Three patients with middle-age-onset hemochromatosis caused by novel mutations in the hemojuvelin gene

Hemochromatosis is a genetically heterogeneous condition. Mutations in the recently described hemojuvelin gene were found in patients with juvenile hemochromatosis, who usually manifest clinical signs of iron overload, including cardiomyopathy and hypogonadism, in their teens and early 20s. In this report, we describe three Japanese patients who showed typical clinical and hepatic histological damage compatible with hemochromatosis at around 50 years of age. Genetic analyses showed that all three patients carried mutations in the hemojuvelin gene. The first patient was homozygous for a novel mutation (745G > C [D249H]), and the second and third patients from the same family were homozygous for another novel mutation (934C > T [Q312X]). No mutations in their HFE, hepcidin, transferrin receptor 2, or ferroportin genes were found. One patient had chronic infection with Helicobacter pylori. The age at initial presentation of hemojuvelin-hemochromatosis occurs over a wider range than previously described.     

Abnormal baroreceptor-mediated vasopressin release as possible marker in early diagnosis of multiple system atrophy

BACKGROUND: Although autonomic failure (AF) is a critical symptom of multiple system atrophy (MSA), it may not appear until late in the disease process. OBJECTIVES: To clarify whether a detailed investigation of the autonomic nervous system in patients with MSA without overt AF demonstrates latent lesions of central cardiovascular control circuits and facilitates the early diagnosis of MSA. METHODS: Autonomic function tests, and plasma noradrenaline (NA) and vasopressin (AVP) responses to head-up tilt (HUT), were studied in 12 patients with MSA with AF (probable MSA), 12 with MSA without overt AF (possible MSA), and 24 controls. RESULTS: Abnormalities of cardiovascular autonomic function tests were prominent in the first group but mild in the second. Plasma NA and AVP increments upon HUT differed significantly among all three groups. CONCLUSIONS: These results indicate that probable MSA involves diffuse degeneration of central cardiovascular control circuits. On the other hand, the discrepancies in possible MSA suggest a vulnerability of the noradrenergic (A1) neurones of the caudal ventrolateral medulla that are involved in AVP secretion. This finding also suggests that AVP increment may be useful as a diagnostic tool in the early stages of MSA.     

Incidence and clinical features of Giardia lamblia

To determine the incidence and clinical features of Giardia lamblia infection, we studied 1790 patients at Kochi Medical School Hospital from April 1998 to July 2001. Fecal samples were examined microscopically by the direct smear method, direct immunofluorescent assay and by Kohn's one-step staining for G. lamblia cysts. Cysts of G. lamblia were found in 17 of 1,790(0.95%) stool samples, indicating that G. lamblia infection is not rare in Kochi. The most characteristic feature was that G. lamblia-positive cases were more frequent in the advanced age group(41-79 years old) and most of the subjects (except 2 cases) with G. lamblia had no history of traveling overseas. Four subjects had symptoms related to G. lamblia infection. Thus, more attention should be given to parasitic infections in laboratory stool examinations in order to detect cyst carriers as potential sources of infection.     

Adrenomedullin concentrations in early 2nd-trimester amniotic fluid: relation to preterm delivery and fetal growth at birth

OBJECTIVE: The purpose of this study was to evaluate whether adrenomedullin concentrations in the early 2nd-trimester amniotic fluid predict preterm delivery or fetal growth at birth. METHODS: The adrenomedullin concentrations in early 2nd-trimester amniotic fluid were measured in 70 pregnancies with term delivery and in 3 pregnancies with preterm delivery. Total and free adrenomedullin concentrations were measured from early 2nd-trimester amniotic fluid samples using an immunoradiometric assay. RESULTS: The amniotic fluid total adrenomedullin concentrations in women with preterm delivery were significantly higher (129.7 +/- 19.6 fmol/ml) than those in women with term delivery (92.5 +/- 28.2 fmol/ml; p < 0.05). There were no significant differences for amniotic fluid free adrenomedullin concentrations and free/total adrenomedullin ratios between the two groups. Total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid showed an inverse correlation both with birth weight (r = 0.27, p < 0.05, and r = 0.21, p < 0.05) and height (r = 0.30, p < 0.05, and r = 0.28, p < 0.05). There were no correlations between placental weight and total or free adrenomedullin concentrations in the early 2nd-trimester amniotic fluid. CONCLUSIONS: These results suggest that adrenomedullin concentrations in the early 2nd-trimester amniotic fluid might be related to further in utero fetal growth and that high levels of adrenomedullin in the early 2nd-trimester amniotic fluid may be involved in the occurrence of preterm delivery.     

Three-dimensional sonographic volume measurement of the fetal spleen

AIM: The objective of this longitudinal study was to evaluate the growth of the fetal spleen in normal pregnancies, using three-dimensional ultrasound. METHODS: Three-dimensional sonographic examinations were performed on 14 appropriate-for-gestational-age fetuses. Fetal splenic volume was measured every 2-3 weeks after 20 weeks of gestational age until delivery. RESULTS: Curvilinear relationships were found between the gestational age and splenic volume (R(2) = 80.2%, P < 0.0001), and normal ranges of splenic volume measurements for estimating the growth of the fetal spleen during normal pregnancy were generated. We found that the splenic volume calculation based on the equation for the volume of the ellipsoid by conventional two-dimensional ultrasound in previous investigations is about twice as large as that using three-dimensional ultrasound in our study, whereas the present data described in this study is quite comparable with previous data from an autopsy series. CONCLUSION: Our findings suggest that the standard curve for the fetal splenic volume using three-dimensional ultrasound provides a superior means for evaluating the normal splenic growth in the fetus and for identifying splenic abnormalities in utero. However, the data and its interpretation in our study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size would be needed to confirm these findings.     

Effects of novel immunosuppressant FK 506 in acute experimental allergic encephalomyelitis]

Experimental allergic encephalomyelitis (EAE) is a T cell-mediated autoimmune disease. It is widely used as an animal model of multiple sclerosis (MS). We studied the prophylactic effects of FK 506 electrophysiologically and immunohistochemically in acute EAE. Female Lewis rats were sensitized with guinea pig spinal cord in complete Freund's adjuvant. FK 506 suspended in distilled water was orally administered at 1.0, 3.2, 5.0 or 10.0 mg/kg per day for 12 successive days starting from the day of sensitization. A placebo was used as the control. Administration of FK 506 at doses of 3.2 mg/kg per day and over significantly delayed the onset of clinical signs. However, the FK 506 group showed a relapse or a chronic state following the onset of EAE. We made a time course recording of cortical somatosensory evoked potential (cortical SEP: P 15). P 15 latency in the placebo group was significantly delayed in accordance with the clinical signs and showed immediate improvement upon recovery. Prolongation of P 15 latency in the FK 506 group also occurred concomitantly with the clinical signs, but the delay continued after the loss of symptoms as well. After the onset of EAE, the infiltrating lymphocyte subset was examined by the avidin-biotin peroxidase complex (ABC) method in the lumbar spinal cord. In the placebo group, the number of OX3+ (Ia) cells and the W 3 25+: OX8+ (helper/inducer T: suppressor/cytotoxic T) ratio clearly reflected the development and remission of EAE. In the FK 506 group, however, increases in OX8+ lymphocytes were observed irrespective of clinical sign fluctuation, and there were corresponding decreases in the W 3/25+: OX8+ ratio.(ABSTRACT TRUNCATED AT 250 WORDS)     

Three-dimensional sonographic features of a fetus with Wolf-Hirschhorn syndrome

We present a case of fetal Wolf-Hirschhorn syndrome diagnosed by conventional two-dimensional and three-dimensional ultrasonography. Conventional two-dimensional ultrasonography revealed a diaphragmatic hernia, nuchal edema, and suspected hypospadias. Three-dimensional ultrasonography clearly showed a flattening of the face, a high forehead, a broad nasal bridge continuing to the forehead, exophthalmos, and micrognathia (resembling the appearance of a Greek warrior helmet), but conventional two-dimensional ultrasonography did not depict these findings. Prenatal chromosomal analysis confirmed the diagnosis of Wolf-Hirschhorn syndrome [46XY, del(4)(p15.2)]. Here we demonstrate how three-dimensional ultrasonography provided a novel visual depiction of the facial dysmorphism, which helped substantially in prenatal counseling.     

Left-sided hepatic hydrothorax diagnosed by contrast-enhanced ultrasonography with intraperitoneal injection of Levovist

A 62-year-old Japanese woman was admitted to our hospital with dyspnea. Chest X-ray revealed massive pleural effusion on the left side. Contrast-enhanced ultrasonography using Levovist was performed to confirm the transdiaphragmatic passage of ascitic fluid into the pleural cavity. After injection of Levovist into the peritoneal cavity, an enhanced pulsative flow into the pleural cavity was detected. This is the first report of hepatic hydrothorax diagnosed by contrast-enhanced ultrasonography. This method is safe and useful for the diagnosis of hepatic hydrothorax, and it allows observation of the real-time movement of ascitic fluid from the peritoneal cavity to the pleural space and detection of the site of the peritoneopleural communication.     

A Japanese version of the Rosenberg Self-Esteem Scale: translation and equivalence assessment

OBJECTIVE: A Japanese version of the Rosenberg Self-Esteem Scale (RSES) was developed through the forward-backward translation procedure. METHODS: Married couples consisting of a native English speaker and a native Japanese speaker acted as translators to enhance the representativeness of language in the target population. Multiple translations were produced, and a panel of reviewers identified problems in conceptual and semantic equivalence between the original scale and the translated version. The Japanese version was altered accordingly with reference to alternate Japanese forms from the original English to Japanese translations. The altered translation was again retranslated into English, and problematic differences were checked. This forward-backward process was repeated until satisfactory agreement had been attained. The RSES was administered to 222 native English speakers, and the developed Japanese version (RSES-J) was administered to 1320 native Japanese speakers. RESULTS: Factor analysis revealed nearly identical factor structure and structural coefficients of the items between two sets of data. Target rotation confirmed the factorial agreement of the two scales in different cultural groups. High Cronbach's alpha coefficients supported the reliability of test scores on both versions. CONCLUSION: The equivalence between the RSES and the RSES-J was supported in this study. It is suggested that the RSES and the RSES-J are potential tools for comparative cross-cultural studies.