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Biomedical subjects

D Tyler

Publications and source records attributed to D Tyler.

At least 19 recordsLinked to original sources
PubMed2003

Carcinoid tumors of the gastrointestinal tract. A review and the Duke University institutional overview.

Carcinoid tumors are relatively rare neoplasms arising from the amine precursor uptake and decarboxylation (APUD) cells of the gastrointestinal tract and bronchial tree. Presenting symptoms vary by site of origin, and various modalities may be used to diagnose them. Initial treatment is surgical, with procedure depending upon site of origin. Several experimental therapies may be used in treatment of metastatic carcinoid tumors.

Antineoplastic Agents↗
PubMed2002

Changes in soil quality and below-ground carbon storage with conversion of traditional agricultural crop lands to bioenergy crop production.

Berm-isolated (0.5 ha) plots have been used since 1995 to quantify changes in soil and water quality with conversion from agricultural to bioenergy crops. Soil quality improvements, including increases in soil carbon storage, have occurred on sites planted to woody or herbaceous species, and no-till corn compared with tilled corn or cotton. Initial increases in soil carbon occurred within the upper 10 cm of the soil profile. Soil carbon on plantings of switchgrass, no-till corn, and sweetgum with a cover crop between the rows increased over the first 3 years. Soil carbon decreased by 6% on the sweetgum plantings without a cover crop and remained lower through the fifth growing season. Overall, the greatest increases in below ground carbon storage have occurred primarily within the upper 40 cm. Former land use, growth characteristics, management practices, and soil characteristics appear to be the primary factors determining the timing, depth. and extent of changes in soil carbon storage for bioenergy and no-till crops.

Agriculture↗
PubMed2002

Improved clean-up for the determination of lasalocid in 'difficult' food matrices.

Methodology has been developed for the determination of lasalocid in analytically 'difficult' matrices such as processed and spiced foods. The procedure was based on an existing silica-based solid-phase extraction (SPE) clean-up to which was added a novel NH2 SPE step before HPLC with fluorescence detection. Use of the additional step enabled the determination of lasalocid in matrices such as baby food, meat pies ('pasties'), etc. Analysis of these matrices was not possible using the standard clean-up on its own. Chromatography showed a massive reduction in the amount of co-extractives and interferences. Validation data were obtained down to the 10-40 mg kg(-1) level for a range of products. Recoveries ranged from 74% at 10 microg kg(-1) for pork sausages to 96% at 40 microg kg(-1) for meat pies.

Animals↗
PubMed2001

Intracranial metastatic parathyroid carcinoma: case report.

OBJECTIVE AND IMPORTANCE: Parathyroid carcinoma is a rare entity, and fewer than 200 cases have been described. It is a slowly progressive disease characterized by frequent recurrences and local metastases. Most patients with parathyroid carcinoma die from metabolic complications of hyperparathyroidism. Five-year survival rates range from 25 to 50%. Functional parathyroid carcinoma is a rare cause of hyperparathyroidism that affects only 0.32 to 5% of all patients who undergo surgery for hypercalcemia. A review of the literature revealed only one other reported case of metastatic intracranial parathyroid carcinoma, in a patient who experienced local recurrence and metastatic disease when she was diagnosed with an intracranial lesion. CLINICAL PRESENTATION: We report the case of a 44-year-old African-American man with recent-onset, right lower-extremity weakness and hypercalcemia 4 years after he underwent a parathyroidectomy for parathyroid carcinoma. At presentation, his parathyroid level was 467 pg/ml, and his serum calcium level was 15.2 mg/dl. Imaging studies revealed an isolated enhancing left mesial frontoparietal mass. A systemic Cardiolite study demonstrated a single focus of radiotracer uptake in this region. No abnormal uptake was demonstrated in the neck or elsewhere. INTERVENTION: The patient underwent a frameless stereotactic interventional magnetic resonance imaging-guided resection via a parasagittal interhemispheric approach. Pathological findings were consistent with parathyroid carcinoma. After resection, his right lower-extremity weakness and secondary hyperparathyroidism resolved. CONCLUSION: The typical natural history of parathyroid carcinoma concludes with death from complications of hyperparathyroidism. This case report supports aggressive surgical management to eliminate all parathyroid hormone-secreting malignant tissue and prevent metabolic complications. In this patient, intraoperative magnetic resonance imaging was helpful to ensure complete resection.

Adult↗
PubMed2000

A pilot study of preoperative continuous infusion 5-fluorouracil, external microwave hyperthermia, and external beam radiotherapy for treatment of locally advanced, unresectable, or recurrent rectal cancer.

PURPOSE: To determine the feasibility of combining external beam radiotherapy, continuous infusion 5-fluorouracil (5-FU), and external microwave hyperthermia in patients with locally advanced, unresectable, or recurrent adenocarcinoma of the rectum. METHODS AND MATERIALS: From 7/95 through 2/99, 15 patients were enrolled in the study. The treatment regimen consisted of continuous infusion 5-FU 250 mg/m(2)/d 7 days/week beginning on day 1, external beam radiotherapy to the pelvis, 4500 cGy, 180 cGy/d 5 days/week using a 3 or 4-field technique, and external microwave hyperthermia on days 3, 8, 15, 22, and 29. Chemotherapy was stopped on the last day of radiotherapy. Surgical resection, if feasible, was scheduled 3-6 weeks after completing thermochemoradiotherapy. For this regimen to be considered feasible, no more than 2 of the 15 patients should fail to complete therapy due to life-threatening toxicity. Toxicity was scored using National Cancer Institute Criteria. RESULTS: All patients completed the chemoradiotherapy portion of the protocol. Eleven of the 15 patients completed all 5 hyperthermia treatments. Of the 4 patients who did not receive the full course of hyperthermia, only 1 patient had treatment stopped due to life-threatening toxicity. The other 3 patients did not complete hyperthermia due to scheduling errors (n = 2) or patient request (n = 1). Five of 15 patients required a treatment interruption due to toxicity > or = Grade 3. Seven patients experienced lesser degrees of toxicity which did not require treatment interruption. Three patients experienced no side effects. The most common toxicities were dermatitis and diarrhea. Of the 14 patients in whom surgery was planned, 11 (79%) were resectable. There was one pathologic complete response. CONCLUSIONS: It is feasible to deliver thermochemoradiotherapy, as prescribed in this study, to patients with locally advanced, unresectable, or recurrent rectal cancer. The therapy is moderately toxic, with one-third of patients requiring temporary treatment interruptions. The regimen appears active against rectal cancer, and appears to warrant further consideration as a treatment option for this patient population.

Adult↗
PubMed2000

Analysis of prognosis and disease progression after local recurrence of melanoma.

BACKGROUND: Local recurrence of melanoma is associated with a grave prognosis. However, the characteristics and the mode of disease progression for patients with local recurrence have not been adequately addressed in the literature. METHODS: A retrospective analysis of patients treated at a single institution revealed a subset of patients (n = 648) with local recurrence of melanoma as a first event. Patient characteristics, histologic determinants, and disease free interval were variables used to identify prognostic factors. RESULTS: In this group of patients, male gender (P = 0. 0163), increasing age (P = 0.0001), head and neck primaries (P = 0. 0001), thicker Breslow depths (P = 0.0022), deeper Clark levels (P = 0.0010), and ulceration of the primary tumor (P = 0.0348) suggested a shorter time until local recurrence. Breslow depth (P = 0.0004), Clark level (P = 0.0043), and ulceration (P = 0.0001) still factored into the survival prognosis after recurrence. Truncal primaries (P = 0.0005) and shorter disease free intervals (P = 0.0098) were also associated with poorer outcomes after recurrence. Of the 648 patients, 124 showed no progression, 196 developed another local recurrence, 178 developed in-transit/lymph node metastases, and 150 had systemic recurrences. Survival was only 33.6% for patients with further metastases, compared with 77.4% for patients with no progression of disease after a median follow-up of 38.9 months. CONCLUSIONS: There was a 48.5% mortality rate at 5 years of follow-up after local recurrence. Long term survival (> 10 years) was estimated to be 34.9%. The patterns of failure after local recurrence suggest that patients may benefit from aggressive locoregional therapy.

Aged↗
PubMed1999

Recurrent ductal carcinoma in situ after total mastectomy.

A case report is presented of a woman with recurrent DCIS occurring several years following a total mastectomy, the diagnosis of which was aided by a subpectoral saline implant. A discussion of factors associated with recurrence and a review of the literature is provided. A role for selective use of mammography in screening postmastectomy reconstructed breasts in patients at high risk for recurrence is suggested.

Adult↗
PubMed1999

Interventional MRI-guided stereotactic aspiration of acute/subacute intracerebral hematomas.

Surgical interventions for hypertensive intracerebral hematomas are still controversial. Many believe only hyperacute intervention is of any real utility. The majority of present interventions require a formal craniotomy with standard neurosurgical techniques. There are, however, a few reports on CT-guided stereotactic aspiration of these hematomas with favorable results. We report 10 patients treated with frameless fiduciless stereotactic means using an intraoperative MRI scanner (GE 0.5 T Signa SP). These patients were initially diagnosed as having hypertensive intracerebral hematoma and operated on within 1-34 days after hemorrhage. The actual operating time averaged less than 120 min, including intraoperative imaging. Clot volumes ranged from 2.5 to 75 cm(3) with a mean of 31 cm(3). There were 2 thalamic hematomas and 8 basal gangliar hematomas. Three patients had intraventricular hematoma extension and all 3, as well as an additional patient, required extraventricular drainage. However, no patients required permanent posthemorrhage ventriculoperitoneal shunting. Aspiration was successful in all cases to 70-90% of clot removal. Two cases utilized intrahematoma t-PA infusion with subsequent 80-90% clot removal. There were no complications or rehemorrhages. All patients showed some form of improvement that included either improved blood pressure control, speech or cognitive abilities. We conclude that using an intraoperative MRI scanner to perform frameless, fiduciless stereotactic aspiration of acute/subacute intracerebral hematoma is a safe and potentially effective means of treating intracerebral hematomas.

Acute Disease↗
PubMed1999

Timing of sentinel lymph node mapping after lymphoscintigraphy.

BACKGROUND: Sentinel lymph node (SLN) mapping is an effective technique for staging patients with melanoma. In an attempt to avoid reinjection of radiolabeled colloid and facilitate SLN mapping at the time of surgery, we examined whether residual radioactivity from preoperative lymphoscintigraphy could be used to accurately identify SLNs during surgery 18 to 24 hours later. METHODS: Forty-six patients with newly diagnosed melanoma underwent injection of 0.22-micron filtered technetium 99m-labeled sulfur colloid followed by lymphoscintigraphy. Patients returned the next day for SLN biopsy with Isosulfan blue dye and the hand-held gamma-probe to identify SLNs. Thirty of 46 patients underwent repeat imaging before operation. No patient had reinjection of radiocolloid. RESULTS: Ninety-five SLNs were identified on initial lymphoscintigraphy, and repeat imaging on the day of surgery confirmed all SLNs previously identified. A total of 122 SLNs (2.65 per patient) were resected from 58 basins. Eighty-four (69%) of 122 SLNs stained blue, and 118 (97%) of 122 SLNs had in vivo gamma-counts greater than 4 times background. Microscopic metastases were present in 13 (10.7%) of 122 SLNs in 12 (26.1%) of 46 patients. There have been no recurrences over a mean follow-up time of 320 days. CONCLUSIONS: Intraoperative gamma-probe detection combined with blue dye injection is highly effective in identifying SLNs 18 to 24 hours after injection of 0.22-micron filtered 99mTc-sulfur colloid. Reinjection of radiocolloid is not required. This technique avoids radiopharmaceutical administration in the operating room, minimizes radiation exposure, and increases scheduling flexibility.

Adult↗
PubMed1998

Diagnosis of pancreatic carcinoma: role of FDG PET.

OBJECTIVE: The purpose of this study was to investigate the role of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in differentiating benign from malignant disease in patients with possible pancreatic malignancy. SUBJECTS AND METHODS: All patients with a possible diagnosis of pancreatic carcinoma based on CT or ERCP findings were eligible for inclusion in this prospective study. PET imaging of the abdomen was performed in 37 patients and was interpreted as positive if FDG activity in the pancreas exceeded background activity and as negative if activity was less than or equal to background activity. Semiquantitative analysis was performed by calculating a standardized uptake ratio. Studies were reviewed independently by two radiologists, and results were correlated with biopsy results and with CT and ERCP findings. Sensitivity and specificity of FDG PET for revealing pancreatic malignancy was determined. RESULTS: FDG activity in the pancreas was increased in 24 patients, and adenocarcinoma was diagnosed in 22 of these patients (92%). Two patients (8%) with increased activity had benign disease, including one patient with chronic pancreatitis who showed no evidence of tumor at laparotomy and one patient with a mucinous cystic tumor who showed no malignant features at laparotomy. FDG uptake was low or normal in 13 patients, 10 of whom (77%) had benign disease. FDG uptake was also low in three patients with adenocarcinoma, whose tumor size ranged from 2 to 4 cm in diameter. The mean standardized uptake ratio value for malignant disease was 5.1 (range, 1.0-10.1) and for benign disease was 1.9 (range, 0.0-5.8) (p < .001). The sensitivity of FDG PET for revealing malignant disease in the pancreas was 88% and the specificity was 83%. CONCLUSION: FDG PET is a sensitive and specific noninvasive technique for the diagnosis of pancreatic malignancy.

Adenocarcinoma↗
PubMed1998

Mucosal melanoma of the female genitalia: a clinicopathologic study of forty-three cases at Duke University Medical Center.

BACKGROUND: Mucosal melanoma of the female genitalia is a rare neoplasm. Only nine reports reviewing more than 40 patients have been published on this subject in the past 30 years. These lesions arise from melanocytes, which can be found within the mucosa lining the female genital tract. Surgical resection is the mainstay of therapy, with little use for other modalities except in palliative roles. The overall prognosis is poor, with reported 5-year survival rates usually below 50%. METHODS: Forty-three patients with primary mucosal melanoma of the female genitalia seen at the Duke University Medical Center Melanoma Clinic during a 25-year period were studied retrospectively. Specific information was obtained from the patients' clinic charts and computerized databases. RESULTS: Thirty vulvar, nine vaginal, and four cervical lesions were identified. The median age at diagnosis was 61.4 years. At initial presentation, two thirds of the patients had localized disease only. Tumor ulceration and thickness of the primary lesion had a measurable impact on prognosis, whereas the presence of regional metastases at presentation did not. All but one patient underwent resection with curative intent. The performance of radical operations did not improve outcome among patients with vulvar melanoma. Many of the treatment failures were the result of local recurrences, hinting at the need to improve local control. Despite therapy, the overall corrected 5-year survival rate was 54%. CONCLUSIONS: Prospective multicenter trials for patients with vulvovaginal melanoma could be helpful in establishing uniform, standardized surgical protocols and delineating the applicability of new modalities and therapies, such as lymphoscintigraphy with sentinel node biopsy and high-dose interferon.

Adult↗
PubMed1997

cash4, a novel achaete-scute homolog induced by Hensen's node during generation of the posterior nervous system.

In vertebrate embryos, the precursor cells of the central nervous system (CNS) are induced by signaling from the organizer region. Here we report the isolation of a novel vertebrate achaete-scute homolog, cash4, which is expressed in the presumptive posterior nervous system in response to such signaling. cash4 is first expressed in epiblast cells flanking the late-phase organizer (Hensen's node), which retains its ability to induce cash4 during regression to the caudal end of the embryo. We show that these node-derived signals can be mimicked in vivo by the activity of fibroblast growth factor (FGF). We demonstrate that cash4 can substitute for the achaete/scute genes in the fly and that it also has proneural activity in vertebrate embryos. Together these results suggest that cash4 functions as a proneural gene downstream of node-derived signals (including FGF) to promote the formation of the neural precursors that will give rise to the posterior CNS in the chick embryo.

Amino Acid Sequence↗
PubMed1997

Advances in prevention of radiation damage to visceral and solid organs in patients requiring radiation therapy of the trunk.

BACKGROUND: As a part of multimodality therapy, many patients with tumors of the trunk receive radiation therapy. The major morbidity of this therapy is often secondary to incidental radiation damage to tissues adjacent to treatment areas. METHODS: We detail our use of saline breast implants placed in polyglycolic acid mesh sheets to displace visceral and solid organs away from the radiation field. RESULTS: Analysis of CT scans and dose volume histograms reveal that this technique successfully displaces uninvolved organs away from the radiation fields, thereby minimizing the radiation dose to such organs and tissues. CONCLUSION: We believe this is a safe and efficacious method to prevent radiation damage to visceral and solid organs adjacent to trunk tumor sites.

Abdominal Muscles↗
PubMed1997

Episodic ocean-induced CO2 greenhouse on Mars: implications for fluvial valley formation.

Pulses of CO2 injected into the martian atmosphere more recently than 4 Ga can place the atmosphere into a stable, higher pressure, warmer greenhouse state. One to two bar pulses of CO2 added to the atmosphere during the past several billion years are sufficient to raise global mean temperatures above 240 or 250 K for tens to hundreds of millions of years, even when accounting for CO2 condensation. Over time, the added CO2 is lost to carbonates, the atmosphere collapses and returns to its buffered state. A substantial amount of water could be transported during the greenhouse periods from the surface of a frozen body of water created by outflow channel discharges to higher elevations, despite global temperatures well below freezing. This water, precipitated as snow, could ultimately form fluvial valleys if deposition sites are associated with localized heat sources, such as magmatic intrusions or volcanoes. Thus, if outflow channel discharges were accompanied by the release of sufficient quantities of CO2, a limited hydrological cycle could have resulted that would have been capable of producing geomorphic change sufficient for fluvial erosion and valley formation. Glacial or periglacial landforms would also be a consequence of such a mechanism.

Atmosphere↗
PubMed1997

Sphingomyelin metabolism is developmentally regulated in rat lung.

We investigated several indices involved in sphingomyelin metabolism in developing rat lung. The levels of sphingomyelin gradually increased during lung maturation, with highest levels observed postnatally. The content of sphingosine and ceramide, biologically active sphingomyelin degradation products, did not significantly change in microsomes during the prenatal period, but increased to peak levels in neonatal and adult lung, respectively. Sphingosine content increased 6-fold between the fetal (Day 21) and neonatal period. The developmental profiles of two enzymes involved in sphingomyelin synthesis, serine palmitoyltransferase and sphingomyelin synthase, were similar. Serine palmitoyltransferase activity increased progressively from the fetal to neonatal period, and plateaued at high levels in the adult lung. The activity of serine palmitoyltransferase correlated with the levels of endogenous sphingolipid in lung tissue. Sphingomyelin synthase activity also increased during fetal lung development, but attained highest levels at Day 21 gestation; postnatally, enzyme activity was detected at lower levels. The activities of the sphingolipid hydrolases, acid and neutral sphingomyelinase and acid and alkaline ceramidase, were elevated in fetal lung, thereafter declining to low levels after birth. Studies conducted in alveolar macrophages, fibroblasts, and alveolar type II epithelial cells revealed that these developmental changes in enzyme activities in lung tissue were also occuring globally at the cellular level and were not restricted to any specific cell population. These studies suggest that the developmental increase in lung sphingomyelin content is due to coordinate regulation of enzymes involved in the biosynthesis and degradation of sphingomyelin. These observations also suggest a regulatory role for serine palmitoyltransferase in the generation of long chain sphingoid bases.

Acyltransferases↗
PubMed1996

A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees.

Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th-18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Bipolar Disorder↗
PubMed1996

Comparison of nebulized glycopyrrolate and metaproterenol in chronic obstructive pulmonary disease.

We assessed the bronchodilating effect of glycopyrrolate (GP) and compared it with that of metaproterenol (MP), alone and in combination (GP+MP), in patients with chronic obstructive pulmonary disease (COPD). In a double-blind study, 11 patients (aged (mean +/- SD) 69 +/- 6 yrs; forced expiratory volume in one second (FEV1) 1.2 +/- 0.4 L) with stable COPD inhaled nebulized GP 1.0 mg, MP 15 mg, or GP 1.0 mg+MP 15 mg. Spirometry was performed before inhalation and at hourly intervals for 8 h after inhalation. It was found that GP produced a bronchodilating effect that was about equal to that of MP but lasted longer (8 vs 5 h). The combination of GP and MP produced a bronchodilating effect that was greater than that of either drug alone and was evident mostly during the effect of MP. The mean peak percentage improvement in FEV1 over baseline was 35% for GP+MP and 25% for either drug alone. These data suggest that nebulized glycopyrrolate is an effective bronchodilator in some patients with chronic obstructive pulmonary disease. Concurrent administration of glycopyrrolate and metaproterenol produces additional bronchodilation that is primarily apparent during the bronchodilator effect of metaproterenol.

Administration, Inhalation↗