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Biomedical subjects

M Burt

Publications and source records attributed to M Burt.

At least 19 recordsLinked to original sources

Difficulty in brainstem death testing in the presence of high spinal cord injury.

In the UK, when the standard brain death criteria are met, further investigations are not necessary. Confirmatory tests can be useful, however, when it is not possible to carry out all of the brainstem tests. We report the case of a patient with multiple trauma and a high spinal cord injury who was apnoeic. Confirmatory tests (EEG, brainstem, auditory evoked potential) were essential in supporting the diagnosis of brainstem death to allow withdrawal of artificial ventilation, as organ donation was being considered.

Brain Death↗

Specific organ gene transfer in vivo by regional organ perfusion with herpes viral amplicon vectors: implications for local gene therapy.

BACKGROUND: Many gene therapy strategies would benefit from efficient, regional organ delivery of therapeutic genes. METHODS: Regional perfusions of lung, liver, or bladder were performed to determine if rapid and efficient gene transfer can be accomplished in vivo, and to determine if in vivo gene transfer can be limited to the organ of interest. In addition, herpes simplex virus tumor necrosis factor (HSVtnf), carrying the human tumor necrosis factoralpha gene was used as a treatment for methylcholanthrene sarcoma in a syngeneic lung metastases model in Fisher rats. RESULTS: A 20-minute perfusion using HSV carrying beta-galactosidase (HSVlac) produced significant expression of this marker gene isolated to the target organs, without organ-specific tissue injury or inflammation. Regional perfusion of organs with HSV carrying the cytokine gene tumor necrosis factor alpha also resulted in high-level local organ production of this cytokine (2851 +/- 53 pg/g tissue in perfused lung versus 0 for the contralateral lung). For the current vector construct, expression of the gene of interest peaked between 2 and 4 days and was undetectable by 2 weeks after perfusion. In animals undergoing perfusion as treatment for pulmonary sarcoma, there was no difference between tumor counts in lungs perfused with HSVlac (17 +/- 6) or HSVtnf (22 +/- 8), but either treatment resulted in lower tumor counts than controls (111 +/- 24 nodules per lung, P <.02). CONCLUSIONS: Regional organ perfusion using herpes viral vectors is an effective and well-tolerated in vivo method of transiently delivering potentially toxic gene products to target organs in directing gene therapy. Regional lung perfusion with HSV amplicons reduces tumor burden in a rat model of pulmonary metastases, though HSVtnf cannot be demonstrated to augment the cytopathic effect of the HSV amplicon alone in the current model.

Animals↗

Evidence-based implementation of free phenytoin therapeutic drug monitoring.

BACKGROUND: The majority of laboratories measure total phenytoin concentration for therapeutic drug monitoring. However, there are substantial interindividual variations in free phenytoin concentrations, the pharmacologically active component. METHODS: We describe the process and data used to implement monitoring of free phenytoin only in an urban medical center. Over a 6-week period, total and free phenytoin concentrations were measured, clinical charts reviewed, and indications for alterations in the percentage of free phenytoin fraction were determined. RESULTS: Of the 189 phenytoin requests from 139 patients, 136 data points were analyzed. Free phenytoin concentrations were 6.8-35.3%, with 50% outside the expected range of 8-12%. Clinical indications likely responsible for variations were hypoalbuminemia, drug interactions, uremia, pregnancy, and age. Overall, 30% of patients demonstrated a discrepancy between therapeutic, subtherapeutic, or supratherapeutic concentrations between free and total phenytoin concentrations. The largest discordance (53%) occurred in the patient group with free phenytoin <8% or >12%. CONCLUSIONS: This study supports previous clinical findings that monitoring total phenytoin is not as reliable as free phenytoin as a clinical indicator for therapeutic and nontherapeutic concentrations. Thus, we recommend that therapeutic monitoring should use free phenytoin concentrations only.

Adolescent↗

Pulmonary metastasectomy for head and neck cancers.

BACKGROUND: Distant metastases from carcinomas that arise from the head and neck region are infrequent. The most common site is the lung. To evaluate the results of resection of pulmonary metastases for head and neck cancers, we reviewed our own cases of these metastases. METHODS: Between November 1966 and March 1995, 83 patients with pulmonary metastases from head and neck cancers underwent 94 thoracic operations. All patients had obtained or had obtainable locoregional control of their primary head and neck cancers. Kaplan-Meier and Cox regression models were used to analyze the prognostic factors for survival after metastasectomy. RESULTS: Median age was 53 years (range, 17-77). Fifty-nine were male and 24 were female. Forty-one patients had squamous cell cancers, and 36 had glandular tumors that consisted mostly of thyroid and adenoid cystic carcinomas. The median disease-free interval from the time of treatment of the head and neck primary cancers to the development of pulmonary metastases was 27 months. Sixty-eight (82%) patients had complete resection. Overall operative mortality rate was 2%. Overall actuarial survival rate after metastasectomy was 50% at 5 years. Patients with glandular tumors had a 5-year survival rate of 64% compared with 34% for patients with squamous cell cancers. When the patients with glandular tumors were analyzed according to their histology, patients with adenoid cystic carcinomas had an 84% 5-year survival, but none remained disease-free. Patients with thyroid cancers fared similarly whether they were treated medically or surgically. On multivariate analysis, the adverse prognostic factors for patients with squamous cell cancers were incomplete resection, age greater than 50 years, and disease-free interval less than or equal to 2 years. CONCLUSIONS: Approximately 30% of patients with pulmonary metastases from squamous cell cancers of the head and neck who underwent complete resection of all their metastases can expect to achieve long-term survival. The role of pulmonary resection for patients with glandular tumors is unclear.

Adenocarcinoma↗

Growth hormone, alone and in combination with insulin, increases whole body and skeletal muscle protein kinetics in cancer patients after surgery.

OBJECTIVE: To investigate the impact of growth hormone, alone and in combination with insulin, on the protein kinetics of patients with upper gastrointestinal (GI) tract cancer who have undergone surgery and are receiving total parenteral nutrition (TPN). SUMMARY BACKGROUND DATA: Patients with malignancies of the upper GI tract are at increased risk for malnutrition and perioperative death and complications. Standard nutritional support has not significantly altered outcome. Growth hormone (GH) and insulin have been shown to have some benefit in patients with cancer; however, their action in patients undergoing resection has not previously been studied. METHODS: Thirty patients undergoing surgery for upper GI tract malignancies were prospectively randomized into one of three nutritional support groups after surgery: 10 patients received standard TPN, 10 received TPN plus daily injections of GH, and 10 received daily GH, systemic insulin, and TPN. The patients underwent a protein kinetic radiotracer study on the fifth day after surgery to determine whole body and skeletal muscle protein kinetics. RESULTS: Patients who received standard TPN only were in a state of negative skeletal muscle protein net balance. Those who received GH and insulin had improved skeletal muscle protein net balance compared with the TPN only group. Whole body protein net balance was improved in the GH and the GH and insulin groups compared with the TPN only group. GH and insulin combined did not improve whole body net balance more than GH alone. GH administration significantly increased serum IGF-1 and GH levels. Insulin infusion significantly increased serum insulin levels and the insulin/glucagon ratio. CONCLUSION: Growth hormone and GH plus insulin regimens improve protein kinetic parameters in patients with upper GI tract cancer who are receiving TPN after undergoing surgery.

Aged↗

Pain at the end of the stem after revision total knee arthroplasty.

A consecutive series of patients undergoing revision total knee arthroplasty was studied prospectively. Clinical and radiographic assessment was performed preoperatively, 6 and 12 months postoperatively, and annually thereafter. Evaluation consisted of a Knee Society clinical score and assessment of patient satisfaction. In addition, patients completed drawings of their lower extremity regarding the location and severity of the pain they experienced preoperatively and at minimum 2-year followup (mean, 36 months; range, 24-48 months). Pain that was localized to the diaphyseal region of the femur or tibia on the drawing was defined as pain at the end of the stem. Clinical, radiographic, and pain drawing data were completed for patients who had 66 of 78 revision total knee arthroplasties performed during the time of the study (85%). All procedures were performed with the same implant system and instrumentation and included fluted cobalt-chrome stems for all patients in whom the stem was implanted without cement and slightly underreamed (press fit). All femoral components had the surface cemented with the stems press fit. Sixteen of the tibial stems were cemented fully, whereas the remaining 50 tibial components were cemented on the surface only with the stems press fit. Localized pain at the end of the stem was present on the femoral side in seven of 66 patients (11%) and in seven of 50 patients with press fit tibial stems (14%). Patients with pain at the end of the stem at 2 to 4 years postoperatively had significantly lower preoperative function scores and overall Knee Society clinical score. Postoperatively, patients with pain at the end of the stem had a significantly lower clinical score; however the postoperative function score and Knee Society clinical score were not significantly different than scores of patients who did not have pain at the end of the stem. There was no correlation between the stem diameter and the occurrence of pain; however, there was a trend for percent canal fill to be higher on the tibial side in patients with pain (71% versus 63%), but this was not statistically significant. Three of the 16 patients with cemented tibial stems (19%) experienced pain at the end of the stem. Patients with press fit stems who had pain at the end of the stem were more likely to express dissatisfaction with the surgical procedure than patients without pain at the end of the stem.

Aged↗

Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin.

Overexpression of P-glycoprotein (Pgp), a multidrug transporter encoded by the MDR1 gene, is associated with chemoresistance in some human solid tumor malignancies. To date, analyses of MDR1 levels in solid tumors have examined constitutive increases in expression at relapse. In the present study, we have evaluated the acute induction of MDR1 gene expression in a solid human tumor as a function of time in response to in vivo exposure to chemotherapy. Five patients with unresectable sarcoma pulmonary metastases underwent isolated single lung perfusion with doxorubicin. Relative MDR1 gene expression was measured in metastatic tumor nodules and normal lung specimens after initiation of chemoperfusion. In four of five patients, a 3-15-fold (median, 6.8) increase in MDR1 RNA levels was detected in tumors at 50 min after administration of doxorubicin. In contrast, normal lung samples had very low levels of MDR1 RNA prior to perfusion, and no acute increases were observed after therapy. These findings demonstrate, for the first time, that MDR1 gene expression can be rapidly activated in human tumors after transient in vivo exposure to cytotoxic chemotherapy.

Adult↗

Primary sarcomas of the mediastinum: results of therapy.

UNLABELLED: Primary sarcomas of the mediastinum are rare, and data concerning treatment and results of therapy are sparse. OBJECTIVE: To assess presentation, management, prognostic factors, and survival in mediastinal sarcomas. METHODS: We reviewed our experience with 47 patients with the diagnosis of primary sarcoma of the mediastinum. Data were collected from a computerized institutional database and medical records. Survival was analyzed by Kaplan-Meier method and comparisons of survival by log rank test. RESULTS: The median age of 47 patients with mediastinal sarcoma was 39 years (range 2.5 to 69 years), with a male/female ratio of 1.6. The most common complaints were chest/shoulder pain (38%) and dyspnea (23%). The most common tumor types were malignant peripheral nerve tumor (26%), spindle cell sarcoma (15%), leiomyosarcoma (9%), and liposarcoma (9%). Operation was the primary treatment modality in 72% of cases (n = 34); 22 sarcomas (47%) were completely resected. The overall 5-year survival was 32%. High-grade lesions had a significantly decreased survival (5-year survival = 27%) compared with low-grade tumors (5-year survival = 66%) (p = 0.05). The overwhelming factor determining survival was the ability to completely resect the tumors (5-year survival 49% for complete resection; 3-year survival 18% for incomplete or no resection) (p = 0.0016). Despite complete resection, local recurrence occurred in 64% of cases. CONCLUSION: Because the overall survival for patients with mediastinal sarcomas is 32% and the local recurrence is 64% for tumors completely resected, aggressive adjuvant therapy should continue to be systematically explored.

Adolescent↗

The total volar forearm musculocutaneous free flap for reconstruction of extended forequarter amputations.

Forequarter amputation is performed for resection of large, invasive tumors of the shoulder girdle region. A substantial defect can usually be closed with local or regional flaps; however, a subset of the forequarter amputation group has emerged at this institution with more complex issues. These patients have extensively more invasive posterior tumors, some with chest wall/rib invasion. Local/regional flaps in these situations are inadequate, and free tissue transfer is the only viable option. The forequarter specimen can sometimes be used as a donor site, thereby eliminating the usual donor site morbidity. Variations of the total forearm free flap have been sparsely described in the literature--the majority being case reports of either pure fasciocutaneous or "filet of forearm" flaps. We report a series of 4 patients treated over a 5 year period at this institution using the previously undescribed total volar forearm musculocutaneous free flap based on the brachial artery and its venae comitantes. This flap includes the entire musculature of the volar forearm with fasciocutaneous extensions on either side of the musculocutaneous unit. All potentially ischemic dorsal musculature is discarded, leaving a flap that has central bulk and a relatively large dimension. The entire flap remains extremely well vascularized, and a substantial surface area of as much as 45 x 25 cm can be attained. A pedicle as long as 20 cm can be dissected as far proximally in the arm as is oncologically safe. A single artery and vein are anastomosed to either the intrathoracic or neck vessels. All four flaps survived completely with uncomplicated wound healing. The total volar forearm musculocutaneous flap is extremely well vascularized and highly reliable. The flap as described provides the ideal combination of large surface area, muscle bulk, and long vascular pedicle. It can be dissected rapidly to minimize ischemic time and could therefore be applicable to traumatic forequarter amputations. It has become the flap of choice for reconstruction of extended oncological forequarter amputation defects.

Adult↗

Prolonged air leak following radical upper lobectomy: an analysis of incidence and possible risk factors.

STUDY OBJECTIVES: To examine the incidence and clinical significance of prolonged air leak (PAL) in patients undergoing radical upper lobectomy and to determine potential risk factors for PAL in this group of patients. DESIGN: Retrospective review of a prospective database. SETTING: Experience of one thoracic surgeon at a tertiary care cancer center. PATIENTS: One hundred consecutive patients undergoing right upper lobectomy and mediastinal lymph node dissection for non-small cell lung cancer over an 11-year period. MEASUREMENTS: PAL was defined as an air leak lasting >7 days. Preoperative, intraoperative, and postoperative clinical data were collected and analyzed to determine the factors associated with PAL. RESULTS: PAL was the most prevalent postoperative complication, comprising 25.5% of all complications seen, and lasting an average of 12.1+/-5.3 days. In 21 of the 26 patients with PAL, this complication was the only morbidity identified. There was no statistically significant difference in patient age, gender, preoperative FEV1 and diffusion of carbon monoxide, exposure to neoadjuvant chemotherapy, status of pulmonary fissures, or pathologic stage between the PAL group vs the remaining 74 patients without this complication. A significantly greater proportion of patients with PAL had FEV1/FVC ratio < or =50% (6/26 vs 5/74; p=0.02). Patients with PAL had significantly longer median length of hospital stay (11 vs 7 days; p=0.0001). Moreover, PAL was the single most common reason for an extended length of hospitalization (21/58, 36% of all causes). CONCLUSION: PAL is an alarmingly common postoperative complication and is the most frequent cause of an extended length of hospital stay in patients undergoing radical upper lobectomy. Severe obstructive pulmonary disease predisposes patients to the development of this complication.

Adult↗

Medical and surgical management of pulmonary metastases from germ cell tumors.

GCT is considered a curable tumor with a greater than 90% overall long-term survival. Pulmonary metastasis is common in patients with disseminated disease. First-line therapy in the management of patients with pulmonary metastases from germ cell tumors is cisplatin-based chemotherapy. Pulmonary metastasectomy has an important adjuvant role in a subset of patients who have residual radiographic abnormalities or progression of disease despite optimal chemotherapy. Surgical resection of residual pulmonary and mediastinal disease provides an accurate response assessment and consolidates the chemotherapy by removal of any viable GCT. Therefore, surgical resection of all residual masses is indicated in patients with NSGCT and normalized serum value of tumor markers after definitive systemic chemotherapy. Surgical resection or biopsy is a reasonable alternative in residual seminoma > or = 3 cm in diameter.

Antineoplastic Agents↗

Isolated lung perfusion with antineoplastic agents for pulmonary metastases.

Lung metastases is a major cause of death in cancer patients. A technique of isolated lung perfusion that uses infusions of high doses of local chemotherapy was developed in an attempt to control local disease. This technique prevents systemic side effects. Animal experiments have been encouraging and human trials are pending.

Animals↗

Glutathione metabolism in patients with non-small cell lung cancers.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Because NSCLC is highly chemoresistant, it is, usually not treatable. Altered glutathione (GSH) metabolism is thought to be one major mechanism of chemoresistance, and GSH levels are reported to be elevated in NSCLC. The main objective of this study is to delineate the potential mechanisms involved in elevation of tissue GSH, including extraction from the circulation by NSCLC. Twenty consecutive patients with NSCLC were enrolled. At the time of lobectomy, pulmonary artery and vein were identified, and blood flow was measured by an electromagnetic probe. Subsequently, blood samples were drawn from pulmonary artery, the vein draining the tumor-bearing lobe, and a normal lobe. Immediately after lobectomy, tumor and lung specimens were snap frozen. NSCLC tumor specimens had higher levels of GSH compared with lung tissue (20.8 +/- 9.4 versus 11.6 +/- 3.0 nmol/mg protein, respectively; P < 0.05). The tumor demonstrated higher activity of the enzyme gamma-glutamyl transpeptidase, a membrane-bound enzyme involved in transmembrane uptake of GSH, than lung tissue (41.9 +/- 26.4 versus 22.4 +/- 12.3 units/mg protein, respectively; P < 0.05). Also, the tumor-bearing lobe showed elevated extraction of GSH and two of its component amino acids compared with lung tissue (GSH uptake: 0.60 +/- 0.67 versus 0.20 +/- 0.40 microM/min, respectively; P < 0.05). NSCLC tumors are able to extract circulating GSH and its constituent amino acids to synthesize intracellular GSH. Increased activity of gamma-glutamyl transpeptidase may be one mechanism underlying increased GSH uptake by NSCLC.

Carcinoma, Non-Small-Cell Lung↗

Regression of uterine low-grade smooth-muscle tumors metastatic to the lung after oophorectomy.

BACKGROUND: Metastatic uterine low-grade smooth-muscle tumors may present with pulmonary symptoms and radiographic lung abnormalities consistent with metastatic neoplasms. Ovarian hormone stimulation of these smooth-muscle tumors has been suggested, but the role of surgical or medical oophorectomy has not been established in patients with metastatic disease. CASES: Two women with histologically confirmed uterine low-grade smooth-muscle tumors metastatic to the lung had progressive and complete tumor regression after oophorectomy and no further therapy. CONCLUSION: Some uterine low-grade smooth-muscle tumors metastatic to the lung regress after oophorectomy. Removing ovarian hormone stimulation may result in complete tumor regression without the need for further therapy.

Adult↗

Promising survival with three-dimensional conformal radiation therapy for non-small cell lung cancer.

PURPOSE: Local failure is a major obstacle to the cure of locally advanced non small-cell lung cancer. Three-dimensional conformal radiation therapy (3-DCRT) selects optimal treatment parameters to increase dose to tumor and reduce normal tissue dose, potentially representing an enhancement of the therapeutic ratio of radiation therapy for lung cancer. We performed this analysis of 45 non-small cell lung cancer patients treated with 3-DCRT alone, to evaluate the ability of computer derived lung dose volume histograms to predict serious pulmonary toxicity, to assess the feasibility of this approach, and to examine the resulting survival. METHODS: There were 28 males (62%) and 17 females (38%). The median age was 65 (range: 38-82). Tumor stage was Stage I/II in 13%, IIIa in 42%, and IIIb in 44%. The histology was squamous in 44%, adenocarcinoma in 36%, and other non-small cell histologies in the others. Only 47% of patients. had combined favorable prognostic factors (i.e. KPS < or = 80, and < or = 5% wt. loss). The median dose of radiation to gross disease was 70.2 Gy (range: 52.2-72 Gy) delivered in fractions of 1.8 Gy, 5 days per week. RESULTS: Seven patients did not complete 3-DCRT due to disease progression outside the port. Follow-up data are mature: the median follow up of the 6 survivors is 43.5 months (35-59). Thoracic progression occurred in 46%. Median survival (all 45 patients.) is 15.7 months and survival is 32% at 2 years and 12% at 59 months. Pulmonary toxicity > or = grade 3 occurred in 9% of patients. Dose volume histograms were available in 31 patients and showed a correlation between risk of pulmonary toxicity and indices of dose to lung parenchyma. Grade 3 or higher pulmonary toxicity occurred in 38% (3/8) of patients with > 30% of lung volume receiving > or = 25 Gy, versus 4% (1/23) of patients with < or = 30% lung receiving > or = 25 Gy (P = 0.04). Grade 3 or higher pulmonary toxicity occurred in 29% (4/14) of patients with a predicted pulmonary normal tissue complication probability of 12% or higher versus 0% (0/17) in patients with a predicted probability of less than 12% (P = 0.03). CONCLUSIONS: Despite adverse prognostic criteria median survival is encouraging and may be higher than some combined modality approaches. Dose volume histogram parameters may be useful to determine the maximum dose for individual patients and thereby permit avoidance of toxicity.

Adult↗

The effects of endobronchial cuff inflation on double-lumen endobronchial tube movement after lateral decubitus positioning.

OBJECT: This study was designed to measure changes in tracheal and bronchial lumen distances from mainstem and secondary carina with lateral positioning, and to assess whether inflation of the endobronchial cuff before lateral positioning would further secure a double-lumen endobronchial tube (DLT) and reduce movement. DESIGN: Prospective study. SETTING: University-affiliated cancer center. PARTICIPANTS: Fifty adult patients scheduled for elective thoracic surgical procedures requiring the placement of a left DLT. INTERVENTIONS: Patients were sequentially assigned to either the endobronchial cuff-inflated group or the deflated group during lateral positioning. After induction of general anesthesia, a left polyvinylchloride (PVC) DLT was placed and the position confirmed. In the supine position, the distance from the tip of the tracheal lumen to main carina was measured using a fiberoptic bronchoscope (FOB) passed through the tracheal lumen, and the distance from the bronchial lumen to secondary carina was measured with the FOB passed through the bronchial lumen. The patients were then positioned laterally and a second set of measurements taken. Overall movement was determined by increases and decreases in tracheal and bronchial distances obtained by substracting supine values from lateral values. MEASUREMENTS AND MAIN RESULTS: There was significant tracheal movement in 40 of 50 patients, with a mean of 0.92 +/- 1.0 cm. This was predominantly in the upward direction, as seen in 35 of 50 patients. There was significant bronchial movement in 37 of 50 patients, with a mean of 0.92 +/- 1.15 cm. Also, predominance in the upward direction was seen in 34 of 50 patients. CONCLUSIONS: DLTs move with lateral positioning, regardless of endobronchial cuff inflation. The movement is predominantly in the upward direction. Therefore, fiberoptic visualization in the supine position should be used only to confirm that the endobronchial lumen is placed on the appropriate side and the cuff is at least 1 cm inside the left mainstem bronchus. Final positioning should always be verified in the lateral position.

Adult↗