Isolated absence of F waves and proximal axonal dysfunction in Guillain-Barré syndrome with antiganglioside antibodies

OBJECTIVES: To investigate the pathophysiology of selective absence of F waves and its relation with antiganglioside antibodies in Guillain-Barré syndrome (GBS). Some patients with GBS show the absence of F waves as an isolated conduction abnormality, which has been interpreted as demyelination in the proximal nerve segments. METHODS: In 62 consecutive patients with GBS, sequential nerve conduction and F wave studies were reviewed, and antibodies against ganglioside GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, and GQ1b were measured by an enzyme linked immunosorbent assay. RESULTS: In the first electrophysiological studies, isolated absence of F waves was found in 12 (19%) patients. Sequential studies in 10 of these patients showed two electrophysiological sequel patterns; rapid restoration of F waves (six patients), and persistent absence of F waves with distal motor nerve degeneration (acute motor axonal neuropathy, four patients). None of the 10 patients showed evidence of demyelination in the proximal, intermediate, or distal nerve segments throughout the course. Of the 62 patients, IgG antibodies against GM1, GM1b, GalNAc-GD1a, or GD1b were significantly associated with the electrodiagnosis of acute motor axonal neuropathy, and patients with these antibodies more often had isolated absence of F waves than patients without them (11 of 36 (31%) v one of 26 (4%); p<0.01). Eleven of the 12 patients with isolated absence of F waves had positive serology for one or more antiganglioside antibodies. CONCLUSIONS: In GBS with antiganglioside antibodies, isolated absence of F waves is a frequent conduction abnormality especially in the early phase of the disease, and may be caused by axonal dysfunction, such as physiological conduction block or axonal degeneration at the nerve roots.     

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Purpose According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC.Methods We retrospectively reviewed the clinical information of 12 patients with LCNEC.Results Three patients with stage I disease underwent curative resection but all relapsed within 20 months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2 months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR.Conclusions The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.     

Association between p53 immunostaining and cigarette smoking in squamous cell carcinoma of the esophagus

BACKGROUND: It is generally accepted that cigarette smoking is closely associated with esophageal squamous cell carcinoma. This study investigated the molecular targets of cigarette smoke in carcinogenesis of the esophagus. METHODS: Seventy-four patients with esophageal squamous cell carcinoma (SCC) were grouped according to daily cigarette consumption: heavy smoking group (group H) (n = 26), moderate smoking group (group M) (n = 39) and non-smoking group (group N) (n = 9). We compared p53 and retinoblastoma (RB) expression among the three groups by immunohistochemistry. In addition, fresh tumor tissues from 30 smokers with esophageal SCC were tested for p53 mutations in exons 5-8 by direct sequencing. RESULTS: Staining for the p53 product was positive in 65.4% of group H, 38.5% of group M and 44.4% of group N. The frequency of positive staining in the group H was significantly higher than in group M (p = 0.033) and in group M + group N (p = 0.034). The difference with respect to the frequency of overexpression of RB was not significant. The patterns of p53 base-pair mutations in direct sequencing study were of five types, most commonly G:C to T:A transversion (35.3%). CONCLUSIONS: Our study suggests that one of the molecular targets of cigarette smoke is the p53 gene. The pattern of p53 point mutations involved a wide range of base-pair changes.     

The effects of pretreatment with lidocaine or bupivacaine on the spatial and temporal expression of c-Fos protein in the spinal cord caused by plantar incision in the rat

We investigated the spatial and temporal patterns of c-Fos protein (Fos) expression in the dorsal horn of the spinal cord caused by plantar incision in the rat and the effects of pretreatment with local anesthetics. Bupivacaine (0.5%), lidocaine (2%), or saline for control was injected for nerve block and local infiltration before the plantar incision was made under anesthesia. Pain behavior and Fos expression in the L4-L5 segments of the spinal cord were assessed at 1, 3, 6, 24, 48, 72, and 120 h after the incision. The withdrawal threshold to mechanical stimulation decreased significantly at 1 h until 120 h (1-72 h, P < 0.01;120 h, P < 0.05), and pretreatment with local anesthetics increased the threshold significantly at 1 h (both groups: P < 0.01), 3 h (both groups: P < 0.01), and 6 h (bupivacaine, P < 0.01; lidocaine, P < 0.05) in comparison with that in the saline group. In the saline group, Fos expression was detected predominantly in laminae I-II and V-VI, and the total Fos expression was maximal at 1 h and then decreased gradually. Pretreatment with local anesthetics suppressed Fos expression significantly in all layers, and this suppression continued for several days. This study provides evidence of spatial and temporal changes in Fos expression induced by plantar incision. Our results indicate that although pretreatment with local anesthetics suppresses Fos expression for several days in the postoperative period, the analgesic effect is observed only for the expected duration of the local anesthetic used. IMPLICATIONS: Prevention of early pain by pretreatment with local anesthetics provides little benefit for postoperative pain relief in the plantar incision model, although c-Fos expression is suppressed. The number of c-Fos-expressing neurons is not necessarily correlated with pain behavior.     

VEGF expression in osteosarcoma correlates with vascular permeability by dynamic MRI

Dynamic enhanced magnetic resonance imaging has been used to assess tumor angiogenesis in osteosarcoma. Vascular endothelial growth factor has been shown to correlate with pulmonary metastasis and a poor prognosis in osteosarcoma. The purpose of this investigation was to determine whether vascular endothelial growth factor expression in osteosarcoma correlates with vascular permeability detected by dynamic enhanced magnetic resonance imaging and to explore the role of dynamic enhanced magnetic resonance imaging as a noninvasive means of assessing tumor angiogenic activity. Fifty-five osteosarcoma patients with osteosarcoma enrolled in a treatment protocol that included dynamic enhanced magnetic resonance imaging. In 15 patients, tumor tissues were available for vascular endothelial growth factor immunohistochemical studies. A two-compartment model used the exchange rate constants (kep) between the plasma and tumor compartments to quantify vascular permeability during dynamic magnetic resonance imaging studies. Immunohistochemical staining for vascular endothelial growth factor was graded according to the intensity and number of positively stained cells. Vascular endothelial growth factor-positive tumors showed higher mean vascular permeability when compared with vascular endothelial growth factor-negative tumors. Vascular permeability also correlated with increasing vascular endothelial growth factor expression. The preliminary results in this study show an association between vascular endothelial growth factor and dynamic MR signal enhancement in osteosarcoma. Dynamic enhanced magnetic resonance imaging should be investigated as a means to prognosticate osteosarcoma patients with osteosarcoma according to their tumor angiogenic activity.     

Comparison of percutaneous electrical nerve stimulation with transcutaneous electrical nerve stimulation for long-term pain relief in patients with chronic low back pain

The long-term effect of percutaneous electrical nerve stimulation (PENS) on chronic low back pain (LBP) is unclear. We evaluated the number of sessions for which PENS should be performed to alleviate chronic LBP and how long analgesia is sustained. Patients underwent treatment on a twice-weekly schedule for 8 wk. Group A (n = 18) received PENS for 8 wk, group B (n = 17) received PENS for the first 4 wk and transcutaneous electrical nerve stimulation (TENS) for the second 4 wk, and group C (n = 18) received TENS for 8 wk. Pain level, degree of physical impairment, and the daily intake of nonsteroidal antiinflammatory drugs (NSAIDs) were assessed before the first treatment, 3 days after Week 2, Week 4, and Week 8 treatments, and at 1 and 2 mo after the sessions. During PENS therapy, the pain level decreased significantly from Week 2 in Groups A and B (P < 0.05 or 0.01), and physical impairment and required NSAIDs decreased significantly from Week 4 (P < 0.05 or 0.01) in Group A but only at Week 4 in Group B (P < 0.05 or 0.01). These effects were sustained until 1-mo follow-up (P < 0.01) in Group A but not in Group B; these effects were not observed at 2-mo follow-up even in Group A. In Group C, pain level decreased significantly only at Week 8 (P < 0.05). Our results indicate that repeated PENS is more effective than TENS for chronic LBP but must be continued to sustain the analgesic effect. IMPLICATIONS: A cumulative analgesic effect was observed in patients with chronic low back pain (LBP) after repeated percutaneous electrical nerve stimulation (PENS), but this effect gradually faded after the treatment was terminated. Results indicate that although PENS is effective for chronic LBP, treatments need to be continued to sustain analgesia.     

Evodiamine,a constituent of Evodiae Fructus,induces anti-proliferating effects in tumor cells

We found that evodiamine, a major alkaloidal component of Evodiae Fructus (Goshuyu in Japan), inhibited proliferation of several tumor cell lines, but had less effect on human peripheral blood mononuclear cells (PBMC). We used human cervical cancer cells, HeLa, as a model to elucidate the molecular mechanisms of evodiamine-induced tumor cell death. The results showed that evodiamine induced oligonucleosomal fragmentation of DNA in HeLa cells and increased the activity of caspase-3, but not that of caspase-1, in vitro . Both evodiamine-induced DNA fragmentation and caspase-3 activity were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-Asp-Glu-Val-Asp-fmk). In addition, evodiamine increased the expression of the apoptosis inducer Bax, but decreased the expression of the apoptosis suppressor Bcl-2 in mitochondria. Taken together, our data indicated that evodiamine alters the balance of Bcl-2 and Bax gene expression and induces apoptosis through the caspase pathway in HeLa cells. (Cancer Sci 2003; 94: 92–98)     

Metastatic esophageal tumors from distant primary lesions: report of three esophagectomies and study of 1835 autopsy cases

Three cases of esophagectomy for secondary esophageal carcinoma metastasized from the ovary, breast and lung are reported. Long-term survival, 14 and 4 years, after esophagectomy was achieved in two patients. The intervals between surgery for primary cancer and dysphagia onset in these two patients were 16 and 7 years, respectively. An aggressive surgical approach appears to be the therapeutic procedure of choice for metastatic esophageal carcinoma when the primary tumor growth rate is suspected to be slow. Autopsy data on 1835 cases revealed 112 (6.1%) had metastasis to the esophagus. The lung was the most common primary tumor-bearing organ and the diffusely infiltrative type was the most common esophageal tumor observed macroscopically which corresponded to the findings in our three patients. When an esophageal stricture with normal mucosa is encountered, a metastatic tumor must be taken into consideration.