Luxatio erecta (inferior dislocation of the shoulder): a report of 5 cases and a review of the literature

Luxatio erecta (inferior dislocation of the glenohumeral joint) is an unusual type of shoulder dislocation. The authors present 5 new cases of luxatio erecta. All cases were hyperabduction injuries. In all cases, closed reduction was accomplished by a traction-countertraction maneuver. Three of the 5 subjects sustained concomitant fractures of the greater tuberosity. One underwent open reduction and internal fixation of the greater tuberosity. One suffered axillary nerve injuries. No vascular injuries were noted in our series. The mechanism of the injury is discussed.     

Cross-sectional area of a bone-patellar tendon-bone graft for anterior cruciate ligament reconstruction

The cross-sectional area of the 10-mm wide patellar tendon graft was measured in 50 consecutive patients (31 males and 19 females) who underwent isolated anterior cruciate ligament (ACL) reconstruction and the relationship between the graft size and various factors such as physical characteristics was assessed. The effect of cross-sectional area of the implanted graft on postoperative stability of the reconstructed knee also was examined. Mean patient age at surgery was 22.3 years (range: 14-40 years). The cross-sectional area was measured using an instrumented area micrometer intraoperatively, and correlations between the measured value and various factors such as age, gender, height, body weight, and bony geometry were examined. Follow-up was performed 24 months postoperatively. The average cross-sectional graft area was 33.4 mm2. The measured cross-sectional area was larger in male patients and correlated with physical characteristics such as height, body weight, and femoral condyle width. No significant correlation between the size of the graft and postoperative stability was observed.     

Activation of Leukocyte Function-Associated Antigen-1 on Adult T-cell Leukemia Cells

Adult T cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium and integrins are tightly regulated by several stimuli such as inflammatory chemokines. We have investigated the mechanisms of extravasation of ATL cells and reported the novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes, and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of PI 3-kinases in an autocrine manner. Furthermore, the cell surface heparan sulfate proteoglycan particularly on ATL cells is involved in chemokine-dependent autocrine stimulation of inte-grin-triggering by immobilizing the chemokine on them. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.     

Intrathecal lithium reduces neuropathic pain responses in a rat model of peripheral neuropathy

We tested the ability of lithium (Li(+)) to block heat hyperalgesia, cold allodynia, mechanical allodynia and mechanical hyperalgesia in rats experimentally subjected to painful peripheral neuropathy. Chronic constrictive injury (CCI) to the sciatic nerve induced persistent hyperalgesia and allodynia. Intrathecal injection of Li(+) (2.5-40 micromol) into the region of lumbar enlargement dose-dependently reduced heat hyperalgesia, cold allodynia and mechanical allodynia for 2-6 h after injection, but had no effect on mechanical hyperalgesia. Li(+) had no significant effect on responses from control and sham-operated animals. Intrathecal injection of myo-inositol (2.5 mg) significantly reversed both the anti-hyperalgesic and anti-allodynic effect of Li(+). These findings suggest that intrathecal Li(+) suppresses neuropathic pain response in CCI rats through the intracellular phosphatidylinositol (PI) second messenger system in spinal cord neurons. Lithium (Li(+)) has already found widespread clinical application; these results suggest that its therapeutic utility may be extended to include treatment of neuropathic pain syndromes resulting from peripheral nerve injury.     

cGMP and a germ-line signal control body size in C. elegans through cGMP-dependent protein kinase EGL-4

Mechanisms involved in the control of body size are largely unknown. In the nematode C. elegans, several small body size mutants were isolated, and the responsible genes were reported to encode putative components of a TGFbeta signalling pathway. Recently, mutants in the egl-4 gene encoding cGMP-dependent protein kinases were found to have a larger body size, and it was suggested that EGL-4 down-regulates the TGFbeta/DBL-1 pathway. We show that a permeable cGMP analogue 8-Br-cGMP significantly reduces body size of the wild-type but not that of an egl-4 mutant, indicating that cGMP controls body size through EGL-4. Laser ablation of germ-line cells revealed that a germ-line signal and EGL-4 function in the same pathway. Targeted expression of EGL-4 indicates that EGL-4 can function in hypodermis, neurones and intestine both cell-autonomously and cell-nonautonomously to control organ and body size. We propose a signal cascade for the control of body size that involves a germ-line signal, cGMP, G-kinase EGL-4 and DBL-1/TGFbeta pathway. It is interesting that two important pathways involving cGMP and TGFbeta, respectively, are related. Also, the results suggest a novel mechanism for the control of organ and body size in which hypodermis plays a key role     

Hepatocyte growth factor in polymorphonuclear leukocytes is increased in patients with systemic inflammatory response syndrome

BACKGROUND: Hepatocyte growth factor (HGF) has a significant effect on the regeneration of epithelial and endothelial cells. Studies have also shown an important role of HGF in wound healing and organ regeneration. Because recent studies indicate that polymorphonuclear leukocytes (PMNLs) store HGF in their specific granules and that HGF can be degranulated in the inflammatory tissue in which activated PMNLs migrate, we evaluated the storage and release of HGF in PMNLs from patients with systemic inflammatory response syndrome (SIRS) and attempted to examine the role of HGF from PMNLs in the systemic inflammatory process. METHODS: Twenty-four patients with SIRS (serum C-reactive protein, 20.2 +/- 12.4 mg/dL [mean +/- SD]) and 18 healthy volunteers were studied. HGF in PMNLs was measured by flow cytometry by using a monoclonal antibody to HGF. The oxidative activity in PMNLs was also measured by flow cytometry. Serum HGF, interleukin (IL)-6, and IL-8 levels in each patient were measured by enzyme-linked immunosorbent assay. HGF degranulation from PMNLs was evaluated in 10 patients. RESULTS: Immunocytochemistry under fluorescence microscopy revealed enhanced expression of HGF in the granules of PMNLs. HGF in PMNLs significantly increased in patients with SIRS compared with PMNLs from healthy volunteers (SIRS, 171.0 +/- 6.6 fluorescence/cell; control, 130.7 +/- 3.8 fluorescence/cell). N-formylmethionyl-leucyl-phenylalanine and lipopolysaccharide stimulation induced further increase of HGF fluorescence in PMNLs from patients. HGF degranulation from PMNLs was also significantly enhanced in patients. Moreover, oxidative activity in PMNLs was significantly enhanced in patients with SIRS. Plasma HGF (pHGF) correlated positively with IL-6 and IL-8 levels in patients (pHGF and IL-6, gamma = 0.635, p < 0.05; pHGF and IL-8, gamma = 0.827, p < 0.01), but these values did not correlate with HGF in PMNLs. CONCLUSION: Activated PMNLs in SIRS patients increased HGF in their granules and demonstrate enhanced degranulation of HGF. The release of HGF from migrated PMNLs in the inflammatory tissue may play an important role in wound healing and organ regeneration under those conditions.     

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.     

Thromboxane A(2) receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

It is thought that thromboxane A₂ (TxA₂) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA₂ is involved in liver repair. The objective of the present study was to examine the role of TxA₂ receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl₄) was used to induce liver injury in TP knockout (TP^−/−) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP^−/− mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP^−/− mice, the accumulation of hepatic CD11b⁺/F4/80⁺ macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl₄-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression.