Biomedical subjects
Publications and source records attributed to P Boland.
The usefulness of a nested PCR assay for detection of Aspergillus sp. DNA was evaluated in 177 bronchoalveolar lavage (BAL) fluid specimens. This test was accurate both to diagnose culture-negative BAL fluid specimens from patients with invasive pulmonary aspergillosis and to confirm culture-positive samples. However, it did not differentiate between infection and colonization.
STUDY DESIGN: Retrospective review of prospectively maintained institutional spine database. OBJECTIVES: To assess the pain, neurologic, and functional outcome of patients with metastatic spinal cord compression using a posterolateral transpedicular approach with circumferential fusion. SUMMARY OF BACKGROUND DATA: Patients with spinal metastases often have patterns of disease requiring both an anterior and posterior surgical decompression and spinal fusion. For patients whose concurrent illness or previous surgery makes an anterior approach difficult, a posterior transpedicular approach was used to resect the involved vertebral bodies, posterior elements, and epidural tumor. This approach provides exposure sufficient to decompress and instrument the anterior and posterior columns. METHODS: During the past 15 months, 25 patients were operated on using a posterolateral transpedicular approach. The primary indications for surgery were back pain (15 patients) and neurologic progression (10 patients). All patients had vertebral body disease, and 21 patients had high-grade spinal cord compression from epidural disease as assessed by magnetic resonance imaging. Seven patients underwent preoperative embolization for vascular tumors. In each patient, the anterior column was reconstructed with polymethyl methacrylate and Steinmann pins and the posterior column with long segmental fixation. RESULTS: All patients achieved immediate stability. Pain relief was significant in all 23 patients who had had moderate or severe pain. Neurologic symptoms were stable or improved in 23 patients. One patient with an acutely evolving myelopathy was immediately worse after surgery, and one patient had a delayed neurologic worsening, progressing to paraplegia. CONCLUSIONS: The posterolateral transpedicular approach provides a wide surgical exposure to decompress and instrument the anterior and posterior spine. This technique avoids the morbidity associated with anterior approaches and provides immediate stability. Vascular tumors may be removed safely after embolization. Patients can be mobilized early after surgery.
OBJECTIVE: To determine the safety of polygeline, a gelatine-derived plasma substitute produced from bovine bones, in terms of safety for bovine spongiform encephalopathy (BSE) by evaluating the ability of the manufacturing process of polygeline to eliminate agents related to transmissible spongiform encephalopathy (TSE) through the validation of three main production steps. DESIGN: Laboratory scale experimental process (in duplicate) using 20% hamster-adapted 263K scrapie-infected brain homogenate as infective titrated source (10(9) LD50/2 ml), added to each material before being processed and titrated in hamsters. Experiment 1: time/temperature dependency of gelatine autoclaving. Experiment 2: cross-linking and distillation. Experiment 3: final sterilization. Monitoring period: 1 year with daily animal clinical observation. Histology of all brains. SETTING: LCG-RBM laboratories, Italy; strict GLP compliance. MEASUREMENTS AND RESULTS: Heating the gelatine (at conditions lower than those used in production process) was very effective in inactivating the infectivity of TSE agents. Clearance factors were reproducible, dependent upon time and temperature, reaching a total theoretical process clearance in the range of 9.2-13.8 [6.9 + 2.3 (+ 4.6)] log10 LD50. CONCLUSIONS: These experimental results provide further important data confirming the safety of the procedural steps; this complements the safety due to the careful sourcing of the raw material. There is high assurance that there is no significant risk of TSE transmission to humans by the therapeutic administration of polygeline.
BACKGROUND: The treatment of superior sulcus lung cancers is evolving and preoperative chemotherapy is increasingly used. To establish a historical benchmark against which new therapies can be assessed, we reviewed our 24-year experience with patients undergoing thoracotomy for lung cancers of the superior sulcus. METHODS: Data were acquired through retrospective chart review. Overall survival was calculated by the method of Kaplan and Meier, and prognostic factors were examined by log rank and Cox proportional hazards modeling. RESULTS: From 1974 to 1998, 225 patients underwent thoracotomy. The patients included 144 men (64%) and 81 women with a median age of 55 years. The majority of patients (55%) received preoperative radiation, but 35% did not have any preoperative treatment. Tumor stages were IIB (T3 N0) in 52%, IIIA in 15%, and IIIB in 27% of patients. Complete resection was achieved in 64% of T3 N0 tumors, 54% of T3 N2 tumors, and 39% of T4 N0 tumors. Operative mortality was 4%. Median survival was 33 months for stage IIB and 12 months for both stages IIIA and IIIB. Actuarial 5-year survivals were 46% for stage IIB, 0% for stage IIIA, and 13% for stage IIIB. By univariate and multivariable analyses, T and N status and complete resection had a significant impact on survival. Locoregional disease was the most common form of relapse. CONCLUSIONS: Our results provide a benchmark against which new treatment regimens can be evaluated. Control of locoregional disease remains the major challenge in treating lung cancers of the superior sulcus. The potential benefit of preoperative chemotherapy or chemoradiotherapy must be assessed by whether it leads to higher rates of complete resection and a lower risk of local relapse.
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In contrast with the prevailing view that most tumors and metastases begin as avascular masses, evidence is presented here that a subset of tumors instead initially grows by coopting existing host vessels. This coopted host vasculature does not immediately undergo angiogenesis to support the tumor but instead regresses, leading to a secondarily avascular tumor and massive tumor cell loss. Ultimately, however, the remaining tumor is rescued by robust angiogenesis at the tumor margin. The expression patterns of the angiogenic antagonist angiopoietin-2 and of pro-angiogenic vascular endothelial growth factor (VEGF) suggest that these proteins may be critical regulators of this balance between vascular regression and growth.
We evaluated the AxSYM immunoassay for the quantification of cardiac troponin I (cTnI). Total assay imprecision, expressed as coefficient of variation, ranged between 5.6% and 8.3% for commercial control serum samples and between 4.2% and 13.9% for pooled patient samples. Linearity was verified up to 42 micrograms/L. Triglycerides (up to 1,000 mg/dL) did not interfere with the assay, but minor hemolysis and clinically relevant hyperbilirubinemia caused a negative bias. In 186 patient samples, AxSYM cTnI levels correlated significantly with data obtained with the Stratus II cTnI fluorometric enzyme immunoassay but were 3 to 4 times higher on AxSYM than on Stratus II. In 111 healthy blood donors, the reference range for cTnI levels on AxSYM was 0.0 to 0.4 microgram/L. After eccentric isokinetic exercise, healthy volunteers showed a rise in creatine kinase MB mass (AxSYM) but not in cTnI. On AxSYM and Stratus II, cTnI levels increased above the manufacturer's cutoff for acute myocardial infarction in all 17 patients followed up after onset of infarction-related chest pain but in only 1 of 91 control subjects. The AxSYM cTnI assay is a valid alternative for the detection of myocardial injury with diagnostic performance comparable to the established Stratus cTnI assay.
Metastases to the spine represent a challenging problem in an oncology practice. Treatment decisions require multidisciplinary review. Radiation therapy remains the primary treatment for metastatic spinal tumor, but advances in radiation therapy, chemotherapy, and surgery have changed the roles of each and lead to improved patient outcomes. Regardless of the treatment, diagnosis and treatment before the development of significant neurologic and functional deficits improve outcomes. Physician awareness and appropriate imaging greatly assist in the early detection of tumor.
Complications are common among patients treated for malignant lesions of the proximal tibia and can be difficult to manage. This investigation was a retrospective review of 40 patients treated with total knee replacements after proximal tibial resections. Various reconstructive methods were used to fix the prosthetic stems, reestablish the extensor mechanism, and provide soft tissue coverage. Thirty-one patients had adequate followup to allow for review of prosthetic outcome (means, 78 months; range, 25-193 months). Seven patients died with less than 2 years followup, and two patients had postoperative acute infections treated by early amputation to allow chemotherapy to resume promptly. The overall 5-, 8-, and 12-year event free prostheses survival rates were 62%, 33%, and 16%, respectively. Prognostic factors for prosthetic survival were analyzed (age, gender, type of excision, type of prosthesis, type of fixation, and percent of bone resected). None were statistically significant. Patients with less than 40% of the tibia resected had better prosthetic survival at 5 years. The durability of uncemented stem fixation exceeded that of cemented stems. Expected survival of prostheses after revision was 52% at 8 years. The major cause of limb loss was infection. Failure to reconstruct soft tissues satisfactorily caused most failures. Aggressive multistage management of infection is needed. Prosthetic knee replacement is most suitable for patients with cancers that require chemotherapy and for those patients who have short potential survival.
Preoperative identification of intraatrial tumor is uncommon. A 23-year-old woman presented with local recurrence and pulmonary metastases after previous resection of a clavicular sarcoma. Evaluation by computed tomography revealed bilateral pulmonary masses. Due to the size and proximal location, magnetic resonance imaging and transesophageal echocardiography were performed, revealing a large intraatrial mass. She then underwent staged surgical excision without intraoperative complications. We summarize this case and review risk factors for intracardiac extension and prevention of tumor emboli.
Capitation creates a financial incentive to deliver care in the most appropriate setting. All major stakeholders in the health care industry (plan members, employers, practitioners, delivery systems, community organizations, and the government) share a common interest in managing risk sooner and better. Capitation can be a catalyst that encourages and reinforces this commonalty of purpose.
All managed care stakeholders--health plan members, employers, providers, community organizations, and government entitites--share a common interest in reducing healthcare costs while improving the quality of care health plan members receive. Although capitation is a usually thought of primarily as a payment mechanism, it can be a powerful tool providers and health plans can use to accomplish these strategic objectives and others, such as restoring and maintaining the health of plan members or improving a community's health status. For capitation to work effectively as a strategic tool, its use must be tied to a corporate agenda of partnering with stakeholders to achieve broader strategic goals. Health plans and providers must develop a partnership strategy in which each stakeholder has well-defined roles and responsibilities. The capitation structure must reinforce interdependence, shift focus from meeting organizational needs to meeting customer needs, and develop risk-driven care strategies.
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Health care reengineering is a powerful methodology that helps organizations reorder priorities, provide more cost-effective care, and increase value to customers. It should be driven by what the customer wants and what the market needs. Systemwide reengineering integrates three levels of activity: managing community and health plan partnerships; consolidating overlapping delivery system functions among participating providers and vendors; and redesigning administrative functions, clinical services, and caregiving programs to improve health status. Reengineering is not a panacea; it is a critical core competency and requisite skill for health care organizations if they are to succeed under managed care in the future.
Nerve growth factor and other neurotrophins signal to neurons through the Trk family of receptor tyrosine kinases. TrkB is relatively promiscuous in vitro, acting as a receptor for brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT4) and, to a lesser extent, NT3 (refs 3-5). Mice lacking TrkB show a more severe phenotype than mice lacking BDNF, suggesting that TrkB may act as a receptor for additional ligands in vivo. To explore this possibility, we generated mice lacking NT4 or BDNF as well as mice lacking both neurotrophins. Unlike mice lacking other Trks or neurotrophins, NT4-deficient mice are long-lived and show no obvious neurological defects. Analysis of mutant phenotypes revealed distinct neuronal populations with different neurotrophin requirements. Thus vestibular and trigeminal sensory neurons require BDNF but not NT4, whereas nodose-petrosal sensory neurons require both BDNF and NT4. Motor neurons, whose numbers are drastically reduced in mice lacking TrkB, are not affected even in mice lacking both BDNF and NT4. These results suggest that another ligand, perhaps NT3, does indeed act on TrkB in vivo.
PURPOSE: To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV). PATIENTS AND METHODS: This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients < 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/microL and platelet counts reach 100,000/uL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy. RESULTS: Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy. CONCLUSION: Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.
Adult motor neurons, like their immature antecedents, express the mRNA for the signaling receptor for brain-derived neurotrophic factor (BDNF) and for neurotrophin-4/5 (NT-4/5). However, while both BDNF and NT-4/5 support the survival of axotomized developing spinal motor neurons in vitro or in vivo, it is not known whether these factors continue to influence spinal motor neurons in adulthood. The present study tests if BDNF or NT-4/5 modulate the reactive responses of adult spinal motor neurons to nerve injury. We utilize sciatic nerve transection to axotomize the spinal motor neurons that form the retrodorsal lateral nucleus (RDLN) and show that, after axotomy, RDLN motor neurons lose ChAT immunoreactivity and also reexpress p75Ingfr, the low affinity receptor for all neurotrophin family members. Treatment with BDNF or NT-4/5 alters these effects of sciatic nerve transection. Both BDNF and NT-4/5 attenuate the loss of ChAT expression in axotomized RDLN motor neurons; thus, as compared to vehicle treatments, BDNF and NT-4/5 produce statistically significant increases in the optical density of ChAT immunostaining. Furthermore, BDNF and NT-4/5 also significantly increase the RDLN reexpression of p75Ingfr after sciatic nerve transection. Interestingly, essentially identical increases in RDLN ChAT and p75Ingfr immunostaining are produced by sciatic nerve crush injuries in the absence of exogenous neurotrophin treatment. These data show that treatment with exogenous BDNF and NT-4/5 changes the response of adult spinal motor neurons to sciatic nerve transection. Furthermore, these neurotrophins elicit reactive responses in axotomized motor neurons that mimic those produced by endogenous agents in regenerating crushed peripheral nerve.
It is not too late for managed care to turn this situation around because the debate over health care reform and managing change is ongoing. It remains to be seen whether managed care companies will support independent third parties (i.e., researchers) in analyzing proprietary data and making value judgments about their effectiveness. There is a perception among managed care organizations that potentially negative findings could damage them in the marketplace. Nonetheless, smart organizations use negative findings as new opportunity targets for service improvement and product refinement. To what extent will managed care companies voluntarily release accurate data on performance factors in order for researchers to conduct cross-company analyses? Perhaps competitive markets such as managed care are not consistent with voluntary data sharing. On the other hand, mandatory reporting will not ensure data accuracy either. It is up to the managed care industry itself to develop a cooperative approach to data collection, analysis, and dissemination.