h mean GH. The 24-h mean GH was closely correlated with GH pulse amplitude (r = 0.94; P less than 0.001), but not with the number of GH pulses. The 24-h mean GH was also highly correlated with 3-h mean GH after sleep and 3-h peak GH after sleep (r = 0.86; P less than 0.001 and r = 0.72; P less than 0.001, respectively). Our data suggest that in healthy prepubertal children of normal stature, (1) spontaneous GH secretion is independent of sex and age, (2) the amount of spontaneous GH secretion is controlled by pulse amplitude, not by number of pulses. (3) 3-h mean GH and 3-h peak GH after sleep might represent 24-h total spontaneous GH secretion.

Different effects of pemphigus antibody and plasmin on the distribution of keratin intermediate filaments and desmoplakins between cultured oral and epidermal keratinocytes.

In order to clarify the molecular mechanism of blister formation in oral mucosa in pemphigus vulgaris (PV) comparing with that in epidermis, we analyzed the effects of PV serum on the distribution of keratin intermediate filaments (KIFs) and desmoplakins in oral as well as epidermal cultured keratinocytes by immunofluorescence microscopy using anti-keratin and anti-desmoplakin I/II monoclonal antibodies. After incubation with PV serum for 96 h at 37 degrees C, clusters of anti-keratin positive dots were formed around the nucleus in some of the keratinocytes from normal gingiva and soft palate but not in keratinocytes from tongue and skin, and desmoplakins also changed their distribution from linear arrangement at cell-cell contacts to clusters of dots around the nucleus in gingiva but not in epidermal keratinocytes. The dotted structures similar to those induced by pemphigus serum were formed also by incubation with human plasmin in gingival keratinocytes. However, no dot-formation of keratins was induced in these cells after incubation with trypsin. Furthermore, in epidermal keratinocytes, no keratin-dot formation was observed even after incubation with plasmin or trypsin. These results suggest that the dotted structures of KIFs caused by PV serum and plasmin might be a feature characteristic for the response of oral keratinocytes to PV serum and that there are some distinct differences in susceptibility to, and mode of, bulla formation between oral epithelium and epidermis.

Partial growth hormone deficiency with pituitary stalk transection.

Partial growth hormone deficiency was found in a 13-year-old Japanese boy who was born by breech delivery. Magnetic resonance imaging showed transection of the pituitary stalk and the presence of an ectopic posterior lobe located at the proximal stump of the transected stalk.

Triphasic AVP secretion in encephalopathy.

A patient with encephalopathy developed triphasic changes in the clinical course, starting with diabetes insipidus (DI), then the syndrome of inappropriate ADH secretion (SIADH), and followed by the final phase of DI. The clinical course of encephalopathy was very rapid. The patient lost consciousness completely within only one day after the onset. During the early phase, he lapsed into a condition of "brain death". We could not identify the etiology of the encephalopathy. The triphasic change referred to above is similar to previous reports of cats model after stereotactic destruction of the supraopticohypophyseal tract. We speculate that our case may have been associated with neurohypophyseal dysfunction caused by supraopticohypophyseal tract damage.

Evaluation of flow electromyography in patients with benign prostatic hyperplasia.

Combined uroflowmetry and external sphincter electromyography studies were done both preoperatively and postoperatively in patients with benign prostatic hyperplasia. In 56 patients preoperative electromyography during voiding showed silent or markedly suppressed activity in 41 patients (73.2%), while the remaining 15 patients (27.8%) revealed active electromyography. In the postoperative studies, 12 patients revealed active electromyography even after the release of obstruction. The urine flow rate following operation was not drastically improved in the active electromyography group compared to the silent electromyography group. We suppose that long-term urethral obstruction with prostatic adenoma could influence the function of relaxation of the external sphincter muscle in some patients with benign prostatic hyperplasia.