Radiation tolerance of the cochlear nerve at the γ-knife in rabbits

Since the first treatment of acoustic neurinoma using the γ-knife by Leksell, a series of cases have been reported with good control rates. However, the most frequent complication is delayed hearing loss which occurs in more than 50% of patients. The purpose of this study was to define a safe dose by analyzing the radiosurgical dose-response relationship and histological effects on the normal cochlear nerve in rabbit. The rabbits had computed tomography (CT)-guided stereotactic radiosurgery on their cochlear nerves in the internal auditory canal with a 4 mm collimator focusing of a γ-unit. Maximum doses of 10, 20, 30, 40, 60, 80, 100, 200 and 500 Gy were administered. After the radiosurgery, auditory brain stem responses (ABR) and the behavior of the rabbits were evaluated periodically. At the conclusion, histological investigations were performed. No physiological or histological findings were observed from doses of 30 Gy or below during the 12 month period after the radiosurgery. A dose of 100 Gy caused a severe ABR threshold elevation, vestibular dysfunction and facial palsy. Necrosis and demyelination of nerves were observed pathologically. In this study, we determined that the safe dose to the normal cochlear nerve during radiosurgery was under 40 Gy in rabbits, and complications seemed to vary due to individual differences in radiation tolerance.     

Changes in levels of serum erythropoietin, serum iron and unsaturated iron binding capacity during chemotherapy for lung cancer

BACKGROUND: The serum erythropoietin level increases markedly during chemotherapy for leukemia. A number of hypotheses have been built for the mechanism, none of them satisfactory. Difficulty in evaluating bone marrow activity hampers the elucidation. Therefore, we focused on patients who had non-hematological cancer and no evidence of bone marrow suppression. METHODS: Twelve patients, who had lung cancer (four with small cell cancer and eight with non-small cell cancer) and who had not undergone any chemotherapy, were studied. During chemotherapy, we measured serum erythropoietin, serum iron, unsaturated iron binding capacity and hemoglobin concentration in these patients. RESULTS: The serum erythropoietin level before chemotherapy (10.8 +/- 7.4 mU/ml) was within the normal range but the peak values after the first treatment (73.4 +/- 90.4 mU/ml) increased in all patients. In the patients with small cell cancer, a transient but marked increase in erythropoietin value (204.6 +/- 167.3 mU/ml) was observed after each session of chemotherapy while hemoglobin concentration decreased gradually. Throughout treatments, elevation of the serum iron concentration and concomitant reduction of unsaturated iron binding capacity were observed after each session of chemotherapy. They regained their original values whilst the serum erythropoietin level decreased after each chemotherapy session was completed. CONCLUSIONS: It is suggested that the suppression of erythroid marrow by chemotherapeutic agents causes the changes in serum erythropoietin level during chemotherapy in patients with lung cancer.      

Correlation between bone marrow edema and collapse of the femoral head in steroid-induced osteonecrosis

OBJECTIVE: The purpose of this study was to clarify whether bone marrow edema is detectable on initial MR imaging of steroid-induced osteonecrosis of the femoral head. SUBJECTS AND METHODS: Forty-eight hips with osteonecrosis were examined consecutively with MR imaging and radiography. In a previously reported screening program, osteonecrosis was diagnosed on MR imaging when subchondral bands of abnormal signals were present. In the screening program, the MR images of 200 hips of 100 patients receiving high-dose steroid therapy were examined prospectively. Subchondral bands were detected in 48 hips at a mean of 14 weeks after the initiation of steroid therapy. RESULTS: On follow-up MR imaging of 47 hips (one hip excluded) bone marrow edema was initially observed in 13 hips after the onset of hip pain. MR imaging of the remaining 34 hips did not reveal bone marrow edema and the patients were all asymptomatic. MR imaging of 31 of the 34 hips continued to show subchondral bands and MR imaging of the other three hips indicated that the subchondral bands had disappeared. When bone marrow edema was detectable, abnormal findings on radiography were slight but 11 (85%) of the 13 hips progressed to advanced osteonecrosis. Bone marrow edema was highly correlated with the subsequent collapse of the femoral head (p<0.0001). CONCLUSION: Bone marrow edema was not present on initial MR imaging of osteonecrosis. Bone marrow edema should be considered a marker for potential progression to advanced osteonecrosis, and careful examinations for osteonecrosis are necessary when bone marrow edema is seen.     

Characteristics of ropivacaine block of Na+ channels in rat dorsal root ganglion neurons

When used for epidural anesthesia, ropivacaine can produce a satisfactory sensory block with a minor motor block. We investigated its effect on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Na(+) currents in rat dorsal root ganglion (DRG) neurons to elucidate the mechanisms underlying the above effects. Whole-cell patch-clamp recordings were made from enzymatically dissociated neurons from rat DRG. A TTX-S Na(+) current was recorded preferentially from large DRG neurons and a TTX-R Na(+) current preferentially from small ones. Ropivacaine shifted the activation curve for the TTX-R Na(+) channel in the depolarizing direction and the inactivation curve for both types of Na(+) channel in the hyperpolarizing direction. Ropivacaine blocked TTX-S and TTX-R Na(+) currents, but its half-maximum inhibitory concentration (IC(50)) was significantly lower for the latter current (116 +/- 35 vs 54 +/- 14 microM; P: < 0.01); similar IC(50) values were obtained with the (R)-isomer of ropivacaine. Ropivacaine produced a use-dependent block of both types of Na(+) channels. Ropivacaine preferentially blocks TTX-R Na(+) channels over TTX-S Na(+) channels. We conclude that because TTX-R Na(+) channels exist mainly in small DRG neurons (which are responsible for nociceptive sensation), such selective action of ropivacaine could underlie the differential block observed during epidural anesthesia with this drug. Implications: Whole-cell patch-clamp recordings of tetrodotoxin-sensitive and tetrodotoxin-resistant Na(+) currents in rat dorsal root ganglion neurons showed ropivacaine preferentially blocked tetrodotoxin-resistant Na(+) channels over tetrodotoxin-sensitive Na(+) channels. This could provide a desirable differential sensory blockade during epidural anesthesia using ropivacaine.     

Leiomyosarcoma of the scrotum: a case report

Leiomyosarcoma of the scrotum is a rare tumor. Up to 1999, only 29 cases have been reported in the literature worldwide. A 27-year-old man presented with a mass on the left side of the scrotum which had been painless and had gradually enlarged over the previous 10 years. During the following 3 months, however, it became painful and he was then referred to our hospital. Physical examination revealed a solid mass on the left side of the scrotum, measuring 7 cm in diameter, which was not adhering to the testis or to the vas deferens. The tumor was surgically resected. The histological examination confirmed the diagnosis of well differentiated leiomyosarcoma. Adjuvant therapy was considered unnecessary. The follow-up at 41 months revealed no local recurrence or distant metastasis.     

Accelerated growth signals and low tumor-infiltrating lymphocyte levels predict poor outcome in T4 esophageal squamous cell carcinoma

BACKGROUND: Little is known about the biological nature of T4 esophageal carcinoma growth signals and host defenses. METHODS: Paraffin-embedded sections from 78 patients with T2 to T4 esophageal squamous cell carcinoma who underwent operation were analyzed with immunohistochemistry. RESULTS: Positive cyclin A showed a significantly greater increase in T4 tumors than in those of other stages, and negative p27 showed a significantly greater decrease in T4 tumors than in large T3 stage tumors (tumor size > or = 4.0 cm). Patients with low-grade tumor-infiltrating lymphocyte (TIL) density showed a significantly greater decrease in T4 than in T2. The combination of p27 and cyclin A was a significant independent prognostic factor among T and N factors in multivariate analysis. TIL density was an independent prognostic factor among immunonutritional variables such as serum albumin concentration and the number of total blood lymphocytes. CONCLUSIONS: T4 esophageal squamous cell carcinoma has a poor prognosis, which is associated with increased p27-negative and cyclin A-positive growth signals in the tumor and with low TIL density in the host.     

Intrathecal dexmedetomidine attenuates hypercapnic but not hypoxic cerebral vasodilation in anesthetized rabbits

BACKGROUND: Systemic dexmedetomidine (DXM) attenuates the cerebral vasodilation induced by hypercapnia and decreases the cerebral blood flow response to hypoxia. We determined whether lumbar intrathecal DXM affected the cerebrovascular reactivity to hypercapnia and hypoxia. METHODS: Rabbits (n = 55) anesthetized with pentobarbital were prepared for measurement of pial vessel diameters using a closed cranial window preparation. The first study evaluated the response to hypercapnia after intrathecal administration of DXM (2 microg/kg; n = 7) or normal saline (n = 8). The second evaluated the response to hypercapnia after intrathecal DXM in the presence of yohimbine (20 microg/kg followed by DXM 2 microg/kg; n = 7). The third evaluated the response to mild or moderate hypoxia after intrathecal DXM (2 microg/kg; n = 7) or normal saline (n = 7). The hypercapnic responses were also examined in the presence of systemic DXM (2, 10 microg/kg; n = 6), topical DXM (10-8 m, 10-6 m; n = 6) and of intrathecal clonidine (2 microg/kg; n = 7). RESULTS: The pial arteriolar dilator response to hypercapnia was significantly attenuated after intrathecal administration of DXM. Pretreatment with yohimbine completely blocked the decreased reactivity to hypercapnia. Intrathecal clonidine, although less than DXM, also attenuate the hypercapnic response. Intrathecal DXM did not affect the vasodilation of pial arterioles induced by mild or moderate hypoxia. The systemic DXM 10 microg/kg and topical DXM 10-6 m, but not systemic 2 microg/kg and topical 10-8 m, attenuated hypercapnic vasodilation of pial arterioles. CONCLUSIONS: The presence of alpha2-adrenoceptor agonist administered intrathecally into the lumbar spinal region attenuates hypercapnic but not hypoxic cerebral vasodilation, probably via a stimulation of central alpha2-adrenergic receptors of the central nervous system.     

A Novel Nonradioactive Method for Measuring Aromatase Activity Using a Human Ovarian Granulosa-Like Tumor Cell Line and an Estrone ELISA

The following sentences should have read: Results, Reproducibility