Bone disorder in long-term survival after gastrectomy with reference to bone mineral content

To investigate post-gastrectomy metabolic bone disorder, the radial bone mineral content (BMC) was measured with 125I-photon absorptiometry in 131 long-term survivors, the postoperative periods ranged 3 to 30 years. Sixty-eight patients (52 per cent) showed abnormally low BMC levels compared with healthy controls. The 43 patients with total gastrectomy manifested a higher incidence of decreased BMC levels than did the other 88 patients with partial gastrectomy. In females, patients subjected to the Billroth II procedure manifested low BMC values. The extent of the decline in BMC was much higher in females than in males, and higher in totally gastrectomized patients than in partial gastrectomy group. At more than 10 years postoperatively many patients manifested markedly low BMC levels; in totally gastrectomized patients this finding was made at less than 5 years postoperatively. A significant correlation was found between the extent of the decreased BMC levels and the postoperative periods. Of the patients with decreased BMC values, 30 per cent of them gave histories of osseous symptom after gastrectomy, however, 70 per cent of patients were asymptomatic. Based on the results, in long-term survival treated by total or partial gastrectomy, many patients present an osteopenic status, however, the number of those with clinically manifested bone disease such as osteomalacia may be low.     

Identification of a cytokine-induced antiapoptotic molecule anamorsin essential for definitive hematopoiesis

Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to known apoptosis regulatory molecules such as Bcl-2 family, caspase family, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin-/- mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin-/- erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin-/- mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokines.     

Prognostic importance of neuroendocrine differentiation in Japanese breast cancer patients

Purpose

To evaluate the frequency and prognostic importance of neuroendocrine differentiation (NED) in Japanese breast cancer patients.

Methods

We used standard immunohistochemical techniques to examine 50 patients who underwent resection of breast cancer between 1988 and 1993 at the Department of Surgery II, Nagoya University Hospital, for NED, defined as positive reactivity for four markers: neuron-specific enolase (NSE), synaptophysin, CD57, and chromogranin A (CGA). Neuroendocrine differentiation was defined by the presence of at least one marker including CGA, CD57, and synaptophysin, or at least two markers when one was positive for NSE.

Results

Neuroendocrine differentiation was found in 13 (26%) of the 50 patients examined. There were no significant differences in the distribution of patients with positive or negative NED in terms of age, menopausal status, tumor size, lymph node metastasis, histological grade, ER, PgR, and HER2. We calculated the cumulative survival rates of patient groups according to NED status, and found no significant difference in overall or disease-free survival between patients with and those without NED.

Conclusion

Neuroendocrine differentiation was identified in a subset (26%) of Japanese breast cancer patients, but this appeared to have no relationship with established prognostic factors or patient outcome.     

An electric field induced in the retina and brain at threshold magnetic flux density causing magnetophosphenes

For magnetic field exposures at extremely low frequencies, the electrostimulatory response with the lowest threshold is the magnetophosphene, a response that corresponds to an adult exposed to a 20 Hz magnetic field of nominally 8.14 mT. In the IEEE standard C95.6 (2002), the corresponding in situ field in the retinal locus of an adult-sized ellipsoidal was calculated to be 53 mV m(-1). However, the associated dose in the retina and brain at a high level of resolution in anatomically correct human models is incompletely characterized. Furthermore, the dose maxima in tissue computed with voxel human models are prone to staircasing errors, particularly for the low-frequency dosimetry. In the analyses presented in this paper, analytical and quasi-static finite-difference time-domain (FDTD) solutions were first compared for a three-layer sphere exposed to a uniform 50 Hz magnetic field. Staircasing errors in the FDTD results were observed at the tissue interface, and were greatest at the skin-air boundary. The 99th percentile value was within 3% of the analytic maximum, depending on model resolution, and thus may be considered a close approximation of the analytic maximum. For the adult anatomical model, TARO, exposed to a uniform magnetic field, the differences in the 99th percentile value of in situ electric fields for 2 mm and 1 mm voxel models were at most several per cent. For various human models exposed at the magnetophosphene threshold at three orthogonal field orientations, the in situ electric field in the brain was between 10% and 70% greater than the analytical IEEE threshold of 53 mV m(-1), and in the retina was lower by roughly 50% for two horizontal orientations (anterior-posterior and lateral), and greater by about 15% for a vertically oriented field. Considering a reduction factor or safety factors of several folds applied to electrostimulatory thresholds, the 99th percentile dose to a tissue calculated with voxel human models may be used as an estimate of the tissue's maximum dose.     

21-Gene expression profile assay on core needle biopsies predicts responses to neoadjuvant endocrine therapy in breast cancer patients

This study examined postmenopausal estrogen receptor-positive breast cancer patients who received prospective neoadjuvant endocrine therapy (NAET) with tamoxifen or anastrozole to determine if the 21-gene recurrence score (RS) predicts NAET responses. RS scores were determined from pretreatment core biopsy specimens. Although half of the specimens yielded insufficient RNA, the remaining samples were highly representative. Patients with a low RS tended to respond better than those with an intermediate or high RS (n = 43). Response rates by RS were similar between the tamoxifen and anastrozole groups. Patients with a low RS tended to have better relapse-free survival (RFS) than those with an intermediate or high RS (5y-RFS; 100% vs. 84% and 73%, respectively). These results suggest that RS predicts responses to NAET with tamoxifen or anastrozole. Because this pilot study examined a small sample size, these results should be validated in larger studies.     

Removal of blood group A/B antigen in organs by ex vivo and in vivo administration of endo-beta-galactosidase (ABase) for ABO-incompatible transplantation

BACKGROUND: ABO incompatibility in organ transplantation is still a high risk factor for antibody-mediated rejection, despite the progress in effective treatments. We have explored the possibility of using the enzyme to remove the blood type A/B antigen in organs. METHODS: Recombinant endo-beta-galactosidase (ABase), which releases A/B antigen, was produced in E. coli BL-21. Human A/B red blood cells (RBC) were digested with ABase, and subjected to flow cytometric analysis after incubation with human sera. Purified recombinant ABase was intravenously administered to a baboon. Biopsies were taken from kidney and liver before and 1, 4 and 24 h after in vivo administration. Excised baboon kidneys were perfused with cold UW solution+/-purified recombinant ABase and preserved at 4 degrees C. Biopsies were taken before and 1 and 4 h after ex vivo perfusion. The change in A/B antigen expression was analyzed by immunohistochemical study. RESULTS: ABase removed 82% of A antigen and 95% of B antigen in human A/B red blood cells, and suppressed anti-A/B antibody binding and complement activation effectively. ABase was also found to remain active at 4 degrees C. In vivo infusion of ABase into a blood type A baboon demonstrated a marked reduction of A antigen expression in the glomeruli of kidney (85% at 1 h, 9% at 4 h and 13% at 24 h) and the sinusoids of liver (47% at 1 h, 1% at 4 h and 3% at 24 h) without serious adverse effects. After ex vivo perfusion and cold storage of excised baboon kidney (blood type B) with ABase, the expression levels of B antigen in glomeruli were reduced to 49% at 1 h and 6% at 4 h. CONCLUSIONS: This alternative approach might be useful for minimizing antibody removal and anti-B cell immunosuppression as an adjuvant therapy in ABO-incompatible kidney, liver and possibly heart transplantation.     

Evaluation of the hepatic blood flow increase in the cases with liver metastasis and prediction of patent cases of liver metastasis using dynamic CT

BACKGROUND/AIMS: This study aimed to measure hepatic blood flow increase in cases with liver metastasis and to diagnose minimal metastasis which cannot be visualized by imaging modalities. METHODOLOGY: The evaluation of hepatic arterial flow increase was performed quantitatively by newly devised index ELR (early-late-ratio) using dynamic computed tomographic (CT) scanning with contrast media. RESULTS: The ratio of the cases with liver metastasis was significantly higher than that of normal liver control. It was revealed that the ratio was correlated with microvessel proliferation in the liver around the metastasis by examination of surgical specimen. Moreover, the patent group which proved to have metastasis within 6 months also had a significant higher ELR value. CONCLUSIONS: ELR not only was useful to evaluate hepatic blood flow increase in the cases with liver metastasis but also could be applied to predict the patent group with micrometastasis.     

Auditory agnosia due to long-term severe hydrocephalus caused by spina bifida - specific auditory pathway versus nonspecific auditory pathway

A 27-year-old female showed auditory agnosia after long-term severe hydrocephalus due to congenital spina bifida. After years of hydrocephalus, she gradually suffered from hearing loss in her right ear at 19 years of age, followed by her left ear. During the time when she retained some ability to hear, she experienced severe difficulty in distinguishing verbal, environmental, and musical instrumental sounds. However, her auditory brainstem response and distortion product otoacoustic emissions were largely intact in the left ear. Her bilateral auditory cortices were preserved, as shown by neuroimaging, whereas her auditory radiations were severely damaged owing to progressive hydrocephalus. Although she had a complete bilateral hearing loss, she felt great pleasure when exposed to music. After years of self-training to read lips, she regained fluent ability to communicate. Clinical manifestations of this patient indicate that auditory agnosia can occur after long-term hydrocephalus due to spina bifida; the secondary auditory pathway may play a role in both auditory perception and hearing rehabilitation.     

Parameter Predicting the Recurrence of Adhesive Small Bowel Obstruction in Patients Managed with a Long Tube

Introduction Some of our patients showed a recurrence of adhesive small bowel obstruction (ASBO) with nonoperative management. The aim of this study was to evaluate the parameters predicting the recurrence of ASBO in patients managed with a long tube. Methods Of 234 patients with ASBO admitted from April 1998 to September 2002, a total of 91 who recovered with nonoperative management after long tube placement were enrolled in this retrospective clinical study. We divided them into two groups for follow-up: the recurrence group and the no-recurrence group. We compared baseline characteristics, the number of previous ASBO admissions, the number of abdominal operations, the interval from the onset of symptoms to long-tube insertion, the duration of long-tube placement, the type of the contrasted intestine through the long tube, the location of the long-tube tip, and the drainage volume through the long tube between the two groups. We then examined the cumulative recurrence rate. Results A significant difference was found in the number of previous ASBO admissions, the duration of long-tube placement (77 hours vs. 43 hours), the contrasted intestine through the long tube, and the location of the long-tube tip. By multivariate analysis, the duration of long-tube placement was an independent parameter predicting the recurrence of ASBO. Conclusions These results suggest that the duration of long-tube placement might serve as a parameter for predicting recurrence of ASBO in patients managed with a long tube.