Serial changes in acute extradural hematoma size and associated changes in level of consciousness and intracranial pressure

The authors report the cases of 37 patients encountered during the past 4 years who exhibited acute extradural hematoma but were initially treated conservatively because no or only small hematomas were observed on admission. The frequency of hematoma enlargement, hematoma size, and changes in the level of consciousness and intracranial pressure (ICP) were examined in these patients. The hematomas enlarged in 24 (64.9%) of the 37 patients, and attained a maximum thickness of 25 mm or greater in 19 patients (51.3%). The level of consciousness could be closely observed during enlargement of the hematomas in 13 patients: the level remained unchanged in eight, deteriorated in two, and improved in three, indicating relative stability in the state of consciousness despite the marked changes in hematoma size. The patients whose hematoma enlarged after the initial examination included three who underwent initial CT examination 5 hours after the injury. In five patients enlargement of extradural hematomas was observed unexpectedly during conservative treatment under ICP monitoring. The ICP also remained stable in three patients until the follow-up examination, but showed a rapid increase in two after a period of stability. However, there was no difference in the final size of the hematomas between the patients showing an increase in ICP and those who did not. These findings suggest that extradural hematomas enlarge progressively at rates varying with the condition of the source of hemorrhage. Moreover, a period of stability in the level of consciousness, such as the lucid interval seen in patients with extradural hematoma, is considered to be a period during which compensatory mechanisms can maintain the stability of the intracranial condition during progressive enlargement of the hematoma.     

Progression of severe atherosclerosis and increased arterial pulse pressure in the newly developed heritable mixed hyperlipidaemic rabbits

We have recently segregated a new line of rabbit, named TGH, with severely high levels of plasma triglyceride and cholesterol. The aim of the present study was to investigate the progression of atherosclerosis and haemodynamic parameters in TGH rabbits. 2. Japanese white (JW) and TGH rabbits (24-27 months old) were anaesthetized with ketamine and xylazine. Plasma concentrations of triglyceride were 63.1 8.0 and 446.0 35.2 mg/dL in JW and TGH rabbits, respectively. Blood pressure was measured by a catheter implanted in the femoral artery. Histological examinations were performed using haematoxylin-eosin and elastica-Masson trichrome staining to detect atherosclerotic lesions. 3. The JW rabbits had no atherosclerotic lesions. In TGH rabbits, severe atherosclerotic lesions were observed throughout the aorta, especially in the aortic arch. Basal femoral arterial pressure was not significantly different between JW and TGH rabbits. However, the basal pulse pressure in TGH rabbits (48.3 4.5 mmHg) was significantly greater than that of JW rabbits (28.0 5.6 mmHg). Intravenous infusion of N(G)-nitro-L-arginine methyl ester (L-NAME; 26.9 mg/kg) increased the blood pressure of TGH and JW rabbits. There was no significant difference in the response to L-NAME between the two rabbit strains. 4. The present study shows that severe atherosclerotic changes develop in TGH rabbits and suggests that the hyperlipidaemia combined with hypercholesterolaemia and hypertriglyceridaemia is an important factor for promoting atherosclerosis in TGH rabbits. The greater pulse pressure in TGH rabbits may be due to the increased vascular stiffness with atherosclerosis. 5. This newly developed TGH rabbit line of heritable hypertriglyceridaemia with hypercholesterolaemia will become a useful animal model for studies on the role of hyperlipidaemia in the progression of atherosclerosis and in many atherosclerosis-related diseases.     

Indication of posterior lumbar interbody fusion for lumbar disc herniation

OBJECTIVE: To examine whether lumbar disc herniation with massive extrusion and/or segmental instability can be an indicator for spinal fusion or not, by comparing the outcome of posterior lumbar interbody fusion (PLIF) and discectomy alone. METHODS: One hundred seventy-four patients with PLIF and 177 patients with discectomy were retrospectively analyzed. We hypothesized two criteria for fusion: massive herniation and segmental instability. The patients were divided into four groups according to our original criteria: group F-F (n = 96) consisted of the patients who fulfilled the criteria for fusion and underwent PLIF; group nF-F (n = 78) consisted of those who did not fulfill the criteria but had PLIF; group F-nF (n = 30) consisted of those who fulfilled the criteria but underwent discectomy; group nF-nF (n = 147) comprised those who did not fulfill the criteria and underwent discectomy. Each patient was evaluated clinically and radiologically at 5 years after operation. RESULTS: Groups F-F and nF-F had significantly superior results on low back pain compared with group F-nF (F-F vs F-nF, P < 0.05; nF-F vs F-nF, P < 0.01). The frequency of additional operation at the involved level was significantly higher in group F-nF (10.0%) than in group F-F (2.0%) (P < 0.05). Postoperative instability of the adjacent segment developed in 15 cases (8.6%) in groups F-F and nF-F and in 3 cases (1.7%) in groups F-nF and nF-nF (P < 0.01). CONCLUSION: Lumbar disc herniation with massive herniation or segmental instability can be well treated with PLIF.     

Direct activation of STAT5 by ETV6-LYN fusion protein promotes induction of myeloproliferative neoplasm with myelofibrosis

Myeloproliferative neoplasms (MPN), a group of haematopoietic stem cell (HSC) disorders, are often accompanied by myelofibrosis. We previously identified the fusion of the ETV6 gene to the LYN gene (ETV6-LYN) in idiopathic myelofibrosis with ins(12;8)(p13;q11q21). The introduction of ETV6-LYN into HSCs resulted in fatal MPN with massive myelofibrosis in mice, implicating the rearranged LYN kinase in the pathogenesis of MPN with myelofibrosis. However, the signalling molecules directly downstream from and activated by ETV6-LYN remain unknown. In this study, we demonstrated that the direct activation of STAT5 by ETV6-LYN is crucial for the development of MPN. ETV6-LYN was constitutively active as a kinase through autophosphorylation. ETV6-LYN, but not its kinase-dead mutant, supported cytokine-free proliferation of haematopoietic cells. STAT5 was activated in a JAK2-independent manner in ETV6-LYN-expressing cells. ETV6-LYN interacted with STAT5 and directly activated STAT5 both in vitro and in vivo. Of note, ETV6-LYN did not support the formation of colonies by Stat5-deficient HSCs under cytokine-free conditions and the capacity of ETV6-LYN to induce MPN with myelofibrosis was profoundly attenuated in a Stat5-null background. These findings define STAT5 as a direct target of ETV6-LYN and unveil the LYN-STAT5 axis as a novel pathway to augment proliferative signals in MPN and leukaemia.     

Preoperative Tegafur Suppositories for Resectable Rectal Cancer: Phase II Trial

Purpose Preoperative radiochemotherapy for rectal cancer causes a high rate of moderate-to-severe toxicities and is associated with only moderate survival benefits. A simpler, safer, and more convenient treatment would be preferable. Preoperative tegafur suppositories (1,500 mg/day) for at least 14 days were piloted. Methods A total of 129 patients with resectable rectal cancer were enrolled. The primary end points were pathologic response, adverse events, rate of sphincter-sparing surgery, recurrence, and survival. Results The total dose of tegafur ranged from 21 to 78 (mean, 32) g. The anal sphincter was preserved in 60.5 percent with microscopic no residual tumor (R0). The overall morbidity rate was 32 percent. Wound infection occurred in 13.2 percent of cases and anastomotic leakage in 9 percent of cases. Pathologic responses were observed in 70 percent of patients, with a complete necrosis occurring in 3.9 percent, two-thirds or more necrosis in 6.2 percent, one-third or more but less than two-thirds necrosis in 18.6 percent, and less than one-third necrosis in 41.9 percent. The mean total dose that patients showing complete or two-thirds or more necrosis received was 42.8 ± 6.4 g (P = 0.01) compared with 31.6 ± 1.2 g administered to patients showing less than two-thirds necrosis. Adverse events were observed in 15.6 percent of patients overall, and Grade III or IV events were observed in 2.3 percent of patients. During a median follow-up of 48 months, distant metastasis occurred in 14.7 percent of patients and local recurrence occurred in 6.2 percent of patients. The four-year, disease-free and overall survival rates were 67.6 and 80.1 percent, respectively. Conclusions Preoperative tegafur suppositories are associated with low toxicity and may lead to analsphincter-sparing surgery with acceptable postoperative complications and favorable local and distal control. Supported in part by the Harnasou Foundation Fund subsidizing Cancer Research in Harunamachi, the Kanetsu Chuo Hospital Research Fund, the Maebashi Norte Hospital Research Fund, the Kato Medical and Surgical Hospital Research Fund in Maebashi, and the Research Fund of the Uchida Clinic in Inamachi, Saitama. Presented in part at the meeting of the American Society of Clinical Oncology, Orlando, FL, May 18 to 21, 2002.