A report on two siblings with vitamin D resistant rickets treated with 1 alpha-hydroxy-vitamin D3 until completion of the growth]

The treatment of vitamin D resistant rickets still raises much controversy. This report describes out experiences on 1 alpha OHD3 treatment in two siblings from childhood till completion of the growth. The treatment began from age 3 and 8 in these two patients respectively. The daily doses were necessary to maintain the healing and increased during the growth period so that the doses per body weight were virtually constant at 1 microgram/kg/day. Under this regimen, the improvement of rickets was recognized in the radiogram, and the lower leg deformity corrected. In one case the bone biopsy confirmed the improvement of disturbed calcification. The final height was 152.5 cm (-0.8 SD) and 149 cm (-1.4 SD) respectively suggesting the effectiveness of 1 alpha OHD3 on the growth promotion. Around the closure of growth plate, the regimen induced hypercalcemia. Thereafter the doses were reduced to one fourth or one fifth of those in the growth period.     

Relationships of site of infarction and history of previous infarction with short- and long-term prognosis after acute myocardial infarction in Japan.

We studied the outcome in 308 patients with acute myocardial infarction (MI) admitted to the coronary care unit of Kobe General Hospital. Short-term outcome (within 28 days after MI) and long-term outcome (more than 28 days) were examined with survival curves to find any relationship with a history of previous MI and with the site of the MI. In the short term, 38 of the 308 patients died of cardiac causes. The group with anterior MI tended to have higher mortality than the group of patients with inferior MI, and among patients without a previous MI, patients with anterior MI had significantly higher mortality (p = 0.01). In multivariate analysis by the logistic regression model, the site of the MI was found to be independently associated with the short-term outcome. In the long term, with a mean follow-up of 3.4 years, 23 of the 308 patients died of cardiac causes. Different sites of the MI did not result in different outcomes in patients with or without a previous MI. Of patients with anterior or inferior MI, those with a previous MI tended to have higher mortality, and of patients with an inferior MI, the difference was significant (p = 0.001). In multivariate analysis by the proportional hazards model, a history of MI was more predictive than the site of the MI. In conclusion, the site of the MI was associated more with the short-term outcome than with the long-term outcome, and a history of MI was associated more closely with the long-term outcome.     

Effect of FK-506 on xenografted human Graves' thyroid tissue in severe combined immunodeficient mice

OBJECTIVE We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenograft-ing, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-7). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS After 4–6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-7 were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.     

Fluid-fluid levels in cavernous hemangioma of soft tissue

Five cases of cavernous hemangioma with fluid-fluid levels on magnetic resonance imaging and/or computed tomography are reported. The signal characteristics were those of blood and histological analysis of the fluid-fluid levels showed that they were blood-filled cavities in the tumor. Although this finding itself is not specific, it may help in confirming the diagnosis of cavernous hemangioma.     

Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

The practice of breast self-examination results in the earlier detection and better clinical course of Japanese women with breast cancer

Using a questionnaire survey, we analyzed the relationship between the frequency of breast self-examination (BSE) and the clinical stage and course of breast cancer in Japanese patients. BSE had been performed monthly by only 5.4% of the patients (M group), occasionally by 35.4% (O group), and not at all by 59.2% (N group). There was a positive relationship between more frequent BSE and an earlier clinical stage, the percentages of Tis/stage 0 and I for the M, O, and N groups being 83%, 44%, and 36%, respectively (P<0.05). The mean maximum tumor diameters for the three groups were 1.7cm, 2.5cm, and 3.0cm, respectively. The tumor size in the M and O groups was significantly smaller than that in the N group atP<0.01 andP<0.05, respectively. The percentages of patients in the M, O, and N groups who underwent breast-conserving therapy were 42%, 11%, and 19%, respectively, with patients who had performed monthly, BSE more frequently undergoing breast-conserving therapy (P<0.05). At a median follow-up time of 34 months, 0%, 3.8%, and 7.6% of the patients from the M, O, and N groups, respectively, had died of breast cancer, the overall survival curve of the M group being significantly better than that of the N group (P<0.01). This retrospective study suggests the positive correlation of BSE frequency with earlier detection, and a more favorable clinical course in Japanese breast cancer patients.     

3D kinematic analysis of the acromioclavicular joint during arm abduction using vertically open MRI.

Many researchers have evaluated the motions of the shoulder girdle, especially scapular and humeral motion. However, few reports exist that describe motions of the acromioclavicular joint. The purpose of the present study was to analyze the 3D kinematics of the acromioclavicular joint during arm abduction using 3D MR images obtained by a vertically open MRI. Fourteen shoulders of seven volunteers were examined in seven static positions from 0 degrees to the maximum abduction in a seated position. 3D surface models of the clavicle and scapula were created, and the movements of the acromioclavicular joint from 0 degrees to each position were calculated using the volume-based registration technique. From these calculations, the translations were evaluated and the rotational motions were analyzed using the concept of the screw axis. In the anteroposterior direction, the clavicle translated most posteriorly (-1.9 +/- 1.3 mm) at 90 degrees of abduction and most anteriorly (1.6 +/- 2.7 mm) at maximum abduction. In the superoinferior direction, the clavicle translated slightly superiorly (0.9 +/- 1.9 mm). When analyzing relative motion of the scapula with respect to the clavicle, the scapula generally rotated about a specific screw axis passing through the insertions of both the acromioclavicular and the coracoclavicular ligaments on the coracoid process. The average rotation was 34.9 +/- 8.4 degrees.     

A case of congenital supratentorial tumor: Atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor?

Two embryonal CNS tumors, atypical teratoid/rabdoid tumor (AT/RT) and primitive neuroectodermal tumor (PNET), may be confused with each other and misdiagnosed. Here we report an infant with a congenital supratentorial tumor, which was detected by fetal MRI at 37 weeks gestation. On routine histological examination, the tumor was composed mainly of small undifferentiated cells, among which many rhabdoid cells and occasional sickle‐shaped embracing cells were observed. No mesenchymal or epithelial areas were evident. Our impression was that the tumor was an atypical example of AT/RT. Immunohistochemically, almost all the tumor cells were strongly positive for vimentin. However, epithelial membrane antigen was notably negative, and most of the tumor cell nuclei were clearly positive for INI1. In addition, many tumor cells were positive for neurofilament protein. There were also occasional small areas containing many tumor cells positive for glial fibrillary acidic protein. Finally, a diagnosis of PNET, with a rhabdoid phenotype and expression of neuronal and glial markers, was made. In the present case, application of INI1 immunostaining was very helpful for distinguishing PNET from AT/RT.