Mitogenic effect of erythropoietin on cultured aortic myocytes

The administration of recombinant erythropoietin (rHuEpo) to anemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. In the present study, experiments were designed to explore the hypothesis that rHuEpo could enhance vascular resistance through mitogenic effect on vascular smooth muscle cells (VSMCs), and that preexisting hypertension might be a predisposing condition. Cultured VSMCs from the thoracic aortae of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth related proto-oncogene expression in the presence of rHuEpo. In cells from both strains, rHuEpo dose-dependently increased DNA synthesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and 3H-inositol phosphate formation, respectively (EC50 approximately 4 U/ml). Exposure of VSMCs to rHuEpo for various times gradually increased the levels of c-myc and junB and transiently induced c-fos expression, as determined by Northern analysis. rHuEpo-induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression did not differ between the two strains. Taken together, these results suggest that rHuEpo may function as a vascular smooth muscle cell growth promoting factor through activation of the phospholipase C cascade and modulation of proto-oncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.     

Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons

Recent studies show that the cytokine interleukin-6 (IL-6) is expressed at elevated levels in the CNS in several disease states and contributes to the neuropathological process. The mechanisms through which IL-6 exerts its CNS effects are primarily unknown. We have investigated the pathophysiological effects of IL-6 on developing CNS neurons using a culture model system and a chronic treatment paradigm. Here, we show, using current- and voltage-clamp recordings, that chronic IL-6 treatment of developing cerebellar granule neurons increases the membrane and current response to NMDA and that these effects are the primary mechanism through which IL-6 produces an enhanced calcium signal to NMDA. We also show that calcium influx through voltage-sensitive calcium channels contributes to the enhanced calcium signal to NMDA in the IL-6-treated neurons in a developmentally regulated manner and that the membrane depolarization to NMDA is more sensitive to the NMDA receptor antagonist ifenprodil in the IL-6-treated neurons compared with control neurons at a late developmental stage, consistent with a larger proportion of NMDA receptors containing the NMDAR2B subunit in the IL-6-treated neurons. Additional studies show that IL-6 treatment reduces the number of granule neurons in culture and enhances neurotoxicity involving NMDA receptors. These results support a pathological role for IL-6 in the CNS and indicate that NMDA receptor-mediated functions are likely to play a critical role in neuropathological changes observed in CNS diseases associated with elevated CNS levels of IL-6.     

Smokeless tobacco use in an outpatient veteran population

Smokeless tobacco use is a significant health risk for carcinoma of the oropharynx, and has a high prevalence in the southern United States. To evaluate the potential demand for a smokeless tobacco cessation program, we surveyed patients attending the General Medicine Clinic of a Veterans Affairs Medical Center. The prevalence of smokeless tobacco use was 5.8%, which did not justify creation of a clinic-based cessation program. Since we observed adults using smokeless tobacco as a means to reduce or stop their smoking, smoking cessation programs should include counseling against smokeless tobacco use.     

Trabeculectomy function after cataract extraction

OBJECTIVE: To examine the effect of cataract extraction (CE) after trabeculectomy on intraocular pressure (IOP) control. DESIGN: Retrospective noncomparative case series. PARTICIPANTS: A total of 115 consecutive patients who underwent extracapsular CE (N = 58) or phacoemulsification (N = 57) with intraocular lens (IOL) placement after trabeculectomy were studied. INTERVENTION: Cataract extraction with IOL after trabeculectomy was performed. MAIN OUTCOME MEASURES: Preoperative, intraoperative, and postoperative factors were evaluated for association with loss of IOP control requiring additional medications, bleb needling, or further glaucoma surgery, using Kaplan-Meier survival analysis and Cox multivariate proportional hazards survival regression. RESULTS: After mean postoperative follow-up of 21.1 +/- 14.3 months, additional glaucoma medication or needling of the filtering bleb to maintain IOP control was required in 35 eyes (30.4%) and was significantly associated with intraoperative iris manipulation and early postoperative peak IOP greater than 25 mmHg. Additional glaucoma surgery was eventually required in 11 eyes (9.6%) and was significantly associated with age of 50 years or younger, preoperative IOP greater than 10 mmHg, and early postoperative peak IOP greater than 25 mmHg. The cumulative proportion of patients who did not require reoperation for glaucoma was 93% and 90% at 1 and 2 years, respectively. The mean IOP at last visit had increased 1.6 mmHg above the pre-CE level and did not vary significantly after the first postoperative month. The median interval from CE to the addition of glaucoma medication or bleb needling was 1.6 months (within 3 months in 20 of 33 eyes) and that from nonsurgical intervention to further glaucoma surgery was 3.6 months (before the 7th postoperative month in 6 of 11 eyes). Of 19 eyes with hypotony (IOP < or = 6 mmHg) before CE, 11 eyes remained hypotonous after CE despite an increase in the mean IOP from 4.6 to 7.5 mmHg. CONCLUSIONS: When CE is performed after trabeculectomy, age of 50 years or younger, preoperative IOP greater than 10 mmHg, intraoperative iris manipulation, and early postoperative IOP greater than 25 mmHg are associated with worsened postoperative IOP control. Most bleb failures occur soon after CE. Resolution of pre-existing hypotony after CE is unpredictable.     

Leiomyosarcoma of the esophagus: results of surgical treatment

BACKGROUND: This study examined the results of surgical treatment of leiomyosarcoma of the esophagus. METHODS: Between January 1920 and December 1996, 17 patients (9 men and 8 women) with leiomyosarcoma of the esophagus were treated surgically at the Mayo Clinic. Median age was 58 years and ranged from 26 to 76 years. Symptoms included dysphagia in 11 patients (64.7%) and odynophagia in 6 (35.3%). The tumor was located in the middle third of the esophagus in 10 patients (58.8%) and in the cervical esophagus in 7 (41.2%). Procedures performed included esophagogastrectomy in 9 patients (Ivor Lewis in 5, left thoracoabdominal in 3, and transhiatal in 1), enucleation in 3, transgastric excision in 1, and exploration without resection in 4. RESULTS: The procedure was considered curative in 11 patients (64.7%). There was one operative death (mortality, 5.9%). Complications occurred in 3 patients (17.6%) and included anastomotic leak in 2 and bleeding requiring reoperation in 1. Growth pattern was infiltrating in 7, polypoid in 5, and intramural in 5. Histologically, the tumor was grade 1 in 6 patients, grade 2 in 2, grade 3 in 7, and grade 4 in 2. The tumor was postsurgically classified as stage I in 2 patients, stage IIA in 7, stage IIB in 1, stage IIIA in 5, stage IV in 1, and unknown in 1. Six patients (35.3%) received adjuvant treatment. Follow-up was complete in 16 patients (94.1%) and ranged from 1 to 182 months (median, 48 months). Five- and 10-year actuarial survivals were 47.0% and 31.0%, respectively. Seven patients (41.2%) are currently alive (median survival, 72 months); all underwent curative resection. Factors affecting survival included completeness of resection, growth pattern, postsurgical stage, tumor grade, and tumor location (p < 0.05). CONCLUSIONS: We conclude that leiomyosarcoma of the esophagus is rare. Complete resection provides long-term survival.     

Deoxyribonucleic acid flow cytometry of squamous cell carcinoma of the penis

This article reports 10 cases of cranial base tumors resected by pre-or retro-auricular intratemporal approach. Among them four were neuronomas, two meningiomas, one malignant giant cell tumor of bone, one osteochondnoma, one parotid mixed neoplasm and one poorly-differentiated squamors cell carcinoma. Total resection in 9 cases and one subtotal resection were performed without operative mortality and serious surgical complications. The surgical management of cranial base tumor and indications for selecting operative approaches were discussed.