Central neuro-inflammatory gene response following soman exposure in the rat.

Effective treatments to improve survivability following exposure to the nerve agent soman have been established and are currently available. Unfortunately, electrographic brain seizures, neuroinflammation and brain cell death are still a potential problem even with treatment. In the present study we have characterized the time course of the central neuro-inflammatory gene response using quantitative real time-PCR (TaqMan). Male Sprague-Dawley rats were pre-treated with HI-6 (1-2-hydroxy-iminomethyl-1-pyridino-3-(4-carbamoyl-1-pyridino-2-oxapropane dichloride); 125 mg/kg, i.p.) and exposed 30 min later to 1.6 x LD(50) of soman (pinacolyl methyl-phosphonofluoridate, 180 microg/kg, s.c.) followed at 1 min by atropine methyl nitrate (4 mg/kg, i.m.). Initially, a significant and dramatic upregulation of tumor necrosis factor-alpha and vascular cell adhesion molecule-1 mRNA levels was measured 2 h post-exposure followed at 6 h by upregulation of interleukin-1beta, interleukin-6, E-selectin, and intercellular adhesion molecule-1 with eventual resolution by 24-48 h. In conclusion, an acute and transient upregulation of the inflammatory gene response is activated following soman exposure that may be involved in the soman-induced brain injury process.

Effectiveness of the "teaching the teachers" diagnostic US training program.

RATIONALE AND OBJECTIVES: The "Teaching the Teachers" training program was meant to establish standardized ultrasound education programs worldwide, reaching the largest possible number of physicians. The authors performed this study to evaluate the results of this training. MATERIALS AND METHODS: An open-ended test question format (ie, uncued testing) that would evoke responses from physicians in a manner ensuring the highest fidelity with a real clinical setting was selected. An examination was administered at the beginning and the end of the program and then again 6 months later to assess baseline knowledge, changes in knowledge, and knowledge retention, respectively. RESULTS: Scores on entry and end-of-program examinations were available for 112 participants. The mean entry test score was 35%, and the mean end-of-program examination score was 73%. All changes in scores were statistically significant (P < .001) as determined with paired t tests. Follow-up examinations were available for 27 of the 112 participants at the time of the analysis. On these examinations, mean total test scores increased by nearly 4 percentage points. Although follow-up test scores were available for only 27 participants, these mean test scores were comparable to those reported for the entire group on the end-of-program examination. CONCLUSION: The examinations administered at the end of the 3-month program showed marked improvement compared with the baseline assessment. That this improvement remained stable over 6 months indicates the success of the educational process.

Interactions within the yeast t-SNARE Sso1p that control SNARE complex assembly.

In the eukaryotic secretory and endocytic pathways, transport vesicles shuttle cargo among intracellular organelles and to and from the plasma membrane. Cargo delivery entails fusion of the transport vesicle with its target, a process thought to be mediated by membrane bridging SNARE protein complexes. Temporal and spatial control of intracellular trafficking depends in part on regulating the assembly of these complexes. In vitro, SNARE assembly is inhibited by the closed conformation adopted by the syntaxin family of SNAREs. To visualize this closed conformation directly, the X-ray crystal structure of a yeast syntaxin, Sso1p, has been determined and refined to 2.1 A resolution. Mutants designed to destabilize the closed conformation exhibit accelerated rates of SNARE assembly. Our results provide insight into the mechanism of SNARE assembly and its intramolecular and intermolecular regulation.

Design, fabrication, and performance of preferential-order volume grating waveguide couplers.

Both a nonfocusing and a focusing preferential-order volume grating waveguide coupler were designed, fabricated, and tested. These volume grating couplers are designed to outcouple a 633-nm wave guided in an adjacent polyimide waveguide film. The slanted-fringe volume gratings are recorded holographically by the interference of two 364-nm waves. The dynamics of the holographic photopolymer HRF600X001 are investigated in relation to the interaction with the guided wave. The fabricated couplers exhibited a preferential coupling of 98%, a spatial coupling rate of 3.6 mm(-1), and a coupling efficiency of 95%. The focusing grating coupler focused the outcoupled beam to a focal line with a full width at half-maximum of 10.49 microm located 25 mm above the grating.

Volume grating preferential-order focusing waveguide coupler.

A volume grating focusing waveguide coupler has been designed, fabricated, and tested. The volume grating is designed to couple a 633-nm wave guided in a single-mode polyimide waveguide preferentially into the air cover. The beam is outcoupled normally to the surface of the waveguide and focused to a line 25 mm above the waveguide. The slanted-fringe volume grating is holographically recorded by the interference of two coherent 364-nm ultraviolet waves focused with a cylindrical lens to produce the chirped grating. The 1-mm-long volume grating coupler exhibits a preferential-coupling ratio of 0.98, a coupling efficiency of 95%, and an almost diffraction-limited focal line with a full width at half-maximum of 10.49mum.

Design of a high-efficiency volume grating coupler for line focusing.

A volume grating for outcoupling and line focusing of waveguided infrared light is designed and optimized. A local grating vector approach is used in combination with the rigorous coupled-wave analysis. By design, this volume grating coupler is holographically constructed on top of a waveguide by the interference of two coherent 364-nm ultraviolet waves formed with two aberration-optimized cylindrical lenses. This focusing coupler exhibits preferential-order coupling (92.9%) into the cover as well as very low focal intensity side lobes. This is accomplished through a chirped, slanted-fringe volume grating with a designed spatial variation in the attenuation coefficient (describing the outcoupling of the guided mode) along the length of the grating. This is achieved by a specific variation in the grating slant angle along the grating length. By design, the 1000-mum-length coupler focuses an 850-nm infrared guided wave to a line with an intensity FWHM of 3.32 mum and a 90% power width of 5.53 mum at a focal distance of 4 mm directly above the grating. Its performance is compared with that of a corresponding electron-beam-written surface-relief coupler design.

Electrocardiographic changes after intravenous administration of magnesium in rabbits.

Magnesium (Mg+2) therapy has a beneficial effect in various cardiovascular diseases. However, overdosage of Mg+2 can be fatal. This study was undertaken to determine the amount of Mg+2 that can be safely administered intravenously to rabbits. Twenty New Zealand White rabbits were allotted to three groups. One hundred milliliters of 0.9% NaCl/kg was infused in group-1 rabbits (n = 10) used as a control group. Rabbits in group 2 (n = 6) and group 3 (n = 4) received MgCl2 (2.5 mmol and 5.0 mmol/kg respectively) in 0.9% NaCl (100 ml/kg). The infusion was delivered intravenously for 30 min (group 2, 8 mg/kg per min; group 3, 16 mg/kg per min). The electrocardiogram was monitored throughout the infusion; the P-R interval, QRS duration, and QTc interval of group-2 and group-3 rabbits were prolonged at dosages of 0.8 mmol/kg, 1.7 mmol/kg, and 5.0 mmol/kg of MgCl2 respectively, compared with readings in group-1 rabbits. We hypothesized that the mean +2 standard deviations of the pre-operative baseline values was the safe limit. On the basis of this hypothesis, the safe limit of the P-R interval is 95.3 milliseconds, which corresponds to 0.6 mmol/kg of infused Mg+2; the QRS duration is 44.4 milliseconds, which corresponds to 1.0 mmol of Mg+2/kg; and the QTc interval is 350.0 milliseconds, which corresponds to 3.6 mmol of Mg+2/kg. These results will provide guidance for avoiding cardiac side effects when researchers investigate the effects of Mg+2 in rabbits.

Colonial medical practice: a case study of Thomas Cadwalader (1708-1779).

In 1745 Doctor Thomas Cadwalader published his classic treatise entitled An essay on the West-India dry-gripes; with the method of preventing this cruel distemper. To which is added, An extraordinary case in physick. Most experts now agree that it proved to be a report of lead poisoning acquired from drinking Jamaica rum distilled through lead pipes. While its very existence is important in medical history as one of the earliest colonial publications, it is Cadwalader's only publication. What it reveals about medical practice in British America is very informative. This paper presents a character sketch of the colonial American physician and examines Thomas Cadwalader's life and the eighteenth-century practice of medicine as recorded in his Essay and surviving Prescription Book.

Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group.

PURPOSE: To assess the efficacy and toxicity of single-agent paclitaxel as first-line chemotherapy in patients with locally advanced or metastatic transitional-cell carcinoma of the urothelium. PATIENTS AND METHODS: Twenty-six eligible patients were enrolled onto this cooperative group study and treated with paclitaxel at a dosage of 250 mg/m2 by 24-hour continuous infusion every 21 days until progression or patient intolerance. All patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 micrograms/kg/d for at least 10 days during each cycle. RESULTS: Eleven of 26 patients (42%; 95% confidence interval [CI], 23% to 63%) demonstrated an objective response, with seven achieving a complete clinical response (CR) (27%; 95% CI, 12% to 48%) and four (15%) a partial response (PR). The median duration of response in the 11 responders is 7+ months (range, 4 to 17), with five responders (four CRs, one PR) remaining progression-free at 5, 6, 10, 12, and 16 months from the start of therapy. The estimated median survival duration for all patients is 8.4 months. Hematologic toxicity consisted of anemia (12% grade 3) and granulocytopenia (4% grade 3, 19% grade 4), with two patients developing granulocytopenic fevers. Nonhematologic toxicity included grade 3 mucositis in 11%, grade 3 neuropathy in 11%, and grade 4 diarrhea in 4%. CONCLUSION: Single-agent paclitaxel at this dosage and schedule is one of the most active single agents in previously untreated patients with advanced urothelial carcinoma, and is well tolerated by this patient population when given with hematopoetic growth factor support.

The surgical lectures of George McClellan.

Although McClellan was the founder of a medical school and professor of surgery, his legacy of written material is pitifully small. Gross observed, "His reputation as a surgeon will be in great measure traditional, for he has left no adequate record of his observations and experience". Through notes such as these, we may develop a picture of the state of medical knowledge, the way in which it was taught and perhaps make inferences about the clinical expertise of Doctor McClellan.

Is prophylactic cranial irradiation indicated in small-cell lung cancer?

Although prophylactic cranial irradiation (PCI) is frequently used in the treatment of patients with limited-extent small-cell lung cancer (SCLC), its role remains controversial. One hundred fourteen SCLC patients with limited disease treated at Indiana University were retrospectively reviewed. Fifty-eight of 114 (51%) patients achieved a complete remission (CR) and were analyzed. Thirty-eight of these 58 CR patients received PCI (+PCI) and 20 of 58 CR patients did not receive PCI (-PCI). Twenty-six of 38 patients who received PCI subsequently relapsed. No patient initially relapsed in the CNS, although one patient had a brain metastasis following recurrence in the chest. Eleven of 38 patients who were treated with PCI survived for longer than 30 months and were considered long-term survivors. Seven of these 11 patients (63%) developed clinically significant neurological toxicity. Sixteen of 20 patients who did not receive PCI relapsed, but there was only one initial relapse in the CNS. Three additional patients who relapsed in the chest subsequently developed CNS metastasis. All responded to palliative radiation with improvement in their symptoms. The high incidence of CNS toxicity in the long-term survivors and the relatively infrequent incidence of isolated CNS recurrent in patients not subjected to PCI raise serious questions concerning the role, if any, of PCI in limited SCLC.

Management of postchemotherapy residual mass in patients with advanced seminoma: Indiana University experience.

Thirty-six patients with advanced seminoma treated with cisplatin combination chemotherapy were evaluated to assess the significance of postchemotherapy residual radiographic mass. All patients had a minimum follow-up of 2 years. Of the 36 patients 21 had an evaluable residual radiographic mass after completion of chemotherapy. Twelve of these patients had a less than 3 cm maximal transverse diameter residual mass, and nine had a greater than 3 cm persistent mass postchemotherapy. Only three of these 21 patients underwent postchemotherapy retroperitoneal lymph node dissection, and the histopathology revealed only necrotic fibrous tissue. The remaining patients were followed by close observation including repeat abdominal computed tomography (CT) every 3 months the first year and every 6 months the second year (or until normal); further therapeutic intervention was given only on evidence of progressive disease. Nineteen of these 21 patients have no evidence of disease, including eight of nine with greater than 3 cm persistent radiographic abnormality. The optimal management for advanced seminoma patients with a persistent radiographic mass postchemotherapy remains unresolved. However, based on this small series, we feel that observation is a viable option, reserving radiotherapy or chemotherapy for those patients who subsequently develop progressive disease.

Ameloblastoma associated with basal cell nevus (Gorlin) syndrome: CT findings.

Multiple jaw cysts are a characteristic manifestation of basal cell nevus (Gorlin) syndrome. In contrast to the frequent odontogenic keratocysts, ameloblastoma only rarely occurs in the jaw. Computed tomography is essential to delineate the extent of these radioresistant lesions, which must undergo marginal resection. We present such a case, not only to stress the importance of CT evaluation but also to briefly review the unusual association of ameloblastoma with Gorlin syndrome.

Serial aortography assesses stability of "atypical" aortic arch ruptures.

The victim of a high speed motor vehicle accident sustained an ascending aortic laceration as well as avulsion of the left subclavian artery. Initial management of the tears was conservative. The case is typical of "atypical" aortic arch tears except that the patient survived without emergent surgery. Serial aortography proved useful in assessing stability of the tears, providing opportunity to observe the natural history of these injuries angiographically. The distribution of aortic arch injuries following blunt trauma is reviewed.

Malignant mesothelioma. The University of Minnesota experience.

Between 1950 and 1981, 31 patients with mesothelioma were treated at the University of Minnesota. An average of 0.2 to 0.6 patients were seen per year between 1950 and 1970, and since 1970 there has been an average of 1.4 to 2.4 patients per year. Twenty-seven of the 28 patients with malignant mesothelioma are known or presumed dead. Mesotheliomas occurred in all areas of Minnesota, and 28.6% of the patients had a definite history of asbestos exposure. This was also a probable cause of the disease in an additional 25% of patients. The clinical findings and course of the disease were similar to other series. The median survival of all patients was eight months. Doxorubicin-treated patients survived a median of 16 months (range, 2-36 months). Malignant mesothelioma is being increasingly recognized in Minnesota and has a grim prognosis in spite of doxorubicin therapy.