Determination of physostigmine in plasma and cerebrospinal fluid by liquid chromatography with electrochemical detection

Physostigmine (Phy) was determined in plasma and cerebrospinal fluid (CSF) by HPLC with electrochemical detection, with use of a normal-phase column and methanolic sodium acetate buffer, pH 4.6. The detection limit of the method was 0.5 micrograms/L for a 2-mL sample of plasma or 0.5 mL of CSF. Analytical recovery of Phy in the range from 0.5 to 40 micrograms/L was 60% (SD 5%) for plasma and 78% (SD 8%) for CSF. Excellent chromatographic separation of Phy without column deterioration during extended usage and constant recovery for a wide range of Phy concentrations makes the routine monitoring of plasma from patients with Alzheimer's disease economically feasible. Using our method, we measured Phy in 13 such patients' plasmas at 105 and 135 min after a 135-min intravenous infusion of 300, 600, and 900 micrograms of Phy per square meter of body surface. Mean values significantly increased with dose (P = 0.001), but differences between 105 and 135 min (P = 0.229) or between dose and time (P = 0.949) were not significant.     

Periosteal osteogenic sarcoma.

A study of 102 osteogenic sarcomas of the bone surface revealed that 79 were parosteal osteogenic sarcomas. Roentgenographically, these 79 were dense, lobulated lesions attached by a broad base to underlying bone, usually the lower femoral shaft. Histologically, they were low-grade osteosarcomas. The other 23 lesions (periosteal osteogenic sarcoma) usually involved the upper tibial shaft and presented as small radiolucent lesions on the surface, with formation of spicules of bone perpendicular to the bone shaft. Histologically, these 23 were relatively high-grade, predominantly chondroblastic osteogenic sarcomas. Thirteen of the 23 patients were males, and most were in the second decade of life. Of five patients who had excision of the tumor, two had recurrence. Seven of 13 patients who underwent amputation initially were alive without disease at last follow-up. Only 4 of the 23 patients have dies of metastatic disease.     

High-grade surface osteosarcomas

Nine patients (seven males and two females) had high-grade, ordinary-type osteosarcomas that were juxtacortically located. The ages of these patients ranged from 9 to 62 years at the time of diagnosis. The roentgenographic appearance of these tumors occasionally is similar to that of periosteal osteosarcomas. Histologically, these tumors were indistinguishable from ordinary high-grade intramedullary osteosarcomas. None of the nine tumors had histologic features of parosteal or periosteal osteosarcomas. All nine patients were treated by ablative surgery. Seven patients died of tumor. Because of its poorer prognosis, this tumor should be differentiated from other juxtacortical osteosarcomas.     

Histogenesis of dermatofibrosarcoma protuberans. An ultrastructural study

Ultrastructural study of five typical lesions of dermatofibrosarcoma protuberans revealed that the basic cell is fusiform and has a somewhat indented nucleus and an even distribution of cytoplasmic organelles. Fragments of basal lamina, intercellular junctions, abundant intercellular fibers, and a tendency to form cellular sheaths also were found. The tumor cells had a strong resemblance to pericytes and perineural cells, as well as marked ultrastructural similarities to neurofibroma. The authors conclude that dermatofibrosarcoma protuberans arises from a primitive fibroblastic cell with a "sheath forming cell" differentiation that has a closer relationship to the perineural cell than to the pericyte.     

Melarsoprol versus eflornithine for treating late-stage Gambian trypanosomiasis in the Republic of the Congo

OBJECTIVE: To compare the effectiveness of melarsoprol and eflornithine in treating late-stage Gambian trypanosomiasis in the Republic of the Congo. METHODS: We analysed the outcomes of death during treatment and relapse within 1 year of discharge for 288 patients treated with eflornithine, 311 patients treated with the standard melarsoprol regimen and 62 patients treated with a short-course (10-day) melarsoprol regimen between April 2001 and April 2005. FINDINGS: A total of 1.7% (5/288) of patients treated with eflornithine died compared with 4.8% (15/311) of those treated with standard melarsoprol and 6.5% (4/62) of those treated with short-course melarsoprol. Patients treated with eflornithine tended to be younger and were more likely to have trypanosomes or higher white blood cell counts in their cerebrospinal fluid. The cumulated incidence of relapse among patients who attended at least one follow-up visit 1 year after discharge was 8.1% (11/136) for those treated with eflornithine, 14% (36/258) for those treated with standard melarsoprol and 15.5% (9/58) for those treated with shortcourse melarsoprol. In a multivariate analysis, when compared with eflornithine, standard melarsoprol was found to be a risk factor for both death (odds ratio (OR) = 2.87; 95% confidence interval (CI) = 1.03-8.00) and relapse (hazard ratio (HR) = 2.47; 95% CI = 1.22-5.03); when compared with eflornithine, short-course melarsoprol was also found to be a risk factor for death (OR = 3.90; 95% CI = 1.02-14.98) and relapse (HR = 6.65; 95% CI = 2.61-16.94). CONCLUSION: The effectiveness of melarsoprol treatment appears to have diminished. Eflornithine seems to be a better first-line therapy for treating late-stage Gambian trypanosomiasis in the Republic of the Congo.     

Treatment outcomes and risk factors for relapse in patients with early-stage human African trypanosomiasis (HAT) in the Republic of the Congo

OBJECTIVE: In 2002-03, the Republic of the Congo increased the threshold separating stage 1 and 2 cases of human African trypanosomiasis (HAT) from a cerebrospinal fluid (CSF) white cell count of 5 cells/mm(3) to 10 cells/mm(3). We aimed to assess whether the increased threshold of 10 cells/mm(3) is a safe indicator of stage 2 disease. METHODS: We assessed patients treated for stage 1 HAT caused by Trypanosoma brucei gambiense in the Republic of the Congo between April 2001 and April 2005. Patients with 0-10 cells/mm(3) in CSF were classed as stage 1 and treated with pentamidine. Patients with CSF of > 10 cells/mm(3) were classed as stage 2 and treated with either melarsoprol or eflornithine. We did a retrospective analysis of all patients treated after the September 2002 increase in threshold for classification of HAT disease stage 2, and who were eligible for at least 1 year of follow-up. Primary outcome was survival without death or relapse within 1 year of discharge. Risk factors for treatment failure, in particular CSF white cell count on diagnosis, were assessed. FINDINGS: Between September 2002 to April 2004, 692 patients eligible for our analysis were treated with pentamidine. All were discharged alive. Relapse rate was 5% (n = 33). The only identified risk factor for relapse was a CSF white cell count of 6-10 cells/mm(3) rather than 0-5 cells/mm(3) (adjusted hazard ratio 3.27 (95% confidence interval, 1.52-7.01); P = 0.002). CONCLUSION: A threshold of 5 white cells/mm(3) in CSF is safer than 10 cells/mm(3) to determine stage 2 HAT and reduce risk of relapse.     

Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions.

Oncogenic osteomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia, normocalcemia, and increased levels of alkaline phosphatase. We collected from the Mayo Clinic files and from our consultation files the records for 17 cases of osteomalacia associated with bone lesions. There were five cases of fibrous dysplasia, three of hemangiopericytoma, and two of phosphaturic mesenchymal tumor. There was one case each of osteosarcoma, chondroblastoma, chondromyxoid fibroma, malignant fibrous histiocytoma, giant cell tumor, metaphyseal fibrous defect, and hemangioma. In this study we can figure out that the most common characteristic histologic features of our cases were hemangiopericytomatous vascular proliferation, fine lace-like stromal calcification, and stromal giant cells. In most of the cases, the clinical and biochemical symptoms and signs resolved soon after complete resection of the lesion. When the lesion recurred or metastasized, the symptoms and signs also recurred.     

Long-term survival following diverticulectomy for cancer in pharyngoesophageal (Zenker's) diverticulum

The incidence of cancer in a pharyngoesophageal (Zenker's) diverticulum was 0.4% among 1,249 patients treated for such diverticula at the Mayo Clinic in a 53-year period. Twenty-four patients with squamous cell carcinoma arising in a pharyngoesophageal diverticulum have been reported by others. However, most of the patients died of the malignancy within 2 years of treatment, and there were no long-term survivors. We describe 2 long-term survivors who were without evidence of tumor or diverticulum recurrence 4 1/4 and 8 years after one-stage pharyngoesophageal diverticulectomy. Review of the literature revealed that most patients with cancer in pharyngoesophageal diverticulum should be managed in a manner similar to that for patients with ordinary cervical esophageal malignancy. However, our data suggest that when the tumor is well localized without full-thickness penetration, nodal metastasis, or extension to the line of resection (as in the 2 patients discussed), diverticulectomy alone can provide satisfactory control of cancer with minimal therapeutic risk.